PARADIGM pathway analysis of mRNASeq expression data - Breast Invasive Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Class IB PI3K non-lipid kinase events	268
Signaling events mediated by Stem cell factor receptor (c-Kit)	261
EGFR-dependent Endothelin signaling events	227
Reelin signaling pathway	218
Signaling mediated by p38-alpha and p38-beta	194
HIF-1-alpha transcription factor network	160
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	156
FOXA2 and FOXA3 transcription factor networks	155
p75(NTR)-mediated signaling	142
Glucocorticoid receptor regulatory network	140

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Class IB PI3K non-lipid kinase events	0.2713	268	804	3	-0.22	-1000	1000	-1000	-0.024	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.2642	261	20425	78	-0.62	0.19	1000	-1000	-0.078	-1000
EGFR-dependent Endothelin signaling events	0.2298	227	4772	21	-0.35	0	1000	-1000	-0.065	-1000
Reelin signaling pathway	0.2206	218	12250	56	-0.49	0	1000	-1000	-0.091	-1000
Signaling mediated by p38-alpha and p38-beta	0.1964	194	8550	44	-0.4	0	1000	-1000	-0.052	-1000
HIF-1-alpha transcription factor network	0.1619	160	12178	76	-0.76	0.018	1000	-1000	-0.09	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1579	156	10664	68	-0.52	0.17	1000	-1000	-0.086	-1000
FOXA2 and FOXA3 transcription factor networks	0.1569	155	7156	46	-1.2	0.025	1000	-1000	-0.025	-1000
p75(NTR)-mediated signaling	0.1437	142	17855	125	-0.39	0	1000	-1000	-0.1	-1000
Glucocorticoid receptor regulatory network	0.1417	140	15996	114	-0.94	0.35	1000	-1000	-0.063	-1000
FOXM1 transcription factor network	0.1377	136	6971	51	-0.43	0.014	1000	-1000	-0.12	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1356	134	11834	88	-0.36	0.037	1000	-1000	-0.1	-1000
IL4-mediated signaling events	0.1336	132	12056	91	-1	0.52	1000	-1000	-0.12	-1000
Wnt signaling	0.1265	125	880	7	-0.18	-0.007	1000	-1000	-0.042	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1255	124	6710	54	-0.49	0.022	1000	-1000	-0.092	-1000
Arf6 signaling events	0.1235	122	7598	62	-0.35	0.017	1000	-1000	-0.059	-1000
Endothelins	0.1215	120	11603	96	-0.38	0.034	1000	-1000	-0.069	-1000
Ephrin B reverse signaling	0.1184	117	5638	48	-0.34	0.19	1000	-1000	-0.068	-1000
EPHB forward signaling	0.1184	117	9981	85	-0.34	0.18	1000	-1000	-0.08	-1000
IGF1 pathway	0.1083	107	6102	57	-0.18	0.08	1000	-1000	-0.083	-1000
Noncanonical Wnt signaling pathway	0.1022	101	2626	26	-0.18	0	1000	-1000	-0.067	-1000
Signaling events regulated by Ret tyrosine kinase	0.1012	100	8257	82	-0.17	0	1000	-1000	-0.071	-1000
Calcium signaling in the CD4+ TCR pathway	0.1012	100	3110	31	-0.32	0.011	1000	-1000	-0.065	-1000
Nongenotropic Androgen signaling	0.0972	96	5003	52	-0.23	0.11	1000	-1000	-0.057	-1000
ErbB2/ErbB3 signaling events	0.0941	93	6062	65	-0.4	0.018	1000	-1000	-0.067	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0941	93	7961	85	-0.24	0.011	1000	-1000	-0.066	-1000
ErbB4 signaling events	0.0931	92	6386	69	-0.42	0.06	1000	-1000	-0.087	-1000
Aurora B signaling	0.0911	90	6093	67	-0.32	0.012	1000	-1000	-0.071	-1000
Glypican 1 network	0.0891	88	4234	48	-0.32	0.03	1000	-1000	-0.048	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0891	88	10643	120	-0.6	0.24	1000	-1000	-0.08	-1000
BMP receptor signaling	0.0870	86	7031	81	-0.55	0.026	1000	-1000	-0.086	-1000
Visual signal transduction: Rods	0.0870	86	4487	52	-0.48	0	1000	-1000	-0.073	-1000
Plasma membrane estrogen receptor signaling	0.0850	84	7259	86	-0.2	0.091	1000	-1000	-0.074	-1000
IL6-mediated signaling events	0.0820	81	6137	75	-0.29	0.052	1000	-1000	-0.068	-1000
Integrins in angiogenesis	0.0810	80	6737	84	-0.33	0	1000	-1000	-0.08	-1000
Signaling events mediated by PTP1B	0.0789	78	5933	76	-0.65	0.073	1000	-1000	-0.071	-1000
amb2 Integrin signaling	0.0779	77	6359	82	-0.51	0	1000	-1000	-0.073	-1000
IL23-mediated signaling events	0.0759	75	4521	60	-0.46	0.018	1000	-1000	-0.13	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0729	72	3751	52	-0.19	0.03	1000	-1000	-0.064	-1000
Ephrin A reverse signaling	0.0688	68	477	7	-0.078	0	1000	-1000	-0.039	-1000
LPA receptor mediated events	0.0668	66	6778	102	-0.3	0.028	1000	-1000	-0.076	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0658	65	2214	34	-0.089	0	1000	-1000	-0.049	-1000
S1P1 pathway	0.0658	65	2364	36	-0.33	0.008	1000	-1000	-0.064	-1000
Syndecan-3-mediated signaling events	0.0638	63	2222	35	-0.35	0	1000	-1000	-0.063	-1000
Signaling events mediated by the Hedgehog family	0.0617	61	3217	52	-0.22	0.03	1000	-1000	-0.07	-1000
PDGFR-alpha signaling pathway	0.0617	61	2688	44	-0.37	0.019	1000	-1000	-0.054	-1000
Syndecan-1-mediated signaling events	0.0587	58	2000	34	-0.21	0	1000	-1000	-0.062	-1000
Fc-epsilon receptor I signaling in mast cells	0.0587	58	5692	97	-0.24	0.027	1000	-1000	-0.086	-1000
E-cadherin signaling in keratinocytes	0.0587	58	2517	43	-0.3	0.041	1000	-1000	-0.066	-1000
TCGA08_rtk_signaling	0.0506	50	1322	26	-0.3	0.026	1000	-1000	-0.029	-1000
Visual signal transduction: Cones	0.0486	48	1839	38	-0.17	0.007	1000	-1000	-0.067	-1000
Nectin adhesion pathway	0.0486	48	3070	63	-0.085	0.002	1000	-1000	-0.067	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0486	48	3591	74	-0.3	0.07	1000	-1000	-0.079	-1000
Rapid glucocorticoid signaling	0.0486	48	976	20	-0.19	0.027	1000	-1000	-0.046	-1000
Ras signaling in the CD4+ TCR pathway	0.0486	48	827	17	-0.12	-0.001	1000	-1000	-0.062	-1000
FAS signaling pathway (CD95)	0.0476	47	2216	47	-0.47	0.013	1000	-1000	-0.047	-1000
Glypican 2 network	0.0476	47	189	4	-0.034	-0.029	1000	-1000	-0.029	-1000
Signaling events mediated by HDAC Class III	0.0466	46	1876	40	-0.57	0.019	1000	-1000	-0.034	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0466	46	1535	33	-0.55	0	1000	-1000	-0.064	-1000
LPA4-mediated signaling events	0.0445	44	529	12	-0.16	0.019	1000	-1000	-0.022	-1000
Signaling events mediated by PRL	0.0445	44	1517	34	-0.18	0.02	1000	-1000	-0.067	-1000
Presenilin action in Notch and Wnt signaling	0.0405	40	2489	61	-0.42	0.014	1000	-1000	-0.058	-1000
Syndecan-4-mediated signaling events	0.0385	38	2547	67	-0.32	0.005	1000	-1000	-0.079	-1000
Regulation of Androgen receptor activity	0.0364	36	2529	70	-0.26	0.022	1000	-1000	-0.061	-1000
IL12-mediated signaling events	0.0354	35	3096	87	-0.36	0.05	1000	-1000	-0.11	-1000
TCR signaling in naïve CD8+ T cells	0.0354	35	3335	93	-0.16	0.078	1000	-1000	-0.071	-1000
Coregulation of Androgen receptor activity	0.0344	34	2647	76	-0.19	0.035	1000	-1000	-0.048	-1000
BCR signaling pathway	0.0344	34	3383	99	-0.14	0.042	1000	-1000	-0.074	-1000
Insulin Pathway	0.0344	34	2578	74	-0.2	0.033	1000	-1000	-0.08	-1000
Osteopontin-mediated events	0.0324	32	1220	38	-0.24	0.025	1000	-1000	-0.083	-1000
IL27-mediated signaling events	0.0324	32	1665	51	-0.29	0.028	1000	-1000	-0.082	-1000
PLK1 signaling events	0.0314	31	2635	85	-0.21	0.033	1000	-1000	-0.056	-1000
Syndecan-2-mediated signaling events	0.0304	30	2095	69	-0.2	0.035	1000	-1000	-0.056	-1000
TCGA08_retinoblastoma	0.0304	30	244	8	-0.049	0.009	1000	-1000	-0.022	-1000
Regulation of nuclear SMAD2/3 signaling	0.0294	29	4072	136	-0.31	0.051	1000	-1000	-0.071	-1000
Canonical Wnt signaling pathway	0.0294	29	1489	51	-0.42	0.14	1000	-1000	-0.053	-1000
Thromboxane A2 receptor signaling	0.0273	27	2925	105	-0.3	0.066	1000	-1000	-0.075	-1000
Regulation of p38-alpha and p38-beta	0.0273	27	1470	54	-0.37	0.027	1000	-1000	-0.072	-1000
Regulation of Telomerase	0.0273	27	2786	102	-0.35	0.021	1000	-1000	-0.084	-1000
IL2 signaling events mediated by STAT5	0.0263	26	572	22	-0.12	0.064	1000	-1000	-0.038	-1000
Arf6 trafficking events	0.0263	26	1846	71	-0.45	0.032	1000	-1000	-0.066	-1000
TCGA08_p53	0.0233	23	167	7	-0.023	0.015	1000	-1000	-0.03	-1000
S1P5 pathway	0.0213	21	365	17	-0.042	0.023	1000	-1000	-0.049	-1000
Hedgehog signaling events mediated by Gli proteins	0.0182	18	1229	65	-0.069	0.04	1000	-1000	-0.074	-1000
S1P4 pathway	0.0182	18	471	25	-0.042	0	1000	-1000	-0.048	-1000
Class I PI3K signaling events mediated by Akt	0.0172	17	1199	68	-0.26	0.053	1000	-1000	-0.059	-1000
Ceramide signaling pathway	0.0172	17	1303	76	-0.18	0.048	1000	-1000	-0.064	-1000
TRAIL signaling pathway	0.0172	17	853	48	-0.076	0.045	1000	-1000	-0.061	-1000
E-cadherin signaling events	0.0172	17	89	5	-0.024	0	1000	-1000	-0.042	-1000
Effects of Botulinum toxin	0.0162	16	441	26	-0.094	0.001	1000	-1000	-0.057	-1000
Caspase cascade in apoptosis	0.0152	15	1119	74	-0.05	0.045	1000	-1000	-0.052	-1000
Cellular roles of Anthrax toxin	0.0152	15	586	39	-0.14	0.019	1000	-1000	-0.028	-1000
Retinoic acid receptors-mediated signaling	0.0152	15	885	58	-0.11	0.037	1000	-1000	-0.065	-1000
Aurora A signaling	0.0142	14	868	60	-0.2	0.007	1000	-1000	-0.059	-1000
PLK2 and PLK4 events	0.0132	13	40	3	-0.011	0.014	1000	-1000	-0.02	-1000
Signaling mediated by p38-gamma and p38-delta	0.0132	13	208	15	-0.017	0.022	1000	-1000	-0.053	-1000
E-cadherin signaling in the nascent adherens junction	0.0132	13	988	76	-0.024	0.048	1000	-1000	-0.073	-1000
S1P3 pathway	0.0132	13	555	42	-0.03	0.021	1000	-1000	-0.051	-1000
IL1-mediated signaling events	0.0121	12	746	62	-0.037	0.031	1000	-1000	-0.089	-1000
BARD1 signaling events	0.0111	11	640	57	-0.11	0.023	1000	-1000	-0.065	-1000
JNK signaling in the CD4+ TCR pathway	0.0111	11	188	17	-0.02	0.043	1000	-1000	-0.057	-1000
IL2 signaling events mediated by PI3K	0.0111	11	675	58	-0.038	0.061	1000	-1000	-0.077	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0101	10	287	28	-0.042	0.017	1000	-1000	-0.053	-1000
mTOR signaling pathway	0.0101	10	535	53	-0.019	0.026	1000	-1000	-0.056	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0091	9	757	83	-0.066	0.05	1000	-1000	-0.064	-1000
p38 MAPK signaling pathway	0.0091	9	406	44	-0.073	0.027	1000	-1000	-0.055	-1000
Signaling events mediated by HDAC Class II	0.0081	8	632	75	-0.15	0	1000	-1000	-0.056	-1000
a4b1 and a4b7 Integrin signaling	0.0081	8	40	5	-0.008	-0.002	1000	-1000	-0.034	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0081	8	329	37	-0.046	0.033	1000	-1000	-0.071	-1000
VEGFR1 specific signals	0.0071	7	433	56	-0.17	0.061	1000	-1000	-0.071	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0061	6	795	125	-0.17	0.083	1000	-1000	-0.098	-1000
PDGFR-beta signaling pathway	0.0061	6	627	97	-0.023	0.052	1000	-1000	-0.08	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0051	5	130	23	-0.029	0.041	1000	-1000	-0.061	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0051	5	268	45	-0.027	0.073	1000	-1000	-0.085	-1000
ceramide signaling pathway	0.0040	4	197	49	-0.029	0.052	1000	-1000	-0.042	-1000
HIF-2-alpha transcription factor network	0.0040	4	207	43	-0.16	0.18	1000	-1000	-0.068	-1000
Signaling events mediated by HDAC Class I	0.0040	4	444	104	-0.093	0.045	1000	-1000	-0.064	-1000
FoxO family signaling	0.0040	4	308	64	-0.04	0.093	1000	-1000	-0.071	-1000
Class I PI3K signaling events	0.0040	4	305	73	-0.04	0.059	1000	-1000	-0.069	-1000
Canonical NF-kappaB pathway	0.0030	3	131	39	-0.02	0.076	1000	-1000	-0.062	-1000
Circadian rhythm pathway	0.0030	3	70	22	-0.016	0.042	1000	-1000	-0.06	-1000
EPO signaling pathway	0.0030	3	200	55	-0.035	0.056	1000	-1000	-0.085	-1000
Insulin-mediated glucose transport	0.0030	3	101	32	-0.13	0.031	1000	-1000	-0.055	-1000
Atypical NF-kappaB pathway	0.0030	3	104	31	-0.02	0.03	1000	-1000	-0.064	-1000
Arf6 downstream pathway	0.0020	2	112	43	-0.011	0.021	1000	-1000	-0.043	-1000
IFN-gamma pathway	0.0020	2	183	68	-0.073	0.075	1000	-1000	-0.086	-1000
Paxillin-dependent events mediated by a4b1	0.0020	2	98	36	-0.011	0.022	1000	-1000	-0.069	-1000
Aurora C signaling	0.0000	0	2	7	-0.16	0	1000	-1000	-0.045	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	7	27	-0.001	0.028	1000	-1000	-0.049	-1000
Arf1 pathway	0.0000	0	5	54	-0.001	0.025	1000	-1000	-0.044	-1000
Alternative NF-kappaB pathway	0.0000	0	1	13	-0.003	0	1000	-1000	-0.061	-1000
Total	NA	7086	419221	7203	-31	-990	131000	-131000	-8.5	-131000

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.22	0.36	0.8	268	-10000	0	268
PI3K Class IB/PDE3B	-0.22	0.36	-10000	0	-0.8	268	268
PDE3B	-0.22	0.36	-10000	0	-0.81	268	268

×

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

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
MAP4K1	-0.16	0.22	-10000	0	-0.39	452	452
CRKL	-0.17	0.23	-10000	0	-0.41	451	451
HRAS	-0.16	0.17	-10000	0	-0.53	33	33
mol:PIP3	-0.17	0.21	-10000	0	-0.4	453	453
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.18	0.24	-10000	0	-0.44	453	453
FOXO3	-0.15	0.21	-10000	0	-0.37	451	451
AKT1	-0.17	0.22	-10000	0	-0.41	452	452
BAD	-0.15	0.21	-10000	0	-0.37	451	451
megakaryocyte differentiation	-0.18	0.24	-10000	0	-0.43	454	454
GSK3B	-0.15	0.21	-10000	0	-0.37	451	451
RAF1	-0.093	0.17	-10000	0	-0.44	25	25
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.18	0.24	-10000	0	-0.44	453	453
STAT1	-0.46	0.56	-10000	0	-1	462	462
HRAS/SPRED1	-0.13	0.14	-10000	0	-0.44	26	26
cell proliferation	-0.18	0.24	-10000	0	-0.44	453	453
PIK3CA	0	0.009	-10000	0	-0.28	1	1
TEC	-0.002	0.044	-10000	0	-0.81	3	3
RPS6KB1	-0.18	0.24	-10000	0	-0.44	453	453
HRAS/SPRED2	-0.13	0.14	-10000	0	-0.44	25	25
LYN/TEC/p62DOK	-0.19	0.2	-10000	0	-0.4	453	453
MAPK3	-0.055	0.13	-10000	0	-0.32	19	19
STAP1	-0.2	0.24	-10000	0	-0.45	455	455
GRAP2	-0.015	0.11	-10000	0	-0.81	17	17
JAK2	-0.4	0.44	-10000	0	-0.88	455	455
STAT1 (dimer)	-0.44	0.55	-10000	0	-1	462	462
mol:Gleevec	0.006	0.009	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.19	0.2	-10000	0	-0.41	452	452
actin filament polymerization	-0.18	0.24	-10000	0	-0.44	453	453
LYN	0	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.27	0.34	-10000	0	-0.63	453	453
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
CBL/CRKL/GRB2	-0.17	0.18	-10000	0	-0.37	451	451
PI3K	-0.19	0.21	-10000	0	-0.41	456	456
PTEN	-0.002	0.036	-10000	0	-0.81	2	2
SCF/KIT/EPO/EPOR	-0.6	0.67	-10000	0	-1.3	451	451
MAPK8	-0.19	0.24	-10000	0	-0.44	453	453
STAT3 (dimer)	-0.18	0.23	-10000	0	-0.43	453	453
positive regulation of transcription	-0.042	0.11	-10000	0	-0.26	19	19
mol:GDP	-0.17	0.18	-10000	0	-0.52	40	40
PIK3C2B	-0.18	0.24	-10000	0	-0.44	453	453
CBL/CRKL	-0.18	0.19	-10000	0	-0.38	451	451
FER	-0.19	0.24	-10000	0	-0.45	459	459
SH2B3	-0.18	0.24	-10000	0	-0.44	453	453
PDPK1	-0.15	0.2	-10000	0	-0.36	452	452
SNAI2	-0.19	0.25	-10000	0	-0.45	455	455
positive regulation of cell proliferation	-0.32	0.41	-10000	0	-0.75	462	462
KITLG	0.001	0.071	-10000	0	-0.48	16	16
cell motility	-0.32	0.41	-10000	0	-0.75	462	462
PTPN6	0.015	0.021	-10000	0	-0.29	1	1
EPOR	-0.098	0.16	-10000	0	-10000	0	0
STAT5A (dimer)	-0.26	0.34	-10000	0	-0.62	463	463
SOCS1	-0.005	0.042	-10000	0	-0.81	1	1
cell migration	0.19	0.24	0.44	461	-10000	0	461
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.043	0.11	-10000	0	-0.3	100	100
VAV1	-0.001	0.029	-10000	0	-0.46	3	3
GRB10	-0.18	0.24	-10000	0	-0.44	453	453
PTPN11	0.013	0.013	-10000	0	-10000	0	0
SCF/KIT	-0.22	0.24	-10000	0	-0.47	454	454
GO:0007205	0.009	0.013	-10000	0	-10000	0	0
MAP2K1	-0.064	0.14	-10000	0	-0.36	19	19
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.62	0.73	-10000	0	-1.4	449	449
MAP2K2	-0.064	0.14	-10000	0	-0.36	19	19
SHC/Grb2/SOS1	-0.19	0.2	-10000	0	-0.4	451	451
STAT5A	-0.27	0.35	-10000	0	-0.64	457	457
GRB2	0	0.009	-10000	0	-0.28	1	1
response to radiation	-0.18	0.24	-10000	0	-0.44	455	455
SHC/GRAP2	-0.011	0.081	-10000	0	-0.62	17	17
PTPRO	-0.18	0.24	-10000	0	-0.44	454	454
SH2B2	-0.19	0.24	-10000	0	-0.44	453	453
DOK1	-0.001	0.013	-10000	0	-0.28	2	2
MATK	-0.2	0.25	-10000	0	-0.45	461	461
CREBBP	0.019	0.018	-10000	0	-10000	0	0
BCL2	-0.14	0.31	-10000	0	-1.5	35	35

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	-0.001	0.02	-9999	-10000	0	0
EGFR	-0.3	0.39	-9999	-0.8	369	369
EGF/EGFR	-0.29	0.32	-9999	-0.56	513	513
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.26	0.28	-9999	-0.51	504	504
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.001	0.026	-9999	-0.81	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.17	0.33	-9999	-0.8	206	206
EGF/EGFR dimer/SHC	-0.3	0.32	-9999	-0.59	504	504
mol:GDP	-0.26	0.27	-9999	-0.5	504	504
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.062	0.22	-9999	-0.8	77	77
GRB2/SOS1	0	0.006	-9999	-10000	0	0
HRAS/GTP	-0.24	0.25	-9999	-0.46	504	504
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.24	0.26	-9999	-0.47	504	504
FRAP1	-0.25	0.26	-9999	-0.48	504	504
EGF/EGFR dimer	-0.35	0.36	-9999	-0.68	504	504
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-0.28	1	1
ETA receptor/Endothelin-1	-0.048	0.17	-9999	-0.62	77	77

×

Reelin signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.007	0.033	-9999	-10000	0	0
VLDLR	-0.025	0.14	-9999	-0.81	30	30
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.002	0.036	-9999	-0.81	2	2
ITGA3	-0.004	0.053	-9999	-0.81	4	4
RELN/VLDLR/Fyn	-0.34	0.28	-9999	-0.55	606	606
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.004	0.041	-9999	-0.45	8	8
AKT1	-0.2	0.17	-9999	-0.33	610	610
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.017	0.067	-9999	-0.28	60	60
RELN/LRP8/DAB1	-0.32	0.25	-9999	-0.52	599	599
LRPAP1/LRP8	-0.019	0.055	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.3	0.24	-9999	-0.49	599	599
DAB1/alpha3/beta1 Integrin	-0.28	0.23	-9999	-0.51	247	247
long-term memory	-0.36	0.3	-9999	-0.55	649	649
DAB1/LIS1	-0.29	0.23	-9999	-0.46	606	606
DAB1/CRLK/C3G	-0.28	0.23	-9999	-0.51	246	246
PIK3CA	0	0.009	-9999	-0.28	1	1
DAB1/NCK2	-0.29	0.24	-9999	-0.47	606	606
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.092	0.25	-9999	-0.76	121	121
CDK5R1	-0.009	0.049	-9999	-10000	0	0
RELN	-0.49	0.39	-9999	-0.8	601	601
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
RELN/LRP8/Fyn	-0.34	0.27	-9999	-0.55	598	598
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.35	0.3	-9999	-0.55	615	615
MAPK8	-0.004	0.057	-9999	-0.81	5	5
RELN/VLDLR/DAB1	-0.32	0.26	-9999	-0.52	606	606
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.31	0.26	-9999	-0.5	608	608
RELN/LRP8	-0.34	0.27	-9999	-0.55	598	598
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.33	0.26	-9999	-0.51	633	633
PI3K	-0.005	0.052	-9999	-0.62	7	7
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.04	-9999	-0.62	4	4
RAP1A	-0.26	0.21	-9999	-0.54	136	136
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.004	0.049	-9999	-0.46	9	9
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.06	0.21	-9999	-0.79	75	75
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.13	0.11	-9999	-0.45	10	10
neuron adhesion	-0.24	0.2	-9999	-0.51	138	138
LRP8	-0.031	0.087	-9999	-10000	0	0
GSK3B	-0.17	0.17	-9999	-0.44	64	64
RELN/VLDLR/DAB1/Fyn	-0.3	0.25	-9999	-0.49	606	606
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.22	0.18	-9999	-0.35	610	610
CDK5	-0.002	0.022	-9999	-0.28	6	6
MAPT	-0.043	0.24	-9999	-0.73	105	105
neuron migration	-0.23	0.24	-9999	-0.42	599	599
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.14	0.11	-9999	-0.46	10	10
RELN/VLDLR	-0.32	0.26	-9999	-0.52	606	606

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.4	0.62	-9999	-1.3	330	330
MKNK1	0	0	-9999	-10000	0	0
MAPK14	-0.081	0.15	-9999	-0.4	15	15
ATF2/c-Jun	-0.054	0.16	-9999	-0.84	16	16
MAPK11	-0.084	0.16	-9999	-0.49	18	18
MITF	-0.093	0.2	-9999	-0.36	337	337
MAPKAPK5	-0.089	0.19	-9999	-0.35	333	333
KRT8	-0.094	0.19	-9999	-0.36	334	334
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0.009	-9999	-10000	0	0
p38alpha-beta/CK2	-0.12	0.24	-9999	-0.45	333	333
CEBPB	-0.089	0.19	-9999	-0.35	333	333
SLC9A1	-0.089	0.19	-9999	-0.35	333	333
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.082	0.19	-9999	-0.34	333	333
p38alpha-beta/MNK1	-0.12	0.17	-9999	-0.55	18	18
JUN	-0.053	0.16	-9999	-0.83	16	16
PPARGC1A	-0.21	0.36	-9999	-0.57	412	412
USF1	-0.089	0.19	-9999	-0.35	333	333
RAB5/GDP/GDI1	-0.085	0.12	-9999	-0.38	18	18
NOS2	-0.093	0.22	-9999	-1.1	11	11
DDIT3	-0.089	0.19	-9999	-0.35	333	333
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.072	0.16	-9999	-0.43	44	44
p38alpha-beta/HBP1	-0.12	0.17	-9999	-0.55	18	18
CREB1	-0.093	0.2	-9999	-0.37	333	333
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.07	0.17	-9999	-0.52	14	14
RPS6KA4	-0.089	0.19	-9999	-0.35	333	333
PLA2G4A	-0.13	0.27	-9999	-0.74	120	120
GDI1	-0.089	0.19	-9999	-0.35	333	333
TP53	-0.11	0.24	-9999	-0.44	333	333
RPS6KA5	-0.094	0.2	-9999	-0.36	341	341
ESR1	-0.17	0.25	-9999	-0.42	454	454
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.09	0.2	-9999	-0.36	333	333
MEF2A	-0.089	0.19	-9999	-0.36	333	333
EIF4EBP1	-0.093	0.2	-9999	-0.37	333	333
KRT19	-0.1	0.21	-9999	-0.38	336	336
ELK4	-0.089	0.19	-9999	-0.35	333	333
ATF6	-0.089	0.19	-9999	-0.35	333	333
ATF1	-0.093	0.2	-9999	-0.37	333	333
p38alpha-beta/MAPKAPK2	-0.12	0.17	-9999	-0.55	19	19
p38alpha-beta/MAPKAPK3	-0.12	0.17	-9999	-0.55	18	18

×

HIF-1-alpha transcription factor network

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
PKM2	-0.41	0.46	-9999	-1	231	231
HDAC7	0	0.001	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.32	0.31	-9999	-0.81	175	175
SMAD4	-0.001	0.026	-9999	-0.8	1	1
ID2	-0.41	0.46	-9999	-1.1	202	202
AP1	-0.19	0.29	-9999	-0.63	299	299
ABCG2	-0.44	0.5	-9999	-1.1	219	219
HIF1A	-0.052	0.062	-9999	-10000	0	0
TFF3	-0.48	0.52	-9999	-1.1	278	278
GATA2	-0.015	0.14	-9999	-0.66	38	38
AKT1	-0.053	0.08	-9999	-10000	0	0
response to hypoxia	-0.075	0.086	-9999	-0.24	44	44
MCL1	-0.41	0.46	-9999	-1.1	219	219
NDRG1	-0.41	0.46	-9999	-1.1	205	205
SERPINE1	-0.41	0.46	-9999	-1	228	228
FECH	-0.41	0.46	-9999	-1	222	222
FURIN	-0.41	0.46	-9999	-1.1	212	212
NCOA2	-0.017	0.14	-9999	-0.81	31	31
EP300	-0.053	0.12	-9999	-0.35	54	54
HMOX1	-0.41	0.46	-9999	-1.1	204	204
BHLHE40	-0.41	0.46	-9999	-1.1	205	205
BHLHE41	-0.42	0.47	-9999	-1.1	204	204
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.05	0.055	-9999	-0.62	1	1
ENG	-0.036	0.061	-9999	-0.56	1	1
JUN	-0.007	0.077	-9999	-0.81	9	9
RORA	-0.41	0.46	-9999	-1.1	205	205
ABCB1	-0.34	0.55	-9999	-1.4	191	191
TFRC	-0.41	0.46	-9999	-1.1	218	218
CXCR4	-0.41	0.46	-9999	-1.1	209	209
TF	-0.65	0.58	-9999	-1.2	470	470
CITED2	-0.41	0.46	-9999	-1.1	200	200
HIF1A/ARNT	-0.5	0.52	-9999	-1.2	269	269
LDHA	-0.049	0.047	-9999	-10000	0	0
ETS1	-0.41	0.46	-9999	-1.1	219	219
PGK1	-0.41	0.46	-9999	-1	227	227
NOS2	-0.41	0.46	-9999	-1.1	220	220
ITGB2	-0.41	0.46	-9999	-1.1	218	218
ALDOA	-0.41	0.46	-9999	-1.1	211	211
Cbp/p300/CITED2	-0.43	0.44	-9999	-1.1	215	215
FOS	-0.24	0.37	-9999	-0.81	298	298
HK2	-0.41	0.46	-9999	-1	238	238
SP1	0.012	0.023	-9999	-10000	0	0
GCK	-0.14	0.38	-9999	-1.6	55	55
HK1	-0.41	0.46	-9999	-1.1	204	204
NPM1	-0.41	0.46	-9999	-1.1	206	206
EGLN1	-0.41	0.46	-9999	-1.1	202	202
CREB1	0.018	0	-9999	-10000	0	0
PGM1	-0.41	0.46	-9999	-1	222	222
SMAD3	0	0	-9999	-10000	0	0
EDN1	-0.2	0.41	-9999	-1.1	128	128
IGFBP1	-0.51	0.53	-9999	-1.2	299	299
VEGFA	-0.24	0.31	-9999	-0.77	100	100
HIF1A/JAB1	-0.028	0.026	-9999	-10000	0	0
CP	-0.52	0.55	-9999	-1.2	328	328
CXCL12	-0.44	0.5	-9999	-1.2	213	213
COPS5	0.008	0.011	-9999	-10000	0	0
SMAD3/SMAD4	-0.001	0.02	-9999	-0.61	1	1
BNIP3	-0.41	0.46	-9999	-1	222	222
EGLN3	-0.42	0.46	-9999	-1.1	209	209
CA9	-0.45	0.48	-9999	-1.1	252	252
TERT	-0.42	0.47	-9999	-1.1	228	228
ENO1	-0.41	0.46	-9999	-1.1	216	216
PFKL	-0.41	0.46	-9999	-1.1	202	202
NCOA1	-0.001	0.026	-9999	-0.81	1	1
ADM	-0.44	0.49	-9999	-1.1	229	229
ARNT	-0.054	0.06	-9999	-10000	0	0
HNF4A	-0.001	0.04	-9999	-0.28	15	15
ADFP	-0.42	0.46	-9999	-1	269	269
SLC2A1	-0.25	0.32	-9999	-0.79	88	88
LEP	-0.76	0.52	-9999	-1.2	514	514
HIF1A/ARNT/Cbp/p300	-0.34	0.33	-9999	-0.81	207	207
EPO	-0.23	0.26	-9999	-0.84	34	34
CREBBP	-0.053	0.12	-9999	-0.35	54	54
HIF1A/ARNT/Cbp/p300/HDAC7	-0.32	0.31	-9999	-0.84	151	151
PFKFB3	-0.41	0.47	-9999	-1.1	204	204
NT5E	-0.41	0.46	-9999	-1	235	235

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.073	0.15	-10000	0	-0.38	130	130
NFATC2	-0.052	0.26	-10000	0	-0.76	103	103
NFATC3	-0.056	0.12	-10000	0	-0.31	58	58
CD40LG	-0.38	0.58	-10000	0	-1.1	349	349
ITCH	0.012	0.1	-10000	0	-10000	0	0
CBLB	0.012	0.1	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.24	0.35	-10000	0	-1	106	106
JUNB	0	0.009	-10000	0	-0.28	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.037	0.1	-10000	0	-0.34	107	107
T cell anergy	-0.029	0.17	-10000	0	-0.48	107	107
TLE4	-0.027	0.25	-10000	0	-0.75	82	82
Jun/NFAT1-c-4/p21SNFT	-0.31	0.45	-10000	0	-0.9	315	315
AP-1/NFAT1-c-4	-0.52	0.66	-10000	0	-1.3	355	355
IKZF1	-0.016	0.2	-10000	0	-0.6	88	88
T-helper 2 cell differentiation	-0.11	0.3	-10000	0	-0.82	102	102
AP-1/NFAT1	-0.23	0.33	-10000	0	-0.64	343	343
CALM1	-0.019	0.055	-10000	0	-10000	0	0
EGR2	-0.3	0.66	-10000	0	-1.2	266	266
EGR3	-0.39	0.74	-10000	0	-1.5	279	279
NFAT1/FOXP3	-0.11	0.21	-10000	0	-0.56	123	123
EGR1	-0.26	0.38	-10000	0	-0.81	316	316
JUN	-0.006	0.079	-10000	0	-0.81	9	9
EGR4	-0.02	0.072	-10000	0	-0.28	71	71
mol:Ca2+	-0.022	0.064	-10000	0	-10000	0	0
GBP3	-0.021	0.22	-10000	0	-0.63	97	97
FOSL1	-0.008	0.055	-10000	0	-0.32	25	25
NFAT1-c-4/MAF/IRF4	-0.32	0.48	-10000	0	-0.94	319	319
DGKA	-0.014	0.2	-10000	0	-0.58	90	90
CREM	0	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.4	0.53	-10000	0	-1.1	329	329
CTLA4	-0.081	0.23	-10000	0	-0.6	93	93
NFAT1-c-4 (dimer)/EGR1	-0.44	0.58	-10000	0	-1.2	327	327
NFAT1-c-4 (dimer)/EGR4	-0.3	0.46	-10000	0	-0.92	316	316
FOS	-0.25	0.38	-10000	0	-0.82	298	298
IFNG	-0.15	0.26	-10000	0	-0.84	96	96
T cell activation	-0.17	0.35	-10000	0	-0.8	178	178
MAF	-0.001	0.026	-10000	0	-0.81	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.17	0.37	0.68	314	-10000	0	314
TNF	-0.32	0.53	-10000	0	-1	313	313
FASLG	-0.37	0.69	-10000	0	-1.3	315	315
TBX21	-0.024	0.16	-10000	0	-0.67	52	52
BATF3	-0.002	0.03	-10000	0	-0.81	1	1
PRKCQ	-0.025	0.16	-10000	0	-0.67	54	54
PTPN1	-0.016	0.2	-10000	0	-0.59	89	89
NFAT1-c-4/ICER1	-0.3	0.45	-10000	0	-0.91	314	314
GATA3	-0.034	0.15	-10000	0	-0.56	63	63
T-helper 1 cell differentiation	-0.15	0.26	-10000	0	-0.82	96	96
IL2RA	-0.23	0.34	-10000	0	-0.92	117	117
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.014	0.2	-10000	0	-0.59	89	89
E2F1	-0.077	0.14	-10000	0	-0.27	321	321
PPARG	-0.19	0.34	-10000	0	-0.81	228	228
SLC3A2	-0.014	0.2	-10000	0	-0.64	65	65
IRF4	-0.072	0.23	-10000	0	-0.75	95	95
PTGS2	-0.48	0.66	-10000	0	-1.2	432	432
CSF2	-0.37	0.56	-10000	0	-1	349	349
JunB/Fra1/NFAT1-c-4	-0.29	0.44	-10000	0	-0.88	314	314
IL4	-0.12	0.31	-10000	0	-0.88	99	99
IL5	-0.36	0.56	-10000	0	-1	347	347
IL2	-0.18	0.36	-10000	0	-0.82	175	175
IL3	-0.064	0.065	-10000	0	-10000	0	0
RNF128	-0.055	0.28	-10000	0	-0.86	107	107
NFATC1	-0.17	0.37	-10000	0	-0.68	314	314
CDK4	0.088	0.23	0.54	83	-10000	0	83
PTPRK	-0.019	0.22	-10000	0	-0.63	92	92
IL8	-0.37	0.57	-10000	0	-1.1	347	347
POU2F1	0.001	0.01	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.24	0.28	-9999	-0.77	115	115
PCK1	-1	0.71	-9999	-1.6	612	612
HNF4A	-0.25	0.28	-9999	-0.85	77	77
KCNJ11	-0.27	0.31	-9999	-0.84	135	135
AKT1	-0.15	0.14	-9999	-0.38	53	53
response to starvation	-0.001	0.007	-9999	-10000	0	0
DLK1	-0.5	0.56	-9999	-1.2	326	326
NKX2-1	-0.056	0.15	-9999	-10000	0	0
ACADM	-0.24	0.28	-9999	-0.78	122	122
TAT	-1.2	0.68	-9999	-1.6	725	725
CEBPB	0.004	0.006	-9999	-10000	0	0
CEBPA	-0.002	0.077	-9999	-0.81	9	9
TTR	-0.45	0.29	-9999	-0.72	413	413
PKLR	-0.25	0.28	-9999	-0.77	118	118
APOA1	-0.3	0.3	-9999	-0.86	111	111
CPT1C	-0.24	0.28	-9999	-0.75	130	130
ALAS1	-0.14	0.15	-9999	-10000	0	0
TFRC	-0.45	0.26	-9999	-0.71	362	362
FOXF1	-0.004	0.057	-9999	-0.58	7	7
NF1	0.017	0.026	-9999	-0.8	1	1
HNF1A (dimer)	0.003	0.023	-9999	-0.28	6	6
CPT1A	-0.24	0.28	-9999	-0.75	131	131
HMGCS1	-0.24	0.28	-9999	-0.76	119	119
NR3C1	-0.11	0.12	-9999	-0.51	36	36
CPT1B	-0.24	0.28	-9999	-0.78	118	118
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.002	0.006	-9999	-10000	0	0
GCK	-0.28	0.36	-9999	-0.93	156	156
CREB1	-0.059	0.067	-9999	-10000	0	0
IGFBP1	-0.46	0.6	-9999	-1.5	230	230
PDX1	-0.13	0.14	-9999	-10000	0	0
UCP2	-0.24	0.28	-9999	-0.77	118	118
ALDOB	-0.27	0.3	-9999	-0.84	114	114
AFP	-0.68	0.61	-9999	-1.3	424	424
BDH1	-0.24	0.28	-9999	-0.74	142	142
HADH	-0.26	0.3	-9999	-0.82	118	118
F2	-0.29	0.3	-9999	-0.88	94	94
HNF1A	0.003	0.023	-9999	-0.28	6	6
G6PC	-0.19	0.12	-9999	-0.64	8	8
SLC2A2	-0.16	0.17	-9999	-0.52	9	9
INS	0.025	0.067	-9999	-10000	0	0
FOXA1	-0.25	0.28	-9999	-0.57	293	293
FOXA3	-0.42	0.22	-9999	-0.53	697	697
FOXA2	-0.32	0.34	-9999	-0.83	196	196
ABCC8	-0.35	0.44	-9999	-1.1	192	192
ALB	-0.94	0.65	-9999	-1.4	633	633

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.02	-9999	-0.62	1	1
Necdin/E2F1	-0.081	0.15	-9999	-0.7	40	40
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.15	0.22	-9999	-0.46	318	318
NGF (dimer)/p75(NTR)/BEX1	-0.27	0.32	-9999	-0.63	392	392
NT-4/5 (dimer)/p75(NTR)	-0.39	0.42	-9999	-0.78	503	503
IKBKB	-0.001	0.013	-9999	-10000	0	0
AKT1	-0.15	0.22	-9999	-0.46	321	321
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.07	0.22	-9999	-0.81	79	79
MGDIs/NGR/p75(NTR)/LINGO1	-0.2	0.25	-9999	-0.56	309	309
FURIN	-0.001	0.013	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.21	0.29	-9999	-0.58	353	353
LINGO1	-0.065	0.12	-9999	-0.28	232	232
Sortilin/TRAF6/NRIF	-0.001	0.026	-9999	-0.8	1	1
proBDNF (dimer)	-0.07	0.22	-9999	-0.8	79	79
NTRK1	-0.01	0.063	-9999	-0.33	29	29
RTN4R	-0.01	0.053	-9999	-0.28	37	37
neuron apoptosis	-0.14	0.27	-9999	-0.54	191	191
IRAK1	-0.001	0.015	-9999	-0.28	3	3
SHC1	-0.16	0.27	-9999	-0.54	316	316
ARHGDIA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	-0.001	0.015	-9999	-0.45	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.16	0.24	-9999	-0.5	316	316
MAGEH1	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.18	0.27	-9999	-0.53	330	330
Mammalian IAPs/DIABLO	-0.006	0.047	-9999	-0.48	9	9
proNGF (dimer)	-0.014	0.1	-9999	-0.8	15	15
MAGED1	-0.001	0.015	-9999	-0.28	3	3
APP	0	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.29	0.38	-9999	-0.8	351	351
ZNF274	0	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.15	0.22	-9999	-0.47	316	316
NGF	-0.014	0.1	-9999	-0.81	15	15
cell cycle arrest	-0.12	0.24	-9999	-0.45	316	316
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.11	0.16	-9999	-0.34	316	316
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.35	0.38	-9999	-0.68	503	503
NCSTN	0	0	-9999	-10000	0	0
mol:GTP	-0.18	0.26	-9999	-0.56	316	316
PSENEN	0	0.009	-9999	-0.28	1	1
mol:ceramide	-0.16	0.23	-9999	-0.49	316	316
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.085	0.13	-9999	-0.48	13	13
p75(NTR)/beta APP	-0.19	0.29	-9999	-0.62	309	309
BEX1	-0.15	0.28	-9999	-0.81	134	134
mol:GDP	-0.16	0.27	-9999	-0.55	316	316
NGF (dimer)	-0.083	0.18	-9999	-0.5	154	154
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.18	0.23	-9999	-0.52	309	309
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
RAC1/GTP	-0.15	0.23	-9999	-0.48	316	316
MYD88	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.18	0.26	-9999	-0.56	316	316
RHOB	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.057	0.082	-9999	-10000	0	0
NT3 (dimer)	-0.13	0.3	-9999	-0.76	170	170
TP53	-0.17	0.24	-9999	-0.47	353	353
PRDM4	-0.16	0.23	-9999	-0.49	316	316
BDNF (dimer)	-0.17	0.24	-9999	-0.58	207	207
PIK3CA	0	0.009	-9999	-0.28	1	1
SORT1	-0.001	0.026	-9999	-0.81	1	1
activation of caspase activity	-0.15	0.22	-9999	-0.46	318	318
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.16	0.24	-9999	-0.5	316	316
RHOC	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.16	0.27	-9999	-0.69	113	113
DIABLO	0	0	-9999	-10000	0	0
SMPD2	-0.16	0.23	-9999	-0.49	316	316
APH1B	-0.001	0.026	-9999	-0.81	1	1
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.18	0.26	-9999	-0.55	316	316
PSEN1	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.29	0.36	-9999	-0.7	401	401
MAPK8	-0.11	0.24	-9999	-0.65	51	51
MAPK9	-0.11	0.24	-9999	-0.65	50	50
APAF1	0	0	-9999	-10000	0	0
NTF3	-0.13	0.3	-9999	-0.77	170	170
NTF4	-0.29	0.39	-9999	-0.81	351	351
NDN	-0.033	0.16	-9999	-0.81	40	40
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.14	0.21	-9999	-0.44	316	316
p75 CTF/Sortilin/TRAF6/NRIF	0	0.015	-9999	-0.48	1	1
RhoA-B-C/GTP	-0.18	0.26	-9999	-0.55	316	316
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.18	0.25	-9999	-0.5	353	353
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.19	0.27	-9999	-0.53	353	353
PRKACB	-0.016	0.074	-9999	-0.81	3	3
proBDNF (dimer)/p75 ECD	-0.053	0.17	-9999	-0.62	79	79
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.01	0.081	-9999	-0.81	9	9
BIRC2	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.13	0.26	-9999	-0.5	269	269
BAD	-0.12	0.25	-9999	-0.58	104	104
RIPK2	-0.001	0.02	-9999	-0.28	5	5
NGFR	-0.25	0.37	-9999	-0.81	309	309
CYCS	-0.15	0.22	-9999	-0.46	316	316
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.16	0.24	-9999	-0.5	316	316
BCL2L11	-0.12	0.25	-9999	-0.58	104	104
BDNF (dimer)/p75(NTR)	-0.24	0.33	-9999	-0.67	353	353
PI3K	-0.16	0.24	-9999	-0.5	321	321
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.16	0.24	-9999	-0.5	316	316
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKCI	0	0.009	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.2	0.3	-9999	-0.63	316	316
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.16	0.24	-9999	-0.5	316	316
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCZ	-0.001	0.026	-9999	-0.81	1	1
PLG	-0.001	0.018	-9999	-0.28	4	4
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.2	0.27	-9999	-0.53	360	360
SQSTM1	0	0.009	-9999	-10000	0	0
NGFRAP1	-0.002	0.036	-9999	-0.81	2	2
CASP3	-0.11	0.23	-9999	-0.53	104	104
E2F1	-0.091	0.13	-9999	-0.28	321	321
CASP9	0	0	-9999	-10000	0	0
IKK complex	-0.067	0.12	-9999	-0.58	19	19
NGF (dimer)/TRKA	-0.017	0.088	-9999	-0.62	18	18
MMP7	-0.12	0.28	-9999	-0.81	141	141
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.15	0.22	-9999	-0.46	316	316
MMP3	-0.12	0.16	-9999	-0.3	387	387
APAF-1/Caspase 9	-0.11	0.16	-9999	-0.66	14	14

