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

Pathway.Name	Avg.Num.Perturbations
Signaling events mediated by Stem cell factor receptor (c-Kit)	241
Signaling mediated by p38-alpha and p38-beta	227
Endothelins	162
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	159
EGFR-dependent Endothelin signaling events	141
Class IB PI3K non-lipid kinase events	137
IGF1 pathway	135
Arf6 signaling events	131
Nongenotropic Androgen signaling	103
HIF-1-alpha transcription factor network	98

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
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.4582	241	18810	78	-1.1	0.35	1000	-1000	-0.052	-1000
Signaling mediated by p38-alpha and p38-beta	0.4316	227	10030	44	-0.73	0.016	1000	-1000	-0.041	-1000
Endothelins	0.3080	162	15577	96	-0.83	0.03	1000	-1000	-0.047	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.3023	159	10868	68	-1	0.47	1000	-1000	-0.069	-1000
EGFR-dependent Endothelin signaling events	0.2681	141	2964	21	-0.45	0.016	1000	-1000	-0.053	-1000
Class IB PI3K non-lipid kinase events	0.2605	137	411	3	-0.18	-1000	1000	-1000	-0.007	-1000
IGF1 pathway	0.2567	135	7741	57	-0.37	0.15	1000	-1000	-0.063	-1000
Arf6 signaling events	0.2490	131	8158	62	-0.45	0.018	1000	-1000	-0.039	-1000
Nongenotropic Androgen signaling	0.1958	103	5381	52	-0.59	0.28	1000	-1000	-0.04	-1000
HIF-1-alpha transcription factor network	0.1863	98	7494	76	-0.51	0.054	1000	-1000	-0.039	-1000
Signaling events mediated by PTP1B	0.1844	97	7424	76	-0.48	0.21	1000	-1000	-0.058	-1000
Calcium signaling in the CD4+ TCR pathway	0.1844	97	3024	31	-0.54	0.026	1000	-1000	-0.054	-1000
S1P1 pathway	0.1806	95	3428	36	-0.67	0.016	1000	-1000	-0.053	-1000
FOXM1 transcription factor network	0.1768	93	4789	51	-0.84	0.017	1000	-1000	-0.084	-1000
Glucocorticoid receptor regulatory network	0.1692	89	10248	114	-1.2	0.3	1000	-1000	-0.056	-1000
Ras signaling in the CD4+ TCR pathway	0.1445	76	1308	17	-0.23	0.013	1000	-1000	-0.032	-1000
PDGFR-alpha signaling pathway	0.1426	75	3316	44	-0.84	0.046	1000	-1000	-0.053	-1000
Ephrin B reverse signaling	0.1350	71	3438	48	-0.26	0.14	1000	-1000	-0.044	-1000
IL6-mediated signaling events	0.1350	71	5391	75	-0.52	0.052	1000	-1000	-0.047	-1000
BMP receptor signaling	0.1331	70	5721	81	-0.6	0.04	1000	-1000	-0.064	-1000
FAS signaling pathway (CD95)	0.1331	70	3303	47	-0.97	0.072	1000	-1000	-0.035	-1000
Fc-epsilon receptor I signaling in mast cells	0.1217	64	6256	97	-0.51	0.039	1000	-1000	-0.061	-1000
IL23-mediated signaling events	0.1141	60	3620	60	-0.93	0.019	1000	-1000	-0.099	-1000
Integrins in angiogenesis	0.1084	57	4843	84	-0.57	0.053	1000	-1000	-0.068	-1000
Plasma membrane estrogen receptor signaling	0.1084	57	4946	86	-0.35	0.16	1000	-1000	-0.064	-1000
Signaling events mediated by PRL	0.1065	56	1927	34	-0.44	0.025	1000	-1000	-0.036	-1000
IL4-mediated signaling events	0.1046	55	5061	91	-0.63	0.23	1000	-1000	-0.15	-1000
E-cadherin signaling in keratinocytes	0.1008	53	2313	43	-0.38	0.044	1000	-1000	-0.049	-1000
p75(NTR)-mediated signaling	0.0913	48	6010	125	-0.25	0.016	1000	-1000	-0.064	-1000
Glypican 1 network	0.0913	48	2348	48	-0.55	0.061	1000	-1000	-0.037	-1000
Nectin adhesion pathway	0.0798	42	2702	63	-0.1	0.016	1000	-1000	-0.057	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0798	42	3148	74	-0.38	0.08	1000	-1000	-0.072	-1000
ErbB4 signaling events	0.0779	41	2830	69	-0.5	0.12	1000	-1000	-0.06	-1000
Signaling events regulated by Ret tyrosine kinase	0.0760	40	3290	82	-0.18	0.018	1000	-1000	-0.065	-1000
Insulin Pathway	0.0760	40	2962	74	-0.39	0.046	1000	-1000	-0.068	-1000
Visual signal transduction: Rods	0.0760	40	2094	52	-0.58	0.029	1000	-1000	-0.056	-1000
EPHB forward signaling	0.0741	39	3337	85	-0.26	0.12	1000	-1000	-0.068	-1000
ErbB2/ErbB3 signaling events	0.0703	37	2448	65	-0.48	0.03	1000	-1000	-0.049	-1000
Presenilin action in Notch and Wnt signaling	0.0684	36	2209	61	-0.53	0.04	1000	-1000	-0.049	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0665	35	3050	85	-0.54	0.035	1000	-1000	-0.062	-1000
Signaling events mediated by the Hedgehog family	0.0646	34	1798	52	-0.22	0.14	1000	-1000	-0.062	-1000
S1P5 pathway	0.0646	34	587	17	-0.25	0.078	1000	-1000	-0.028	-1000
TCGA08_retinoblastoma	0.0646	34	277	8	-0.043	0.021	1000	-1000	-0.008	-1000
Syndecan-3-mediated signaling events	0.0589	31	1097	35	-0.51	0.016	1000	-1000	-0.048	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0589	31	3833	120	-0.42	0.18	1000	-1000	-0.05	-1000
S1P4 pathway	0.0589	31	786	25	-0.25	0.03	1000	-1000	-0.03	-1000
TCGA08_rtk_signaling	0.0570	30	802	26	-0.38	0.028	1000	-1000	-0.015	-1000
Syndecan-2-mediated signaling events	0.0551	29	2002	69	-0.46	0.046	1000	-1000	-0.037	-1000
LPA receptor mediated events	0.0532	28	2900	102	-0.51	0.045	1000	-1000	-0.052	-1000
S1P3 pathway	0.0532	28	1217	42	-0.25	0.041	1000	-1000	-0.032	-1000
Regulation of nuclear SMAD2/3 signaling	0.0513	27	3749	136	-0.52	0.065	1000	-1000	-0.042	-1000
Ceramide signaling pathway	0.0513	27	2113	76	-0.35	0.098	1000	-1000	-0.041	-1000
Reelin signaling pathway	0.0513	27	1526	56	-0.1	0.044	1000	-1000	-0.054	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0513	27	1443	52	-0.53	0.089	1000	-1000	-0.039	-1000
FOXA2 and FOXA3 transcription factor networks	0.0494	26	1207	46	-0.84	0.075	1000	-1000	-0.02	-1000
IL27-mediated signaling events	0.0494	26	1353	51	-0.52	0.04	1000	-1000	-0.055	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0475	25	710	28	-0.25	0.03	1000	-1000	-0.033	-1000
amb2 Integrin signaling	0.0456	24	2043	82	-0.62	0.049	1000	-1000	-0.053	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0456	24	2164	88	-0.55	0.068	1000	-1000	-0.071	-1000
mTOR signaling pathway	0.0437	23	1256	53	-0.072	0.042	1000	-1000	-0.052	-1000
Wnt signaling	0.0437	23	164	7	-0.029	0.012	1000	-1000	-0.019	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0418	22	2850	125	-0.52	0.059	1000	-1000	-0.081	-1000
E-cadherin signaling events	0.0418	22	113	5	-0.039	0.014	1000	-1000	-0.029	-1000
Thromboxane A2 receptor signaling	0.0399	21	2244	105	-0.38	0.098	1000	-1000	-0.056	-1000
IL1-mediated signaling events	0.0399	21	1319	62	-0.12	0.082	1000	-1000	-0.065	-1000
Canonical Wnt signaling pathway	0.0399	21	1073	51	-0.53	0.2	1000	-1000	-0.04	-1000
Regulation of Telomerase	0.0399	21	2213	102	-0.51	0.067	1000	-1000	-0.078	-1000
Aurora B signaling	0.0399	21	1443	67	-0.52	0.077	1000	-1000	-0.055	-1000
IL12-mediated signaling events	0.0380	20	1818	87	-0.88	0.027	1000	-1000	-0.073	-1000
Osteopontin-mediated events	0.0380	20	791	38	-0.51	0.062	1000	-1000	-0.062	-1000
Regulation of Androgen receptor activity	0.0380	20	1455	70	-0.6	0.061	1000	-1000	-0.048	-1000
Coregulation of Androgen receptor activity	0.0361	19	1509	76	-0.25	0.026	1000	-1000	-0.034	-1000
Insulin-mediated glucose transport	0.0361	19	608	32	-0.11	0.049	1000	-1000	-0.044	-1000
Regulation of p38-alpha and p38-beta	0.0361	19	1075	54	-0.43	0.051	1000	-1000	-0.045	-1000
Syndecan-4-mediated signaling events	0.0323	17	1184	67	-0.55	0.05	1000	-1000	-0.064	-1000
Caspase cascade in apoptosis	0.0304	16	1191	74	-0.22	0.074	1000	-1000	-0.029	-1000
PLK2 and PLK4 events	0.0285	15	46	3	-0.019	-0.009	1000	-1000	-0.008	-1000
Noncanonical Wnt signaling pathway	0.0285	15	409	26	-0.042	0.032	1000	-1000	-0.055	-1000
Hedgehog signaling events mediated by Gli proteins	0.0285	15	1014	65	-0.25	0.08	1000	-1000	-0.058	-1000
IL2 signaling events mediated by PI3K	0.0266	14	851	58	-0.11	0.04	1000	-1000	-0.065	-1000
E-cadherin signaling in the nascent adherens junction	0.0266	14	1129	76	-0.055	0.046	1000	-1000	-0.066	-1000
Arf6 trafficking events	0.0266	14	1035	71	-0.41	0.054	1000	-1000	-0.055	-1000
BCR signaling pathway	0.0266	14	1405	99	-0.24	0.076	1000	-1000	-0.066	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0247	13	618	45	-0.049	0.07	1000	-1000	-0.062	-1000
Class I PI3K signaling events mediated by Akt	0.0228	12	845	68	-0.24	0.069	1000	-1000	-0.046	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0190	10	586	54	-0.1	0.044	1000	-1000	-0.073	-1000
JNK signaling in the CD4+ TCR pathway	0.0190	10	177	17	-0.083	0.057	1000	-1000	-0.04	-1000
EPO signaling pathway	0.0190	10	591	55	-0.13	0.064	1000	-1000	-0.057	-1000
TRAIL signaling pathway	0.0190	10	526	48	-0.024	0.047	1000	-1000	-0.054	-1000
VEGFR1 specific signals	0.0190	10	564	56	-0.52	0.071	1000	-1000	-0.054	-1000
Cellular roles of Anthrax toxin	0.0171	9	372	39	-0.14	0.023	1000	-1000	-0.023	-1000
Signaling events mediated by HDAC Class III	0.0171	9	385	40	-0.1	0.029	1000	-1000	-0.025	-1000
FoxO family signaling	0.0171	9	605	64	-0.027	0.11	1000	-1000	-0.032	-1000
Signaling mediated by p38-gamma and p38-delta	0.0171	9	138	15	0	0.03	1000	-1000	-0.013	-1000
Signaling events mediated by HDAC Class II	0.0152	8	602	75	-0.18	0.043	1000	-1000	-0.036	-1000
Retinoic acid receptors-mediated signaling	0.0152	8	491	58	-0.1	0.042	1000	-1000	-0.054	-1000
Syndecan-1-mediated signaling events	0.0133	7	263	34	-0.1	0.016	1000	-1000	-0.054	-1000
IFN-gamma pathway	0.0133	7	506	68	-0.055	0.086	1000	-1000	-0.063	-1000
TCR signaling in naïve CD8+ T cells	0.0133	7	690	93	-0.083	0.089	1000	-1000	-0.05	-1000
Visual signal transduction: Cones	0.0114	6	231	38	-0.03	0.026	1000	-1000	-0.044	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0114	6	254	37	-0.055	0.051	1000	-1000	-0.036	-1000
ceramide signaling pathway	0.0114	6	336	49	-0.13	0.06	1000	-1000	-0.033	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0114	6	555	83	-0.13	0.066	1000	-1000	-0.057	-1000
Paxillin-dependent events mediated by a4b1	0.0114	6	236	36	-0.055	0.029	1000	-1000	-0.05	-1000
p38 MAPK signaling pathway	0.0114	6	305	44	-0.036	0.039	1000	-1000	-0.052	-1000
HIF-2-alpha transcription factor network	0.0095	5	244	43	-0.21	0.22	1000	-1000	-0.11	-1000
Atypical NF-kappaB pathway	0.0076	4	154	31	-0.055	0.063	1000	-1000	-0.034	-1000
IL2 signaling events mediated by STAT5	0.0076	4	92	22	-0.054	0.087	1000	-1000	-0.019	-1000
Class I PI3K signaling events	0.0076	4	294	73	-0.027	0.089	1000	-1000	-0.046	-1000
PDGFR-beta signaling pathway	0.0076	4	455	97	-0.19	0.045	1000	-1000	-0.069	-1000
Aurora A signaling	0.0057	3	208	60	-0.087	0.047	1000	-1000	-0.045	-1000
Arf6 downstream pathway	0.0057	3	132	43	-0.039	0.04	1000	-1000	-0.032	-1000
Signaling events mediated by HDAC Class I	0.0057	3	412	104	-0.24	0.074	1000	-1000	-0.052	-1000
LPA4-mediated signaling events	0.0019	1	13	12	0	0.042	1000	-1000	-0.007	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0019	1	40	34	-0.004	0.057	1000	-1000	-0.042	-1000
Ephrin A reverse signaling	0.0019	1	7	7	0	0.03	1000	-1000	-0.02	-1000
Effects of Botulinum toxin	0.0019	1	29	26	-0.046	0.024	1000	-1000	-0.038	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	18	23	-0.029	0.063	1000	-1000	-0.046	-1000
Canonical NF-kappaB pathway	0.0000	0	4	39	-0.018	0.11	1000	-1000	-0.06	-1000
BARD1 signaling events	0.0000	0	12	57	-0.078	0.052	1000	-1000	-0.044	-1000
Circadian rhythm pathway	0.0000	0	13	22	-0.053	0.065	1000	-1000	-0.053	-1000
a4b1 and a4b7 Integrin signaling	0.0000	0	0	5	-0.003	0.016	1000	-1000	-0.036	-1000
Aurora C signaling	0.0000	0	1	7	-0.014	0.021	1000	-1000	-0.028	-1000
PLK1 signaling events	0.0000	0	45	85	-0.09	0.067	1000	-1000	-0.033	-1000
TCGA08_p53	0.0000	0	0	7	-0.004	0.015	1000	-1000	-0.012	-1000
Glypican 2 network	0.0000	0	0	4	-0.007	-1000	1000	-1000	-0.02	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.039	1000	-1000	-0.042	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0000	0	18	33	-0.017	0.05	1000	-1000	-0.048	-1000
Rapid glucocorticoid signaling	0.0000	0	16	20	-0.003	0.016	1000	-1000	-0.024	-1000
Arf1 pathway	0.0000	0	6	54	-0.001	0.045	1000	-1000	-0.034	-1000
Alternative NF-kappaB pathway	0.0000	0	3	13	-0.002	0.016	1000	-1000	-0.046	-1000
Total	NA	4535	276112	7203	-41	-2000	131000	-131000	-6.3	-131000

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

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
MAP4K1	-0.3	0.16	-10000	0	-0.39	414	414
CRKL	-0.33	0.18	-10000	0	-0.42	414	414
HRAS	-0.25	0.15	-10000	0	-0.38	28	28
mol:PIP3	-0.33	0.18	-10000	0	-0.42	411	411
SPRED1	0.013	0.045	-10000	0	-0.72	2	2
SPRED2	0.016	0	-10000	0	-10000	0	0
GAB1	-0.36	0.18	-10000	0	-0.45	415	415
FOXO3	-0.3	0.16	-10000	0	-0.38	413	413
AKT1	-0.33	0.18	-10000	0	-0.41	414	414
BAD	-0.3	0.16	-10000	0	-0.38	413	413
megakaryocyte differentiation	-0.35	0.18	-10000	0	-0.44	414	414
GSK3B	-0.3	0.16	-10000	0	-0.38	413	413
RAF1	-0.2	0.13	-10000	0	-0.36	5	5
SHC1	0.016	0	-10000	0	-10000	0	0
STAT3	-0.36	0.18	-10000	0	-0.44	414	414
STAT1	-0.87	0.45	-10000	0	-1	442	442
HRAS/SPRED1	-0.21	0.11	-10000	0	-0.42	6	6
cell proliferation	-0.35	0.18	-10000	0	-0.44	414	414
PIK3CA	0.015	0.007	-10000	0	-10000	0	0
TEC	0.016	0	-10000	0	-10000	0	0
RPS6KB1	-0.35	0.18	-10000	0	-0.44	414	414
HRAS/SPRED2	-0.21	0.1	-10000	0	-0.31	16	16
LYN/TEC/p62DOK	-0.33	0.16	-10000	0	-0.41	413	413
MAPK3	-0.14	0.098	-10000	0	-0.29	2	2
STAP1	-0.36	0.18	-10000	0	-0.45	419	419
GRAP2	0.014	0.019	-10000	0	-10000	0	0
JAK2	-0.72	0.34	-10000	0	-0.87	423	423
STAT1 (dimer)	-0.85	0.43	-10000	0	-1	442	442
mol:Gleevec	0.013	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.33	0.16	-10000	0	-0.41	413	413
actin filament polymerization	-0.36	0.18	-10000	0	-0.44	421	421
LYN	0.016	0.01	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.49	0.25	-10000	0	-0.61	420	420
PIK3R1	-0.056	0.22	-10000	0	-0.72	51	51
CBL/CRKL/GRB2	-0.3	0.15	-10000	0	-0.37	414	414
PI3K	-0.36	0.21	-10000	0	-0.45	416	416
PTEN	-0.002	0.12	-10000	0	-0.72	13	13
SCF/KIT/EPO/EPOR	-1	0.55	-10000	0	-1.3	413	413
MAPK8	-0.36	0.18	-10000	0	-0.45	414	414
STAT3 (dimer)	-0.35	0.18	-10000	0	-0.44	414	414
positive regulation of transcription	-0.11	0.084	-10000	0	-0.23	2	2
mol:GDP	-0.28	0.13	-10000	0	-0.37	129	129
PIK3C2B	-0.36	0.18	-10000	0	-0.45	414	414
CBL/CRKL	-0.3	0.17	-10000	0	-0.38	414	414
FER	-0.36	0.18	-10000	0	-0.44	414	414
SH2B3	-0.36	0.18	-10000	0	-0.44	414	414
PDPK1	-0.3	0.16	-10000	0	-0.38	410	410
SNAI2	-0.41	0.23	-10000	0	-0.5	427	427
positive regulation of cell proliferation	-0.61	0.31	-10000	0	-0.74	442	442
KITLG	-0.019	0.077	-10000	0	-0.75	3	3
cell motility	-0.61	0.31	-10000	0	-0.74	442	442
PTPN6	0.032	0.018	-10000	0	-10000	0	0
EPOR	-0.22	0.14	-10000	0	-0.62	1	1
STAT5A (dimer)	-0.5	0.26	-10000	0	-0.6	443	443
SOCS1	0.015	0.012	-10000	0	-10000	0	0
cell migration	0.35	0.18	0.44	416	-10000	0	416
SOS1	0.016	0	-10000	0	-10000	0	0
EPO	-0.02	0.058	-10000	0	-10000	0	0
VAV1	0.012	0.027	-10000	0	-10000	0	0
GRB10	-0.36	0.19	-10000	0	-0.45	414	414
PTPN11	0.029	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.38	0.19	-10000	0	-0.48	417	417
GO:0007205	0.018	0.01	-10000	0	-10000	0	0
MAP2K1	-0.15	0.11	-10000	0	-0.32	2	2
CBL	0.016	0	-10000	0	-10000	0	0
KIT	-1.1	0.58	-10000	0	-1.4	414	414
MAP2K2	-0.15	0.11	-10000	0	-0.32	2	2
SHC/Grb2/SOS1	-0.33	0.16	-10000	0	-0.41	413	413
STAT5A	-0.51	0.26	-10000	0	-0.62	443	443
GRB2	0.013	0.022	-10000	0	-10000	0	0
response to radiation	-0.4	0.22	-10000	0	-0.49	427	427
SHC/GRAP2	-0.001	0.009	-10000	0	-10000	0	0
PTPRO	-0.36	0.18	-10000	0	-0.45	414	414
SH2B2	-0.36	0.18	-10000	0	-0.45	421	421
DOK1	0.014	0.019	-10000	0	-10000	0	0
MATK	-0.36	0.18	-10000	0	-0.45	416	416
CREBBP	0.006	0.037	-10000	0	-0.72	1	1
BCL2	-0.44	0.55	-10000	0	-1.5	105	105

×

Signaling mediated by p38-alpha and p38-beta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.73	0.63	-9999	-1.2	317	317
MKNK1	0.016	0	-9999	-10000	0	0
MAPK14	-0.18	0.16	-9999	-0.37	78	78
ATF2/c-Jun	-0.26	0.38	-9999	-1	97	97
MAPK11	-0.18	0.16	-9999	-0.31	317	317
MITF	-0.21	0.21	-9999	-0.37	319	319
MAPKAPK5	-0.2	0.2	-9999	-0.37	317	317
KRT8	-0.21	0.21	-9999	-0.37	317	317
MAPKAPK3	0.015	0.012	-9999	-10000	0	0
MAPKAPK2	0.016	0.01	-9999	-10000	0	0
p38alpha-beta/CK2	-0.27	0.25	-9999	-0.47	317	317
CEBPB	-0.21	0.21	-9999	-0.37	317	317
SLC9A1	-0.2	0.2	-9999	-0.37	317	317
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.22	0.23	-9999	-0.38	317	317
p38alpha-beta/MNK1	-0.22	0.18	-9999	-0.37	317	317
JUN	-0.26	0.38	-9999	-1	97	97
PPARGC1A	-0.27	0.3	-9999	-0.45	328	328
USF1	-0.21	0.2	-9999	-0.37	317	317
RAB5/GDP/GDI1	-0.16	0.13	-9999	-0.33	82	82
NOS2	-0.22	0.2	-9999	-0.38	317	317
DDIT3	-0.21	0.2	-9999	-0.37	317	317
RAB5A	0.016	0	-9999	-10000	0	0
HSPB1	-0.17	0.18	-9999	-0.36	125	125
p38alpha-beta/HBP1	-0.22	0.18	-9999	-0.37	317	317
CREB1	-0.22	0.21	-9999	-0.38	317	317
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.17	0.18	-9999	-0.4	78	78
RPS6KA4	-0.2	0.2	-9999	-0.37	317	317
PLA2G4A	-0.43	0.34	-9999	-0.66	328	328
GDI1	-0.21	0.2	-9999	-0.37	317	317
TP53	-0.26	0.25	-9999	-0.46	317	317
RPS6KA5	-0.22	0.22	-9999	-0.38	330	330
ESR1	-0.32	0.27	-9999	-0.45	390	390
HBP1	0.016	0	-9999	-10000	0	0
MEF2C	-0.24	0.26	-9999	-0.41	325	325
MEF2A	-0.2	0.2	-9999	-0.37	317	317
EIF4EBP1	-0.22	0.21	-9999	-0.38	317	317
KRT19	-0.22	0.22	-9999	-0.39	319	319
ELK4	-0.2	0.2	-9999	-0.37	317	317
ATF6	-0.2	0.2	-9999	-0.37	317	317
ATF1	-0.22	0.21	-9999	-0.38	317	317
p38alpha-beta/MAPKAPK2	-0.22	0.18	-9999	-0.46	79	79
p38alpha-beta/MAPKAPK3	-0.22	0.18	-9999	-0.46	81	81

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.11	0.24	-9999	-0.46	172	172
PTK2B	0.016	0.001	-9999	-10000	0	0
mol:Ca2+	-0.14	0.3	-9999	-0.75	76	76
EDN1	-0.21	0.35	-9999	-0.72	169	169
EDN3	-0.6	0.28	-9999	-0.72	437	437
EDN2	-0.061	0.09	-9999	-0.72	2	2
HRAS/GDP	-0.24	0.25	-9999	-0.5	199	199
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.11	0.19	-9999	-0.38	133	133
ADCY4	-0.096	0.21	-9999	-0.38	174	174
ADCY5	-0.094	0.2	-9999	-0.38	173	173
ADCY6	-0.092	0.2	-9999	-0.38	172	172
ADCY7	-0.092	0.2	-9999	-0.38	172	172
ADCY1	-0.093	0.2	-9999	-0.38	172	172
ADCY2	-0.098	0.21	-9999	-0.39	176	176
ADCY3	-0.092	0.2	-9999	-0.38	172	172
ADCY8	-0.092	0.2	-9999	-0.38	172	172
ADCY9	-0.092	0.2	-9999	-0.38	172	172
arachidonic acid secretion	-0.53	0.37	-9999	-0.7	399	399
ETB receptor/Endothelin-1/Gq/GTP	-0.26	0.25	-9999	-0.43	322	322
GNAO1	0.016	0	-9999	-10000	0	0
HRAS	0.009	0.014	-9999	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.095	0.24	-9999	-0.42	171	171
ETA receptor/Endothelin-1/Gs/GTP	-0.093	0.23	-9999	-0.41	172	172
mol:GTP	-0.007	0.009	-9999	-10000	0	0
COL3A1	-0.11	0.24	-9999	-0.46	161	161
EDNRB	-0.35	0.37	-9999	-0.72	260	260
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.11	0.24	-9999	-0.47	133	133
CYSLTR1	-0.11	0.25	-9999	-0.46	173	173
SLC9A1	-0.063	0.14	-9999	-0.27	81	81
mol:GDP	-0.27	0.27	-9999	-0.54	211	211
SLC9A3	-0.4	0.41	-9999	-0.68	314	314
RAF1	-0.36	0.29	-9999	-0.56	303	303
JUN	-0.24	0.47	-9999	-1.1	109	109
JAK2	-0.11	0.25	-9999	-0.46	171	171
mol:IP3	-0.23	0.24	-9999	-0.47	210	210
ETA receptor/Endothelin-1	-0.12	0.29	-9999	-0.54	171	171
PLCB1	-0.1	0.25	-9999	-0.73	74	74
PLCB2	0.005	0.008	-9999	-10000	0	0
ETA receptor/Endothelin-3	-0.44	0.21	-9999	-0.54	437	437
FOS	-0.71	0.47	-9999	-1	374	374
Gai/GDP	-0.1	0.16	-9999	-0.35	47	47
CRK	0.014	0.032	-9999	-0.72	1	1
mol:Ca ++	-0.3	0.33	-9999	-0.66	202	202
BCAR1	0.017	0.001	-9999	-10000	0	0
PRKCB1	-0.22	0.24	-9999	-0.48	188	188
GNAQ	-0.008	0.01	-9999	-10000	0	0
GNAZ	0.008	0.078	-9999	-0.72	6	6
GNAL	0.012	0.056	-9999	-0.72	3	3
Gs family/GDP	-0.25	0.22	-9999	-0.48	208	208
ETA receptor/Endothelin-1/Gq/GTP	-0.085	0.17	-9999	-0.32	151	151
MAPK14	-0.24	0.25	-9999	-0.49	208	208
TRPC6	-0.15	0.32	-9999	-0.8	76	76
GNAI2	0.016	0.007	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
GNAI1	-0.25	0.35	-9999	-0.72	189	189
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.27	0.27	-9999	-0.46	298	298
ETB receptor/Endothelin-2	-0.29	0.29	-9999	-0.58	262	262
ETB receptor/Endothelin-3	-0.67	0.34	-9999	-0.78	455	455
ETB receptor/Endothelin-1	-0.41	0.38	-9999	-0.68	329	329
MAPK3	-0.62	0.42	-9999	-0.86	380	380
MAPK1	-0.62	0.42	-9999	-0.86	380	380
Rac1/GDP	-0.24	0.25	-9999	-0.5	203	203
cAMP biosynthetic process	-0.039	0.19	-9999	-0.33	104	104
MAPK8	-0.16	0.29	-9999	-0.62	118	118
SRC	0.016	0.007	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.3	0.32	-9999	-0.58	245	245
p130Cas/CRK/Src/PYK2	-0.24	0.29	-9999	-0.56	189	189
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.24	0.25	-9999	-0.5	198	198
COL1A2	-0.32	0.35	-9999	-0.69	193	193
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	0.03	0.077	-9999	-0.53	4	4
mol:DAG	-0.23	0.24	-9999	-0.46	216	216
MAP2K2	-0.47	0.34	-9999	-0.66	381	381
MAP2K1	-0.47	0.34	-9999	-0.66	381	381
EDNRA	0.024	0.053	-9999	-0.71	2	2
positive regulation of muscle contraction	-0.089	0.21	-9999	-0.39	172	172
Gq family/GDP	-0.22	0.21	-9999	-0.48	157	157
HRAS/GTP	-0.28	0.26	-9999	-0.44	309	309
PRKCH	-0.22	0.24	-9999	-0.47	194	194
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	-0.22	0.24	-9999	-0.47	194	194
PRKCB	-0.23	0.24	-9999	-0.46	221	221
PRKCE	-0.22	0.24	-9999	-0.47	192	192
PRKCD	-0.22	0.24	-9999	-0.47	196	196
PRKCG	-0.22	0.24	-9999	-0.47	194	194
regulation of vascular smooth muscle contraction	-0.83	0.55	-9999	-1.2	374	374
PRKCQ	-0.23	0.24	-9999	-0.48	192	192
PLA2G4A	-0.6	0.44	-9999	-0.8	399	399
GNA14	-0.018	0.09	-9999	-0.73	6	6
GNA15	0.006	0.021	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
GNA11	0.009	0.008	-9999	-10000	0	0
Rac1/GTP	-0.094	0.24	-9999	-0.42	171	171
MMP1	0.026	0.14	-9999	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.022	0.012	-10000	0	-10000	0	0
NFATC2	-0.065	0.22	-10000	0	-0.54	80	80
NFATC3	-0.17	0.14	-10000	0	-0.31	157	157
CD40LG	-0.79	0.56	-10000	0	-1.1	363	363
ITCH	-0.056	0.15	-10000	0	-0.59	1	1
CBLB	-0.057	0.15	-10000	0	-1.1	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.33	0.24	-10000	0	-0.68	80	80
JUNB	0.012	0.056	-10000	0	-0.72	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.12	0.15	-10000	0	-0.31	197	197
T cell anergy	-0.13	0.24	-10000	0	-0.43	197	197
TLE4	-0.048	0.23	-10000	0	-0.56	61	61
Jun/NFAT1-c-4/p21SNFT	-0.7	0.54	-10000	0	-1	352	352
AP-1/NFAT1-c-4	-1	0.74	-10000	0	-1.4	362	362
IKZF1	-0.029	0.16	-10000	0	-0.52	21	21
T-helper 2 cell differentiation	-0.15	0.29	-10000	0	-0.74	65	65
AP-1/NFAT1	-0.47	0.35	-10000	0	-0.65	376	376
CALM1	-0.039	0.095	-10000	0	-0.3	1	1
EGR2	-0.89	0.85	-10000	0	-1.7	256	256
EGR3	-0.98	0.85	-10000	0	-1.6	319	319
NFAT1/FOXP3	-0.035	0.16	-10000	0	-0.38	61	61
EGR1	-0.6	0.28	-10000	0	-0.72	436	436
JUN	-0.12	0.29	-10000	0	-0.72	97	97
EGR4	0.001	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.062	0.1	-10000	0	-0.34	1	1
GBP3	-0.073	0.28	-10000	0	-0.81	52	52
FOSL1	0.016	0.01	-10000	0	-10000	0	0
NFAT1-c-4/MAF/IRF4	-0.64	0.51	-10000	0	-0.96	344	344
DGKA	-0.028	0.16	-10000	0	-0.61	12	12
CREM	0.016	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.92	0.57	-10000	0	-1.3	363	363
CTLA4	-0.02	0.14	-10000	0	-0.53	11	11
NFAT1-c-4 (dimer)/EGR1	-0.95	0.58	-10000	0	-1.3	362	362
NFAT1-c-4 (dimer)/EGR4	-0.64	0.52	-10000	0	-0.96	362	362
FOS	-0.51	0.34	-10000	0	-0.72	374	374
IFNG	-0.19	0.26	-10000	0	-0.92	40	40
T cell activation	-0.48	0.39	-10000	0	-0.78	285	285
MAF	-0.051	0.21	-10000	0	-0.72	48	48
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.47	0.43	0.75	353	-10000	0	353
TNF	-0.76	0.52	-10000	0	-1.1	359	359
FASLG	-0.95	0.82	-10000	0	-1.4	362	362
TBX21	-0.034	0.19	-10000	0	-0.72	35	35
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.01	0.047	-10000	0	-0.72	1	1
PTPN1	-0.03	0.16	-10000	0	-0.53	24	24
NFAT1-c-4/ICER1	-0.64	0.51	-10000	0	-0.96	360	360
GATA3	-0.076	0.19	-10000	0	-0.72	38	38
T-helper 1 cell differentiation	-0.19	0.25	-10000	0	-0.89	41	41
IL2RA	-0.34	0.24	-10000	0	-0.57	189	189
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.027	0.16	-10000	0	-0.52	21	21
E2F1	0.004	0.055	-10000	0	-10000	0	0
PPARG	-0.53	0.32	-10000	0	-0.72	388	388
SLC3A2	-0.028	0.16	-10000	0	-0.52	21	21
IRF4	0.011	0.03	-10000	0	-10000	0	0
PTGS2	-0.96	0.64	-10000	0	-1.3	387	387
CSF2	-0.79	0.56	-10000	0	-1.1	361	361
JunB/Fra1/NFAT1-c-4	-0.61	0.49	-10000	0	-0.92	352	352
IL4	-0.16	0.31	-10000	0	-0.78	63	63
IL5	-0.79	0.56	-10000	0	-1.1	360	360
IL2	-0.48	0.4	-10000	0	-0.81	280	280
IL3	-0.085	0.051	-10000	0	-10000	0	0
RNF128	-0.26	0.4	-10000	0	-0.78	197	197
NFATC1	-0.47	0.43	-10000	0	-0.75	353	353
CDK4	0.28	0.26	0.53	163	-10000	0	163
PTPRK	-0.081	0.3	-10000	0	-0.9	54	54
IL8	-0.8	0.57	-10000	0	-1.1	366	366
POU2F1	0.026	0	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.015	0.012	-9999	-10000	0	0
EGFR	-0.38	0.37	-9999	-0.72	277	277
EGF/EGFR	-0.45	0.34	-9999	-0.6	393	393
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.33	0.26	-9999	-0.47	372	372
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.013	0.046	-9999	-0.72	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.24	0.35	-9999	-0.72	178	178
EGF/EGFR dimer/SHC	-0.39	0.29	-9999	-0.55	372	372
mol:GDP	-0.33	0.25	-9999	-0.46	372	372
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.22	0.34	-9999	-0.72	169	169
GRB2/SOS1	-0.001	0.011	-9999	-10000	0	0
HRAS/GTP	-0.3	0.23	-9999	-0.67	96	96
SHC1	0.016	0	-9999	-10000	0	0
HRAS/GDP	-0.3	0.24	-9999	-0.68	96	96
FRAP1	-0.29	0.26	-9999	-0.7	94	94
EGF/EGFR dimer	-0.45	0.33	-9999	-0.64	372	372
SOS1	0.016	0	-9999	-10000	0	0
GRB2	0.013	0.022	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.18	0.25	-9999	-0.54	171	171

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.18	0.32	0.72	137	-10000	0	137
PI3K Class IB/PDE3B	-0.18	0.32	-10000	0	-0.72	137	137
PDE3B	-0.18	0.32	-10000	0	-0.72	137	137

×

IGF1 pathway

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
NCK2	0.016	0.01	-10000	0	-10000	0	0
PTK2	0.015	0.014	-10000	0	-10000	0	0
CRKL	-0.23	0.29	-10000	0	-0.46	280	280
GRB2/SOS1/SHC	0.002	0.011	-10000	0	-10000	0	0
HRAS	0.015	0.012	-10000	0	-10000	0	0
IRS1/Crk	-0.23	0.29	-10000	0	-0.47	280	280
IGF-1R heterotetramer/IGF1/PTP1B	-0.25	0.26	-10000	0	-0.49	265	265
AKT1	-0.21	0.28	-10000	0	-0.62	118	118
BAD	-0.18	0.26	-10000	0	-0.61	100	100
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.23	0.29	-10000	0	-0.46	280	280
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.23	0.29	-10000	0	-0.47	280	280
RAF1	-0.17	0.24	-10000	0	-0.58	95	95
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.23	0.26	-10000	0	-0.45	266	266
YWHAZ	0.014	0.017	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.26	0.31	-10000	0	-0.51	280	280
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
RPS6KB1	-0.21	0.28	-10000	0	-0.62	119	119
GNB2L1	0.016	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.14	0.21	-10000	0	-0.48	95	95
PXN	0.016	0	-10000	0	-10000	0	0
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	-0.001	0.011	-10000	0	-10000	0	0
HRAS/GTP	-0.2	0.23	-10000	0	-0.62	78	78
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.19	0.21	-10000	0	-0.38	265	265
IGF-1R heterotetramer	-0.074	0.18	-10000	0	-0.62	37	37
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.25	0.28	-10000	0	-0.47	280	280
Crk/p130 Cas/Paxillin	-0.22	0.25	-10000	0	-0.42	265	265
IGF1R	-0.074	0.18	-10000	0	-0.62	37	37
IGF1	-0.37	0.38	-10000	0	-0.75	262	262
IRS2/Crk	-0.31	0.37	-10000	0	-0.57	307	307
PI3K	-0.27	0.3	-10000	0	-0.5	276	276
apoptosis	0.15	0.22	0.52	95	-10000	0	95
HRAS/GDP	-0.001	0.007	-10000	0	-10000	0	0
PRKCD	-0.23	0.3	-10000	0	-0.51	265	265
RAF1/14-3-3 E	-0.14	0.21	-10000	0	-0.48	95	95
BAD/14-3-3	-0.16	0.24	-10000	0	-0.56	95	95
PRKCZ	-0.22	0.28	-10000	0	-0.44	276	276
Crk/p130 Cas/Paxillin/FAK1	-0.19	0.21	-10000	0	-0.57	95	95
PTPN1	0.008	0.036	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.26	0.31	-10000	0	-0.54	265	265
BCAR1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.22	0.24	-10000	0	-0.43	265	265
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.23	0.29	-10000	0	-0.46	280	280
GRB10	0.011	0.064	-10000	0	-0.72	4	4
PTPN11	-0.23	0.29	-10000	0	-0.46	280	280
IRS1	-0.26	0.31	-10000	0	-0.51	280	280
IRS2	-0.34	0.38	-10000	0	-0.6	307	307
IGF-1R heterotetramer/IGF1	-0.31	0.32	-10000	0	-0.62	265	265
GRB2	0.013	0.022	-10000	0	-10000	0	0
PDPK1	-0.23	0.3	-10000	0	-0.46	276	276
YWHAE	0.015	0.032	-10000	0	-0.72	1	1
PRKD1	-0.3	0.36	-10000	0	-0.6	281	281
SHC1	0.016	0	-10000	0	-10000	0	0

×

Arf6 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.001	0.021	-9999	-0.48	1	1
ARNO/beta Arrestin1-2	-0.19	0.18	-9999	-0.35	285	285
EGFR	-0.38	0.37	-9999	-0.72	277	277
EPHA2	0.005	0.09	-9999	-0.72	8	8
USP6	0.015	0.016	-9999	-10000	0	0
IQSEC1	0.016	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.45	0.33	-9999	-0.64	372	372
ARRB2	0.018	0.037	-9999	-0.41	4	4
mol:GTP	0.008	0.005	-9999	-10000	0	0
ARRB1	0.014	0.035	-9999	-0.72	1	1
FBXO8	0.016	0	-9999	-10000	0	0
TSHR	0.01	0.064	-9999	-0.72	4	4
EGF	-0.24	0.35	-9999	-0.72	178	178
somatostatin receptor activity	0	0	-9999	-0.001	314	314
ARAP2	0	0	-9999	0	313	313
mol:GDP	-0.16	0.14	-9999	-0.29	232	232
mol:PI-3-4-5-P3	0	0	-9999	-0.001	313	313
ITGA2B	0.016	0.01	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.004	0.053	-9999	-0.41	8	8
ADAP1	0	0	-9999	0	279	279
KIF13B	0.015	0.032	-9999	-0.72	1	1
HGF/MET	-0.054	0.16	-9999	-0.54	52	52
PXN	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.18	0.13	-9999	-0.27	313	313
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.39	0.29	-9999	-0.55	372	372
ADRB2	-0.38	0.37	-9999	-0.72	284	284
receptor agonist activity	0	0	-9999	0	314	314
actin filament binding	0	0	-9999	-0.001	315	315
SRC	0.016	0.007	-9999	-10000	0	0
ITGB3	0.014	0.02	-9999	-10000	0	0
GNAQ	0	0	-9999	-0.001	306	306
EFA6/PI-4-5-P2	-0.001	0	-9999	-0.001	313	313
ARF6/GDP	-0.029	0.057	-9999	-0.25	4	4
ARF6/GDP/GULP/ACAP1	-0.2	0.2	-9999	-0.42	189	189
alphaIIb/beta3 Integrin/paxillin/GIT1	0.002	0.015	-9999	-10000	0	0
ACAP1	0	0	-9999	0	6	6
ACAP2	0	0	-9999	0	314	314
LHCGR/beta Arrestin2	0.015	0.054	-9999	-0.6	4	4
EFNA1	0.013	0.022	-9999	-10000	0	0
HGF	0.015	0.01	-9999	-10000	0	0
CYTH3	0	0	-9999	-0.001	314	314
CYTH2	-0.003	0.002	-9999	-0.004	315	315
NCK1	0.016	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	276	276
endosomal lumen acidification	0	0	-9999	0	181	181
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.12	0.29	-9999	-0.72	97	97
GNAQ/ARNO	-0.004	0.003	-9999	-0.006	306	306
mol:Phosphatidic acid	0	0	-9999	0	314	314
PIP3-E	0.011	0.049	-9999	-0.72	2	2
MET	-0.057	0.22	-9999	-0.72	52	52
GNA14	-0.008	0.09	-9999	-0.72	6	6
GNA15	0.014	0.02	-9999	-10000	0	0
GIT1	0.015	0.016	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	314	314
GNA11	0.016	0	-9999	-10000	0	0
LHCGR	0.009	0.066	-9999	-0.72	4	4
AGTR1	-0.32	0.35	-9999	-0.72	224	224
desensitization of G-protein coupled receptor protein signaling pathway	0.015	0.053	-9999	-0.59	4	4
IPCEF1/ARNO	-0.31	0.24	-9999	-0.44	373	373
alphaIIb/beta3 Integrin	-0.001	0.011	-9999	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.013	0.009	-10000	0	-10000	0	0
GNB1/GNG2	-0.049	0.15	-10000	0	-0.43	70	70
regulation of S phase of mitotic cell cycle	-0.044	0.15	-10000	0	-0.33	112	112
GNAO1	0.016	0	-10000	0	-10000	0	0
HRAS	0.013	0.012	-10000	0	-10000	0	0
SHBG/T-DHT	0.006	0.005	-10000	0	-10000	0	0
PELP1	0.014	0.002	-10000	0	-10000	0	0
AKT1	0.014	0.013	-10000	0	-10000	0	0
MAP2K1	-0.08	0.15	-10000	0	-0.43	69	69
T-DHT/AR	-0.07	0.19	-10000	0	-0.56	69	69
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.005	0.004	-10000	0	-0.007	374	374
GNAI2	0.016	0.007	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	-0.25	0.35	-10000	0	-0.72	189	189
mol:GDP	-0.098	0.21	-10000	0	-0.51	90	90
cell proliferation	-0.26	0.23	-10000	0	-0.4	374	374
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
FOS	-0.59	0.42	-10000	0	-0.85	374	374
mol:Ca2+	-0.036	0.039	-10000	0	-0.076	244	244
MAPK3	-0.18	0.19	-10000	0	-0.56	61	61
MAPK1	-0.13	0.12	-10000	0	-0.29	64	64
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
mol:IP3	-0.003	0.002	-10000	0	-0.005	374	374
cAMP biosynthetic process	0.03	0.032	-10000	0	-10000	0	0
GNG2	0.015	0.032	-10000	0	-0.72	1	1
potassium channel inhibitor activity	-0.003	0.002	-10000	0	-0.005	374	374
HRAS/GTP	-0.067	0.14	-10000	0	-0.42	69	69
actin cytoskeleton reorganization	-0.036	0.11	-10000	0	-0.37	51	51
SRC	0.014	0.008	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.003	0.002	-10000	0	-0.005	374	374
PI3K	-0.045	0.14	-10000	0	-0.47	51	51
apoptosis	0.28	0.22	0.41	374	-10000	0	374
T-DHT/AR/PELP1	-0.056	0.17	-10000	0	-0.48	69	69
HRAS/GDP	-0.082	0.2	-10000	0	-0.57	69	69
CREB1	-0.3	0.24	-10000	0	-0.44	374	374
RAC1-CDC42/GTP	-0.036	0.11	-10000	0	-0.38	51	51
AR	-0.085	0.25	-10000	0	-0.73	69	69
GNB1	0.016	0.01	-10000	0	-10000	0	0
RAF1	-0.067	0.15	-10000	0	-0.43	69	69
RAC1-CDC42/GDP	-0.086	0.19	-10000	0	-0.53	69	69
T-DHT/AR/PELP1/Src	-0.051	0.15	-10000	0	-0.44	69	69
MAP2K2	-0.08	0.15	-10000	0	-0.43	69	69
T-DHT/AR/PELP1/Src/PI3K	-0.044	0.15	-10000	0	-0.33	112	112
GNAZ	0.007	0.078	-10000	0	-0.72	6	6
SHBG	0.016	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.061	0.13	-10000	0	-0.38	14	14
mol:T-DHT	-0.002	0.002	-10000	0	-0.003	313	313
RAC1	0.016	0	-10000	0	-10000	0	0
GNRH1	-0.014	0.12	-10000	0	-0.55	26	26
Gi family/GTP	-0.11	0.13	-10000	0	-0.26	193	193
CDC42	0.016	0	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.1	0.47	-10000	0	-0.75	127	127
HDAC7	0.002	0.005	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.14	0.3	0.56	1	-0.64	82	83
SMAD4	0.015	0.045	-10000	0	-0.72	2	2
ID2	-0.1	0.47	-10000	0	-0.77	121	121
AP1	-0.47	0.35	-10000	0	-0.67	375	375
ABCG2	-0.12	0.5	-10000	0	-0.82	126	126
HIF1A	0.001	0.12	-10000	0	-0.55	7	7
TFF3	-0.18	0.54	-10000	0	-0.85	156	156
GATA2	0.003	0.043	-10000	0	-10000	0	0
AKT1	0.006	0.1	-10000	0	-0.25	7	7
response to hypoxia	-0.014	0.11	-10000	0	-0.16	43	43
MCL1	-0.1	0.47	-10000	0	-0.74	132	132
NDRG1	-0.11	0.48	-10000	0	-0.74	133	133
SERPINE1	-0.1	0.48	-10000	0	-0.77	122	122
FECH	-0.1	0.47	-10000	0	-0.76	125	125
FURIN	-0.1	0.47	-10000	0	-0.77	121	121
NCOA2	0.017	0.014	-10000	0	-10000	0	0
EP300	0.032	0.15	-10000	0	-0.2	2	2
HMOX1	-0.1	0.48	-10000	0	-0.76	123	123
BHLHE40	-0.12	0.47	-10000	0	-0.72	146	146
BHLHE41	-0.12	0.47	-10000	0	-0.72	146	146
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.029	0.083	-10000	0	-0.5	7	7
ENG	0.052	0.14	-10000	0	-0.45	7	7
JUN	-0.12	0.29	-10000	0	-0.73	97	97
RORA	-0.11	0.49	-10000	0	-0.79	125	125
ABCB1	-0.41	0.57	-10000	0	-1.2	169	169
TFRC	-0.11	0.48	-10000	0	-0.76	132	132
CXCR4	-0.11	0.48	-10000	0	-0.75	129	129
TF	-0.12	0.49	-10000	0	-0.79	130	130
CITED2	-0.11	0.48	-10000	0	-0.78	121	121
HIF1A/ARNT	-0.23	0.44	0.65	20	-0.88	118	138
LDHA	-0.022	0.038	-10000	0	-10000	0	0
ETS1	-0.1	0.47	-10000	0	-0.76	123	123
PGK1	-0.1	0.47	-10000	0	-0.76	125	125
NOS2	-0.12	0.47	-10000	0	-0.72	146	146
ITGB2	-0.1	0.48	-10000	0	-0.76	126	126
ALDOA	-0.1	0.47	-10000	0	-0.75	127	127
Cbp/p300/CITED2	-0.12	0.47	-10000	0	-0.81	105	105
FOS	-0.51	0.34	-10000	0	-0.73	374	374
HK2	-0.1	0.47	-10000	0	-0.76	125	125
SP1	0.004	0.049	-10000	0	-10000	0	0
GCK	0.054	0.2	-10000	0	-10000	0	0
HK1	-0.1	0.47	-10000	0	-0.76	125	125
NPM1	-0.1	0.47	-10000	0	-0.77	121	121
EGLN1	-0.1	0.47	-10000	0	-0.76	125	125
CREB1	0.026	0.002	-10000	0	-10000	0	0
PGM1	-0.11	0.48	-10000	0	-0.76	128	128
SMAD3	0.017	0.033	-10000	0	-0.72	1	1
EDN1	-0.46	0.64	-10000	0	-1.4	169	169
IGFBP1	-0.1	0.47	-10000	0	-0.77	122	122
VEGFA	-0.033	0.37	-10000	0	-0.59	83	83
HIF1A/JAB1	-0.013	0.061	-10000	0	-0.6	4	4
CP	-0.22	0.56	-10000	0	-0.85	180	180
CXCL12	-0.22	0.6	-10000	0	-0.94	176	176
COPS5	0.018	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.003	0.04	-10000	0	-0.54	3	3
BNIP3	-0.11	0.48	-10000	0	-0.76	127	127
EGLN3	-0.11	0.48	-10000	0	-0.78	125	125
CA9	-0.11	0.48	-10000	0	-0.76	132	132
TERT	-0.1	0.47	-10000	0	-0.76	123	123
ENO1	-0.1	0.47	-10000	0	-0.76	125	125
PFKL	-0.1	0.47	-10000	0	-0.77	122	122
NCOA1	0.015	0.032	-10000	0	-0.72	1	1
ADM	-0.25	0.55	-10000	0	-0.84	190	190
ARNT	0.008	0.09	-10000	0	-10000	0	0
HNF4A	0.022	0	-10000	0	-10000	0	0
ADFP	-0.12	0.5	-10000	0	-0.81	131	131
SLC2A1	-0.03	0.36	-10000	0	-0.58	81	81
LEP	-0.3	0.6	-10000	0	-0.87	233	233
HIF1A/ARNT/Cbp/p300	-0.13	0.34	-10000	0	-0.66	85	85
EPO	0.004	0.32	-10000	0	-0.5	43	43
CREBBP	0.032	0.15	-10000	0	-0.3	3	3
HIF1A/ARNT/Cbp/p300/HDAC7	-0.15	0.3	0.56	1	-0.64	88	89
PFKFB3	-0.11	0.48	-10000	0	-0.77	122	122
NT5E	-0.11	0.49	-10000	0	-0.79	122	122

