PARADIGM pathway analysis of mRNASeq expression data - Liver Hepatocellular Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
PDGFR-alpha signaling pathway	97
Plasma membrane estrogen receptor signaling	97
FOXM1 transcription factor network	93
Signaling events regulated by Ret tyrosine kinase	91
Nongenotropic Androgen signaling	84
Glypican 2 network	81
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	79
IL4-mediated signaling events	72
EPO signaling pathway	72
Signaling mediated by p38-alpha and p38-beta	72

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
PDGFR-alpha signaling pathway	0.2615	97	4289	44	-0.74	0.033	1000	-1000	-0.048	-1000
Plasma membrane estrogen receptor signaling	0.2615	97	8363	86	-0.55	0.5	1000	-1000	-0.069	-1000
FOXM1 transcription factor network	0.2507	93	4753	51	-0.25	0.46	1000	-1000	-0.11	-1000
Signaling events regulated by Ret tyrosine kinase	0.2453	91	7536	82	-0.48	0.014	1000	-1000	-0.079	-1000
Nongenotropic Androgen signaling	0.2264	84	4386	52	-0.43	0.24	1000	-1000	-0.05	-1000
Glypican 2 network	0.2183	81	324	4	0.043	0.15	1000	-1000	-0.022	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2129	79	5436	68	-0.77	0.25	1000	-1000	-0.063	-1000
IL4-mediated signaling events	0.1941	72	6632	91	-0.99	0.5	1000	-1000	-0.096	-1000
EPO signaling pathway	0.1941	72	4012	55	-0.3	0	1000	-1000	-0.079	-1000
Signaling mediated by p38-alpha and p38-beta	0.1941	72	3197	44	-0.4	0	1000	-1000	-0.038	-1000
IGF1 pathway	0.1941	72	4119	57	-0.34	0.13	1000	-1000	-0.071	-1000
p75(NTR)-mediated signaling	0.1914	71	8961	125	-0.55	0.2	1000	-1000	-0.079	-1000
IL6-mediated signaling events	0.1914	71	5373	75	-0.52	0.04	1000	-1000	-0.061	-1000
FOXA2 and FOXA3 transcription factor networks	0.1887	70	3263	46	-0.72	0.035	1000	-1000	-0.014	-1000
TCGA08_retinoblastoma	0.1860	69	556	8	-0.085	0.21	1000	-1000	-0.011	-1000
Aurora B signaling	0.1860	69	4644	67	-0.019	0.29	1000	-1000	-0.055	-1000
HIF-1-alpha transcription factor network	0.1833	68	5228	76	-0.53	0.014	1000	-1000	-0.046	-1000
EPHB forward signaling	0.1779	66	5693	85	-0.25	0.2	1000	-1000	-0.075	-1000
Ephrin A reverse signaling	0.1752	65	455	7	-0.17	0.011	1000	-1000	-0.022	-1000
Reelin signaling pathway	0.1725	64	3634	56	-0.29	0.065	1000	-1000	-0.074	-1000
Ephrin B reverse signaling	0.1725	64	3114	48	-0.3	0.084	1000	-1000	-0.048	-1000
Wnt signaling	0.1725	64	453	7	-0.24	0.019	1000	-1000	-0.031	-1000
Endothelins	0.1509	56	5399	96	-0.55	0.15	1000	-1000	-0.054	-1000
LPA receptor mediated events	0.1509	56	5759	102	-0.42	0.032	1000	-1000	-0.071	-1000
Noncanonical Wnt signaling pathway	0.1456	54	1416	26	-0.24	0.019	1000	-1000	-0.055	-1000
IL23-mediated signaling events	0.1429	53	3239	60	-0.33	0.031	1000	-1000	-0.096	-1000
PLK1 signaling events	0.1402	52	4429	85	-0.05	0.27	1000	-1000	-0.041	-1000
Calcium signaling in the CD4+ TCR pathway	0.1402	52	1623	31	-0.46	0.002	1000	-1000	-0.048	-1000
Glypican 1 network	0.1321	49	2364	48	-0.36	0.059	1000	-1000	-0.037	-1000
ErbB2/ErbB3 signaling events	0.1267	47	3094	65	-0.36	0.066	1000	-1000	-0.057	-1000
Thromboxane A2 receptor signaling	0.1186	44	4693	105	-0.15	0.075	1000	-1000	-0.056	-1000
Signaling events mediated by the Hedgehog family	0.1159	43	2250	52	-0.4	0.27	1000	-1000	-0.05	-1000
S1P5 pathway	0.1159	43	738	17	-0.41	0.15	1000	-1000	-0.037	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1159	43	3821	88	-0.27	0.008	1000	-1000	-0.082	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.1132	42	3606	85	-0.46	0.016	1000	-1000	-0.057	-1000
Syndecan-1-mediated signaling events	0.1051	39	1351	34	-0.46	0.072	1000	-1000	-0.062	-1000
Syndecan-4-mediated signaling events	0.1051	39	2632	67	-0.36	0.18	1000	-1000	-0.063	-1000
S1P1 pathway	0.0997	37	1359	36	-0.43	0.15	1000	-1000	-0.057	-1000
amb2 Integrin signaling	0.0943	35	2922	82	-0.42	0.08	1000	-1000	-0.05	-1000
IL12-mediated signaling events	0.0916	34	2969	87	-0.66	0.018	1000	-1000	-0.095	-1000
ErbB4 signaling events	0.0916	34	2379	69	-0.28	0.066	1000	-1000	-0.066	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0916	34	4091	120	-0.6	0.18	1000	-1000	-0.053	-1000
Osteopontin-mediated events	0.0889	33	1279	38	-0.42	0.055	1000	-1000	-0.07	-1000
Glucocorticoid receptor regulatory network	0.0889	33	3814	114	-0.76	0.21	1000	-1000	-0.06	-1000
BCR signaling pathway	0.0889	33	3355	99	-0.42	0.016	1000	-1000	-0.079	-1000
Signaling events mediated by PRL	0.0889	33	1143	34	-0.34	0.052	1000	-1000	-0.048	-1000
S1P4 pathway	0.0863	32	808	25	-0.41	0.15	1000	-1000	-0.043	-1000
Ras signaling in the CD4+ TCR pathway	0.0863	32	553	17	-0.21	0.002	1000	-1000	-0.053	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0836	31	1688	54	-0.31	0.03	1000	-1000	-0.082	-1000
Arf6 signaling events	0.0782	29	1806	62	-0.46	0.075	1000	-1000	-0.048	-1000
Aurora C signaling	0.0755	28	201	7	0	0.17	1000	-1000	-0.026	-1000
S1P3 pathway	0.0728	27	1150	42	-0.41	0.15	1000	-1000	-0.038	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0674	25	706	28	-0.41	0.15	1000	-1000	-0.049	-1000
Fc-epsilon receptor I signaling in mast cells	0.0674	25	2487	97	-0.42	0.05	1000	-1000	-0.069	-1000
Coregulation of Androgen receptor activity	0.0647	24	1832	76	-0.25	0.22	1000	-1000	-0.037	-1000
Integrins in angiogenesis	0.0647	24	2021	84	-0.34	0.069	1000	-1000	-0.078	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0647	24	1808	74	-0.46	0.075	1000	-1000	-0.082	-1000
p38 MAPK signaling pathway	0.0647	24	1069	44	-0.42	0.012	1000	-1000	-0.05	-1000
BMP receptor signaling	0.0620	23	1881	81	-0.18	0.065	1000	-1000	-0.069	-1000
Nectin adhesion pathway	0.0620	23	1500	63	-0.11	0.007	1000	-1000	-0.058	-1000
TCR signaling in naïve CD8+ T cells	0.0620	23	2211	93	-0.26	0.12	1000	-1000	-0.069	-1000
Presenilin action in Notch and Wnt signaling	0.0593	22	1402	61	-0.42	0.11	1000	-1000	-0.059	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0566	21	723	34	-0.074	0.017	1000	-1000	-0.056	-1000
PLK2 and PLK4 events	0.0566	21	64	3	-0.002	0.053	1000	-1000	-0.012	-1000
IL1-mediated signaling events	0.0566	21	1331	62	-0.16	0.004	1000	-1000	-0.076	-1000
LPA4-mediated signaling events	0.0539	20	246	12	-0.21	0.02	1000	-1000	-0.006	-1000
Visual signal transduction: Rods	0.0539	20	1059	52	-0.21	0.043	1000	-1000	-0.058	-1000
FAS signaling pathway (CD95)	0.0512	19	914	47	-0.46	0.04	1000	-1000	-0.033	-1000
IL27-mediated signaling events	0.0512	19	1018	51	-0.21	0.13	1000	-1000	-0.047	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0485	18	676	37	-0.3	0.007	1000	-1000	-0.06	-1000
Regulation of nuclear SMAD2/3 signaling	0.0458	17	2360	136	-0.48	0.4	1000	-1000	-0.054	-1000
Regulation of Androgen receptor activity	0.0458	17	1197	70	-0.3	0.064	1000	-1000	-0.055	-1000
Canonical Wnt signaling pathway	0.0404	15	765	51	-0.19	0.13	1000	-1000	-0.055	-1000
IL2 signaling events mediated by STAT5	0.0404	15	348	22	-0.067	0.17	1000	-1000	-0.041	-1000
Regulation of Telomerase	0.0404	15	1627	102	-0.47	0.2	1000	-1000	-0.076	-1000
JNK signaling in the CD4+ TCR pathway	0.0377	14	248	17	-0.074	0.024	1000	-1000	-0.043	-1000
HIF-2-alpha transcription factor network	0.0377	14	634	43	-0.24	0.078	1000	-1000	-0.052	-1000
FoxO family signaling	0.0377	14	951	64	-0.2	0.27	1000	-1000	-0.059	-1000
Syndecan-3-mediated signaling events	0.0377	14	493	35	-0.19	0.012	1000	-1000	-0.047	-1000
IL2 signaling events mediated by PI3K	0.0377	14	869	58	-0.075	0.14	1000	-1000	-0.069	-1000
Signaling events mediated by HDAC Class III	0.0350	13	544	40	-0.35	0.013	1000	-1000	-0.032	-1000
E-cadherin signaling events	0.0350	13	66	5	-0.051	0	1000	-1000	-0.026	-1000
Syndecan-2-mediated signaling events	0.0323	12	868	69	-0.19	0.062	1000	-1000	-0.046	-1000
Signaling events mediated by PTP1B	0.0323	12	947	76	-0.19	0.12	1000	-1000	-0.052	-1000
E-cadherin signaling in keratinocytes	0.0323	12	519	43	-0.095	0.02	1000	-1000	-0.049	-1000
Hedgehog signaling events mediated by Gli proteins	0.0296	11	739	65	-0.41	0.15	1000	-1000	-0.07	-1000
Aurora A signaling	0.0296	11	688	60	-0.02	0.21	1000	-1000	-0.044	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0296	11	521	45	-0.1	0.027	1000	-1000	-0.067	-1000
Class IB PI3K non-lipid kinase events	0.0296	11	33	3	-0.025	-1000	1000	-1000	-0.015	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0296	11	868	78	-0.31	0.025	1000	-1000	-0.075	-1000
Cellular roles of Anthrax toxin	0.0270	10	393	39	-0.089	0.014	1000	-1000	-0.02	-1000
Ceramide signaling pathway	0.0270	10	820	76	-0.34	0.075	1000	-1000	-0.046	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0270	10	557	52	-0.13	0.04	1000	-1000	-0.036	-1000
Effects of Botulinum toxin	0.0270	10	279	26	-0.12	0.013	1000	-1000	-0.033	-1000
E-cadherin signaling in the nascent adherens junction	0.0270	10	787	76	-0.051	0.026	1000	-1000	-0.07	-1000
EGFR-dependent Endothelin signaling events	0.0270	10	212	21	-0.023	0.075	1000	-1000	-0.058	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0270	10	343	33	-0.02	0.22	1000	-1000	-0.05	-1000
Insulin-mediated glucose transport	0.0243	9	291	32	-0.039	0.18	1000	-1000	-0.05	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0243	9	753	83	-0.15	0.18	1000	-1000	-0.063	-1000
Retinoic acid receptors-mediated signaling	0.0243	9	560	58	-0.17	0.038	1000	-1000	-0.056	-1000
TCGA08_rtk_signaling	0.0243	9	238	26	-0.34	0.022	1000	-1000	-0.02	-1000
Rapid glucocorticoid signaling	0.0216	8	167	20	-0.026	0.051	1000	-1000	-0.027	-1000
Caspase cascade in apoptosis	0.0189	7	578	74	-0.033	0.031	1000	-1000	-0.036	-1000
Signaling events mediated by HDAC Class II	0.0189	7	525	75	-0.48	0.008	1000	-1000	-0.038	-1000
a4b1 and a4b7 Integrin signaling	0.0189	7	38	5	-0.025	-0.012	1000	-1000	-0.03	-1000
Regulation of p38-alpha and p38-beta	0.0189	7	407	54	-0.15	0.032	1000	-1000	-0.051	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0189	7	912	125	-0.07	0.049	1000	-1000	-0.095	-1000
BARD1 signaling events	0.0162	6	349	57	-0.012	0.11	1000	-1000	-0.05	-1000
Arf6 downstream pathway	0.0135	5	230	43	-0.046	0.029	1000	-1000	-0.028	-1000
Class I PI3K signaling events mediated by Akt	0.0135	5	405	68	-0.1	0.18	1000	-1000	-0.05	-1000
Paxillin-dependent events mediated by a4b1	0.0135	5	205	36	-0.041	0.018	1000	-1000	-0.048	-1000
Visual signal transduction: Cones	0.0108	4	187	38	-0.012	0.031	1000	-1000	-0.033	-1000
IFN-gamma pathway	0.0108	4	308	68	-0.42	0.067	1000	-1000	-0.068	-1000
TRAIL signaling pathway	0.0108	4	210	48	-0.018	0.009	1000	-1000	-0.053	-1000
Signaling mediated by p38-gamma and p38-delta	0.0108	4	61	15	-0.009	0.061	1000	-1000	-0.039	-1000
Class I PI3K signaling events	0.0108	4	347	73	-0.15	0.025	1000	-1000	-0.062	-1000
PDGFR-beta signaling pathway	0.0108	4	459	97	-0.12	0.046	1000	-1000	-0.067	-1000
mTOR signaling pathway	0.0081	3	193	53	-0.072	0.027	1000	-1000	-0.044	-1000
Atypical NF-kappaB pathway	0.0081	3	110	31	-0.03	0.018	1000	-1000	-0.052	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0054	2	53	23	-0.051	0.034	1000	-1000	-0.038	-1000
ceramide signaling pathway	0.0054	2	107	49	-0.04	0.039	1000	-1000	-0.035	-1000
Signaling events mediated by HDAC Class I	0.0054	2	222	104	-0.031	0.006	1000	-1000	-0.045	-1000
Insulin Pathway	0.0054	2	213	74	-0.081	0.04	1000	-1000	-0.081	-1000
VEGFR1 specific signals	0.0054	2	117	56	-0.019	0.05	1000	-1000	-0.055	-1000
Canonical NF-kappaB pathway	0.0027	1	54	39	-0.031	0.065	1000	-1000	-0.069	-1000
Arf6 trafficking events	0.0027	1	139	71	-0.033	0.029	1000	-1000	-0.055	-1000
Arf1 pathway	0.0027	1	90	54	-0.07	0.016	1000	-1000	-0.032	-1000
Circadian rhythm pathway	0.0000	0	16	22	-0.011	0.036	1000	-1000	-0.054	-1000
TCGA08_p53	0.0000	0	0	7	-0.057	0.027	1000	-1000	-0.019	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	1	27	0	0.001	1000	-1000	-0.043	-1000
Alternative NF-kappaB pathway	0.0000	0	3	13	0	0.002	1000	-1000	-0.03	-1000
Total	NA	3723	220524	7203	-33	-990	131000	-131000	-6.9	-131000

PDGFR-alpha signaling pathway

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
PDGFRA	-0.36	0.43	-10000	0	-0.89	149	149
PDGF/PDGFRA/CRKL	-0.27	0.33	-10000	0	-0.68	149	149
positive regulation of JUN kinase activity	-0.21	0.26	-10000	0	-0.53	149	149
CRKL	0	0	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.28	0.33	-10000	0	-0.68	149	149
AP1	-0.74	0.68	-10000	0	-1.4	179	179
mol:IP3	-0.29	0.35	-10000	0	-0.71	149	149
PLCG1	-0.29	0.35	-10000	0	-0.71	149	149
PDGF/PDGFRA/alphaV Integrin	-0.27	0.33	-10000	0	-0.68	149	149
RAPGEF1	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.28	0.35	-10000	0	-0.71	149	149
CAV3	0	0	-10000	0	-10000	0	0
CAV1	0	0	-10000	0	-10000	0	0
SHC/Grb2/SOS1	-0.21	0.26	-10000	0	-0.53	149	149
PDGF/PDGFRA/Shf	-0.31	0.36	-10000	0	-0.7	161	161
FOS	-0.71	0.67	-10000	0	-1.4	179	179
JUN	-0.048	0.095	-10000	0	-0.75	6	6
oligodendrocyte development	-0.27	0.33	-10000	0	-0.68	149	149
GRB2	0	0	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
mol:DAG	-0.29	0.35	-10000	0	-0.71	149	149
PDGF/PDGFRA	-0.36	0.43	-10000	0	-0.89	149	149
actin cytoskeleton reorganization	-0.27	0.33	-10000	0	-0.68	150	150
SRF	0.025	0.02	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
PI3K	-0.24	0.3	-10000	0	-0.59	150	150
PDGF/PDGFRA/Crk/C3G	-0.24	0.29	-10000	0	-0.59	149	149
JAK1	-0.26	0.34	-10000	0	-0.68	149	149
ELK1/SRF	-0.22	0.26	-10000	0	-0.55	149	149
SHB	-0.002	0.045	-10000	0	-0.86	1	1
SHF	-0.044	0.19	-10000	0	-0.86	19	19
CSNK2A1	0.033	0.026	-10000	0	-10000	0	0
GO:0007205	-0.29	0.35	-10000	0	-0.72	149	149
SOS1	0	0	-10000	0	-10000	0	0
Ras protein signal transduction	-0.21	0.26	-10000	0	-0.53	149	149
PDGF/PDGFRA/SHB	-0.28	0.33	-10000	0	-0.68	150	150
PDGF/PDGFRA/Caveolin-1	-0.27	0.33	-10000	0	-0.68	149	149
ITGAV	0.001	0.016	0.32	1	-10000	0	1
ELK1	-0.27	0.32	-10000	0	-0.66	149	149
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
PDGF/PDGFRA/Crk	-0.27	0.33	-10000	0	-0.68	149	149
JAK-STAT cascade	-0.26	0.34	-10000	0	-0.68	149	149
cell proliferation	-0.3	0.35	-10000	0	-0.7	161	161

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.28	0.26	-10000	0	-0.51	206	206
ER alpha/Gai/GDP/Gbeta gamma	-0.5	0.46	-10000	0	-0.77	236	236
AKT1	-0.54	0.48	-10000	0	-0.96	206	206
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.55	0.5	-10000	0	-0.99	206	206
mol:Ca2+	-0.19	0.3	-10000	0	-0.77	70	70
IGF1R	-0.015	0.13	0.32	4	-0.86	8	12
E2/ER alpha (dimer)/Striatin	-0.34	0.3	-10000	0	-0.6	214	214
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.5	0.46	0.9	206	-10000	0	206
RhoA/GTP	-0.24	0.22	-10000	0	-0.44	205	205
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.44	0.36	-10000	0	-0.74	205	205
regulation of stress fiber formation	0.18	0.2	0.53	15	-10000	0	15
E2/ERA-ERB (dimer)	-0.32	0.29	-10000	0	-0.59	205	205
KRAS	0	0	-10000	0	-10000	0	0
G13/GTP	-0.3	0.27	-10000	0	-0.54	205	205
pseudopodium formation	-0.18	0.2	-10000	0	-0.53	15	15
E2/ER alpha (dimer)/PELP1	-0.32	0.29	-10000	0	-0.59	205	205
GRB2	0	0	-10000	0	-10000	0	0
GNG2	-0.007	0.077	-10000	0	-0.86	3	3
GNAO1	-0.41	0.43	-10000	0	-0.86	178	178
HRAS	0.002	0.023	0.32	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.42	0.4	-10000	0	-0.75	206	206
E2/ER beta (dimer)	0.001	0.016	0.21	2	-10000	0	2
mol:GDP	-0.32	0.29	-10000	0	-0.59	205	205
mol:NADP	-0.42	0.4	-10000	0	-0.75	206	206
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
mol:IP3	-0.22	0.32	-10000	0	-0.83	70	70
IGF-1R heterotetramer	-0.015	0.13	0.32	4	-0.86	8	12
PLCB1	-0.22	0.32	-10000	0	-0.86	66	66
PLCB2	-0.23	0.33	-10000	0	-0.86	70	70
IGF1	-0.34	0.42	-10000	0	-0.86	145	145
mol:L-citrulline	-0.42	0.4	-10000	0	-0.75	206	206
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.44	0.49	-10000	0	-0.93	178	178
JNK cascade	0.001	0.016	0.21	2	-10000	0	2
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0.002	0.023	0.32	2	-10000	0	2
GNAQ	-0.002	0.045	-10000	0	-0.86	1	1
ESR1	-0.48	0.43	-10000	0	-0.86	205	205
Gq family/GDP/Gbeta gamma	-0.093	0.2	-10000	0	-0.79	15	15
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.2	0.19	-10000	0	-0.38	131	131
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.44	0.36	-10000	0	-0.74	205	205
GNAZ	0.15	0.17	0.32	176	-0.86	1	177
E2/ER alpha (dimer)	-0.37	0.34	-10000	0	-0.67	205	205
STRN	-0.028	0.15	-10000	0	-0.86	12	12
GNAL	0.051	0.12	0.32	60	-10000	0	60
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.007	0.034	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.063	-10000	0	-0.86	2	2
HBEGF	-0.4	0.38	-10000	0	-0.78	165	165
cAMP biosynthetic process	-0.25	0.25	-10000	0	-0.48	205	205
SRC	-0.45	0.43	-10000	0	-0.88	161	161
PI3K	-0.005	0.071	-10000	0	-0.94	2	2
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.29	0.26	-10000	0	-0.52	206	206
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.42	0.32	-10000	0	-0.66	226	226
Gs family/GTP	-0.26	0.26	-10000	0	-0.48	205	205
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.001	0.014	-10000	0	-10000	0	0
vasodilation	-0.39	0.37	-10000	0	-0.7	206	206
mol:DAG	-0.22	0.32	-10000	0	-0.83	70	70
Gs family/GDP/Gbeta gamma	-0.26	0.24	-10000	0	-0.47	206	206
MSN	-0.2	0.22	-10000	0	-0.72	9	9
Gq family/GTP	-0.24	0.34	-10000	0	-0.89	70	70
mol:PI-3-4-5-P3	-0.52	0.47	-10000	0	-0.93	206	206
NRAS	0	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.39	0.37	0.7	206	-10000	0	206
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.3	0.27	-10000	0	-0.55	205	205
NOS3	-0.46	0.44	-10000	0	-0.82	206	206
GNA11	-0.028	0.15	-10000	0	-0.86	12	12
MAPKKK cascade	-0.43	0.39	-10000	0	-0.76	214	214
E2/ER alpha (dimer)/PELP1/Src	-0.47	0.39	-10000	0	-0.8	205	205
ruffle organization	-0.18	0.2	-10000	0	-0.53	15	15
ROCK2	-0.24	0.22	-10000	0	-0.66	14	14
GNA14	-0.15	0.32	-10000	0	-0.86	63	63
GNA15	-0.001	0.05	0.32	2	-0.86	1	3
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.41	0.39	-10000	0	-0.8	164	164
MMP2	-0.42	0.4	-10000	0	-0.89	139	139

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.38	0.52	1	87	-0.85	15	102
PLK1	0.28	0.23	0.62	76	-10000	0	76
BIRC5	0.3	0.23	0.59	97	-10000	0	97
HSPA1B	0.39	0.53	1.1	85	-0.86	14	99
MAP2K1	0.12	0.12	0.35	37	-10000	0	37
BRCA2	0.38	0.55	1.1	84	-0.97	17	101
FOXM1	0.44	0.63	1.2	96	-1	16	112
XRCC1	0.39	0.53	1.1	83	-0.88	13	96
FOXM1B/p19	0.21	0.48	0.69	147	-0.84	24	171
Cyclin D1/CDK4	0.23	0.53	0.9	75	-0.93	24	99
CDC2	0.41	0.57	1.1	94	-0.88	16	110
TGFA	0.17	0.67	0.95	79	-1	58	137
SKP2	0.38	0.52	1.1	83	-0.88	13	96
CCNE1	0.14	0.16	0.35	134	-10000	0	134
CKS1B	0.39	0.53	1.1	83	-0.88	13	96
RB1	0.15	0.33	0.64	98	-10000	0	98
FOXM1C/SP1	0.24	0.52	0.8	138	-0.97	16	154
AURKB	0.27	0.23	0.6	80	-10000	0	80
CENPF	0.45	0.57	1.1	102	-0.85	15	117
CDK4	0.044	0.046	-10000	0	-10000	0	0
MYC	0.26	0.55	0.92	80	-0.86	32	112
CHEK2	0.12	0.13	0.38	40	-10000	0	40
ONECUT1	0.27	0.55	0.97	79	-0.94	24	103
CDKN2A	0.1	0.18	0.3	120	-10000	0	120
LAMA4	0.39	0.53	1.1	89	-0.85	15	104
FOXM1B/HNF6	0.26	0.58	0.98	79	-1.1	24	103
FOS	-0.13	0.86	1.1	76	-1.1	131	207
SP1	-0.009	0.035	-10000	0	-10000	0	0
CDC25B	0.39	0.53	1.1	83	-0.88	13	96
response to radiation	0.074	0.089	-10000	0	-10000	0	0
CENPB	0.38	0.52	1.1	84	-0.86	14	98
CENPA	0.44	0.57	1.2	97	-0.88	13	110
NEK2	0.46	0.56	1.1	103	-0.84	14	117
HIST1H2BA	0.38	0.52	1	84	-0.87	14	98
CCNA2	0.19	0.17	0.35	197	-10000	0	197
EP300	0	0	-10000	0	-10000	0	0
CCNB1/CDK1	0.4	0.57	1.1	84	-0.96	15	99
CCNB2	0.46	0.57	1.1	101	-0.86	14	115
CCNB1	0.43	0.59	1.2	88	-0.9	15	103
ETV5	0.38	0.52	1.1	83	-0.88	13	96
ESR1	-0.25	0.74	1.1	44	-1	121	165
CCND1	0.28	0.56	0.99	79	-0.94	26	105
GSK3A	0.084	0.086	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.25	0.21	0.49	141	-10000	0	141
CDK2	0.031	0.031	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.11	0.12	0.35	37	-10000	0	37
FOXM1B/Cbp/p300	-0.082	0.21	-10000	0	-0.88	16	16
GAS1	0.2	0.76	1.1	84	-1.1	66	150
MMP2	0.35	0.6	1.1	83	-1.1	25	108
RB1/FOXM1C	0.32	0.52	0.95	80	-0.89	21	101
CREBBP	0	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.1	0.077	-10000	0	-10000	0	0
Crk/p130 Cas/Paxillin	-0.26	0.2	-10000	0	-0.5	89	89
JUN	-0.29	0.26	-10000	0	-0.67	84	84
HRAS	0.002	0.023	0.32	2	-10000	0	2
RET51/GFRalpha1/GDNF/GRB10	-0.43	0.37	-10000	0	-0.67	244	244
RAP1A	0	0	-10000	0	-10000	0	0
FRS2	0	0	-10000	0	-10000	0	0
RAP1A/GDP	0	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.43	0.37	-10000	0	-0.67	244	244
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.15	0.25	-10000	0	-0.54	109	109
RHOA	0	0	-10000	0	-10000	0	0
RAP1A/GTP	-0.39	0.34	-10000	0	-0.6	244	244
GRB7	-0.004	0.098	0.32	6	-0.86	4	10
RET51/GFRalpha1/GDNF	-0.43	0.37	-10000	0	-0.67	244	244
MAPKKK cascade	-0.35	0.29	-10000	0	-0.81	67	67
BCAR1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.15	0.25	-10000	0	-0.54	109	109
lamellipodium assembly	-0.22	0.18	-10000	0	-0.43	111	111
RET51/GFRalpha1/GDNF/SHC	-0.43	0.37	-10000	0	-0.67	244	244
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
RET9/GFRalpha1/GDNF/SHC	-0.15	0.25	-10000	0	-0.54	109	109
RET9/GFRalpha1/GDNF/Shank3	-0.15	0.25	-10000	0	-0.54	109	109
MAPK3	-0.37	0.31	-10000	0	-0.56	244	244
DOK1	0	0	-10000	0	-10000	0	0
DOK6	-0.12	0.31	0.32	4	-0.86	55	59
PXN	0	0	-10000	0	-10000	0	0
neurite development	-0.36	0.3	-10000	0	-0.56	236	236
DOK5	-0.005	0.11	0.32	8	-0.86	5	13
GFRA1	-0.25	0.39	-10000	0	-0.86	109	109
MAPK8	-0.3	0.27	-10000	0	-0.71	80	80
HRAS/GTP	-0.41	0.35	-10000	0	-0.62	244	244
tube development	-0.14	0.24	-10000	0	-0.51	109	109
MAPK1	-0.37	0.31	-10000	0	-0.56	244	244
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.1	0.17	-10000	0	-0.36	109	109
Rac1/GDP	0	0	-10000	0	-10000	0	0
SRC	0.004	0.036	0.32	5	-10000	0	5
PDLIM7	0.003	0.028	0.32	3	-10000	0	3
RET51/GFRalpha1/GDNF/Dok6	-0.48	0.41	-10000	0	-0.71	255	255
SHC1	0	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.43	0.37	-10000	0	-0.67	244	244
RET51/GFRalpha1/GDNF/Dok5	-0.44	0.38	-10000	0	-0.67	246	246
PRKCA	0	0	-10000	0	-10000	0	0
HRAS/GDP	0.001	0.016	-10000	0	-10000	0	0
CREB1	-0.22	0.24	-10000	0	-0.56	106	106
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.17	-10000	0	-0.36	105	105
RET51/GFRalpha1/GDNF/Grb7	-0.44	0.37	-10000	0	-0.67	246	246
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.46	0.43	0.32	2	-0.86	200	202
DOK4	0	0	-10000	0	-10000	0	0
JNK cascade	-0.27	0.27	-10000	0	-0.65	84	84
RET9/GFRalpha1/GDNF/FRS2	-0.15	0.25	-10000	0	-0.54	109	109
SHANK3	0.001	0.016	0.32	1	-10000	0	1
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
NCK1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.1	0.17	-10000	0	-0.36	105	105
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.29	0.25	-10000	0	-0.45	236	236
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.29	0.26	-10000	0	-0.46	236	236
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.34	0.35	-10000	0	-0.54	236	236
PI3K	-0.36	0.32	-10000	0	-0.74	111	111
SOS1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.14	0.24	-10000	0	-0.51	109	109
GRB10	0	0	-10000	0	-10000	0	0
activation of MAPKK activity	-0.23	0.21	-10000	0	-0.49	106	106
RET51/GFRalpha1/GDNF/FRS2	-0.43	0.37	-10000	0	-0.67	244	244
GAB1	0	0	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
IRS2	-0.016	0.12	-10000	0	-0.86	7	7
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.34	0.35	-10000	0	-0.54	236	236
RET51/GFRalpha1/GDNF/PKC alpha	-0.43	0.37	-10000	0	-0.67	244	244
GRB2	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
GDNF	0.014	0.064	0.32	16	-10000	0	16
RAC1	0	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.43	0.37	-10000	0	-0.67	244	244
Rac1/GTP	-0.27	0.22	-10000	0	-0.54	111	111
RET9/GFRalpha1/GDNF	-0.17	0.28	-10000	0	-0.59	109	109
GFRalpha1/GDNF	-0.19	0.31	-10000	0	-0.67	109	109

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.15	0.25	-10000	0	-0.55	103	103
regulation of S phase of mitotic cell cycle	-0.099	0.16	-10000	0	-0.36	101	101
GNAO1	-0.41	0.43	-10000	0	-0.86	178	178
HRAS	0.002	0.023	0.31	2	-10000	0	2
SHBG/T-DHT	-0.23	0.29	-10000	0	-0.6	143	143
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.008	0.003	-10000	0	-10000	0	0
MAP2K1	-0.14	0.22	-10000	0	-0.48	101	101
T-DHT/AR	-0.18	0.3	-10000	0	-0.68	101	101
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.003	0.004	-10000	0	-0.006	179	179
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.063	-10000	0	-0.86	2	2
mol:GDP	-0.18	0.29	-10000	0	-0.66	102	102
cell proliferation	-0.26	0.28	-10000	0	-0.52	154	154
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
FOS	-0.43	0.44	-10000	0	-0.88	179	179
mol:Ca2+	-0.051	0.056	-10000	0	-0.1	166	166
MAPK3	-0.21	0.25	-10000	0	-0.55	101	101
MAPK1	-0.12	0.13	-10000	0	-0.32	56	56
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
mol:IP3	-0.002	0.002	-10000	0	-0.004	179	179
cAMP biosynthetic process	-0.18	0.29	-10000	0	-0.54	143	143
GNG2	-0.007	0.077	-10000	0	-0.86	3	3
potassium channel inhibitor activity	-0.002	0.002	-10000	0	-0.004	179	179
HRAS/GTP	-0.15	0.22	-10000	0	-0.51	101	101
actin cytoskeleton reorganization	-0.004	0.054	-10000	0	-0.7	2	2
SRC	0.004	0.036	0.32	5	-10000	0	5
voltage-gated calcium channel activity	-0.002	0.002	-10000	0	-0.004	179	179
PI3K	-0.005	0.065	-10000	0	-0.85	2	2
apoptosis	0.24	0.26	0.48	180	-10000	0	180
T-DHT/AR/PELP1	-0.16	0.26	-10000	0	-0.6	101	101
HRAS/GDP	-0.17	0.28	-10000	0	-0.62	102	102
CREB1	-0.26	0.28	-10000	0	-0.52	180	180
RAC1-CDC42/GTP	-0.004	0.055	-10000	0	-0.72	2	2
AR	-0.24	0.38	-10000	0	-0.86	101	101
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.15	0.21	-10000	0	-0.5	101	101
RAC1-CDC42/GDP	-0.16	0.27	-10000	0	-0.59	102	102
T-DHT/AR/PELP1/Src	-0.15	0.25	-10000	0	-0.55	101	101
MAP2K2	-0.14	0.22	-10000	0	-0.48	101	101
T-DHT/AR/PELP1/Src/PI3K	-0.099	0.17	-10000	0	-0.37	101	101
GNAZ	0.15	0.17	0.32	176	-0.86	1	177
SHBG	-0.33	0.42	-10000	0	-0.86	143	143
Gi family/GNB1/GNG2/GDP	-0.24	0.29	-10000	0	-0.51	178	178
mol:T-DHT	-0.001	0.002	-10000	0	-0.003	123	123
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.01	0.01	-10000	0	-10000	0	0
Gi family/GTP	-0.21	0.27	-10000	0	-0.51	129	129
CDC42	0	0	-10000	0	-10000	0	0

×

Glypican 2 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.18	0.16	0.32	208	-9999	208
GPC2	0.043	0.11	0.32	50	-9999	50
GPC2/Midkine	0.15	0.14	0.44	33	-9999	33
neuron projection morphogenesis	0.15	0.14	0.44	33	-9999	33

×

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	0.005	0.15	0.32	18	-0.86	8	26
NFATC2	-0.18	0.38	0.64	1	-0.81	85	86
NFATC3	-0.058	0.12	-10000	0	-0.3	29	29
CD40LG	-0.57	0.61	0.76	1	-1.2	168	169
ITCH	-0.004	0.033	-10000	0	-10000	0	0
CBLB	-0.004	0.033	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.34	0.5	0.57	9	-1.1	83	92
JUNB	-0.044	0.19	-10000	0	-0.86	19	19
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.041	-10000	0	-0.35	5	5
T cell anergy	0.002	0.084	-10000	0	-0.5	5	5
TLE4	-0.11	0.3	-10000	0	-0.63	81	81
Jun/NFAT1-c-4/p21SNFT	-0.41	0.56	0.67	1	-1.1	133	134
AP-1/NFAT1-c-4	-0.77	0.85	0.72	4	-1.6	167	171
IKZF1	-0.12	0.33	0.58	1	-0.66	83	84
T-helper 2 cell differentiation	-0.26	0.4	-10000	0	-0.93	82	82
AP-1/NFAT1	-0.41	0.42	0.41	4	-0.74	208	212
CALM1	-0.003	0.022	-10000	0	-10000	0	0
EGR2	-0.54	0.85	0.58	1	-1.7	125	126
EGR3	-0.45	0.78	-10000	0	-1.6	94	94
NFAT1/FOXP3	-0.13	0.32	0.42	9	-0.65	83	92
EGR1	-0.3	0.41	-10000	0	-0.86	128	128
JUN	-0.015	0.11	-10000	0	-0.86	6	6
EGR4	0.002	0.029	0.31	3	-10000	0	3
mol:Ca2+	-0.003	0.024	-10000	0	-10000	0	0
GBP3	-0.15	0.37	-10000	0	-0.74	90	90
FOSL1	-0.035	0.18	0.32	3	-0.86	16	19
NFAT1-c-4/MAF/IRF4	-0.47	0.6	0.63	2	-1.2	143	145
DGKA	-0.1	0.3	0.58	1	-0.65	70	71
CREM	0	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.4	0.55	0.55	1	-1.1	132	133
CTLA4	-0.077	0.31	0.42	15	-0.62	73	88
NFAT1-c-4 (dimer)/EGR1	-0.56	0.68	0.55	1	-1.3	143	144
NFAT1-c-4 (dimer)/EGR4	-0.4	0.56	0.55	1	-1.1	133	134
FOS	-0.42	0.43	-10000	0	-0.87	179	179
IFNG	-0.2	0.34	0.55	1	-0.86	56	57
T cell activation	-0.34	0.44	-10000	0	-0.94	112	112
MAF	-0.002	0.045	-10000	0	-0.86	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.25	0.43	0.77	130	-10000	0	130
TNF	-0.44	0.58	-10000	0	-1.1	146	146
FASLG	-0.53	0.8	-10000	0	-1.5	133	133
TBX21	-0.009	0.14	-10000	0	-0.86	9	9
BATF3	-0.008	0.09	0.32	1	-0.86	4	5
PRKCQ	-0.027	0.17	0.35	2	-0.86	15	17
PTPN1	-0.1	0.29	-10000	0	-0.64	70	70
NFAT1-c-4/ICER1	-0.41	0.55	0.54	1	-1.1	132	133
GATA3	-0.062	0.22	0.32	1	-0.86	27	28
T-helper 1 cell differentiation	-0.2	0.33	0.55	1	-0.84	56	57
IL2RA	-0.34	0.46	0.54	10	-0.91	111	121
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.11	0.29	-10000	0	-0.62	81	81
E2F1	0.2	0.15	0.32	230	-10000	0	230
PPARG	0.001	0.016	0.32	1	-10000	0	1
SLC3A2	-0.1	0.29	-10000	0	-0.61	80	80
IRF4	-0.16	0.35	0.32	9	-0.86	74	83
PTGS2	-0.65	0.69	-10000	0	-1.4	167	167
CSF2	-0.55	0.61	-10000	0	-1.2	166	166
JunB/Fra1/NFAT1-c-4	-0.42	0.58	0.54	2	-1.1	133	135
IL4	-0.28	0.43	-10000	0	-1	78	78
IL5	-0.55	0.61	-10000	0	-1.2	162	162
IL2	-0.35	0.45	-10000	0	-0.97	110	110
IL3	-0.084	0.066	-10000	0	-10000	0	0
RNF128	-0.012	0.11	-10000	0	-0.92	5	5
NFATC1	-0.25	0.44	-10000	0	-0.78	130	130
CDK4	0.21	0.29	0.65	78	-10000	0	78
PTPRK	-0.1	0.29	-10000	0	-0.61	81	81
IL8	-0.63	0.65	0.59	1	-1.2	182	183
POU2F1	0.002	0.005	-10000	0	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.44	0.6	-10000	0	-1.1	126	126
STAT6 (cleaved dimer)	-0.55	0.56	-10000	0	-1.1	175	175
IGHG1	-0.14	0.24	0.52	2	-0.41	72	74
IGHG3	-0.43	0.57	-10000	0	-0.98	167	167
AKT1	-0.21	0.35	0.6	1	-0.69	82	83
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.16	0.3	0.58	1	-0.58	76	77
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.2	0.33	-10000	0	-0.61	81	81
THY1	-0.42	0.62	0.88	1	-1.2	117	118
MYB	0.032	0.096	0.32	38	-10000	0	38
HMGA1	0.017	0.071	0.32	20	-10000	0	20
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.3	0.46	0.65	2	-0.8	135	137
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.2	0.33	-10000	0	-0.61	80	80
SP1	0.019	0.022	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.021	0.025	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.54	0.55	-10000	0	-1.1	144	144
SOCS1	-0.29	0.39	-10000	0	-0.75	111	111
SOCS3	-0.33	0.55	-10000	0	-1.2	84	84
FCER2	-0.41	0.58	0.78	1	-1	142	143
PARP14	-0.001	0.045	-10000	0	-0.86	1	1
CCL17	-0.44	0.6	-10000	0	-1.1	128	128
GRB2	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.15	0.27	-10000	0	-0.55	35	35
T cell proliferation	-0.46	0.62	-10000	0	-1.2	133	133
IL4R/JAK1	-0.45	0.6	-10000	0	-1.1	130	130
EGR2	-0.64	0.82	-10000	0	-1.5	153	153
JAK2	-0.004	0.064	-10000	0	-0.89	1	1
JAK3	0.009	0.057	0.34	4	-0.84	1	5
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
JAK1	0.01	0.02	-10000	0	-10000	0	0
COL1A2	-0.11	0.26	-10000	0	-1.7	4	4
CCL26	-0.43	0.61	-10000	0	-1.2	114	114
IL4R	-0.47	0.65	-10000	0	-1.2	129	129
PTPN6	0.016	0.014	-10000	0	-10000	0	0
IL13RA2	-0.99	0.76	-10000	0	-1.4	258	258
IL13RA1	-0.002	0.044	-10000	0	-10000	0	0
IRF4	-0.35	0.67	0.72	1	-1.6	79	80
ARG1	-0.33	0.61	-10000	0	-1.6	68	68
CBL	-0.28	0.43	0.6	1	-0.75	131	132
GTF3A	0.025	0.032	-10000	0	-10000	0	0
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
IL13RA1/JAK2	-0.001	0.076	-10000	0	-0.7	1	1
IRF4/BCL6	-0.36	0.58	-10000	0	-1.5	79	79
CD40LG	-0.02	0.17	0.39	2	-0.87	14	16
MAPK14	-0.31	0.48	0.6	1	-0.86	123	124
mitosis	-0.2	0.34	0.59	1	-0.65	82	83
STAT6	-0.52	0.73	0.91	2	-1.2	155	157
SPI1	-0.018	0.096	-10000	0	-0.58	6	6
RPS6KB1	-0.19	0.32	0.58	1	-0.64	73	74
STAT6 (dimer)	-0.52	0.73	0.91	2	-1.2	155	157
STAT6 (dimer)/PARP14	-0.49	0.64	-10000	0	-1.1	154	154
mast cell activation	0.008	0.019	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.21	0.35	0.6	1	-0.65	84	85
FRAP1	-0.21	0.35	0.6	1	-0.69	82	83
LTA	-0.44	0.6	-10000	0	-1.1	125	125
FES	-0.012	0.099	-10000	0	-0.86	5	5
T-helper 1 cell differentiation	0.5	0.7	1.2	155	-0.91	2	157
CCL11	-0.42	0.58	-10000	0	-1.1	127	127
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.21	0.35	0.6	1	-0.66	81	82
IL2RG	0.002	0.11	0.31	7	-0.85	5	12
IL10	-0.52	0.69	-10000	0	-1.3	142	142
IRS1	0	0	-10000	0	-10000	0	0
IRS2	-0.016	0.12	-10000	0	-0.86	7	7
IL4	-0.08	0.18	-10000	0	-10000	0	0
IL5	-0.44	0.6	-10000	0	-1.1	127	127
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.33	0.48	0.83	1	-0.84	132	133
COL1A1	-0.13	0.36	0.74	1	-1.8	10	11
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.46	0.61	-10000	0	-1.2	112	112
IL2R gamma/JAK3	-0.003	0.1	0.4	2	-0.77	5	7
TFF3	-0.45	0.62	-10000	0	-1.2	131	131
ALOX15	-0.44	0.6	-10000	0	-1.1	126	126
MYBL1	0.005	0.04	0.32	6	-10000	0	6
T-helper 2 cell differentiation	-0.36	0.5	-10000	0	-0.91	133	133
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	-0.011	0.056	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.2	0.32	-10000	0	-0.6	82	82
mol:PI-3-4-5-P3	-0.21	0.35	0.6	1	-0.69	82	83
PI3K	-0.23	0.37	0.6	1	-0.74	80	81
DOK2	-0.012	0.099	-10000	0	-0.86	5	5
ETS1	0.012	0.048	-10000	0	-0.82	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.14	0.26	-10000	0	-0.55	24	24
ITGB3	-0.5	0.68	-10000	0	-1.3	133	133
PIGR	-0.6	0.74	-10000	0	-1.3	157	157
IGHE	0.021	0.059	-10000	0	-10000	0	0
MAPKKK cascade	-0.13	0.25	-10000	0	-0.54	24	24
BCL6	0	0.002	-10000	0	-10000	0	0
OPRM1	-0.45	0.6	-10000	0	-1.1	127	127
RETNLB	-0.45	0.6	-10000	0	-1.1	130	130
SELP	-0.66	0.81	-10000	0	-1.5	163	163
AICDA	-0.43	0.57	-10000	0	-1.1	128	128

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.11	0.24	-10000	0	-10000	0	0
CRKL	-0.16	0.21	-10000	0	-0.43	137	137
mol:DAG	-0.17	0.24	-10000	0	-0.48	136	136
HRAS	-0.13	0.17	-10000	0	-10000	0	0
MAPK8	-0.2	0.28	-10000	0	-0.53	147	147
RAP1A	-0.16	0.21	-10000	0	-0.43	137	137
GAB1	-0.16	0.21	-10000	0	-0.43	137	137
MAPK14	-0.18	0.24	-10000	0	-0.5	136	136
EPO	-0.3	0.42	0.32	12	-0.86	136	148
PLCG1	-0.18	0.24	-10000	0	-0.49	136	136
EPOR/TRPC2/IP3 Receptors	-0.011	0.016	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.28	0.34	-10000	0	-0.62	168	168
GAB1/SHC/GRB2/SOS1	-0.14	0.18	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.24	0.33	-10000	0	-0.66	136	136
IRS2	-0.17	0.22	-10000	0	-0.44	141	141
STAT1	-0.14	0.26	-10000	0	-0.49	136	136
STAT5B	-0.18	0.24	-10000	0	-0.49	136	136
cell proliferation	-0.17	0.27	-10000	0	-0.5	147	147
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.13	0.17	-10000	0	-0.74	1	1
TEC	-0.16	0.22	-10000	0	-0.44	141	141
SOCS3	-0.12	0.29	-10000	0	-0.86	50	50
STAT1 (dimer)	-0.14	0.26	-10000	0	-0.47	136	136
JAK2	-0.014	0.047	-10000	0	-0.86	1	1
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
EPO/EPOR (dimer)/JAK2	-0.14	0.25	-10000	0	-0.46	137	137
EPO/EPOR	-0.24	0.33	-10000	0	-0.66	136	136
LYN	0	0	-10000	0	-10000	0	0
TEC/VAV2	-0.16	0.21	-10000	0	-0.42	141	141
elevation of cytosolic calcium ion concentration	-0.011	0.016	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.2	0.28	-10000	0	-0.56	136	136
mol:IP3	-0.17	0.24	-10000	0	-0.48	136	136
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.15	0.2	-10000	0	-0.93	3	3
SH2B3	-0.011	0.016	-10000	0	-10000	0	0
NFKB1	-0.18	0.24	-10000	0	-0.5	136	136
EPO/EPOR (dimer)/JAK2/SOCS3	-0.18	0.21	-10000	0	-0.4	168	168
PTPN6	-0.17	0.22	-10000	0	-0.46	137	137
TEC/VAV2/GRB2	-0.15	0.2	-10000	0	-0.57	6	6
EPOR	-0.011	0.016	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.14	0.18	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	-0.016	0.12	-10000	0	-0.86	7	7
CRKL/CBL/C3G	-0.14	0.2	-10000	0	-10000	0	0
VAV2	-0.16	0.21	-10000	0	-0.43	137	137
CBL	-0.16	0.21	-10000	0	-0.43	137	137
SHC/Grb2/SOS1	-0.14	0.2	-10000	0	-10000	0	0
STAT5A	-0.18	0.24	-10000	0	-0.49	136	136
GRB2	0	0	-10000	0	-10000	0	0
STAT5 (dimer)	-0.16	0.22	-10000	0	-10000	0	0
LYN/PLCgamma2	-0.013	0.091	-10000	0	-0.67	7	7
PTPN11	0	0	-10000	0	-10000	0	0
BTK	-0.17	0.22	-10000	0	-0.44	142	142
BCL2	-0.12	0.24	-10000	0	-0.99	1	1

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.4	0.65	-10000	0	-1.3	125	125
MKNK1	0	0	-10000	0	-10000	0	0
MAPK14	-0.078	0.16	-10000	0	-0.38	7	7
ATF2/c-Jun	-0.086	0.2	-10000	0	-1.2	8	8
MAPK11	-0.067	0.18	0.35	12	-0.3	113	125
MITF	-0.081	0.2	-10000	0	-0.36	113	113
MAPKAPK5	-0.082	0.2	-10000	0	-0.36	113	113
KRT8	-0.084	0.2	-10000	0	-0.36	115	115
MAPKAPK3	0	0	-10000	0	-10000	0	0
MAPKAPK2	0	0	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.11	0.25	0.37	1	-0.46	114	115
CEBPB	-0.082	0.2	-10000	0	-0.36	113	113
SLC9A1	-0.081	0.2	-10000	0	-0.36	113	113
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.083	0.22	-10000	0	-0.37	115	115
p38alpha-beta/MNK1	-0.1	0.19	-10000	0	-0.48	6	6
JUN	-0.065	0.2	-10000	0	-1.1	8	8
PPARGC1A	-0.15	0.29	-10000	0	-0.47	141	141
USF1	-0.082	0.2	-10000	0	-0.36	113	113
RAB5/GDP/GDI1	-0.082	0.12	-10000	0	-0.35	6	6
NOS2	-0.065	0.21	-10000	0	-10000	0	0
DDIT3	-0.081	0.2	-10000	0	-0.36	111	111
RAB5A	0	0	-10000	0	-10000	0	0
HSPB1	-0.059	0.16	-10000	0	-0.39	4	4
p38alpha-beta/HBP1	-0.1	0.19	-10000	0	-0.48	6	6
CREB1	-0.092	0.22	-10000	0	-0.39	114	114
RAB5/GDP	0	0	-10000	0	-10000	0	0
EIF4E	-0.069	0.17	-10000	0	-0.43	5	5
RPS6KA4	-0.082	0.2	-10000	0	-0.36	113	113
PLA2G4A	-0.12	0.26	-10000	0	-0.74	39	39
GDI1	-0.082	0.2	-10000	0	-0.36	113	113
TP53	-0.11	0.24	-10000	0	-0.45	114	114
RPS6KA5	-0.096	0.23	-10000	0	-0.4	116	116
ESR1	-0.38	0.38	-10000	0	-0.58	247	247
HBP1	0	0	-10000	0	-10000	0	0
MEF2C	-0.082	0.2	-10000	0	-0.36	113	113
MEF2A	-0.082	0.2	-10000	0	-0.36	113	113
EIF4EBP1	-0.092	0.22	-10000	0	-0.39	114	114
KRT19	-0.26	0.4	-10000	0	-0.6	182	182
ELK4	-0.082	0.2	-10000	0	-0.36	113	113
ATF6	-0.082	0.2	-10000	0	-0.36	113	113
ATF1	-0.092	0.22	-10000	0	-0.39	114	114
p38alpha-beta/MAPKAPK2	-0.1	0.19	0.31	1	-0.44	9	10
p38alpha-beta/MAPKAPK3	-0.1	0.19	0.31	1	-0.48	6	7