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.023	0.077	0.32	18	-10000	0	18
SMARCC2	0.012	0.01	-10000	0	-10000	0	0
SMARCC1	0.012	0.01	-10000	0	-10000	0	0
TBX21	-0.14	0.26	-10000	0	-0.76	90	90
SUMO2	0	0.01	-10000	0	-0.28	1	1
STAT1 (dimer)	0.013	0.039	-10000	0	-0.27	18	18
FKBP4	-0.002	0.025	-10000	0	-0.28	8	8
FKBP5	-0.013	0.1	-10000	0	-0.81	15	15
GR alpha/HSP90/FKBP51/HSP90	0.11	0.14	0.33	75	-0.44	17	92
PRL	-0.089	0.12	-10000	0	-0.56	1	1
cortisol/GR alpha (dimer)/TIF2	0.28	0.28	0.53	442	-0.57	18	460
RELA	-0.04	0.083	-10000	0	-10000	0	0
FGG	0.24	0.22	0.48	305	-0.53	2	307
GR beta/TIF2	0.11	0.18	0.33	134	-0.58	33	167
IFNG	-0.42	0.35	-10000	0	-0.76	446	446
apoptosis	-0.27	0.3	0.59	3	-0.68	241	244
CREB1	-0.007	0.028	-10000	0	-10000	0	0
histone acetylation	0.022	0.14	0.41	32	-0.41	25	57
BGLAP	-0.1	0.15	-10000	0	-0.58	6	6
GR/PKAc	0.12	0.12	0.34	47	-0.56	2	49
NF kappa B1 p50/RelA	-0.067	0.15	-10000	0	-0.42	34	34
SMARCD1	0.012	0.01	-10000	0	-10000	0	0
MDM2	0.12	0.1	0.25	246	-10000	0	246
GATA3	-0.026	0.16	-10000	0	-0.56	63	63
AKT1	0	0.004	-10000	0	-10000	0	0
CSF2	-0.04	0.11	0.39	1	-0.59	7	8
GSK3B	0	0.004	-10000	0	-10000	0	0
NR1I3	-0.21	0.26	0.56	3	-0.64	135	138
CSN2	0.2	0.18	0.41	223	-0.54	1	224
BRG1/BAF155/BAF170/BAF60A	-0.002	0.033	-10000	0	-0.46	5	5
NFATC1	0	0.045	-10000	0	-0.81	3	3
POU2F1	0.007	0.013	-10000	0	-10000	0	0
CDKN1A	0.045	0.075	-10000	0	-1.5	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.007	0.008	-10000	0	-10000	0	0
SFN	-0.015	0.098	-10000	0	-0.51	30	30
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.1	0.14	0.33	59	-0.42	18	77
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.37	0.44	0.74	1	-0.92	335	336
JUN	-0.32	0.29	-10000	0	-0.58	442	442
IL4	-0.13	0.16	-10000	0	-0.53	32	32
CDK5R1	-0.009	0.05	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.42	0.41	-10000	0	-0.74	541	541
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.13	0.33	60	-0.43	10	70
cortisol/GR alpha (monomer)	0.35	0.32	0.63	469	-0.55	2	471
NCOA2	-0.025	0.14	-10000	0	-0.81	31	31
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.29	0.39	-10000	0	-0.87	298	298
AP-1/NFAT1-c-4	-0.66	0.52	-10000	0	-1	620	620
AFP	-0.6	0.7	-10000	0	-1.6	327	327
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.19	0.16	0.44	145	-10000	0	145
TP53	0.031	0.025	-10000	0	-0.51	2	2
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.84	0.81	-10000	0	-1.7	442	442
KRT14	-0.84	0.77	-10000	0	-1.6	526	526
TBP	0.019	0.004	-10000	0	-10000	0	0
CREBBP	0.14	0.14	0.29	294	-10000	0	294
HDAC1	0	0.003	-10000	0	-10000	0	0
HDAC2	0.001	0.004	-10000	0	-10000	0	0
AP-1	-0.66	0.53	-10000	0	-1	623	623
MAPK14	0	0.003	-10000	0	-10000	0	0
MAPK10	-0.13	0.3	-10000	0	-0.81	154	154
MAPK11	-0.002	0.045	-10000	0	-0.82	3	3
KRT5	-0.94	0.82	-10000	0	-1.7	535	535
interleukin-1 receptor activity	-0.001	0.003	-10000	0	-10000	0	0
NCOA1	0.009	0.027	-10000	0	-0.8	1	1
STAT1	0.013	0.039	-10000	0	-0.27	18	18
CGA	-0.16	0.18	-10000	0	-0.5	89	89
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.2	0.18	0.37	491	-10000	0	491
MAPK3	0	0.004	-10000	0	-10000	0	0
MAPK1	0	0.003	-10000	0	-10000	0	0
ICAM1	-0.18	0.25	-10000	0	-0.71	83	83
NFKB1	-0.04	0.083	-10000	0	-10000	0	0
MAPK8	-0.23	0.22	-10000	0	-0.45	385	385
MAPK9	0	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.29	0.31	0.59	3	-0.72	241	244
BAX	0.047	0.032	-10000	0	-10000	0	0
POMC	-0.19	0.3	-10000	0	-0.91	83	83
EP300	0.14	0.14	0.29	288	-10000	0	288
cortisol/GR alpha (dimer)/p53	0.31	0.26	0.55	450	-0.58	1	451
proteasomal ubiquitin-dependent protein catabolic process	0.087	0.079	0.23	61	-10000	0	61
SGK1	0.23	0.2	-10000	0	-1.2	5	5
IL13	-0.32	0.28	-10000	0	-0.67	235	235
IL6	-0.5	0.63	-10000	0	-1.3	372	372
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.27	0.22	-10000	0	-0.63	123	123
IL2	-0.42	0.35	-10000	0	-0.76	426	426
CDK5	-0.001	0.022	-10000	0	-0.28	6	6
PRKACB	-0.016	0.074	-10000	0	-0.81	3	3
HSP90AA1	0	0.009	-10000	0	-0.28	1	1
IL8	-0.2	0.3	-10000	0	-0.7	170	170
CDK5R1/CDK5	-0.007	0.036	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.059	0.098	-10000	0	-0.59	4	4
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.29	0.24	0.51	444	-0.54	1	445
SMARCA4	0.012	0.013	-10000	0	-0.28	1	1
chromatin remodeling	0.2	0.16	0.39	259	-10000	0	259
NF kappa B1 p50/RelA/Cbp	0.061	0.17	0.35	47	-10000	0	47
JUN (dimer)	-0.32	0.29	-10000	0	-0.58	442	442
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.14	0.25	-10000	0	-0.72	100	100
NR3C1	0.2	0.2	0.46	253	-0.6	4	257
NR4A1	-0.057	0.23	-10000	0	-0.75	96	96
TIF2/SUV420H1	-0.019	0.11	-10000	0	-0.62	31	31
MAPKKK cascade	-0.27	0.3	0.59	3	-0.68	241	244
cortisol/GR alpha (dimer)/Src-1	0.3	0.26	0.54	449	-0.58	1	450
PBX1	0.005	0.04	-10000	0	-0.54	4	4
POU1F1	0.003	0.015	-10000	0	-0.28	2	2
SELE	-0.23	0.37	-10000	0	-0.82	185	185
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.16	0.39	257	-10000	0	257
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.29	0.24	0.51	444	-0.54	1	445
mol:cortisol	0.2	0.2	0.36	491	-10000	0	491
MMP1	-0.21	0.11	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.22	0.42	-10000	0	-0.86	183	183
PLK1	-0.078	0.098	-10000	0	-10000	0	0
BIRC5	-0.088	0.095	-10000	0	-10000	0	0
HSPA1B	-0.22	0.42	-10000	0	-0.88	164	164
MAP2K1	0.009	0.029	-10000	0	-10000	0	0
BRCA2	-0.22	0.42	-10000	0	-0.88	175	175
FOXM1	-0.26	0.49	-10000	0	-0.97	226	226
XRCC1	-0.22	0.42	-10000	0	-0.93	131	131
FOXM1B/p19	-0.27	0.4	0.38	1	-0.86	234	235
Cyclin D1/CDK4	-0.2	0.4	-10000	0	-0.87	133	133
CDC2	-0.23	0.44	-10000	0	-0.87	213	213
TGFA	-0.2	0.41	-10000	0	-0.92	130	130
SKP2	-0.22	0.42	-10000	0	-0.92	140	140
CCNE1	-0.053	0.12	-10000	0	-0.29	200	200
CKS1B	-0.22	0.42	-10000	0	-0.87	173	173
RB1	-0.11	0.12	-10000	0	-1	2	2
FOXM1C/SP1	-0.27	0.43	-10000	0	-0.9	228	228
AURKB	-0.07	0.099	-10000	0	-10000	0	0
CENPF	-0.24	0.44	-10000	0	-0.95	151	151
CDK4	0.008	0.018	-10000	0	-0.28	2	2
MYC	-0.2	0.4	-10000	0	-0.83	169	169
CHEK2	0.008	0.032	-10000	0	-0.3	2	2
ONECUT1	-0.22	0.42	-10000	0	-0.87	171	171
CDKN2A	-0.035	0.11	-10000	0	-0.27	167	167
LAMA4	-0.22	0.42	-10000	0	-0.89	164	164
FOXM1B/HNF6	-0.25	0.47	-10000	0	-0.98	179	179
FOS	-0.43	0.67	-10000	0	-1.3	340	340
SP1	0	0	-10000	0	-10000	0	0
CDC25B	-0.22	0.42	-10000	0	-0.87	175	175
response to radiation	-0.006	0.029	-10000	0	-10000	0	0
CENPB	-0.22	0.42	-10000	0	-0.86	183	183
CENPA	-0.24	0.44	-10000	0	-0.89	206	206
NEK2	-0.26	0.43	-10000	0	-0.9	199	199
HIST1H2BA	-0.22	0.42	-10000	0	-0.9	158	158
CCNA2	-0.11	0.15	-10000	0	-0.29	407	407
EP300	0	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.25	0.47	-10000	0	-0.97	193	193
CCNB2	-0.25	0.44	-10000	0	-0.91	187	187
CCNB1	-0.24	0.44	-10000	0	-0.92	190	190
ETV5	-0.22	0.42	-10000	0	-0.93	135	135
ESR1	-0.32	0.57	-10000	0	-1.3	208	208
CCND1	-0.2	0.41	-10000	0	-0.88	137	137
GSK3A	0.014	0.021	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.079	0.14	-10000	0	-0.32	136	136
CDK2	0.006	0.009	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.009	0.035	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.31	0.36	-10000	0	-0.84	242	242
GAS1	-0.25	0.48	-10000	0	-1	191	191
MMP2	-0.22	0.43	-10000	0	-0.89	172	172
RB1/FOXM1C	-0.22	0.42	-10000	0	-0.88	174	174
CREBBP	0	0	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.12	0.41	-10000	0	-0.91	204	204
NCK1/PAK1/Dok-R	-0.088	0.17	-10000	0	-0.42	204	204
NCK1/Dok-R	-0.24	0.47	-10000	0	-1.1	204	204
PIK3CA	0.003	0.01	-10000	0	-0.28	1	1
mol:beta2-estradiol	0.035	0.098	0.24	170	-10000	0	170
RELA	0	0	-10000	0	-10000	0	0
SHC1	0.003	0.005	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.037	0.1	0.25	167	-0.3	7	174
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.22	0.43	-10000	0	-1.1	204	204
FN1	-0.11	0.14	-10000	0	-0.28	398	398
PLD2	-0.19	0.52	-10000	0	-1.2	204	204
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.099	0.22	-10000	0	-0.46	212	212
ELK1	-0.15	0.46	-10000	0	-1	204	204
GRB7	-0.02	0.075	-10000	0	-0.29	70	70
PAK1	-0.006	0.041	-10000	0	-0.28	22	22
Tie2/Ang1/alpha5/beta1 Integrin	-0.19	0.48	-10000	0	-1.1	204	204
CDKN1A	-0.06	0.27	-10000	0	-0.64	115	115
ITGA5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.24	0.47	-10000	0	-1.1	204	204
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.064	0.31	-10000	0	-0.66	204	204
PLG	-0.19	0.52	-10000	0	-1.2	204	204
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.17	0.36	-10000	0	-0.88	204	204
GRB2	0	0.009	-10000	0	-0.28	1	1
PIK3R1	-0.003	0.068	-10000	0	-0.81	7	7
ANGPT2	-0.11	0.27	-10000	0	-0.75	98	98
BMX	-0.36	0.58	-10000	0	-1.4	204	204
ANGPT1	-0.23	0.56	-10000	0	-1.4	180	180
tube development	-0.077	0.3	-10000	0	-0.68	164	164
ANGPT4	-0.25	0.38	-10000	0	-0.81	307	307
response to hypoxia	-0.01	0.03	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.27	0.54	-10000	0	-1.3	204	204
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.32	0.4	-10000	0	-0.81	395	395
STAT5A (dimer)	-0.093	0.34	-10000	0	-0.84	124	124
mol:L-citrulline	-0.064	0.31	-10000	0	-0.66	204	204
AGTR1	-0.2	0.34	-10000	0	-0.7	288	288
MAPK14	-0.18	0.5	-10000	0	-1.1	204	204
Tie2/SHP2	-0.095	0.28	-10000	0	-1.3	45	45
TEK	-0.1	0.32	-10000	0	-1.5	45	45
RPS6KB1	-0.11	0.39	-10000	0	-0.87	204	204
Angiotensin II/AT1	-0.15	0.26	-10000	0	-0.62	230	230
Tie2/Ang1/GRB2	-0.25	0.51	-10000	0	-1.2	204	204
MAPK3	-0.16	0.47	-10000	0	-1.1	204	204
MAPK1	-0.16	0.47	-10000	0	-1.1	204	204
Tie2/Ang1/GRB7	-0.25	0.52	-10000	0	-1.2	204	204
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.19	0.52	-10000	0	-1.2	204	204
PI3K	-0.15	0.47	-10000	0	-1.1	204	204
FES	-0.18	0.49	-10000	0	-1.1	204	204
Crk/Dok-R	-0.24	0.47	-10000	0	-1.1	204	204
Tie2/Ang1/ABIN2	-0.25	0.51	-10000	0	-1.2	204	204
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.096	0.37	-10000	0	-0.8	204	204
STAT5A	-0.007	0.072	-10000	0	-0.81	8	8
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.11	0.39	-10000	0	-0.87	204	204
Tie2/Ang2	-0.13	0.41	-10000	0	-0.97	145	145
Tie2/Ang1	-0.22	0.57	-10000	0	-1.3	204	204
FOXO1	-0.093	0.37	-10000	0	-0.81	204	204
ELF1	0.013	0.022	-10000	0	-10000	0	0
ELF2	-0.19	0.51	-10000	0	-1.2	204	204
mol:Choline	-0.17	0.49	-10000	0	-1.1	204	204
cell migration	-0.038	0.1	-10000	0	-0.24	169	169
FYN	-0.094	0.34	-10000	0	-0.78	163	163
DOK2	-0.003	0.04	-10000	0	-0.46	6	6
negative regulation of cell cycle	-0.05	0.25	-10000	0	-0.58	115	115
ETS1	-0.026	0.11	-10000	0	-0.98	4	4
PXN	-0.075	0.33	-10000	0	-0.71	204	204
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.082	0.35	-10000	0	-0.75	204	204
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.04	0.14	-10000	0	-0.83	17	17
MAPKKK cascade	-0.17	0.49	-10000	0	-1.1	204	204
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.23	0.52	-10000	0	-1.2	204	204
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.051	0.28	-10000	0	-0.59	204	204
mol:Phosphatidic acid	-0.17	0.49	-10000	0	-1.1	204	204
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.064	0.31	-10000	0	-0.66	204	204
Rac1/GTP	-0.17	0.33	-10000	0	-0.81	204	204
MMP2	-0.19	0.52	-10000	0	-1.2	205	205

×

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	-0.46	0.46	-10000	0	-1.1	232	232
STAT6 (cleaved dimer)	-0.5	0.44	-10000	0	-0.97	384	384
IGHG1	-0.16	0.16	-10000	0	-0.35	166	166
IGHG3	-0.45	0.44	-10000	0	-0.95	345	345
AKT1	-0.21	0.24	-10000	0	-0.63	99	99
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.15	0.2	-10000	0	-0.58	62	62
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.22	0.24	-10000	0	-0.62	125	125
THY1	-0.46	0.46	-10000	0	-1.1	228	228
MYB	-0.015	0.11	-10000	0	-0.75	20	20
HMGA1	-0.012	0.057	-10000	0	-0.28	43	43
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.28	0.29	-10000	0	-0.67	226	226
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.21	0.23	-10000	0	-0.58	108	108
SP1	0.018	0.004	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.024	0.03	-10000	0	-0.78	1	1
STAT6 (dimer)/ETS1	-0.49	0.44	-10000	0	-1	328	328
SOCS1	-0.3	0.31	-10000	0	-0.73	194	194
SOCS3	-0.23	0.26	-10000	0	-0.8	69	69
FCER2	-0.6	0.65	-10000	0	-1.4	330	330
PARP14	0.002	0.018	-10000	0	-0.29	3	3
CCL17	-0.47	0.46	-10000	0	-1.1	282	282
GRB2	0	0.009	-10000	0	-0.28	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.17	0.19	-10000	0	-0.58	32	32
T cell proliferation	-0.46	0.48	-10000	0	-1.1	254	254
IL4R/JAK1	-0.46	0.46	-10000	0	-1.1	249	249
EGR2	-0.61	0.64	-10000	0	-1.4	318	318
JAK2	-0.008	0.037	-10000	0	-0.83	1	1
JAK3	0.008	0.037	-10000	0	-0.29	1	1
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
JAK1	0.005	0.011	-10000	0	-10000	0	0
COL1A2	-0.14	0.16	-10000	0	-1.7	2	2
CCL26	-0.46	0.46	-10000	0	-1.1	213	213
IL4R	-0.49	0.49	-10000	0	-1.2	250	250
PTPN6	0.022	0.018	-10000	0	-10000	0	0
IL13RA2	-0.46	0.46	-10000	0	-1.1	215	215
IL13RA1	-0.007	0.026	-10000	0	-10000	0	0
IRF4	-0.22	0.48	-10000	0	-1.6	103	103
ARG1	-0.11	0.12	-10000	0	-10000	0	0
CBL	-0.26	0.28	-10000	0	-0.64	205	205
GTF3A	0.013	0.015	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.28	1	1
IL13RA1/JAK2	-0.014	0.042	-10000	0	-0.63	1	1
IRF4/BCL6	-0.2	0.43	-10000	0	-1.4	106	106
CD40LG	-0.033	0.18	-10000	0	-0.7	64	64
MAPK14	-0.26	0.28	-10000	0	-0.64	200	200
mitosis	-0.2	0.23	-10000	0	-0.6	99	99
STAT6	-0.53	0.54	-10000	0	-1.2	314	314
SPI1	0.006	0.024	-10000	0	-0.27	6	6
RPS6KB1	-0.19	0.22	-10000	0	-0.59	86	86
STAT6 (dimer)	-0.53	0.54	-10000	0	-1.2	314	314
STAT6 (dimer)/PARP14	-0.52	0.51	-10000	0	-1.1	344	344
mast cell activation	0.012	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.21	0.23	-10000	0	-0.59	101	101
FRAP1	-0.21	0.24	-10000	0	-0.63	99	99
LTA	-0.47	0.46	-10000	0	-1.1	249	249
FES	-0.002	0.044	-10000	0	-0.81	3	3
T-helper 1 cell differentiation	0.52	0.52	1.1	319	-10000	0	319
CCL11	-0.48	0.44	-10000	0	-1.1	272	272
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.21	0.24	-10000	0	-0.6	103	103
IL2RG	-0.005	0.09	-10000	0	-0.41	28	28
IL10	-0.46	0.46	-10000	0	-1.1	213	213
IRS1	-0.033	0.16	-10000	0	-0.81	41	41
IRS2	-0.033	0.16	-10000	0	-0.81	40	40
IL4	-0.11	0.11	-10000	0	-10000	0	0
IL5	-0.47	0.46	-10000	0	-1.1	236	236
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.38	0.36	-10000	0	-0.82	277	277
COL1A1	-0.18	0.17	-10000	0	-1.8	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.47	0.47	-10000	0	-1.2	201	201
IL2R gamma/JAK3	-0.014	0.073	-10000	0	-0.44	22	22
TFF3	-0.56	0.59	-10000	0	-1.3	299	299
ALOX15	-0.55	0.58	-10000	0	-1.3	286	286
MYBL1	-0.041	0.099	-10000	0	-0.28	146	146
T-helper 2 cell differentiation	-0.4	0.38	-10000	0	-0.84	306	306
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	0.008	0.009	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.21	0.24	-10000	0	-0.58	120	120
mol:PI-3-4-5-P3	-0.21	0.24	-10000	0	-0.63	99	99
PI3K	-0.22	0.26	-10000	0	-0.68	97	97
DOK2	-0.003	0.04	-10000	0	-0.46	6	6
ETS1	0.019	0.052	-10000	0	-0.77	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.16	0.18	-10000	0	-0.58	24	24
ITGB3	-0.48	0.49	-10000	0	-1.2	208	208
PIGR	-1	0.75	-10000	0	-1.5	637	637
IGHE	0.046	0.039	-10000	0	-10000	0	0
MAPKKK cascade	-0.15	0.18	-10000	0	-0.57	24	24
BCL6	0.002	0.052	-10000	0	-0.8	4	4
OPRM1	-0.47	0.46	-10000	0	-1.1	215	215
RETNLB	-0.47	0.46	-10000	0	-1.1	213	213
SELP	-0.63	0.68	-10000	0	-1.5	305	305
AICDA	-0.45	0.44	-10000	0	-1.1	227	227

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.16	0.25	-9999	-0.45	347	347
FZD6	-0.007	0.072	-9999	-0.81	8	8
WNT6	-0.17	0.32	-9999	-0.72	229	229
WNT4	-0.022	0.12	-9999	-0.54	40	40
FZD3	-0.009	0.085	-9999	-0.81	11	11
WNT5A	-0.013	0.096	-9999	-0.58	23	23
WNT11	-0.18	0.33	-9999	-0.78	222	222

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.025	0.14	-9999	-0.81	30	30
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.34	0.27	-9999	-0.55	598	598
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0.009	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.3	0.24	-9999	-0.5	598	598
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.017	0.067	-9999	-0.28	60	60
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.016	0.093	-9999	-0.41	39	39
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0.009	-9999	-0.28	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.019	0.055	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.009	0.049	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.041	0.099	-9999	-0.28	145	145
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.35	0.28	-9999	-0.56	606	606
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.24	0.19	-9999	-0.48	91	91
MAP1B	-0.007	0.049	-9999	-0.38	17	17
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.27	0.22	-9999	-0.44	598	598
RELN	-0.49	0.39	-9999	-0.8	601	601
PAFAH/LIS1	-0.009	0.058	-9999	-0.53	10	10
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.18	0.15	-9999	-0.43	4	4
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.21	0.17	-9999	-0.34	609	609
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.26	0.21	-9999	-0.49	172	172
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.022	0	-9999	-10000	0	0
PAFAH1B3	-0.03	0.087	-9999	-10000	0	0
PAFAH1B2	-0.003	0.051	-9999	-0.81	4	4
MAP1B/LIS1/Dynein heavy chain	-0.004	0.031	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.23	0.18	-9999	-0.5	27	27
LRP8	-0.031	0.087	-9999	-10000	0	0
NDEL1/Katanin 60	-0.24	0.19	-9999	-0.48	92	92
P39/CDK5	-0.28	0.23	-9999	-0.46	598	598
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.27	0.24	-9999	-0.46	598	598
PPP2R5D	0	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.3	0.24	-9999	-0.48	606	606
RELN/VLDLR	-0.32	0.26	-9999	-0.52	606	606
CDC42	0	0	-9999	-10000	0	0

×

Arf6 signaling events

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
CENTA1/KIF3B	-0.004	0.046	-9999	-0.66	4	4
ARNO/beta Arrestin1-2	-0.13	0.19	-9999	-0.44	235	235
EGFR	-0.3	0.39	-9999	-0.8	369	369
EPHA2	-0.005	0.063	-9999	-0.81	6	6
USP6	0	0	-9999	-10000	0	0
IQSEC1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.35	0.36	-9999	-0.68	504	504
ARRB2	-0.057	0.16	-9999	-0.44	138	138
mol:GTP	0.017	0.019	-9999	-0.15	5	5
ARRB1	-0.002	0.037	-9999	-0.63	3	3
FBXO8	0	0	-9999	-10000	0	0
TSHR	-0.036	0.16	-9999	-0.76	47	47
EGF	-0.17	0.33	-9999	-0.8	206	206
somatostatin receptor activity	0	0	-9999	-0.001	337	337
ARAP2	-0.005	0.063	-9999	-0.81	6	6
mol:GDP	-0.14	0.18	-9999	-0.35	307	307
mol:PI-3-4-5-P3	0	0	-9999	-0.001	234	234
ITGA2B	-0.017	0.075	-9999	-0.81	3	3
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.004	0.038	-9999	-0.48	6	6
ADAP1	-0.004	0.05	-9999	-0.44	10	10
KIF13B	-0.002	0.036	-9999	-0.81	2	2
HGF/MET	-0.14	0.28	-9999	-0.67	211	211
PXN	0	0	-9999	-10000	0	0
ARF6/GTP	-0.13	0.15	-9999	-0.32	311	311
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.3	0.32	-9999	-0.59	504	504
ADRB2	-0.19	0.34	-9999	-0.81	234	234
receptor agonist activity	0	0	-9999	0	315	315
actin filament binding	0	0	-9999	-0.001	323	323
SRC	0	0.009	-9999	-10000	0	0
ITGB3	-0.024	0.14	-9999	-0.81	28	28
GNAQ	-0.002	0.036	-9999	-0.81	2	2
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	292	292
ARF6/GDP	-0.015	0.085	-9999	-0.43	17	17
ARF6/GDP/GULP/ACAP1	-0.15	0.2	-9999	-0.54	158	158
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.022	0.089	-9999	-0.49	31	31
ACAP1	-0.019	0.096	-9999	-0.81	10	10
ACAP2	0	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.093	0.23	-9999	-0.67	138	138
EFNA1	0	0	-9999	-10000	0	0
HGF	-0.055	0.2	-9999	-0.81	67	67
CYTH3	0.01	0.02	-9999	-0.63	1	1
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	260	260
endosomal lumen acidification	0	0	-9999	-0.001	263	263
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.054	0.2	-9999	-0.81	66	66
GNAQ/ARNO	0.003	0.022	-9999	-0.46	2	2
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	325	325
MET	-0.14	0.3	-9999	-0.81	165	165
GNA14	-0.015	0.091	-9999	-0.44	33	33
GNA15	-0.003	0.035	-9999	-0.34	8	8
GIT1	-0.001	0.02	-9999	-0.28	5	5
mol:PI-4-5-P2	0	0	-9999	-0.001	306	306
GNA11	-0.002	0.036	-9999	-0.81	2	2
LHCGR	-0.11	0.28	-9999	-0.81	138	138
AGTR1	-0.2	0.34	-9999	-0.7	288	288
desensitization of G-protein coupled receptor protein signaling pathway	-0.093	0.23	-9999	-0.66	138	138
IPCEF1/ARNO	-0.24	0.26	-9999	-0.48	504	504
alphaIIb/beta3 Integrin	-0.029	0.12	-9999	-0.63	31	31

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.013	0.19	-9999	-0.59	80	80
PTK2B	0	0	-9999	-10000	0	0
mol:Ca2+	0.02	0.19	-9999	-0.92	29	29
EDN1	-0.04	0.24	-9999	-0.82	79	79
EDN3	-0.38	0.4	-9999	-0.81	460	460
EDN2	-0.075	0.13	-9999	-0.81	6	6
HRAS/GDP	-0.03	0.2	-9999	-0.53	88	88
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.004	0.14	-9999	-0.42	59	59
ADCY4	-0.15	0.29	-9999	-0.57	283	283
ADCY5	-0.28	0.36	-9999	-0.61	465	465
ADCY6	-0.13	0.27	-9999	-0.54	266	266
ADCY7	-0.13	0.27	-9999	-0.54	266	266
ADCY1	-0.15	0.29	-9999	-0.56	280	280
ADCY2	-0.17	0.32	-9999	-0.6	293	293
ADCY3	-0.13	0.27	-9999	-0.54	266	266
ADCY8	-0.14	0.27	-9999	-0.55	266	266
ADCY9	-0.13	0.27	-9999	-0.54	266	266
arachidonic acid secretion	-0.1	0.29	-9999	-0.47	325	325
ETB receptor/Endothelin-1/Gq/GTP	-0.032	0.17	-9999	-0.39	142	142
GNAO1	-0.032	0.14	-9999	-0.48	66	66
HRAS	-0.001	0.02	-9999	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.034	0.2	-9999	-0.55	80	80
ETA receptor/Endothelin-1/Gs/GTP	-0.095	0.32	-9999	-0.57	266	266
mol:GTP	-0.001	0.006	-9999	-10000	0	0
COL3A1	-0.021	0.2	-9999	-0.6	80	80
EDNRB	-0.066	0.24	-9999	-0.81	91	91
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.024	0.23	-9999	-0.67	93	93
CYSLTR1	-0.024	0.23	-9999	-0.67	93	93
SLC9A1	0	0.1	-9999	-0.3	79	79
mol:GDP	-0.038	0.22	-9999	-0.56	97	97
SLC9A3	-0.049	0.28	-9999	-0.63	159	159
RAF1	-0.085	0.25	-9999	-0.54	150	150
JUN	0.024	0.18	-9999	-0.8	31	31
JAK2	-0.013	0.2	-9999	-0.6	80	80
mol:IP3	-0.029	0.17	-9999	-0.54	61	61
ETA receptor/Endothelin-1	0.03	0.25	-9999	-0.63	96	96
PLCB1	-0.055	0.2	-9999	-0.81	67	67
PLCB2	0.006	0.028	-9999	-0.81	1	1
ETA receptor/Endothelin-3	-0.28	0.32	-9999	-0.62	461	461
FOS	-0.26	0.5	-9999	-0.98	308	308
Gai/GDP	-0.023	0.16	-9999	-0.74	32	32
CRK	0	0	-9999	-10000	0	0
mol:Ca ++	-0.05	0.25	-9999	-0.67	101	101
BCAR1	0.001	0.004	-9999	-10000	0	0
PRKCB1	-0.032	0.17	-9999	-0.48	76	76
GNAQ	0.008	0.038	-9999	-0.81	2	2
GNAZ	-0.007	0.072	-9999	-0.81	8	8
GNAL	-0.19	0.34	-9999	-0.81	233	233
Gs family/GDP	-0.17	0.26	-9999	-0.57	250	250
ETA receptor/Endothelin-1/Gq/GTP	0.015	0.13	-9999	-0.39	57	57
MAPK14	-0.03	0.17	-9999	-0.57	53	53
TRPC6	0.018	0.21	-9999	-1	29	29
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.042	0.18	-9999	-0.81	51	51
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.038	0.18	-9999	-0.46	103	103
ETB receptor/Endothelin-2	-0.1	0.2	-9999	-0.66	96	96
ETB receptor/Endothelin-3	-0.34	0.34	-9999	-0.66	510	510
ETB receptor/Endothelin-1	-0.08	0.27	-9999	-0.66	159	159
MAPK3	-0.2	0.41	-9999	-0.78	314	314
MAPK1	-0.2	0.41	-9999	-0.78	314	314
Rac1/GDP	-0.03	0.2	-9999	-0.53	88	88
cAMP biosynthetic process	-0.18	0.3	-9999	-0.6	281	281
MAPK8	0.019	0.18	-9999	-0.68	38	38
SRC	0	0.009	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.048	0.19	-9999	-0.42	142	142
p130Cas/CRK/Src/PYK2	-0.015	0.21	-9999	-0.6	70	70
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.03	0.2	-9999	-0.53	88	88
COL1A2	-0.055	0.25	-9999	-0.68	92	92
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.031	0.11	-9999	-0.57	8	8
mol:DAG	-0.029	0.18	-9999	-0.54	61	61
MAP2K2	-0.13	0.32	-9999	-0.56	314	314
MAP2K1	-0.13	0.32	-9999	-0.56	314	314
EDNRA	0.025	0.067	-9999	-0.44	4	4
positive regulation of muscle contraction	-0.013	0.17	-9999	-0.52	80	80
Gq family/GDP	-0.074	0.16	-9999	-0.6	53	53
HRAS/GTP	-0.052	0.21	-9999	-0.48	120	120
PRKCH	-0.023	0.17	-9999	-0.58	46	46
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.034	0.2	-9999	-0.62	64	64
PRKCB	-0.035	0.19	-9999	-0.62	58	58
PRKCE	-0.024	0.17	-9999	-0.54	55	55
PRKCD	-0.024	0.17	-9999	-0.54	54	54
PRKCG	-0.032	0.17	-9999	-0.54	59	59
regulation of vascular smooth muscle contraction	-0.3	0.57	-9999	-1.1	308	308
PRKCQ	-0.045	0.21	-9999	-0.59	92	92
PLA2G4A	-0.12	0.33	-9999	-0.52	325	325
GNA14	-0.006	0.093	-9999	-0.44	33	33
GNA15	0.006	0.036	-9999	-0.34	8	8
GNA12	0	0	-9999	-10000	0	0
GNA11	0.007	0.037	-9999	-0.81	2	2
Rac1/GTP	0.034	0.2	-9999	-0.55	80	80
MMP1	-0.12	0.12	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0	0	-10000	0	-10000	0	0
EPHB2	-0.004	0.038	-10000	0	-0.28	18	18
EFNB1	0.016	0.054	-10000	0	-0.62	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.18	0.21	-10000	0	-0.42	416	416
Ephrin B2/EPHB1-2	-0.21	0.24	-10000	0	-0.49	415	415
neuron projection morphogenesis	-0.17	0.2	-10000	0	-0.4	416	416
Ephrin B1/EPHB1-2/Tiam1	-0.19	0.23	-10000	0	-0.46	416	416
DNM1	-0.006	0.068	-10000	0	-0.74	8	8
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.004	0.13	-10000	0	-0.75	29	29
YES1	-0.025	0.17	-10000	0	-0.99	28	28
Ephrin B1/EPHB1-2/NCK2	-0.19	0.23	-10000	0	-0.46	416	416
PI3K	-0.025	0.14	-10000	0	-0.73	34	34
mol:GDP	-0.19	0.22	-10000	0	-0.45	416	416
ITGA2B	-0.017	0.075	-10000	0	-0.81	3	3
endothelial cell proliferation	0	0.005	-10000	0	-10000	0	0
FYN	-0.025	0.16	-10000	0	-0.99	28	28
MAP3K7	-0.022	0.14	-10000	0	-0.81	28	28
FGR	-0.027	0.17	-10000	0	-1	28	28
TIAM1	-0.001	0.018	-10000	0	-10000	0	0
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.041	0.16	-10000	0	-0.63	58	58
LYN	-0.025	0.16	-10000	0	-0.99	28	28
Ephrin B1/EPHB1-2/Src Family Kinases	-0.026	0.16	-10000	0	-0.93	28	28
Ephrin B1/EPHB1-2	-0.029	0.14	-10000	0	-0.88	28	28
SRC	-0.027	0.17	-10000	0	-1	28	28
ITGB3	-0.024	0.14	-10000	0	-0.81	28	28
EPHB1	-0.34	0.4	-10000	0	-0.81	415	415
EPHB4	0	0.009	-10000	0	-0.28	1	1
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.029	0.12	-10000	0	-0.63	31	31
BLK	-0.026	0.17	-10000	0	-1	28	28
HCK	-0.027	0.17	-10000	0	-1	28	28
regulation of stress fiber formation	0.19	0.22	0.45	416	-10000	0	416
MAPK8	0.002	0.14	-10000	0	-0.73	31	31
Ephrin B1/EPHB1-2/RGS3	-0.19	0.23	-10000	0	-0.46	416	416
endothelial cell migration	-0.016	0.12	-10000	0	-0.71	28	28
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.016	0.16	-10000	0	-0.92	28	28
regulation of focal adhesion formation	0.19	0.22	0.45	416	-10000	0	416
chemotaxis	0.19	0.22	0.45	416	-10000	0	416
PIK3CA	0	0.009	-10000	0	-0.28	1	1
Rac1/GTP	-0.18	0.21	-10000	0	-0.41	416	416
angiogenesis	-0.029	0.14	-10000	0	-0.87	28	28
LCK	-0.029	0.17	-10000	0	-1	28	28

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.055	0.16	-10000	0	-0.54	95	95
cell-cell adhesion	0.18	0.22	0.69	71	-10000	0	71
Ephrin B/EPHB2/RasGAP	-0.041	0.13	-10000	0	-0.45	85	85
ITSN1	-0.002	0.036	-10000	0	-0.81	2	2
PIK3CA	0	0.009	-10000	0	-0.28	1	1
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.002	0.016	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.23	0.27	-10000	0	-0.54	415	415
HRAS/GDP	-0.19	0.23	-10000	0	-0.67	90	90
Ephrin B/EPHB1/GRB7	-0.24	0.28	-10000	0	-0.53	434	434
Endophilin/SYNJ1	-0.038	0.12	-10000	0	-0.42	85	85
KRAS	-0.001	0.013	-10000	0	-0.28	2	2
Ephrin B/EPHB1/Src	-0.23	0.28	-10000	0	-0.52	433	433
endothelial cell migration	-0.003	0.038	-10000	0	-0.45	7	7
GRB2	0	0.009	-10000	0	-0.28	1	1
GRB7	-0.02	0.075	-10000	0	-0.29	70	70
PAK1	-0.048	0.14	-10000	0	-0.47	94	94
HRAS	-0.001	0.02	-10000	0	-10000	0	0
RRAS	-0.039	0.12	-10000	0	-0.43	85	85
DNM1	-0.006	0.068	-10000	0	-0.74	8	8
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.22	0.27	-10000	0	-0.5	433	433
lamellipodium assembly	-0.18	0.22	-10000	0	-0.69	71	71
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.16	0.19	-10000	0	-0.37	415	415
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
EPHB2	-0.005	0.037	-10000	0	-0.28	18	18
EPHB3	-0.003	0.031	-10000	0	-0.28	12	12
EPHB1	-0.34	0.4	-10000	0	-0.81	415	415
EPHB4	0	0.009	-10000	0	-0.28	1	1
mol:GDP	-0.16	0.22	-10000	0	-0.65	89	89
Ephrin B/EPHB2	-0.041	0.13	-10000	0	-0.46	85	85
Ephrin B/EPHB3	-0.041	0.13	-10000	0	-0.46	85	85
JNK cascade	-0.19	0.22	-10000	0	-0.44	415	415
Ephrin B/EPHB1	-0.23	0.28	-10000	0	-0.53	433	433
RAP1/GDP	-0.14	0.18	-10000	0	-0.56	85	85
EFNB2	0	0	-10000	0	-10000	0	0
EFNB3	-0.069	0.23	-10000	0	-0.81	85	85
EFNB1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.21	0.24	-10000	0	-0.49	415	415
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.19	0.24	-10000	0	-0.7	88	88
Rap1/GTP	-0.18	0.22	-10000	0	-0.72	70	70
axon guidance	-0.055	0.16	-10000	0	-0.54	95	95
MAPK3	-0.11	0.19	-10000	0	-0.53	67	67
MAPK1	-0.11	0.19	-10000	0	-0.53	67	67
Rac1/GDP	-0.15	0.19	-10000	0	-0.59	86	86
actin cytoskeleton reorganization	-0.14	0.17	-10000	0	-0.53	71	71
CDC42/GDP	-0.15	0.19	-10000	0	-0.59	86	86
PI3K	-0.003	0.039	-10000	0	-0.46	7	7
EFNA5	-0.078	0.24	-10000	0	-0.8	96	96
Ephrin B2/EPHB4	0	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.03	0.1	-10000	0	-0.34	85	85
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.18	0.22	-10000	0	-0.68	72	72
PTK2	0.045	0.051	-10000	0	-10000	0	0
MAP4K4	-0.19	0.22	-10000	0	-0.45	415	415
SRC	0	0.009	-10000	0	-10000	0	0
KALRN	-0.016	0.11	-10000	0	-0.81	19	19
Intersectin/N-WASP	-0.001	0.028	-10000	0	-0.62	2	2
neuron projection morphogenesis	-0.14	0.18	-10000	0	-0.55	76	76
MAP2K1	-0.15	0.18	-10000	0	-0.56	68	68
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.2	0.24	-10000	0	-0.48	415	415
cell migration	-0.14	0.23	-10000	0	-0.38	415	415
NRAS	-0.001	0.013	-10000	0	-10000	0	0
SYNJ1	-0.039	0.12	-10000	0	-0.43	85	85
PXN	0	0	-10000	0	-10000	0	0
TF	-0.25	0.27	-10000	0	-0.47	569	569
HRAS/GTP	-0.2	0.24	-10000	0	-0.76	71	71
Ephrin B1/EPHB1-2	-0.21	0.24	-10000	0	-0.49	415	415
cell adhesion mediated by integrin	0.007	0.13	0.42	85	-10000	0	85
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.21	0.26	-10000	0	-0.48	433	433
RAC1-CDC42/GTP	-0.18	0.22	-10000	0	-0.7	71	71
RASA1	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.14	0.18	-10000	0	-0.56	85	85
ruffle organization	-0.18	0.22	-10000	0	-0.71	71	71
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	0.001	0.14	-10000	0	-0.43	87	87
Ephrin B/EPHB2/KALRN	-0.049	0.15	-10000	0	-0.5	94	94
ROCK1	-0.002	0.02	-10000	0	-0.49	1	1
RAS family/GDP	-0.12	0.16	-10000	0	-0.53	68	68
Rac1/GTP	-0.19	0.24	-10000	0	-0.76	71	71
Ephrin B/EPHB1/Src/Paxillin	-0.17	0.2	-10000	0	-0.38	433	433

×

IGF1 pathway

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
NCK2	0	0	-10000	0	-10000	0	0
PTK2	0	0	-10000	0	-10000	0	0
CRKL	-0.1	0.24	-10000	0	-0.5	239	239
GRB2/SOS1/SHC	0	0.004	-10000	0	-10000	0	0
HRAS	-0.001	0.02	-10000	0	-10000	0	0
IRS1/Crk	-0.12	0.23	-10000	0	-0.5	239	239
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.24	-10000	0	-0.55	225	225
AKT1	-0.067	0.22	-10000	0	-0.74	43	43
BAD	-0.055	0.2	-10000	0	-0.68	43	43
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.1	0.24	-10000	0	-0.5	239	239
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.23	-10000	0	-0.5	239	239
RAF1	-0.047	0.19	-10000	0	-0.64	40	40
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.11	0.22	-10000	0	-0.47	239	239
YWHAZ	-0.001	0.015	-10000	0	-0.28	3	3
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.25	-10000	0	-0.54	239	239
PIK3CA	0	0.009	-10000	0	-0.28	1	1
RPS6KB1	-0.068	0.22	-10000	0	-0.43	226	226
GNB2L1	0	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.04	0.16	-10000	0	-0.52	42	42
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
HRAS/GTP	-0.1	0.2	-10000	0	-0.75	40	40
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.099	0.19	-10000	0	-0.44	225	225
IGF-1R heterotetramer	-0.036	0.14	-10000	0	-0.85	25	25
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.12	0.23	-10000	0	-0.5	239	239
Crk/p130 Cas/Paxillin	-0.11	0.21	-10000	0	-0.46	225	225
IGF1R	-0.036	0.14	-10000	0	-0.86	25	25
IGF1	-0.18	0.35	-10000	0	-0.83	215	215
IRS2/Crk	-0.13	0.25	-10000	0	-0.52	251	251
PI3K	-0.12	0.23	-10000	0	-0.48	240	240
apoptosis	0.08	0.15	0.56	43	-10000	0	43
HRAS/GDP	-0.001	0.013	-10000	0	-10000	0	0
PRKCD	-0.094	0.25	-10000	0	-0.54	225	225
RAF1/14-3-3 E	-0.075	0.14	-10000	0	-0.53	40	40
BAD/14-3-3	-0.085	0.16	-10000	0	-0.61	43	43
PRKCZ	-0.068	0.22	-10000	0	-0.74	44	44
Crk/p130 Cas/Paxillin/FAK1	-0.084	0.16	-10000	0	-0.64	40	40
PTPN1	-0.003	0.029	-10000	0	-0.28	11	11
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.13	0.25	-10000	0	-0.58	225	225
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.21	-10000	0	-0.48	225	225
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.12	0.23	-10000	0	-0.5	239	239
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	-0.1	0.24	-10000	0	-0.5	239	239
IRS1	-0.13	0.25	-10000	0	-0.54	239	239
IRS2	-0.12	0.28	-10000	0	-0.55	251	251
IGF-1R heterotetramer/IGF1	-0.16	0.29	-10000	0	-0.68	225	225
GRB2	0	0.009	-10000	0	-0.28	1	1
PDPK1	-0.11	0.21	-10000	0	-0.46	226	226
YWHAE	0	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.28	-10000	0	-0.58	237	237
SHC1	0	0	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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
NFATC2	-0.066	0.22	-9999	-0.81	81	81
GNB1/GNG2	-0.14	0.23	-9999	-0.65	114	114
mol:DAG	-0.13	0.2	-9999	-0.6	102	102
PLCG1	-0.13	0.21	-9999	-0.63	102	102
YES1	-0.15	0.23	-9999	-0.67	108	108
FZD3	-0.009	0.085	-9999	-0.81	11	11
FZD6	-0.007	0.072	-9999	-0.81	8	8
G protein	-0.13	0.22	-9999	-0.64	104	104
MAP3K7	-0.069	0.19	-9999	-0.49	100	100
mol:Ca2+	-0.094	0.21	-9999	-0.58	102	102
mol:IP3	-0.13	0.2	-9999	-0.6	102	102
NLK	-0.005	0.01	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
CAMK2A	-0.083	0.2	-9999	-0.53	106	106
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.16	0.25	-9999	-0.45	347	347
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.15	0.23	-9999	-0.41	347	347
GO:0007205	-0.094	0.22	-9999	-0.59	102	102
WNT6	-0.17	0.32	-9999	-0.72	229	229
WNT4	-0.022	0.12	-9999	-0.54	40	40
NFAT1/CK1 alpha	-0.16	0.23	-9999	-0.57	171	171
GNG2	-0.009	0.085	-9999	-0.81	11	11
WNT5A	-0.013	0.096	-9999	-0.58	23	23
WNT11	-0.18	0.33	-9999	-0.78	222	222
CDC42	-0.11	0.24	-9999	-0.67	94	94

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.035	0.05	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.081	0.16	-9999	-0.4	183	183
JUN	-0.049	0.14	-9999	-0.42	59	59
HRAS	-0.001	0.02	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.15	0.2	-9999	-0.54	186	186
RAP1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.028	-9999	-0.28	10	10
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.15	0.2	-9999	-0.54	186	186
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.1	0.19	-9999	-0.5	177	177
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.13	0.18	-9999	-0.48	186	186
GRB7	-0.02	0.075	-9999	-0.29	70	70
RET51/GFRalpha1/GDNF	-0.15	0.2	-9999	-0.54	186	186
MAPKKK cascade	-0.097	0.17	-9999	-0.43	183	183
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.12	0.24	-9999	-0.58	187	187
lamellipodium assembly	-0.081	0.15	-9999	-0.37	187	187
RET51/GFRalpha1/GDNF/SHC	-0.15	0.2	-9999	-0.54	186	186
PIK3CA	0	0.009	-9999	-0.28	1	1
RET9/GFRalpha1/GDNF/SHC	-0.1	0.19	-9999	-0.5	177	177
RET9/GFRalpha1/GDNF/Shank3	-0.1	0.19	-9999	-0.5	177	177
MAPK3	-0.12	0.17	-9999	-0.45	183	183
DOK1	-0.001	0.013	-9999	-0.28	2	2
DOK6	-0.011	0.091	-9999	-0.63	18	18
PXN	0	0	-9999	-10000	0	0
neurite development	-0.11	0.16	-9999	-0.54	52	52
DOK5	-0.019	0.12	-9999	-0.7	26	26
GFRA1	-0.16	0.31	-9999	-0.68	231	231
MAPK8	-0.074	0.13	-9999	-0.34	186	186
HRAS/GTP	-0.1	0.2	-9999	-0.5	183	183
tube development	-0.095	0.18	-9999	-0.47	177	177
MAPK1	-0.12	0.17	-9999	-0.45	183	183
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.064	0.13	-9999	-0.34	177	177
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.14	0.2	-9999	-0.52	191	191
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.15	0.2	-9999	-0.54	186	186
RET51/GFRalpha1/GDNF/Dok5	-0.16	0.22	-9999	-0.56	199	199
PRKCA	-0.02	0.12	-9999	-0.81	24	24
HRAS/GDP	-0.001	0.013	-9999	-10000	0	0
CREB1	-0.071	0.15	-9999	-0.38	177	177
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.064	0.13	-9999	-0.34	177	177
RET51/GFRalpha1/GDNF/Grb7	-0.16	0.21	-9999	-0.55	188	188
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.11	0.16	-9999	-0.3	371	371
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.048	0.14	-9999	-0.41	59	59
RET9/GFRalpha1/GDNF/FRS2	-0.1	0.19	-9999	-0.5	181	181
SHANK3	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.064	0.13	-9999	-0.34	177	177
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.081	0.14	-9999	-0.36	183	183
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.08	0.14	-9999	-0.36	183	183
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.082	0.15	-9999	-0.37	183	183
PI3K	-0.13	0.25	-9999	-0.58	204	204
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.095	0.18	-9999	-0.47	177	177
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.076	0.13	-9999	-0.34	177	177
RET51/GFRalpha1/GDNF/FRS2	-0.15	0.2	-9999	-0.54	186	186
GAB1	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.81	41	41
IRS2	-0.033	0.16	-9999	-0.81	40	40
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.082	0.15	-9999	-0.37	183	183
RET51/GFRalpha1/GDNF/PKC alpha	-0.16	0.22	-9999	-0.55	208	208
GRB2	0	0.009	-9999	-0.28	1	1
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.015	0.063	-9999	-0.28	54	54
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.24	-9999	-0.61	195	195
Rac1/GTP	-0.097	0.18	-9999	-0.45	184	184
RET9/GFRalpha1/GDNF	-0.11	0.21	-9999	-0.55	181	181
GFRalpha1/GDNF	-0.13	0.24	-9999	-0.62	181	181

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	0.01	0.04	-9999	-0.55	3	3
NFATC2	-0.035	0.16	-9999	-0.56	81	81
NFATC3	0.011	0.025	-9999	-10000	0	0
CD40LG	-0.22	0.37	-9999	-0.71	289	289
PTGS2	-0.32	0.47	-9999	-0.84	401	401
JUNB	0	0.009	-9999	-0.28	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.009	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.009	-9999	-10000	0	0
CALM1	0	0.003	-9999	-10000	0	0
JUN	-0.007	0.078	-9999	-0.82	9	9
mol:Ca2+	-0.006	0.009	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-9999	-10000	0	0
FOSL1	-0.008	0.055	-9999	-0.32	25	25
CREM	0	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.073	0.15	-9999	-0.48	98	98
FOS	-0.25	0.38	-9999	-0.82	298	298
IFNG	-0.21	0.35	-9999	-0.68	294	294
AP-1/NFAT1-c-4	-0.31	0.38	-9999	-0.82	296	296
FASLG	-0.21	0.35	-9999	-0.68	283	283
NFAT1-c-4/ICER1	-0.055	0.14	-9999	-0.48	84	84
IL2RA	-0.21	0.35	-9999	-0.69	283	283
FKBP12/FK506	0	0.006	-9999	-10000	0	0
CSF2	-0.2	0.34	-9999	-0.67	287	287
JunB/Fra1/NFAT1-c-4	-0.052	0.13	-9999	-0.46	86	86
IL4	-0.2	0.34	-9999	-0.66	290	290
IL2	-0.01	0.024	-9999	-10000	0	0
IL3	-0.024	0.027	-9999	-10000	0	0
FKBP1A	0	0.009	-9999	-0.28	1	1
BATF3	-0.002	0.03	-9999	-0.81	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.001	0.01	-9999	-10000	0	0