×

Signaling events mediated by PTP1B

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
PDGFRB	0.016	0	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.34	0.22	-10000	0	-0.5	338	338
PTP1B/AKT1	-0.17	0.13	-10000	0	-0.28	297	297
FYN	0.013	0.045	-10000	0	-0.72	2	2
p210 bcr-abl/PTP1B	-0.21	0.15	-10000	0	-0.32	298	298
EGFR	-0.39	0.37	-10000	0	-0.74	277	277
EGF/EGFR	-0.48	0.32	-10000	0	-0.66	372	372
CSF1	0.016	0.007	-10000	0	-10000	0	0
AKT1	0.013	0.02	-10000	0	-10000	0	0
INSR	0.016	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.2	0.15	-10000	0	-0.31	312	312
Insulin Receptor/Insulin	-0.12	0.084	-10000	0	-10000	0	0
HCK	0.013	0.024	-10000	0	-10000	0	0
CRK	0.015	0.032	-10000	0	-0.72	1	1
TYK2	-0.19	0.14	-10000	0	-0.3	297	297
EGF	-0.25	0.35	-10000	0	-0.74	178	178
YES1	0.015	0.032	-10000	0	-0.72	1	1
CAV1	-0.43	0.26	-10000	0	-0.57	385	385
TXN	0.004	0.012	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.22	0.19	-10000	0	-0.35	299	299
cell migration	0.21	0.15	0.32	298	-10000	0	298
STAT3	0.014	0.001	-10000	0	-10000	0	0
PRLR	-0.021	0.07	-10000	0	-10000	0	0
ITGA2B	0.013	0.01	-10000	0	-10000	0	0
CSF1R	0.016	0	-10000	0	-10000	0	0
Prolactin Receptor/Prolactin	0.05	0.024	-10000	0	-10000	0	0
FGR	0.016	0	-10000	0	-10000	0	0
PTP1B/p130 Cas	-0.19	0.14	-10000	0	-0.3	297	297
Crk/p130 Cas	-0.17	0.14	-10000	0	-0.28	297	297
DOK1	-0.15	0.12	-10000	0	-0.28	70	70
JAK2	-0.094	0.088	-10000	0	-0.78	1	1
Jak2/Leptin Receptor/Leptin	-0.36	0.23	-10000	0	-0.5	347	347
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
PTPN1	-0.21	0.15	-10000	0	-0.33	298	298
LYN	0.016	0.01	-10000	0	-10000	0	0
CDH2	-0.013	0.062	-10000	0	-10000	0	0
SRC	-0.057	0.055	-10000	0	-10000	0	0
ITGB3	0.011	0.02	-10000	0	-10000	0	0
CAT1/PTP1B	-0.15	0.14	-10000	0	-0.41	25	25
CAPN1	0.003	0.016	-10000	0	-10000	0	0
CSK	0.016	0.01	-10000	0	-10000	0	0
PI3K	-0.14	0.14	-10000	0	-0.5	51	51
mol:H2O2	-0.007	0.006	-10000	0	-10000	0	0
STAT3 (dimer)	-0.32	0.21	-10000	0	-0.44	343	343
negative regulation of transcription	-0.093	0.088	-10000	0	-0.76	1	1
FCGR2A	0.013	0.023	-10000	0	-10000	0	0
FER	0.004	0.007	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.002	0.011	-10000	0	-10000	0	0
BLK	0.002	0.045	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-10000	0	-10000	0	0
RHOA	0.005	0.007	-10000	0	-10000	0	0
LEPR	-0.47	0.35	-10000	0	-0.72	344	344
BCAR1	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.013	0.022	-10000	0	-10000	0	0
mol:NADPH	-0.007	0.004	-10000	0	-10000	0	0
TRPV6	0.026	0.059	-10000	0	-0.37	3	3
PRL	0.021	0.003	-10000	0	-10000	0	0
SOCS3	0.003	0.25	-10000	0	-1.4	15	15
SPRY2	-0.48	0.35	-10000	0	-0.73	350	350
Insulin Receptor/Insulin/IRS1	-0.061	0.16	-10000	0	-0.46	69	69
CSF1/CSF1R	-0.17	0.14	-10000	0	-0.28	297	297
Ras protein signal transduction	0.076	0.044	-10000	0	-10000	0	0
IRS1	-0.081	0.25	-10000	0	-0.72	69	69
INS	0.016	0.001	-10000	0	-10000	0	0
LEP	-0.35	0.37	-10000	0	-0.72	258	258
STAT5B	-0.16	0.12	-10000	0	-0.25	292	292
STAT5A	-0.16	0.12	-10000	0	-0.26	293	293
GRB2	0.013	0.022	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.19	0.14	-10000	0	-0.3	297	297
CSN2	0.071	0.031	-10000	0	-10000	0	0
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
LAT	-0.056	0.056	-10000	0	-10000	0	0
YBX1	0.018	0.017	-10000	0	-10000	0	0
LCK	0	0.049	-10000	0	-10000	0	0
SHC1	0.016	0	-10000	0	-10000	0	0
NOX4	-0.019	0.069	-10000	0	-0.74	1	1

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.016	0.036	-9999	-0.47	2	2
NFATC2	0.018	0.029	-9999	-0.47	1	1
NFATC3	0.018	0.02	-9999	-10000	0	0
CD40LG	-0.34	0.32	-9999	-0.58	298	298
PTGS2	-0.54	0.44	-9999	-0.82	343	343
JUNB	0.012	0.056	-9999	-0.72	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	0.002	0.006	-9999	-10000	0	0
CaM/Ca2+	0.002	0.006	-9999	-10000	0	0
CALM1	0.015	0.005	-9999	-10000	0	0
JUN	-0.12	0.29	-9999	-0.73	97	97
mol:Ca2+	-0.006	0.006	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.001	0.005	-9999	-10000	0	0
FOSL1	0.016	0.01	-9999	-10000	0	0
CREM	0.016	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.084	0.16	-9999	-0.4	98	98
FOS	-0.51	0.34	-9999	-0.73	374	374
IFNG	-0.35	0.33	-9999	-0.59	303	303
AP-1/NFAT1-c-4	-0.41	0.39	-9999	-0.7	303	303
FASLG	-0.34	0.32	-9999	-0.58	299	299
NFAT1-c-4/ICER1	0.001	0.035	-9999	-0.37	3	3
IL2RA	-0.34	0.32	-9999	-0.58	299	299
FKBP12/FK506	0	0.006	-9999	-10000	0	0
CSF2	-0.34	0.32	-9999	-0.58	297	297
JunB/Fra1/NFAT1-c-4	0.01	0.046	-9999	-0.35	6	6
IL4	-0.34	0.32	-9999	-0.57	297	297
IL2	-0.011	0.067	-9999	-1.5	1	1
IL3	-0.009	0.019	-9999	-10000	0	0
FKBP1A	0.016	0.01	-9999	-10000	0	0
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.026	0	-9999	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.097	0.17	-9999	-0.36	147	147
PDGFRB	0.007	0.008	-9999	-10000	0	0
SPHK1	-0.049	0.098	-9999	-1.1	4	4
mol:S1P	-0.059	0.095	-9999	-1	4	4
S1P1/S1P/Gi	-0.34	0.34	-9999	-0.69	215	215
GNAO1	0.007	0.009	-9999	-10000	0	0
PDGFB-D/PDGFRB/PLCgamma1	-0.28	0.29	-9999	-0.59	204	204
PLCG1	-0.31	0.31	-9999	-0.64	206	206
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.007	0.008	-9999	-10000	0	0
GNAI2	0.007	0.012	-9999	-10000	0	0
GNAI3	0.007	0.009	-9999	-10000	0	0
GNAI1	-0.26	0.36	-9999	-0.73	189	189
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.22	0.38	-9999	-0.83	147	147
S1P1/S1P	-0.24	0.31	-9999	-0.73	147	147
negative regulation of cAMP metabolic process	-0.33	0.33	-9999	-0.66	215	215
MAPK3	-0.43	0.4	-9999	-0.71	323	323
calcium-dependent phospholipase C activity	-0.005	0.004	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.037	0.09	-9999	-10000	0	0
PLCB2	-0.19	0.28	-9999	-0.62	147	147
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.19	0.25	-9999	-0.58	147	147
receptor internalization	-0.22	0.28	-9999	-0.66	147	147
PTGS2	-0.67	0.57	-9999	-1.1	318	318
Rac1/GTP	-0.19	0.25	-9999	-0.58	147	147
RHOA	0.016	0	-9999	-10000	0	0
VEGFA	-0.06	0.12	-9999	-0.36	30	30
negative regulation of T cell proliferation	-0.33	0.33	-9999	-0.66	215	215
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.001	0.079	-9999	-0.73	6	6
MAPK1	-0.43	0.4	-9999	-0.71	323	323
S1P1/S1P/PDGFB-D/PDGFRB	-0.24	0.34	-9999	-0.77	147	147
ABCC1	0.008	0.027	-9999	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.29	0.46	-10000	0	-0.86	135	135
PLK1	0.01	0.055	-10000	0	-10000	0	0
BIRC5	-0.025	0.071	-10000	0	-10000	0	0
HSPA1B	-0.3	0.46	-10000	0	-0.8	192	192
MAP2K1	0.011	0.036	-10000	0	-10000	0	0
BRCA2	-0.3	0.47	-10000	0	-0.89	127	127
FOXM1	-0.36	0.55	-10000	0	-0.99	165	165
XRCC1	-0.29	0.46	-10000	0	-0.86	135	135
FOXM1B/p19	-0.41	0.42	0.5	1	-0.88	194	195
Cyclin D1/CDK4	-0.29	0.45	-10000	0	-0.85	130	130
CDC2	-0.32	0.49	-10000	0	-0.89	155	155
TGFA	-0.32	0.5	-10000	0	-0.99	122	122
SKP2	-0.29	0.46	-10000	0	-0.91	110	110
CCNE1	-0.023	0.071	-10000	0	-10000	0	0
CKS1B	-0.29	0.46	-10000	0	-0.92	102	102
RB1	-0.13	0.14	-10000	0	-1.2	2	2
FOXM1C/SP1	-0.33	0.51	-10000	0	-0.92	168	168
AURKB	0.003	0.062	-10000	0	-10000	0	0
CENPF	-0.31	0.47	-10000	0	-0.88	144	144
CDK4	0.009	0.024	-10000	0	-10000	0	0
MYC	-0.28	0.45	-10000	0	-0.85	130	130
CHEK2	0.009	0.044	-10000	0	-10000	0	0
ONECUT1	-0.3	0.47	-10000	0	-0.86	150	150
CDKN2A	-0.015	0.06	-10000	0	-10000	0	0
LAMA4	-0.3	0.47	-10000	0	-0.95	100	100
FOXM1B/HNF6	-0.35	0.55	-10000	0	-1	147	147
FOS	-0.84	0.7	-10000	0	-1.3	378	378
SP1	0.017	0.003	-10000	0	-10000	0	0
CDC25B	-0.3	0.46	-10000	0	-0.89	121	121
response to radiation	-0.01	0.036	-10000	0	-10000	0	0
CENPB	-0.29	0.46	-10000	0	-0.91	108	108
CENPA	-0.31	0.47	-10000	0	-0.92	115	115
NEK2	-0.32	0.47	-10000	0	-0.97	94	94
HIST1H2BA	-0.29	0.46	-10000	0	-0.9	110	110
CCNA2	-0.045	0.082	-10000	0	-10000	0	0
EP300	0.016	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.34	0.52	-10000	0	-1.1	100	100
CCNB2	-0.31	0.47	-10000	0	-0.87	145	145
CCNB1	-0.32	0.49	-10000	0	-0.9	146	146
ETV5	-0.31	0.49	-10000	0	-0.93	132	132
ESR1	-0.44	0.63	-10000	0	-1.2	174	174
CCND1	-0.29	0.47	-10000	0	-0.88	127	127
GSK3A	0.015	0.029	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.023	0.088	-10000	0	-10000	0	0
CDK2	0.007	0.027	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.013	0.042	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.38	0.39	-10000	0	-0.83	194	194
GAS1	-0.5	0.67	-10000	0	-1.3	181	181
MMP2	-0.3	0.47	-10000	0	-0.91	116	116
RB1/FOXM1C	-0.29	0.47	-10000	0	-0.87	138	138
CREBBP	0.015	0.032	-10000	0	-0.72	1	1

×

Glucocorticoid receptor regulatory network

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
PCK2	0.016	0.071	0.39	1	-10000	0	1
SMARCC2	0.016	0	-10000	0	-10000	0	0
SMARCC1	0.014	0.02	-10000	0	-10000	0	0
TBX21	-0.091	0.27	-10000	0	-1	36	36
SUMO2	0.003	0.009	-10000	0	-10000	0	0
STAT1 (dimer)	-0.001	0.064	-10000	0	-10000	0	0
FKBP4	0.01	0.031	-10000	0	-10000	0	0
FKBP5	-0.002	0.11	-10000	0	-0.72	11	11
GR alpha/HSP90/FKBP51/HSP90	0.09	0.15	0.33	29	-0.43	6	35
PRL	-0.037	0.1	-10000	0	-0.48	1	1
cortisol/GR alpha (dimer)/TIF2	0.26	0.25	0.48	275	-10000	0	275
RELA	-0.1	0.081	-10000	0	-0.3	9	9
FGG	0.26	0.21	0.45	229	-10000	0	229
GR beta/TIF2	0.11	0.15	0.31	60	-0.44	7	67
IFNG	-0.51	0.32	-10000	0	-0.75	293	293
apoptosis	-0.25	0.15	0.56	1	-0.53	19	20
CREB1	0.026	0.004	-10000	0	-10000	0	0
histone acetylation	0.05	0.15	0.45	45	-0.32	13	58
BGLAP	-0.05	0.13	-10000	0	-0.52	2	2
GR/PKAc	0.11	0.14	0.32	23	-0.39	8	31
NF kappa B1 p50/RelA	-0.18	0.15	-10000	0	-0.36	84	84
SMARCD1	0.016	0	-10000	0	-10000	0	0
MDM2	0.13	0.091	0.22	209	-10000	0	209
GATA3	-0.063	0.19	-10000	0	-0.71	38	38
AKT1	-0.002	0.02	-10000	0	-10000	0	0
CSF2	0.001	0.11	-10000	0	-0.46	1	1
GSK3B	0.002	0.012	-10000	0	-10000	0	0
NR1I3	-0.2	0.16	0.54	1	-0.6	1	2
CSN2	0.22	0.18	0.39	216	-10000	0	216
BRG1/BAF155/BAF170/BAF60A	0.002	0.013	-10000	0	-10000	0	0
NFATC1	0.024	0.046	-10000	0	-0.71	2	2
POU2F1	0.026	0	-10000	0	-10000	0	0
CDKN1A	0.058	0.099	-10000	0	-1.5	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.012	0.006	-10000	0	-10000	0	0
SFN	0.012	0.048	-10000	0	-0.72	2	2
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.1	0.14	0.33	26	-0.4	4	30
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.7	0.37	0.52	1	-0.87	436	437
JUN	-0.24	0.27	-10000	0	-0.56	182	182
IL4	-0.052	0.13	-10000	0	-0.45	14	14
CDK5R1	0.001	0.019	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.64	0.36	-10000	0	-0.77	420	420
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.1	0.14	0.33	29	-0.38	7	36
cortisol/GR alpha (monomer)	0.3	0.3	0.56	274	-0.47	1	275
NCOA2	0.015	0.014	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.59	0.34	-10000	0	-0.8	374	374
AP-1/NFAT1-c-4	-0.86	0.48	-10000	0	-1.1	404	404
AFP	-0.18	0.22	-10000	0	-0.6	58	58
SUV420H1	0.016	0	-10000	0	-10000	0	0
IRF1	0.19	0.16	0.5	25	-10000	0	25
TP53	0.043	0.032	-10000	0	-0.47	2	2
PPP5C	0.014	0.02	-10000	0	-10000	0	0
KRT17	-1.1	0.75	-10000	0	-1.7	338	338
KRT14	-0.94	0.72	-10000	0	-1.5	334	334
TBP	0.028	0.001	-10000	0	-10000	0	0
CREBBP	0.17	0.14	0.28	303	-0.46	1	304
HDAC1	0.003	0.005	-10000	0	-10000	0	0
HDAC2	0.011	0.017	-10000	0	-10000	0	0
AP-1	-0.87	0.5	-10000	0	-1.1	404	404
MAPK14	0.003	0.007	-10000	0	-10000	0	0
MAPK10	-0.016	0.11	-10000	0	-0.73	12	12
MAPK11	0.003	0.007	-10000	0	-10000	0	0
KRT5	-1.2	0.73	-10000	0	-1.7	365	365
interleukin-1 receptor activity	-0.003	0.002	-10000	0	-10000	0	0
NCOA1	0.019	0.032	-10000	0	-0.71	1	1
STAT1	-0.001	0.064	-10000	0	-10000	0	0
CGA	-0.068	0.14	-10000	0	-0.56	2	2
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.17	0.18	0.33	269	-0.37	4	273
MAPK3	0.003	0.007	-10000	0	-10000	0	0
MAPK1	0.003	0.007	-10000	0	-10000	0	0
ICAM1	-0.28	0.23	-10000	0	-0.55	124	124
NFKB1	-0.1	0.081	-10000	0	-0.24	28	28
MAPK8	-0.13	0.18	-10000	0	-0.41	88	88
MAPK9	0.003	0.01	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.26	0.15	0.56	1	-0.56	19	20
BAX	0.063	0.035	-10000	0	-10000	0	0
POMC	-0.14	0.2	-10000	0	-0.76	15	15
EP300	0.17	0.14	0.29	249	-10000	0	249
cortisol/GR alpha (dimer)/p53	0.28	0.26	0.5	274	-10000	0	274
proteasomal ubiquitin-dependent protein catabolic process	0.086	0.078	0.23	25	-10000	0	25
SGK1	0.25	0.16	0.37	333	-10000	0	333
IL13	-0.36	0.24	-10000	0	-0.79	58	58
IL6	-0.88	0.53	-10000	0	-1.2	391	391
PRKACG	0.015	0.032	-10000	0	-0.72	1	1
IL5	-0.31	0.2	-10000	0	-0.64	50	50
IL2	-0.5	0.32	-10000	0	-0.75	288	288
CDK5	-0.001	0.027	-10000	0	-10000	0	0
PRKACB	-0.007	0.099	-10000	0	-0.72	8	8
HSP90AA1	0.016	0.01	-10000	0	-10000	0	0
IL8	-0.28	0.23	-10000	0	-0.48	245	245
CDK5R1/CDK5	-0.003	0.018	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.1	0.13	-10000	0	-0.52	17	17
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.26	0.24	0.47	254	-10000	0	254
SMARCA4	0.015	0.014	-10000	0	-10000	0	0
chromatin remodeling	0.2	0.16	0.34	234	-10000	0	234
NF kappa B1 p50/RelA/Cbp	-0.014	0.16	0.38	10	-0.43	2	12
JUN (dimer)	-0.24	0.27	-10000	0	-0.56	182	182
YWHAH	0.015	0.012	-10000	0	-10000	0	0
VIPR1	-0.053	0.17	-10000	0	-0.62	28	28
NR3C1	0.18	0.2	0.36	204	-0.54	10	214
NR4A1	-0.01	0.16	-10000	0	-0.72	26	26
TIF2/SUV420H1	-0.001	0.007	-10000	0	-10000	0	0
MAPKKK cascade	-0.25	0.15	0.56	1	-0.53	19	20
cortisol/GR alpha (dimer)/Src-1	0.27	0.26	0.49	273	-10000	0	273
PBX1	0.008	0.065	-10000	0	-0.72	2	2
POU1F1	0.025	0.032	-10000	0	-0.72	1	1
SELE	-0.35	0.38	-10000	0	-0.92	101	101
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.16	0.34	232	-10000	0	232
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.26	0.24	0.47	254	-10000	0	254
mol:cortisol	0.19	0.17	0.32	287	-10000	0	287
MMP1	-0.17	0.08	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.23	0.2	-9999	-0.36	374	374
MAP3K8	-0.093	0.25	-9999	-0.73	70	70
FOS	-0.12	0.12	-9999	-0.3	58	58
PRKCA	0.005	0.013	-9999	-10000	0	0
PTPN7	-0.003	0.038	-9999	-10000	0	0
HRAS	0.013	0.012	-9999	-10000	0	0
PRKCB	-0.013	0.01	-9999	-0.019	374	374
NRAS	0.012	0.019	-9999	-10000	0	0
RAS family/GTP	-0.002	0.015	-9999	-10000	0	0
MAPK3	-0.052	0.065	-9999	-10000	0	0
MAP2K1	-0.055	0.091	-9999	-0.27	58	58
ELK1	0	0.018	-9999	-10000	0	0
BRAF	-0.018	0.015	-9999	-10000	0	0
mol:GTP	-0.004	0.003	-9999	-0.006	374	374
MAPK1	-0.052	0.065	-9999	-10000	0	0
RAF1	-0.018	0.015	-9999	-10000	0	0
KRAS	0.01	0.026	-9999	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.099	0.25	-9999	-0.76	64	64
PDGF/PDGFRA/CRKL	-0.068	0.18	-9999	-0.56	64	64
positive regulation of JUN kinase activity	-0.05	0.14	-9999	-0.42	64	64
CRKL	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.071	0.19	-9999	-0.57	65	65
AP1	-0.84	0.54	-9999	-1.2	375	375
mol:IP3	-0.084	0.19	-9999	-0.6	64	64
PLCG1	-0.084	0.19	-9999	-0.6	64	64
PDGF/PDGFRA/alphaV Integrin	-0.07	0.18	-9999	-0.56	65	65
RAPGEF1	0.016	0	-9999	-10000	0	0
CRK	0.015	0.032	-9999	-0.72	1	1
mol:Ca2+	-0.084	0.19	-9999	-0.59	64	64
CAV3	0.013	0.046	-9999	-0.72	2	2
CAV1	-0.52	0.33	-9999	-0.72	385	385
SHC/Grb2/SOS1	-0.05	0.14	-9999	-0.42	64	64
PDGF/PDGFRA/Shf	-0.068	0.18	-9999	-0.56	64	64
FOS	-0.8	0.55	-9999	-1.1	376	376
JUN	-0.15	0.23	-9999	-0.62	97	97
oligodendrocyte development	-0.07	0.18	-9999	-0.56	65	65
GRB2	0.013	0.022	-9999	-10000	0	0
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
mol:DAG	-0.084	0.19	-9999	-0.6	64	64
PDGF/PDGFRA	-0.099	0.25	-9999	-0.76	64	64
actin cytoskeleton reorganization	-0.07	0.18	-9999	-0.56	65	65
SRF	0.046	0.012	-9999	-10000	0	0
SHC1	0.016	0	-9999	-10000	0	0
PI3K	-0.1	0.23	-9999	-0.56	95	95
PDGF/PDGFRA/Crk/C3G	-0.058	0.16	-9999	-0.48	64	64
JAK1	-0.058	0.19	-9999	-0.56	66	66
ELK1/SRF	-0.024	0.16	-9999	-0.45	64	64
SHB	0.013	0.037	-9999	-0.72	1	1
SHF	0.015	0.012	-9999	-10000	0	0
CSNK2A1	0.046	0.028	-9999	-10000	0	0
GO:0007205	-0.091	0.2	-9999	-0.62	64	64
SOS1	0.016	0	-9999	-10000	0	0
Ras protein signal transduction	-0.05	0.14	-9999	-0.42	64	64
PDGF/PDGFRA/SHB	-0.07	0.18	-9999	-0.56	65	65
PDGF/PDGFRA/Caveolin-1	-0.47	0.31	-9999	-0.64	387	387
ITGAV	0.014	0.034	-9999	-0.72	1	1
ELK1	-0.099	0.18	-9999	-0.57	64	64
PIK3CA	0.016	0.007	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.069	0.19	-9999	-0.57	64	64
JAK-STAT cascade	-0.058	0.19	-9999	-0.56	66	66
cell proliferation	-0.068	0.18	-9999	-0.56	64	64

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.008	0.079	-10000	0	-0.72	6	6
EPHB2	0.005	0.04	-10000	0	-10000	0	0
EFNB1	0.027	0.036	-10000	0	-0.54	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.12	0.18	-10000	0	-0.35	197	197
Ephrin B2/EPHB1-2	-0.15	0.22	-10000	0	-0.43	198	198
neuron projection morphogenesis	-0.12	0.17	-10000	0	-0.33	197	197
Ephrin B1/EPHB1-2/Tiam1	-0.13	0.2	-10000	0	-0.38	197	197
DNM1	0.016	0.007	-10000	0	-10000	0	0
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.046	0.22	-10000	0	-0.65	58	58
YES1	-0.084	0.28	-10000	0	-0.91	52	52
Ephrin B1/EPHB1-2/NCK2	-0.13	0.2	-10000	0	-0.38	197	197
PI3K	-0.082	0.25	-10000	0	-0.58	95	95
mol:GDP	-0.14	0.19	-10000	0	-0.38	197	197
ITGA2B	0.016	0.01	-10000	0	-10000	0	0
endothelial cell proliferation	-0.005	0.055	-10000	0	-0.47	7	7
FYN	-0.084	0.27	-10000	0	-0.91	52	52
MAP3K7	-0.065	0.22	-10000	0	-0.72	52	52
FGR	-0.085	0.27	-10000	0	-0.91	52	52
TIAM1	0.015	0.012	-10000	0	-10000	0	0
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
RGS3	0.016	0	-10000	0	-10000	0	0
cell adhesion	-0.057	0.23	-10000	0	-0.65	55	55
LYN	-0.084	0.27	-10000	0	-0.91	52	52
Ephrin B1/EPHB1-2/Src Family Kinases	-0.081	0.26	-10000	0	-0.85	52	52
Ephrin B1/EPHB1-2	-0.076	0.23	-10000	0	-0.78	52	52
SRC	-0.085	0.27	-10000	0	-0.91	52	52
ITGB3	0.014	0.02	-10000	0	-10000	0	0
EPHB1	-0.26	0.36	-10000	0	-0.72	197	197
EPHB4	0.011	0.039	-10000	0	-0.72	1	1
RAC1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.005	0.055	-10000	0	-0.47	7	7
alphaIIb/beta3 Integrin	-0.001	0.011	-10000	0	-10000	0	0
BLK	-0.084	0.27	-10000	0	-0.91	52	52
HCK	-0.085	0.27	-10000	0	-0.91	52	52
regulation of stress fiber formation	0.14	0.19	0.38	197	-10000	0	197
MAPK8	-0.035	0.21	-10000	0	-0.62	58	58
Ephrin B1/EPHB1-2/RGS3	-0.13	0.2	-10000	0	-0.38	197	197
endothelial cell migration	-0.058	0.2	-10000	0	-0.6	57	57
NCK2	0.016	0.01	-10000	0	-10000	0	0
PTPN13	-0.073	0.25	-10000	0	-0.83	52	52
regulation of focal adhesion formation	0.14	0.19	0.38	197	-10000	0	197
chemotaxis	0.14	0.19	0.38	197	-10000	0	197
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
Rac1/GTP	-0.12	0.17	-10000	0	-0.34	197	197
angiogenesis	-0.076	0.23	-10000	0	-0.77	52	52
LCK	-0.083	0.27	-10000	0	-0.91	52	52

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.082	0.26	-10000	0	-0.77	27	27
CRP	-0.082	0.26	-10000	0	-0.78	26	26
cell cycle arrest	-0.099	0.3	-10000	0	-0.62	105	105
TIMP1	-0.099	0.23	-10000	0	-0.52	76	76
IL6ST	-0.01	0.15	-10000	0	-0.72	21	21
Rac1/GDP	-0.16	0.22	-10000	0	-0.47	117	117
AP1	-0.29	0.26	-10000	0	-0.48	291	291
GAB2	0.019	0.018	-10000	0	-10000	0	0
TNFSF11	-0.089	0.26	-10000	0	-0.74	32	32
HSP90B1	0.02	0.065	-10000	0	-0.96	1	1
GAB1	0.017	0.034	-10000	0	-0.72	1	1
MAPK14	-0.2	0.24	-10000	0	-0.76	56	56
AKT1	0.044	0.079	-10000	0	-10000	0	0
FOXO1	-0.004	0.17	-10000	0	-0.41	50	50
MAP2K6	-0.21	0.24	-10000	0	-0.52	124	124
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.12	0.23	-10000	0	-0.48	114	114
MITF	-0.19	0.24	-10000	0	-0.51	117	117
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.016	0	-10000	0	-10000	0	0
A2M	-0.16	0.5	-10000	0	-1.5	65	65
CEBPB	0.025	0.033	-10000	0	-0.72	1	1
GRB2/SOS1/GAB family/SHP2	-0.025	0.093	0.3	1	-10000	0	1
STAT3	-0.11	0.32	-10000	0	-0.66	106	106
STAT1	-0.001	0.034	-10000	0	-10000	0	0
CEBPD	-0.16	0.42	-10000	0	-1.1	71	71
PIK3CA	0.018	0.007	-10000	0	-10000	0	0
PI3K	-0.028	0.17	-10000	0	-0.54	51	51
JUN	-0.12	0.29	-10000	0	-0.72	97	97
PIAS3/MITF	-0.18	0.23	-10000	0	-0.55	84	84
MAPK11	-0.2	0.24	-10000	0	-0.76	56	56
STAT3 (dimer)/FOXO1	-0.12	0.32	-10000	0	-0.68	94	94
GRB2/SOS1/GAB family	-0.17	0.17	-10000	0	-0.64	42	42
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.22	0.23	-10000	0	-0.48	126	126
GRB2	0.016	0.023	-10000	0	-10000	0	0
JAK2	0.015	0.033	-10000	0	-0.72	1	1
LBP	-0.088	0.22	-10000	0	-0.65	25	25
PIK3R1	-0.054	0.22	-10000	0	-0.72	51	51
JAK1	0.017	0.046	-10000	0	-0.73	2	2
MYC	-0.11	0.34	-10000	0	-1.1	38	38
FGG	-0.083	0.26	-10000	0	-0.77	27	27
macrophage differentiation	-0.099	0.3	-10000	0	-0.62	105	105
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.3	0.22	-10000	0	-0.4	396	396
JUNB	-0.092	0.26	-10000	0	-0.69	38	38
FOS	-0.51	0.34	-10000	0	-0.72	374	374
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.21	0.24	-10000	0	-0.53	120	120
STAT1/PIAS1	-0.17	0.23	-10000	0	-0.51	108	108
GRB2/SOS1/GAB family/SHP2/PI3K	0.029	0.082	-10000	0	-10000	0	0
STAT3 (dimer)	-0.1	0.31	-10000	0	-0.65	105	105
PRKCD	-0.092	0.24	-10000	0	-0.48	111	111
IL6R	0.018	0.033	-10000	0	-0.72	1	1
SOCS3	-0.2	0.27	-10000	0	-0.86	55	55
gp130 (dimer)/JAK1/JAK1/LMO4	0.017	0.15	-10000	0	-0.47	44	44
Rac1/GTP	-0.15	0.23	-10000	0	-0.48	115	115
HCK	0.013	0.024	-10000	0	-10000	0	0
MAPKKK cascade	0.005	0.083	-10000	0	-10000	0	0
bone resorption	-0.093	0.25	-10000	0	-0.68	34	34
IRF1	-0.084	0.26	-10000	0	-0.76	28	28
mol:GDP	-0.18	0.23	-10000	0	-0.5	118	118
SOS1	0.02	0.008	-10000	0	-10000	0	0
VAV1	-0.19	0.24	-10000	0	-0.5	118	118
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.22	0.24	-10000	0	-0.78	56	56
PTPN11	-0.009	0.02	-10000	0	-10000	0	0
IL6/IL6RA	-0.38	0.25	-10000	0	-0.53	391	391
gp130 (dimer)/TYK2/TYK2/LMO4	0.011	0.14	-10000	0	-0.47	43	43
gp130 (dimer)/JAK2/JAK2/LMO4	0.01	0.15	-10000	0	-0.48	43	43
IL6	-0.52	0.32	-10000	0	-0.72	391	391
PIAS3	0.016	0	-10000	0	-10000	0	0
PTPRE	0.002	0.045	-10000	0	-0.72	2	2
PIAS1	0.016	0.007	-10000	0	-10000	0	0
RAC1	0.017	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.23	0.21	-10000	0	-0.33	372	372
LMO4	-0.017	0.15	-10000	0	-0.72	22	22
STAT3 (dimer)/PIAS3	-0.17	0.26	-10000	0	-0.64	105	105
MCL1	0.052	0.073	-10000	0	-10000	0	0

×

BMP receptor signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.036	0.077	-9999	-0.42	9	9
SMAD6-7/SMURF1	0	0.004	-9999	-10000	0	0
NOG	0.014	0.035	-9999	-0.72	1	1
SMAD9	-0.084	0.18	-9999	-0.91	20	20
SMAD4	0.013	0.045	-9999	-0.72	2	2
SMAD5	-0.15	0.21	-9999	-0.56	69	69
BMP7/USAG1	-0.4	0.24	-9999	-0.55	377	377
SMAD5/SKI	-0.13	0.2	-9999	-0.56	61	61
SMAD1	0.025	0.045	-9999	-10000	0	0
BMP2	-0.34	0.37	-9999	-0.72	252	252
SMAD1/SMAD1/SMAD4	-0.002	0.021	-9999	-10000	0	0
BMPR1A	0.009	0.072	-9999	-0.72	5	5
BMPR1B	-0.046	0.079	-9999	-10000	0	0
BMPR1A-1B/BAMBI	-0.012	0.16	-9999	-0.51	41	41
AHSG	0.016	0	-9999	-10000	0	0
CER1	0.016	0.007	-9999	-10000	0	0
BMP2-4/CER1	-0.28	0.28	-9999	-0.51	289	289
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.14	0.21	-9999	-0.5	97	97
BMP2-4 (homodimer)	-0.33	0.32	-9999	-0.6	289	289
RGMB	0.016	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.14	0.23	-9999	-0.45	182	182
RGMA	-0.097	0.27	-9999	-0.72	81	81
SMURF1	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.16	0.22	-9999	-0.54	95	95
BMP2-4/USAG1	-0.6	0.34	-9999	-0.7	444	444
SMAD6/SMURF1/SMAD5	-0.13	0.2	-9999	-0.56	61	61
SOSTDC1	-0.51	0.33	-9999	-0.72	377	377
BMP7/BMPR2/BMPR1A-1B	0.038	0.065	-9999	-0.44	5	5
SKI	0.016	0.007	-9999	-10000	0	0
BMP6 (homodimer)	-0.24	0.35	-9999	-0.72	180	180
HFE2	0.011	0.056	-9999	-0.72	3	3
ZFYVE16	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0.01	-9999	-10000	0	0
BMP2-4/CHRD	-0.28	0.28	-9999	-0.51	289	289
SMAD5/SMAD5/SMAD4	-0.14	0.2	-9999	-0.56	62	62
MAPK1	0.016	0	-9999	-10000	0	0
TAK1/TAB family	-0.13	0.16	-9999	-0.46	76	76
BMP7 (homodimer)	-0.002	0.051	-9999	-10000	0	0
NUP214	0.016	0	-9999	-10000	0	0
BMP6/FETUA	-0.18	0.26	-9999	-0.54	180	180
SMAD1/SKI	0.033	0.043	-9999	-10000	0	0
SMAD6	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.28	0.28	-9999	-0.51	289	289
MAP3K7IP1	0.016	0	-9999	-10000	0	0
GREM1	-0.002	0.051	-9999	-10000	0	0
BMPR2 (homodimer)	0.016	0	-9999	-10000	0	0
GADD34/PP1CA	0.001	0.032	-9999	-0.46	2	2
BMPR1A-1B (homodimer)	-0.035	0.065	-9999	-0.57	5	5
CHRDL1	-0.42	0.36	-9999	-0.72	309	309
ENDOFIN/SMAD1	0.033	0.043	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0	0.014	-9999	-10000	0	0
SMAD6/SMURF1	0.016	0	-9999	-10000	0	0
BAMBI	-0.064	0.19	-9999	-0.72	37	37
SMURF2	0.015	0.012	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.53	0.4	-9999	-0.74	378	378
BMP2-4/GREM1	-0.28	0.28	-9999	-0.52	289	289
SMAD7	0.016	0.007	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.06	0.18	-9999	-0.85	21	21
SMAD1/SMAD6	0.033	0.043	-9999	-10000	0	0
TAK1/SMAD6	0	0.005	-9999	-10000	0	0
BMP7	-0.002	0.051	-9999	-10000	0	0
BMP6	-0.24	0.35	-9999	-0.72	180	180
MAP3K7IP2	0.015	0.032	-9999	-0.72	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.14	0.21	-9999	-0.51	95	95
PPM1A	0.016	0	-9999	-10000	0	0
SMAD1/SMURF2	0.033	0.043	-9999	-10000	0	0
SMAD7/SMURF1	0	0.003	-9999	-10000	0	0
CTDSPL	0.013	0.045	-9999	-0.72	2	2
PPP1CA	0.01	0.032	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
PPP1R15A	0.013	0.045	-9999	-0.72	2	2
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.15	0.22	-9999	-0.51	97	97
CHRD	0.013	0.022	-9999	-10000	0	0
BMPR2	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.19	0.25	-9999	-0.64	95	95
BMP4	-0.088	0.26	-9999	-0.72	73	73
FST	0.009	0.066	-9999	-0.72	4	4
BMP2-4/NOG	-0.28	0.28	-9999	-0.51	290	290
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.04	0.064	-9999	-0.4	5	5

×

FAS signaling pathway (CD95)

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
SPTAN1	0.054	0.11	0.27	104	-10000	0	104
RFC1	0.054	0.11	0.27	104	-10000	0	104
PRKDC	0.052	0.11	0.27	99	-10000	0	99
RIPK1	0.023	0.004	-10000	0	-10000	0	0
CASP7	-0.047	0.054	-10000	0	-0.99	1	1
FASLG/FAS/FADD/FAF1	-0.033	0.1	0.25	11	-0.37	25	36
MAP2K4	-0.17	0.16	-10000	0	-0.38	70	70
mol:ceramide	-0.1	0.13	-10000	0	-0.45	34	34
GSN	-0.073	0.23	0.28	76	-0.46	115	191
FASLG/FAS/FADD/FAF1/Caspase 8	-0.047	0.097	-10000	0	-0.35	22	22
FAS	-0.045	0.18	-10000	0	-0.74	35	35
BID	-0.002	0.008	-10000	0	-10000	0	0
MAP3K1	-0.074	0.11	-10000	0	-0.32	25	25
MAP3K7	0.004	0.012	-10000	0	-10000	0	0
RB1	0.053	0.11	0.27	103	-0.45	1	104
CFLAR	0.02	0.044	-10000	0	-0.69	2	2
HGF/MET	-0.089	0.2	-10000	0	-0.49	97	97
ARHGDIB	0.052	0.11	0.28	102	-0.45	1	103
FADD	-0.01	0.049	-10000	0	-10000	0	0
actin filament polymerization	0.072	0.23	0.45	115	-0.27	76	191
NFKB1	-0.15	0.093	-10000	0	-0.27	30	30
MAPK8	-0.29	0.23	-10000	0	-0.42	391	391
DFFA	0.054	0.11	0.27	104	-10000	0	104
DNA fragmentation during apoptosis	0.054	0.11	0.27	104	-10000	0	104
FAS/FADD/MET	-0.083	0.19	-10000	0	-0.52	80	80
CFLAR/RIP1	-0.002	0.031	-10000	0	-0.5	2	2
FAIM3	0.015	0.03	-10000	0	-10000	0	0
FAF1	0.005	0.008	-10000	0	-10000	0	0
PARP1	0.047	0.11	0.28	87	-10000	0	87
DFFB	0.054	0.11	0.27	104	-10000	0	104
CHUK	-0.13	0.084	-10000	0	-0.59	1	1
FASLG	-0.011	0.056	-10000	0	-0.73	1	1
FAS/FADD	-0.044	0.14	-10000	0	-0.57	35	35
HGF	0.016	0.01	-10000	0	-10000	0	0
LMNA	0.05	0.1	0.25	101	-10000	0	101
CASP6	0.054	0.11	0.27	102	-10000	0	102
CASP10	0.004	0.011	-10000	0	-10000	0	0
CASP3	0.064	0.13	0.33	104	-10000	0	104
PTPN13	-0.057	0.22	-10000	0	-0.72	52	52
CASP8	-0.002	0.009	-10000	0	-10000	0	0
IL6	-0.97	0.6	-10000	0	-1.3	391	391
MET	-0.057	0.22	-10000	0	-0.72	52	52
ICAD/CAD	0.051	0.1	0.26	104	-10000	0	104
FASLG/FAS/FADD/FAF1/Caspase 10	-0.1	0.13	-10000	0	-0.47	32	32
activation of caspase activity by cytochrome c	-0.002	0.008	-10000	0	-10000	0	0
PAK2	0.054	0.11	0.27	104	-10000	0	104
BCL2	-0.13	0.29	-10000	0	-0.72	104	104

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	-0.089	0.26	-9999	-0.72	75	75
LAT2	-0.048	0.18	-9999	-0.4	92	92
AP1	-0.32	0.25	-9999	-0.58	215	215
mol:PIP3	-0.047	0.23	-9999	-0.46	101	101
IKBKB	-0.016	0.14	-9999	-0.28	68	68
AKT1	-0.07	0.24	-9999	-0.62	58	58
IKBKG	-0.016	0.14	-9999	-0.28	72	72
MS4A2	-0.12	0.28	-9999	-0.72	92	92
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.015	0.007	-9999	-10000	0	0
MAP3K1	-0.013	0.16	-9999	-0.42	47	47
mol:Ca2+	-0.027	0.18	-9999	-0.34	101	101
LYN	0.014	0.012	-9999	-10000	0	0
CBLB	-0.047	0.18	-9999	-0.4	92	92
SHC1	0.016	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.18	0.21	-9999	-0.42	225	225
positive regulation of cell migration	-0.14	0.25	-9999	-0.55	147	147
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.085	0.24	-9999	-0.46	139	139
PTPN13	-0.072	0.22	-9999	-0.58	54	54
PTPN11	0.015	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.017	0.18	-9999	-0.39	57	57
SYK	0.009	0.031	-9999	-10000	0	0
GRB2	0.013	0.022	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.2	-9999	-0.47	101	101
LAT	-0.048	0.18	-9999	-0.39	93	93
PAK2	-0.021	0.17	-9999	-0.44	49	49
NFATC2	-0.041	0.073	-9999	-0.61	1	1
HRAS	-0.034	0.18	-9999	-0.48	51	51
GAB2	0.015	0.016	-9999	-10000	0	0
PLA2G1B	0.039	0.021	-9999	-10000	0	0
Fc epsilon R1	-0.15	0.27	-9999	-0.58	138	138
Antigen/IgE/Fc epsilon R1	-0.14	0.25	-9999	-0.53	138	138
mol:GDP	-0.043	0.19	-9999	-0.5	51	51
JUN	-0.12	0.29	-9999	-0.72	97	97
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.056	0.22	-9999	-0.72	51	51
FOS	-0.51	0.34	-9999	-0.72	374	374
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.092	0.17	-9999	-0.41	100	100
CHUK	-0.016	0.14	-9999	-0.29	69	69
KLRG1	-0.047	0.17	-9999	-0.36	92	92
VAV1	-0.051	0.18	-9999	-0.4	93	93
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.047	0.18	-9999	-0.39	92	92
negative regulation of mast cell degranulation	-0.076	0.14	-9999	-0.34	92	92
BTK	-0.048	0.19	-9999	-0.49	53	53
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.087	0.26	-9999	-0.46	138	138
GAB2/PI3K/SHP2	-0.14	0.23	-9999	-0.7	57	57
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.064	0.21	-9999	-0.37	138	138
RAF1	0.023	0.025	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.13	0.24	-9999	-0.5	138	138
FCER1G	0.016	0.017	-9999	-10000	0	0
FCER1A	-0.11	0.28	-9999	-0.74	88	88
Antigen/IgE/Fc epsilon R1/Fyn	-0.13	0.24	-9999	-0.5	138	138
MAPK3	0.037	0.021	-9999	-10000	0	0
MAPK1	0.037	0.021	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.011	0.077	-9999	-0.42	8	8
DUSP1	-0.3	0.36	-9999	-0.72	225	225
NF-kappa-B/RelA	-0.037	0.06	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.046	0.18	-9999	-0.51	44	44
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.1	0.18	-9999	-0.51	63	63
FER	-0.047	0.18	-9999	-0.39	92	92
RELA	0.016	0	-9999	-10000	0	0
ITK	-0.021	0.049	-9999	-0.56	2	2
SOS1	0.016	0	-9999	-10000	0	0
PLCG1	-0.039	0.2	-9999	-0.51	51	51
cytokine secretion	-0.027	0.044	-9999	-10000	0	0
SPHK1	-0.052	0.19	-9999	-0.41	96	96
PTK2	-0.049	0.19	-9999	-0.54	43	43
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.21	-9999	-0.49	101	101
EDG1	-0.14	0.25	-9999	-0.55	147	147
mol:DAG	-0.082	0.26	-9999	-0.52	112	112
MAP2K2	0.032	0.022	-9999	-10000	0	0
MAP2K1	0.032	0.022	-9999	-10000	0	0
MAP2K7	0.016	0	-9999	-10000	0	0
KLRG1/SHP2	-0.074	0.14	-9999	-0.46	42	42
MAP2K4	0.011	0.11	-9999	-0.92	7	7
Fc epsilon R1/FcgammaRIIB	-0.14	0.26	-9999	-0.53	138	138
mol:Choline	-0.084	0.24	-9999	-0.45	139	139
SHC/Grb2/SOS1	-0.07	0.15	-9999	-0.48	42	42
FYN	0.013	0.045	-9999	-0.72	2	2
DOK1	0.014	0.019	-9999	-10000	0	0
PXN	-0.035	0.18	-9999	-0.49	42	42
HCLS1	-0.047	0.18	-9999	-0.39	92	92
PRKCB	-0.041	0.18	-9999	-0.36	106	106
FCGR2B	0.01	0.065	-9999	-0.72	4	4
IGHE	-0.001	0.007	-9999	-10000	0	0
KLRG1/SHIP	-0.078	0.14	-9999	-0.43	53	53
LCP2	0.012	0.024	-9999	-10000	0	0
PLA2G4A	-0.29	0.26	-9999	-0.44	354	354
RASA1	0.015	0.012	-9999	-10000	0	0
mol:Phosphatidic acid	-0.084	0.24	-9999	-0.45	139	139
IKK complex	0.007	0.11	-9999	-0.22	45	45
WIPF1	0.013	0.024	-9999	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.35	0.46	-10000	0	-1.4	48	48
IL23A	-0.31	0.38	-10000	0	-1	40	40
NF kappa B1 p50/RelA/I kappa B alpha	-0.35	0.3	-10000	0	-0.76	102	102
positive regulation of T cell mediated cytotoxicity	-0.35	0.41	-10000	0	-0.77	153	153
ITGA3	-0.31	0.38	-10000	0	-1	41	41
IL17F	-0.22	0.3	-10000	0	-0.64	71	71
IL12B	0.012	0.035	-10000	0	-10000	0	0
STAT1 (dimer)	-0.34	0.4	-10000	0	-0.75	157	157
CD4	-0.31	0.37	-10000	0	-0.98	40	40
IL23	-0.3	0.37	-10000	0	-0.98	40	40
IL23R	-0.04	0.13	-10000	0	-1.6	2	2
IL1B	-0.32	0.39	-10000	0	-1.1	40	40
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.31	0.37	-10000	0	-0.98	40	40
TYK2	0.009	0.019	-10000	0	-10000	0	0
STAT4	0.005	0.086	-10000	0	-0.72	7	7
STAT3	0.017	0	-10000	0	-10000	0	0
IL18RAP	-0.046	0.21	-10000	0	-0.72	45	45
IL12RB1	0.009	0.019	-10000	0	-10000	0	0
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.006	0.026	-10000	0	-10000	0	0
IL23R/JAK2	-0.048	0.14	-10000	0	-1.2	3	3
positive regulation of chronic inflammatory response	-0.35	0.41	-10000	0	-0.77	153	153
natural killer cell activation	0.003	0.009	0.079	2	-10000	0	2
JAK2	0.011	0.043	-10000	0	-0.76	1	1
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
NFKB1	0.014	0.004	-10000	0	-10000	0	0
RELA	0.014	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.29	0.36	-10000	0	-0.94	40	40
ALOX12B	-0.31	0.37	-10000	0	-0.98	40	40
CXCL1	-0.77	0.7	-10000	0	-1.4	303	303
T cell proliferation	-0.35	0.41	-10000	0	-0.77	153	153
NFKBIA	0.013	0.033	-10000	0	-0.73	1	1
IL17A	-0.15	0.25	-10000	0	-0.49	57	57
PI3K	-0.39	0.34	-10000	0	-0.84	117	117
IFNG	-0.012	0.03	0.15	2	-0.11	6	8
STAT3 (dimer)	-0.36	0.32	-10000	0	-0.91	80	80
IL18R1	0.015	0.035	-10000	0	-0.72	1	1
IL23/IL23R/JAK2/TYK2/SOCS3	-0.18	0.25	-10000	0	-0.55	50	50
IL18/IL18R	-0.01	0.15	-10000	0	-0.47	45	45
macrophage activation	-0.021	0.016	-10000	0	-0.042	40	40
TNF	-0.32	0.38	-10000	0	-1	40	40
STAT3/STAT4	-0.36	0.32	0.36	1	-0.71	158	159
STAT4 (dimer)	-0.34	0.4	-10000	0	-0.76	150	150
IL18	0.003	0.055	-10000	0	-0.72	1	1
IL19	-0.32	0.37	-10000	0	-0.97	43	43
STAT5A (dimer)	-0.34	0.39	-10000	0	-0.82	101	101
STAT1	-0.011	0.061	-10000	0	-10000	0	0
SOCS3	-0.005	0.12	-10000	0	-0.72	15	15
CXCL9	-0.33	0.39	-10000	0	-1	47	47
MPO	-0.31	0.37	-10000	0	-0.98	40	40
positive regulation of humoral immune response	-0.35	0.41	-10000	0	-0.77	153	153
IL23/IL23R/JAK2/TYK2	-0.36	0.43	-10000	0	-0.8	151	151
IL6	-0.93	0.66	-10000	0	-1.3	391	391
STAT5A	0.013	0.045	-10000	0	-0.72	2	2
IL2	0.019	0.034	-10000	0	-0.72	1	1
positive regulation of tyrosine phosphorylation of STAT protein	0.003	0.009	0.079	2	-10000	0	2
CD3E	-0.31	0.37	-10000	0	-0.98	41	41
keratinocyte proliferation	-0.35	0.41	-10000	0	-0.77	153	153
NOS2	-0.32	0.37	-10000	0	-0.69	159	159