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	-0.001	0.048	0.32	1	-0.86	1	2
PTK2	0	0	-10000	0	-10000	0	0
CRKL	-0.19	0.24	-10000	0	-0.48	150	150
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0.002	0.023	0.32	2	-10000	0	2
IRS1/Crk	-0.2	0.24	-10000	0	-0.48	150	150
IGF-1R heterotetramer/IGF1/PTP1B	-0.22	0.28	-10000	0	-0.56	150	150
AKT1	-0.16	0.21	-10000	0	-0.41	150	150
BAD	-0.13	0.21	-10000	0	-0.38	147	147
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.19	0.24	-10000	0	-0.48	150	150
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.2	0.24	-10000	0	-0.48	150	150
RAF1	-0.12	0.2	-10000	0	-0.71	5	5
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.18	0.23	-10000	0	-0.46	150	150
YWHAZ	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.21	0.26	-10000	0	-0.52	150	150
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
RPS6KB1	-0.16	0.21	-10000	0	-0.41	150	150
GNB2L1	0	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.1	0.18	-10000	0	-0.57	5	5
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.16	0.2	-10000	0	-0.82	3	3
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.18	0.23	-10000	0	-0.45	150	150
IGF-1R heterotetramer	-0.053	0.14	0.27	4	-0.91	8	12
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.2	0.25	-10000	0	-0.49	150	150
Crk/p130 Cas/Paxillin	-0.17	0.22	-10000	0	-0.43	150	150
IGF1R	-0.053	0.14	0.27	4	-0.91	8	12
IGF1	-0.34	0.42	-10000	0	-0.87	145	145
IRS2/Crk	-0.19	0.24	-10000	0	-0.46	154	154
PI3K	-0.19	0.24	-10000	0	-0.46	150	150
apoptosis	0.13	0.16	0.63	5	-10000	0	5
HRAS/GDP	0.001	0.016	-10000	0	-10000	0	0
PRKCD	-0.22	0.27	-10000	0	-0.54	150	150
RAF1/14-3-3 E	-0.12	0.16	-10000	0	-0.58	5	5
BAD/14-3-3	-0.14	0.18	-10000	0	-0.69	5	5
PRKCZ	-0.18	0.24	-10000	0	-0.44	153	153
Crk/p130 Cas/Paxillin/FAK1	-0.14	0.17	-10000	0	-0.7	5	5
PTPN1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.23	0.28	-10000	0	-0.57	150	150
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.2	0.25	-10000	0	-0.49	150	150
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.19	0.24	-10000	0	-0.48	150	150
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	-0.19	0.24	-10000	0	-0.48	150	150
IRS1	-0.21	0.26	-10000	0	-0.52	150	150
IRS2	-0.2	0.25	-10000	0	-0.49	154	154
IGF-1R heterotetramer/IGF1	-0.28	0.34	-10000	0	-0.69	150	150
GRB2	0	0	-10000	0	-10000	0	0
PDPK1	-0.18	0.22	-10000	0	-0.44	150	150
YWHAE	0	0	-10000	0	-10000	0	0
PRKD1	-0.22	0.27	-10000	0	-0.54	152	152
SHC1	0	0	-10000	0	-10000	0	0

×

p75(NTR)-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
Sortilin/TRAF6	0.006	0.054	-10000	0	-0.67	1	1
Necdin/E2F1	0.12	0.17	0.44	9	-0.64	9	18
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.23	0.32	-10000	0	-0.58	150	150
NGF (dimer)/p75(NTR)/BEX1	-0.4	0.43	-10000	0	-0.74	209	209
NT-4/5 (dimer)/p75(NTR)	-0.26	0.33	-10000	0	-0.67	143	143
IKBKB	0	0	-10000	0	-10000	0	0
AKT1	-0.22	0.29	-10000	0	-0.55	146	146
IKBKG	0	0	-10000	0	-10000	0	0
BDNF	0.01	0.056	0.32	12	-10000	0	12
MGDIs/NGR/p75(NTR)/LINGO1	-0.2	0.32	-10000	0	-0.59	144	144
FURIN	-0.016	0.12	-10000	0	-0.86	7	7
proBDNF (dimer)/p75(NTR)/Sortilin	-0.21	0.29	0.39	2	-0.58	143	145
LINGO1	0.049	0.13	0.32	60	-0.86	1	61
Sortilin/TRAF6/NRIF	-0.001	0.023	-10000	0	-0.44	1	1
proBDNF (dimer)	0.01	0.056	0.32	12	-10000	0	12
NTRK1	0.002	0.023	0.32	2	-10000	0	2
RTN4R	-0.009	0.089	-10000	0	-0.86	4	4
neuron apoptosis	-0.11	0.27	-10000	0	-0.45	136	136
IRAK1	0.001	0.016	0.32	1	-10000	0	1
SHC1	-0.25	0.32	-10000	0	-0.63	146	146
ARHGDIA	0	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.23	0.32	-10000	0	-0.59	147	147
MAGEH1	-0.011	0.1	0.32	1	-0.86	5	6
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.23	0.33	0.38	1	-0.6	148	149
Mammalian IAPs/DIABLO	0.005	0.054	-10000	0	-0.53	2	2
proNGF (dimer)	-0.038	0.18	0.32	1	-0.86	17	18
MAGED1	-0.007	0.077	-10000	0	-0.86	3	3
APP	-0.009	0.089	-10000	0	-0.86	4	4
NT-4/5 (dimer)	0.003	0.028	0.32	3	-10000	0	3
ZNF274	0	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.21	0.28	-10000	0	-0.55	146	146
NGF	-0.039	0.18	0.32	1	-0.86	17	18
cell cycle arrest	-0.17	0.31	-10000	0	-0.53	146	146
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.15	0.2	-10000	0	-0.39	146	146
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.23	0.29	-10000	0	-0.59	144	144
NCSTN	0	0	-10000	0	-10000	0	0
mol:GTP	-0.25	0.32	-10000	0	-0.63	147	147
PSENEN	0	0	-10000	0	-10000	0	0
mol:ceramide	-0.22	0.29	-10000	0	-0.57	146	146
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.14	0.19	-10000	0	-0.61	29	29
p75(NTR)/beta APP	-0.26	0.33	-10000	0	-0.67	145	145
BEX1	-0.24	0.42	0.32	32	-0.86	113	145
mol:GDP	-0.25	0.32	-10000	0	-0.63	146	146
NGF (dimer)	-0.23	0.32	-10000	0	-0.6	150	150
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.18	0.3	-10000	0	-0.54	144	144
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
RAC1/GTP	-0.22	0.29	-10000	0	-0.56	146	146
MYD88	0	0	-10000	0	-10000	0	0
CHUK	0	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.25	0.32	-10000	0	-0.63	147	147
RHOB	-0.044	0.19	-10000	0	-0.86	19	19
RHOA	0	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.14	0.11	-10000	0	-10000	0	0
NT3 (dimer)	-0.42	0.43	-10000	0	-0.86	183	183
TP53	-0.18	0.23	-10000	0	-0.47	144	144
PRDM4	-0.22	0.3	-10000	0	-0.57	146	146
BDNF (dimer)	-0.19	0.29	0.42	4	-0.54	142	146
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
SORT1	0.012	0.06	0.32	14	-10000	0	14
activation of caspase activity	-0.23	0.31	-10000	0	-0.57	150	150
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.22	0.31	-10000	0	-0.58	146	146
RHOC	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.17	0.29	-10000	0	-0.5	146	146
DIABLO	0	0	-10000	0	-10000	0	0
SMPD2	-0.22	0.3	-10000	0	-0.57	146	146
APH1B	0	0	-10000	0	-10000	0	0
APH1A	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.24	0.33	-10000	0	-0.63	146	146
PSEN1	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.55	0.5	-10000	0	-0.93	218	218
MAPK8	-0.17	0.27	-10000	0	-0.48	146	146
MAPK9	-0.15	0.26	-10000	0	-0.47	146	146
APAF1	0	0	-10000	0	-10000	0	0
NTF3	-0.42	0.43	-10000	0	-0.86	183	183
NTF4	0.003	0.028	0.32	3	-10000	0	3
NDN	-0.012	0.14	0.32	10	-0.86	9	19
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.22	0.29	-10000	0	-0.55	152	152
p75 CTF/Sortilin/TRAF6/NRIF	0.006	0.047	-10000	0	-0.53	1	1
RhoA-B-C/GTP	-0.25	0.32	-10000	0	-0.62	147	147
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.18	0.25	0.36	2	-0.5	144	146
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.2	0.27	0.38	2	-0.53	144	146
PRKACB	-0.002	0.045	-10000	0	-0.86	1	1
proBDNF (dimer)/p75 ECD	0.007	0.039	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.007	0.088	0.32	14	-0.86	2	16
BIRC2	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.17	0.33	0.24	63	-0.53	148	211
BAD	-0.16	0.27	-10000	0	-0.48	146	146
RIPK2	0	0	-10000	0	-10000	0	0
NGFR	-0.33	0.42	-10000	0	-0.86	143	143
CYCS	-0.21	0.28	-10000	0	-0.54	148	148
ADAM17	0	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.23	0.3	-10000	0	-0.58	146	146
BCL2L11	-0.16	0.27	-10000	0	-0.48	146	146
BDNF (dimer)/p75(NTR)	-0.25	0.33	-10000	0	-0.67	143	143
PI3K	-0.23	0.31	-10000	0	-0.59	146	146
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.22	0.3	-10000	0	-0.58	146	146
NDNL2	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.28	0.36	0.22	1	-0.72	146	147
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.23	0.31	-10000	0	-0.58	148	148
TRAF6	-0.002	0.045	-10000	0	-0.86	1	1
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.039	0.18	-10000	0	-0.86	17	17
PLG	-0.13	0.31	-10000	0	-0.86	58	58
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.22	0.3	-10000	0	-0.58	146	146
SQSTM1	0.004	0.036	0.32	5	-10000	0	5
NGFRAP1	-0.036	0.18	0.32	1	-0.86	16	17
CASP3	-0.14	0.25	-10000	0	-0.44	146	146
E2F1	0.2	0.15	0.32	230	-10000	0	230
CASP9	0	0	-10000	0	-10000	0	0
IKK complex	-0.12	0.19	-10000	0	-0.7	26	26
NGF (dimer)/TRKA	-0.029	0.14	-10000	0	-0.67	17	17
MMP7	-0.18	0.39	0.32	30	-0.86	88	118
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.21	0.29	-10000	0	-0.55	146	146
MMP3	0.018	0.073	0.32	21	-10000	0	21
APAF-1/Caspase 9	-0.16	0.21	-10000	0	-0.7	15	15

×

IL6-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	-0.31	0.37	-10000	0	-0.74	128	128
CRP	-0.52	0.56	-10000	0	-1.1	174	174
cell cycle arrest	-0.38	0.46	-10000	0	-0.89	136	136
TIMP1	-0.28	0.34	-10000	0	-0.69	116	116
IL6ST	-0.21	0.38	-10000	0	-0.87	91	91
Rac1/GDP	-0.23	0.28	-10000	0	-0.59	112	112
AP1	-0.22	0.26	-10000	0	-0.49	158	158
GAB2	0.004	0.011	-10000	0	-10000	0	0
TNFSF11	-0.44	0.51	-10000	0	-1	138	138
HSP90B1	-0.023	0.06	-10000	0	-10000	0	0
GAB1	0.003	0.008	-10000	0	-10000	0	0
MAPK14	-0.23	0.34	-10000	0	-0.74	84	84
AKT1	0.022	0.043	-10000	0	-0.53	1	1
FOXO1	0.035	0.064	-10000	0	-0.47	5	5
MAP2K6	-0.23	0.31	-10000	0	-0.58	122	122
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
MAP2K4	-0.23	0.32	-10000	0	-0.61	120	120
MITF	-0.19	0.28	-10000	0	-0.54	111	111
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0	0	-10000	0	-10000	0	0
A2M	-0.2	0.54	-10000	0	-1.5	52	52
CEBPB	0.014	0.003	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.046	0.091	-10000	0	-0.29	1	1
STAT3	-0.41	0.51	-10000	0	-0.97	136	136
STAT1	-0.019	0.033	0.26	1	-10000	0	1
CEBPD	-0.32	0.38	-10000	0	-0.76	129	129
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
PI3K	-0.005	0.071	-10000	0	-0.93	2	2
JUN	-0.014	0.11	-10000	0	-0.86	6	6
PIAS3/MITF	-0.2	0.24	-10000	0	-0.52	103	103
MAPK11	-0.22	0.34	-10000	0	-0.63	113	113
STAT3 (dimer)/FOXO1	-0.28	0.37	-10000	0	-0.67	144	144
GRB2/SOS1/GAB family	-0.14	0.22	-10000	0	-0.69	30	30
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.19	0.27	-10000	0	-0.49	135	135
GRB2	0.003	0.008	-10000	0	-10000	0	0
JAK2	-0.002	0.045	-10000	0	-0.86	1	1
LBP	-0.28	0.36	-10000	0	-0.7	121	121
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
JAK1	-0.001	0.007	-10000	0	-10000	0	0
MYC	-0.37	0.45	-10000	0	-0.87	137	137
FGG	-0.36	0.44	-10000	0	-0.85	135	135
macrophage differentiation	-0.38	0.46	-10000	0	-0.89	136	136
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.23	0.3	-10000	0	-0.59	139	139
JUNB	-0.32	0.39	-10000	0	-0.76	131	131
FOS	-0.42	0.43	-10000	0	-0.86	179	179
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.21	0.29	-10000	0	-0.5	154	154
STAT1/PIAS1	-0.22	0.25	-10000	0	-0.55	104	104
GRB2/SOS1/GAB family/SHP2/PI3K	0.007	0.04	-10000	0	-0.43	2	2
STAT3 (dimer)	-0.41	0.5	-10000	0	-0.96	136	136
PRKCD	-0.26	0.34	-10000	0	-0.62	143	143
IL6R	-0.022	0.13	-10000	0	-0.87	9	9
SOCS3	-0.25	0.47	-10000	0	-1.2	61	61
gp130 (dimer)/JAK1/JAK1/LMO4	-0.15	0.26	-10000	0	-0.6	92	92
Rac1/GTP	-0.25	0.29	-10000	0	-0.61	118	118
HCK	-0.027	0.15	-10000	0	-0.86	12	12
MAPKKK cascade	-0.003	0.082	-10000	0	-10000	0	0
bone resorption	-0.4	0.46	-10000	0	-0.89	153	153
IRF1	-0.31	0.37	-10000	0	-0.74	128	128
mol:GDP	-0.22	0.31	-10000	0	-0.58	121	121
SOS1	0.004	0.011	-10000	0	-10000	0	0
VAV1	-0.22	0.32	-10000	0	-0.6	119	119
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.2	0.29	-10000	0	-0.56	108	108
PTPN11	-0.018	0.027	-10000	0	-10000	0	0
IL6/IL6RA	-0.11	0.26	-10000	0	-0.69	61	61
gp130 (dimer)/TYK2/TYK2/LMO4	-0.15	0.26	-10000	0	-0.6	92	92
gp130 (dimer)/JAK2/JAK2/LMO4	-0.15	0.26	-10000	0	-0.6	92	92
IL6	-0.11	0.31	0.32	8	-0.88	52	60
PIAS3	0	0	-10000	0	-10000	0	0
PTPRE	0.014	0.07	0.32	2	-0.86	2	4
PIAS1	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.18	0.24	-10000	0	-0.46	135	135
LMO4	0	0.067	-10000	0	-0.89	2	2
STAT3 (dimer)/PIAS3	-0.41	0.4	-10000	0	-0.87	136	136
MCL1	0.04	0.035	-10000	0	-0.47	1	1

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.34	0.58	-10000	0	-1.1	108	108
PCK1	-0.72	0.85	-10000	0	-1.6	170	170
HNF4A	-0.4	0.69	-10000	0	-1.3	106	106
KCNJ11	-0.34	0.61	-10000	0	-1.1	107	107
AKT1	-0.13	0.22	-10000	0	-0.41	95	95
response to starvation	-0.005	0.025	-10000	0	-10000	0	0
DLK1	-0.32	0.61	0.74	1	-1.1	106	107
NKX2-1	-0.087	0.23	0.64	1	-10000	0	1
ACADM	-0.35	0.6	-10000	0	-1.1	110	110
TAT	-0.72	0.86	-10000	0	-1.7	160	160
CEBPB	-0.001	0.024	-10000	0	-10000	0	0
CEBPA	-0.005	0.085	0.32	1	-0.89	3	4
TTR	-0.42	0.66	-10000	0	-1.4	101	101
PKLR	-0.37	0.64	-10000	0	-1.2	116	116
APOA1	-0.48	0.78	-10000	0	-1.5	112	112
CPT1C	-0.34	0.58	-10000	0	-1.1	103	103
ALAS1	-0.14	0.31	-10000	0	-1.5	7	7
TFRC	-0.29	0.48	-10000	0	-0.86	109	109
FOXF1	-0.091	0.26	-10000	0	-0.86	39	39
NF1	0.01	0.046	-10000	0	-0.86	1	1
HNF1A (dimer)	-0.005	0.12	-10000	0	-0.69	6	6
CPT1A	-0.34	0.58	-10000	0	-1.1	105	105
HMGCS1	-0.34	0.58	-10000	0	-1.1	111	111
NR3C1	-0.068	0.1	-10000	0	-0.3	15	15
CPT1B	-0.34	0.58	-10000	0	-1.1	105	105
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.01	0.058	-10000	0	-10000	0	0
GCK	-0.59	0.76	-10000	0	-1.3	172	172
CREB1	-0.048	0.086	-10000	0	-0.26	9	9
IGFBP1	-0.47	0.7	-10000	0	-1.6	97	97
PDX1	-0.18	0.48	0.63	1	-1.2	49	50
UCP2	-0.34	0.58	-10000	0	-1.1	104	104
ALDOB	-0.49	0.78	-10000	0	-1.5	120	120
AFP	-0.092	0.33	-10000	0	-1.1	27	27
BDH1	-0.36	0.63	-10000	0	-1.2	111	111
HADH	-0.33	0.59	-10000	0	-1.1	105	105
F2	-0.4	0.69	-10000	0	-1.3	103	103
HNF1A	-0.005	0.12	-10000	0	-0.69	6	6
G6PC	-0.3	0.6	-10000	0	-1.6	64	64
SLC2A2	-0.28	0.6	-10000	0	-1.6	49	49
INS	0.035	0.082	0.3	7	-10000	0	7
FOXA1	-0.006	0.16	-10000	0	-0.74	10	10
FOXA3	-0.16	0.29	-10000	0	-0.7	57	57
FOXA2	-0.4	0.72	0.84	1	-1.2	119	120
ABCC8	-0.32	0.6	0.74	1	-1.2	98	99
ALB	-0.22	0.51	-10000	0	-1.4	55	55

×

TCGA08_retinoblastoma

Figure S15. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S15. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.023	0.064	0.32	16	-10000	0	16
CDKN2C	0.03	0.084	0.31	30	-10000	0	30
CDKN2A	0.21	0.14	0.31	254	-10000	0	254
CCND2	-0.07	0.057	-10000	0	-0.17	52	52
RB1	0.078	0.064	0.19	54	-10000	0	54
CDK4	-0.075	0.058	-10000	0	-0.18	40	40
CDK6	-0.085	0.077	-10000	0	-0.23	56	56
G1/S progression	-0.078	0.064	-10000	0	-0.19	54	54

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.14	0.11	0.25	145	-10000	0	145
STMN1	0.096	0.085	0.28	8	-10000	0	8
Aurora B/RasGAP/Survivin	0.22	0.18	0.38	187	-0.52	2	189
Chromosomal passenger complex/Cul3 protein complex	0.12	0.1	0.22	143	-0.28	5	148
BIRC5	0.22	0.15	0.32	245	-10000	0	245
DES	0.021	0.25	0.42	2	-0.5	46	48
Aurora C/Aurora B/INCENP	0.1	0.094	0.36	2	-10000	0	2
Aurora B/TACC1	0.1	0.094	-10000	0	-10000	0	0
Aurora B/PP2A	0.12	0.1	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.036	0.031	-10000	0	-10000	0	0
mitotic metaphase/anaphase transition	-0.008	0.005	-10000	0	-10000	0	0
NDC80	0.17	0.11	0.27	186	-10000	0	186
Cul3 protein complex	-0.018	0.1	-10000	0	-0.58	12	12
KIF2C	0.18	0.12	0.26	243	-10000	0	243
PEBP1	-0.01	0.1	-10000	0	-0.86	5	5
KIF20A	0.22	0.14	0.31	260	-10000	0	260
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.11	0.12	-10000	0	-0.64	2	2
SEPT1	0.001	0.016	0.32	1	-10000	0	1
SMC2	0.001	0.016	0.32	1	-10000	0	1
SMC4	0.003	0.028	0.32	3	-10000	0	3
NSUN2/NPM1/Nucleolin	0.16	0.12	0.31	46	-10000	0	46
PSMA3	0	0	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.005	0.005	-10000	0	-10000	0	0
H3F3B	0.073	0.066	-10000	0	-10000	0	0
AURKB	0.17	0.16	0.31	196	-10000	0	196
AURKC	0.001	0.016	0.32	1	-10000	0	1
CDCA8	0.16	0.16	0.33	176	-10000	0	176
cytokinesis	0.2	0.18	0.37	183	-10000	0	183
Aurora B/Septin1	0.22	0.2	0.4	190	-10000	0	190
AURKA	0.089	0.14	0.31	106	-10000	0	106
INCENP	0.012	0.025	0.33	2	-10000	0	2
KLHL13	-0.019	0.14	0.32	2	-0.86	9	11
BUB1	0.21	0.14	0.31	256	-10000	0	256
hSgo1/Aurora B/Survivin	0.29	0.22	0.47	206	-10000	0	206
EVI5	0.008	0.007	-10000	0	-10000	0	0
RhoA/GTP	0.19	0.22	0.42	166	-10000	0	166
SGOL1	0.12	0.15	0.32	146	-10000	0	146
CENPA	0.2	0.13	0.31	199	-10000	0	199
NCAPG	0.21	0.15	0.32	246	-10000	0	246
Aurora B/HC8 Proteasome	0.12	0.1	-10000	0	-10000	0	0
NCAPD2	0.004	0.036	0.32	5	-10000	0	5
Aurora B/PP1-gamma	0.12	0.1	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
NCAPH	0.15	0.16	0.32	177	-10000	0	177
NPM1	0.1	0.093	-10000	0	-10000	0	0
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
KLHL9	-0.007	0.077	-10000	0	-0.86	3	3
mitotic prometaphase	0.002	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.12	0.1	-10000	0	-10000	0	0
PPP1CC	0	0	-10000	0	-10000	0	0
Centraspindlin	0.22	0.25	0.48	168	-10000	0	168
RhoA/GDP	0	0	-10000	0	-10000	0	0
NSUN2	0.1	0.093	-10000	0	-10000	0	0
MYLK	0.063	0.088	-10000	0	-0.34	8	8
KIF23	0.15	0.16	0.33	170	-10000	0	170
VIM	0.088	0.073	-10000	0	-10000	0	0
RACGAP1	0.055	0.11	0.34	49	-10000	0	49
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.1	0.093	-10000	0	-10000	0	0
Chromosomal passenger complex	0.21	0.14	0.3	233	-10000	0	233
Chromosomal passenger complex/EVI5	0.28	0.21	0.46	201	-10000	0	201
TACC1	0	0	-10000	0	-10000	0	0
PPP2R5D	0	0	-10000	0	-10000	0	0
CUL3	0	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.24	0.5	-10000	0	-1	77	77
HDAC7	0.001	0.017	0.32	1	-10000	0	1
HIF1A/ARNT/Cbp/p300/Src-1	-0.34	0.43	0.69	7	-0.9	99	106
SMAD4	-0.002	0.044	-10000	0	-0.86	1	1
ID2	-0.25	0.5	-10000	0	-1	80	80
AP1	-0.33	0.35	-10000	0	-0.68	179	179
ABCG2	-0.31	0.55	-10000	0	-1.1	90	90
HIF1A	-0.025	0.068	-10000	0	-10000	0	0
TFF3	-0.25	0.51	-10000	0	-1	82	82
GATA2	-0.003	0.067	0.32	2	-0.86	2	4
AKT1	-0.038	0.12	-10000	0	-10000	0	0
response to hypoxia	-0.053	0.12	0.28	1	-0.23	62	63
MCL1	-0.24	0.49	-10000	0	-1	79	79
NDRG1	-0.24	0.5	-10000	0	-1	79	79
SERPINE1	-0.36	0.59	-10000	0	-1.1	120	120
FECH	-0.24	0.5	-10000	0	-1	75	75
FURIN	-0.25	0.51	-10000	0	-1.1	77	77
NCOA2	-0.11	0.29	-10000	0	-0.86	48	48
EP300	-0.074	0.21	0.43	4	-0.33	110	114
HMOX1	-0.26	0.51	-10000	0	-1.1	79	79
BHLHE40	-0.25	0.5	-10000	0	-1.1	77	77
BHLHE41	-0.25	0.51	0.8	1	-1.1	77	78
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.025	0.067	0.35	1	-0.42	1	2
ENG	-0.017	0.066	-10000	0	-10000	0	0
JUN	-0.014	0.11	-10000	0	-0.86	6	6
RORA	-0.25	0.5	-10000	0	-1	77	77
ABCB1	-0.22	0.45	-10000	0	-1.4	45	45
TFRC	-0.24	0.49	-10000	0	-1	76	76
CXCR4	-0.25	0.5	-10000	0	-1	79	79
TF	-0.28	0.53	-10000	0	-1.1	86	86
CITED2	-0.25	0.5	-10000	0	-1	78	78
HIF1A/ARNT	-0.32	0.56	0.79	12	-1.2	75	87
LDHA	-0.056	0.054	-10000	0	-10000	0	0
ETS1	-0.24	0.5	-10000	0	-1	75	75
PGK1	-0.24	0.49	-10000	0	-1	75	75
NOS2	-0.23	0.51	-10000	0	-1	74	74
ITGB2	-0.25	0.5	-10000	0	-1	76	76
ALDOA	-0.24	0.49	-10000	0	-1	75	75
Cbp/p300/CITED2	-0.39	0.54	-10000	0	-1.1	103	103
FOS	-0.42	0.43	-10000	0	-0.86	179	179
HK2	-0.24	0.51	-10000	0	-1	81	81
SP1	0.008	0.029	-10000	0	-10000	0	0
GCK	-0.52	0.8	-10000	0	-1.5	145	145
HK1	-0.24	0.49	-10000	0	-1	75	75
NPM1	-0.24	0.49	-10000	0	-1	75	75
EGLN1	-0.24	0.49	-10000	0	-1	75	75
CREB1	0.014	0	-10000	0	-10000	0	0
PGM1	-0.25	0.5	-10000	0	-1	75	75
SMAD3	0	0	-10000	0	-10000	0	0
EDN1	-0.25	0.34	-10000	0	-0.64	115	115
IGFBP1	-0.36	0.58	-10000	0	-1.1	107	107
VEGFA	-0.24	0.39	-10000	0	-0.76	87	87
HIF1A/JAB1	-0.015	0.041	-10000	0	-10000	0	0
CP	-0.3	0.56	-10000	0	-1.1	89	89
CXCL12	-0.44	0.58	-10000	0	-1.1	135	135
COPS5	-0.001	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.002	0.034	-10000	0	-0.66	1	1
BNIP3	-0.25	0.49	-10000	0	-1	76	76
EGLN3	-0.24	0.52	0.84	2	-1.1	76	78
CA9	-0.35	0.58	0.82	1	-1.1	118	119
TERT	-0.19	0.53	0.84	3	-1	75	78
ENO1	-0.24	0.49	-10000	0	-1	75	75
PFKL	-0.24	0.49	-10000	0	-1	76	76
NCOA1	0	0.005	-10000	0	-10000	0	0
ADM	-0.24	0.49	-10000	0	-1	75	75
ARNT	-0.024	0.065	-10000	0	-10000	0	0
HNF4A	-0.032	0.12	-10000	0	-0.9	6	6
ADFP	-0.25	0.5	-10000	0	-1	82	82
SLC2A1	-0.24	0.4	0.77	2	-0.78	88	90
LEP	-0.24	0.5	0.83	2	-1	78	80
HIF1A/ARNT/Cbp/p300	-0.34	0.44	0.73	6	-0.91	101	107
EPO	-0.53	0.63	-10000	0	-1.2	155	155
CREBBP	-0.074	0.21	0.43	4	-0.33	111	115
HIF1A/ARNT/Cbp/p300/HDAC7	-0.32	0.42	0.73	6	-0.9	93	99
PFKFB3	-0.26	0.52	-10000	0	-1.1	78	78
NT5E	-0.26	0.51	-10000	0	-1.1	77	77

×

EPHB forward 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
Ephrin A5/EPHB2	-0.084	0.28	0.39	5	-0.58	82	87
cell-cell adhesion	0.2	0.26	0.5	149	-10000	0	149
Ephrin B/EPHB2/RasGAP	-0.12	0.25	0.36	1	-0.5	107	108
ITSN1	0	0	-10000	0	-10000	0	0
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.055	0.18	-10000	0	-0.59	38	38
Ephrin B1/EPHB1	-0.13	0.25	-10000	0	-0.59	82	82
HRAS/GDP	-0.2	0.27	-10000	0	-0.53	131	131
Ephrin B/EPHB1/GRB7	-0.25	0.34	-10000	0	-0.63	151	151
Endophilin/SYNJ1	-0.12	0.22	-10000	0	-0.46	106	106
KRAS	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.25	0.34	-10000	0	-0.63	148	148
endothelial cell migration	-0.004	0.057	-10000	0	-0.73	2	2
GRB2	0	0	-10000	0	-10000	0	0
GRB7	-0.004	0.098	0.32	6	-0.86	4	10
PAK1	-0.12	0.23	-10000	0	-0.47	106	106
HRAS	0.002	0.023	0.32	2	-10000	0	2
RRAS	-0.12	0.22	-10000	0	-0.47	106	106
DNM1	0.004	0.13	0.32	21	-0.86	6	27
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.24	0.32	-10000	0	-0.6	148	148
lamellipodium assembly	-0.2	0.26	-10000	0	-0.5	149	149
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.16	0.22	-10000	0	-0.48	82	82
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
EPHB2	0.062	0.14	0.32	76	-0.86	1	77
EPHB3	-0.078	0.26	0.32	9	-0.86	37	46
EPHB1	-0.19	0.36	-10000	0	-0.86	82	82
EPHB4	0.001	0.016	0.32	1	-10000	0	1
mol:GDP	-0.18	0.27	-10000	0	-0.52	120	120
Ephrin B/EPHB2	-0.12	0.25	0.35	1	-0.5	106	107
Ephrin B/EPHB3	-0.19	0.31	0.35	1	-0.6	119	120
JNK cascade	-0.097	0.21	-10000	0	-0.49	83	83
Ephrin B/EPHB1	-0.25	0.34	-10000	0	-0.64	148	148
RAP1/GDP	-0.16	0.22	-10000	0	-0.49	92	92
EFNB2	0	0	-10000	0	-10000	0	0
EFNB3	-0.24	0.39	0.32	1	-0.86	105	106
EFNB1	-0.002	0.045	-10000	0	-0.86	1	1
Ephrin B2/EPHB1-2	-0.09	0.24	-10000	0	-0.53	83	83
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.2	0.3	-10000	0	-0.55	138	138
Rap1/GTP	-0.2	0.27	-10000	0	-0.54	119	119
axon guidance	-0.084	0.28	0.38	5	-0.58	82	87
MAPK3	-0.11	0.21	-10000	0	-0.56	40	40
MAPK1	-0.11	0.21	-10000	0	-0.56	40	40
Rac1/GDP	-0.16	0.24	-10000	0	-0.52	92	92
actin cytoskeleton reorganization	-0.15	0.2	-10000	0	-0.56	42	42
CDC42/GDP	-0.16	0.24	-10000	0	-0.52	92	92
PI3K	-0.004	0.059	-10000	0	-0.75	2	2
EFNA5	-0.17	0.38	0.32	25	-0.86	81	106
Ephrin B2/EPHB4	0.001	0.01	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.082	0.17	-10000	0	-0.34	106	106
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.2	0.26	-10000	0	-0.75	42	42
PTK2	0.024	0.044	-10000	0	-10000	0	0
MAP4K4	-0.098	0.22	-10000	0	-0.49	83	83
SRC	0.004	0.036	0.32	5	-10000	0	5
KALRN	-0.005	0.063	-10000	0	-0.86	2	2
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.14	0.22	-10000	0	-0.57	42	42
MAP2K1	-0.15	0.2	-10000	0	-0.46	81	81
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.089	0.25	-10000	0	-0.53	83	83
cell migration	-0.14	0.25	-10000	0	-0.44	129	129
NRAS	0	0	-10000	0	-10000	0	0
SYNJ1	-0.12	0.22	-10000	0	-0.47	106	106
PXN	0	0	-10000	0	-10000	0	0
TF	-0.15	0.23	-10000	0	-0.46	129	129
HRAS/GTP	-0.21	0.3	-10000	0	-0.54	149	149
Ephrin B1/EPHB1-2	-0.091	0.25	-10000	0	-0.54	83	83
cell adhesion mediated by integrin	0.15	0.24	0.52	106	-10000	0	106
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.22	0.33	-10000	0	-0.58	149	149
RAC1-CDC42/GTP	-0.24	0.31	-10000	0	-0.58	133	133
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
RAC1-CDC42/GDP	-0.16	0.22	-10000	0	-0.49	91	91
ruffle organization	-0.2	0.27	-10000	0	-0.54	120	120
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	-0.12	0.22	-10000	0	-0.45	110	110
Ephrin B/EPHB2/KALRN	-0.12	0.26	0.36	1	-0.5	106	107
ROCK1	-0.053	0.16	-10000	0	-0.54	38	38
RAS family/GDP	-0.15	0.19	-10000	0	-0.54	42	42
Rac1/GTP	-0.22	0.29	-10000	0	-0.54	149	149
Ephrin B/EPHB1/Src/Paxillin	-0.18	0.24	-10000	0	-0.44	147	147

×

Ephrin A reverse 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
MAPKKK cascade	-0.11	0.26	0.38	4	-0.59	81	85
EFNA5	-0.17	0.38	0.32	25	-0.86	81	106
FYN	-0.11	0.23	-10000	0	-0.54	81	81
neuron projection morphogenesis	-0.11	0.26	0.38	4	-0.59	81	85
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	-0.11	0.26	0.39	4	-0.59	81	85
EPHA5	0.011	0.058	0.32	13	-10000	0	13

×

Reelin signaling 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
CDK5R1/CDK5	0.002	0.023	-10000	0	-10000	0	0
VLDLR	-0.034	0.26	0.32	42	-0.86	30	72
CRKL	0	0	-10000	0	-10000	0	0
LRPAP1	0	0	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
ITGA3	0.02	0.093	0.32	26	-0.86	1	27
RELN/VLDLR/Fyn	-0.22	0.34	-10000	0	-0.64	138	138
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.03	0.13	-10000	0	-0.52	23	23
AKT1	-0.18	0.23	-10000	0	-0.41	161	161
MAP2K7	0	0	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
DAB1	-0.13	0.31	0.32	1	-0.86	56	57
RELN/LRP8/DAB1	-0.25	0.31	-10000	0	-0.57	167	167
LRPAP1/LRP8	0.021	0.064	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.24	0.29	-10000	0	-0.54	167	167
DAB1/alpha3/beta1 Integrin	-0.24	0.31	0.36	3	-0.56	147	150
long-term memory	-0.21	0.28	-10000	0	-0.51	167	167
DAB1/LIS1	-0.25	0.32	-10000	0	-0.55	176	176
DAB1/CRLK/C3G	-0.24	0.31	-10000	0	-0.55	153	153
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
DAB1/NCK2	-0.25	0.33	-10000	0	-0.56	173	173
ARHGEF2	0.003	0.033	0.32	4	-10000	0	4
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.053	0.12	0.32	62	-10000	0	62
CDK5R1	0.003	0.033	0.32	4	-10000	0	4
RELN	-0.29	0.41	0.32	3	-0.86	125	128
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
RELN/LRP8/Fyn	-0.18	0.29	-10000	0	-0.58	125	125
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.22	0.3	0.36	5	-0.53	167	172
MAPK8	-0.046	0.19	-10000	0	-0.86	20	20
RELN/VLDLR/DAB1	-0.29	0.36	-10000	0	-0.63	178	178
ITGB1	0	0	-10000	0	-10000	0	0
MAP1B	-0.26	0.32	-10000	0	-0.57	178	178
RELN/LRP8	-0.18	0.29	-10000	0	-0.58	125	125
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.24	0.29	-10000	0	-0.54	167	167
PI3K	-0.005	0.071	-10000	0	-0.94	2	2
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.014	0.066	-10000	0	-0.67	1	1
RAP1A	-0.24	0.27	-10000	0	-0.78	37	37
PAFAH1B1	0	0	-10000	0	-10000	0	0
MAPK8IP1	-0.009	0.089	-10000	0	-0.86	4	4
CRLK/C3G	0	0	-10000	0	-10000	0	0
GRIN2B	0	0	-10000	0	-10000	0	0
NCK2	-0.001	0.048	0.32	1	-0.86	1	2
neuron differentiation	-0.13	0.17	-10000	0	-0.55	26	26
neuron adhesion	-0.21	0.26	-10000	0	-0.79	32	32
LRP8	0.03	0.092	0.32	35	-10000	0	35
GSK3B	-0.17	0.22	-10000	0	-0.66	34	34
RELN/VLDLR/DAB1/Fyn	-0.27	0.34	-10000	0	-0.59	178	178
MAP3K11	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.2	0.25	-10000	0	-0.43	174	174
CDK5	0	0	-10000	0	-10000	0	0
MAPT	0.065	0.06	-10000	0	-10000	0	0
neuron migration	-0.18	0.27	-10000	0	-0.48	141	141
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.13	0.17	-10000	0	-0.55	26	26
RELN/VLDLR	-0.19	0.33	0.38	7	-0.59	138	145

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0	0	-10000	0	-10000	0	0
EPHB2	0.062	0.14	0.32	76	-0.87	1	77
EFNB1	0.011	0.1	-10000	0	-0.67	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.1	0.26	-10000	0	-0.5	99	99
Ephrin B2/EPHB1-2	-0.089	0.24	-10000	0	-0.53	83	83
neuron projection morphogenesis	-0.11	0.24	-10000	0	-0.48	99	99
Ephrin B1/EPHB1-2/Tiam1	-0.11	0.28	-10000	0	-0.54	99	99
DNM1	0.004	0.13	0.32	21	-0.86	6	27
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.2	0.36	-10000	0	-0.8	99	99
YES1	-0.27	0.46	-10000	0	-1	99	99
Ephrin B1/EPHB1-2/NCK2	-0.084	0.25	0.47	1	-0.51	87	88
PI3K	-0.22	0.37	-10000	0	-0.82	100	100
mol:GDP	-0.11	0.28	-10000	0	-0.54	99	99
ITGA2B	0.007	0.046	0.32	8	-10000	0	8
endothelial cell proliferation	0.001	0.01	-10000	0	-10000	0	0
FYN	-0.27	0.46	-10000	0	-1	99	99
MAP3K7	-0.23	0.38	-10000	0	-0.85	99	99
FGR	-0.28	0.46	-10000	0	-1	99	99
TIAM1	-0.046	0.19	-10000	0	-0.86	20	20
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.23	0.38	-10000	0	-0.77	113	113
LYN	-0.27	0.46	-10000	0	-1	99	99
Ephrin B1/EPHB1-2/Src Family Kinases	-0.26	0.43	-10000	0	-0.97	99	99
Ephrin B1/EPHB1-2	-0.25	0.41	-10000	0	-0.92	99	99
SRC	-0.27	0.46	-10000	0	-1	99	99
ITGB3	-0.07	0.23	-10000	0	-0.86	30	30
EPHB1	-0.19	0.36	-10000	0	-0.86	82	82
EPHB4	0.001	0.016	0.32	1	-10000	0	1
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.001	0.01	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.049	0.19	-10000	0	-0.67	30	30
BLK	-0.3	0.47	-10000	0	-1.1	99	99
HCK	-0.28	0.46	-10000	0	-1	99	99
regulation of stress fiber formation	0.084	0.25	0.5	87	-0.46	1	88
MAPK8	-0.21	0.37	-10000	0	-0.76	111	111
Ephrin B1/EPHB1-2/RGS3	-0.083	0.25	-10000	0	-0.51	87	87
endothelial cell migration	-0.2	0.34	-10000	0	-0.75	99	99
NCK2	-0.001	0.048	0.32	1	-0.86	1	2
PTPN13	-0.25	0.44	0.32	2	-0.97	99	101
regulation of focal adhesion formation	0.084	0.25	0.5	87	-0.46	1	88
chemotaxis	0.083	0.25	0.5	87	-10000	0	87
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
Rac1/GTP	-0.1	0.26	-10000	0	-0.5	99	99
angiogenesis	-0.24	0.4	-10000	0	-0.91	99	99
LCK	-0.28	0.46	-10000	0	-1	99	99

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.2	0.3	-10000	0	-0.48	169	169
FZD6	-0.001	0.048	0.32	1	-0.86	1	2
WNT6	0.019	0.075	0.32	22	-10000	0	22
WNT4	-0.12	0.35	0.32	36	-0.86	65	101
FZD3	-0.021	0.13	-10000	0	-0.86	9	9
WNT5A	-0.088	0.27	0.32	5	-0.86	40	45
WNT11	-0.24	0.39	-10000	0	-0.86	105	105

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.046	0.16	0.34	1	-0.57	25	26
PTK2B	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.048	0.25	0.46	3	-0.63	33	36
EDN1	-0.039	0.16	0.26	2	-0.53	23	25
EDN3	0.008	0.049	0.32	9	-10000	0	9
EDN2	-0.069	0.25	0.32	6	-0.86	32	38
HRAS/GDP	-0.15	0.26	0.33	1	-0.61	65	66
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.084	0.21	0.27	2	-0.45	70	72
ADCY4	-0.03	0.14	-10000	0	-0.54	18	18
ADCY5	-0.12	0.25	0.27	1	-0.56	77	78
ADCY6	-0.03	0.14	-10000	0	-0.5	22	22
ADCY7	-0.03	0.14	-10000	0	-0.54	18	18
ADCY1	-0.21	0.29	-10000	0	-0.54	149	149
ADCY2	-0.027	0.14	0.39	1	-0.54	18	19
ADCY3	-0.029	0.14	-10000	0	-0.54	18	18
ADCY8	-0.01	0.16	0.28	6	-0.51	21	27
ADCY9	-0.03	0.14	-10000	0	-0.54	18	18
arachidonic acid secretion	-0.22	0.34	0.36	3	-0.52	179	182
ETB receptor/Endothelin-1/Gq/GTP	-0.1	0.28	-10000	0	-0.54	82	82
GNAO1	-0.41	0.43	-10000	0	-0.86	178	178
HRAS	0.002	0.023	0.32	2	-10000	0	2
ETA receptor/Endothelin-1/G12/GTP	-0.041	0.16	0.4	3	-0.55	23	26
ETA receptor/Endothelin-1/Gs/GTP	-0.016	0.16	0.37	3	-0.51	24	27
mol:GTP	-0.001	0.007	-10000	0	-10000	0	0
COL3A1	-0.073	0.27	0.44	4	-0.94	28	32
EDNRB	-0.057	0.22	-10000	0	-0.86	26	26
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.056	0.2	-10000	0	-0.7	27	27
CYSLTR1	-0.061	0.22	-10000	0	-0.77	26	26
SLC9A1	-0.026	0.085	0.25	1	-0.32	18	19
mol:GDP	-0.14	0.3	0.32	2	-0.6	84	86
SLC9A3	-0.033	0.27	0.39	4	-0.79	32	36
RAF1	-0.21	0.34	-10000	0	-0.61	109	109
JUN	-0.066	0.28	-10000	0	-0.77	33	33
JAK2	-0.047	0.17	0.34	1	-0.57	26	27
mol:IP3	-0.12	0.28	0.28	1	-0.57	78	79
ETA receptor/Endothelin-1	-0.059	0.19	0.41	5	-0.66	25	30
PLCB1	0.01	0.055	0.31	12	-10000	0	12
PLCB2	-0.018	0.13	-10000	0	-0.86	8	8
ETA receptor/Endothelin-3	-0.011	0.083	0.31	1	-0.76	2	3
FOS	-0.47	0.54	-10000	0	-1	186	186
Gai/GDP	-0.35	0.42	-10000	0	-0.76	178	178
CRK	0	0	-10000	0	-10000	0	0
mol:Ca ++	-0.11	0.32	0.38	1	-0.76	53	54
BCAR1	0	0.001	-10000	0	-10000	0	0
PRKCB1	-0.11	0.27	0.27	1	-0.55	78	79
GNAQ	0	0.046	-10000	0	-0.86	1	1
GNAZ	0.15	0.17	0.32	176	-0.86	1	177
GNAL	0.051	0.12	0.32	60	-10000	0	60
Gs family/GDP	-0.13	0.25	0.25	21	-0.55	74	95
ETA receptor/Endothelin-1/Gq/GTP	-0.077	0.23	0.32	2	-0.48	74	76
MAPK14	-0.08	0.24	-10000	0	-0.52	60	60
TRPC6	-0.052	0.26	0.48	2	-0.71	28	30
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.063	-10000	0	-0.86	2	2
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.1	0.25	-10000	0	-0.48	85	85
ETB receptor/Endothelin-2	-0.098	0.25	-10000	0	-0.69	56	56
ETB receptor/Endothelin-3	-0.04	0.18	-10000	0	-0.67	26	26
ETB receptor/Endothelin-1	-0.067	0.23	0.28	1	-0.73	34	35
MAPK3	-0.39	0.47	-10000	0	-0.84	186	186
MAPK1	-0.39	0.47	-10000	0	-0.84	186	186
Rac1/GDP	-0.15	0.25	0.29	3	-0.59	69	72
cAMP biosynthetic process	-0.09	0.21	-10000	0	-0.5	58	58
MAPK8	-0.085	0.31	0.41	3	-0.73	47	50
SRC	0.004	0.036	0.32	5	-10000	0	5
ETB receptor/Endothelin-1/Gi/GTP	-0.14	0.23	-10000	0	-0.48	68	68
p130Cas/CRK/Src/PYK2	-0.098	0.29	0.38	3	-0.62	64	67
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.15	0.25	0.29	3	-0.61	66	69
COL1A2	-0.073	0.26	0.43	5	-0.85	26	31
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.067	0.2	0.38	2	-0.68	34	36
mol:DAG	-0.12	0.28	0.28	1	-0.57	78	79
MAP2K2	-0.29	0.38	-10000	0	-0.62	187	187
MAP2K1	-0.29	0.38	-10000	0	-0.62	187	187
EDNRA	-0.022	0.11	0.41	3	-0.54	6	9
positive regulation of muscle contraction	-0.037	0.14	0.3	1	-0.52	23	24
Gq family/GDP	-0.2	0.3	-10000	0	-0.7	82	82
HRAS/GTP	-0.16	0.31	0.29	1	-0.59	92	93
PRKCH	-0.11	0.27	-10000	0	-0.55	78	78
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.11	0.27	-10000	0	-0.59	65	65
PRKCB	-0.15	0.33	-10000	0	-0.65	87	87
PRKCE	-0.11	0.27	-10000	0	-0.55	78	78
PRKCD	-0.11	0.27	-10000	0	-0.55	77	77
PRKCG	-0.11	0.27	-10000	0	-0.56	76	76
regulation of vascular smooth muscle contraction	-0.55	0.62	-10000	0	-1.2	186	186
PRKCQ	-0.13	0.3	-10000	0	-0.61	77	77
PLA2G4A	-0.25	0.38	0.37	3	-0.57	179	182
GNA14	-0.14	0.33	-10000	0	-0.86	63	63
GNA15	0.001	0.051	0.32	2	-0.86	1	3
GNA12	0	0	-10000	0	-10000	0	0
GNA11	-0.026	0.15	-10000	0	-0.86	12	12
Rac1/GTP	-0.041	0.16	0.4	3	-0.53	25	28
MMP1	0.077	0.13	0.45	9	-10000	0	9

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.14	0.26	0.32	2	-0.57	92	94
NF kappa B1 p50/RelA/I kappa B alpha	-0.049	0.084	-10000	0	-0.43	5	5
AP1	-0.35	0.38	-10000	0	-0.64	206	206
mol:PIP3	-0.13	0.22	-10000	0	-0.46	98	98
AKT1	-0.095	0.16	-10000	0	-0.39	77	77
PTK2B	-0.056	0.15	-10000	0	-0.3	94	94
RHOA	-0.014	0.069	-10000	0	-0.53	1	1
PIK3CB	0	0	-10000	0	-10000	0	0
mol:Ca2+	0.006	0.09	-10000	0	-0.48	5	5
MAGI3	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
apoptosis	-0.11	0.21	0.26	1	-0.45	98	99
HRAS/GDP	0.001	0.016	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.026	0.13	-10000	0	-0.37	13	13
NF kappa B1 p50/RelA	-0.11	0.22	-10000	0	-0.46	88	88
endothelial cell migration	-0.17	0.33	0.37	2	-0.68	98	100
ADCY4	-0.26	0.34	-10000	0	-0.76	98	98
ADCY5	-0.34	0.42	-10000	0	-0.88	119	119
ADCY6	-0.26	0.34	-10000	0	-0.58	153	153
ADCY7	-0.26	0.34	-10000	0	-0.74	101	101
ADCY1	-0.41	0.45	-10000	0	-0.87	155	155
ADCY2	-0.26	0.34	-10000	0	-0.75	101	101
ADCY3	-0.26	0.34	-10000	0	-0.76	98	98
ADCY8	-0.26	0.34	-10000	0	-0.65	126	126
ADCY9	-0.26	0.34	-10000	0	-0.74	101	101
GSK3B	-0.047	0.14	-10000	0	-0.35	29	29
arachidonic acid secretion	-0.28	0.32	-10000	0	-0.58	153	153
GNG2	-0.007	0.077	-10000	0	-0.86	3	3
TRIP6	-0.002	0.062	-10000	0	-0.48	5	5
GNAO1	-0.42	0.39	-10000	0	-0.71	223	223
HRAS	0.002	0.023	0.32	2	-10000	0	2
NFKBIA	-0.023	0.12	-10000	0	-0.42	10	10
GAB1	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.053	0.23	-10000	0	-0.99	21	21
JUN	-0.014	0.11	-10000	0	-0.86	6	6
LPA/LPA2/NHERF2	0.001	0.075	-10000	0	-0.58	4	4
TIAM1	-0.065	0.28	-10000	0	-1.2	21	21
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
mol:IP3	0.005	0.092	-10000	0	-0.49	5	5
PLCB3	-0.003	0.059	-10000	0	-0.53	4	4
FOS	-0.42	0.43	-10000	0	-0.86	179	179
positive regulation of mitosis	-0.28	0.32	-10000	0	-0.58	153	153
LPA/LPA1-2-3	-0.12	0.28	0.37	7	-0.56	95	102
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
stress fiber formation	-0.072	0.19	-10000	0	-0.38	93	93
GNAZ	-0.088	0.32	0.28	4	-0.58	98	102
EGFR/PI3K-beta/Gab1	-0.13	0.23	-10000	0	-0.49	97	97
positive regulation of dendritic cell cytokine production	-0.12	0.28	0.36	7	-0.56	95	102
LPA/LPA2/MAGI-3	0.006	0.053	-10000	0	-0.58	1	1
ARHGEF1	-0.13	0.23	-10000	0	-0.53	91	91
GNAI2	-0.15	0.27	0.2	2	-0.59	98	100
GNAI3	-0.15	0.27	-10000	0	-0.59	98	98
GNAI1	-0.16	0.28	-10000	0	-0.6	99	99
LPA/LPA3	0.015	0.064	0.22	30	-10000	0	30
LPA/LPA2	0.005	0.06	0.22	16	-0.67	1	17
LPA/LPA1	-0.18	0.31	0.3	4	-0.68	98	102
HB-EGF/EGFR	-0.015	0.15	-10000	0	-0.57	24	24
HBEGF	0.016	0.15	-10000	0	-0.67	14	14
mol:DAG	0.005	0.092	-10000	0	-0.49	5	5
cAMP biosynthetic process	-0.35	0.39	-10000	0	-0.63	221	221
NFKB1	0	0	-10000	0	-10000	0	0
SRC	0.004	0.036	0.32	5	-10000	0	5
GNB1	0	0	-10000	0	-10000	0	0
LYN	-0.023	0.12	-10000	0	-0.44	8	8
GNAQ	0.008	0.05	-10000	0	-0.46	2	2
LPAR2	0.011	0.079	0.32	16	-0.86	1	17
LPAR3	0.026	0.087	0.32	31	-10000	0	31
LPAR1	-0.21	0.38	0.36	4	-0.88	91	95
IL8	-0.21	0.28	0.35	4	-0.53	143	147
PTK2	-0.13	0.24	-10000	0	-0.54	91	91
Rac1/GDP	0	0	-10000	0	-10000	0	0
CASP3	-0.11	0.21	0.26	1	-0.45	98	99
EGFR	-0.023	0.14	-10000	0	-0.86	10	10
PLCG1	-0.021	0.083	-10000	0	-0.33	10	10
PLD2	-0.13	0.24	-10000	0	-0.54	91	91
G12/G13	-0.14	0.25	0.32	2	-0.56	91	93
PI3K-beta	-0.11	0.19	-10000	0	-0.45	79	79
cell migration	-0.046	0.1	-10000	0	-0.28	31	31
SLC9A3R2	-0.007	0.077	-10000	0	-0.86	3	3
PXN	-0.073	0.19	-10000	0	-0.39	92	92
HRAS/GTP	-0.29	0.34	-10000	0	-0.61	153	153
RAC1	0	0	-10000	0	-10000	0	0
MMP9	0.032	0.2	0.32	70	-0.86	12	82
PRKCE	-0.001	0.047	0.32	1	-0.86	1	2
PRKCD	0.012	0.088	-10000	0	-0.46	5	5
Gi(beta/gamma)	-0.26	0.32	-10000	0	-0.73	99	99
mol:LPA	-0.003	0.033	-10000	0	-0.22	7	7
TRIP6/p130 Cas/FAK1/Paxillin	-0.11	0.23	-10000	0	-0.49	90	90
MAPKKK cascade	-0.28	0.32	-10000	0	-0.58	153	153
contractile ring contraction involved in cytokinesis	-0.007	0.071	-10000	0	-0.52	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.068	0.18	-10000	0	-0.44	64	64
GNA15	0.009	0.05	-10000	0	-0.41	2	2
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
MAPT	-0.027	0.14	-10000	0	-0.38	13	13
GNA11	-0.006	0.094	-10000	0	-0.46	13	13
Rac1/GTP	-0.057	0.25	-10000	0	-1.1	21	21
MMP2	-0.17	0.34	0.37	2	-0.68	98	100