×

Nongenotropic Androgen 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.066	0.17	-10000	0	-0.5	131	131
regulation of S phase of mitotic cell cycle	-0.04	0.12	-10000	0	-0.35	123	123
GNAO1	-0.032	0.14	-10000	0	-0.48	66	66
HRAS	-0.001	0.02	-10000	0	-10000	0	0
SHBG/T-DHT	0	0	-10000	0	-10000	0	0
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.011	0.001	-10000	0	-10000	0	0
MAP2K1	-0.042	0.16	-10000	0	-0.44	121	121
T-DHT/AR	-0.077	0.21	-10000	0	-0.63	122	122
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.004	-10000	0	-0.007	298	298
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.042	0.18	-10000	0	-0.81	51	51
mol:GDP	-0.077	0.21	-10000	0	-0.62	123	123
cell proliferation	-0.1	0.24	-10000	0	-0.42	301	301
PIK3CA	0	0.009	-10000	0	-0.28	1	1
FOS	-0.23	0.42	-10000	0	-0.87	298	298
mol:Ca2+	-0.016	0.028	-10000	0	-0.077	131	131
MAPK3	-0.074	0.2	-10000	0	-0.47	121	121
MAPK1	-0.046	0.12	-10000	0	-0.31	56	56
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
mol:IP3	-0.001	0.002	-10000	0	-0.005	298	298
cAMP biosynthetic process	0.012	0.024	-10000	0	-10000	0	0
GNG2	-0.009	0.085	-10000	0	-0.81	11	11
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.005	298	298
HRAS/GTP	-0.064	0.15	-10000	0	-0.47	121	121
actin cytoskeleton reorganization	-0.003	0.037	-10000	0	-0.43	7	7
SRC	0	0.009	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.005	298	298
PI3K	-0.004	0.046	-10000	0	-0.54	7	7
apoptosis	0.11	0.23	0.43	300	-10000	0	300
T-DHT/AR/PELP1	-0.067	0.18	-10000	0	-0.55	121	121
HRAS/GDP	-0.074	0.2	-10000	0	-0.6	121	121
CREB1	-0.12	0.24	-10000	0	-0.46	300	300
RAC1-CDC42/GTP	-0.003	0.037	-10000	0	-0.44	7	7
AR	-0.1	0.27	-10000	0	-0.81	122	122
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.042	0.16	-10000	0	-0.45	121	121
RAC1-CDC42/GDP	-0.07	0.19	-10000	0	-0.56	121	121
T-DHT/AR/PELP1/Src	-0.062	0.16	-10000	0	-0.5	121	121
MAP2K2	-0.042	0.16	-10000	0	-0.44	121	121
T-DHT/AR/PELP1/Src/PI3K	-0.043	0.12	-10000	0	-0.35	123	123
GNAZ	-0.007	0.072	-10000	0	-0.81	8	8
SHBG	0	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.038	0.1	-10000	0	-0.48	35	35
mol:T-DHT	-0.001	0.001	0.001	55	-0.003	243	298
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.004	0.064	-10000	0	-0.63	10	10
Gi family/GTP	-0.049	0.1	-10000	0	-0.3	84	84
CDC42	0	0	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.013	0.01	-9999	-10000	0	0
RAS family/GTP	-0.11	0.14	-9999	-0.4	12	12
NFATC4	-0.089	0.16	-9999	-0.36	25	25
ERBB2IP	0.007	0.008	-9999	-10000	0	0
HSP90 (dimer)	0	0.009	-9999	-0.28	1	1
mammary gland morphogenesis	-0.15	0.19	-9999	-0.4	363	363
JUN	-0.018	0.08	-9999	-0.4	5	5
HRAS	-0.001	0.02	-9999	-10000	0	0
DOCK7	-0.13	0.19	-9999	-0.39	162	162
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.18	0.23	-9999	-0.48	363	363
AKT1	0.007	0.006	-9999	-10000	0	0
BAD	0.018	0.006	-9999	-10000	0	0
MAPK10	-0.11	0.14	-9999	-0.36	155	155
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.16	0.2	-9999	-0.43	363	363
RAF1	-0.081	0.16	-9999	-0.43	8	8
ErbB2/ErbB3/neuregulin 2	-0.26	0.26	-9999	-0.52	490	490
STAT3	0	0.004	-9999	-10000	0	0
cell migration	-0.063	0.13	-9999	-0.31	79	79
mol:PI-3-4-5-P3	-0.002	0.003	-9999	-10000	0	0
cell proliferation	-0.14	0.23	-9999	-0.51	156	156
FOS	-0.16	0.26	-9999	-0.54	300	300
NRAS	-0.001	0.013	-9999	-10000	0	0
mol:Ca2+	-0.15	0.19	-9999	-0.4	363	363
MAPK3	-0.11	0.19	-9999	-0.48	60	60
MAPK1	-0.11	0.19	-9999	-0.48	60	60
JAK2	-0.13	0.19	-9999	-0.46	23	23
NF2	-0.007	0.01	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.13	0.17	-9999	-0.36	363	363
NRG1	-0.3	0.39	-9999	-0.81	362	362
GRB2/SOS1	0	0.006	-9999	-10000	0	0
MAPK8	-0.11	0.17	-9999	-0.33	365	365
MAPK9	-0.07	0.089	-9999	-0.23	12	12
ERBB2	-0.016	0.053	-9999	-10000	0	0
ERBB3	-0.002	0.036	-9999	-0.81	2	2
SHC1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.015	0.017	-9999	-10000	0	0
STAT3 (dimer)	0	0.004	-9999	-10000	0	0
RNF41	0.018	0.014	-9999	-10000	0	0
FRAP1	0.007	0.005	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.099	0.13	-9999	-0.32	23	23
ErbB2/ErbB2/HSP90 (dimer)	-0.012	0.041	-9999	-10000	0	0
CHRNA1	-0.089	0.16	-9999	-0.41	54	54
myelination	-0.083	0.16	-9999	-0.36	25	25
PPP3CB	-0.13	0.17	-9999	-0.38	71	71
KRAS	-0.001	0.013	-9999	-0.28	2	2
RAC1-CDC42/GDP	-0.11	0.15	-9999	-0.36	24	24
NRG2	-0.4	0.4	-9999	-0.81	488	488
mol:GDP	-0.13	0.17	-9999	-0.36	363	363
SOS1	0	0	-9999	-10000	0	0
MAP2K2	-0.072	0.15	-9999	-0.44	7	7
SRC	0	0.009	-9999	-10000	0	0
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	-0.14	0.18	-9999	-0.46	23	23
MAP2K1	-0.13	0.21	-9999	-0.49	153	153
heart morphogenesis	-0.15	0.19	-9999	-0.4	363	363
RAS family/GDP	-0.11	0.14	-9999	-0.51	4	4
GRB2	0	0.009	-9999	-0.28	1	1
PRKACA	-0.011	0.014	-9999	-10000	0	0
CHRNE	0.007	0.023	-9999	-0.19	5	5
HSP90AA1	0	0.009	-9999	-0.28	1	1
activation of caspase activity	-0.007	0.006	-9999	-10000	0	0
nervous system development	-0.15	0.19	-9999	-0.4	363	363
CDC42	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.1	0.23	-10000	0	-0.62	165	165
CRKL	-0.04	0.16	-10000	0	-0.36	165	165
mol:PIP3	-0.018	0.037	0.79	2	-10000	0	2
AKT1	0.003	0.023	0.49	2	-10000	0	2
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.03	0.15	-10000	0	-0.33	165	165
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.28	1	1
HGF/MET/SHIP2	-0.12	0.25	-10000	0	-0.58	211	211
MAP3K5	-0.021	0.15	-10000	0	-0.53	24	24
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.11	0.23	-10000	0	-0.53	211	211
AP1	-0.19	0.27	-10000	0	-0.6	299	299
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.24	0.36	-10000	0	-0.78	299	299
STAT3 (dimer)	-0.072	0.15	-10000	0	-0.34	211	211
GAB1/CRKL/SHP2/PI3K	-0.064	0.13	-10000	0	-0.52	28	28
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.066	0.13	-10000	0	-0.55	21	21
PTPN11	0	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.036	-10000	0	-0.81	2	2
ELK1	-0.043	0.1	-10000	0	-0.27	165	165
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.046	0.094	-10000	0	-0.42	21	21
PAK1	0.008	0.028	0.45	2	-10000	0	2
HGF/MET/RANBP10	-0.12	0.25	-10000	0	-0.58	211	211
HRAS	-0.15	0.3	-10000	0	-0.78	167	167
DOCK1	-0.03	0.15	-10000	0	-0.33	165	165
GAB1	-0.05	0.16	-10000	0	-0.36	211	211
CRK	-0.04	0.16	-10000	0	-0.36	165	165
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.15	0.3	-10000	0	-0.72	211	211
JUN	-0.007	0.077	-10000	0	-0.81	9	9
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.077	0.15	-10000	0	-0.36	211	211
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
cell morphogenesis	-0.018	0.17	-10000	0	-0.6	25	25
GRB2/SHC	-0.066	0.13	-10000	0	-0.34	165	165
FOS	-0.24	0.37	-10000	0	-0.81	298	298
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.043	0.1	-10000	0	-0.27	165	165
HGF/MET/MUC20	-0.13	0.25	-10000	0	-0.59	211	211
cell migration	-0.065	0.13	-10000	0	-0.33	165	165
GRB2	0	0.009	-10000	0	-0.28	1	1
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.1	0.23	-10000	0	-0.62	165	165
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.077	0.16	-10000	0	-0.36	211	211
MET/MUC20	-0.1	0.23	-10000	0	-0.63	165	165
RAP1B	-0.021	0.14	-10000	0	-0.5	21	21
RAP1A	-0.021	0.14	-10000	0	-0.5	21	21
HGF/MET/RANBP9	-0.12	0.25	-10000	0	-0.58	211	211
RAF1	-0.1	0.29	-10000	0	-0.72	165	165
STAT3	-0.073	0.15	-10000	0	-0.34	211	211
cell proliferation	-0.061	0.23	-10000	0	-0.49	211	211
RPS6KB1	-0.027	0.053	-10000	0	-0.19	21	21
MAPK3	-0.044	0.092	-10000	0	-0.25	165	165
MAPK1	-0.044	0.092	-10000	0	-0.25	165	165
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	-0.002	0.13	-10000	0	-0.45	28	28
SRC	-0.071	0.14	-10000	0	-0.62	21	21
PI3K	-0.07	0.14	-10000	0	-0.35	171	171
MET/Glomulin	-0.094	0.21	-10000	0	-0.56	165	165
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.085	0.27	-10000	0	-0.65	165	165
MET	-0.14	0.3	-10000	0	-0.81	165	165
MAP4K1	-0.03	0.15	-10000	0	-0.33	166	166
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.085	0.27	-10000	0	-0.65	165	165
BAD	0.011	0.021	0.45	2	-10000	0	2
MAP2K4	-0.011	0.14	-10000	0	-0.47	25	25
SHP2/GRB2/SOS1/GAB1	-0.096	0.2	-10000	0	-0.51	165	165
INPPL1	0	0	-10000	0	-10000	0	0
PXN	0	0	-10000	0	-10000	0	0
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	-0.071	0.14	-10000	0	-0.36	165	165
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.055	0.2	-10000	0	-0.81	67	67
RASA1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
PTPRJ	0	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.067	0.14	-10000	0	-0.34	165	165
PDPK1	-0.006	0.027	0.57	2	-10000	0	2
HGF/MET/SHIP	-0.12	0.25	-10000	0	-0.58	211	211

×

ErbB4 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
ErbB4/ErbB4/HBEGF/HBEGF	-0.027	0.064	-10000	0	-0.48	3	3
epithelial cell differentiation	-0.022	0.064	-10000	0	-0.49	6	6
ITCH	0.009	0.021	-10000	0	-10000	0	0
WWP1	0.007	0.069	-10000	0	-10000	0	0
FYN	-0.002	0.036	-10000	0	-0.81	2	2
EGFR	-0.3	0.39	-10000	0	-0.8	369	369
PRL	-0.004	0.032	-10000	0	-0.28	13	13
neuron projection morphogenesis	-0.11	0.21	-10000	0	-0.48	61	61
PTPRZ1	-0.42	0.4	-10000	0	-0.8	522	522
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.16	0.2	-10000	0	-0.53	68	68
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.2	0.24	-10000	0	-0.51	362	362
ADAM17	0.009	0.021	-10000	0	-10000	0	0
ErbB4/ErbB4	0	0.087	-10000	0	-0.51	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.06	0.14	-10000	0	-0.54	63	63
NCOR1	-0.001	0.026	-10000	0	-0.81	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.18	0.23	-10000	0	-0.48	362	362
GRIN2B	-0.18	0.26	-10000	0	-0.47	413	413
ErbB4/ErbB2/betacellulin	-0.048	0.11	-10000	0	-0.48	53	53
STAT1	-0.005	0.037	-10000	0	-0.28	18	18
HBEGF	-0.002	0.036	-10000	0	-0.81	2	2
PRLR	-0.006	0.066	-10000	0	-0.81	6	6
E4ICDs/ETO2	-0.036	0.095	-10000	0	-0.56	20	20
axon guidance	0.043	0.12	-10000	0	-0.42	2	2
NEDD4	0.008	0.033	-10000	0	-0.78	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.007	0.054	-10000	0	-0.62	6	6
CBFA2T3	-0.017	0.11	-10000	0	-0.7	24	24
ErbB4/ErbB2/HBEGF	-0.025	0.051	-10000	0	-0.45	2	2
MAPK3	-0.15	0.19	-10000	0	-0.5	65	65
STAT1 (dimer)	-0.028	0.064	-10000	0	-0.45	1	1
MAPK1	-0.15	0.19	-10000	0	-0.5	65	65
JAK2	-0.001	0.026	-10000	0	-0.81	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.19	0.23	-10000	0	-0.48	362	362
NRG1	-0.21	0.31	-10000	0	-0.62	362	362
NRG3	-0.057	0.2	-10000	0	-0.81	62	62
NRG2	-0.4	0.4	-10000	0	-0.81	488	488
NRG4	-0.005	0.037	-10000	0	-0.28	18	18
heart development	0.043	0.12	-10000	0	-0.42	2	2
neural crest cell migration	-0.19	0.22	-10000	0	-0.47	362	362
ERBB2	0.01	0.056	-10000	0	-10000	0	0
WWOX/E4ICDs	-0.026	0.06	-10000	0	-0.45	1	1
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.2	0.22	-10000	0	-0.47	365	365
apoptosis	0.06	0.15	0.53	63	-10000	0	63
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.27	0.25	-10000	0	-0.52	489	489
ErbB4/ErbB2/epiregulin	-0.083	0.15	-10000	0	-0.47	113	113
ErbB4/ErbB4/betacellulin/betacellulin	-0.053	0.13	-10000	0	-0.52	54	54
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.022	0.067	-10000	0	-0.58	6	6
MDM2	0.009	0.075	-10000	0	-0.45	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.18	0.23	-10000	0	-0.48	362	362
STAT5A	0.043	0.12	-10000	0	-0.47	7	7
ErbB4/EGFR/neuregulin 1 beta	-0.35	0.36	-10000	0	-0.67	501	501
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0.006	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.024	0.057	-10000	0	-0.45	2	2
STAT5A (dimer)	-0.022	0.068	-10000	0	-0.6	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.022	0.066	-10000	0	-0.45	4	4
LRIG1	-0.002	0.036	-10000	0	-0.81	2	2
EREG	-0.11	0.26	-10000	0	-0.81	113	113
BTC	-0.044	0.18	-10000	0	-0.79	55	55
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.043	0.12	-10000	0	-0.42	2	2
ERBB4	-0.031	0.073	-10000	0	-0.52	1	1
STAT5B	-0.002	0.044	-10000	0	-0.81	3	3
YAP1	-0.01	0.045	-10000	0	-0.65	4	4
GRB2	0	0.009	-10000	0	-0.28	1	1
ErbB4/ErbB2/neuregulin 4	-0.026	0.052	-10000	0	-10000	0	0
glial cell differentiation	0.024	0.057	0.44	2	-10000	0	2
WWOX	-0.001	0.013	-10000	0	-10000	0	0
cell proliferation	-0.12	0.24	-10000	0	-0.58	64	64

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.05	0.059	-9999	-10000	0	0
STMN1	-0.1	0.12	-9999	-0.35	75	75
Aurora B/RasGAP/Survivin	-0.17	0.13	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.15	0.15	-9999	-0.32	398	398
BIRC5	-0.2	0.13	-9999	-10000	0	0
DES	-0.28	0.33	-9999	-0.64	454	454
Aurora C/Aurora B/INCENP	-0.064	0.072	-9999	-0.62	1	1
Aurora B/TACC1	-0.094	0.12	-9999	-0.62	34	34
Aurora B/PP2A	-0.094	0.091	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.006	0.015	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.003	-9999	-10000	0	0
NDC80	-0.2	0.17	-9999	-0.35	510	510
Cul3 protein complex	-0.22	0.26	-9999	-0.53	398	398
KIF2C	-0.036	0.027	-9999	-10000	0	0
PEBP1	0.001	0.004	-9999	-10000	0	0
KIF20A	-0.22	0.12	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.094	0.091	-9999	-10000	0	0
SEPT1	-0.007	0.045	-9999	-10000	0	0
SMC2	0	0	-9999	-10000	0	0
SMC4	-0.004	0.033	-9999	-0.28	14	14
NSUN2/NPM1/Nucleolin	0.012	0.015	-9999	-10000	0	0
PSMA3	0	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.002	-9999	-10000	0	0
H3F3B	-0.032	0.04	-9999	-10000	0	0
AURKB	-0.16	0.15	-9999	-10000	0	0
AURKC	-0.004	0.041	-9999	-0.81	1	1
CDCA8	-0.098	0.14	-9999	-0.28	348	348
cytokinesis	-0.1	0.069	-9999	-10000	0	0
Aurora B/Septin1	-0.085	0.079	-9999	-10000	0	0
AURKA	-0.13	0.14	-9999	-0.28	471	471
INCENP	0.003	0.005	-9999	-10000	0	0
KLHL13	-0.32	0.4	-9999	-0.81	396	396
BUB1	-0.19	0.13	-9999	-0.28	679	679
hSgo1/Aurora B/Survivin	-0.24	0.17	-9999	-0.39	504	504
EVI5	0.008	0.005	-9999	-10000	0	0
RhoA/GTP	-0.091	0.092	-9999	-10000	0	0
SGOL1	-0.18	0.13	-9999	-0.28	640	640
CENPA	-0.048	0.055	-9999	-10000	0	0
NCAPG	-0.15	0.14	-9999	-0.28	516	516
Aurora B/HC8 Proteasome	-0.094	0.091	-9999	-10000	0	0
NCAPD2	-0.002	0.025	-9999	-0.28	8	8
Aurora B/PP1-gamma	-0.094	0.091	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.12	0.14	-9999	-0.28	417	417
NPM1	-0.013	0.02	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	-0.002	0.044	-9999	-0.81	3	3
mitotic prometaphase	-0.006	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.094	0.091	-9999	-10000	0	0
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.1	0.1	-9999	-0.34	35	35
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.013	0.02	-9999	-10000	0	0
MYLK	-0.081	0.14	-9999	-0.47	113	113
KIF23	-0.088	0.13	-9999	-10000	0	0
VIM	-0.09	0.1	-9999	-0.69	2	2
RACGAP1	-0.011	0.058	-9999	-0.28	42	42
mitosis	0	0	-9999	-10000	0	0
NCL	-0.013	0.02	-9999	-10000	0	0
Chromosomal passenger complex	-0.072	0.069	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	-0.15	0.17	-9999	-10000	0	0
TACC1	-0.028	0.15	-9999	-0.81	34	34
PPP2R5D	0	0	-9999	-10000	0	0
CUL3	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.22	0.27	-10000	0	-0.54	401	401
fibroblast growth factor receptor signaling pathway	-0.22	0.27	-10000	0	-0.54	401	401
LAMA1	-0.096	0.26	-10000	0	-0.81	117	117
PRNP	-0.011	0.095	-10000	0	-0.81	14	14
GPC1/SLIT2	-0.065	0.19	-10000	0	-0.62	103	103
SMAD2	-0.019	0.093	-10000	0	-0.48	38	38
GPC1/PrPc/Cu2+	-0.009	0.067	-10000	0	-0.54	15	15
GPC1/Laminin alpha1	-0.075	0.2	-10000	0	-0.62	118	118
TDGF1	-0.008	0.081	-10000	0	-0.76	11	11
CRIPTO/GPC1	-0.008	0.066	-10000	0	-0.62	11	11
APP/GPC1	-0.001	0.023	-10000	0	-0.62	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.018	0.062	-10000	0	-0.53	12	12
FLT1	-0.001	0.026	-10000	0	-0.81	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.021	0.1	-10000	0	-0.53	38	38
SERPINC1	-0.014	0.061	-10000	0	-0.28	50	50
FYN	0.017	0.065	-10000	0	-0.53	13	13
FGR	0.018	0.062	-10000	0	-0.53	12	12
positive regulation of MAPKKK cascade	0.03	0.075	-10000	0	-0.53	13	13
SLIT2	-0.083	0.25	-10000	0	-0.81	102	102
GPC1/NRG	-0.23	0.3	-10000	0	-0.62	363	363
NRG1	-0.3	0.39	-10000	0	-0.81	362	362
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.003	0.029	-10000	0	-0.53	2	2
LYN	0.018	0.06	-10000	0	-0.53	11	11
mol:Spermine	0.01	0.024	-10000	0	-0.63	1	1
cell growth	-0.22	0.27	-10000	0	-0.54	401	401
BMP signaling pathway	0.002	0.031	0.38	5	-10000	0	5
SRC	0.018	0.06	-10000	0	-0.53	11	11
TGFBR1	0	0.009	-10000	0	-0.28	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.27	0.38	-10000	0	-0.77	352	352
GPC1	-0.002	0.031	-10000	0	-0.38	5	5
TGFBR1 (dimer)	0	0.009	-10000	0	-0.28	1	1
VEGFA	-0.003	0.029	-10000	0	-0.28	11	11
BLK	-0.006	0.087	-10000	0	-0.57	13	13
HCK	0.017	0.062	-10000	0	-0.53	11	11
FGF2	-0.32	0.4	-10000	0	-0.81	395	395
FGFR1	-0.01	0.086	-10000	0	-0.69	14	14
VEGFR1 homodimer	-0.001	0.026	-10000	0	-0.8	1	1
TGFBR2	-0.03	0.15	-10000	0	-0.81	37	37
cell death	-0.001	0.023	-10000	0	-0.62	1	1
ATIII/GPC1	-0.01	0.045	-10000	0	-0.63	1	1
PLA2G2A/GPC1	-0.21	0.29	-10000	0	-0.62	326	326
LCK	0.005	0.092	-10000	0	-0.54	24	24
neuron differentiation	-0.23	0.3	-10000	0	-0.62	363	363
PrPc/Cu2+	-0.009	0.074	-10000	0	-0.63	14	14
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.03	0.15	-10000	0	-0.8	37	37

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.11	0.12	-10000	0	-0.34	77	77
NT3 (dimer)/TRKC	-0.31	0.37	-10000	0	-0.71	425	425
NT3 (dimer)/TRKB	-0.51	0.45	-10000	0	-0.8	630	630
SHC/Grb2/SOS1/GAB1/PI3K	-0.002	0.027	-10000	0	-0.33	7	7
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.07	0.22	-10000	0	-0.81	79	79
PIK3CA	0	0.009	-10000	0	-0.28	1	1
DYNLT1	0	0.009	-10000	0	-0.28	1	1
NTRK1	-0.01	0.063	-10000	0	-0.33	29	29
NTRK2	-0.42	0.4	-10000	0	-0.81	516	516
NTRK3	-0.28	0.38	-10000	0	-0.8	348	348
NT-4/5 (dimer)/TRKB	-0.6	0.5	-10000	0	-0.88	680	680
neuron apoptosis	0.24	0.24	0.59	276	-10000	0	276
SHC 2-3/Grb2	-0.27	0.28	-10000	0	-0.66	276	276
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.25	0.29	-10000	0	-0.68	261	261
SHC3	-0.25	0.28	-10000	0	-0.66	265	265
STAT3 (dimer)	-0.005	0.027	-10000	0	-0.38	3	3
NT3 (dimer)/TRKA	-0.26	0.32	-10000	0	-0.62	401	401
RIN/GDP	-0.069	0.12	-10000	0	-0.28	68	68
GIPC1	-0.001	0.013	-10000	0	-0.28	2	2
KRAS	-0.001	0.013	-10000	0	-0.28	2	2
DNAJA3	-0.14	0.2	-10000	0	-0.43	316	316
RIN/GTP	0	0.008	-10000	0	-10000	0	0
CCND1	0.019	0.069	-10000	0	-1	3	3
MAGED1	-0.001	0.015	-10000	0	-0.28	3	3
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.29	0.38	-10000	0	-0.8	351	351
SHC/GRB2/SOS1	0	0.004	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-0.28	1	1
NGF (dimer)/TRKA/MATK	-0.028	0.11	-10000	0	-0.55	35	35
TRKA/NEDD4-2	-0.007	0.048	-10000	0	-0.62	4	4
ELMO1	0	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.014	0.1	-10000	0	-0.81	15	15
HRAS	-0.001	0.02	-10000	0	-10000	0	0
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.003	0.026	-10000	0	-0.28	9	9
RIT2	-0.001	0.013	-10000	0	-0.28	2	2
RIT1	0	0	-10000	0	-10000	0	0
FRS2	-0.003	0.028	-10000	0	-0.28	10	10
DNM1	-0.006	0.068	-10000	0	-0.74	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.14	0.2	-10000	0	-0.42	316	316
mol:GDP	-0.11	0.18	-10000	0	-0.37	215	215
NGF (dimer)	-0.014	0.1	-10000	0	-0.8	15	15
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	-0.065	0.12	-10000	0	-0.27	67	67
TIAM1	-0.001	0.018	-10000	0	-10000	0	0
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
BDNF (dimer)/TRKB	-0.32	0.31	-10000	0	-0.58	542	542
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.013	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0.004	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.13	0.3	-10000	0	-0.76	170	170
RAP1/GDP	-0.075	0.086	-10000	0	-0.25	39	39
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.07	0.22	-10000	0	-0.8	79	79
ubiquitin-dependent protein catabolic process	-0.015	0.076	-10000	0	-0.53	19	19
Schwann cell development	-0.06	0.045	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.001	0.012	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0	0.001	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.44	0.39	-10000	0	-0.88	375	375
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
Rap1/GTP	-0.11	0.1	-10000	0	-10000	0	0
STAT3	-0.005	0.027	-10000	0	-0.38	3	3
axon guidance	-0.41	0.36	-10000	0	-0.81	375	375
MAPK3	-0.024	0.096	-10000	0	-0.5	35	35
MAPK1	-0.024	0.096	-10000	0	-0.5	35	35
CDC42/GDP	-0.065	0.12	-10000	0	-0.28	54	54
NTF3	-0.13	0.3	-10000	0	-0.77	170	170
NTF4	-0.29	0.39	-10000	0	-0.81	351	351
NGF (dimer)/TRKA/FAIM	-0.014	0.075	-10000	0	-0.53	18	18
PI3K	-0.005	0.052	-10000	0	-0.62	7	7
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.16	0.21	-10000	0	-0.45	319	319
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.25	0.34	-10000	0	-0.62	427	427
RGS19	-0.001	0.015	-10000	0	-0.28	3	3
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.003	0.082	-10000	0	-10000	0	0
Rac1/GDP	-0.065	0.12	-10000	0	-0.28	51	51
NGF (dimer)/TRKA/GRIT	-0.015	0.076	-10000	0	-0.54	18	18
neuron projection morphogenesis	-0.11	0.21	-10000	0	-0.41	307	307
NGF (dimer)/TRKA/NEDD4-2	-0.015	0.076	-10000	0	-0.53	19	19
MAP2K1	0	0.003	-10000	0	-10000	0	0
NGFR	-0.25	0.37	-10000	0	-0.81	309	309
NGF (dimer)/TRKA/GIPC/GAIP	-0.009	0.054	-10000	0	-0.34	24	24
RAS family/GTP/PI3K	-0.003	0.029	-10000	0	-0.34	7	7
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.01	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-10000	0	0
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.026	-10000	0	-0.81	1	1
MAPKKK cascade	-0.065	0.11	-10000	0	-0.81	18	18
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.007	0.044	-10000	0	-0.62	3	3
SQSTM1	0	0.009	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.29	0.28	-10000	0	-0.53	542	542
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.012	0.064	-10000	0	-0.45	19	19
MATK	-0.022	0.12	-10000	0	-0.81	18	18
NEDD4L	-0.001	0.026	-10000	0	-0.81	1	1
RAS family/GDP	-0.067	0.08	-10000	0	-0.23	8	8
NGF (dimer)/TRKA	-0.15	0.22	-10000	0	-0.46	316	316
Rac1/GTP	-0.13	0.14	-10000	0	-0.34	237	237
FRS2 family/SHP2/CRK family	-0.001	0.01	-10000	0	-10000	0	0

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.11	0.2	-9999	-0.6	121	121
SMAD6-7/SMURF1	-0.001	0.017	-9999	-0.53	1	1
NOG	-0.023	0.12	-9999	-0.81	22	22
SMAD9	-0.11	0.26	-9999	-0.78	106	106
SMAD4	-0.001	0.026	-9999	-0.81	1	1
SMAD5	-0.075	0.18	-9999	-0.55	83	83
BMP7/USAG1	-0.35	0.35	-9999	-0.68	509	509
SMAD5/SKI	-0.087	0.16	-9999	-0.54	70	70
SMAD1	0.026	0.03	-9999	-10000	0	0
BMP2	-0.14	0.31	-9999	-0.8	175	175
SMAD1/SMAD1/SMAD4	-0.002	0.015	-9999	-10000	0	0
BMPR1A	-0.002	0.036	-9999	-0.81	2	2
BMPR1B	-0.13	0.17	-9999	-0.81	23	23
BMPR1A-1B/BAMBI	-0.09	0.14	-9999	-0.61	54	54
AHSG	-0.003	0.028	-9999	-10000	0	0
CER1	-0.001	0.015	-9999	-10000	0	0
BMP2-4/CER1	-0.13	0.25	-9999	-0.58	220	220
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.1	0.2	-9999	-0.54	123	123
BMP2-4 (homodimer)	-0.15	0.28	-9999	-0.66	220	220
RGMB	-0.001	0.026	-9999	-0.81	1	1
BMP6/BMPR2/BMPR1A-1B	-0.096	0.16	-9999	-0.55	99	99
RGMA	-0.11	0.28	-9999	-0.81	133	133
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.11	0.2	-9999	-0.62	97	97
BMP2-4/USAG1	-0.38	0.37	-9999	-0.66	571	571
SMAD6/SMURF1/SMAD5	-0.087	0.16	-9999	-0.54	70	70
SOSTDC1	-0.4	0.4	-9999	-0.8	489	489
BMP7/BMPR2/BMPR1A-1B	-0.1	0.17	-9999	-0.58	97	97
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.063	0.22	-9999	-0.8	76	76
HFE2	-0.002	0.025	-9999	-10000	0	0
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0.009	-9999	-0.28	1	1
BMP2-4/CHRD	-0.14	0.27	-9999	-0.62	222	222
SMAD5/SMAD5/SMAD4	-0.087	0.16	-9999	-0.54	71	71
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.086	0.17	-9999	-0.53	94	94
BMP7 (homodimer)	-0.075	0.22	-9999	-0.8	78	78
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.05	0.17	-9999	-0.62	76	76
SMAD1/SKI	-0.004	0.013	-9999	-10000	0	0
SMAD6	-0.001	0.026	-9999	-0.81	1	1
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.13	0.25	-9999	-0.58	220	220
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.037	0.12	-9999	-0.81	12	12
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	-0.001	0.01	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.088	0.12	-9999	-0.63	25	25
CHRDL1	-0.55	0.38	-9999	-0.81	673	673
ENDOFIN/SMAD1	-0.004	0.013	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.003	0.014	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.035	0.14	-9999	-0.5	70	70
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.48	0.38	-9999	-0.69	690	690
BMP2-4/GREM1	-0.15	0.26	-9999	-0.59	224	224
SMAD7	0	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.098	0.24	-9999	-0.74	106	106
SMAD1/SMAD6	-0.004	0.013	-9999	-10000	0	0
TAK1/SMAD6	0	0.006	-9999	-10000	0	0
BMP7	-0.075	0.22	-9999	-0.81	78	78
BMP6	-0.063	0.22	-9999	-0.81	76	76
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.099	0.19	-9999	-0.6	94	94
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	-0.004	0.013	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
PPP1CA	-0.001	0.02	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.13	0.24	-9999	-0.58	156	156
CHRD	-0.032	0.13	-9999	-0.41	78	78
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.13	0.24	-9999	-0.54	181	181
BMP4	-0.053	0.2	-9999	-0.8	66	66
FST	-0.035	0.16	-9999	-0.76	46	46
BMP2-4/NOG	-0.14	0.26	-9999	-0.59	233	233
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.092	0.16	-9999	-0.54	97	97

×

Visual signal transduction: Rods

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
mol:K +	0	0	-9999	-10000	0	0
GNAT1/GTP	-0.003	0.022	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.01	0.037	-9999	-0.3	2	2
PDE6G/GNAT1/GTP	-0.008	0.034	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.004	0.033	-9999	-0.28	14	14
GRK1	-0.003	0.028	-9999	-0.28	10	10
CNG Channel	-0.14	0.2	-9999	-0.44	297	297
mol:Na +	-0.14	0.19	-9999	-0.43	291	291
mol:ADP	-0.003	0.028	-9999	-0.28	10	10
RGS9-1/Gbeta5/R9AP	-0.065	0.17	-9999	-0.54	102	102
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.14	0.2	-9999	-0.44	291	291
CNGB1	-0.015	0.062	-9999	-0.28	52	52
RDH5	-0.48	0.4	-9999	-0.81	594	594
SAG	-0.014	0.061	-9999	-10000	0	0
mol:Ca2+	-0.13	0.18	-9999	-0.41	290	290
Na + (4 Units)	-0.12	0.18	-9999	-0.4	290	290
RGS9	-0.087	0.25	-9999	-0.75	115	115
GNB1/GNGT1	-0.028	0.064	-9999	-10000	0	0
GNAT1/GDP	-0.057	0.14	-9999	-0.47	102	102
GUCY2D	-0.006	0.049	-9999	-0.81	2	2
GNGT1	-0.044	0.1	-9999	-0.28	155	155
GUCY2F	-0.001	0.013	-9999	-0.28	2	2
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.018	0.071	-9999	-0.46	20	20
mol:11-cis-retinal	-0.48	0.39	-9999	-0.8	594	594
mol:cGMP	-0.01	0.047	-9999	-0.47	7	7
GNB1	0	0	-9999	-10000	0	0
Rhodopsin	-0.38	0.3	-9999	-0.62	594	594
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.24	0.37	-9999	-0.8	292	292
Metarhodopsin II	-0.003	0.02	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.01	0.05	-9999	-0.5	7	7
RGS9BP	-0.016	0.065	-9999	-10000	0	0
Metarhodopsin II/Transducin	-0.008	0.018	-9999	-10000	0	0
GCAP Family/Ca ++	-0.008	0.044	-9999	-0.5	5	5
PDE6A/B	-0.017	0.09	-9999	-0.62	20	20
mol:Pi	-0.064	0.16	-9999	-0.54	102	102
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.021	0.047	-9999	-10000	0	0
PDE6B	-0.017	0.11	-9999	-0.76	22	22
PDE6A	-0.006	0.04	-9999	-0.28	21	21
PDE6G	-0.012	0.056	-9999	-10000	0	0
RHO	-0.004	0.033	-9999	-0.28	14	14
PDE6	-0.065	0.15	-9999	-0.46	118	118
GUCA1A	-0.012	0.056	-9999	-0.28	41	41
GC2/GCAP Family	-0.008	0.044	-9999	-0.5	5	5
GUCA1C	0	0.009	-9999	-0.28	1	1
GUCA1B	-0.004	0.057	-9999	-0.81	5	5

×

Plasma membrane estrogen receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.097	0.18	-10000	0	-0.48	177	177
ER alpha/Gai/GDP/Gbeta gamma	-0.091	0.19	-10000	0	-0.48	157	157
AKT1	-0.098	0.32	-10000	0	-0.84	149	149
PIK3CA	0	0.009	-10000	0	-0.28	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.12	0.31	-10000	0	-0.86	147	147
mol:Ca2+	-0.027	0.15	-10000	0	-0.47	78	78
IGF1R	-0.022	0.12	-10000	0	-0.62	36	36
E2/ER alpha (dimer)/Striatin	-0.1	0.2	-10000	0	-0.55	157	157
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.091	0.3	0.8	149	-10000	0	149
RhoA/GTP	-0.07	0.14	-10000	0	-0.4	147	147
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.091	0.21	-10000	0	-0.55	154	154
regulation of stress fiber formation	0.02	0.14	0.47	6	-10000	0	6
E2/ERA-ERB (dimer)	-0.11	0.21	-10000	0	-0.55	170	170
KRAS	-0.001	0.013	-10000	0	-0.28	2	2
G13/GTP	-0.089	0.18	-10000	0	-0.5	147	147
pseudopodium formation	-0.02	0.14	-10000	0	-0.47	6	6
E2/ER alpha (dimer)/PELP1	-0.098	0.19	-10000	0	-0.54	147	147
GRB2	0	0.009	-10000	0	-0.28	1	1
GNG2	-0.009	0.085	-10000	0	-0.81	11	11
GNAO1	-0.032	0.14	-10000	0	-0.48	66	66
HRAS	-0.001	0.02	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.06	0.22	-10000	0	-0.55	156	156
E2/ER beta (dimer)	-0.015	0.096	-10000	0	-0.63	24	24
mol:GDP	-0.087	0.21	-10000	0	-0.54	170	170
mol:NADP	-0.06	0.22	-10000	0	-0.55	156	156
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
mol:IP3	-0.029	0.16	-10000	0	-0.49	78	78
IGF-1R heterotetramer	-0.022	0.12	-10000	0	-0.62	36	36
PLCB1	-0.063	0.15	-10000	0	-0.51	77	77
PLCB2	-0.035	0.095	-10000	0	-0.67	14	14
IGF1	-0.18	0.33	-10000	0	-0.81	215	215
mol:L-citrulline	-0.06	0.22	-10000	0	-0.55	156	156
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.04	0.15	-10000	0	-0.86	25	25
JNK cascade	-0.015	0.096	-10000	0	-0.62	24	24
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	-0.02	0.12	-10000	0	-0.81	24	24
GNAQ	-0.002	0.036	-10000	0	-0.81	2	2
ESR1	-0.15	0.29	-10000	0	-0.57	264	264
Gq family/GDP/Gbeta gamma	-0.007	0.072	-10000	0	-0.72	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.024	0.13	-10000	0	-0.32	147	147
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.091	0.21	-10000	0	-0.55	154	154
GNAZ	-0.007	0.072	-10000	0	-0.81	8	8
E2/ER alpha (dimer)	-0.12	0.22	-10000	0	-0.63	147	147
STRN	-0.01	0.088	-10000	0	-0.81	12	12
GNAL	-0.19	0.34	-10000	0	-0.81	233	233
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.003	0.093	-10000	0	-0.56	26	26
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.042	0.18	-10000	0	-0.81	51	51
HBEGF	-0.069	0.19	-10000	0	-0.45	160	160
cAMP biosynthetic process	-0.19	0.26	-10000	0	-0.52	353	353
SRC	-0.05	0.2	-10000	0	-0.45	157	157
PI3K	-0.005	0.052	-10000	0	-0.62	7	7
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.079	0.19	-10000	0	-0.48	162	162
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.15	0.23	-10000	0	-0.55	194	194
Gs family/GTP	-0.2	0.27	-10000	0	-0.53	353	353
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.011	-10000	0	-10000	0	0
vasodilation	-0.056	0.21	-10000	0	-0.52	156	156
mol:DAG	-0.029	0.16	-10000	0	-0.49	78	78
Gs family/GDP/Gbeta gamma	-0.16	0.23	-10000	0	-0.52	211	211
MSN	-0.023	0.15	-10000	0	-0.52	6	6
Gq family/GTP	-0.038	0.1	-10000	0	-0.66	15	15
mol:PI-3-4-5-P3	-0.096	0.31	-10000	0	-0.82	147	147
NRAS	-0.001	0.013	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.056	0.21	0.52	156	-10000	0	156
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
RhoA/GDP	-0.08	0.19	-10000	0	-0.5	170	170
NOS3	-0.064	0.24	-10000	0	-0.58	156	156
GNA11	-0.002	0.036	-10000	0	-0.81	2	2
MAPKKK cascade	-0.064	0.26	-10000	0	-0.64	157	157
E2/ER alpha (dimer)/PELP1/Src	-0.096	0.22	-10000	0	-0.58	154	154
ruffle organization	-0.02	0.14	-10000	0	-0.47	6	6
ROCK2	-0.07	0.14	-10000	0	-0.45	20	20
GNA14	-0.015	0.09	-10000	0	-0.44	33	33
GNA15	-0.003	0.035	-10000	0	-0.34	8	8
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.094	0.2	-10000	0	-0.53	117	117
MMP2	-0.043	0.19	-10000	0	-0.43	161	161

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.059	0.22	-9999	-0.62	55	55
CRP	-0.064	0.22	-9999	-0.63	54	54
cell cycle arrest	-0.077	0.24	-9999	-0.67	73	73
TIMP1	-0.057	0.2	-9999	-0.57	51	51
IL6ST	-0.073	0.25	-9999	-0.8	105	105
Rac1/GDP	-0.14	0.21	-9999	-0.66	76	76
AP1	-0.13	0.24	-9999	-0.49	245	245
GAB2	0.003	0.028	-9999	-0.28	9	9
TNFSF11	-0.069	0.22	-9999	-0.61	61	61
HSP90B1	0.016	0.047	-9999	-10000	0	0
GAB1	0	0.002	-9999	-10000	0	0
MAPK14	-0.12	0.24	-9999	-0.73	79	79
AKT1	0.04	0.034	-9999	-10000	0	0
FOXO1	0.048	0.056	-9999	-0.42	11	11
MAP2K6	-0.14	0.25	-9999	-0.68	99	99
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.08	0.22	-9999	-0.63	74	74
MITF	-0.13	0.25	-9999	-0.48	201	201
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0	0	-9999	-10000	0	0
A2M	0.013	0.13	-9999	-1.5	7	7
CEBPB	0.015	0.007	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.053	0.07	-9999	-10000	0	0
STAT3	-0.085	0.26	-9999	-0.73	72	72
STAT1	-0.013	0.022	-9999	-10000	0	0
CEBPD	-0.061	0.22	-9999	-0.65	55	55
PIK3CA	0.012	0.009	-9999	-0.28	1	1
PI3K	-0.005	0.052	-9999	-0.62	7	7
JUN	-0.007	0.077	-9999	-0.81	9	9
PIAS3/MITF	-0.15	0.21	-9999	-0.68	79	79
MAPK11	-0.12	0.25	-9999	-0.74	79	79
STAT3 (dimer)/FOXO1	-0.029	0.22	-9999	-0.57	66	66
GRB2/SOS1/GAB family	-0.14	0.19	-9999	-0.72	55	55
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.15	0.25	-9999	-0.46	244	244
GRB2	0	0.009	-9999	-0.28	1	1
JAK2	-0.001	0.026	-9999	-0.81	1	1
LBP	-0.22	0.44	-9999	-0.95	246	246
PIK3R1	0.003	0.069	-9999	-0.81	7	7
JAK1	0.001	0.004	-9999	-10000	0	0
MYC	-0.073	0.26	-9999	-0.83	59	59
FGG	-0.068	0.22	-9999	-0.62	60	60
macrophage differentiation	-0.077	0.24	-9999	-0.67	73	73
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.23	0.28	-9999	-0.51	442	442
JUNB	-0.058	0.21	-9999	-0.59	60	60
FOS	-0.24	0.37	-9999	-0.81	298	298
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.15	0.26	-9999	-0.4	402	402
STAT1/PIAS1	-0.14	0.22	-9999	-0.5	149	149
GRB2/SOS1/GAB family/SHP2/PI3K	0	0.024	-9999	-10000	0	0
STAT3 (dimer)	-0.08	0.25	-9999	-0.71	70	70
PRKCD	-0.055	0.22	-9999	-0.6	68	68
IL6R	-0.026	0.14	-9999	-0.81	33	33
SOCS3	-0.12	0.24	-9999	-0.76	70	70
gp130 (dimer)/JAK1/JAK1/LMO4	-0.049	0.17	-9999	-0.53	108	108
Rac1/GTP	-0.14	0.2	-9999	-0.64	81	81
HCK	-0.003	0.029	-9999	-10000	0	0
MAPKKK cascade	-0.002	0.071	-9999	-10000	0	0
bone resorption	-0.065	0.21	-9999	-0.58	62	62
IRF1	-0.06	0.22	-9999	-0.62	58	58
mol:GDP	-0.12	0.24	-9999	-0.48	189	189
SOS1	0	0.003	-9999	-10000	0	0
VAV1	-0.13	0.25	-9999	-0.49	188	188
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.17	0.24	-9999	-0.8	75	75
PTPN11	-0.013	0.019	-9999	-10000	0	0
IL6/IL6RA	-0.24	0.32	-9999	-0.64	377	377
gp130 (dimer)/TYK2/TYK2/LMO4	-0.052	0.17	-9999	-0.53	108	108
gp130 (dimer)/JAK2/JAK2/LMO4	-0.052	0.17	-9999	-0.54	108	108
IL6	-0.29	0.4	-9999	-0.8	363	363
PIAS3	0	0	-9999	-10000	0	0
PTPRE	0.003	0.027	-9999	-0.81	1	1
PIAS1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.18	0.24	-9999	-0.4	441	441
LMO4	0.009	0.051	-9999	-0.45	9	9
STAT3 (dimer)/PIAS3	-0.14	0.21	-9999	-0.76	63	63
MCL1	0.052	0.026	-9999	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.004	0.043	-9999	-0.62	4	4
alphaV beta3 Integrin	-0.23	0.28	-9999	-0.55	407	407
PTK2	-0.088	0.19	-9999	-0.65	35	35
IGF1R	-0.022	0.12	-9999	-0.62	36	36
PI4KB	0	0	-9999	-10000	0	0
MFGE8	-0.012	0.094	-9999	-0.64	19	19
SRC	0	0.009	-9999	-10000	0	0
CDKN1B	-0.086	0.12	-9999	-0.87	8	8
VEGFA	-0.003	0.029	-9999	-0.28	11	11
ILK	-0.083	0.11	-9999	-0.4	20	20
ROCK1	-0.001	0.026	-9999	-0.81	1	1
AKT1	-0.073	0.096	-9999	-0.72	5	5
PTK2B	-0.016	0.088	-9999	-0.5	29	29
alphaV/beta3 Integrin/JAM-A	-0.2	0.24	-9999	-0.48	410	410
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.016	0.09	-9999	-0.54	28	28
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.14	0.26	-9999	-0.56	239	239
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.01	0.056	-9999	-0.46	6	6
alphaV/beta3 Integrin/Syndecan-1	-0.026	0.097	-9999	-0.55	29	29
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.33	0.36	-9999	-0.64	483	483
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.28	1	1
alphaV/beta3 Integrin/Osteopontin	-0.052	0.1	-9999	-0.55	28	28
RPS6KB1	-0.3	0.32	-9999	-0.7	314	314
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.33	0.39	-9999	-0.77	407	407
GPR124	-0.009	0.085	-9999	-0.81	11	11
MAPK1	-0.33	0.39	-9999	-0.77	407	407
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
alphaV/beta3 Integrin/Tumstatin	-0.11	0.22	-9999	-0.54	205	205
cell adhesion	-0.021	0.1	-9999	-0.52	38	38
ANGPTL3	-0.001	0.02	-9999	-0.28	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.004	0.037	-9999	-0.53	4	4
IGF-1R heterotetramer	-0.022	0.12	-9999	-0.62	36	36
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.03	0.15	-9999	-0.81	37	37
ITGB3	-0.024	0.14	-9999	-0.81	28	28
IGF1	-0.18	0.33	-9999	-0.81	215	215
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.021	0.11	-9999	-0.6	34	34
apoptosis	0	0	-9999	-10000	0	0
CD47	-0.001	0.026	-9999	-0.81	1	1
alphaV/beta3 Integrin/CD47	-0.016	0.09	-9999	-0.53	29	29
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.043	0.17	-9999	-0.67	60	60
CSF1	-0.006	0.068	-9999	-0.81	7	7
PIK3C2A	-0.084	0.11	-9999	-0.81	6	6
PI4 Kinase/Pyk2	-0.17	0.21	-9999	-0.59	59	59
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.017	0.094	-9999	-0.54	29	29
FAK1/Vinculin	-0.064	0.15	-9999	-0.5	33	33
alphaV beta3/Integrin/ppsTEM5	-0.021	0.12	-9999	-0.6	34	34
RHOA	0	0	-9999	-10000	0	0
VTN	-0.023	0.09	-9999	-0.32	73	73
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.32	0.4	-9999	-0.81	395	395
F11R	-0.23	0.31	-9999	-0.62	395	395
alphaV/beta3 Integrin/Lactadherin	-0.023	0.12	-9999	-0.58	37	37
alphaV/beta3 Integrin/TGFBR2	-0.035	0.16	-9999	-0.66	51	51
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.041	-9999	-0.48	7	7
HSP90AA1	0	0.009	-9999	-0.28	1	1
alphaV/beta3 Integrin/Talin	-0.014	0.082	-9999	-0.49	28	28
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.11	0.14	-9999	-0.28	398	398
alphaV/beta3 Integrin/Pyk2	-0.016	0.089	-9999	-0.5	29	29
SDC1	-0.021	0.076	-9999	-0.81	1	1
VAV3	-0.008	0.054	-9999	-0.45	14	14
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.81	41	41
FAK1/Paxillin	-0.064	0.15	-9999	-0.5	31	31
cell migration	-0.05	0.14	-9999	-0.45	31	31
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.18	0.22	-9999	-0.44	412	412
SPP1	-0.075	0.12	-9999	-0.28	265	265
KDR	-0.003	0.051	-9999	-0.81	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.15	0.31	-9999	-0.81	181	181
angiogenesis	-0.3	0.39	-9999	-0.74	409	409
Rac1/GTP	-0.007	0.049	-9999	-0.41	14	14
EDIL3	-0.044	0.18	-9999	-0.68	64	64
cell proliferation	-0.035	0.15	-9999	-0.66	51	51

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.051	-10000	0	-0.81	4	4
Jak2/Leptin Receptor	-0.16	0.24	-10000	0	-0.54	266	266
PTP1B/AKT1	-0.071	0.11	-10000	0	-0.34	105	105
FYN	-0.002	0.036	-10000	0	-0.81	2	2
p210 bcr-abl/PTP1B	-0.073	0.13	-10000	0	-0.38	111	111
EGFR	-0.3	0.39	-10000	0	-0.81	369	369
EGF/EGFR	-0.3	0.32	-10000	0	-0.58	505	505
CSF1	-0.006	0.068	-10000	0	-0.81	7	7
AKT1	0	0.001	-10000	0	-10000	0	0
INSR	0	0.009	-10000	0	-0.28	1	1
PTP1B/N-cadherin	-0.096	0.12	-10000	0	-0.37	111	111
Insulin Receptor/Insulin	-0.05	0.081	-10000	0	-0.43	16	16
HCK	-0.003	0.029	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
TYK2	-0.061	0.12	-10000	0	-0.36	106	106
EGF	-0.17	0.33	-10000	0	-0.81	206	206
YES1	-0.001	0.026	-10000	0	-0.81	1	1
CAV1	-0.18	0.24	-10000	0	-0.51	264	264
TXN	-0.001	0.015	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.088	0.15	-10000	0	-0.41	136	136
cell migration	0.073	0.13	0.38	111	-10000	0	111
STAT3	0	0	-10000	0	-10000	0	0
PRLR	-0.004	0.066	-10000	0	-0.81	6	6
ITGA2B	-0.017	0.076	-10000	0	-0.6	5	5
CSF1R	-0.001	0.027	-10000	0	-0.54	2	2
Prolactin Receptor/Prolactin	-0.006	0.054	-10000	0	-0.62	6	6
FGR	-0.001	0.027	-10000	0	-0.81	1	1
PTP1B/p130 Cas	-0.076	0.12	-10000	0	-0.36	105	105
Crk/p130 Cas	-0.07	0.11	-10000	0	-0.36	84	84
DOK1	-0.047	0.12	-10000	0	-0.32	106	106
JAK2	-0.043	0.079	-10000	0	-0.34	20	20
Jak2/Leptin Receptor/Leptin	-0.37	0.19	-10000	0	-0.5	506	506
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
PTPN1	-0.073	0.13	-10000	0	-0.38	111	111
LYN	0	0	-10000	0	-10000	0	0
CDH2	-0.054	0.11	-10000	0	-0.28	186	186
SRC	-0.014	0.047	-10000	0	-10000	0	0
ITGB3	-0.024	0.14	-10000	0	-0.81	28	28
CAT1/PTP1B	-0.086	0.17	-10000	0	-0.44	101	101
CAPN1	0.001	0.002	-10000	0	-10000	0	0
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.043	0.087	-10000	0	-0.57	12	12
mol:H2O2	-0.006	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.33	0.16	-10000	0	-0.44	498	498
negative regulation of transcription	-0.042	0.079	-10000	0	-0.34	20	20
FCGR2A	0	0.009	-10000	0	-10000	0	0
FER	-0.01	0.09	-10000	0	-0.82	12	12
alphaIIb/beta3 Integrin	-0.029	0.12	-10000	0	-0.63	31	31
BLK	-0.04	0.1	-10000	0	-0.81	3	3
Insulin Receptor/Insulin/Shc	0	0.005	-10000	0	-10000	0	0
RHOA	0.001	0.002	-10000	0	-10000	0	0
LEPR	-0.21	0.36	-10000	0	-0.81	261	261
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0.009	-10000	0	-0.28	1	1
mol:NADPH	-0.005	0.005	-10000	0	-10000	0	0
TRPV6	-0.031	0.13	-10000	0	-0.46	20	20
PRL	-0.004	0.032	-10000	0	-0.28	13	13
SOCS3	0.017	0.12	-10000	0	-1.5	6	6
SPRY2	-0.095	0.26	-10000	0	-0.82	115	115
Insulin Receptor/Insulin/IRS1	-0.023	0.11	-10000	0	-0.55	41	41
CSF1/CSF1R	-0.073	0.12	-10000	0	-0.36	109	109
Ras protein signal transduction	0.037	0.036	-10000	0	-0.19	1	1
IRS1	-0.033	0.16	-10000	0	-0.81	41	41
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.65	0.32	-10000	0	-0.81	797	797
STAT5B	-0.06	0.11	-10000	0	-0.31	110	110
STAT5A	-0.061	0.11	-10000	0	-0.32	112	112
GRB2	0	0.009	-10000	0	-0.28	1	1
PDGFB-D/PDGFRB	-0.078	0.12	-10000	0	-0.38	107	107
CSN2	0.019	0.034	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.28	1	1
LAT	-0.015	0.053	-10000	0	-0.58	2	2
YBX1	-0.001	0.014	-10000	0	-10000	0	0
LCK	-0.02	0.1	-10000	0	-0.81	13	13
SHC1	0	0	-10000	0	-10000	0	0
NOX4	-0.004	0.046	-10000	0	-0.38	11	11