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.01	0.026	-9999	-10000	0	0
alphaV beta3 Integrin	-0.35	0.2	-9999	-0.46	403	403
PTK2	-0.096	0.11	-9999	-0.56	1	1
IGF1R	-0.023	0.15	-9999	-0.72	23	23
PI4KB	0.016	0	-9999	-10000	0	0
MFGE8	-0.023	0.16	-9999	-0.72	26	26
SRC	0.016	0.007	-9999	-10000	0	0
CDKN1B	-0.14	0.12	-9999	-0.93	9	9
VEGFA	-0.005	0.054	-9999	-10000	0	0
ILK	-0.12	0.068	-9999	-10000	0	0
ROCK1	0.016	0	-9999	-10000	0	0
AKT1	-0.095	0.078	-9999	-10000	0	0
PTK2B	0.04	0.032	-9999	-0.38	1	1
alphaV/beta3 Integrin/JAM-A	-0.29	0.16	-9999	-0.38	403	403
CBL	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.001	0.023	-9999	-0.46	1	1
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.28	0.31	-9999	-0.52	280	280
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.053	0.013	-9999	-10000	0	0
alphaV/beta3 Integrin/Syndecan-1	0.021	0.043	-9999	-0.46	1	1
PI4KA	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.54	0.34	-9999	-0.66	412	412
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.016	0.007	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.028	0.062	-9999	-0.46	4	4
RPS6KB1	-0.49	0.3	-9999	-0.61	412	412
TLN1	0.016	0	-9999	-10000	0	0
MAPK3	-0.57	0.33	-9999	-0.74	403	403
GPR124	-0.015	0.15	-9999	-0.72	22	22
MAPK1	-0.57	0.33	-9999	-0.74	403	403
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
alphaV/beta3 Integrin/Tumstatin	0.001	0.023	-9999	-0.46	1	1
cell adhesion	-0.023	0.096	-9999	-0.36	37	37
ANGPTL3	0.016	0.001	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.011	0.027	-9999	-10000	0	0
IGF-1R heterotetramer	-0.023	0.15	-9999	-0.72	23	23
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.037	0.19	-9999	-0.72	38	38
ITGB3	0.014	0.02	-9999	-10000	0	0
IGF1	-0.35	0.37	-9999	-0.72	262	262
RAC1	0.016	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.018	0.094	-9999	-0.46	23	23
apoptosis	0.014	0.034	-9999	-0.72	1	1
CD47	0.001	0.11	-9999	-0.72	11	11
alphaV/beta3 Integrin/CD47	-0.009	0.069	-9999	-0.46	12	12
VCL	0.016	0.007	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.012	0.1	-9999	-0.46	25	25
CSF1	0.016	0.007	-9999	-10000	0	0
PIK3C2A	-0.12	0.068	-9999	-10000	0	0
PI4 Kinase/Pyk2	-0.24	0.14	-9999	-0.46	5	5
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.012	0.036	-9999	-0.41	1	1
FAK1/Vinculin	-0.073	0.091	-9999	-0.43	1	1
alphaV beta3/Integrin/ppsTEM5	-0.018	0.095	-9999	-0.46	23	23
RHOA	0.016	0	-9999	-10000	0	0
VTN	0.015	0.012	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
FGF2	-0.55	0.31	-9999	-0.72	403	403
F11R	-0.41	0.24	-9999	-0.54	403	403
alphaV/beta3 Integrin/Lactadherin	-0.021	0.1	-9999	-0.46	27	27
alphaV/beta3 Integrin/TGFBR2	-0.033	0.12	-9999	-0.46	39	39
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0	0.019	-9999	-0.41	1	1
HSP90AA1	0.016	0.01	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	0.001	0.021	-9999	-0.42	1	1
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.098	0.074	-9999	-10000	0	0
alphaV/beta3 Integrin/Pyk2	0.041	0.032	-9999	-0.38	1	1
SDC1	-0.027	0.072	-9999	-10000	0	0
VAV3	0.037	0.089	-9999	-0.38	22	22
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	-0.081	0.25	-9999	-0.72	69	69
FAK1/Paxillin	-0.073	0.091	-9999	-0.43	1	1
cell migration	-0.06	0.087	-9999	-0.39	1	1
ITGAV	0.014	0.034	-9999	-0.72	1	1
PI3K	-0.29	0.19	-9999	-0.63	64	64
SPP1	-0.057	0.094	-9999	-0.72	3	3
KDR	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.014	0.034	-9999	-0.72	1	1
COL4A3	0.016	0	-9999	-10000	0	0
angiogenesis	-0.55	0.33	-9999	-0.71	403	403
Rac1/GTP	-0.004	0.077	-9999	-0.34	22	22
EDIL3	-0.036	0.16	-9999	-0.72	24	24
cell proliferation	-0.033	0.12	-9999	-0.46	39	39

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.07	0.18	-10000	0	-0.39	118	118
ER alpha/Gai/GDP/Gbeta gamma	-0.14	0.2	-10000	0	-0.42	120	120
AKT1	-0.18	0.35	-10000	0	-0.82	117	117
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.18	0.36	-10000	0	-0.83	117	117
mol:Ca2+	-0.05	0.16	-10000	0	-0.39	77	77
IGF1R	-0.023	0.15	-10000	0	-0.72	23	23
E2/ER alpha (dimer)/Striatin	-0.091	0.21	-10000	0	-0.47	118	118
SHC1	0.016	0	-10000	0	-10000	0	0
apoptosis	0.16	0.34	0.77	117	-10000	0	117
RhoA/GTP	-0.069	0.15	-10000	0	-0.34	117	117
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.15	0.2	-10000	0	-0.48	120	120
regulation of stress fiber formation	0.02	0.13	0.33	3	-10000	0	3
E2/ERA-ERB (dimer)	-0.089	0.2	-10000	0	-0.47	117	117
KRAS	0.012	0.025	-10000	0	-10000	0	0
G13/GTP	-0.081	0.19	-10000	0	-0.43	117	117
pseudopodium formation	-0.02	0.13	-10000	0	-0.33	3	3
E2/ER alpha (dimer)/PELP1	-0.089	0.2	-10000	0	-0.47	117	117
GRB2	0.013	0.022	-10000	0	-10000	0	0
GNG2	0.015	0.032	-10000	0	-0.72	1	1
GNAO1	0.016	0	-10000	0	-10000	0	0
HRAS	0.015	0.012	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.12	0.22	-10000	0	-0.51	118	118
E2/ER beta (dimer)	0	0	-10000	0	-10000	0	0
mol:GDP	-0.092	0.21	-10000	0	-0.49	117	117
mol:NADP	-0.12	0.22	-10000	0	-0.51	118	118
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
mol:IP3	-0.053	0.17	-10000	0	-0.41	77	77
IGF-1R heterotetramer	-0.023	0.15	-10000	0	-0.72	23	23
PLCB1	-0.064	0.17	-10000	0	-0.43	77	77
PLCB2	-0.006	0.095	-10000	0	-0.63	6	6
IGF1	-0.35	0.37	-10000	0	-0.72	262	262
mol:L-citrulline	-0.12	0.22	-10000	0	-0.51	118	118
RHOA	0.016	0	-10000	0	-10000	0	0
Gai/GDP	-0.096	0.13	-10000	0	-0.77	2	2
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.016	0	-10000	0	-10000	0	0
ESR2	0.016	0	-10000	0	-10000	0	0
GNAQ	0	0	-10000	0	-10000	0	0
ESR1	-0.18	0.3	-10000	0	-0.72	117	117
Gq family/GDP/Gbeta gamma	0.032	0.052	-10000	0	-0.78	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.043	0.13	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.15	0.2	-10000	0	-0.48	120	120
GNAZ	0.008	0.078	-10000	0	-0.72	6	6
E2/ER alpha (dimer)	-0.14	0.22	-10000	0	-0.55	117	117
STRN	0.014	0.034	-10000	0	-0.72	1	1
GNAL	0.012	0.056	-10000	0	-0.72	3	3
PELP1	0.016	0	-10000	0	-10000	0	0
MAPK11	0.024	0	-10000	0	-10000	0	0
GNAI2	0.016	0.007	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	-0.25	0.35	-10000	0	-0.72	189	189
HBEGF	-0.12	0.18	-10000	0	-0.4	87	87
cAMP biosynthetic process	-0.076	0.17	-10000	0	-0.38	119	119
SRC	-0.12	0.19	-10000	0	-0.39	120	120
PI3K	-0.052	0.16	-10000	0	-0.54	51	51
GNB1	0.016	0.01	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.077	0.19	-10000	0	-0.42	118	118
SOS1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.27	0.24	-10000	0	-0.49	247	247
Gs family/GTP	-0.075	0.17	-10000	0	-0.38	119	119
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.003	0.016	-10000	0	-10000	0	0
vasodilation	-0.12	0.22	-10000	0	-0.48	118	118
mol:DAG	-0.053	0.17	-10000	0	-0.41	77	77
Gs family/GDP/Gbeta gamma	-0.079	0.17	-10000	0	-0.39	117	117
MSN	-0.023	0.14	-10000	0	-0.36	3	3
Gq family/GTP	-0.032	0.094	-10000	0	-0.68	6	6
mol:PI-3-4-5-P3	-0.17	0.34	-10000	0	-0.79	117	117
NRAS	0.014	0.019	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.12	0.22	0.48	118	-10000	0	118
GRB2/SOS1	-0.001	0.011	-10000	0	-10000	0	0
RhoA/GDP	-0.083	0.2	-10000	0	-0.45	117	117
NOS3	-0.13	0.24	-10000	0	-0.53	118	118
GNA11	0.016	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.12	0.27	-10000	0	-0.6	118	118
E2/ER alpha (dimer)/PELP1/Src	-0.16	0.21	-10000	0	-0.51	120	120
ruffle organization	-0.02	0.13	-10000	0	-0.33	3	3
ROCK2	-0.036	0.15	-10000	0	-0.37	16	16
GNA14	-0.008	0.09	-10000	0	-0.72	6	6
GNA15	0.014	0.02	-10000	0	-10000	0	0
GNA13	0.015	0.014	-10000	0	-10000	0	0
MMP9	-0.13	0.18	-10000	0	-0.43	84	84
MMP2	-0.11	0.18	-10000	0	-0.56	22	22

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.018	0.066	-9999	-10000	0	0
mol:Halofuginone	0.004	0.002	-9999	-10000	0	0
ITGA1	0.013	0.045	-9999	-0.72	2	2
CDKN1A	-0.12	0.079	-9999	-0.59	2	2
PRL-3/alpha Tubulin	-0.003	0.016	-9999	-10000	0	0
mol:Ca2+	-0.02	0.04	-9999	-10000	0	0
AGT	-0.013	0.062	-9999	-10000	0	0
CCNA2	-0.32	0.17	-9999	-0.43	169	169
TUBA1B	0.015	0.012	-9999	-10000	0	0
EGR1	-0.44	0.21	-9999	-0.53	436	436
CDK2/Cyclin E1	-0.098	0.082	-9999	-0.55	2	2
MAPK3	0.025	0.02	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	-0.001	0.011	-9999	-10000	0	0
MAPK1	0.025	0.02	-9999	-10000	0	0
PTP4A1	-0.32	0.17	-9999	-0.4	436	436
PTP4A3	0.01	0.031	-9999	-10000	0	0
PTP4A2	0.013	0.022	-9999	-10000	0	0
ITGB1	0.025	0.02	-9999	-10000	0	0
SRC	0.016	0.007	-9999	-10000	0	0
RAC1	-0.12	0.072	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.29	0.16	-9999	-0.37	436	436
RABGGTA	0.016	0	-9999	-10000	0	0
BCAR1	-0.001	0.008	-9999	-10000	0	0
RHOC	-0.12	0.072	-9999	-10000	0	0
RHOA	-0.12	0.072	-9999	-10000	0	0
cell motility	-0.12	0.078	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.29	0.16	-9999	-0.44	6	6
PRL-3/alpha1 Integrin	-0.005	0.036	-9999	-0.54	2	2
ROCK1	-0.12	0.078	-9999	-10000	0	0
RABGGTB	0.016	0	-9999	-10000	0	0
CDK2	0.013	0.024	-9999	-10000	0	0
mitosis	-0.32	0.17	-9999	-0.4	436	436
ATF5	0.015	0.012	-9999	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.21	0.48	-10000	0	-0.97	102	102
STAT6 (cleaved dimer)	-0.3	0.38	-10000	0	-0.93	112	112
IGHG1	-0.046	0.22	-10000	0	-0.34	61	61
IGHG3	-0.22	0.46	-10000	0	-0.92	108	108
AKT1	-0.069	0.28	-10000	0	-0.52	51	51
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.009	0.2	-10000	0	-0.47	8	8
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.084	0.3	-10000	0	-0.58	64	64
THY1	-0.21	0.48	-10000	0	-0.97	100	100
MYB	-0.049	0.2	-10000	0	-0.72	41	41
HMGA1	0.011	0.028	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.083	0.3	-10000	0	-0.51	95	95
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.058	0.26	-10000	0	-0.49	36	36
SP1	0.023	0.01	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.018	0.036	-10000	0	-0.72	1	1
STAT6 (dimer)/ETS1	-0.28	0.37	-10000	0	-0.92	107	107
SOCS1	-0.098	0.34	-10000	0	-0.62	98	98
SOCS3	-0.07	0.33	-10000	0	-1.3	16	16
FCER2	-0.21	0.42	-10000	0	-0.78	81	81
PARP14	0.011	0.033	-10000	0	-10000	0	0
CCL17	-0.21	0.48	-10000	0	-0.97	100	100
GRB2	0.013	0.022	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.032	0.22	-10000	0	-0.45	15	15
T cell proliferation	-0.24	0.49	-10000	0	-0.95	122	122
IL4R/JAK1	-0.22	0.48	-10000	0	-0.99	103	103
EGR2	-0.63	0.81	-10000	0	-1.4	264	264
JAK2	0.014	0.054	-10000	0	-0.76	1	1
JAK3	0.021	0.008	-10000	0	-10000	0	0
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
JAK1	0.016	0.051	-10000	0	-0.72	2	2
COL1A2	-0.041	0.22	-10000	0	-1.6	3	3
CCL26	-0.21	0.48	-10000	0	-0.97	102	102
IL4R	-0.23	0.52	-10000	0	-1	103	103
PTPN6	0.02	0.021	-10000	0	-10000	0	0
IL13RA2	-0.22	0.5	-10000	0	-1	107	107
IL13RA1	0.016	0.043	-10000	0	-10000	0	0
IRF4	0.017	0.13	-10000	0	-10000	0	0
ARG1	-0.007	0.2	-10000	0	-1.3	4	4
CBL	-0.068	0.28	-10000	0	-0.47	94	94
GTF3A	0.012	0.015	-10000	0	-10000	0	0
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
IL13RA1/JAK2	0.021	0.072	-10000	0	-0.58	1	1
IRF4/BCL6	-0.027	0.17	-10000	0	-0.52	25	25
CD40LG	0.025	0.022	-10000	0	-10000	0	0
MAPK14	-0.069	0.29	-10000	0	-0.6	39	39
mitosis	-0.064	0.27	-10000	0	-0.5	52	52
STAT6	-0.24	0.55	-10000	0	-1.1	104	104
SPI1	0.019	0.031	-10000	0	-10000	0	0
RPS6KB1	-0.055	0.26	-10000	0	-0.5	40	40
STAT6 (dimer)	-0.24	0.55	-10000	0	-1.1	104	104
STAT6 (dimer)/PARP14	-0.23	0.49	-10000	0	-1	104	104
mast cell activation	0.001	0.019	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.041	0.25	-10000	0	-0.48	26	26
FRAP1	-0.069	0.28	-10000	0	-0.52	51	51
LTA	-0.21	0.48	-10000	0	-0.97	102	102
FES	0.013	0.045	-10000	0	-0.72	2	2
T-helper 1 cell differentiation	0.23	0.54	1.1	104	-10000	0	104
CCL11	-0.22	0.46	-10000	0	-0.94	102	102
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.041	0.25	-10000	0	-0.48	25	25
IL2RG	0.011	0.041	-10000	0	-10000	0	0
IL10	-0.21	0.48	-10000	0	-0.97	100	100
IRS1	-0.081	0.25	-10000	0	-0.72	69	69
IRS2	-0.18	0.32	-10000	0	-0.72	137	137
IL4	-0.007	0.16	-10000	0	-10000	0	0
IL5	-0.21	0.48	-10000	0	-0.97	102	102
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.16	0.41	-10000	0	-0.77	99	99
COL1A1	-0.053	0.21	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.22	0.49	-10000	0	-1	103	103
IL2R gamma/JAK3	0.033	0.021	-10000	0	-10000	0	0
TFF3	-0.36	0.67	-10000	0	-1.3	151	151
ALOX15	-0.21	0.49	-10000	0	-0.97	103	103
MYBL1	-0.022	0.069	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.16	0.42	-10000	0	-0.76	111	111
SHC1	0.016	0	-10000	0	-10000	0	0
CEBPB	0.022	0.035	-10000	0	-0.72	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.1	0.29	-10000	0	-0.52	92	92
mol:PI-3-4-5-P3	-0.069	0.28	-10000	0	-0.52	51	51
PI3K	-0.074	0.29	-10000	0	-0.55	51	51
DOK2	0.013	0.046	-10000	0	-0.72	2	2
ETS1	0.017	0.038	-10000	0	-0.68	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.023	0.21	-10000	0	-0.53	6	6
ITGB3	-0.21	0.48	-10000	0	-0.97	102	102
PIGR	-0.57	0.8	-10000	0	-1.4	223	223
IGHE	0.001	0.064	-10000	0	-10000	0	0
MAPKKK cascade	-0.022	0.21	-10000	0	-0.52	6	6
BCL6	-0.06	0.22	-10000	0	-0.72	53	53
OPRM1	-0.21	0.48	-10000	0	-0.97	101	101
RETNLB	-0.21	0.48	-10000	0	-0.97	102	102
SELP	-0.44	0.78	-10000	0	-1.5	160	160
AICDA	-0.21	0.46	-10000	0	-0.94	102	102

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.008	0.13	-10000	0	-0.37	51	51
adherens junction organization	0.013	0.096	-10000	0	-0.28	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.17	0.22	-10000	0	-0.57	58	58
FMN1	0.011	0.09	-10000	0	-0.28	38	38
mol:IP3	-0.041	0.1	-10000	0	-0.34	51	51
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.011	0.094	-10000	0	-0.29	38	38
CTNNB1	0.01	0.065	-10000	0	-0.72	4	4
AKT1	0.009	0.12	-10000	0	-0.33	51	51
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.016	0.13	-10000	0	-0.46	37	37
CTNND1	0.015	0.009	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.02	0.089	-10000	0	-0.49	1	1
VASP	0.016	0.091	-10000	0	-0.27	38	38
ZYX	0.02	0.091	-10000	0	-0.27	39	39
JUB	0.006	0.12	-10000	0	-0.42	21	21
EGFR(dimer)	-0.19	0.23	-10000	0	-0.39	277	277
E-cadherin/beta catenin-gamma catenin	-0.026	0.12	-10000	0	-0.44	38	38
mol:PI-3-4-5-P3	-0.046	0.11	-10000	0	-0.35	51	51
PIK3CA	0.015	0.009	-10000	0	-10000	0	0
PI3K	-0.046	0.11	-10000	0	-0.36	51	51
FYN	0.023	0.11	-10000	0	-0.48	3	3
mol:Ca2+	0.003	0.12	-10000	0	-0.33	51	51
JUP	0.014	0.035	-10000	0	-0.72	1	1
PIK3R1	-0.054	0.22	-10000	0	-0.72	51	51
mol:DAG	-0.041	0.1	-10000	0	-0.34	51	51
CDH1	-0.033	0.18	-10000	0	-0.72	33	33
RhoA/GDP	-0.17	0.22	-10000	0	-0.55	62	62
establishment of polarity of embryonic epithelium	0.016	0.09	-10000	0	-0.27	38	38
SRC	0.016	0.007	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
EGFR	-0.38	0.37	-10000	0	-0.72	277	277
CASR	0.013	0.12	-10000	0	-0.31	51	51
RhoA/GTP	-0.036	0.092	-10000	0	-0.3	51	51
AKT2	0.009	0.12	-10000	0	-0.33	51	51
actin cable formation	0.015	0.089	-10000	0	-0.26	38	38
apoptosis	0.044	0.11	0.35	51	-10000	0	51
CTNNA1	0.016	0.005	-10000	0	-10000	0	0
mol:GDP	-0.19	0.24	-10000	0	-0.39	293	293
PIP5K1A	0.019	0.09	-10000	0	-0.5	1	1
PLCG1	-0.042	0.11	-10000	0	-0.34	51	51
Rac1/GTP	-0.19	0.18	-10000	0	-0.35	277	277
homophilic cell adhesion	0	0.004	-10000	0	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0	0.003	-9999	-10000	0	0
Necdin/E2F1	-0.15	0.24	-9999	-0.56	135	135
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.087	0.18	-9999	-0.42	110	110
NGF (dimer)/p75(NTR)/BEX1	-0.078	0.19	-9999	-0.48	94	94
NT-4/5 (dimer)/p75(NTR)	-0.098	0.21	-9999	-0.55	94	94
IKBKB	0.014	0.02	-9999	-10000	0	0
AKT1	-0.076	0.21	-9999	-0.43	131	131
IKBKG	0.016	0	-9999	-10000	0	0
BDNF	0.006	0.057	-9999	-0.72	2	2
MGDIs/NGR/p75(NTR)/LINGO1	-0.072	0.19	-9999	-0.47	94	94
FURIN	0.013	0.024	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.081	0.18	-9999	-0.46	96	96
LINGO1	-0.01	0.059	-9999	-10000	0	0
Sortilin/TRAF6/NRIF	0.002	0.016	-9999	-10000	0	0
proBDNF (dimer)	0.006	0.057	-9999	-0.72	2	2
NTRK1	0.014	0.019	-9999	-10000	0	0
RTN4R	0.007	0.037	-9999	-10000	0	0
neuron apoptosis	-0.015	0.17	-9999	-0.38	94	94
IRAK1	0.014	0.02	-9999	-10000	0	0
SHC1	-0.064	0.19	-9999	-0.47	94	94
ARHGDIA	0.015	0.014	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0.004	0.027	-9999	-0.38	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.086	0.18	-9999	-0.44	103	103
MAGEH1	-0.003	0.12	-9999	-0.72	14	14
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.18	0.27	-9999	-0.52	186	186
Mammalian IAPs/DIABLO	-0.025	0.11	-9999	-0.42	35	35
proNGF (dimer)	0	0	-9999	-10000	0	0
MAGED1	0.006	0.04	-9999	-10000	0	0
APP	0.006	0.074	-9999	-0.72	5	5
NT-4/5 (dimer)	0	0	-9999	-10000	0	0
ZNF274	0.015	0.014	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.045	0.16	-9999	-0.4	94	94
NGF	0	0	-9999	-10000	0	0
cell cycle arrest	-0.062	0.15	-9999	-0.38	94	94
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.02	0.13	-9999	-0.3	94	94
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.084	0.18	-9999	-0.47	94	94
NCSTN	0.016	0	-9999	-10000	0	0
mol:GTP	-0.086	0.2	-9999	-0.5	96	96
PSENEN	0.014	0.019	-9999	-10000	0	0
mol:ceramide	-0.047	0.17	-9999	-0.42	94	94
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.009	0.11	-9999	-0.26	5	5
p75(NTR)/beta APP	-0.1	0.22	-9999	-0.55	97	97
BEX1	-0.006	0.056	-9999	-10000	0	0
mol:GDP	-0.076	0.19	-9999	-0.48	94	94
NGF (dimer)	-0.068	0.16	-9999	-0.42	86	86
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.059	0.17	-9999	-0.42	94	94
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
RAC1/GTP	-0.073	0.16	-9999	-0.41	94	94
MYD88	0.016	0.01	-9999	-10000	0	0
CHUK	0.015	0.032	-9999	-0.72	1	1
NGF (dimer)/p75(NTR)/PKA	-0.087	0.2	-9999	-0.5	96	96
RHOB	0.013	0.046	-9999	-0.72	2	2
RHOA	0.016	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.01	0.026	-9999	-10000	0	0
NT3 (dimer)	-0.2	0.33	-9999	-0.72	150	150
TP53	-0.02	0.16	-9999	-0.36	96	96
PRDM4	-0.048	0.17	-9999	-0.42	94	94
BDNF (dimer)	-0.032	0.2	-9999	-0.46	89	89
PIK3CA	0.016	0.007	-9999	-10000	0	0
SORT1	0.016	0.007	-9999	-10000	0	0
activation of caspase activity	-0.086	0.17	-9999	-0.41	110	110
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.075	0.16	-9999	-0.42	94	94
RHOC	0.016	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.014	0.17	-9999	-0.36	94	94
DIABLO	0.016	0	-9999	-10000	0	0
SMPD2	-0.048	0.17	-9999	-0.42	94	94
APH1B	0.015	0.033	-9999	-0.72	1	1
APH1A	0.01	0.032	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.084	0.18	-9999	-0.47	94	94
PSEN1	0.016	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0.003	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.25	0.31	-9999	-0.6	216	216
MAPK8	-0.008	0.17	-9999	-0.36	94	94
MAPK9	-0.007	0.17	-9999	-0.36	94	94
APAF1	0.016	0.007	-9999	-10000	0	0
NTF3	-0.2	0.33	-9999	-0.72	150	150
NTF4	0	0	-9999	-10000	0	0
NDN	-0.17	0.32	-9999	-0.72	135	135
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.067	0.16	-9999	-0.39	97	97
p75 CTF/Sortilin/TRAF6/NRIF	0.001	0.009	-9999	-10000	0	0
RhoA-B-C/GTP	-0.086	0.2	-9999	-0.5	96	96
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.065	0.15	-9999	-0.38	96	96
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.072	0.16	-9999	-0.41	96	96
PRKACB	-0.007	0.099	-9999	-0.72	8	8
proBDNF (dimer)/p75 ECD	-0.006	0.037	-9999	-0.54	2	2
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.038	0.18	-9999	-0.72	35	35
BIRC2	0.016	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.14	0.23	-9999	-0.54	107	107
BAD	-0.003	0.17	-9999	-0.36	94	94
RIPK2	0.014	0.02	-9999	-10000	0	0
NGFR	-0.12	0.28	-9999	-0.72	94	94
CYCS	-0.04	0.16	-9999	-0.39	94	94
ADAM17	0.016	0.007	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.075	0.16	-9999	-0.42	94	94
BCL2L11	-0.003	0.17	-9999	-0.36	94	94
BDNF (dimer)/p75(NTR)	-0.1	0.21	-9999	-0.54	96	96
PI3K	-0.12	0.21	-9999	-0.46	131	131
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.075	0.16	-9999	-0.42	94	94
NDNL2	0.016	0	-9999	-10000	0	0
YWHAE	0.015	0.032	-9999	-0.72	1	1
PRKCI	0.013	0.022	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.098	0.21	-9999	-0.55	94	94
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.072	0.17	-9999	-0.43	94	94
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
PLG	0.015	0.032	-9999	-0.72	1	1
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.048	0.18	-9999	-0.43	96	96
SQSTM1	0.016	0.007	-9999	-10000	0	0
NGFRAP1	-0.016	0.15	-9999	-0.72	23	23
CASP3	0.001	0.16	-9999	-0.33	94	94
E2F1	-0.006	0.055	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
IKK complex	-0.03	0.07	-9999	-0.37	1	1
NGF (dimer)/TRKA	-0.001	0.011	-9999	-10000	0	0
MMP7	-0.1	0.27	-9999	-0.72	85	85
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.069	0.15	-9999	-0.39	94	94
MMP3	-0.078	0.11	-9999	-0.72	8	8
APAF-1/Caspase 9	-0.068	0.14	-9999	-0.59	10	10

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.36	0.21	-9999	-0.47	407	407
fibroblast growth factor receptor signaling pathway	-0.36	0.21	-9999	-0.47	407	407
LAMA1	0.016	0.01	-9999	-10000	0	0
PRNP	-0.003	0.12	-9999	-0.72	14	14
GPC1/SLIT2	-0.071	0.18	-9999	-0.54	69	69
SMAD2	0.009	0.12	-9999	-0.41	38	38
GPC1/PrPc/Cu2+	-0.012	0.076	-9999	-0.47	14	14
GPC1/Laminin alpha1	-0.001	0.008	-9999	-10000	0	0
TDGF1	0.016	0	-9999	-10000	0	0
CRIPTO/GPC1	0	0.006	-9999	-10000	0	0
APP/GPC1	-0.007	0.053	-9999	-0.54	5	5
mol:NO	0	0	-9999	-10000	0	0
YES1	0.034	0.022	-9999	-0.46	1	1
FLT1	0.016	0.01	-9999	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.032	0.12	-9999	-0.46	38	38
SERPINC1	0.012	0.025	-9999	-10000	0	0
FYN	0.033	0.031	-9999	-0.46	2	2
FGR	0.035	0.006	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.061	0.021	-9999	-10000	0	0
SLIT2	-0.081	0.25	-9999	-0.72	69	69
GPC1/NRG	-0.07	0.18	-9999	-0.54	67	67
NRG1	-0.079	0.25	-9999	-0.72	67	67
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.011	0.028	-9999	-10000	0	0
LYN	0.035	0.008	-9999	-10000	0	0
mol:Spermine	0.014	0.008	-9999	-10000	0	0
cell growth	-0.36	0.21	-9999	-0.47	407	407
BMP signaling pathway	-0.015	0.012	-9999	-10000	0	0
SRC	0.035	0.007	-9999	-10000	0	0
TGFBR1	0.014	0.017	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	-0.1	0.26	-9999	-0.72	79	79
GPC1	0.015	0.012	-9999	-10000	0	0
TGFBR1 (dimer)	0.014	0.017	-9999	-10000	0	0
VEGFA	-0.005	0.054	-9999	-10000	0	0
BLK	0.028	0.025	-9999	-10000	0	0
HCK	0.033	0.014	-9999	-10000	0	0
FGF2	-0.55	0.31	-9999	-0.72	403	403
FGFR1	-0.007	0.12	-9999	-0.72	15	15
VEGFR1 homodimer	0.016	0.01	-9999	-10000	0	0
TGFBR2	-0.037	0.19	-9999	-0.72	38	38
cell death	-0.007	0.053	-9999	-0.54	5	5
ATIII/GPC1	-0.002	0.013	-9999	-10000	0	0
PLA2G2A/GPC1	-0.086	0.19	-9999	-0.54	79	79
LCK	0.027	0.026	-9999	-10000	0	0
neuron differentiation	-0.069	0.18	-9999	-0.54	67	67
PrPc/Cu2+	-0.015	0.089	-9999	-0.55	14	14
APP	0.006	0.074	-9999	-0.72	5	5
TGFBR2 (dimer)	-0.037	0.19	-9999	-0.72	38	38

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.002	0.026	-9999	-0.54	1	1
PTK2	-0.083	0.19	-9999	-0.49	89	89
positive regulation of JNK cascade	-0.054	0.12	-9999	-0.32	89	89
CDC42/GDP	-0.008	0.19	-9999	-0.43	89	89
Rac1/GDP	-0.006	0.19	-9999	-0.42	89	89
RAP1B	0.016	0.01	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.01	0.065	-9999	-0.72	4	4
CDC42/GTP	-0.066	0.15	-9999	-0.39	89	89
nectin-3/I-afadin	-0.095	0.21	-9999	-0.56	89	89
RAPGEF1	-0.022	0.21	-9999	-0.48	89	89
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.04	0.24	-9999	-0.56	89	89
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
TLN1	-0.02	0.16	-9999	-0.64	23	23
Rap1/GTP	-0.056	0.13	-9999	-0.33	89	89
IQGAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.007	0.058	-9999	-0.42	10	10
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.095	0.21	-9999	-0.56	89	89
PVR	0.014	0.017	-9999	-10000	0	0
Necl-5(dimer)	0.014	0.017	-9999	-10000	0	0
mol:GDP	-0.025	0.23	-9999	-0.53	89	89
MLLT4	0.002	0.1	-9999	-0.72	10	10
PIK3CA	0.016	0.007	-9999	-10000	0	0
PI3K	-0.1	0.2	-9999	-0.44	124	124
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.011	0.074	-9999	-0.54	10	10
positive regulation of lamellipodium assembly	-0.056	0.12	-9999	-0.33	89	89
PVRL1	0.016	0.01	-9999	-10000	0	0
PVRL3	-0.1	0.27	-9999	-0.72	83	83
PVRL2	0.01	0.032	-9999	-10000	0	0
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
CDH1	-0.032	0.18	-9999	-0.72	33	33
CLDN1	-0.055	0.2	-9999	-0.72	42	42
JAM-A/CLDN1	-0.1	0.22	-9999	-0.48	116	116
SRC	-0.1	0.24	-9999	-0.63	89	89
ITGB3	0.014	0.02	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin	-0.011	0.074	-9999	-0.54	10	10
FARP2	-0.03	0.22	-9999	-0.52	89	89
RAC1	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.08	0.18	-9999	-0.48	89	89
nectin-1/I-afadin	-0.011	0.074	-9999	-0.54	10	10
nectin-2/I-afadin	-0.014	0.075	-9999	-0.54	10	10
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.081	0.18	-9999	-0.48	89	89
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.012	0.027	-9999	-10000	0	0
positive regulation of filopodium formation	-0.054	0.12	-9999	-0.32	89	89
alphaV/beta3 Integrin/Talin	0	0.15	-9999	-0.61	21	21
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.014	0.075	-9999	-0.54	10	10
nectin-2(dimer)/I-afadin/I-afadin	-0.014	0.075	-9999	-0.54	10	10
PIP5K1C	-0.032	0.17	-9999	-0.68	23	23
VAV2	-0.032	0.23	-9999	-0.53	89	89
RAP1/GDP	-0.066	0.15	-9999	-0.39	89	89
ITGAV	0.014	0.034	-9999	-0.72	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.079	0.19	-9999	-0.48	89	89
nectin-3(dimer)/I-afadin/I-afadin	-0.095	0.21	-9999	-0.56	89	89
Rac1/GTP	-0.068	0.15	-9999	-0.4	89	89
PTPRM	-0.048	0.19	-9999	-0.37	96	96
E-cadherin/beta catenin/alpha catenin	-0.027	0.11	-9999	-0.37	46	46
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.002	0.11	-10000	0	-0.29	60	60
epithelial cell differentiation	-0.026	0.1	-10000	0	-0.39	37	37
CYFIP2	-0.002	0.051	-10000	0	-10000	0	0
ENAH	0.058	0.085	-10000	0	-0.43	2	2
EGFR	-0.38	0.37	-10000	0	-0.72	277	277
EPHA2	0.005	0.09	-10000	0	-0.72	8	8
MYO6	0.019	0.11	-10000	0	-0.37	38	38
CTNNB1	0.01	0.065	-10000	0	-0.72	4	4
ABI1/Sra1/Nap1	0.009	0.026	-10000	0	-10000	0	0
AQP5	-0.18	0.26	-10000	0	-0.55	157	157
CTNND1	0.016	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.019	0.1	-10000	0	-0.36	37	37
regulation of calcium-dependent cell-cell adhesion	-0.015	0.15	-10000	0	-0.37	79	79
EGF	-0.24	0.35	-10000	0	-0.72	178	178
NCKAP1	0.016	0	-10000	0	-10000	0	0
AQP3	-0.081	0.2	-10000	0	-0.56	65	65
cortical microtubule organization	-0.026	0.1	-10000	0	-0.39	37	37
GO:0000145	0.019	0.099	-10000	0	-0.34	37	37
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.026	0.1	-10000	0	-0.39	37	37
MLLT4	0.002	0.1	-10000	0	-0.72	10	10
ARF6/GDP	-0.025	0.085	-10000	0	-0.64	2	2
ARF6	0.016	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.004	0.053	-10000	0	-0.41	8	8
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.034	0.1	-10000	0	-0.33	37	37
PVRL2	0.01	0.032	-10000	0	-10000	0	0
ZYX	0.018	0.11	-10000	0	-0.36	38	38
ARF6/GTP	-0.003	0.048	-10000	0	-0.37	8	8
CDH1	-0.032	0.18	-10000	0	-0.72	33	33
EGFR/EGFR/EGF/EGF	-0.33	0.26	-10000	0	-0.46	382	382
RhoA/GDP	-0.024	0.092	-10000	0	-0.36	37	37
actin cytoskeleton organization	0.026	0.1	-10000	0	-0.34	38	38
IGF-1R heterotetramer	-0.023	0.15	-10000	0	-0.72	23	23
GIT1	0.015	0.016	-10000	0	-10000	0	0
IGF1R	-0.023	0.15	-10000	0	-0.72	23	23
IGF1	-0.35	0.37	-10000	0	-0.72	262	262
DIAPH1	0.012	0.026	-10000	0	-10000	0	0
Wnt receptor signaling pathway	0.026	0.1	0.39	37	-10000	0	37
RHOA	0.016	0	-10000	0	-10000	0	0
RhoA/GTP	-0.025	0.086	-10000	0	-0.64	2	2
CTNNA1	0.016	0	-10000	0	-10000	0	0
VCL	0.026	0.11	-10000	0	-0.35	38	38
EFNA1	0.013	0.022	-10000	0	-10000	0	0
LPP	0.029	0.1	-10000	0	-0.34	37	37
Ephrin A1/EPHA2	-0.028	0.1	-10000	0	-0.36	43	43
SEC6/SEC8	-0.027	0.091	-10000	0	-0.44	4	4
MGAT3	-0.015	0.15	-10000	0	-0.38	79	79
HGF/MET	-0.057	0.14	-10000	0	-0.37	84	84
HGF	0.016	0.01	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.002	0.11	-10000	0	-0.3	60	60
actin cable formation	0.08	0.081	-10000	0	-0.32	3	3
KIAA1543	0.028	0.1	-10000	0	-0.34	37	37
KIFC3	0.019	0.1	-10000	0	-0.36	37	37
NCK1	0.016	0	-10000	0	-10000	0	0
EXOC3	0.016	0	-10000	0	-10000	0	0
ACTN1	0.019	0.1	-10000	0	-0.36	37	37
NCK1/GIT1	-0.001	0.008	-10000	0	-10000	0	0
mol:GDP	-0.026	0.1	-10000	0	-0.39	37	37
EXOC4	0.016	0	-10000	0	-10000	0	0
STX4	0.019	0.1	-10000	0	-0.36	37	37
PIP5K1C	0.019	0.1	-10000	0	-0.36	37	37
LIMA1	-0.016	0.15	-10000	0	-0.72	23	23
ABI1	0.016	0	-10000	0	-10000	0	0
ROCK1	-0.02	0.075	-10000	0	-0.54	2	2
adherens junction assembly	0.05	0.097	-10000	0	-0.37	1	1
IGF-1R heterotetramer/IGF1	-0.21	0.22	-10000	0	-0.39	290	290
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.014	0.075	-10000	0	-0.54	10	10
MET	-0.057	0.22	-10000	0	-0.72	52	52
PLEKHA7	0.019	0.1	-10000	0	-0.36	37	37
mol:GTP	-0.004	0.052	-10000	0	-0.41	8	8
establishment of epithelial cell apical/basal polarity	0.044	0.11	-10000	0	-0.41	4	4
cortical actin cytoskeleton stabilization	0.002	0.11	-10000	0	-0.29	60	60
regulation of cell-cell adhesion	0.026	0.1	-10000	0	-0.34	38	38
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.002	0.11	-10000	0	-0.3	60	60

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.003	0.09	-10000	0	-0.42	8	8
epithelial cell differentiation	0.026	0.08	-10000	0	-10000	0	0
ITCH	0.025	0.02	-10000	0	-10000	0	0
WWP1	0.008	0.077	-10000	0	-10000	0	0
FYN	0.013	0.045	-10000	0	-0.72	2	2
EGFR	-0.38	0.37	-10000	0	-0.72	277	277
PRL	0.016	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.012	0.14	-10000	0	-0.41	10	10
PTPRZ1	-0.5	0.34	-10000	0	-0.72	370	370
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.053	0.12	-10000	0	-0.45	13	13
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.04	0.16	-10000	0	-0.43	70	70
ADAM17	0.024	0.021	-10000	0	-10000	0	0
ErbB4/ErbB4	0	0.097	-10000	0	-0.46	4	4
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.005	0.087	-10000	0	-0.41	6	6
NCOR1	0.015	0.032	-10000	0	-0.72	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.031	0.16	-10000	0	-0.41	67	67
GRIN2B	-0.028	0.16	-10000	0	-0.38	79	79
ErbB4/ErbB2/betacellulin	0	0.11	-10000	0	-0.42	26	26
STAT1	-0.011	0.061	-10000	0	-10000	0	0
HBEGF	0.011	0.064	-10000	0	-0.72	4	4
PRLR	-0.026	0.071	-10000	0	-10000	0	0
E4ICDs/ETO2	-0.054	0.19	-10000	0	-0.5	71	71
axon guidance	0.12	0.12	-10000	0	-0.3	7	7
NEDD4	0.017	0.073	-10000	0	-0.7	5	5
Prolactin receptor/Prolactin receptor/Prolactin	-0.02	0.034	-10000	0	-10000	0	0
CBFA2T3	-0.084	0.25	-10000	0	-0.72	70	70
ErbB4/ErbB2/HBEGF	0.017	0.075	-10000	0	-0.4	6	6
MAPK3	0.002	0.14	-10000	0	-0.43	11	11
STAT1 (dimer)	0.007	0.095	-10000	0	-0.4	4	4
MAPK1	0.002	0.14	-10000	0	-0.43	11	11
JAK2	0.015	0.033	-10000	0	-0.72	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.038	0.16	-10000	0	-0.41	69	69
NRG1	-0.04	0.19	-10000	0	-0.55	67	67
NRG3	0.009	0.052	-10000	0	-0.72	2	2
NRG2	-0.48	0.35	-10000	0	-0.72	353	353
NRG4	0.015	0.014	-10000	0	-10000	0	0
heart development	0.12	0.12	-10000	0	-0.3	7	7
neural crest cell migration	-0.037	0.16	-10000	0	-0.4	69	69
ERBB2	0.021	0.044	-10000	0	-0.53	1	1
WWOX/E4ICDs	0.007	0.083	-10000	0	-0.4	4	4
SHC1	0.016	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.23	0.18	-10000	0	-0.4	281	281
apoptosis	0.017	0.066	0.36	6	-10000	0	6
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.31	0.22	-10000	0	-0.45	354	354
ErbB4/ErbB2/epiregulin	0.019	0.076	-10000	0	-0.42	4	4
ErbB4/ErbB4/betacellulin/betacellulin	-0.015	0.13	-10000	0	-0.45	28	28
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.004	0.083	-10000	0	-0.41	4	4
MDM2	0.009	0.084	-10000	0	-0.4	4	4
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.061	0.14	-10000	0	-0.41	67	67
STAT5A	0.12	0.11	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.25	0.26	-10000	0	-0.46	290	290
DLG4	0.016	0	-10000	0	-10000	0	0
GRB2/SHC	-0.001	0.011	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.024	0.061	-10000	0	-0.38	6	6
STAT5A (dimer)	0.032	0.093	-10000	0	-10000	0	0
MAP3K7IP2	0.015	0.032	-10000	0	-0.72	1	1
STAT5B (dimer)	0.11	0.1	-10000	0	-10000	0	0
LRIG1	-0.019	0.16	-10000	0	-0.72	25	25
EREG	-0.001	0.064	-10000	0	-0.72	2	2
BTC	-0.019	0.16	-10000	0	-0.72	24	24
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.12	0.12	-10000	0	-0.3	7	7
ERBB4	0	0.097	-10000	0	-0.47	4	4
STAT5B	0.016	0.007	-10000	0	-10000	0	0
YAP1	-0.011	0.058	-10000	0	-0.63	4	4
GRB2	0.013	0.022	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.02	0.069	-10000	0	-0.46	2	2
glial cell differentiation	0.024	0.061	0.38	6	-10000	0	6
WWOX	0.009	0.033	-10000	0	-10000	0	0
cell proliferation	0.022	0.16	-10000	0	-0.45	16	16

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.011	0.038	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.13	0.17	-9999	-0.47	82	82
JUN	-0.074	0.19	-9999	-0.42	98	98
HRAS	0.015	0.012	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	0.01	0.18	-9999	-0.43	72	72
RAP1A	0.016	0	-9999	-10000	0	0
FRS2	0.011	0.039	-9999	-0.72	1	1
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.013	0.18	-9999	-0.42	68	68
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.015	0.032	-9999	-0.72	1	1
RET9/GFRalpha1/GDNF/Enigma	-0.017	0.16	-9999	-0.42	68	68
RHOA	0.016	0	-9999	-10000	0	0
RAP1A/GTP	0.01	0.15	-9999	-0.37	68	68
GRB7	0.001	0.048	-9999	-10000	0	0
RET51/GFRalpha1/GDNF	0.015	0.18	-9999	-0.42	68	68
MAPKKK cascade	-0.003	0.13	-9999	-0.38	14	14
BCAR1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.074	0.25	-9999	-0.53	109	109
lamellipodium assembly	-0.12	0.17	-9999	-0.4	103	103
RET51/GFRalpha1/GDNF/SHC	0.015	0.18	-9999	-0.42	68	68
PIK3CA	0.016	0.007	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.017	0.16	-9999	-0.42	68	68
RET9/GFRalpha1/GDNF/Shank3	-0.017	0.16	-9999	-0.42	68	68
MAPK3	-0.057	0.12	-9999	-0.35	68	68
DOK1	0.014	0.019	-9999	-10000	0	0
DOK6	0.009	0.06	-9999	-0.72	3	3
PXN	0.016	0	-9999	-10000	0	0
neurite development	-0.034	0.12	-9999	-0.38	15	15
DOK5	-0.018	0.15	-9999	-0.72	23	23
GFRA1	-0.16	0.23	-9999	-0.72	68	68
MAPK8	-0.005	0.1	-9999	-0.3	14	14
HRAS/GTP	0.01	0.16	-9999	-0.39	68	68
tube development	-0.013	0.15	-9999	-0.39	68	68
MAPK1	-0.057	0.12	-9999	-0.35	68	68
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.01	0.11	-9999	-0.29	69	69
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.016	0.007	-9999	-10000	0	0
PDLIM7	0.016	0.007	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	0.018	0.17	-9999	-0.41	69	69
SHC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	0.015	0.18	-9999	-0.42	68	68
RET51/GFRalpha1/GDNF/Dok5	-0.009	0.21	-9999	-0.45	88	88
PRKCA	0.016	0.01	-9999	-10000	0	0
HRAS/GDP	-0.001	0.007	-9999	-10000	0	0
CREB1	-0.011	0.12	-9999	-0.32	68	68
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.01	0.11	-9999	-0.29	69	69
RET51/GFRalpha1/GDNF/Grb7	0.011	0.18	-9999	-0.44	68	68
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.062	0.081	-9999	-10000	0	0
DOK4	0.016	0	-9999	-10000	0	0
JNK cascade	-0.072	0.19	-9999	-0.41	98	98
RET9/GFRalpha1/GDNF/FRS2	-0.017	0.16	-9999	-0.42	69	69
SHANK3	0.016	0	-9999	-10000	0	0
RASA1	0.015	0.012	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.009	0.11	-9999	-0.3	68	68
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.009	0.11	-9999	-0.29	69	69
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.007	0.11	-9999	-0.29	68	68
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.006	0.11	-9999	-0.29	68	68
PI3K	-0.16	0.3	-9999	-0.68	103	103
SOS1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.01	0.15	-9999	-0.39	68	68
GRB10	0.011	0.064	-9999	-0.72	4	4
activation of MAPKK activity	-0.012	0.1	-9999	-0.3	13	13
RET51/GFRalpha1/GDNF/FRS2	0.012	0.18	-9999	-0.42	69	69
GAB1	0.014	0.034	-9999	-0.72	1	1
IRS1	-0.081	0.25	-9999	-0.72	69	69
IRS2	-0.18	0.32	-9999	-0.72	137	137
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.007	0.11	-9999	-0.29	69	69
RET51/GFRalpha1/GDNF/PKC alpha	0.015	0.18	-9999	-0.42	68	68
GRB2	0.013	0.022	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GDNF	0.016	0.007	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.044	0.27	-9999	-0.54	109	109
Rac1/GTP	-0.14	0.21	-9999	-0.5	103	103
RET9/GFRalpha1/GDNF	-0.027	0.17	-9999	-0.47	68	68
GFRalpha1/GDNF	-0.11	0.17	-9999	-0.54	68	68

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.25	0.23	-9999	-0.42	311	311
TC10/GTP	-0.2	0.18	-9999	-0.35	292	292
Insulin Receptor/Insulin/IRS1/Shp2	-0.053	0.14	-9999	-0.42	69	69
HRAS	0.015	0.012	-9999	-10000	0	0
APS homodimer	0	0	-9999	-10000	0	0
GRB14	-0.091	0.23	-9999	-0.72	57	57
FOXO3	-0.016	0.031	-9999	-10000	0	0
AKT1	-0.06	0.2	-9999	-0.57	30	30
INSR	0.019	0.002	-9999	-10000	0	0
Insulin Receptor/Insulin	0.046	0.036	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.011	0.064	-9999	-0.72	4	4
SORBS1	-0.39	0.37	-9999	-0.72	292	292
CRK	0.015	0.032	-9999	-0.72	1	1
PTPN1	0.045	0.036	-9999	-10000	0	0
CAV1	-0.33	0.25	-9999	-0.46	394	394
CBL/APS/CAP/Crk-II/C3G	-0.22	0.2	-9999	-0.39	292	292
Insulin Receptor/Insulin/IRS1/NCK2	-0.054	0.14	-9999	-0.42	69	69
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.083	0.16	-9999	-0.38	113	113
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.016	0.098	-9999	-10000	0	0
RPS6KB1	-0.046	0.19	-9999	-0.55	25	25
PARD6A	0.015	0.016	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.002	0.012	-9999	-10000	0	0
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.093	0.16	-9999	-0.57	24	24
HRAS/GTP	-0.04	0.1	-9999	-0.37	3	3
Insulin Receptor	0.018	0.002	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.047	0.13	-9999	-0.38	69	69
PRKCI	-0.02	0.058	-9999	-0.63	2	2
Insulin Receptor/Insulin/GRB14/PDK1	-0.11	0.19	-9999	-0.57	39	39
SHC1	0.016	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.002	0.013	-9999	-10000	0	0
PI3K	-0.084	0.17	-9999	-0.39	113	113
NCK2	0.016	0.01	-9999	-10000	0	0
RHOQ	0.015	0.032	-9999	-0.72	1	1
mol:H2O2	-0.001	0.004	-9999	-10000	0	0
HRAS/GDP	-0.001	0.007	-9999	-10000	0	0
AKT2	-0.06	0.2	-9999	-0.63	24	24
PRKCZ	-0.026	0.059	-9999	-0.64	2	2
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	-0.014	0.14	-9999	-0.37	69	69
F2RL2	-0.007	0.075	-9999	-0.72	3	3
TRIP10	0.015	0.032	-9999	-0.72	1	1
Insulin Receptor/Insulin/Shc	0.001	0.005	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	-0.002	0.029	-9999	-0.47	2	2
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.004	0.015	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
RASA1	0.015	0.012	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.23	0.21	-9999	-0.42	292	292
TC10/GDP	-0.001	0.024	-9999	-0.55	1	1
Insulin Receptor/Insulin/SHC/GRB10	-0.001	0.037	-9999	-0.42	4	4
INPP5D	-0.026	0.15	-9999	-0.4	69	69
SOS1	0.016	0	-9999	-10000	0	0
SGK1	-0.01	0.016	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	-0.081	0.25	-9999	-0.72	69	69
p62DOK/RasGAP	0.002	0.013	-9999	-10000	0	0
INS	0.019	0.002	-9999	-10000	0	0
mol:PI-3-4-P2	-0.025	0.14	-9999	-0.4	69	69
GRB2	0.013	0.022	-9999	-10000	0	0
EIF4EBP1	-0.049	0.19	-9999	-0.54	28	28
PTPRA	0.019	0.002	-9999	-10000	0	0
PIK3CA	0.016	0.007	-9999	-10000	0	0
TC10/GTP/CIP4	-0.002	0.029	-9999	-0.47	2	2
PDPK1	0.016	0.007	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.006	0.11	-9999	-0.31	2	2
Insulin Receptor/Insulin/IRS1	-0.055	0.14	-9999	-0.43	69	69
Insulin Receptor/Insulin/IRS3	0.001	0.003	-9999	-10000	0	0
Par3/Par6	0.007	0.047	-9999	-0.39	5	5