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.16	0.33	-10000	0	-0.86	67	67
GNB1/GNG2	-0.18	0.28	-10000	0	-0.76	48	48
mol:DAG	-0.16	0.25	-10000	0	-0.67	48	48
PLCG1	-0.17	0.26	-10000	0	-0.7	48	48
YES1	-0.19	0.28	-10000	0	-0.46	160	160
FZD3	-0.021	0.13	-10000	0	-0.86	9	9
FZD6	-0.001	0.048	0.32	1	-0.86	1	2
G protein	-0.17	0.26	-10000	0	-0.71	48	48
MAP3K7	-0.11	0.22	-10000	0	-0.53	47	47
mol:Ca2+	-0.16	0.24	-10000	0	-0.64	48	48
mol:IP3	-0.16	0.25	-10000	0	-0.67	48	48
NLK	-0.009	0.013	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
CAMK2A	-0.12	0.23	-10000	0	-0.59	48	48
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.2	0.3	-10000	0	-0.48	169	169
CSNK1A1	0	0	-10000	0	-10000	0	0
GNAS	-0.19	0.28	-10000	0	-0.46	160	160
GO:0007205	-0.14	0.25	-10000	0	-0.65	48	48
WNT6	0.019	0.075	0.32	22	-10000	0	22
WNT4	-0.12	0.35	0.32	36	-0.86	65	101
NFAT1/CK1 alpha	-0.24	0.31	-10000	0	-0.68	95	95
GNG2	-0.007	0.077	-10000	0	-0.86	3	3
WNT5A	-0.088	0.27	0.32	5	-0.86	40	45
WNT11	-0.24	0.39	-10000	0	-0.86	105	105
CDC42	-0.18	0.27	-10000	0	-0.73	47	47

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.19	0.62	0.8	4	-1.2	86	90
IL23A	-0.18	0.6	0.81	4	-1.2	79	83
NF kappa B1 p50/RelA/I kappa B alpha	-0.29	0.45	-10000	0	-1	81	81
positive regulation of T cell mediated cytotoxicity	-0.18	0.64	0.81	10	-1.2	81	91
ITGA3	-0.14	0.56	0.81	7	-1.1	67	74
IL17F	-0.068	0.38	0.63	3	-0.67	77	80
IL12B	0.024	0.066	0.46	3	-10000	0	3
STAT1 (dimer)	-0.28	0.53	0.57	22	-1.1	81	103
CD4	-0.18	0.6	0.8	3	-1.1	83	86
IL23	-0.2	0.56	0.77	3	-1.1	74	77
IL23R	0.022	0.13	0.52	1	-10000	0	1
IL1B	-0.24	0.7	0.81	3	-1.4	88	91
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.14	0.54	0.88	2	-1.1	69	71
TYK2	0.018	0.034	-10000	0	-10000	0	0
STAT4	-0.034	0.17	0.32	1	-0.86	15	16
STAT3	0	0	-10000	0	-10000	0	0
IL18RAP	-0.052	0.21	-10000	0	-0.86	23	23
IL12RB1	-0.013	0.17	-10000	0	-0.9	13	13
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
IL12Rbeta1/TYK2	-0.008	0.14	-10000	0	-0.71	13	13
IL23R/JAK2	0.027	0.16	0.55	2	-0.69	1	3
positive regulation of chronic inflammatory response	-0.18	0.64	0.81	10	-1.2	81	91
natural killer cell activation	-0.001	0.012	-10000	0	-0.048	3	3
JAK2	0.031	0.066	-10000	0	-0.89	1	1
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
NFKB1	0.001	0.005	-10000	0	-10000	0	0
RELA	0.001	0.005	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.17	0.54	0.76	3	-1.1	75	78
ALOX12B	-0.14	0.54	0.84	3	-1	81	84
CXCL1	-0.33	0.74	0.82	7	-1.3	126	133
T cell proliferation	-0.18	0.64	0.81	10	-1.2	81	91
NFKBIA	0.001	0.005	-10000	0	-10000	0	0
IL17A	-0.026	0.31	0.59	5	-0.55	55	60
PI3K	-0.3	0.47	-10000	0	-1.1	81	81
IFNG	-0.003	0.052	0.16	11	-0.11	15	26
STAT3 (dimer)	-0.28	0.44	-10000	0	-1	81	81
IL18R1	-0.13	0.31	-10000	0	-0.86	58	58
IL23/IL23R/JAK2/TYK2/SOCS3	-0.092	0.43	0.63	10	-0.78	73	83
IL18/IL18R	-0.13	0.3	-10000	0	-0.7	73	73
macrophage activation	-0.012	0.023	0.063	14	-0.045	59	73
TNF	-0.18	0.61	0.82	3	-1.2	77	80
STAT3/STAT4	-0.31	0.48	0.5	1	-1.1	81	82
STAT4 (dimer)	-0.29	0.54	0.57	21	-1.2	81	102
IL18	-0.02	0.14	0.31	3	-0.86	10	13
IL19	-0.15	0.54	0.81	2	-1	81	83
STAT5A (dimer)	-0.28	0.53	0.57	20	-1.1	81	101
STAT1	0.002	0.023	0.32	2	-10000	0	2
SOCS3	-0.12	0.29	-10000	0	-0.86	50	50
CXCL9	-0.14	0.55	0.84	5	-1	82	87
MPO	-0.16	0.56	0.82	2	-1	87	89
positive regulation of humoral immune response	-0.18	0.64	0.81	10	-1.2	81	91
IL23/IL23R/JAK2/TYK2	-0.21	0.71	0.82	10	-1.3	81	91
IL6	-0.24	0.66	0.81	3	-1.2	101	104
STAT5A	0.001	0.016	0.32	1	-10000	0	1
IL2	0.005	0.013	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	-0.001	0.012	-10000	0	-0.048	3	3
CD3E	-0.15	0.56	0.84	3	-1	81	84
keratinocyte proliferation	-0.18	0.64	0.81	10	-1.2	81	91
NOS2	-0.13	0.54	0.81	3	-1.1	64	67

×

PLK1 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
regulation of centriole-centriole cohesion	-0.05	0.049	-10000	0	-0.11	144	144
BUB1B	0.1	0.063	0.17	83	-10000	0	83
PLK1	0.055	0.029	0.094	85	-10000	0	85
PLK1S1	0.032	0.016	0.14	3	-10000	0	3
KIF2A	0.056	0.025	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.055	0.029	0.093	85	-10000	0	85
GOLGA2	0	0	-10000	0	-10000	0	0
Hec1/SPC24	0.26	0.18	0.36	269	-10000	0	269
WEE1	0.057	0.046	-10000	0	-0.6	1	1
cytokinesis	0.14	0.099	0.24	83	-10000	0	83
PP2A-alpha B56	0	0.001	-10000	0	-10000	0	0
AURKA	0.06	0.05	0.14	98	-10000	0	98
PICH/PLK1	0.1	0.12	0.26	105	-10000	0	105
CENPE	0.075	0.043	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.056	0.025	-10000	0	-10000	0	0
PPP2CA	0	0	-10000	0	-10000	0	0
FZR1	0	0	-10000	0	-10000	0	0
TPX2	0.045	0.041	0.14	51	-10000	0	51
PAK1	0	0	-10000	0	-10000	0	0
SPC24	0.15	0.16	0.32	179	-10000	0	179
FBXW11	0	0	-10000	0	-10000	0	0
CLSPN	0.069	0.061	0.16	117	-10000	0	117
GORASP1	0	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.027	0.013	0.053	1	-10000	0	1
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-10000	0	0
STAG2	0	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0	0.002	-10000	0	-10000	0	0
spindle elongation	0.055	0.029	0.093	85	-10000	0	85
ODF2	0.003	0.005	-10000	0	-10000	0	0
BUB1	0.14	0.097	0.41	1	-10000	0	1
TPT1	0.031	0.013	-10000	0	-10000	0	0
CDC25C	0.13	0.067	0.17	281	-10000	0	281
CDC25B	0.009	0.019	0.33	1	-10000	0	1
SGOL1	0.05	0.049	0.11	144	-10000	0	144
RHOA	0	0	-10000	0	-10000	0	0
CCNB1/CDK1	0.092	0.1	0.38	1	-0.37	1	2
CDC14B	-0.014	0.12	-10000	0	-0.68	11	11
CDC20	0.23	0.14	0.32	265	-10000	0	265
PLK1/PBIP1	0.018	0.048	0.16	28	-10000	0	28
mitosis	-0.004	0.006	-10000	0	-10000	0	0
FBXO5	0.048	0.021	-10000	0	-10000	0	0
CDC2	0.006	0.005	0.011	87	-10000	0	87
NDC80	0.22	0.15	0.32	254	-10000	0	254
metaphase plate congression	0.038	0.019	-10000	0	-10000	0	0
ERCC6L	0.1	0.11	0.26	68	-0.34	1	69
NLP/gamma Tubulin	0.032	0.014	0.089	1	-10000	0	1
microtubule cytoskeleton organization	0.031	0.013	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-10000	0	-10000	0	0
PPP1R12A	0	0	-10000	0	-10000	0	0
interphase	-0.001	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	0.27	0.19	0.38	263	-10000	0	263
GRASP65/GM130/RAB1/GTP/PLK1	0	0	-10000	0	-10000	0	0
RAB1A	0	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.048	0.025	-10000	0	-10000	0	0
mitotic prometaphase	0.001	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.068	0.061	-10000	0	-10000	0	0
microtubule-based process	0.18	0.12	0.26	260	-10000	0	260
Golgi organization	0.055	0.029	0.093	85	-10000	0	85
Cohesin/SA2	0	0	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	0.22	0.14	0.32	260	-10000	0	260
APC/C/CDC20	0.19	0.12	0.26	265	-10000	0	265
PPP2R1A	0	0	-10000	0	-10000	0	0
chromosome segregation	0.017	0.048	0.15	28	-10000	0	28
PRC1	0.16	0.16	0.32	186	-10000	0	186
ECT2	0.066	0.037	-10000	0	-10000	0	0
C13orf34	0.049	0.023	-10000	0	-10000	0	0
NUDC	0.038	0.019	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.1	0.063	0.17	83	-10000	0	83
spindle assembly	0.045	0.021	0.094	2	-10000	0	2
spindle stabilization	0.032	0.016	0.14	3	-10000	0	3
APC/C/HCDH1	-0.018	0.1	-10000	0	-0.59	11	11
MKLP2/PLK1	0.18	0.12	0.26	260	-10000	0	260
CCNB1	0.15	0.16	0.32	172	-10000	0	172
PPP1CB	0	0	-10000	0	-10000	0	0
BTRC	0	0	-10000	0	-10000	0	0
ROCK2	0.026	0.1	-10000	0	-0.5	14	14
TUBG1	0.032	0.014	0.14	1	-10000	0	1
G2/M transition of mitotic cell cycle	0.055	0.064	-10000	0	-0.36	1	1
MLF1IP	0.02	0.047	-10000	0	-10000	0	0
INCENP	0.003	0.023	0.32	2	-10000	0	2

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.006	0.065	-10000	0	-0.6	4	4
NFATC2	-0.11	0.23	-10000	0	-0.6	67	67
NFATC3	0	0.018	-10000	0	-10000	0	0
CD40LG	-0.35	0.36	0.47	4	-0.78	130	134
PTGS2	-0.46	0.47	0.43	3	-1	142	145
JUNB	-0.044	0.19	-10000	0	-0.86	19	19
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.011	-10000	0	-10000	0	0
CaM/Ca2+	-0.001	0.011	-10000	0	-10000	0	0
CALM1	0	0.005	-10000	0	-10000	0	0
JUN	-0.013	0.11	-10000	0	-0.86	6	6
mol:Ca2+	-0.003	0.008	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.001	-10000	0	-10000	0	0
FOSL1	-0.035	0.18	0.32	3	-0.86	16	19
CREM	0	0	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.11	0.23	0.42	3	-0.52	76	79
FOS	-0.42	0.43	-10000	0	-0.87	179	179
IFNG	-0.33	0.35	0.53	5	-0.75	129	134
AP-1/NFAT1-c-4	-0.42	0.46	0.59	6	-0.97	129	135
FASLG	-0.35	0.36	0.58	3	-0.78	130	133
NFAT1-c-4/ICER1	-0.099	0.21	0.31	1	-0.52	69	70
IL2RA	-0.34	0.36	0.52	6	-0.76	131	137
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSF2	-0.33	0.35	0.43	3	-0.75	129	132
JunB/Fra1/NFAT1-c-4	-0.14	0.26	0.35	2	-0.54	93	95
IL4	-0.33	0.36	0.49	1	-0.75	129	130
IL2	-0.017	0.023	-10000	0	-10000	0	0
IL3	-0.033	0.028	-10000	0	-10000	0	0
FKBP1A	0	0	-10000	0	-10000	0	0
BATF3	-0.008	0.09	0.32	1	-0.86	4	5
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.002	0.005	-10000	0	-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	-0.078	0.24	0.39	1	-0.67	46	47
fibroblast growth factor receptor signaling pathway	-0.077	0.24	0.39	1	-0.66	46	47
LAMA1	-0.087	0.3	0.32	20	-0.86	45	65
PRNP	-0.053	0.21	-10000	0	-0.86	23	23
GPC1/SLIT2	-0.1	0.27	0.44	1	-0.71	58	59
SMAD2	-0.037	0.14	-10000	0	-0.53	26	26
GPC1/PrPc/Cu2+	-0.076	0.22	-10000	0	-0.67	42	42
GPC1/Laminin alpha1	-0.12	0.28	0.44	1	-0.7	67	68
TDGF1	0.021	0.26	0.32	87	-0.86	23	110
CRIPTO/GPC1	-0.04	0.26	-10000	0	-0.68	47	47
APP/GPC1	-0.053	0.18	-10000	0	-0.67	30	30
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.053	0.21	-10000	0	-0.59	47	47
FLT1	0	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.04	0.15	-10000	0	-0.58	26	26
SERPINC1	-0.12	0.29	-10000	0	-0.86	50	50
FYN	-0.053	0.21	-10000	0	-0.59	47	47
FGR	-0.056	0.22	-10000	0	-0.59	49	49
positive regulation of MAPKKK cascade	-0.078	0.26	-10000	0	-0.64	54	54
SLIT2	-0.075	0.27	0.32	13	-0.86	37	50
GPC1/NRG	-0.32	0.36	-10000	0	-0.7	170	170
NRG1	-0.36	0.42	-10000	0	-0.86	156	156
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.04	0.15	-10000	0	-0.58	26	26
LYN	-0.053	0.21	-10000	0	-0.59	47	47
mol:Spermine	-0.039	0.18	-10000	0	-0.67	26	26
cell growth	-0.077	0.24	0.39	1	-0.66	46	47
BMP signaling pathway	0.059	0.22	0.86	26	-0.32	1	27
SRC	-0.051	0.22	-10000	0	-0.59	47	47
TGFBR1	0	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.32	0.46	0.32	35	-0.86	152	187
GPC1	-0.059	0.22	0.32	1	-0.86	26	27
TGFBR1 (dimer)	0	0	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.16	0.31	-10000	0	-0.63	102	102
HCK	-0.072	0.24	-10000	0	-0.61	57	57
FGF2	-0.047	0.21	0.32	5	-0.86	22	27
FGFR1	-0.011	0.11	0.32	3	-0.86	6	9
VEGFR1 homodimer	0	0	-10000	0	-10000	0	0
TGFBR2	0	0	-10000	0	-10000	0	0
cell death	-0.053	0.18	-10000	0	-0.66	30	30
ATIII/GPC1	-0.14	0.27	-10000	0	-0.67	75	75
PLA2G2A/GPC1	-0.3	0.39	-10000	0	-0.71	164	164
LCK	-0.07	0.24	-10000	0	-0.61	56	56
neuron differentiation	-0.32	0.36	-10000	0	-0.7	170	170
PrPc/Cu2+	-0.042	0.16	-10000	0	-0.67	23	23
APP	-0.009	0.089	-10000	0	-0.86	4	4
TGFBR2 (dimer)	0	0	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	0.01	0.009	-10000	0	-10000	0	0
RAS family/GTP	-0.13	0.16	-10000	0	-0.55	4	4
NFATC4	-0.12	0.17	-10000	0	-0.33	74	74
ERBB2IP	0.006	0.007	-10000	0	-10000	0	0
HSP90 (dimer)	0	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.19	0.22	-10000	0	-0.43	161	161
JUN	-0.056	0.092	-10000	0	-0.5	7	7
HRAS	0.002	0.023	0.32	2	-10000	0	2
DOCK7	-0.18	0.21	-10000	0	-0.41	161	161
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.23	0.26	-10000	0	-0.52	161	161
AKT1	0.005	0.005	-10000	0	-10000	0	0
BAD	0.01	0.009	-10000	0	-10000	0	0
MAPK10	-0.1	0.12	0.16	2	-0.37	28	30
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.2	0.24	-10000	0	-0.47	161	161
RAF1	-0.11	0.17	-10000	0	-0.48	5	5
ErbB2/ErbB3/neuregulin 2	0.025	0.12	-10000	0	-0.53	9	9
STAT3	0	0.025	-10000	0	-10000	0	0
cell migration	-0.082	0.12	-10000	0	-0.31	23	23
mol:PI-3-4-5-P3	-0.003	0.004	-10000	0	-10000	0	0
cell proliferation	-0.2	0.22	-10000	0	-0.52	73	73
FOS	-0.27	0.28	-10000	0	-0.54	179	179
NRAS	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.19	0.22	-10000	0	-0.43	161	161
MAPK3	-0.16	0.18	-10000	0	-0.43	73	73
MAPK1	-0.16	0.18	-10000	0	-0.43	73	73
JAK2	-0.18	0.21	-10000	0	-0.41	161	161
NF2	-0.01	0.012	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.17	0.19	-10000	0	-0.39	158	158
NRG1	-0.36	0.42	-10000	0	-0.86	156	156
GRB2/SOS1	0	0	-10000	0	-10000	0	0
MAPK8	-0.17	0.18	-10000	0	-0.36	175	175
MAPK9	-0.088	0.1	-10000	0	-0.3	4	4
ERBB2	-0.011	0.086	-10000	0	-0.68	6	6
ERBB3	-0.007	0.077	-10000	0	-0.86	3	3
SHC1	0	0.001	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.003	0.011	-10000	0	-10000	0	0
STAT3 (dimer)	0	0.025	-10000	0	-10000	0	0
RNF41	0.013	0.012	-10000	0	-10000	0	0
FRAP1	0.005	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.12	0.14	-10000	0	-0.37	8	8
ErbB2/ErbB2/HSP90 (dimer)	-0.01	0.075	-10000	0	-0.59	6	6
CHRNA1	-0.11	0.14	0.35	1	-0.39	8	9
myelination	-0.12	0.18	-10000	0	-0.33	76	76
PPP3CB	-0.16	0.19	-10000	0	-0.38	161	161
KRAS	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.14	0.16	-10000	0	-0.58	4	4
NRG2	0.066	0.13	0.32	78	-10000	0	78
mol:GDP	-0.16	0.19	-10000	0	-0.38	158	158
SOS1	0	0	-10000	0	-10000	0	0
MAP2K2	-0.099	0.16	-10000	0	-0.47	5	5
SRC	0.004	0.036	0.32	5	-10000	0	5
mol:cAMP	-0.002	0.003	-10000	0	-10000	0	0
PTPN11	-0.18	0.2	-10000	0	-0.41	161	161
MAP2K1	-0.19	0.2	-10000	0	-0.5	70	70
heart morphogenesis	-0.19	0.22	-10000	0	-0.43	161	161
RAS family/GDP	-0.14	0.16	-10000	0	-0.56	4	4
GRB2	0	0	-10000	0	-10000	0	0
PRKACA	-0.014	0.016	-10000	0	-10000	0	0
CHRNE	-0.007	0.037	-10000	0	-0.25	7	7
HSP90AA1	0	0	-10000	0	-10000	0	0
activation of caspase activity	-0.005	0.005	-10000	0	-10000	0	0
nervous system development	-0.19	0.22	-10000	0	-0.43	161	161
CDC42	0	0	-10000	0	-10000	0	0

×

Thromboxane A2 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.009	0.089	-10000	0	-0.86	4	4
GNB1/GNG2	-0.066	0.088	-10000	0	-0.19	108	108
AKT1	-0.026	0.13	0.23	1	-0.22	64	65
EGF	0.075	0.13	0.32	88	-10000	0	88
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.058	0.14	-10000	0	-0.46	24	24
mol:Ca2+	-0.051	0.17	0.27	1	-0.31	108	109
LYN	-0.056	0.14	-10000	0	-0.45	22	22
RhoA/GTP	-0.038	0.057	-10000	0	-0.14	5	5
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.058	0.2	-10000	0	-0.35	108	108
GNG2	-0.007	0.077	-10000	0	-0.86	3	3
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.039	0.15	-10000	0	-0.53	19	19
G beta5/gamma2	-0.087	0.12	-10000	0	-0.26	108	108
PRKCH	-0.063	0.2	-10000	0	-0.36	107	107
DNM1	0.004	0.13	0.32	21	-0.86	6	27
TXA2/TP beta/beta Arrestin3	-0.009	0.054	0.17	1	-0.32	6	7
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.049	0.2	-10000	0	-0.86	21	21
G12 family/GTP	-0.095	0.14	-10000	0	-0.31	107	107
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	0.008	0.072	0.32	12	-0.86	1	13
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.048	0.16	0.38	43	-10000	0	43
mol:NADP	-0.005	0.063	-10000	0	-0.86	2	2
RAB11A	0	0	-10000	0	-10000	0	0
PRKG1	-0.041	0.19	0.32	1	-0.86	18	19
mol:IP3	-0.072	0.21	-10000	0	-0.39	108	108
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.11	0.28	-10000	0	-0.53	108	108
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.12	0.21	-10000	0	-0.47	82	82
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.068	0.16	-10000	0	-0.47	32	32
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.083	0.26	-10000	0	-0.86	36	36
PRKCB1	-0.071	0.21	-10000	0	-0.38	108	108
GNAQ	-0.002	0.045	-10000	0	-0.86	1	1
mol:L-citrulline	-0.005	0.063	-10000	0	-0.86	2	2
TXA2/TXA2-R family	-0.11	0.29	-10000	0	-0.55	107	107
LCK	-0.067	0.16	-10000	0	-0.47	31	31
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.075	0.18	-10000	0	-0.6	23	23
TXA2-R family/G12 family/GDP/G beta/gamma	-0.02	0.048	-10000	0	-0.37	2	2
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.075	0.18	-10000	0	-0.59	23	23
MAPK14	-0.027	0.14	0.24	1	-0.23	107	108
TGM2/GTP	-0.085	0.24	-10000	0	-0.44	108	108
MAPK11	-0.026	0.14	0.26	2	-0.23	108	110
ARHGEF1	-0.025	0.1	0.18	1	-0.19	47	48
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	-0.072	0.22	-10000	0	-0.4	107	107
RAB11/GDP	0	0	-10000	0	-10000	0	0
ICAM1	-0.043	0.16	-10000	0	-0.28	107	107
cAMP biosynthetic process	-0.067	0.2	-10000	0	-0.36	108	108
Gq family/GTP/EBP50	-0.055	0.13	-10000	0	-0.29	71	71
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.054	0.14	-10000	0	-0.45	22	22
GNB5	0.001	0.016	0.32	1	-10000	0	1
GNB1	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.021	0.14	-10000	0	-0.34	32	32
VCAM1	-0.053	0.18	0.27	5	-0.32	106	111
TP beta/Gq family/GDP/G beta5/gamma2	-0.039	0.15	-10000	0	-0.53	19	19
platelet activation	-0.038	0.18	0.3	2	-0.31	107	109
PGI2/IP	-0.065	0.2	-10000	0	-0.68	36	36
PRKACA	-0.064	0.17	-10000	0	-0.45	53	53
Gq family/GDP/G beta5/gamma2	-0.039	0.14	-10000	0	-0.43	29	29
TXA2/TP beta/beta Arrestin2	-0.006	0.1	-10000	0	-0.69	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.087	0.21	-10000	0	-0.48	67	67
mol:DAG	-0.083	0.23	-10000	0	-0.43	108	108
EGFR	-0.023	0.14	-10000	0	-0.86	10	10
TXA2/TP alpha	-0.099	0.27	-10000	0	-0.5	108	108
Gq family/GTP	-0.058	0.14	-10000	0	-0.32	71	71
YES1	-0.056	0.14	-10000	0	-0.44	23	23
GNAI2/GTP	-0.065	0.16	-10000	0	-0.53	23	23
PGD2/DP	-0.038	0.16	-10000	0	-0.68	21	21
SLC9A3R1	-0.002	0.045	-10000	0	-0.86	1	1
FYN	-0.056	0.14	-10000	0	-0.45	22	22
mol:NO	-0.005	0.063	-10000	0	-0.86	2	2
GNA15	-0.001	0.05	0.32	2	-0.86	1	3
PGK/cGMP	-0.031	0.13	-10000	0	-0.59	20	20
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.082	0.2	-10000	0	-0.63	26	26
NOS3	-0.005	0.063	-10000	0	-0.86	2	2
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.062	0.2	-10000	0	-0.36	107	107
PRKCB	-0.085	0.23	-10000	0	-0.4	120	120
PRKCE	-0.062	0.2	-10000	0	-0.36	107	107
PRKCD	-0.071	0.21	-10000	0	-0.39	107	107
PRKCG	-0.073	0.21	-10000	0	-0.39	107	107
muscle contraction	-0.097	0.27	-10000	0	-0.5	107	107
PRKCZ	-0.068	0.2	-10000	0	-0.36	114	114
ARR3	0.001	0.016	0.32	1	-10000	0	1
TXA2/TP beta	-0.072	0.19	-10000	0	-0.62	23	23
PRKCQ	-0.072	0.21	-10000	0	-0.38	113	113
MAPKKK cascade	-0.095	0.25	-10000	0	-0.47	108	108
SELE	-0.082	0.22	0.27	2	-0.42	107	109
TP beta/GNAI2/GDP/G beta/gamma	-0.077	0.18	-10000	0	-0.61	24	24
ROCK1	0	0	-10000	0	-10000	0	0
GNA14	-0.15	0.32	-10000	0	-0.86	63	63
chemotaxis	-0.13	0.32	-10000	0	-0.63	107	107
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.028	0.15	-10000	0	-0.86	12	12
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.038	0.28	0.54	13	-0.89	23	36
IHH	0.013	0.18	0.37	17	-0.88	11	28
SHH Np/Cholesterol/GAS1	-0.12	0.24	-10000	0	-0.57	79	79
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.12	0.24	0.56	79	-10000	0	79
SMO/beta Arrestin2	-0.023	0.25	0.34	1	-0.8	28	29
SMO	-0.024	0.27	0.38	1	-0.84	29	30
AKT1	0.001	0.14	0.25	1	-0.4	21	22
ARRB2	0	0	-10000	0	-10000	0	0
BOC	0.009	0.054	0.32	11	-10000	0	11
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.022	0.26	0.38	1	-0.81	29	30
STIL	-0.004	0.24	0.35	8	-0.69	28	36
DHH N/PTCH2	-0.002	0.053	-10000	0	-0.67	2	2
DHH N/PTCH1	-0.016	0.23	0.36	2	-0.76	26	28
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
DHH	0.001	0.016	0.32	1	-10000	0	1
PTHLH	0.045	0.29	0.52	13	-0.88	23	36
determination of left/right symmetry	-0.022	0.26	0.38	1	-0.81	29	30
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
skeletal system development	0.046	0.28	0.51	13	-0.87	23	36
IHH N/Hhip	-0.34	0.38	0.27	1	-0.72	179	180
DHH N/Hhip	-0.31	0.34	-10000	0	-0.67	173	173
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.022	0.26	0.38	1	-0.81	29	30
pancreas development	-0.4	0.43	0.32	1	-0.86	173	174
HHAT	-0.001	0.05	0.32	2	-0.86	1	3
PI3K	-0.005	0.071	-10000	0	-0.94	2	2
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.16	0.34	0.32	1	-0.86	70	71
somite specification	-0.022	0.26	0.38	1	-0.81	29	30
SHH Np/Cholesterol/PTCH1	-0.029	0.24	0.33	1	-0.69	34	35
SHH Np/Cholesterol/PTCH2	-0.021	0.12	-10000	0	-0.57	15	15
SHH Np/Cholesterol/Megalin	-0.081	0.22	-10000	0	-0.55	64	64
SHH	-0.007	0.14	-10000	0	-0.71	13	13
catabolic process	0.012	0.26	0.46	1	-0.74	32	33
SMO/Vitamin D3	-0.025	0.26	0.42	1	-0.72	36	37
SHH Np/Cholesterol/Hhip	-0.27	0.28	-10000	0	-0.55	182	182
LRP2	-0.099	0.32	0.32	25	-0.86	52	77
receptor-mediated endocytosis	-0.07	0.27	-10000	0	-0.76	33	33
SHH Np/Cholesterol/BOC	-0.014	0.11	-10000	0	-0.57	13	13
SHH Np/Cholesterol/CDO	-0.02	0.11	-10000	0	-0.57	13	13
mesenchymal cell differentiation	0.27	0.28	0.55	182	-10000	0	182
mol:Vitamin D3	0.007	0.25	0.42	1	-0.69	34	35
IHH N/PTCH2	0	0.13	0.27	1	-0.61	13	14
CDON	0	0	-10000	0	-10000	0	0
IHH N/PTCH1	-0.002	0.27	0.41	17	-0.75	32	49
Megalin/LRPAP1	-0.079	0.24	-10000	0	-0.67	52	52
PTCH2	-0.003	0.067	0.32	2	-0.86	2	4
SHH Np/Cholesterol	-0.019	0.11	-10000	0	-0.58	13	13
PTCH1	0.012	0.26	0.46	1	-0.75	32	33
HHIP	-0.4	0.43	0.32	1	-0.86	173	174

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.14	0.15	0.68	4	-10000	0	4
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.007	0.069	-10000	0	-0.59	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.41	0.43	-10000	0	-0.86	178	178
RhoA/GTP	-0.14	0.16	-10000	0	-0.7	4	4
negative regulation of cAMP metabolic process	-0.14	0.19	-10000	0	-0.33	181	181
GNAZ	0.15	0.17	0.32	176	-0.86	1	177
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	-0.011	0.1	0.32	1	-0.86	5	6
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.14	0.2	-10000	0	-0.33	181	181
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.063	-10000	0	-0.86	2	2

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.12	0.44	-10000	0	-0.99	74	74
NCK1/PAK1/Dok-R	-0.092	0.18	-10000	0	-0.44	74	74
NCK1/Dok-R	-0.24	0.47	-10000	0	-1.2	74	74
PIK3CA	0	0.045	-10000	0	-0.86	1	1
mol:beta2-estradiol	-0.001	0.029	0.25	3	-10000	0	3
RELA	0	0	-10000	0	-10000	0	0
SHC1	0.001	0.003	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.048	0.22	-10000	0	-0.86	24	24
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.22	0.43	-10000	0	-1.1	74	74
FN1	-0.002	0.045	-10000	0	-0.86	1	1
PLD2	-0.19	0.51	-10000	0	-1.2	74	74
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.014	0.11	-10000	0	-0.86	6	6
ELK1	-0.16	0.46	-10000	0	-1.1	74	74
GRB7	-0.004	0.098	0.32	6	-0.86	4	10
PAK1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.23	0.45	-10000	0	-1.1	74	74
CDKN1A	-0.072	0.33	-10000	0	-0.7	77	77
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	-1.2	74	74
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.067	0.32	-10000	0	-0.7	74	74
PLG	-0.26	0.54	-10000	0	-1.3	75	75
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.18	0.38	-10000	0	-0.92	74	74
GRB2	0	0	-10000	0	-10000	0	0
PIK3R1	-0.004	0.063	-10000	0	-0.86	2	2
ANGPT2	0	0.16	-10000	0	-0.61	10	10
BMX	-0.23	0.56	-10000	0	-1.3	74	74
ANGPT1	-0.004	0.18	-10000	0	-1.5	3	3
tube development	-0.083	0.35	-10000	0	-0.76	74	74
ANGPT4	0.007	0.043	0.32	7	-10000	0	7
response to hypoxia	-0.01	0.029	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.26	0.5	-10000	0	-1.2	74	74
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.047	0.21	0.32	5	-0.86	22	27
STAT5A (dimer)	-0.11	0.41	-10000	0	-0.89	77	77
mol:L-citrulline	-0.067	0.32	-10000	0	-0.7	74	74
AGTR1	-0.075	0.24	-10000	0	-0.86	33	33
MAPK14	-0.2	0.54	-10000	0	-1.3	74	74
Tie2/SHP2	-0.25	0.49	-10000	0	-1.2	73	73
TEK	-0.27	0.55	-10000	0	-1.4	73	73
RPS6KB1	-0.12	0.42	-10000	0	-0.94	74	74
Angiotensin II/AT1	-0.056	0.19	-10000	0	-0.67	33	33
Tie2/Ang1/GRB2	-0.25	0.5	-10000	0	-1.2	74	74
MAPK3	-0.16	0.47	-10000	0	-1.1	74	74
MAPK1	-0.16	0.47	-10000	0	-1.1	74	74
Tie2/Ang1/GRB7	-0.25	0.5	-10000	0	-1.2	74	74
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.21	0.53	-10000	0	-1.2	74	74
PI3K	-0.16	0.5	-10000	0	-1.2	74	74
FES	-0.2	0.54	-10000	0	-1.3	74	74
Crk/Dok-R	-0.24	0.47	-10000	0	-1.2	74	74
Tie2/Ang1/ABIN2	-0.25	0.5	-10000	0	-1.2	74	74
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.1	0.39	-10000	0	-0.86	74	74
STAT5A	0.001	0.016	0.32	1	-10000	0	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.12	0.42	-10000	0	-0.94	74	74
Tie2/Ang2	-0.15	0.49	-10000	0	-1.1	74	74
Tie2/Ang1	-0.21	0.56	-10000	0	-1.3	74	74
FOXO1	-0.099	0.4	-10000	0	-0.88	74	74
ELF1	-0.009	0.078	-10000	0	-0.9	2	2
ELF2	-0.2	0.52	-10000	0	-1.2	74	74
mol:Choline	-0.18	0.49	-10000	0	-1.1	74	74
cell migration	-0.05	0.096	-10000	0	-0.24	74	74
FYN	-0.11	0.4	-10000	0	-0.89	74	74
DOK2	-0.012	0.099	-10000	0	-0.86	5	5
negative regulation of cell cycle	-0.058	0.3	-10000	0	-0.62	77	77
ETS1	0.008	0.053	-10000	0	-0.89	1	1
PXN	-0.078	0.34	-10000	0	-0.76	74	74
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.087	0.37	-10000	0	-0.82	74	74
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.019	0.17	0.33	2	-0.87	14	16
MAPKKK cascade	-0.18	0.49	-10000	0	-1.1	74	74
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
Tie2/Ang1/Shc	-0.23	0.51	-10000	0	-1.2	74	74
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.052	0.29	-10000	0	-0.62	74	74
mol:Phosphatidic acid	-0.18	0.49	-10000	0	-1.1	74	74
mol:Angiotensin II	0.002	0.005	-10000	0	-10000	0	0
mol:NADP	-0.067	0.32	-10000	0	-0.7	74	74
Rac1/GTP	-0.18	0.35	-10000	0	-0.87	74	74
MMP2	-0.2	0.55	-10000	0	-1.3	74	74

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.001	0.036	-10000	0	-0.67	1	1
CRKL	-0.13	0.15	-10000	0	-0.49	2	2
mol:PIP3	-0.006	0.057	0.76	2	-10000	0	2
AKT1	0.009	0.035	0.48	2	-10000	0	2
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.12	0.15	-10000	0	-0.46	2	2
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
HGF/MET/SHIP2	-0.32	0.29	-10000	0	-0.58	201	201
MAP3K5	-0.16	0.23	-10000	0	-0.65	50	50
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.29	0.27	-10000	0	-0.54	201	201
AP1	-0.3	0.32	-10000	0	-0.62	179	179
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.42	0.44	-10000	0	-0.88	179	179
STAT3 (dimer)	-0.18	0.17	-10000	0	-0.33	202	202
GAB1/CRKL/SHP2/PI3K	-0.13	0.12	-10000	0	-0.62	3	3
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.14	0.13	-10000	0	-0.46	2	2
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	-0.005	0.063	-10000	0	-0.86	2	2
ELK1	-0.014	0.022	-10000	0	-0.29	1	1
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.11	0.1	-10000	0	-0.34	2	2
PAK1	0.016	0.032	0.44	2	-10000	0	2
HGF/MET/RANBP10	-0.32	0.29	-10000	0	-0.58	201	201
HRAS	-0.23	0.22	-10000	0	-1.1	1	1
DOCK1	-0.13	0.17	-10000	0	-0.63	10	10
GAB1	-0.15	0.16	-10000	0	-0.29	201	201
CRK	-0.13	0.15	-10000	0	-0.49	2	2
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.32	0.3	-10000	0	-0.6	201	201
JUN	-0.014	0.11	-10000	0	-0.86	6	6
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.15	0.14	-10000	0	-0.27	201	201
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
cell morphogenesis	-0.15	0.19	-10000	0	-0.61	4	4
GRB2/SHC	-0.12	0.12	-10000	0	-0.56	1	1
FOS	-0.42	0.43	-10000	0	-0.86	179	179
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.014	0.022	-10000	0	-0.29	1	1
HGF/MET/MUC20	-0.32	0.3	-10000	0	-0.59	201	201
cell migration	-0.12	0.11	-10000	0	-0.55	1	1
GRB2	0	0	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.001	0.036	-10000	0	-0.67	1	1
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.19	0.18	-10000	0	-0.35	202	202
MET/MUC20	-0.001	0.037	0.21	1	-0.67	1	2
RAP1B	-0.11	0.14	-10000	0	-0.42	2	2
RAP1A	-0.11	0.14	-10000	0	-0.53	1	1
HGF/MET/RANBP9	-0.32	0.29	-10000	0	-0.58	201	201
RAF1	-0.2	0.22	-10000	0	-1	1	1
STAT3	-0.18	0.17	-10000	0	-0.34	202	202
cell proliferation	-0.22	0.25	-10000	0	-0.45	201	201
RPS6KB1	-0.051	0.047	-10000	0	-0.19	1	1
MAPK3	-0.014	0.018	-10000	0	-0.26	1	1
MAPK1	-0.014	0.018	-10000	0	-0.26	1	1
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	-0.14	0.22	-10000	0	-0.54	61	61
SRC	-0.18	0.17	-10000	0	-0.66	2	2
PI3K	-0.13	0.12	-10000	0	-0.67	3	3
MET/Glomulin	-0.001	0.034	0.23	1	-0.61	1	2
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.18	0.2	-10000	0	-0.87	1	1
MET	-0.001	0.048	0.32	1	-0.86	1	2
MAP4K1	-0.12	0.16	-10000	0	-0.51	9	9
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.18	0.2	-10000	0	-0.87	1	1
BAD	0.016	0.032	0.44	2	-10000	0	2
MAP2K4	-0.14	0.21	-10000	0	-0.57	50	50
SHP2/GRB2/SOS1/GAB1	-0.13	0.12	-10000	0	-0.76	1	1
INPPL1	0	0	-10000	0	-10000	0	0
PXN	0	0	-10000	0	-10000	0	0
SH3KBP1	-0.002	0.045	-10000	0	-0.86	1	1
HGS	-0.13	0.12	-10000	0	-0.59	1	1
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.46	0.43	0.32	1	-0.86	201	202
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
NCK1	0	0	-10000	0	-10000	0	0
PTPRJ	0	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.14	0.13	-10000	0	-0.59	1	1
PDPK1	0.002	0.041	0.55	2	-10000	0	2
HGF/MET/SHIP	-0.32	0.29	-10000	0	-0.58	201	201

×

Syndecan-1-mediated signaling events

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
TGFB1	0.004	0.036	0.32	5	-10000	0	5
CCL5	-0.019	0.14	0.32	2	-0.86	9	11
SDCBP	0	0	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.047	0.21	0.3	1	-0.49	35	36
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.071	0.19	0.32	4	-0.66	17	21
Syndecan-1/Syntenin	-0.074	0.18	0.26	1	-0.57	23	24
MAPK3	-0.062	0.17	-10000	0	-0.65	14	14
HGF/MET	-0.36	0.34	-10000	0	-0.67	201	201
TGFB1/TGF beta receptor Type II	0.004	0.036	0.32	5	-10000	0	5
BSG	0.002	0.023	0.32	2	-10000	0	2
keratinocyte migration	-0.07	0.19	0.32	4	-0.58	21	25
Syndecan-1/RANTES	-0.085	0.22	0.37	2	-0.78	20	22
Syndecan-1/CD147	-0.086	0.16	-10000	0	-0.7	14	14
Syndecan-1/Syntenin/PIP2	-0.089	0.16	-10000	0	-0.55	23	23
LAMA5	0.004	0.036	0.32	5	-10000	0	5
positive regulation of cell-cell adhesion	-0.087	0.16	-10000	0	-0.54	23	23
MMP7	-0.18	0.39	0.32	30	-0.86	88	118
HGF	-0.46	0.43	0.32	1	-0.86	201	202
Syndecan-1/CASK	-0.049	0.2	0.25	1	-0.47	35	36
Syndecan-1/HGF/MET	-0.34	0.32	0.3	2	-0.59	199	201
regulation of cell adhesion	-0.017	0.18	-10000	0	-0.63	14	14
HPSE	-0.048	0.2	0.32	1	-0.86	21	22
positive regulation of cell migration	-0.047	0.21	0.3	1	-0.49	35	36
SDC1	-0.047	0.21	0.3	1	-0.5	35	36
Syndecan-1/Collagen	-0.047	0.21	0.3	1	-0.49	35	36
PPIB	0	0	-10000	0	-10000	0	0
MET	-0.001	0.048	0.32	1	-0.86	1	2
PRKACA	0	0	-10000	0	-10000	0	0
MMP9	0.032	0.2	0.32	70	-0.86	12	82
MAPK1	-0.062	0.17	-10000	0	-0.65	14	14
homophilic cell adhesion	-0.046	0.21	0.3	1	-0.48	35	36
MMP1	0.072	0.13	0.32	85	-10000	0	85

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.013	0.057	-10000	0	-0.84	1	1
Syndecan-4/Syndesmos	-0.09	0.27	-10000	0	-0.82	37	37
positive regulation of JNK cascade	-0.27	0.29	-10000	0	-0.54	172	172
Syndecan-4/ADAM12	-0.079	0.28	-10000	0	-0.81	38	38
CCL5	-0.019	0.14	0.32	2	-0.86	9	11
Rac1/GDP	0	0	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
ITGA5	0	0	-10000	0	-10000	0	0
SDCBP	0	0	-10000	0	-10000	0	0
PLG	-0.13	0.31	-10000	0	-0.84	58	58
ADAM12	0.03	0.11	0.32	38	-0.86	1	39
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.022	0.041	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.14	0.3	-10000	0	-0.64	80	80
Syndecan-4/CXCL12/CXCR4	-0.29	0.32	-10000	0	-0.58	172	172
Syndecan-4/Laminin alpha3	-0.068	0.3	0.34	6	-0.83	37	43
MDK	0.18	0.16	0.32	208	-10000	0	208
Syndecan-4/FZD7	-0.1	0.28	-10000	0	-0.76	45	45
Syndecan-4/Midkine	0.008	0.32	-10000	0	-0.81	37	37
FZD7	-0.015	0.13	0.32	4	-0.86	8	12
Syndecan-4/FGFR1/FGF	-0.13	0.27	-10000	0	-0.78	45	45
THBS1	-0.12	0.3	-10000	0	-0.86	54	54
integrin-mediated signaling pathway	-0.12	0.28	0.33	2	-0.68	61	63
positive regulation of MAPKKK cascade	-0.27	0.29	-10000	0	-0.54	172	172
Syndecan-4/TACI	-0.084	0.28	-10000	0	-0.81	39	39
CXCR4	-0.007	0.077	-10000	0	-0.86	3	3
cell adhesion	-0.001	0.021	-10000	0	-0.4	1	1
Syndecan-4/Dynamin	-0.09	0.27	-10000	0	-0.82	37	37
Syndecan-4/TSP1	-0.16	0.32	-10000	0	-0.66	85	85
Syndecan-4/GIPC	-0.09	0.27	-10000	0	-0.82	37	37
Syndecan-4/RANTES	-0.1	0.29	-10000	0	-0.8	43	43
ITGB1	0	0	-10000	0	-10000	0	0
LAMA1	-0.087	0.3	0.32	20	-0.86	45	65
LAMA3	0.038	0.15	0.32	55	-0.86	4	59
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0.021	0.052	-10000	0	-10000	0	0
Syndecan-4/alpha-Actinin	-0.09	0.27	-10000	0	-0.82	37	37
TFPI	-0.035	0.17	-10000	0	-0.86	15	15
F2	-0.051	0.21	-10000	0	-0.84	24	24
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
positive regulation of cell adhesion	-0.12	0.3	-10000	0	-0.65	66	66
ACTN1	0	0	-10000	0	-10000	0	0
TNC	-0.068	0.24	0.32	5	-0.86	31	36
Syndecan-4/CXCL12	-0.28	0.35	-10000	0	-0.6	172	172
FGF6	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
CXCL12	-0.36	0.42	-10000	0	-0.86	157	157
TNFRSF13B	0	0.073	0.32	5	-0.86	2	7
FGF2	-0.047	0.21	0.32	5	-0.86	22	27
FGFR1	-0.011	0.11	0.32	3	-0.86	6	9
Syndecan-4/PI-4-5-P2	-0.069	0.28	-10000	0	-0.83	37	37
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0	0.043	-10000	0	-0.81	1	1
cell migration	-0.006	0.013	-10000	0	-10000	0	0
PRKCD	0.002	0.008	-10000	0	-10000	0	0
vasculogenesis	-0.15	0.3	-10000	0	-0.63	85	85
SDC4	-0.075	0.31	-10000	0	-0.9	37	37
Syndecan-4/Tenascin C	-0.13	0.3	0.34	2	-0.72	61	63
Syndecan-4/PI-4-5-P2/PKC alpha	-0.017	0.032	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.09	0.27	-10000	0	-0.82	37	37
MMP9	0.032	0.2	0.32	70	-0.86	12	82
Rac1/GTP	-0.001	0.022	-10000	0	-0.41	1	1
cytoskeleton organization	-0.085	0.26	-10000	0	-0.77	37	37
GIPC1	0.001	0.016	0.32	1	-10000	0	1
Syndecan-4/TFPI	-0.11	0.3	-10000	0	-0.83	45	45

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.016	0.1	-10000	0	-0.67	9	9
PDGFRB	0.007	0.046	0.32	8	-10000	0	8
SPHK1	-0.012	0.14	-10000	0	-1	5	5
mol:S1P	-0.02	0.14	-10000	0	-0.94	5	5
S1P1/S1P/Gi	-0.25	0.3	-10000	0	-0.61	109	109
GNAO1	-0.42	0.43	-10000	0	-0.87	178	178
PDGFB-D/PDGFRB/PLCgamma1	-0.21	0.25	0.29	3	-0.6	75	78
PLCG1	-0.22	0.28	-10000	0	-0.65	76	76
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.007	0.046	0.31	8	-10000	0	8
GNAI2	0	0.001	-10000	0	-10000	0	0
GNAI3	0	0.001	-10000	0	-10000	0	0
GNAI1	-0.005	0.064	-10000	0	-0.87	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.003	0.093	-10000	0	-0.59	9	9
S1P1/S1P	-0.037	0.14	-10000	0	-0.65	12	12
negative regulation of cAMP metabolic process	-0.24	0.29	-10000	0	-0.59	109	109
MAPK3	-0.3	0.36	-10000	0	-0.72	128	128
calcium-dependent phospholipase C activity	-0.004	0.004	-10000	0	-10000	0	0
Rac1/GDP	0	0	-10000	0	-10000	0	0
RhoA/GDP	0	0	-10000	0	-10000	0	0
KDR	-0.021	0.13	-10000	0	-0.86	9	9
PLCB2	-0.026	0.15	-10000	0	-0.56	19	19
RAC1	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.044	0.1	-10000	0	-0.52	12	12
receptor internalization	-0.035	0.13	-10000	0	-0.59	12	12
PTGS2	-0.43	0.54	-10000	0	-1.2	125	125
Rac1/GTP	-0.044	0.1	-10000	0	-0.52	12	12
RHOA	0	0	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
negative regulation of T cell proliferation	-0.24	0.29	-10000	0	-0.59	109	109
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.15	0.16	0.31	176	-0.87	1	177
MAPK1	-0.3	0.36	-10000	0	-0.72	128	128
S1P1/S1P/PDGFB-D/PDGFRB	-0.036	0.15	-10000	0	-0.66	12	12
ABCC1	0.007	0.046	0.32	8	-10000	0	8

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.043	0.17	-10000	0	-0.69	22	22
alphaM/beta2 Integrin/GPIbA	-0.026	0.12	0.34	1	-0.64	13	14
alphaM/beta2 Integrin/proMMP-9	0	0.18	0.4	1	-0.69	18	19
PLAUR	-0.002	0.069	0.32	3	-0.86	2	5
HMGB1	-0.006	0.016	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.02	0.1	-10000	0	-0.67	8	8
AGER	-0.003	0.038	0.32	4	-10000	0	4
RAP1A	0	0	-10000	0	-10000	0	0
SELPLG	-0.005	0.063	-10000	0	-0.86	2	2
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.04	0.13	-10000	0	-0.67	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.032	0.2	0.32	70	-0.86	12	82
CYR61	-0.1	0.28	-10000	0	-0.86	43	43
TLN1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.099	0.17	-10000	0	-0.54	34	34
RHOA	0	0	-10000	0	-10000	0	0
P-selectin oligomer	-0.26	0.39	-10000	0	-0.86	112	112
MYH2	-0.14	0.29	-10000	0	-0.53	95	95
MST1R	0.027	0.16	0.32	51	-0.86	7	58
leukocyte activation during inflammatory response	-0.28	0.28	-10000	0	-0.53	192	192
APOB	-0.037	0.18	-10000	0	-0.86	16	16
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	-0.034	0.18	0.32	6	-0.86	17	23
JAM3	0.001	0.016	0.32	1	-10000	0	1
GP1BA	-0.007	0.11	0.32	5	-0.86	5	10
alphaM/beta2 Integrin/CTGF	-0.034	0.15	-10000	0	-0.7	15	15
alphaM/beta2 Integrin	-0.12	0.2	-10000	0	-0.51	52	52
JAM3 homodimer	0.001	0.016	0.32	1	-10000	0	1
ICAM2	0.001	0.016	0.32	1	-10000	0	1
ICAM1	0	0	-10000	0	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.12	0.2	-10000	0	-0.5	52	52
cell adhesion	-0.025	0.12	0.34	1	-0.64	13	14
NFKB1	-0.07	0.19	-10000	0	-0.74	14	14
THY1	0.08	0.14	0.32	94	-10000	0	94
RhoA/GDP	0	0	-10000	0	-10000	0	0
Lipoprotein(a)	-0.31	0.32	-10000	0	-0.61	186	186
alphaM/beta2 Integrin/LRP/tPA	-0.025	0.13	-10000	0	-0.62	14	14
IL6	-0.1	0.39	-10000	0	-1	54	54
ITGB2	-0.015	0.092	0.32	1	-0.87	4	5
elevation of cytosolic calcium ion concentration	-0.015	0.11	0.37	2	-0.6	10	12
alphaM/beta2 Integrin/JAM2/JAM3	-0.035	0.14	0.38	1	-0.6	20	21
JAM2	-0.029	0.16	0.32	1	-0.86	13	14
alphaM/beta2 Integrin/ICAM1	-0.039	0.17	-10000	0	-0.5	40	40
alphaM/beta2 Integrin/uPA/Plg	-0.099	0.21	-10000	0	-0.55	65	65
RhoA/GTP	-0.17	0.29	-10000	0	-0.49	125	125
positive regulation of phagocytosis	-0.094	0.18	-10000	0	-0.64	29	29
Ron/MSP	-0.034	0.2	-10000	0	-0.65	32	32
alphaM/beta2 Integrin/uPAR/uPA	-0.015	0.11	0.38	2	-0.6	10	12
alphaM/beta2 Integrin/uPAR	-0.022	0.11	-10000	0	-0.66	10	10
PLAU	0.005	0.04	0.32	6	-10000	0	6
PLAT	-0.01	0.11	0.32	4	-0.86	6	10
actin filament polymerization	-0.13	0.26	-10000	0	-0.5	95	95
MST1	-0.058	0.22	-10000	0	-0.86	25	25
alphaM/beta2 Integrin/lipoprotein(a)	-0.28	0.28	-10000	0	-0.54	192	192
TNF	-0.039	0.27	-10000	0	-1	18	18
RAP1B	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.017	0.11	-10000	0	-0.67	8	8
fibrinolysis	-0.098	0.21	-10000	0	-0.54	65	65
HCK	-0.028	0.15	-10000	0	-0.86	12	12
dendritic cell antigen processing and presentation	-0.12	0.2	-10000	0	-0.5	52	52
VTN	-0.03	0.16	-10000	0	-0.86	13	13
alphaM/beta2 Integrin/CYR61	-0.087	0.23	-10000	0	-0.66	46	46
LPA	-0.42	0.43	-10000	0	-0.86	179	179
LRP1	-0.002	0.045	-10000	0	-0.86	1	1
cell migration	-0.035	0.21	-10000	0	-0.65	31	31
FN1	-0.002	0.045	-10000	0	-0.86	1	1
alphaM/beta2 Integrin/Thy1	0.032	0.14	0.4	2	-0.67	8	10
MPO	-0.02	0.13	0.32	1	-0.86	9	10
KNG1	-0.067	0.23	-10000	0	-0.86	29	29
RAP1/GDP	0	0	-10000	0	-10000	0	0
ROCK1	-0.13	0.27	-10000	0	-0.56	67	67
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.13	0.31	-10000	0	-0.86	58	58
CTGF	-0.021	0.13	-10000	0	-0.86	9	9
alphaM/beta2 Integrin/Hck	-0.038	0.18	-10000	0	-0.88	14	14
ITGAM	-0.017	0.1	0.3	2	-0.88	5	7
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.18	0.28	-10000	0	-0.58	115	115
HP	-0.27	0.4	-10000	0	-0.86	117	117
leukocyte adhesion	-0.01	0.17	-10000	0	-0.66	10	10
SELP	-0.26	0.4	-10000	0	-0.86	112	112