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.023	0.063	-9999	-0.58	10	10
alphaM/beta2 Integrin/GPIbA	-0.025	0.06	-9999	-0.56	8	8
alphaM/beta2 Integrin/proMMP-9	-0.08	0.078	-9999	-0.42	5	5
PLAUR	-0.021	0.074	-9999	-10000	0	0
HMGB1	-0.013	0.018	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.018	0.028	-9999	-10000	0	0
AGER	-0.015	0.042	-9999	-0.86	2	2
RAP1A	0	0	-9999	-10000	0	0
SELPLG	0	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.075	0.097	-9999	-0.4	12	12
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.14	-9999	-0.28	444	444
CYR61	-0.044	0.18	-9999	-0.81	54	54
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.056	0.11	-9999	-0.53	20	20
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.19	0.34	-9999	-0.8	233	233
MYH2	-0.067	0.16	-9999	-0.4	109	109
MST1R	-0.011	0.085	-9999	-0.54	20	20
leukocyte activation during inflammatory response	-0.31	0.23	-9999	-0.48	625	625
APOB	-0.51	0.39	-9999	-0.81	625	625
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.008	0.081	-9999	-0.81	10	10
JAM3	-0.006	0.068	-9999	-0.81	7	7
GP1BA	-0.012	0.079	-9999	-0.81	7	7
alphaM/beta2 Integrin/CTGF	-0.025	0.071	-9999	-0.59	13	13
alphaM/beta2 Integrin	-0.07	0.13	-9999	-0.36	89	89
JAM3 homodimer	-0.006	0.068	-9999	-0.8	7	7
ICAM2	-0.004	0.057	-9999	-0.81	5	5
ICAM1	-0.004	0.034	-9999	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.059	0.14	-9999	-0.31	162	162
cell adhesion	-0.025	0.059	-9999	-0.56	8	8
NFKB1	-0.14	0.18	-9999	-0.66	14	14
THY1	-0.002	0.023	-9999	-0.28	7	7
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.35	0.26	-9999	-0.55	625	625
alphaM/beta2 Integrin/LRP/tPA	-0.034	0.11	-9999	-0.55	41	41
IL6	-0.31	0.49	-9999	-0.94	362	362
ITGB2	-0.017	0.036	-9999	-0.29	13	13
elevation of cytosolic calcium ion concentration	-0.024	0.048	-9999	-0.38	1	1
alphaM/beta2 Integrin/JAM2/JAM3	-0.044	0.13	-9999	-0.56	58	58
JAM2	-0.046	0.19	-9999	-0.81	56	56
alphaM/beta2 Integrin/ICAM1	-0.022	0.084	-9999	-0.55	20	20
alphaM/beta2 Integrin/uPA/Plg	-0.019	0.032	-9999	-10000	0	0
RhoA/GTP	-0.085	0.17	-9999	-0.38	198	198
positive regulation of phagocytosis	-0.048	0.089	-9999	-0.46	17	17
Ron/MSP	-0.016	0.1	-9999	-0.68	21	21
alphaM/beta2 Integrin/uPAR/uPA	-0.024	0.048	-9999	-0.38	1	1
alphaM/beta2 Integrin/uPAR	-0.028	0.046	-9999	-0.42	1	1
PLAU	-0.008	0.046	-9999	-0.28	28	28
PLAT	-0.029	0.15	-9999	-0.81	34	34
actin filament polymerization	-0.064	0.16	-9999	-0.38	113	113
MST1	-0.011	0.093	-9999	-0.71	16	16
alphaM/beta2 Integrin/lipoprotein(a)	-0.31	0.23	-9999	-0.49	625	625
TNF	-0.09	0.22	-9999	-0.96	18	18
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.021	0.035	-9999	-10000	0	0
fibrinolysis	-0.019	0.032	-9999	-10000	0	0
HCK	-0.003	0.029	-9999	-10000	0	0
dendritic cell antigen processing and presentation	-0.059	0.14	-9999	-0.31	162	162
VTN	-0.023	0.09	-9999	-0.32	73	73
alphaM/beta2 Integrin/CYR61	-0.047	0.13	-9999	-0.58	54	54
LPA	-0.001	0.02	-9999	-0.28	5	5
LRP1	-0.008	0.081	-9999	-0.81	10	10
cell migration	-0.071	0.082	-9999	-0.48	15	15
FN1	-0.11	0.14	-9999	-0.28	398	398
alphaM/beta2 Integrin/Thy1	-0.019	0.03	-9999	-10000	0	0
MPO	-0.053	0.2	-9999	-0.78	67	67
KNG1	-0.003	0.031	-9999	-0.28	12	12
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.063	0.16	-9999	-0.4	105	105
ELA2	0	0	-9999	-10000	0	0
PLG	-0.001	0.018	-9999	-0.28	4	4
CTGF	-0.011	0.093	-9999	-0.74	15	15
alphaM/beta2 Integrin/Hck	-0.019	0.033	-9999	-10000	0	0
ITGAM	-0.015	0.028	-9999	-0.31	4	4
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.13	0.22	-9999	-0.52	233	233
HP	-0.16	0.31	-9999	-0.81	184	184
leukocyte adhesion	-0.076	0.13	-9999	-0.59	41	41
SELP	-0.19	0.34	-9999	-0.81	233	233

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.16	0.4	-9999	-0.98	93	93
IL23A	-0.17	0.4	-9999	-1.1	80	80
NF kappa B1 p50/RelA/I kappa B alpha	-0.24	0.32	-9999	-0.89	125	125
positive regulation of T cell mediated cytotoxicity	-0.19	0.43	-9999	-0.94	152	152
ITGA3	-0.16	0.39	-9999	-1.1	65	65
IL17F	-0.1	0.29	-9999	-0.66	81	81
IL12B	-0.042	0.12	-9999	-0.28	141	141
STAT1 (dimer)	-0.22	0.38	-9999	-0.94	130	130
CD4	-0.16	0.38	-9999	-0.97	81	81
IL23	-0.17	0.39	-9999	-1	75	75
IL23R	-0.012	0.088	-9999	-10000	0	0
IL1B	-0.18	0.42	-9999	-1.1	82	82
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.17	0.38	-9999	-0.98	84	84
TYK2	0.011	0.017	-9999	-10000	0	0
STAT4	-0.035	0.16	-9999	-0.8	43	43
STAT3	0	0	-9999	-10000	0	0
IL18RAP	-0.028	0.15	-9999	-0.75	41	41
IL12RB1	0	0.064	-9999	-0.3	37	37
PIK3CA	0	0.009	-9999	-0.28	1	1
IL12Rbeta1/TYK2	-0.001	0.048	-9999	-0.66	1	1
IL23R/JAK2	-0.009	0.11	-9999	-0.65	1	1
positive regulation of chronic inflammatory response	-0.19	0.43	-9999	-0.94	152	152
natural killer cell activation	0.002	0.008	-9999	-10000	0	0
JAK2	0.018	0.035	-9999	-0.84	1	1
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
NFKB1	0.002	0.005	-9999	-10000	0	0
RELA	0.002	0.005	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.16	0.38	-9999	-0.96	83	83
ALOX12B	-0.16	0.38	-9999	-0.96	86	86
CXCL1	-0.35	0.64	-9999	-1.4	261	261
T cell proliferation	-0.19	0.43	-9999	-0.94	152	152
NFKBIA	0.002	0.005	-9999	-10000	0	0
IL17A	-0.068	0.24	-9999	-0.54	50	50
PI3K	-0.24	0.33	-9999	-0.9	132	132
IFNG	-0.004	0.026	-9999	-0.091	21	21
STAT3 (dimer)	-0.23	0.31	-9999	-0.87	122	122
IL18R1	-0.01	0.1	-9999	-0.8	16	16
IL23/IL23R/JAK2/TYK2/SOCS3	-0.081	0.24	-9999	-0.58	40	40
IL18/IL18R	-0.032	0.12	-9999	-0.55	51	51
macrophage activation	-0.013	0.017	-9999	-0.041	105	105
TNF	-0.18	0.41	-9999	-1.1	81	81
STAT3/STAT4	-0.26	0.35	-9999	-0.9	164	164
STAT4 (dimer)	-0.23	0.4	-9999	-0.94	164	164
IL18	-0.004	0.046	-9999	-0.28	26	26
IL19	-0.17	0.38	-9999	-0.96	91	91
STAT5A (dimer)	-0.22	0.38	-9999	-0.94	135	135
STAT1	-0.005	0.037	-9999	-0.28	18	18
SOCS3	-0.005	0.063	-9999	-0.81	6	6
CXCL9	-0.18	0.39	-9999	-0.97	100	100
MPO	-0.21	0.47	-9999	-1.2	125	125
positive regulation of humoral immune response	-0.19	0.43	-9999	-0.94	152	152
IL23/IL23R/JAK2/TYK2	-0.19	0.45	-9999	-1	139	139
IL6	-0.46	0.71	-9999	-1.3	370	370
STAT5A	-0.007	0.072	-9999	-0.81	8	8
IL2	0.003	0.029	-9999	-0.29	8	8
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.008	-9999	-10000	0	0
CD3E	-0.17	0.42	-9999	-1	105	105
keratinocyte proliferation	-0.19	0.43	-9999	-0.94	152	152
NOS2	-0.16	0.39	-9999	-1	85	85

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.017	0.031	-9999	-10000	0	0
VDR	0	0	-9999	-10000	0	0
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.039	0.16	-9999	-0.31	252	252
RXRs/LXRs/DNA/Oxysterols	-0.018	0.15	-9999	-0.49	18	18
MED1	-0.007	0.043	-9999	-0.28	24	24
mol:9cRA	0.005	0.008	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.023	0.092	-9999	-0.36	61	61
RXRs/NUR77	-0.16	0.25	-9999	-0.51	306	306
RXRs/PPAR	-0.13	0.23	-9999	-0.38	409	409
NCOR2	0	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.007	0.052	-9999	-0.46	12	12
RARA	-0.004	0.033	-9999	-10000	0	0
NCOA1	-0.001	0.026	-9999	-0.81	1	1
VDR/VDR/DNA	0	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	-0.007	0.052	-9999	-0.47	12	12
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.03	0.053	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.022	0.088	-9999	-0.35	61	61
THRA	-0.001	0.026	-9999	-0.81	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.21	-9999	-0.48	249	249
NR1H4	-0.002	0.025	-9999	-10000	0	0
RXRs/LXRs/DNA	-0.11	0.19	-9999	-0.44	249	249
NR1H2	0.016	0.006	-9999	-10000	0	0
NR1H3	0.016	0.007	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.12	0.2	-9999	-0.45	249	249
NR4A1	-0.067	0.22	-9999	-0.81	82	82
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.046	0.13	-9999	-0.27	249	249
RXRG	-0.19	0.35	-9999	-0.8	252	252
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.016	0.006	-9999	-10000	0	0
RXRB	0.015	0.007	-9999	-10000	0	0
THRB	-0.043	0.18	-9999	-0.81	53	53
PPARG	-0.19	0.34	-9999	-0.81	228	228
PPARD	0	0	-9999	-10000	0	0
TNF	-0.02	0.2	-9999	-1.3	14	14
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	-0.018	0.15	-9999	-0.49	18	18
PPARA	-0.002	0.044	-9999	-0.81	3	3
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.01	0.088	-9999	-0.81	12	12
RXRs/NUR77/BCL2	-0.12	0.2	-9999	-0.38	326	326
SREBF1	-0.008	0.14	-9999	-0.63	7	7
RXRs/RXRs/DNA/9cRA	-0.12	0.21	-9999	-0.48	249	249
ABCA1	-0.011	0.16	-9999	-0.98	9	9
RARs/THRs	-0.032	0.12	-9999	-0.49	61	61
RXRs/FXR	-0.12	0.21	-9999	-0.48	249	249
BCL2	-0.029	0.15	-9999	-0.81	35	35

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.053	0.16	-9999	-0.54	95	95
EFNA5	-0.078	0.24	-9999	-0.8	96	96
FYN	-0.049	0.15	-9999	-0.5	96	96
neuron projection morphogenesis	-0.053	0.16	-9999	-0.54	95	95
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.053	0.16	-9999	-0.55	95	95
EPHA5	-0.001	0.018	-9999	-10000	0	0

×

LPA receptor mediated events

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
GNB1/GNG2	-0.017	0.096	-9999	-0.54	28	28
NF kappa B1 p50/RelA/I kappa B alpha	-0.045	0.11	-9999	-0.41	11	11
AP1	-0.19	0.26	-9999	-0.49	385	385
mol:PIP3	-0.2	0.25	-9999	-0.47	407	407
AKT1	-0.013	0.072	-9999	-0.59	8	8
PTK2B	0.014	0.061	-9999	-0.3	21	21
RHOA	0.028	0.027	-9999	-0.24	1	1
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	-0.009	0.13	-9999	-0.36	119	119
MAGI3	-0.001	0.026	-9999	-0.81	1	1
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.063	0.15	-9999	-0.42	142	142
HRAS/GDP	-0.001	0.013	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.019	0.15	-9999	-0.42	108	108
NF kappa B1 p50/RelA	-0.054	0.14	-9999	-0.5	21	21
endothelial cell migration	0.008	0.12	-9999	-0.66	28	28
ADCY4	-0.003	0.15	-9999	-0.65	35	35
ADCY5	-0.071	0.19	-9999	-0.62	68	68
ADCY6	0.007	0.13	-9999	-0.62	26	26
ADCY7	0.007	0.13	-9999	-0.62	26	26
ADCY1	-0.001	0.14	-9999	-0.65	31	31
ADCY2	-0.012	0.16	-9999	-0.63	40	40
ADCY3	0.007	0.13	-9999	-0.62	26	26
ADCY8	0.004	0.13	-9999	-0.62	26	26
ADCY9	0.007	0.13	-9999	-0.62	26	26
GSK3B	0.021	0.058	-9999	-0.36	9	9
arachidonic acid secretion	0.01	0.13	-9999	-0.58	28	28
GNG2	-0.009	0.085	-9999	-0.81	11	11
TRIP6	-0.001	0.017	-9999	-0.52	1	1
GNAO1	-0.007	0.13	-9999	-0.54	50	50
HRAS	-0.001	0.02	-9999	-10000	0	0
NFKBIA	-0.005	0.15	-9999	-0.4	119	119
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0	0.03	-9999	-0.94	1	1
JUN	-0.007	0.077	-9999	-0.81	9	9
LPA/LPA2/NHERF2	-0.002	0.013	-9999	-10000	0	0
TIAM1	0	0.036	-9999	-1.1	1	1
PIK3R1	-0.006	0.068	-9999	-0.8	7	7
mol:IP3	-0.009	0.13	-9999	-0.36	119	119
PLCB3	-0.001	0.011	-9999	-10000	0	0
FOS	-0.24	0.37	-9999	-0.81	298	298
positive regulation of mitosis	0.01	0.13	-9999	-0.58	28	28
LPA/LPA1-2-3	-0.075	0.18	-9999	-0.5	134	134
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
stress fiber formation	0.001	0.1	-9999	-0.4	20	20
GNAZ	0.009	0.1	-9999	-0.49	35	35
EGFR/PI3K-beta/Gab1	-0.21	0.27	-9999	-0.49	406	406
positive regulation of dendritic cell cytokine production	-0.074	0.17	-9999	-0.5	134	134
LPA/LPA2/MAGI-3	-0.002	0.021	-9999	-0.54	1	1
ARHGEF1	-0.01	0.068	-9999	-0.46	19	19
GNAI2	0.013	0.085	-9999	-0.47	28	28
GNAI3	0.013	0.085	-9999	-0.47	28	28
GNAI1	-0.015	0.16	-9999	-0.56	72	72
LPA/LPA3	-0.083	0.2	-9999	-0.62	119	119
LPA/LPA2	-0.002	0.016	-9999	-10000	0	0
LPA/LPA1	-0.015	0.094	-9999	-0.55	28	28
HB-EGF/EGFR	-0.26	0.26	-9999	-0.59	364	364
HBEGF	-0.069	0.1	-9999	-0.62	3	3
mol:DAG	-0.009	0.13	-9999	-0.36	119	119
cAMP biosynthetic process	-0.011	0.15	-9999	-0.56	50	50
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
GNB1	0	0	-9999	-10000	0	0
LYN	-0.005	0.15	-9999	-0.4	119	119
GNAQ	-0.055	0.14	-9999	-0.42	121	121
LPAR2	-0.001	0.015	-9999	-0.28	3	3
LPAR3	-0.11	0.26	-9999	-0.68	156	156
LPAR1	-0.017	0.11	-9999	-0.81	19	19
IL8	-0.19	0.23	-9999	-0.44	385	385
PTK2	-0.069	0.16	-9999	-0.46	134	134
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.063	0.15	-9999	-0.42	142	142
EGFR	-0.3	0.39	-9999	-0.8	369	369
PLCG1	-0.056	0.14	-9999	-0.43	120	120
PLD2	-0.069	0.16	-9999	-0.46	134	134
G12/G13	-0.012	0.073	-9999	-0.49	19	19
PI3K-beta	-0.016	0.086	-9999	-0.72	8	8
cell migration	-0.022	0.055	-9999	-0.24	8	8
SLC9A3R2	-0.001	0.013	-9999	-0.28	2	2
PXN	0.001	0.1	-9999	-0.41	20	20
HRAS/GTP	-0.033	0.12	-9999	-0.6	28	28
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.13	0.14	-9999	-0.28	444	444
PRKCE	-0.001	0.026	-9999	-0.81	1	1
PRKCD	-0.001	0.13	-9999	-0.34	119	119
Gi(beta/gamma)	-0.035	0.12	-9999	-0.6	31	31
mol:LPA	-0.002	0.021	-9999	-0.22	9	9
TRIP6/p130 Cas/FAK1/Paxillin	-0.057	0.14	-9999	-0.48	28	28
MAPKKK cascade	0.01	0.13	-9999	-0.58	28	28
contractile ring contraction involved in cytokinesis	0.028	0.026	-9999	-0.23	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.06	0.15	-9999	-0.43	127	127
GNA15	-0.055	0.14	-9999	-0.42	120	120
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	-0.02	0.15	-9999	-0.43	108	108
GNA11	-0.055	0.14	-9999	-0.42	121	121
Rac1/GTP	0	0.033	-9999	-1	1	1
MMP2	0.008	0.12	-9999	-0.67	28	28

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.089	0.19	0.64	97	-10000	0	97
KIRREL	-0.08	0.24	-10000	0	-0.81	97	97
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.089	0.19	-10000	0	-0.65	97	97
PLCG1	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.064	0.15	-10000	0	-0.5	97	97
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.039	0.11	-10000	0	-0.37	97	97
FYN	-0.06	0.14	-10000	0	-0.47	97	97
mol:Ca2+	-0.064	0.15	-10000	0	-0.49	97	97
mol:DAG	-0.064	0.15	-10000	0	-0.49	97	97
NPHS2	-0.009	0.028	-10000	0	-0.28	4	4
mol:IP3	-0.064	0.15	-10000	0	-0.49	97	97
regulation of endocytosis	-0.032	0.14	-10000	0	-0.44	97	97
Nephrin/NEPH1/podocin/Cholesterol	-0.067	0.15	-10000	0	-0.5	97	97
establishment of cell polarity	-0.089	0.19	-10000	0	-0.64	97	97
Nephrin/NEPH1/podocin/NCK1-2	-0.052	0.14	-10000	0	-0.45	97	97
Nephrin/NEPH1/beta Arrestin2	-0.032	0.14	-10000	0	-0.45	97	97
NPHS1	-0.05	0.1	-10000	0	-0.28	162	162
Nephrin/NEPH1/podocin	-0.055	0.14	-10000	0	-0.48	97	97
TJP1	-0.001	0.026	-10000	0	-0.81	1	1
NCK1	0	0	-10000	0	-10000	0	0
NCK2	0	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.064	0.15	-10000	0	-0.5	97	97
CD2AP	0	0.009	-10000	0	-0.28	1	1
Nephrin/NEPH1/podocin/GRB2	-0.064	0.15	-10000	0	-0.5	97	97
GRB2	0	0.009	-10000	0	-0.28	1	1
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.068	0.16	-10000	0	-0.51	105	105
cytoskeleton organization	-0.049	0.14	-10000	0	-0.46	97	97
Nephrin/NEPH1	-0.064	0.14	-10000	0	-0.49	97	97
Nephrin/NEPH1/ZO-1	-0.07	0.16	-10000	0	-0.54	97	97

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.005	0.044	-9999	-0.63	4	4
PDGFRB	0.004	0.052	-9999	-0.81	4	4
SPHK1	-0.025	0.057	-9999	-1.1	2	2
mol:S1P	-0.031	0.059	-9999	-0.98	2	2
S1P1/S1P/Gi	-0.1	0.23	-9999	-0.39	341	341
GNAO1	-0.025	0.14	-9999	-0.49	66	66
PDGFB-D/PDGFRB/PLCgamma1	-0.12	0.18	-9999	-0.6	64	64
PLCG1	-0.089	0.22	-9999	-0.56	83	83
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.052	-9999	-0.81	4	4
GNAI2	0.008	0.006	-9999	-10000	0	0
GNAI3	0.007	0.006	-9999	-10000	0	0
GNAI1	-0.035	0.18	-9999	-0.82	51	51
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.006	0.042	-9999	-0.55	4	4
S1P1/S1P	-0.044	0.074	-9999	-0.64	6	6
negative regulation of cAMP metabolic process	-0.096	0.22	-9999	-0.38	342	342
MAPK3	-0.16	0.31	-9999	-0.57	331	331
calcium-dependent phospholipase C activity	-0.003	0.004	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.003	0.052	-9999	-0.82	4	4
PLCB2	-0.008	0.086	-9999	-0.54	7	7
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.037	0.061	-9999	-0.52	6	6
receptor internalization	-0.042	0.069	-9999	-0.58	6	6
PTGS2	-0.33	0.55	-9999	-1.1	331	331
Rac1/GTP	-0.037	0.061	-9999	-0.52	6	6
RHOA	0	0	-9999	-10000	0	0
VEGFA	-0.003	0.029	-9999	-0.28	11	11
negative regulation of T cell proliferation	-0.096	0.22	-9999	-0.38	342	342
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.001	0.074	-9999	-0.81	8	8
MAPK1	-0.16	0.31	-9999	-0.57	331	331
S1P1/S1P/PDGFB-D/PDGFRB	-0.02	0.11	-9999	-0.69	8	8
ABCC1	0	0	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.003	0.026	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.18	0.21	-9999	-0.42	428	428
Syndecan-3/Neurocan	-0.007	0.026	-9999	-10000	0	0
POMC	-0.023	0.12	-9999	-0.47	48	48
EGFR	-0.3	0.39	-9999	-0.8	369	369
Syndecan-3/EGFR	-0.17	0.22	-9999	-0.45	364	364
AGRP	-0.003	0.028	-9999	-0.28	10	10
NCSTN	0	0	-9999	-10000	0	0
PSENEN	0	0.009	-9999	-0.28	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	-0.001	0.026	-9999	-0.81	1	1
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.019	0.07	-9999	-10000	0	0
long-term memory	-0.002	0.021	-9999	-0.42	2	2
Syndecan-3/IL8	-0.015	0.066	-9999	-0.45	19	19
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	-0.002	0.018	-9999	-10000	0	0
FYN	-0.002	0.036	-9999	-0.81	2	2
limb bud formation	0	0.003	-9999	-10000	0	0
MC4R	-0.003	0.029	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
PTN	-0.35	0.4	-9999	-0.81	428	428
FGFR/FGF/Syndecan-3	0	0.003	-9999	-10000	0	0
neuron projection morphogenesis	-0.18	0.2	-9999	-0.4	428	428
Syndecan-3/AgRP	-0.001	0.011	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.002	0.014	-9999	-10000	0	0
Fyn/Cortactin	-0.003	0.032	-9999	-0.62	2	2
SDC3	0	0.003	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.015	0.066	-9999	-0.45	19	19
IL8	-0.033	0.13	-9999	-0.4	80	80
Syndecan-3/Fyn/Cortactin	-0.002	0.021	-9999	-0.43	2	2
Syndecan-3/CASK	0	0.003	-9999	-10000	0	0
alpha-MSH/MC4R	-0.018	0.088	-9999	-0.61	18	18
Gamma Secretase	-0.001	0.015	-9999	-0.45	1	1

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.057	0.3	-10000	0	-0.82	122	122
IHH	-0.013	0.078	-10000	0	-0.35	8	8
SHH Np/Cholesterol/GAS1	-0.03	0.12	-10000	0	-0.5	55	55
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.03	0.12	0.5	55	-10000	0	55
SMO/beta Arrestin2	-0.077	0.23	-10000	0	-0.85	74	74
SMO	-0.045	0.26	-10000	0	-0.86	83	83
AKT1	0.002	0.11	-10000	0	-0.39	23	23
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.06	0.21	-10000	0	-0.81	73	73
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.037	0.26	-10000	0	-0.84	83	83
STIL	-0.04	0.21	-10000	0	-0.72	76	76
DHH N/PTCH2	-0.067	0.2	-10000	0	-0.65	101	101
DHH N/PTCH1	-0.091	0.24	-10000	0	-0.76	104	104
PIK3CA	0	0.009	-10000	0	-0.28	1	1
DHH	-0.023	0.13	-10000	0	-0.77	29	29
PTHLH	-0.087	0.39	-10000	0	-1.1	122	122
determination of left/right symmetry	-0.037	0.26	-10000	0	-0.84	83	83
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
skeletal system development	-0.085	0.38	-10000	0	-1.1	122	122
IHH N/Hhip	-0.01	0.05	-10000	0	-0.44	5	5
DHH N/Hhip	-0.02	0.11	-10000	0	-0.63	29	29
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.037	0.26	-10000	0	-0.84	83	83
pancreas development	-0.004	0.045	-10000	0	-0.37	11	11
HHAT	-0.001	0.026	-10000	0	-0.81	1	1
PI3K	-0.005	0.052	-10000	0	-0.62	7	7
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.044	0.18	-10000	0	-0.81	54	54
somite specification	-0.037	0.26	-10000	0	-0.84	83	83
SHH Np/Cholesterol/PTCH1	-0.072	0.21	-10000	0	-0.75	77	77
SHH Np/Cholesterol/PTCH2	-0.043	0.14	-10000	0	-0.5	81	81
SHH Np/Cholesterol/Megalin	-0.14	0.22	-10000	0	-0.5	258	258
SHH	0.01	0.035	-10000	0	-0.63	1	1
catabolic process	-0.049	0.26	-10000	0	-0.84	86	86
SMO/Vitamin D3	-0.076	0.23	-10000	0	-0.82	75	75
SHH Np/Cholesterol/Hhip	-0.005	0.037	-10000	0	-0.5	3	3
LRP2	-0.22	0.35	-10000	0	-0.81	257	257
receptor-mediated endocytosis	-0.15	0.26	-10000	0	-0.82	95	95
SHH Np/Cholesterol/BOC	-0.04	0.13	-10000	0	-0.5	74	74
SHH Np/Cholesterol/CDO	-0.01	0.061	-10000	0	-0.5	14	14
mesenchymal cell differentiation	0.005	0.037	0.5	3	-10000	0	3
mol:Vitamin D3	-0.032	0.22	-10000	0	-0.73	82	82
IHH N/PTCH2	-0.062	0.19	-10000	0	-0.68	83	83
CDON	-0.011	0.092	-10000	0	-0.81	13	13
IHH N/PTCH1	-0.047	0.26	-10000	0	-0.85	86	86
Megalin/LRPAP1	-0.16	0.27	-10000	0	-0.62	257	257
PTCH2	-0.065	0.22	-10000	0	-0.81	80	80
SHH Np/Cholesterol	-0.003	0.025	-10000	0	-0.51	1	1
PTCH1	-0.05	0.26	-10000	0	-0.84	86	86
HHIP	-0.004	0.045	-10000	0	-0.38	11	11

×

PDGFR-alpha 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
PDGFRA	-0.059	0.2	-9999	-0.82	63	63
PDGF/PDGFRA/CRKL	-0.039	0.15	-9999	-0.62	62	62
positive regulation of JUN kinase activity	-0.03	0.12	-9999	-0.48	62	62
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.043	0.15	-9999	-0.63	62	62
AP1	-0.37	0.54	-9999	-1.1	332	332
mol:IP3	-0.034	0.16	-9999	-0.64	62	62
PLCG1	-0.034	0.16	-9999	-0.65	62	62
PDGF/PDGFRA/alphaV Integrin	-0.039	0.15	-9999	-0.62	62	62
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	-0.034	0.16	-9999	-0.64	62	62
CAV3	-0.001	0.015	-9999	-0.28	3	3
CAV1	-0.17	0.33	-9999	-0.81	208	208
SHC/Grb2/SOS1	-0.03	0.12	-9999	-0.48	62	62
PDGF/PDGFRA/Shf	-0.04	0.15	-9999	-0.63	62	62
FOS	-0.33	0.55	-9999	-1.1	332	332
JUN	-0.026	0.07	-9999	-0.69	9	9
oligodendrocyte development	-0.039	0.15	-9999	-0.62	62	62
GRB2	0	0.009	-9999	-0.28	1	1
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
mol:DAG	-0.034	0.16	-9999	-0.64	62	62
PDGF/PDGFRA	-0.059	0.2	-9999	-0.82	63	63
actin cytoskeleton reorganization	-0.04	0.15	-9999	-0.62	63	63
SRF	0.015	0.021	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.037	0.14	-9999	-0.53	69	69
PDGF/PDGFRA/Crk/C3G	-0.033	0.13	-9999	-0.53	62	62
JAK1	-0.023	0.16	-9999	-0.62	62	62
ELK1/SRF	-0.026	0.12	-9999	-0.49	62	62
SHB	-0.001	0.027	-9999	-0.54	2	2
SHF	-0.001	0.027	-9999	-0.81	1	1
CSNK2A1	0.019	0.027	-9999	-10000	0	0
GO:0007205	-0.036	0.17	-9999	-0.66	62	62
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.03	0.12	-9999	-0.48	62	62
PDGF/PDGFRA/SHB	-0.04	0.15	-9999	-0.62	63	63
PDGF/PDGFRA/Caveolin-1	-0.17	0.32	-9999	-0.72	231	231
ITGAV	0	0	-9999	-10000	0	0
ELK1	-0.034	0.15	-9999	-0.6	62	62
PIK3CA	0	0.009	-9999	-0.28	1	1
PDGF/PDGFRA/Crk	-0.039	0.15	-9999	-0.62	62	62
JAK-STAT cascade	-0.023	0.15	-9999	-0.62	62	62
cell proliferation	-0.04	0.15	-9999	-0.63	62	62

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0.009	-9999	-10000	0	0
CCL5	-0.014	0.077	-9999	-0.81	5	5
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.074	0.11	-9999	-0.34	98	98
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.068	0.097	-9999	-0.35	41	41
Syndecan-1/Syntenin	-0.068	0.097	-9999	-0.5	5	5
MAPK3	-0.043	0.095	-9999	-0.48	5	5
HGF/MET	-0.14	0.28	-9999	-0.67	211	211
TGFB1/TGF beta receptor Type II	0	0.009	-9999	-10000	0	0
BSG	0	0	-9999	-10000	0	0
keratinocyte migration	-0.067	0.096	-9999	-0.34	41	41
Syndecan-1/RANTES	-0.075	0.11	-9999	-0.39	44	44
Syndecan-1/CD147	-0.059	0.094	-9999	-0.52	5	5
Syndecan-1/Syntenin/PIP2	-0.065	0.094	-9999	-0.48	5	5
LAMA5	0	0.009	-9999	-0.28	1	1
positive regulation of cell-cell adhesion	-0.064	0.092	-9999	-0.47	5	5
MMP7	-0.12	0.28	-9999	-0.81	141	141
HGF	-0.055	0.2	-9999	-0.81	67	67
Syndecan-1/CASK	-0.07	0.1	-9999	-0.32	98	98
Syndecan-1/HGF/MET	-0.16	0.25	-9999	-0.6	213	213
regulation of cell adhesion	-0.037	0.092	-9999	-0.49	4	4
HPSE	-0.007	0.052	-9999	-0.81	2	2
positive regulation of cell migration	-0.074	0.11	-9999	-0.34	98	98
SDC1	-0.074	0.11	-9999	-0.34	98	98
Syndecan-1/Collagen	-0.074	0.11	-9999	-0.34	98	98
PPIB	-0.001	0.015	-9999	-0.28	3	3
MET	-0.14	0.3	-9999	-0.81	165	165
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.13	0.14	-9999	-0.28	444	444
MAPK1	-0.043	0.095	-9999	-0.48	5	5
homophilic cell adhesion	-0.073	0.11	-9999	-0.34	98	98
MMP1	-0.21	0.12	-9999	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	-0.002	0.036	-9999	-0.81	2	2
LAT2	-0.062	0.14	-9999	-0.43	81	81
AP1	-0.16	0.22	-9999	-0.58	139	139
mol:PIP3	-0.027	0.2	-9999	-0.48	94	94
IKBKB	0.002	0.12	-9999	-0.32	46	46
AKT1	-0.081	0.17	-9999	-0.68	35	35
IKBKG	0.002	0.12	-9999	-0.32	48	48
MS4A2	-0.066	0.22	-9999	-0.81	80	80
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.28	1	1
MAP3K1	0.007	0.13	-9999	-0.44	34	34
mol:Ca2+	-0.013	0.15	-9999	-0.31	194	194
LYN	0.011	0.004	-9999	-10000	0	0
CBLB	-0.061	0.14	-9999	-0.53	41	41
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.067	0.17	-9999	-0.49	134	134
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.097	0.21	-9999	-0.49	194	194
PTPN13	-0.03	0.17	-9999	-0.54	57	57
PTPN11	0.01	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.007	0.14	-9999	-0.42	35	35
SYK	0.011	0.01	-9999	-0.28	1	1
GRB2	0	0.009	-9999	-0.28	1	1
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.085	0.18	-9999	-0.43	194	194
LAT	-0.063	0.14	-9999	-0.43	82	82
PAK2	-0.002	0.14	-9999	-0.49	35	35
NFATC2	-0.095	0.24	-9999	-0.83	81	81
HRAS	-0.012	0.15	-9999	-0.55	35	35
GAB2	-0.003	0.026	-9999	-0.28	9	9
PLA2G1B	0.027	0.018	-9999	-10000	0	0
Fc epsilon R1	-0.12	0.25	-9999	-0.61	194	194
Antigen/IgE/Fc epsilon R1	-0.11	0.24	-9999	-0.56	194	194
mol:GDP	-0.018	0.15	-9999	-0.56	35	35
JUN	-0.007	0.077	-9999	-0.81	9	9
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
FOS	-0.24	0.37	-9999	-0.81	298	298
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.066	0.14	-9999	-0.45	82	82
CHUK	0.002	0.12	-9999	-0.32	46	46
KLRG1	-0.061	0.13	-9999	-0.55	36	36
VAV1	-0.062	0.14	-9999	-0.43	82	82
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.061	0.14	-9999	-0.53	41	41
negative regulation of mast cell degranulation	-0.055	0.12	-9999	-0.51	35	35
BTK	-0.06	0.13	-9999	-0.57	34	34
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.085	0.2	-9999	-0.43	196	196
GAB2/PI3K/SHP2	-0.089	0.19	-9999	-0.74	38	38
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.068	0.16	-9999	-0.35	194	194
RAF1	0.015	0.022	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.1	0.22	-9999	-0.52	196	196
FCER1G	0.002	0.015	-9999	-0.28	2	2
FCER1A	-0.11	0.29	-9999	-0.82	145	145
Antigen/IgE/Fc epsilon R1/Fyn	-0.1	0.22	-9999	-0.53	194	194
MAPK3	0.026	0.018	-9999	-10000	0	0
MAPK1	0.026	0.018	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.011	0.066	-9999	-0.61	6	6
DUSP1	-0.11	0.28	-9999	-0.81	134	134
NF-kappa-B/RelA	-0.027	0.054	-9999	-0.23	4	4
actin cytoskeleton reorganization	-0.026	0.15	-9999	-0.55	35	35
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.055	0.12	-9999	-0.51	41	41
FER	-0.066	0.15	-9999	-0.45	89	89
RELA	0	0	-9999	-10000	0	0
ITK	-0.034	0.11	-9999	-0.61	34	34
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.016	0.16	-9999	-0.58	35	35
cytokine secretion	-0.019	0.04	-9999	-10000	0	0
SPHK1	-0.064	0.14	-9999	-0.43	84	84
PTK2	-0.028	0.15	-9999	-0.57	35	35
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.088	0.19	-9999	-0.45	194	194
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.022	0.2	-9999	-0.41	194	194
MAP2K2	0.022	0.019	-9999	-10000	0	0
MAP2K1	0.022	0.019	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.057	0.12	-9999	-0.51	35	35
MAP2K4	0.016	0.034	-9999	-1	1	1
Fc epsilon R1/FcgammaRIIB	-0.11	0.23	-9999	-0.55	196	196
mol:Choline	-0.095	0.2	-9999	-0.48	194	194
SHC/Grb2/SOS1	-0.055	0.12	-9999	-0.54	33	33
FYN	-0.002	0.036	-9999	-0.81	2	2
DOK1	-0.001	0.013	-9999	-0.28	2	2
PXN	-0.018	0.14	-9999	-0.53	33	33
HCLS1	-0.061	0.14	-9999	-0.42	81	81
PRKCB	-0.015	0.16	-9999	-0.37	98	98
FCGR2B	-0.004	0.052	-9999	-0.81	4	4
IGHE	0	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.056	0.12	-9999	-0.52	35	35
LCP2	0	0.009	-9999	-0.28	1	1
PLA2G4A	-0.11	0.21	-9999	-0.55	143	143
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.095	0.2	-9999	-0.48	194	194
IKK complex	0.019	0.093	-9999	-0.23	44	44
WIPF1	0	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.008	0.045	-10000	0	-0.43	7	7
adherens junction organization	0.031	0.066	-10000	0	-0.31	30	30
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.14	0.18	-10000	0	-0.38	369	369
FMN1	0.022	0.094	-10000	0	-0.47	22	22
mol:IP3	-0.008	0.044	-10000	0	-0.4	7	7
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.011	0.055	-10000	0	-0.32	30	30
CTNNB1	0.001	0.004	-10000	0	-10000	0	0
AKT1	-0.009	0.046	-10000	0	-0.39	7	7
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.015	0.086	-10000	0	-0.51	29	29
CTNND1	0.011	0.009	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.032	0.059	-10000	0	-10000	0	0
VASP	0.032	0.06	-10000	0	-10000	0	0
ZYX	0.032	0.06	-10000	0	-10000	0	0
JUB	0.03	0.066	-10000	0	-0.42	4	4
EGFR(dimer)	-0.17	0.21	-10000	0	-0.43	379	379
E-cadherin/beta catenin-gamma catenin	-0.016	0.089	-10000	0	-0.52	30	30
mol:PI-3-4-5-P3	-0.009	0.05	-10000	0	-0.42	7	7
PIK3CA	0	0.009	-10000	0	-10000	0	0
PI3K	-0.009	0.05	-10000	0	-0.43	7	7
FYN	0.041	0.05	-10000	0	-0.35	9	9
mol:Ca2+	-0.008	0.043	-10000	0	-0.39	7	7
JUP	-0.001	0.029	-10000	0	-0.81	1	1
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
mol:DAG	-0.008	0.044	-10000	0	-0.4	7	7
CDH1	-0.024	0.14	-10000	0	-0.81	29	29
RhoA/GDP	-0.14	0.18	-10000	0	-0.38	369	369
establishment of polarity of embryonic epithelium	0.032	0.059	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
EGFR	-0.3	0.39	-10000	0	-0.8	369	369
CASR	-0.008	0.041	-10000	0	-0.37	7	7
RhoA/GTP	-0.007	0.038	-10000	0	-0.36	7	7
AKT2	-0.009	0.046	-10000	0	-0.39	7	7
actin cable formation	0.029	0.092	-10000	0	-0.44	22	22
apoptosis	0.009	0.046	0.41	7	-10000	0	7
CTNNA1	0.011	0.002	-10000	0	-10000	0	0
mol:GDP	-0.16	0.2	-10000	0	-0.41	369	369
PIP5K1A	0.032	0.06	-10000	0	-10000	0	0
PLCG1	-0.008	0.044	-10000	0	-0.41	7	7
Rac1/GTP	-0.15	0.2	-10000	0	-0.4	365	365
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.051	0.2	-10000	0	-0.81	62	62
HRAS	-0.001	0.02	-10000	0	-10000	0	0
EGFR	-0.3	0.39	-10000	0	-0.8	369	369
AKT	0.015	0.074	-10000	0	-0.56	14	14
FOXO3	-0.002	0.036	-10000	0	-0.81	2	2
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	-0.009	0.085	-10000	0	-0.81	11	11
AKT3	-0.011	0.095	-10000	0	-0.81	14	14
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.14	0.3	-10000	0	-0.81	165	165
PIK3CA	0	0.009	-10000	0	-0.28	1	1
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.013	-10000	0	-10000	0	0
PIK3CG	-0.011	0.09	-10000	0	-0.7	15	15
PIK3R3	0	0.009	-10000	0	-0.28	1	1
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	-0.001	0.026	-10000	0	-0.81	1	1
RAS	-0.094	0.16	0.26	1	-0.37	187	188
ERBB2	-0.023	0.076	-10000	0	-0.28	80	80
proliferation/survival/translation	-0.005	0.056	0.26	9	-10000	0	9
PI3K	-0.084	0.16	-10000	0	-0.26	378	378
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
KRAS	-0.001	0.013	-10000	0	-0.28	2	2
FOXO	0.026	0.029	-10000	0	-0.5	1	1
AKT2	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.036	-10000	0	-0.81	2	2

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.008	0.058	-9999	-0.47	15	15
RGS9BP	-0.016	0.065	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.003	0.028	-9999	-0.28	10	10
mol:Na +	-0.019	0.05	-9999	-10000	0	0
mol:ADP	0.007	0.028	-9999	-10000	0	0
GNAT2	-0.001	0.018	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.065	0.17	-9999	-0.54	102	102
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.014	-9999	-10000	0	0
GRK7	-0.003	0.028	-9999	-10000	0	0
CNGB3	-0.01	0.052	-9999	-0.28	35	35
Cone Metarhodopsin II/X-Arrestin	-0.002	0.017	-9999	-10000	0	0
mol:Ca2+	-0.093	0.077	-9999	-10000	0	0
Cone PDE6	-0.056	0.14	-9999	-0.47	102	102
Cone Metarhodopsin II	-0.003	0.019	-9999	-10000	0	0
Na + (4 Units)	-0.093	0.076	-9999	-10000	0	0
GNAT2/GDP	-0.055	0.14	-9999	-0.47	102	102
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0.005	0.015	-9999	-10000	0	0
Cone Transducin	-0.008	0.061	-9999	-0.49	15	15
SLC24A2	-0.17	0.14	-9999	-0.28	603	603
GNB3/GNGT2	-0.01	0.076	-9999	-0.62	15	15
GNB3	-0.011	0.093	-9999	-0.81	13	13
GNAT2/GTP	-0.001	0.012	-9999	-10000	0	0
CNGA3	-0.026	0.081	-9999	-10000	0	0
ARR3	-0.002	0.025	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.019	0.05	-9999	-10000	0	0
mol:Pi	-0.064	0.16	-9999	-0.54	102	102
Cone CNG Channel	-0.015	0.037	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.17	0.14	-9999	-0.28	603	603
RGS9	-0.087	0.25	-9999	-0.75	115	115
PDE6C	0	0.009	-9999	-10000	0	0
GNGT2	-0.002	0.036	-9999	-0.81	2	2
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.001	0.02	-9999	-0.28	5	5

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.051	-9999	-0.81	4	4
alphaV beta3 Integrin	-0.018	0.1	-9999	-0.62	28	28
PTK2	-0.063	0.18	-9999	-0.56	105	105
positive regulation of JNK cascade	-0.036	0.1	-9999	-0.34	105	105
CDC42/GDP	0	0.16	-9999	-0.46	105	105
Rac1/GDP	0.002	0.16	-9999	-0.45	105	105
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.045	0.13	-9999	-0.42	105	105
nectin-3/I-afadin	-0.068	0.2	-9999	-0.64	105	105
RAPGEF1	-0.008	0.18	-9999	-0.52	105	105
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.022	0.21	-9999	-0.61	105	105
PDGFB-D/PDGFRB	-0.003	0.051	-9999	-0.8	4	4
TLN1	0.001	0.1	-9999	-0.55	13	13
Rap1/GTP	-0.039	0.11	-9999	-0.36	105	105
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.038	-9999	-0.49	6	6
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.068	0.2	-9999	-0.64	105	105
PVR	0	0	-9999	-10000	0	0
Necl-5(dimer)	0	0	-9999	-10000	0	0
mol:GDP	-0.011	0.2	-9999	-0.58	105	105
MLLT4	-0.005	0.063	-9999	-0.73	7	7
PIK3CA	0	0.009	-9999	-0.28	1	1
PI3K	-0.055	0.17	-9999	-0.5	109	109
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.004	0.048	-9999	-0.62	6	6
positive regulation of lamellipodium assembly	-0.038	0.11	-9999	-0.35	105	105
PVRL1	0	0	-9999	-10000	0	0
PVRL3	-0.085	0.25	-9999	-0.81	104	104
PVRL2	-0.001	0.013	-9999	-0.28	2	2
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
CDH1	-0.024	0.14	-9999	-0.81	29	29
CLDN1	-0.036	0.16	-9999	-0.58	62	62
JAM-A/CLDN1	-0.074	0.19	-9999	-0.54	131	131
SRC	-0.075	0.22	-9999	-0.69	105	105
ITGB3	-0.024	0.14	-9999	-0.81	28	28
nectin-1(dimer)/I-afadin/I-afadin	-0.004	0.048	-9999	-0.62	6	6
FARP2	-0.016	0.19	-9999	-0.57	105	105
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.059	0.18	-9999	-0.56	105	105
nectin-1/I-afadin	-0.004	0.048	-9999	-0.62	6	6
nectin-2/I-afadin	-0.004	0.049	-9999	-0.62	6	6
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	-0.059	0.18	-9999	-0.56	105	105
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.036	0.1	-9999	-0.34	105	105
alphaV/beta3 Integrin/Talin	-0.037	0.12	-9999	-0.6	33	33
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.049	-9999	-0.62	6	6
nectin-2(dimer)/I-afadin/I-afadin	-0.004	0.049	-9999	-0.62	6	6
PIP5K1C	-0.032	0.1	-9999	-0.59	13	13
VAV2	-0.017	0.2	-9999	-0.58	105	105
RAP1/GDP	-0.045	0.13	-9999	-0.42	105	105
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.059	0.18	-9999	-0.56	105	105
nectin-3(dimer)/I-afadin/I-afadin	-0.068	0.2	-9999	-0.64	105	105
Rac1/GTP	-0.047	0.14	-9999	-0.44	105	105
PTPRM	-0.036	0.12	-9999	-0.33	109	109
E-cadherin/beta catenin/alpha catenin	-0.015	0.082	-9999	-0.44	34	34
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.01	0.058	-10000	0	-0.33	31	31
epithelial cell differentiation	-0.013	0.077	-10000	0	-0.45	29	29
CYFIP2	-0.01	0.063	-10000	0	-0.33	29	29
ENAH	0.056	0.062	-10000	0	-10000	0	0
EGFR	-0.3	0.39	-10000	0	-0.8	369	369
EPHA2	-0.005	0.063	-10000	0	-0.81	6	6
MYO6	-0.013	0.074	-10000	0	-0.43	30	30
CTNNB1	0	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.005	0.036	-10000	0	-0.53	3	3
AQP5	-0.24	0.3	-10000	0	-0.6	395	395
CTNND1	0	0.009	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.012	0.071	-10000	0	-0.42	29	29
regulation of calcium-dependent cell-cell adhesion	-0.035	0.12	-10000	0	-0.43	78	78
EGF	-0.17	0.33	-10000	0	-0.8	206	206
NCKAP1	0	0	-10000	0	-10000	0	0
AQP3	-0.038	0.14	-10000	0	-0.59	49	49
cortical microtubule organization	-0.013	0.077	-10000	0	-0.45	29	29
GO:0000145	0.024	0.074	-10000	0	-0.4	29	29
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.014	0.078	-10000	0	-0.46	29	29
MLLT4	-0.005	0.063	-10000	0	-0.73	7	7
ARF6/GDP	-0.013	0.065	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.004	0.038	-10000	0	-0.48	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.035	0.078	-10000	0	-0.4	29	29
PVRL2	-0.001	0.013	-10000	0	-0.28	2	2
ZYX	-0.013	0.073	-10000	0	-0.43	29	29
ARF6/GTP	-0.003	0.035	-10000	0	-0.44	6	6
CDH1	-0.024	0.14	-10000	0	-0.81	29	29
EGFR/EGFR/EGF/EGF	-0.25	0.27	-10000	0	-0.48	518	518
RhoA/GDP	-0.013	0.072	-10000	0	-0.42	29	29
actin cytoskeleton organization	0.031	0.077	-10000	0	-0.4	30	30
IGF-1R heterotetramer	-0.022	0.12	-10000	0	-0.62	36	36
GIT1	-0.001	0.02	-10000	0	-0.28	5	5
IGF1R	-0.022	0.12	-10000	0	-0.62	36	36
IGF1	-0.18	0.33	-10000	0	-0.81	215	215
DIAPH1	-0.001	0.038	-10000	0	-0.67	3	3
Wnt receptor signaling pathway	0.013	0.077	0.45	29	-10000	0	29
RHOA	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.013	0.066	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
VCL	0.031	0.079	-10000	0	-0.42	30	30
EFNA1	0	0	-10000	0	-10000	0	0
LPP	0.029	0.083	-10000	0	-0.4	35	35
Ephrin A1/EPHA2	-0.015	0.076	-10000	0	-0.41	35	35
SEC6/SEC8	-0.014	0.072	-10000	0	-0.77	1	1
MGAT3	-0.035	0.12	-10000	0	-0.44	78	78
HGF/MET	-0.11	0.21	-10000	0	-0.47	232	232
HGF	-0.055	0.2	-10000	0	-0.81	67	67
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.01	0.058	-10000	0	-0.33	31	31
actin cable formation	0.07	0.059	-10000	0	-10000	0	0
KIAA1543	0.031	0.087	-10000	0	-0.44	29	29
KIFC3	-0.014	0.075	-10000	0	-0.43	31	31
NCK1	0	0	-10000	0	-10000	0	0
EXOC3	0	0	-10000	0	-10000	0	0
ACTN1	-0.013	0.074	-10000	0	-0.43	30	30
NCK1/GIT1	-0.001	0.012	-10000	0	-10000	0	0
mol:GDP	-0.013	0.077	-10000	0	-0.45	29	29
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.013	0.073	-10000	0	-0.43	29	29
PIP5K1C	-0.013	0.073	-10000	0	-0.43	29	29
LIMA1	-0.002	0.036	-10000	0	-0.81	2	2
ABI1	0	0	-10000	0	-10000	0	0
ROCK1	-0.012	0.058	-10000	0	-10000	0	0
adherens junction assembly	0.046	0.084	-10000	0	-0.65	4	4
IGF-1R heterotetramer/IGF1	-0.11	0.2	-10000	0	-0.44	250	250
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.004	0.049	-10000	0	-0.62	6	6
MET	-0.14	0.3	-10000	0	-0.81	165	165
PLEKHA7	-0.014	0.08	-10000	0	-0.46	29	29
mol:GTP	-0.003	0.038	-10000	0	-0.48	6	6
establishment of epithelial cell apical/basal polarity	-0.013	0.068	-10000	0	-0.72	1	1
cortical actin cytoskeleton stabilization	-0.01	0.058	-10000	0	-0.33	31	31
regulation of cell-cell adhesion	0.031	0.077	-10000	0	-0.4	30	30
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.01	0.058	-10000	0	-0.33	31	31