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.016	0	-9999	-10000	0	0
GNAT1/GTP	0	0.004	-9999	-10000	0	0
Metarhodopsin II/Arrestin	0.009	0.039	-9999	-0.47	2	2
PDE6G/GNAT1/GTP	0.001	0.006	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.016	0.007	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
CNG Channel	-0.16	0.18	-9999	-0.36	238	238
mol:Na +	-0.15	0.18	-9999	-0.57	11	11
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.018	0.13	-9999	-0.47	35	35
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.16	0.18	-9999	-0.6	11	11
CNGB1	0.016	0	-9999	-10000	0	0
RDH5	-0.58	0.29	-9999	-0.72	428	428
SAG	-0.013	0.074	-9999	-0.72	2	2
mol:Ca2+	-0.11	0.2	-9999	-0.55	11	11
Na + (4 Units)	-0.14	0.16	-9999	-0.53	11	11
RGS9	-0.03	0.18	-9999	-0.72	32	32
GNB1/GNGT1	-0.018	0.034	-9999	-10000	0	0
GNAT1/GDP	-0.013	0.11	-9999	-0.4	35	35
GUCY2D	0.016	0	-9999	-10000	0	0
GNGT1	-0.022	0.068	-9999	-10000	0	0
GUCY2F	0.012	0.047	-9999	-0.72	2	2
GNB5	0.015	0.032	-9999	-0.72	1	1
mol:GMP (4 units)	0.029	0.069	-9999	-0.39	14	14
mol:11-cis-retinal	-0.58	0.29	-9999	-0.72	428	428
mol:cGMP	-0.01	0.073	-9999	-0.44	13	13
GNB1	0.016	0.01	-9999	-10000	0	0
Rhodopsin	-0.44	0.21	-9999	-0.54	428	428
SLC24A1	0.016	0	-9999	-10000	0	0
CNGA1	-0.31	0.36	-9999	-0.72	230	230
Metarhodopsin II	0	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.009	0.069	-9999	-0.44	12	12
RGS9BP	-0.015	0.076	-9999	-0.72	2	2
Metarhodopsin II/Transducin	0.029	0.005	-9999	-10000	0	0
GCAP Family/Ca ++	-0.009	0.071	-9999	-0.46	12	12
PDE6A/B	-0.015	0.087	-9999	-0.54	14	14
mol:Pi	-0.018	0.12	-9999	-0.47	35	35
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.018	0.033	-9999	-10000	0	0
PDE6B	-0.005	0.12	-9999	-0.72	14	14
PDE6A	0.016	0.01	-9999	-10000	0	0
PDE6G	0.015	0.012	-9999	-10000	0	0
RHO	0.016	0	-9999	-10000	0	0
PDE6	-0.02	0.12	-9999	-0.39	47	47
GUCA1A	0.003	0.096	-9999	-0.72	9	9
GC2/GCAP Family	-0.01	0.078	-9999	-0.47	13	13
GUCA1C	0.011	0.057	-9999	-0.72	3	3
GUCA1B	0.015	0.033	-9999	-0.72	1	1

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.003	0.028	-10000	0	-0.47	1	1
cell-cell adhesion	0.12	0.16	0.45	21	-10000	0	21
Ephrin B/EPHB2/RasGAP	0.001	0.053	-10000	0	-0.38	8	8
ITSN1	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
SHC1	0.016	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.001	0.03	-10000	0	-0.47	2	2
Ephrin B1/EPHB1	-0.18	0.23	-10000	0	-0.47	197	197
HRAS/GDP	-0.12	0.16	-10000	0	-0.52	15	15
Ephrin B/EPHB1/GRB7	-0.15	0.2	-10000	0	-0.4	198	198
Endophilin/SYNJ1	0.038	0.052	-10000	0	-0.36	8	8
KRAS	0.012	0.025	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.15	0.2	-10000	0	-0.39	198	198
endothelial cell migration	-0.041	0.13	-10000	0	-0.4	56	56
GRB2	0.013	0.022	-10000	0	-10000	0	0
GRB7	0.001	0.048	-10000	0	-10000	0	0
PAK1	0.053	0.059	-10000	0	-0.38	8	8
HRAS	0.015	0.012	-10000	0	-10000	0	0
RRAS	0.038	0.052	-10000	0	-0.36	8	8
DNM1	0.016	0.007	-10000	0	-10000	0	0
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.11	0.21	-10000	0	-0.37	199	199
lamellipodium assembly	-0.12	0.16	-10000	0	-0.45	21	21
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.08	0.18	-10000	0	-0.3	198	198
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
EPHB2	0.006	0.04	-10000	0	-10000	0	0
EPHB3	0.014	0.017	-10000	0	-10000	0	0
EPHB1	-0.26	0.36	-10000	0	-0.72	197	197
EPHB4	0.011	0.039	-10000	0	-0.72	1	1
mol:GDP	-0.1	0.14	-10000	0	-0.62	10	10
Ephrin B/EPHB2	0	0.052	-10000	0	-0.39	8	8
Ephrin B/EPHB3	-0.005	0.049	-10000	0	-0.39	8	8
JNK cascade	-0.12	0.21	-10000	0	-0.38	197	197
Ephrin B/EPHB1	-0.15	0.2	-10000	0	-0.4	198	198
RAP1/GDP	-0.083	0.12	-10000	0	-0.52	10	10
EFNB2	0.008	0.079	-10000	0	-0.72	6	6
EFNB3	0.016	0	-10000	0	-10000	0	0
EFNB1	0.013	0.045	-10000	0	-0.72	2	2
Ephrin B2/EPHB1-2	-0.16	0.22	-10000	0	-0.43	198	198
RAP1B	0.016	0.01	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.12	0.16	-10000	0	-0.62	9	9
Rap1/GTP	-0.12	0.15	-10000	0	-0.47	16	16
axon guidance	0.003	0.028	-10000	0	-0.47	1	1
MAPK3	-0.053	0.16	-10000	0	-0.66	7	7
MAPK1	-0.053	0.16	-10000	0	-0.66	7	7
Rac1/GDP	-0.054	0.16	-10000	0	-0.55	10	10
actin cytoskeleton reorganization	-0.088	0.12	-10000	0	-0.46	9	9
CDC42/GDP	-0.054	0.16	-10000	0	-0.55	10	10
PI3K	-0.041	0.13	-10000	0	-0.4	56	56
EFNA5	0.014	0.034	-10000	0	-0.72	1	1
Ephrin B2/EPHB4	-0.005	0.055	-10000	0	-0.47	7	7
Ephrin B/EPHB2/Intersectin/N-WASP	0.041	0.043	-10000	0	-0.29	9	9
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	-0.11	0.15	-10000	0	-0.57	8	8
PTK2	0.039	0.051	-10000	0	-10000	0	0
MAP4K4	-0.12	0.21	-10000	0	-0.38	197	197
SRC	0.016	0.007	-10000	0	-10000	0	0
KALRN	0.016	0	-10000	0	-10000	0	0
Intersectin/N-WASP	-0.001	0.023	-10000	0	-0.54	1	1
neuron projection morphogenesis	-0.032	0.16	-10000	0	-0.46	9	9
MAP2K1	-0.066	0.17	-10000	0	-0.7	7	7
WASL	0.015	0.032	-10000	0	-0.72	1	1
Ephrin B1/EPHB1-2/NCK1	-0.15	0.21	-10000	0	-0.42	197	197
cell migration	-0.07	0.18	-10000	0	-0.72	7	7
NRAS	0.014	0.019	-10000	0	-10000	0	0
SYNJ1	0.038	0.052	-10000	0	-0.36	8	8
PXN	0.016	0	-10000	0	-10000	0	0
TF	0.033	0.088	-10000	0	-0.35	26	26
HRAS/GTP	-0.12	0.17	-10000	0	-0.5	16	16
Ephrin B1/EPHB1-2	-0.16	0.21	-10000	0	-0.43	197	197
cell adhesion mediated by integrin	-0.028	0.063	0.36	8	-10000	0	8
RAC1	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.13	0.18	-10000	0	-0.36	198	198
RAC1-CDC42/GTP	-0.11	0.15	-10000	0	-0.47	15	15
RASA1	0.015	0.012	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.083	0.12	-10000	0	-0.52	10	10
ruffle organization	-0.072	0.19	-10000	0	-0.45	21	21
NCK1	0.016	0	-10000	0	-10000	0	0
receptor internalization	0.047	0.051	-10000	0	-0.34	8	8
Ephrin B/EPHB2/KALRN	0	0.052	-10000	0	-0.38	8	8
ROCK1	0.03	0.029	-10000	0	-0.42	2	2
RAS family/GDP	-0.074	0.1	-10000	0	-0.47	8	8
Rac1/GTP	-0.12	0.17	-10000	0	-0.48	21	21
Ephrin B/EPHB1/Src/Paxillin	-0.085	0.18	-10000	0	-0.3	198	198

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.023	0.013	-9999	-10000	0	0
RAS family/GTP	-0.022	0.11	-9999	-0.34	10	10
NFATC4	-0.019	0.098	-9999	-0.3	14	14
ERBB2IP	0.017	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.016	0.01	-9999	-10000	0	0
mammary gland morphogenesis	-0.034	0.13	-9999	-0.35	68	68
JUN	-0.035	0.083	-9999	-10000	0	0
HRAS	0.014	0.012	-9999	-10000	0	0
DOCK7	-0.029	0.12	-9999	-0.37	15	15
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.056	0.14	-9999	-0.41	68	68
AKT1	0.012	0.014	-9999	-10000	0	0
BAD	0.024	0.011	-9999	-10000	0	0
MAPK10	-0.025	0.07	-9999	-0.3	12	12
mol:GTP	-0.002	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.036	0.14	-9999	-0.38	68	68
RAF1	-0.022	0.11	-9999	-0.34	18	18
ErbB2/ErbB3/neuregulin 2	-0.3	0.21	-9999	-0.44	354	354
STAT3	0.004	0.009	-9999	-10000	0	0
cell migration	0.017	0.078	-9999	-0.29	4	4
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.24	0.28	-9999	-0.62	133	133
FOS	-0.34	0.29	-9999	-0.52	375	375
NRAS	0.013	0.019	-9999	-10000	0	0
mol:Ca2+	-0.034	0.13	-9999	-0.35	68	68
MAPK3	-0.15	0.21	-9999	-0.49	99	99
MAPK1	-0.15	0.21	-9999	-0.48	101	101
JAK2	-0.029	0.12	-9999	-0.34	54	54
NF2	0.001	0.008	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.015	0.12	-9999	-0.33	67	67
NRG1	-0.08	0.25	-9999	-0.72	67	67
GRB2/SOS1	-0.001	0.011	-9999	-10000	0	0
MAPK8	-0.023	0.11	-9999	-0.31	55	55
MAPK9	-0.02	0.056	-9999	-10000	0	0
ERBB2	-0.013	0.041	-9999	-0.56	1	1
ERBB3	0.008	0.03	-9999	-10000	0	0
SHC1	0.015	0.001	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
apoptosis	0.013	0.014	-9999	-10000	0	0
STAT3 (dimer)	0.004	0.009	-9999	-10000	0	0
RNF41	0.03	0.013	-9999	-10000	0	0
FRAP1	0.024	0.011	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.031	0.079	-9999	-0.26	14	14
ErbB2/ErbB2/HSP90 (dimer)	-0.009	0.03	-9999	-0.47	1	1
CHRNA1	-0.11	0.17	-9999	-0.36	96	96
myelination	0.011	0.1	-9999	-0.32	2	2
PPP3CB	-0.027	0.11	-9999	-0.35	15	15
KRAS	0.011	0.025	-9999	-10000	0	0
RAC1-CDC42/GDP	0.006	0.1	-9999	-0.28	12	12
NRG2	-0.48	0.35	-9999	-0.72	353	353
mol:GDP	-0.015	0.12	-9999	-0.32	67	67
SOS1	0.015	0.001	-9999	-10000	0	0
MAP2K2	-0.026	0.12	-9999	-0.37	16	16
SRC	0.016	0.007	-9999	-10000	0	0
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.029	0.12	-9999	-0.37	15	15
MAP2K1	-0.16	0.2	-9999	-0.48	65	65
heart morphogenesis	-0.034	0.13	-9999	-0.35	68	68
RAS family/GDP	-0.016	0.1	-9999	-0.34	5	5
GRB2	0.012	0.022	-9999	-10000	0	0
PRKACA	-0.002	0.008	-9999	-10000	0	0
CHRNE	0.007	0.02	-9999	-10000	0	0
HSP90AA1	0.016	0.01	-9999	-10000	0	0
activation of caspase activity	-0.012	0.014	-9999	-10000	0	0
nervous system development	-0.034	0.13	-9999	-0.35	68	68
CDC42	0.016	0	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	0.002	0.01	-10000	0	-10000	0	0
HDAC1	0.014	0.011	-10000	0	-10000	0	0
AES	0.016	0.004	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
DTX1	0.012	0.056	-10000	0	-0.72	3	3
LRP6/FZD1	-0.001	0.024	-10000	0	-0.54	1	1
TLE1	-0.009	0.13	-10000	0	-0.72	18	18
AP1	-0.26	0.2	-10000	0	-0.38	374	374
NCSTN	0.016	0	-10000	0	-10000	0	0
ADAM10	0.015	0.012	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.015	0.094	-10000	0	-0.58	2	2
NICD/RBPSUH	0.002	0.009	-10000	0	-10000	0	0
WIF1	-0.53	0.32	-10000	0	-0.72	392	392
NOTCH1	0.002	0.008	-10000	0	-10000	0	0
PSENEN	0.014	0.019	-10000	0	-10000	0	0
KREMEN2	-0.076	0.08	-10000	0	-10000	0	0
DKK1	-0.075	0.21	-10000	0	-0.72	46	46
beta catenin/beta TrCP1	-0.004	0.053	-10000	0	-0.48	4	4
APH1B	0.015	0.033	-10000	0	-0.72	1	1
APH1A	0.01	0.032	-10000	0	-10000	0	0
AXIN1	0.006	0.006	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.027	0.074	0.3	2	-0.3	18	20
PSEN1	0.016	0	-10000	0	-10000	0	0
FOS	-0.51	0.34	-10000	0	-0.72	374	374
JUN	-0.12	0.29	-10000	0	-0.72	97	97
MAP3K7	0.015	0.011	-10000	0	-10000	0	0
CTNNB1	-0.015	0.055	-10000	0	-0.51	4	4
MAPK3	0.016	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.04	0.068	-10000	0	-0.5	5	5
HNF1A	0.015	0.012	-10000	0	-10000	0	0
CTBP1	0.015	0.008	-10000	0	-10000	0	0
MYC	-0.055	0.34	-10000	0	-1.5	29	29
NKD1	0.014	0.018	-10000	0	-10000	0	0
FZD1	0.015	0.032	-10000	0	-0.72	1	1
NOTCH1 precursor/Deltex homolog 1	0	0.03	-10000	0	-0.38	3	3
apoptosis	-0.26	0.2	-10000	0	-0.38	374	374
Delta 1/NOTCHprecursor	0.002	0.009	-10000	0	-10000	0	0
DLL1	0.016	0	-10000	0	-10000	0	0
PPARD	0.022	0.027	-10000	0	-10000	0	0
Gamma Secretase	0.004	0.027	-10000	0	-0.38	1	1
APC	0.006	0.006	-10000	0	-10000	0	0
DVL1	-0.041	0.025	-10000	0	-10000	0	0
CSNK2A1	0.016	0.004	-10000	0	-10000	0	0
MAP3K7IP1	0.015	0.005	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.027	0.16	-10000	0	-0.5	46	46
LRP6	0.015	0.012	-10000	0	-10000	0	0
CSNK1A1	0.016	0.004	-10000	0	-10000	0	0
NLK	0.029	0.015	-10000	0	-10000	0	0
CCND1	-0.02	0.23	-10000	0	-1.5	12	12
WNT1	0.016	0	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.006	0.045	-10000	0	-0.33	1	1
DKK2	0.007	0.074	-10000	0	-0.72	5	5
NOTCH1 precursor/DVL1	-0.008	0.012	-10000	0	-10000	0	0
GSK3B	0.015	0.01	-10000	0	-10000	0	0
FRAT1	0.015	0.01	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0	0.03	-10000	0	-0.38	3	3
PPP2R5D	-0.021	0.016	-10000	0	-10000	0	0
MAPK1	0.016	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.31	0.18	-10000	0	-0.41	392	392
RBPJ	0.016	0	-10000	0	-10000	0	0
CREBBP	0.018	0.033	-10000	0	-0.73	1	1

×

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

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
MET/RANBP9	-0.054	0.16	-10000	0	-0.54	52	52
CRKL	0.018	0.1	-10000	0	-0.29	53	53
mol:PIP3	-0.014	0.1	0.62	13	-10000	0	13
AKT1	0.008	0.068	0.42	13	-10000	0	13
PTK2B	0.016	0	-10000	0	-10000	0	0
RAPGEF1	0.027	0.098	-10000	0	-0.37	1	1
RANBP10	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
HGF/MET/SHIP2	-0.044	0.14	-10000	0	-0.46	52	52
MAP3K5	0.013	0.14	-10000	0	-0.38	35	35
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.041	0.12	-10000	0	-0.41	53	53
AP1	-0.42	0.32	-10000	0	-0.6	375	375
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.016	0	-10000	0	-10000	0	0
apoptosis	-0.54	0.37	-10000	0	-0.76	375	375
STAT3 (dimer)	0.023	0.097	-10000	0	-0.28	2	2
GAB1/CRKL/SHP2/PI3K	-0.054	0.12	-10000	0	-0.59	7	7
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.026	0.099	-10000	0	-0.35	2	2
PTPN11	0.016	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.016	0.007	-10000	0	-10000	0	0
PTEN	-0.002	0.12	-10000	0	-0.72	13	13
ELK1	-0.022	0.076	-10000	0	-0.25	52	52
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.017	0.052	-10000	0	-10000	0	0
PAK1	0.005	0.067	0.39	13	-10000	0	13
HGF/MET/RANBP10	-0.045	0.14	-10000	0	-0.46	52	52
HRAS	-0.022	0.22	-10000	0	-0.68	52	52
DOCK1	0.024	0.1	-10000	0	-0.35	5	5
GAB1	0.008	0.11	-10000	0	-0.31	53	53
CRK	0.017	0.1	-10000	0	-0.29	54	54
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.062	0.19	-10000	0	-0.64	52	52
JUN	-0.12	0.29	-10000	0	-0.72	97	97
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.032	0.098	-10000	0	-0.33	52	52
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
cell morphogenesis	0.022	0.15	-10000	0	-0.57	7	7
GRB2/SHC	0.007	0.094	-10000	0	-0.28	52	52
FOS	-0.51	0.34	-10000	0	-0.72	374	374
GLMN	0	0.002	-10000	0	-10000	0	0
cell motility	-0.022	0.076	-10000	0	-0.25	52	52
HGF/MET/MUC20	-0.046	0.14	-10000	0	-0.47	52	52
cell migration	0.007	0.093	-10000	0	-0.27	52	52
GRB2	0.013	0.022	-10000	0	-10000	0	0
CBL	0.016	0	-10000	0	-10000	0	0
MET/RANBP10	-0.053	0.16	-10000	0	-0.54	52	52
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.015	0.1	-10000	0	-0.29	52	52
MET/MUC20	-0.055	0.16	-10000	0	-0.55	52	52
RAP1B	0.035	0.093	-10000	0	-0.34	1	1
RAP1A	0.035	0.093	-10000	0	-0.34	1	1
HGF/MET/RANBP9	-0.045	0.14	-10000	0	-0.46	52	52
RAF1	-0.01	0.21	-10000	0	-0.63	52	52
STAT3	0.023	0.098	-10000	0	-0.28	2	2
cell proliferation	0.023	0.14	-10000	0	-0.41	52	52
RPS6KB1	0.005	0.04	-10000	0	-10000	0	0
MAPK3	-0.027	0.069	-10000	0	-10000	0	0
MAPK1	-0.027	0.069	-10000	0	-0.24	52	52
RANBP9	0.016	0.007	-10000	0	-10000	0	0
MAPK8	0.027	0.12	-10000	0	-0.42	10	10
SRC	0.025	0.095	-10000	0	-10000	0	0
PI3K	-0.033	0.16	-10000	0	-0.35	96	96
MET/Glomulin	-0.035	0.15	-10000	0	-0.49	52	52
SOS1	0.016	0	-10000	0	-10000	0	0
MAP2K1	0.002	0.19	-10000	0	-0.57	52	52
MET	-0.057	0.22	-10000	0	-0.72	52	52
MAP4K1	0.03	0.098	-10000	0	-0.37	1	1
PTK2	0.015	0.014	-10000	0	-10000	0	0
MAP2K2	0.002	0.19	-10000	0	-0.57	52	52
BAD	0.016	0.062	0.4	13	-10000	0	13
MAP2K4	0.018	0.14	-10000	0	-0.43	16	16
SHP2/GRB2/SOS1/GAB1	-0.041	0.13	-10000	0	-0.42	52	52
INPPL1	0.015	0.012	-10000	0	-10000	0	0
PXN	0.016	0	-10000	0	-10000	0	0
SH3KBP1	0.015	0.033	-10000	0	-0.72	1	1
HGS	-0.003	0.097	-10000	0	-0.3	52	52
PLCgamma1/PKC	0	0.004	-10000	0	-10000	0	0
HGF	0.016	0.01	-10000	0	-10000	0	0
RASA1	0.015	0.012	-10000	0	-10000	0	0
NCK1	0.016	0	-10000	0	-10000	0	0
PTPRJ	0.014	0.019	-10000	0	-10000	0	0
NCK/PLCgamma1	0.01	0.092	-10000	0	-10000	0	0
PDPK1	-0.002	0.078	0.48	13	-10000	0	13
HGF/MET/SHIP	-0.046	0.14	-10000	0	-0.47	52	52

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.055	0.26	-10000	0	-0.55	103	103
IHH	0.009	0.047	-10000	0	-10000	0	0
SHH Np/Cholesterol/GAS1	-0.14	0.2	-10000	0	-0.43	169	169
LRPAP1	0.016	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.14	0.2	0.42	169	-10000	0	169
SMO/beta Arrestin2	-0.003	0.16	-10000	0	-0.65	8	8
SMO	-0.012	0.17	-10000	0	-0.66	9	9
AKT1	-0.014	0.17	-10000	0	-0.56	29	29
ARRB2	0.016	0	-10000	0	-10000	0	0
BOC	-0.15	0.31	-10000	0	-0.72	117	117
ADRBK1	0.016	0	-10000	0	-10000	0	0
heart looping	-0.011	0.17	-10000	0	-0.65	9	9
STIL	0.011	0.12	-10000	0	-0.43	6	6
DHH N/PTCH2	0	0	-10000	0	-10000	0	0
DHH N/PTCH1	0.001	0.12	-10000	0	-0.39	3	3
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
DHH	0.016	0	-10000	0	-10000	0	0
PTHLH	-0.15	0.47	-10000	0	-1.1	103	103
determination of left/right symmetry	-0.011	0.17	-10000	0	-0.65	9	9
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
skeletal system development	-0.15	0.46	-10000	0	-1.1	103	103
IHH N/Hhip	0.023	0.023	-10000	0	-10000	0	0
DHH N/Hhip	0	0.006	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.011	0.17	-10000	0	-0.65	9	9
pancreas development	0.015	0.012	-10000	0	-10000	0	0
HHAT	0.006	0.074	-10000	0	-0.72	5	5
PI3K	-0.052	0.16	-10000	0	-0.54	51	51
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.22	0.34	-10000	0	-0.72	166	166
somite specification	-0.011	0.17	-10000	0	-0.65	9	9
SHH Np/Cholesterol/PTCH1	0.008	0.12	-10000	0	-0.6	1	1
SHH Np/Cholesterol/PTCH2	-0.005	0.041	-10000	0	-0.42	5	5
SHH Np/Cholesterol/Megalin	-0.12	0.2	-10000	0	-0.43	149	149
SHH	0.022	0.057	-10000	0	-0.54	5	5
catabolic process	-0.009	0.14	-10000	0	-0.4	6	6
SMO/Vitamin D3	0.004	0.14	-10000	0	-0.52	9	9
SHH Np/Cholesterol/Hhip	-0.004	0.041	-10000	0	-0.42	5	5
LRP2	-0.19	0.33	-10000	0	-0.72	147	147
receptor-mediated endocytosis	-0.12	0.17	-10000	0	-0.54	42	42
SHH Np/Cholesterol/BOC	-0.098	0.18	-10000	0	-0.43	121	121
SHH Np/Cholesterol/CDO	-0.007	0.057	-10000	0	-0.48	7	7
mesenchymal cell differentiation	0.004	0.041	0.42	5	-10000	0	5
mol:Vitamin D3	0.012	0.12	-10000	0	-0.6	1	1
IHH N/PTCH2	0.023	0.022	-10000	0	-10000	0	0
CDON	0.012	0.056	-10000	0	-0.72	3	3
IHH N/PTCH1	-0.007	0.14	-10000	0	-0.4	6	6
Megalin/LRPAP1	-0.15	0.24	-10000	0	-0.54	147	147
PTCH2	0.016	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.003	0.043	-10000	0	-0.43	5	5
PTCH1	-0.009	0.14	-10000	0	-0.4	6	6
HHIP	0.015	0.012	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.078	0.11	0.48	3	-10000	0	3
GNAI2	0.016	0.007	-10000	0	-10000	0	0
S1P/S1P5/G12	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.016	0	-10000	0	-10000	0	0
RhoA/GTP	-0.08	0.11	-10000	0	-0.49	3	3
negative regulation of cAMP metabolic process	-0.067	0.14	-10000	0	-0.25	193	193
GNAZ	0.008	0.078	-10000	0	-0.72	6	6
GNAI3	0.016	0	-10000	0	-10000	0	0
GNA12	0.016	0	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.068	0.14	-10000	0	-0.25	193	193
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
GNAI1	-0.25	0.35	-10000	0	-0.72	189	189

×

TCGA08_retinoblastoma

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
CDKN2B	0.007	0.061	-10000	0	-0.69	3	3
CDKN2C	-0.043	0.2	-10000	0	-0.7	44	44
CDKN2A	-0.008	0.066	-10000	0	-10000	0	0
CCND2	0.016	0.059	0.2	42	-0.17	7	49
RB1	-0.018	0.063	0.18	3	-0.22	42	45
CDK4	0.021	0.066	0.23	45	-10000	0	45
CDK6	0.017	0.067	0.22	42	-0.26	4	46
G1/S progression	0.002	0.068	0.22	42	-0.18	3	45

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.009	0.034	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.25	0.18	-9999	-0.45	48	48
Syndecan-3/Neurocan	-0.004	0.073	-9999	-0.66	6	6
POMC	0.012	0.038	-9999	-0.72	1	1
EGFR	-0.38	0.37	-9999	-0.72	277	277
Syndecan-3/EGFR	-0.21	0.21	-9999	-0.4	278	278
AGRP	0.016	0.01	-9999	-10000	0	0
NCSTN	0.016	0	-9999	-10000	0	0
PSENEN	0.014	0.019	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.015	0.033	-9999	-0.72	1	1
APH1A	0.01	0.032	-9999	-10000	0	0
NCAN	0.01	0.03	-9999	-10000	0	0
long-term memory	-0.003	0.072	-9999	-0.55	8	8
Syndecan-3/IL8	0.003	0.079	-9999	-0.63	7	7
PSEN1	0.016	0	-9999	-10000	0	0
Src/Cortactin	-0.004	0.016	-9999	-10000	0	0
FYN	0.013	0.045	-9999	-0.72	2	2
limb bud formation	-0.007	0.073	-9999	-0.69	6	6
MC4R	0.015	0.012	-9999	-10000	0	0
SRC	0.016	0.007	-9999	-10000	0	0
PTN	-0.51	0.34	-9999	-0.72	373	373
FGFR/FGF/Syndecan-3	-0.008	0.074	-9999	-0.7	6	6
neuron projection morphogenesis	-0.24	0.17	-9999	-0.46	40	40
Syndecan-3/AgRP	-0.006	0.071	-9999	-0.66	6	6
Syndecan-3/AgRP/MC4R	-0.005	0.069	-9999	-0.64	6	6
Fyn/Cortactin	-0.006	0.037	-9999	-0.54	2	2
SDC3	-0.008	0.075	-9999	-0.71	6	6
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.003	0.077	-9999	-0.62	7	7
IL8	-0.006	0.063	-9999	-0.72	1	1
Syndecan-3/Fyn/Cortactin	-0.003	0.074	-9999	-0.57	8	8
Syndecan-3/CASK	-0.007	0.072	-9999	-0.67	6	6
alpha-MSH/MC4R	-0.003	0.026	-9999	-0.54	1	1
Gamma Secretase	0.004	0.027	-9999	-0.38	1	1

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.059	0.094	-10000	0	-0.31	5	5
NT3 (dimer)/TRKC	-0.17	0.26	-10000	0	-0.55	161	161
NT3 (dimer)/TRKB	-0.42	0.39	-10000	0	-0.67	329	329
SHC/Grb2/SOS1/GAB1/PI3K	0.015	0.1	-10000	0	-0.3	4	4
RAPGEF1	0.016	0	-10000	0	-10000	0	0
BDNF	0.006	0.057	-10000	0	-0.72	2	2
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
DYNLT1	0.016	0	-10000	0	-10000	0	0
NTRK1	0.014	0.019	-10000	0	-10000	0	0
NTRK2	-0.34	0.37	-10000	0	-0.72	252	252
NTRK3	-0.006	0.13	-10000	0	-0.72	16	16
NT-4/5 (dimer)/TRKB	-0.3	0.32	-10000	0	-0.58	274	274
neuron apoptosis	0.18	0.23	0.54	124	-10000	0	124
SHC 2-3/Grb2	-0.2	0.26	-10000	0	-0.6	124	124
SHC1	0.016	0	-10000	0	-10000	0	0
SHC2	-0.2	0.27	-10000	0	-0.63	121	121
SHC3	-0.17	0.24	-10000	0	-0.6	105	105
STAT3 (dimer)	0.019	0.059	-10000	0	-0.36	12	12
NT3 (dimer)/TRKA	-0.21	0.27	-10000	0	-0.51	216	216
RIN/GDP	-0.002	0.099	-10000	0	-0.26	5	5
GIPC1	0.015	0.012	-10000	0	-10000	0	0
KRAS	0.012	0.025	-10000	0	-10000	0	0
DNAJA3	-0.09	0.18	-10000	0	-0.44	94	94
RIN/GTP	-0.001	0.024	-10000	0	-0.55	1	1
CCND1	-0.001	0.15	-10000	0	-0.94	12	12
MAGED1	0.006	0.04	-10000	0	-10000	0	0
PTPN11	0.016	0	-10000	0	-10000	0	0
RICS	0.012	0.026	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.002	0.011	-10000	0	-10000	0	0
GRB2	0.013	0.022	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.003	0.015	-10000	0	-10000	0	0
TRKA/NEDD4-2	-0.017	0.09	-10000	0	-0.54	15	15
ELMO1	0.016	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	-0.004	0.041	-10000	0	-0.47	4	4
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.015	0.012	-10000	0	-10000	0	0
DOCK1	0.011	0.064	-10000	0	-0.72	4	4
GAB2	0.015	0.016	-10000	0	-10000	0	0
RIT2	0.015	0.032	-10000	0	-0.72	1	1
RIT1	0.016	0	-10000	0	-10000	0	0
FRS2	0.011	0.039	-10000	0	-0.72	1	1
DNM1	0.016	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.015	0.032	-10000	0	-0.72	1	1
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.087	0.18	-10000	0	-0.43	94	94
mol:GDP	-0.017	0.14	-10000	0	-0.37	10	10
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0	0	-10000	0	-10000	0	0
RIT1/GDP	-0.002	0.098	-10000	0	-0.24	8	8
TIAM1	0.015	0.012	-10000	0	-10000	0	0
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
BDNF (dimer)/TRKB	-0.22	0.23	-10000	0	-0.46	254	254
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0.006	-10000	0	-10000	0	0
FRS2 family/SHP2	0.001	0.023	-10000	0	-0.46	1	1
SHC/GRB2/SOS1/GAB1	0.001	0.022	-10000	0	-0.41	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.2	0.33	-10000	0	-0.72	150	150
RAP1/GDP	-0.035	0.057	-10000	0	-0.23	3	3
KIDINS220/CRKL	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)	0.006	0.057	-10000	0	-0.72	2	2
ubiquitin-dependent protein catabolic process	-0.012	0.078	-10000	0	-0.47	15	15
Schwann cell development	-0.044	0.037	-10000	0	-10000	0	0
EHD4	0.016	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.003	0.025	-10000	0	-0.41	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.05	0.018	-10000	0	-10000	0	0
RAP1B	0.016	0.01	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.27	0.26	-10000	0	-0.68	110	110
ABL1	0.016	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	-0.001	0.011	-10000	0	-10000	0	0
Rap1/GTP	-0.07	0.075	-10000	0	-10000	0	0
STAT3	0.02	0.059	-10000	0	-0.36	12	12
axon guidance	-0.26	0.25	-10000	0	-0.64	110	110
MAPK3	0.029	0.016	-10000	0	-10000	0	0
MAPK1	0.029	0.016	-10000	0	-10000	0	0
CDC42/GDP	-0.002	0.098	-10000	0	-0.26	4	4
NTF3	-0.2	0.33	-10000	0	-0.72	150	150
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.001	0.009	-10000	0	-10000	0	0
PI3K	-0.052	0.16	-10000	0	-0.54	51	51
FRS3	0.016	0	-10000	0	-10000	0	0
FAIM	0.016	0.007	-10000	0	-10000	0	0
GAB1	0.014	0.034	-10000	0	-0.72	1	1
RASGRF1	-0.092	0.18	-10000	0	-0.44	96	96
SOS1	0.016	0	-10000	0	-10000	0	0
MCF2L	-0.12	0.24	-10000	0	-0.47	161	161
RGS19	0.012	0.027	-10000	0	-10000	0	0
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	0.037	0.07	-10000	0	-10000	0	0
Rac1/GDP	-0.002	0.098	-10000	0	-0.24	8	8
NGF (dimer)/TRKA/GRIT	0.003	0.014	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.053	0.19	-10000	0	-0.42	89	89
NGF (dimer)/TRKA/NEDD4-2	-0.012	0.079	-10000	0	-0.47	15	15
MAP2K1	0.048	0.022	-10000	0	-0.38	1	1
NGFR	-0.12	0.28	-10000	0	-0.72	94	94
NGF (dimer)/TRKA/GIPC/GAIP	0.039	0.003	-10000	0	-10000	0	0
RAS family/GTP/PI3K	0.007	0.099	-10000	0	-0.3	51	51
FRS2 family/SHP2/GRB2/SOS1	0.003	0.024	-10000	0	-0.38	1	1
NRAS	0.014	0.019	-10000	0	-10000	0	0
GRB2/SOS1	-0.001	0.011	-10000	0	-10000	0	0
PRKCI	0.013	0.022	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.042	0.047	-10000	0	-10000	0	0
RASA1	0.015	0.012	-10000	0	-10000	0	0
TRKA/c-Abl	-0.001	0.009	-10000	0	-10000	0	0
SQSTM1	0.016	0.007	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.2	0.21	-10000	0	-0.41	254	254
NGF (dimer)/TRKA/p62/Atypical PKCs	0.002	0.013	-10000	0	-10000	0	0
MATK	0.011	0.029	-10000	0	-10000	0	0
NEDD4L	-0.005	0.12	-10000	0	-0.72	15	15
RAS family/GDP	-0.033	0.053	-10000	0	-0.22	1	1
NGF (dimer)/TRKA	-0.097	0.2	-10000	0	-0.47	94	94
Rac1/GTP	-0.073	0.1	-10000	0	-0.34	40	40
FRS2 family/SHP2/CRK family	0	0.028	-10000	0	-0.41	2	2

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.08	0.11	-9999	-0.49	3	3
PLCG1	-0.054	0.13	-9999	-0.53	3	3
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.016	0.007	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	-0.001	0.007	-9999	-10000	0	0
cell migration	-0.078	0.11	-9999	-0.48	3	3
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
MAPK3	-0.054	0.13	-9999	-0.51	3	3
MAPK1	-0.054	0.13	-9999	-0.22	193	193
S1P/S1P5/Gi	-0.068	0.14	-9999	-0.25	193	193
GNAI1	-0.25	0.35	-9999	-0.72	189	189
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	0	0	-9999	-10000	0	0
RHOA	0.03	0.006	-9999	-10000	0	0
S1P/S1P4/Gi	-0.068	0.14	-9999	-0.25	193	193
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.008	0.078	-9999	-0.72	6	6
S1P/S1P4/G12/G13	0.001	0.006	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.015	0.014	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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
PDGFRA	-0.074	0.24	-10000	0	-0.72	64	64
HRAS	0.015	0.012	-10000	0	-10000	0	0
EGFR	-0.38	0.37	-10000	0	-0.72	277	277
AKT	0.023	0.044	-10000	0	-0.26	2	2
FOXO3	0.016	0.007	-10000	0	-10000	0	0
AKT1	0.014	0.02	-10000	0	-10000	0	0
FOXO1	-0.085	0.25	-10000	0	-0.72	72	72
AKT3	0.014	0.017	-10000	0	-10000	0	0
FOXO4	0.016	0	-10000	0	-10000	0	0
MET	-0.057	0.22	-10000	0	-0.72	52	52
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
PIK3CB	0.016	0.01	-10000	0	-10000	0	0
NRAS	0.014	0.019	-10000	0	-10000	0	0
PIK3CG	0.013	0.023	-10000	0	-10000	0	0
PIK3R3	0.006	0.039	-10000	0	-10000	0	0
PIK3R2	0.014	0.019	-10000	0	-10000	0	0
NF1	0.016	0	-10000	0	-10000	0	0
RAS	-0.11	0.15	-10000	0	-0.38	87	87
ERBB2	-0.004	0.06	-10000	0	-0.72	1	1
proliferation/survival/translation	-0.009	0.073	0.23	22	-0.19	4	26
PI3K	-0.1	0.16	0.22	9	-0.31	142	151
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
KRAS	0.012	0.025	-10000	0	-10000	0	0
FOXO	0.028	0.04	0.2	5	-0.23	1	6
AKT2	0.016	0	-10000	0	-10000	0	0
PTEN	-0.002	0.12	-10000	0	-0.72	13	13

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.046	0.11	-9999	-0.47	20	20
EPHB2	0.006	0.04	-9999	-10000	0	0
Syndecan-2/TACI	0.012	0.093	-9999	-0.46	20	20
LAMA1	0.016	0.01	-9999	-10000	0	0
Syndecan-2/alpha2 ITGB1	-0.16	0.22	-9999	-0.42	196	196
HRAS	0.015	0.012	-9999	-10000	0	0
Syndecan-2/CASK	-0.018	0.089	-9999	-0.47	20	20
ITGA5	0.016	0.007	-9999	-10000	0	0
BAX	0.033	0.087	-9999	-10000	0	0
EPB41	0.016	0.007	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.017	0.081	-9999	-0.42	21	21
LAMA3	-0.23	0.35	-9999	-0.72	176	176
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.46	0.35	-9999	-0.72	338	338
Syndecan-2/MMP2	0.008	0.12	-9999	-0.54	21	21
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.02	0.1	-9999	-0.54	19	19
dendrite morphogenesis	0.015	0.094	-9999	-0.45	20	20
Syndecan-2/GM-CSF	0.013	0.096	-9999	-0.46	20	20
determination of left/right symmetry	0.003	0.11	-9999	-0.54	20	20
Syndecan-2/PKC delta	0.012	0.094	-9999	-0.46	20	20
GNB2L1	0.016	0	-9999	-10000	0	0
MAPK3	0.021	0.088	-9999	-0.41	20	20
MAPK1	0.021	0.088	-9999	-0.41	20	20
Syndecan-2/RACK1	-0.015	0.075	-9999	-0.39	20	20
NF1	0.016	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.003	0.11	-9999	-0.54	20	20
ITGA2	-0.011	0.14	-9999	-0.72	19	19
MAPK8	0.024	0.097	-9999	-0.45	21	21
Syndecan-2/alpha2/beta1 Integrin	-0.027	0.11	-9999	-0.43	35	35
Syndecan-2/Kininogen	0.012	0.093	-9999	-0.46	20	20
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.031	0.078	-9999	-0.36	20	20
Syndecan-2/CASK/Protein 4.1	-0.016	0.08	-9999	-0.42	20	20
extracellular matrix organization	0.012	0.093	-9999	-0.45	20	20
actin cytoskeleton reorganization	0.046	0.11	-9999	-0.46	20	20
Syndecan-2/Caveolin-2/Ras	-0.28	0.22	-9999	-0.44	338	338
Syndecan-2/Laminin alpha3	-0.15	0.25	-9999	-0.48	189	189
Syndecan-2/RasGAP	-0.013	0.071	-9999	-0.36	20	20
alpha5/beta1 Integrin	0	0.003	-9999	-10000	0	0
PRKCD	0.014	0.019	-9999	-10000	0	0
Syndecan-2 dimer	0.015	0.095	-9999	-0.46	20	20
GO:0007205	0.004	0.002	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.04	0.077	-9999	-0.35	20	20
RHOA	0.016	0	-9999	-10000	0	0
SDCBP	0.015	0.032	-9999	-0.72	1	1
TNFRSF13B	0.016	0.01	-9999	-10000	0	0
RASA1	0.015	0.012	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.02	0.1	-9999	-0.54	19	19
Syndecan-2/Synbindin	0.012	0.093	-9999	-0.46	20	20
TGFB1	0.016	0.01	-9999	-10000	0	0
CASP3	0.023	0.087	-9999	-0.41	20	20
FN1	-0.098	0.074	-9999	-10000	0	0
Syndecan-2/IL8	0.017	0.1	-9999	-0.46	21	21
SDC2	0.003	0.11	-9999	-0.54	20	20
KNG1	0.016	0.007	-9999	-10000	0	0
Syndecan-2/Neurofibromin	0.012	0.093	-9999	-0.46	20	20
TRAPPC4	0.016	0	-9999	-10000	0	0
CSF2	0.01	0.03	-9999	-10000	0	0
Syndecan-2/TGFB1	0.012	0.093	-9999	-0.46	20	20
Syndecan-2/Syntenin/PI-4-5-P2	-0.017	0.082	-9999	-0.42	21	21
Syndecan-2/Ezrin	-0.016	0.08	-9999	-0.42	20	20
PRKACA	0.024	0.086	-9999	-0.41	20	20
angiogenesis	0.017	0.099	-9999	-0.46	21	21
MMP2	0.009	0.072	-9999	-0.72	5	5
IL8	-0.006	0.063	-9999	-0.72	1	1
calcineurin-NFAT signaling pathway	0.012	0.093	-9999	-0.45	20	20

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.003	0.037	-9999	-0.34	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.026	-9999	-0.31	1	1
AP1	-0.34	0.25	-9999	-0.47	376	376
mol:PIP3	-0.21	0.2	-9999	-0.38	294	294
AKT1	0.028	0.1	-9999	-0.39	5	5
PTK2B	0.024	0.023	-9999	-0.2	5	5
RHOA	0.027	0.025	-9999	-0.21	3	3
PIK3CB	0.015	0.01	-9999	-10000	0	0
mol:Ca2+	0.032	0.027	-9999	-0.37	1	1
MAGI3	0.003	0.066	-9999	-0.72	3	3
RELA	0.016	0	-9999	-10000	0	0
apoptosis	0.018	0.027	-9999	-0.25	5	5
HRAS/GDP	-0.001	0.007	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.038	0.036	-9999	-0.34	3	3
NF kappa B1 p50/RelA	-0.003	0.024	-9999	-0.29	2	2
endothelial cell migration	0.017	0.081	-9999	-0.81	5	5
ADCY4	-0.038	0.12	-9999	-0.4	11	11
ADCY5	-0.036	0.12	-9999	-0.42	8	8
ADCY6	-0.036	0.12	-9999	-0.42	8	8
ADCY7	-0.036	0.12	-9999	-0.42	8	8
ADCY1	-0.036	0.12	-9999	-0.42	8	8
ADCY2	-0.039	0.12	-9999	-0.41	12	12
ADCY3	-0.036	0.12	-9999	-0.42	8	8
ADCY8	-0.036	0.12	-9999	-0.42	8	8
ADCY9	-0.036	0.12	-9999	-0.42	8	8
GSK3B	0.032	0.022	-9999	-0.21	1	1
arachidonic acid secretion	-0.024	0.11	-9999	-0.42	7	7
GNG2	0.015	0.032	-9999	-0.72	1	1
TRIP6	0.024	0.023	-9999	-0.48	1	1
GNAO1	0.022	0.032	-9999	-0.3	5	5
HRAS	0.015	0.012	-9999	-10000	0	0
NFKBIA	0.044	0.033	-9999	-0.32	2	2
GAB1	0.014	0.034	-9999	-0.72	1	1
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.003	0.009	-9999	-10000	0	0
JUN	-0.12	0.29	-9999	-0.72	97	97
LPA/LPA2/NHERF2	-0.002	0.023	-9999	-0.47	1	1
TIAM1	0.003	0.008	-9999	-10000	0	0
PIK3R1	-0.056	0.22	-9999	-0.72	51	51
mol:IP3	0.033	0.028	-9999	-0.38	1	1
PLCB3	0.025	0.023	-9999	-0.42	1	1
FOS	-0.51	0.34	-9999	-0.72	374	374
positive regulation of mitosis	-0.024	0.11	-9999	-0.42	7	7
LPA/LPA1-2-3	-0.003	0.027	-9999	-0.28	5	5
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
stress fiber formation	0.031	0.024	-9999	-0.2	5	5
GNAZ	0.016	0.061	-9999	-0.39	11	11
EGFR/PI3K-beta/Gab1	-0.22	0.22	-9999	-0.39	294	294
positive regulation of dendritic cell cytokine production	-0.003	0.027	-9999	-0.28	5	5
LPA/LPA2/MAGI-3	-0.007	0.04	-9999	-0.47	3	3
ARHGEF1	0.038	0.028	-9999	-10000	0	0
GNAI2	0.022	0.032	-9999	-0.3	5	5
GNAI3	0.022	0.032	-9999	-0.3	5	5
GNAI1	-0.16	0.24	-9999	-0.47	190	190
LPA/LPA3	-0.001	0.013	-9999	-0.13	5	5
LPA/LPA2	-0.001	0.013	-9999	-0.13	5	5
LPA/LPA1	-0.004	0.036	-9999	-0.36	5	5
HB-EGF/EGFR	-0.26	0.25	-9999	-0.49	277	277
HBEGF	-0.024	0.07	-9999	-0.54	4	4
mol:DAG	0.033	0.028	-9999	-0.38	1	1
cAMP biosynthetic process	-0.03	0.12	-9999	-0.42	8	8
NFKB1	0.016	0	-9999	-10000	0	0
SRC	0.016	0.007	-9999	-10000	0	0
GNB1	0.015	0.01	-9999	-10000	0	0
LYN	0.045	0.027	-9999	-0.27	1	1
GNAQ	0.004	0.011	-9999	-0.1	5	5
LPAR2	0	0	-9999	-10000	0	0
LPAR3	0	0	-9999	-10000	0	0
LPAR1	0.004	0.021	-9999	-0.2	5	5
IL8	-0.27	0.18	-9999	-0.4	318	318
PTK2	0.02	0.027	-9999	-0.25	5	5
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	0.018	0.027	-9999	-0.26	5	5
EGFR	-0.38	0.37	-9999	-0.72	277	277
PLCG1	0.018	0.021	-9999	-0.15	6	6
PLD2	0.019	0.032	-9999	-0.28	6	6
G12/G13	-0.002	0.026	-9999	-0.26	5	5
PI3K-beta	-0.033	0.097	-9999	-0.32	51	51
cell migration	0.004	0.016	-9999	-10000	0	0
SLC9A3R2	0.014	0.034	-9999	-0.72	1	1
PXN	0.031	0.024	-9999	-0.21	5	5
HRAS/GTP	-0.059	0.085	-9999	-0.43	7	7
RAC1	0.016	0	-9999	-10000	0	0
MMP9	-0.059	0.081	-9999	-10000	0	0
PRKCE	0.016	0	-9999	-10000	0	0
PRKCD	0.04	0.028	-9999	-0.35	1	1
Gi(beta/gamma)	-0.031	0.12	-9999	-0.48	7	7
mol:LPA	0.004	0.021	-9999	-0.2	5	5
TRIP6/p130 Cas/FAK1/Paxillin	-0.001	0.023	-9999	-10000	0	0
MAPKKK cascade	-0.024	0.11	-9999	-0.42	7	7
contractile ring contraction involved in cytokinesis	0.027	0.025	-9999	-0.21	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNA14	0.004	0.048	-9999	-0.37	7	7
GNA15	0.013	0.012	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.015	0.014	-9999	-10000	0	0
MAPT	0.038	0.037	-9999	-0.36	3	3
GNA11	0.014	0.011	-9999	-10000	0	0
Rac1/GTP	0.004	0.011	-9999	-10000	0	0
MMP2	0.017	0.082	-9999	-0.82	5	5

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
mol:S1P	0.002	0.001	-9999	-10000	0	0
S1P1/S1P/Gi	-0.15	0.22	-9999	-0.35	259	259
GNAO1	0.018	0.001	-9999	-10000	0	0
S1P/S1P3/G12/G13	0.025	0.005	-9999	-10000	0	0
AKT1	-0.022	0.042	-9999	-10000	0	0
AKT3	0.005	0.08	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
GNAI2	0.018	0.007	-9999	-10000	0	0
GNAI3	0.018	0	-9999	-10000	0	0
GNAI1	-0.25	0.36	-9999	-0.72	189	189
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.002	0.001	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	-0.19	0.33	-9999	-0.72	147	147
mol:Ca2+	-0.054	0.14	-9999	-0.23	193	193
MAPK3	-0.041	0.13	-9999	-0.62	2	2
MAPK1	-0.041	0.13	-9999	-0.62	2	2
JAK2	-0.038	0.13	-9999	-0.52	3	3
CXCR4	-0.046	0.13	-9999	-0.33	12	12
FLT1	0.019	0.01	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	-0.041	0.13	-9999	-0.62	2	2
S1P/S1P3/Gi	-0.054	0.14	-9999	-0.24	193	193
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.075	0.1	-9999	-0.6	2	2
VEGFA	-0.001	0.054	-9999	-10000	0	0
S1P/S1P2/Gi	-0.059	0.14	-9999	-0.24	193	193
VEGFR1 homodimer/VEGFA homodimer	0.041	0.02	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.021	0.036	-9999	-0.31	6	6
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.01	0.078	-9999	-0.72	6	6
G12/G13	-0.001	0.007	-9999	-10000	0	0
GNA14	-0.008	0.09	-9999	-0.72	6	6
GNA15	0.014	0.02	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.015	0.014	-9999	-10000	0	0
GNA11	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.075	0.1	-9999	-0.6	2	2