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.005	0.14	0.31	1	-0.43	24	25
TBX21	-0.16	0.42	-10000	0	-1.1	43	43
B2M	-0.002	0.009	-10000	0	-10000	0	0
TYK2	0.009	0.019	-10000	0	-10000	0	0
IL12RB1	-0.022	0.17	-10000	0	-0.9	13	13
GADD45B	-0.28	0.57	-10000	0	-1.2	92	92
IL12RB2	-0.009	0.17	0.31	12	-0.87	12	24
GADD45G	-0.26	0.54	-10000	0	-1.2	85	85
natural killer cell activation	-0.003	0.023	-10000	0	-10000	0	0
RELB	0.002	0.023	0.32	2	-10000	0	2
RELA	0	0	-10000	0	-10000	0	0
IL18	-0.012	0.15	0.32	3	-0.87	10	13
IL2RA	-0.007	0.13	0.32	11	-0.86	7	18
IFNG	0.014	0.064	0.32	16	-10000	0	16
STAT3 (dimer)	-0.15	0.35	0.55	1	-0.76	65	66
HLA-DRB5	-0.021	0.15	0.31	5	-0.86	11	16
FASLG	-0.17	0.44	0.74	1	-1.1	45	46
NF kappa B2 p52/RelB	-0.21	0.34	-10000	0	-0.9	57	57
CD4	-0.07	0.24	-10000	0	-0.87	30	30
SOCS1	-0.001	0.071	0.32	4	-0.86	2	6
EntrezGene:6955	-0.014	0.019	-10000	0	-10000	0	0
CD3D	-0.018	0.17	0.31	16	-0.87	12	28
CD3E	-0.038	0.17	0.32	1	-0.88	15	16
CD3G	-0.026	0.16	0.31	7	-0.88	12	19
IL12Rbeta2/JAK2	-0.004	0.14	-10000	0	-0.68	13	13
CCL3	-0.21	0.52	-10000	0	-1.3	53	53
CCL4	-0.18	0.48	0.64	1	-1.3	42	43
HLA-A	-0.002	0.008	-10000	0	-10000	0	0
IL18/IL18R	-0.11	0.33	-10000	0	-0.72	73	73
NOS2	-0.13	0.39	-10000	0	-0.96	42	42
IL12/IL12R/TYK2/JAK2/SPHK2	-0.004	0.13	-10000	0	-0.42	23	23
IL1R1	-0.15	0.41	0.64	1	-1.1	40	41
IL4	0.003	0.023	-10000	0	-10000	0	0
JAK2	0.007	0.051	-10000	0	-0.89	1	1
EntrezGene:6957	-0.012	0.018	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.16	0.49	0.4	1	-1.3	50	51
RAB7A	-0.18	0.39	-10000	0	-0.79	80	80
lysosomal transport	-0.17	0.37	-10000	0	-0.72	87	87
FOS	-0.66	0.75	-10000	0	-1.4	181	181
STAT4 (dimer)	-0.18	0.41	0.56	1	-0.86	72	73
STAT5A (dimer)	-0.2	0.36	0.41	7	-0.92	54	61
GZMA	-0.16	0.42	0.7	1	-1.1	41	42
GZMB	-0.16	0.43	0.7	1	-1.1	44	45
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.16	0.46	0.64	1	-1	62	63
TCR/CD3/MHC II/CD4	-0.15	0.31	0.27	2	-0.71	53	55
IL2/IL2R	-0.049	0.21	0.38	2	-0.66	33	35
MAPK14	-0.25	0.5	0.57	1	-0.9	115	116
CCR5	-0.15	0.4	-10000	0	-0.93	54	54
IL1B	-0.14	0.34	-10000	0	-0.88	64	64
STAT6	-0.027	0.14	0.4	1	-0.3	25	26
STAT4	-0.034	0.17	0.32	1	-0.86	15	16
STAT3	0	0	-10000	0	-10000	0	0
STAT1	0.002	0.023	0.32	2	-10000	0	2
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0	-10000	0	-10000	0	0
IL12B	0.006	0.037	0.34	3	-10000	0	3
CD8A	-0.053	0.21	0.32	4	-0.87	23	27
CD8B	-0.039	0.21	0.32	12	-0.87	20	32
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.005	0.14	0.43	24	-0.31	1	25
IL2RB	-0.067	0.23	-10000	0	-0.86	29	29
proteasomal ubiquitin-dependent protein catabolic process	-0.16	0.37	0.56	1	-0.77	72	73
IL2RG	-0.006	0.11	0.32	7	-0.86	5	12
IL12	0.018	0.054	-10000	0	-10000	0	0
STAT5A	0.001	0.016	0.32	1	-10000	0	1
CD247	-0.007	0.067	0.32	1	-0.87	2	3
IL2	0	0	-10000	0	-10000	0	0
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.018	0.058	0.33	8	-10000	0	8
IL12/IL12R/TYK2/JAK2	-0.18	0.52	0.72	1	-1.1	66	67
MAP2K3	-0.25	0.5	0.57	1	-0.9	113	114
RIPK2	0	0	-10000	0	-10000	0	0
MAP2K6	-0.25	0.5	0.57	1	-0.9	114	115
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.013	0.11	0.32	1	-0.86	6	7
IL18RAP	-0.045	0.21	-10000	0	-0.87	23	23
IL12Rbeta1/TYK2	-0.014	0.14	-10000	0	-0.71	13	13
EOMES	-0.16	0.48	-10000	0	-1.5	44	44
STAT1 (dimer)	-0.13	0.34	0.69	1	-0.77	57	58
T cell proliferation	-0.15	0.32	0.5	1	-0.62	89	90
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.13	0.32	-10000	0	-0.87	58	58
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.25	0.32	-10000	0	-0.72	98	98
ATF2	-0.22	0.45	-10000	0	-0.82	114	114

×

ErbB4 signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.002	0.044	-10000	0	-0.55	2	2
epithelial cell differentiation	-0.057	0.093	-10000	0	-0.45	14	14
ITCH	0	0.004	-10000	0	-10000	0	0
WWP1	0.017	0.02	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
EGFR	-0.023	0.14	-10000	0	-0.86	10	10
PRL	0.003	0.028	0.32	3	-10000	0	3
neuron projection morphogenesis	-0.14	0.22	-10000	0	-0.52	1	1
PTPRZ1	0.01	0.056	0.32	12	-10000	0	12
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.19	0.22	-10000	0	-0.46	150	150
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.22	0.26	-10000	0	-0.53	156	156
ADAM17	0	0.004	-10000	0	-10000	0	0
ErbB4/ErbB4	0.001	0.02	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.083	0.21	0.29	1	-0.55	59	60
NCOR1	-0.005	0.063	-10000	0	-0.86	2	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.21	0.25	-10000	0	-0.5	156	156
GRIN2B	-0.2	0.23	-10000	0	-0.47	156	156
ErbB4/ErbB2/betacellulin	-0.007	0.067	-10000	0	-0.5	6	6
STAT1	0.002	0.023	0.32	2	-10000	0	2
HBEGF	-0.005	0.063	-10000	0	-0.86	2	2
PRLR	-0.025	0.15	-10000	0	-0.86	11	11
E4ICDs/ETO2	-0.081	0.2	-10000	0	-0.55	55	55
axon guidance	-0.055	0.094	-10000	0	-10000	0	0
NEDD4	-0.005	0.063	-10000	0	-0.86	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.019	0.12	-10000	0	-0.67	11	11
CBFA2T3	-0.13	0.31	-10000	0	-0.86	55	55
ErbB4/ErbB2/HBEGF	-0.011	0.073	-10000	0	-0.5	8	8
MAPK3	-0.18	0.21	-10000	0	-0.54	1	1
STAT1 (dimer)	0.002	0.023	-10000	0	-10000	0	0
MAPK1	-0.18	0.21	-10000	0	-0.43	96	96
JAK2	-0.002	0.045	-10000	0	-0.86	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.22	0.26	-10000	0	-0.51	159	159
NRG1	-0.28	0.34	-10000	0	-0.68	156	156
NRG3	-0.13	0.32	0.32	6	-0.86	59	65
NRG2	0.066	0.13	0.32	78	-10000	0	78
NRG4	-0.12	0.3	0.32	1	-0.86	53	54
heart development	-0.055	0.094	-10000	0	-10000	0	0
neural crest cell migration	-0.22	0.25	-10000	0	-0.5	159	159
ERBB2	0.007	0.088	-10000	0	-0.68	6	6
WWOX/E4ICDs	0.001	0.016	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.087	0.2	-10000	0	-0.53	61	61
apoptosis	0.056	0.16	0.41	59	-0.24	1	60
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.051	0.099	0.29	3	-10000	0	3
ErbB4/ErbB2/epiregulin	0.011	0.092	-10000	0	-0.5	6	6
ErbB4/ErbB4/betacellulin/betacellulin	0.003	0.027	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.017	0.092	-10000	0	-0.47	14	14
MDM2	0.033	0.016	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.22	0.25	-10000	0	-0.51	156	156
STAT5A	-0.045	0.089	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.22	0.26	-10000	0	-0.51	162	162
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.004	0.039	-10000	0	-0.52	2	2
STAT5A (dimer)	-0.06	0.1	-10000	0	-0.49	13	13
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.063	0.073	-10000	0	-10000	0	0
LRIG1	0	0	-10000	0	-10000	0	0
EREG	0.027	0.089	0.32	32	-10000	0	32
BTC	0.003	0.028	0.32	3	-10000	0	3
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.06	0.091	-10000	0	-10000	0	0
ERBB4	0.001	0.02	-10000	0	-10000	0	0
STAT5B	0	0	-10000	0	-10000	0	0
YAP1	0.001	0.006	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.079	0.18	-10000	0	-0.5	59	59
glial cell differentiation	0.003	0.039	0.51	2	-10000	0	2
WWOX	0	0	-10000	0	-10000	0	0
cell proliferation	-0.19	0.26	-10000	0	-0.49	157	157

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.15	0.16	-10000	0	-0.52	26	26
NT3 (dimer)/TRKC	-0.36	0.35	-10000	0	-0.69	194	194
NT3 (dimer)/TRKB	-0.6	0.57	-10000	0	-1	224	224
SHC/Grb2/SOS1/GAB1/PI3K	-0.003	0.041	-10000	0	-0.53	2	2
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	0.01	0.056	0.32	12	-10000	0	12
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
DYNLT1	0	0	-10000	0	-10000	0	0
NTRK1	0.002	0.023	0.32	2	-10000	0	2
NTRK2	-0.18	0.36	0.32	9	-0.86	82	91
NTRK3	-0.038	0.19	0.32	4	-0.86	18	22
NT-4/5 (dimer)/TRKB	-0.34	0.42	-10000	0	-0.78	165	165
neuron apoptosis	0.18	0.24	0.57	76	-0.29	1	77
SHC 2-3/Grb2	-0.19	0.26	0.3	1	-0.64	76	77
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.2	0.28	-10000	0	-0.5	142	142
SHC3	-0.18	0.26	0.29	2	-0.48	129	131
STAT3 (dimer)	-0.014	0.075	-10000	0	-0.39	14	14
NT3 (dimer)/TRKA	-0.49	0.46	-10000	0	-0.84	218	218
RIN/GDP	-0.088	0.12	-10000	0	-0.26	26	26
GIPC1	0.001	0.016	0.32	1	-10000	0	1
KRAS	0	0	-10000	0	-10000	0	0
DNAJA3	-0.19	0.25	0.27	2	-0.48	145	147
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	-0.017	0.21	-10000	0	-1.1	14	14
MAGED1	-0.007	0.077	-10000	0	-0.86	3	3
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.003	0.028	0.32	3	-10000	0	3
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.028	0.14	-10000	0	-0.58	20	20
TRKA/NEDD4-2	0.001	0.016	-10000	0	-10000	0	0
ELMO1	-0.002	0.045	-10000	0	-0.86	1	1
RhoG/GTP/ELMO1/DOCK1	-0.014	0.098	-10000	0	-0.65	8	8
NGF	-0.039	0.18	0.32	1	-0.86	17	18
HRAS	0.002	0.023	0.32	2	-10000	0	2
DOCK1	-0.019	0.12	-10000	0	-0.86	8	8
GAB2	0	0	-10000	0	-10000	0	0
RIT2	0	0	-10000	0	-10000	0	0
RIT1	0	0	-10000	0	-10000	0	0
FRS2	0	0	-10000	0	-10000	0	0
DNM1	0.004	0.13	0.32	21	-0.86	6	27
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	-0.18	0.24	0.26	2	-0.47	145	147
mol:GDP	-0.13	0.18	-10000	0	-0.38	65	65
NGF (dimer)	-0.038	0.18	0.32	1	-0.86	17	18
RhoG/GDP	-0.002	0.035	-10000	0	-0.67	1	1
RIT1/GDP	-0.085	0.12	-10000	0	-0.27	14	14
TIAM1	-0.046	0.19	-10000	0	-0.86	20	20
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
BDNF (dimer)/TRKB	-0.12	0.25	0.39	2	-0.58	82	84
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.004	0.049	-10000	0	-0.67	2	2
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.42	0.43	-10000	0	-0.86	183	183
RAP1/GDP	-0.09	0.086	-10000	0	-0.26	1	1
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	0.01	0.056	0.32	12	-10000	0	12
ubiquitin-dependent protein catabolic process	-0.025	0.12	-10000	0	-0.58	17	17
Schwann cell development	-0.055	0.045	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0	0	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.33	0.34	-10000	0	-0.59	211	211
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.042	0.089	-10000	0	-10000	0	0
STAT3	-0.014	0.075	-10000	0	-0.39	14	14
axon guidance	-0.31	0.32	-10000	0	-0.56	211	211
MAPK3	-0.027	0.12	-10000	0	-0.53	20	20
MAPK1	-0.027	0.12	-10000	0	-0.53	20	20
CDC42/GDP	-0.085	0.12	-10000	0	-0.26	18	18
NTF3	-0.42	0.43	-10000	0	-0.86	183	183
NTF4	0.003	0.028	0.32	3	-10000	0	3
NGF (dimer)/TRKA/FAIM	-0.025	0.12	-10000	0	-0.58	17	17
PI3K	-0.005	0.071	-10000	0	-0.94	2	2
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0.001	0.016	0.32	1	-10000	0	1
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.18	0.25	0.27	2	-0.48	145	147
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.31	0.31	-10000	0	-0.6	194	194
RGS19	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.019	0.092	-10000	0	-10000	0	0
Rac1/GDP	-0.085	0.12	-10000	0	-0.26	24	24
NGF (dimer)/TRKA/GRIT	-0.025	0.12	-10000	0	-0.59	17	17
neuron projection morphogenesis	-0.16	0.25	-10000	0	-0.47	141	141
NGF (dimer)/TRKA/NEDD4-2	-0.025	0.12	-10000	0	-0.58	17	17
MAP2K1	0	0	-10000	0	-10000	0	0
NGFR	-0.33	0.42	-10000	0	-0.86	143	143
NGF (dimer)/TRKA/GIPC/GAIP	-0.015	0.089	-10000	0	-0.34	23	23
RAS family/GTP/PI3K	-0.002	0.037	-10000	0	-0.48	2	2
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-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	-0.039	0.18	-10000	0	-0.86	17	17
MAPKKK cascade	-0.071	0.16	-10000	0	-0.78	17	17
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
TRKA/c-Abl	0.001	0.016	-10000	0	-10000	0	0
SQSTM1	0.004	0.036	0.32	5	-10000	0	5
BDNF (dimer)/TRKB/GIPC	-0.11	0.23	0.38	2	-0.53	82	84
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.043	0.15	-10000	0	-0.51	33	33
MATK	-0.004	0.082	0.32	3	-0.86	3	6
NEDD4L	0	0	-10000	0	-10000	0	0
RAS family/GDP	-0.085	0.081	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.2	0.26	0.3	2	-0.51	145	147
Rac1/GTP	-0.16	0.16	-10000	0	-0.37	130	130
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.035	0.2	-10000	0	-0.5	51	51
NF kappa B1 p50/RelA/I kappa B alpha	-0.059	0.15	-10000	0	-0.82	3	3
alphaV/beta3 Integrin/Osteopontin/Src	0.036	0.21	0.36	2	-0.66	24	26
AP1	-0.27	0.37	0.42	1	-0.94	57	58
ILK	-0.04	0.2	-10000	0	-0.53	51	51
bone resorption	-0.044	0.22	-10000	0	-0.88	11	11
PTK2B	0	0	-10000	0	-10000	0	0
PYK2/p130Cas	-0.005	0.23	0.37	1	-0.5	52	53
ITGAV	0.001	0.017	0.32	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.024	0.14	-10000	0	-0.67	16	16
alphaV/beta3 Integrin/Osteopontin	-0.012	0.25	0.4	1	-0.59	51	52
MAP3K1	-0.041	0.21	-10000	0	-0.54	51	51
JUN	-0.014	0.11	-10000	0	-0.86	6	6
MAPK3	-0.006	0.2	-10000	0	-0.5	51	51
MAPK1	-0.006	0.2	-10000	0	-0.5	51	51
Rac1/GDP	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.04	0.26	-10000	0	-0.59	59	59
ITGB3	-0.069	0.23	-10000	0	-0.85	30	30
NFKBIA	0.003	0.2	-10000	0	-0.48	51	51
FOS	-0.42	0.43	-10000	0	-0.86	179	179
CD44	0.002	0.078	0.32	8	-0.86	2	10
CHUK	0	0	-10000	0	-10000	0	0
PLAU	-0.006	0.19	-10000	0	-0.82	3	3
NF kappa B1 p50/RelA	-0.054	0.15	-10000	0	-0.8	3	3
BCAR1	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin	-0.053	0.18	-10000	0	-0.66	30	30
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.046	0.22	-10000	0	-0.56	52	52
VAV3	-0.017	0.22	-10000	0	-0.53	52	52
MAP3K14	-0.015	0.21	-10000	0	-0.53	51	51
ROCK2	-0.032	0.16	-10000	0	-0.86	14	14
SPP1	0.055	0.28	0.32	127	-0.85	24	151
RAC1	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.04	0.19	-10000	0	-0.48	52	52
MMP2	-0.22	0.3	0.43	2	-0.75	59	61

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.068	0.38	-10000	0	-1.2	33	33
SMARCC2	-0.002	0.009	-10000	0	-10000	0	0
SMARCC1	-0.002	0.009	-10000	0	-10000	0	0
TBX21	-0.091	0.23	-10000	0	-1.1	11	11
SUMO2	0.003	0.01	-10000	0	-10000	0	0
STAT1 (dimer)	0.016	0.023	0.32	2	-10000	0	2
FKBP4	0	0	-10000	0	-10000	0	0
FKBP5	-0.002	0.045	-10000	0	-0.86	1	1
GR alpha/HSP90/FKBP51/HSP90	0.07	0.11	0.33	5	-0.47	1	6
PRL	-0.066	0.16	-10000	0	-0.58	13	13
cortisol/GR alpha (dimer)/TIF2	0.088	0.37	0.53	85	-0.59	43	128
RELA	-0.067	0.11	-10000	0	-0.29	8	8
FGG	0.031	0.37	0.48	30	-0.92	37	67
GR beta/TIF2	-0.019	0.27	0.34	11	-0.65	48	59
IFNG	-0.14	0.26	0.55	1	-0.66	24	25
apoptosis	-0.17	0.31	0.63	6	-0.73	48	54
CREB1	0.017	0.033	-10000	0	-10000	0	0
histone acetylation	-0.068	0.13	-10000	0	-0.38	22	22
BGLAP	-0.041	0.13	-10000	0	-0.5	2	2
GR/PKAc	0.069	0.1	0.36	2	-0.52	1	3
NF kappa B1 p50/RelA	-0.12	0.2	-10000	0	-0.45	48	48
SMARCD1	-0.002	0.009	-10000	0	-10000	0	0
MDM2	0.056	0.093	0.25	21	-10000	0	21
GATA3	-0.051	0.23	0.33	1	-0.85	27	28
AKT1	0.014	0.045	-10000	0	-10000	0	0
CSF2	-0.054	0.11	-10000	0	-0.49	2	2
GSK3B	0.003	0.01	-10000	0	-10000	0	0
NR1I3	-0.24	0.44	0.6	6	-0.96	82	88
CSN2	0.067	0.18	0.41	11	-0.46	5	16
BRG1/BAF155/BAF170/BAF60A	-0.006	0.032	-10000	0	-10000	0	0
NFATC1	-0.009	0.089	-10000	0	-0.86	4	4
POU2F1	0.002	0.009	-10000	0	-10000	0	0
CDKN1A	-0.006	0.26	-10000	0	-1.6	10	10
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.004	0.011	-10000	0	-10000	0	0
SFN	0.18	0.17	0.32	214	-0.86	2	216
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.17	0.15	0.38	58	-0.42	3	61
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.33	0.48	0.57	6	-0.93	131	137
JUN	-0.023	0.24	0.43	12	-0.6	31	43
IL4	-0.061	0.14	-10000	0	-0.72	4	4
CDK5R1	0.004	0.032	0.31	4	-10000	0	4
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.28	0.28	-10000	0	-0.53	180	180
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.072	0.1	0.36	2	-0.42	1	3
cortisol/GR alpha (monomer)	0.21	0.34	0.61	103	-0.54	8	111
NCOA2	-0.11	0.29	-10000	0	-0.86	48	48
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.38	0.45	-10000	0	-0.84	179	179
AP-1/NFAT1-c-4	-0.25	0.41	0.5	7	-0.67	152	159
AFP	-0.017	0.34	-10000	0	-1.2	19	19
SUV420H1	0.001	0.016	0.32	1	-10000	0	1
IRF1	0.099	0.15	0.51	3	-10000	0	3
TP53	0.012	0.083	-10000	0	-0.48	10	10
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.15	0.37	0.51	10	-0.82	47	57
KRT14	-0.038	0.15	-10000	0	-10000	0	0
TBP	0.016	0.009	-10000	0	-10000	0	0
CREBBP	-0.007	0.05	-10000	0	-10000	0	0
HDAC1	0	0	-10000	0	-10000	0	0
HDAC2	0	0	-10000	0	-10000	0	0
AP-1	-0.25	0.41	0.5	8	-0.66	152	160
MAPK14	0.003	0.008	-10000	0	-10000	0	0
MAPK10	-0.048	0.22	0.3	7	-0.86	24	31
MAPK11	0.015	0.059	0.31	14	-10000	0	14
KRT5	-0.13	0.28	0.5	8	-0.62	39	47
interleukin-1 receptor activity	-0.001	0.001	-10000	0	-10000	0	0
NCOA1	-0.005	0.019	-10000	0	-10000	0	0
STAT1	0.016	0.023	0.32	2	-10000	0	2
CGA	-0.034	0.14	-10000	0	-0.5	2	2
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.031	0.13	0.36	4	-0.43	2	6
MAPK3	0.003	0.009	-10000	0	-10000	0	0
MAPK1	0.003	0.008	-10000	0	-10000	0	0
ICAM1	-0.15	0.24	-10000	0	-0.63	42	42
NFKB1	-0.067	0.11	-10000	0	-0.3	4	4
MAPK8	-0.074	0.24	0.38	9	-0.53	52	61
MAPK9	0.003	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.18	0.33	0.64	6	-0.78	48	54
BAX	0.027	0.069	-10000	0	-10000	0	0
POMC	-0.12	0.26	-10000	0	-0.79	21	21
EP300	-0.007	0.05	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.18	0.29	0.54	94	-0.54	5	99
proteasomal ubiquitin-dependent protein catabolic process	0.038	0.072	0.25	2	-10000	0	2
SGK1	0	0.28	-10000	0	-1.5	12	12
IL13	-0.15	0.29	0.54	1	-0.92	26	27
IL6	-0.29	0.54	0.42	1	-1.3	70	71
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.14	0.24	-10000	0	-0.8	23	23
IL2	-0.15	0.26	-10000	0	-0.68	21	21
CDK5	0.001	0.004	-10000	0	-10000	0	0
PRKACB	-0.002	0.045	-10000	0	-0.86	1	1
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.38	0.62	0.44	1	-1.4	97	98
CDK5R1/CDK5	0.004	0.023	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.093	0.13	-10000	0	-0.58	4	4
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.18	0.26	0.51	85	-0.48	2	87
SMARCA4	-0.002	0.009	-10000	0	-10000	0	0
chromatin remodeling	0.094	0.17	0.38	35	-0.42	7	42
NF kappa B1 p50/RelA/Cbp	-0.11	0.15	-10000	0	-0.54	9	9
JUN (dimer)	-0.022	0.24	0.42	13	-0.6	31	44
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.76	0.58	-10000	0	-1.2	243	243
NR3C1	0.11	0.18	0.42	47	-10000	0	47
NR4A1	-0.13	0.32	-10000	0	-0.83	61	61
TIF2/SUV420H1	-0.086	0.22	-10000	0	-0.67	48	48
MAPKKK cascade	-0.17	0.31	0.63	6	-0.73	48	54
cortisol/GR alpha (dimer)/Src-1	0.17	0.29	0.53	94	-0.51	10	104
PBX1	-0.074	0.25	0.32	1	-0.86	33	34
POU1F1	0.002	0.018	0.32	1	-10000	0	1
SELE	-0.41	0.64	-10000	0	-1.4	101	101
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.094	0.17	0.38	35	-0.42	7	42
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.18	0.26	0.51	85	-0.48	2	87
mol:cortisol	0.094	0.19	0.34	99	-0.27	14	113
MMP1	0.012	0.16	0.44	9	-10000	0	9

×

BCR signaling pathway

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
JUN	-0.077	0.16	0.36	1	-0.42	27	28
IKBKB	-0.02	0.079	-10000	0	-0.29	5	5
AKT1	-0.053	0.12	0.23	3	-0.27	38	41
IKBKG	-0.018	0.083	-10000	0	-0.27	11	11
CALM1	-0.05	0.12	-10000	0	-0.48	11	11
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
MAP3K1	-0.11	0.21	0.44	1	-0.56	32	33
MAP3K7	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.065	0.13	-10000	0	-0.52	11	11
DOK1	0	0	-10000	0	-10000	0	0
AP-1	-0.11	0.13	0.26	1	-0.27	88	89
LYN	0	0	-10000	0	-10000	0	0
BLNK	-0.021	0.13	-10000	0	-0.86	9	9
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.15	0.29	0.44	2	-0.67	85	87
CD22	-0.21	0.3	0.35	1	-0.62	108	109
CAMK2G	-0.041	0.12	-10000	0	-0.48	8	8
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.11	0.2	-10000	0	-0.86	5	5
GO:0007205	-0.06	0.13	-10000	0	-0.52	11	11
SYK	-0.007	0.077	-10000	0	-0.86	3	3
ELK1	-0.051	0.12	-10000	0	-0.49	11	11
NFATC1	-0.099	0.19	-10000	0	-0.43	59	59
B-cell antigen/BCR complex	-0.15	0.29	0.44	2	-0.67	85	87
PAG1/CSK	-0.002	0.051	-10000	0	-0.67	2	2
NFKBIB	0.001	0.028	-10000	0	-0.1	1	1
HRAS	-0.042	0.14	-10000	0	-0.5	11	11
NFKBIA	0.001	0.027	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.006	0.022	-10000	0	-10000	0	0
RasGAP/Csk	-0.35	0.36	0.35	2	-0.62	214	216
mol:GDP	-0.047	0.12	0.26	1	-0.49	11	12
PTEN	-0.005	0.063	-10000	0	-0.86	2	2
CD79B	0.003	0.028	0.32	3	-10000	0	3
NF-kappa-B/RelA/I kappa B alpha	0.006	0.022	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.12	0.22	0.34	1	-0.49	87	88
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
mol:IP3	-0.066	0.13	-10000	0	-0.53	11	11
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.27	0.28	-10000	0	-0.53	181	181
CHUK	-0.018	0.083	-10000	0	-0.28	10	10
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.062	0.12	-10000	0	-0.52	17	17
PTPN6	-0.2	0.28	0.32	1	-0.63	87	88
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0.001	0.041	-10000	0	-0.14	24	24
VAV2	-0.16	0.24	-10000	0	-0.59	63	63
ubiquitin-dependent protein catabolic process	0.004	0.027	-10000	0	-10000	0	0
BTK	-0.029	0.16	-10000	0	-1.2	7	7
CD19	-0.17	0.25	0.35	1	-0.57	76	77
MAP4K1	-0.014	0.12	0.32	3	-0.86	7	10
CD72	-0.007	0.093	0.32	3	-0.86	4	7
PAG1	-0.003	0.067	0.32	2	-0.86	2	4
MAPK14	-0.09	0.18	0.43	1	-0.53	21	22
SH3BP5	-0.005	0.063	-10000	0	-0.86	2	2
PIK3AP1	-0.054	0.14	-10000	0	-0.52	14	14
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.12	0.22	-10000	0	-0.5	86	86
RAF1	-0.033	0.13	-10000	0	-0.46	11	11
RasGAP/p62DOK/SHIP	-0.34	0.34	-10000	0	-0.6	214	214
CD79A	-0.19	0.37	0.32	9	-0.86	85	94
re-entry into mitotic cell cycle	-0.11	0.13	0.26	1	-0.27	82	83
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
MAPK3	-0.015	0.11	-10000	0	-0.41	8	8
MAPK1	-0.015	0.11	-10000	0	-0.41	8	8
CD72/SHP1	-0.18	0.27	0.49	1	-0.59	89	90
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.11	0.21	0.43	1	-0.53	38	39
actin cytoskeleton organization	-0.12	0.21	-10000	0	-0.49	63	63
NF-kappa-B/RelA	0.016	0.044	-10000	0	-10000	0	0
Calcineurin	-0.051	0.093	-10000	0	-0.44	8	8
PI3K	-0.16	0.21	-10000	0	-0.53	73	73
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.067	0.13	0.28	1	-0.54	11	12
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.16	0.27	0.66	1	-0.97	23	24
DAPP1	-0.18	0.29	0.5	1	-1.1	21	22
cytokine secretion	-0.092	0.17	-10000	0	-0.4	61	61
mol:DAG	-0.066	0.13	-10000	0	-0.53	11	11
PLCG2	-0.016	0.12	-10000	0	-0.86	7	7
MAP2K1	-0.024	0.12	-10000	0	-0.46	8	8
B-cell antigen/BCR complex/FcgammaRIIB	-0.4	0.4	0.39	2	-0.72	213	215
mol:PI-3-4-5-P3	-0.11	0.14	0.35	1	-0.36	70	71
ETS1	-0.032	0.11	-10000	0	-0.44	9	9
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.12	0.24	0.36	2	-0.52	92	94
B-cell antigen/BCR complex/LYN	-0.19	0.26	0.35	1	-0.56	101	102
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	-0.002	0.045	-10000	0	-0.86	1	1
RAC1	-0.13	0.23	-10000	0	-0.53	63	63
B-cell antigen/BCR complex/LYN/SYK	-0.22	0.31	0.39	2	-0.7	92	94
CARD11	-0.063	0.16	-10000	0	-0.61	18	18
FCGR2B	-0.42	0.43	0.32	2	-0.86	184	186
PPP3CA	0	0	-10000	0	-10000	0	0
BCL10	0	0	-10000	0	-10000	0	0
IKK complex	-0.002	0.038	0.12	2	-0.14	1	3
PTPRC	-0.066	0.23	0.32	1	-0.86	29	30
PDPK1	-0.067	0.1	0.21	3	-0.27	34	37
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.004	0.034	0.12	1	-0.15	14	15

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.11	0.15	0.32	134	-10000	0	134
mol:Halofuginone	0	0.003	-10000	0	-10000	0	0
ITGA1	-0.005	0.063	-10000	0	-0.86	2	2
CDKN1A	-0.083	0.14	-10000	0	-0.65	11	11
PRL-3/alpha Tubulin	0.036	0.081	-10000	0	-10000	0	0
mol:Ca2+	-0.041	0.1	-10000	0	-0.68	4	4
AGT	-0.009	0.089	-10000	0	-0.86	4	4
CCNA2	-0.12	0.26	-10000	0	-0.5	62	62
TUBA1B	0	0	-10000	0	-10000	0	0
EGR1	-0.22	0.33	-10000	0	-0.67	128	128
CDK2/Cyclin E1	-0.018	0.16	-10000	0	-0.68	7	7
MAPK3	0.041	0.052	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.041	0.052	-10000	0	-10000	0	0
PTP4A1	-0.16	0.27	-10000	0	-0.53	128	128
PTP4A3	0.052	0.12	0.32	61	-10000	0	61
PTP4A2	0	0	-10000	0	-10000	0	0
ITGB1	0.041	0.052	-10000	0	-10000	0	0
SRC	0.004	0.036	0.32	5	-10000	0	5
RAC1	-0.04	0.12	-10000	0	-0.32	1	1
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.34	0.34	-10000	0	-0.6	207	207
RABGGTA	0	0	-10000	0	-10000	0	0
BCAR1	-0.034	0.076	-10000	0	-10000	0	0
RHOC	-0.04	0.12	-10000	0	-0.32	1	1
RHOA	-0.04	0.12	-10000	0	-0.32	1	1
cell motility	-0.03	0.13	-10000	0	-0.35	1	1
PRL-1/alpha Tubulin	-0.17	0.24	-10000	0	-0.49	127	127
PRL-3/alpha1 Integrin	0.032	0.096	-10000	0	-0.67	2	2
ROCK1	-0.03	0.13	-10000	0	-0.36	1	1
RABGGTB	0	0	-10000	0	-10000	0	0
CDK2	0	0	-10000	0	-10000	0	0
mitosis	-0.16	0.27	-10000	0	-0.52	128	128
ATF5	-0.3	0.41	-10000	0	-0.86	128	128

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.41	0.43	-10000	0	-0.86	178	178
CDC42/GTP	-0.14	0.15	-10000	0	-0.63	3	3
PLCG1	-0.12	0.18	-10000	0	-0.34	82	82
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
G12/G13	0	0	-10000	0	-10000	0	0
cell migration	-0.14	0.15	-10000	0	-0.61	3	3
S1PR5	-0.011	0.1	0.32	1	-0.86	5	6
S1PR4	-0.001	0.048	0.32	1	-0.86	1	2
MAPK3	-0.12	0.18	-10000	0	-0.65	3	3
MAPK1	-0.12	0.18	-10000	0	-0.34	82	82
S1P/S1P5/Gi	-0.14	0.2	-10000	0	-0.33	181	181
GNAI1	-0.005	0.063	-10000	0	-0.86	2	2
CDC42/GDP	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.007	0.069	-10000	0	-0.59	5	5
RHOA	-0.001	0.026	-10000	0	-0.5	1	1
S1P/S1P4/Gi	-0.14	0.19	-10000	0	-0.36	82	82
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.15	0.17	0.32	176	-0.86	1	177
S1P/S1P4/G12/G13	-0.001	0.03	-10000	0	-0.54	1	1
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.21	0.23	-10000	0	-0.42	180	180
MAP3K8	-0.005	0.063	-10000	0	-0.86	2	2
FOS	-0.1	0.18	-10000	0	-0.55	27	27
PRKCA	0	0	-10000	0	-10000	0	0
PTPN7	-0.001	0.071	0.32	4	-0.86	2	6
HRAS	0.002	0.023	0.31	2	-10000	0	2
PRKCB	-0.075	0.24	-10000	0	-0.87	32	32
NRAS	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.001	0.013	-10000	0	-10000	0	0
MAPK3	-0.047	0.11	-10000	0	-0.75	3	3
MAP2K1	-0.064	0.18	-10000	0	-0.63	32	32
ELK1	-0.006	0.007	-10000	0	-10000	0	0
BRAF	-0.065	0.16	-10000	0	-0.59	32	32
mol:GTP	-0.003	0.003	-10000	0	-0.006	178	178
MAPK1	-0.047	0.11	-10000	0	-0.32	27	27
RAF1	-0.065	0.16	-10000	0	-0.59	32	32
KRAS	0	0	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0	0	-10000	0	-10000	0	0
VLDLR	-0.034	0.26	0.32	42	-0.86	30	72
LRPAP1	0	0	-10000	0	-10000	0	0
NUDC	0	0	-10000	0	-10000	0	0
RELN/LRP8	-0.18	0.29	-10000	0	-0.58	125	125
CaM/Ca2+	0	0	-10000	0	-10000	0	0
KATNA1	0	0	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.17	0.25	-10000	0	-0.52	125	125
IQGAP1/CaM	0	0	-10000	0	-10000	0	0
DAB1	-0.13	0.31	0.32	1	-0.86	56	57
IQGAP1	0	0	-10000	0	-10000	0	0
PLA2G7	0.007	0.088	0.32	14	-0.86	2	16
CALM1	0	0	-10000	0	-10000	0	0
DYNLT1	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.021	0.064	-10000	0	-10000	0	0
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0	0	-10000	0	-10000	0	0
CDK5R1	0.003	0.033	0.32	4	-10000	0	4
LIS1/Poliovirus Protein 3A	0	0	-10000	0	-10000	0	0
CDK5R2	0.009	0.051	0.32	10	-10000	0	10
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.31	0.38	-10000	0	-0.67	178	178
YWHAE	0	0	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.13	0.19	-10000	0	-10000	0	0
MAP1B	0.002	0.013	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
p35/CDK5	-0.15	0.22	-10000	0	-0.46	110	110
RELN	-0.29	0.41	0.32	3	-0.86	125	128
PAFAH/LIS1	0.005	0.061	-10000	0	-0.58	2	2
LIS1/CLIP170	0	0	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.11	0.15	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.19	0.27	-10000	0	-0.45	145	145
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.14	0.21	-10000	0	-0.44	81	81
LIS1/IQGAP1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PAFAH1B1	0.018	0	-10000	0	-10000	0	0
PAFAH1B3	0.03	0.11	0.32	38	-0.86	1	39
PAFAH1B2	-0.005	0.063	-10000	0	-0.86	2	2
MAP1B/LIS1/Dynein heavy chain	0	0	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.13	0.18	-10000	0	-10000	0	0
LRP8	0.03	0.092	0.32	35	-10000	0	35
NDEL1/Katanin 60	-0.13	0.19	-10000	0	-10000	0	0
P39/CDK5	-0.15	0.23	-10000	0	-0.47	111	111
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-10000	0	-10000	0	0
CDK5	-0.16	0.24	-10000	0	-0.49	125	125
PPP2R5D	0	0	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.27	0.34	-10000	0	-0.59	178	178
RELN/VLDLR	-0.19	0.33	0.38	7	-0.59	138	145
CDC42	0	0	-10000	0	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.006	0.094	-10000	0	-0.59	8	8
ARNO/beta Arrestin1-2	-0.059	0.15	-10000	0	-0.44	49	49
EGFR	-0.023	0.14	-10000	0	-0.86	10	10
EPHA2	-0.053	0.21	-10000	0	-0.86	23	23
USP6	-0.002	0.045	-10000	0	-0.86	1	1
IQSEC1	0	0	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.032	0.15	-10000	0	-0.66	10	10
ARRB2	0	0	-10000	0	-10000	0	0
mol:GTP	0.005	0.047	-10000	0	-0.22	9	9
ARRB1	-0.012	0.099	-10000	0	-0.86	5	5
FBXO8	0	0	-10000	0	-10000	0	0
TSHR	0	0	-10000	0	-10000	0	0
EGF	0.075	0.13	0.32	88	-10000	0	88
somatostatin receptor activity	0	0	-10000	0	-0.001	74	74
ARAP2	-0.028	0.15	-10000	0	-0.86	12	12
mol:GDP	-0.074	0.13	-10000	0	-0.33	53	53
mol:PI-3-4-5-P3	0	0	-10000	0	-0.001	48	48
ITGA2B	0.007	0.046	0.32	8	-10000	0	8
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.037	0.14	-10000	0	-0.53	26	26
ADAP1	-0.007	0.14	0.32	13	-0.86	8	21
KIF13B	0	0	-10000	0	-10000	0	0
HGF/MET	-0.36	0.34	-10000	0	-0.67	201	201
PXN	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.076	0.14	-10000	0	-0.31	72	72
EGFR/EGFR/EGF/EGF/ARFGEP100	0.031	0.13	-10000	0	-0.57	10	10
ADRB2	-0.1	0.28	-10000	0	-0.86	44	44
receptor agonist activity	0	0	-10000	0	0	73	73
actin filament binding	0	0	-10000	0	-0.001	78	78
SRC	0.004	0.036	0.32	5	-10000	0	5
ITGB3	-0.07	0.23	-10000	0	-0.86	30	30
GNAQ	-0.002	0.045	-10000	0	-0.86	1	1
EFA6/PI-4-5-P2	0	0	-10000	0	-0.001	58	58
ARF6/GDP	-0.023	0.12	-10000	0	-0.39	21	21
ARF6/GDP/GULP/ACAP1	-0.1	0.2	0.23	1	-0.52	57	58
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.039	0.15	-10000	0	-0.53	30	30
ACAP1	-0.021	0.14	0.32	3	-0.86	10	13
ACAP2	0	0	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0	0	-10000	0	-10000	0	0
EFNA1	-0.007	0.077	-10000	0	-0.86	3	3
HGF	-0.46	0.43	0.32	1	-0.86	201	202
CYTH3	0.009	0.011	-10000	0	-10000	0	0
CYTH2	0.005	0.002	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
fibronectin binding	0	0	-10000	0	0	81	81
endosomal lumen acidification	0	0	-10000	0	-0.001	67	67
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.035	0.28	0.32	51	-0.86	34	85
GNAQ/ARNO	-0.001	0.026	-10000	0	-0.5	1	1
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
PIP3-E	0	0	-10000	0	0	14	14
MET	-0.001	0.048	0.32	1	-0.86	1	2
GNA14	-0.15	0.32	-10000	0	-0.86	63	63
GNA15	-0.001	0.05	0.32	2	-0.86	1	3
GIT1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-0.001	61	61
GNA11	-0.028	0.15	-10000	0	-0.86	12	12
LHCGR	0	0	-10000	0	-10000	0	0
AGTR1	-0.077	0.24	-10000	0	-0.86	33	33
desensitization of G-protein coupled receptor protein signaling pathway	0	0	-10000	0	-10000	0	0
IPCEF1/ARNO	0.028	0.11	-10000	0	-0.46	10	10
alphaIIb/beta3 Integrin	-0.049	0.19	-10000	0	-0.67	30	30

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.002	0.023	0.32	2	-9999	2
Aurora C/Aurora B/INCENP	0.1	0.097	0.37	2	-9999	2
metaphase	0	0	-10000	0	-9999	0
mitosis	0	0	-10000	0	-9999	0
H3F3B	0	0	-10000	0	-9999	0
AURKB	0.17	0.16	0.32	196	-9999	196
AURKC	0.001	0.016	0.32	1	-9999	1

×

S1P3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.007	0.046	0.32	8	-10000	0	8
mol:S1P	0.001	0.001	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.1	0.16	-10000	0	-0.3	84	84
GNAO1	-0.41	0.43	-10000	0	-0.86	178	178
S1P/S1P3/G12/G13	-0.015	0.092	-10000	0	-0.54	11	11
AKT1	-0.041	0.08	0.2	3	-0.25	2	5
AKT3	-0.059	0.18	-10000	0	-1.5	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.007	0.046	0.32	8	-10000	0	8
GNAI2	0	0.002	-10000	0	-10000	0	0
GNAI3	0	0.001	-10000	0	-10000	0	0
GNAI1	-0.005	0.063	-10000	0	-0.86	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	-0.025	0.15	0.32	1	-0.86	11	12
S1PR2	-0.007	0.077	-10000	0	-0.86	3	3
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.15	0.23	-10000	0	-0.42	88	88
MAPK3	-0.12	0.22	-10000	0	-0.86	12	12
MAPK1	-0.12	0.22	-10000	0	-0.86	12	12
JAK2	-0.12	0.22	-10000	0	-0.39	88	88
CXCR4	-0.13	0.23	-10000	0	-0.4	90	90
FLT1	0	0.003	-10000	0	-10000	0	0
RhoA/GDP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0	0	-10000	0	-10000	0	0
SRC	-0.12	0.22	-10000	0	-0.85	12	12
S1P/S1P3/Gi	-0.15	0.23	-10000	0	-0.42	88	88
RAC1	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.15	0.19	-10000	0	-0.83	12	12
VEGFA	0	0.003	-10000	0	-10000	0	0
S1P/S1P2/Gi	-0.14	0.2	-10000	0	-0.37	86	86
VEGFR1 homodimer/VEGFA homodimer	0	0.007	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.086	0.18	-10000	0	-0.4	80	80
GNAQ	-0.002	0.045	-10000	0	-0.86	1	1
GNAZ	0.15	0.17	0.32	176	-0.86	1	177
G12/G13	0	0	-10000	0	-10000	0	0
GNA14	-0.15	0.32	-10000	0	-0.86	63	63
GNA15	-0.001	0.05	0.32	2	-0.86	1	3
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.028	0.15	-10000	0	-0.86	12	12
Rac1/GTP	-0.15	0.19	-10000	0	-0.83	12	12

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0	0	-10000	0	-10000	0	0
SPHK1	0.044	0.16	0.32	65	-0.86	5	70
GNAI2	0	0	-10000	0	-10000	0	0
mol:S1P	0.018	0.069	0.22	7	-0.38	5	12
GNAO1	-0.41	0.43	-10000	0	-0.86	178	178
mol:Sphinganine-1-P	0.033	0.098	-10000	0	-0.67	5	5
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	-0.008	0.06	-10000	0	-0.59	3	3
GNAI3	0	0	-10000	0	-10000	0	0
G12/G13	0	0	-10000	0	-10000	0	0
S1PR3	-0.025	0.15	0.32	1	-0.86	11	12
S1PR2	-0.007	0.077	-10000	0	-0.86	3	3
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.011	0.052	-10000	0	-0.33	5	5
S1PR5	-0.011	0.1	0.32	1	-0.86	5	6
S1PR4	-0.001	0.048	0.32	1	-0.86	1	2
GNAI1	-0.005	0.063	-10000	0	-0.86	2	2
S1P/S1P5/G12	-0.01	0.075	-10000	0	-0.58	5	5
S1P/S1P3/Gq	-0.065	0.16	-10000	0	-0.37	65	65
S1P/S1P4/Gi	-0.12	0.18	-10000	0	-0.36	74	74
GNAQ	-0.002	0.045	-10000	0	-0.86	1	1
GNAZ	0.15	0.17	0.32	176	-0.86	1	177
GNA14	-0.15	0.32	-10000	0	-0.86	63	63
GNA15	-0.001	0.05	0.32	2	-0.86	1	3
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.028	0.15	-10000	0	-0.86	12	12
ABCC1	0.007	0.046	0.32	8	-10000	0	8