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.12	0.21	-10000	0	-0.48	236	236
MAPK9	0.008	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.02	-10000	0	-10000	0	0
GNB1/GNG2	-0.006	0.057	-10000	0	-0.54	11	11
GNB1	0	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.008	0	-10000	0	-10000	0	0
Gs family/GTP	-0.12	0.22	-10000	0	-0.51	233	233
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.027	0.049	0.12	233	-10000	0	233
GNAL	-0.19	0.34	-10000	0	-0.81	233	233
GNG2	-0.009	0.085	-10000	0	-0.81	11	11
CRH	-0.003	0.029	-10000	0	-0.28	11	11
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.033	-10000	0	-0.45	5	5
MAPK11	0.007	0.025	-10000	0	-0.45	3	3

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.12	0.18	-9999	-0.39	300	300
MAP3K8	-0.004	0.058	-9999	-0.81	5	5
FOS	-0.035	0.13	-9999	-0.46	32	32
PRKCA	-0.012	0.13	-9999	-0.78	26	26
PTPN7	-0.007	0.068	-9999	-0.32	17	17
HRAS	-0.001	0.02	-9999	-10000	0	0
PRKCB	-0.012	0.12	-9999	-0.71	24	24
NRAS	-0.001	0.013	-9999	-10000	0	0
RAS family/GTP	-0.001	0.012	-9999	-10000	0	0
MAPK3	-0.008	0.072	-9999	-10000	0	0
MAP2K1	-0.013	0.14	-9999	-0.61	41	41
ELK1	-0.003	0.005	-9999	-10000	0	0
BRAF	-0.032	0.12	-9999	-0.59	41	41
mol:GTP	-0.002	0.003	-9999	-0.006	298	298
MAPK1	-0.008	0.072	-9999	-10000	0	0
RAF1	-0.032	0.12	-9999	-0.59	41	41
KRAS	-0.001	0.013	-9999	-0.28	2	2

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.011	0.053	0.29	35	-10000	0	35
RFC1	0.011	0.053	0.29	35	-10000	0	35
PRKDC	0.01	0.054	0.29	35	-10000	0	35
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	-0.023	0.036	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.016	0.065	0.25	15	-0.38	13	28
MAP2K4	-0.058	0.16	-10000	0	-0.41	29	29
mol:ceramide	-0.03	0.11	-10000	0	-0.57	16	16
GSN	0.004	0.079	0.29	34	-0.5	13	47
FASLG/FAS/FADD/FAF1/Caspase 8	-0.029	0.069	-10000	0	-0.46	13	13
FAS	0.004	0.046	-10000	0	-0.82	3	3
BID	0.001	0.005	-10000	0	-10000	0	0
MAP3K1	-0.021	0.093	-10000	0	-0.29	13	13
MAP3K7	0	0.009	-10000	0	-0.28	1	1
RB1	0.01	0.056	0.29	34	-0.42	2	36
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.14	0.27	-10000	0	-0.61	224	224
ARHGDIB	0.01	0.054	0.29	35	-10000	0	35
FADD	0.002	0.039	-10000	0	-0.3	10	10
actin filament polymerization	-0.004	0.079	0.5	13	-0.29	34	47
NFKB1	-0.076	0.1	-10000	0	-0.29	14	14
MAPK8	-0.12	0.24	-10000	0	-0.43	365	365
DFFA	0.011	0.053	0.29	35	-10000	0	35
DNA fragmentation during apoptosis	0.011	0.053	0.29	35	-10000	0	35
FAS/FADD/MET	-0.095	0.21	-10000	0	-0.56	165	165
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.001	0.046	-10000	0	-0.28	22	22
FAF1	0.008	0.006	-10000	0	-10000	0	0
PARP1	0.01	0.053	0.29	35	-10000	0	35
DFFB	0.011	0.053	0.29	35	-10000	0	35
CHUK	-0.066	0.088	-10000	0	-10000	0	0
FASLG	-0.013	0.1	-10000	0	-0.4	48	48
FAS/FADD	-0.005	0.045	-10000	0	-0.69	3	3
HGF	-0.055	0.2	-10000	0	-0.81	67	67
LMNA	0.01	0.048	0.26	35	-10000	0	35
CASP6	0.01	0.053	0.29	35	-10000	0	35
CASP10	0.004	0.053	-10000	0	-0.82	4	4
CASP3	0.013	0.064	0.35	35	-10000	0	35
PTPN13	-0.023	0.13	-10000	0	-0.81	28	28
CASP8	0.002	0.013	-10000	0	-10000	0	0
IL6	-0.47	0.67	-10000	0	-1.4	362	362
MET	-0.14	0.3	-10000	0	-0.81	165	165
ICAD/CAD	0.01	0.049	0.26	35	-10000	0	35
FASLG/FAS/FADD/FAF1/Caspase 10	-0.03	0.12	-10000	0	-0.58	16	16
activation of caspase activity by cytochrome c	0.001	0.005	-10000	0	-10000	0	0
PAK2	0.011	0.053	0.28	35	-10000	0	35
BCL2	-0.024	0.15	-10000	0	-0.81	35	35

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.011	0.054	-9999	-0.28	39	39
GPC2	-0.034	0.098	-9999	-0.29	114	114
GPC2/Midkine	-0.029	0.077	-9999	-0.4	18	18
neuron projection morphogenesis	-0.029	0.077	-9999	-0.39	18	18

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.026	-10000	0	-0.81	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.011	0.074	0.62	1	-10000	0	1
CDKN1A	-0.002	0.043	-10000	0	-0.96	2	2
KAT2B	-0.001	0.026	-10000	0	-0.81	1	1
BAX	-0.001	0.018	-10000	0	-0.28	4	4
FOXO3	-0.001	0.015	-10000	0	-0.33	2	2
FOXO1	-0.009	0.085	-10000	0	-0.81	11	11
FOXO4	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
TAT	-0.57	0.36	-10000	0	-0.79	716	716
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.01	0.03	-10000	0	-0.62	1	1
PPARGC1A	-0.17	0.33	-10000	0	-0.81	208	208
FHL2	-0.005	0.063	-10000	0	-0.81	6	6
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.007	-10000	0	-10000	0	0
HIST2H4A	-0.011	0.074	-10000	0	-0.62	1	1
SIRT1/FOXO3a	0	0.013	-10000	0	-0.25	2	2
SIRT1	0	0.009	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.018	-10000	0	-0.53	1	1
SIRT1/Histone H1b	-0.002	0.011	-10000	0	-10000	0	0
apoptosis	0	0.011	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.12	0.22	-10000	0	-0.54	208	208
p53/SIRT1	0.001	0.02	0.43	2	-10000	0	2
SIRT1/FOXO4	0	0.008	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.008	0.064	-10000	0	-0.49	17	17
HIST1H1E	-0.004	0.012	-10000	0	-10000	0	0
SIRT1/p300	0	0.007	-10000	0	-10000	0	0
muscle cell differentiation	0.002	0.024	0.53	1	-10000	0	1
TP53	0	0.009	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.011	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
MEF2D	0	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.44	0.28	-10000	0	-0.62	689	689
ACSS2	0.019	0.021	-10000	0	-0.62	1	1
SIRT1/PCAF/MYOD	-0.002	0.024	-10000	0	-0.53	1	1

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.55	0.38	-9999	-0.81	677	677
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	-0.004	0.032	-9999	-10000	0	0
TCEB1	-0.001	0.015	-9999	-0.28	3	3
HIF1A/p53	-0.001	0.005	-9999	-10000	0	0
HIF1A	-0.002	0.007	-9999	-10000	0	0
COPS5	0	0.009	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.002	0.012	-9999	-10000	0	0
FIH (dimer)	0	0	-9999	-10000	0	0
CDKN2A	-0.047	0.1	-9999	-0.28	167	167
ARNT/IPAS	-0.42	0.29	-9999	-0.62	677	677
HIF1AN	0	0	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
HIF1A/ARNT	-0.001	0.005	-9999	-10000	0	0
CUL2	0	0	-9999	-10000	0	0
OS9	0	0.009	-9999	-0.28	1	1
RACK1/Elongin B/Elongin C	-0.002	0.017	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.001	0.006	-9999	-10000	0	0
PHD1-3/OS9	-0.01	0.037	-9999	-0.48	2	2
HIF1A/RACK1/Elongin B/Elongin C	0	0.012	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-0.28	1	1
HIF1A/JAB1	-0.001	0.007	-9999	-10000	0	0
EGLN3	-0.022	0.078	-9999	-0.81	1	1
EGLN2	-0.001	0.02	-9999	-0.28	5	5
EGLN1	-0.001	0.026	-9999	-0.81	1	1
TP53	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0	0.004	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.017	0.037	-9999	-10000	0	0

×

LPA4-mediated signaling events

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
ADCY4	-0.003	0.11	-9999	-0.54	40	40
ADCY5	-0.16	0.26	-9999	-0.54	316	316
ADCY6	0.019	0.018	-9999	-0.54	1	1
ADCY7	0.019	0.018	-9999	-0.54	1	1
ADCY1	-0.007	0.097	-9999	-0.54	25	25
ADCY2	-0.03	0.15	-9999	-0.54	76	76
ADCY3	0.019	0.019	-9999	-0.54	1	1
ADCY8	0.009	0.032	-9999	-0.54	1	1
PRKCE	0.01	0.02	-9999	-0.63	1	1
ADCY9	0.019	0.018	-9999	-0.54	1	1
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.032	0.1	-9999	-0.32	66	66

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.056	0.11	-9999	-0.28	200	200
mol:Halofuginone	0	0.002	-9999	-10000	0	0
ITGA1	-0.006	0.068	-9999	-0.81	7	7
CDKN1A	-0.059	0.091	-9999	-0.86	2	2
PRL-3/alpha Tubulin	-0.002	0.017	-9999	-10000	0	0
mol:Ca2+	-0.034	0.097	-9999	-0.63	14	14
AGT	-0.048	0.13	-9999	-0.33	143	143
CCNA2	-0.17	0.24	-9999	-0.56	175	175
TUBA1B	0	0	-9999	-10000	0	0
EGR1	-0.18	0.3	-9999	-0.61	316	316
CDK2/Cyclin E1	-0.068	0.091	-9999	-0.82	2	2
MAPK3	0.02	0.019	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0.006	-9999	-10000	0	0
MAPK1	0.02	0.019	-9999	-10000	0	0
PTP4A1	-0.13	0.24	-9999	-0.47	316	316
PTP4A3	-0.003	0.026	-9999	-0.28	9	9
PTP4A2	0	0.009	-9999	-0.28	1	1
ITGB1	0.02	0.019	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
RAC1	-0.057	0.084	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.14	0.2	-9999	-0.6	3	3
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0.001	0.008	-9999	-10000	0	0
RHOC	-0.057	0.084	-9999	-10000	0	0
RHOA	-0.057	0.084	-9999	-10000	0	0
cell motility	-0.037	0.11	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.14	0.2	-9999	-0.62	2	2
PRL-3/alpha1 Integrin	-0.006	0.054	-9999	-0.62	7	7
ROCK1	-0.037	0.11	-9999	-10000	0	0
RABGGTB	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
mitosis	-0.12	0.24	-9999	-0.47	316	316
ATF5	-0.001	0.018	-9999	-0.28	4	4

×

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)	-0.004	0.048	-10000	0	-0.52	8	8
HDAC1	0.002	0.008	-10000	0	-10000	0	0
AES	0.001	0.004	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.074	0.23	-10000	0	-0.81	90	90
LRP6/FZD1	0	0.006	-10000	0	-10000	0	0
TLE1	-0.006	0.072	-10000	0	-0.81	8	8
AP1	-0.12	0.18	-10000	0	-0.38	302	302
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	-0.001	0.036	-10000	0	-0.81	2	2
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.008	0.045	-10000	0	-10000	0	0
NICD/RBPSUH	-0.001	0.032	-10000	0	-0.71	2	2
WIF1	-0.42	0.4	-10000	0	-0.79	524	524
NOTCH1	-0.002	0.034	-10000	0	-0.76	2	2
PSENEN	0	0.009	-10000	0	-0.28	1	1
KREMEN2	-0.13	0.14	-10000	0	-10000	0	0
DKK1	-0.078	0.19	-10000	0	-0.81	49	49
beta catenin/beta TrCP1	-0.009	0.024	0.22	2	-10000	0	2
APH1B	-0.001	0.026	-10000	0	-0.81	1	1
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	0.003	0.013	-10000	0	-0.22	2	2
CtBP/CBP/TCF1/TLE1/AES	0.003	0.041	-10000	0	-0.35	6	6
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.24	0.37	-10000	0	-0.81	298	298
JUN	-0.007	0.077	-10000	0	-0.81	9	9
MAP3K7	0.001	0.01	-10000	0	-0.28	1	1
CTNNB1	-0.003	0.035	0.23	3	-10000	0	3
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.078	0.11	-10000	0	-0.61	25	25
HNF1A	-0.001	0.022	-10000	0	-0.28	6	6
CTBP1	0.001	0.004	-10000	0	-10000	0	0
MYC	-0.035	0.23	-10000	0	-1.5	23	23
NKD1	-0.009	0.072	-10000	0	-0.42	22	22
FZD1	0	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.042	0.13	-10000	0	-0.45	92	92
apoptosis	-0.11	0.18	-10000	0	-0.37	302	302
Delta 1/NOTCHprecursor	-0.004	0.047	-10000	0	-0.51	8	8
DLL1	-0.005	0.063	-10000	0	-0.81	6	6
PPARD	-0.001	0.013	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.015	-10000	0	-0.45	1	1
APC	0.003	0.013	-10000	0	-0.22	2	2
DVL1	-0.038	0.037	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.11	0.14	-10000	0	-0.58	50	50
LRP6	0	0.009	-10000	0	-0.28	1	1
CSNK1A1	0	0	-10000	0	-10000	0	0
NLK	0.002	0.01	-10000	0	-10000	0	0
CCND1	-0.01	0.086	-10000	0	-1.5	3	3
WNT1	-0.001	0.013	-10000	0	-0.28	2	2
Axin1/APC/beta catenin	0.01	0.037	-10000	0	-10000	0	0
DKK2	-0.021	0.13	-10000	0	-0.81	25	25
NOTCH1 precursor/DVL1	-0.019	0.033	-10000	0	-0.64	2	2
GSK3B	0	0.002	-10000	0	-10000	0	0
FRAT1	0	0.003	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.042	0.13	-10000	0	-0.45	92	92
PPP2R5D	-0.015	0.039	0.36	6	-10000	0	6
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.25	0.24	-10000	0	-0.48	511	511
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.014	0.004	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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
PTK2	0.002	0.031	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.019	0.033	-9999	-0.64	1	1
positive regulation of JNK cascade	-0.045	0.11	-9999	-0.46	6	6
Syndecan-4/ADAM12	-0.027	0.051	-9999	-0.55	2	2
CCL5	-0.014	0.077	-9999	-0.81	5	5
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
ITGA5	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
PLG	0	0.019	-9999	-0.28	4	4
ADAM12	-0.019	0.077	-9999	-0.3	65	65
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	-0.001	0.015	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.054	0.043	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.07	0.14	-9999	-0.46	63	63
Syndecan-4/CXCL12/CXCR4	-0.047	0.11	-9999	-0.49	6	6
Syndecan-4/Laminin alpha3	-0.13	0.2	-9999	-0.5	118	118
MDK	-0.011	0.054	-9999	-0.28	39	39
Syndecan-4/FZD7	-0.028	0.069	-9999	-0.47	14	14
Syndecan-4/Midkine	-0.021	0.039	-9999	-0.64	1	1
FZD7	-0.017	0.12	-9999	-0.81	21	21
Syndecan-4/FGFR1/FGF	-0.18	0.21	-9999	-0.5	107	107
THBS1	-0.002	0.044	-9999	-0.81	3	3
integrin-mediated signaling pathway	-0.027	0.069	-9999	-0.48	13	13
positive regulation of MAPKKK cascade	-0.045	0.11	-9999	-0.46	6	6
Syndecan-4/TACI	-0.029	0.066	-9999	-0.5	7	7
CXCR4	-0.008	0.045	-9999	-10000	0	0
cell adhesion	-0.025	0.055	-9999	-0.34	24	24
Syndecan-4/Dynamin	-0.018	0.032	-9999	-0.64	1	1
Syndecan-4/TSP1	-0.02	0.04	-9999	-0.52	3	3
Syndecan-4/GIPC	-0.019	0.033	-9999	-0.64	1	1
Syndecan-4/RANTES	-0.025	0.05	-9999	-0.51	5	5
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.096	0.26	-9999	-0.81	117	117
LAMA3	-0.2	0.35	-9999	-0.81	245	245
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.004	0.12	-9999	-0.77	24	24
Syndecan-4/alpha-Actinin	-0.019	0.035	-9999	-0.55	2	2
TFPI	-0.038	0.17	-9999	-0.81	46	46
F2	0.001	0.028	-9999	-0.28	9	9
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.16	0.24	-9999	-0.6	106	106
ACTN1	-0.001	0.026	-9999	-0.81	1	1
TNC	-0.018	0.12	-9999	-0.67	27	27
Syndecan-4/CXCL12	-0.051	0.11	-9999	-0.46	35	35
FGF6	-0.002	0.036	-9999	-0.81	2	2
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.061	0.21	-9999	-0.81	75	75
TNFRSF13B	-0.026	0.11	-9999	-0.81	15	15
FGF2	-0.32	0.4	-9999	-0.81	395	395
FGFR1	-0.01	0.086	-9999	-0.69	14	14
Syndecan-4/PI-4-5-P2	-0.013	0.043	-9999	-0.65	1	1
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.11	0.14	-9999	-0.29	398	398
cell migration	-0.025	0.019	-9999	-10000	0	0
PRKCD	0.005	0.013	-9999	-0.27	1	1
vasculogenesis	-0.019	0.038	-9999	-0.5	3	3
SDC4	-0.013	0.046	-9999	-0.69	1	1
Syndecan-4/Tenascin C	-0.028	0.072	-9999	-0.5	13	13
Syndecan-4/PI-4-5-P2/PKC alpha	-0.043	0.034	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.018	0.032	-9999	-0.64	1	1
MMP9	-0.12	0.15	-9999	-0.28	444	444
Rac1/GTP	-0.025	0.056	-9999	-0.35	24	24
cytoskeleton organization	-0.018	0.032	-9999	-0.62	1	1
GIPC1	-0.001	0.013	-9999	-0.28	2	2
Syndecan-4/TFPI	-0.039	0.096	-9999	-0.47	30	30

×

Regulation of Androgen receptor activity

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
HDAC1	0.02	0.006	-9999	-10000	0	0
SMARCC1	0.004	0.02	-9999	-0.57	1	1
REL	-0.003	0.078	-9999	-0.81	9	9
HDAC7	0.009	0.13	-9999	-0.6	13	13
JUN	-0.007	0.077	-9999	-0.81	9	9
EP300	0	0	-9999	-10000	0	0
KAT2B	-0.001	0.026	-9999	-0.81	1	1
KAT5	0.002	0.004	-9999	-10000	0	0
MAPK14	0.006	0.095	-9999	-0.63	21	21
FOXO1	-0.009	0.085	-9999	-0.81	11	11
T-DHT/AR	-0.005	0.14	-9999	-0.56	21	21
MAP2K6	-0.017	0.12	-9999	-0.79	22	22
BRM/BAF57	-0.001	0.011	-9999	-10000	0	0
MAP2K4	0	0.026	-9999	-0.81	1	1
SMARCA2	0	0	-9999	-10000	0	0
PDE9A	-0.093	0.3	-9999	-1.2	61	61
NCOA2	-0.025	0.14	-9999	-0.81	31	31
CEBPA	-0.006	0.077	-9999	-0.81	9	9
EHMT2	0	0	-9999	-10000	0	0
cell proliferation	0.015	0.14	-9999	-0.5	24	24
NR0B1	-0.01	0.052	-9999	-0.28	36	36
EGR1	-0.26	0.38	-9999	-0.81	316	316
RXRs/9cRA	-0.12	0.21	-9999	-0.49	249	249
AR/RACK1/Src	-0.004	0.11	-9999	-0.49	26	26
AR/GR	-0.05	0.12	-9999	-0.44	45	45
GNB2L1	0.001	0.003	-9999	-10000	0	0
PKN1	0	0.009	-9999	-0.28	1	1
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.003	-9999	-10000	0	0
MAPK8	0.016	0.052	-9999	-0.62	6	6
T-DHT/AR/TIF2/CARM1	-0.009	0.14	-9999	-0.51	52	52
SRC	0.022	0.091	-9999	-0.48	26	26
NR3C1	-0.01	0.088	-9999	-0.81	12	12
KLK3	-0.22	0.43	-9999	-1.2	155	155
APPBP2	-0.001	0.015	-9999	-10000	0	0
TRIM24	0.001	0.01	-9999	-0.28	1	1
T-DHT/AR/TIP60	-0.026	0.094	-9999	-0.52	26	26
TMPRSS2	-0.17	0.42	-9999	-1.2	132	132
RXRG	-0.2	0.35	-9999	-0.8	252	252
mol:9cRA	-0.001	0.002	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0.001	0.003	-9999	-10000	0	0
NR2C2	-0.005	0.063	-9999	-0.81	6	6
KLK2	-0.041	0.25	-9999	-0.78	86	86
AR	-0.025	0.14	-9999	-0.34	143	143
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-0.28	1	1
MDM2	0.005	0.023	-9999	-0.28	4	4
SRY	0.003	0.01	-9999	-10000	0	0
GATA2	-0.025	0.13	-9999	-0.65	38	38
MYST2	0.001	0.01	-9999	-0.28	1	1
HOXB13	-0.13	0.14	-9999	-0.28	456	456
T-DHT/AR/RACK1/Src	-0.026	0.093	-9999	-0.5	26	26
positive regulation of transcription	-0.025	0.13	-9999	-0.65	38	38
DNAJA1	0	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.013	-9999	-10000	0	0
NCOA1	0.012	0.028	-9999	-0.84	1	1
SPDEF	-0.056	0.2	-9999	-0.81	65	65
T-DHT/AR/TIF2	0.016	0.09	-9999	-0.49	13	13
T-DHT/AR/Hsp90	-0.033	0.091	-9999	-0.52	26	26
GSK3B	0.001	0.004	-9999	-10000	0	0
NR2C1	0.002	0.006	-9999	-10000	0	0
mol:T-DHT	0.015	0.096	-9999	-0.52	26	26
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0.006	0.014	-9999	-10000	0	0
POU2F1	0.021	0.027	-9999	-0.41	1	1
T-DHT/AR/DAX-1	-0.034	0.096	-9999	-0.53	26	26
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	-0.001	0.016	-9999	-0.29	3	3

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.002	0.13	-10000	0	-0.41	49	49
TBX21	-0.011	0.34	-10000	0	-1.3	50	50
B2M	0.011	0.005	-10000	0	-10000	0	0
TYK2	0.017	0.015	-10000	0	-10000	0	0
IL12RB1	0.005	0.066	-10000	0	-0.31	36	36
GADD45B	0.034	0.22	-10000	0	-0.85	30	30
IL12RB2	-0.058	0.2	-10000	0	-0.44	164	164
GADD45G	0.026	0.22	-10000	0	-0.86	30	30
natural killer cell activation	0.007	0.017	-10000	0	-10000	0	0
RELB	-0.003	0.026	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL18	0.007	0.047	-10000	0	-0.28	26	26
IL2RA	-0.028	0.11	-10000	0	-0.36	77	77
IFNG	-0.039	0.096	-10000	0	-0.28	137	137
STAT3 (dimer)	0.028	0.21	-10000	0	-0.66	49	49
HLA-DRB5	-0.017	0.094	-10000	0	-0.49	14	14
FASLG	0.008	0.28	-10000	0	-1.1	38	38
NF kappa B2 p52/RelB	-0.077	0.2	-10000	0	-0.81	47	47
CD4	0.008	0.006	-10000	0	-10000	0	0
SOCS1	-0.005	0.042	-10000	0	-0.81	1	1
EntrezGene:6955	-0.006	0.014	-10000	0	-10000	0	0
CD3D	-0.026	0.14	-10000	0	-0.67	38	38
CD3E	-0.022	0.14	-10000	0	-0.51	58	58
CD3G	-0.035	0.17	-10000	0	-0.57	74	74
IL12Rbeta2/JAK2	-0.027	0.16	-10000	0	-0.64	50	50
CCL3	0.015	0.26	-10000	0	-0.99	36	36
CCL4	0.018	0.25	-10000	0	-0.9	39	39
HLA-A	0.009	0.026	-10000	0	-0.34	1	1
IL18/IL18R	0.021	0.14	-10000	0	-0.56	51	51
NOS2	0.021	0.25	-10000	0	-1	33	33
IL12/IL12R/TYK2/JAK2/SPHK2	-0.001	0.13	-10000	0	-0.42	46	46
IL1R1	0.005	0.3	-10000	0	-1.2	40	40
IL4	-0.005	0.018	-10000	0	-10000	0	0
JAK2	0.016	0.031	-10000	0	-0.82	1	1
EntrezGene:6957	-0.005	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.032	0.26	-10000	0	-1	45	45
RAB7A	0.049	0.19	-10000	0	-0.73	26	26
lysosomal transport	0.05	0.19	-10000	0	-0.68	27	27
FOS	-0.36	0.67	-10000	0	-1.3	313	313
STAT4 (dimer)	0.023	0.26	-10000	0	-0.91	47	47
STAT5A (dimer)	-0.081	0.21	-10000	0	-0.74	63	63
GZMA	0.006	0.28	-10000	0	-1.1	35	35
GZMB	-0.004	0.3	-10000	0	-1.1	42	42
HLX	-0.001	0.013	-10000	0	-0.28	2	2
LCK	0.007	0.29	-10000	0	-0.87	60	60
TCR/CD3/MHC II/CD4	-0.066	0.2	-10000	0	-0.57	79	79
IL2/IL2R	-0.029	0.097	-10000	0	-0.46	38	38
MAPK14	0.038	0.22	-10000	0	-0.82	35	35
CCR5	0.028	0.22	-10000	0	-0.87	32	32
IL1B	0.003	0.1	-10000	0	-0.73	18	18
STAT6	0.027	0.086	-10000	0	-0.26	5	5
STAT4	-0.035	0.16	-10000	0	-0.8	43	43
STAT3	0	0	-10000	0	-10000	0	0
STAT1	-0.005	0.037	-10000	0	-0.28	18	18
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0.009	-10000	0	-0.28	1	1
IL12B	-0.04	0.12	-10000	0	-0.27	179	179
CD8A	-0.001	0.074	-10000	0	-0.37	30	30
CD8B	-0.024	0.15	-10000	0	-0.56	61	61
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.002	0.13	0.41	49	-10000	0	49
IL2RB	-0.011	0.055	-10000	0	-0.28	40	40
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.24	-10000	0	-0.81	47	47
IL2RG	-0.018	0.087	-10000	0	-0.81	7	7
IL12	-0.047	0.16	-10000	0	-0.6	58	58
STAT5A	-0.007	0.072	-10000	0	-0.81	8	8
CD247	-0.014	0.12	-10000	0	-0.6	36	36
IL2	-0.003	0.026	-10000	0	-10000	0	0
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.032	0.19	-10000	0	-0.7	68	68
IL12/IL12R/TYK2/JAK2	0.011	0.29	-10000	0	-0.85	62	62
MAP2K3	0.034	0.22	-10000	0	-0.84	34	34
RIPK2	-0.001	0.02	-10000	0	-0.28	5	5
MAP2K6	0.03	0.23	-10000	0	-0.83	37	37
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.007	0.028	-10000	0	-0.81	1	1
IL18RAP	-0.018	0.16	-10000	0	-0.77	40	40
IL12Rbeta1/TYK2	0.014	0.051	-10000	0	-0.67	1	1
EOMES	-0.022	0.18	-10000	0	-1.5	14	14
STAT1 (dimer)	0.032	0.21	-10000	0	-0.71	38	38
T cell proliferation	0.034	0.2	-10000	0	-0.63	49	49
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.001	0.1	-10000	0	-0.81	16	16
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.061	0.17	-10000	0	-0.77	40	40
ATF2	0.046	0.21	-10000	0	-0.78	32	32

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.036	0.13	-10000	0	-0.62	36	36
FYN	0.015	0.18	-10000	0	-0.75	42	42
LAT/GRAP2/SLP76	-0.029	0.15	-10000	0	-0.65	42	42
IKBKB	-0.001	0.013	-10000	0	-10000	0	0
AKT1	0.03	0.12	-10000	0	-0.47	41	41
B2M	0.011	0.004	-10000	0	-10000	0	0
IKBKG	-0.008	0.027	-10000	0	-0.13	23	23
MAP3K8	-0.004	0.058	-10000	0	-0.81	5	5
mol:Ca2+	-0.025	0.048	-10000	0	-0.12	191	191
integrin-mediated signaling pathway	-0.002	0.03	-10000	0	-0.54	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.021	0.18	-10000	0	-0.71	43	43
TRPV6	-0.16	0.32	-10000	0	-0.78	205	205
CD28	-0.007	0.063	-10000	0	-0.47	14	14
SHC1	0.01	0.19	-10000	0	-0.8	39	39
receptor internalization	-0.003	0.21	-10000	0	-0.82	47	47
PRF1	-0.003	0.23	-10000	0	-1.2	32	32
KRAS	-0.001	0.013	-10000	0	-0.28	2	2
GRB2	0	0.009	-10000	0	-0.28	1	1
COT/AKT1	0.032	0.1	-10000	0	-0.38	40	40
LAT	0.007	0.19	-10000	0	-0.79	42	42
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	-0.023	0.14	-10000	0	-0.82	27	27
CD3E	-0.018	0.14	-10000	0	-0.5	58	58
CD3G	-0.034	0.17	-10000	0	-0.56	74	74
RASGRP2	-0.006	0.04	-10000	0	-0.18	44	44
RASGRP1	0.036	0.12	-10000	0	-0.47	41	41
HLA-A	0.009	0.025	-10000	0	-10000	0	0
RASSF5	-0.003	0.045	-10000	0	-0.68	4	4
RAP1A/GTP/RAPL	-0.002	0.03	-10000	0	-0.54	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.033	0.043	-10000	0	-0.12	39	39
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.015	0.048	-10000	0	-0.23	31	31
PRKCA	-0.012	0.085	-10000	0	-0.32	51	51
GRAP2	-0.015	0.11	-10000	0	-0.81	17	17
mol:IP3	0.018	0.15	0.27	164	-0.45	40	204
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.008	0.22	-10000	0	-0.94	38	38
ORAI1	0.078	0.15	0.38	191	-10000	0	191
CSK	0.007	0.19	-10000	0	-0.82	39	39
B7 family/CD28	-0.023	0.18	-10000	0	-0.72	47	47
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.004	0.22	-10000	0	-0.81	54	54
PTPN6	0.006	0.19	-10000	0	-0.8	41	41
VAV1	0.009	0.19	-10000	0	-0.79	41	41
Monovalent TCR/CD3	-0.032	0.21	-10000	0	-0.71	63	63
CBL	0	0	-10000	0	-10000	0	0
LCK	0.008	0.2	-10000	0	-0.82	41	41
PAG1	0.007	0.19	-10000	0	-0.8	41	41
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.004	0.22	-10000	0	-0.82	51	51
CD80	-0.076	0.12	-10000	0	-10000	0	0
CD86	-0.001	0.02	-10000	0	-10000	0	0
PDK1/CARD11/BCL10/MALT1	-0.018	0.058	-10000	0	-0.27	35	35
HRAS	-0.001	0.02	-10000	0	-10000	0	0
GO:0035030	-0.046	0.14	-10000	0	-0.58	47	47
CD8A	0	0.074	-10000	0	-0.37	30	30
CD8B	-0.024	0.15	-10000	0	-0.56	61	61
PTPRC	-0.01	0.078	-10000	0	-0.5	19	19
PDK1/PKC theta	0.033	0.16	-10000	0	-0.59	44	44
CSK/PAG1	0.012	0.18	-10000	0	-0.79	39	39
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.001	0.015	-10000	0	-10000	0	0
GRAP2/SLP76	-0.036	0.17	-10000	0	-0.77	42	42
STIM1	0.041	0.079	-10000	0	-10000	0	0
RAS family/GTP	0.041	0.054	-10000	0	-0.18	29	29
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.008	0.23	-10000	0	-0.91	47	47
mol:DAG	-0.007	0.1	-10000	0	-0.41	40	40
RAP1A/GDP	0.015	0.018	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
CD247	-0.014	0.12	-10000	0	-0.73	25	25
cytotoxic T cell degranulation	0	0.22	-10000	0	-1	35	35
RAP1A/GTP	-0.003	0.014	-10000	0	-0.07	15	15
mol:PI-3-4-5-P3	0.026	0.14	-10000	0	-0.56	43	43
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.012	0.18	0.29	155	-0.61	40	195
NRAS	-0.001	0.013	-10000	0	-10000	0	0
ZAP70	-0.03	0.13	-10000	0	-0.44	68	68
GRB2/SOS1	0	0.006	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.026	0.14	-10000	0	-0.63	40	40
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.032	0.14	-10000	0	-0.58	50	50
CARD11	-0.008	0.055	-10000	0	-0.32	24	24
PRKCB	-0.012	0.087	-10000	0	-0.34	46	46
PRKCE	-0.007	0.069	-10000	0	-0.28	38	38
PRKCQ	0.023	0.18	-10000	0	-0.68	46	46
LCP2	0	0.009	-10000	0	-0.28	1	1
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.031	0.1	-10000	0	-0.4	41	41
IKK complex	0.041	0.044	-10000	0	-0.12	27	27
RAS family/GDP	-0.002	0.006	-10000	0	-10000	0	0
MAP3K14	0.036	0.08	-10000	0	-0.3	35	35
PDPK1	0.033	0.12	-10000	0	-0.46	38	38
TCR/CD3/MHC I/CD8/Fyn	-0.008	0.24	-10000	0	-0.96	47	47

×

Coregulation of Androgen receptor activity

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
NRIP1	-0.003	0.034	-10000	0	-0.81	1	1
SVIL	-0.004	0.049	-10000	0	-0.81	3	3
ZNF318	0.024	0.059	0.2	7	-10000	0	7
JMJD2C	-0.003	0.042	-10000	0	-0.14	77	77
T-DHT/AR/Ubc9	-0.078	0.18	-10000	0	-0.56	122	122
CARM1	0	0	-10000	0	-10000	0	0
PRDX1	0.002	0.012	-10000	0	-0.28	1	1
PELP1	0.005	0.013	-10000	0	-10000	0	0
CTNNB1	-0.001	0.015	-10000	0	-10000	0	0
AKT1	0.008	0.019	-10000	0	-10000	0	0
PTK2B	-0.004	0.01	-10000	0	-10000	0	0
MED1	0.002	0.048	-10000	0	-0.28	20	20
MAK	0.013	0.11	0.28	2	-0.78	11	13
response to oxidative stress	0.001	0.004	-10000	0	-10000	0	0
HIP1	-0.005	0.055	-10000	0	-0.81	4	4
GSN	-0.013	0.094	-10000	0	-0.81	13	13
NCOA2	-0.025	0.14	-10000	0	-0.81	31	31
NCOA6	-0.002	0.021	-10000	0	-0.28	1	1
DNA-PK	0.022	0.06	0.23	1	-10000	0	1
NCOA4	0	0	-10000	0	-10000	0	0
PIAS3	-0.001	0.015	-10000	0	-10000	0	0
cell proliferation	-0.007	0.12	-10000	0	-0.89	11	11
XRCC5	0.007	0.016	-10000	0	-10000	0	0
UBE3A	-0.006	0.032	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.091	0.21	-10000	0	-0.6	134	134
FHL2	-0.017	0.13	-10000	0	-1.3	6	6
RANBP9	-0.001	0.019	-10000	0	-10000	0	0
JMJD1A	-0.012	0.056	-10000	0	-0.14	141	141
CDK6	-0.006	0.078	-10000	0	-0.71	11	11
TGFB1I1	-0.004	0.049	-10000	0	-0.81	3	3
T-DHT/AR/CyclinD1	-0.09	0.19	-10000	0	-0.56	129	129
XRCC6	0.007	0.016	-10000	0	-10000	0	0
T-DHT/AR	-0.065	0.21	-10000	0	-0.55	137	137
CTDSP1	0	0	-10000	0	-10000	0	0
CTDSP2	0.016	0.04	-10000	0	-10000	0	0
BRCA1	-0.003	0.036	-10000	0	-0.48	3	3
TCF4	0.004	0.087	-10000	0	-0.8	10	10
CDKN2A	-0.038	0.11	-10000	0	-0.28	143	143
SRF	0.024	0.02	-10000	0	-10000	0	0
NKX3-1	-0.081	0.2	-10000	0	-1.3	18	18
KLK3	-0.19	0.52	-10000	0	-1.6	127	127
TMF1	0	0	-10000	0	-10000	0	0
HNRNPA1	0.009	0.022	-10000	0	-10000	0	0
AOF2	-0.009	0.024	-10000	0	-0.072	127	127
APPL1	0.035	0.034	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.07	0.19	-10000	0	-0.55	122	122
AR	-0.097	0.27	-10000	0	-0.81	122	122
UBA3	0	0	-10000	0	-10000	0	0
PATZ1	0.009	0.022	-10000	0	-10000	0	0
PAWR	-0.001	0.026	-10000	0	-0.81	1	1
PRKDC	0.006	0.022	-10000	0	-0.28	2	2
PA2G4	0.012	0.029	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.066	0.17	-10000	0	-0.51	121	121
RPS6KA3	-0.006	0.056	-10000	0	-0.81	4	4
T-DHT/AR/ARA70	-0.082	0.18	-10000	0	-0.56	121	121
LATS2	0.01	0.024	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.061	0.18	0.19	1	-0.51	121	122
Cyclin D3/CDK11 p58	0	0.006	-10000	0	-10000	0	0
VAV3	-0.011	0.078	-10000	0	-0.7	9	9
KLK2	-0.12	0.33	-10000	0	-1.2	77	77
CASP8	0.004	0.011	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.089	0.19	-10000	0	-0.54	143	143
TMPRSS2	-0.18	0.4	-10000	0	-1.2	132	132
CCND1	-0.015	0.069	-10000	0	-0.32	39	39
PIAS1	-0.006	0.032	-10000	0	-10000	0	0
mol:T-DHT	-0.009	0.034	-10000	0	-0.079	172	172
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.013	0.051	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.08	0.19	-10000	0	-0.56	131	131
CMTM2	0.003	0.013	-10000	0	-0.28	1	1
SNURF	-0.02	0.13	-10000	0	-0.81	25	25
ZMIZ1	0.003	0.031	-10000	0	-0.35	1	1
CCND3	0.002	0.01	-10000	0	-10000	0	0
TGIF1	0.009	0.022	-10000	0	-10000	0	0
FKBP4	-0.004	0.032	-10000	0	-0.29	8	8

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.003	0.12	-10000	0	-0.45	34	34
IKBKB	0.015	0.054	-10000	0	-0.27	3	3
AKT1	0.004	0.081	0.25	1	-0.26	32	33
IKBKG	0.017	0.056	-10000	0	-0.24	17	17
CALM1	-0.012	0.096	-10000	0	-0.46	29	29
PIK3CA	0	0.009	-10000	0	-0.28	1	1
MAP3K1	-0.01	0.15	-10000	0	-0.63	35	35
MAP3K7	0	0.009	-10000	0	-0.28	1	1
mol:Ca2+	-0.021	0.1	-10000	0	-0.49	29	29
DOK1	-0.001	0.013	-10000	0	-0.28	2	2
AP-1	-0.043	0.11	-10000	0	-0.25	86	86
LYN	0	0	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.081	0.22	-10000	0	-0.64	110	110
CD22	-0.063	0.19	-10000	0	-0.56	94	94
CAMK2G	-0.003	0.09	-10000	0	-0.42	29	29
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.049	0.14	-10000	0	-0.46	91	91
GO:0007205	-0.021	0.1	-10000	0	-0.5	29	29
SYK	0	0.009	-10000	0	-0.28	1	1
ELK1	-0.012	0.097	-10000	0	-0.47	29	29
NFATC1	-0.018	0.14	-10000	0	-0.39	92	92
B-cell antigen/BCR complex	-0.081	0.22	-10000	0	-0.64	110	110
PAG1/CSK	-0.001	0.012	-10000	0	-10000	0	0
NFKBIB	0.015	0.02	-10000	0	-10000	0	0
HRAS	-0.01	0.1	-10000	0	-0.48	29	29
NFKBIA	0.015	0.02	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.019	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.06	0.17	-10000	0	-0.54	93	93
mol:GDP	-0.021	0.094	-10000	0	-0.47	29	29
PTEN	-0.002	0.036	-10000	0	-0.81	2	2
CD79B	-0.029	0.14	-10000	0	-0.59	49	49
NF-kappa-B/RelA/I kappa B alpha	0.019	0.016	-10000	0	-10000	0	0
GRB2	0	0.009	-10000	0	-0.28	1	1
PI3K/BCAP/CD19	-0.027	0.16	-10000	0	-0.48	92	92
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
mol:IP3	-0.031	0.1	-10000	0	-0.51	29	29
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.14	0.23	-10000	0	-0.45	318	318
CHUK	0.017	0.056	-10000	0	-0.24	16	16
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.024	0.081	-10000	0	-0.49	17	17
PTPN6	-0.059	0.17	-10000	0	-0.76	39	39
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0.015	0.02	-10000	0	-0.12	1	1
VAV2	-0.071	0.17	-10000	0	-0.54	91	91
ubiquitin-dependent protein catabolic process	0.019	0.019	-10000	0	-10000	0	0
BTK	-0.004	0.006	-10000	0	-10000	0	0
CD19	-0.081	0.18	-10000	0	-0.55	91	91
MAP4K1	-0.012	0.064	-10000	0	-0.81	2	2
CD72	-0.008	0.051	-10000	0	-0.3	26	26
PAG1	-0.001	0.02	-10000	0	-0.28	5	5
MAPK14	0.001	0.13	-10000	0	-0.52	34	34
SH3BP5	0	0	-10000	0	-10000	0	0
PIK3AP1	-0.012	0.11	-10000	0	-0.55	29	29
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.043	0.14	-10000	0	-0.48	80	80
RAF1	-0.002	0.1	-10000	0	-0.45	29	29
RasGAP/p62DOK/SHIP	-0.056	0.16	-10000	0	-0.51	93	93
CD79A	-0.083	0.22	-10000	0	-0.56	147	147
re-entry into mitotic cell cycle	-0.042	0.11	-10000	0	-0.26	81	81
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.015	0.085	-10000	0	-0.43	17	17
MAPK1	0.015	0.085	-10000	0	-0.43	17	17
CD72/SHP1	-0.055	0.16	-10000	0	-0.7	40	40
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.13	-10000	0	-0.52	37	37
actin cytoskeleton organization	-0.026	0.15	-10000	0	-0.45	91	91
NF-kappa-B/RelA	0.042	0.032	-10000	0	-10000	0	0
Calcineurin	-0.021	0.074	-10000	0	-0.45	17	17
PI3K	-0.058	0.13	-10000	0	-0.54	39	39
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.033	0.11	-10000	0	-0.58	29	29
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.049	0.18	-10000	0	-0.84	34	34
DAPP1	-0.053	0.2	-10000	0	-0.98	34	34
cytokine secretion	-0.015	0.13	-10000	0	-0.36	92	92
mol:DAG	-0.031	0.1	-10000	0	-0.51	29	29
PLCG2	-0.002	0.037	-10000	0	-0.63	3	3
MAP2K1	0.007	0.093	-10000	0	-0.48	17	17
B-cell antigen/BCR complex/FcgammaRIIB	-0.071	0.2	-10000	0	-0.62	93	93
mol:PI-3-4-5-P3	-0.043	0.093	0.34	1	-0.37	38	39
ETS1	0.003	0.091	-10000	0	-0.49	19	19
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.058	0.16	-10000	0	-0.53	91	91
B-cell antigen/BCR complex/LYN	-0.06	0.19	-10000	0	-0.57	96	96
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0.001	-10000	0	-10000	0	0
RAC1	-0.03	0.17	-10000	0	-0.48	91	91
B-cell antigen/BCR complex/LYN/SYK	-0.059	0.18	-10000	0	-0.57	93	93
CARD11	-0.016	0.1	-10000	0	-0.5	29	29
FCGR2B	-0.004	0.052	-10000	0	-0.81	4	4
PPP3CA	-0.001	0.013	-10000	0	-0.28	2	2
BCL10	0	0	-10000	0	-10000	0	0
IKK complex	0.017	0.027	-10000	0	-0.097	2	2
PTPRC	-0.01	0.078	-10000	0	-0.5	19	19
PDPK1	-0.028	0.062	0.22	1	-0.27	22	23
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.019	0.014	-10000	0	-0.14	1	1

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.13	0.22	-9999	-0.48	256	256
TC10/GTP	-0.1	0.18	-9999	-0.42	242	242
Insulin Receptor/Insulin/IRS1/Shp2	-0.021	0.1	-9999	-0.5	41	41
HRAS	-0.001	0.02	-9999	-10000	0	0
APS homodimer	-0.012	0.057	-9999	-0.28	43	43
GRB14	-0.099	0.22	-9999	-0.46	212	212
FOXO3	-0.013	0.063	-9999	-0.7	7	7
AKT1	-0.056	0.13	-9999	-0.52	10	10
INSR	0	0.009	-9999	-0.27	1	1
Insulin Receptor/Insulin	-0.003	0.026	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.2	0.35	-9999	-0.81	242	242
CRK	0	0	-9999	-10000	0	0
PTPN1	0.033	0.03	-9999	-10000	0	0
CAV1	-0.12	0.23	-9999	-0.52	225	225
CBL/APS/CAP/Crk-II/C3G	-0.12	0.2	-9999	-0.46	242	242
Insulin Receptor/Insulin/IRS1/NCK2	-0.021	0.1	-9999	-0.5	41	41
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.021	0.094	-9999	-0.44	48	48
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.012	0.056	-9999	-10000	0	0
RPS6KB1	-0.007	0.13	-9999	-0.47	10	10
PARD6A	-0.001	0.02	-9999	-0.28	5	5
CBL	0	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	-0.006	0.068	-9999	-0.81	7	7
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.049	0.11	-9999	-0.49	10	10
HRAS/GTP	-0.016	0.076	-9999	-0.47	2	2
Insulin Receptor	0	0.009	-9999	-0.27	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.019	0.093	-9999	-0.47	41	41
PRKCI	-0.013	0.032	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.061	0.14	-9999	-0.42	120	120
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.002	-9999	-10000	0	0
PI3K	-0.022	0.096	-9999	-0.45	48	48
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0.003	-9999	-10000	0	0
HRAS/GDP	-0.001	0.013	-9999	-10000	0	0
AKT2	-0.056	0.13	-9999	-0.38	120	120
PRKCZ	-0.013	0.037	-9999	-0.61	1	1
SH2B2	-0.012	0.057	-9999	-0.28	43	43
SHC/SHIP	-0.018	0.088	-9999	-0.44	41	41
F2RL2	-0.058	0.15	-9999	-0.81	21	21
TRIP10	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0.004	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0.004	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.12	0.21	-9999	-0.49	242	242
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0.003	-9999	-10000	0	0
INPP5D	-0.02	0.094	-9999	-0.47	41	41
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.008	0.071	-9999	-1	5	5
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	-0.033	0.16	-9999	-0.81	41	41
p62DOK/RasGAP	0	0.002	-9999	-10000	0	0
INS	0.003	0.004	-9999	-10000	0	0
mol:PI-3-4-P2	-0.019	0.093	-9999	-0.47	41	41
GRB2	0	0.009	-9999	-0.28	1	1
EIF4EBP1	-0.013	0.14	-9999	-0.46	23	23
PTPRA	0	0.001	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.28	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.014	0.066	-9999	-0.33	41	41
Insulin Receptor/Insulin/IRS1	-0.021	0.1	-9999	-0.51	41	41
Insulin Receptor/Insulin/IRS3	-0.001	0.007	-9999	-10000	0	0
Par3/Par6	-0.025	0.075	-9999	-0.46	21	21