×

Regulation of nuclear SMAD2/3 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.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.019	0.011	-10000	0	-10000	0	0
HSPA8	0.016	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.13	0.23	0.3	1	-0.52	121	122
AKT1	0.017	0.02	-10000	0	-10000	0	0
GSC	-0.097	0.43	-10000	0	-1.5	46	46
NKX2-5	-0.003	0.057	-10000	0	-10000	0	0
muscle cell differentiation	0.035	0.11	0.45	22	-10000	0	22
SMAD2-3/SMAD4/SP1	0.026	0.094	-10000	0	-0.45	6	6
SMAD4	-0.013	0.082	-10000	0	-0.38	11	11
CBFB	0.016	0.01	-10000	0	-10000	0	0
SAP18	0.016	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.26	0.23	-10000	0	-0.46	302	302
SMAD3/SMAD4/VDR	0	0.065	-10000	0	-0.45	6	6
MYC	-0.028	0.17	-10000	0	-0.73	29	29
CDKN2B	0.023	0.13	-10000	0	-1.5	3	3
AP1	-0.35	0.39	-10000	0	-0.73	185	185
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.065	0.04	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.016	0.11	-10000	0	-0.33	19	19
SP3	0.019	0.005	-10000	0	-10000	0	0
CREB1	0.016	0	-10000	0	-10000	0	0
FOXH1	0.01	0.035	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	-0.058	0.17	-10000	0	-0.55	49	49
GATA3	-0.067	0.19	-10000	0	-0.7	38	38
SKI/SIN3/HDAC complex/NCoR1	0.056	0.021	-10000	0	-10000	0	0
MEF2C/TIF2	-0.012	0.2	-10000	0	-0.71	34	34
endothelial cell migration	-0.032	0.047	-10000	0	-10000	0	0
MAX	0.014	0.002	-10000	0	-10000	0	0
RBBP7	0.012	0.026	-10000	0	-10000	0	0
RBBP4	0.016	0.007	-10000	0	-10000	0	0
RUNX2	0.013	0.022	-10000	0	-10000	0	0
RUNX3	-0.045	0.2	-10000	0	-0.72	42	42
RUNX1	-0.006	0.12	-10000	0	-0.72	15	15
CTBP1	0.016	0.007	-10000	0	-10000	0	0
NR3C1	-0.051	0.21	-10000	0	-0.73	46	46
VDR	0.013	0.046	-10000	0	-0.72	2	2
CDKN1A	0.033	0.11	-10000	0	-1.4	2	2
KAT2B	0	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.019	0.1	-10000	0	-0.39	18	18
DCP1A	0.016	0	-10000	0	-10000	0	0
SKI	0.016	0.007	-10000	0	-10000	0	0
SERPINE1	0.03	0.048	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	-0.013	0.067	-10000	0	-0.46	5	5
SMAD3/SMAD4/ATF3	-0.18	0.25	-10000	0	-0.52	175	175
SAP30	0.016	0.007	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.01	0.039	-10000	0	-0.42	1	1
JUN	-0.34	0.38	-10000	0	-0.76	170	170
SMAD3/SMAD4/IRF7	-0.011	0.068	-10000	0	-0.45	5	5
TFE3	0.015	0.036	-10000	0	-10000	0	0
COL1A2	0.043	0.12	-10000	0	-1.1	3	3
mesenchymal cell differentiation	0.014	0.068	0.46	5	-10000	0	5
DLX1	0.006	0.04	-10000	0	-10000	0	0
TCF3	0.014	0.019	-10000	0	-10000	0	0
FOS	-0.52	0.35	-10000	0	-0.74	374	374
SMAD3/SMAD4/Max	-0.015	0.067	-10000	0	-0.46	5	5
Cbp/p300/SNIP1	0.004	0.026	-10000	0	-0.44	1	1
ZBTB17	0.014	0.005	-10000	0	-10000	0	0
LAMC1	-0.009	0.21	-10000	0	-0.75	37	37
TGIF2/HDAC complex/SMAD3/SMAD4	-0.014	0.067	-10000	0	-0.46	5	5
IRF7	0.018	0.023	-10000	0	-10000	0	0
ESR1	-0.18	0.3	-10000	0	-0.73	117	117
HNF4A	0.016	0	-10000	0	-10000	0	0
MEF2C	-0.004	0.21	-10000	0	-0.76	34	34
SMAD2-3/SMAD4	-0.02	0.081	-10000	0	-0.41	10	10
Cbp/p300/Src-1	0.006	0.036	-10000	0	-0.44	2	2
IGHV3OR16-13	-0.011	0.032	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.016	0.01	-10000	0	-10000	0	0
CREBBP	0.016	0.032	-10000	0	-0.7	1	1
SKIL	-0.001	0.049	-10000	0	-10000	0	0
HDAC1	0.016	0.001	-10000	0	-10000	0	0
HDAC2	0.014	0.017	-10000	0	-10000	0	0
SNIP1	0.015	0.004	-10000	0	-10000	0	0
GCN5L2	0.018	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.02	0.1	-10000	0	-0.4	29	29
MSG1/HSC70	-0.31	0.27	-10000	0	-0.54	302	302
SMAD2	0.014	0.035	-10000	0	-10000	0	0
SMAD3	-0.003	0.058	-10000	0	-0.78	1	1
SMAD3/E2F4-5/DP1/p107/SMAD4	0.016	0.055	-10000	0	-0.35	3	3
SMAD2/SMAD2/SMAD4	0.011	0.041	-10000	0	-0.42	2	2
NCOR1	0.015	0.032	-10000	0	-0.72	1	1
NCOA2	0.015	0.014	-10000	0	-10000	0	0
NCOA1	0.015	0.032	-10000	0	-0.72	1	1
MYOD/E2A	-0.004	0.035	-10000	0	-0.54	2	2
SMAD2-3/SMAD4/SP1/MIZ-1	0.045	0.089	-10000	0	-0.41	6	6
IFNB1	0.026	0.073	-10000	0	-0.46	3	3
SMAD3/SMAD4/MEF2C	-0.027	0.21	-10000	0	-0.75	35	35
CITED1	-0.41	0.36	-10000	0	-0.72	302	302
SMAD2-3/SMAD4/ARC105	-0.013	0.071	-10000	0	-0.42	6	6
RBL1	0.007	0.037	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.023	0.12	-10000	0	-0.38	15	15
RUNX1-3/PEBPB2	-0.048	0.15	-10000	0	-0.48	55	55
SMAD7	-0.18	0.24	-10000	0	-0.54	115	115
MYC/MIZ-1	-0.029	0.13	-10000	0	-0.55	29	29
SMAD3/SMAD4	0.03	0.076	0.28	20	-10000	0	20
IL10	-0.013	0.14	-10000	0	-0.47	38	38
PIASy/HDAC complex	0.014	0.016	-10000	0	-10000	0	0
PIAS3	0.017	0.003	-10000	0	-10000	0	0
CDK2	0.015	0.024	-10000	0	-10000	0	0
IL5	-0.013	0.14	-10000	0	-0.46	38	38
CDK4	0.017	0.018	-10000	0	-10000	0	0
PIAS4	0.014	0.016	-10000	0	-10000	0	0
ATF3	-0.22	0.34	-10000	0	-0.72	170	170
SMAD3/SMAD4/SP1	-0.006	0.073	-10000	0	-0.47	6	6
FOXG1	0.004	0.041	-10000	0	-10000	0	0
FOXO3	0.033	0.015	-10000	0	-10000	0	0
FOXO1	-0.045	0.2	-10000	0	-0.54	72	72
FOXO4	0.033	0.015	-10000	0	-10000	0	0
heart looping	-0.003	0.21	-10000	0	-0.74	34	34
CEBPB	0.016	0.033	-10000	0	-0.72	1	1
SMAD3/SMAD4/DLX1	-0.016	0.072	-10000	0	-0.48	5	5
MYOD1	0.011	0.049	-10000	0	-0.72	2	2
SMAD3/SMAD4/HNF4	-0.013	0.067	-10000	0	-0.46	5	5
SMAD3/SMAD4/GATA3	-0.028	0.16	-10000	0	-0.53	40	40
SnoN/SIN3/HDAC complex/NCoR1	-0.001	0.049	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.046	0.15	-10000	0	-0.45	58	58
SMAD3/SMAD4/SP1-3	0.002	0.071	-10000	0	-0.46	6	6
MED15	0.016	0	-10000	0	-10000	0	0
SP1	0.026	0.014	-10000	0	-10000	0	0
SIN3B	0.015	0.016	-10000	0	-10000	0	0
SIN3A	0.016	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.014	0.13	-10000	0	-0.42	30	30
ITGB5	0.045	0.093	-10000	0	-0.68	5	5
TGIF/SIN3/HDAC complex/CtBP	0.059	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.079	0.19	-10000	0	-0.53	71	71
AR	-0.082	0.25	-10000	0	-0.72	69	69
negative regulation of cell growth	-0.041	0.12	-10000	0	-0.42	9	9
SMAD3/SMAD4/MYOD	-0.016	0.073	-10000	0	-0.47	7	7
E2F5	-0.002	0.051	-10000	0	-10000	0	0
E2F4	0.016	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.006	0.075	-10000	0	-0.37	8	8
SMAD2-3/SMAD4/FOXO1-3a-4	0.017	0.12	-10000	0	-0.34	21	21
TFDP1	0.012	0.027	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.35	0.4	-10000	0	-0.77	174	174
SMAD3/SMAD4/RUNX2	-0.014	0.068	-10000	0	-0.46	5	5
TGIF2	0.016	0.01	-10000	0	-10000	0	0
TGIF1	0.015	0.032	-10000	0	-0.72	1	1
ATF2	0.016	0	-10000	0	-10000	0	0

×

Ceramide signaling 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
SPHK2	-0.026	0.17	-10000	0	-0.54	51	51
MAP4K4	0.044	0.066	-10000	0	-10000	0	0
BAG4	0.011	0.029	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.03	0.073	0.16	36	-10000	0	36
NFKBIA	0.015	0.032	-10000	0	-0.72	1	1
BIRC3	-0.038	0.18	-10000	0	-0.72	35	35
BAX	-0.003	0.039	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AKT1	0.028	0.024	-10000	0	-10000	0	0
BAD	-0.018	0.076	0.19	36	-10000	0	36
SMPD1	0.032	0.027	-10000	0	-0.23	1	1
RB1	-0.019	0.078	0.19	35	-0.3	2	37
FADD/Caspase 8	0.052	0.066	-10000	0	-10000	0	0
MAP2K4	-0.019	0.093	-10000	0	-0.42	11	11
NSMAF	0.012	0.056	-10000	0	-0.72	3	3
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.008	0.072	-10000	0	-10000	0	0
EGF	-0.24	0.35	-10000	0	-0.72	178	178
mol:ceramide	-0.03	0.082	0.2	36	-10000	0	36
MADD	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.034	0.19	-10000	0	-0.57	54	54
ASAH1	0.005	0.086	-10000	0	-0.72	7	7
negative regulation of cell cycle	-0.02	0.077	0.19	35	-0.3	2	37
cell proliferation	-0.17	0.16	-10000	0	-0.34	224	224
BID	0.031	0.052	-10000	0	-10000	0	0
MAP3K1	-0.024	0.085	0.19	35	-0.43	4	39
EIF2A	-0.003	0.071	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
MAPK3	0.007	0.068	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.007	0.068	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.026	0.076	0.18	36	-0.17	4	40
FADD	0.038	0.07	-10000	0	-10000	0	0
KSR1	-0.018	0.076	0.19	36	-10000	0	36
MAPK8	-0.015	0.08	0.18	35	-0.27	11	46
PRKRA	-0.018	0.076	0.19	36	-10000	0	36
PDGFA	-0.055	0.22	-10000	0	-0.72	51	51
TRAF2	0.015	0.012	-10000	0	-10000	0	0
IGF1	-0.35	0.37	-10000	0	-0.72	262	262
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.03	0.081	0.19	36	-10000	0	36
CTSD	0.001	0.047	-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	0.19	-10000	0	-0.37	224	224
PRKCD	0.014	0.019	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.034	0.19	-10000	0	-0.57	54	54
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.013	0.037	-10000	0	-0.72	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.036	0.069	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.004	0.019	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	-0.026	0.17	-10000	0	-0.54	51	51
MAP2K1	0.002	0.069	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
CYCS	0.026	0.087	0.2	66	-10000	0	66
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.003	0.014	-10000	0	-10000	0	0
EIF2AK2	-0.013	0.074	0.19	33	-10000	0	33
TNF-alpha/TNFR1A/FAN	0	0.037	-10000	0	-0.46	3	3
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.046	0.041	-10000	0	-10000	0	0
MAP2K2	0.002	0.069	-10000	0	-10000	0	0
SMPD3	0.035	0.03	-10000	0	-0.22	1	1
TNF	0.012	0.025	-10000	0	-10000	0	0
PKC zeta/PAR4	-0.002	0.026	-10000	0	-0.55	1	1
mol:PHOSPHOCHOLINE	0.098	0.14	0.26	214	-10000	0	214
NF kappa B1/RelA/I kappa B alpha	0	0.026	-10000	0	-0.39	2	2
AIFM1	0.026	0.087	0.2	66	-10000	0	66
BCL2	-0.13	0.29	-10000	0	-0.72	104	104

×

Reelin signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.003	0.016	-9999	-10000	0	0
VLDLR	-0.1	0.27	-9999	-0.72	83	83
CRKL	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
FYN	0.013	0.045	-9999	-0.72	2	2
ITGA3	0.013	0.046	-9999	-0.72	2	2
RELN/VLDLR/Fyn	-0.09	0.19	-9999	-0.48	100	100
MAPK8IP1/MKK7/MAP3K11/JNK1	0.002	0.022	-9999	-0.38	1	1
AKT1	-0.05	0.19	-9999	-0.34	133	133
MAP2K7	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
DAB1	0.016	0	-9999	-10000	0	0
RELN/LRP8/DAB1	0.004	0.095	-9999	-0.44	20	20
LRPAP1/LRP8	-0.022	0.035	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	0.005	0.093	-9999	-0.41	22	22
DAB1/alpha3/beta1 Integrin	-0.056	0.16	-9999	-0.46	30	30
long-term memory	0.001	0.11	-9999	-0.41	31	31
DAB1/LIS1	-0.053	0.17	-9999	-0.39	98	98
DAB1/CRLK/C3G	-0.054	0.16	-9999	-0.46	28	28
PIK3CA	0.016	0.007	-9999	-10000	0	0
DAB1/NCK2	-0.053	0.17	-9999	-0.39	98	98
ARHGEF2	0.012	0.026	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	0.016	0.007	-9999	-10000	0	0
CDK5R1	0.014	0.019	-9999	-10000	0	0
RELN	-0.013	0.14	-9999	-0.72	20	20
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
RELN/LRP8/Fyn	0.001	0.11	-9999	-0.48	22	22
GRIN2A/RELN/LRP8/DAB1/Fyn	0.008	0.094	-9999	-0.4	22	22
MAPK8	0.015	0.032	-9999	-0.72	1	1
RELN/VLDLR/DAB1	-0.082	0.18	-9999	-0.44	98	98
ITGB1	0.016	0	-9999	-10000	0	0
MAP1B	-0.087	0.22	-9999	-0.44	133	133
RELN/LRP8	0.003	0.1	-9999	-0.48	20	20
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.001	0.12	-9999	-0.43	31	31
PI3K	-0.052	0.16	-9999	-0.54	51	51
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.002	0.034	-9999	-0.54	2	2
RAP1A	-0.019	0.16	-9999	-0.42	28	28
PAFAH1B1	0.016	0	-9999	-10000	0	0
MAPK8IP1	0.016	0.007	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.002	0.11	-9999	-0.72	12	12
NCK2	0.016	0.01	-9999	-10000	0	0
neuron differentiation	0.044	0.049	-9999	-10000	0	0
neuron adhesion	-0.001	0.16	-9999	-0.63	6	6
LRP8	-0.029	0.072	-9999	-10000	0	0
GSK3B	-0.038	0.18	-9999	-0.64	23	23
RELN/VLDLR/DAB1/Fyn	-0.077	0.16	-9999	-0.41	100	100
MAP3K11	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.063	0.2	-9999	-0.37	133	133
CDK5	0.012	0.027	-9999	-10000	0	0
MAPT	0.014	0.06	-9999	-0.66	3	3
neuron migration	-0.018	0.18	-9999	-0.52	24	24
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.044	0.049	-9999	-10000	0	0
RELN/VLDLR	-0.063	0.19	-9999	-0.45	98	98

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0.013	-9999	-10000	0	0
VDR	0.013	0.046	-9999	-0.72	2	2
FAM120B	0.016	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.074	0.041	-9999	-10000	0	0
RXRs/LXRs/DNA/Oxysterols	0.084	0.043	-9999	-0.36	2	2
MED1	0.006	0.039	-9999	-10000	0	0
mol:9cRA	0.008	0.004	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.035	0.17	-9999	-0.32	117	117
RXRs/NUR77	0.034	0.11	-9999	-0.4	31	31
RXRs/PPAR	-0.19	0.16	-9999	-0.32	63	63
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.034	-9999	-0.55	2	2
RARs/VDR/DNA/Vit D3	-0.064	0.15	-9999	-0.39	86	86
RARA	0.015	0.016	-9999	-10000	0	0
NCOA1	0.015	0.032	-9999	-0.72	1	1
VDR/VDR/DNA	0.013	0.046	-9999	-0.72	2	2
RARs/RARs/DNA/9cRA	-0.063	0.15	-9999	-0.4	85	85
RARG	0.016	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.023	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.034	0.16	-9999	-0.32	117	117
THRA	-0.031	0.18	-9999	-0.72	33	33
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.034	-9999	-0.55	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	0.048	0.049	-9999	-0.4	5	5
NR1H4	0.016	0.01	-9999	-10000	0	0
RXRs/LXRs/DNA	0.08	0.049	-9999	-0.35	6	6
NR1H2	0.024	0.003	-9999	-10000	0	0
NR1H3	0.024	0.032	-9999	-0.71	1	1
RXRs/VDR/DNA/Vit D3	0.051	0.05	-9999	-0.38	7	7
NR4A1	-0.02	0.16	-9999	-0.72	26	26
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.049	0.029	-9999	-0.23	5	5
RXRG	0.016	0.072	-9999	-0.72	5	5
RXR alpha/CCPG	0.027	0.01	-9999	-10000	0	0
RXRA	0.024	0.003	-9999	-10000	0	0
RXRB	0.025	0.004	-9999	-10000	0	0
THRB	0.006	0.085	-9999	-0.72	7	7
PPARG	-0.53	0.32	-9999	-0.72	388	388
PPARD	0.016	0.01	-9999	-10000	0	0
TNF	0.089	0.041	-9999	-10000	0	0
mol:Oxysterols	0.008	0.004	-9999	-10000	0	0
cholesterol transport	0.084	0.043	-9999	-0.36	2	2
PPARA	0.015	0.032	-9999	-0.72	1	1
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.1	0.27	-9999	-0.72	85	85
RXRs/NUR77/BCL2	-0.04	0.16	-9999	-0.3	129	129
SREBF1	0.088	0.042	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	0.048	0.049	-9999	-0.4	5	5
ABCA1	0.087	0.082	-9999	-1.1	2	2
RARs/THRs	-0.09	0.18	-9999	-0.41	117	117
RXRs/FXR	0.057	0.045	-9999	-0.4	5	5
BCL2	-0.13	0.29	-9999	-0.72	104	104

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	0.032	0.16	-9999	-0.54	2	2
PCK1	-0.84	0.6	-9999	-1.2	400	400
HNF4A	0.042	0.16	-9999	-10000	0	0
KCNJ11	0.034	0.18	-9999	-0.6	2	2
AKT1	0.014	0.11	-9999	-0.33	3	3
response to starvation	0.008	0.002	-9999	-10000	0	0
DLK1	0.034	0.18	-9999	-0.6	2	2
NKX2-1	0.075	0.11	-9999	-10000	0	0
ACADM	0.024	0.2	-9999	-0.98	7	7
TAT	-0.023	0.2	-9999	-0.81	10	10
CEBPB	0.021	0.033	-9999	-0.72	1	1
CEBPA	0.02	0.056	-9999	-0.72	3	3
TTR	-0.035	0.24	-9999	-0.59	62	62
PKLR	0.032	0.16	-9999	-0.54	2	2
APOA1	0.041	0.19	-9999	-10000	0	0
CPT1C	0.032	0.16	-9999	-0.55	1	1
ALAS1	0.034	0.12	-9999	-10000	0	0
TFRC	-0.004	0.19	-9999	-10000	0	0
FOXF1	-0.002	0.018	-9999	-10000	0	0
NF1	0.026	0	-9999	-10000	0	0
HNF1A (dimer)	0.041	0.016	-9999	-10000	0	0
CPT1A	0.033	0.16	-9999	-0.54	2	2
HMGCS1	0.032	0.16	-9999	-0.54	2	2
NR3C1	-0.031	0.21	-9999	-0.71	46	46
CPT1B	0.032	0.16	-9999	-0.54	2	2
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.025	0.008	-9999	-10000	0	0
GCK	0.032	0.16	-9999	-0.54	2	2
CREB1	-0.16	0.11	-9999	-0.24	285	285
IGFBP1	0.008	0.15	-9999	-0.94	2	2
PDX1	0.043	0.14	-9999	-1.5	1	1
UCP2	0.033	0.16	-9999	-0.54	2	2
ALDOB	0.033	0.18	-9999	-0.6	2	2
AFP	-0.095	0.15	-9999	-0.43	69	69
BDH1	0.032	0.16	-9999	-0.54	2	2
HADH	0.029	0.2	-9999	-0.99	4	4
F2	0.041	0.19	-9999	-10000	0	0
HNF1A	0.041	0.016	-9999	-10000	0	0
G6PC	-0.083	0.11	-9999	-0.54	2	2
SLC2A2	0.04	0.15	-9999	-1.3	1	1
INS	0	0.009	-9999	-10000	0	0
FOXA1	-0.12	0.26	-9999	-0.71	80	80
FOXA3	-0.13	0.13	-9999	-0.38	39	39
FOXA2	0.038	0.23	-9999	-0.6	5	5
ABCC8	-0.1	0.43	-9999	-1	91	91
ALB	-0.098	0.16	-9999	-0.45	73	73

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.029	0.01	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.04	0.18	0.69	21	-0.51	1	22
IL27/IL27R/JAK1	-0.082	0.27	-10000	0	-1	26	26
TBX21	-0.059	0.24	-10000	0	-0.66	54	54
IL12B	0.013	0.024	-10000	0	-10000	0	0
IL12A	0.002	0.082	-10000	0	-0.55	11	11
IL6ST	-0.02	0.15	-10000	0	-0.73	21	21
IL27RA/JAK1	-0.029	0.25	-10000	0	-1.3	19	19
IL27	-0.067	0.23	-10000	0	-0.73	58	58
TYK2	0.014	0.008	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.22	0.15	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.04	0.18	0.69	21	-0.51	1	22
T cell proliferation during immune response	0.04	0.18	0.69	21	-0.51	1	22
MAPKKK cascade	-0.04	0.18	0.51	1	-0.69	21	22
STAT3	0.016	0	-10000	0	-10000	0	0
STAT2	0.016	0	-10000	0	-10000	0	0
STAT1	-0.011	0.061	-10000	0	-10000	0	0
IL12RB1	0.017	0.001	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.047	0.21	-10000	0	-0.62	39	39
IL27/IL27R/JAK2/TYK2	-0.041	0.18	0.51	1	-0.7	21	22
positive regulation of T cell mediated cytotoxicity	-0.04	0.18	0.51	1	-0.69	21	22
STAT1 (dimer)	-0.075	0.31	0.49	23	-1	30	53
JAK2	0.011	0.034	-10000	0	-0.73	1	1
JAK1	0.013	0.046	-10000	0	-0.72	2	2
STAT2 (dimer)	-0.031	0.17	0.44	1	-0.66	21	22
T cell proliferation	-0.33	0.25	0.47	1	-0.53	186	187
IL12/IL12R/TYK2/JAK2	0.035	0.047	-10000	0	-10000	0	0
IL17A	-0.22	0.15	-10000	0	-10000	0	0
mast cell activation	0.04	0.18	0.69	21	-0.51	1	22
IFNG	0.002	0.027	0.12	1	-0.09	10	11
T cell differentiation	-0.004	0.007	0.034	1	-0.025	21	22
STAT3 (dimer)	-0.031	0.17	0.44	1	-0.66	21	22
STAT5A (dimer)	-0.032	0.17	0.44	1	-0.66	22	23
STAT4 (dimer)	-0.036	0.18	0.44	1	-0.62	27	28
STAT4	0.005	0.086	-10000	0	-0.72	7	7
T cell activation	-0.006	0.026	0.13	18	-10000	0	18
IL27R/JAK2/TYK2	-0.048	0.24	-10000	0	-1.2	19	19
GATA3	-0.094	0.37	-10000	0	-1.4	38	38
IL18	0.005	0.038	-10000	0	-0.55	1	1
positive regulation of mast cell cytokine production	-0.03	0.16	0.44	1	-0.64	21	22
IL27/EBI3	-0.058	0.17	-10000	0	-0.55	58	58
IL27RA	-0.053	0.26	0.44	1	-1.4	18	19
IL6	-0.52	0.32	-10000	0	-0.71	391	391
STAT5A	0.013	0.045	-10000	0	-0.72	2	2
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.019	0.11	0.5	18	-1.4	1	19
IL1B	0.006	0.062	-10000	0	-0.55	6	6
EBI3	0.013	0.013	-10000	0	-10000	0	0
TNF	0.012	0.017	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.016	0	-9999	-10000	0	0
SPHK1	0.004	0.071	-9999	-0.72	4	4
GNAI2	0.016	0.007	-9999	-10000	0	0
mol:S1P	0.025	0.032	-9999	-0.34	4	4
GNAO1	0.016	0	-9999	-10000	0	0
mol:Sphinganine-1-P	0.021	0.053	-9999	-0.54	4	4
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0	0.023	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	-0.001	0.007	-9999	-10000	0	0
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	-0.19	0.33	-9999	-0.72	147	147
S1P1/S1P	-0.1	0.22	-9999	-0.46	147	147
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
GNAI1	-0.25	0.35	-9999	-0.72	189	189
S1P/S1P5/G12	-0.001	0.023	-9999	-0.26	4	4
S1P/S1P3/Gq	0.03	0.041	-9999	-0.32	6	6
S1P/S1P4/Gi	-0.057	0.14	-9999	-0.24	193	193
GNAQ	0	0	-9999	-10000	0	0
GNAZ	0.008	0.078	-9999	-0.72	6	6
GNA14	-0.008	0.09	-9999	-0.72	6	6
GNA15	0.014	0.02	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.015	0.014	-9999	-10000	0	0
GNA11	0.016	0	-9999	-10000	0	0
ABCC1	0.012	0.026	-9999	-10000	0	0

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.027	0.056	-9999	-0.51	5	5
alphaM/beta2 Integrin/GPIbA	-0.023	0.036	-9999	-10000	0	0
alphaM/beta2 Integrin/proMMP-9	-0.04	0.073	-9999	-10000	0	0
PLAUR	-0.022	0.069	-9999	-10000	0	0
HMGB1	-0.017	0.022	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.023	0.029	-9999	-10000	0	0
AGER	-0.018	0.04	-9999	-0.78	1	1
RAP1A	0.016	0	-9999	-10000	0	0
SELPLG	0.014	0.034	-9999	-0.72	1	1
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.13	0.089	-9999	-0.63	1	1
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.059	0.081	-9999	-10000	0	0
CYR61	-0.21	0.34	-9999	-0.72	161	161
TLN1	0.016	0	-9999	-10000	0	0
Rap1/GTP	-0.002	0.027	-9999	-0.36	1	1
RHOA	0.016	0	-9999	-10000	0	0
P-selectin oligomer	-0.19	0.33	-9999	-0.72	150	150
MYH2	0.047	0.057	-9999	-0.37	5	5
MST1R	0.005	0.041	-9999	-10000	0	0
leukocyte activation during inflammatory response	-0.011	0.022	-9999	-10000	0	0
APOB	0.016	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.009	0.072	-9999	-0.72	5	5
JAM3	-0.038	0.19	-9999	-0.72	39	39
GP1BA	0.011	0.029	-9999	-10000	0	0
alphaM/beta2 Integrin/CTGF	-0.042	0.1	-9999	-0.52	22	22
alphaM/beta2 Integrin	0.027	0.039	-9999	-0.43	1	1
JAM3 homodimer	-0.038	0.19	-9999	-0.72	39	39
ICAM2	0.004	0.096	-9999	-0.72	9	9
ICAM1	0.008	0.045	-9999	-0.72	1	1
phagocytosis triggered by activation of immune response cell surface activating receptor	0.027	0.039	-9999	-0.43	1	1
cell adhesion	-0.023	0.036	-9999	-10000	0	0
NFKB1	-0.22	0.18	-9999	-0.41	25	25
THY1	0.013	0.024	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	-0.11	0.19	-9999	-0.45	118	118
IL6	-0.62	0.41	-9999	-0.86	391	391
ITGB2	-0.026	0.041	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	-0.022	0.069	-9999	-10000	0	0
alphaM/beta2 Integrin/JAM2/JAM3	-0.17	0.27	-9999	-0.56	152	152
JAM2	-0.19	0.33	-9999	-0.72	150	150
alphaM/beta2 Integrin/ICAM1	-0.005	0.04	-9999	-0.43	1	1
alphaM/beta2 Integrin/uPA/Plg	-0.019	0.047	-9999	-0.46	1	1
RhoA/GTP	0.043	0.05	-9999	-0.34	7	7
positive regulation of phagocytosis	0.001	0.029	-9999	-10000	0	0
Ron/MSP	-0.005	0.02	-9999	-10000	0	0
alphaM/beta2 Integrin/uPAR/uPA	-0.022	0.071	-9999	-10000	0	0
alphaM/beta2 Integrin/uPAR	-0.028	0.058	-9999	-10000	0	0
PLAU	-0.009	0.059	-9999	-10000	0	0
PLAT	-0.15	0.31	-9999	-0.72	118	118
actin filament polymerization	0.046	0.055	-9999	-0.36	5	5
MST1	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/lipoprotein(a)	-0.01	0.023	-9999	-10000	0	0
TNF	-0.2	0.17	-9999	-0.67	1	1
RAP1B	0.016	0.01	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.031	0.049	-9999	-10000	0	0
fibrinolysis	-0.019	0.047	-9999	-0.46	1	1
HCK	0.013	0.024	-9999	-10000	0	0
dendritic cell antigen processing and presentation	0.027	0.039	-9999	-0.43	1	1
VTN	0.015	0.012	-9999	-10000	0	0
alphaM/beta2 Integrin/CYR61	-0.17	0.23	-9999	-0.51	161	161
LPA	0.016	0	-9999	-10000	0	0
LRP1	0.016	0	-9999	-10000	0	0
cell migration	-0.044	0.063	-9999	-0.46	5	5
FN1	-0.098	0.074	-9999	-10000	0	0
alphaM/beta2 Integrin/Thy1	-0.024	0.033	-9999	-10000	0	0
MPO	0.015	0.016	-9999	-10000	0	0
KNG1	0.016	0.007	-9999	-10000	0	0
RAP1/GDP	0	0.004	-9999	-10000	0	0
ROCK1	0.049	0.048	-9999	-0.49	1	1
ELA2	0.016	0	-9999	-10000	0	0
PLG	0.015	0.032	-9999	-0.72	1	1
CTGF	-0.015	0.15	-9999	-0.72	22	22
alphaM/beta2 Integrin/Hck	-0.024	0.034	-9999	-10000	0	0
ITGAM	-0.017	0.025	-9999	-0.2	2	2
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.14	0.21	-9999	-0.46	150	150
HP	0.016	0	-9999	-10000	0	0
leukocyte adhesion	-0.21	0.23	-9999	-0.56	138	138
SELP	-0.19	0.33	-9999	-0.72	150	150

×

Angiopoietin receptor Tie2-mediated 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
AKT1	0.051	0.24	-10000	0	-0.94	24	24
NCK1/PAK1/Dok-R	-0.029	0.093	-10000	0	-0.43	24	24
NCK1/Dok-R	-0.048	0.23	-10000	0	-1.1	24	24
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.008	0.041	0.24	14	-10000	0	14
RELA	0.016	0	-10000	0	-10000	0	0
SHC1	0.018	0.002	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.008	0.042	0.26	13	-10000	0	13
TNIP2	0.015	0.012	-10000	0	-10000	0	0
NF kappa B/RelA	-0.045	0.21	-10000	0	-1	24	24
FN1	-0.098	0.074	-10000	0	-10000	0	0
PLD2	0.039	0.26	-10000	0	-1.1	24	24
PTPN11	0.016	0	-10000	0	-10000	0	0
GRB14	-0.091	0.23	-10000	0	-0.72	57	57
ELK1	0.054	0.24	-10000	0	-1	24	24
GRB7	0.001	0.048	-10000	0	-10000	0	0
PAK1	-0.01	0.06	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	0.051	0.26	-10000	0	-1.1	24	24
CDKN1A	0.05	0.19	-10000	0	-0.68	19	19
ITGA5	0.016	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.047	0.23	-10000	0	-1.1	24	24
CRK	0.015	0.032	-10000	0	-0.72	1	1
mol:NO	0.066	0.19	-10000	0	-0.67	24	24
PLG	0.039	0.26	-10000	0	-1.1	24	24
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.003	0.21	-10000	0	-0.9	24	24
GRB2	0.013	0.022	-10000	0	-10000	0	0
PIK3R1	-0.054	0.22	-10000	0	-0.72	51	51
ANGPT2	-0.027	0.2	-10000	0	-0.63	17	17
BMX	-0.21	0.34	-10000	0	-1.4	24	24
ANGPT1	0.015	0.23	-10000	0	-1.4	14	14
tube development	0.042	0.21	-10000	0	-0.68	25	25
ANGPT4	0.016	0.001	-10000	0	-10000	0	0
response to hypoxia	0.004	0.016	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.001	0.31	-10000	0	-1.3	24	24
alpha5/beta1 Integrin	0	0.003	-10000	0	-10000	0	0
FGF2	-0.55	0.31	-10000	0	-0.72	403	403
STAT5A (dimer)	0.045	0.23	-10000	0	-0.84	21	21
mol:L-citrulline	0.066	0.19	-10000	0	-0.67	24	24
AGTR1	-0.31	0.35	-10000	0	-0.72	224	224
MAPK14	0.035	0.27	-10000	0	-1.2	24	24
Tie2/SHP2	-0.032	0.18	-10000	0	-1.2	12	12
TEK	0.027	0.21	-10000	0	-1.3	12	12
RPS6KB1	0.048	0.23	-10000	0	-0.9	24	24
Angiotensin II/AT1	-0.23	0.27	-10000	0	-0.55	224	224
Tie2/Ang1/GRB2	0.036	0.27	-10000	0	-1.2	24	24
MAPK3	0.049	0.24	-10000	0	-1	24	24
MAPK1	0.049	0.24	-10000	0	-1	24	24
Tie2/Ang1/GRB7	0.039	0.27	-10000	0	-1.2	24	24
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.039	0.26	-10000	0	-1.1	24	24
PI3K	0.034	0.27	-10000	0	-1.1	24	24
FES	0.033	0.27	-10000	0	-1.2	24	24
Crk/Dok-R	-0.048	0.23	-10000	0	-1.1	24	24
Tie2/Ang1/ABIN2	0.035	0.27	-10000	0	-1.2	24	24
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.055	0.22	-10000	0	-0.83	24	24
STAT5A	0.014	0.045	-10000	0	-0.72	2	2
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.049	0.23	-10000	0	-0.9	24	24
Tie2/Ang2	0.024	0.26	-10000	0	-0.97	24	24
Tie2/Ang1	0.028	0.28	-10000	0	-1.2	24	24
FOXO1	0.04	0.26	-10000	0	-0.87	25	25
ELF1	0.026	0.018	-10000	0	-10000	0	0
ELF2	0.036	0.26	-10000	0	-1.1	24	24
mol:Choline	0.041	0.25	-10000	0	-1.1	24	24
cell migration	-0.013	0.054	-10000	0	-0.24	24	24
FYN	0.037	0.23	-10000	0	-0.8	24	24
DOK2	0.013	0.046	-10000	0	-0.72	2	2
negative regulation of cell cycle	0.052	0.18	-10000	0	-0.61	19	19
ETS1	0.022	0.057	-10000	0	-0.89	1	1
PXN	0.061	0.2	-10000	0	-0.73	24	24
ITGB1	0.016	0	-10000	0	-10000	0	0
NOS3	0.063	0.21	-10000	0	-0.78	24	24
RAC1	0.016	0	-10000	0	-10000	0	0
TNF	0.02	0.046	-10000	0	-10000	0	0
MAPKKK cascade	0.041	0.25	-10000	0	-1.1	24	24
RASA1	0.015	0.012	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.033	0.27	-10000	0	-1.2	24	24
NCK1	0.016	0	-10000	0	-10000	0	0
vasculogenesis	0.068	0.17	-10000	0	-0.6	24	24
mol:Phosphatidic acid	0.041	0.25	-10000	0	-1.1	24	24
mol:Angiotensin II	0.002	0.001	-10000	0	-10000	0	0
mol:NADP	0.066	0.19	-10000	0	-0.67	24	24
Rac1/GTP	-0.053	0.18	-10000	0	-0.83	24	24
MMP2	0.036	0.27	-10000	0	-1.2	24	24

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.016	0.007	-10000	0	-10000	0	0
MKNK1	0.016	0	-10000	0	-10000	0	0
mol:PIP3	-0.072	0.16	0.32	6	-0.36	106	112
FRAP1	0.009	0.049	-10000	0	-10000	0	0
AKT1	-0.032	0.15	0.25	6	-0.32	106	112
INSR	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.049	0.1	-10000	0	-0.31	52	52
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.014	0.033	-10000	0	-10000	0	0
TSC2	0.016	0	-10000	0	-10000	0	0
RHEB/GDP	-0.042	0.092	0.18	1	-0.4	8	9
TSC1	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.033	0.14	-10000	0	-0.39	69	69
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.017	0.039	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.016	0.007	-10000	0	-10000	0	0
RPS6KB1	0.002	0.091	-10000	0	-0.31	7	7
MAP3K5	-0.015	0.11	-10000	0	-0.42	35	35
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
apoptosis	-0.015	0.11	-10000	0	-0.42	35	35
mol:LY294002	0	0.001	-10000	0	-0.002	62	62
EIF4B	0.012	0.083	-10000	0	-0.27	7	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.026	0.058	-10000	0	-0.4	1	1
eIF4E/eIF4G1/eIF4A1	-0.005	0.015	-10000	0	-10000	0	0
KIAA1303	0.016	0.01	-10000	0	-10000	0	0
PI3K	-0.057	0.18	-10000	0	-0.38	113	113
mTOR/RHEB/GTP/Raptor/GBL	0.031	0.071	-10000	0	-10000	0	0
FKBP1A	0.016	0.01	-10000	0	-10000	0	0
RHEB/GTP	-0.042	0.091	0.23	1	-0.39	8	9
mol:Amino Acids	0	0.001	-10000	0	-0.002	62	62
FKBP12/Rapamycin	0	0.006	-10000	0	-10000	0	0
PDPK1	-0.066	0.14	0.26	6	-0.33	106	112
EIF4E	0.016	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.02	0.16	-10000	0	-0.62	35	35
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.042	0.006	-10000	0	-10000	0	0
TSC1/TSC2	-0.052	0.11	-10000	0	-0.33	52	52
tumor necrosis factor receptor activity	0	0.001	0.002	62	-10000	0	62
RPS6	0.015	0.032	-10000	0	-0.72	1	1
PPP5C	0.014	0.02	-10000	0	-10000	0	0
EIF4G1	0.016	0	-10000	0	-10000	0	0
IRS1	-0.046	0.15	-10000	0	-0.42	69	69
INS	0.016	0	-10000	0	-10000	0	0
PTEN	-0.002	0.11	-10000	0	-0.72	13	13
PDK2	-0.066	0.14	0.26	6	-0.34	106	112
EIF4EBP1	0.022	0.019	-10000	0	-10000	0	0
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
PPP2R5D	0.017	0.046	-10000	0	-10000	0	0
peptide biosynthetic process	0.032	0	-10000	0	-10000	0	0
RHEB	0.016	0.007	-10000	0	-10000	0	0
EIF4A1	0.016	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	13	-0.003	51	64
EEF2	0.033	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.029	0.014	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.016	0.18	-9999	-0.41	72	72
FZD6	-0.024	0.16	-9999	-0.72	26	26
WNT6	0.012	0.048	-9999	-0.72	2	2
WNT4	0.005	0.05	-9999	-0.72	1	1
FZD3	-0.019	0.16	-9999	-0.72	25	25
WNT5A	-0.029	0.17	-9999	-0.72	28	28
WNT11	-0.001	0.1	-9999	-0.72	10	10

×

Signaling events mediated by VEGFR1 and VEGFR2

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.002	0.026	-9999	-0.54	1	1
AKT1	-0.006	0.2	-9999	-0.54	31	31
PTK2B	0.001	0.14	-9999	-0.52	23	23
VEGFR2 homodimer/Frs2	-0.006	0.14	-9999	-0.52	32	32
CAV1	-0.52	0.33	-9999	-0.72	385	385
CALM1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.057	0.15	-9999	-0.58	26	26
endothelial cell proliferation	0.015	0.19	-9999	-0.5	29	29
mol:Ca2+	-0.043	0.22	-9999	-0.69	29	29
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.05	0.13	-9999	-0.54	25	25
RP11-342D11.1	-0.054	0.22	-9999	-0.69	30	30
CDH5	0.016	0	-9999	-10000	0	0
VEGFA homodimer	0.003	0.053	-9999	-0.44	4	4
SHC1	0.016	0	-9999	-10000	0	0
SHC2	-0.023	0.17	-9999	-0.72	28	28
HRAS/GDP	-0.078	0.16	-9999	-0.58	29	29
SH2D2A	-0.006	0.056	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.063	0.15	-9999	-0.52	29	29
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.05	0.16	-9999	-0.58	26	26
VEGFR1 homodimer	0.016	0.01	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.084	0.18	-9999	-0.65	29	29
GRB10	-0.046	0.23	-9999	-0.73	30	30
PTPN11	0.016	0	-9999	-10000	0	0
GRB2	0.013	0.022	-9999	-10000	0	0
PAK1	-0.01	0.06	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.047	0.13	-9999	-0.51	28	28
HRAS	0.015	0.012	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.026	0.085	-9999	-0.29	4	4
HIF1A	0.008	0.067	-9999	-0.72	4	4
FRS2	0.011	0.039	-9999	-0.72	1	1
oxygen and reactive oxygen species metabolic process	-0.049	0.13	-9999	-0.54	25	25
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.016	0	-9999	-10000	0	0
Nck/Pak	-0.013	0.029	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.059	0.15	-9999	-0.58	27	27
mol:GDP	-0.083	0.17	-9999	-0.63	29	29
mol:NADP	0.007	0.16	-9999	-0.45	27	27
eNOS/Hsp90	0.015	0.16	-9999	-0.42	27	27
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
mol:IP3	-0.044	0.22	-9999	-0.7	29	29
HIF1A/ARNT	-0.005	0.048	-9999	-0.54	4	4
SHB	0.013	0.037	-9999	-0.72	1	1
VEGFA	-0.018	0.068	-9999	-10000	0	0
VEGFC	-0.002	0.12	-9999	-0.72	13	13
FAK1/Vinculin	0.027	0.14	-9999	-0.49	23	23
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.049	0.14	-9999	-0.54	25	25
PTPN6	0.015	0.014	-9999	-10000	0	0
EPAS1	-0.03	0.18	-9999	-0.76	31	31
mol:L-citrulline	0.007	0.16	-9999	-0.45	27	27
ITGAV	0.014	0.034	-9999	-0.72	1	1
PIK3CA	0.016	0.007	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.049	0.14	-9999	-0.54	26	26
VEGFR2 homodimer/VEGFA homodimer	-0.11	0.21	-9999	-0.75	30	30
VEGFR2/3 heterodimer	-0.006	0.14	-9999	-0.52	31	31
VEGFB	0.016	0	-9999	-10000	0	0
MAPK11	-0.04	0.22	-9999	-0.69	30	30
VEGFR2 homodimer	-0.016	0.16	-9999	-0.61	31	31
FLT1	0.016	0.01	-9999	-10000	0	0
NEDD4	-0.004	0.079	-9999	-0.74	5	5
MAPK3	-0.032	0.2	-9999	-0.63	29	29
MAPK1	-0.032	0.2	-9999	-0.63	29	29
VEGFA145/NRP2	-0.005	0.041	-9999	-10000	0	0
VEGFR1/2 heterodimer	-0.005	0.14	-9999	-0.52	31	31
KDR	-0.016	0.16	-9999	-0.61	31	31
VEGFA165/NRP1/VEGFR2 homodimer	-0.092	0.19	-9999	-0.69	29	29
SRC	0.016	0.007	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.031	0.21	-9999	-0.64	29	29
PI3K	-0.098	0.19	-9999	-0.65	33	33
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.057	0.14	-9999	-0.58	25	25
FES	-0.047	0.23	-9999	-0.71	31	31
GAB1	-0.066	0.15	-9999	-0.6	26	26
VEGFR2 homodimer/VEGFA homodimer/Src	-0.057	0.14	-9999	-0.58	25	25
CTNNB1	0.01	0.065	-9999	-0.72	4	4
SOS1	0.016	0	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.23	0.24	-9999	-0.52	149	149
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.058	0.14	-9999	-0.58	26	26
PI3K/GAB1	-0.015	0.22	-9999	-0.55	47	47
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.037	0.14	-9999	-0.54	23	23
PRKACA	0.016	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.046	0.13	-9999	-0.51	36	36
HSP90AA1	0.016	0.01	-9999	-10000	0	0
CDC42	-0.045	0.22	-9999	-0.71	29	29
actin cytoskeleton reorganization	-0.05	0.15	-9999	-0.58	26	26
PTK2	0.019	0.15	-9999	-0.53	23	23
EDG1	-0.17	0.4	-9999	-0.79	149	149
mol:DAG	-0.044	0.22	-9999	-0.7	29	29
CaM/Ca2+	-0.09	0.17	-9999	-0.64	29	29
MAP2K3	-0.033	0.21	-9999	-0.67	29	29
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.099	0.21	-9999	-0.76	30	30
PLCG1	-0.045	0.22	-9999	-0.71	29	29
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.05	0.14	-9999	-0.54	26	26
IQGAP1	0.016	0	-9999	-10000	0	0
YES1	0.015	0.032	-9999	-0.72	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.057	0.14	-9999	-0.58	25	25
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.056	0.14	-9999	-0.57	27	27
cell migration	0.059	0.13	-9999	-0.4	23	23
mol:PI-3-4-5-P3	-0.025	0.22	-9999	-0.59	35	35
FYN	0.013	0.045	-9999	-0.72	2	2
VEGFB/NRP1	-0.095	0.18	-9999	-0.65	29	29
mol:NO	0.007	0.16	-9999	-0.45	27	27
PXN	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.084	0.15	-9999	-0.58	29	29
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.042	0.24	-9999	-0.75	30	30
VHL	0.012	0.027	-9999	-10000	0	0
ITGB3	0.014	0.02	-9999	-10000	0	0
NOS3	0.003	0.18	-9999	-0.51	27	27
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.08	0.18	-9999	-0.61	39	39
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	-0.031	0.21	-9999	-0.65	29	29
PRKCB	-0.041	0.21	-9999	-0.66	29	29
VCL	0.016	0.007	-9999	-10000	0	0
VEGFA165/NRP1	-0.048	0.22	-9999	-0.69	30	30
VEGFR1/2 heterodimer/VEGFA homodimer	-0.056	0.14	-9999	-0.58	25	25
VEGFA165/NRP2	-0.005	0.041	-9999	-10000	0	0
MAPKKK cascade	-0.072	0.17	-9999	-0.61	30	30
NRP2	0.015	0.016	-9999	-10000	0	0
VEGFC homodimer	-0.002	0.11	-9999	-0.72	13	13
NCK1	0.016	0	-9999	-10000	0	0
ROCK1	0.016	0	-9999	-10000	0	0
FAK1/Paxillin	0.028	0.14	-9999	-0.49	23	23
MAP3K13	-0.045	0.22	-9999	-0.71	29	29
PDPK1	-0.011	0.2	-9999	-0.53	30	30

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.032	0.12	-9999	-0.46	38	38
E-cadherin/beta catenin	-0.039	0.14	-9999	-0.54	37	37
CTNNB1	0.01	0.065	-9999	-0.72	4	4
JUP	0.014	0.035	-9999	-0.72	1	1
CDH1	-0.032	0.18	-9999	-0.72	33	33

×

Thromboxane A2 receptor signaling

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
TGM2	0.002	0.048	-10000	0	-10000	0	0
GNB1/GNG2	-0.017	0.051	-10000	0	-0.17	52	52
AKT1	0.072	0.088	-10000	0	-0.19	51	51
EGF	-0.24	0.35	-10000	0	-0.72	178	178
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	0.06	0.036	-10000	0	-10000	0	0
mol:Ca2+	0.075	0.12	-10000	0	-0.28	52	52
LYN	0.06	0.036	-10000	0	-10000	0	0
RhoA/GTP	-0.011	0.035	-10000	0	-0.13	7	7
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.08	0.14	-10000	0	-0.32	52	52
GNG2	0.015	0.032	-10000	0	-0.72	1	1
ARRB2	0.016	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.041	0.037	-10000	0	-0.45	2	2
G beta5/gamma2	-0.022	0.066	-10000	0	-0.22	51	51
PRKCH	0.073	0.14	-10000	0	-0.34	52	52
DNM1	0.016	0.007	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3	-0.001	0.005	-10000	0	-10000	0	0
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	0.006	0.081	-10000	0	-0.72	6	6
G12 family/GTP	-0.027	0.086	-10000	0	-0.28	52	52
ADRBK1	0.016	0	-10000	0	-10000	0	0
ADRBK2	0.014	0.045	-10000	0	-0.72	2	2
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.064	0.079	0.35	5	-10000	0	5
mol:NADP	0.016	0	-10000	0	-10000	0	0
RAB11A	0.016	0.01	-10000	0	-10000	0	0
PRKG1	0.016	0	-10000	0	-10000	0	0
mol:IP3	0.077	0.14	-10000	0	-0.35	52	52
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	0.076	0.18	-10000	0	-0.47	52	52
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	0.063	0.038	-10000	0	-10000	0	0
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.061	0.036	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
PTGIR	0.016	0	-10000	0	-10000	0	0
PRKCB1	0.074	0.14	-10000	0	-0.35	52	52
GNAQ	0	0	-10000	0	-10000	0	0
mol:L-citrulline	0.016	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.076	0.19	-10000	0	-0.5	52	52
LCK	0.064	0.038	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.002	0.028	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.04	0.014	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.002	0.028	-10000	0	-10000	0	0
MAPK14	0.076	0.098	-10000	0	-0.21	52	52
TGM2/GTP	0.082	0.16	-10000	0	-0.38	52	52
MAPK11	0.076	0.098	-10000	0	-0.21	52	52
ARHGEF1	0.061	0.076	-10000	0	-0.16	52	52
GNAI2	0.016	0.007	-10000	0	-10000	0	0
JNK cascade	0.078	0.15	-10000	0	-0.37	52	52
RAB11/GDP	0.014	0.01	-10000	0	-10000	0	0
ICAM1	0.071	0.12	-10000	0	-0.28	52	52
cAMP biosynthetic process	0.074	0.13	-10000	0	-0.32	52	52
Gq family/GTP/EBP50	0.021	0.027	-10000	0	-0.22	6	6
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.06	0.036	-10000	0	-10000	0	0
GNB5	0.015	0.032	-10000	0	-0.72	1	1
GNB1	0.016	0.01	-10000	0	-10000	0	0
EGF/EGFR	-0.038	0.096	-10000	0	-0.32	6	6
VCAM1	0.068	0.13	-10000	0	-0.31	52	52
TP beta/Gq family/GDP/G beta5/gamma2	0.041	0.037	-10000	0	-0.45	2	2
platelet activation	0.098	0.13	-10000	0	-0.28	52	52
PGI2/IP	0	0.001	-10000	0	-10000	0	0
PRKACA	0.024	0.039	-10000	0	-0.34	6	6
Gq family/GDP/G beta5/gamma2	0.039	0.037	-10000	0	-0.43	2	2
TXA2/TP beta/beta Arrestin2	0	0.003	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.034	0.037	-10000	0	-0.31	6	6
mol:DAG	0.075	0.16	-10000	0	-0.4	52	52
EGFR	-0.38	0.37	-10000	0	-0.72	277	277
TXA2/TP alpha	0.084	0.17	-10000	0	-0.43	52	52
Gq family/GTP	-0.003	0.03	-10000	0	-0.28	6	6
YES1	0.06	0.043	-10000	0	-0.53	1	1
GNAI2/GTP	-0.004	0.032	-10000	0	-10000	0	0
PGD2/DP	-0.008	0.059	-10000	0	-0.55	6	6
SLC9A3R1	-0.022	0.069	-10000	0	-10000	0	0
FYN	0.059	0.043	-10000	0	-0.31	2	2
mol:NO	0.016	0	-10000	0	-10000	0	0
GNA15	0.014	0.02	-10000	0	-10000	0	0
PGK/cGMP	0	0	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.007	0.043	-10000	0	-10000	0	0
NOS3	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.075	0.14	-10000	0	-0.33	52	52
PRKCB	0.068	0.14	-10000	0	-0.34	52	52
PRKCE	0.076	0.14	-10000	0	-0.34	52	52
PRKCD	0.073	0.15	-10000	0	-0.37	52	52
PRKCG	0.074	0.15	-10000	0	-0.36	52	52
muscle contraction	0.081	0.18	-10000	0	-0.46	52	52
PRKCZ	0.074	0.14	-10000	0	-0.33	52	52
ARR3	0.016	0	-10000	0	-10000	0	0
TXA2/TP beta	-0.004	0.035	-10000	0	-0.34	2	2
PRKCQ	0.073	0.14	-10000	0	-0.34	52	52
MAPKKK cascade	0.076	0.16	-10000	0	-0.41	52	52
SELE	0.058	0.16	-10000	0	-0.4	52	52
TP beta/GNAI2/GDP/G beta/gamma	-0.003	0.032	-10000	0	-10000	0	0
ROCK1	0.016	0	-10000	0	-10000	0	0
GNA14	-0.008	0.09	-10000	0	-0.72	6	6
chemotaxis	0.071	0.23	-10000	0	-0.6	52	52
GNA12	0.016	0	-10000	0	-10000	0	0
GNA13	0.015	0.014	-10000	0	-10000	0	0
GNA11	0.016	0	-10000	0	-10000	0	0
Rac1/GTP	0.01	0.006	-10000	0	-10000	0	0