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0	0	-10000	0	-10000	0	0
LAT2	-0.037	0.1	-10000	0	-0.49	6	6
AP1	-0.24	0.24	-10000	0	-0.46	179	179
mol:PIP3	-0.019	0.19	-10000	0	-0.45	51	51
IKBKB	-0.004	0.12	-10000	0	-0.34	23	23
AKT1	-0.053	0.14	-10000	0	-0.5	5	5
IKBKG	-0.004	0.12	-10000	0	-0.34	23	23
MS4A2	0.005	0.044	0.32	7	-10000	0	7
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
MAP3K1	0.003	0.14	-10000	0	-0.62	9	9
mol:Ca2+	-0.007	0.14	-10000	0	-0.34	51	51
LYN	0	0	-10000	0	-10000	0	0
CBLB	-0.035	0.099	-10000	0	-0.47	5	5
SHC1	0	0	-10000	0	-10000	0	0
RasGAP/p62DOK	-0.054	0.16	-10000	0	-0.55	36	36
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.059	0.16	-10000	0	-0.48	47	47
PTPN13	-0.13	0.25	-10000	0	-0.51	100	100
PTPN11	0	0.003	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.017	0.12	-10000	0	-0.35	6	6
SYK	-0.007	0.078	-10000	0	-0.87	3	3
GRB2	0	0	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.072	0.17	-10000	0	-0.47	52	52
LAT	-0.034	0.099	-10000	0	-0.47	5	5
PAK2	-0.006	0.15	-10000	0	-0.73	9	9
NFATC2	-0.16	0.3	-10000	0	-0.77	67	67
HRAS	-0.016	0.17	-10000	0	-0.61	17	17
GAB2	0	0	-10000	0	-10000	0	0
PLA2G1B	0.05	0.032	-10000	0	-10000	0	0
Fc epsilon R1	-0.07	0.2	-10000	0	-0.59	47	47
Antigen/IgE/Fc epsilon R1	-0.065	0.18	-10000	0	-0.55	47	47
mol:GDP	-0.025	0.18	-10000	0	-0.65	19	19
JUN	-0.014	0.11	-10000	0	-0.86	6	6
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
FOS	-0.42	0.43	-10000	0	-0.86	179	179
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.037	0.11	-10000	0	-0.44	7	7
CHUK	-0.004	0.12	-10000	0	-0.34	23	23
KLRG1	-0.039	0.11	-10000	0	-0.49	8	8
VAV1	-0.057	0.16	-10000	0	-0.62	18	18
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.035	0.099	-10000	0	-0.47	5	5
negative regulation of mast cell degranulation	-0.035	0.1	-10000	0	-0.5	6	6
BTK	-0.05	0.16	-10000	0	-0.83	10	10
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.24	0.3	-10000	0	-0.47	192	192
GAB2/PI3K/SHP2	-0.058	0.15	-10000	0	-0.44	46	46
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.039	0.11	-10000	0	-0.33	21	21
RAF1	0.04	0.037	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.31	0.33	-10000	0	-0.6	195	195
FCER1G	-0.006	0.078	0.31	1	-0.86	3	4
FCER1A	-0.1	0.28	0.32	1	-0.87	44	45
Antigen/IgE/Fc epsilon R1/Fyn	-0.06	0.17	-10000	0	-0.51	47	47
MAPK3	0.045	0.031	-10000	0	-10000	0	0
MAPK1	0.045	0.031	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.02	0.14	-10000	0	-0.57	20	20
DUSP1	-0.081	0.25	-10000	0	-0.86	35	35
NF-kappa-B/RelA	-0.027	0.059	-10000	0	-0.24	1	1
actin cytoskeleton reorganization	-0.007	0.11	-10000	0	-0.46	5	5
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.054	0.15	-10000	0	-0.61	19	19
FER	-0.035	0.099	-10000	0	-0.47	5	5
RELA	0	0	-10000	0	-10000	0	0
ITK	-0.037	0.13	-10000	0	-0.58	20	20
SOS1	0	0	-10000	0	-10000	0	0
PLCG1	-0.021	0.18	-10000	0	-0.64	18	18
cytokine secretion	-0.019	0.042	-10000	0	-10000	0	0
SPHK1	-0.027	0.13	-10000	0	-0.59	8	8
PTK2	-0.008	0.11	-10000	0	-0.48	5	5
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.075	0.18	-10000	0	-0.49	51	51
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.016	0.18	-10000	0	-0.44	51	51
MAP2K2	0.043	0.032	-10000	0	-10000	0	0
MAP2K1	0.043	0.032	-10000	0	-10000	0	0
MAP2K7	0	0	-10000	0	-10000	0	0
KLRG1/SHP2	-0.038	0.11	-10000	0	-0.52	6	6
MAP2K4	0.013	0.009	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.33	0.35	-10000	0	-0.63	195	195
mol:Choline	-0.058	0.16	-10000	0	-0.47	47	47
SHC/Grb2/SOS1	-0.031	0.091	-10000	0	-0.58	2	2
FYN	0	0	-10000	0	-10000	0	0
DOK1	0	0	-10000	0	-10000	0	0
PXN	-0.001	0.1	-10000	0	-0.46	4	4
HCLS1	-0.037	0.11	-10000	0	-0.52	7	7
PRKCB	-0.022	0.17	-10000	0	-0.38	58	58
FCGR2B	-0.42	0.43	0.32	2	-0.86	184	186
IGHE	0	0.005	-10000	0	-10000	0	0
KLRG1/SHIP	-0.036	0.1	-10000	0	-0.51	6	6
LCP2	-0.014	0.11	-10000	0	-0.86	6	6
PLA2G4A	-0.079	0.19	-10000	0	-0.57	37	37
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
mol:Phosphatidic acid	-0.058	0.16	-10000	0	-0.47	47	47
IKK complex	0.013	0.094	-10000	0	-0.26	17	17
WIPF1	0	0	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.002	0.046	-10000	0	-0.86	1	1
SVIL	-0.004	0.063	-10000	0	-0.85	2	2
ZNF318	0.002	0.024	-10000	0	-10000	0	0
JMJD2C	0.012	0.033	0.12	31	-10000	0	31
T-DHT/AR/Ubc9	-0.18	0.28	-10000	0	-0.62	101	101
CARM1	0	0	-10000	0	-10000	0	0
PRDX1	0	0.002	-10000	0	-10000	0	0
PELP1	0.001	0.004	-10000	0	-10000	0	0
CTNNB1	0	0.007	-10000	0	-10000	0	0
AKT1	0.001	0.006	-10000	0	-10000	0	0
PTK2B	0.001	0.005	-10000	0	-10000	0	0
MED1	0.001	0.006	-10000	0	-10000	0	0
MAK	0.002	0.024	-10000	0	-10000	0	0
response to oxidative stress	0	0.002	-10000	0	-10000	0	0
HIP1	-0.018	0.12	-10000	0	-0.86	8	8
GSN	0.001	0.02	0.34	1	-10000	0	1
NCOA2	-0.11	0.29	-10000	0	-0.86	48	48
NCOA6	0.001	0.009	-10000	0	-10000	0	0
DNA-PK	0.003	0.023	-10000	0	-10000	0	0
NCOA4	0	0	-10000	0	-10000	0	0
PIAS3	0	0.007	-10000	0	-10000	0	0
cell proliferation	-0.032	0.05	-10000	0	-10000	0	0
XRCC5	0.001	0.006	-10000	0	-10000	0	0
UBE3A	0	0.014	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.19	0.29	-10000	0	-0.63	107	107
FHL2	-0.19	0.4	-10000	0	-1.3	38	38
RANBP9	0.001	0.009	-10000	0	-10000	0	0
JMJD1A	-0.013	0.055	-10000	0	-0.13	66	66
CDK6	-0.058	0.22	-10000	0	-0.86	25	25
TGFB1I1	0	0.009	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.2	0.3	-10000	0	-0.64	112	112
XRCC6	0.001	0.006	-10000	0	-10000	0	0
T-DHT/AR	-0.18	0.31	-10000	0	-0.63	109	109
CTDSP1	0.001	0.003	-10000	0	-10000	0	0
CTDSP2	0.002	0.015	-10000	0	-10000	0	0
BRCA1	0.001	0.019	0.32	1	-10000	0	1
TCF4	0.001	0.011	-10000	0	-10000	0	0
CDKN2A	0.22	0.15	0.32	254	-10000	0	254
SRF	0.003	0.037	-10000	0	-10000	0	0
NKX3-1	-0.24	0.45	-10000	0	-1.2	59	59
KLK3	-0.017	0.21	-10000	0	-1.6	6	6
TMF1	0	0.002	-10000	0	-10000	0	0
HNRNPA1	0.001	0.008	-10000	0	-10000	0	0
AOF2	0	0.01	-10000	0	-0.072	6	6
APPL1	0.017	0.014	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.18	0.28	-10000	0	-0.62	101	101
AR	-0.25	0.39	-10000	0	-0.88	101	101
UBA3	0.001	0.003	-10000	0	-10000	0	0
PATZ1	0.001	0.008	-10000	0	-10000	0	0
PAWR	0	0.002	-10000	0	-10000	0	0
PRKDC	0.001	0.006	-10000	0	-10000	0	0
PA2G4	0.001	0.011	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.16	0.26	-10000	0	-0.58	101	101
RPS6KA3	-0.006	0.078	-10000	0	-0.86	3	3
T-DHT/AR/ARA70	-0.18	0.28	-10000	0	-0.62	101	101
LATS2	0.001	0.009	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.16	0.26	-10000	0	-0.58	101	101
Cyclin D3/CDK11 p58	0	0	-10000	0	-10000	0	0
VAV3	0.003	0.06	0.32	6	-0.86	1	7
KLK2	-0.048	0.13	-10000	0	-10000	0	0
CASP8	0	0.003	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.23	0.34	-10000	0	-0.69	120	120
TMPRSS2	-0.15	0.31	-10000	0	-1.4	18	18
CCND1	-0.032	0.16	0.32	1	-0.86	14	15
PIAS1	0	0.014	-10000	0	-10000	0	0
mol:T-DHT	-0.009	0.034	-10000	0	-0.084	52	52
CDC2L1	0	0.001	-10000	0	-10000	0	0
PIAS4	0	0.023	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.22	0.31	-10000	0	-0.65	118	118
CMTM2	0.002	0.023	0.32	2	-10000	0	2
SNURF	-0.012	0.13	0.32	8	-0.86	8	16
ZMIZ1	-0.006	0.031	0.3	1	-10000	0	1
CCND3	0	0	-10000	0	-10000	0	0
TGIF1	0.001	0.008	-10000	0	-10000	0	0
FKBP4	0.001	0.009	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.016	0.1	-10000	0	-0.67	9	9
alphaV beta3 Integrin	-0.077	0.22	-10000	0	-0.65	46	46
PTK2	-0.015	0.2	-10000	0	-0.59	30	30
IGF1R	-0.015	0.13	0.32	4	-0.86	8	12
PI4KB	0	0	-10000	0	-10000	0	0
MFGE8	0.004	0.036	0.32	5	-10000	0	5
SRC	0.004	0.036	0.32	5	-10000	0	5
CDKN1B	-0.048	0.14	-10000	0	-0.66	13	13
VEGFA	0	0	-10000	0	-10000	0	0
ILK	-0.048	0.14	-10000	0	-0.66	13	13
ROCK1	0	0	-10000	0	-10000	0	0
AKT1	-0.044	0.13	-10000	0	-0.62	13	13
PTK2B	-0.052	0.17	-10000	0	-0.56	34	34
alphaV/beta3 Integrin/JAM-A	-0.085	0.21	-10000	0	-0.56	58	58
CBL	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.11	0.24	-10000	0	-0.62	64	64
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.22	0.27	-10000	0	-0.54	150	150
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.039	0.11	-10000	0	-0.57	5	5
alphaV/beta3 Integrin/Syndecan-1	-0.053	0.17	-10000	0	-0.58	34	34
PI4KA	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.25	0.31	-10000	0	-0.55	168	168
PI4 Kinase	0	0	-10000	0	-10000	0	0
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
alphaV/beta3 Integrin/Osteopontin	-0.019	0.26	0.39	1	-0.6	51	52
RPS6KB1	-0.23	0.28	-10000	0	-0.88	33	33
TLN1	0	0	-10000	0	-10000	0	0
MAPK3	-0.16	0.28	-10000	0	-0.86	46	46
GPR124	-0.007	0.077	-10000	0	-0.86	3	3
MAPK1	-0.16	0.28	-10000	0	-0.86	46	46
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
alphaV/beta3 Integrin/Tumstatin	-0.063	0.22	-10000	0	-0.66	42	42
cell adhesion	-0.091	0.21	-10000	0	-0.53	61	61
ANGPTL3	-0.09	0.26	-10000	0	-0.86	39	39
VEGFR2 homodimer/VEGFA homodimer/Src	-0.011	0.093	-10000	0	-0.58	9	9
IGF-1R heterotetramer	-0.015	0.13	0.32	4	-0.86	8	12
Rac1/GDP	0	0	-10000	0	-10000	0	0
TGFBR2	0	0	-10000	0	-10000	0	0
ITGB3	-0.07	0.23	-10000	0	-0.86	30	30
IGF1	-0.34	0.42	-10000	0	-0.86	145	145
RAC1	0	0	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	-0.051	0.16	-10000	0	-0.58	33	33
apoptosis	0.001	0.016	0.32	1	-10000	0	1
CD47	-0.002	0.045	-10000	0	-0.86	1	1
alphaV/beta3 Integrin/CD47	-0.048	0.16	-10000	0	-0.58	31	31
VCL	0.001	0.016	0.32	1	-10000	0	1
alphaV/beta3 Integrin/Del1	-0.003	0.19	0.39	1	-0.58	30	31
CSF1	-0.008	0.092	0.32	2	-0.86	4	6
PIK3C2A	-0.048	0.14	-10000	0	-0.66	13	13
PI4 Kinase/Pyk2	-0.081	0.2	-10000	0	-0.94	9	9
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.055	0.18	-10000	0	-0.6	34	34
FAK1/Vinculin	-0.002	0.16	-10000	0	-0.45	30	30
alphaV beta3/Integrin/ppsTEM5	-0.051	0.17	-10000	0	-0.58	33	33
RHOA	0	0	-10000	0	-10000	0	0
VTN	-0.03	0.16	-10000	0	-0.86	13	13
BCAR1	0	0	-10000	0	-10000	0	0
FGF2	-0.047	0.21	0.32	5	-0.86	22	27
F11R	-0.021	0.16	-10000	0	-0.67	22	22
alphaV/beta3 Integrin/Lactadherin	-0.044	0.16	-10000	0	-0.58	30	30
alphaV/beta3 Integrin/TGFBR2	-0.046	0.16	-10000	0	-0.58	30	30
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.004	0.058	-10000	0	-0.53	4	4
HSP90AA1	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.043	0.15	-10000	0	-0.54	30	30
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.002	0.045	-10000	0	-0.86	1	1
alphaV/beta3 Integrin/Pyk2	-0.052	0.17	-10000	0	-0.57	34	34
SDC1	-0.009	0.089	-10000	0	-0.86	4	4
VAV3	-0.003	0.064	-10000	0	-0.5	5	5
PTPN11	0	0	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
FAK1/Paxillin	-0.002	0.16	-10000	0	-0.45	30	30
cell migration	0.009	0.15	-10000	0	-0.49	11	11
ITGAV	0.001	0.016	0.32	1	-10000	0	1
PI3K	-0.081	0.21	-10000	0	-0.93	9	9
SPP1	0.053	0.28	0.32	127	-0.86	24	151
KDR	-0.021	0.13	-10000	0	-0.86	9	9
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.001	0.016	0.32	1	-10000	0	1
COL4A3	-0.026	0.2	0.32	19	-0.86	18	37
angiogenesis	-0.13	0.3	-10000	0	-0.79	53	53
Rac1/GTP	-0.002	0.058	-10000	0	-0.45	5	5
EDIL3	0.069	0.13	0.32	81	-10000	0	81
cell proliferation	-0.046	0.16	-10000	0	-0.58	30	30

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.021	0.083	-10000	0	-0.35	22	22
epithelial cell differentiation	-0.03	0.12	-10000	0	-0.5	22	22
CYFIP2	-0.051	0.2	-10000	0	-0.86	22	22
ENAH	0.016	0.12	-10000	0	-0.51	7	7
EGFR	-0.023	0.14	-10000	0	-0.86	10	10
EPHA2	-0.053	0.21	-10000	0	-0.86	23	23
MYO6	-0.031	0.13	-10000	0	-0.52	22	22
CTNNB1	0	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.034	0.14	-10000	0	-0.58	22	22
AQP5	-0.016	0.1	-10000	0	-10000	0	0
CTNND1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.028	0.11	-10000	0	-0.47	22	22
regulation of calcium-dependent cell-cell adhesion	-0.017	0.13	-10000	0	-0.46	24	24
EGF	0.075	0.13	0.32	88	-10000	0	88
NCKAP1	0	0	-10000	0	-10000	0	0
AQP3	-0.074	0.2	-10000	0	-0.68	30	30
cortical microtubule organization	-0.03	0.12	-10000	0	-0.5	22	22
GO:0000145	0.003	0.11	-10000	0	-0.44	22	22
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.03	0.12	-10000	0	-0.5	22	22
MLLT4	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.051	0.15	-10000	0	-0.78	7	7
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.037	0.14	-10000	0	-0.53	26	26
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.027	0.1	-10000	0	-0.44	22	22
PVRL2	0	0	-10000	0	-10000	0	0
ZYX	-0.028	0.11	-10000	0	-0.48	22	22
ARF6/GTP	-0.034	0.12	-10000	0	-0.49	26	26
CDH1	-0.051	0.2	-10000	0	-0.86	22	22
EGFR/EGFR/EGF/EGF	-0.013	0.16	-10000	0	-0.52	28	28
RhoA/GDP	-0.028	0.11	-10000	0	-0.47	22	22
actin cytoskeleton organization	-0.029	0.12	-10000	0	-0.48	22	22
IGF-1R heterotetramer	-0.015	0.13	0.32	4	-0.86	8	12
GIT1	0	0	-10000	0	-10000	0	0
IGF1R	-0.015	0.13	0.32	4	-0.86	8	12
IGF1	-0.34	0.42	-10000	0	-0.86	145	145
DIAPH1	-0.05	0.18	-10000	0	-0.74	23	23
Wnt receptor signaling pathway	0.03	0.12	0.5	22	-10000	0	22
RHOA	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.051	0.15	-10000	0	-0.78	7	7
CTNNA1	0	0	-10000	0	-10000	0	0
VCL	-0.03	0.12	-10000	0	-0.5	22	22
EFNA1	-0.007	0.077	-10000	0	-0.86	3	3
LPP	-0.028	0.11	-10000	0	-0.45	23	23
Ephrin A1/EPHA2	-0.059	0.18	-10000	0	-0.54	41	41
SEC6/SEC8	-0.025	0.099	-10000	0	-10000	0	0
MGAT3	-0.018	0.13	-10000	0	-0.47	24	24
HGF/MET	-0.28	0.27	-10000	0	-0.5	206	206
HGF	-0.46	0.43	0.32	1	-0.86	201	202
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.021	0.084	-10000	0	-0.36	22	22
actin cable formation	0.026	0.11	-10000	0	-0.4	12	12
KIAA1543	-0.035	0.13	-10000	0	-0.5	26	26
KIFC3	-0.028	0.11	-10000	0	-0.48	22	22
NCK1	0	0	-10000	0	-10000	0	0
EXOC3	0	0	-10000	0	-10000	0	0
ACTN1	-0.028	0.11	-10000	0	-0.48	22	22
NCK1/GIT1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.03	0.12	-10000	0	-0.5	22	22
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.028	0.11	-10000	0	-0.48	22	22
PIP5K1C	-0.028	0.11	-10000	0	-0.48	22	22
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0	0	-10000	0	-10000	0	0
ROCK1	-0.044	0.13	-10000	0	-0.64	7	7
adherens junction assembly	0.012	0.14	-10000	0	-0.47	26	26
IGF-1R heterotetramer/IGF1	-0.22	0.25	-10000	0	-0.48	167	167
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-10000	0	-10000	0	0
MET	-0.001	0.048	0.32	1	-0.86	1	2
PLEKHA7	-0.032	0.12	-10000	0	-0.48	25	25
mol:GTP	-0.037	0.13	-10000	0	-0.53	26	26
establishment of epithelial cell apical/basal polarity	-0.024	0.094	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	-0.021	0.083	-10000	0	-0.35	22	22
regulation of cell-cell adhesion	-0.029	0.12	-10000	0	-0.48	22	22
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.021	0.084	-10000	0	-0.36	22	22

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.061	0.17	-10000	0	-0.51	44	44
TRAF2/ASK1	-0.068	0.19	-10000	0	-0.59	43	43
ATM	0	0	-10000	0	-10000	0	0
MAP2K3	-0.054	0.099	-10000	0	-0.3	24	24
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.083	0.18	-10000	0	-0.55	45	45
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.11	0.29	-10000	0	-0.86	48	48
TXN	0	0	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
GADD45A	-0.014	0.11	-10000	0	-0.86	6	6
GADD45B	-0.13	0.31	-10000	0	-0.86	56	56
MAP3K1	0	0	-10000	0	-10000	0	0
MAP3K6	0.001	0.016	0.32	1	-10000	0	1
MAP3K7	0	0	-10000	0	-10000	0	0
MAP3K4	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.077	0.21	-10000	0	-0.67	43	43
TAK1/TAB family	-0.003	0.017	-10000	0	-0.22	1	1
RAC1/OSM/MEKK3	0	0	-10000	0	-10000	0	0
TRAF2	0	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.048	0.066	-10000	0	-10000	0	0
TRAF6	-0.001	0.025	-10000	0	-0.47	1	1
RAC1	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.42	0.43	-10000	0	-0.86	181	181
CCM2	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.29	0.29	-10000	0	-0.59	181	181
MAPK11	0.012	0.06	0.32	14	-10000	0	14
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.32	0.32	-10000	0	-0.6	200	200
OSM/MEKK3	0	0	-10000	0	-10000	0	0
TAOK1	-0.003	0.034	-10000	0	-0.47	2	2
TAOK2	0	0	-10000	0	-10000	0	0
TAOK3	0	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	-0.1	0.28	-10000	0	-0.86	43	43
MAP3K10	0	0	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
TRX/ASK1	-0.067	0.18	-10000	0	-0.58	43	43
GADD45/MTK1/MTK1	-0.15	0.27	-10000	0	-0.59	93	93

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.13	0.26	0.36	1	-0.52	103	104
SMAD6-7/SMURF1	-0.023	0.11	-10000	0	-0.58	15	15
NOG	0.004	0.036	0.32	5	-10000	0	5
SMAD9	-0.051	0.15	-10000	0	-0.65	18	18
SMAD4	-0.002	0.045	-10000	0	-0.86	1	1
SMAD5	-0.06	0.17	-10000	0	-0.38	71	71
BMP7/USAG1	0.065	0.12	0.44	13	-10000	0	13
SMAD5/SKI	-0.086	0.14	-10000	0	-0.36	70	70
SMAD1	0.013	0.06	-10000	0	-0.59	2	2
BMP2	-0.008	0.092	0.32	2	-0.86	4	6
SMAD1/SMAD1/SMAD4	-0.023	0.088	-10000	0	-0.57	3	3
BMPR1A	0	0	-10000	0	-10000	0	0
BMPR1B	-0.18	0.35	0.32	4	-0.86	77	81
BMPR1A-1B/BAMBI	-0.16	0.29	-10000	0	-0.64	92	92
AHSG	-0.13	0.31	-10000	0	-0.86	58	58
CER1	0.004	0.036	0.32	5	-10000	0	5
BMP2-4/CER1	0.013	0.085	-10000	0	-0.58	4	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.071	0.15	-10000	0	-0.59	8	8
BMP2-4 (homodimer)	0.011	0.092	-10000	0	-0.66	4	4
RGMB	-0.004	0.065	0.32	1	-0.86	2	3
BMP6/BMPR2/BMPR1A-1B	-0.11	0.23	-10000	0	-0.54	81	81
RGMA	0.028	0.09	0.32	33	-10000	0	33
SMURF1	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.077	0.16	-10000	0	-0.56	10	10
BMP2-4/USAG1	0.046	0.12	0.39	6	-0.57	4	10
SMAD6/SMURF1/SMAD5	-0.086	0.14	-10000	0	-0.36	70	70
SOSTDC1	0.055	0.12	0.32	65	-10000	0	65
BMP7/BMPR2/BMPR1A-1B	-0.086	0.24	0.38	1	-0.53	77	78
SKI	0	0	-10000	0	-10000	0	0
BMP6 (homodimer)	-0.009	0.1	0.32	3	-0.86	5	8
HFE2	-0.095	0.27	-10000	0	-0.86	41	41
ZFYVE16	0	0	-10000	0	-10000	0	0
MAP3K7	0	0	-10000	0	-10000	0	0
BMP2-4/CHRD	0	0.12	-10000	0	-0.57	11	11
SMAD5/SMAD5/SMAD4	-0.087	0.14	-10000	0	-0.36	71	71
MAPK1	0	0	-10000	0	-10000	0	0
TAK1/TAB family	-0.074	0.12	-10000	0	-0.54	8	8
BMP7 (homodimer)	0.039	0.1	0.32	46	-10000	0	46
NUP214	0	0	-10000	0	-10000	0	0
BMP6/FETUA	-0.11	0.25	-10000	0	-0.67	63	63
SMAD1/SKI	-0.014	0.045	-10000	0	-0.55	2	2
SMAD6	-0.03	0.16	-10000	0	-0.86	13	13
CTDSP2	0	0	-10000	0	-10000	0	0
BMP2-4/FETUA	-0.082	0.23	-10000	0	-0.58	62	62
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.06	0.28	0.32	30	-0.86	37	67
BMPR2 (homodimer)	0	0	-10000	0	-10000	0	0
GADD34/PP1CA	0.001	0.01	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	-0.14	0.27	-10000	0	-0.67	77	77
CHRDL1	-0.14	0.33	0.32	10	-0.86	64	74
ENDOFIN/SMAD1	-0.014	0.045	-10000	0	-0.55	2	2
SMAD6-7/SMURF1/SMAD1	-0.028	0.098	-10000	0	-0.47	15	15
SMAD6/SMURF1	0	0	-10000	0	-10000	0	0
BAMBI	-0.057	0.22	0.32	1	-0.86	25	26
SMURF2	0	0	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.087	0.24	-10000	0	-0.58	67	67
BMP2-4/GREM1	-0.033	0.2	0.39	1	-0.58	41	42
SMAD7	-0.005	0.063	-10000	0	-0.86	2	2
SMAD8A/SMAD8A/SMAD4	-0.053	0.14	-10000	0	-0.6	19	19
SMAD1/SMAD6	-0.014	0.045	-10000	0	-0.55	2	2
TAK1/SMAD6	0	0	-10000	0	-10000	0	0
BMP7	0.039	0.1	0.32	46	-10000	0	46
BMP6	-0.009	0.1	0.32	3	-0.86	5	8
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.061	0.13	-10000	0	-0.5	9	9
PPM1A	0	0	-10000	0	-10000	0	0
SMAD1/SMURF2	-0.014	0.045	-10000	0	-0.55	2	2
SMAD7/SMURF1	-0.004	0.049	-10000	0	-0.67	2	2
CTDSPL	0	0	-10000	0	-10000	0	0
PPP1CA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
CTDSP1	0	0	-10000	0	-10000	0	0
PPP1R15A	0.001	0.016	0.32	1	-10000	0	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.095	0.18	-10000	0	-0.56	25	25
CHRD	-0.015	0.12	0.32	1	-0.86	7	8
BMPR2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.078	0.16	-10000	0	-0.65	8	8
BMP4	0.026	0.086	0.32	30	-10000	0	30
FST	-0.071	0.24	0.32	1	-0.86	31	32
BMP2-4/NOG	0.013	0.085	-10000	0	-0.58	4	4
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.081	0.22	0.36	1	-0.5	77	78

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.007	0.046	0.32	8	-10000	0	8
alphaV beta3 Integrin	-0.053	0.18	-10000	0	-0.67	30	30
PTK2	-0.094	0.24	-10000	0	-0.66	49	49
positive regulation of JNK cascade	-0.051	0.12	-10000	0	-0.36	51	51
CDC42/GDP	-0.067	0.17	-10000	0	-0.5	49	49
Rac1/GDP	-0.028	0.18	-10000	0	-0.49	49	49
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CTNNB1	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.064	0.16	-10000	0	-0.45	51	51
nectin-3/I-afadin	-0.088	0.23	-10000	0	-0.67	49	49
RAPGEF1	-0.038	0.21	-10000	0	-0.56	49	49
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.055	0.24	-10000	0	-0.66	49	49
PDGFB-D/PDGFRB	0.007	0.046	0.32	8	-10000	0	8
TLN1	-0.035	0.099	-10000	0	-0.73	2	2
Rap1/GTP	-0.052	0.13	-10000	0	-0.38	49	49
IQGAP1	0	0	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0	0	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.088	0.23	-10000	0	-0.67	49	49
PVR	0	0	-10000	0	-10000	0	0
Necl-5(dimer)	0	0	-10000	0	-10000	0	0
mol:GDP	-0.047	0.23	-10000	0	-0.63	49	49
MLLT4	0	0	-10000	0	-10000	0	0
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
PI3K	-0.066	0.18	-10000	0	-0.52	50	50
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.001	0.011	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	-0.052	0.13	-10000	0	-0.38	49	49
PVRL1	0.001	0.016	0.32	1	-10000	0	1
PVRL3	-0.11	0.29	-10000	0	-0.86	49	49
PVRL2	0	0	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
CDH1	-0.051	0.2	-10000	0	-0.86	22	22
CLDN1	-0.012	0.099	-10000	0	-0.86	5	5
JAM-A/CLDN1	-0.077	0.19	-10000	0	-0.54	53	53
SRC	-0.1	0.26	-10000	0	-0.76	49	49
ITGB3	-0.07	0.23	-10000	0	-0.86	30	30
nectin-1(dimer)/I-afadin/I-afadin	0.001	0.011	-10000	0	-10000	0	0
FARP2	-0.053	0.23	-10000	0	-0.62	51	51
RAC1	0	0	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.077	0.2	-10000	0	-0.58	49	49
nectin-1/I-afadin	0.001	0.011	-10000	0	-10000	0	0
nectin-2/I-afadin	0	0	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.076	0.2	-10000	0	-0.58	49	49
CDC42/GTP/IQGAP1/filamentous actin	0	0	-10000	0	-10000	0	0
F11R	0	0	-10000	0	-10000	0	0
positive regulation of filopodium formation	-0.051	0.12	-10000	0	-0.36	51	51
alphaV/beta3 Integrin/Talin	-0.069	0.18	-10000	0	-0.63	30	30
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-10000	0	-10000	0	0
PIP5K1C	-0.039	0.11	-10000	0	-0.29	50	50
VAV2	-0.05	0.23	-10000	0	-0.62	49	49
RAP1/GDP	-0.063	0.16	-10000	0	-0.46	49	49
ITGAV	0.001	0.016	0.32	1	-10000	0	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.077	0.2	-10000	0	-0.58	49	49
nectin-3(dimer)/I-afadin/I-afadin	-0.088	0.23	-10000	0	-0.67	49	49
Rac1/GTP	-0.064	0.16	-10000	0	-0.46	49	49
PTPRM	-0.044	0.12	-10000	0	-0.33	50	50
E-cadherin/beta catenin/alpha catenin	-0.028	0.11	-10000	0	-0.48	22	22
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.055	0.16	-10000	0	-0.62	25	25
FYN	-0.026	0.26	0.36	3	-0.86	28	31
LAT/GRAP2/SLP76	-0.044	0.2	0.64	1	-0.63	31	32
IKBKB	0	0	-10000	0	-10000	0	0
AKT1	0.009	0.16	0.35	4	-0.48	30	34
B2M	0	0.002	-10000	0	-10000	0	0
IKBKG	-0.014	0.04	-10000	0	-0.18	9	9
MAP3K8	-0.005	0.063	-10000	0	-0.86	2	2
mol:Ca2+	-0.041	0.06	-10000	0	-0.13	112	112
integrin-mediated signaling pathway	-0.006	0.06	-10000	0	-0.58	4	4
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.01	0.24	0.39	4	-0.74	30	34
TRPV6	-0.26	0.4	-10000	0	-0.87	113	113
CD28	-0.001	0.048	0.32	1	-0.86	1	2
SHC1	-0.017	0.24	0.38	3	-0.81	27	30
receptor internalization	-0.022	0.24	0.37	4	-0.7	33	37
PRF1	-0.022	0.26	-10000	0	-1	19	19
KRAS	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
COT/AKT1	0.014	0.13	0.32	4	-0.4	27	31
LAT	-0.016	0.24	0.38	4	-0.75	31	35
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	-0.014	0.17	0.32	16	-0.87	12	28
CD3E	-0.034	0.17	0.33	1	-0.87	15	16
CD3G	-0.022	0.16	0.32	7	-0.86	12	19
RASGRP2	-0.002	0.029	0.13	5	-0.19	3	8
RASGRP1	0.016	0.17	0.41	4	-0.49	30	34
HLA-A	0.001	0.003	-10000	0	-10000	0	0
RASSF5	-0.009	0.089	-10000	0	-0.86	4	4
RAP1A/GTP/RAPL	-0.006	0.061	-10000	0	-0.59	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.029	0.057	0.22	6	-0.12	20	26
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.026	0.072	-10000	0	-0.27	25	25
PRKCA	-0.013	0.093	0.28	2	-0.3	23	25
GRAP2	-0.016	0.14	0.32	6	-0.86	9	15
mol:IP3	0.027	0.2	0.29	89	-0.46	29	118
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.028	0.24	0.31	4	-0.8	25	29
ORAI1	0.12	0.18	0.39	113	-10000	0	113
CSK	-0.02	0.25	0.38	3	-0.83	27	30
B7 family/CD28	-0.087	0.24	0.5	1	-0.71	40	41
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.036	0.29	0.38	4	-0.91	31	35
PTPN6	-0.024	0.25	0.46	1	-0.85	27	28
VAV1	-0.029	0.28	0.38	3	-0.86	31	34
Monovalent TCR/CD3	-0.037	0.18	0.37	1	-0.56	29	30
CBL	0	0	-10000	0	-10000	0	0
LCK	-0.034	0.29	0.48	1	-0.87	32	33
PAG1	-0.02	0.25	0.38	3	-0.78	31	34
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.078	0.28	0.36	4	-0.91	31	35
CD80	-0.032	0.16	0.32	1	-0.86	14	15
CD86	-0.023	0.14	-10000	0	-0.86	10	10
PDK1/CARD11/BCL10/MALT1	-0.03	0.089	-10000	0	-0.33	24	24
HRAS	0.002	0.023	0.32	2	-10000	0	2
GO:0035030	-0.068	0.19	0.42	1	-0.57	40	41
CD8A	-0.05	0.21	0.32	4	-0.87	23	27
CD8B	-0.036	0.21	0.32	12	-0.87	20	32
PTPRC	-0.067	0.23	0.32	1	-0.86	29	30
PDK1/PKC theta	0.007	0.2	0.39	4	-0.61	30	34
CSK/PAG1	-0.015	0.24	0.37	3	-0.81	27	30
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	0	0	-10000	0	-10000	0	0
GRAP2/SLP76	-0.057	0.23	0.64	1	-0.75	31	32
STIM1	0.063	0.094	-10000	0	-10000	0	0
RAS family/GTP	0.032	0.072	0.29	4	-0.19	16	20
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.028	0.27	0.37	4	-0.77	33	37
mol:DAG	-0.015	0.14	0.18	2	-0.42	29	31
RAP1A/GDP	0.013	0.026	0.13	4	-10000	0	4
PLCG1	0	0	-10000	0	-10000	0	0
CD247	-0.004	0.066	0.32	1	-0.87	2	3
cytotoxic T cell degranulation	-0.018	0.24	-10000	0	-0.94	19	19
RAP1A/GTP	-0.002	0.008	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.001	0.19	0.38	4	-0.58	30	34
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.015	0.24	0.31	82	-0.63	29	111
NRAS	0	0	-10000	0	-10000	0	0
ZAP70	-0.005	0.097	0.32	5	-0.86	4	9
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.045	0.2	0.62	1	-0.64	30	31
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	-0.002	0.045	-10000	0	-0.86	1	1
CD8 heterodimer	-0.065	0.26	0.45	4	-0.82	34	38
CARD11	-0.019	0.14	0.32	5	-0.86	10	15
PRKCB	-0.034	0.14	0.28	2	-0.42	38	40
PRKCE	-0.014	0.095	0.25	3	-0.28	30	33
PRKCQ	-0.006	0.23	0.4	4	-0.71	31	35
LCP2	-0.014	0.11	-10000	0	-0.86	6	6
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.014	0.14	0.34	4	-0.4	30	34
IKK complex	0.032	0.058	0.21	5	-0.13	20	25
RAS family/GDP	-0.003	0.007	-10000	0	-10000	0	0
MAP3K14	0.022	0.1	0.28	4	-0.31	22	26
PDPK1	0.013	0.16	0.35	4	-0.45	29	33
TCR/CD3/MHC I/CD8/Fyn	-0.046	0.32	0.39	4	-1	31	35

×

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)	-0.011	0.094	-10000	0	-0.58	8	8
HDAC1	0.007	0.017	-10000	0	-10000	0	0
AES	0.003	0.008	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.24	0.39	-10000	0	-0.86	104	104
LRP6/FZD1	-0.014	0.098	-10000	0	-0.67	8	8
TLE1	-0.001	0.045	-10000	0	-0.86	1	1
AP1	-0.19	0.24	-10000	0	-0.39	188	188
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	-0.002	0.045	-10000	0	-0.86	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.035	0.1	-10000	0	-0.68	2	2
NICD/RBPSUH	-0.002	0.039	-10000	0	-0.75	1	1
WIF1	0.031	0.095	0.32	37	-10000	0	37
NOTCH1	-0.002	0.041	-10000	0	-0.8	1	1
PSENEN	0	0	-10000	0	-10000	0	0
KREMEN2	0.034	0.098	0.32	40	-10000	0	40
DKK1	0.11	0.15	0.32	126	-10000	0	126
beta catenin/beta TrCP1	-0.007	0.046	-10000	0	-10000	0	0
APH1B	0	0	-10000	0	-10000	0	0
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	0.004	0.029	0.35	1	-10000	0	1
CtBP/CBP/TCF1/TLE1/AES	0.018	0.078	0.28	8	-0.48	3	11
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.42	0.43	-10000	0	-0.86	179	179
JUN	-0.014	0.11	-10000	0	-0.86	6	6
MAP3K7	0.003	0.009	-10000	0	-10000	0	0
CTNNB1	0.006	0.058	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.047	0.09	0.39	4	-10000	0	4
HNF1A	-0.006	0.089	-10000	0	-0.86	4	4
CTBP1	0.003	0.008	-10000	0	-10000	0	0
MYC	-0.18	0.5	-10000	0	-1.6	43	43
NKD1	0.029	0.23	0.32	80	-0.86	17	97
FZD1	-0.018	0.13	0.32	1	-0.86	8	9
NOTCH1 precursor/Deltex homolog 1	-0.14	0.22	-10000	0	-0.5	105	105
apoptosis	-0.19	0.24	-10000	0	-0.39	188	188
Delta 1/NOTCHprecursor	-0.011	0.093	-10000	0	-0.58	8	8
DLL1	-0.017	0.13	0.32	2	-0.86	8	10
PPARD	-0.011	0.03	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	0.004	0.029	0.35	1	-10000	0	1
DVL1	-0.002	0.012	-10000	0	-10000	0	0
CSNK2A1	0	0.001	-10000	0	-10000	0	0
MAP3K7IP1	0.001	0.007	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.089	0.12	0.39	21	-10000	0	21
LRP6	0	0	-10000	0	-10000	0	0
CSNK1A1	0	0.001	-10000	0	-10000	0	0
NLK	0.007	0.019	-10000	0	-10000	0	0
CCND1	-0.066	0.3	-10000	0	-1.6	14	14
WNT1	0.003	0.033	0.32	4	-10000	0	4
Axin1/APC/beta catenin	0.024	0.04	0.33	1	-10000	0	1
DKK2	0.04	0.1	0.32	47	-10000	0	47
NOTCH1 precursor/DVL1	-0.003	0.036	-10000	0	-0.68	1	1
GSK3B	0.002	0.004	-10000	0	-10000	0	0
FRAT1	0	0.045	-10000	0	-0.86	1	1
NOTCH/Deltex homolog 1	-0.14	0.22	-10000	0	-0.5	105	105
PPP2R5D	0.002	0.084	0.36	17	-10000	0	17
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.01	0.1	-10000	0	-0.54	8	8
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.01	0.004	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.045	0.2	0.67	33	-10000	0	33
KIRREL	-0.074	0.25	0.32	2	-0.86	33	35
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.045	0.2	-10000	0	-0.67	33	33
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	-0.032	0.16	-10000	0	-0.52	33	33
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.026	0.12	-10000	0	-0.41	29	29
FYN	-0.039	0.14	-10000	0	-0.49	33	33
mol:Ca2+	-0.032	0.16	-10000	0	-0.51	33	33
mol:DAG	-0.032	0.16	-10000	0	-0.52	33	33
NPHS2	0	0.043	0.31	5	-10000	0	5
mol:IP3	-0.032	0.16	-10000	0	-0.52	33	33
regulation of endocytosis	-0.028	0.14	-10000	0	-0.46	33	33
Nephrin/NEPH1/podocin/Cholesterol	-0.033	0.16	-10000	0	-0.52	33	33
establishment of cell polarity	-0.045	0.2	-10000	0	-0.67	33	33
Nephrin/NEPH1/podocin/NCK1-2	-0.029	0.15	-10000	0	-0.49	33	33
Nephrin/NEPH1/beta Arrestin2	-0.028	0.14	-10000	0	-0.46	33	33
NPHS1	0.017	0.083	0.32	25	-10000	0	25
Nephrin/NEPH1/podocin	-0.03	0.15	-10000	0	-0.49	33	33
TJP1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
NCK2	-0.001	0.048	0.32	1	-0.86	1	2
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.032	0.16	-10000	0	-0.52	33	33
CD2AP	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.032	0.16	-10000	0	-0.52	33	33
GRB2	0	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.018	0.16	-10000	0	-0.48	33	33
cytoskeleton organization	-0.035	0.15	-10000	0	-0.5	33	33
Nephrin/NEPH1	-0.033	0.16	-10000	0	-0.51	33	33
Nephrin/NEPH1/ZO-1	-0.037	0.17	-10000	0	-0.56	33	33

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.002	0.045	-10000	0	-0.86	1	1
PLK4	0.053	0.12	0.32	62	-10000	0	62
regulation of centriole replication	0.039	0.064	-10000	0	-0.67	1	1

×

IL1-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
UBC13/UEV1A	0	0	-10000	0	-10000	0	0
PRKCZ	-0.039	0.18	-10000	0	-0.86	17	17
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.088	0.17	-10000	0	-0.42	45	45
IRAK/TOLLIP	0	0.008	-10000	0	-10000	0	0
IKBKB	0	0	-10000	0	-10000	0	0
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0	0.04	-10000	0	-0.67	1	1
IL1A	0.002	0.023	0.32	2	-10000	0	2
IL1B	-0.1	0.27	-10000	0	-0.68	64	64
IRAK/TRAF6/p62/Atypical PKCs	-0.02	0.1	-10000	0	-0.46	16	16
IL1R2	-0.001	0.048	0.32	1	-0.86	1	2
IL1R1	-0.007	0.077	-10000	0	-0.86	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.07	0.14	0.23	4	-0.65	10	14
TOLLIP	0	0	-10000	0	-10000	0	0
TICAM2	-0.002	0.045	-10000	0	-0.86	1	1
MAP3K3	0	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	-0.005	0.029	-10000	0	-10000	0	0
JUN	-0.003	0.14	-10000	0	-0.46	31	31
MAP3K7	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.15	0.27	-10000	0	-0.54	100	100
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.066	0.19	-10000	0	-0.57	44	44
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.062	0.18	-10000	0	-0.54	44	44
IL1 beta fragment/IL1R1/IL1RAP	-0.16	0.28	-10000	0	-0.6	100	100
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.032	0.12	-10000	0	-0.47	27	27
IRAK1	0	0.01	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.083	0.22	-10000	0	-0.67	46	46
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
TRAF6	-0.002	0.045	-10000	0	-0.86	1	1
PI3K	-0.005	0.071	-10000	0	-0.94	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.096	0.19	-10000	0	-0.45	45	45
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.16	0.28	-10000	0	-0.6	100	100
IL1 beta/IL1R2	-0.1	0.23	-10000	0	-0.6	64	64
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.025	-10000	0	-0.47	1	1
NF kappa B1 p50/RelA	-0.13	0.24	-10000	0	-0.49	100	100
IRAK3	-0.02	0.13	0.32	1	-0.86	9	10
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.14	0.26	-10000	0	-0.53	101	101
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.044	0.13	-10000	0	-0.38	44	44
IL1 alpha/IL1R1/IL1RAP	-0.072	0.21	-10000	0	-0.62	44	44
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.004	0.036	0.32	5	-10000	0	5
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	-0.001	0.027	-10000	0	-0.5	1	1
IL1RAP	-0.1	0.28	-10000	0	-0.86	44	44
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.12	0.21	-10000	0	-0.85	10	10
CASP1	-0.005	0.063	-10000	0	-0.86	2	2
IL1RN/IL1R2	-0.078	0.22	-10000	0	-0.68	43	43
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.15	0.27	-10000	0	-0.56	100	100
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.034	0.1	-10000	0	-0.68	3	3
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
IL1RN	-0.1	0.28	-10000	0	-0.86	43	43
TRAF6/TAK1/TAB1/TAB2	-0.001	0.026	-10000	0	-0.49	1	1
MAP2K6	-0.007	0.081	-10000	0	-0.54	7	7

×

LPA4-mediated signaling events

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
ADCY4	0.015	0.032	-10000	0	-0.59	1	1
ADCY5	-0.091	0.23	-10000	0	-0.59	66	66
ADCY6	0.015	0.032	-10000	0	-0.59	1	1
ADCY7	0.015	0.032	-10000	0	-0.59	1	1
ADCY1	-0.21	0.3	-10000	0	-0.59	140	140
ADCY2	0.012	0.034	-10000	0	-0.59	1	1
ADCY3	0.016	0.032	-10000	0	-0.59	1	1
ADCY8	0.02	0.042	-10000	0	-0.59	1	1
PRKCE	0.007	0.036	0.15	1	-0.68	1	2
ADCY9	0.015	0.032	-10000	0	-0.59	1	1
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.035	0.089	-10000	0	-0.26	31	31

×

Visual signal transduction: Rods

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
mol:K +	0	0	-10000	0	-10000	0	0
GNAT1/GTP	0.003	0.024	0.21	5	-10000	0	5
Metarhodopsin II/Arrestin	0.01	0.042	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	-0.02	0.12	-10000	0	-0.59	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.004	0.036	0.32	5	-10000	0	5
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	-0.12	0.23	-10000	0	-0.48	101	101
mol:Na +	-0.11	0.21	-10000	0	-0.47	94	94
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.001	0.12	0.39	2	-0.58	11	13
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.11	0.22	-10000	0	-0.48	94	94
CNGB1	0.01	0.056	0.32	12	-10000	0	12
RDH5	-0.12	0.3	-10000	0	-0.86	51	51
SAG	0.001	0.016	0.32	1	-10000	0	1
mol:Ca2+	-0.11	0.2	-10000	0	-0.45	84	84
Na + (4 Units)	-0.11	0.19	-10000	0	-0.44	84	84
RGS9	-0.012	0.16	0.32	16	-0.86	11	27
GNB1/GNGT1	0.03	0.075	-10000	0	-10000	0	0
GNAT1/GDP	0.002	0.1	0.35	3	-0.5	11	14
GUCY2D	0.039	0.1	0.32	46	-10000	0	46
GNGT1	0.043	0.11	0.32	51	-10000	0	51
GUCY2F	0	0	-10000	0	-10000	0	0
GNB5	0.001	0.016	0.32	1	-10000	0	1
mol:GMP (4 units)	-0.008	0.12	-10000	0	-0.54	15	15
mol:11-cis-retinal	-0.12	0.3	-10000	0	-0.86	51	51
mol:cGMP	0.003	0.08	-10000	0	-0.52	7	7
GNB1	0	0	-10000	0	-10000	0	0
Rhodopsin	-0.084	0.23	-10000	0	-0.66	51	51
SLC24A1	0	0	-10000	0	-10000	0	0
CNGA1	-0.21	0.37	-10000	0	-0.86	90	90
Metarhodopsin II	0.009	0.039	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.014	0.1	0.37	1	-0.54	7	8
RGS9BP	0.011	0.058	0.32	13	-10000	0	13
Metarhodopsin II/Transducin	0.02	0.042	-10000	0	-10000	0	0
GCAP Family/Ca ++	-0.009	0.076	-10000	0	-0.55	7	7
PDE6A/B	0.013	0.077	-10000	0	-0.67	2	2
mol:Pi	-0.001	0.12	0.39	2	-0.58	11	13
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.029	0.069	0.37	1	-10000	0	1
PDE6B	0.01	0.092	0.32	17	-0.86	2	19
PDE6A	0.01	0.056	0.32	12	-10000	0	12
PDE6G	-0.032	0.16	-10000	0	-0.86	14	14
RHO	0.015	0.068	0.32	18	-10000	0	18
PDE6	-0.01	0.15	-10000	0	-0.51	25	25
GUCA1A	0.002	0.023	0.32	2	-10000	0	2
GC2/GCAP Family	-0.009	0.076	-10000	0	-0.55	7	7
GUCA1C	0	0	-10000	0	-10000	0	0
GUCA1B	-0.016	0.12	-10000	0	-0.86	7	7

×

FAS signaling pathway (CD95)

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
SPTAN1	0.002	0.037	0.48	1	-0.39	1	2
RFC1	0.002	0.037	0.48	1	-0.39	1	2
PRKDC	0.002	0.037	0.48	1	-0.39	1	2
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	-0.011	0.044	0.27	2	-10000	0	2
FASLG/FAS/FADD/FAF1	0.04	0.15	0.27	69	-0.39	14	83
MAP2K4	-0.012	0.14	-10000	0	-0.44	15	15
mol:ceramide	-0.043	0.13	-10000	0	-0.52	16	16
GSN	0.002	0.037	0.48	1	-0.39	1	2
FASLG/FAS/FADD/FAF1/Caspase 8	0.019	0.14	0.32	3	-0.43	11	14
FAS	-0.027	0.15	-10000	0	-0.86	12	12
BID	0.003	0.035	0.32	4	-10000	0	4
MAP3K1	0.003	0.085	-10000	0	-0.3	7	7
MAP3K7	0	0.002	-10000	0	-10000	0	0
RB1	0.002	0.037	0.48	1	-0.39	1	2
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.46	0.44	-10000	0	-0.79	215	215
ARHGDIB	0.002	0.037	0.48	1	-0.39	1	2
FADD	0.001	0.017	0.32	1	-10000	0	1
actin filament polymerization	-0.002	0.037	0.38	1	-0.48	1	2
NFKB1	-0.032	0.082	-10000	0	-0.3	7	7
MAPK8	-0.053	0.21	-10000	0	-0.46	71	71
DFFA	0.002	0.037	0.48	1	-0.39	1	2
DNA fragmentation during apoptosis	0	0.047	0.48	1	-0.47	2	3
FAS/FADD/MET	-0.02	0.11	-10000	0	-0.58	13	13
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.007	0.091	0.32	1	-0.86	4	5
FAF1	0.001	0.005	-10000	0	-10000	0	0
PARP1	0.002	0.037	0.48	1	-0.39	1	2
DFFB	0	0.047	0.48	1	-0.47	2	3
CHUK	-0.027	0.072	-10000	0	-10000	0	0
FASLG	-0.029	0.17	0.32	3	-0.87	14	17
FAS/FADD	-0.021	0.12	-10000	0	-0.67	12	12
HGF	-0.46	0.43	0.32	1	-0.86	201	202
LMNA	0.002	0.033	0.42	1	-0.35	1	2
CASP6	0.002	0.037	0.48	1	-0.39	1	2
CASP10	0.001	0.004	-10000	0	-10000	0	0
CASP3	0.002	0.047	0.35	4	-0.44	1	5
PTPN13	-0.23	0.38	0.32	2	-0.86	99	101
CASP8	0.004	0.05	0.47	4	-10000	0	4
IL6	-0.17	0.49	-10000	0	-1.4	52	52
MET	-0.001	0.048	0.32	1	-0.86	1	2
ICAD/CAD	0	0.044	0.43	1	-0.44	2	3
FASLG/FAS/FADD/FAF1/Caspase 10	-0.043	0.13	-10000	0	-0.52	16	16
activation of caspase activity by cytochrome c	0.003	0.034	0.32	4	-10000	0	4
PAK2	0.002	0.037	0.48	1	-0.39	1	2
BCL2	-0.002	0.045	-10000	0	-0.86	1	1

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.037	0.32	5	-10000	0	5
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.13	0.24	0.79	22	-10000	0	22
IL27/IL27R/JAK1	-0.2	0.29	-10000	0	-0.87	25	25
TBX21	-0.12	0.25	-10000	0	-0.67	28	28
IL12B	0.004	0.03	0.33	3	-10000	0	3
IL12A	0.013	0.025	-10000	0	-10000	0	0
IL6ST	-0.21	0.37	-10000	0	-0.86	91	91
IL27RA/JAK1	-0.005	0.019	-10000	0	-10000	0	0
IL27	-0.13	0.32	-10000	0	-0.86	58	58
TYK2	0.007	0.009	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.036	0.14	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.13	0.24	0.79	22	-10000	0	22
T cell proliferation during immune response	0.13	0.24	0.79	22	-10000	0	22
MAPKKK cascade	-0.13	0.24	-10000	0	-0.79	22	22
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	0.002	0.023	0.32	2	-10000	0	2
IL12RB1	-0.029	0.16	-10000	0	-0.86	13	13
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.12	0.26	-10000	0	-0.69	29	29
IL27/IL27R/JAK2/TYK2	-0.14	0.24	-10000	0	-0.81	22	22
positive regulation of T cell mediated cytotoxicity	-0.13	0.24	-10000	0	-0.79	22	22
STAT1 (dimer)	-0.19	0.32	0.53	13	-0.96	24	37
JAK2	0	0.046	-10000	0	-0.87	1	1
JAK1	0.001	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.14	0.22	-10000	0	-0.85	18	18
T cell proliferation	-0.19	0.28	-10000	0	-0.65	67	67
IL12/IL12R/TYK2/JAK2	0.014	0.079	-10000	0	-10000	0	0
IL17A	-0.036	0.14	-10000	0	-10000	0	0
mast cell activation	0.13	0.24	0.79	22	-10000	0	22
IFNG	-0.01	0.034	0.11	4	-0.092	14	18
T cell differentiation	-0.005	0.007	-10000	0	-0.024	13	13
STAT3 (dimer)	-0.14	0.22	-10000	0	-0.85	18	18
STAT5A (dimer)	-0.14	0.22	-10000	0	-0.85	18	18
STAT4 (dimer)	-0.16	0.24	-10000	0	-0.81	30	30
STAT4	-0.034	0.17	0.32	1	-0.86	15	16
T cell activation	-0.012	0.01	-10000	0	-0.13	1	1
IL27R/JAK2/TYK2	-0.12	0.23	-10000	0	-0.52	85	85
GATA3	-0.071	0.4	-10000	0	-1.5	27	27
IL18	-0.008	0.11	-10000	0	-0.68	10	10
positive regulation of mast cell cytokine production	-0.14	0.21	-10000	0	-0.82	18	18
IL27/EBI3	-0.13	0.27	-10000	0	-0.67	76	76
IL27RA	-0.01	0.022	-10000	0	-10000	0	0
IL6	-0.11	0.3	0.32	8	-0.86	52	60
STAT5A	0.001	0.016	0.32	1	-10000	0	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.009	0.018	-10000	0	-10000	0	0
IL1B	-0.11	0.26	-10000	0	-0.68	64	64
EBI3	-0.04	0.18	-10000	0	-0.86	18	18
TNF	-0.016	0.13	-10000	0	-0.68	14	14

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.02	0.11	-10000	0	-0.55	14	14
CRKL	0	0	-10000	0	-10000	0	0
Rac1/GDP	0	0	-10000	0	-10000	0	0
DOCK1	-0.019	0.12	-10000	0	-0.86	8	8
ITGA4	-0.02	0.13	0.32	1	-0.86	9	10
alpha4/beta7 Integrin/MAdCAM1	-0.015	0.11	0.38	1	-0.53	14	15
EPO	-0.3	0.43	0.32	12	-0.86	136	148
alpha4/beta7 Integrin	-0.025	0.13	-10000	0	-0.67	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.016	0.1	-10000	0	-0.67	9	9
EPO/EPOR (dimer)	-0.24	0.33	-10000	0	-0.67	136	136
lamellipodium assembly	-0.003	0.053	-10000	0	-0.7	2	2
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
PI3K	-0.005	0.071	-10000	0	-0.94	2	2
ARF6	0	0	-10000	0	-10000	0	0
JAK2	-0.15	0.21	-10000	0	-0.41	140	140
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
MADCAM1	0.007	0.046	0.32	8	-10000	0	8
cell adhesion	-0.015	0.11	0.37	1	-0.53	14	15
CRKL/CBL	0	0	-10000	0	-10000	0	0
ITGB1	0	0	-10000	0	-10000	0	0
SRC	-0.038	0.15	-10000	0	-0.56	27	27
ITGB7	-0.012	0.099	-10000	0	-0.86	5	5
RAC1	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.041	0.17	-10000	0	-0.62	27	27
p130Cas/Crk/Dock1	-0.043	0.16	-10000	0	-0.54	29	29
VCAM1	-0.041	0.2	0.32	6	-0.86	20	26
RHOA	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.012	0.082	-10000	0	-0.53	9	9
BCAR1	-0.036	0.14	-10000	0	-0.52	27	27
EPOR	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
GIT1	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.003	0.056	-10000	0	-0.73	2	2