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.033	0.079	-9999	-0.44	28	28
NF kappa B1 p50/RelA/I kappa B alpha	-0.02	0.065	-9999	-0.44	6	6
alphaV/beta3 Integrin/Osteopontin/Src	-0.044	0.072	-9999	-10000	0	0
AP1	-0.14	0.21	-9999	-0.56	116	116
ILK	-0.003	0.1	-9999	-0.48	28	28
bone resorption	-0.031	0.093	-9999	-0.63	11	11
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	0.008	0.087	-9999	-0.43	28	28
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.012	0.083	-9999	-0.62	18	18
alphaV/beta3 Integrin/Osteopontin	-0.046	0.099	-9999	-0.53	28	28
MAP3K1	-0.004	0.11	-9999	-0.5	28	28
JUN	-0.007	0.077	-9999	-0.81	9	9
MAPK3	0.012	0.1	-9999	-0.44	28	28
MAPK1	0.012	0.1	-9999	-0.44	28	28
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	0.006	0.12	-9999	-0.52	30	30
ITGB3	-0.024	0.13	-9999	-0.8	28	28
NFKBIA	0.025	0.096	-9999	-0.42	28	28
FOS	-0.24	0.37	-9999	-0.81	298	298
CD44	-0.001	0.015	-9999	-0.28	3	3
CHUK	0	0	-9999	-10000	0	0
PLAU	0.023	0.096	-9999	-0.5	2	2
NF kappa B1 p50/RelA	-0.019	0.062	-9999	-0.45	4	4
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.018	0.1	-9999	-0.61	28	28
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.005	0.1	-9999	-0.48	28	28
VAV3	0.001	0.11	-9999	-0.46	35	35
MAP3K14	-0.001	0.1	-9999	-0.48	28	28
ROCK2	-0.015	0.11	-9999	-0.81	18	18
SPP1	-0.072	0.12	-9999	-0.27	265	265
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.033	0.08	-9999	-0.41	35	35
MMP2	-0.076	0.21	-9999	-0.67	34	34

×

IL27-mediated signaling events

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
TGFB1	0.002	0.011	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.028	0.12	0.55	10	-10000	0	10
IL27/IL27R/JAK1	-0.065	0.18	-10000	0	-0.74	23	23
TBX21	-0.038	0.21	-10000	0	-0.65	60	60
IL12B	-0.048	0.11	-10000	0	-0.28	191	191
IL12A	-0.028	0.14	-10000	0	-0.53	68	68
IL6ST	-0.081	0.25	-10000	0	-0.82	105	105
IL27RA/JAK1	-0.006	0.062	-10000	0	-1.3	2	2
IL27	-0.023	0.086	-10000	0	-0.28	63	63
TYK2	0.01	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.13	0.18	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.028	0.12	0.55	10	-10000	0	10
T cell proliferation during immune response	0.028	0.12	0.55	10	-10000	0	10
MAPKKK cascade	-0.028	0.12	-10000	0	-0.55	10	10
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	-0.005	0.038	-10000	0	-0.28	18	18
IL12RB1	-0.011	0.059	-10000	0	-0.3	38	38
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.053	0.23	-10000	0	-0.63	85	85
IL27/IL27R/JAK2/TYK2	-0.029	0.12	-10000	0	-0.56	10	10
positive regulation of T cell mediated cytotoxicity	-0.028	0.12	-10000	0	-0.55	10	10
STAT1 (dimer)	-0.084	0.22	0.52	8	-0.8	36	44
JAK2	0.004	0.027	-10000	0	-0.81	1	1
JAK1	0.001	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.039	0.11	-10000	0	-0.55	8	8
T cell proliferation	-0.18	0.25	-10000	0	-0.5	272	272
IL12/IL12R/TYK2/JAK2	0.014	0.069	-10000	0	-10000	0	0
IL17A	-0.13	0.18	-10000	0	-10000	0	0
mast cell activation	0.028	0.12	0.55	10	-10000	0	10
IFNG	0.001	0.023	-10000	0	-0.085	3	3
T cell differentiation	-0.003	0.006	-10000	0	-0.02	9	9
STAT3 (dimer)	-0.039	0.11	-10000	0	-0.55	8	8
STAT5A (dimer)	-0.043	0.12	-10000	0	-0.55	15	15
STAT4 (dimer)	-0.059	0.14	-10000	0	-0.53	50	50
STAT4	-0.035	0.16	-10000	0	-0.8	43	43
T cell activation	-0.008	0.008	0.13	2	-10000	0	2
IL27R/JAK2/TYK2	-0.054	0.16	-10000	0	-0.94	5	5
GATA3	-0.038	0.27	-10000	0	-1.5	34	34
IL18	0.006	0.032	-10000	0	-10000	0	0
positive regulation of mast cell cytokine production	-0.039	0.1	-10000	0	-0.54	8	8
IL27/EBI3	-0.025	0.083	-10000	0	-0.5	16	16
IL27RA	0	0.069	-10000	0	-1.4	2	2
IL6	-0.29	0.39	-10000	0	-0.81	362	362
STAT5A	-0.007	0.072	-10000	0	-0.81	8	8
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.003	0.027	0.48	2	-10000	0	2
IL1B	0.001	0.079	-10000	0	-0.63	15	15
EBI3	-0.006	0.081	-10000	0	-0.49	21	21
TNF	-0.002	0.08	-10000	0	-0.63	14	14

×

PLK1 signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.026	0.027	-9999	-10000	0	0
BUB1B	-0.036	0.047	-9999	-10000	0	0
PLK1	-0.006	0.021	-9999	-10000	0	0
PLK1S1	0.001	0.012	-9999	-10000	0	0
KIF2A	0.004	0.019	-9999	-10000	0	0
regulation of mitotic centrosome separation	-0.006	0.021	-9999	-10000	0	0
GOLGA2	0	0	-9999	-10000	0	0
Hec1/SPC24	-0.16	0.11	-9999	-0.27	463	463
WEE1	-0.001	0.022	-9999	-10000	0	0
cytokinesis	-0.045	0.05	-9999	-0.26	3	3
PP2A-alpha B56	0.033	0.022	-9999	-10000	0	0
AURKA	0.003	0.011	-9999	-10000	0	0
PICH/PLK1	-0.071	0.091	-9999	-0.32	10	10
CENPE	-0.047	0.082	-9999	-0.2	2	2
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.004	0.019	-9999	-10000	0	0
PPP2CA	0	0	-9999	-10000	0	0
FZR1	0	0	-9999	-10000	0	0
TPX2	-0.002	0.014	-9999	-10000	0	0
PAK1	-0.006	0.041	-9999	-0.28	22	22
SPC24	-0.17	0.14	-9999	-0.28	610	610
FBXW11	0	0	-9999	-10000	0	0
CLSPN	-0.002	0.015	-9999	-10000	0	0
GORASP1	0	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	-0.004	0.012	-9999	-10000	0	0
G2 phase of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
STAG2	-0.001	0.026	-9999	-0.81	1	1
GRASP65/GM130/RAB1/GTP	0.008	0.009	-9999	-10000	0	0
spindle elongation	-0.006	0.021	-9999	-10000	0	0
ODF2	0	0	-9999	-10000	0	0
BUB1	0.028	0.019	-9999	-10000	0	0
TPT1	0.001	0.012	-9999	-10000	0	0
CDC25C	-0.002	0.013	-9999	-10000	0	0
CDC25B	-0.003	0.038	-9999	-0.28	18	18
SGOL1	-0.026	0.027	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.02	0.039	-9999	-10000	0	0
CDC14B	-0.009	0.11	-9999	-0.64	30	30
CDC20	-0.15	0.14	-9999	-0.28	540	540
PLK1/PBIP1	-0.027	0.051	-9999	-0.17	4	4
mitosis	-0.006	0.007	-9999	-0.022	2	2
FBXO5	0.002	0.021	-9999	-10000	0	0
CDC2	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.17	0.14	-9999	-10000	0	0
metaphase plate congression	-0.001	0.014	-9999	-10000	0	0
ERCC6L	-0.062	0.083	-9999	-10000	0	0
NLP/gamma Tubulin	0	0.012	-9999	-10000	0	0
microtubule cytoskeleton organization	0.001	0.012	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-9999	-10000	0	0
PPP1R12A	0	0	-9999	-10000	0	0
interphase	-0.001	0.001	-9999	-10000	0	0
PLK1/PRC1-2	-0.13	0.096	-9999	-0.27	229	229
GRASP65/GM130/RAB1/GTP/PLK1	-0.001	0.002	-9999	-10000	0	0
RAB1A	0	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	-0.001	0.022	-9999	-10000	0	0
mitotic prometaphase	-0.002	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.01	0.049	-9999	-0.29	25	25
microtubule-based process	-0.11	0.063	-9999	-10000	0	0
Golgi organization	-0.006	0.021	-9999	-10000	0	0
Cohesin/SA2	-0.008	0.017	-9999	-0.47	1	1
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.21	0.12	-9999	-10000	0	0
APC/C/CDC20	-0.083	0.075	-9999	-0.2	2	2
PPP2R1A	0	0	-9999	-10000	0	0
chromosome segregation	-0.027	0.051	-9999	-0.17	4	4
PRC1	-0.072	0.12	-9999	-0.28	256	256
ECT2	-0.002	0.037	-9999	-10000	0	0
C13orf34	0.001	0.02	-9999	-10000	0	0
NUDC	-0.001	0.014	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.036	0.047	-9999	-10000	0	0
spindle assembly	-0.002	0.018	-9999	-10000	0	0
spindle stabilization	0.001	0.012	-9999	-10000	0	0
APC/C/HCDH1	-0.017	0.094	-9999	-0.55	30	30
MKLP2/PLK1	-0.11	0.063	-9999	-10000	0	0
CCNB1	-0.058	0.11	-9999	-0.28	207	207
PPP1CB	0	0	-9999	-10000	0	0
BTRC	0	0	-9999	-10000	0	0
ROCK2	-0.003	0.071	-9999	-0.52	18	18
TUBG1	0.001	0.013	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.02	0.038	-9999	-10000	0	0
MLF1IP	-0.027	0.073	-9999	-0.19	158	158
INCENP	0	0.001	-9999	-10000	0	0

×

Syndecan-2-mediated 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
Syndecan-2/Fibronectin	-0.057	0.073	-9999	-0.41	6	6
EPHB2	-0.005	0.037	-9999	-0.28	18	18
Syndecan-2/TACI	-0.017	0.077	-9999	-0.54	18	18
LAMA1	-0.096	0.26	-9999	-0.81	117	117
Syndecan-2/alpha2 ITGB1	-0.13	0.22	-9999	-0.48	260	260
HRAS	-0.001	0.02	-9999	-10000	0	0
Syndecan-2/CASK	-0.002	0.031	-9999	-0.54	3	3
ITGA5	0	0	-9999	-10000	0	0
BAX	0.035	0.053	-9999	-0.53	8	8
EPB41	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.002	0.028	-9999	-0.49	3	3
LAMA3	-0.2	0.35	-9999	-0.81	245	245
EZR	-0.001	0.015	-9999	-0.28	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.1	0.27	-9999	-0.81	127	127
Syndecan-2/MMP2	-0.007	0.072	-9999	-0.68	10	10
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.016	0.097	-9999	-0.62	25	25
dendrite morphogenesis	-0.005	0.035	-9999	-0.53	3	3
Syndecan-2/GM-CSF	-0.005	0.037	-9999	-0.54	3	3
determination of left/right symmetry	0.017	0.037	-9999	-0.36	7	7
Syndecan-2/PKC delta	-0.002	0.031	-9999	-0.53	3	3
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	0.022	0.037	-9999	-0.48	3	3
MAPK1	0.022	0.037	-9999	-0.48	3	3
Syndecan-2/RACK1	-0.002	0.027	-9999	-0.46	3	3
NF1	-0.001	0.026	-9999	-0.81	1	1
FGFR/FGF/Syndecan-2	0.017	0.037	-9999	-0.36	7	7
ITGA2	-0.02	0.13	-9999	-0.81	25	25
MAPK8	0.029	0.055	-9999	-0.57	8	8
Syndecan-2/alpha2/beta1 Integrin	-0.067	0.18	-9999	-0.52	128	128
Syndecan-2/Kininogen	-0.004	0.034	-9999	-0.54	3	3
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.002	0.025	-9999	-0.43	3	3
Syndecan-2/CASK/Protein 4.1	-0.002	0.028	-9999	-0.49	3	3
extracellular matrix organization	-0.002	0.031	-9999	-0.53	3	3
actin cytoskeleton reorganization	-0.057	0.073	-9999	-0.41	6	6
Syndecan-2/Caveolin-2/Ras	-0.065	0.17	-9999	-0.5	127	127
Syndecan-2/Laminin alpha3	-0.14	0.23	-9999	-0.54	248	248
Syndecan-2/RasGAP	-0.002	0.025	-9999	-0.43	3	3
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0	0.009	-9999	-0.28	1	1
Syndecan-2 dimer	-0.005	0.035	-9999	-0.53	3	3
GO:0007205	0	0.001	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.024	-9999	-0.41	3	3
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.026	0.11	-9999	-0.81	15	15
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.016	0.097	-9999	-0.62	25	25
Syndecan-2/Synbindin	-0.002	0.03	-9999	-0.53	3	3
TGFB1	0	0.009	-9999	-10000	0	0
CASP3	0.03	0.03	-9999	-0.48	3	3
FN1	-0.11	0.14	-9999	-0.28	398	398
Syndecan-2/IL8	-0.021	0.085	-9999	-0.53	22	22
SDC2	0.017	0.037	-9999	-0.37	7	7
KNG1	-0.003	0.031	-9999	-0.28	12	12
Syndecan-2/Neurofibromin	-0.003	0.035	-9999	-0.53	4	4
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.006	0.042	-9999	-0.28	23	23
Syndecan-2/TGFB1	-0.002	0.031	-9999	-0.53	3	3
Syndecan-2/Syntenin/PI-4-5-P2	-0.002	0.028	-9999	-0.49	3	3
Syndecan-2/Ezrin	-0.002	0.028	-9999	-0.48	3	3
PRKACA	0.029	0.034	-9999	-0.48	4	4
angiogenesis	-0.021	0.084	-9999	-0.53	22	22
MMP2	-0.008	0.081	-9999	-0.81	10	10
IL8	-0.033	0.13	-9999	-0.4	80	80
calcineurin-NFAT signaling pathway	-0.017	0.077	-9999	-0.53	18	18

×

TCGA08_retinoblastoma

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
CDKN2B	-0.003	0.063	-10000	0	-0.66	8	8
CDKN2C	0.006	0.04	-10000	0	-0.8	2	2
CDKN2A	-0.049	0.11	-10000	0	-0.29	167	167
CCND2	0.006	0.031	0.23	8	-0.16	11	19
RB1	-0.007	0.03	0.15	6	-0.23	8	14
CDK4	0.009	0.029	0.25	8	-10000	0	8
CDK6	0.006	0.035	0.27	7	-0.22	8	15
G1/S progression	-0.007	0.034	0.23	8	-0.19	3	11

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.002	0.01	-10000	0	-10000	0	0
HSPA8	0	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.1	0.21	0.26	1	-0.57	147	148
AKT1	0.013	0.006	-10000	0	-10000	0	0
GSC	-0.041	0.31	-10000	0	-1.5	41	41
NKX2-5	-0.042	0.098	-10000	0	-0.28	149	149
muscle cell differentiation	0.006	0.05	0.77	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.003	0.037	-10000	0	-0.46	2	2
SMAD4	0.013	0.043	-10000	0	-0.85	1	1
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0	0	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.2	0.26	-10000	0	-0.53	379	379
SMAD3/SMAD4/VDR	0.005	0.031	-10000	0	-0.45	2	2
MYC	-0.018	0.12	-10000	0	-0.81	23	23
CDKN2B	0.029	0.12	-10000	0	-1.5	6	6
AP1	-0.13	0.21	-10000	0	-0.43	299	299
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.001	0.015	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0	0.042	-10000	0	-0.35	1	1
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.037	0.11	-10000	0	-0.4	4	4
SMAD3/SMAD4/GR	-0.009	0.07	-10000	0	-0.58	13	13
GATA3	-0.036	0.15	-10000	0	-0.57	60	60
SKI/SIN3/HDAC complex/NCoR1	0.002	0.014	-10000	0	-10000	0	0
MEF2C/TIF2	-0.044	0.11	-10000	0	-0.6	25	25
endothelial cell migration	-0.01	0.037	-10000	0	-10000	0	0
MAX	0.001	0.004	-10000	0	-10000	0	0
RBBP7	-0.002	0.025	-10000	0	-0.28	8	8
RBBP4	-0.001	0.026	-10000	0	-0.81	1	1
RUNX2	-0.004	0.032	-10000	0	-10000	0	0
RUNX3	-0.005	0.059	-10000	0	-0.61	8	8
RUNX1	-0.001	0.026	-10000	0	-0.81	1	1
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	-0.009	0.089	-10000	0	-0.81	12	12
VDR	0	0	-10000	0	-10000	0	0
CDKN1A	0.049	0.081	-10000	0	-1.5	2	2
KAT2B	0	0.026	-10000	0	-0.81	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.022	0.071	-10000	0	-0.46	5	5
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0	-10000	0	-10000	0	0
SERPINE1	0.009	0.037	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	-0.002	0.034	-10000	0	-0.55	2	2
SMAD3/SMAD4/ATF3	-0.086	0.2	-10000	0	-0.57	148	148
SAP30	-0.001	0.018	-10000	0	-0.28	4	4
Cbp/p300/PIAS3	0.006	0.023	-10000	0	-10000	0	0
JUN	-0.081	0.23	-10000	0	-0.42	299	299
SMAD3/SMAD4/IRF7	-0.01	0.063	-10000	0	-0.55	1	1
TFE3	0.017	0.006	-10000	0	-10000	0	0
COL1A2	0.028	0.1	-10000	0	-1.3	2	2
mesenchymal cell differentiation	0.004	0.034	0.55	1	-10000	0	1
DLX1	-0.052	0.13	-10000	0	-0.81	10	10
TCF3	0	0.009	-10000	0	-0.28	1	1
FOS	-0.23	0.38	-10000	0	-0.8	298	298
SMAD3/SMAD4/Max	-0.002	0.03	-10000	0	-0.56	1	1
Cbp/p300/SNIP1	0	0	-10000	0	-10000	0	0
ZBTB17	0	0.005	-10000	0	-10000	0	0
LAMC1	0.042	0.049	-10000	0	-0.64	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.029	-10000	0	-0.56	1	1
IRF7	-0.026	0.082	-10000	0	-0.35	22	22
ESR1	-0.15	0.29	-10000	0	-0.58	263	263
HNF4A	-0.004	0.034	-10000	0	-0.28	15	15
MEF2C	-0.002	0.092	-10000	0	-0.69	4	4
SMAD2-3/SMAD4	-0.003	0.034	-10000	0	-0.55	1	1
Cbp/p300/Src-1	0.003	0.023	-10000	0	-0.53	1	1
IGHV3OR16-13	-0.001	0.01	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	0.002	0.007	-10000	0	-10000	0	0
SKIL	-0.003	0.028	-10000	0	-0.28	10	10
HDAC1	0	0	-10000	0	-10000	0	0
HDAC2	0	0	-10000	0	-10000	0	0
SNIP1	0	0.002	-10000	0	-10000	0	0
GCN5L2	0.001	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.001	0.031	-10000	0	-0.55	1	1
MSG1/HSC70	-0.24	0.3	-10000	0	-0.62	379	379
SMAD2	0.014	0.021	-10000	0	-10000	0	0
SMAD3	0.014	0.029	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.007	0.026	-10000	0	-0.36	1	1
SMAD2/SMAD2/SMAD4	0.026	0.041	-10000	0	-1.1	1	1
NCOR1	-0.001	0.026	-10000	0	-0.81	1	1
NCOA2	-0.025	0.14	-10000	0	-0.81	31	31
NCOA1	-0.001	0.026	-10000	0	-0.81	1	1
MYOD/E2A	-0.003	0.021	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.008	0.04	-10000	0	-0.42	2	2
IFNB1	0.014	0.085	-10000	0	-0.48	1	1
SMAD3/SMAD4/MEF2C	-0.025	0.074	-10000	0	-0.77	3	3
CITED1	-0.31	0.39	-10000	0	-0.79	393	393
SMAD2-3/SMAD4/ARC105	-0.001	0.03	-10000	0	-0.49	1	1
RBL1	-0.001	0.013	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.038	0.063	-10000	0	-0.49	6	6
RUNX1-3/PEBPB2	-0.004	0.047	-10000	0	-0.63	5	5
SMAD7	-0.078	0.14	-10000	0	-0.59	10	10
MYC/MIZ-1	-0.014	0.095	-10000	0	-0.62	23	23
SMAD3/SMAD4	0.019	0.06	0.27	38	-0.45	1	39
IL10	0.018	0.12	-10000	0	-0.53	36	36
PIASy/HDAC complex	0.001	0.003	-10000	0	-10000	0	0
PIAS3	0.001	0.005	-10000	0	-10000	0	0
CDK2	0.002	0.008	-10000	0	-10000	0	0
IL5	0.014	0.11	-10000	0	-0.52	34	34
CDK4	0.001	0.015	-10000	0	-0.28	2	2
PIAS4	0.001	0.003	-10000	0	-10000	0	0
ATF3	-0.12	0.29	-10000	0	-0.81	147	147
SMAD3/SMAD4/SP1	0	0.034	-10000	0	-0.53	2	2
FOXG1	-0.021	0.073	-10000	0	-10000	0	0
FOXO3	0.025	0.03	-10000	0	-0.62	2	2
FOXO1	0.019	0.068	-10000	0	-0.62	11	11
FOXO4	0.026	0.008	-10000	0	-10000	0	0
heart looping	-0.002	0.091	-10000	0	-0.68	4	4
CEBPB	0.012	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.029	0.082	-10000	0	-0.57	11	11
MYOD1	-0.004	0.032	-10000	0	-0.28	13	13
SMAD3/SMAD4/HNF4	-0.006	0.036	-10000	0	-0.69	1	1
SMAD3/SMAD4/GATA3	-0.023	0.11	-10000	0	-0.58	34	34
SnoN/SIN3/HDAC complex/NCoR1	-0.003	0.028	-10000	0	-0.28	10	10
SMAD3/SMAD4/RUNX1-3/PEBPB2	0	0.05	-10000	0	-0.56	6	6
SMAD3/SMAD4/SP1-3	0.003	0.03	-10000	0	-0.46	2	2
MED15	0	0	-10000	0	-10000	0	0
SP1	0.019	0.013	-10000	0	-10000	0	0
SIN3B	0	0	-10000	0	-10000	0	0
SIN3A	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.007	0.088	-10000	0	-0.49	5	5
ITGB5	0.051	0.046	-10000	0	-0.43	1	1
TGIF/SIN3/HDAC complex/CtBP	0	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.071	0.19	-10000	0	-0.57	122	122
AR	-0.099	0.26	-10000	0	-0.8	122	122
negative regulation of cell growth	-0.026	0.074	-10000	0	-0.45	1	1
SMAD3/SMAD4/MYOD	-0.007	0.035	-10000	0	-0.56	1	1
E2F5	-0.006	0.039	-10000	0	-0.28	20	20
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.002	0.056	-10000	0	-0.55	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	0	0.044	-10000	0	-0.35	3	3
TFDP1	-0.001	0.018	-10000	0	-0.28	4	4
SMAD3/SMAD4/AP1	-0.12	0.22	-10000	0	-0.43	299	299
SMAD3/SMAD4/RUNX2	-0.004	0.034	-10000	0	-0.56	1	1
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	-0.001	0.026	-10000	0	-0.81	1	1

×

Canonical 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.004	0.017	-10000	0	-10000	0	0
AES	0.004	0.014	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0.006	-10000	0	-10000	0	0
SMAD4	-0.001	0.026	-10000	0	-0.81	1	1
DKK2	-0.021	0.13	-10000	0	-0.81	25	25
TLE1	-0.003	0.074	-10000	0	-0.81	8	8
MACF1	0	0.001	-10000	0	-10000	0	0
CTNNB1	0.1	0.087	-10000	0	-10000	0	0
WIF1	-0.42	0.4	-10000	0	-0.79	524	524
beta catenin/RanBP3	0.014	0.076	0.37	38	-10000	0	38
KREMEN2	-0.13	0.14	-10000	0	-10000	0	0
DKK1	-0.078	0.19	-10000	0	-0.81	49	49
beta catenin/beta TrCP1	0.1	0.084	-10000	0	-10000	0	0
FZD1	0	0.001	-10000	0	-10000	0	0
AXIN2	-0.011	0.2	-10000	0	-1.5	16	16
AXIN1	0.006	0.006	-10000	0	-10000	0	0
RAN	0	0.002	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.005	0.019	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.092	0.079	-10000	0	-0.5	6	6
Axin1/APC/GSK3	0.001	0.014	0.24	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.077	0.033	-10000	0	-10000	0	0
HNF1A	0.002	0.026	-10000	0	-0.28	2	2
CTBP1	0.004	0.015	-10000	0	-10000	0	0
MYC	-0.02	0.24	-10000	0	-1.6	23	23
RANBP3	0	0.002	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.078	0.11	-10000	0	-0.61	25	25
NKD1	-0.009	0.072	-10000	0	-0.42	22	22
TCF4	-0.004	0.082	-10000	0	-0.8	10	10
TCF3	0.003	0.016	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0	0.006	-10000	0	-10000	0	0
Ran/GTP	0	0	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.013	0.095	0.44	40	-0.43	1	41
LEF1	-0.035	0.1	-10000	0	-0.29	120	120
DVL1	0.071	0.065	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.099	0.091	-10000	0	-0.64	4	4
DKK1/LRP6/Kremen 2	-0.11	0.14	-10000	0	-0.58	50	50
LRP6	0	0.009	-10000	0	-0.28	1	1
CSNK1A1	0.004	0.017	-10000	0	-10000	0	0
NLK	0.01	0.014	-10000	0	-10000	0	0
CCND1	0.003	0.1	-10000	0	-1.6	3	3
WNT1	0	0.012	-10000	0	-0.28	2	2
GSK3A	0.006	0.006	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
FRAT1	0	0	-10000	0	-10000	0	0
PPP2R5D	0.043	0.046	0.34	7	-10000	0	7
APC	0	0.006	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.14	0.13	0.27	511	-10000	0	511
CREBBP	0.004	0.015	-10000	0	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.005	0.035	-10000	0	-10000	0	0
GNB1/GNG2	-0.015	0.048	-10000	0	-0.21	35	35
AKT1	0.05	0.072	-10000	0	-0.22	16	16
EGF	-0.17	0.33	-10000	0	-0.8	206	206
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.01	0.052	-10000	0	-0.56	2	2
mol:Ca2+	0.046	0.099	-10000	0	-0.3	59	59
LYN	-0.01	0.049	-10000	0	-0.52	1	1
RhoA/GTP	-0.009	0.03	-10000	0	-0.14	2	2
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.052	0.11	-10000	0	-0.35	59	59
GNG2	-0.009	0.085	-10000	0	-0.81	11	11
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.029	0.056	-10000	0	-0.54	6	6
G beta5/gamma2	-0.019	0.065	-10000	0	-0.29	31	31
PRKCH	0.048	0.11	-10000	0	-0.36	53	53
DNM1	-0.006	0.068	-10000	0	-0.74	8	8
TXA2/TP beta/beta Arrestin3	-0.004	0.028	-10000	0	-0.31	7	7
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.031	0.15	-10000	0	-0.72	42	42
G12 family/GTP	-0.022	0.074	-10000	0	-0.31	59	59
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	-0.003	0.051	-10000	0	-0.81	4	4
RhoA/GTP/ROCK1	-0.001	0.017	-10000	0	-0.54	1	1
mol:GDP	-0.036	0.079	0.36	20	-10000	0	20
mol:NADP	0	0	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.28	2	2
PRKG1	-0.048	0.19	-10000	0	-0.81	59	59
mol:IP3	0.047	0.12	-10000	0	-0.38	59	59
cell morphogenesis	-0.001	0.017	-10000	0	-0.54	1	1
PLCB2	0.044	0.15	-10000	0	-0.52	59	59
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.001	0.063	-10000	0	-0.44	5	5
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.009	0.05	-10000	0	-0.52	1	1
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.003	0.026	-10000	0	-0.28	9	9
PRKCB1	0.045	0.12	-10000	0	-0.38	59	59
GNAQ	-0.002	0.036	-10000	0	-0.81	2	2
mol:L-citrulline	0	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.046	0.16	-10000	0	-0.54	59	59
LCK	-0.013	0.074	-10000	0	-0.48	14	14
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.012	0.057	-10000	0	-0.35	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.024	0.034	-10000	0	-0.29	6	6
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.011	0.055	-10000	0	-0.34	1	1
MAPK14	0.051	0.079	-10000	0	-0.24	28	28
TGM2/GTP	0.047	0.13	-10000	0	-0.43	59	59
MAPK11	0.05	0.082	-10000	0	-0.26	28	28
ARHGEF1	0.038	0.061	-10000	0	-0.19	14	14
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	0.049	0.12	-10000	0	-0.4	59	59
RAB11/GDP	-0.001	0.012	-10000	0	-0.28	2	2
ICAM1	0.046	0.093	-10000	0	-0.28	59	59
cAMP biosynthetic process	0.043	0.12	-10000	0	-0.36	59	59
Gq family/GTP/EBP50	-0.006	0.032	-10000	0	-0.25	15	15
actin cytoskeleton reorganization	-0.001	0.017	-10000	0	-0.54	1	1
SRC	-0.01	0.049	-10000	0	-0.52	1	1
GNB5	0	0	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.031	0.11	-10000	0	-0.35	23	23
VCAM1	0.044	0.1	-10000	0	-0.32	59	59
TP beta/Gq family/GDP/G beta5/gamma2	0.029	0.056	-10000	0	-0.54	6	6
platelet activation	0.066	0.1	-10000	0	-0.31	59	59
PGI2/IP	-0.002	0.018	-10000	0	-10000	0	0
PRKACA	-0.014	0.07	-10000	0	-0.38	35	35
Gq family/GDP/G beta5/gamma2	0.026	0.058	-10000	0	-0.54	6	6
TXA2/TP beta/beta Arrestin2	-0.006	0.056	-10000	0	-0.66	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.013	0.065	-10000	0	-0.35	35	35
mol:DAG	0.046	0.13	-10000	0	-0.42	59	59
EGFR	-0.3	0.39	-10000	0	-0.8	369	369
TXA2/TP alpha	0.048	0.15	-10000	0	-0.5	59	59
Gq family/GTP	-0.004	0.035	-10000	0	-0.28	15	15
YES1	-0.01	0.05	-10000	0	-0.44	2	2
GNAI2/GTP	-0.011	0.057	-10000	0	-0.46	3	3
PGD2/DP	-0.024	0.12	-10000	0	-0.63	35	35
SLC9A3R1	-0.023	0.077	-10000	0	-0.28	83	83
FYN	-0.011	0.053	-10000	0	-0.5	3	3
mol:NO	0	0	-10000	0	-10000	0	0
GNA15	-0.003	0.035	-10000	0	-0.34	8	8
PGK/cGMP	-0.032	0.13	-10000	0	-0.54	59	59
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.014	0.079	-10000	0	-0.66	7	7
NOS3	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0.042	0.12	-10000	0	-0.38	59	59
PRKCB	0.043	0.12	-10000	0	-0.38	64	64
PRKCE	0.049	0.11	-10000	0	-0.36	53	53
PRKCD	0.048	0.12	-10000	0	-0.38	59	59
PRKCG	0.044	0.12	-10000	0	-0.39	59	59
muscle contraction	0.05	0.15	-10000	0	-0.5	59	59
PRKCZ	0.052	0.11	-10000	0	-0.35	60	60
ARR3	-0.002	0.025	-10000	0	-10000	0	0
TXA2/TP beta	-0.013	0.064	-10000	0	-0.49	4	4
PRKCQ	0.037	0.14	-10000	0	-0.4	69	69
MAPKKK cascade	0.044	0.14	-10000	0	-0.47	59	59
SELE	0.038	0.12	-10000	0	-0.42	59	59
TP beta/GNAI2/GDP/G beta/gamma	-0.015	0.078	-10000	0	-0.58	10	10
ROCK1	-0.001	0.026	-10000	0	-0.81	1	1
GNA14	-0.015	0.09	-10000	0	-0.44	33	33
chemotaxis	0.045	0.18	-10000	0	-0.63	59	59
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.002	0.036	-10000	0	-0.81	2	2
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.017	0.12	-9999	-0.81	21	21
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	-0.001	0.026	-9999	-0.81	1	1
RAC1-CDC42/GTP/PAK family	-0.13	0.14	-9999	-0.28	457	457
response to UV	0	0	-9999	-10000	0	0
YES1	-0.001	0.026	-9999	-0.81	1	1
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
FYN	-0.002	0.036	-9999	-0.81	2	2
MAP3K12	0	0	-9999	-10000	0	0
FGR	-0.001	0.027	-9999	-0.81	1	1
p38 alpha/TAB1	-0.007	0.034	-9999	-0.32	4	4
PRKG1	-0.048	0.19	-9999	-0.81	59	59
DUSP8	-0.003	0.045	-9999	-0.68	4	4
PGK/cGMP/p38 alpha	-0.03	0.1	-9999	-0.4	62	62
apoptosis	-0.007	0.033	-9999	-0.34	3	3
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0	0	-9999	-10000	0	0
DUSP1	-0.11	0.28	-9999	-0.81	134	134
PAK1	-0.006	0.041	-9999	-0.28	22	22
SRC	0	0.009	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0.006	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	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	-0.001	0.013	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.016	0.069	-9999	-0.35	18	18
BLK	-0.04	0.1	-9999	-0.81	3	3
HCK	-0.003	0.029	-9999	-10000	0	0
MAP2K3	0	0.009	-9999	-0.28	1	1
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.001	0.015	-9999	-0.28	3	3
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.027	0.049	-9999	-0.35	4	4
positive regulation of innate immune response	0.022	0.075	-9999	-0.37	18	18
LCK	-0.02	0.1	-9999	-0.81	13	13
p38alpha-beta/MKP7	-0.012	0.055	-9999	-0.35	17	17
p38alpha-beta/MKP5	-0.012	0.056	-9999	-0.35	17	17
PGK/cGMP	-0.037	0.15	-9999	-0.63	59	59
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.062	0.14	-9999	-0.42	89	89
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.37	0.4	-9999	-0.81	457	457

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.05	0.11	-9999	-0.64	3	3
RAD9A	0	0.009	-9999	-0.28	1	1
AP1	-0.19	0.29	-9999	-0.63	299	299
IFNAR2	0.01	0.005	-9999	-10000	0	0
AKT1	-0.037	0.11	-9999	-0.29	147	147
ER alpha/Oestrogen	-0.12	0.22	-9999	-0.63	147	147
NFX1/SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
EGF	-0.17	0.33	-9999	-0.8	206	206
SMG5	0	0	-9999	-10000	0	0
SMG6	0	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.063	0.084	-9999	-0.6	3	3
SAP18	0	0	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.14	0.14	-9999	-10000	0	0
WRN	0	0	-9999	-10000	0	0
SP1	0.011	0.005	-9999	-10000	0	0
SP3	0	0.002	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.048	0.074	-9999	-0.57	2	2
Mad/Max	0	0.006	-9999	-10000	0	0
TERT	-0.051	0.12	-9999	-0.66	3	3
CCND1	-0.043	0.12	-9999	-1.3	3	3
MAX	0.001	0.004	-9999	-10000	0	0
RBBP7	-0.002	0.025	-9999	-0.28	8	8
RBBP4	-0.001	0.026	-9999	-0.81	1	1
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
Telomerase/911	0.004	0.016	-9999	-10000	0	0
CDKN1B	0.008	0.074	-9999	-0.88	3	3
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	-0.001	0.018	-9999	-0.28	4	4
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0	0	-9999	-10000	0	0
JUN	-0.006	0.077	-9999	-0.81	9	9
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.24	0.37	-9999	-0.81	298	298
IFN-gamma/IRF1	-0.024	0.06	-9999	-0.35	5	5
PARP2	0	0	-9999	-10000	0	0
BLM	-0.03	0.087	-9999	-0.28	107	107
Telomerase	-0.004	0.025	-9999	-10000	0	0
IRF1	-0.001	0.018	-9999	-0.27	3	3
ESR1	-0.15	0.29	-9999	-0.57	264	264
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0.007	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0.008	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC2	0.01	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.021	0.006	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0.001	0.01	-9999	-0.28	1	1
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.015	-9999	-0.28	3	3
TERT/NF kappa B1/14-3-3	-0.062	0.099	-9999	-0.66	3	3
NR2F2	0	0.045	-9999	-0.81	3	3
MAPK3	0.014	0.02	-9999	-10000	0	0
MAPK1	0.014	0.02	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0	0.009	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	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	0	-9999	-10000	0	0
EGFR	-0.3	0.39	-9999	-0.8	369	369
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.35	0.36	-9999	-0.68	504	504
MYC	-0.01	0.12	-9999	-0.81	23	23
IL2	0.004	0.028	-9999	-0.28	6	6
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0.009	-9999	-0.28	1	1
TGFB1	0	0.009	-9999	-10000	0	0
TRF2/BLM	-0.017	0.049	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.059	0.082	-9999	-0.59	3	3
SP1/HDAC2	0	0	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.048	0.074	-9999	-0.57	2	2
Smad3/Myc	-0.012	0.08	-9999	-0.53	23	23
911 complex	0	0.004	-9999	-10000	0	0
IFNG	-0.037	0.094	-9999	-10000	0	0
Telomerase/PinX1	-0.048	0.074	-9999	-0.57	2	2
Telomerase/AKT1/mTOR/p70S6K	0.004	0.054	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.048	0.074	-9999	-0.57	2	2
response to DNA damage stimulus	0.003	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	-0.048	0.074	-9999	-0.57	2	2
E2F1	-0.083	0.14	-9999	-0.28	321	321
ZNFX1	0	0	-9999	-10000	0	0
PIF1	-0.056	0.11	-9999	-10000	0	0
NCL	0	0	-9999	-10000	0	0
DKC1	-0.001	0.013	-9999	-0.28	2	2
telomeric DNA binding	0	0	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	-0.003	0.026	-9999	-0.28	9	9
ELF1	-0.011	0.047	-9999	-0.38	12	12
CCNA2	-0.12	0.14	-9999	-0.28	407	407
PIK3CA	0	0.009	-9999	-0.28	1	1
JAK3	-0.005	0.035	-9999	-10000	0	0
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
JAK1	0	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.059	0.073	-9999	-0.61	6	6
SHC1	0	0	-9999	-10000	0	0
SP1	-0.005	0.042	-9999	-0.38	12	12
IL2RA	0.004	0.12	-9999	-1	12	12
IL2RB	-0.011	0.055	-9999	-0.28	40	40
SOS1	0	0	-9999	-10000	0	0
IL2RG	-0.018	0.087	-9999	-0.81	7	7
G1/S transition of mitotic cell cycle	0.008	0.12	-9999	-0.83	18	18
PTPN11	0	0	-9999	-10000	0	0
CCND2	0.016	0.12	-9999	-1	12	12
LCK	-0.02	0.1	-9999	-0.81	13	13
GRB2	0	0.009	-9999	-0.28	1	1
IL2	-0.002	0.026	-9999	-10000	0	0
CDK6	-0.008	0.078	-9999	-0.71	11	11
CCND3	0.064	0.064	-9999	-0.58	4	4

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.45	0.4	-10000	0	-0.81	553	553
CLTC	0.027	0.016	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.024	0.018	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.006	0.026	-10000	0	-10000	0	0
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.025	0.016	-10000	0	-10000	0	0
CPE	0.005	0.083	-10000	0	-0.54	22	22
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.001	0.017	-10000	0	-10000	0	0
CTNND1	-0.005	0.023	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.029	0.013	-10000	0	-10000	0	0
TSHR	-0.007	0.12	-10000	0	-0.54	43	43
INS	0.011	0.005	-10000	0	-10000	0	0
BIN1	-0.008	0.077	-10000	0	-0.75	10	10
mol:Choline	-0.001	0.017	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.035	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.006	0.026	-10000	0	-10000	0	0
JUP	0.025	0.016	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.005	0.049	-10000	0	-0.49	10	10
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.016	0.052	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0.009	-10000	0	-0.28	1	1
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	-0.004	0.034	-10000	0	-0.28	15	15
substrate adhesion-dependent cell spreading	0	0.001	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.033	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.018	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0.005	-10000	0	-10000	0	0
ACAP1	-0.001	0.018	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.02	0.014	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.032	0.02	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0	0	-10000	0	-10000	0	0
exocyst	0	0.001	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	-0.005	0.022	-10000	0	-10000	0	0
NME1	0.01	0.035	-10000	0	-10000	0	0
clathrin coat assembly	0.027	0.016	-10000	0	-10000	0	0
IL2RA	0.018	0.042	-10000	0	-0.37	6	6
VAMP3	0.018	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.23	0.2	-10000	0	-0.41	553	553
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.002	0.029	-10000	0	-0.34	7	7
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.03	0.013	-10000	0	-10000	0	0
SDC1	0.021	0.023	-10000	0	-0.35	1	1
ARF6/GDP	-0.007	0.031	-10000	0	-10000	0	0
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.009	0.034	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.001	0.017	-10000	0	-10000	0	0
endocytosis	0.005	0.049	0.49	10	-10000	0	10
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.077	0.2	-10000	0	-0.44	234	234
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	-0.001	0.026	-10000	0	-0.81	1	1
Dynamin 2/GDP	-0.006	0.026	-10000	0	-10000	0	0
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	-0.15	0.23	-10000	0	-0.43	380	380
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.007	0.029	-10000	0	-10000	0	0

×

TCGA08_p53

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
CDKN2A	-0.023	0.074	-9999	-0.19	167	167
TP53	-0.008	0.018	-9999	-10000	0	0
Senescence	-0.008	0.018	-9999	-10000	0	0
Apoptosis	-0.008	0.018	-9999	-10000	0	0
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.015	0.038	-9999	-10000	0	0
MDM4	0	0	-9999	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.023	0.078	0.32	35	-10000	0	35
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.005	0.036	-10000	0	-0.54	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.032	0.14	-10000	0	-0.48	66	66
RhoA/GTP	-0.024	0.079	-10000	0	-0.33	35	35
negative regulation of cAMP metabolic process	-0.027	0.088	-10000	0	-0.31	82	82
GNAZ	-0.007	0.072	-10000	0	-0.81	8	8
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	-0.008	0.059	-10000	0	-0.81	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.027	0.089	-10000	0	-0.31	82	82
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	-0.042	0.18	-10000	0	-0.81	51	51

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.001	0.003	-9999	-10000	0	0
HDAC2	0.001	0.004	-9999	-10000	0	0
GNB1/GNG2	-0.01	0.076	-9999	-0.56	18	18
forebrain development	-0.027	0.2	-9999	-0.52	124	124
GNAO1	-0.032	0.14	-9999	-0.48	66	66
SMO/beta Arrestin2	-0.005	0.056	-9999	-0.62	8	8
SMO	0.004	0.074	-9999	-0.75	9	9
ARRB2	0.003	0.005	-9999	-10000	0	0
GLI3/SPOP	-0.002	0.036	-9999	-10000	0	0
mol:GTP	0	0.003	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0	0.001	-9999	-10000	0	0
SIN3/HDAC complex	0	0.007	-9999	-10000	0	0
GNAI1	-0.042	0.18	-9999	-0.81	51	51
XPO1	0.011	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.056	0.16	-9999	-0.52	75	75
SAP30	0	0.018	-9999	-0.28	4	4
mol:GDP	0.004	0.074	-9999	-0.75	9	9
MIM/GLI2A	0.002	0.028	-9999	-0.28	9	9
IFT88	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GLI2	0.04	0.034	-9999	-10000	0	0
GLI3	0.039	0.041	-9999	-0.3	12	12
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0.001	0.003	-9999	-10000	0	0
embryonic digit morphogenesis	0	0	-9999	-10000	0	0
GNG2	-0.009	0.085	-9999	-0.81	11	11
Gi family/GTP	-0.024	0.097	-9999	-0.35	52	52
SIN3B	0.001	0.004	-9999	-10000	0	0
SIN3A	0.001	0.003	-9999	-10000	0	0
GLI3/Su(fu)	-0.003	0.027	-9999	-0.45	1	1
GLI2/Su(fu)	-0.005	0.038	-9999	-0.4	6	6
FOXA2	-0.013	0.032	-9999	-10000	0	0
neural tube patterning	-0.027	0.2	-9999	-0.52	124	124
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.003	0.027	-9999	-0.46	1	1
GNB1	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	0.002	0.028	-9999	-0.28	9	9
embryonic limb morphogenesis	-0.027	0.2	-9999	-0.52	124	124
SUFU	-0.003	0.03	-9999	-0.31	9	9
LGALS3	-0.011	0.092	-9999	-0.81	13	13
catabolic process	-0.004	0.028	-9999	-10000	0	0
GLI3A/CBP	-0.026	0.096	-9999	-0.38	67	67
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.029	0.21	-9999	-0.54	124	124
RAB23	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	-0.001	0.026	-9999	-0.81	1	1
RBBP7	-0.001	0.025	-9999	-0.28	8	8
Su(fu)/Galectin3	-0.009	0.067	-9999	-0.54	14	14
GNAZ	-0.007	0.072	-9999	-0.81	8	8
RBBP4	0	0.026	-9999	-0.81	1	1
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	-0.003	0.025	-9999	-10000	0	0
STK36	0.01	0.026	-9999	-0.81	1	1
Gi family/GNB1/GNG2/GDP	-0.028	0.097	-9999	-0.55	14	14
PTCH1	-0.069	0.35	-9999	-1.1	85	85
MIM/GLI1	-0.055	0.19	-9999	-0.52	104	104
CREBBP	-0.026	0.096	-9999	-0.38	67	67
Su(fu)/SIN3/HDAC complex	0.006	0.021	-9999	-10000	0	0

×

S1P4 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.032	0.14	-9999	-0.48	66	66
CDC42/GTP	-0.025	0.078	-9999	-0.5	4	4
PLCG1	-0.026	0.081	-9999	-0.32	37	37
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.024	0.077	-9999	-0.48	4	4
S1PR5	-0.008	0.059	-9999	-0.81	3	3
S1PR4	-0.014	0.08	-9999	-0.36	40	40
MAPK3	-0.026	0.081	-9999	-0.32	37	37
MAPK1	-0.026	0.081	-9999	-0.32	37	37
S1P/S1P5/Gi	-0.027	0.089	-9999	-0.31	82	82
GNAI1	-0.042	0.18	-9999	-0.81	51	51
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.005	0.036	-9999	-0.54	3	3
RHOA	-0.006	0.04	-9999	-0.46	6	6
S1P/S1P4/Gi	-0.029	0.088	-9999	-0.3	87	87
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.007	0.072	-9999	-0.81	8	8
S1P/S1P4/G12/G13	-0.007	0.044	-9999	-0.49	6	6
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.022	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0.007	-10000	0	-10000	0	0
CDKN1B	0.035	0.026	-10000	0	-0.43	3	3
CDKN1A	0.036	0.022	-10000	0	-0.43	2	2
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.015	-10000	0	-0.28	3	3
FOXO3	0.036	0.021	-10000	0	-0.43	2	2
AKT1	0	0.001	-10000	0	-10000	0	0
BAD	0	0.009	-10000	0	-0.28	1	1
AKT3	0.01	0.054	-10000	0	-0.44	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.037	0.002	-10000	0	-10000	0	0
AKT1/ASK1	-0.001	0.023	-10000	0	-0.42	3	3
BAD/YWHAZ	-0.001	0.009	-10000	0	-10000	0	0
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0	0	-10000	0	-10000	0	0
JNK cascade	0.001	0.022	0.41	3	-10000	0	3
TSC1	0.037	0.002	-10000	0	-10000	0	0
YWHAZ	-0.001	0.015	-10000	0	-0.28	3	3
AKT1/RAF1	0	0.001	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.001	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.037	0.002	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	0.022	0.039	-10000	0	-0.53	5	5
MAP3K5	-0.002	0.044	-10000	0	-0.81	3	3
MAPKAP1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.039	0.022	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
AKT1S1	0.037	0.002	-10000	0	-10000	0	0
CASP9	0.037	0.002	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	-0.001	0.022	-10000	0	-0.41	3	3
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0	0.006	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.001	0.019	-10000	0	-0.42	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.001	-10000	0	-10000	0	0
CHUK	0.037	0.002	-10000	0	-10000	0	0
BAD/BCL-XL	0	0.003	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.053	0.03	-10000	0	-10000	0	0
PDPK1	0	0	-10000	0	-10000	0	0
MDM2	0.036	0.008	-10000	0	-10000	0	0
MAPKKK cascade	0	0.001	-10000	0	-10000	0	0
MDM2/Cbp/p300	0	0.005	-10000	0	-10000	0	0
TSC1/TSC2	0.043	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.004	-10000	0	-10000	0	0
glucose import	-0.26	0.26	-10000	0	-0.48	555	555
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.031	0.002	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.26	0.26	-10000	0	-0.49	555	555
GSK3A	0.037	0.002	-10000	0	-10000	0	0
FOXO1	0.031	0.049	-10000	0	-0.43	11	11
GSK3B	0.037	0.002	-10000	0	-10000	0	0
SFN	-0.015	0.098	-10000	0	-0.51	30	30
G1/S transition of mitotic cell cycle	0.043	0.002	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.042	0.032	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
KPNA1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0.009	-10000	0	-0.28	1	1
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.021	0.02	-10000	0	-0.62	1	1
MAP4K4	0.04	0.048	-10000	0	-0.69	1	1
BAG4	-0.004	0.046	-10000	0	-0.37	12	12
PKC zeta/ceramide	-0.025	0.049	-10000	0	-0.59	1	1
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.081	-10000	0	-0.81	9	9
BAX	-0.009	0.022	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.024	0.01	-10000	0	-10000	0	0
BAD	-0.023	0.047	0.2	1	-0.24	1	2
SMPD1	0.025	0.035	-10000	0	-0.25	14	14
RB1	-0.024	0.051	0.2	1	-0.48	2	3
FADD/Caspase 8	0.047	0.049	-10000	0	-0.66	1	1
MAP2K4	-0.016	0.048	0.2	1	-0.46	2	3
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.015	0.047	0.2	1	-0.3	3	4
EGF	-0.17	0.33	-10000	0	-0.8	206	206
mol:ceramide	-0.034	0.049	0.21	1	-10000	0	1
MADD	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.021	0.023	-10000	0	-0.62	1	1
ASAH1	-0.001	0.015	-10000	0	-0.28	3	3
negative regulation of cell cycle	-0.024	0.05	0.2	1	-0.48	2	3
cell proliferation	-0.095	0.16	-10000	0	-0.39	215	215
BID	0.022	0.036	-10000	0	-0.4	1	1
MAP3K1	-0.024	0.049	0.2	1	-0.48	1	2
EIF2A	-0.006	0.042	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
MAPK3	-0.003	0.044	-10000	0	-0.42	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.003	0.044	-10000	0	-0.42	1	1
Cathepsin D/ceramide	-0.029	0.05	-10000	0	-0.24	1	1
FADD	0.038	0.052	-10000	0	-0.47	3	3
KSR1	-0.024	0.049	0.2	1	-0.33	3	4
MAPK8	-0.013	0.054	0.2	1	-0.37	7	8
PRKRA	-0.023	0.046	0.2	1	-10000	0	1
PDGFA	-0.001	0.026	-10000	0	-0.81	1	1
TRAF2	-0.001	0.018	-10000	0	-0.28	4	4
IGF1	-0.18	0.33	-10000	0	-0.81	215	215
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.034	0.049	0.21	1	-10000	0	1
CTSD	-0.01	0.053	-10000	0	-10000	0	0
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	-0.1	0.17	-10000	0	-0.42	215	215
PRKCD	0	0.009	-10000	0	-0.28	1	1
PRKCZ	-0.001	0.026	-10000	0	-0.81	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.021	0.023	-10000	0	-0.62	1	1
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.001	0.026	-10000	0	-0.81	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.006	0.044	-10000	0	-0.74	1	1
TNFR1A/BAG4/TNF-alpha	-0.013	0.072	-10000	0	-0.54	16	16
mol:Sphingosine-1-phosphate	0.021	0.02	-10000	0	-0.62	1	1
MAP2K1	-0.007	0.045	-10000	0	-0.43	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	-0.008	0.045	0.18	24	-10000	0	24
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.003	0.033	-10000	0	-0.62	2	2
EIF2AK2	-0.015	0.044	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.01	0.066	-10000	0	-0.53	14	14
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.003	0.022	-10000	0	-0.33	1	1
MAP2K2	-0.007	0.045	-10000	0	-0.43	1	1
SMPD3	0.024	0.044	-10000	0	-0.28	18	18
TNF	-0.017	0.1	-10000	0	-0.81	14	14
PKC zeta/PAR4	-0.001	0.028	-10000	0	-0.62	2	2
mol:PHOSPHOCHOLINE	0.048	0.12	0.27	205	-10000	0	205
NF kappa B1/RelA/I kappa B alpha	-0.001	0.02	-10000	0	-0.45	2	2
AIFM1	-0.008	0.045	0.18	24	-10000	0	24
BCL2	-0.029	0.15	-10000	0	-0.81	35	35