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0.006	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
MAP3K7IP2	0.015	0.032	-9999	-0.72	1	1
ERC1	0.013	0.022	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.037	0.086	-9999	-0.35	21	21
IRAK/TOLLIP	0.031	0.012	-9999	-10000	0	0
IKBKB	0.014	0.02	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.008	0.045	-9999	-0.54	3	3
IL1A	0.014	0.02	-9999	-10000	0	0
IL1B	-0.043	0.2	-9999	-0.57	62	62
IRAK/TRAF6/p62/Atypical PKCs	0.002	0.013	-9999	-10000	0	0
IL1R2	0.004	0.065	-9999	-0.72	3	3
IL1R1	-0.067	0.23	-9999	-0.72	59	59
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.013	0.14	-9999	-0.46	19	19
TOLLIP	0.016	0.007	-9999	-10000	0	0
TICAM2	0	0	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	-0.001	0.021	-9999	-0.46	1	1
IKK complex/ELKS	0.082	0.02	-9999	-10000	0	0
JUN	-0.01	0.16	-9999	-0.59	5	5
MAP3K7	0.016	0.01	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.12	0.24	-9999	-0.54	99	99
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.044	0.13	-9999	-0.41	59	59
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.04	0.12	-9999	-0.38	59	59
IL1 beta fragment/IL1R1/IL1RAP	-0.098	0.21	-9999	-0.49	104	104
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.054	0.062	-9999	-10000	0	0
IRAK1	0.022	0.012	-9999	-10000	0	0
IL1RN/IL1R1	-0.071	0.17	-9999	-0.55	59	59
IRAK4	0.016	0.01	-9999	-10000	0	0
PRKCI	0.013	0.022	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
PI3K	-0.052	0.16	-9999	-0.54	51	51
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.017	0.15	-9999	-0.48	23	23
CHUK	0.015	0.032	-9999	-0.72	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.098	0.21	-9999	-0.49	104	104
IL1 beta/IL1R2	-0.057	0.17	-9999	-0.49	64	64
IRAK/TRAF6/TAK1/TAB1/TAB2	0.001	0.018	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.11	0.21	-9999	-0.67	45	45
IRAK3	0.012	0.039	-9999	-0.72	1	1
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.087	0.19	-9999	-0.44	104	104
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.01	0.11	-9999	-0.3	1	1
IL1 alpha/IL1R1/IL1RAP	-0.05	0.14	-9999	-0.46	59	59
RELA	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0.016	0	-9999	-10000	0	0
SQSTM1	0.016	0.007	-9999	-10000	0	0
MYD88	0.016	0.01	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.041	0.004	-9999	-10000	0	0
IL1RAP	0.016	0	-9999	-10000	0	0
UBE2N	0.016	0.01	-9999	-10000	0	0
IRAK/TRAF6	-0.07	0.16	-9999	-0.61	21	21
CASP1	-0.068	0.24	-9999	-0.72	60	60
IL1RN/IL1R2	-0.018	0.052	-9999	-0.54	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.09	0.2	-9999	-0.46	104	104
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.009	0.12	-9999	-0.34	59	59
PIK3CA	0.016	0.007	-9999	-10000	0	0
IL1RN	-0.006	0.056	-9999	-10000	0	0
TRAF6/TAK1/TAB1/TAB2	0	0.017	-9999	-0.36	1	1
MAP2K6	0.047	0.063	-9999	-0.35	13	13

×

Canonical Wnt signaling pathway

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
HDAC1	0.011	0.028	-10000	0	-10000	0	0
AES	0.01	0.023	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	-0.001	0.024	-10000	0	-0.54	1	1
SMAD4	0.013	0.045	-10000	0	-0.72	2	2
DKK2	0.007	0.074	-10000	0	-0.72	5	5
TLE1	-0.016	0.14	-10000	0	-0.72	18	18
MACF1	0.017	0	-10000	0	-10000	0	0
CTNNB1	0.16	0.077	0.3	1	-10000	0	1
WIF1	-0.53	0.32	-10000	0	-0.72	392	392
beta catenin/RanBP3	0.04	0.13	0.46	46	-10000	0	46
KREMEN2	-0.076	0.08	-10000	0	-10000	0	0
DKK1	-0.075	0.21	-10000	0	-0.72	46	46
beta catenin/beta TrCP1	0.16	0.072	-10000	0	-10000	0	0
FZD1	0.016	0.032	-10000	0	-0.72	1	1
AXIN2	-0.018	0.21	-10000	0	-1.5	9	9
AXIN1	0.017	0.01	-10000	0	-10000	0	0
RAN	0.016	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.019	0.042	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.13	0.1	0.33	3	-0.48	4	7
Axin1/APC/GSK3	0.002	0.014	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.11	0.033	-10000	0	-10000	0	0
HNF1A	0.01	0.028	0.27	1	-10000	0	1
CTBP1	0.01	0.026	-10000	0	-10000	0	0
MYC	-0.068	0.36	-10000	0	-1.5	29	29
RANBP3	0.016	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.04	0.068	-10000	0	-0.5	5	5
NKD1	0.013	0.019	-10000	0	-10000	0	0
TCF4	0	0.086	-10000	0	-0.71	7	7
TCF3	0.009	0.03	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0	0.02	-10000	0	-0.4	1	1
Ran/GTP	0.002	0.006	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.032	0.15	0.47	44	-0.41	1	45
LEF1	-0.015	0.068	-10000	0	-10000	0	0
DVL1	0.11	0.062	0.23	3	-10000	0	3
CSNK2A1	0.017	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.12	0.11	-10000	0	-0.46	3	3
DKK1/LRP6/Kremen 2	-0.025	0.16	-10000	0	-0.5	46	46
LRP6	0.016	0.012	-10000	0	-10000	0	0
CSNK1A1	0.011	0.028	-10000	0	-10000	0	0
NLK	0.005	0.041	-10000	0	-10000	0	0
CCND1	-0.033	0.24	-10000	0	-1.6	12	12
WNT1	0.017	0.002	-10000	0	-10000	0	0
GSK3A	0.018	0.001	-10000	0	-10000	0	0
GSK3B	0.015	0.01	-10000	0	-10000	0	0
FRAT1	0.015	0.01	-10000	0	-10000	0	0
PPP2R5D	0.065	0.029	-10000	0	-10000	0	0
APC	0.054	0.02	-10000	0	-0.37	1	1
WNT1/LRP6/FZD1	0.2	0.12	0.27	391	-10000	0	391
CREBBP	0.009	0.041	-10000	0	-0.73	1	1

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.067	0.13	-10000	0	-0.66	9	9
RAD9A	0.016	0	-10000	0	-10000	0	0
AP1	-0.46	0.35	-10000	0	-0.65	375	375
IFNAR2	0.018	0.003	-10000	0	-10000	0	0
AKT1	-0.034	0.12	-10000	0	-0.25	118	118
ER alpha/Oestrogen	-0.14	0.22	-10000	0	-0.55	117	117
NFX1/SIN3/HDAC complex	0.06	0.01	-10000	0	-10000	0	0
EGF	-0.23	0.35	-10000	0	-0.72	178	178
SMG5	0.014	0.02	-10000	0	-10000	0	0
SMG6	0.016	0	-10000	0	-10000	0	0
SP3/HDAC2	0.023	0.015	-10000	0	-10000	0	0
TERT/c-Abl	-0.063	0.11	-10000	0	-0.64	7	7
SAP18	0.017	0.001	-10000	0	-10000	0	0
MRN complex	0	0.004	-10000	0	-10000	0	0
WT1	-0.04	0.077	-10000	0	-10000	0	0
WRN	0.016	0.01	-10000	0	-10000	0	0
SP1	0.019	0.003	-10000	0	-10000	0	0
SP3	0.017	0.003	-10000	0	-10000	0	0
TERF2IP	0.016	0	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.052	0.091	-10000	0	-0.61	5	5
Mad/Max	0.022	0.011	-10000	0	-10000	0	0
TERT	-0.07	0.13	-10000	0	-0.7	8	8
CCND1	-0.072	0.2	-10000	0	-1.2	13	13
MAX	0.017	0.003	-10000	0	-10000	0	0
RBBP7	0.012	0.026	-10000	0	-10000	0	0
RBBP4	0.016	0.007	-10000	0	-10000	0	0
TERF2	-0.001	0.029	-10000	0	-0.66	1	1
PTGES3	0.015	0.032	-10000	0	-0.72	1	1
SIN3A	0.017	0.001	-10000	0	-10000	0	0
Telomerase/911	0.037	0.025	-10000	0	-10000	0	0
CDKN1B	0.011	0.12	-10000	0	-0.76	10	10
RAD1	0.015	0.012	-10000	0	-10000	0	0
XRCC5	0.016	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
SAP30	0.016	0.007	-10000	0	-10000	0	0
TRF2/PARP2	-0.001	0.023	-10000	0	-0.53	1	1
UBE3A	0.017	0.003	-10000	0	-10000	0	0
JUN	-0.12	0.29	-10000	0	-0.72	97	97
E6	0.001	0.001	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.012	0.006	-10000	0	-10000	0	0
FOS	-0.51	0.34	-10000	0	-0.72	374	374
IFN-gamma/IRF1	0	0.073	-10000	0	-0.35	10	10
PARP2	0.016	0	-10000	0	-10000	0	0
BLM	-0.033	0.074	-10000	0	-10000	0	0
Telomerase	0.008	0.026	-10000	0	-10000	0	0
IRF1	0.01	0.046	-10000	0	-10000	0	0
ESR1	-0.18	0.3	-10000	0	-0.72	117	117
KU/TER	0	0	-10000	0	-10000	0	0
ATM/TRF2	-0.001	0.019	-10000	0	-0.43	1	1
ubiquitin-dependent protein catabolic process	0.067	0.01	-10000	0	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.067	0.01	-10000	0	-10000	0	0
HDAC1	0.017	0.001	-10000	0	-10000	0	0
HDAC2	0.017	0.018	-10000	0	-10000	0	0
ATM	0	0.011	0.25	1	-10000	0	1
SMAD3	0.026	0.026	-10000	0	-0.54	1	1
ABL1	0.016	0	-10000	0	-10000	0	0
MXD1	0.017	0.008	-10000	0	-10000	0	0
MRE11A	0.016	0	-10000	0	-10000	0	0
HUS1	0.015	0.012	-10000	0	-10000	0	0
RPS6KB1	0.013	0.024	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.056	0.12	-10000	0	-0.62	10	10
NR2F2	-0.007	0.12	-10000	0	-0.72	14	14
MAPK3	0.03	0.026	-10000	0	-0.54	1	1
MAPK1	0.03	0.026	-10000	0	-0.54	1	1
TGFB1/TGF beta receptor Type II	0.015	0.01	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
HNRNPC	0.016	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0.011	0.25	1	-10000	0	1
NBN	0.016	0.007	-10000	0	-10000	0	0
EGFR	-0.37	0.37	-10000	0	-0.72	277	277
mol:Oestrogen	0	0.001	-10000	0	-10000	0	0
EGF/EGFR	-0.45	0.33	-10000	0	-0.64	372	372
MYC	-0.023	0.17	-10000	0	-0.72	29	29
IL2	0.018	0.033	-10000	0	-0.72	1	1
KU	0	0	-10000	0	-10000	0	0
RAD50	0.016	0	-10000	0	-10000	0	0
HSP90AA1	0.016	0.01	-10000	0	-10000	0	0
TGFB1	0.015	0.01	-10000	0	-10000	0	0
TRF2/BLM	0.022	0.042	-10000	0	-0.53	1	1
FRAP1	0.016	0	-10000	0	-10000	0	0
KU/TERT	-0.056	0.11	-10000	0	-0.63	7	7
SP1/HDAC2	0.026	0.016	-10000	0	-10000	0	0
PINX1	0.016	0	-10000	0	-10000	0	0
Telomerase/EST1A	-0.052	0.091	-10000	0	-0.64	4	4
Smad3/Myc	0.004	0.11	-10000	0	-0.46	30	30
911 complex	0	0.009	-10000	0	-10000	0	0
IFNG	-0.016	0.074	-10000	0	-0.71	1	1
Telomerase/PinX1	-0.052	0.091	-10000	0	-0.61	5	5
Telomerase/AKT1/mTOR/p70S6K	0.015	0.062	-10000	0	-0.48	2	2
SIN3B	0.015	0.016	-10000	0	-10000	0	0
YWHAE	0.015	0.032	-10000	0	-0.72	1	1
Telomerase/EST1B	-0.053	0.092	-10000	0	-0.61	5	5
response to DNA damage stimulus	0.004	0.003	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	-0.001	0.018	-10000	0	-0.4	1	1
TRF2/WRN	-0.001	0.024	-10000	0	-0.53	1	1
Telomerase/hnRNP C1/C2	-0.052	0.091	-10000	0	-0.61	5	5
E2F1	-0.004	0.056	-10000	0	-10000	0	0
ZNFX1	0.014	0.022	-10000	0	-10000	0	0
PIF1	0.01	0.032	-10000	0	-10000	0	0
NCL	0.016	0	-10000	0	-10000	0	0
DKC1	0.015	0.014	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.024	0.024	-9999	-10000	0	0
STMN1	-0.008	0.068	-9999	-10000	0	0
Aurora B/RasGAP/Survivin	0.018	0.077	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.18	0.13	-9999	-0.26	384	384
BIRC5	-0.087	0.078	-9999	-10000	0	0
DES	0.006	0.1	-9999	-0.61	13	13
Aurora C/Aurora B/INCENP	0.028	0.036	-9999	-10000	0	0
Aurora B/TACC1	-0.011	0.12	-9999	-0.49	31	31
Aurora B/PP2A	0.022	0.031	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.017	0.011	-9999	-0.19	1	1
mitotic metaphase/anaphase transition	-0.001	0.002	-9999	-10000	0	0
NDC80	-0.053	0.078	-9999	-10000	0	0
Cul3 protein complex	-0.34	0.22	-9999	-0.47	384	384
KIF2C	0.017	0.012	-9999	-10000	0	0
PEBP1	0.013	0.033	-9999	-0.74	1	1
KIF20A	-0.091	0.077	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.023	0.03	-9999	-10000	0	0
SEPT1	0.013	0.023	-9999	-10000	0	0
SMC2	0.009	0.034	-9999	-10000	0	0
SMC4	-0.002	0.051	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.036	0.012	-9999	-10000	0	0
PSMA3	0.016	0.007	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.001	-9999	-10000	0	0
H3F3B	0.014	0.024	-9999	-0.41	1	1
AURKB	-0.015	0.064	-9999	-10000	0	0
AURKC	0.013	0.022	-9999	-10000	0	0
CDCA8	-0.064	0.081	-9999	-10000	0	0
cytokinesis	-0.009	0.03	-9999	-10000	0	0
Aurora B/Septin1	0.009	0.035	-9999	-10000	0	0
AURKA	-0.05	0.08	-9999	-10000	0	0
INCENP	0	0.046	-9999	-10000	0	0
KLHL13	-0.52	0.33	-9999	-0.72	382	382
BUB1	-0.12	0.059	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	-0.009	0.098	-9999	-10000	0	0
EVI5	0.015	0.032	-9999	-0.73	1	1
RhoA/GTP	0.018	0.069	-9999	-10000	0	0
SGOL1	-0.029	0.073	-9999	-10000	0	0
CENPA	0.012	0.019	-9999	-10000	0	0
NCAPG	0	0	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.023	0.029	-9999	-10000	0	0
NCAPD2	0.009	0.034	-9999	-10000	0	0
Aurora B/PP1-gamma	0.023	0.029	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
NCAPH	-0.036	0.076	-9999	-10000	0	0
NPM1	0.017	0.009	-9999	-10000	0	0
RASA1	0.015	0.012	-9999	-10000	0	0
KLHL9	0.004	0.096	-9999	-0.72	9	9
mitotic prometaphase	-0.002	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.029	-9999	-10000	0	0
PPP1CC	0.016	0	-9999	-10000	0	0
Centraspindlin	-0.003	0.079	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	0.017	0.009	-9999	-10000	0	0
MYLK	-0.11	0.19	-9999	-0.41	151	151
KIF23	-0.081	0.08	-9999	-10000	0	0
VIM	-0.044	0.17	-9999	-0.56	49	49
RACGAP1	-0.029	0.074	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.017	0.009	-9999	-10000	0	0
Chromosomal passenger complex	0.004	0.031	-9999	-0.23	1	1
Chromosomal passenger complex/EVI5	0.077	0.091	-9999	-0.59	1	1
TACC1	-0.028	0.17	-9999	-0.72	31	31
PPP2R5D	0.015	0.012	-9999	-10000	0	0
CUL3	0.012	0.056	-9999	-0.72	3	3
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

IL12-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
IL12/IL12R/TYK2/JAK2/SOCS1	0.012	0.074	-10000	0	-0.28	7	7
TBX21	-0.095	0.39	-10000	0	-1.3	39	39
B2M	0.016	0.033	-10000	0	-0.72	1	1
TYK2	0.009	0.017	-10000	0	-10000	0	0
IL12RB1	0.009	0.017	-10000	0	-10000	0	0
GADD45B	-0.036	0.25	-10000	0	-0.78	34	34
IL12RB2	-0.018	0.076	-10000	0	-0.72	2	2
GADD45G	-0.03	0.22	-10000	0	-0.7	32	32
natural killer cell activation	-0.004	0.019	-10000	0	-10000	0	0
RELB	0.013	0.024	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL18	0.007	0.055	-10000	0	-0.73	1	1
IL2RA	0.006	0.039	-10000	0	-10000	0	0
IFNG	-0.021	0.074	-10000	0	-0.72	1	1
STAT3 (dimer)	-0.019	0.21	-10000	0	-0.55	36	36
HLA-DRB5	0.005	0.008	-10000	0	-10000	0	0
FASLG	-0.045	0.24	-10000	0	-0.78	21	21
NF kappa B2 p52/RelB	-0.09	0.19	-10000	0	-0.52	73	73
CD4	0.005	0.008	-10000	0	-10000	0	0
SOCS1	0.015	0.012	-10000	0	-10000	0	0
EntrezGene:6955	-0.017	0.014	-10000	0	-10000	0	0
CD3D	-0.002	0.037	-10000	0	-10000	0	0
CD3E	0.005	0.011	-10000	0	-10000	0	0
CD3G	-0.022	0.11	-10000	0	-0.73	10	10
IL12Rbeta2/JAK2	-0.002	0.065	-10000	0	-0.55	3	3
CCL3	-0.042	0.24	-10000	0	-0.78	19	19
CCL4	-0.042	0.24	-10000	0	-0.78	19	19
HLA-A	0.014	0.025	-10000	0	-10000	0	0
IL18/IL18R	0.027	0.16	-10000	0	-0.49	45	45
NOS2	-0.045	0.24	-10000	0	-0.53	76	76
IL12/IL12R/TYK2/JAK2/SPHK2	0.012	0.074	-10000	0	-0.27	11	11
IL1R1	-0.14	0.46	-10000	0	-1.3	64	64
IL4	0.022	0.017	-10000	0	-10000	0	0
JAK2	0.008	0.037	-10000	0	-0.74	1	1
EntrezGene:6957	-0.015	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.005	0.076	-10000	0	-0.44	7	7
RAB7A	0.009	0.21	-10000	0	-0.69	18	18
lysosomal transport	0.011	0.2	-10000	0	-0.6	27	27
FOS	-0.88	0.64	-10000	0	-1.3	374	374
STAT4 (dimer)	-0.006	0.24	-10000	0	-0.67	39	39
STAT5A (dimer)	-0.089	0.21	-10000	0	-0.54	75	75
GZMA	-0.051	0.23	-10000	0	-0.54	74	74
GZMB	-0.046	0.24	-10000	0	-0.67	36	36
HLX	0.013	0.045	-10000	0	-0.72	2	2
LCK	-0.053	0.25	-10000	0	-0.56	74	74
TCR/CD3/MHC II/CD4	-0.12	0.13	-10000	0	-0.35	44	44
IL2/IL2R	0.007	0.039	-10000	0	-0.41	1	1
MAPK14	-0.008	0.24	-10000	0	-0.72	34	34
CCR5	-0.033	0.22	-10000	0	-0.71	32	32
IL1B	-0.001	0.083	-10000	0	-0.74	6	6
STAT6	-0.028	0.16	-10000	0	-0.45	39	39
STAT4	0.005	0.086	-10000	0	-0.72	7	7
STAT3	0.016	0	-10000	0	-10000	0	0
STAT1	-0.011	0.061	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
NFKB2	0.015	0.012	-10000	0	-10000	0	0
IL12B	0.007	0.029	-10000	0	-10000	0	0
CD8A	0.002	0.002	-10000	0	-10000	0	0
CD8B	0.014	0.027	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.012	0.073	0.28	7	-10000	0	7
IL2RB	0.013	0.023	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.002	0.23	-10000	0	-0.62	39	39
IL2RG	0.006	0.039	-10000	0	-10000	0	0
IL12	0	0.087	-10000	0	-0.55	11	11
STAT5A	0.013	0.045	-10000	0	-0.72	2	2
CD247	-0.041	0.16	-10000	0	-0.73	25	25
IL2	0.015	0.033	-10000	0	-0.72	1	1
SPHK2	0.016	0	-10000	0	-10000	0	0
FRAP1	0.016	0	-10000	0	-10000	0	0
IL12A	-0.008	0.11	-10000	0	-0.73	11	11
IL12/IL12R/TYK2/JAK2	-0.053	0.26	-10000	0	-0.6	74	74
MAP2K3	-0.013	0.24	-10000	0	-0.72	35	35
RIPK2	0.014	0.02	-10000	0	-10000	0	0
MAP2K6	-0.017	0.24	-10000	0	-0.71	37	37
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.004	0.033	-10000	0	-0.74	1	1
IL18RAP	-0.043	0.21	-10000	0	-0.73	45	45
IL12Rbeta1/TYK2	0.011	0.025	-10000	0	-10000	0	0
EOMES	0.016	0.031	-10000	0	-10000	0	0
STAT1 (dimer)	-0.011	0.21	-10000	0	-0.55	36	36
T cell proliferation	-0.004	0.2	-10000	0	-0.55	38	38
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.018	0.036	-10000	0	-0.73	1	1
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.07	0.18	-10000	0	-0.64	37	37
ATF2	0.003	0.23	-10000	0	-0.66	34	34

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.039	0.052	-9999	-0.36	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.016	0.036	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin/Src	0.033	0.066	-9999	-0.52	4	4
AP1	-0.29	0.25	-9999	-0.68	106	106
ILK	0.031	0.051	-9999	-0.38	4	4
bone resorption	0.062	0.049	-9999	-10000	0	0
PTK2B	0.016	0	-9999	-10000	0	0
PYK2/p130Cas	0.047	0.065	-9999	-10000	0	0
ITGAV	0.02	0.033	-9999	-0.71	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.003	0.034	-9999	-0.54	2	2
alphaV/beta3 Integrin/Osteopontin	0.041	0.065	-9999	-0.43	4	4
MAP3K1	0.028	0.066	-9999	-0.41	8	8
JUN	-0.12	0.29	-9999	-0.72	97	97
MAPK3	0.044	0.052	-9999	-0.34	4	4
MAPK1	0.044	0.052	-9999	-0.34	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.034	0.065	-9999	-0.37	9	9
ITGB3	0.019	0.019	-9999	-10000	0	0
NFKBIA	0.056	0.052	-9999	-10000	0	0
FOS	-0.51	0.34	-9999	-0.72	374	374
CD44	0.014	0.034	-9999	-0.72	1	1
CHUK	0.015	0.032	-9999	-0.72	1	1
PLAU	0.033	0.058	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.018	0.04	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.001	0.026	-9999	-0.52	1	1
mol:GDP	0	0	-9999	-10000	0	0
SYK	0.027	0.055	-9999	-0.38	4	4
VAV3	0.013	0.1	-9999	-0.4	25	25
MAP3K14	0.035	0.051	-9999	-0.38	4	4
ROCK2	0.015	0.033	-9999	-0.72	1	1
SPP1	-0.049	0.092	-9999	-0.71	3	3
RAC1	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.011	0.081	-9999	-0.36	25	25
MMP2	-0.22	0.22	-9999	-0.54	104	104

×

Regulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.03	0	-9999	-10000	0	0
SMARCC1	0.011	0.026	-9999	-10000	0	0
REL	0.011	0.027	-9999	-10000	0	0
HDAC7	-0.003	0.14	-9999	-0.58	8	8
JUN	-0.12	0.29	-9999	-0.72	97	97
EP300	0.016	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
KAT5	0	0	-9999	-10000	0	0
MAPK14	0.013	0.088	-9999	-0.55	12	12
FOXO1	-0.085	0.25	-9999	-0.72	72	72
T-DHT/AR	0.002	0.15	-9999	-0.61	8	8
MAP2K6	-0.003	0.11	-9999	-0.73	12	12
BRM/BAF57	0	0.005	-9999	-10000	0	0
MAP2K4	0.005	0.085	-9999	-0.72	7	7
SMARCA2	0.017	0	-9999	-10000	0	0
PDE9A	-0.093	0.28	-9999	-1.2	30	30
NCOA2	0.016	0.014	-9999	-10000	0	0
CEBPA	0.012	0.056	-9999	-0.72	3	3
EHMT2	0.017	0	-9999	-10000	0	0
cell proliferation	0.061	0.14	-9999	-0.45	6	6
NR0B1	-0.17	0.31	-9999	-0.72	124	124
EGR1	-0.6	0.28	-9999	-0.72	436	436
RXRs/9cRA	-0.004	0.041	-9999	-0.42	5	5
AR/RACK1/Src	0.032	0.1	-9999	-0.46	9	9
AR/GR	-0.043	0.17	-9999	-0.42	61	61
GNB2L1	0.017	0	-9999	-10000	0	0
PKN1	0.016	0.012	-9999	-10000	0	0
RCHY1	0.011	0.064	-9999	-0.72	4	4
epidermal growth factor receptor activity	0.001	0	-9999	-10000	0	0
MAPK8	0.018	0.072	-9999	-0.54	8	8
T-DHT/AR/TIF2/CARM1	0.029	0.1	-9999	-0.47	9	9
SRC	0.032	0.093	-9999	-0.41	19	19
NR3C1	-0.048	0.21	-9999	-0.72	46	46
KLK3	-0.068	0.09	-9999	-10000	0	0
APPBP2	0.012	0.016	-9999	-10000	0	0
TRIM24	0.016	0.014	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.034	0.087	-9999	-0.44	19	19
TMPRSS2	-0.28	0.5	-9999	-1.2	126	126
RXRG	0.009	0.072	-9999	-0.72	5	5
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.016	0	-9999	-10000	0	0
RXRB	0.016	0	-9999	-10000	0	0
CARM1	0.015	0.017	-9999	-10000	0	0
NR2C2	0.014	0.019	-9999	-10000	0	0
KLK2	0.05	0.088	-9999	-0.53	1	1
AR	-0.011	0.13	-9999	-0.29	77	77
SENP1	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0.01	-9999	-10000	0	0
MDM2	0.01	0.025	-9999	-10000	0	0
SRY	0.006	0.073	-9999	-0.72	5	5
GATA2	0.007	0.037	-9999	-10000	0	0
MYST2	0.012	0.037	-9999	-0.72	1	1
HOXB13	-0.04	0.077	-9999	-10000	0	0
T-DHT/AR/RACK1/Src	0.027	0.1	-9999	-0.47	9	9
positive regulation of transcription	0.007	0.037	-9999	-10000	0	0
DNAJA1	0.013	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.034	-9999	-0.36	4	4
NCOA1	0.022	0.034	-9999	-0.75	1	1
SPDEF	-0.06	0.22	-9999	-0.72	54	54
T-DHT/AR/TIF2	0.038	0.066	-9999	-0.38	1	1
T-DHT/AR/Hsp90	0.013	0.1	-9999	-0.43	19	19
GSK3B	0.015	0.011	-9999	-10000	0	0
NR2C1	0.014	0.032	-9999	-0.72	1	1
mol:T-DHT	0.02	0.1	-9999	-0.45	19	19
SIRT1	0.016	0.007	-9999	-10000	0	0
ZMIZ2	0.015	0	-9999	-10000	0	0
POU2F1	0.024	0.024	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.086	0.21	-9999	-0.42	136	136
CREBBP	0.015	0.032	-9999	-0.72	1	1
SMARCE1	0.017	0.01	-9999	-10000	0	0

×

Coregulation 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.003	0.1	-9999	-0.72	10	10
SVIL	0.001	0.11	-9999	-0.72	12	12
ZNF318	0.007	0.006	-9999	-10000	0	0
JMJD2C	0.026	0.001	-9999	-10000	0	0
T-DHT/AR/Ubc9	-0.061	0.17	-9999	-0.48	69	69
CARM1	0.015	0.017	-9999	-10000	0	0
PRDX1	0.014	0.016	-9999	-10000	0	0
PELP1	0.015	0	-9999	-10000	0	0
CTNNB1	0.012	0.065	-9999	-0.72	4	4
AKT1	0.013	0.02	-9999	-10000	0	0
PTK2B	0.017	0	-9999	-10000	0	0
MED1	0.005	0.039	-9999	-10000	0	0
MAK	-0.001	0.034	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.018	0.007	-9999	-10000	0	0
GSN	-0.18	0.33	-9999	-0.72	143	143
NCOA2	0.015	0.014	-9999	-10000	0	0
NCOA6	0.018	0.007	-9999	-10000	0	0
DNA-PK	0.003	0.014	-9999	-10000	0	0
NCOA4	0.014	0.045	-9999	-0.72	2	2
PIAS3	0.018	0	-9999	-10000	0	0
cell proliferation	-0.02	0.033	-9999	-10000	0	0
XRCC5	0.015	0	-9999	-10000	0	0
UBE3A	0.019	0.001	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.072	0.17	-9999	-0.42	88	88
FHL2	-0.15	0.36	-9999	-1.1	58	58
RANBP9	0.018	0.007	-9999	-10000	0	0
JMJD1A	-0.008	0.062	-9999	-10000	0	0
CDK6	0.005	0.086	-9999	-0.72	7	7
TGFB1I1	0.014	0.056	-9999	-0.72	3	3
T-DHT/AR/CyclinD1	-0.07	0.2	-9999	-0.5	81	81
XRCC6	0.015	0	-9999	-10000	0	0
T-DHT/AR	-0.076	0.2	-9999	-0.46	88	88
CTDSP1	0.017	0	-9999	-10000	0	0
CTDSP2	0.013	0.001	-9999	-10000	0	0
BRCA1	0.014	0.025	-9999	-10000	0	0
TCF4	0.004	0.085	-9999	-0.72	7	7
CDKN2A	-0.013	0.061	-9999	-10000	0	0
SRF	0.01	0.043	-9999	-10000	0	0
NKX3-1	-0.08	0.11	-9999	-0.25	126	126
KLK3	0.013	0.038	-9999	-10000	0	0
TMF1	0.017	0	-9999	-10000	0	0
HNRNPA1	0.015	0	-9999	-10000	0	0
AOF2	0.018	0.007	-9999	-10000	0	0
APPL1	0.025	0.013	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.084	0.16	-9999	-0.48	69	69
AR	-0.096	0.25	-9999	-0.73	69	69
UBA3	0.001	0	-9999	-10000	0	0
PATZ1	0.014	0.007	-9999	-10000	0	0
PAWR	0.013	0.037	-9999	-0.72	1	1
PRKDC	0.009	0.03	-9999	-10000	0	0
PA2G4	0.014	0.007	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.056	0.16	-9999	-0.45	69	69
RPS6KA3	0.015	0.046	-9999	-0.72	2	2
T-DHT/AR/ARA70	-0.062	0.18	-9999	-0.48	71	71
LATS2	0.001	0.1	-9999	-0.72	10	10
T-DHT/AR/PRX1	-0.077	0.15	-9999	-0.45	69	69
Cyclin D3/CDK11 p58	0	0.004	-9999	-10000	0	0
VAV3	-0.031	0.15	-9999	-0.72	21	21
KLK2	0.001	0.076	-9999	-10000	0	0
CASP8	0.016	0	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.043	0.16	-9999	-0.44	69	69
TMPRSS2	-0.25	0.49	-9999	-1.1	126	126
CCND1	-0.027	0.12	-9999	-0.72	12	12
PIAS1	0.019	0.007	-9999	-10000	0	0
mol:T-DHT	-0.018	0.041	-9999	-0.081	146	146
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.019	0.016	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.09	0.17	-9999	-0.49	76	76
CMTM2	0.016	0	-9999	-10000	0	0
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	0.001	0.037	-9999	-10000	0	0
CCND3	0.016	0.007	-9999	-10000	0	0
TGIF1	0.013	0.032	-9999	-0.72	1	1
FKBP4	0.012	0.031	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.11	0.099	0.18	1	-0.34	1	2
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.014	0.02	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
STXBP4	0.014	0.02	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.1	0.14	-10000	0	-0.22	289	289
YWHAZ	0.014	0.017	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
TBC1D4	0.005	0.11	-10000	0	-0.54	21	21
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.015	0.012	-10000	0	-10000	0	0
YWHAB	0.015	0.012	-10000	0	-10000	0	0
SNARE/Synip	0.001	0.01	-10000	0	-10000	0	0
YWHAG	0.016	0.01	-10000	0	-10000	0	0
ASIP	0	0	-10000	0	-10000	0	0
PRKCI	0.013	0.022	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.015	0.032	-10000	0	-0.72	1	1
GYS1	0.04	0.003	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
TRIP10	0.015	0.032	-10000	0	-0.72	1	1
TC10/GTP/CIP4/Exocyst	-0.002	0.029	-10000	0	-0.47	2	2
AS160/14-3-3	0.049	0.047	-10000	0	-10000	0	0
VAMP2	0.016	0	-10000	0	-10000	0	0
SLC2A4	-0.11	0.15	-10000	0	-0.24	289	289
STX4	0.016	0	-10000	0	-10000	0	0
GSK3B	0.033	0.002	-10000	0	-10000	0	0
SFN	0.012	0.048	-10000	0	-0.72	2	2
LNPEP	0.015	0.016	-10000	0	-10000	0	0
YWHAE	0.015	0.032	-10000	0	-0.72	1	1

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.002	0.11	-9999	-0.72	12	12
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.006	0.085	-9999	-0.72	7	7
RAC1-CDC42/GTP/PAK family	-0.14	0.14	-9999	-0.25	321	321
response to UV	0	0	-9999	-10000	0	0
YES1	0.015	0.032	-9999	-0.72	1	1
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
FYN	0.013	0.045	-9999	-0.72	2	2
MAP3K12	0.016	0	-9999	-10000	0	0
FGR	0.016	0	-9999	-10000	0	0
p38 alpha/TAB1	0.02	0.04	-9999	-0.35	1	1
PRKG1	0.016	0	-9999	-10000	0	0
DUSP8	0.016	0.007	-9999	-10000	0	0
PGK/cGMP/p38 alpha	-0.005	0.028	-9999	-0.34	1	1
apoptosis	-0.005	0.028	-9999	-0.34	1	1
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.016	0.01	-9999	-10000	0	0
DUSP1	-0.3	0.36	-9999	-0.72	225	225
PAK1	-0.01	0.06	-9999	-10000	0	0
SRC	0.016	0.007	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0.004	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.036	0.06	-9999	-0.28	12	12
BLK	0.002	0.045	-9999	-10000	0	0
HCK	0.013	0.024	-9999	-10000	0	0
MAP2K3	0.016	0.007	-9999	-10000	0	0
DUSP16	0.014	0.034	-9999	-0.72	1	1
DUSP10	0.013	0.037	-9999	-0.72	1	1
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0.016	0	-9999	-10000	0	0
MAPK14	0.045	0.047	-9999	-0.38	1	1
positive regulation of innate immune response	0.044	0.066	-9999	-0.3	12	12
LCK	0	0.049	-9999	-10000	0	0
p38alpha-beta/MKP7	0.051	0.066	-9999	-0.34	2	2
p38alpha-beta/MKP5	0.051	0.066	-9999	-0.32	3	3
PGK/cGMP	0	0	-9999	-10000	0	0
PAK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.1	0.19	-9999	-0.34	151	151
CDC42	0.016	0	-9999	-10000	0	0
RALB	0.016	0	-9999	-10000	0	0
RALA	0.016	0	-9999	-10000	0	0
PAK3	-0.43	0.36	-9999	-0.72	321	321

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.027	0.01	-9999	-10000	0	0
Syndecan-4/Syndesmos	0.043	0.02	-9999	-10000	0	0
positive regulation of JNK cascade	-0.073	0.17	-9999	-0.39	8	8
Syndecan-4/ADAM12	0.05	0.03	-9999	-10000	0	0
CCL5	0.006	0.08	-9999	-0.72	6	6
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.016	0.007	-9999	-10000	0	0
ITGA5	0.016	0.007	-9999	-10000	0	0
SDCBP	0.015	0.032	-9999	-0.72	1	1
PLG	0.003	0.031	-9999	-0.7	1	1
ADAM12	-0.013	0.069	-9999	-0.72	1	1
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.015	0.012	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.038	0.025	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	0.042	0.02	-9999	-10000	0	0
Syndecan-4/CXCL12/CXCR4	-0.07	0.18	-9999	-0.41	8	8
Syndecan-4/Laminin alpha3	-0.091	0.19	-9999	-0.38	3	3
MDK	0.004	0.043	-9999	-10000	0	0
Syndecan-4/FZD7	-0.076	0.18	-9999	-0.38	4	4
Syndecan-4/Midkine	0.046	0.025	-9999	-10000	0	0
FZD7	-0.2	0.34	-9999	-0.72	156	156
Syndecan-4/FGFR1/FGF	-0.25	0.16	-9999	-0.65	13	13
THBS1	0.012	0.027	-9999	-10000	0	0
integrin-mediated signaling pathway	0.042	0.026	-9999	-10000	0	0
positive regulation of MAPKKK cascade	-0.073	0.17	-9999	-0.39	8	8
Syndecan-4/TACI	0.042	0.02	-9999	-10000	0	0
CXCR4	0.004	0.043	-9999	-10000	0	0
cell adhesion	0.032	0.008	-9999	-10000	0	0
Syndecan-4/Dynamin	0.042	0.02	-9999	-10000	0	0
Syndecan-4/TSP1	0.044	0.021	-9999	-10000	0	0
Syndecan-4/GIPC	0.043	0.02	-9999	-10000	0	0
Syndecan-4/RANTES	0.038	0.046	-9999	-10000	0	0
ITGB1	0.016	0	-9999	-10000	0	0
LAMA1	0.016	0.01	-9999	-10000	0	0
LAMA3	-0.23	0.35	-9999	-0.72	176	176
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.017	0.014	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	0.042	0.02	-9999	-10000	0	0
TFPI	-0.28	0.36	-9999	-0.72	207	207
F2	0.018	0.001	-9999	-10000	0	0
alpha5/beta1 Integrin	0	0.003	-9999	-10000	0	0
positive regulation of cell adhesion	-0.079	0.19	-9999	-0.4	2	2
ACTN1	0.016	0	-9999	-10000	0	0
TNC	0.01	0.042	-9999	-0.72	1	1
Syndecan-4/CXCL12	-0.082	0.18	-9999	-0.38	2	2
FGF6	0.013	0.045	-9999	-0.72	2	2
RHOA	0.016	0	-9999	-10000	0	0
CXCL12	-0.21	0.34	-9999	-0.72	164	164
TNFRSF13B	0.016	0.01	-9999	-10000	0	0
FGF2	-0.55	0.31	-9999	-0.72	403	403
FGFR1	-0.007	0.12	-9999	-0.72	15	15
Syndecan-4/PI-4-5-P2	0.031	0.02	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.1	0.077	-9999	-10000	0	0
cell migration	-0.02	0.012	-9999	-10000	0	0
PRKCD	0.002	0.019	-9999	-10000	0	0
vasculogenesis	0.043	0.021	-9999	-10000	0	0
SDC4	0.034	0.021	-9999	-10000	0	0
Syndecan-4/Tenascin C	0.043	0.027	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2/PKC alpha	-0.03	0.02	-9999	-10000	0	0
Syndecan-4/Syntenin	0.042	0.027	-9999	-10000	0	0
MMP9	-0.057	0.081	-9999	-10000	0	0
Rac1/GTP	0.025	0.014	-9999	-10000	0	0
cytoskeleton organization	0.042	0.02	-9999	-10000	0	0
GIPC1	0.015	0.012	-9999	-10000	0	0
Syndecan-4/TFPI	-0.11	0.19	-9999	-0.38	3	3

×

Caspase cascade in apoptosis

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
TOP1	0.052	0.046	0.23	15	-10000	0	15
ACTA1	-0.005	0.088	0.27	4	-0.35	1	5
NUMA1	0.052	0.048	0.23	15	-10000	0	15
SPTAN1	0.048	0.057	0.3	2	-10000	0	2
LIMK1	0.038	0.063	0.28	14	-10000	0	14
BIRC3	-0.038	0.18	-10000	0	-0.72	35	35
BIRC2	0.016	0	-10000	0	-10000	0	0
BAX	0.015	0.014	-10000	0	-10000	0	0
CASP10	0.031	0.04	-10000	0	-0.46	2	2
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.053	0.047	0.23	15	-10000	0	15
DIABLO	0.016	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.048	0.057	0.28	11	-10000	0	11
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
GSN	-0.067	0.19	-10000	0	-0.38	126	126
MADD	0.016	0	-10000	0	-10000	0	0
TFAP2A	0.041	0.01	-10000	0	-10000	0	0
BID	0.029	0.02	-10000	0	-0.24	2	2
MAP3K1	0.026	0.05	-10000	0	-0.42	4	4
TRADD	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.006	0.012	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.046	0.06	0.27	15	-0.32	1	16
CASP9	0.017	0.001	-10000	0	-10000	0	0
DNA repair	-0.032	0.052	-10000	0	-0.23	33	33
neuron apoptosis	0.031	0.065	-10000	0	-0.62	5	5
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.056	0.053	0.29	2	-10000	0	2
APAF1	0.016	0.007	-10000	0	-10000	0	0
CASP6	0.057	0.025	-10000	0	-10000	0	0
TRAF2	0.015	0.012	-10000	0	-10000	0	0
ICAD/CAD	0.056	0.054	0.3	2	-10000	0	2
CASP7	0.018	0.085	0.32	35	-0.56	1	36
KRT18	0.035	0.014	-10000	0	-10000	0	0
apoptosis	0.038	0.098	0.31	10	-0.31	4	14
DFFA	0.048	0.057	0.27	15	-10000	0	15
DFFB	0.048	0.057	0.28	11	-10000	0	11
PARP1	0.032	0.052	0.23	33	-10000	0	33
actin filament polymerization	0.031	0.16	0.36	91	-0.3	2	93
TNF	0.012	0.025	-10000	0	-10000	0	0
CYCS	0.041	0.032	-10000	0	-0.18	2	2
SATB1	0.016	0.13	-10000	0	-0.35	51	51
SLK	0.047	0.06	0.27	15	-0.38	1	16
p15 BID/BAX	0.034	0.018	-10000	0	-10000	0	0
CASP2	0.05	0.056	-10000	0	-10000	0	0
JNK cascade	-0.026	0.05	0.42	4	-10000	0	4
CASP3	0.041	0.062	0.29	15	-10000	0	15
LMNB2	0.063	0.026	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
CASP4	0.005	0.09	-10000	0	-0.72	8	8
Mammalian IAPs/DIABLO	-0.025	0.11	-10000	0	-0.42	35	35
negative regulation of DNA binding	0.041	0.01	-10000	0	-10000	0	0
stress fiber formation	0.047	0.06	0.27	15	-0.38	1	16
GZMB	0.021	0.046	-10000	0	-0.54	2	2
CASP1	-0.036	0.18	-10000	0	-0.49	60	60
LMNB1	0.074	0.028	-10000	0	-10000	0	0
APP	0.031	0.066	-10000	0	-0.63	5	5
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.015	0	-10000	0	-10000	0	0
VIM	0.031	0.1	0.29	16	-0.28	11	27
LMNA	0.06	0.026	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.042	0.059	-10000	0	-10000	0	0
LRDD	0.016	0	-10000	0	-10000	0	0
SREBF1	0.041	0.061	0.28	14	-10000	0	14
APAF-1/Caspase 9	0.012	0.043	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.052	0.048	0.23	15	-10000	0	15
CFL2	-0.032	0.17	0.3	2	-0.37	91	93
GAS2	-0.22	0.2	0.27	4	-0.38	318	322
positive regulation of apoptosis	0.072	0.028	-10000	0	-10000	0	0
PRF1	0.012	0.025	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.019	0.15	-9999	-0.72	23	23
PLK4	-0.009	0.059	-9999	-10000	0	0
regulation of centriole replication	-0.014	0.12	-9999	-0.56	23	23

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.015	0.032	-9999	-0.72	1	1
GNB1/GNG2	-0.042	0.15	-9999	-0.68	19	19
mol:DAG	0.013	0.15	-9999	-0.6	19	19
PLCG1	0.012	0.16	-9999	-0.63	19	19
YES1	-0.006	0.17	-9999	-0.73	18	18
FZD3	-0.019	0.16	-9999	-0.72	25	25
FZD6	-0.024	0.16	-9999	-0.72	26	26
G protein	0.011	0.16	-9999	-0.64	19	19
MAP3K7	0.032	0.13	-9999	-0.48	19	19
mol:Ca2+	0.014	0.14	-9999	-0.58	19	19
mol:IP3	0.013	0.15	-9999	-0.6	19	19
NLK	0.031	0.016	-9999	-10000	0	0
GNB1	0.016	0.01	-9999	-10000	0	0
CAMK2A	0.023	0.14	-9999	-0.53	19	19
MAP3K7IP1	0.016	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.016	0.18	-9999	-0.41	72	72
CSNK1A1	0.016	0	-9999	-10000	0	0
GNAS	-0.007	0.17	-9999	-0.71	18	18
GO:0007205	0.013	0.15	-9999	-0.59	19	19
WNT6	0.012	0.048	-9999	-0.72	2	2
WNT4	0.005	0.05	-9999	-0.72	1	1
NFAT1/CK1 alpha	-0.036	0.14	-9999	-0.64	18	18
GNG2	0.015	0.032	-9999	-0.72	1	1
WNT5A	-0.029	0.17	-9999	-0.72	28	28
WNT11	-0.001	0.1	-9999	-0.72	10	10
CDC42	0.004	0.16	-9999	-0.68	18	18