×

Regulation of nuclear SMAD2/3 signaling

Figure S71. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S71. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	-0.005	0.008	-10000	0	-10000	0	0
HSPA8	0.002	0.045	-10000	0	-0.86	1	1
SMAD3/SMAD4/ER alpha	-0.36	0.31	-10000	0	-0.63	205	205
AKT1	0.002	0.009	-10000	0	-10000	0	0
GSC	0.038	0.065	-10000	0	-10000	0	0
NKX2-5	0.015	0.068	0.32	18	-10000	0	18
muscle cell differentiation	0.013	0.05	0.64	1	-10000	0	1
SMAD2-3/SMAD4/SP1	-0.004	0.072	-10000	0	-0.48	2	2
SMAD4	-0.011	0.069	-10000	0	-0.92	1	1
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0.003	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.002	0.035	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	-0.019	0.093	-10000	0	-0.53	9	9
MYC	-0.1	0.28	-10000	0	-0.87	43	43
CDKN2B	0.069	0.085	0.5	2	-10000	0	2
AP1	-0.24	0.27	-10000	0	-0.49	179	179
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0	0.023	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.005	0.048	-10000	0	-10000	0	0
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	0.029	0.091	0.33	32	-10000	0	32
SMAD3/SMAD4/GR	-0.017	0.057	-10000	0	-0.63	1	1
GATA3	-0.079	0.24	0.32	1	-0.92	27	28
SKI/SIN3/HDAC complex/NCoR1	0.017	0.032	-10000	0	-10000	0	0
MEF2C/TIF2	-0.054	0.16	-10000	0	-0.46	44	44
endothelial cell migration	0.4	0.67	1.5	101	-10000	0	101
MAX	0.015	0.025	-10000	0	-10000	0	0
RBBP7	0.003	0.005	-10000	0	-10000	0	0
RBBP4	0.003	0.005	-10000	0	-10000	0	0
RUNX2	-0.02	0.14	0.32	4	-0.86	10	14
RUNX3	-0.019	0.12	-10000	0	-0.86	8	8
RUNX1	-0.002	0.045	-10000	0	-0.86	1	1
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	0.015	0.025	-10000	0	-10000	0	0
VDR	-0.009	0.14	0.32	11	-0.86	8	19
CDKN1A	-0.011	0.24	-10000	0	-1.4	10	10
KAT2B	-0.007	0.078	-10000	0	-0.87	3	3
SMAD2/SMAD2/SMAD4/FOXH1	0.02	0.078	0.34	5	-0.57	1	6
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0.003	0.005	-10000	0	-10000	0	0
SERPINE1	-0.41	0.68	-10000	0	-1.5	101	101
SMAD3/SMAD4/ATF2	-0.028	0.089	-10000	0	-0.61	6	6
SMAD3/SMAD4/ATF3	-0.043	0.14	-10000	0	-0.66	15	15
SAP30	0.003	0.005	-10000	0	-10000	0	0
Cbp/p300/PIAS3	-0.008	0.013	-10000	0	-10000	0	0
JUN	-0.21	0.28	-10000	0	-0.48	179	179
SMAD3/SMAD4/IRF7	-0.029	0.094	-10000	0	-0.66	6	6
TFE3	-0.009	0.017	-10000	0	-10000	0	0
COL1A2	0.1	0.18	0.46	10	-1.2	4	14
mesenchymal cell differentiation	0.034	0.12	0.67	11	-0.34	1	12
DLX1	0.026	0.086	0.32	30	-10000	0	30
TCF3	0	0	-10000	0	-10000	0	0
FOS	-0.41	0.43	-10000	0	-0.86	179	179
SMAD3/SMAD4/Max	-0.017	0.057	-10000	0	-0.63	1	1
Cbp/p300/SNIP1	-0.001	0.002	-10000	0	-10000	0	0
ZBTB17	-0.001	0.005	-10000	0	-10000	0	0
LAMC1	0.009	0.069	-10000	0	-0.54	1	1
TGIF2/HDAC complex/SMAD3/SMAD4	-0.02	0.059	-10000	0	-0.62	1	1
IRF7	-0.012	0.099	-10000	0	-0.86	5	5
ESR1	-0.48	0.43	-10000	0	-0.86	205	205
HNF4A	-0.014	0.11	-10000	0	-0.86	6	6
MEF2C	0.014	0.048	-10000	0	-0.47	1	1
SMAD2-3/SMAD4	-0.016	0.061	-10000	0	-0.62	1	1
Cbp/p300/Src-1	-0.003	0.005	-10000	0	-10000	0	0
IGHV3OR16-13	-0.005	0.021	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	-0.001	0.004	-10000	0	-10000	0	0
SKIL	0	0	-10000	0	-10000	0	0
HDAC1	0.003	0.005	-10000	0	-10000	0	0
HDAC2	0.003	0.005	-10000	0	-10000	0	0
SNIP1	0.004	0.007	-10000	0	-10000	0	0
GCN5L2	-0.008	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.022	0.064	-10000	0	-0.62	1	1
MSG1/HSC70	0.013	0.052	-10000	0	-0.62	1	1
SMAD2	0.005	0.013	-10000	0	-10000	0	0
SMAD3	-0.013	0.052	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0	0.048	-10000	0	-0.39	2	2
SMAD2/SMAD2/SMAD4	-0.009	0.057	-10000	0	-0.48	4	4
NCOR1	-0.002	0.063	-10000	0	-0.86	2	2
NCOA2	-0.11	0.29	-10000	0	-0.86	48	48
NCOA1	0	0	-10000	0	-10000	0	0
MYOD/E2A	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.001	0.07	-10000	0	-0.51	1	1
IFNB1	-0.008	0.091	-10000	0	-0.59	6	6
SMAD3/SMAD4/MEF2C	0.005	0.058	-10000	0	-0.49	1	1
CITED1	0.013	0.058	0.32	13	-10000	0	13
SMAD2-3/SMAD4/ARC105	-0.009	0.053	-10000	0	-0.56	1	1
RBL1	0.011	0.058	0.32	13	-10000	0	13
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.005	0.051	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.014	0.097	-10000	0	-0.64	8	8
SMAD7	-0.16	0.21	-10000	0	-0.82	9	9
MYC/MIZ-1	-0.081	0.22	-10000	0	-0.68	43	43
SMAD3/SMAD4	-0.14	0.21	-10000	0	-0.47	101	101
IL10	-0.13	0.34	-10000	0	-0.86	61	61
PIASy/HDAC complex	0.011	0.016	-10000	0	-10000	0	0
PIAS3	0	0	-10000	0	-10000	0	0
CDK2	0	0.001	-10000	0	-10000	0	0
IL5	-0.062	0.21	-10000	0	-0.68	28	28
CDK4	0	0.001	-10000	0	-10000	0	0
PIAS4	0.011	0.016	-10000	0	-10000	0	0
ATF3	-0.032	0.16	-10000	0	-0.86	14	14
SMAD3/SMAD4/SP1	-0.015	0.076	-10000	0	-0.54	2	2
FOXG1	0.008	0.052	0.32	10	-10000	0	10
FOXO3	0.023	0.01	-10000	0	-10000	0	0
FOXO1	0.016	0.071	-10000	0	-0.66	4	4
FOXO4	0.023	0.01	-10000	0	-10000	0	0
heart looping	0.014	0.048	-10000	0	-0.47	1	1
CEBPB	0.001	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.007	0.082	0.31	2	-0.63	1	3
MYOD1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.03	0.096	-10000	0	-0.62	7	7
SMAD3/SMAD4/GATA3	-0.091	0.22	-10000	0	-0.61	48	48
SnoN/SIN3/HDAC complex/NCoR1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.023	0.1	-10000	0	-0.62	9	9
SMAD3/SMAD4/SP1-3	-0.008	0.066	-10000	0	-0.48	2	2
MED15	0	0	-10000	0	-10000	0	0
SP1	0	0.023	-10000	0	-10000	0	0
SIN3B	0.003	0.005	-10000	0	-10000	0	0
SIN3A	0.003	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.03	0.092	0.38	10	-0.52	1	11
ITGB5	-0.007	0.056	-10000	0	-0.49	1	1
TGIF/SIN3/HDAC complex/CtBP	0.012	0.021	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.18	0.28	-10000	0	-0.63	102	102
AR	-0.23	0.38	-10000	0	-0.86	101	101
negative regulation of cell growth	-0.01	0.067	-10000	0	-0.41	2	2
SMAD3/SMAD4/MYOD	-0.023	0.061	-10000	0	-0.63	1	1
E2F5	0.006	0.068	0.32	10	-0.86	1	11
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.017	0.066	-10000	0	-0.48	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	0.001	0.05	-10000	0	-10000	0	0
TFDP1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.23	0.28	-10000	0	-0.49	179	179
SMAD3/SMAD4/RUNX2	-0.034	0.12	0.34	1	-0.67	11	12
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	-0.012	0.099	-10000	0	-0.86	5	5

×

Regulation of Androgen receptor activity

Figure S72. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S72. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.003	-10000	0	-10000	0	0
SMARCC1	0.005	0.009	-10000	0	-10000	0	0
REL	-0.03	0.16	-10000	0	-0.86	13	13
HDAC7	-0.034	0.17	-10000	0	-0.53	28	28
JUN	-0.013	0.11	-10000	0	-0.86	6	6
EP300	0	0	-10000	0	-10000	0	0
KAT2B	-0.007	0.077	-10000	0	-0.86	3	3
KAT5	0	0.001	-10000	0	-10000	0	0
MAPK14	0.007	0.096	-10000	0	-0.67	7	7
FOXO1	-0.009	0.089	-10000	0	-0.86	4	4
T-DHT/AR	-0.044	0.18	-10000	0	-0.56	28	28
MAP2K6	-0.011	0.12	0.32	6	-0.86	7	13
BRM/BAF57	-0.016	0.11	-10000	0	-0.67	10	10
MAP2K4	0.001	0.004	-10000	0	-10000	0	0
SMARCA2	-0.022	0.14	-10000	0	-0.86	10	10
PDE9A	-0.13	0.37	-10000	0	-1.2	36	36
NCOA2	-0.11	0.29	-10000	0	-0.86	48	48
CEBPA	-0.006	0.079	0.32	1	-0.86	3	4
EHMT2	0.001	0.004	-10000	0	-10000	0	0
cell proliferation	-0.016	0.17	-10000	0	-0.51	23	23
NR0B1	0.054	0.12	0.32	63	-10000	0	63
EGR1	-0.3	0.41	-10000	0	-0.86	128	128
RXRs/9cRA	0.015	0.094	-10000	0	-0.54	6	6
AR/RACK1/Src	-0.048	0.15	-10000	0	-0.53	27	27
AR/GR	-0.11	0.18	-10000	0	-0.37	94	94
GNB2L1	0.001	0.004	-10000	0	-10000	0	0
PKN1	0.001	0.016	0.32	1	-10000	0	1
RCHY1	0	0	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0.001	0.002	-10000	0	-10000	0	0
MAPK8	-0.019	0.16	-10000	0	-0.67	20	20
T-DHT/AR/TIF2/CARM1	-0.12	0.27	-10000	0	-0.7	56	56
SRC	-0.002	0.14	-10000	0	-0.5	27	27
NR3C1	0	0	-10000	0	-10000	0	0
KLK3	-0.014	0.2	-10000	0	-1.2	7	7
APPBP2	0	0.001	-10000	0	-10000	0	0
TRIM24	0.001	0.006	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.069	0.15	-10000	0	-0.58	27	27
TMPRSS2	-0.078	0.29	-10000	0	-1.3	18	18
RXRG	0.026	0.14	0.32	44	-0.86	5	49
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	-0.002	0.045	-10000	0	-0.86	1	1
RXRB	0	0	-10000	0	-10000	0	0
CARM1	0.001	0.004	-10000	0	-10000	0	0
NR2C2	-0.014	0.11	-10000	0	-0.86	6	6
KLK2	-0.031	0.2	-10000	0	-0.56	26	26
AR	-0.12	0.2	-10000	0	-0.39	115	115
SENP1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
MDM2	0.001	0.005	-10000	0	-10000	0	0
SRY	0.002	0.029	0.32	3	-10000	0	3
GATA2	-0.003	0.067	0.32	2	-0.86	2	4
MYST2	0	0	-10000	0	-10000	0	0
HOXB13	0.064	0.13	0.32	74	-10000	0	74
T-DHT/AR/RACK1/Src	-0.057	0.15	-10000	0	-0.55	27	27
positive regulation of transcription	-0.003	0.067	0.32	2	-0.86	2	4
DNAJA1	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.001	0.004	-10000	0	-10000	0	0
NCOA1	0.008	0.011	-10000	0	-10000	0	0
SPDEF	0.05	0.12	0.32	57	-10000	0	57
T-DHT/AR/TIF2	-0.051	0.2	-10000	0	-0.55	41	41
T-DHT/AR/Hsp90	-0.069	0.15	-10000	0	-0.58	27	27
GSK3B	0.003	0.005	-10000	0	-10000	0	0
NR2C1	0	0.001	-10000	0	-10000	0	0
mol:T-DHT	-0.01	0.15	-10000	0	-0.54	27	27
SIRT1	-0.005	0.063	-10000	0	-0.86	2	2
ZMIZ2	0.001	0.005	-10000	0	-10000	0	0
POU2F1	0.01	0.031	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.035	0.18	-10000	0	-0.58	27	27
CREBBP	0	0	-10000	0	-10000	0	0
SMARCE1	0.001	0.005	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.044	0.27	1	-10000	0	1
AES	0.015	0.038	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
LRP6/FZD1	-0.014	0.098	-10000	0	-0.67	8	8
SMAD4	-0.002	0.045	-10000	0	-0.86	1	1
DKK2	0.04	0.1	0.32	47	-10000	0	47
TLE1	0.013	0.059	-10000	0	-0.86	1	1
MACF1	0	0	-10000	0	-10000	0	0
CTNNB1	0.038	0.073	-10000	0	-0.4	1	1
WIF1	0.032	0.095	0.32	37	-10000	0	37
beta catenin/RanBP3	0.05	0.17	0.42	58	-0.4	1	59
KREMEN2	0.034	0.098	0.32	40	-10000	0	40
DKK1	0.11	0.15	0.32	126	-10000	0	126
beta catenin/beta TrCP1	0.001	0.06	-10000	0	-10000	0	0
FZD1	-0.018	0.13	0.32	1	-0.86	8	9
AXIN2	-0.073	0.39	-10000	0	-1.6	19	19
AXIN1	0	0	-10000	0	-10000	0	0
RAN	0.001	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.011	0.032	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.059	0.072	0.32	1	-0.51	2	3
Axin1/APC/GSK3	-0.001	0.047	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.031	0.079	-10000	0	-0.48	6	6
HNF1A	0.006	0.098	0.24	1	-0.85	4	5
CTBP1	0.016	0.04	-10000	0	-10000	0	0
MYC	-0.19	0.54	-10000	0	-1.7	43	43
RANBP3	0.001	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.047	0.09	0.39	4	-10000	0	4
NKD1	0.029	0.23	0.32	80	-0.86	17	97
TCF4	0.016	0.04	-10000	0	-10000	0	0
TCF3	0.016	0.04	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.009	0.081	-10000	0	-0.54	8	8
Ran/GTP	0.001	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.089	0.23	0.56	58	-0.65	1	59
LEF1	0.13	0.15	0.32	108	-0.73	1	109
DVL1	0.009	0.036	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.049	0.12	-10000	0	-0.5	4	4
DKK1/LRP6/Kremen 2	0.089	0.12	0.39	21	-10000	0	21
LRP6	0	0	-10000	0	-10000	0	0
CSNK1A1	0.017	0.044	-10000	0	-10000	0	0
NLK	0.002	0.004	-10000	0	-10000	0	0
CCND1	-0.082	0.34	-10000	0	-1.4	19	19
WNT1	0.003	0.033	0.32	4	-10000	0	4
GSK3A	0	0	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
FRAT1	-0.002	0.045	-10000	0	-0.86	1	1
PPP2R5D	0.005	0.09	0.37	17	-10000	0	17
APC	-0.01	0.073	-10000	0	-0.5	8	8
WNT1/LRP6/FZD1	-0.012	0.059	-10000	0	-0.36	8	8
CREBBP	0.016	0.04	-10000	0	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0	0	-10000	0	-10000	0	0
ELF1	-0.007	0.086	-10000	0	-0.49	9	9
CCNA2	0.17	0.16	0.32	197	-10000	0	197
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
JAK3	0.001	0.055	0.32	4	-0.86	1	5
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
JAK1	0	0	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.029	0.14	0.3	1	-0.63	15	16
SHC1	0	0	-10000	0	-10000	0	0
SP1	0.002	0.018	-10000	0	-10000	0	0
IL2RA	0.008	0.16	-10000	0	-0.98	9	9
IL2RB	-0.067	0.23	-10000	0	-0.86	29	29
SOS1	0	0	-10000	0	-10000	0	0
IL2RG	-0.006	0.11	0.32	7	-0.86	5	12
G1/S transition of mitotic cell cycle	0.054	0.15	-10000	0	-0.46	25	25
PTPN11	0	0	-10000	0	-10000	0	0
CCND2	0.027	0.031	-10000	0	-10000	0	0
LCK	-0.025	0.15	0.32	1	-0.86	11	12
GRB2	0	0	-10000	0	-10000	0	0
IL2	0	0	-10000	0	-10000	0	0
CDK6	-0.058	0.22	-10000	0	-0.86	25	25
CCND3	0.033	0.13	-10000	0	-0.72	6	6

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.097	0.16	-10000	0	-0.57	3	3
RAD9A	0	0	-10000	0	-10000	0	0
AP1	-0.32	0.35	-10000	0	-0.68	179	179
IFNAR2	0.012	0.015	-10000	0	-10000	0	0
AKT1	-0.15	0.16	-10000	0	-0.3	115	115
ER alpha/Oestrogen	-0.37	0.34	-10000	0	-0.67	205	205
NFX1/SIN3/HDAC complex	0.028	0.035	-10000	0	-10000	0	0
EGF	0.08	0.13	0.32	88	-10000	0	88
SMG5	0	0	-10000	0	-10000	0	0
SMG6	0	0	-10000	0	-10000	0	0
SP3/HDAC2	0.02	0.024	-10000	0	-10000	0	0
TERT/c-Abl	-0.023	0.067	-10000	0	-0.56	2	2
SAP18	0.004	0.006	-10000	0	-10000	0	0
MRN complex	0	0	-10000	0	-10000	0	0
WT1	0.036	0.086	0.33	29	-10000	0	29
WRN	0	0	-10000	0	-10000	0	0
SP1	0.019	0.019	-10000	0	-10000	0	0
SP3	0.007	0.009	-10000	0	-10000	0	0
TERF2IP	0	0	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.017	0.059	-10000	0	-0.54	1	1
Mad/Max	0.017	0.024	-10000	0	-10000	0	0
TERT	0.097	0.17	-10000	0	-0.59	3	3
CCND1	0.065	0.28	-10000	0	-1.2	14	14
MAX	0.008	0.01	-10000	0	-10000	0	0
RBBP7	0.004	0.006	-10000	0	-10000	0	0
RBBP4	0.004	0.006	-10000	0	-10000	0	0
TERF2	0	0	-10000	0	-10000	0	0
PTGES3	0	0	-10000	0	-10000	0	0
SIN3A	0.004	0.006	-10000	0	-10000	0	0
Telomerase/911	0.034	0.049	-10000	0	-10000	0	0
CDKN1B	0.023	0.03	-10000	0	-10000	0	0
RAD1	0	0	-10000	0	-10000	0	0
XRCC5	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
SAP30	0.004	0.006	-10000	0	-10000	0	0
TRF2/PARP2	0	0	-10000	0	-10000	0	0
UBE3A	0.007	0.009	-10000	0	-10000	0	0
JUN	-0.01	0.11	-10000	0	-0.86	6	6
E6	0.004	0.005	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.012	0.015	-10000	0	-10000	0	0
FOS	-0.41	0.43	-10000	0	-0.86	179	179
IFN-gamma/IRF1	0.028	0.051	-10000	0	-10000	0	0
PARP2	0	0	-10000	0	-10000	0	0
BLM	0.11	0.15	0.32	124	-10000	0	124
Telomerase	0.044	0.064	-10000	0	-10000	0	0
IRF1	0.01	0.012	-10000	0	-10000	0	0
ESR1	-0.47	0.43	-10000	0	-0.86	205	205
KU/TER	0	0	-10000	0	-10000	0	0
ATM/TRF2	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.029	0.036	-10000	0	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.029	0.036	-10000	0	-10000	0	0
HDAC1	0.004	0.006	-10000	0	-10000	0	0
HDAC2	0.014	0.017	-10000	0	-10000	0	0
ATM	0	0	-10000	0	-10000	0	0
SMAD3	0.013	0.019	-10000	0	-10000	0	0
ABL1	0	0	-10000	0	-10000	0	0
MXD1	0.009	0.019	0.33	1	-10000	0	1
MRE11A	0	0	-10000	0	-10000	0	0
HUS1	0	0	-10000	0	-10000	0	0
RPS6KB1	0	0	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.035	0.11	-10000	0	-0.62	2	2
NR2F2	0.001	0.003	-10000	0	-10000	0	0
MAPK3	0.02	0.011	-10000	0	-10000	0	0
MAPK1	0.02	0.011	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.004	0.036	0.32	5	-10000	0	5
NFKB1	0	0	-10000	0	-10000	0	0
HNRNPC	0	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-10000	0	-10000	0	0
NBN	0	0	-10000	0	-10000	0	0
EGFR	-0.017	0.14	-10000	0	-0.85	10	10
mol:Oestrogen	0.001	0.002	-10000	0	-10000	0	0
EGF/EGFR	0.041	0.15	-10000	0	-0.65	10	10
MYC	-0.092	0.28	-10000	0	-0.86	43	43
IL2	0.016	0.017	-10000	0	-10000	0	0
KU	0	0	-10000	0	-10000	0	0
RAD50	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
TGFB1	0.004	0.036	0.32	5	-10000	0	5
TRF2/BLM	0.07	0.099	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	-0.021	0.066	-10000	0	-0.55	2	2
SP1/HDAC2	0.03	0.037	-10000	0	-10000	0	0
PINX1	0	0	-10000	0	-10000	0	0
Telomerase/EST1A	-0.017	0.059	-10000	0	-0.54	1	1
Smad3/Myc	-0.066	0.19	-10000	0	-0.58	43	43
911 complex	0	0	-10000	0	-10000	0	0
IFNG	0.023	0.066	0.33	16	-10000	0	16
Telomerase/PinX1	-0.017	0.059	-10000	0	-0.54	1	1
Telomerase/AKT1/mTOR/p70S6K	0.013	0.082	-10000	0	-10000	0	0
SIN3B	0.004	0.006	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
Telomerase/EST1B	-0.017	0.059	-10000	0	-0.54	1	1
response to DNA damage stimulus	0.002	0	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-10000	0	-10000	0	0
TRF2/WRN	0	0	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	-0.017	0.059	-10000	0	-0.54	1	1
E2F1	0.2	0.16	0.33	230	-10000	0	230
ZNFX1	0.004	0.006	-10000	0	-10000	0	0
PIF1	0.088	0.14	0.32	103	-10000	0	103
NCL	0	0	-10000	0	-10000	0	0
DKC1	0	0	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR 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
LAT/GRAP2/SLP76/HPK1	-0.025	0.16	0.56	1	-0.64	18	19
MAP4K1	-0.014	0.12	0.32	3	-0.86	7	10
MAP3K8	-0.005	0.063	-10000	0	-0.86	2	2
PRKCB	-0.074	0.24	-10000	0	-0.86	32	32
DBNL	0	0	-10000	0	-10000	0	0
CRKL	0	0	-10000	0	-10000	0	0
MAP3K1	-0.017	0.1	-10000	0	-0.91	3	3
JUN	-0.071	0.25	-10000	0	-0.64	56	56
MAP3K7	-0.017	0.1	-10000	0	-0.76	4	4
GRAP2	-0.016	0.14	0.32	6	-0.86	9	15
CRK	0	0	-10000	0	-10000	0	0
MAP2K4	0.024	0.11	-10000	0	-0.44	14	14
LAT	0.002	0.023	0.32	2	-10000	0	2
LCP2	-0.014	0.11	-10000	0	-0.86	6	6
MAPK8	-0.073	0.25	-10000	0	-0.67	52	52
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.018	0.11	0.25	1	-0.49	13	14
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.024	0.15	0.53	1	-0.6	18	19

×

HIF-2-alpha transcription factor network

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
MMP14	-0.003	0.052	0.49	1	-10000	0	1
oxygen homeostasis	0.001	0.019	-10000	0	-10000	0	0
TCEB2	0.001	0.016	0.32	1	-10000	0	1
TCEB1	0	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.03	0.07	-10000	0	-0.44	4	4
EPO	-0.24	0.47	0.67	3	-0.8	139	142
FIH (dimer)	0.011	0.015	-10000	0	-10000	0	0
APEX1	0.002	0.017	-10000	0	-10000	0	0
SERPINE1	-0.14	0.44	0.72	1	-0.81	101	102
FLT1	-0.014	0.066	-10000	0	-1.2	1	1
ADORA2A	-0.025	0.27	0.67	1	-0.73	12	13
germ cell development	0.009	0.27	0.66	5	-0.61	18	23
SLC11A2	-0.009	0.26	0.72	1	-0.64	18	19
BHLHE40	-0.017	0.28	0.72	1	-0.85	14	15
HIF1AN	0.011	0.015	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.076	0.17	0.46	6	-0.54	11	17
ETS1	0.016	0.047	-10000	0	-0.86	1	1
CITED2	-0.018	0.1	-10000	0	-1.4	2	2
KDR	-0.042	0.2	-10000	0	-1.3	10	10
PGK1	-0.009	0.26	0.72	1	-0.7	12	13
SIRT1	-0.004	0.063	-10000	0	-0.86	2	2
response to hypoxia	-0.005	0.008	-10000	0	-10000	0	0
HIF2A/ARNT	-0.08	0.26	0.67	5	-0.76	18	23
EPAS1	0.015	0.14	0.49	1	-0.46	9	10
SP1	0.017	0.017	-10000	0	-10000	0	0
ABCG2	-0.082	0.36	0.72	1	-0.76	56	57
EFNA1	-0.013	0.27	0.72	1	-0.74	15	16
FXN	-0.025	0.27	0.67	1	-0.65	18	19
POU5F1	0.007	0.27	0.66	5	-0.64	18	23
neuron apoptosis	0.078	0.25	0.73	18	-0.66	5	23
EP300	0	0	-10000	0	-10000	0	0
EGLN3	0.012	0.18	0.33	33	-0.87	11	44
EGLN2	0.011	0.015	-10000	0	-10000	0	0
EGLN1	0.011	0.015	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.001	0.01	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.002	0.017	-10000	0	-10000	0	0
SLC2A1	-0.026	0.28	0.75	1	-0.77	15	16
TWIST1	-0.023	0.27	0.75	1	-0.65	18	19
ELK1	0.014	0.001	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.037	0.13	0.57	1	-0.54	4	5
VEGFA	-0.009	0.26	0.72	1	-0.7	12	13
CREBBP	0	0	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.2	0.56	-10000	0	-1.4	63	63
PLK1	0.28	0.25	0.69	8	-0.76	3	11
CDKN1B	0.18	0.16	0.46	10	-0.35	3	13
FOXO3	0.24	0.24	0.49	126	-0.74	5	131
KAT2B	0.045	0.089	-10000	0	-0.86	3	3
FOXO1/SIRT1	-0.066	0.16	-10000	0	-0.4	65	65
CAT	0.19	0.36	0.59	8	-1.3	15	23
CTNNB1	0	0	-10000	0	-10000	0	0
AKT1	0.047	0.038	-10000	0	-10000	0	0
FOXO1	-0.029	0.18	-10000	0	-0.42	65	65
MAPK10	0.011	0.14	-10000	0	-0.5	24	24
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
FOXO4	0.07	0.13	-10000	0	-0.51	9	9
response to oxidative stress	0.04	0.041	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.029	0.18	0.42	33	-0.79	6	39
XPO1	0	0	-10000	0	-10000	0	0
EP300	-0.001	0.019	-10000	0	-10000	0	0
BCL2L11	0.075	0.057	-10000	0	-10000	0	0
FOXO1/SKP2	-0.067	0.15	-10000	0	-0.38	64	64
mol:GDP	0.04	0.04	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
GADD45A	0.16	0.2	0.48	1	-0.85	9	10
YWHAQ	0	0	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.075	0.051	-10000	0	-10000	0	0
MST1	-0.006	0.22	-10000	0	-0.82	25	25
CSNK1D	0	0	-10000	0	-10000	0	0
CSNK1E	0.001	0.016	0.32	1	-10000	0	1
FOXO4/14-3-3 family	0.074	0.072	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	0.013	0.13	-10000	0	-0.52	20	20
MAPK9	0.042	0.019	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
YWHAZ	0	0	-10000	0	-10000	0	0
SIRT1	0	0.066	-10000	0	-0.86	2	2
SOD2	0.18	0.2	0.49	6	-0.76	6	12
RBL2	0.18	0.28	0.51	6	-1.3	9	15
RAL/GDP	0.033	0.033	-10000	0	-10000	0	0
CHUK	0.053	0.036	-10000	0	-10000	0	0
Ran/GTP	0	0	-10000	0	-10000	0	0
CSNK1G2	0	0	-10000	0	-10000	0	0
RAL/GTP	0.046	0.027	-10000	0	-10000	0	0
CSNK1G1	0	0	-10000	0	-10000	0	0
FASLG	0.022	0.31	-10000	0	-1.5	14	14
SKP2	0	0	-10000	0	-10000	0	0
USP7	0	0	-10000	0	-10000	0	0
IKBKB	0.053	0.036	-10000	0	-10000	0	0
CCNB1	0.27	0.24	0.69	8	-0.76	3	11
FOXO1-3a-4/beta catenin	-0.022	0.087	-10000	0	-0.41	11	11
proteasomal ubiquitin-dependent protein catabolic process	-0.066	0.15	-10000	0	-0.38	64	64
CSNK1A1	0	0	-10000	0	-10000	0	0
SGK1	0.024	0.16	-10000	0	-0.84	12	12
CSNK1G3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
ZFAND5	0.073	0.12	-10000	0	-0.57	4	4
SFN	0.18	0.17	0.32	214	-0.86	2	216
CDK2	-0.013	0.03	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.14	0.076	-10000	0	-10000	0	0
CREBBP	-0.013	0.03	-10000	0	-10000	0	0
FBXO32	0.23	0.24	0.69	8	-0.92	4	12
BCL6	0.2	0.18	0.5	8	-0.65	4	12
RALB	0	0	-10000	0	-10000	0	0
RALA	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0	0	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	-0.064	0.17	-10000	0	-0.47	53	53
Syndecan-3/Neurocan	0.001	0.048	-10000	0	-0.77	1	1
POMC	-0.004	0.084	0.32	4	-0.86	3	7
EGFR	-0.023	0.14	-10000	0	-0.86	10	10
Syndecan-3/EGFR	-0.015	0.09	-10000	0	-0.52	11	11
AGRP	0.012	0.06	0.32	14	-10000	0	14
NCSTN	0	0	-10000	0	-10000	0	0
PSENEN	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0	0	-10000	0	-10000	0	0
APH1A	0	0	-10000	0	-10000	0	0
NCAN	0.005	0.04	0.32	6	-10000	0	6
long-term memory	-0.002	0.037	-10000	0	-0.71	1	1
Syndecan-3/IL8	-0.11	0.22	-10000	0	-0.51	85	85
PSEN1	0	0	-10000	0	-10000	0	0
Src/Cortactin	0.003	0.025	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
limb bud formation	-0.002	0.041	-10000	0	-0.78	1	1
MC4R	0.001	0.016	0.32	1	-10000	0	1
SRC	0.004	0.036	0.32	5	-10000	0	5
PTN	-0.12	0.3	0.32	3	-0.86	53	56
FGFR/FGF/Syndecan-3	-0.002	0.041	-10000	0	-0.79	1	1
neuron projection morphogenesis	-0.06	0.16	-10000	0	-0.45	53	53
Syndecan-3/AgRP	0.006	0.056	-10000	0	-0.77	1	1
Syndecan-3/AgRP/MC4R	0.006	0.055	-10000	0	-0.74	1	1
Fyn/Cortactin	0	0	-10000	0	-10000	0	0
SDC3	-0.002	0.042	-10000	0	-0.81	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	-0.11	0.22	-10000	0	-0.5	85	85
IL8	-0.19	0.37	0.32	10	-0.86	85	95
Syndecan-3/Fyn/Cortactin	-0.002	0.038	-10000	0	-0.73	1	1
Syndecan-3/CASK	-0.002	0.04	-10000	0	-0.77	1	1
alpha-MSH/MC4R	-0.003	0.066	-10000	0	-0.67	3	3
Gamma Secretase	0	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.005	0.16	-10000	0	-0.77	12	12
UGCG	-0.071	0.22	-10000	0	-0.75	32	32
AKT1/mTOR/p70S6K/Hsp90/TERT	0.055	0.13	0.32	1	-0.37	8	9
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.053	0.22	-10000	0	-0.74	32	32
mol:DAG	-0.001	0.005	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.059	0.14	-10000	0	-0.61	9	9
FRAP1	0.002	0.2	0.34	1	-0.46	38	39
FOXO3	0.001	0.19	-10000	0	-0.44	44	44
AKT1	-0.008	0.21	0.33	1	-0.46	53	54
GAB2	0	0.001	-10000	0	-10000	0	0
SMPD1	-0.007	0.029	-10000	0	-10000	0	0
SGMS1	-0.007	0.029	-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	0.012	0.066	-10000	0	-0.84	2	2
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	-0.04	0.2	-10000	0	-0.37	72	72
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	-0.005	0.071	-10000	0	-0.93	2	2
RPS6KB1	0.026	0.038	-10000	0	-10000	0	0
mol:sphingomyelin	-0.001	0.005	-10000	0	-10000	0	0
natural killer cell activation	0	0.004	-10000	0	-10000	0	0
JAK3	0.002	0.056	0.32	4	-0.86	1	5
PIK3R1	-0.004	0.063	-10000	0	-0.86	2	2
JAK1	0.001	0.003	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MYC	-0.075	0.37	-10000	0	-1	47	47
MYB	0.13	0.1	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.003	0.18	0.33	1	-0.61	18	19
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.002	0.005	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.004	0.17	0.33	1	-0.59	18	19
Rac1/GDP	-0.004	0.059	-10000	0	-0.77	2	2
T cell proliferation	-0.009	0.19	-10000	0	-0.52	32	32
SHC1	0	0.001	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.015	0.03	0.1	38	-10000	0	38
PRKCZ	-0.012	0.2	-10000	0	-0.54	32	32
NF kappa B1 p50/RelA	-0.058	0.14	-10000	0	-0.61	9	9
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.036	0.17	-10000	0	-0.87	12	12
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL2RA	-0.007	0.13	0.32	11	-0.86	7	18
IL2RB	-0.066	0.23	-10000	0	-0.86	29	29
TERT	0.13	0.16	0.32	157	-10000	0	157
E2F1	0.14	0.1	0.35	37	-10000	0	37
SOS1	0	0.001	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.006	0.012	-10000	0	-0.043	38	38
PTPN11	0	0.001	-10000	0	-10000	0	0
IL2RG	-0.005	0.11	0.32	7	-0.86	5	12
actin cytoskeleton organization	-0.009	0.19	-10000	0	-0.52	32	32
GRB2	0	0.001	-10000	0	-10000	0	0
IL2	0.001	0.004	-10000	0	-10000	0	0
PIK3CA	-0.001	0.045	-10000	0	-0.86	1	1
Rac1/GTP	0.018	0.06	-10000	0	-0.75	2	2
LCK	-0.024	0.15	0.32	1	-0.86	11	12
BCL2	0.016	0.16	-10000	0	-0.6	7	7

×

Signaling events mediated by HDAC Class III

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
EP300	0	0	-10000	0	-10000	0	0
HDAC4	0.001	0.016	0.32	1	-10000	0	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.013	0.066	0.61	2	-0.26	1	3
CDKN1A	-0.027	0.16	-10000	0	-1	10	10
KAT2B	-0.007	0.077	-10000	0	-0.86	3	3
BAX	0	0	-10000	0	-10000	0	0
FOXO3	0.001	0.012	-10000	0	-10000	0	0
FOXO1	-0.009	0.089	-10000	0	-0.86	4	4
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	-0.35	0.42	-10000	0	-0.86	152	152
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.003	0.061	-10000	0	-0.67	3	3
PPARGC1A	-0.11	0.28	-10000	0	-0.86	46	46
FHL2	-0.088	0.26	-10000	0	-0.86	38	38
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.052	-10000	0	-0.63	2	2
HIST2H4A	0.013	0.066	0.26	1	-0.61	2	3
SIRT1/FOXO3a	0.001	0.047	-10000	0	-0.55	2	2
SIRT1	0.001	0.068	-10000	0	-0.82	2	2
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.047	-10000	0	-0.55	2	2
SIRT1/Histone H1b	0.005	0.048	-10000	0	-0.51	2	2
apoptosis	0	0.046	0.55	2	-10000	0	2
SIRT1/PGC1A	-0.073	0.2	-10000	0	-0.59	47	47
p53/SIRT1	0.007	0.081	0.43	9	-0.61	2	11
SIRT1/FOXO4	0.001	0.047	-10000	0	-0.54	2	2
FOXO1/FHL2/SIRT1	-0.061	0.18	-10000	0	-0.54	43	43
HIST1H1E	0.005	0.024	-10000	0	-10000	0	0
SIRT1/p300	0	0.052	-10000	0	-0.63	2	2
muscle cell differentiation	0.004	0.079	0.7	4	-10000	0	4
TP53	0.005	0.032	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.046	-10000	0	-0.55	2	2
CREBBP	0	0	-10000	0	-10000	0	0
MEF2D	0	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.28	0.33	-10000	0	-0.67	152	152
ACSS2	0	0.051	-10000	0	-0.63	2	2
SIRT1/PCAF/MYOD	-0.004	0.08	-10000	0	-0.7	4	4

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	-0.034	0.14	-9999	-0.58	22	22
E-cadherin/beta catenin	-0.04	0.16	-9999	-0.67	22	22
CTNNB1	0	0	-9999	-10000	0	0
JUP	0	0	-9999	-10000	0	0
CDH1	-0.051	0.2	-9999	-0.86	22	22

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	-0.002	0.03	-10000	0	-0.58	1	1
EPHB2	0.062	0.14	0.32	76	-0.86	1	77
Syndecan-2/TACI	0	0.05	-10000	0	-0.58	2	2
LAMA1	-0.087	0.3	0.32	20	-0.86	45	65
Syndecan-2/alpha2 ITGB1	0.058	0.13	0.38	29	-0.5	4	33
HRAS	0.002	0.023	0.32	2	-10000	0	2
Syndecan-2/CASK	0	0	-10000	0	-10000	0	0
ITGA5	0	0	-10000	0	-10000	0	0
BAX	0.003	0.12	-10000	0	-0.52	20	20
EPB41	0	0	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0	0	-10000	0	-10000	0	0
LAMA3	0.038	0.15	0.32	55	-0.86	4	59
EZR	-0.002	0.045	-10000	0	-0.86	1	1
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	-0.023	0.14	-10000	0	-0.86	10	10
Syndecan-2/MMP2	-0.023	0.13	-10000	0	-0.58	17	17
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.038	0.083	-10000	0	-10000	0	0
dendrite morphogenesis	0.044	0.096	-10000	0	-0.58	1	1
Syndecan-2/GM-CSF	0	0	-10000	0	-10000	0	0
determination of left/right symmetry	0.015	0.001	-10000	0	-10000	0	0
Syndecan-2/PKC delta	0	0	-10000	0	-10000	0	0
GNB2L1	0	0	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
Syndecan-2/RACK1	0.001	0.014	-10000	0	-10000	0	0
NF1	-0.002	0.045	-10000	0	-0.86	1	1
FGFR/FGF/Syndecan-2	0.015	0.001	-10000	0	-10000	0	0
ITGA2	0.055	0.12	0.32	65	-10000	0	65
MAPK8	-0.004	0.14	-10000	0	-0.58	20	20
Syndecan-2/alpha2/beta1 Integrin	-0.02	0.2	0.38	7	-0.49	45	52
Syndecan-2/Kininogen	-0.046	0.16	-10000	0	-0.58	29	29
ITGB1	0	0	-10000	0	-10000	0	0
SRC	0.003	0.023	-10000	0	-10000	0	0
Syndecan-2/CASK/Protein 4.1	0	0	-10000	0	-10000	0	0
extracellular matrix organization	0.003	0.026	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.002	0.03	-10000	0	-0.58	1	1
Syndecan-2/Caveolin-2/Ras	-0.013	0.088	-10000	0	-0.53	10	10
Syndecan-2/Laminin alpha3	0.027	0.1	0.22	55	-0.58	4	59
Syndecan-2/RasGAP	-0.002	0.036	-10000	0	-0.47	2	2
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
PRKCD	0	0	-10000	0	-10000	0	0
Syndecan-2 dimer	0.044	0.096	-10000	0	-0.58	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0	0.039	-10000	0	-0.45	2	2
RHOA	0	0	-10000	0	-10000	0	0
SDCBP	0	0	-10000	0	-10000	0	0
TNFRSF13B	0	0.073	0.32	5	-0.86	2	7
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
alpha2/beta1 Integrin	0.038	0.083	-10000	0	-10000	0	0
Syndecan-2/Synbindin	0	0	-10000	0	-10000	0	0
TGFB1	0.004	0.036	0.32	5	-10000	0	5
CASP3	-0.001	0.028	-10000	0	-0.54	1	1
FN1	-0.002	0.045	-10000	0	-0.86	1	1
Syndecan-2/IL8	-0.13	0.25	-10000	0	-0.58	85	85
SDC2	0.016	0.001	-10000	0	-10000	0	0
KNG1	-0.067	0.23	-10000	0	-0.86	29	29
Syndecan-2/Neurofibromin	-0.002	0.03	-10000	0	-0.58	1	1
TRAPPC4	0	0	-10000	0	-10000	0	0
CSF2	0	0	-10000	0	-10000	0	0
Syndecan-2/TGFB1	0.003	0.026	-10000	0	-10000	0	0
Syndecan-2/Syntenin/PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-2/Ezrin	-0.001	0.028	-10000	0	-0.53	1	1
PRKACA	-0.001	0.027	-10000	0	-0.53	1	1
angiogenesis	-0.13	0.25	-10000	0	-0.58	85	85
MMP2	-0.034	0.18	0.32	6	-0.86	17	23
IL8	-0.19	0.37	0.32	10	-0.86	85	95
calcineurin-NFAT signaling pathway	0	0.05	-10000	0	-0.58	2	2

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.007	0.046	0.32	8	-10000	0	8
Jak2/Leptin Receptor	-0.06	0.19	0.22	3	-0.46	62	65
PTP1B/AKT1	-0.007	0.032	-10000	0	-0.26	2	2
FYN	0	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.05	0.059	-10000	0	-0.29	2	2
EGFR	-0.019	0.14	-10000	0	-0.86	10	10
EGF/EGFR	0.034	0.13	0.24	40	-0.5	10	50
CSF1	-0.008	0.092	0.32	2	-0.86	4	6
AKT1	0	0.001	-10000	0	-10000	0	0
INSR	0	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.021	0.086	-10000	0	-0.46	12	12
Insulin Receptor/Insulin	-0.003	0.036	0.24	1	-10000	0	1
HCK	-0.028	0.15	-10000	0	-0.86	12	12
CRK	0	0	-10000	0	-10000	0	0
TYK2	0.054	0.056	-10000	0	-0.28	1	1
EGF	0.076	0.14	0.32	88	-10000	0	88
YES1	0	0	-10000	0	-10000	0	0
CAV1	0.058	0.065	-10000	0	-0.31	1	1
TXN	0.002	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.007	0.029	-10000	0	-10000	0	0
cell migration	-0.05	0.059	0.29	2	-10000	0	2
STAT3	0	0	-10000	0	-10000	0	0
PRLR	-0.023	0.15	-10000	0	-0.86	11	11
ITGA2B	0.007	0.046	0.32	8	-10000	0	8
CSF1R	-0.021	0.13	-10000	0	-0.86	9	9
Prolactin Receptor/Prolactin	-0.012	0.12	-10000	0	-0.67	11	11
FGR	-0.005	0.063	-10000	0	-0.86	2	2
PTP1B/p130 Cas	-0.008	0.031	-10000	0	-0.27	2	2
Crk/p130 Cas	-0.007	0.029	-10000	0	-10000	0	0
DOK1	0.057	0.053	-10000	0	-10000	0	0
JAK2	0.038	0.072	-10000	0	-0.34	4	4
Jak2/Leptin Receptor/Leptin	-0.11	0.22	-10000	0	-0.63	51	51
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
PTPN1	0.05	0.059	-10000	0	-0.3	2	2
LYN	0	0	-10000	0	-10000	0	0
CDH2	-0.025	0.15	-10000	0	-0.86	11	11
SRC	0.036	0.031	-10000	0	-10000	0	0
ITGB3	-0.07	0.24	-10000	0	-0.86	30	30
CAT1/PTP1B	-0.061	0.19	-10000	0	-0.49	32	32
CAPN1	0.002	0.005	-10000	0	-10000	0	0
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.006	0.063	-10000	0	-0.75	2	2
mol:H2O2	-0.001	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.11	0.24	-10000	0	-0.67	51	51
negative regulation of transcription	0.038	0.071	-10000	0	-0.34	4	4
FCGR2A	0.002	0.023	0.32	2	-10000	0	2
FER	0.002	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.049	0.19	-10000	0	-0.67	30	30
BLK	-0.15	0.33	0.32	2	-0.86	65	67
Insulin Receptor/Insulin/Shc	0.003	0.023	-10000	0	-10000	0	0
RHOA	0.002	0.005	-10000	0	-10000	0	0
LEPR	-0.14	0.32	-10000	0	-0.86	62	62
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0	-10000	0	-10000	0	0
mol:NADPH	0.002	0.002	-10000	0	-10000	0	0
TRPV6	-0.13	0.23	-10000	0	-0.66	32	32
PRL	0.004	0.029	0.32	3	-10000	0	3
SOCS3	-0.19	0.52	-10000	0	-1.5	50	50
SPRY2	-0.01	0.1	-10000	0	-0.87	5	5
Insulin Receptor/Insulin/IRS1	0.003	0.023	-10000	0	-10000	0	0
CSF1/CSF1R	-0.021	0.089	0.27	2	-0.45	13	15
Ras protein signal transduction	-0.004	0.02	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
INS	0.005	0.037	0.32	5	-10000	0	5
LEP	0.01	0.056	0.32	12	-10000	0	12
STAT5B	0.048	0.057	-10000	0	-0.24	3	3
STAT5A	0.049	0.057	-10000	0	-0.24	3	3
GRB2	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.002	0.052	0.27	8	-0.27	2	10
CSN2	-0.014	0.041	-10000	0	-10000	0	0
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
LAT	0.036	0.032	0.32	1	-10000	0	1
YBX1	0	0	-10000	0	-10000	0	0
LCK	-0.025	0.15	0.32	1	-0.86	11	12
SHC1	0	0	-10000	0	-10000	0	0
NOX4	0.12	0.15	0.32	142	-10000	0	142

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.014	0.065	-10000	0	-0.67	2	2
adherens junction organization	0.015	0.086	-10000	0	-0.32	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.024	0.1	-10000	0	-0.54	11	11
FMN1	-0.017	0.078	-10000	0	-0.32	21	21
mol:IP3	-0.014	0.064	-10000	0	-0.64	2	2
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.021	0.081	-10000	0	-0.34	22	22
CTNNB1	0.001	0.005	-10000	0	-10000	0	0
AKT1	-0.016	0.068	-10000	0	-0.63	2	2
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.033	0.13	-10000	0	-0.56	22	22
CTNND1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.014	0.083	-10000	0	-0.31	22	22
VASP	-0.02	0.076	-10000	0	-0.32	22	22
ZYX	-0.02	0.076	-10000	0	-0.32	22	22
JUB	-0.021	0.079	-10000	0	-0.32	23	23
EGFR(dimer)	-0.033	0.12	-10000	0	-0.42	28	28
E-cadherin/beta catenin-gamma catenin	-0.033	0.13	-10000	0	-0.56	22	22
mol:PI-3-4-5-P3	-0.017	0.074	-10000	0	-0.68	2	2
PIK3CA	-0.002	0.046	-10000	0	-0.88	1	1
PI3K	-0.017	0.076	-10000	0	-0.71	2	2
FYN	-0.047	0.17	-10000	0	-0.38	72	72
mol:Ca2+	-0.014	0.063	-10000	0	-0.62	2	2
JUP	0.001	0.005	-10000	0	-10000	0	0
PIK3R1	-0.005	0.064	-10000	0	-0.87	2	2
mol:DAG	-0.014	0.064	-10000	0	-0.64	2	2
CDH1	-0.051	0.2	-10000	0	-0.86	22	22
RhoA/GDP	-0.024	0.1	-10000	0	-0.54	11	11
establishment of polarity of embryonic epithelium	0.014	0.083	-10000	0	-0.31	22	22
SRC	0.004	0.036	0.32	5	-10000	0	5
RAC1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
EGFR	-0.023	0.14	-10000	0	-0.86	10	10
CASR	-0.095	0.19	-10000	0	-0.46	72	72
RhoA/GTP	-0.012	0.056	-10000	0	-0.55	2	2
AKT2	-0.016	0.068	-10000	0	-0.63	2	2
actin cable formation	0.02	0.083	-10000	0	-10000	0	0
apoptosis	0.015	0.067	0.63	2	-10000	0	2
CTNNA1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.026	0.11	-10000	0	-0.6	11	11
PIP5K1A	-0.02	0.076	-10000	0	-0.32	22	22
PLCG1	-0.014	0.066	-10000	0	-0.66	2	2
Rac1/GTP	-0.03	0.11	-10000	0	-0.56	10	10
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0	0.001	-10000	0	-10000	0	0
HDAC2	0	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.011	0.079	-10000	0	-0.58	7	7
forebrain development	-0.025	0.14	-10000	0	-0.52	19	19
GNAO1	-0.41	0.43	-10000	0	-0.86	178	178
SMO/beta Arrestin2	-0.007	0.069	-10000	0	-0.67	4	4
SMO	-0.009	0.089	-10000	0	-0.86	4	4
ARRB2	0	0	-10000	0	-10000	0	0
GLI3/SPOP	-0.003	0.029	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.063	-10000	0	-0.86	2	2
XPO1	0.01	0.003	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.045	0.11	-10000	0	-0.5	18	18
SAP30	0	0.001	-10000	0	-10000	0	0
mol:GDP	-0.009	0.089	-10000	0	-0.86	4	4
MIM/GLI2A	0.014	0.007	-10000	0	-10000	0	0
IFT88	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GLI2	0.017	0.07	-10000	0	-10000	0	0
GLI3	0.032	0.04	0.3	1	-0.32	3	4
CSNK1D	0	0	-10000	0	-10000	0	0
CSNK1E	0.001	0.016	0.32	1	-10000	0	1
SAP18	0	0.001	-10000	0	-10000	0	0
embryonic digit morphogenesis	0	0	-10000	0	-10000	0	0
GNG2	-0.007	0.077	-10000	0	-0.86	3	3
Gi family/GTP	-0.14	0.2	-10000	0	-0.34	179	179
SIN3B	0	0.001	-10000	0	-10000	0	0
SIN3A	0	0.001	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.003	0.027	-10000	0	-10000	0	0
GLI2/Su(fu)	-0.015	0.056	-10000	0	-0.44	1	1
FOXA2	-0.007	0.096	-10000	0	-1.3	2	2
neural tube patterning	-0.025	0.14	-10000	0	-0.52	19	19
SPOP	0	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	-0.003	0.028	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
CSNK1G2	0	0	-10000	0	-10000	0	0
CSNK1G3	0	0	-10000	0	-10000	0	0
MTSS1	0.014	0.007	-10000	0	-10000	0	0
embryonic limb morphogenesis	-0.025	0.14	-10000	0	-0.52	19	19
SUFU	-0.003	0.032	-10000	0	-0.31	4	4
LGALS3	0.024	0.084	0.32	28	-10000	0	28
catabolic process	-0.013	0.047	-10000	0	-0.42	1	1
GLI3A/CBP	0.006	0.039	-10000	0	-0.39	1	1
KIF3A	0	0	-10000	0	-10000	0	0
GLI1	-0.025	0.14	-10000	0	-0.53	19	19
RAB23	0	0	-10000	0	-10000	0	0
CSNK1A1	0	0	-10000	0	-10000	0	0
IFT172	0	0	-10000	0	-10000	0	0
RBBP7	0	0.001	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.014	0.066	-10000	0	-10000	0	0
GNAZ	0.15	0.17	0.32	176	-0.86	1	177
RBBP4	0	0.001	-10000	0	-10000	0	0
CSNK1G1	0	0	-10000	0	-10000	0	0
PIAS1	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
GLI2/SPOP	-0.016	0.054	-10000	0	-10000	0	0
STK36	0.01	0.003	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.11	0.17	-10000	0	-0.6	7	7
PTCH1	-0.056	0.29	-10000	0	-1.2	19	19
MIM/GLI1	-0.015	0.14	-10000	0	-0.52	18	18
CREBBP	0.006	0.039	-10000	0	-0.39	1	1
Su(fu)/SIN3/HDAC complex	0.002	0.013	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.001	0.084	-10000	0	-0.59	6	6
BIRC5	0.21	0.15	0.32	245	-10000	0	245
NFKBIA	0.02	0.033	-10000	0	-10000	0	0
CPEB1	0.01	0.056	0.32	12	-10000	0	12
AKT1	0.02	0.033	-10000	0	-10000	0	0
NDEL1	0	0	-10000	0	-10000	0	0
Aurora A/BRCA1	0.011	0.034	0.24	1	-10000	0	1
NDEL1/TACC3	0.035	0.073	-10000	0	-10000	0	0
GADD45A	-0.014	0.11	-10000	0	-0.86	6	6
GSK3B	0	0.001	-10000	0	-10000	0	0
PAK1/Aurora A	0.011	0.036	-10000	0	-10000	0	0
MDM2	0	0	-10000	0	-10000	0	0
JUB	-0.002	0.045	-10000	0	-0.86	1	1
TPX2	0.037	0.048	-10000	0	-10000	0	0
TP53	0.017	0.027	-10000	0	-10000	0	0
DLG7	0.007	0.037	-10000	0	-10000	0	0
AURKAIP1	0	0	-10000	0	-10000	0	0
ARHGEF7	0	0	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.037	0.077	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.01	0.034	0.24	1	-10000	0	1
AURKA	0.012	0.053	-10000	0	-10000	0	0
AURKB	0.1	0.084	0.19	172	-10000	0	172
CDC25B	0.019	0.034	-10000	0	-10000	0	0
G2/M transition checkpoint	0.008	0.043	-10000	0	-0.53	1	1
mRNA polyadenylation	0.014	0.047	0.24	5	-10000	0	5
Aurora A/CPEB	0.014	0.048	0.24	5	-10000	0	5
Aurora A/TACC1/TRAP/chTOG	0.017	0.031	-10000	0	-10000	0	0
BRCA1	0.001	0.016	0.32	1	-10000	0	1
centrosome duplication	0.011	0.036	-10000	0	-10000	0	0
regulation of centrosome cycle	0.034	0.071	-10000	0	-10000	0	0
spindle assembly	0.017	0.03	-10000	0	-10000	0	0
TDRD7	0	0	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.12	0.1	0.4	1	-0.46	2	3
CENPA	0.11	0.092	0.2	178	-10000	0	178
Aurora A/PP2A	0.011	0.036	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.032	0.029	-10000	0	-10000	0	0
negative regulation of DNA binding	0.016	0.027	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0	0	-10000	0	-10000	0	0
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
Ajuba/Aurora A	0.009	0.043	-10000	0	-0.54	1	1
mitotic prometaphase	-0.02	0.019	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.052	-10000	0	-10000	0	0
TACC1	0	0	-10000	0	-10000	0	0
TACC3	0.039	0.1	0.32	46	-10000	0	46
Aurora A/Antizyme1	0.014	0.032	-10000	0	-10000	0	0
Aurora A/RasGAP	0.008	0.057	-10000	0	-0.59	2	2
OAZ1	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0	0.001	-10000	0	-10000	0	0
GIT1	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.037	0.048	-10000	0	-10000	0	0
PPP2R5D	0	0	-10000	0	-10000	0	0
Aurora A/TPX2	0.031	0.059	-10000	0	-10000	0	0
PAK1	0	0	-10000	0	-10000	0	0
CKAP5	0	0	-10000	0	-10000	0	0