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.008	0.077	-10000	0	-0.75	10	10
positive regulation of NF-kappaB transcription factor activity	-0.064	0.19	-10000	0	-0.62	102	102
MAP2K4	0.041	0.04	-10000	0	-0.43	1	1
IKBKB	-0.001	0.013	-10000	0	-10000	0	0
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.005	0.063	-10000	0	-0.81	6	6
SMPD1	-0.003	0.027	-10000	0	-0.29	9	9
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.076	0.24	-10000	0	-0.8	94	94
TRAIL/TRAILR2	-0.006	0.059	-10000	0	-0.62	9	9
TRAIL/TRAILR3	-0.009	0.073	-10000	0	-0.66	11	11
TRAIL/TRAILR1	-0.01	0.076	-10000	0	-0.62	15	15
TRAIL/TRAILR4	-0.064	0.19	-10000	0	-0.62	102	102
TRAIL/TRAILR1/DAP3/GTP	-0.008	0.06	-10000	0	-0.49	15	15
IKK complex	-0.003	0.021	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0.006	-10000	0	-10000	0	0
MAPK3	0.016	0.061	-10000	0	-0.62	9	9
MAP3K1	-0.004	0.034	-10000	0	-0.32	10	10
TRAILR4 (trimer)	-0.076	0.24	-10000	0	-0.8	94	94
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.005	0.063	-10000	0	-0.8	6	6
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.006	0.04	-10000	0	-0.33	15	15
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.016	0.061	-10000	0	-0.62	9	9
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.009	0.057	-10000	0	-0.46	15	15
mol:ceramide	-0.003	0.027	-10000	0	-0.29	9	9
FADD	-0.005	0.035	-10000	0	-10000	0	0
MAPK8	0.045	0.053	-10000	0	-0.47	6	6
TRAF2	-0.001	0.018	-10000	0	-0.28	4	4
TRAILR3 (trimer)	-0.005	0.051	-10000	0	-0.42	11	11
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.01	0.068	-10000	0	-0.54	15	15
DAP3	0	0.009	-10000	0	-0.28	1	1
CASP10	0.02	0.11	0.31	88	-0.5	13	101
JNK cascade	-0.064	0.19	-10000	0	-0.62	102	102
TRAIL (trimer)	-0.008	0.077	-10000	0	-0.75	10	10
TNFRSF10C	-0.005	0.051	-10000	0	-0.42	11	11
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.009	0.059	-10000	0	-0.47	15	15
TRAIL/TRAILR2/FADD	-0.007	0.053	-10000	0	-0.53	9	9
cell death	-0.003	0.027	-10000	0	-0.29	9	9
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.004	0.031	-10000	0	-0.33	9	9
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0.001	0.015	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.006	0.044	-10000	0	-0.45	9	9

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.016	0.092	-9999	-0.53	30	30
E-cadherin/beta catenin	-0.018	0.1	-9999	-0.62	29	29
CTNNB1	0	0	-9999	-10000	0	0
JUP	-0.001	0.029	-9999	-0.81	1	1
CDH1	-0.024	0.14	-9999	-0.81	29	29

×

Effects of Botulinum toxin

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.003	0.039	-9999	-0.19	40	40
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.046	0.13	-9999	-0.62	42	42
STXBP1	-0.004	0.057	-9999	-0.81	5	5
ACh/CHRNA1	-0.059	0.078	-9999	-0.27	9	9
RAB3GAP2/RIMS1/UNC13B	-0.038	0.11	-9999	-0.53	42	42
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	-0.066	0.18	-9999	-0.81	42	42
mol:ACh	0.001	0.031	-9999	-0.15	33	33
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.037	0.093	-9999	-0.4	47	47
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.058	0.077	-9999	-0.27	9	9
UNC13B	0	0	-9999	-10000	0	0
CHRNA1	-0.094	0.13	-9999	-10000	0	0
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.06	0.13	-9999	-0.53	47	47
SNAP25	-0.016	0.069	-9999	-0.38	33	33
VAMP2	0	0	-9999	-10000	0	0
SYT1	-0.089	0.18	-9999	-0.81	40	40
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.009	0.047	-9999	-0.54	5	5
STX1A/SNAP25 fragment 1/VAMP2	-0.037	0.093	-9999	-0.4	47	47

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.006	0.095	-10000	0	-0.46	32	32
ACTA1	-0.016	0.13	-10000	0	-0.66	31	31
NUMA1	0.006	0.095	-10000	0	-0.48	29	29
SPTAN1	-0.004	0.13	-10000	0	-0.65	29	29
LIMK1	-0.004	0.13	-10000	0	-0.65	29	29
BIRC3	-0.01	0.081	-10000	0	-0.81	9	9
BIRC2	0	0	-10000	0	-10000	0	0
BAX	-0.001	0.018	-10000	0	-0.28	4	4
CASP10	-0.014	0.15	-10000	0	-0.69	33	33
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.006	0.095	-10000	0	-0.46	32	32
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.003	0.12	-10000	0	-0.63	29	29
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	-0.01	0.14	-10000	0	-0.65	38	38
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	0.012	0.09	-10000	0	-0.69	15	15
BID	0.005	0.062	-10000	0	-0.3	32	32
MAP3K1	0.004	0.042	-10000	0	-0.27	9	9
TRADD	0	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	-0.004	0.13	-10000	0	-0.65	29	29
CASP9	0.001	0.002	-10000	0	-10000	0	0
DNA repair	-0.002	0.03	0.18	7	-0.22	4	11
neuron apoptosis	0.021	0.013	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.004	0.12	-10000	0	-0.62	29	29
APAF1	0	0.001	-10000	0	-10000	0	0
CASP6	0.023	0.058	-10000	0	-0.42	4	4
TRAF2	-0.001	0.018	-10000	0	-0.28	4	4
ICAD/CAD	0.004	0.12	-10000	0	-0.62	29	29
CASP7	-0.007	0.038	0.36	9	-10000	0	9
KRT18	0.016	0.016	-10000	0	-10000	0	0
apoptosis	0.009	0.11	-10000	0	-0.55	29	29
DFFA	-0.004	0.13	-10000	0	-0.65	29	29
DFFB	-0.004	0.13	-10000	0	-0.65	29	29
PARP1	0.002	0.031	0.22	4	-0.18	7	11
actin filament polymerization	-0.003	0.12	0.58	32	-10000	0	32
TNF	-0.017	0.1	-10000	0	-0.81	14	14
CYCS	0.008	0.049	-10000	0	-0.22	30	30
SATB1	0.018	0.098	-10000	0	-0.49	25	25
SLK	-0.004	0.13	-10000	0	-0.65	29	29
p15 BID/BAX	-0.013	0.048	-10000	0	-0.35	8	8
CASP2	0.042	0.042	-10000	0	-0.46	1	1
JNK cascade	-0.004	0.041	0.27	9	-10000	0	9
CASP3	-0.012	0.13	-10000	0	-0.65	33	33
LMNB2	0.04	0.039	-10000	0	-0.35	3	3
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.001	0.026	-10000	0	-0.81	1	1
Mammalian IAPs/DIABLO	-0.006	0.047	-10000	0	-0.48	9	9
negative regulation of DNA binding	0.012	0.089	-10000	0	-0.68	15	15
stress fiber formation	-0.003	0.12	-10000	0	-0.63	29	29
GZMB	-0.027	0.15	-10000	0	-0.67	40	40
CASP1	0.013	0.033	-10000	0	-0.44	5	5
LMNB1	0.044	0.04	-10000	0	-0.35	3	3
APP	0.021	0.013	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0	-10000	0	-10000	0	0
VIM	0.004	0.1	-10000	0	-0.53	29	29
LMNA	0.039	0.039	-10000	0	-0.35	3	3
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.005	0.038	-10000	0	-0.49	1	1
LRDD	-0.001	0.015	-10000	0	-0.28	3	3
SREBF1	-0.006	0.13	-10000	0	-0.65	29	29
APAF-1/Caspase 9	-0.003	0.02	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.006	0.093	-10000	0	-0.46	31	31
CFL2	0.003	0.12	-10000	0	-0.6	32	32
GAS2	-0.05	0.19	-10000	0	-0.53	118	118
positive regulation of apoptosis	0.045	0.039	-10000	0	-0.34	3	3
PRF1	-0.019	0.12	-10000	0	-0.81	20	20

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.001	0.027	-10000	0	-0.54	2	2
ANTXR2	-0.008	0.081	-10000	0	-0.81	10	10
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.011	-10000	0	-0.1	11	11
monocyte activation	0.003	0.074	-10000	0	-0.46	25	25
MAP2K2	0	0.004	-10000	0	-10000	0	0
MAP2K1	-0.001	0.009	-10000	0	-10000	0	0
MAP2K7	-0.001	0.009	-10000	0	-10000	0	0
MAP2K6	-0.011	0.07	-10000	0	-0.48	21	21
CYAA	-0.005	0.05	-10000	0	-0.47	11	11
MAP2K4	-0.001	0.018	-10000	0	-0.48	1	1
IL1B	0.006	0.067	-10000	0	-0.35	29	29
Channel	-0.006	0.053	-10000	0	-0.5	11	11
NLRP1	-0.008	0.059	-10000	0	-0.49	14	14
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.001	0.013	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.011	0.1	11	-10000	0	11
MAPK3	-0.001	0.009	-10000	0	-10000	0	0
MAPK1	-0.001	0.009	-10000	0	-10000	0	0
PGR	-0.14	0.21	-10000	0	-0.48	275	275
PA/Cellular Receptors	-0.006	0.057	-10000	0	-0.54	11	11
apoptosis	-0.001	0.011	-10000	0	-0.1	11	11
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.005	0.049	-10000	0	-0.47	11	11
macrophage activation	0.019	0.01	-10000	0	-10000	0	0
TNF	-0.017	0.1	-10000	0	-0.81	14	14
VCAM1	-0.012	0.072	-10000	0	-0.46	25	25
platelet activation	-0.001	0.013	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.022	0.11	21	-10000	0	21
IL18	0.011	0.036	-10000	0	-0.21	14	14
negative regulation of macrophage activation	-0.001	0.011	-10000	0	-0.1	11	11
LEF	-0.001	0.011	-10000	0	-0.1	11	11
CASP1	-0.004	0.029	-10000	0	-0.23	14	14
mol:cAMP	-0.001	0.013	-10000	0	-10000	0	0
necrosis	-0.001	0.011	-10000	0	-0.1	11	11
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.005	0.05	-10000	0	-0.48	11	11
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-10000	0	-10000	0	0
HDAC3	0	0	-10000	0	-10000	0	0
VDR	0	0	-10000	0	-10000	0	0
Cbp/p300/PCAF	-0.001	0.017	-10000	0	-0.53	1	1
EP300	0	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.037	0.038	-10000	0	-0.32	3	3
KAT2B	-0.001	0.026	-10000	0	-0.81	1	1
MAPK14	0	0	-10000	0	-10000	0	0
AKT1	0.02	0.048	0.24	4	-0.35	10	14
RAR alpha/9cRA/Cyclin H	-0.011	0.06	-10000	0	-0.37	24	24
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.034	0.048	-10000	0	-0.32	13	13
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.01	0.059	-10000	0	-0.59	6	6
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	0.006	0.12	-10000	0	-0.58	26	26
NCOA2	-0.025	0.14	-10000	0	-0.81	31	31
NCOA3	0	0.009	-10000	0	-10000	0	0
NCOA1	-0.001	0.026	-10000	0	-0.81	1	1
VDR/VDR/DNA	0	0	-10000	0	-10000	0	0
RARG	0.008	0.005	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.058	-10000	0	-0.81	5	5
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.042	0.11	-10000	0	-0.62	24	24
RARA	0.015	0.057	-10000	0	-0.3	29	29
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.025	0.073	-10000	0	-0.29	42	42
PRKCA	-0.006	0.13	-10000	0	-0.8	24	24
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.006	0.12	-10000	0	-0.61	26	26
RXRG	-0.11	0.21	-10000	0	-0.45	268	268
RXRA	0.023	0.061	-10000	0	-0.32	29	29
RXRB	0.011	0.073	-10000	0	-0.44	24	24
VDR/Vit D3/DNA	0	0	-10000	0	-10000	0	0
RBP1	-0.023	0.094	-10000	0	-0.33	68	68
CRBP1/9-cic-RA	-0.016	0.068	-10000	0	-0.63	7	7
RARB	0.003	0.09	-10000	0	-0.81	12	12
PRKCG	-0.002	0.057	-10000	0	-0.28	41	41
MNAT1	0	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.028	0.11	-10000	0	-0.62	26	26
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.013	0.1	-10000	0	-0.49	27	27
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.052	-10000	0	-0.42	3	3
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.006	0.12	-10000	0	-0.61	26	26
positive regulation of DNA binding	-0.01	0.057	-10000	0	-0.35	24	24
NRIP1	-0.004	0.12	-10000	0	-0.86	7	7
RXRs/RARs	-0.012	0.12	-10000	0	-0.58	29	29
RXRs/RXRs/DNA/9cRA	-0.045	0.11	-10000	0	-0.65	24	24
PRKACA	0	0	-10000	0	-10000	0	0
CDK7	0	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.005	0.031	-10000	0	-10000	0	0
CCNH	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.025	0.029	-9999	-10000	0	0
BIRC5	-0.2	0.13	-9999	-10000	0	0
NFKBIA	-0.023	0.032	-9999	-10000	0	0
CPEB1	-0.15	0.32	-9999	-0.81	189	189
AKT1	-0.023	0.032	-9999	-10000	0	0
NDEL1	0	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.023	0.032	-9999	-0.56	1	1
NDEL1/TACC3	-0.037	0.056	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GSK3B	0.003	0.003	-9999	-10000	0	0
PAK1/Aurora A	-0.028	0.037	-9999	-10000	0	0
MDM2	-0.001	0.018	-9999	-0.28	4	4
JUB	-0.003	0.051	-9999	-0.81	4	4
TPX2	-0.1	0.096	-9999	-10000	0	0
TP53	-0.01	0.015	-9999	-10000	0	0
DLG7	-0.029	0.034	-9999	-10000	0	0
AURKAIP1	-0.002	0.022	-9999	-10000	0	0
ARHGEF7	0	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.04	0.06	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.022	0.032	-9999	-0.55	1	1
AURKA	-0.036	0.043	-9999	-10000	0	0
AURKB	-0.003	0.008	-9999	-10000	0	0
CDC25B	-0.017	0.024	-9999	-10000	0	0
G2/M transition checkpoint	-0.024	0.04	-9999	-0.5	4	4
mRNA polyadenylation	-0.12	0.2	-9999	-0.53	189	189
Aurora A/CPEB	-0.12	0.2	-9999	-0.54	189	189
Aurora A/TACC1/TRAP/chTOG	-0.029	0.087	-9999	-0.48	34	34
BRCA1	-0.001	0.029	-9999	-0.81	1	1
centrosome duplication	-0.028	0.036	-9999	-10000	0	0
regulation of centrosome cycle	-0.037	0.056	-9999	-10000	0	0
spindle assembly	-0.029	0.086	-9999	-0.48	34	34
TDRD7	0	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.098	0.068	-9999	-0.62	1	1
CENPA	0	0.01	-9999	-10000	0	0
Aurora A/PP2A	-0.025	0.029	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.007	0.027	-9999	-10000	0	0
negative regulation of DNA binding	-0.01	0.015	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	-0.001	0.012	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.024	0.04	-9999	-0.51	4	4
mitotic prometaphase	-0.013	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.036	0.043	-9999	-10000	0	0
TACC1	-0.028	0.15	-9999	-0.81	34	34
TACC3	-0.043	0.1	-9999	-0.28	152	152
Aurora A/Antizyme1	-0.019	0.022	-9999	-10000	0	0
Aurora A/RasGAP	-0.025	0.029	-9999	-10000	0	0
OAZ1	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.003	0.003	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.28	5	5
GIT1/beta-PIX/PAK1	-0.004	0.022	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.1	0.096	-9999	-10000	0	0
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.1	0.084	-9999	-10000	0	0
PAK1	-0.006	0.041	-9999	-0.28	22	22
CKAP5	0	0	-9999	-10000	0	0

×

PLK2 and PLK4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0	0.009	-9999	-0.28	1	1
PLK4	-0.011	0.054	-9999	-0.28	39	39
regulation of centriole replication	0.014	0.039	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.03	0.007	-9999	-10000	0	0
SNTA1	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.017	0.044	-9999	-10000	0	0
MAPK12	0.017	0.082	-9999	-0.48	25	25
CCND1	0.015	0.041	-9999	-0.41	4	4
p38 gamma/SNTA1	-0.012	0.072	-9999	-0.47	21	21
MAP2K3	0	0.009	-9999	-0.28	1	1
PKN1	0	0.009	-9999	-0.28	1	1
G2/M transition checkpoint	0.017	0.081	-9999	-0.47	25	25
MAP2K6	0.011	0.084	-9999	-0.5	25	25
MAPT	-0.017	0.14	-9999	-0.41	102	102
MAPK13	0.022	0.009	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.014	0.029	-9999	-0.44	4	4

×

E-cadherin signaling in the nascent adherens junction

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.018	0.1	-9999	-0.59	29	29
KLHL20	-0.008	0.033	-9999	-0.24	3	3
CYFIP2	-0.01	0.063	-9999	-0.33	29	29
Rac1/GDP	0.048	0.07	-9999	-0.35	29	29
ENAH	-0.018	0.099	-9999	-0.58	29	29
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.009	0.05	-9999	-0.5	1	1
ABI1/Sra1/Nap1	-0.006	0.024	-9999	-0.17	3	3
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.086	-9999	-0.48	31	31
RAPGEF1	0.037	0.092	-9999	-0.49	29	29
CTNND1	0	0.009	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.018	0.1	-9999	-0.61	29	29
CRK	0.029	0.1	-9999	-0.54	29	29
E-cadherin/gamma catenin/alpha catenin	-0.016	0.092	-9999	-0.53	30	30
alphaE/beta7 Integrin	-0.006	0.039	-9999	-0.62	2	2
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.003	0.038	-9999	-0.49	6	6
DLG1	-0.018	0.099	-9999	-0.58	29	29
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.04	-9999	-0.32	2	2
MLLT4	-0.005	0.063	-9999	-0.73	7	7
ARF6/GTP/NME1/Tiam1	-0.006	0.027	-9999	-10000	0	0
PI3K	-0.01	0.051	-9999	-0.43	2	2
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.019	0.11	-9999	-0.62	30	30
TIAM1	-0.001	0.018	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	-0.014	0.078	-9999	-0.46	29	29
AKT1	-0.006	0.029	-9999	-0.24	1	1
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
CDH1	-0.024	0.14	-9999	-0.81	29	29
RhoA/GDP	0.047	0.07	-9999	-0.35	29	29
actin cytoskeleton organization	-0.006	0.024	-9999	-0.18	3	3
CDC42/GDP	0.047	0.07	-9999	-0.35	29	29
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.01	0.058	-9999	-0.34	30	30
ITGB7	-0.008	0.056	-9999	-0.32	26	26
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.014	0.082	-9999	-0.48	29	29
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.014	0.079	-9999	-0.47	29	29
mol:GDP	0.045	0.082	-9999	-0.42	29	29
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	-0.001	0.029	-9999	-0.81	1	1
p120 catenin/RhoA/GDP	-0.011	0.061	-9999	-0.36	29	29
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.007	0.028	-9999	-0.21	6	6
NME1	-0.014	0.061	-9999	-0.28	49	49
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.018	0.1	-9999	-0.58	30	30
regulation of cell-cell adhesion	-0.008	0.044	-9999	-0.42	1	1
WASF2	-0.003	0.012	-9999	-10000	0	0
Rap1/GTP	-0.011	0.058	-9999	-0.6	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.081	-9999	-0.45	32	32
CCND1	-0.008	0.034	-9999	-0.26	6	6
VAV2	0.033	0.096	-9999	-0.52	29	29
RAP1/GDP	-0.01	0.058	-9999	-0.57	1	1
adherens junction assembly	-0.017	0.096	-9999	-0.56	30	30
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.016	0.076	-9999	-0.43	32	32
E-cadherin/beta catenin	-0.015	0.084	-9999	-0.5	29	29
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.018	0.099	-9999	-0.58	29	29
PIK3CA	0	0.009	-9999	-0.28	1	1
Rac1/GTP	-0.011	0.053	-9999	-0.37	5	5
E-cadherin/beta catenin/alpha catenin	-0.016	0.09	-9999	-0.53	29	29
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.019	0.11	-9999	-0.62	29	29

×

S1P3 pathway

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
PDGFRB	-0.003	0.051	-9999	-0.81	4	4
mol:S1P	0.001	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	-0.029	0.094	-9999	-0.34	81	81
GNAO1	-0.021	0.14	-9999	-0.48	66	66
S1P/S1P3/G12/G13	-0.001	0.012	-9999	-10000	0	0
AKT1	-0.011	0.053	-9999	-0.68	4	4
AKT3	0.017	0.18	-9999	-1.4	14	14
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.003	0.051	-9999	-0.8	4	4
GNAI2	0.012	0.003	-9999	-10000	0	0
GNAI3	0.012	0.002	-9999	-10000	0	0
GNAI1	-0.03	0.18	-9999	-0.81	51	51
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.009	0.028	-9999	-0.28	9	9
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.1	-9999	-0.39	36	36
MAPK3	0.018	0.099	-9999	-0.52	11	11
MAPK1	0.018	0.099	-9999	-0.52	11	11
JAK2	0.02	0.1	-9999	-0.45	17	17
CXCR4	0.015	0.1	-9999	-0.48	16	16
FLT1	0.013	0.027	-9999	-0.82	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.018	0.099	-9999	-0.52	11	11
S1P/S1P3/Gi	0.01	0.1	-9999	-0.39	36	36
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.024	0.083	-9999	-0.5	11	11
VEGFA	0.01	0.031	-9999	-0.28	11	11
S1P/S1P2/Gi	-0.026	0.088	-9999	-0.31	81	81
VEGFR1 homodimer/VEGFA homodimer	0.021	0.031	-9999	-0.64	1	1
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.006	0.042	-9999	-0.34	15	15
GNAQ	-0.002	0.036	-9999	-0.81	2	2
GNAZ	0.005	0.074	-9999	-0.81	8	8
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.015	0.09	-9999	-0.44	33	33
GNA15	-0.003	0.035	-9999	-0.34	8	8
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.002	0.036	-9999	-0.81	2	2
Rac1/GTP	-0.024	0.083	-9999	-0.5	11	11

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0.008	-10000	0	-10000	0	0
PRKCZ	-0.001	0.026	-10000	0	-0.81	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.007	0.039	-10000	0	-0.42	3	3
IRAK/TOLLIP	-0.001	0.009	-10000	0	-10000	0	0
IKBKB	-0.001	0.013	-10000	0	-10000	0	0
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.03	0.12	-10000	0	-0.6	38	38
IL1A	-0.005	0.038	-10000	0	-0.28	19	19
IL1B	0.009	0.097	-10000	0	-0.71	16	16
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.014	-10000	0	-0.41	1	1
IL1R2	-0.037	0.16	-10000	0	-0.57	64	64
IL1R1	-0.015	0.11	-10000	0	-0.81	18	18
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.001	0.061	0.24	29	-0.32	15	44
TOLLIP	0	0.009	-10000	0	-0.28	1	1
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0	0.004	-10000	0	-10000	0	0
JUN	0.031	0.08	-10000	0	-0.39	34	34
MAP3K7	0	0.009	-10000	0	-0.28	1	1
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.019	0.098	-10000	0	-0.47	40	40
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.011	0.066	-10000	0	-0.48	18	18
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.062	-10000	0	-0.45	18	18
IL1 beta fragment/IL1R1/IL1RAP	-0.018	0.1	-10000	0	-0.54	33	33
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.028	0.071	-10000	0	-0.4	26	26
IRAK1	0.021	0.012	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.019	0.092	-10000	0	-0.62	20	20
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0.009	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
PI3K	-0.005	0.052	-10000	0	-0.62	7	7
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.01	0.057	-10000	0	-0.34	20	20
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.018	0.1	-10000	0	-0.54	33	33
IL1 beta/IL1R2	-0.033	0.13	-10000	0	-0.57	50	50
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.007	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.017	0.087	-10000	0	-0.88	3	3
IRAK3	-0.029	0.15	-10000	0	-0.79	36	36
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.016	0.092	-10000	0	-0.48	33	33
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.006	0.044	-10000	0	-0.33	18	18
IL1 alpha/IL1R1/IL1RAP	-0.012	0.073	-10000	0	-0.53	18	18
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0	0.009	-10000	0	-10000	0	0
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0	0.007	-10000	0	-10000	0	0
IL1RAP	0	0	-10000	0	-10000	0	0
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.013	0.074	-10000	0	-0.78	3	3
CASP1	-0.003	0.051	-10000	0	-0.81	4	4
IL1RN/IL1R2	-0.035	0.12	-10000	0	-0.59	42	42
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.017	0.097	-10000	0	-0.5	33	33
TMEM189-UBE2V1	-0.001	0.013	-10000	0	-0.28	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.007	0.05	-10000	0	-0.38	18	18
PIK3CA	0	0.009	-10000	0	-0.28	1	1
IL1RN	-0.012	0.064	-10000	0	-0.81	2	2
TRAF6/TAK1/TAB1/TAB2	0	0.005	-10000	0	-10000	0	0
MAP2K6	-0.009	0.062	-10000	0	-0.43	21	21

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.007	0.065	-10000	0	-0.62	11	11
ATM	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
PRKDC	-0.001	0.015	-10000	0	-0.28	3	3
ATR	0	0	-10000	0	-10000	0	0
UBE2L3	0	0	-10000	0	-10000	0	0
FANCD2	0.023	0.01	-10000	0	-10000	0	0
protein ubiquitination	-0.025	0.066	-10000	0	-0.51	12	12
XRCC5	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0	0	-10000	0	-10000	0	0
DNA-PK	0	0.007	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.002	0.011	-10000	0	-10000	0	0
FANCF	0	0.009	-10000	0	-10000	0	0
BRCA1	-0.001	0.029	-10000	0	-0.81	1	1
CCNE1	-0.056	0.11	-10000	0	-0.28	200	200
CDK2/Cyclin E1	-0.036	0.071	-10000	0	-10000	0	0
FANCG	0	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.008	0.068	-10000	0	-0.62	12	12
FANCE	0	0	-10000	0	-10000	0	0
FANCC	0	0	-10000	0	-10000	0	0
NBN	0	0	-10000	0	-10000	0	0
FANCA	-0.051	0.11	-10000	0	-0.28	182	182
DNA repair	0.011	0.087	-10000	0	-0.46	6	6
BRCA1/BARD1/ubiquitin	-0.008	0.068	-10000	0	-0.62	12	12
BARD1/DNA-PK	-0.006	0.051	-10000	0	-0.48	11	11
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.007	0.065	0.62	11	-10000	0	11
BRCA1/BARD1/CTIP/M/R/N Complex	-0.004	0.034	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.007	0.059	-10000	0	-0.53	12	12
BRCA1/BARD1/P53	-0.006	0.053	-10000	0	-0.48	12	12
BARD1/CSTF1/BRCA1	-0.007	0.059	-10000	0	-0.53	12	12
BRCA1/BACH1	-0.001	0.028	-10000	0	-0.45	3	3
BARD1	-0.009	0.085	-10000	0	-0.81	11	11
PCNA	-0.001	0.015	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.007	0.059	-10000	0	-0.53	12	12
BRCA1/BARD1/UbcH7	-0.007	0.059	-10000	0	-0.53	12	12
BRCA1/BARD1/RAD51/PCNA	-0.049	0.078	-10000	0	-0.54	12	12
BARD1/DNA-PK/P53	-0.005	0.048	-10000	0	-0.45	11	11
BRCA1/BARD1/Ubiquitin	-0.008	0.068	-10000	0	-0.62	12	12
BRCA1/BARD1/CTIP	-0.006	0.053	-10000	0	-0.48	12	12
FA complex	-0.004	0.009	-10000	0	-10000	0	0
BARD1/EWS	-0.007	0.065	-10000	0	-0.62	11	11
RBBP8	0.022	0.006	-10000	0	-10000	0	0
TP53	0	0	-10000	0	-10000	0	0
TOPBP1	0	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.006	0.053	0.48	12	-10000	0	12
BRCA1/BARD1	-0.025	0.067	-10000	0	-0.51	12	12
CSTF1	0	0.009	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.007	0.066	-10000	0	-0.63	11	11
CDK2	0	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.11	0.14	-10000	0	-10000	0	0
RAD50	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.008	0.068	-10000	0	-0.62	12	12
EWSR1	0	0	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.017	0.085	-9999	-0.52	22	22
MAP4K1	-0.012	0.064	-9999	-0.81	2	2
MAP3K8	-0.004	0.058	-9999	-0.81	5	5
PRKCB	-0.02	0.12	-9999	-0.81	19	19
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	-0.007	0.048	-9999	-0.48	4	4
JUN	0.016	0.11	-9999	-0.58	33	33
MAP3K7	-0.007	0.046	-9999	-0.49	3	3
GRAP2	-0.015	0.11	-9999	-0.81	17	17
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.043	0.057	-9999	-0.46	5	5
LAT	-0.006	0.049	-9999	-0.34	16	16
LCP2	0	0.009	-9999	-0.28	1	1
MAPK8	0.013	0.11	-9999	-0.66	24	24
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.008	0.05	-9999	-0.36	17	17
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.016	0.079	-9999	-0.5	20	20

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.046	0.059	-10000	0	-0.48	4	4
UGCG	-0.008	0.083	-10000	0	-0.8	10	10
AKT1/mTOR/p70S6K/Hsp90/TERT	0.054	0.09	-10000	0	-0.39	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.016	0.085	-10000	0	-0.79	10	10
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.025	0.089	-10000	0	-0.48	13	13
FRAP1	0.052	0.13	-10000	0	-0.44	40	40
FOXO3	0.061	0.11	-10000	0	-0.57	9	9
AKT1	0.056	0.11	-10000	0	-0.44	30	30
GAB2	0.007	0.028	-10000	0	-0.28	9	9
SMPD1	-0.002	0.014	-10000	0	-10000	0	0
SGMS1	-0.002	0.014	-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	0.018	0.048	-10000	0	-0.54	7	7
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	0.034	0.083	-10000	0	-0.49	12	12
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	-0.005	0.052	-10000	0	-0.62	7	7
RPS6KB1	0.021	0.032	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.002	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-0.012	23	23
JAK3	0.008	0.037	-10000	0	-10000	0	0
PIK3R1	0.007	0.069	-10000	0	-0.81	7	7
JAK1	0.013	0.004	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MYC	0.046	0.18	-10000	0	-0.98	26	26
MYB	0.012	0.18	-10000	0	-1.3	18	18
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.054	0.089	-10000	0	-0.61	7	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.003	0.021	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.053	0.087	-10000	0	-0.59	7	7
Rac1/GDP	-0.004	0.041	-10000	0	-0.49	7	7
T cell proliferation	0.059	0.083	-10000	0	-0.52	8	8
SHC1	0.01	0.004	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.01	-10000	0	-0.062	20	20
PRKCZ	0.059	0.086	-10000	0	-0.54	8	8
NF kappa B1 p50/RelA	-0.025	0.087	-10000	0	-0.52	10	10
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.04	0.063	-10000	0	-0.53	4	4
HSP90AA1	0	0.009	-10000	0	-0.28	1	1
RELA	0	0	-10000	0	-10000	0	0
IL2RA	-0.019	0.11	-10000	0	-0.36	77	77
IL2RB	0.001	0.057	-10000	0	-0.28	40	40
TERT	-0.038	0.096	-10000	0	-0.28	135	135
E2F1	0.024	0.063	-10000	0	-0.44	18	18
SOS1	0.01	0.004	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.004	0.027	20	-10000	0	20
PTPN11	0.01	0.004	-10000	0	-10000	0	0
IL2RG	-0.005	0.089	-10000	0	-0.81	7	7
actin cytoskeleton organization	0.059	0.083	-10000	0	-0.52	8	8
GRB2	0.009	0.01	-10000	0	-0.28	1	1
IL2	0.006	0.028	-10000	0	-0.28	3	3
PIK3CA	0.013	0.01	-10000	0	-0.28	1	1
Rac1/GTP	0.027	0.043	-10000	0	-0.47	7	7
LCK	-0.008	0.11	-10000	0	-0.8	13	13
BCL2	0.038	0.2	-10000	0	-0.9	38	38

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0	0	-9999	-10000	0	0
SPHK1	-0.006	0.051	-9999	-0.81	2	2
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	-0.001	0.017	-9999	-0.36	2	2
GNAO1	-0.032	0.14	-9999	-0.48	66	66
mol:Sphinganine-1-P	0.017	0.038	-9999	-0.62	2	2
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.001	0.011	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	-0.003	0.026	-9999	-0.28	9	9
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.001	0.015	-9999	-0.31	2	2
S1PR5	-0.008	0.059	-9999	-0.81	3	3
S1PR4	-0.014	0.08	-9999	-0.36	40	40
GNAI1	-0.042	0.18	-9999	-0.81	51	51
S1P/S1P5/G12	-0.005	0.033	-9999	-0.48	3	3
S1P/S1P3/Gq	-0.005	0.037	-9999	-0.29	15	15
S1P/S1P4/Gi	-0.027	0.085	-9999	-0.34	39	39
GNAQ	-0.002	0.036	-9999	-0.81	2	2
GNAZ	-0.007	0.072	-9999	-0.81	8	8
GNA14	-0.015	0.09	-9999	-0.44	33	33
GNA15	-0.003	0.035	-9999	-0.34	8	8
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	-0.002	0.036	-9999	-0.81	2	2
ABCC1	0	0	-9999	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	-0.017	0.078	0.33	1	-0.36	47	48
FRAP1	0.011	0.02	-10000	0	-10000	0	0
AKT1	-0.015	0.067	0.24	1	-0.3	47	48
INSR	0	0.009	-10000	0	-0.28	1	1
Insulin Receptor/Insulin	0	0.005	-10000	0	-10000	0	0
mol:GTP	-0.012	0.051	-10000	0	-0.34	8	8
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.016	-10000	0	-10000	0	0
TSC2	0	0.001	-10000	0	-10000	0	0
RHEB/GDP	-0.01	0.044	-10000	0	-0.31	8	8
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.017	0.084	-10000	0	-0.42	41	41
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.004	0.019	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.019	0.042	-10000	0	-0.26	8	8
MAP3K5	0.009	0.025	-10000	0	-0.44	3	3
PIK3R1	-0.006	0.068	-10000	0	-0.81	7	7
apoptosis	0.009	0.025	-10000	0	-0.44	3	3
mol:LY294002	0	0	-10000	0	-0.002	41	41
EIF4B	0.025	0.038	0.19	1	-0.22	8	9
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.006	0.028	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.001	0.007	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.019	0.083	-10000	0	-0.38	48	48
mTOR/RHEB/GTP/Raptor/GBL	0.026	0.029	0.18	1	-0.19	7	8
FKBP1A	0	0.009	-10000	0	-0.28	1	1
RHEB/GTP	-0.01	0.044	-10000	0	-0.31	8	8
mol:Amino Acids	0	0	-10000	0	-0.002	41	41
FKBP12/Rapamycin	0	0.006	-10000	0	-10000	0	0
PDPK1	-0.015	0.07	0.26	1	-0.32	47	48
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.003	0.036	-10000	0	-0.63	3	3
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.016	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.012	0.055	-10000	0	-0.37	8	8
tumor necrosis factor receptor activity	0	0	0.002	41	-10000	0	41
RPS6	0	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
EIF4G1	0	0	-10000	0	-10000	0	0
IRS1	-0.011	0.092	-10000	0	-0.45	41	41
INS	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.036	-10000	0	-0.8	2	2
PDK2	-0.017	0.076	0.26	1	-0.34	50	51
EIF4EBP1	0.014	0.014	-10000	0	-10000	0	0
PIK3CA	0	0.009	-10000	0	-0.28	1	1
PPP2R5D	0.018	0.019	-10000	0	-10000	0	0
peptide biosynthetic process	0	0.004	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
EIF4A1	0	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	2	-0.003	7	9
EEF2	0	0.004	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.048	0.03	-10000	0	-0.36	4	4
NFATC2	0.018	0.06	-10000	0	-0.3	8	8
NFATC3	-0.001	0.016	-10000	0	-0.52	1	1
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.012	0.096	-10000	0	-0.4	32	32
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.018	0.075	-10000	0	-0.5	14	14
BCL2/BAX	-0.023	0.12	-10000	0	-0.62	35	35
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+	-0.001	0.003	-10000	0	-10000	0	0
BAX	-0.001	0.018	-10000	0	-0.28	4	4
MAPK14	0	0	-10000	0	-10000	0	0
BAD	0	0.009	-10000	0	-0.28	1	1
CABIN1/MEF2D	-0.02	0.082	-10000	0	-0.56	14	14
Calcineurin A alpha-beta B1/BCL2	-0.029	0.15	-10000	0	-0.8	35	35
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.02	0.081	0.55	14	-10000	0	14
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	-0.029	0.085	-10000	0	-0.28	103	103
XPO1	0	0	-10000	0	-10000	0	0
SFN	-0.015	0.098	-10000	0	-0.51	30	30
MAP3K8	-0.004	0.058	-10000	0	-0.81	5	5
NFAT4/CK1 alpha	-0.001	0.018	-10000	0	-0.39	2	2
MEF2D/NFAT1/Cbp/p300	-0.035	0.091	-10000	0	-0.47	3	3
CABIN1	0.012	0.097	-10000	0	-0.41	32	32
CALM1	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.026	-10000	0	-0.81	1	1
CAMK4	-0.01	0.051	-10000	0	-0.28	34	34
mol:Ca2+	-0.001	0.006	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.01	0.043	-10000	0	-0.62	1	1
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	-0.004	0.057	-10000	0	-0.81	5	5
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0.009	-10000	0	-0.28	1	1
NFAT1-c-4/YWHAQ	-0.002	0.022	-10000	0	-0.41	1	1
PRKCH	-0.001	0.026	-10000	0	-0.81	1	1
CABIN1/Cbp/p300	-0.001	0.003	-10000	0	-10000	0	0
CASP3	0	0	-10000	0	-10000	0	0
PIM1	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-10000	0	-10000	0	0
apoptosis	-0.007	0.036	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.024	-10000	0	-10000	0	0
PRKCB	-0.02	0.12	-10000	0	-0.81	19	19
PRKCE	-0.001	0.026	-10000	0	-0.81	1	1
JNK2/NFAT4	0	0.015	-10000	0	-0.47	1	1
BAD/BCL-XL	0	0.006	-10000	0	-10000	0	0
PRKCD	0	0.009	-10000	0	-0.28	1	1
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	-0.001	0.026	-10000	0	-0.81	1	1
PRKCA	-0.02	0.12	-10000	0	-0.81	24	24
PRKCG	-0.012	0.056	-10000	0	-0.28	41	41
PRKCQ	-0.037	0.16	-10000	0	-0.67	54	54
FKBP38/BCL2	-0.022	0.11	-10000	0	-0.62	35	35
EP300	0	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	0.048	0.044	-10000	0	-0.38	6	6
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0.006	-10000	0	-10000	0	0
CSNK1A1	0.018	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.005	0.026	-10000	0	-10000	0	0
NFATc/ERK1	0.048	0.033	-10000	0	-0.36	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.018	0.074	-10000	0	-0.5	14	14
NR4A1	-0.066	0.2	-10000	0	-0.72	82	82
GSK3B	0	0	-10000	0	-10000	0	0
positive T cell selection	-0.001	0.016	-10000	0	-0.52	1	1
NFAT1/CK1 alpha	-0.014	0.036	-10000	0	-0.26	5	5
RCH1/ KPNB1	-0.018	0.054	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
AKAP5	-0.015	0.066	-10000	0	-0.29	51	51
MEF2D	0	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	-0.001	0.015	-10000	0	-0.28	3	3
NFATc/p38 alpha	0.05	0.031	-10000	0	-0.36	1	1
CREBBP	0	0.001	-10000	0	-10000	0	0
BCL2	-0.029	0.15	-10000	0	-0.81	35	35

×

p38 MAPK 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.001	0.026	-10000	0	-0.47	3	3
TRAF2/ASK1	-0.002	0.031	-10000	0	-0.54	3	3
ATM	0	0	-10000	0	-10000	0	0
MAP2K3	0.025	0.044	-10000	0	-0.42	2	2
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.027	0.06	-10000	0	-0.36	7	7
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.03	0.087	-10000	0	-0.28	108	108
TXN	0.008	0.005	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
GADD45A	0	0	-10000	0	-10000	0	0
GADD45B	0	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.026	-10000	0	-0.81	1	1
MAP3K6	-0.001	0.026	-10000	0	-0.81	1	1
MAP3K7	0	0.009	-10000	0	-0.28	1	1
MAP3K4	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.002	0.039	-10000	0	-0.62	4	4
TAK1/TAB family	0.001	0.012	0.22	3	-10000	0	3
RAC1/OSM/MEKK3	0	0.005	-10000	0	-10000	0	0
TRAF2	-0.001	0.018	-10000	0	-0.28	4	4
RAC1/OSM/MEKK3/MKK3	-0.006	0.022	-10000	0	-0.4	1	1
TRAF6	0.008	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.073	0.22	-10000	0	-0.81	74	74
CCM2	-0.001	0.013	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.047	0.14	-10000	0	-0.54	74	74
MAPK11	-0.002	0.044	-10000	0	-0.81	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.044	0.13	-10000	0	-0.5	76	76
OSM/MEKK3	0	0.008	-10000	0	-10000	0	0
TAOK1	0	0.084	-10000	0	-0.44	34	34
TAOK2	0.016	0	-10000	0	-10000	0	0
TAOK3	0.016	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	-0.002	0.044	-10000	0	-0.81	3	3
MAP3K10	0	0.009	-10000	0	-0.28	1	1
MAP3K3	0	0	-10000	0	-10000	0	0
TRX/ASK1	-0.002	0.029	-10000	0	-0.53	3	3
GADD45/MTK1/MTK1	-0.011	0.032	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.005	0.051	-10000	0	-0.48	11	11
HDAC3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.013	-10000	0	-0.41	1	1
GATA1/HDAC4	-0.003	0.028	-10000	0	-0.62	1	1
GATA1/HDAC5	-0.002	0.02	-10000	0	-10000	0	0
GATA2/HDAC5	-0.019	0.1	-10000	0	-0.62	27	27
HDAC5/BCL6/BCoR	-0.003	0.041	-10000	0	-0.53	6	6
HDAC9	-0.01	0.078	-10000	0	-0.81	8	8
Glucocorticoid receptor/Hsp90/HDAC6	-0.007	0.058	-10000	0	-0.53	12	12
HDAC4/ANKRA2	-0.001	0.02	-10000	0	-0.62	1	1
HDAC5/YWHAB	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
GATA2	-0.025	0.13	-10000	0	-0.65	38	38
HDAC4/RFXANK	-0.001	0.023	-10000	0	-0.62	1	1
BCOR	-0.002	0.036	-10000	0	-0.81	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0	-10000	0	-10000	0	0
HDAC5	0	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.007	0.065	-10000	0	-0.62	11	11
Histones	-0.003	0.025	-10000	0	-10000	0	0
ADRBK1	0	0	-10000	0	-10000	0	0
HDAC4	-0.001	0.026	-10000	0	-0.81	1	1
XPO1	0	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0	0	-10000	0	-10000	0	0
HDAC4/Ubc9	-0.001	0.02	-10000	0	-0.62	1	1
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0	0	-10000	0	-10000	0	0
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0	0	-10000	0	-10000	0	0
HDAC5/RFXANK	-0.001	0.011	-10000	0	-10000	0	0
CAMK4	-0.01	0.051	-10000	0	-0.28	34	34
Tubulin/HDAC6	0	0.006	-10000	0	-10000	0	0
SUMO1	0	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
GATA1	-0.004	0.032	-10000	0	-0.28	13	13
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
NR3C1	-0.01	0.088	-10000	0	-0.81	12	12
SUMO1/HDAC4	0	0.014	-10000	0	-0.45	1	1
SRF	0	0	-10000	0	-10000	0	0
HDAC4/YWHAB	-0.001	0.02	-10000	0	-0.62	1	1
Tubulin	0	0.008	-10000	0	-10000	0	0
HDAC4/14-3-3 E	-0.001	0.02	-10000	0	-0.62	1	1
GNB1	0	0	-10000	0	-10000	0	0
RANGAP1	0	0	-10000	0	-10000	0	0
BCL6/BCoR	-0.004	0.048	-10000	0	-0.62	6	6
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.017	-10000	0	-0.53	1	1
HDAC4/SRF	-0.005	0.03	-10000	0	-0.53	1	1
HDAC4/ER alpha	-0.11	0.22	-10000	0	-0.62	148	148
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.002	0.025	-10000	0	-10000	0	0
cell motility	0	0.006	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0	0	-10000	0	-10000	0	0
BCL6	-0.003	0.051	-10000	0	-0.81	4	4
HDAC4/CaMK II delta B	-0.001	0.026	-10000	0	-0.8	1	1
Hsp90/HDAC6	0	0.006	-10000	0	-10000	0	0
ESR1	-0.15	0.29	-10000	0	-0.57	264	264
HDAC6/HDAC11	0	0.008	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	-0.002	0.036	-10000	0	-0.81	2	2
RAN	0	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.001	0.025	-10000	0	-0.45	3	3
GNG2	-0.009	0.085	-10000	0	-0.81	11	11
NCOR2	0	0	-10000	0	-10000	0	0
TUBB2A	-0.001	0.013	-10000	0	-0.28	2	2
HDAC11	-0.001	0.013	-10000	0	-10000	0	0
HSP90AA1	0	0.009	-10000	0	-0.28	1	1
RANBP2	0	0	-10000	0	-10000	0	0
ANKRA2	0	0	-10000	0	-10000	0	0
RFXANK	-0.001	0.018	-10000	0	-0.28	4	4
nuclear import	0	0.014	0.44	1	-10000	0	1

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.008	0.056	-9999	-0.32	26	26
ITGA4	-0.003	0.026	-9999	-0.28	9	9
alpha4/beta7 Integrin	-0.007	0.044	-9999	-0.46	5	5
alpha4/beta1 Integrin	-0.002	0.017	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	-0.003	0.024	-9999	-0.41	2	2
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.003	0.026	-9999	-0.28	9	9
alpha4/beta7 Integrin/MAdCAM1	-0.009	0.041	-9999	-0.45	3	3
EPO	-0.046	0.1	-9999	-0.28	163	163
alpha4/beta7 Integrin	-0.007	0.044	-9999	-0.46	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.017	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.029	0.065	-9999	-10000	0	0
lamellipodium assembly	-0.002	0.035	-9999	-0.41	7	7
PIK3CA	0	0.009	-9999	-0.28	1	1
PI3K	-0.005	0.052	-9999	-0.62	7	7
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.009	0.024	-9999	-0.51	1	1
PXN	0	0	-9999	-10000	0	0
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
MADCAM1	-0.011	0.054	-9999	-0.28	39	39
cell adhesion	-0.009	0.041	-9999	-0.45	3	3
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.007	0.052	-9999	-0.48	11	11
ITGB7	-0.008	0.056	-9999	-0.32	26	26
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.008	0.058	-9999	-0.53	11	11
p130Cas/Crk/Dock1	-0.006	0.043	-9999	-10000	0	0
VCAM1	-0.011	0.087	-9999	-0.81	11	11
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.002	0.013	-9999	-10000	0	0
BCAR1	0.033	0.054	-9999	-0.45	11	11
EPOR	0	0.009	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.28	5	5
Rac1/GTP	-0.002	0.036	-9999	-0.42	7	7