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-9999	-10000	0	0
HDAC2	0.014	0.017	-9999	-10000	0	0
GNB1/GNG2	-0.018	0.095	-9999	-0.46	23	23
forebrain development	-0.018	0.19	-9999	-0.52	53	53
GNAO1	0.017	0	-9999	-10000	0	0
SMO/beta Arrestin2	0.006	0.11	-9999	-0.54	22	22
SMO	-0.015	0.15	-9999	-0.72	22	22
ARRB2	0.018	0	-9999	-10000	0	0
GLI3/SPOP	0.051	0.074	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
GSK3B	0.016	0.01	-9999	-10000	0	0
GNAI2	0.017	0.007	-9999	-10000	0	0
SIN3/HDAC complex	0.001	0.009	-9999	-10000	0	0
GNAI1	-0.25	0.35	-9999	-0.72	189	189
XPO1	0.021	0.001	-9999	-10000	0	0
GLI1/Su(fu)	-0.048	0.14	-9999	-0.86	8	8
SAP30	0.016	0.007	-9999	-10000	0	0
mol:GDP	-0.015	0.15	-9999	-0.72	22	22
MIM/GLI2A	0.017	0.04	-9999	-10000	0	0
IFT88	0.015	0.032	-9999	-0.72	1	1
GNAI3	0.017	0	-9999	-10000	0	0
GLI2	0.053	0.038	-9999	-10000	0	0
GLI3	0.045	0.078	-9999	-10000	0	0
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.015	0.032	-9999	-0.72	1	1
GNG2	0.015	0.032	-9999	-0.72	1	1
Gi family/GTP	-0.066	0.16	-9999	-0.25	204	204
SIN3B	0.014	0.016	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
GLI3/Su(fu)	0.067	0.059	-9999	-0.39	1	1
GLI2/Su(fu)	0.066	0.059	-9999	-0.34	1	1
FOXA2	0.009	0.028	-9999	-10000	0	0
neural tube patterning	-0.018	0.19	-9999	-0.52	53	53
SPOP	0.016	0.007	-9999	-10000	0	0
Su(fu)/PIAS1	0.033	0.055	-9999	-0.41	1	1
GNB1	0.016	0.01	-9999	-10000	0	0
CSNK1G2	0.016	0	-9999	-10000	0	0
CSNK1G3	0.016	0	-9999	-10000	0	0
MTSS1	0.017	0.04	-9999	-10000	0	0
embryonic limb morphogenesis	-0.018	0.19	-9999	-0.52	53	53
SUFU	0.027	0.061	-9999	-0.46	1	1
LGALS3	-0.074	0.24	-9999	-0.72	64	64
catabolic process	0.08	0.073	-9999	-10000	0	0
GLI3A/CBP	-0.012	0.12	-9999	-0.37	54	54
KIF3A	0.016	0	-9999	-10000	0	0
GLI1	-0.012	0.19	-9999	-0.53	53	53
RAB23	0.014	0.017	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
IFT172	0.015	0.032	-9999	-0.72	1	1
RBBP7	0.012	0.026	-9999	-10000	0	0
Su(fu)/Galectin3	-0.022	0.16	-9999	-0.43	65	65
GNAZ	0.009	0.078	-9999	-0.72	6	6
RBBP4	0.016	0.007	-9999	-10000	0	0
CSNK1G1	0.016	0.01	-9999	-10000	0	0
PIAS1	0.016	0.007	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GLI2/SPOP	0.057	0.036	-9999	-10000	0	0
STK36	0.019	0.032	-9999	-0.72	1	1
Gi family/GNB1/GNG2/GDP	-0.057	0.15	-9999	-0.52	14	14
PTCH1	-0.004	0.17	-9999	-0.82	7	7
MIM/GLI1	0.001	0.19	-9999	-0.55	39	39
CREBBP	-0.012	0.12	-9999	-0.37	54	54
Su(fu)/SIN3/HDAC complex	0.058	0.017	-9999	-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	0.047	0.08	-10000	0	-10000	0	0
UGCG	0.009	0.046	-10000	0	-0.75	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.017	0.17	-10000	0	-0.37	40	40
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	0.028	0.047	-10000	0	-0.74	1	1
mol:DAG	-0.005	0.075	-10000	0	-0.99	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.087	0.15	-10000	0	-0.46	40	40
FRAP1	-0.012	0.23	-10000	0	-0.53	42	42
FOXO3	0.027	0.16	-10000	0	-0.45	20	20
AKT1	0.017	0.17	-10000	0	-0.43	35	35
GAB2	0.012	0.017	-10000	0	-10000	0	0
SMPD1	-0.001	0.018	-10000	0	-10000	0	0
SGMS1	-0.005	0.053	-10000	0	-0.66	3	3
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	-0.025	0.14	-10000	0	-0.46	51	51
CALM1	0.016	0	-10000	0	-10000	0	0
cell proliferation	0.026	0.091	-10000	0	-0.26	27	27
EIF3A	0.016	0.007	-10000	0	-10000	0	0
PI3K	-0.03	0.17	-10000	0	-0.54	51	51
RPS6KB1	0.009	0.071	-10000	0	-10000	0	0
mol:sphingomyelin	-0.005	0.075	-10000	0	-0.99	3	3
natural killer cell activation	-0.001	0.005	-10000	0	-0.013	28	28
JAK3	0.017	0.007	-10000	0	-10000	0	0
PIK3R1	-0.056	0.22	-10000	0	-0.72	51	51
JAK1	0.013	0.046	-10000	0	-0.72	2	2
NFKB1	0.016	0	-10000	0	-10000	0	0
MYC	-0.006	0.27	-10000	0	-1	29	29
MYB	-0.062	0.36	-10000	0	-1.3	41	41
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.04	0.11	-10000	0	-0.35	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.026	0.07	-10000	0	-0.59	1	1
mol:PI-3-4-5-P3	0.04	0.11	-10000	0	-0.34	2	2
Rac1/GDP	-0.015	0.13	-10000	0	-0.41	51	51
T cell proliferation	0.039	0.1	-10000	0	-0.32	2	2
SHC1	0.014	0.007	-10000	0	-10000	0	0
RAC1	0.016	0.001	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.001	0.02	-10000	0	-0.067	41	41
PRKCZ	0.038	0.1	-10000	0	-0.34	2	2
NF kappa B1 p50/RelA	-0.084	0.15	-10000	0	-0.45	40	40
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.032	0.087	-10000	0	-10000	0	0
HSP90AA1	0.016	0.01	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL2RA	0.004	0.039	-10000	0	-10000	0	0
IL2RB	0.014	0.024	-10000	0	-10000	0	0
TERT	0.013	0.036	-10000	0	-0.72	1	1
E2F1	0.001	0.13	-10000	0	-0.44	41	41
SOS1	0.013	0.008	-10000	0	-10000	0	0
RPS6	0.015	0.032	-10000	0	-0.72	1	1
mol:cAMP	-0.001	0.009	0.031	41	-10000	0	41
PTPN11	0.014	0.008	-10000	0	-10000	0	0
IL2RG	0.006	0.039	-10000	0	-10000	0	0
actin cytoskeleton organization	0.039	0.1	-10000	0	-0.32	2	2
GRB2	0.01	0.023	-10000	0	-10000	0	0
IL2	0.014	0.034	-10000	0	-0.72	1	1
PIK3CA	0.016	0.011	-10000	0	-10000	0	0
Rac1/GTP	-0.007	0.13	-10000	0	-0.39	51	51
LCK	0	0.049	-10000	0	-10000	0	0
BCL2	-0.11	0.41	-10000	0	-0.91	104	104

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.007	0.15	-9999	-0.53	37	37
KLHL20	-0.014	0.049	-9999	-0.25	4	4
CYFIP2	-0.002	0.051	-9999	-10000	0	0
Rac1/GDP	0.046	0.1	-9999	-0.31	37	37
ENAH	0.01	0.15	-9999	-0.53	37	37
AP1M1	0.016	0	-9999	-10000	0	0
RAP1B	0.016	0.01	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.01	0.065	-9999	-0.72	4	4
CDC42/GTP	-0.019	0.064	-9999	-0.45	1	1
ABI1/Sra1/Nap1	-0.011	0.032	-9999	-0.18	3	3
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.028	0.11	-9999	-0.41	37	37
RAPGEF1	0.03	0.13	-9999	-0.44	37	37
CTNND1	0.016	0.007	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.039	0.14	-9999	-0.55	37	37
CRK	0.02	0.14	-9999	-0.49	37	37
E-cadherin/gamma catenin/alpha catenin	-0.028	0.11	-9999	-0.46	34	34
alphaE/beta7 Integrin	0	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
NCKAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.007	0.058	-9999	-0.42	10	10
DLG1	0.01	0.15	-9999	-0.53	37	37
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.029	0.064	-9999	-0.31	3	3
MLLT4	0.002	0.1	-9999	-0.72	10	10
ARF6/GTP/NME1/Tiam1	0.003	0.015	-9999	-10000	0	0
PI3K	-0.038	0.083	-9999	-0.42	3	3
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.036	0.13	-9999	-0.54	34	34
TIAM1	0.015	0.012	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	-0.026	0.1	-9999	-0.39	37	37
AKT1	-0.02	0.048	-9999	-0.22	3	3
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
CDH1	-0.032	0.18	-9999	-0.72	33	33
RhoA/GDP	0.046	0.1	-9999	-0.31	37	37
actin cytoskeleton organization	-0.007	0.039	-9999	-0.18	4	4
CDC42/GDP	0.046	0.1	-9999	-0.31	37	37
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.01	0.083	-9999	-0.3	34	34
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.028	0.11	-9999	-0.41	37	37
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.027	0.1	-9999	-0.4	37	37
mol:GDP	0.039	0.12	-9999	-0.36	37	37
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.014	0.035	-9999	-0.72	1	1
p120 catenin/RhoA/GDP	-0.023	0.081	-9999	-0.38	3	3
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0.003	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.018	0.059	-9999	-0.22	17	17
NME1	0.011	0.029	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.009	0.15	-9999	-0.53	38	38
regulation of cell-cell adhesion	-0.017	0.056	-9999	-0.38	1	1
WASF2	-0.004	0.017	-9999	-10000	0	0
Rap1/GTP	-0.021	0.075	-9999	-0.53	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.023	0.095	-9999	-0.38	34	34
CCND1	0.019	0.072	-9999	-0.27	17	17
VAV2	0.024	0.14	-9999	-0.47	37	37
RAP1/GDP	-0.015	0.081	-9999	-0.52	1	1
adherens junction assembly	0.01	0.15	-9999	-0.51	38	38
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
PIP5K1C	0.016	0.007	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.024	0.093	-9999	-0.36	38	38
E-cadherin/beta catenin	-0.029	0.11	-9999	-0.45	33	33
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.003	0.15	-9999	-0.53	37	37
PIK3CA	0.016	0.007	-9999	-10000	0	0
Rac1/GTP	-0.025	0.077	-9999	-0.35	10	10
E-cadherin/beta catenin/alpha catenin	-0.031	0.12	-9999	-0.46	37	37
ITGAE	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.04	0.14	-9999	-0.56	37	37

×

Arf6 trafficking 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.41	0.36	-10000	0	-0.72	302	302
CLTC	0.038	0.014	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.026	0.04	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.001	0.009	-10000	0	-10000	0	0
EXOC4	0.016	0	-10000	0	-10000	0	0
CD59	0.029	0.041	-10000	0	-0.32	3	3
CPE	-0.065	0.19	-10000	0	-0.47	95	95
CTNNB1	0.01	0.065	-10000	0	-0.72	4	4
membrane fusion	0.025	0.043	-10000	0	-10000	0	0
CTNND1	0.039	0.013	-10000	0	-10000	0	0
DNM2	0.016	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.037	0.023	-10000	0	-10000	0	0
TSHR	0.02	0.043	-10000	0	-0.47	4	4
INS	0.024	0.008	-10000	0	-10000	0	0
BIN1	0.016	0.007	-10000	0	-10000	0	0
mol:Choline	0.025	0.043	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.021	0.015	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.008	-10000	0	-10000	0	0
JUP	0.032	0.022	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0	0.003	-10000	0	-10000	0	0
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.015	0.069	-10000	0	-0.34	1	1
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.013	0.046	-10000	0	-0.72	2	2
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.008	0.036	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.054	0.015	-10000	0	-0.29	1	1
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.016	0.007	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.012	0.049	0.36	4	-10000	0	4
positive regulation of phagocytosis	0.024	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	-0.002	0.029	-10000	0	-0.47	2	2
ACAP1	0.023	0.033	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.031	0.02	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.041	0.027	-10000	0	-10000	0	0
JIP4/KLC1	0	0.003	-10000	0	-10000	0	0
EXOC1	0.016	0	-10000	0	-10000	0	0
exocyst	0.054	0.015	-10000	0	-0.3	1	1
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0.003	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.039	0.013	-10000	0	-10000	0	0
NME1	0.021	0.015	-10000	0	-10000	0	0
clathrin coat assembly	0.038	0.014	-10000	0	-10000	0	0
IL2RA	0.031	0.019	-10000	0	-10000	0	0
VAMP3	0.024	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.2	0.17	-10000	0	-0.34	302	302
EXOC6	0.014	0.034	-10000	0	-0.72	1	1
PLD1	-0.013	0.062	-10000	0	-0.32	21	21
PLD2	-0.001	0.014	-10000	0	-0.32	1	1
EXOC5	0.016	0	-10000	0	-10000	0	0
PIP5K1C	0.037	0.023	-10000	0	-10000	0	0
SDC1	0.026	0.021	-10000	0	-10000	0	0
ARF6/GDP	0.02	0.015	-10000	0	-10000	0	0
EXOC7	0.016	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.012	0.05	-10000	0	-0.37	4	4
mol:Phosphatidic acid	0.025	0.043	-10000	0	-10000	0	0
endocytosis	0	0.003	-10000	0	-10000	0	0
SCAMP2	0.016	0	-10000	0	-10000	0	0
ADRB2	-0.17	0.2	-10000	0	-0.36	284	284
EXOC3	0.016	0	-10000	0	-10000	0	0
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.03	0.014	-10000	0	-10000	0	0
KLC1	0.016	0	-10000	0	-10000	0	0
AVPR2	0.044	0.028	-10000	0	-0.36	2	2
RALA	0.016	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.009	0.044	-10000	0	-0.37	1	1

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.002	0.13	-10000	0	-0.4	15	15
IKBKB	0.047	0.045	0.23	1	-10000	0	1
AKT1	0.032	0.082	0.26	13	-0.24	9	22
IKBKG	0.051	0.045	0.23	1	-10000	0	1
CALM1	0.028	0.074	-10000	0	-0.36	12	12
PIK3CA	0.016	0.007	-10000	0	-10000	0	0
MAP3K1	0.049	0.1	-10000	0	-0.56	13	13
MAP3K7	0.016	0.01	-10000	0	-10000	0	0
mol:Ca2+	0.019	0.078	0.24	15	-0.39	12	27
DOK1	0.014	0.019	-10000	0	-10000	0	0
AP-1	-0.11	0.12	-10000	0	-0.26	114	114
LYN	0.016	0.01	-10000	0	-10000	0	0
BLNK	0.011	0.029	-10000	0	-10000	0	0
SHC1	0.016	0	-10000	0	-10000	0	0
BCR complex	-0.018	0.086	-10000	0	-0.54	13	13
CD22	-0.019	0.11	-10000	0	-0.69	13	13
CAMK2G	0.036	0.071	-10000	0	-0.33	12	12
CSNK2A1	0.016	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.006	0.052	-10000	0	-0.37	1	1
GO:0007205	0.019	0.079	0.24	15	-0.4	12	27
SYK	0.01	0.03	-10000	0	-10000	0	0
ELK1	0.027	0.075	-10000	0	-0.37	12	12
NFATC1	0.037	0.085	-10000	0	-0.43	15	15
B-cell antigen/BCR complex	-0.018	0.086	-10000	0	-0.54	13	13
PAG1/CSK	-0.002	0.015	-10000	0	-10000	0	0
NFKBIB	0.033	0.019	0.12	1	-10000	0	1
HRAS	0.033	0.068	-10000	0	-0.35	12	12
NFKBIA	0.033	0.019	0.12	1	-10000	0	1
NF-kappa-B/RelA/I kappa B beta	0.036	0.018	0.13	1	-10000	0	1
RasGAP/Csk	-0.007	0.088	-10000	0	-0.5	13	13
mol:GDP	0.018	0.074	0.23	15	-0.37	12	27
PTEN	-0.002	0.12	-10000	0	-0.72	13	13
CD79B	-0.003	0.12	-10000	0	-0.72	13	13
NF-kappa-B/RelA/I kappa B alpha	0.036	0.018	0.13	1	-10000	0	1
GRB2	0.013	0.022	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.013	0.14	-10000	0	-0.54	15	15
PIK3R1	-0.055	0.22	-10000	0	-0.72	51	51
mol:IP3	0.019	0.08	0.24	15	-0.4	12	27
CSK	0.016	0.01	-10000	0	-10000	0	0
FOS	-0.24	0.19	-10000	0	-0.36	361	361
CHUK	0.05	0.049	-10000	0	-0.44	1	1
IBTK	0.016	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.008	0.049	-10000	0	-0.4	4	4
PTPN6	-0.017	0.1	-10000	0	-0.64	13	13
RELA	0.016	0	-10000	0	-10000	0	0
BCL2A1	0.032	0.015	-10000	0	-10000	0	0
VAV2	-0.015	0.1	-10000	0	-0.65	13	13
ubiquitin-dependent protein catabolic process	0.037	0.019	0.13	1	-10000	0	1
BTK	0.005	0.014	-10000	0	-10000	0	0
CD19	-0.023	0.11	-10000	0	-0.69	13	13
MAP4K1	0.013	0.023	-10000	0	-10000	0	0
CD72	-0.017	0.065	-10000	0	-10000	0	0
PAG1	0.012	0.026	-10000	0	-10000	0	0
MAPK14	0.056	0.09	-10000	0	-0.46	13	13
SH3BP5	-0.006	0.13	-10000	0	-0.72	16	16
PIK3AP1	0.026	0.086	0.27	13	-0.44	12	25
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.038	0.073	-10000	0	-0.62	4	4
RAF1	0.041	0.065	-10000	0	-0.38	5	5
RasGAP/p62DOK/SHIP	-0.007	0.084	-10000	0	-0.49	13	13
CD79A	0.007	0.037	-10000	0	-10000	0	0
re-entry into mitotic cell cycle	-0.1	0.12	-10000	0	-0.25	112	112
RASA1	0.015	0.012	-10000	0	-10000	0	0
MAPK3	0.056	0.057	-10000	0	-0.33	4	4
MAPK1	0.056	0.057	-10000	0	-0.33	4	4
CD72/SHP1	0.042	0.11	-10000	0	-0.59	13	13
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.055	0.091	-10000	0	-0.46	13	13
actin cytoskeleton organization	0.038	0.098	-10000	0	-0.54	13	13
NF-kappa-B/RelA	0.076	0.035	0.24	1	-10000	0	1
Calcineurin	-0.014	0.062	-10000	0	-0.37	5	5
PI3K	-0.037	0.1	-10000	0	-0.47	14	14
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.003	0.089	0.27	15	-0.47	12	27
SOS1	0.016	0	-10000	0	-10000	0	0
Bam32/HPK1	0.033	0.12	-10000	0	-0.72	13	13
DAPP1	-0.005	0.14	-10000	0	-0.83	13	13
cytokine secretion	0.037	0.08	-10000	0	-0.4	15	15
mol:DAG	0.019	0.08	0.24	15	-0.4	12	27
PLCG2	0	0.11	-10000	0	-0.72	11	11
MAP2K1	0.049	0.062	-10000	0	-0.37	4	4
B-cell antigen/BCR complex/FcgammaRIIB	-0.012	0.099	-10000	0	-0.59	13	13
mol:PI-3-4-5-P3	-0.021	0.094	0.34	13	-0.33	14	27
ETS1	0.043	0.068	-10000	0	-0.38	5	5
B-cell antigen/BCR complex/LYN/SYK/BLNK	0	0.069	-10000	0	-0.38	13	13
B-cell antigen/BCR complex/LYN	-0.016	0.12	-10000	0	-0.73	13	13
MALT1	0.016	0.007	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
RAC1	0.038	0.1	-10000	0	-0.59	13	13
B-cell antigen/BCR complex/LYN/SYK	-0.012	0.1	-10000	0	-0.62	13	13
CARD11	0.025	0.076	-10000	0	-0.37	12	12
FCGR2B	0.01	0.065	-10000	0	-0.72	4	4
PPP3CA	0.01	0.065	-10000	0	-0.72	4	4
BCL10	0.016	0.007	-10000	0	-10000	0	0
IKK complex	0.036	0.027	0.14	2	-0.12	1	3
PTPRC	0.006	0.057	-10000	0	-0.72	2	2
PDPK1	0.022	0.076	0.23	13	-0.25	6	19
PPP3CB	0.016	0	-10000	0	-10000	0	0
PPP3CC	0.006	0.085	-10000	0	-0.72	7	7
POU2F2	0.033	0.013	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.011	0.029	-9999	-10000	0	0
Caspase 8 (4 units)	-0.039	0.13	-9999	-0.56	16	16
NEF	0.002	0.015	-9999	-10000	0	0
NFKBIA	0.01	0.048	-9999	-0.85	1	1
BIRC3	0	0.2	-9999	-0.74	35	35
CYCS	0.013	0.13	-9999	-0.52	15	15
RIPK1	0.016	0	-9999	-10000	0	0
CD247	-0.027	0.16	-9999	-0.72	25	25
MAP2K7	0.022	0.12	-9999	-0.48	12	12
protein ubiquitination	0.068	0.068	-9999	-0.37	1	1
CRADD	0.016	0	-9999	-10000	0	0
DAXX	0.016	0.007	-9999	-10000	0	0
FAS	-0.033	0.18	-9999	-0.72	35	35
BID	0.003	0.14	-9999	-0.54	16	16
NF-kappa-B/RelA/I kappa B alpha	-0.023	0.083	-9999	-0.32	35	35
TRADD	0.016	0	-9999	-10000	0	0
MAP3K5	-0.033	0.18	-9999	-0.72	35	35
CFLAR	0.013	0.045	-9999	-0.72	2	2
FADD	0.002	0.046	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.023	0.084	-9999	-0.32	35	35
MAPK8	0.03	0.11	-9999	-0.49	10	10
APAF1	0.016	0.007	-9999	-10000	0	0
TRAF1	0.015	0.016	-9999	-10000	0	0
TRAF2	0.015	0.012	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.006	0.14	-9999	-0.35	64	64
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.056	0.076	-9999	-0.34	1	1
CHUK	0.07	0.071	-9999	-0.41	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.044	0.15	-9999	-0.42	64	64
TCRz/NEF	-0.031	0.12	-9999	-0.55	25	25
TNF	0.012	0.025	-9999	-10000	0	0
FASLG	-0.004	0.12	-9999	-0.48	25	25
NFKB1	0.012	0.03	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.004	0.019	-9999	-10000	0	0
CASP6	-0.03	0.096	-9999	-0.61	7	7
CASP7	0.028	0.2	-9999	-0.58	41	41
RELA	0.012	0.03	-9999	-10000	0	0
CASP2	0.016	0.007	-9999	-10000	0	0
CASP3	0.029	0.19	-9999	-0.58	41	41
TNFRSF1A	0.016	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.003	0.014	-9999	-10000	0	0
CASP8	0.016	0	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
MAP3K14	0.064	0.073	-9999	-10000	0	0
APAF-1/Caspase 9	-0.049	0.13	-9999	-0.48	40	40
BCL2	-0.036	0.18	-9999	-0.42	36	36

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.029	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.001	0.01	-10000	0	-10000	0	0
CDKN1B	0.047	0.053	-10000	0	-0.36	9	9
CDKN1A	0.052	0.026	-10000	0	-0.36	2	2
FRAP1	0.016	0	-10000	0	-10000	0	0
PRKDC	0.01	0.03	-10000	0	-10000	0	0
FOXO3	0.054	0.003	-10000	0	-10000	0	0
AKT1	0.003	0.011	-10000	0	-10000	0	0
BAD	0.016	0	-10000	0	-10000	0	0
AKT3	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.054	0.002	-10000	0	-10000	0	0
AKT1/ASK1	-0.02	0.088	-10000	0	-0.35	35	35
BAD/YWHAZ	0.001	0.009	-10000	0	-10000	0	0
RICTOR	0.016	0	-10000	0	-10000	0	0
RAF1	0.016	0.007	-10000	0	-10000	0	0
JNK cascade	0.02	0.085	0.34	35	-10000	0	35
TSC1	0.054	0.002	-10000	0	-10000	0	0
YWHAZ	0.014	0.017	-10000	0	-10000	0	0
AKT1/RAF1	0.053	0.003	-10000	0	-10000	0	0
EP300	0.016	0	-10000	0	-10000	0	0
mol:GDP	0.003	0.011	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.054	0.002	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
TBC1D4	0.012	0.095	-10000	0	-0.45	21	21
MAP3K5	-0.033	0.18	-10000	0	-0.72	35	35
MAPKAP1	0.016	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.055	0.017	-10000	0	-10000	0	0
YWHAH	0.015	0.012	-10000	0	-10000	0	0
AKT1S1	0.053	0.007	-10000	0	-10000	0	0
CASP9	0.054	0.002	-10000	0	-10000	0	0
YWHAB	0.015	0.012	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.054	0.051	-10000	0	-0.33	9	9
GBL	0.016	0.007	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.001	0.007	-10000	0	-10000	0	0
YWHAE	0.015	0.032	-10000	0	-0.72	1	1
SRC	0.016	0.007	-10000	0	-10000	0	0
AKT2/p21CIP1	0.002	0.025	-10000	0	-0.34	2	2
KIAA1303	0.016	0.01	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.048	0.001	-10000	0	-10000	0	0
CHUK	0.053	0.018	-10000	0	-0.36	1	1
BAD/BCL-XL	0.069	0.002	-10000	0	-10000	0	0
mTORC2	0	0.004	-10000	0	-10000	0	0
AKT2	0.022	0.002	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.062	0.048	-10000	0	-10000	0	0
PDPK1	0.016	0.007	-10000	0	-10000	0	0
MDM2	0.052	0.011	-10000	0	-10000	0	0
MAPKKK cascade	-0.052	0.003	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.066	0.019	-10000	0	-10000	0	0
TSC1/TSC2	0.062	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.003	0.02	-10000	0	-10000	0	0
glucose import	-0.23	0.24	-10000	0	-0.42	310	310
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.062	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.24	0.24	-10000	0	-0.43	310	310
GSK3A	0.054	0.002	-10000	0	-10000	0	0
FOXO1	-0.002	0.14	-10000	0	-0.36	72	72
GSK3B	0.054	0.005	-10000	0	-10000	0	0
SFN	0.012	0.048	-10000	0	-0.72	2	2
G1/S transition of mitotic cell cycle	0.062	0.004	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.061	0.021	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
KPNA1	0.016	0	-10000	0	-10000	0	0
HSP90AA1	0.016	0.01	-10000	0	-10000	0	0
YWHAG	0.016	0.01	-10000	0	-10000	0	0
RHEB	0.016	0.007	-10000	0	-10000	0	0
CREBBP	0.015	0.032	-10000	0	-0.72	1	1

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.016	0	-9999	-10000	0	0
VLDLR	-0.1	0.27	-9999	-0.72	83	83
LRPAP1	0.016	0	-9999	-10000	0	0
NUDC	0.016	0	-9999	-10000	0	0
RELN/LRP8	0.003	0.1	-9999	-0.48	20	20
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.016	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	0.005	0.093	-9999	-0.43	20	20
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	0.016	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
PLA2G7	-0.023	0.11	-9999	-0.72	10	10
CALM1	0.016	0	-9999	-10000	0	0
DYNLT1	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.022	0.035	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.015	0.033	-9999	-0.72	1	1
CDK5R1	0.014	0.019	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0.022	0	-9999	-10000	0	0
CDK5R2	0.016	0	-9999	-10000	0	0
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.089	0.19	-9999	-0.48	98	98
YWHAE	0.015	0.032	-9999	-0.72	1	1
NDEL1/14-3-3 E	0.043	0.079	-9999	-0.37	1	1
MAP1B	-0.035	0.11	-9999	-0.36	52	52
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	0.022	0.085	-9999	-0.37	20	20
RELN	-0.013	0.14	-9999	-0.72	20	20
PAFAH/LIS1	0.033	0.071	-9999	-0.46	10	10
LIS1/CLIP170	0.033	0.022	-9999	-0.46	1	1
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.009	0.045	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.012	0.14	-9999	-0.58	5	5
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.035	0.081	-9999	-0.38	7	7
LIS1/IQGAP1	0.034	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.029	0	-9999	-10000	0	0
PAFAH1B3	-0.039	0.077	-9999	-10000	0	0
PAFAH1B2	0.016	0.007	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.008	0.075	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.004	0.06	-9999	-10000	0	0
LRP8	-0.029	0.072	-9999	-10000	0	0
NDEL1/Katanin 60	0.044	0.077	-9999	-10000	0	0
P39/CDK5	0.023	0.084	-9999	-0.37	20	20
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.034	0	-9999	-10000	0	0
CDK5	0.014	0.089	-9999	-0.4	20	20
PPP2R5D	0.015	0.012	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.001	0.018	-9999	-0.4	1	1
CSNK2A1	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.074	0.16	-9999	-0.4	98	98
RELN/VLDLR	-0.063	0.19	-9999	-0.45	98	98
CDC42	0	0	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.001	0.03	-9999	-10000	0	0
MAP4K1	0.013	0.023	-9999	-10000	0	0
MAP3K8	-0.083	0.25	-9999	-0.72	70	70
PRKCB	0	0	-9999	-10000	0	0
DBNL	0.015	0.012	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
MAP3K1	0.052	0.042	-9999	-0.36	4	4
JUN	-0.046	0.17	-9999	-0.39	98	98
MAP3K7	0.057	0.015	-9999	-10000	0	0
GRAP2	0.014	0.019	-9999	-10000	0	0
CRK	0.015	0.032	-9999	-0.72	1	1
MAP2K4	0.038	0.074	-9999	-0.48	3	3
LAT	0.012	0.026	-9999	-10000	0	0
LCP2	0.013	0.024	-9999	-10000	0	0
MAPK8	0.023	0.034	-9999	-0.57	1	1
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.05	0.015	-9999	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55	0.004	0.03	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.026	0.16	-9999	-0.48	1	1
CRKL	0.036	0.055	-9999	-0.42	1	1
mol:DAG	0.039	0.069	-9999	-0.34	1	1
HRAS	0.064	0.053	-9999	-0.35	1	1
MAPK8	0.031	0.038	-9999	-0.42	1	1
RAP1A	0.036	0.055	-9999	-0.42	1	1
GAB1	0.035	0.059	-9999	-0.44	2	2
MAPK14	0.031	0.033	-9999	-10000	0	0
EPO	-0.005	0.056	-9999	-10000	0	0
PLCG1	0.039	0.07	-9999	-0.35	1	1
EPOR/TRPC2/IP3 Receptors	0.016	0.008	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.007	0.087	-9999	-0.48	15	15
GAB1/SHC/GRB2/SOS1	-0.001	0.034	-9999	-0.37	2	2
EPO/EPOR (dimer)	0.027	0.037	-9999	-10000	0	0
IRS2	-0.071	0.2	-9999	-0.4	138	138
STAT1	0.032	0.12	-9999	-0.45	1	1
STAT5B	0.034	0.094	-9999	-0.4	1	1
cell proliferation	0.038	0.037	-9999	-0.38	1	1
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.036	0.092	-9999	-0.35	18	18
TEC	0.036	0.055	-9999	-0.42	1	1
SOCS3	-0.005	0.12	-9999	-0.72	15	15
STAT1 (dimer)	0.032	0.12	-9999	-0.38	2	2
JAK2	0.014	0.034	-9999	-0.73	1	1
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
EPO/EPOR (dimer)/JAK2	0.05	0.068	-9999	-0.45	1	1
EPO/EPOR	0.027	0.037	-9999	-10000	0	0
LYN	0.015	0.014	-9999	-10000	0	0
TEC/VAV2	0.047	0.055	-9999	-0.4	1	1
elevation of cytosolic calcium ion concentration	0.016	0.008	-9999	-10000	0	0
SHC1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.041	0.039	-9999	-10000	0	0
mol:IP3	0.039	0.069	-9999	-0.34	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.13	0.19	-9999	-0.38	178	178
SH2B3	0.015	0.008	-9999	-10000	0	0
NFKB1	0.031	0.033	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.006	0.046	-9999	-0.26	16	16
PTPN6	0.027	0.057	-9999	-0.45	1	1
TEC/VAV2/GRB2	0.054	0.054	-9999	-0.38	1	1
EPOR	0.016	0.008	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.001	0.035	-9999	-0.37	2	2
SOS1	0.016	0	-9999	-10000	0	0
PLCG2	0	0.11	-9999	-0.72	11	11
CRKL/CBL/C3G	0.053	0.052	-9999	-0.38	1	1
VAV2	0.036	0.056	-9999	-0.42	1	1
CBL	0.036	0.055	-9999	-0.42	1	1
SHC/Grb2/SOS1	-0.001	0.034	-9999	-0.38	1	1
STAT5A	0.032	0.097	-9999	-0.38	3	3
GRB2	0.013	0.022	-9999	-10000	0	0
STAT5 (dimer)	0.031	0.15	-9999	-0.55	1	1
LYN/PLCgamma2	-0.012	0.078	-9999	-0.54	11	11
PTPN11	0.016	0	-9999	-10000	0	0
BTK	0.037	0.057	-9999	-0.42	1	1
BCL2	-0.1	0.42	-9999	-0.94	104	104

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.015	0.15	-9999	-0.72	22	22
positive regulation of NF-kappaB transcription factor activity	-0.022	0.11	-9999	-0.54	22	22
MAP2K4	0.039	0.081	-9999	-0.36	8	8
IKBKB	0.014	0.02	-9999	-10000	0	0
TNFRSF10B	0.015	0.033	-9999	-0.72	1	1
TNFRSF10A	0.014	0.034	-9999	-0.72	1	1
SMPD1	0.013	0.058	-9999	-0.26	23	23
IKBKG	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.024	0.11	-9999	-0.54	23	23
TRAIL/TRAILR3	-0.023	0.11	-9999	-0.54	22	22
TRAIL/TRAILR1	-0.024	0.11	-9999	-0.54	23	23
TRAIL/TRAILR4	-0.023	0.11	-9999	-0.54	22	22
TRAIL/TRAILR1/DAP3/GTP	-0.018	0.087	-9999	-0.42	23	23
IKK complex	-0.005	0.047	-9999	-0.77	1	1
RIPK1	0.016	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	-0.001	0.008	-9999	-10000	0	0
MAPK3	0.006	0.11	-9999	-0.54	22	22
MAP3K1	0.037	0.07	-9999	-0.34	3	3
TRAILR4 (trimer)	0.016	0	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.014	0.034	-9999	-0.72	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.032	0.069	-9999	-0.29	23	23
CFLAR	0.013	0.045	-9999	-0.72	2	2
MAPK1	0.006	0.11	-9999	-0.54	22	22
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.009	0.085	-9999	-0.39	23	23
mol:ceramide	0.013	0.058	-9999	-0.26	23	23
FADD	0.002	0.046	-9999	-10000	0	0
MAPK8	0.047	0.082	-9999	-0.37	9	9
TRAF2	0.015	0.012	-9999	-10000	0	0
TRAILR3 (trimer)	0.016	0.01	-9999	-10000	0	0
CHUK	0.015	0.032	-9999	-0.72	1	1
TRAIL/TRAILR1/FADD	-0.013	0.1	-9999	-0.47	23	23
DAP3	0.015	0.014	-9999	-10000	0	0
CASP10	-0.021	0.09	-9999	-0.45	22	22
JNK cascade	-0.022	0.11	-9999	-0.54	22	22
TRAIL (trimer)	-0.015	0.15	-9999	-0.72	22	22
TNFRSF10C	0.016	0.01	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.01	0.086	-9999	-0.4	23	23
TRAIL/TRAILR2/FADD	-0.013	0.098	-9999	-0.46	23	23
cell death	0.013	0.058	-9999	-0.26	23	23
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.032	0.069	-9999	-0.29	23	23
TRAILR2 (trimer)	0.015	0.033	-9999	-0.72	1	1
CASP8	0.005	0.034	-9999	-0.3	1	1
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.009	0.084	-9999	-0.38	23	23

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.036	0.043	-9999	-0.44	4	4
VEGFR1 homodimer/NRP1	-0.004	0.04	-9999	-0.45	4	4
mol:DAG	0.046	0.04	-9999	-0.39	4	4
VEGFR1 homodimer/NRP1/VEGFR 121	0.007	0.047	-9999	-0.42	4	4
CaM/Ca2+	0.053	0.037	-9999	-10000	0	0
HIF1A	0.019	0.066	-9999	-0.7	4	4
GAB1	0.014	0.034	-9999	-0.72	1	1
AKT1	0.03	0.13	-9999	-0.7	1	1
PLCG1	0.046	0.04	-9999	-0.39	4	4
NOS3	0.064	0.056	-9999	-0.44	1	1
CBL	0.016	0	-9999	-10000	0	0
mol:NO	0.063	0.055	-9999	-0.42	1	1
FLT1	0.033	0.05	-9999	-0.52	4	4
PGF	0.016	0.01	-9999	-10000	0	0
VEGFR1 homodimer/NRP2/VEGFR121	0.01	0.05	-9999	-0.46	1	1
CALM1	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0.007	-9999	-10000	0	0
eNOS/Hsp90	0.071	0.053	-9999	-10000	0	0
endothelial cell proliferation	0.053	0.041	-9999	-0.4	1	1
mol:Ca2+	0.046	0.039	-9999	-0.38	4	4
MAPK3	0.062	0.035	-9999	-10000	0	0
MAPK1	0.062	0.035	-9999	-10000	0	0
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
PLGF homodimer	0.016	0.01	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.52	0.33	-9999	-0.72	385	385
VEGFA homodimer	-0.005	0.054	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.043	0.049	-9999	-0.46	4	4
platelet activating factor biosynthetic process	0.069	0.034	-9999	-10000	0	0
PI3K	-0.038	0.12	-9999	-0.6	2	2
PRKCA	0.054	0.037	-9999	-10000	0	0
PRKCB	0.044	0.037	-9999	-0.36	4	4
VEGFR1 homodimer/PLGF homodimer	0.036	0.043	-9999	-0.44	4	4
VEGFA	-0.005	0.054	-9999	-10000	0	0
VEGFB	0.016	0	-9999	-10000	0	0
mol:IP3	0.046	0.04	-9999	-0.39	4	4
RASA1	0.047	0.04	-9999	-0.39	4	4
NRP2	0.015	0.016	-9999	-10000	0	0
VEGFR1 homodimer	0.033	0.05	-9999	-0.52	4	4
VEGFB homodimer	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.21	0.18	-9999	-0.45	50	50
PTPN11	0.016	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.037	0.12	-9999	-0.59	2	2
mol:L-citrulline	0.063	0.055	-9999	-0.42	1	1
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.011	0.049	-9999	-0.43	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.009	0.049	-9999	-0.46	1	1
CD2AP	0.016	0.01	-9999	-10000	0	0
PI3K/GAB1	-0.036	0.11	-9999	-0.72	1	1
PDPK1	0.021	0.13	-9999	-0.7	1	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.009	0.049	-9999	-0.46	1	1
mol:NADP	0.063	0.055	-9999	-0.42	1	1
HSP90AA1	0.016	0.01	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.01	0.047	-9999	-0.42	1	1
VEGFR1 homodimer/NRP2	0.037	0.043	-9999	-0.44	4	4

×

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	0.013	0.037	-10000	0	-0.72	1	1
ANTXR2	0.002	0.1	-10000	0	-0.72	10	10
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.013	-10000	0	-0.091	11	11
monocyte activation	0.012	0.069	-10000	0	-0.45	11	11
MAP2K2	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	-0.002	0.011	-10000	0	-10000	0	0
MAP2K7	-0.002	0.011	-10000	0	-10000	0	0
MAP2K6	-0.011	0.065	-10000	0	-0.43	12	12
CYAA	0.01	0.061	-10000	0	-0.4	11	11
MAP2K4	-0.007	0.05	-10000	0	-0.43	7	7
IL1B	0.004	0.068	-10000	0	-0.39	12	12
Channel	-0.008	0.062	-10000	0	-0.43	11	11
NLRP1	-0.006	0.047	-10000	0	-0.43	6	6
CALM1	0.016	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.002	0.015	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.013	0.091	11	-10000	0	11
MAPK3	-0.002	0.011	-10000	0	-10000	0	0
MAPK1	-0.002	0.011	-10000	0	-10000	0	0
PGR	-0.14	0.18	-10000	0	-0.42	160	160
PA/Cellular Receptors	-0.009	0.068	-10000	0	-0.47	11	11
apoptosis	-0.002	0.013	-10000	0	-0.091	11	11
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.012	0.061	-10000	0	-0.4	11	11
macrophage activation	0.023	0.012	-10000	0	-10000	0	0
TNF	0.012	0.025	-10000	0	-10000	0	0
VCAM1	0.012	0.069	-10000	0	-0.46	11	11
platelet activation	-0.002	0.015	-10000	0	-10000	0	0
MAPKKK cascade	-0.015	0.027	0.19	4	-10000	0	4
IL18	0.003	0.053	-10000	0	-0.34	7	7
negative regulation of macrophage activation	-0.002	0.013	-10000	0	-0.091	11	11
LEF	-0.002	0.013	-10000	0	-0.092	11	11
CASP1	-0.012	0.046	-10000	0	-0.27	10	10
mol:cAMP	-0.002	0.015	-10000	0	-10000	0	0
necrosis	-0.002	0.013	-10000	0	-0.091	11	11
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.008	0.059	-10000	0	-0.41	11	11
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.016	0	-10000	0	-10000	0	0
HDAC4	0.016	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.011	0.009	-10000	0	-10000	0	0
CDKN1A	-0.004	0.055	-10000	0	-0.88	2	2
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.015	0.014	-10000	0	-10000	0	0
FOXO3	0	0.002	-10000	0	-10000	0	0
FOXO1	-0.085	0.25	-10000	0	-0.72	72	72
FOXO4	0.029	0.016	-10000	0	-0.33	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
TAT	0.008	0.06	-10000	0	-0.72	3	3
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.011	0.037	-10000	0	-0.55	2	2
PPARGC1A	-0.066	0.23	-10000	0	-0.72	57	57
FHL2	-0.067	0.23	-10000	0	-0.72	58	58
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.011	-10000	0	-10000	0	0
HIST2H4A	0.011	0.009	-10000	0	-10000	0	0
SIRT1/FOXO3a	0	0.01	-10000	0	-10000	0	0
SIRT1	0.001	0.015	0.21	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.011	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.005	0.018	-10000	0	-0.28	1	1
apoptosis	-0.002	0.012	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.049	0.15	-10000	0	-0.47	57	57
p53/SIRT1	0.002	0.028	0.43	2	-10000	0	2
SIRT1/FOXO4	0.001	0.017	-10000	0	-0.28	1	1
FOXO1/FHL2/SIRT1	-0.1	0.2	-10000	0	-0.47	116	116
HIST1H1E	0.022	0.018	-10000	0	-0.33	1	1
SIRT1/p300	0.001	0.011	-10000	0	-10000	0	0
muscle cell differentiation	0.002	0.031	0.47	2	-10000	0	2
TP53	0	0.016	0.21	2	-10000	0	2
KU70/SIRT1/BAX	0.002	0.012	-10000	0	-10000	0	0
CREBBP	0.015	0.032	-10000	0	-0.72	1	1
MEF2D	0.016	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.004	0.044	-10000	0	-0.54	3	3
ACSS2	0.026	0.009	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.002	0.032	-10000	0	-0.47	2	2

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.023	0.12	-9999	-10000	0	0
PLK1	0.072	0.17	-9999	-0.53	13	13
CDKN1B	0.094	0.16	-9999	-0.49	11	11
FOXO3	0.069	0.18	-9999	-0.44	35	35
KAT2B	0.007	0.02	-9999	-0.043	61	61
FOXO1/SIRT1	-0.027	0.1	-9999	-0.31	2	2
CAT	0.009	0.37	-9999	-1.2	42	42
CTNNB1	0.01	0.064	-9999	-0.72	4	4
AKT1	0.029	0.026	-9999	-0.21	1	1
FOXO1	0.014	0.13	-9999	-0.31	73	73
MAPK10	0.036	0.07	-9999	-0.39	12	12
mol:GTP	0.002	0.004	-9999	-10000	0	0
FOXO4	0.1	0.1	-9999	-0.38	2	2
response to oxidative stress	0.013	0.022	-9999	-0.041	41	41
FOXO3A/SIRT1	-0.025	0.14	-9999	-0.48	20	20
XPO1	0.017	0.001	-9999	-10000	0	0
EP300	0.02	0.002	-9999	-10000	0	0
BCL2L11	0.043	0.028	-9999	-10000	0	0
FOXO1/SKP2	0.018	0.12	-9999	-0.33	7	7
mol:GDP	0.013	0.022	-9999	-0.041	41	41
RAN	0.017	0.004	-9999	-10000	0	0
GADD45A	0.086	0.18	-9999	-0.94	10	10
YWHAQ	0.016	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.086	0.04	-9999	-10000	0	0
MST1	0.024	0.017	-9999	-10000	0	0
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.072	0.028	-9999	-10000	0	0
YWHAB	0.015	0.012	-9999	-10000	0	0
MAPK8	0.046	0.029	-9999	-0.38	1	1
MAPK9	0.046	0.022	-9999	-10000	0	0
YWHAG	0.016	0.01	-9999	-10000	0	0
YWHAE	0.015	0.032	-9999	-0.72	1	1
YWHAZ	0.014	0.017	-9999	-10000	0	0
SIRT1	0.006	0.011	-9999	-10000	0	0
SOD2	0.11	0.17	-9999	-0.49	8	8
RBL2	0.093	0.14	-9999	-0.55	1	1
RAL/GDP	0.036	0.02	-9999	-10000	0	0
CHUK	0.023	0.038	-9999	-0.75	1	1
Ran/GTP	0.016	0.006	-9999	-10000	0	0
CSNK1G2	0.016	0	-9999	-10000	0	0
RAL/GTP	0.043	0.025	-9999	-10000	0	0
CSNK1G1	0.016	0.01	-9999	-10000	0	0
FASLG	0.035	0.077	-9999	-1.6	1	1
SKP2	0.012	0.025	-9999	-10000	0	0
USP7	0.017	0.005	-9999	-10000	0	0
IKBKB	0.022	0.028	-9999	-10000	0	0
CCNB1	0.064	0.17	-9999	-0.58	9	9
FOXO1-3a-4/beta catenin	0.006	0.18	-9999	-0.4	54	54
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.12	-9999	-0.33	7	7
CSNK1A1	0.016	0	-9999	-10000	0	0
SGK1	0.007	0.02	-9999	-0.043	61	61
CSNK1G3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.028	0.01	-9999	-10000	0	0
ZFAND5	0.1	0.092	-9999	-10000	0	0
SFN	0.012	0.048	-9999	-0.72	2	2
CDK2	0.018	0.024	-9999	-10000	0	0
FOXO3A/14-3-3	0.078	0.044	-9999	-0.34	1	1
CREBBP	0.02	0.032	-9999	-0.72	1	1
FBXO32	0.028	0.33	-9999	-1.2	29	29
BCL6	-0.014	0.41	-9999	-1.2	53	53
RALB	0.017	0.002	-9999	-10000	0	0
RALA	0.017	0.002	-9999	-10000	0	0
YWHAH	0.015	0.012	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.034	0.028	-9999	-0.46	1	1
SNTA1	0.015	0.032	-9999	-0.72	1	1
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.02	0.043	-9999	-0.46	1	1
MAPK12	0.016	0.09	-9999	-0.35	29	29
CCND1	0.01	0.093	-9999	-0.54	12	12
p38 gamma/SNTA1	0.022	0.086	-9999	-0.38	14	14
MAP2K3	0.016	0.007	-9999	-10000	0	0
PKN1	0.015	0.012	-9999	-10000	0	0
G2/M transition checkpoint	0.016	0.09	-9999	-0.35	29	29
MAP2K6	0.008	0.097	-9999	-0.39	29	29
MAPT	0.03	0.044	-9999	-0.34	4	4
MAPK13	0.025	0.032	-9999	-0.54	1	1
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.008	0.076	-9999	-0.41	17	17

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0	0.019	-10000	0	-0.41	1	1
HDAC3	0.016	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.001	-10000	0	-10000	0	0
GATA1/HDAC4	0	0	-10000	0	-10000	0	0
GATA1/HDAC5	0	0	-10000	0	-10000	0	0
GATA2/HDAC5	-0.004	0.018	-10000	0	-10000	0	0
HDAC5/BCL6/BCoR	-0.046	0.14	-10000	0	-0.46	53	53
HDAC9	0.014	0.017	-10000	0	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	-0.04	0.13	-10000	0	-0.46	46	46
HDAC4/ANKRA2	-0.003	0.041	-10000	0	-0.54	3	3
HDAC5/YWHAB	0	0.006	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.027	0.003	-10000	0	-10000	0	0
GATA2	0.007	0.037	-10000	0	-10000	0	0
HDAC4/RFXANK	0	0.003	-10000	0	-10000	0	0
BCOR	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.014	0.034	-10000	0	-0.72	1	1
HDAC5	0.016	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.001	0.024	-10000	0	-0.54	1	1
Histones	0.043	0.012	-10000	0	-10000	0	0
ADRBK1	0.016	0	-10000	0	-10000	0	0
HDAC4	0.016	0	-10000	0	-10000	0	0
XPO1	0.016	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	-0.003	0.041	-10000	0	-0.54	3	3
HDAC4/Ubc9	0	0	-10000	0	-10000	0	0
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	-0.001	0.023	-10000	0	-0.54	1	1
TUBA1B	0.015	0.012	-10000	0	-10000	0	0
HDAC6	0.016	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0	0.003	-10000	0	-10000	0	0
CAMK4	0.014	0.017	-10000	0	-10000	0	0
Tubulin/HDAC6	-0.007	0.06	-10000	0	-0.46	9	9
SUMO1	0.016	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.015	0.012	-10000	0	-10000	0	0
GATA1	0.016	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.015	0.032	-10000	0	-0.72	1	1
NR3C1	-0.048	0.21	-10000	0	-0.72	46	46
SUMO1/HDAC4	0.038	0.002	-10000	0	-10000	0	0
SRF	0.016	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0	0.006	-10000	0	-10000	0	0
Tubulin	-0.01	0.07	-10000	0	-0.54	9	9
HDAC4/14-3-3 E	-0.001	0.023	-10000	0	-0.54	1	1
GNB1	0.016	0.01	-10000	0	-10000	0	0
RANGAP1	0.01	0.031	-10000	0	-10000	0	0
BCL6/BCoR	-0.054	0.16	-10000	0	-0.54	53	53
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-10000	0	-10000	0	0
HDAC4/SRF	0.001	0.009	-10000	0	-10000	0	0
HDAC4/ER alpha	-0.14	0.22	-10000	0	-0.54	117	117
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.043	0.012	-10000	0	-10000	0	0
cell motility	-0.007	0.06	-10000	0	-0.46	9	9
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.016	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0	0	-10000	0	-10000	0	0
BCL6	-0.058	0.22	-10000	0	-0.72	53	53
HDAC4/CaMK II delta B	0.016	0	-10000	0	-10000	0	0
Hsp90/HDAC6	0	0.005	-10000	0	-10000	0	0
ESR1	-0.18	0.3	-10000	0	-0.72	117	117
HDAC6/HDAC11	-0.003	0.014	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.001	0.006	-10000	0	-10000	0	0
NPC	0	0.003	-10000	0	-10000	0	0
MEF2C	-0.029	0.18	-10000	0	-0.72	32	32
RAN	0.016	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.023	0.091	-10000	0	-0.38	32	32
GNG2	0.015	0.032	-10000	0	-0.72	1	1
NCOR2	0.016	0	-10000	0	-10000	0	0
TUBB2A	0.003	0.096	-10000	0	-0.72	9	9
HDAC11	0.01	0.03	-10000	0	-10000	0	0
HSP90AA1	0.016	0.01	-10000	0	-10000	0	0
RANBP2	0.016	0.007	-10000	0	-10000	0	0
ANKRA2	0.012	0.056	-10000	0	-0.72	3	3
RFXANK	0.016	0.007	-10000	0	-10000	0	0
nuclear import	-0.036	0.018	0.39	1	-10000	0	1