×

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

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
BAG4	-0.028	0.15	-10000	0	-0.86	12	12
Caspase 8 (4 units)	-0.06	0.16	-10000	0	-0.8	10	10
NEF	-0.007	0.042	-10000	0	-10000	0	0
NFKBIA	0.001	0.012	-10000	0	-10000	0	0
BIRC3	0.007	0.086	-10000	0	-0.86	2	2
CYCS	-0.02	0.17	-10000	0	-0.77	10	10
RIPK1	0	0	-10000	0	-10000	0	0
CD247	-0.011	0.082	0.39	1	-0.96	2	3
MAP2K7	-0.018	0.16	-10000	0	-0.39	44	44
protein ubiquitination	0.023	0.1	-10000	0	-0.49	5	5
CRADD	-0.002	0.045	-10000	0	-0.86	1	1
DAXX	0	0	-10000	0	-10000	0	0
FAS	-0.028	0.15	-10000	0	-0.86	12	12
BID	-0.061	0.17	-10000	0	-0.42	49	49
NF-kappa-B/RelA/I kappa B alpha	0.005	0.044	-10000	0	-0.35	2	2
TRADD	-0.002	0.045	-10000	0	-0.86	1	1
MAP3K5	-0.1	0.28	-10000	0	-0.86	43	43
CFLAR	0	0	-10000	0	-10000	0	0
FADD	0.001	0.016	0.32	1	-10000	0	1
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.005	0.045	-10000	0	-0.35	2	2
MAPK8	-0.035	0.19	-10000	0	-0.55	33	33
APAF1	0	0	-10000	0	-10000	0	0
TRAF1	0.001	0.016	0.32	1	-10000	0	1
TRAF2	0	0	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.065	0.18	-10000	0	-0.42	58	58
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.035	0.11	-10000	0	-0.7	5	5
CHUK	0.022	0.11	-10000	0	-0.55	5	5
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.073	0.2	-10000	0	-0.56	49	49
TCRz/NEF	-0.016	0.097	0.38	1	-0.44	15	16
TNF	-0.031	0.17	0.32	2	-0.86	14	16
FASLG	-0.036	0.19	0.37	1	-0.94	15	16
NFKB1	0.001	0.012	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.04	0.15	-10000	0	-0.58	26	26
CASP6	-0.044	0.12	-10000	0	-0.55	10	10
CASP7	0.027	0.14	-10000	0	-0.52	12	12
RELA	0.001	0.012	-10000	0	-10000	0	0
CASP2	0	0	-10000	0	-10000	0	0
CASP3	0.027	0.14	-10000	0	-0.52	13	13
TNFRSF1A	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.022	0.12	-10000	0	-0.67	12	12
CASP8	0	0	-10000	0	-10000	0	0
CASP9	0	0	-10000	0	-10000	0	0
MAP3K14	0.015	0.12	-10000	0	-0.63	5	5
APAF-1/Caspase 9	-0.031	0.11	0.26	1	-0.48	12	13
BCL2	-0.026	0.18	-10000	0	-0.5	34	34

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.025	0.14	0.86	11	-10000	0	11
PI3K Class IB/PDE3B	-0.025	0.15	-10000	0	-0.86	11	11
PDE3B	-0.025	0.15	-10000	0	-0.86	11	11

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.004	0.1	-10000	0	-0.44	17	17
CRKL	0.006	0.082	-10000	0	-0.42	11	11
HRAS	-0.025	0.12	-10000	0	-0.63	7	7
mol:PIP3	-0.006	0.081	-10000	0	-0.4	12	12
SPRED1	-0.002	0.045	-10000	0	-0.86	1	1
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.02	0.08	-10000	0	-0.44	11	11
FOXO3	0.011	0.076	-10000	0	-0.38	11	11
AKT1	0.004	0.081	-10000	0	-0.42	11	11
BAD	0.011	0.076	-10000	0	-0.38	11	11
megakaryocyte differentiation	-0.028	0.15	-10000	0	-0.49	31	31
GSK3B	0.011	0.076	-10000	0	-0.38	11	11
RAF1	0.013	0.1	-10000	0	-0.48	7	7
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.02	0.08	-10000	0	-0.44	11	11
STAT1	-0.041	0.21	-10000	0	-1.1	11	11
HRAS/SPRED1	-0.023	0.092	-10000	0	-0.48	7	7
cell proliferation	-0.027	0.14	-10000	0	-0.5	29	29
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
TEC	-0.014	0.11	-10000	0	-0.86	6	6
RPS6KB1	0	0.086	-10000	0	-0.44	11	11
HRAS/SPRED2	-0.022	0.09	-10000	0	-0.48	7	7
LYN/TEC/p62DOK	-0.025	0.089	-10000	0	-0.43	17	17
MAPK3	0.024	0.076	-10000	0	-0.32	7	7
STAP1	-0.02	0.081	-10000	0	-0.45	11	11
GRAP2	-0.016	0.14	0.32	6	-0.86	9	15
JAK2	-0.066	0.16	-10000	0	-0.87	12	12
STAT1 (dimer)	-0.039	0.21	-10000	0	-1.1	11	11
mol:Gleevec	-0.001	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.039	0.13	-10000	0	-0.47	27	27
actin filament polymerization	0	0.085	-10000	0	-0.43	11	11
LYN	0	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.027	0.11	-10000	0	-0.62	11	11
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
CBL/CRKL/GRB2	-0.015	0.063	-10000	0	-0.38	2	2
PI3K	-0.022	0.092	-10000	0	-0.49	12	12
PTEN	-0.005	0.063	-10000	0	-0.86	2	2
SCF/KIT/EPO/EPOR	-0.21	0.33	-10000	0	-1.5	11	11
MAPK8	-0.047	0.14	-10000	0	-0.51	29	29
STAT3 (dimer)	0	0.085	-10000	0	-0.44	11	11
positive regulation of transcription	0.024	0.064	-10000	0	-0.26	7	7
mol:GDP	-0.033	0.13	0.29	1	-0.65	9	10
PIK3C2B	-0.02	0.08	-10000	0	-0.44	11	11
CBL/CRKL	-0.015	0.069	-10000	0	-0.39	11	11
FER	-0.02	0.08	-10000	0	-0.44	11	11
SH2B3	-0.02	0.08	-10000	0	-0.44	11	11
PDPK1	0.001	0.076	-10000	0	-0.38	11	11
SNAI2	-0.021	0.089	-10000	0	-0.46	13	13
positive regulation of cell proliferation	-0.018	0.15	-10000	0	-0.77	11	11
KITLG	0.012	0.032	0.31	4	-10000	0	4
cell motility	-0.018	0.15	-10000	0	-0.77	11	11
PTPN6	0.005	0.007	-10000	0	-10000	0	0
EPOR	0.013	0.065	-10000	0	-10000	0	0
STAT5A (dimer)	-0.013	0.13	-10000	0	-0.63	11	11
SOCS1	-0.001	0.071	0.32	4	-0.86	2	6
cell migration	0.004	0.1	0.48	13	-10000	0	13
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.31	0.43	0.32	12	-0.86	136	148
VAV1	-0.039	0.18	-10000	0	-0.86	17	17
GRB10	-0.02	0.08	-10000	0	-0.44	11	11
PTPN11	0.001	0.004	-10000	0	-10000	0	0
SCF/KIT	-0.024	0.085	-10000	0	-0.47	11	11
GO:0007205	0	0.005	-10000	0	-10000	0	0
MAP2K1	0.022	0.083	-10000	0	-0.36	7	7
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.021	0.26	-10000	0	-1.5	11	11
MAP2K2	0.022	0.083	-10000	0	-0.36	7	7
SHC/Grb2/SOS1	-0.018	0.07	-10000	0	-0.41	11	11
STAT5A	-0.013	0.13	-10000	0	-0.65	11	11
GRB2	0	0	-10000	0	-10000	0	0
response to radiation	-0.002	0.093	-10000	0	-0.45	13	13
SHC/GRAP2	-0.013	0.11	-10000	0	-0.67	9	9
PTPRO	-0.048	0.14	-10000	0	-0.5	31	31
SH2B2	-0.019	0.08	-10000	0	-0.44	11	11
DOK1	0	0	-10000	0	-10000	0	0
MATK	-0.023	0.096	-10000	0	-0.49	13	13
CREBBP	0.025	0.014	-10000	0	-10000	0	0
BCL2	0.012	0.1	-10000	0	-1.6	1	1

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.015	0.12	0.32	1	-0.86	7	8
ANTXR2	-0.012	0.099	-10000	0	-0.86	5	5
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.019	-10000	0	-0.11	12	12
monocyte activation	-0.044	0.17	-10000	0	-0.57	30	30
MAP2K2	-0.001	0.014	-10000	0	-10000	0	0
MAP2K1	-0.003	0.016	-10000	0	-10000	0	0
MAP2K7	-0.003	0.016	-10000	0	-10000	0	0
MAP2K6	-0.012	0.073	-10000	0	-0.52	7	7
CYAA	-0.016	0.091	-10000	0	-0.51	12	12
MAP2K4	-0.003	0.016	-10000	0	-10000	0	0
IL1B	-0.078	0.2	-10000	0	-0.52	64	64
Channel	-0.017	0.097	-10000	0	-0.54	12	12
NLRP1	-0.003	0.016	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.004	0.023	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.019	0.11	12	-10000	0	12
MAPK3	-0.003	0.016	-10000	0	-10000	0	0
MAPK1	-0.003	0.016	-10000	0	-10000	0	0
PGR	-0.089	0.2	-10000	0	-0.53	61	61
PA/Cellular Receptors	-0.018	0.1	-10000	0	-0.59	12	12
apoptosis	-0.003	0.019	-10000	0	-0.11	12	12
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.016	0.091	-10000	0	-0.51	12	12
macrophage activation	0.014	0.017	-10000	0	-10000	0	0
TNF	-0.031	0.17	0.32	2	-0.86	14	16
VCAM1	-0.044	0.18	-10000	0	-0.58	30	30
platelet activation	-0.004	0.023	-10000	0	-10000	0	0
MAPKKK cascade	-0.009	0.025	0.097	19	-10000	0	19
IL18	-0.001	0.089	-10000	0	-0.53	10	10
negative regulation of macrophage activation	-0.003	0.019	-10000	0	-0.11	12	12
LEF	-0.003	0.019	-10000	0	-0.11	12	12
CASP1	-0.003	0.017	-10000	0	-0.091	11	11
mol:cAMP	-0.004	0.023	-10000	0	-10000	0	0
necrosis	-0.003	0.019	-10000	0	-0.11	12	12
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.016	0.092	-10000	0	-0.52	12	12
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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
SPHK2	0.027	0.034	-10000	0	-10000	0	0
MAP4K4	-0.008	0.06	-10000	0	-10000	0	0
BAG4	-0.028	0.15	-10000	0	-0.86	12	12
PKC zeta/ceramide	-0.027	0.11	-10000	0	-0.52	17	17
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	0.007	0.088	0.32	14	-0.86	2	16
BAX	0.003	0.007	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.016	0.02	-10000	0	-10000	0	0
BAD	0.003	0.014	-10000	0	-10000	0	0
SMPD1	0.014	0.056	-10000	0	-0.26	14	14
RB1	0.003	0.014	-10000	0	-10000	0	0
FADD/Caspase 8	-0.007	0.056	-10000	0	-10000	0	0
MAP2K4	0.01	0.014	-10000	0	-10000	0	0
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.01	0.014	-10000	0	-10000	0	0
EGF	0.075	0.13	0.32	88	-10000	0	88
mol:ceramide	-0.004	0.015	-10000	0	-10000	0	0
MADD	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.027	0.036	-10000	0	-10000	0	0
ASAH1	0.001	0.016	0.32	1	-10000	0	1
negative regulation of cell cycle	0.003	0.014	-10000	0	-10000	0	0
cell proliferation	-0.16	0.2	-10000	0	-0.4	145	145
BID	0.022	0.046	-10000	0	-10000	0	0
MAP3K1	0.003	0.014	-10000	0	-10000	0	0
EIF2A	0.016	0.013	-10000	0	-10000	0	0
TRADD	-0.002	0.045	-10000	0	-0.86	1	1
CRADD	-0.002	0.045	-10000	0	-0.86	1	1
MAPK3	0.019	0.013	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.019	0.013	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.003	0.007	-10000	0	-10000	0	0
FADD	-0.008	0.06	-10000	0	-10000	0	0
KSR1	0.004	0.014	-10000	0	-10000	0	0
MAPK8	-0.019	0.12	-10000	0	-0.34	34	34
PRKRA	0.003	0.014	-10000	0	-10000	0	0
PDGFA	0.02	0.078	0.32	24	-10000	0	24
TRAF2	0	0	-10000	0	-10000	0	0
IGF1	-0.34	0.42	-10000	0	-0.86	145	145
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.004	0.015	-10000	0	-10000	0	0
CTSD	0	0	-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	-0.17	0.21	-10000	0	-0.43	145	145
PRKCD	0	0	-10000	0	-10000	0	0
PRKCZ	-0.039	0.18	-10000	0	-0.86	17	17
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.027	0.036	-10000	0	-10000	0	0
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.009	0.064	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.04	0.15	-10000	0	-0.58	26	26
mol:Sphingosine-1-phosphate	0.027	0.034	-10000	0	-10000	0	0
MAP2K1	0.016	0.013	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	0.004	0.014	0.2	1	-10000	0	1
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.022	0.12	-10000	0	-0.67	12	12
EIF2AK2	0.01	0.014	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.021	0.11	-10000	0	-0.58	14	14
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.004	0.036	-10000	0	-10000	0	0
MAP2K2	0.016	0.013	-10000	0	-10000	0	0
SMPD3	-0.026	0.15	-10000	0	-0.38	48	48
TNF	-0.031	0.17	0.32	2	-0.86	14	16
PKC zeta/PAR4	-0.031	0.14	-10000	0	-0.67	17	17
mol:PHOSPHOCHOLINE	-0.038	0.045	-10000	0	-0.18	7	7
NF kappa B1/RelA/I kappa B alpha	-0.023	0.1	-10000	0	-0.5	17	17
AIFM1	0.004	0.014	0.2	1	-10000	0	1
BCL2	-0.002	0.045	-10000	0	-0.86	1	1

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.007	0.035	-10000	0	-10000	0	0
VDR	-0.009	0.14	0.32	11	-0.86	8	19
FAM120B	-0.002	0.045	-10000	0	-0.86	1	1
RXRs/LXRs/DNA/9cRA	-0.001	0.084	-10000	0	-0.32	8	8
RXRs/LXRs/DNA/Oxysterols	-0.008	0.1	-10000	0	-0.4	17	17
MED1	0	0	-10000	0	-10000	0	0
mol:9cRA	0.003	0.013	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.019	0.079	-10000	0	-0.35	20	20
RXRs/NUR77	-0.072	0.22	-10000	0	-0.53	63	63
RXRs/PPAR	0.008	0.061	-10000	0	-0.34	6	6
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.008	0.1	-10000	0	-0.67	8	8
RARs/VDR/DNA/Vit D3	-0.029	0.14	-10000	0	-0.52	24	24
RARA	0	0	-10000	0	-10000	0	0
NCOA1	0	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.009	0.14	0.32	11	-0.86	8	19
RARs/RARs/DNA/9cRA	-0.023	0.11	-10000	0	-0.51	17	17
RARG	0	0	-10000	0	-10000	0	0
RPS6KB1	0.007	0.029	-10000	0	-10000	0	0
RARs/THRs/DNA/SMRT	-0.019	0.079	-10000	0	-0.35	20	20
THRA	0	0	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	-0.008	0.1	-10000	0	-0.67	8	8
RXRs/PPAR/9cRA/PGJ2/DNA	0.01	0.1	-10000	0	-0.52	6	6
NR1H4	-0.023	0.14	-10000	0	-0.86	10	10
RXRs/LXRs/DNA	0.01	0.1	-10000	0	-0.48	6	6
NR1H2	0.011	0.009	-10000	0	-10000	0	0
NR1H3	0.011	0.011	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.006	0.12	0.36	4	-0.5	14	18
NR4A1	-0.13	0.31	-10000	0	-0.86	58	58
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.006	0.083	-10000	0	-0.35	15	15
RXRG	0.034	0.14	0.32	44	-0.86	5	49
RXR alpha/CCPG	-0.004	0.049	-10000	0	-0.66	2	2
RXRA	0.008	0.046	-10000	0	-0.86	1	1
RXRB	0.01	0.011	-10000	0	-10000	0	0
THRB	-0.007	0.077	-10000	0	-0.86	3	3
PPARG	0.001	0.016	0.32	1	-10000	0	1
PPARD	0	0	-10000	0	-10000	0	0
TNF	0.01	0.25	-10000	0	-1.2	14	14
mol:Oxysterols	0.003	0.011	-10000	0	-10000	0	0
cholesterol transport	-0.008	0.1	-10000	0	-0.39	17	17
PPARA	0	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	-0.039	0.18	-10000	0	-0.86	17	17
RXRs/NUR77/BCL2	-0.05	0.14	-10000	0	-0.35	64	64
SREBF1	0.04	0.12	-10000	0	-1.2	1	1
RXRs/RXRs/DNA/9cRA	0.01	0.1	-10000	0	-0.52	6	6
ABCA1	0.035	0.15	-10000	0	-1.2	3	3
RARs/THRs	-0.027	0.11	-10000	0	-0.5	20	20
RXRs/FXR	-0.001	0.14	-10000	0	-0.56	15	15
BCL2	-0.002	0.045	-10000	0	-0.86	1	1

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.014	0.025	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.002	0.022	-10000	0	-10000	0	0
STXBP1	-0.005	0.063	-10000	0	-0.86	2	2
ACh/CHRNA1	0.003	0.061	0.26	15	-10000	0	15
RAB3GAP2/RIMS1/UNC13B	0.002	0.021	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.003	0.028	0.32	3	-10000	0	3
mol:ACh	0	0.048	-10000	0	-0.16	30	30
RAB3GAP2	0	0	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.015	0.068	-10000	0	-0.53	2	2
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.003	0.061	0.26	15	-10000	0	15
UNC13B	0.001	0.016	0.32	1	-10000	0	1
CHRNA1	0.013	0.062	0.32	15	-10000	0	15
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.094	0.24	0.24	20	-0.63	60	80
SNAP25	-0.021	0.12	-10000	0	-0.39	30	30
VAMP2	0	0	-10000	0	-10000	0	0
SYT1	-0.12	0.33	0.32	22	-0.86	60	82
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.001	0.048	-10000	0	-0.59	2	2
STX1A/SNAP25 fragment 1/VAMP2	-0.015	0.068	-10000	0	-0.53	2	2

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.036	0.14	-10000	0	-0.61	22	22
KLHL20	-0.026	0.069	-10000	0	-0.25	15	15
CYFIP2	-0.051	0.2	-10000	0	-0.86	22	22
Rac1/GDP	0.026	0.099	-10000	0	-0.37	21	21
ENAH	-0.035	0.14	-10000	0	-0.61	22	22
AP1M1	0	0	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CTNNB1	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.018	0.073	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.027	0.061	-10000	0	-0.2	26	26
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.035	0.14	-10000	0	-0.53	27	27
RAPGEF1	0.012	0.13	-10000	0	-0.51	22	22
CTNND1	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.038	0.15	-10000	0	-0.63	22	22
CRK	0.003	0.14	-10000	0	-0.56	22	22
E-cadherin/gamma catenin/alpha catenin	-0.034	0.14	-10000	0	-0.58	22	22
alphaE/beta7 Integrin	-0.005	0.083	-10000	0	-0.67	5	5
IQGAP1	0	0	-10000	0	-10000	0	0
NCKAP1	0	0	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0	0	-10000	0	-10000	0	0
DLG1	-0.036	0.14	-10000	0	-0.61	22	22
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.015	0.056	-10000	0	-0.37	1	1
MLLT4	0	0	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.028	0.12	-10000	0	-0.54	20	20
PI3K	-0.019	0.074	-10000	0	-0.51	1	1
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	-0.04	0.16	-10000	0	-0.67	22	22
TIAM1	-0.046	0.19	-10000	0	-0.86	20	20
E-cadherin(dimer)/Ca2+	-0.03	0.12	-10000	0	-0.5	22	22
AKT1	-0.011	0.041	-10000	0	-0.26	1	1
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
CDH1	-0.051	0.2	-10000	0	-0.86	22	22
RhoA/GDP	0.026	0.099	-10000	0	-0.37	21	21
actin cytoskeleton organization	-0.019	0.051	0.11	1	-0.24	5	6
CDC42/GDP	0.026	0.099	-10000	0	-0.37	21	21
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.021	0.085	-10000	0	-0.36	22	22
ITGB7	-0.012	0.099	-10000	0	-0.86	5	5
RAC1	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.031	0.12	-10000	0	-0.53	22	22
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.03	0.12	-10000	0	-0.51	22	22
mol:GDP	0.022	0.12	-10000	0	-0.44	22	22
CDC42/GTP/IQGAP1	0	0	-10000	0	-10000	0	0
JUP	0	0	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	-0.022	0.088	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.018	0.058	0.2	1	-0.28	14	15
NME1	0.002	0.023	0.32	2	-10000	0	2
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.036	0.14	-10000	0	-0.61	22	22
regulation of cell-cell adhesion	-0.016	0.064	-10000	0	-10000	0	0
WASF2	-0.014	0.031	-10000	0	-0.14	1	1
Rap1/GTP	-0.021	0.084	-10000	0	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.033	0.13	-10000	0	-0.5	27	27
CCND1	-0.022	0.074	0.23	1	-0.36	14	15
VAV2	0.007	0.14	-10000	0	-0.54	22	22
RAP1/GDP	-0.021	0.084	-10000	0	-10000	0	0
adherens junction assembly	-0.035	0.14	-10000	0	-0.58	22	22
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0	0	-10000	0	-10000	0	0
PIP5K1C	0	0	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.031	0.13	-10000	0	-0.48	27	27
E-cadherin/beta catenin	-0.031	0.12	-10000	0	-0.53	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.035	0.14	-10000	0	-0.61	22	22
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
Rac1/GTP	-0.043	0.12	0.21	1	-0.43	15	16
E-cadherin/beta catenin/alpha catenin	-0.034	0.14	-10000	0	-0.58	22	22
ITGAE	0.006	0.043	0.32	7	-10000	0	7
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.039	0.15	-10000	0	-0.65	22	22

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.002	0.023	0.32	2	-10000	0	2
EGFR	-0.023	0.14	-10000	0	-0.86	10	10
EGF/EGFR	0.009	0.14	0.3	1	-0.48	21	22
EGF/EGFR dimer/SHC/GRB2/SOS1	0.03	0.12	-10000	0	-0.49	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	-0.002	0.069	0.32	3	-0.86	2	5
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.075	0.13	0.32	88	-10000	0	88
EGF/EGFR dimer/SHC	0.031	0.13	-10000	0	-0.57	10	10
mol:GDP	0.026	0.11	-10000	0	-0.48	10	10
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	-0.02	0.13	0.32	1	-0.86	9	10
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	0.013	0.089	-10000	0	-0.46	7	7
SHC1	0	0	-10000	0	-10000	0	0
HRAS/GDP	0.021	0.1	-10000	0	-0.47	7	7
FRAP1	0.004	0.084	-10000	0	-0.47	10	10
EGF/EGFR dimer	0.032	0.15	-10000	0	-0.66	10	10
SOS1	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.017	0.12	-10000	0	-0.67	11	11

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.02	0.16	0.32	9	-0.86	12	21
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.001	0.016	0.32	1	-10000	0	1
TCEB1	0	0	-10000	0	-10000	0	0
HIF1A/p53	-0.003	0.019	-10000	0	-10000	0	0
HIF1A	0	0.024	-10000	0	-10000	0	0
COPS5	0	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.001	0.01	-10000	0	-10000	0	0
FIH (dimer)	0	0	-10000	0	-10000	0	0
CDKN2A	0.22	0.15	0.32	254	-10000	0	254
ARNT/IPAS	-0.016	0.12	-10000	0	-0.67	12	12
HIF1AN	0	0	-10000	0	-10000	0	0
GNB2L1	0	0	-10000	0	-10000	0	0
HIF1A/ARNT	-0.003	0.019	-10000	0	-10000	0	0
CUL2	0	0	-10000	0	-10000	0	0
OS9	0	0	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.001	0.01	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.003	0.019	-10000	0	-10000	0	0
PHD1-3/OS9	0.002	0.11	-10000	0	-0.53	11	11
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.019	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
HIF1A/JAB1	-0.003	0.019	-10000	0	-10000	0	0
EGLN3	0.003	0.18	0.32	33	-0.86	11	44
EGLN2	0	0	-10000	0	-10000	0	0
EGLN1	0	0	-10000	0	-10000	0	0
TP53	0	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0	0.006	-10000	0	-10000	0	0
ARNT	0	0	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0	0	-10000	0	-10000	0	0
HIF1A/p19ARF	0.13	0.1	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.021	0.085	-10000	0	-0.38	17	17
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0	0	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
STXBP4	0.003	0.028	0.32	3	-10000	0	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.026	0.11	-10000	0	-0.42	17	17
YWHAZ	0	0	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	0.012	0.061	-10000	0	-0.67	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
SNARE/Synip	0.002	0.018	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
ASIP	0.001	0.016	0.32	1	-10000	0	1
PRKCI	0	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0	0	-10000	0	-10000	0	0
GYS1	0	0.004	-10000	0	-10000	0	0
PRKCZ	-0.039	0.18	-10000	0	-0.86	17	17
TRIP10	0	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.057	0.061	-10000	0	-10000	0	0
VAMP2	0	0	-10000	0	-10000	0	0
SLC2A4	0.025	0.12	-10000	0	-0.47	17	17
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
SFN	0.18	0.17	0.32	214	-0.86	2	216
LNPEP	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.021	0.093	-10000	0	-0.44	6	6
NFATC2	-0.035	0.11	-10000	0	-0.33	25	25
NFATC3	-0.025	0.12	-10000	0	-0.55	17	17
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.006	0.12	-10000	0	-0.3	41	41
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.062	0.15	-10000	0	-0.49	35	35
BCL2/BAX	-0.002	0.035	-10000	0	-0.67	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.002	0.004	-10000	0	-10000	0	0
CaM/Ca2+	-0.002	0.004	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.032	0.1	-10000	0	-0.62	7	7
Calcineurin A alpha-beta B1/BCL2	-0.002	0.044	-10000	0	-0.86	1	1
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.031	0.1	0.61	7	-10000	0	7
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	0.003	0.028	0.32	3	-10000	0	3
XPO1	0	0	-10000	0	-10000	0	0
SFN	0.18	0.17	0.32	214	-0.86	2	216
MAP3K8	-0.005	0.063	-10000	0	-0.86	2	2
NFAT4/CK1 alpha	-0.017	0.078	-10000	0	-0.4	2	2
MEF2D/NFAT1/Cbp/p300	-0.088	0.15	-10000	0	-0.52	16	16
CABIN1	-0.006	0.12	-10000	0	-0.31	41	41
CALM1	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	0	0	-10000	0	-10000	0	0
CAMK4	-0.066	0.23	0.32	1	-0.86	29	30
mol:Ca2+	-0.002	0.007	-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	0.001	0.016	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	-0.046	0.19	-10000	0	-0.86	20	20
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.033	0.1	-10000	0	-0.46	18	18
PRKCH	-0.002	0.045	-10000	0	-0.86	1	1
CABIN1/Cbp/p300	-0.002	0.005	-10000	0	-10000	0	0
CASP3	-0.002	0.045	-10000	0	-0.86	1	1
PIM1	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.001	0.011	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.053	0.051	-10000	0	-10000	0	0
PRKCB	-0.074	0.24	-10000	0	-0.86	32	32
PRKCE	-0.001	0.048	0.32	1	-0.86	1	2
JNK2/NFAT4	-0.023	0.1	-10000	0	-0.5	17	17
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0	0	-10000	0	-10000	0	0
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	-0.039	0.18	-10000	0	-0.86	17	17
PRKCA	0	0	-10000	0	-10000	0	0
PRKCG	0.003	0.033	0.32	4	-10000	0	4
PRKCQ	-0.033	0.17	0.32	2	-0.86	15	17
FKBP38/BCL2	-0.002	0.035	-10000	0	-0.67	1	1
EP300	-0.001	0.002	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	-0.041	0.13	-10000	0	-0.49	22	22
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.046	0.16	-10000	0	-0.59	29	29
NFATc/ERK1	-0.018	0.078	-10000	0	-0.53	2	2
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.062	0.15	-10000	0	-0.49	35	35
NR4A1	-0.15	0.28	-10000	0	-0.78	59	59
GSK3B	0	0	-10000	0	-10000	0	0
positive T cell selection	-0.025	0.12	-10000	0	-0.55	17	17
NFAT1/CK1 alpha	-0.045	0.076	-10000	0	-0.4	4	4
RCH1/ KPNB1	0.002	0.02	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
AKAP5	0.002	0.023	0.32	2	-10000	0	2
MEF2D	-0.001	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0	0	-10000	0	-10000	0	0
NFATc/p38 alpha	-0.018	0.078	-10000	0	-0.54	2	2
CREBBP	-0.001	0.002	-10000	0	-10000	0	0
BCL2	-0.002	0.045	-10000	0	-0.86	1	1

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-10000	0	-10000	0	0
HDAC3	0	0	-10000	0	-10000	0	0
VDR	-0.009	0.14	0.32	11	-0.86	8	19
Cbp/p300/PCAF	-0.005	0.052	-10000	0	-0.58	3	3
EP300	0	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.016	0.066	-10000	0	-0.34	2	2
KAT2B	-0.007	0.077	-10000	0	-0.86	3	3
MAPK14	0	0	-10000	0	-10000	0	0
AKT1	0.038	0.12	0.24	64	-0.36	12	76
RAR alpha/9cRA/Cyclin H	-0.016	0.064	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.01	0.078	-10000	0	-0.29	20	20
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.038	0.16	-10000	0	-0.7	20	20
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.008	0.1	-10000	0	-0.67	8	8
RXRs/RARs/NRIP1/9cRA	0.033	0.09	-10000	0	-0.51	2	2
NCOA2	-0.11	0.29	-10000	0	-0.86	48	48
NCOA3	0	0	-10000	0	-10000	0	0
NCOA1	0	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.009	0.14	0.32	11	-0.86	8	19
RARG	0	0	-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	-0.046	0.19	-10000	0	-0.86	20	20
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.015	0.093	-10000	0	-0.47	8	8
RARA	-0.016	0.073	-10000	0	-0.32	20	20
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.03	0.15	-10000	0	-0.34	63	63
PRKCA	0.01	0.004	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.02	0.082	-10000	0	-0.54	2	2
RXRG	0.027	0.071	-10000	0	-0.46	5	5
RXRA	0.01	0.075	-10000	0	-0.29	21	21
RXRB	0.02	0.014	-10000	0	-10000	0	0
VDR/Vit D3/DNA	-0.008	0.1	-10000	0	-0.67	8	8
RBP1	-0.17	0.35	0.32	7	-0.86	74	81
CRBP1/9-cic-RA	-0.13	0.27	0.21	7	-0.67	74	81
RARB	-0.038	0.18	-10000	0	-0.86	17	17
PRKCG	0.008	0.033	0.32	4	-10000	0	4
MNAT1	0	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.023	0.12	0.35	1	-0.52	1	2
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.035	0.085	-10000	0	-0.44	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.081	-10000	0	-0.44	2	2
RXRs/RARs/NRIP1/9cRA/HDAC3	0.02	0.082	-10000	0	-0.54	2	2
positive regulation of DNA binding	-0.015	0.061	-10000	0	-10000	0	0
NRIP1	0.02	0.096	-10000	0	-1.3	1	1
RXRs/RARs	0.017	0.074	-10000	0	-0.44	2	2
RXRs/RXRs/DNA/9cRA	-0.006	0.058	-10000	0	-10000	0	0
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	-0.011	0.044	-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

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.34	0.42	-10000	0	-0.86	149	149
HRAS	0.002	0.023	0.32	2	-10000	0	2
EGFR	-0.023	0.14	-10000	0	-0.86	10	10
AKT	0.016	0.052	-10000	0	-0.5	3	3
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	-0.009	0.089	-10000	0	-0.86	4	4
AKT3	-0.006	0.079	0.32	1	-0.86	3	4
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.001	0.048	0.32	1	-0.86	1	2
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
PIK3CG	-0.028	0.16	0.32	3	-0.86	13	16
PIK3R3	0.001	0.016	0.32	1	-10000	0	1
PIK3R2	0.001	0.016	0.32	1	-10000	0	1
NF1	-0.002	0.045	-10000	0	-0.86	1	1
RAS	-0.068	0.11	-10000	0	-0.41	9	9
ERBB2	-0.014	0.11	-10000	0	-0.86	6	6
proliferation/survival/translation	-0.017	0.035	0.23	2	-10000	0	2
PI3K	-0.057	0.11	-10000	0	-0.29	23	23
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
KRAS	0	0	-10000	0	-10000	0	0
FOXO	0.022	0.023	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
PTEN	-0.005	0.063	-10000	0	-0.86	2	2

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.025	0.081	-10000	0	-0.51	3	3
MAPK9	0	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.003	0.015	-10000	0	-10000	0	0
GNB1/GNG2	-0.005	0.053	-10000	0	-0.59	3	3
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	0	-10000	0	-10000	0	0
Gs family/GTP	0.029	0.066	0.18	60	-10000	0	60
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	0	-10000	0	-10000	0	0
GNAL	0.051	0.12	0.32	60	-10000	0	60
GNG2	-0.007	0.077	-10000	0	-0.86	3	3
CRH	0.003	0.033	0.32	4	-10000	0	4
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	-0.026	0.11	-10000	0	-0.47	20	20
MAPK11	0.005	0.025	0.13	14	-10000	0	14

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.003	0.097	-10000	0	-0.44	16	16
ACTA1	-0.003	0.12	-10000	0	-0.58	15	15
NUMA1	0.003	0.097	-10000	0	-0.44	16	16
SPTAN1	-0.004	0.12	-10000	0	-0.58	15	15
LIMK1	-0.003	0.12	-10000	0	-0.58	15	15
BIRC3	0.007	0.088	0.32	14	-0.86	2	16
BIRC2	0	0	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
CASP10	-0.002	0.13	-10000	0	-0.61	16	16
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.003	0.097	-10000	0	-0.44	16	16
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.003	0.12	-10000	0	-0.57	15	15
response to UV	0	0	-10000	0	-10000	0	0
CRADD	-0.002	0.045	-10000	0	-0.86	1	1
GSN	-0.004	0.12	-10000	0	-0.58	15	15
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	0.02	0.15	0.37	2	-0.64	14	16
BID	-0.012	0.06	-10000	0	-0.29	16	16
MAP3K1	0.004	0.04	-10000	0	-0.25	1	1
TRADD	-0.002	0.045	-10000	0	-0.86	1	1
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	0.12	-10000	0	-0.58	15	15
CASP9	0	0	-10000	0	-10000	0	0
DNA repair	0	0.033	0.18	1	-0.22	1	2
neuron apoptosis	0.009	0.077	-10000	0	-0.72	4	4
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0	0.12	-10000	0	-0.55	16	16
APAF1	0	0	-10000	0	-10000	0	0
CASP6	0.016	0.06	-10000	0	-0.36	2	2
TRAF2	0	0	-10000	0	-10000	0	0
ICAD/CAD	0.002	0.12	-10000	0	-0.55	16	16
CASP7	-0.012	0.037	0.37	2	-10000	0	2
KRT18	0.011	0.017	-10000	0	-10000	0	0
apoptosis	0.007	0.11	-10000	0	-0.5	15	15
DFFA	-0.004	0.12	-10000	0	-0.58	15	15
DFFB	-0.005	0.13	-10000	0	-0.57	16	16
PARP1	0	0.033	0.22	1	-0.18	1	2
actin filament polymerization	-0.002	0.12	0.52	17	-10000	0	17
TNF	-0.031	0.17	0.32	2	-0.86	14	16
CYCS	0.01	0.048	-10000	0	-0.21	16	16
SATB1	-0.033	0.17	-10000	0	-0.48	42	42
SLK	-0.004	0.12	-10000	0	-0.58	15	15
p15 BID/BAX	-0.011	0.052	-10000	0	-0.36	1	1
CASP2	-0.006	0.059	-10000	0	-10000	0	0
JNK cascade	-0.004	0.04	0.24	1	-10000	0	1
CASP3	-0.011	0.13	-10000	0	-0.61	15	15
LMNB2	0.03	0.051	-10000	0	-0.3	1	1
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.002	0.045	-10000	0	-0.86	1	1
Mammalian IAPs/DIABLO	0.005	0.054	-10000	0	-0.53	2	2
negative regulation of DNA binding	0.021	0.15	0.37	2	-0.64	14	16
stress fiber formation	-0.003	0.12	-10000	0	-0.57	15	15
GZMB	-0.012	0.15	-10000	0	-0.7	16	16
CASP1	-0.004	0.042	-10000	0	-0.47	3	3
LMNB1	0.028	0.051	-10000	0	-0.3	1	1
APP	0.009	0.078	-10000	0	-0.72	4	4
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0	-10000	0	-10000	0	0
VIM	0.002	0.1	-10000	0	-0.48	15	15
LMNA	0.028	0.051	-10000	0	-0.3	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.009	0.063	-10000	0	-10000	0	0
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.005	0.13	-10000	0	-0.57	16	16
APAF-1/Caspase 9	-0.005	0.022	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.003	0.095	-10000	0	-0.43	16	16
CFL2	0.001	0.12	-10000	0	-0.54	17	17
GAS2	-0.022	0.15	-10000	0	-0.54	28	28
positive regulation of apoptosis	0.031	0.051	-10000	0	-0.3	1	1
PRF1	-0.016	0.12	-10000	0	-0.86	7	7

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.004	0.048	-10000	0	-0.53	3	3
HDAC3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-10000	0	-10000	0	0
GATA1/HDAC4	0.002	0.023	-10000	0	-10000	0	0
GATA1/HDAC5	0.002	0.02	-10000	0	-10000	0	0
GATA2/HDAC5	-0.002	0.051	-10000	0	-0.67	2	2
HDAC5/BCL6/BCoR	-0.002	0.03	-10000	0	-0.58	1	1
HDAC9	-0.042	0.18	-10000	0	-0.86	18	18
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
HDAC4/ANKRA2	-0.001	0.036	-10000	0	-0.67	1	1
HDAC5/YWHAB	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
GATA2	-0.003	0.067	0.32	2	-0.86	2	4
HDAC4/RFXANK	0.002	0.02	-10000	0	-10000	0	0
BCOR	-0.002	0.045	-10000	0	-0.86	1	1
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	-0.005	0.06	-10000	0	-0.67	3	3
Histones	-0.01	0.064	-10000	0	-10000	0	0
ADRBK1	0	0	-10000	0	-10000	0	0
HDAC4	0.001	0.016	0.32	1	-10000	0	1
XPO1	0	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	-0.002	0.035	-10000	0	-0.67	1	1
HDAC4/Ubc9	0.001	0.011	-10000	0	-10000	0	0
HDAC7	0.001	0.016	0.32	1	-10000	0	1
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	0.016	-10000	0	-10000	0	0
CAMK4	-0.066	0.23	0.32	1	-0.86	29	30
Tubulin/HDAC6	0	0	-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	0.003	0.028	0.32	3	-10000	0	3
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
NR3C1	0	0	-10000	0	-10000	0	0
SUMO1/HDAC4	0.001	0.011	-10000	0	-10000	0	0
SRF	0	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.001	0.011	-10000	0	-10000	0	0
Tubulin	0	0	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.001	0.011	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
RANGAP1	0	0	-10000	0	-10000	0	0
BCL6/BCoR	-0.002	0.035	-10000	0	-0.67	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0.001	0.01	-10000	0	-10000	0	0
HDAC4/SRF	-0.044	0.16	-10000	0	-0.58	29	29
HDAC4/ER alpha	-0.37	0.33	-10000	0	-0.67	205	205
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.01	0.064	-10000	0	-10000	0	0
cell motility	0	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.001	0.011	-10000	0	-10000	0	0
BCL6	0	0	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.001	0.016	0.32	1	-10000	0	1
Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
ESR1	-0.48	0.43	-10000	0	-0.86	205	205
HDAC6/HDAC11	0.005	0.034	-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	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.001	0.01	-10000	0	-10000	0	0
GNG2	-0.007	0.077	-10000	0	-0.86	3	3
NCOR2	0	0	-10000	0	-10000	0	0
TUBB2A	0	0	-10000	0	-10000	0	0
HDAC11	0.008	0.049	0.32	9	-10000	0	9
HSP90AA1	0	0	-10000	0	-10000	0	0
RANBP2	0	0	-10000	0	-10000	0	0
ANKRA2	-0.002	0.045	-10000	0	-0.86	1	1
RFXANK	0.002	0.023	0.32	2	-10000	0	2
nuclear import	0	0.007	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0	0	-10000	0	-10000	0	0
ITGB7	-0.012	0.099	-10000	0	-0.86	5	5
ITGA4	-0.02	0.13	0.32	1	-0.86	9	10
alpha4/beta7 Integrin	-0.025	0.13	-10000	0	-0.67	14	14
alpha4/beta1 Integrin	-0.016	0.1	-10000	0	-0.67	9	9

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0	0	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.011	0.12	0.32	6	-0.86	7	13
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.009	0.028	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
YES1	0	0	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
MAP3K12	0.002	0.023	0.32	2	-10000	0	2
FGR	-0.005	0.063	-10000	0	-0.86	2	2
p38 alpha/TAB1	-0.034	0.075	-10000	0	-0.34	12	12
PRKG1	-0.041	0.19	0.32	1	-0.86	18	19
DUSP8	-0.004	0.065	0.32	1	-0.86	2	3
PGK/cGMP/p38 alpha	-0.052	0.12	0.24	1	-0.41	28	29
apoptosis	-0.033	0.072	-10000	0	-0.32	12	12
RAL/GTP	0	0	-10000	0	-10000	0	0
LYN	0	0	-10000	0	-10000	0	0
DUSP1	-0.081	0.25	-10000	0	-0.86	35	35
PAK1	0	0	-10000	0	-10000	0	0
SRC	0.004	0.036	0.32	5	-10000	0	5
RAC1/OSM/MEKK3/MKK3	0	0	-10000	0	-10000	0	0
TRAF6	-0.002	0.045	-10000	0	-0.86	1	1
RAC1	0	0	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
MAPK11	-0.006	0.13	-10000	0	-0.44	14	14
BLK	-0.15	0.33	0.32	2	-0.86	65	67
HCK	-0.028	0.15	-10000	0	-0.86	12	12
MAP2K3	0	0	-10000	0	-10000	0	0
DUSP16	-0.002	0.045	-10000	0	-0.86	1	1
DUSP10	-0.009	0.089	-10000	0	-0.86	4	4
TRAF6/MEKK3	-0.001	0.028	-10000	0	-0.54	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.003	0.1	-10000	0	-0.35	13	13
positive regulation of innate immune response	-0.003	0.14	-10000	0	-0.47	14	14
LCK	-0.025	0.15	0.32	1	-0.86	11	12
p38alpha-beta/MKP7	-0.052	0.11	-10000	0	-0.44	15	15
p38alpha-beta/MKP5	-0.055	0.12	-10000	0	-0.45	18	18
PGK/cGMP	-0.032	0.14	0.21	1	-0.67	18	19
PAK2	0	0	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.087	0.16	-10000	0	-0.46	46	46
CDC42	0	0	-10000	0	-10000	0	0
RALB	0	0	-10000	0	-10000	0	0
RALA	0	0	-10000	0	-10000	0	0
PAK3	0.032	0.096	0.32	38	-10000	0	38

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.053	0.18	-10000	0	-0.67	30	30
AKT1	0.049	0.12	-10000	0	-0.67	9	9
PTK2B	-0.056	0.19	-10000	0	-1	9	9
VEGFR2 homodimer/Frs2	-0.023	0.15	-10000	0	-0.96	9	9
CAV1	0	0	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.022	0.14	-10000	0	-0.89	9	9
endothelial cell proliferation	0.039	0.14	-10000	0	-0.64	9	9
mol:Ca2+	-0.022	0.13	-10000	0	-0.81	10	10
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.021	0.13	-10000	0	-0.85	9	9
RP11-342D11.1	-0.022	0.13	-10000	0	-0.81	10	10
CDH5	-0.002	0.045	-10000	0	-0.86	1	1
VEGFA homodimer	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.019	0.12	-10000	0	-0.86	8	8
HRAS/GDP	-0.018	0.11	-10000	0	-0.71	9	9
SH2D2A	-0.016	0.14	0.32	6	-0.86	9	15
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.019	0.11	-10000	0	-0.69	9	9
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.031	0.17	-10000	0	-0.74	17	17
VEGFR1 homodimer	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.021	0.13	-10000	0	-0.82	9	9
GRB10	-0.022	0.13	-10000	0	-0.84	9	9
PTPN11	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
PAK1	0	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.021	0.14	-10000	0	-0.87	9	9
HRAS	0.002	0.023	0.32	2	-10000	0	2
VEGF/Rho/ROCK1/Integrin Complex	-0.031	0.11	-10000	0	-0.55	9	9
HIF1A	0	0	-10000	0	-10000	0	0
FRS2	0	0	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.02	0.13	-10000	0	-0.83	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	-0.002	0.045	-10000	0	-0.86	1	1
Nck/Pak	0	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.022	0.14	-10000	0	-0.89	9	9
mol:GDP	-0.02	0.12	-10000	0	-0.78	9	9
mol:NADP	0.046	0.1	-10000	0	-0.56	10	10
eNOS/Hsp90	0.047	0.097	-10000	0	-0.52	10	10
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
mol:IP3	-0.022	0.14	-10000	0	-0.82	10	10
HIF1A/ARNT	0	0	-10000	0	-10000	0	0
SHB	-0.002	0.045	-10000	0	-0.86	1	1
VEGFA	0	0	-10000	0	-10000	0	0
VEGFC	0.001	0.016	0.32	1	-10000	0	1
FAK1/Vinculin	-0.041	0.16	-10000	0	-0.93	9	9
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.059	0.21	-10000	0	-0.65	34	34
PTPN6	0	0	-10000	0	-10000	0	0
EPAS1	-0.01	0.06	-10000	0	-0.39	9	9
mol:L-citrulline	0.046	0.1	-10000	0	-0.56	10	10
ITGAV	0.001	0.016	0.32	1	-10000	0	1
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.021	0.13	-10000	0	-0.85	9	9
VEGFR2 homodimer/VEGFA homodimer	-0.024	0.15	-10000	0	-0.9	10	10
VEGFR2/3 heterodimer	-0.024	0.16	-10000	0	-1	9	9
VEGFB	-0.019	0.14	0.32	2	-0.86	9	11
MAPK11	0.029	0.15	-10000	0	-0.84	10	10
VEGFR2 homodimer	0.002	0.17	-10000	0	-1.1	9	9
FLT1	0	0	-10000	0	-10000	0	0
NEDD4	-0.005	0.063	-10000	0	-0.86	2	2
MAPK3	0.019	0.14	-10000	0	-0.74	10	10
MAPK1	0.019	0.14	-10000	0	-0.74	10	10
VEGFA145/NRP2	-0.005	0.061	-10000	0	-0.67	3	3
VEGFR1/2 heterodimer	-0.023	0.15	-10000	0	-0.96	9	9
KDR	0.002	0.17	-10000	0	-1.1	9	9
VEGFA165/NRP1/VEGFR2 homodimer	-0.025	0.15	-10000	0	-0.8	12	12
SRC	0.004	0.036	0.32	5	-10000	0	5
platelet activating factor biosynthetic process	0.021	0.14	-10000	0	-0.76	10	10
PI3K	-0.026	0.14	-10000	0	-0.87	9	9
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.022	0.14	-10000	0	-0.89	9	9
FES	-0.029	0.15	-10000	0	-0.72	15	15
GAB1	-0.021	0.13	-10000	0	-0.84	9	9
VEGFR2 homodimer/VEGFA homodimer/Src	-0.019	0.14	-10000	0	-0.89	9	9
CTNNB1	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
ARNT	0	0	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.047	0.097	-10000	0	-0.52	10	10
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.022	0.14	-10000	0	-0.89	9	9
PI3K/GAB1	-0.02	0.11	-10000	0	-0.7	9	9
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.02	0.13	-10000	0	-0.82	9	9
PRKACA	0	0	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.022	0.15	-10000	0	-0.95	9	9
HSP90AA1	0	0	-10000	0	-10000	0	0
CDC42	-0.023	0.14	-10000	0	-0.84	10	10
actin cytoskeleton reorganization	-0.03	0.16	-10000	0	-0.74	17	17
PTK2	0.007	0.19	-10000	0	-1	9	9
EDG1	-0.022	0.13	-10000	0	-0.81	10	10
mol:DAG	-0.022	0.14	-10000	0	-0.82	10	10
CaM/Ca2+	-0.02	0.12	-10000	0	-0.79	9	9
MAP2K3	0.025	0.15	-10000	0	-0.83	9	9
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.023	0.14	-10000	0	-0.9	9	9
PLCG1	-0.023	0.14	-10000	0	-0.84	10	10
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.019	0.14	-10000	0	-0.85	9	9
IQGAP1	0	0	-10000	0	-10000	0	0
YES1	0	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.022	0.14	-10000	0	-0.89	9	9
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.022	0.14	-10000	0	-0.89	9	9
cell migration	0.037	0.15	-10000	0	-0.74	9	9
mol:PI-3-4-5-P3	-0.023	0.13	-10000	0	-0.77	9	9
FYN	0	0	-10000	0	-10000	0	0
VEGFB/NRP1	-0.031	0.14	-10000	0	-0.63	18	18
mol:NO	0.046	0.1	-10000	0	-0.56	10	10
PXN	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.018	0.11	-10000	0	-0.72	9	9
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.023	0.14	-10000	0	-0.9	9	9
VHL	0	0	-10000	0	-10000	0	0
ITGB3	-0.07	0.23	-10000	0	-0.86	30	30
NOS3	0.045	0.12	-10000	0	-0.65	10	10
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.033	0.16	-10000	0	-0.72	17	17
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0.032	0.13	-10000	0	-0.79	9	9
PRKCB	-0.013	0.2	-10000	0	-0.55	40	40
VCL	0.001	0.016	0.32	1	-10000	0	1
VEGFA165/NRP1	-0.022	0.14	-10000	0	-0.82	10	10
VEGFR1/2 heterodimer/VEGFA homodimer	-0.022	0.14	-10000	0	-0.89	9	9
VEGFA165/NRP2	-0.005	0.061	-10000	0	-0.67	3	3
MAPKKK cascade	-0.018	0.11	-10000	0	-0.72	9	9
NRP2	-0.006	0.079	0.32	1	-0.86	3	4
VEGFC homodimer	0.001	0.016	0.32	1	-10000	0	1
NCK1	0	0	-10000	0	-10000	0	0
ROCK1	0	0	-10000	0	-10000	0	0
FAK1/Paxillin	-0.042	0.16	-10000	0	-0.93	9	9
MAP3K13	-0.028	0.15	-10000	0	-0.72	15	15
PDPK1	-0.02	0.11	-10000	0	-0.66	9	9