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	-0.001	0.029	-9999	-0.91	1	1
VEGFR1 homodimer/NRP1	-0.001	0.029	-9999	-0.92	1	1
mol:DAG	0.038	0.033	-9999	-0.65	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	-0.002	0.03	-9999	-0.86	1	1
CaM/Ca2+	-0.002	0.029	-9999	-0.62	2	2
HIF1A	0	0.012	-9999	-0.38	1	1
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.004	0.044	-9999	-0.72	1	1
PLCG1	0.038	0.033	-9999	-0.66	2	2
NOS3	0.061	0.032	-9999	-0.56	2	2
CBL	0	0	-9999	-10000	0	0
mol:NO	0.061	0.031	-9999	-0.54	2	2
FLT1	0.028	0.033	-9999	-1	1	1
PGF	-0.002	0.03	-9999	-0.41	4	4
VEGFR1 homodimer/NRP2/VEGFR121	-0.004	0.049	-9999	-0.79	3	3
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.28	1	1
eNOS/Hsp90	-0.002	0.025	-9999	-0.65	1	1
endothelial cell proliferation	0.036	0.091	-9999	-0.7	5	5
mol:Ca2+	0.037	0.033	-9999	-0.65	2	2
MAPK3	0.039	0.082	-9999	-0.45	24	24
MAPK1	0.039	0.082	-9999	-0.45	25	25
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
PLGF homodimer	-0.002	0.03	-9999	-0.41	4	4
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.17	0.33	-9999	-0.81	208	208
VEGFA homodimer	-0.003	0.029	-9999	-0.28	11	11
VEGFR1 homodimer/VEGFA homodimer	-0.002	0.032	-9999	-0.91	1	1
platelet activating factor biosynthetic process	0.046	0.08	-9999	-1.1	1	1
PI3K	-0.005	0.048	-9999	-0.49	9	9
PRKCA	0.033	0.086	-9999	-0.48	25	25
PRKCB	0.033	0.08	-9999	-0.49	20	20
VEGFR1 homodimer/PLGF homodimer	-0.002	0.034	-9999	-0.72	2	2
VEGFA	-0.003	0.029	-9999	-0.28	11	11
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.038	0.033	-9999	-0.65	2	2
RASA1	0.039	0.028	-9999	-0.84	1	1
NRP2	-0.003	0.045	-9999	-0.68	4	4
VEGFR1 homodimer	0.028	0.033	-9999	-1	1	1
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.081	0.16	-9999	-0.67	5	5
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.005	0.047	-9999	-0.48	9	9
mol:L-citrulline	0.061	0.031	-9999	-0.54	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.002	0.028	-9999	-0.81	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.002	0.029	-9999	-0.85	1	1
CD2AP	0	0.009	-9999	-0.28	1	1
PI3K/GAB1	-0.004	0.045	-9999	-0.46	9	9
PDPK1	-0.004	0.044	-9999	-0.45	9	9
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.002	0.029	-9999	-0.85	1	1
mol:NADP	0.061	0.031	-9999	-0.54	2	2
HSP90AA1	0	0.009	-9999	-0.28	1	1
ubiquitin-dependent protein catabolic process	-0.002	0.028	-9999	-0.79	1	1
VEGFR1 homodimer/NRP2	-0.003	0.05	-9999	-0.81	3	3

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.018	0.1	-9999	-0.62	28	28
AKT1	0.081	0.066	-9999	-0.68	6	6
PTK2B	-0.017	0.1	-9999	-1	6	6
VEGFR2 homodimer/Frs2	-0.006	0.074	-9999	-0.98	5	5
CAV1	-0.17	0.33	-9999	-0.81	208	208
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.007	0.07	-9999	-0.92	5	5
endothelial cell proliferation	0.083	0.083	-9999	-0.64	7	7
mol:Ca2+	0.051	0.067	-9999	-0.92	4	4
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.003	0.066	-9999	-0.99	4	4
RP11-342D11.1	0.043	0.067	-9999	-0.76	6	6
CDH5	-0.007	0.072	-9999	-0.81	8	8
VEGFA homodimer	-0.001	0.011	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.02	0.13	-9999	-0.81	25	25
HRAS/GDP	-0.003	0.052	-9999	-0.77	4	4
SH2D2A	-0.033	0.094	-9999	-0.81	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.002	0.05	-9999	-0.71	4	4
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.018	0.08	-9999	-0.83	7	7
VEGFR1 homodimer	-0.001	0.026	-9999	-0.8	1	1
SHC/GRB2/SOS1	-0.003	0.061	-9999	-0.89	4	4
GRB10	0.051	0.067	-9999	-0.92	4	4
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0.009	-9999	-0.28	1	1
PAK1	-0.006	0.041	-9999	-0.28	22	22
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.007	0.089	-9999	-1.1	6	6
HRAS	-0.001	0.02	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.009	0.059	-9999	-0.59	6	6
HIF1A	0	0	-9999	-10000	0	0
FRS2	-0.003	0.028	-9999	-0.28	10	10
oxygen and reactive oxygen species metabolic process	-0.003	0.064	-9999	-0.96	4	4
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.002	0.044	-9999	-0.81	3	3
Nck/Pak	-0.004	0.026	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.007	0.078	-9999	-0.94	6	6
mol:GDP	-0.003	0.057	-9999	-0.84	4	4
mol:NADP	0.074	0.047	-9999	-0.57	4	4
eNOS/Hsp90	0.075	0.044	-9999	-0.53	4	4
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
mol:IP3	0.051	0.069	-9999	-0.94	4	4
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	-0.001	0.027	-9999	-0.54	2	2
VEGFA	-0.003	0.029	-9999	-0.27	11	11
VEGFC	0	0	-9999	-10000	0	0
FAK1/Vinculin	-0.011	0.081	-9999	-0.96	5	5
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.016	0.11	-9999	-0.58	29	29
PTPN6	-0.001	0.013	-9999	-0.28	2	2
EPAS1	-0.004	0.061	-9999	-0.78	5	5
mol:L-citrulline	0.074	0.047	-9999	-0.57	4	4
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.28	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.002	0.067	-9999	-0.88	5	5
VEGFR2 homodimer/VEGFA homodimer	-0.004	0.07	-9999	-0.84	6	6
VEGFR2/3 heterodimer	-0.006	0.086	-9999	-1.1	6	6
VEGFB	0	0	-9999	-10000	0	0
MAPK11	0.056	0.073	-9999	-0.99	4	4
VEGFR2 homodimer	0.029	0.083	-9999	-1.1	5	5
FLT1	-0.001	0.026	-9999	-0.81	1	1
NEDD4	-0.001	0.026	-9999	-0.8	1	1
MAPK3	0.051	0.08	-9999	-0.81	6	6
MAPK1	0.051	0.08	-9999	-0.81	6	6
VEGFA145/NRP2	-0.004	0.041	-9999	-0.66	3	3
VEGFR1/2 heterodimer	-0.005	0.08	-9999	-1.1	5	5
KDR	0.029	0.083	-9999	-1.1	5	5
VEGFA165/NRP1/VEGFR2 homodimer	-0.005	0.079	-9999	-1	5	5
SRC	0	0.009	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.054	0.081	-9999	-0.92	5	5
PI3K	-0.007	0.075	-9999	-0.9	6	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.006	0.069	-9999	-0.92	5	5
FES	0.05	0.076	-9999	-0.96	4	4
GAB1	-0.004	0.065	-9999	-0.99	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	-0.006	0.069	-9999	-0.92	5	5
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.009	0.17	-9999	-0.59	10	10
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.006	0.071	-9999	-0.84	6	6
PI3K/GAB1	0.08	0.071	-9999	-0.72	6	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0	0.065	-9999	-0.95	4	4
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.006	0.081	-9999	-1	6	6
HSP90AA1	0	0.009	-9999	-0.28	1	1
CDC42	0.051	0.071	-9999	-0.96	4	4
actin cytoskeleton reorganization	-0.017	0.078	-9999	-0.81	7	7
PTK2	0.054	0.1	-9999	-1	6	6
EDG1	0.043	0.067	-9999	-0.76	6	6
mol:DAG	0.051	0.069	-9999	-0.94	4	4
CaM/Ca2+	-0.005	0.058	-9999	-0.85	4	4
MAP2K3	0.058	0.07	-9999	-0.9	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.004	0.067	-9999	-0.98	4	4
PLCG1	0.051	0.071	-9999	-0.96	4	4
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.004	0.068	-9999	-0.99	4	4
IQGAP1	0	0	-9999	-10000	0	0
YES1	-0.001	0.026	-9999	-0.81	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.006	0.069	-9999	-0.92	5	5
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.006	0.069	-9999	-0.92	5	5
cell migration	0.08	0.081	-9999	-0.8	5	5
mol:PI-3-4-5-P3	-0.006	0.066	-9999	-0.79	6	6
FYN	-0.002	0.036	-9999	-0.81	2	2
VEGFB/NRP1	-0.005	0.059	-9999	-0.87	4	4
mol:NO	0.074	0.047	-9999	-0.57	4	4
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.005	0.053	-9999	-0.78	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.004	0.067	-9999	-0.98	4	4
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.024	0.14	-9999	-0.81	28	28
NOS3	0.076	0.053	-9999	-0.67	4	4
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.018	0.1	-9999	-0.55	30	30
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.047	0.1	-9999	-1.1	4	4
PRKCB	0.047	0.1	-9999	-0.94	6	6
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.004	0.064	-9999	-0.76	6	6
VEGFR1/2 heterodimer/VEGFA homodimer	-0.006	0.076	-9999	-1	5	5
VEGFA165/NRP2	-0.004	0.041	-9999	-0.66	3	3
MAPKKK cascade	-0.003	0.054	-9999	-0.78	4	4
NRP2	-0.003	0.045	-9999	-0.68	4	4
VEGFC homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
ROCK1	-0.001	0.026	-9999	-0.81	1	1
FAK1/Paxillin	-0.011	0.081	-9999	-0.96	5	5
MAP3K13	0.05	0.074	-9999	-0.96	4	4
PDPK1	0.074	0.064	-9999	-0.67	6	6

×

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	-0.005	0.048	-9999	-0.57	6	6
PDGFB-D/PDGFRB/SLAP	-0.004	0.042	-9999	-0.62	4	4
PDGFB-D/PDGFRB/APS/CBL	-0.008	0.043	-9999	-0.53	4	4
AKT1	-0.01	0.046	-9999	-0.56	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.005	0.05	-9999	-0.6	6	6
PIK3CA	0	0.009	-9999	-0.28	1	1
FGR	-0.003	0.04	-9999	-0.54	5	5
mol:Ca2+	0.032	0.05	-9999	-0.69	4	4
MYC	0.037	0.14	-9999	-0.83	25	25
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.003	0.03	-9999	-0.43	4	4
LRP1/PDGFRB/PDGFB	-0.007	0.07	-9999	-0.61	12	12
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.032	0.051	-9999	-0.7	4	4
PTEN	-0.002	0.036	-9999	-0.81	2	2
GRB2	0	0.009	-9999	-0.28	1	1
GRB7	-0.02	0.075	-9999	-0.29	70	70
PDGFB-D/PDGFRB/SHP2	-0.002	0.039	-9999	-0.62	4	4
PDGFB-D/PDGFRB/GRB10	-0.002	0.039	-9999	-0.62	4	4
cell cycle arrest	-0.004	0.042	-9999	-0.61	4	4
HRAS	-0.001	0.02	-9999	-10000	0	0
HIF1A	0.052	0.055	-9999	-0.48	2	2
GAB1	0.035	0.058	-9999	-0.68	4	4
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.039	0.055	-9999	-0.62	4	4
PDGFB-D/PDGFRB	-0.003	0.037	-9999	-0.54	4	4
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.002	0.039	-9999	-0.62	4	4
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.006	0.052	-9999	-0.58	6	6
positive regulation of MAPKKK cascade	-0.002	0.039	-9999	-0.61	4	4
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
mol:IP3	0.032	0.052	-9999	-0.71	4	4
E5	0	0.001	-9999	-10000	0	0
CSK	0	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.016	0.062	-9999	-0.62	5	5
SHB	-0.001	0.027	-9999	-0.54	2	2
BLK	-0.002	0.053	-9999	-0.59	7	7
PTPN2	0.001	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.002	0.039	-9999	-0.62	4	4
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.039	0.065	-9999	-0.62	5	5
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.002	0.039	-9999	-0.62	4	4
LCK	-0.011	0.085	-9999	-0.64	16	16
PDGFRB	0.008	0.052	-9999	-0.81	4	4
ACP1	0	0	-9999	-10000	0	0
HCK	-0.003	0.035	-9999	-0.52	4	4
ABL1	0.033	0.052	-9999	-0.64	4	4
PDGFB-D/PDGFRB/CBL	0.033	0.064	-9999	-0.8	4	4
PTPN1	-0.003	0.029	-9999	-0.28	11	11
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	-0.005	0.037	-9999	-0.28	18	18
cell proliferation	0.039	0.12	-9999	-0.72	25	25
SLA	-0.003	0.026	-9999	-0.28	9	9
actin cytoskeleton reorganization	-0.003	0.03	-9999	-0.41	5	5
SRC	-0.003	0.035	-9999	-0.52	4	4
PI3K	-0.011	0.052	-9999	-0.64	2	2
PDGFB-D/PDGFRB/GRB7/SHC	-0.012	0.051	-9999	-0.53	5	5
SH2B2	-0.012	0.057	-9999	-0.28	43	43
PLCgamma1/SPHK1	-0.005	0.052	-9999	-0.62	6	6
LYN	-0.003	0.035	-9999	-0.52	4	4
LRP1	-0.008	0.081	-9999	-0.81	10	10
SOS1	0	0	-9999	-10000	0	0
STAT5B	-0.002	0.044	-9999	-0.81	3	3
STAT5A	-0.007	0.072	-9999	-0.81	8	8
NCK1-2/p130 Cas	-0.003	0.028	-9999	-0.43	4	4
SPHK1	-0.006	0.051	-9999	-0.81	2	2
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.032	0.052	-9999	-0.71	4	4
PLCG1	0.032	0.054	-9999	-0.74	4	4
NHERF/PDGFRB	-0.014	0.05	-9999	-0.53	4	4
YES1	-0.003	0.04	-9999	-0.54	5	5
cell migration	-0.014	0.05	-9999	-0.53	4	4
SHC/Grb2/SOS1	-0.003	0.029	-9999	-0.43	4	4
SLC9A3R2	-0.001	0.013	-9999	-0.28	2	2
SLC9A3R1	-0.023	0.077	-9999	-0.28	83	83
NHERF1-2/PDGFRB/PTEN	-0.012	0.048	-9999	-0.48	6	6
FYN	-0.004	0.064	-9999	-0.91	4	4
DOK1	0.002	0.036	-9999	-0.48	4	4
HRAS/GTP	-0.001	0.013	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.045	0.085	-9999	-0.45	27	27
PRKCD	0.029	0.037	-9999	-0.49	4	4
FER	0.023	0.071	-9999	-0.52	15	15
MAPKKK cascade	-0.002	0.029	-9999	-0.42	4	4
RASA1	0.029	0.037	-9999	-0.49	4	4
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	-0.002	0.03	-9999	-0.44	4	4
PDGFB-D/PDGFRB/SHB	-0.003	0.044	-9999	-0.62	5	5
chemotaxis	0.033	0.05	-9999	-0.62	4	4
STAT1-3-5/STAT1-3-5	-0.008	0.058	-9999	-0.48	13	13
Bovine Papilomavirus E5/PDGFRB	-0.003	0.04	-9999	-0.63	4	4
PTPRJ	0	0	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.001	0.026	-9999	-0.81	1	1
SMAD2	0.014	0.005	-9999	-10000	0	0
SMAD3	0.041	0	-9999	-10000	0	0
SMAD3/SMAD4	0.005	0.017	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	-0.001	0.017	-9999	-0.53	1	1
SMAD2/SMAD2/SMAD4	-0.009	0.03	-9999	-0.53	1	1
PPM1A	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
SMAD2/SMAD4	0	0.015	-9999	-0.48	1	1
MAP3K1	-0.001	0.026	-9999	-0.81	1	1
TRAP-1/SMAD4	-0.007	0.065	-9999	-0.62	11	11
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
NUP214	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
CTDSP2	0	0	-9999	-10000	0	0
CTDSPL	0	0	-9999	-10000	0	0
KPNB1	0	0	-9999	-10000	0	0
TGFBRAP1	-0.008	0.081	-9999	-0.81	10	10
UBE2I	0	0	-9999	-10000	0	0
NUP153	0	0.009	-9999	-0.28	1	1
KPNA2	-0.029	0.085	-9999	-0.28	103	103
PIAS4	0	0	-9999	-10000	0	0

×

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

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
BAG4	-0.004	0.046	-9999	-0.37	12	12
Caspase 8 (4 units)	-0.008	0.046	-9999	-1	1	1
NEF	-0.005	0.024	-9999	-10000	0	0
NFKBIA	-0.001	0.011	-9999	-10000	0	0
BIRC3	0.034	0.085	-9999	-0.81	9	9
CYCS	0.041	0.057	-9999	-0.95	1	1
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.027	0.13	-9999	-0.7	30	30
MAP2K7	0.042	0.047	-9999	-0.81	1	1
protein ubiquitination	0.065	0.035	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.002	0.044	-9999	-0.81	3	3
BID	-0.009	0.051	-9999	-1	1	1
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.034	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
MAP3K5	-0.002	0.044	-9999	-0.81	3	3
CFLAR	0	0	-9999	-10000	0	0
FADD	-0.005	0.035	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.034	-9999	-10000	0	0
MAPK8	0.046	0.055	-9999	-0.46	6	6
APAF1	0	0	-9999	-10000	0	0
TRAF1	-0.001	0.018	-9999	-0.28	4	4
TRAF2	-0.001	0.018	-9999	-0.28	4	4
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.01	0.055	-9999	-0.38	12	12
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.002	0.033	-9999	-0.37	2	2
CHUK	0.067	0.037	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.004	0.045	-9999	-0.57	5	5
TCRz/NEF	-0.025	0.11	-9999	-0.54	37	37
TNF	-0.017	0.1	-9999	-0.81	14	14
FASLG	-0.006	0.14	-9999	-0.64	37	37
NFKB1	-0.001	0.011	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.072	-9999	-0.54	16	16
CASP6	-0.004	0.031	-9999	-0.71	1	1
CASP7	0.073	0.077	-9999	-0.63	9	9
RELA	-0.001	0.011	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.073	0.077	-9999	-0.63	9	9
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.003	0.033	-9999	-0.62	2	2
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.062	0.039	-9999	-0.35	1	1
APAF-1/Caspase 9	-0.009	0.055	-9999	-0.52	9	9
BCL2	0.037	0.1	-9999	-0.42	39	39

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.044	0.049	-10000	0	-0.56	1	1
BAG4	-0.004	0.046	-10000	0	-0.37	12	12
BAD	0.032	0.018	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.081	-10000	0	-0.81	9	9
BAX	0.031	0.019	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.015	0.013	-10000	0	-0.1	2	2
IKBKB	0.05	0.047	-10000	0	-0.52	1	1
MAP2K2	0.044	0.025	-10000	0	-0.47	1	1
MAP2K1	0.044	0.025	-10000	0	-0.47	1	1
SMPD1	0.02	0.013	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.049	0.051	-10000	0	-0.45	3	3
MAP2K4	0.038	0.026	-10000	0	-0.39	2	2
protein ubiquitination	0.052	0.047	-10000	0	-0.52	1	1
EnzymeConsortium:2.7.1.37	0.049	0.028	-10000	0	-0.5	1	1
response to UV	0	0	-10000	0	-0.003	1	1
RAF1	0.038	0.026	-10000	0	-0.5	1	1
CRADD	0	0	-10000	0	-10000	0	0
mol:ceramide	0.025	0.019	-10000	0	-0.15	2	2
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0	0	-10000	0	-10000	0	0
MAP3K1	0.031	0.023	-10000	0	-0.42	1	1
TRADD	0	0	-10000	0	-10000	0	0
RELA/p50	0	0	-10000	0	-10000	0	0
MAPK3	0.046	0.025	-10000	0	-0.46	1	1
MAPK1	0.046	0.025	-10000	0	-0.46	1	1
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.042	0.053	-10000	0	-0.47	3	3
KSR1	0.032	0.026	-10000	0	-0.53	1	1
MAPK8	0.041	0.043	-10000	0	-0.46	6	6
TRAF2	-0.001	0.018	-10000	0	-0.28	4	4
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	0.051	0.046	-10000	0	-0.52	1	1
TNF R/SODD	-0.003	0.033	-10000	0	-0.62	2	2
TNF	-0.017	0.1	-10000	0	-0.81	14	14
CYCS	0.037	0.027	0.15	30	-10000	0	30
IKBKG	0.051	0.046	-10000	0	-0.52	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.038	0.051	-10000	0	-0.36	9	9
RELA	0	0	-10000	0	-10000	0	0
RIPK1	0	0.001	-10000	0	-10000	0	0
AIFM1	0.037	0.027	0.15	30	-10000	0	30
TNF/TNF R/SODD	-0.013	0.072	-10000	0	-0.54	16	16
TNFRSF1A	0	0.001	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	0.027	0.013	-10000	0	-10000	0	0
NSMAF	0.044	0.048	-10000	0	-0.55	1	1
response to hydrogen peroxide	0	0	-10000	0	-0.003	1	1
BCL2	-0.029	0.15	-10000	0	-0.81	35	35

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0	0.016	-10000	0	-10000	0	0
oxygen homeostasis	0.012	0.012	-10000	0	-10000	0	0
TCEB2	-0.004	0.032	-10000	0	-10000	0	0
TCEB1	-0.001	0.015	-10000	0	-0.28	3	3
VHL/Elongin B/Elongin C/HIF2A	-0.004	0.034	-10000	0	-0.43	2	2
EPO	0.15	0.15	-10000	0	-0.71	2	2
FIH (dimer)	0.023	0.011	-10000	0	-10000	0	0
APEX1	0.022	0.014	-10000	0	-0.3	1	1
SERPINE1	0.16	0.15	-10000	0	-0.68	4	4
FLT1	-0.002	0.079	-10000	0	-1.1	4	4
ADORA2A	0.14	0.16	-10000	0	-0.67	4	4
germ cell development	0.16	0.15	-10000	0	-0.64	7	7
SLC11A2	0.16	0.15	-10000	0	-0.68	4	4
BHLHE40	0.16	0.15	-10000	0	-0.81	5	5
HIF1AN	0.023	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.017	0.07	-10000	0	-0.44	4	4
ETS1	0.022	0.054	-10000	0	-0.82	4	4
CITED2	0.001	0.01	-10000	0	-10000	0	0
KDR	-0.005	0.11	-10000	0	-1.3	6	6
PGK1	0.16	0.15	-10000	0	-0.68	4	4
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.18	0.16	-10000	0	-0.77	5	5
EPAS1	0.095	0.079	-10000	0	-0.42	4	4
SP1	0.018	0.002	-10000	0	-10000	0	0
ABCG2	0.13	0.25	-10000	0	-0.7	68	68
EFNA1	0.16	0.15	-10000	0	-0.68	4	4
FXN	0.16	0.14	-10000	0	-0.67	4	4
POU5F1	0.16	0.15	-10000	0	-0.67	7	7
neuron apoptosis	-0.16	0.16	0.74	5	-10000	0	5
EP300	0	0	-10000	0	-10000	0	0
EGLN3	0	0.082	-10000	0	-0.39	6	6
EGLN2	0.021	0.023	-10000	0	-0.26	5	5
EGLN1	0.022	0.029	-10000	0	-0.82	1	1
VHL/Elongin B/Elongin C	-0.002	0.017	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.023	0.009	-10000	0	-10000	0	0
SLC2A1	0.15	0.15	-10000	0	-0.66	5	5
TWIST1	0.14	0.2	-10000	0	-0.72	34	34
ELK1	0.018	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.01	0.063	-10000	0	-0.61	1	1
VEGFA	0.16	0.15	-10000	0	-0.71	4	4
CREBBP	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.005	0.059	-9999	-0.49	14	14
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.049	-9999	-0.41	14	14
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.002	0.023	-9999	-0.28	7	7
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	-0.003	0.024	-9999	-10000	0	0
YY1/LSF	0	0.009	-9999	-0.3	1	1
SMG5	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.006	0.043	-9999	-0.36	14	14
I kappa B alpha/HDAC1	-0.004	0.029	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	-0.005	0.038	-9999	-0.32	14	14
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
HDAC3/TR2	-0.004	0.029	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0.007	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.004	0.034	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.025	0.13	-9999	-0.65	38	38
GATA1	-0.004	0.032	-9999	-0.28	13	13
Mad/Max	0	0.006	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0	0.008	-9999	-10000	0	0
RBBP7	-0.002	0.025	-9999	-0.28	8	8
NPC	0	0	-9999	-10000	0	0
RBBP4	-0.001	0.026	-9999	-0.81	1	1
MAX	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NFKBIA	-0.005	0.034	-9999	-10000	0	0
KAT2B	-0.001	0.026	-9999	-0.81	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0.008	-9999	-10000	0	0
SIN3 complex	0	0.007	-9999	-10000	0	0
SMURF1	0	0	-9999	-10000	0	0
CHD3	0	0	-9999	-10000	0	0
SAP30	-0.001	0.018	-9999	-0.28	4	4
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	-0.001	0.026	-9999	-0.81	1	1
YY1/HDAC3	-0.004	0.027	-9999	-10000	0	0
YY1/HDAC2	0	0.009	-9999	-0.3	1	1
YY1/HDAC1	0	0.009	-9999	-0.3	1	1
NuRD/MBD2 Complex (MeCP1)	0	0.007	-9999	-10000	0	0
PPARG	-0.093	0.17	-9999	-0.38	237	237
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.004	0.029	-9999	-10000	0	0
MBD3L2	-0.001	0.013	-9999	-0.28	2	2
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.007	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC3	-0.005	0.034	-9999	-10000	0	0
HDAC2	0	0	-9999	-10000	0	0
YY1	0	0.011	-9999	-0.35	1	1
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0	0	-9999	-10000	0	0
NCOR2	0	0	-9999	-10000	0	0
MXD1	0	0.009	-9999	-0.28	1	1
STAT3	0.025	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0	0.008	-9999	-10000	0	0
YY1/SAP30/HDAC1	-0.001	0.011	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.025	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.033	-9999	-10000	0	0
histone deacetylation	0.045	0.008	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.004	0.026	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0	-9999	-10000	0	0
GATA2/HDAC3	-0.019	0.084	-9999	-0.48	27	27
GATA1/HDAC1	-0.002	0.02	-9999	-10000	0	0
GATA1/HDAC3	-0.006	0.032	-9999	-10000	0	0
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.012	0.077	-9999	-0.62	14	14
SIN3/HDAC complex/Mad/Max	0	0.007	-9999	-10000	0	0
NuRD Complex	0	0.007	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.024	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
MTA2	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	-0.001	0.018	-9999	-0.48	1	1
GATA1/Fog1	-0.004	0.025	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.017	0.1	-9999	-0.81	14	14
negative regulation of cell growth	0.045	0.009	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0	0.007	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.007	0.051	-9999	-0.43	14	14
SIN3/HDAC complex/NCoR1	0	0.011	-9999	-10000	0	0
TFCP2	0	0	-9999	-10000	0	0
NR2C1	0	0	-9999	-10000	0	0
MBD3	0	0.009	-9999	-0.28	1	1
MBD2	0	0	-9999	-10000	0	0

×

FoxO family signaling

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
G6PC	0.029	0.039	-9999	-10000	0	0
PLK1	0.014	0.11	-9999	-0.63	4	4
CDKN1B	0.083	0.066	-9999	-0.54	3	3
FOXO3	0.045	0.1	-9999	-0.56	8	8
KAT2B	0.008	0.03	-9999	-0.84	1	1
FOXO1/SIRT1	0.006	0.04	-9999	-0.33	10	10
CAT	0.048	0.11	-9999	-1	4	4
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0.015	0.011	-9999	-10000	0	0
FOXO1	0.031	0.042	-9999	-0.36	11	11
MAPK10	-0.04	0.18	-9999	-0.46	154	154
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.063	0.087	-9999	-10000	0	0
response to oxidative stress	0.005	0.011	-9999	-10000	0	0
FOXO3A/SIRT1	-0.012	0.062	-9999	-0.5	6	6
XPO1	0	0	-9999	-10000	0	0
EP300	0.005	0.006	-9999	-10000	0	0
BCL2L11	0.029	0.018	-9999	-10000	0	0
FOXO1/SKP2	-0.004	0.034	-9999	-0.33	10	10
mol:GDP	0.005	0.011	-9999	-10000	0	0
RAN	0.012	0.003	-9999	-10000	0	0
GADD45A	0.07	0.059	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.068	0.027	-9999	-10000	0	0
MST1	-0.003	0.095	-9999	-0.77	14	14
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.002	0.04	-9999	-0.35	4	4
YWHAB	0	0	-9999	-10000	0	0
MAPK8	0.034	0.036	-9999	-0.46	5	5
MAPK9	0.036	0.006	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
YWHAZ	-0.001	0.015	-9999	-0.28	3	3
SIRT1	0.002	0.008	-9999	-10000	0	0
SOD2	0.093	0.071	-9999	-10000	0	0
RBL2	0.063	0.076	-9999	-0.55	1	1
RAL/GDP	0.011	0.015	-9999	-10000	0	0
CHUK	0.009	0.012	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
RAL/GTP	0.03	0.009	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
FASLG	0.008	0.17	-9999	-1.5	11	11
SKP2	0	0	-9999	-10000	0	0
USP7	0.01	0.005	-9999	-10000	0	0
IKBKB	0.008	0.017	-9999	-10000	0	0
CCNB1	0.039	0.11	-9999	-0.71	2	2
FOXO1-3a-4/beta catenin	-0.008	0.037	-9999	-0.42	4	4
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.034	-9999	-0.32	10	10
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.004	0.06	-9999	-0.82	5	5
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.068	0.077	-9999	-10000	0	0
SFN	-0.015	0.098	-9999	-0.51	30	30
CDK2	0.002	0.005	-9999	-10000	0	0
FOXO3A/14-3-3	0.023	0.05	-9999	-10000	0	0
CREBBP	0.002	0.005	-9999	-10000	0	0
FBXO32	0.047	0.12	-9999	-1.2	4	4
BCL6	0.059	0.11	-9999	-1.3	4	4
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.026	0.3	2	-10000	0	2
DAPP1	0.035	0.055	-10000	0	-0.59	4	4
Src family/SYK family/BLNK-LAT/BTK-ITK	0.046	0.081	-10000	0	-0.57	10	10
mol:DAG	0.052	0.05	0.21	1	-0.27	7	8
HRAS	-0.001	0.02	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
ARF5/GDP	-0.003	0.024	-10000	0	-0.3	1	1
PLCG2	-0.002	0.037	-10000	0	-0.63	3	3
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0.009	-10000	0	-0.28	1	1
mol:GTP	-0.001	0.023	0.27	2	-0.4	2	4
ARF1/GTP	-0.001	0.023	0.28	2	-0.38	2	4
RHOA	0	0	-10000	0	-10000	0	0
YES1	-0.001	0.026	-10000	0	-0.81	1	1
RAP1A/GTP	-0.001	0.022	0.25	2	-0.39	2	4
ADAP1	-0.003	0.033	-10000	0	-0.42	3	3
ARAP3	-0.001	0.023	0.26	2	-0.4	2	4
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	-0.01	0.056	-10000	0	-0.29	34	34
ARHGEF6	-0.011	0.092	-10000	0	-0.81	13	13
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	-0.001	0.012	-10000	0	-10000	0	0
FYN	-0.002	0.036	-10000	0	-0.81	2	2
ARF6	0	0	-10000	0	-10000	0	0
FGR	-0.001	0.027	-10000	0	-0.81	1	1
mol:Ca2+	0.039	0.029	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.001	0.018	-10000	0	-10000	0	0
ZAP70	-0.03	0.13	-10000	0	-0.43	68	68
mol:IP3	0.047	0.038	-10000	0	-0.22	1	1
LYN	0	0	-10000	0	-10000	0	0
ARF1/GDP	-0.003	0.024	-10000	0	-0.3	1	1
RhoA/GDP	-0.002	0.022	0.28	2	-10000	0	2
PDK1/Src/Hsp90	0	0.006	-10000	0	-10000	0	0
BLNK	0	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.061	0.033	-10000	0	-10000	0	0
SRC	0	0.009	-10000	0	-10000	0	0
PLEKHA2	0.03	0.007	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.035	-10000	0	-0.78	2	2
HSP90AA1	0	0.009	-10000	0	-0.28	1	1
ARF6/GTP	-0.001	0.022	0.3	2	-10000	0	2
RhoA/GTP	-0.001	0.021	-10000	0	-0.37	2	2
Src family/SYK family/BLNK-LAT	-0.01	0.059	-10000	0	-0.55	6	6
BLK	-0.04	0.1	-10000	0	-0.81	3	3
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	-0.001	0.021	-10000	0	-10000	0	0
HCK	-0.003	0.029	-10000	0	-10000	0	0
CYTH3	-0.001	0.025	-10000	0	-0.42	1	1
CYTH2	-0.001	0.021	-10000	0	-10000	0	0
KRAS	-0.001	0.012	-10000	0	-0.28	2	2
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.004	0.051	-10000	0	-0.57	7	7
SGK1	-0.003	0.053	-10000	0	-0.72	5	5
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.034	0.031	-10000	0	-0.27	3	3
SOS1	0	0	-10000	0	-10000	0	0
SYK	0	0.009	-10000	0	-0.28	1	1
ARF6/GDP	-0.001	0.023	0.29	2	-10000	0	2
mol:PI-3-4-5-P3	-0.001	0.025	0.36	2	-0.4	2	4
ARAP3/RAP1A/GTP	-0.001	0.023	-10000	0	-0.4	2	2
VAV1	-0.001	0.029	-10000	0	-0.46	3	3
mol:PI-3-4-P2	0.022	0	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	-0.002	0.019	-10000	0	-0.4	2	2
PLEKHA1	0.029	0.019	-10000	0	-0.53	1	1
Rac1/GDP	-0.003	0.024	-10000	0	-0.3	1	1
LAT	-0.006	0.049	-10000	0	-0.34	16	16
Rac1/GTP	-0.005	0.043	-10000	0	-0.36	13	13
ITK	-0.018	0.084	0.26	1	-0.45	33	34
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.059	0.065	0.24	1	-0.4	7	8
LCK	-0.02	0.1	-10000	0	-0.81	13	13
BTK	-0.001	0.022	-10000	0	-10000	0	0

×

Canonical 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
FBXW11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.076	0.035	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
RIP2/NOD2	-0.006	0.038	-9999	-0.48	2	2
NFKBIA	0.047	0	-9999	-10000	0	0
BIRC2	0	0	-9999	-10000	0	0
IKBKB	-0.001	0.013	-9999	-10000	0	0
RIPK2	-0.001	0.02	-9999	-0.28	5	5
IKBKG	0	0.008	-9999	-10000	0	0
IKK complex/A20	-0.004	0.048	-9999	-0.38	14	14
NEMO/A20/RIP2	-0.001	0.02	-9999	-0.28	5	5
XPO1	0	0	-9999	-10000	0	0
NEMO/ATM	0	0.008	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	0	0.007	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.009	0.053	-9999	-0.3	29	29
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
TNF/TNFR1A	-0.012	0.077	-9999	-0.62	14	14
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.02	0.12	-9999	-0.81	24	24
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.017	0.1	-9999	-0.81	14	14
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.047	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
IKK complex	0	0.009	-9999	-10000	0	0
CYLD	0	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.009	0.059	-9999	-0.38	24	24

×

Circadian rhythm 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
chromatin modification	0	0.019	-9999	-10000	0	0
CLOCK	0.008	0.068	-9999	-0.8	7	7
TIMELESS/CRY2	-0.001	0.009	-9999	-10000	0	0
DEC1/BMAL1	-0.001	0.011	-9999	-10000	0	0
ATR	0	0	-9999	-10000	0	0
NR1D1	0.041	0.015	-9999	-10000	0	0
ARNTL	0.014	0.002	-9999	-10000	0	0
TIMELESS	0.04	0.018	-9999	-10000	0	0
NPAS2	0.008	0.065	-9999	-0.8	6	6
CRY2	0	0	-9999	-10000	0	0
mol:CO	-0.013	0.003	-9999	-10000	0	0
CHEK1	-0.007	0.045	-9999	-10000	0	0
mol:HEME	0.013	0.003	-9999	-10000	0	0
PER1	-0.016	0.11	-9999	-0.81	20	20
BMAL/CLOCK/NPAS2	-0.007	0.06	-9999	-0.52	13	13
BMAL1/CLOCK	0.042	0.047	-9999	-10000	0	0
S phase of mitotic cell cycle	0	0.019	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0	0.019	-9999	-10000	0	0
mol:NADPH	0.013	0.003	-9999	-10000	0	0
PER1/TIMELESS	-0.011	0.067	-9999	-0.47	20	20
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.001	0.018	-9999	-0.28	4	4

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.057	0.078	-9999	-0.52	1	1
CRKL	0.028	0.048	-9999	-0.5	1	1
mol:DAG	-0.002	0.028	-9999	-0.4	1	1
HRAS	-0.005	0.021	-9999	-10000	0	0
MAPK8	0.012	0.063	-9999	-0.53	5	5
RAP1A	0.028	0.048	-9999	-0.5	1	1
GAB1	0.028	0.048	-9999	-0.5	1	1
MAPK14	0.015	0.049	-9999	-10000	0	0
EPO	-0.035	0.11	-9999	-0.3	10	10
PLCG1	-0.002	0.028	-9999	-0.4	1	1
EPOR/TRPC2/IP3 Receptors	0.012	0.01	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.023	0.065	-9999	-0.64	6	6
GAB1/SHC/GRB2/SOS1	-0.007	0.022	-9999	-0.42	1	1
EPO/EPOR (dimer)	-0.028	0.063	-9999	-10000	0	0
IRS2	0.009	0.11	-9999	-0.48	41	41
STAT1	0.048	0.057	-9999	-0.51	1	1
STAT5B	-0.003	0.045	-9999	-0.44	4	4
cell proliferation	0.021	0.059	-9999	-0.49	5	5
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.008	0.037	-9999	-0.43	3	3
TEC	0.027	0.056	-9999	-0.49	4	4
SOCS3	-0.005	0.063	-9999	-0.81	6	6
STAT1 (dimer)	0.048	0.056	-9999	-0.5	1	1
JAK2	0	0.026	-9999	-0.82	1	1
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
EPO/EPOR (dimer)/JAK2	0.054	0.042	-9999	-0.53	1	1
EPO/EPOR	-0.028	0.063	-9999	-10000	0	0
LYN	0.012	0.002	-9999	-10000	0	0
TEC/VAV2	-0.012	0.037	-9999	-0.47	4	4
elevation of cytosolic calcium ion concentration	0.012	0.01	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.017	0.047	-9999	-10000	0	0
mol:IP3	-0.002	0.028	-9999	-0.4	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.028	0.093	-9999	-0.49	20	20
SH2B3	0.001	0.002	-9999	-10000	0	0
NFKB1	0.015	0.049	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.009	0.031	-9999	-0.32	7	7
PTPN6	0.021	0.05	-9999	-0.52	1	1
TEC/VAV2/GRB2	-0.01	0.035	-9999	-0.45	4	4
EPOR	0.012	0.01	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.007	0.022	-9999	-0.43	1	1
SOS1	0	0	-9999	-10000	0	0
PLCG2	-0.002	0.037	-9999	-0.63	3	3
CRKL/CBL/C3G	-0.009	0.025	-9999	-0.45	1	1
VAV2	0.028	0.049	-9999	-0.5	1	1
CBL	0.028	0.048	-9999	-0.5	1	1
SHC/Grb2/SOS1	0.005	0.029	-9999	-0.45	1	1
STAT5A	-0.006	0.058	-9999	-0.48	9	9
GRB2	0	0.009	-9999	-0.28	1	1
STAT5 (dimer)	0.056	0.088	-9999	-0.57	5	5
LYN/PLCgamma2	-0.001	0.028	-9999	-0.62	2	2
PTPN11	0	0	-9999	-10000	0	0
BTK	0.028	0.049	-9999	-0.5	1	1
BCL2	0.034	0.2	-9999	-0.99	35	35

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.13	0.12	-9999	-0.53	7	7
CaM/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
STXBP4	-0.001	0.013	-9999	-0.28	2	2
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.12	0.15	-9999	-0.31	20	20
YWHAZ	-0.001	0.015	-9999	-0.28	3	3
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.019	0.045	-9999	-0.62	5	5
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
SNARE/Synip	0	0.006	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	-0.002	0.023	-9999	-0.28	7	7
PRKCI	0	0.009	-9999	-10000	0	0
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0.031	0	-9999	-10000	0	0
PRKCZ	-0.001	0.026	-9999	-0.81	1	1
TRIP10	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	-0.004	0.031	-9999	-10000	0	0
VAMP2	0	0	-9999	-10000	0	0
SLC2A4	-0.13	0.16	-9999	-0.34	20	20
STX4	0	0	-9999	-10000	0	0
GSK3B	0.025	0	-9999	-10000	0	0
SFN	-0.015	0.098	-9999	-0.51	30	30
LNPEP	-0.005	0.063	-9999	-0.81	6	6
YWHAE	0	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0	0.008	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.005	0.051	-9999	-0.53	9	9
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.025	-9999	-10000	0	0
NFKBIA	0.023	0.035	-9999	-0.27	13	13
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0.006	-9999	-10000	0	0
ARRB2	0.016	0	-9999	-10000	0	0
REL	-0.007	0.077	-9999	-0.81	9	9
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.001	0.009	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0	0.006	-9999	-10000	0	0
PIK3CA	0	0.009	-9999	-0.28	1	1
NF kappa B1 p50 dimer	0	0.008	-9999	-10000	0	0
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
NFKB1	0.022	0.009	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.03	0.035	-9999	-0.27	13	13
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.003	0.024	-9999	-10000	0	0
SRC	0	0.009	-9999	-10000	0	0
PI3K	-0.005	0.052	-9999	-0.62	7	7
NF kappa B1 p50/RelA	-0.004	0.031	-9999	-0.27	13	13
IKBKB	-0.001	0.013	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	0	0.009	-9999	-0.28	1	1
I kappa B alpha/PIK3R1	-0.007	0.047	-9999	-0.45	7	7
cell death	-0.003	0.023	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.005	0.051	-9999	-0.53	9	9
LCK	-0.02	0.1	-9999	-0.81	13	13
BCL3	-0.001	0.013	-9999	-0.28	2	2

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.028	0.042	-10000	0	-10000	0	0
regulation of axonogenesis	0.003	0.027	0.32	7	-10000	0	7
myoblast fusion	0.008	0.025	-10000	0	-10000	0	0
mol:GTP	-0.005	0.015	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.008	0.028	-10000	0	-10000	0	0
ARF1/GTP	-0.002	0.007	-10000	0	-10000	0	0
mol:GM1	0.006	0.014	-10000	0	-10000	0	0
mol:Choline	0.021	0.047	-10000	0	-0.52	7	7
lamellipodium assembly	-0.004	0.031	-10000	0	-10000	0	0
MAPK3	0.02	0.023	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.008	0.028	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.008	0.026	-10000	0	-10000	0	0
ARF1/GDP	-0.004	0.024	-10000	0	-10000	0	0
ARF6	0.007	0.007	-10000	0	-10000	0	0
RAB11A	-0.001	0.013	-10000	0	-0.28	2	2
TIAM1	0.01	0.019	-10000	0	-10000	0	0
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0.023	-10000	0	-10000	0	0
actin filament bundle formation	0.006	0.021	-10000	0	-10000	0	0
KALRN	-0.011	0.069	-10000	0	-0.49	19	19
RAB11FIP3/RAB11A	0	0.008	-10000	0	-10000	0	0
RhoA/GDP	-0.006	0.021	-10000	0	-10000	0	0
NME1	-0.003	0.063	-10000	0	-0.28	49	49
Rac1/GDP	-0.006	0.021	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.005	0.015	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.004	0.031	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
liver development	-0.005	0.015	-10000	0	-10000	0	0
ARF6/GTP	-0.005	0.015	-10000	0	-10000	0	0
RhoA/GTP	-0.002	0.007	-10000	0	-10000	0	0
mol:GDP	-0.005	0.028	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.001	0.006	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PLD1	0.012	0.053	-10000	0	-0.59	7	7
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	-0.004	0.031	-10000	0	-10000	0	0
ruffle organization	-0.003	0.027	-10000	0	-0.32	7	7
regulation of epithelial cell migration	-0.005	0.015	-10000	0	-10000	0	0
PLD2	0.016	0.013	-10000	0	-10000	0	0
PIP5K1A	-0.003	0.027	-10000	0	-0.32	7	7
mol:Phosphatidic acid	0.021	0.047	-10000	0	-0.52	7	7
Rac1/GTP	-0.004	0.031	-10000	0	-10000	0	0

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.012	0.035	-9999	-0.43	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.006	0.025	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.001	0.017	-9999	-0.54	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.006	0.039	-9999	-0.4	1	1
CaM/Ca2+	0.01	0.031	-9999	-0.4	1	1
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.011	0.032	-9999	-0.41	1	1
AKT1	-0.008	0.037	-9999	-0.46	1	1
MAP2K1	0.04	0.041	-9999	-0.4	1	1
MAP3K11	0.031	0.039	-9999	-0.4	1	1
IFNGR1	0.001	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.025	0.099	-9999	-0.41	21	21
Rap1/GTP	-0.003	0.012	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.011	0.034	-9999	-0.45	1	1
CEBPB	0.075	0.038	-9999	-0.42	1	1
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.009	0.056	-9999	-1.3	1	1
STAT1	-0.01	0.032	-9999	-0.41	1	1
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.037	0.094	-9999	-0.28	1	1
PIK3CA	0	0.009	-9999	-0.28	1	1
STAT1 (dimer)/PIAS1	-0.008	0.029	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.001	0.013	-9999	-10000	0	0
mol:Ca2+	0.011	0.033	-9999	-0.43	1	1
MAPK3	0.054	0.038	-9999	-10000	0	0
STAT1 (dimer)	-0.005	0.053	-9999	-0.6	1	1
MAPK1	0.054	0.038	-9999	-0.44	1	1
JAK2	0	0.026	-9999	-0.8	1	1
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
JAK1	0.001	0.002	-9999	-10000	0	0
CAMK2D	-0.002	0.044	-9999	-0.81	3	3
DAPK1	0.069	0.032	-9999	-10000	0	0
SMAD7	0.05	0.037	-9999	-10000	0	0
CBL/CRKL/C3G	-0.006	0.018	-9999	-10000	0	0
PI3K	0.006	0.046	-9999	-0.42	7	7
IFNG	-0.037	0.094	-9999	-0.28	1	1
apoptosis	0.053	0.028	-9999	-10000	0	0
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.009	0.049	-9999	-0.28	31	31
CAMK2B	-0.073	0.22	-9999	-0.81	74	74
FRAP1	0.04	0.048	-9999	-0.43	1	1
PRKCD	-0.008	0.037	-9999	-0.46	1	1
RAP1B	0	0	-9999	-10000	0	0
negative regulation of cell growth	-0.006	0.039	-9999	-0.4	1	1
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.064	0.044	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.008	0.03	-9999	-10000	0	0
SOCS1	0	0.051	-9999	-1.5	1	1
mol:GDP	-0.006	0.018	-9999	-10000	0	0
CASP1	0.049	0.044	-9999	-0.36	4	4
PTGES2	0	0.009	-9999	-0.28	1	1
IRF9	0.057	0.02	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.003	0.042	-9999	-0.41	7	7
RAP1/GDP	-0.003	0.012	-9999	-10000	0	0
CBL	-0.009	0.025	-9999	-0.4	1	1
MAP3K1	0.031	0.042	-9999	-0.42	2	2
PIAS1	0	0	-9999	-10000	0	0
PIAS4	0	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.006	0.039	-9999	-0.4	1	1
PTPN11	-0.01	0.028	-9999	-0.43	1	1
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.003	0.026	-9999	-0.28	9	9
RAC1	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.007	0.044	-9999	-0.46	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.013	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	-0.005	0.031	-9999	-0.48	2	2
lamellipodium assembly	-0.003	0.039	-9999	-0.46	7	7
PIK3CA	0	0.009	-9999	-0.28	1	1
PI3K	-0.005	0.052	-9999	-0.62	7	7
ARF6	0	0	-9999	-10000	0	0
TLN1	0	0	-9999	-10000	0	0
PXN	0.022	0	-9999	-10000	0	0
PIK3R1	-0.006	0.068	-9999	-0.81	7	7
ARF6/GTP	-0.001	0.009	-9999	-10000	0	0
cell adhesion	-0.001	0.009	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.001	0.011	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.008	0.056	-9999	-0.32	26	26
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.006	0.049	-9999	-0.45	11	11
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.011	0.087	-9999	-0.81	11	11
alpha4/beta1 Integrin/Paxillin/Talin	-0.001	0.009	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.001	0.011	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	0.001	0.011	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GIT1	-0.001	0.02	-9999	-0.28	5	5
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.001	0.009	-9999	-10000	0	0
Rac1/GTP	-0.003	0.044	-9999	-0.52	7	7

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.071	0.064	-9999	-0.62	1	1
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.018	0.016	-9999	-10000	0	0
AURKB	-0.16	0.14	-9999	-10000	0	0
AURKC	-0.004	0.041	-9999	-0.81	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.012	-9999	-0.38	1	1
MDM2/SUMO1	0	0.006	-9999	-10000	0	0
HDAC4	-0.001	0.026	-9999	-0.81	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.028	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
SUMO1/HDAC4	0	0.014	-9999	-0.45	1	1
SUMO1/HDAC1	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0	0.007	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	0	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	-0.001	0.018	-9999	-0.28	4	4
UBE2I	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
EntrezGene:9972	0	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	0.008	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	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	-0.001	0.02	-9999	-0.28	5	5
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.003	-9999	-10000	0	0
CD4	0	0	-9999	-10000	0	0
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.01	0.015	-9999	-10000	0	0
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	0.007	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	-0.001	0.008	-9999	-10000	0	0
AP2M1	0	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	0.009	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.025	0.002	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.004	-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	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	0.001	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.01	0.015	-9999	-10000	0	0
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	0.01	0.015	-9999	-10000	0	0
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	0	-9999	-10000	0	0

×

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	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.001	0.01	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAP3K14	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.002	0.017	-9999	-10000	0	0
RELB	-0.003	0.026	-9999	-10000	0	0
NFKB2	0	0.009	-9999	-0.28	1	1
NF kappa B2 p52/RelB	-0.001	0.014	-9999	-10000	0	0
regulation of B cell activation	-0.001	0.014	-9999	-10000	0	0

pid_entity	TCGA.PE.A5DE	TCGA.PE.A5DD	TCGA.PE.A5DC	TCGA.OL.A66K
109_MAP3K5	0.042	0.053	0.053	0.053
47_PPARGC1A	0	0	-0.81	0
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	0	0	0	0
105_BMP2	0	0	0	0
131_RELN/VLDLR	-0.48	-0.48	-0.48	-0.48
30_TGFB1/TGF beta receptor Type II	0	0	0	0
84_STAT5B	-0.1	-0.075	-0.13	-0.1
84_STAT5A	-0.1	-0.075	-0.13	-0.1