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.012	0.051	-10000	0	-10000	0	0
ATM	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
PRKDC	0	0	-10000	0	-10000	0	0
ATR	0	0	-10000	0	-10000	0	0
UBE2L3	0	0	-10000	0	-10000	0	0
FANCD2	0.038	0.063	-10000	0	-10000	0	0
protein ubiquitination	0.072	0.098	0.33	17	-10000	0	17
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	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.023	0.054	-10000	0	-0.5	1	1
FANCF	0	0	-10000	0	-10000	0	0
BRCA1	0.001	0.016	0.32	1	-10000	0	1
CCNE1	0.11	0.15	0.32	134	-10000	0	134
CDK2/Cyclin E1	0.079	0.1	-10000	0	-10000	0	0
FANCG	0.002	0.023	0.32	2	-10000	0	2
BRCA1/BACH1/BARD1	0.013	0.052	-10000	0	-10000	0	0
FANCE	0.01	0.056	0.32	12	-10000	0	12
FANCC	-0.002	0.045	-10000	0	-0.86	1	1
NBN	0	0	-10000	0	-10000	0	0
FANCA	0	0	-10000	0	-10000	0	0
DNA repair	0.089	0.048	-10000	0	-10000	0	0
BRCA1/BARD1/ubiquitin	0.013	0.052	-10000	0	-10000	0	0
BARD1/DNA-PK	0.011	0.045	-10000	0	-10000	0	0
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.012	0.05	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.007	0.027	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0.012	0.048	-10000	0	-10000	0	0
BRCA1/BARD1/P53	0.012	0.046	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	0.012	0.048	-10000	0	-10000	0	0
BRCA1/BACH1	0.001	0.016	0.32	1	-10000	0	1
BARD1	0.018	0.073	0.32	21	-10000	0	21
PCNA	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.012	0.048	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	0.012	0.048	-10000	0	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.066	0.11	0.38	16	-10000	0	16
BARD1/DNA-PK/P53	0.011	0.043	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.013	0.052	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP	0.012	0.049	-10000	0	-10000	0	0
FA complex	0.004	0.027	-10000	0	-10000	0	0
BARD1/EWS	0.012	0.051	-10000	0	-10000	0	0
RBBP8	0.018	0	-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	-0.011	0.045	-10000	0	-10000	0	0
BRCA1/BARD1	0.078	0.11	0.36	17	-10000	0	17
CSTF1	0	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.012	0.049	0.21	21	-10000	0	21
CDK2	0	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.089	0.14	0.32	105	-10000	0	105
RAD50	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.013	0.052	-10000	0	-10000	0	0
EWSR1	0	0	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.026	0.1	-10000	0	-1.3	2	2
regulation of axonogenesis	0.019	0.081	0.34	21	-10000	0	21
myoblast fusion	0.002	0.036	0.43	2	-10000	0	2
mol:GTP	-0.001	0.02	-10000	0	-0.24	2	2
regulation of calcium-dependent cell-cell adhesion	0.029	0.13	0.56	20	-10000	0	20
ARF1/GTP	0	0.015	-10000	0	-10000	0	0
mol:GM1	0.007	0.016	-10000	0	-10000	0	0
mol:Choline	-0.011	0.14	-10000	0	-0.57	21	21
lamellipodium assembly	0.004	0.048	-10000	0	-0.46	2	2
MAPK3	0.02	0.032	-10000	0	-0.35	2	2
ARF6/GTP/NME1/Tiam1	-0.029	0.13	-10000	0	-0.56	20	20
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.002	0.036	-10000	0	-0.43	2	2
ARF1/GDP	0.003	0.04	-10000	0	-0.39	2	2
ARF6	0	0.011	-10000	0	-10000	0	0
RAB11A	0	0	-10000	0	-10000	0	0
TIAM1	-0.046	0.19	-10000	0	-0.86	20	20
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0.032	-10000	0	-0.35	2	2
actin filament bundle formation	0.003	0.03	0.39	2	-10000	0	2
KALRN	0	0.051	-10000	0	-0.43	4	4
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.003	0.031	-10000	0	-0.39	2	2
NME1	0.002	0.023	0.32	2	-10000	0	2
Rac1/GDP	-0.003	0.031	-10000	0	-0.39	2	2
substrate adhesion-dependent cell spreading	-0.001	0.02	-10000	0	-0.24	2	2
cortical actin cytoskeleton organization	0.004	0.048	-10000	0	-0.47	2	2
RAC1	0	0	-10000	0	-10000	0	0
liver development	-0.001	0.02	-10000	0	-0.24	2	2
ARF6/GTP	-0.001	0.02	-10000	0	-0.24	2	2
RhoA/GTP	0	0.015	-10000	0	-10000	0	0
mol:GDP	0.004	0.046	-10000	0	-0.43	2	2
ARF6/GTP/RAB11FIP3/RAB11A	0	0.013	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PLD1	-0.036	0.15	-10000	0	-0.64	21	21
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	0.004	0.048	-10000	0	-0.46	2	2
ruffle organization	-0.019	0.081	-10000	0	-0.34	21	21
regulation of epithelial cell migration	-0.001	0.02	-10000	0	-0.24	2	2
PLD2	0	0.015	-10000	0	-10000	0	0
PIP5K1A	-0.019	0.081	-10000	0	-0.34	21	21
mol:Phosphatidic acid	-0.011	0.14	-10000	0	-0.57	21	21
Rac1/GTP	0.004	0.049	-10000	0	-0.47	2	2

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.018	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-10000	0	-10000	0	0
CDKN1B	0.031	0.003	-10000	0	-10000	0	0
CDKN1A	0.017	0.083	-10000	0	-0.48	10	10
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0	0	-10000	0	-10000	0	0
FOXO3	0.031	0.003	-10000	0	-10000	0	0
AKT1	0.001	0.007	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
AKT3	-0.003	0.042	-10000	0	-0.47	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.031	0.003	-10000	0	-10000	0	0
AKT1/ASK1	-0.054	0.15	-10000	0	-0.46	43	43
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0	0	-10000	0	-10000	0	0
JNK cascade	0.052	0.14	0.45	43	-10000	0	43
TSC1	0.031	0.003	-10000	0	-10000	0	0
YWHAZ	0	0	-10000	0	-10000	0	0
AKT1/RAF1	0	0	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
mol:GDP	0.001	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.028	0.038	-10000	0	-0.48	2	2
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	-0.005	0.051	-10000	0	-0.57	3	3
MAP3K5	-0.1	0.28	-10000	0	-0.86	43	43
MAPKAP1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.059	0.031	0.24	1	-10000	0	1
YWHAH	0	0	-10000	0	-10000	0	0
AKT1S1	0.031	0.003	-10000	0	-10000	0	0
CASP9	0.031	0.003	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0	0	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.003	0.023	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
SRC	0.004	0.036	0.32	5	-10000	0	5
AKT2/p21CIP1	-0.012	0.075	-10000	0	-0.46	10	10
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.014	0.001	-10000	0	-10000	0	0
CHUK	0.031	0.003	-10000	0	-10000	0	0
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.075	0.035	-10000	0	-10000	0	0
PDPK1	0	0	-10000	0	-10000	0	0
MDM2	0.031	0.003	-10000	0	-10000	0	0
MAPKKK cascade	0	0	-10000	0	-10000	0	0
MDM2/Cbp/p300	0	0	-10000	0	-10000	0	0
TSC1/TSC2	0.033	0.036	-10000	0	-0.46	2	2
proteasomal ubiquitin-dependent protein catabolic process	0	0	-10000	0	-10000	0	0
glucose import	0.013	0.09	-10000	0	-0.52	10	10
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.026	0.002	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.013	0.091	-10000	0	-0.53	10	10
GSK3A	0.031	0.003	-10000	0	-10000	0	0
FOXO1	0.025	0.053	-10000	0	-0.48	4	4
GSK3B	0.031	0.003	-10000	0	-10000	0	0
SFN	0.18	0.17	0.32	214	-0.86	2	216
G1/S transition of mitotic cell cycle	0.036	0.003	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.057	0.054	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
KPNA1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.002	0.01	-10000	0	-10000	0	0
DOCK1	-0.019	0.12	-10000	0	-0.86	8	8
ITGA4	-0.02	0.13	0.32	1	-0.86	9	10
RAC1	0	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.025	0.13	-10000	0	-0.67	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.014	0.09	-10000	0	-0.58	9	9
alpha4/beta7 Integrin/Paxillin	-0.019	0.1	-10000	0	-0.53	14	14
lamellipodium assembly	-0.01	0.077	-10000	0	-0.5	8	8
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
PI3K	-0.005	0.071	-10000	0	-0.94	2	2
ARF6	0	0	-10000	0	-10000	0	0
TLN1	0	0	-10000	0	-10000	0	0
PXN	0.018	0	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
ARF6/GTP	-0.011	0.071	-10000	0	-0.46	9	9
cell adhesion	-0.011	0.077	-10000	0	-0.49	9	9
CRKL/CBL	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.012	0.083	-10000	0	-0.53	9	9
ITGB1	0	0	-10000	0	-10000	0	0
ITGB7	-0.012	0.099	-10000	0	-0.86	5	5
ARF6/GDP	0.002	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.035	0.15	-10000	0	-0.54	27	27
p130Cas/Crk/Dock1	-0.013	0.084	-10000	0	-0.58	8	8
VCAM1	-0.041	0.2	0.32	6	-0.86	20	26
alpha4/beta1 Integrin/Paxillin/Talin	-0.012	0.077	-10000	0	-0.5	9	9
alpha4/beta1 Integrin/Paxillin/GIT1	-0.012	0.077	-10000	0	-0.5	9	9
BCAR1	0	0	-10000	0	-10000	0	0
mol:GDP	0.011	0.077	0.49	9	-10000	0	9
CBL	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
GIT1	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.012	0.077	-10000	0	-0.5	9	9
Rac1/GTP	-0.011	0.091	-10000	0	-0.58	8	8

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.001	0.061	-10000	0	-0.51	4	4
RGS9BP	0.011	0.058	0.32	13	-10000	0	13
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
mol:Na +	0.019	0.059	0.38	1	-10000	0	1
mol:ADP	0.003	0.004	-10000	0	-10000	0	0
GNAT2	0.001	0.016	0.32	1	-10000	0	1
RGS9-1/Gbeta5/R9AP	-0.001	0.12	0.39	2	-0.58	11	13
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.001	0.01	-10000	0	-10000	0	0
GRK7	0	0	-10000	0	-10000	0	0
CNGB3	0.031	0.094	0.32	36	-10000	0	36
Cone Metarhodopsin II/X-Arrestin	0.001	0.011	0.21	1	-10000	0	1
mol:Ca2+	0.007	0.021	-10000	0	-10000	0	0
Cone PDE6	0.009	0.11	0.35	4	-0.5	11	15
Cone Metarhodopsin II	0	0	-10000	0	-10000	0	0
Na + (4 Units)	0.018	0.056	0.36	1	-10000	0	1
GNAT2/GDP	0	0.1	0.35	2	-0.5	11	13
GNB5	0.001	0.016	0.32	1	-10000	0	1
mol:GMP (4 units)	0.01	0.041	-10000	0	-10000	0	0
Cone Transducin	-0.001	0.064	-10000	0	-0.54	4	4
SLC24A2	0	0	-10000	0	-10000	0	0
GNB3/GNGT2	-0.002	0.077	-10000	0	-0.67	4	4
GNB3	0.008	0.049	0.32	9	-10000	0	9
GNAT2/GTP	0.001	0.011	0.21	1	-10000	0	1
CNGA3	0.002	0.023	0.32	2	-10000	0	2
ARR3	0.001	0.016	0.32	1	-10000	0	1
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.02	0.06	0.39	1	-10000	0	1
mol:Pi	-0.001	0.12	0.39	2	-0.58	11	13
Cone CNG Channel	0.023	0.057	0.3	3	-10000	0	3
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0	0	-10000	0	-10000	0	0
RGS9	-0.012	0.16	0.32	16	-0.86	11	27
PDE6C	0.016	0.07	0.32	19	-10000	0	19
GNGT2	-0.009	0.089	-10000	0	-0.86	4	4
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0	0	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.007	0.047	-10000	0	-0.46	1	1
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0	0.026	-10000	0	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.031	-10000	0	-0.58	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.053	0.065	-10000	0	-0.39	5	5
CaM/Ca2+	0.006	0.041	-10000	0	-0.43	1	1
RAP1A	0	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.004	0.034	-10000	0	-0.44	1	1
AKT1	-0.001	0.061	-10000	0	-0.72	2	2
MAP2K1	0.046	0.025	-10000	0	-0.41	1	1
MAP3K11	0.002	0.028	-10000	0	-0.44	1	1
IFNGR1	0.001	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.17	0.2	-10000	0	-0.45	6	6
Rap1/GTP	-0.001	0.017	-10000	0	-10000	0	0
CRKL/C3G	0	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.007	0.047	-10000	0	-0.49	1	1
CEBPB	0.065	0.042	-10000	0	-10000	0	0
STAT3	0	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0	0.1	-10000	0	-1.3	2	2
STAT1	0.004	0.033	-10000	0	-0.44	1	1
CALM1	0	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.014	0.065	0.32	16	-10000	0	16
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
STAT1 (dimer)/PIAS1	0.004	0.032	-10000	0	-0.41	1	1
CEBPB/PTGES2/Cbp/p300	-0.002	0.021	-10000	0	-10000	0	0
mol:Ca2+	0.007	0.045	-10000	0	-0.46	1	1
MAPK3	0.051	0.028	-10000	0	-10000	0	0
STAT1 (dimer)	-0.069	0.093	-10000	0	-0.65	4	4
MAPK1	0.051	0.028	-10000	0	-10000	0	0
JAK2	-0.002	0.045	-10000	0	-0.86	1	1
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
JAK1	0.001	0.003	-10000	0	-10000	0	0
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	0.059	0.056	-10000	0	-0.66	2	2
SMAD7	0.002	0.063	-10000	0	-0.4	2	2
CBL/CRKL/C3G	-0.001	0.02	-10000	0	-10000	0	0
PI3K	0.001	0.075	-10000	0	-0.85	2	2
IFNG	0.014	0.066	0.32	16	-10000	0	16
apoptosis	0.037	0.042	-10000	0	-0.46	2	2
CAMK2G	0	0	-10000	0	-10000	0	0
STAT3 (dimer)	0	0	-10000	0	-10000	0	0
CAMK2A	0.024	0.084	0.32	28	-10000	0	28
CAMK2B	-0.42	0.43	-10000	0	-0.86	181	181
FRAP1	0.044	0.055	-10000	0	-0.64	2	2
PRKCD	-0.001	0.063	-10000	0	-0.75	2	2
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.053	0.065	-10000	0	-0.39	5	5
PTPN2	0	0	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
IRF1	0.067	0.034	-10000	0	-10000	0	0
STAT1 (dimer)/PIASy	0.004	0.034	-10000	0	-0.41	1	1
SOCS1	-0.005	0.12	-10000	0	-1.5	2	2
mol:GDP	-0.001	0.02	-10000	0	-10000	0	0
CASP1	0.002	0.063	-10000	0	-0.34	3	3
PTGES2	0.001	0.016	0.32	1	-10000	0	1
IRF9	0.049	0.014	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.067	-10000	0	-0.78	2	2
RAP1/GDP	-0.001	0.017	-10000	0	-10000	0	0
CBL	0.002	0.028	-10000	0	-0.44	1	1
MAP3K1	0.003	0.029	-10000	0	-0.44	1	1
PIAS1	0	0	-10000	0	-10000	0	0
PIAS4	0	0.001	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.053	0.065	-10000	0	-0.39	5	5
PTPN11	0.002	0.028	-10000	0	-0.46	1	1
CREBBP	0	0	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.012	0.099	-10000	0	-0.86	5	5
positive regulation of NF-kappaB transcription factor activity	-0.011	0.084	-10000	0	-0.66	6	6
MAP2K4	-0.007	0.045	-10000	0	-0.33	6	6
IKBKB	0	0	-10000	0	-10000	0	0
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.012	0.099	-10000	0	-0.86	5	5
SMPD1	-0.004	0.035	-10000	0	-0.3	5	5
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.002	0.045	-10000	0	-0.86	1	1
TRAIL/TRAILR2	-0.009	0.077	-10000	0	-0.67	5	5
TRAIL/TRAILR3	-0.007	0.089	-10000	0	-0.67	6	6
TRAIL/TRAILR1	-0.018	0.11	-10000	0	-0.67	10	10
TRAIL/TRAILR4	-0.011	0.084	-10000	0	-0.67	6	6
TRAIL/TRAILR1/DAP3/GTP	-0.014	0.087	-10000	0	-0.54	10	10
IKK complex	-0.005	0.03	-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	-10000	0	-10000	0	0
MAPK3	0.009	0.079	-10000	0	-0.66	5	5
MAP3K1	-0.008	0.048	-10000	0	-0.35	6	6
TRAILR4 (trimer)	-0.002	0.044	-10000	0	-0.86	1	1
TRADD	-0.002	0.045	-10000	0	-0.86	1	1
TRAILR1 (trimer)	-0.012	0.099	-10000	0	-0.86	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.01	0.06	-10000	0	-0.35	11	11
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.009	0.079	-10000	0	-0.66	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.014	0.085	-10000	0	-0.5	11	11
mol:ceramide	-0.004	0.035	-10000	0	-0.3	5	5
FADD	0.001	0.016	0.32	1	-10000	0	1
MAPK8	0.008	0.13	-10000	0	-0.48	21	21
TRAF2	0	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.003	0.06	0.32	6	-0.86	1	7
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.015	0.095	-10000	0	-0.58	10	10
DAP3	0	0	-10000	0	-10000	0	0
CASP10	-0.01	0.073	0.31	1	-0.55	5	6
JNK cascade	-0.011	0.084	-10000	0	-0.66	6	6
TRAIL (trimer)	-0.012	0.099	-10000	0	-0.86	5	5
TNFRSF10C	0.003	0.06	0.32	6	-0.86	1	7
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.013	0.082	-10000	0	-0.5	10	10
TRAIL/TRAILR2/FADD	-0.007	0.068	-10000	0	-0.58	5	5
cell death	-0.004	0.035	-10000	0	-0.3	5	5
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.005	0.045	-10000	0	-0.35	6	6
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0.001	0.019	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.008	0.064	-10000	0	-0.5	6	6

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.032	0.07	-10000	0	-0.58	4	4
SNTA1	0.002	0.023	0.32	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	0.037	0.074	-10000	0	-0.58	4	4
MAPK12	0.023	0.077	-10000	0	-0.52	7	7
CCND1	-0.001	0.1	-10000	0	-0.49	14	14
p38 gamma/SNTA1	0.003	0.073	-10000	0	-0.48	7	7
MAP2K3	0	0	-10000	0	-10000	0	0
PKN1	0.001	0.016	0.32	1	-10000	0	1
G2/M transition checkpoint	0.023	0.076	-10000	0	-0.51	7	7
MAP2K6	-0.009	0.079	-10000	0	-0.57	7	7
MAPT	0.061	0.063	-10000	0	-0.29	4	4
MAPK13	0.034	0.09	-10000	0	-0.67	4	4
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0	0.007	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	0.002	0.023	-10000	0	-10000	0	0
DAPP1	-0.032	0.16	-10000	0	-0.61	15	15
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.039	0.21	0.33	1	-0.73	20	21
mol:DAG	0.01	0.092	0.26	1	-0.31	11	12
HRAS	0.002	0.023	0.32	2	-10000	0	2
RAP1A	0	0	-10000	0	-10000	0	0
ARF5/GDP	-0.02	0.067	-10000	0	-0.48	3	3
PLCG2	-0.016	0.12	-10000	0	-0.86	7	7
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0	-10000	0	-10000	0	0
mol:GTP	0.001	0.019	-10000	0	-10000	0	0
ARF1/GTP	0.002	0.022	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
YES1	0	0	-10000	0	-10000	0	0
RAP1A/GTP	0.001	0.018	-10000	0	-10000	0	0
ADAP1	-0.004	0.074	-10000	0	-0.47	8	8
ARAP3	0.001	0.019	-10000	0	-10000	0	0
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	0	0	-10000	0	-10000	0	0
ARHGEF6	0	0	-10000	0	-10000	0	0
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
FGR	-0.005	0.063	-10000	0	-0.86	2	2
mol:Ca2+	0.014	0.05	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.046	0.19	-10000	0	-0.86	20	20
ZAP70	-0.005	0.096	0.32	5	-0.86	4	9
mol:IP3	0.015	0.068	0.22	1	-0.23	7	8
LYN	0	0	-10000	0	-10000	0	0
ARF1/GDP	-0.02	0.067	-10000	0	-0.48	3	3
RhoA/GDP	-0.006	0.033	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.003	0.023	-10000	0	-10000	0	0
BLNK	-0.021	0.13	-10000	0	-0.86	9	9
actin cytoskeleton reorganization	0.036	0.068	-10000	0	-10000	0	0
SRC	0.004	0.036	0.32	5	-10000	0	5
PLEKHA2	0.023	0.031	-10000	0	-0.58	1	1
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.005	0.061	-10000	0	-0.84	2	2
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	0.002	0.022	-10000	0	-10000	0	0
RhoA/GTP	0.001	0.018	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.069	0.17	0.28	1	-0.74	13	14
BLK	-0.15	0.33	0.32	2	-0.86	65	67
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	0.002	0.019	-10000	0	-10000	0	0
HCK	-0.028	0.15	-10000	0	-0.86	12	12
CYTH3	0.002	0.021	-10000	0	-10000	0	0
CYTH2	0.002	0.019	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.016	0.1	-10000	0	-0.57	12	12
SGK1	-0.018	0.11	-10000	0	-0.63	12	12
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.008	0.081	-10000	0	-0.51	3	3
SOS1	0	0	-10000	0	-10000	0	0
SYK	-0.007	0.077	-10000	0	-0.86	3	3
ARF6/GDP	-0.006	0.034	0.28	2	-10000	0	2
mol:PI-3-4-5-P3	0.002	0.027	0.37	2	-10000	0	2
ARAP3/RAP1A/GTP	0.001	0.018	-10000	0	-10000	0	0
VAV1	-0.039	0.18	-10000	0	-0.86	17	17
mol:PI-3-4-P2	0.018	0	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.001	0.014	-10000	0	-10000	0	0
PLEKHA1	0.025	0	-10000	0	-10000	0	0
Rac1/GDP	-0.02	0.067	-10000	0	-0.48	3	3
LAT	0.002	0.023	0.32	2	-10000	0	2
Rac1/GTP	-0.031	0.1	-10000	0	-0.4	20	20
ITK	-0.023	0.11	-10000	0	-0.47	20	20
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.005	0.12	0.29	1	-0.46	11	12
LCK	-0.025	0.15	0.32	1	-0.86	11	12
BTK	-0.007	0.067	-10000	0	-0.47	7	7

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.017	0.11	0.31	2	-0.52	5	7
PDGFB-D/PDGFRB/SLAP	-0.015	0.12	-10000	0	-0.67	11	11
PDGFB-D/PDGFRB/APS/CBL	0.006	0.038	0.39	1	-10000	0	1
AKT1	-0.009	0.065	-10000	0	-0.45	6	6
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.019	0.11	0.31	2	-0.53	5	7
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
FGR	-0.008	0.066	-10000	0	-0.82	2	2
mol:Ca2+	0.014	0.051	-10000	0	-10000	0	0
MYC	-0.064	0.3	-10000	0	-0.88	43	43
SHC1	0	0	-10000	0	-10000	0	0
HRAS/GDP	0	0.037	-10000	0	-0.46	2	2
LRP1/PDGFRB/PDGFB	0.003	0.043	-10000	0	-0.58	1	1
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
GO:0007205	0.014	0.051	-10000	0	-10000	0	0
PTEN	-0.005	0.063	-10000	0	-0.86	2	2
GRB2	0	0	-10000	0	-10000	0	0
GRB7	-0.004	0.098	0.32	6	-0.86	4	10
PDGFB-D/PDGFRB/SHP2	0.005	0.032	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.005	0.032	-10000	0	-10000	0	0
cell cycle arrest	-0.015	0.12	-10000	0	-0.67	11	11
HRAS	0.002	0.023	0.32	2	-10000	0	2
HIF1A	0.046	0.064	-10000	0	-0.61	1	1
GAB1	0.002	0.087	-10000	0	-0.5	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.009	0.087	-10000	0	-0.52	1	1
PDGFB-D/PDGFRB	0.008	0.03	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.005	0.032	-10000	0	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.008	0.13	0.36	2	-0.59	5	7
positive regulation of MAPKKK cascade	0.005	0.031	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
mol:IP3	0.014	0.052	-10000	0	-10000	0	0
E5	0	0.001	-10000	0	-10000	0	0
CSK	0	0.001	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.001	0.08	-10000	0	-0.66	4	4
SHB	-0.002	0.045	-10000	0	-0.86	1	1
BLK	-0.12	0.25	-10000	0	-0.65	65	65
PTPN2	0	0.001	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.005	0.032	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
VAV2	-0.004	0.11	-10000	0	-0.5	3	3
CBL	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.005	0.032	-10000	0	-10000	0	0
LCK	-0.023	0.12	-10000	0	-0.7	11	11
PDGFRB	0.009	0.046	0.32	8	-10000	0	8
ACP1	0	0	-10000	0	-10000	0	0
HCK	-0.021	0.12	-10000	0	-0.64	12	12
ABL1	0.002	0.076	-10000	0	-0.35	3	3
PDGFB-D/PDGFRB/CBL	0	0.088	-10000	0	-0.57	1	1
PTPN1	0	0.001	-10000	0	-10000	0	0
SNX15	0	0	-10000	0	-10000	0	0
STAT3	0	0	-10000	0	-10000	0	0
STAT1	0.002	0.023	0.32	2	-10000	0	2
cell proliferation	-0.051	0.26	-10000	0	-0.76	43	43
SLA	-0.025	0.15	-10000	0	-0.86	11	11
actin cytoskeleton reorganization	0.004	0.045	-10000	0	-0.44	2	2
SRC	0	0.031	-10000	0	-10000	0	0
PI3K	-0.01	0.073	-10000	0	-0.48	8	8
PDGFB-D/PDGFRB/GRB7/SHC	0.001	0.071	-10000	0	-0.57	4	4
SH2B2	0.003	0.033	0.32	4	-10000	0	4
PLCgamma1/SPHK1	0.019	0.12	0.32	2	-0.55	5	7
LYN	-0.003	0.024	-10000	0	-10000	0	0
LRP1	-0.002	0.045	-10000	0	-0.86	1	1
SOS1	0	0	-10000	0	-10000	0	0
STAT5B	0	0	-10000	0	-10000	0	0
STAT5A	0.001	0.016	0.32	1	-10000	0	1
NCK1-2/p130 Cas	0.003	0.038	0.32	1	-0.48	1	2
SPHK1	0.044	0.16	0.32	65	-0.86	5	70
EDG1	0.001	0.003	-10000	0	-10000	0	0
mol:DAG	0.014	0.052	-10000	0	-10000	0	0
PLCG1	0.014	0.052	-10000	0	-10000	0	0
NHERF/PDGFRB	-0.002	0.067	-10000	0	-0.58	4	4
YES1	-0.003	0.024	-10000	0	-10000	0	0
cell migration	-0.002	0.067	-10000	0	-0.58	4	4
SHC/Grb2/SOS1	0.004	0.025	-10000	0	-10000	0	0
SLC9A3R2	-0.007	0.077	-10000	0	-0.86	3	3
SLC9A3R1	-0.002	0.045	-10000	0	-0.86	1	1
NHERF1-2/PDGFRB/PTEN	-0.004	0.074	-10000	0	-0.53	6	6
FYN	-0.002	0.023	-10000	0	-10000	0	0
DOK1	0.006	0.015	-10000	0	-10000	0	0
HRAS/GTP	0.001	0.016	-10000	0	-10000	0	0
PDGFB	0.001	0.016	0.32	1	-10000	0	1
RAC1	-0.019	0.17	-10000	0	-0.46	43	43
PRKCD	0.006	0.015	-10000	0	-10000	0	0
FER	0.006	0.015	-10000	0	-10000	0	0
MAPKKK cascade	0.001	0.011	-10000	0	-10000	0	0
RASA1	0.003	0.042	-10000	0	-0.54	2	2
NCK1	0	0	-10000	0	-10000	0	0
NCK2	-0.001	0.048	0.32	1	-0.86	1	2
p62DOK/Csk	0.004	0.014	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.002	0.044	-10000	0	-0.63	1	1
chemotaxis	0.002	0.074	-10000	0	-0.34	3	3
STAT1-3-5/STAT1-3-5	0.004	0.02	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.007	0.031	0.21	8	-10000	0	8
PTPRJ	0	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	-0.002	0.059	0.34	2	-0.7	2	4
FRAP1	0.013	0.024	-10000	0	-10000	0	0
AKT1	-0.003	0.053	0.24	2	-0.64	2	4
INSR	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.003	0.023	-10000	0	-10000	0	0
mol:GTP	-0.005	0.047	-10000	0	-0.43	4	4
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.014	-10000	0	-10000	0	0
TSC2	-0.005	0.063	-10000	0	-0.86	2	2
RHEB/GDP	-0.005	0.043	-10000	0	-0.39	4	4
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0	0	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.016	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.022	0.034	-10000	0	-0.35	2	2
MAP3K5	-0.046	0.15	-10000	0	-0.46	43	43
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
apoptosis	-0.046	0.15	-10000	0	-0.46	43	43
mol:LY294002	0	0	0.001	2	-10000	0	2
EIF4B	0.027	0.031	-10000	0	-0.37	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.002	0.022	-10000	0	-0.34	1	1
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.004	0.056	-10000	0	-0.73	2	2
mTOR/RHEB/GTP/Raptor/GBL	0.025	0.026	-10000	0	-0.26	2	2
FKBP1A	0	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.005	0.042	-10000	0	-0.38	4	4
mol:Amino Acids	0	0	0.001	2	-10000	0	2
FKBP12/Rapamycin	0	0.001	-10000	0	-10000	0	0
PDPK1	-0.002	0.053	0.26	2	-0.65	2	4
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.072	0.2	-10000	0	-0.63	43	43
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0	0.002	-10000	0	-10000	0	0
TSC1/TSC2	-0.006	0.052	-10000	0	-0.47	4	4
tumor necrosis factor receptor activity	0	0	-10000	0	-0.001	2	2
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	0.007	0.002	-10000	0	-10000	0	0
INS	0.004	0.036	0.32	5	-10000	0	5
PTEN	-0.005	0.063	-10000	0	-0.86	2	2
PDK2	-0.003	0.058	0.26	2	-0.59	3	5
EIF4EBP1	0.008	0.016	0.31	1	-10000	0	1
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
PPP2R5D	0.018	0.023	-10000	0	-10000	0	0
peptide biosynthetic process	0.001	0.009	-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	0.004	2	-0.004	2	4
EEF2	0.001	0.009	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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
BCL3/RelA	0	0	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	-0.02	0.11	-10000	0	-0.58	13	13
NF kappa B1 p50/RelA/I kappa B alpha	-0.01	0.064	-10000	0	-0.7	2	2
NFKBIA	0.012	0.079	-10000	0	-0.38	12	12
MAPK14	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
REL	-0.03	0.16	-10000	0	-0.86	13	13
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0	0	-10000	0	-10000	0	0
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
NF kappa B1 p50 dimer	0	0	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
NFKB1	0.018	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	-0.009	0.063	-10000	0	-0.33	12	12
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.01	0.062	-10000	0	-0.68	2	2
SRC	0.004	0.036	0.32	5	-10000	0	5
PI3K	-0.005	0.071	-10000	0	-0.94	2	2
NF kappa B1 p50/RelA	-0.009	0.064	-10000	0	-0.34	12	12
IKBKB	0	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-10000	0	-10000	0	0
SYK	-0.007	0.077	-10000	0	-0.86	3	3
I kappa B alpha/PIK3R1	-0.014	0.078	-10000	0	-0.62	4	4
cell death	-0.009	0.059	-10000	0	-0.64	2	2
NF kappa B1 p105/c-Rel	-0.02	0.11	-10000	0	-0.58	13	13
LCK	-0.025	0.15	0.32	1	-0.86	11	12
BCL3	0	0	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.002	0.045	-10000	0	-0.86	1	1
SMAD2	0.012	0	-10000	0	-10000	0	0
SMAD3	0.034	0	-10000	0	-10000	0	0
SMAD3/SMAD4	0	0.022	-10000	0	-0.32	1	1
SMAD4/Ubc9/PIASy	-0.002	0.03	-10000	0	-0.58	1	1
SMAD2/SMAD2/SMAD4	0	0.029	-10000	0	-0.46	1	1
PPM1A	0	0	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
SMAD2/SMAD4	-0.001	0.027	-10000	0	-0.53	1	1
MAP3K1	0	0	-10000	0	-10000	0	0
TRAP-1/SMAD4	-0.041	0.16	-10000	0	-0.67	23	23
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
NUP214	0	0	-10000	0	-10000	0	0
CTDSP1	0	0	-10000	0	-10000	0	0
CTDSP2	0	0	-10000	0	-10000	0	0
CTDSPL	0	0	-10000	0	-10000	0	0
KPNB1	0	0	-10000	0	-10000	0	0
TGFBRAP1	-0.051	0.2	-10000	0	-0.86	22	22
UBE2I	0	0	-10000	0	-10000	0	0
NUP153	0	0	-10000	0	-10000	0	0
KPNA2	0.003	0.028	0.32	3	-10000	0	3
PIAS4	0	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.032	0.065	-10000	0	-10000	0	0
BAG4	-0.028	0.15	-10000	0	-0.86	12	12
BAD	0.025	0.026	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	0.007	0.088	0.32	14	-0.86	2	16
BAX	0.025	0.026	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.011	0.019	-10000	0	-10000	0	0
IKBKB	0.038	0.062	-10000	0	-10000	0	0
MAP2K2	0.034	0.03	-10000	0	-10000	0	0
MAP2K1	0.034	0.029	-10000	0	-10000	0	0
SMPD1	0.015	0.019	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.038	0.064	-10000	0	-10000	0	0
MAP2K4	0.03	0.027	-10000	0	-10000	0	0
protein ubiquitination	0.039	0.063	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.038	0.033	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.03	0.029	-10000	0	-10000	0	0
CRADD	-0.002	0.045	-10000	0	-0.86	1	1
mol:ceramide	0.019	0.027	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0	0	-10000	0	-10000	0	0
MAP3K1	0.025	0.027	-10000	0	-10000	0	0
TRADD	-0.002	0.045	-10000	0	-0.86	1	1
RELA/p50	0	0	-10000	0	-10000	0	0
MAPK3	0.036	0.029	-10000	0	-10000	0	0
MAPK1	0.036	0.029	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.032	0.065	-10000	0	-10000	0	0
KSR1	0.025	0.028	-10000	0	-10000	0	0
MAPK8	0.01	0.11	-10000	0	-0.44	20	20
TRAF2	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.038	0.062	-10000	0	-10000	0	0
TNF R/SODD	-0.022	0.12	-10000	0	-0.67	12	12
TNF	-0.031	0.17	0.32	2	-0.86	14	16
CYCS	0.026	0.025	-10000	0	-10000	0	0
IKBKG	0.038	0.062	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.006	0.064	-10000	0	-0.36	2	2
RELA	0	0	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AIFM1	0.026	0.025	-10000	0	-10000	0	0
TNF/TNF R/SODD	-0.04	0.15	-10000	0	-0.58	26	26
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	-0.001	0.014	-10000	0	-10000	0	0
NSMAF	0.032	0.065	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	-0.002	0.045	-10000	0	-0.86	1	1

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.019	0.1	-10000	0	-0.54	14	14
Ran/GTP/Exportin 1/HDAC1	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.016	0.085	-10000	0	-0.44	14	14
SUMO1	0	0	-10000	0	-10000	0	0
ZFPM1	-0.005	0.063	-10000	0	-0.86	2	2
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
FKBP3	0	0	-10000	0	-10000	0	0
Histones	-0.009	0.043	-10000	0	-10000	0	0
YY1/LSF	-0.006	0.05	-10000	0	-0.42	5	5
SMG5	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	-0.014	0.075	-10000	0	-0.39	14	14
I kappa B alpha/HDAC1	-0.01	0.051	-10000	0	-10000	0	0
SAP18	0	0	-10000	0	-10000	0	0
RELA	-0.012	0.065	-10000	0	-0.34	14	14
HDAC1/Smad7	-0.003	0.043	-10000	0	-0.58	2	2
RANGAP1	0	0	-10000	0	-10000	0	0
HDAC3/TR2	-0.01	0.051	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.002	0.013	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.012	0.059	-10000	0	-0.31	14	14
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.003	0.067	0.32	2	-0.86	2	4
GATA1	0.003	0.028	0.32	3	-10000	0	3
Mad/Max	0.001	0.011	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.002	0.025	-10000	0	-10000	0	0
RBBP7	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
RBBP4	0	0	-10000	0	-10000	0	0
MAX	0	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
NFKBIA	-0.011	0.057	-10000	0	-0.3	14	14
KAT2B	-0.007	0.077	-10000	0	-0.86	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0	0	-10000	0	-10000	0	0
SIN3 complex	0	0	-10000	0	-10000	0	0
SMURF1	0	0	-10000	0	-10000	0	0
CHD3	0.006	0.043	0.32	7	-10000	0	7
SAP30	0	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	-0.005	0.063	-10000	0	-0.86	2	2
YY1/HDAC3	-0.011	0.055	-10000	0	-0.52	1	1
YY1/HDAC2	-0.003	0.028	-10000	0	-0.32	3	3
YY1/HDAC1	-0.003	0.028	-10000	0	-0.32	3	3
NuRD/MBD2 Complex (MeCP1)	0.002	0.013	-10000	0	-10000	0	0
PPARG	-0.019	0.1	-10000	0	-0.51	15	15
HDAC8/hEST1B	0	0	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.01	0.051	-10000	0	-10000	0	0
MBD3L2	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.003	0.042	-10000	0	-0.58	2	2
CREBBP	0	0	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.002	0.014	-10000	0	-10000	0	0
HDAC1	0	0	-10000	0	-10000	0	0
HDAC3	-0.011	0.057	-10000	0	-0.3	14	14
HDAC2	0	0	-10000	0	-10000	0	0
YY1	-0.003	0.033	-10000	0	-0.37	3	3
HDAC8	0	0	-10000	0	-10000	0	0
SMAD7	-0.005	0.063	-10000	0	-0.86	2	2
NCOR2	0	0	-10000	0	-10000	0	0
MXD1	0.001	0.016	0.32	1	-10000	0	1
STAT3	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0	0	-10000	0	-10000	0	0
YY1/LSF/HDAC1	-0.005	0.046	-10000	0	-0.52	2	2
YY1/SAP30/HDAC1	-0.002	0.026	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.011	0.057	-10000	0	-0.3	14	14
histone deacetylation	0.002	0.013	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.009	0.046	-10000	0	-10000	0	0
nuclear export	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
GATAD2B	0	0	-10000	0	-10000	0	0
GATAD2A	0	0	-10000	0	-10000	0	0
GATA2/HDAC3	-0.011	0.066	-10000	0	-0.53	2	2
GATA1/HDAC1	0.002	0.02	-10000	0	-10000	0	0
GATA1/HDAC3	-0.008	0.056	-10000	0	-10000	0	0
CHD4	0	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	-0.024	0.13	-10000	0	-0.67	14	14
SIN3/HDAC complex/Mad/Max	0	0.005	-10000	0	-10000	0	0
NuRD Complex	0.002	0.014	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.008	0.042	-10000	0	-10000	0	0
SIN3B	0	0	-10000	0	-10000	0	0
MTA2	0	0	-10000	0	-10000	0	0
SIN3A	0	0	-10000	0	-10000	0	0
XPO1	0	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0	0	-10000	0	-10000	0	0
HDAC complex	0	0	-10000	0	-10000	0	0
GATA1/Fog1	-0.002	0.053	-10000	0	-0.67	2	2
FKBP25/HDAC1/HDAC2	0	0	-10000	0	-10000	0	0
TNF	-0.031	0.17	0.32	2	-0.86	14	16
negative regulation of cell growth	0	0.005	-10000	0	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.002	0.013	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.017	0.09	-10000	0	-0.47	14	14
SIN3/HDAC complex/NCoR1	-0.001	0.016	-10000	0	-10000	0	0
TFCP2	-0.005	0.063	-10000	0	-0.86	2	2
NR2C1	0	0	-10000	0	-10000	0	0
MBD3	0	0	-10000	0	-10000	0	0
MBD2	0	0	-10000	0	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0	0.038	-10000	0	-0.45	2	2
TC10/GTP	-0.002	0.034	-10000	0	-0.44	2	2
Insulin Receptor/Insulin/IRS1/Shp2	0.003	0.022	-10000	0	-10000	0	0
HRAS	0.002	0.023	0.32	2	-10000	0	2
APS homodimer	0.003	0.033	0.32	4	-10000	0	4
GRB14	-0.014	0.11	-10000	0	-0.86	6	6
FOXO3	-0.025	0.13	-10000	0	-0.74	12	12
AKT1	-0.01	0.069	-10000	0	-0.46	8	8
INSR	0	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.003	0.023	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0	0	-10000	0	-10000	0	0
SORBS1	-0.005	0.063	-10000	0	-0.86	2	2
CRK	0	0	-10000	0	-10000	0	0
PTPN1	0.031	0.005	-10000	0	-10000	0	0
CAV1	0.001	0.008	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II/C3G	-0.001	0.039	-10000	0	-0.48	2	2
Insulin Receptor/Insulin/IRS1/NCK2	0.002	0.038	-10000	0	-0.55	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.002	0.057	-10000	0	-0.71	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.002	0.014	-10000	0	-10000	0	0
RPS6KB1	0.04	0.069	-10000	0	-0.42	7	7
PARD6A	0.001	0.016	0.32	1	-10000	0	1
CBL	0	0	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0	0	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.007	0.063	-10000	0	-0.68	1	1
HRAS/GTP	0	0	-10000	0	-10000	0	0
Insulin Receptor	0	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.003	0.022	-10000	0	-10000	0	0
PRKCI	-0.003	0.017	-10000	0	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.011	0.076	-10000	0	-0.5	8	8
SHC1	0	0	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	-0.003	0.037	-10000	0	-0.51	2	2
PI3K	-0.002	0.059	-10000	0	-0.73	2	2
NCK2	-0.001	0.048	0.32	1	-0.86	1	2
RHOQ	0	0	-10000	0	-10000	0	0
mol:H2O2	0	0	-10000	0	-10000	0	0
HRAS/GDP	0.001	0.016	-10000	0	-10000	0	0
AKT2	-0.01	0.069	-10000	0	-0.46	8	8
PRKCZ	-0.033	0.14	-10000	0	-0.68	17	17
SH2B2	0.003	0.033	0.32	4	-10000	0	4
SHC/SHIP	0.001	0.008	-10000	0	-10000	0	0
F2RL2	-0.081	0.27	0.32	8	-0.86	38	46
TRIP10	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.003	0.022	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.003	0.022	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
RASA1	-0.005	0.063	-10000	0	-0.86	2	2
NCK1	0	0	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	-0.001	0.042	-10000	0	-0.51	2	2
TC10/GDP	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.003	0.022	-10000	0	-10000	0	0
INPP5D	0.001	0.008	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
SGK1	-0.035	0.19	-10000	0	-1.1	12	12
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
p62DOK/RasGAP	-0.003	0.038	-10000	0	-0.52	2	2
INS	0.007	0.037	0.32	5	-10000	0	5
mol:PI-3-4-P2	0.001	0.008	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
EIF4EBP1	0.04	0.07	-10000	0	-0.42	8	8
PTPRA	0	0.002	-10000	0	-10000	0	0
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
TC10/GTP/CIP4	0	0	-10000	0	-10000	0	0
PDPK1	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.002	0.013	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.003	0.022	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.003	0.025	-10000	0	-10000	0	0
Par3/Par6	-0.047	0.16	-10000	0	-0.5	38	38

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.013	0.091	-10000	0	-0.58	9	9
VEGFR1 homodimer/NRP1	0	0	-10000	0	-10000	0	0
mol:DAG	0.002	0.016	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-10000	0	-10000	0	0
CaM/Ca2+	0.002	0.014	-10000	0	-10000	0	0
HIF1A	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
AKT1	-0.002	0.054	-10000	0	-0.68	2	2
PLCG1	0.002	0.016	-10000	0	-10000	0	0
NOS3	0.05	0.036	-10000	0	-0.4	2	2
CBL	0	0	-10000	0	-10000	0	0
mol:NO	0.05	0.035	-10000	0	-0.38	2	2
FLT1	0.024	0	-10000	0	-10000	0	0
PGF	0.005	0.04	0.32	6	-10000	0	6
VEGFR1 homodimer/NRP2/VEGFR121	-0.004	0.049	-10000	0	-0.53	3	3
CALM1	0	0	-10000	0	-10000	0	0
PIK3CA	-0.002	0.045	-10000	0	-0.86	1	1
eNOS/Hsp90	-0.003	0.028	-10000	0	-10000	0	0
endothelial cell proliferation	0.014	0.11	-10000	0	-10000	0	0
mol:Ca2+	0.002	0.016	-10000	0	-10000	0	0
MAPK3	0.045	0.006	-10000	0	-10000	0	0
MAPK1	0.045	0.006	-10000	0	-10000	0	0
PIK3R1	-0.005	0.063	-10000	0	-0.86	2	2
PLGF homodimer	0.005	0.04	0.32	6	-10000	0	6
PRKACA	0	0	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0	0	-10000	0	-10000	0	0
VEGFA homodimer	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0	0	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.05	0.005	-10000	0	-10000	0	0
PI3K	-0.001	0.063	-10000	0	-0.74	2	2
PRKCA	0.04	0.007	-10000	0	-10000	0	0
PRKCB	-0.007	0.15	-10000	0	-0.5	32	32
VEGFR1 homodimer/PLGF homodimer	0.004	0.029	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
VEGFB	-0.019	0.14	0.32	2	-0.86	9	11
mol:IP3	0.002	0.016	-10000	0	-10000	0	0
RASA1	-0.015	0.09	-10000	0	-0.52	11	11
NRP2	-0.006	0.079	0.32	1	-0.86	3	4
VEGFR1 homodimer	0.023	0	-10000	0	-10000	0	0
VEGFB homodimer	-0.019	0.13	0.32	2	-0.86	9	11
NCK1	0	0	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.003	0.028	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.061	-10000	0	-0.72	2	2
mol:L-citrulline	0.05	0.035	-10000	0	-0.38	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0	0	-10000	0	-10000	0	0
CD2AP	0	0	-10000	0	-10000	0	0
PI3K/GAB1	-0.001	0.06	-10000	0	-0.71	2	2
PDPK1	-0.002	0.054	-10000	0	-0.68	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-10000	0	-10000	0	0
mol:NADP	0.05	0.035	-10000	0	-0.38	2	2
HSP90AA1	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	-0.004	0.053	-10000	0	-0.58	3	3

×

Canonical NF-kappaB 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
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.065	0.021	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
RIP2/NOD2	-0.007	0.069	-10000	0	-0.67	4	4
NFKBIA	0.039	0	-10000	0	-10000	0	0
BIRC2	0	0	-10000	0	-10000	0	0
IKBKB	0	0	-10000	0	-10000	0	0
RIPK2	0	0	-10000	0	-10000	0	0
IKBKG	-0.003	0.03	-10000	0	-10000	0	0
IKK complex/A20	-0.018	0.09	-10000	0	-0.45	14	14
NEMO/A20/RIP2	0	0	-10000	0	-10000	0	0
XPO1	0	0	-10000	0	-10000	0	0
NEMO/ATM	-0.003	0.028	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
Exportin 1/RanGTP	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	-0.003	0.024	-10000	0	-10000	0	0
BCL10/MALT1/TRAF6	-0.002	0.03	-10000	0	-0.58	1	1
NOD2	-0.009	0.089	-10000	0	-0.86	4	4
NFKB1	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
MALT1	0	0	-10000	0	-10000	0	0
cIAP1/UbcH5C	0	0	-10000	0	-10000	0	0
ATM	0	0	-10000	0	-10000	0	0
TNF/TNFR1A	-0.024	0.13	-10000	0	-0.67	14	14
TRAF6	-0.002	0.045	-10000	0	-0.86	1	1
PRKCA	0	0	-10000	0	-10000	0	0
CHUK	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
TNF	-0.031	0.17	0.32	2	-0.86	14	16
NF kappa B1 p50/RelA	0	0	-10000	0	-10000	0	0
BCL10	0	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.039	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
IKK complex	-0.003	0.026	-10000	0	-10000	0	0
CYLD	0	0	-10000	0	-10000	0	0
IKK complex/PKC alpha	-0.003	0.025	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.004	0.13	0.32	14	-0.86	7	21
CLTC	0.021	0.017	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	-0.011	0.046	-10000	0	-10000	0	0
Dynamin 2/GTP	0.001	0.008	-10000	0	-10000	0	0
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.018	0.023	-10000	0	-10000	0	0
CPE	0.003	0.042	-10000	0	-0.59	1	1
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.012	0.05	-10000	0	-10000	0	0
CTNND1	0	0.005	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.019	0.029	-10000	0	-10000	0	0
TSHR	0	0	-10000	0	-10000	0	0
INS	0.01	0.02	-10000	0	-10000	0	0
BIN1	-0.002	0.045	-10000	0	-0.86	1	1
mol:Choline	-0.012	0.05	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.001	0.013	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	0.001	0.008	-10000	0	-10000	0	0
JUP	0.018	0.023	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0	0.033	-10000	0	-0.54	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	-0.001	0.086	-10000	0	-0.33	22	22
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0	-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	0.016	0.057	-10000	0	-10000	0	0
positive regulation of phagocytosis	0	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	-0.012	0.046	-10000	0	-0.34	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.003	0.04	-10000	0	-0.32	4	4
clathrin heavy chain/ACAP1	0.021	0.035	-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	-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	0.005	-10000	0	-10000	0	0
NME1	0.001	0.013	-10000	0	-10000	0	0
clathrin coat assembly	0.021	0.017	-10000	0	-10000	0	0
IL2RA	0.012	0.051	-10000	0	-0.31	7	7
VAMP3	0	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.007	0.074	-10000	0	-0.44	7	7
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.02	0.083	-10000	0	-0.36	21	21
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.02	0.029	-10000	0	-10000	0	0
SDC1	0.014	0.039	-10000	0	-0.29	4	4
ARF6/GDP	0.001	0.008	-10000	0	-10000	0	0
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.016	0.059	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.012	0.05	-10000	0	-10000	0	0
endocytosis	0	0.032	0.53	1	-10000	0	1
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.033	0.16	-10000	0	-0.47	44	44
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	0.003	0.028	0.32	3	-10000	0	3
Dynamin 2/GDP	0.001	0.011	-10000	0	-10000	0	0
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	0.029	0.019	-10000	0	-10000	0	0
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.014	0.053	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	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	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0	-9999	-10000	0	0
CD4	-0.07	0.23	-9999	-0.86	30	30
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	0	-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	0	-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	0	-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	0	-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	0	-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	-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	-0.023	0.079	-9999	-0.29	30	30
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.009	0	-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	0.009	0	-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	-0.047	0.16	-9999	-0.58	30	30

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.003	0.033	-10000	0	-10000	0	0
CLOCK	-0.002	0.044	-10000	0	-0.86	1	1
TIMELESS/CRY2	-0.001	0.019	-10000	0	-10000	0	0
DEC1/BMAL1	0	0.001	-10000	0	-10000	0	0
ATR	0	0	-10000	0	-10000	0	0
NR1D1	0.03	0.078	-10000	0	-1.5	1	1
ARNTL	0	0.002	-10000	0	-10000	0	0
TIMELESS	0.033	0.023	-10000	0	-10000	0	0
NPAS2	-0.002	0.044	-10000	0	-0.86	1	1
CRY2	0	0	-10000	0	-10000	0	0
mol:CO	-0.011	0.008	0.14	1	-10000	0	1
CHEK1	0.006	0.043	0.32	7	-10000	0	7
mol:HEME	0.011	0.008	-10000	0	-0.14	1	1
PER1	0	0	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	-0.003	0.042	-10000	0	-0.57	2	2
BMAL1/CLOCK	0.036	0.056	-10000	0	-0.91	1	1
S phase of mitotic cell cycle	0.003	0.033	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.003	0.033	-10000	0	-10000	0	0
mol:NADPH	0.011	0.008	-10000	0	-0.14	1	1
PER1/TIMELESS	-0.001	0.019	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0	0	-10000	0	-10000	0	0

×

TCGA08_p53

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
CDKN2A	0.1	0.064	-9999	-9999
TP53	0.027	0.019	-9999	-9999
Senescence	0.027	0.019	-9999	-9999
Apoptosis	0.027	0.019	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	-0.057	0.039	-9999	-9999
MDM4	0	0	-9999	-9999

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-10000	0	-9999	0
Ran/GTP/Exportin 1/HDAC4	0	0	-10000	0	-9999	0
MDM2/SUMO1	0	0	-10000	0	-9999	0
HDAC4	0.001	0.016	0.32	1	-9999	1
Ran/GTP/Exportin 1/HDAC1	0	0	-10000	0	-9999	0
SUMO1	0	0	-10000	0	-9999	0
NPC/RanGAP1/SUMO1	0	0	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
XPO1	0	0	-10000	0	-9999	0
EntrezGene:23636	0	0	-10000	0	-9999	0
RAN	0	0	-10000	0	-9999	0
EntrezGene:8021	0	0	-10000	0	-9999	0
RANBP2	0	0	-10000	0	-9999	0
SUMO1/HDAC4	0.001	0.011	-10000	0	-9999	0
SUMO1/HDAC1	0	0	-10000	0	-9999	0
RANGAP1	0	0	-10000	0	-9999	0
MDM2/SUMO1/SUMO1	0	0	-10000	0	-9999	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	0	-10000	0	-9999	0
Ran/GTP	0	0	-10000	0	-9999	0
EntrezGene:23225	0	0	-10000	0	-9999	0
MDM2	0	0	-10000	0	-9999	0
UBE2I	0	0	-10000	0	-9999	0
Ran/GTP/Exportin 1	0	0	-10000	0	-9999	0
NPC	0	0	-10000	0	-9999	0
PIAS2	0	0	-10000	0	-9999	0
PIAS1	0	0	-10000	0	-9999	0
EntrezGene:9972	0	0	-10000	0	-9999	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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.001	0.011	-10000	0	-9999	0
FBXW11	0	0	-10000	0	-9999	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-10000	0	-9999	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-10000	0	-9999	0
CHUK	0	0	-10000	0	-9999	0
NF kappa B2 p100/RelB	0.002	0.017	-10000	0	-9999	0
NFKB1	0	0	-10000	0	-9999	0
MAP3K14	0.001	0.016	0.32	1	-9999	1
NF kappa B1 p50/RelB	0.001	0.016	-10000	0	-9999	0
RELB	0.002	0.023	0.32	2	-9999	2
NFKB2	0	0	-10000	0	-9999	0
NF kappa B2 p52/RelB	0.001	0.014	-10000	0	-9999	0
regulation of B cell activation	0.001	0.014	-10000	0	-9999	0

pid_entity	TCGA.ZS.A9CG	TCGA.ZS.A9CF	TCGA.ZS.A9CE	TCGA.ZS.A9CD
109_MAP3K5	-0.23	-0.23	-0.23	0.044
47_PPARGC1A	0	0	0	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	0.2	-1	0	0
30_TGFB1/TGF beta receptor Type II	0	0	0	0
84_STAT5B	0.085	0.1	0.034	0.033
84_STAT5A	0.085	0.1	0.034	0.033