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-10000	0	-10000	0	0
HDAC3	0.016	0	-10000	0	-10000	0	0
VDR	0.013	0.046	-10000	0	-0.72	2	2
Cbp/p300/PCAF	-0.001	0.02	-10000	0	-0.47	1	1
EP300	0.016	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.016	0.09	-10000	0	-0.41	2	2
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.016	0	-10000	0	-10000	0	0
AKT1	-0.009	0.13	0.24	20	-0.3	79	99
RAR alpha/9cRA/Cyclin H	-0.003	0.024	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.004	0.11	-10000	0	-0.24	85	85
CDC2	-0.066	0.081	-10000	0	-10000	0	0
response to UV	0.001	0.004	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.002	0.026	-10000	0	-0.57	1	1
NCOR2	0.016	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.034	-10000	0	-0.55	2	2
RXRs/RARs/NRIP1/9cRA	0.024	0.13	-10000	0	-0.51	11	11
NCOA2	0.015	0.014	-10000	0	-10000	0	0
NCOA3	0.016	0.01	-10000	0	-10000	0	0
NCOA1	0.015	0.032	-10000	0	-0.72	1	1
VDR/VDR/DNA	0.013	0.046	-10000	0	-0.72	2	2
RARG	0.017	0.002	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.017	0.002	-10000	0	-10000	0	0
MAPK1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.016	0.032	-10000	0	-0.72	1	1
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.007	0.045	-10000	0	-10000	0	0
RARA	0.038	0.02	-10000	0	-0.27	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.005	0.1	-10000	0	-0.23	85	85
PRKCA	0.019	0.012	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.018	0.13	-10000	0	-0.55	12	12
RXRG	0.033	0.044	-10000	0	-0.39	5	5
RXRA	0.042	0.032	-10000	0	-10000	0	0
RXRB	0.037	0.013	-10000	0	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.034	-10000	0	-0.55	2	2
RBP1	-0.023	0.16	-10000	0	-0.72	26	26
CRBP1/9-cic-RA	-0.029	0.12	-10000	0	-0.55	26	26
RARB	-0.1	0.27	-10000	0	-0.72	85	85
PRKCG	0.02	0.007	-10000	0	-10000	0	0
MNAT1	0.016	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.022	0.12	-10000	0	-0.45	1	1
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.029	0.11	-10000	0	-0.33	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.088	-10000	0	-0.44	2	2
RXRs/RARs/NRIP1/9cRA/HDAC3	0.018	0.13	-10000	0	-0.55	12	12
positive regulation of DNA binding	-0.003	0.022	-10000	0	-10000	0	0
NRIP1	0.009	0.2	-10000	0	-1.3	10	10
RXRs/RARs	0.017	0.11	-10000	0	-0.4	13	13
RXRs/RXRs/DNA/9cRA	0.016	0.052	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
CDK7	0.016	0.007	-10000	0	-10000	0	0
TFIIH	0	0.004	-10000	0	-10000	0	0
RAR alpha/9cRA	0	0.008	-10000	0	-10000	0	0
CCNH	0.016	0	-10000	0	-10000	0	0
CREBBP	0.015	0.032	-10000	0	-0.72	1	1
RAR gamma2/9cRA	0	0.002	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.016	0.01	-9999	-10000	0	0
CCL5	0.006	0.08	-9999	-0.72	6	6
SDCBP	0.015	0.032	-9999	-0.72	1	1
FGFR/FGF2/Syndecan-1	-0.026	0.099	-9999	-0.29	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.015	0.094	-9999	-10000	0	0
Syndecan-1/Syntenin	-0.016	0.095	-9999	-0.39	1	1
MAPK3	0.004	0.087	-9999	-10000	0	0
HGF/MET	-0.054	0.16	-9999	-0.54	52	52
TGFB1/TGF beta receptor Type II	0.016	0.01	-9999	-10000	0	0
BSG	0.015	0.014	-9999	-10000	0	0
keratinocyte migration	-0.014	0.093	-9999	-10000	0	0
Syndecan-1/RANTES	-0.019	0.11	-9999	-0.55	6	6
Syndecan-1/CD147	-0.004	0.091	-9999	-10000	0	0
Syndecan-1/Syntenin/PIP2	-0.023	0.087	-9999	-0.38	1	1
LAMA5	0.015	0.014	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.023	0.086	-9999	-0.37	1	1
MMP7	-0.1	0.27	-9999	-0.72	85	85
HGF	0.016	0.01	-9999	-10000	0	0
Syndecan-1/CASK	-0.026	0.093	-9999	-0.27	1	1
Syndecan-1/HGF/MET	-0.044	0.16	-9999	-0.46	52	52
regulation of cell adhesion	0.014	0.085	-9999	-10000	0	0
HPSE	0.003	0.044	-9999	-10000	0	0
positive regulation of cell migration	-0.026	0.099	-9999	-0.29	1	1
SDC1	-0.026	0.099	-9999	-0.29	1	1
Syndecan-1/Collagen	-0.026	0.099	-9999	-0.29	1	1
PPIB	0.016	0.01	-9999	-10000	0	0
MET	-0.057	0.22	-9999	-0.72	52	52
PRKACA	0.016	0	-9999	-10000	0	0
MMP9	-0.059	0.081	-9999	-10000	0	0
MAPK1	0.004	0.087	-9999	-10000	0	0
homophilic cell adhesion	-0.026	0.098	-9999	-0.28	1	1
MMP1	-0.089	0.077	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.047	0.07	-9999	-0.35	13	13
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.004	0.065	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.004	0.07	-9999	-0.46	12	12
antigen processing and presentation of peptide antigen via MHC class I	-0.033	0.096	-9999	-0.35	26	26
CaM/Ca2+	0.012	0.065	-9999	-0.33	7	7
RAP1A	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.027	0.074	-9999	-0.33	13	13
AKT1	0.015	0.13	-9999	-0.46	17	17
MAP2K1	0.045	0.07	-9999	-0.36	1	1
MAP3K11	0.038	0.063	-9999	-0.33	13	13
IFNGR1	0.005	0.095	-9999	-0.72	9	9
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	0.006	0.07	-9999	-0.5	5	5
Rap1/GTP	-0.006	0.036	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.014	0.074	-9999	-0.37	13	13
CEBPB	0.086	0.073	-9999	-0.46	1	1
STAT3	0.016	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.021	0.072	-9999	-10000	0	0
STAT1	0.031	0.075	-9999	-0.33	13	13
CALM1	0.016	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.018	0.072	-9999	-0.72	1	1
PIK3CA	0.016	0.007	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.046	0.068	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.004	0.032	-9999	-10000	0	0
mol:Ca2+	0.012	0.07	-9999	-0.35	13	13
MAPK3	0.061	0.07	-9999	-10000	0	0
STAT1 (dimer)	-0.038	0.14	-9999	-0.52	26	26
MAPK1	0.061	0.07	-9999	-10000	0	0
JAK2	0.015	0.033	-9999	-0.72	1	1
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
JAK1	0.014	0.046	-9999	-0.72	2	2
CAMK2D	0.01	0.065	-9999	-0.72	4	4
DAPK1	0.083	0.054	-9999	-10000	0	0
SMAD7	0.043	0.074	-9999	-0.17	22	22
CBL/CRKL/C3G	-0.001	0.047	-9999	-10000	0	0
PI3K	-0.025	0.13	-9999	-0.45	25	25
IFNG	-0.018	0.072	-9999	-0.72	1	1
apoptosis	0.059	0.052	-9999	-10000	0	0
CAMK2G	0.016	0	-9999	-10000	0	0
STAT3 (dimer)	0.016	0	-9999	-10000	0	0
CAMK2A	0.016	0	-9999	-10000	0	0
CAMK2B	-0.006	0.094	-9999	-0.72	7	7
FRAP1	0.025	0.13	-9999	-0.48	10	10
PRKCD	0.016	0.14	-9999	-0.45	19	19
RAP1B	0.016	0.01	-9999	-10000	0	0
negative regulation of cell growth	-0.033	0.096	-9999	-0.35	26	26
PTPN2	0.016	0.01	-9999	-10000	0	0
EP300	0.017	0	-9999	-10000	0	0
IRF1	0.066	0.073	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.008	0.06	-9999	-10000	0	0
SOCS1	0.009	0.015	-9999	-10000	0	0
mol:GDP	-0.002	0.045	-9999	-10000	0	0
CASP1	0.018	0.14	-9999	-0.34	60	60
PTGES2	0.016	0.007	-9999	-10000	0	0
IRF9	0.071	0.03	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.028	0.13	-9999	-0.43	25	25
RAP1/GDP	-0.005	0.037	-9999	-10000	0	0
CBL	0.037	0.063	-9999	-0.33	13	13
MAP3K1	0.036	0.073	-9999	-0.34	17	17
PIAS1	0.016	0.007	-9999	-10000	0	0
PIAS4	0.014	0.016	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.033	0.096	-9999	-0.35	26	26
PTPN11	0.026	0.066	-9999	-0.35	13	13
CREBBP	0.016	0.032	-9999	-0.72	1	1
RAPGEF1	0.016	0	-9999	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.008	0.055	-10000	0	-0.36	8	8
FYN	0.068	0.08	-10000	0	-0.42	9	9
LAT/GRAP2/SLP76	-0.009	0.059	-10000	0	-0.36	8	8
IKBKB	0.014	0.02	-10000	0	-10000	0	0
AKT1	0.075	0.068	-10000	0	-0.29	9	9
B2M	0.017	0.033	-10000	0	-0.73	1	1
IKBKG	-0.002	0.012	-10000	0	-10000	0	0
MAP3K8	-0.083	0.25	-10000	0	-0.72	70	70
mol:Ca2+	-0.004	0.018	-10000	0	-0.095	18	18
integrin-mediated signaling pathway	0.001	0.009	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.078	0.085	-10000	0	-0.39	9	9
TRPV6	-0.03	0.14	-10000	0	-0.74	18	18
CD28	-0.003	0.11	-10000	0	-0.72	11	11
SHC1	0.065	0.084	-10000	0	-0.43	9	9
receptor internalization	0.047	0.11	-10000	0	-0.36	28	28
PRF1	0.053	0.067	-10000	0	-10000	0	0
KRAS	0.012	0.025	-10000	0	-10000	0	0
GRB2	0.013	0.022	-10000	0	-10000	0	0
COT/AKT1	0.03	0.12	-10000	0	-0.25	75	75
LAT	0.063	0.087	-10000	0	-0.43	9	9
EntrezGene:6955	0.002	0.001	-10000	0	-10000	0	0
CD3D	0.011	0.034	-10000	0	-10000	0	0
CD3E	0.018	0.008	-10000	0	-10000	0	0
CD3G	-0.009	0.11	-10000	0	-0.72	10	10
RASGRP2	0.016	0.031	-10000	0	-0.17	13	13
RASGRP1	0.084	0.07	-10000	0	-0.28	7	7
HLA-A	0.015	0.025	-10000	0	-10000	0	0
RASSF5	0.013	0.021	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.001	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.056	0.031	-10000	0	-10000	0	0
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.004	0.02	-10000	0	-10000	0	0
PRKCA	-0.004	0.034	-10000	0	-0.18	7	7
GRAP2	0.014	0.019	-10000	0	-10000	0	0
mol:IP3	0.002	0.07	0.27	18	-0.29	7	25
EntrezGene:6957	0.003	0.002	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.037	0.072	-10000	0	-0.37	9	9
ORAI1	0.018	0.07	0.37	18	-10000	0	18
CSK	0.063	0.082	-10000	0	-0.42	9	9
B7 family/CD28	-0.012	0.094	-10000	0	-0.5	13	13
CHUK	0.015	0.032	-10000	0	-0.72	1	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.057	0.091	-10000	0	-0.48	9	9
PTPN6	0.06	0.082	-10000	0	-0.42	9	9
VAV1	0.063	0.086	-10000	0	-0.43	9	9
Monovalent TCR/CD3	0.013	0.098	-10000	0	-0.37	28	28
CBL	0.016	0	-10000	0	-10000	0	0
LCK	0.064	0.076	-10000	0	-0.39	9	9
PAG1	0.062	0.082	-10000	0	-0.42	9	9
RAP1A	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.054	0.092	-10000	0	-0.42	13	13
CD80	0.006	0.041	-10000	0	-10000	0	0
CD86	0.016	0.012	-10000	0	-10000	0	0
PDK1/CARD11/BCL10/MALT1	-0.005	0.026	-10000	0	-10000	0	0
HRAS	0.015	0.012	-10000	0	-10000	0	0
GO:0035030	0.056	0.097	-10000	0	-0.43	13	13
CD8A	0.003	0.002	-10000	0	-10000	0	0
CD8B	0.014	0.026	-10000	0	-10000	0	0
PTPRC	0.006	0.057	-10000	0	-0.73	2	2
PDK1/PKC theta	0.089	0.081	-10000	0	-0.33	9	9
CSK/PAG1	0.067	0.077	-10000	0	-0.4	7	7
SOS1	0.016	0	-10000	0	-10000	0	0
peptide-MHC class I	0.025	0.029	-10000	0	-0.55	1	1
GRAP2/SLP76	-0.01	0.066	-10000	0	-0.4	9	9
STIM1	0.01	0.036	-10000	0	-10000	0	0
RAS family/GTP	0.072	0.037	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.047	0.11	-10000	0	-0.38	28	28
mol:DAG	-0.006	0.047	-10000	0	-0.26	7	7
RAP1A/GDP	0.027	0.013	-10000	0	-10000	0	0
PLCG1	0.016	0.007	-10000	0	-10000	0	0
CD247	-0.028	0.16	-10000	0	-0.72	25	25
cytotoxic T cell degranulation	0.053	0.066	-10000	0	-10000	0	0
RAP1A/GTP	-0.002	0.009	-10000	0	-0.061	13	13
mol:PI-3-4-5-P3	0.076	0.077	-10000	0	-0.34	9	9
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.002	0.08	0.29	17	-0.35	7	24
NRAS	0.014	0.019	-10000	0	-10000	0	0
ZAP70	0.012	0.026	-10000	0	-10000	0	0
GRB2/SOS1	-0.001	0.011	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.01	0.06	-10000	0	-0.36	7	7
MALT1	0.016	0.007	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
CD8 heterodimer	0.013	0.018	-10000	0	-10000	0	0
CARD11	0.011	0.029	-10000	0	-10000	0	0
PRKCB	-0.005	0.034	-10000	0	-0.19	7	7
PRKCE	-0.004	0.033	-10000	0	-0.18	7	7
PRKCQ	0.083	0.086	-10000	0	-0.37	9	9
LCP2	0.012	0.024	-10000	0	-10000	0	0
BCL10	0.016	0.007	-10000	0	-10000	0	0
regulation of survival gene product expression	0.072	0.062	-10000	0	-0.25	9	9
IKK complex	0.064	0.03	-10000	0	-0.11	1	1
RAS family/GDP	0	0.003	-10000	0	-10000	0	0
MAP3K14	0.037	0.1	-10000	0	-0.28	7	7
PDPK1	0.077	0.066	-10000	0	-0.28	8	8
TCR/CD3/MHC I/CD8/Fyn	0.05	0.086	-10000	0	-0.52	8	8

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.003	0.035	-9999	-0.4	4	4
RGS9BP	-0.015	0.076	-9999	-0.72	2	2
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	0.006	0.037	-9999	-0.47	2	2
mol:ADP	0.013	0.025	-9999	-0.55	1	1
GNAT2	0.01	0.065	-9999	-0.72	4	4
RGS9-1/Gbeta5/R9AP	-0.018	0.13	-9999	-0.47	35	35
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.004	0.046	-9999	-0.47	5	5
GRK7	0.015	0.033	-9999	-0.72	1	1
CNGB3	0.008	0.034	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	0.022	0.037	-9999	-0.42	2	2
Cone PDE6	-0.011	0.11	-9999	-0.39	37	37
Cone Metarhodopsin II	-0.001	0.019	-9999	-0.44	1	1
Na + (4 Units)	0.008	0.036	-9999	-0.42	2	2
GNAT2/GDP	-0.016	0.11	-9999	-0.4	39	39
GNB5	0.015	0.032	-9999	-0.72	1	1
mol:GMP (4 units)	0.026	0.05	-9999	-0.43	6	6
Cone Transducin	-0.003	0.037	-9999	-0.42	4	4
SLC24A2	0.016	0.01	-9999	-10000	0	0
GNB3/GNGT2	0	0.003	-9999	-10000	0	0
GNB3	0.016	0.007	-9999	-10000	0	0
GNAT2/GTP	-0.005	0.048	-9999	-0.55	4	4
CNGA3	0.002	0.061	-9999	-0.72	2	2
ARR3	0.016	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0.006	0.037	-9999	-0.47	2	2
mol:Pi	-0.018	0.12	-9999	-0.47	35	35
Cone CNG Channel	0.004	0.055	-9999	-0.39	8	8
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.016	0.01	-9999	-10000	0	0
RGS9	-0.03	0.18	-9999	-0.72	32	32
PDE6C	0.014	0.034	-9999	-0.72	1	1
GNGT2	0.016	0	-9999	-10000	0	0
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.013	0.036	-9999	-0.72	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.039	0.003	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.011	0.064	-9999	-0.72	4	4
ITGA4	0.01	0.032	-9999	-10000	0	0
alpha4/beta7 Integrin/MAdCAM1	0.004	0.019	-9999	-10000	0	0
EPO	-0.006	0.056	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.003	0.015	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.015	0.032	-9999	-0.72	1	1
alpha4/beta1 Integrin	-0.003	0.015	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.011	0.027	-9999	-10000	0	0
lamellipodium assembly	-0.031	0.11	-9999	-0.35	51	51
PIK3CA	0.016	0.007	-9999	-10000	0	0
PI3K	-0.052	0.16	-9999	-0.54	51	51
ARF6	0.016	0	-9999	-10000	0	0
JAK2	0.04	0.023	-9999	-0.44	1	1
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
MADCAM1	0.015	0.014	-9999	-10000	0	0
cell adhesion	0.004	0.018	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.03	0.067	-9999	-0.41	11	11
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.008	0.069	-9999	-0.46	11	11
p130Cas/Crk/Dock1	0.051	0.069	-9999	-10000	0	0
VCAM1	-0.001	0.11	-9999	-0.72	11	11
RHOA	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.004	0.019	-9999	-10000	0	0
BCAR1	0.039	0.063	-9999	-0.37	11	11
EPOR	0.016	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
GIT1	0.015	0.016	-9999	-10000	0	0
Rac1/GTP	-0.033	0.11	-9999	-0.36	51	51

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.046	0.085	-10000	0	-10000	0	0
BAG4	0.011	0.029	-10000	0	-10000	0	0
BAD	0.037	0.029	-10000	0	-10000	0	0
NFKBIA	0.015	0.032	-10000	0	-0.72	1	1
BIRC3	-0.039	0.18	-10000	0	-0.72	35	35
BAX	0.036	0.029	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.016	0.021	-10000	0	-10000	0	0
IKBKB	0.053	0.083	-10000	0	-10000	0	0
MAP2K2	0.053	0.025	-10000	0	-10000	0	0
MAP2K1	0.053	0.025	-10000	0	-10000	0	0
SMPD1	0.024	0.021	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.049	0.086	-10000	0	-10000	0	0
MAP2K4	0.036	0.062	-10000	0	-0.34	11	11
protein ubiquitination	0.055	0.084	-10000	0	-0.37	1	1
EnzymeConsortium:2.7.1.37	0.057	0.029	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAF1	0.046	0.026	-10000	0	-10000	0	0
CRADD	0.017	0	-10000	0	-10000	0	0
mol:ceramide	0.028	0.03	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	-0.001	0.02	-10000	0	-0.47	1	1
MADD	0.017	0	-10000	0	-10000	0	0
MAP3K1	0.032	0.047	-10000	0	-0.37	4	4
TRADD	0.017	0	-10000	0	-10000	0	0
RELA/p50	0.016	0	-10000	0	-10000	0	0
MAPK3	0.056	0.024	-10000	0	-10000	0	0
MAPK1	0.056	0.024	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	-0.001	0.023	-10000	0	-0.54	1	1
FADD	0.04	0.089	-10000	0	-10000	0	0
KSR1	0.038	0.028	-10000	0	-10000	0	0
MAPK8	0.043	0.06	-10000	0	-0.31	12	12
TRAF2	0.015	0.012	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.053	0.086	-10000	0	-0.62	1	1
TNF R/SODD	-0.001	0.014	-10000	0	-10000	0	0
TNF	0.013	0.025	-10000	0	-10000	0	0
CYCS	0.06	0.052	0.16	86	-10000	0	86
IKBKG	0.054	0.082	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.037	0.089	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
RIPK1	0.016	0.001	-10000	0	-10000	0	0
AIFM1	0.06	0.052	0.16	78	-10000	0	78
TNF/TNF R/SODD	0.004	0.02	-10000	0	-10000	0	0
TNFRSF1A	0.016	0.001	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.034	0.024	-10000	0	-10000	0	0
NSMAF	0.044	0.091	-10000	0	-0.65	1	1
response to hydrogen peroxide	0.001	0	-10000	0	-10000	0	0
BCL2	-0.13	0.29	-10000	0	-0.72	104	104

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.016	0	-9999	-10000	0	0
NFATC1	0.059	0.026	-9999	-10000	0	0
NFATC2	0.024	0.062	-9999	-0.21	5	5
NFATC3	0.019	0.004	-9999	-10000	0	0
YWHAE	0.015	0.032	-9999	-0.72	1	1
Calcineurin A alpha-beta B1/CABIN1	0.049	0.027	-9999	-0.23	4	4
Exportin 1/Ran/NUP214	0	0	-9999	-10000	0	0
mol:DAG	0	0.002	-9999	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.001	0.018	-9999	-10000	0	0
BCL2/BAX	-0.11	0.22	-9999	-0.54	104	104
CaM/Ca2+/Calcineurin A alpha-beta B1	0.014	0.005	-9999	-10000	0	0
CaM/Ca2+	0.014	0.005	-9999	-10000	0	0
BAX	0.015	0.014	-9999	-10000	0	0
MAPK14	0.016	0.004	-9999	-10000	0	0
BAD	0.016	0	-9999	-10000	0	0
CABIN1/MEF2D	0.054	0.025	-9999	-10000	0	0
Calcineurin A alpha-beta B1/BCL2	-0.13	0.29	-9999	-0.72	104	104
FKBP8	0.016	0.007	-9999	-10000	0	0
activation-induced cell death of T cells	-0.054	0.025	-9999	-10000	0	0
KPNB1	0.016	0.007	-9999	-10000	0	0
KPNA2	-0.029	0.072	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
SFN	0.012	0.048	-9999	-0.72	2	2
MAP3K8	-0.083	0.25	-9999	-0.72	70	70
NFAT4/CK1 alpha	0	0.037	-9999	-0.38	4	4
MEF2D/NFAT1/Cbp/p300	-0.023	0.073	-9999	-0.43	6	6
CABIN1	0.049	0.027	-9999	-0.23	4	4
CALM1	0.016	0.004	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
MAP3K1	0.005	0.071	-9999	-0.72	4	4
CAMK4	0.014	0.017	-9999	-10000	0	0
mol:Ca2+	0.001	0.004	-9999	-10000	0	0
MAPK3	0.016	0	-9999	-10000	0	0
YWHAH	0.015	0.012	-9999	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.007	0.038	-9999	-0.54	2	2
YWHAB	0.015	0.012	-9999	-10000	0	0
MAPK8	0.015	0.032	-9999	-0.72	1	1
MAPK9	0.016	0.007	-9999	-10000	0	0
YWHAG	0.016	0.01	-9999	-10000	0	0
FKBP1A	0.016	0.01	-9999	-10000	0	0
NFAT1-c-4/YWHAQ	0.002	0.02	-9999	-10000	0	0
PRKCH	0.011	0.064	-9999	-0.72	4	4
CABIN1/Cbp/p300	-0.001	0.023	-9999	-0.54	1	1
CASP3	0.016	0.004	-9999	-10000	0	0
PIM1	0.015	0.016	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.005	-9999	-10000	0	0
apoptosis	-0.032	0.065	-9999	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.054	0.018	-9999	-10000	0	0
PRKCB	0	0	-9999	-10000	0	0
PRKCE	0.016	0	-9999	-10000	0	0
JNK2/NFAT4	0.027	0.005	-9999	-10000	0	0
BAD/BCL-XL	0	0	-9999	-10000	0	0
PRKCD	0.014	0.019	-9999	-10000	0	0
NUP214	0.016	0	-9999	-10000	0	0
PRKCZ	0	0.002	-9999	-10000	0	0
PRKCA	0.016	0.01	-9999	-10000	0	0
PRKCG	0.016	0	-9999	-10000	0	0
PRKCQ	0.008	0.046	-9999	-0.72	1	1
FKBP38/BCL2	-0.11	0.22	-9999	-0.54	104	104
EP300	0.017	0.003	-9999	-10000	0	0
PRKCB1	0.008	0.036	-9999	-10000	0	0
CSNK2A1	0.016	0	-9999	-10000	0	0
NFATc/JNK1	0.064	0.033	-9999	-10000	0	0
CaM/Ca2+/FKBP38	0	0.003	-9999	-10000	0	0
FKBP12/FK506	0	0.006	-9999	-10000	0	0
CSNK1A1	0.025	0.006	-9999	-10000	0	0
CaM/Ca2+/CAMK IV	0.001	0.008	-9999	-10000	0	0
NFATc/ERK1	0.066	0.025	-9999	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.001	0.018	-9999	-10000	0	0
NR4A1	0.034	0.16	-9999	-0.65	27	27
GSK3B	0.016	0.011	-9999	-10000	0	0
positive T cell selection	0.019	0.004	-9999	-10000	0	0
NFAT1/CK1 alpha	-0.014	0.033	-9999	-10000	0	0
RCH1/ KPNB1	-0.022	0.035	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0.004	-9999	-10000	0	0
AKAP5	0.004	0.059	-9999	-0.72	2	2
MEF2D	0.017	0.003	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
YWHAZ	0.014	0.017	-9999	-10000	0	0
NFATc/p38 alpha	0.064	0.028	-9999	-10000	0	0
CREBBP	0.015	0.032	-9999	-0.72	1	1
BCL2	-0.13	0.29	-9999	-0.72	104	104

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0.001	0.004	-9999	-10000	0	0
DOCK1	0.011	0.064	-9999	-0.72	4	4
ITGA4	0.01	0.032	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.003	0.015	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.015	0.032	-9999	-0.72	1	1
alpha4/beta1 Integrin	0.003	0.016	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.004	0.018	-9999	-10000	0	0
lamellipodium assembly	-0.041	0.13	-9999	-0.42	51	51
PIK3CA	0.016	0.007	-9999	-10000	0	0
PI3K	-0.052	0.16	-9999	-0.54	51	51
ARF6	0.016	0	-9999	-10000	0	0
TLN1	0.016	0	-9999	-10000	0	0
PXN	0.029	0	-9999	-10000	0	0
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
ARF6/GTP	0.004	0.017	-9999	-10000	0	0
cell adhesion	0.004	0.018	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.004	0.018	-9999	-10000	0	0
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.016	0	-9999	-10000	0	0
ARF6/GDP	0.001	0.004	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.003	0.059	-9999	-0.38	11	11
p130Cas/Crk/Dock1	-0.004	0.044	-9999	-0.46	5	5
VCAM1	-0.001	0.11	-9999	-0.72	11	11
alpha4/beta1 Integrin/Paxillin/Talin	0.004	0.019	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.005	0.021	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
mol:GDP	-0.005	0.02	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GIT1	0.015	0.016	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.004	0.019	-9999	-10000	0	0
Rac1/GTP	-0.046	0.14	-9999	-0.47	51	51

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.027	0.1	-9999	-0.4	36	36
TRAF2/ASK1	-0.031	0.12	-9999	-0.47	35	35
ATM	0.016	0	-9999	-10000	0	0
MAP2K3	0.039	0.073	-9999	-0.36	4	4
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.028	0.12	-9999	-0.37	35	35
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.014	0.019	-9999	-10000	0	0
TXN	0.011	0.002	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
GADD45A	0.004	0.096	-9999	-0.72	9	9
GADD45B	0.01	0.065	-9999	-0.72	4	4
MAP3K1	0.005	0.071	-9999	-0.72	4	4
MAP3K6	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0.01	-9999	-10000	0	0
MAP3K4	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.036	0.13	-9999	-0.54	35	35
TAK1/TAB family	-0.001	0.021	-9999	-0.49	1	1
RAC1/OSM/MEKK3	0	0	-9999	-10000	0	0
TRAF2	0.015	0.012	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.011	0.04	-9999	-10000	0	0
TRAF6	0.021	0.019	-9999	-0.41	1	1
RAC1	0.016	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.006	0.094	-9999	-0.72	7	7
CCM2	0.016	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.001	0.057	-9999	-0.47	7	7
MAPK11	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.029	0.12	-9999	-0.43	42	42
OSM/MEKK3	0	0	-9999	-10000	0	0
TAOK1	0.021	0.007	-9999	-10000	0	0
TAOK2	0.022	0	-9999	-10000	0	0
TAOK3	0.022	0	-9999	-10000	0	0
MAP3K7IP1	0.016	0	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
MAP3K7IP2	0.015	0.032	-9999	-0.72	1	1
MAP3K5	-0.033	0.18	-9999	-0.72	35	35
MAP3K10	0.012	0.047	-9999	-0.72	2	2
MAP3K3	0.016	0	-9999	-10000	0	0
TRX/ASK1	-0.012	0.12	-9999	-0.46	35	35
GADD45/MTK1/MTK1	-0.008	0.066	-9999	-0.42	12	12

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.005	0.018	-10000	0	-10000	0	0
oxygen homeostasis	0.015	0.014	-10000	0	-10000	0	0
TCEB2	0.016	0.01	-10000	0	-10000	0	0
TCEB1	0.014	0.019	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.008	0.072	-10000	0	-0.35	10	10
EPO	0.19	0.18	-10000	0	-0.54	5	5
FIH (dimer)	0.031	0.014	-10000	0	-10000	0	0
APEX1	0.032	0.015	-10000	0	-10000	0	0
SERPINE1	0.19	0.18	-10000	0	-0.65	5	5
FLT1	0.005	0.046	-10000	0	-0.94	1	1
ADORA2A	0.17	0.18	-10000	0	-0.6	6	6
germ cell development	0.18	0.18	-10000	0	-0.59	6	6
SLC11A2	0.19	0.18	-10000	0	-0.58	7	7
BHLHE40	0.18	0.18	-10000	0	-0.51	12	12
HIF1AN	0.031	0.014	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.051	0.13	-10000	0	-0.41	11	11
ETS1	0.034	0.036	-10000	0	-0.72	1	1
CITED2	-0.011	0.14	-10000	0	-1.2	7	7
KDR	0.005	0.047	-10000	0	-0.94	1	1
PGK1	0.19	0.18	-10000	0	-0.61	6	6
SIRT1	0.016	0.007	-10000	0	-10000	0	0
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	0.22	0.21	-10000	0	-0.59	12	12
EPAS1	0.098	0.12	-10000	0	-0.39	16	16
SP1	0.025	0.006	-10000	0	-10000	0	0
ABCG2	0.16	0.25	-10000	0	-0.71	27	27
EFNA1	0.18	0.19	-10000	0	-0.62	6	6
FXN	0.18	0.18	-10000	0	-0.6	6	6
POU5F1	0.19	0.19	-10000	0	-0.62	6	6
neuron apoptosis	-0.21	0.21	0.57	12	-10000	0	12
EP300	0.016	0	-10000	0	-10000	0	0
EGLN3	0.012	0.072	-10000	0	-0.73	1	1
EGLN2	0.031	0.02	-10000	0	-10000	0	0
EGLN1	0.029	0.021	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.004	0.017	-10000	0	-10000	0	0
VHL	0.012	0.027	-10000	0	-10000	0	0
ARNT	0.033	0.012	-10000	0	-10000	0	0
SLC2A1	0.18	0.18	-10000	0	-0.58	7	7
TWIST1	0.13	0.28	-10000	0	-0.62	56	56
ELK1	0.025	0.016	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.043	0.12	-10000	0	-0.46	9	9
VEGFA	0.18	0.19	-10000	0	-0.6	7	7
CREBBP	0.015	0.032	-10000	0	-0.72	1	1

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.001	0.007	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.034	0.014	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.058	0.013	-9999	-10000	0	0
NFKBIA	0.035	0.015	-9999	-0.24	1	1
MAPK14	0.016	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.033	0.01	-9999	-10000	0	0
ARRB2	0.022	0	-9999	-10000	0	0
REL	0.012	0.027	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.033	0.011	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.033	0.01	-9999	-10000	0	0
PIK3CA	0.016	0.007	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.027	0.007	-9999	-10000	0	0
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
NFKB1	0.028	0.013	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.044	0.006	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.063	0.013	-9999	-10000	0	0
SRC	0.016	0.007	-9999	-10000	0	0
PI3K	-0.052	0.16	-9999	-0.54	51	51
NF kappa B1 p50/RelA	0.044	0.007	-9999	-10000	0	0
IKBKB	0.014	0.02	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
SYK	0.01	0.03	-9999	-10000	0	0
I kappa B alpha/PIK3R1	0.001	0.12	-9999	-0.38	51	51
cell death	0.06	0.012	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.034	0.014	-9999	-10000	0	0
LCK	0	0.049	-9999	-10000	0	0
BCL3	0.015	0.014	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.016	0.016	-9999	-10000	0	0
ELF1	0.027	0.007	-9999	-10000	0	0
CCNA2	-0.04	0.077	-9999	-10000	0	0
PIK3CA	0.017	0.007	-9999	-10000	0	0
JAK3	0.017	0	-9999	-10000	0	0
PIK3R1	-0.054	0.22	-9999	-0.72	51	51
JAK1	0.015	0.045	-9999	-0.72	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.081	0.066	-9999	-10000	0	0
SHC1	0.017	0	-9999	-10000	0	0
SP1	0.02	0.051	-9999	-0.36	9	9
IL2RA	0.034	0.026	-9999	-10000	0	0
IL2RB	0.014	0.023	-9999	-10000	0	0
SOS1	0.017	0	-9999	-10000	0	0
IL2RG	0.008	0.039	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	0.033	0.14	-9999	-0.76	13	13
PTPN11	0.017	0	-9999	-10000	0	0
CCND2	0.023	0.13	-9999	-0.94	9	9
LCK	0.001	0.049	-9999	-10000	0	0
GRB2	0.014	0.022	-9999	-10000	0	0
IL2	0.016	0.033	-9999	-0.72	1	1
CDK6	0.005	0.086	-9999	-0.72	7	7
CCND3	0.087	0.061	-9999	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	0.006	0.042	0.27	13	-10000	0	13
DAPP1	0.055	0.022	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK	0.084	0.024	-10000	0	-10000	0	0
mol:DAG	0.077	0.036	0.22	10	-10000	0	10
HRAS	0.016	0.012	-10000	0	-10000	0	0
RAP1A	0.017	0.002	-10000	0	-10000	0	0
ARF5/GDP	0.041	0.047	-10000	0	-0.29	1	1
PLCG2	0	0.11	-10000	0	-0.72	11	11
PLCG1	0.016	0.007	-10000	0	-10000	0	0
ARF5	0.016	0	-10000	0	-10000	0	0
mol:GTP	0.005	0.039	0.26	10	-10000	0	10
ARF1/GTP	0.005	0.038	0.26	10	-10000	0	10
RHOA	0.016	0	-10000	0	-10000	0	0
YES1	0.015	0.032	-10000	0	-0.72	1	1
RAP1A/GTP	0.005	0.037	0.24	10	-10000	0	10
ADAP1	0.005	0.036	0.24	10	-10000	0	10
ARAP3	0.005	0.038	0.26	10	-10000	0	10
INPPL1	0.015	0.012	-10000	0	-10000	0	0
PREX1	-0.027	0.091	-10000	0	-0.72	4	4
ARHGEF6	-0.013	0.14	-10000	0	-0.72	21	21
ARHGEF7	0.015	0.012	-10000	0	-10000	0	0
ARF1	0.016	0.01	-10000	0	-10000	0	0
NRAS	0.015	0.018	-10000	0	-10000	0	0
FYN	0.013	0.045	-10000	0	-0.72	2	2
ARF6	0.016	0	-10000	0	-10000	0	0
FGR	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0.052	0.024	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.015	0.012	-10000	0	-10000	0	0
ZAP70	0.012	0.026	-10000	0	-10000	0	0
mol:IP3	0.064	0.031	-10000	0	-10000	0	0
LYN	0.016	0.01	-10000	0	-10000	0	0
ARF1/GDP	0.041	0.047	-10000	0	-0.29	1	1
RhoA/GDP	0.004	0.041	0.26	9	-10000	0	9
PDK1/Src/Hsp90	0.001	0.007	-10000	0	-10000	0	0
BLNK	0.011	0.029	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.062	0.047	-10000	0	-10000	0	0
SRC	0.016	0.007	-10000	0	-10000	0	0
PLEKHA2	0.025	0.009	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PTEN	-0.017	0.11	-10000	0	-0.7	13	13
HSP90AA1	0.016	0.01	-10000	0	-10000	0	0
ARF6/GTP	0.006	0.042	0.28	10	-10000	0	10
RhoA/GTP	0.005	0.037	0.25	10	-10000	0	10
Src family/SYK family/BLNK-LAT	0.069	0.023	-10000	0	-10000	0	0
BLK	0.002	0.045	-10000	0	-10000	0	0
PDPK1	0.016	0.007	-10000	0	-10000	0	0
CYTH1	0.005	0.036	0.24	10	-10000	0	10
HCK	0.013	0.024	-10000	0	-10000	0	0
CYTH3	0.005	0.036	0.24	10	-10000	0	10
CYTH2	0.005	0.036	0.24	10	-10000	0	10
KRAS	0.013	0.025	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.005	0.031	0.21	10	-10000	0	10
SGK1	0.005	0.032	0.21	13	-10000	0	13
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.032	0.05	-10000	0	-0.24	3	3
SOS1	0.016	0	-10000	0	-10000	0	0
SYK	0.01	0.03	-10000	0	-10000	0	0
ARF6/GDP	0.004	0.043	0.26	12	-10000	0	12
mol:PI-3-4-5-P3	0.007	0.052	0.33	13	-10000	0	13
ARAP3/RAP1A/GTP	0.005	0.037	0.24	10	-10000	0	10
VAV1	0.012	0.027	-10000	0	-10000	0	0
mol:PI-3-4-P2	0.014	0.008	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.034	0.019	-10000	0	-10000	0	0
PLEKHA1	0.021	0.044	-10000	0	-0.47	4	4
Rac1/GDP	0.041	0.047	-10000	0	-0.29	1	1
LAT	0.012	0.026	-10000	0	-10000	0	0
Rac1/GTP	0.034	0.075	-10000	0	-0.32	20	20
ITK	0.003	0.044	0.25	10	-0.36	2	12
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.089	0.043	-10000	0	-10000	0	0
LCK	0	0.049	-10000	0	-10000	0	0
BTK	0.004	0.038	0.25	10	-10000	0	10

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.065	0.2	-9999	-0.44	39	39
PDGFB-D/PDGFRB/SLAP	0.001	0.011	-9999	-10000	0	0
PDGFB-D/PDGFRB/APS/CBL	0	0	-9999	-10000	0	0
AKT1	0.014	0.12	-9999	-0.4	5	5
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.018	0.079	-9999	-0.49	4	4
PIK3CA	0.016	0.007	-9999	-10000	0	0
FGR	-0.011	0.025	-9999	-10000	0	0
mol:Ca2+	0.023	0.05	-9999	-10000	0	0
MYC	-0.002	0.22	-9999	-0.85	29	29
SHC1	0.016	0	-9999	-10000	0	0
HRAS/GDP	0	0.011	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	0.001	0.008	-9999	-10000	0	0
GRB10	0.011	0.064	-9999	-0.72	4	4
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0.022	0.051	-9999	-10000	0	0
PTEN	-0.002	0.12	-9999	-0.72	13	13
GRB2	0.013	0.022	-9999	-10000	0	0
GRB7	0.001	0.048	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHP2	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	-0.004	0.047	-9999	-0.54	4	4
cell cycle arrest	0.001	0.011	-9999	-10000	0	0
HRAS	0.015	0.012	-9999	-10000	0	0
HIF1A	0.021	0.12	-9999	-0.38	7	7
GAB1	0.008	0.088	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.002	0.1	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.005	0.02	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.002	0.034	-9999	-0.55	2	2
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.11	0.18	-9999	-0.47	36	36
positive regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PIK3R1	-0.055	0.22	-9999	-0.72	51	51
mol:IP3	0.023	0.051	-9999	-10000	0	0
E5	-0.001	0.002	-9999	-10000	0	0
CSK	0.015	0.01	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0	0.025	-9999	-10000	0	0
SHB	0.013	0.037	-9999	-0.72	1	1
BLK	-0.006	0.029	-9999	-10000	0	0
PTPN2	0.015	0.011	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
VAV2	0.008	0.1	-9999	-0.37	10	10
CBL	0.016	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0	0.009	-9999	-10000	0	0
LCK	-0.007	0.03	-9999	-10000	0	0
PDGFRB	0.013	0.009	-9999	-10000	0	0
ACP1	0.013	0.045	-9999	-0.72	2	2
HCK	-0.009	0.024	-9999	-10000	0	0
ABL1	0.019	0.064	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	0.013	0.079	-9999	-10000	0	0
PTPN1	0.007	0.037	-9999	-10000	0	0
SNX15	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
STAT1	-0.011	0.061	-9999	-10000	0	0
cell proliferation	0.003	0.19	-9999	-0.74	29	29
SLA	0.013	0.022	-9999	-10000	0	0
actin cytoskeleton reorganization	0.045	0.037	-9999	-10000	0	0
SRC	-0.01	0.023	-9999	-10000	0	0
PI3K	-0.041	0.11	-9999	-0.4	12	12
PDGFB-D/PDGFRB/GRB7/SHC	0.008	0.023	-9999	-10000	0	0
SH2B2	0	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.018	0.08	-9999	-0.5	4	4
LYN	-0.011	0.024	-9999	-10000	0	0
LRP1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
STAT5B	0.016	0.007	-9999	-10000	0	0
STAT5A	0.013	0.045	-9999	-0.72	2	2
NCK1-2/p130 Cas	0.005	0.019	-9999	-10000	0	0
SPHK1	0.001	0.072	-9999	-0.73	4	4
EDG1	-0.19	0.33	-9999	-0.72	147	147
mol:DAG	0.023	0.051	-9999	-10000	0	0
PLCG1	0.023	0.052	-9999	-10000	0	0
NHERF/PDGFRB	0.018	0.04	-9999	-0.46	1	1
YES1	-0.013	0.041	-9999	-0.78	1	1
cell migration	0.018	0.04	-9999	-0.46	1	1
SHC/Grb2/SOS1	0.006	0.021	-9999	-10000	0	0
SLC9A3R2	0.014	0.034	-9999	-0.72	1	1
SLC9A3R1	-0.022	0.069	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.009	0.08	-9999	-0.42	14	14
FYN	-0.013	0.057	-9999	-0.85	2	2
DOK1	0.036	0.021	-9999	-10000	0	0
HRAS/GTP	-0.001	0.007	-9999	-10000	0	0
PDGFB	0.015	0.016	-9999	-10000	0	0
RAC1	0.012	0.14	-9999	-0.44	29	29
PRKCD	0.036	0.022	-9999	-10000	0	0
FER	0.036	0.022	-9999	-10000	0	0
MAPKKK cascade	0	0.01	-9999	-10000	0	0
RASA1	0.036	0.022	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
NCK2	0.016	0.01	-9999	-10000	0	0
p62DOK/Csk	0.016	0.026	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.001	0.025	-9999	-0.54	1	1
chemotaxis	0.019	0.063	-9999	-10000	0	0
STAT1-3-5/STAT1-3-5	0.012	0.035	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.008	0.007	-9999	-10000	0	0
PTPRJ	0.014	0.019	-9999	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.015	0.067	-9999	-0.49	9	9
BIRC5	-0.087	0.078	-9999	-10000	0	0
NFKBIA	0.017	0.03	-9999	-0.5	1	1
CPEB1	-0.003	0.12	-9999	-0.72	13	13
AKT1	0.017	0.023	-9999	-10000	0	0
NDEL1	0.016	0	-9999	-10000	0	0
Aurora A/BRCA1	0.008	0.016	-9999	-10000	0	0
NDEL1/TACC3	0.02	0.047	-9999	-10000	0	0
GADD45A	0.004	0.096	-9999	-0.72	9	9
GSK3B	0.011	0.01	-9999	-10000	0	0
PAK1/Aurora A	0.023	0.035	-9999	-10000	0	0
MDM2	0.012	0.025	-9999	-10000	0	0
JUB	-0.01	0.14	-9999	-0.72	19	19
TPX2	-0.052	0.046	-9999	-10000	0	0
TP53	0.026	0.011	-9999	-10000	0	0
DLG7	-0.046	0.053	-9999	-10000	0	0
AURKAIP1	0.015	0.012	-9999	-10000	0	0
ARHGEF7	0.015	0.012	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.021	0.05	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.008	0.016	-9999	-10000	0	0
AURKA	0.006	0.025	-9999	-10000	0	0
AURKB	0.018	0.015	-9999	-10000	0	0
CDC25B	0.004	0.029	-9999	-10000	0	0
G2/M transition checkpoint	-0.006	0.083	-9999	-0.44	19	19
mRNA polyadenylation	-0.001	0.07	-9999	-0.44	13	13
Aurora A/CPEB	-0.001	0.07	-9999	-0.44	13	13
Aurora A/TACC1/TRAP/chTOG	-0.001	0.1	-9999	-0.39	31	31
BRCA1	0.012	0.025	-9999	-10000	0	0
centrosome duplication	0.023	0.035	-9999	-10000	0	0
regulation of centrosome cycle	0.017	0.046	-9999	-10000	0	0
spindle assembly	-0.009	0.097	-9999	-0.39	31	31
TDRD7	0.016	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	0.047	0.044	-9999	-10000	0	0
CENPA	0.025	0.021	-9999	-10000	0	0
Aurora A/PP2A	0.023	0.011	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.001	0.033	-9999	-10000	0	0
negative regulation of DNA binding	0.026	0.011	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	-0.001	0.009	-9999	-10000	0	0
RASA1	0.015	0.012	-9999	-10000	0	0
Ajuba/Aurora A	-0.006	0.084	-9999	-0.44	19	19
mitotic prometaphase	-0.003	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.025	-9999	-10000	0	0
TACC1	-0.028	0.17	-9999	-0.72	31	31
TACC3	-0.058	0.08	-9999	-10000	0	0
Aurora A/Antizyme1	0.017	0.014	-9999	-10000	0	0
Aurora A/RasGAP	0.024	0.009	-9999	-10000	0	0
OAZ1	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.012	0.002	-9999	-10000	0	0
GIT1	0.015	0.016	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.014	0.031	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.052	0.045	-9999	-10000	0	0
PPP2R5D	0.015	0.012	-9999	-10000	0	0
Aurora A/TPX2	-0.033	0.044	-9999	-10000	0	0
PAK1	-0.01	0.06	-9999	-10000	0	0
CKAP5	0.014	0.019	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.037	0.033	-10000	0	-10000	0	0
regulation of axonogenesis	-0.021	0.061	0.27	22	-10000	0	22
myoblast fusion	-0.016	0.016	-10000	0	-10000	0	0
mol:GTP	-0.003	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.039	0.018	-10000	0	-10000	0	0
ARF1/GTP	0.002	0.007	-10000	0	-10000	0	0
mol:GM1	0.009	0.009	-10000	0	-10000	0	0
mol:Choline	0.013	0.095	-10000	0	-0.44	22	22
lamellipodium assembly	0.001	0.01	-10000	0	-10000	0	0
MAPK3	0.03	0.014	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.04	0.018	-10000	0	-10000	0	0
ARF1	0.016	0.01	-10000	0	-10000	0	0
ARF6/GDP	0.017	0.016	-10000	0	-10000	0	0
ARF1/GDP	0.028	0.015	-10000	0	-10000	0	0
ARF6	0.013	0.004	-10000	0	-10000	0	0
RAB11A	0.016	0.01	-10000	0	-10000	0	0
TIAM1	0.017	0.012	-10000	0	-10000	0	0
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.03	0.014	-10000	0	-10000	0	0
actin filament bundle formation	-0.002	0.004	-10000	0	-10000	0	0
KALRN	-0.001	0.002	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	-0.001	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.002	0.004	-10000	0	-10000	0	0
NME1	0.013	0.029	-10000	0	-10000	0	0
Rac1/GDP	0.002	0.004	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.003	0.005	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.001	0.01	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
liver development	-0.003	0.005	-10000	0	-10000	0	0
ARF6/GTP	-0.003	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.003	0.004	-10000	0	-10000	0	0
mol:GDP	-0.001	0.009	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.006	0.011	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
PLD1	0.002	0.1	-10000	0	-0.5	21	21
RAB11FIP3	0.015	0.012	-10000	0	-10000	0	0
tube morphogenesis	0.001	0.01	-10000	0	-10000	0	0
ruffle organization	0.021	0.061	-10000	0	-0.27	22	22
regulation of epithelial cell migration	-0.003	0.005	-10000	0	-10000	0	0
PLD2	0.022	0.024	-10000	0	-0.5	1	1
PIP5K1A	0.021	0.061	-10000	0	-0.27	22	22
mol:Phosphatidic acid	0.013	0.095	-10000	0	-0.44	22	22
Rac1/GTP	0.001	0.01	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.002	0.015	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0.001	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.06	0.016	-9999	-10000	0	0
SUMO1	0.016	0	-9999	-10000	0	0
ZFPM1	0.016	0.007	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.027	0.003	-9999	-10000	0	0
FKBP3	0.016	0.007	-9999	-10000	0	0
Histones	0.002	0.012	-9999	-10000	0	0
YY1/LSF	0.03	0.038	-9999	-0.4	4	4
SMG5	0.014	0.02	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.043	0.016	-9999	-0.32	1	1
I kappa B alpha/HDAC1	0.04	0.02	-9999	-0.41	1	1
SAP18	0.016	0	-9999	-10000	0	0
RELA	0.048	0.013	-9999	-10000	0	0
HDAC1/Smad7	0	0.004	-9999	-10000	0	0
RANGAP1	0.01	0.031	-9999	-10000	0	0
HDAC3/TR2	0.04	0.02	-9999	-0.41	1	1
NuRD/MBD3 Complex	0.06	0.003	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.051	0.012	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.007	0.037	-9999	-10000	0	0
GATA1	0.016	0	-9999	-10000	0	0
Mad/Max	0	0.003	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.074	0.004	-9999	-10000	0	0
RBBP7	0.012	0.026	-9999	-10000	0	0
NPC	0	0.003	-9999	-10000	0	0
RBBP4	0.016	0.007	-9999	-10000	0	0
MAX	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
NFKBIA	0.035	0.022	-9999	-0.46	1	1
KAT2B	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.055	0.003	-9999	-10000	0	0
SIN3 complex	0.001	0.009	-9999	-10000	0	0
SMURF1	0.016	0	-9999	-10000	0	0
CHD3	0.015	0.012	-9999	-10000	0	0
SAP30	0.016	0.007	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.015	0.032	-9999	-0.72	1	1
YY1/HDAC3	0.049	0.012	-9999	-10000	0	0
YY1/HDAC2	0.033	0.015	-9999	-0.28	1	1
YY1/HDAC1	0.032	0.013	-9999	-0.28	1	1
NuRD/MBD2 Complex (MeCP1)	0.06	0.003	-9999	-10000	0	0
PPARG	-0.24	0.15	-9999	-0.33	388	388
HDAC8/hEST1B	0.001	0.01	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.041	0.003	-9999	-10000	0	0
MBD3L2	0.015	0.032	-9999	-0.72	1	1
ubiquitin-dependent protein catabolic process	0	0.003	-9999	-10000	0	0
CREBBP	0.015	0.032	-9999	-0.72	1	1
NuRD/MBD3/MBD3L2 Complex	0.07	0.011	-9999	-10000	0	0
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	0.036	0.004	-9999	-10000	0	0
HDAC2	0.014	0.017	-9999	-10000	0	0
YY1	0.029	0.016	-9999	-0.33	1	1
HDAC8	0.016	0	-9999	-10000	0	0
SMAD7	0.016	0.007	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
MXD1	0.016	0.007	-9999	-10000	0	0
STAT3	0.032	0.019	-9999	-0.39	1	1
NFKB1	0.016	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0.007	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.003	0.032	-9999	-0.4	3	3
YY1/SAP30/HDAC1	0	0.011	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.032	0.019	-9999	-0.39	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.035	0.022	-9999	-0.46	1	1
histone deacetylation	0.06	0.003	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.052	0.014	-9999	-10000	0	0
nuclear export	-0.001	0.01	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GATAD2B	0.016	0	-9999	-10000	0	0
GATAD2A	0.012	0.026	-9999	-10000	0	0
GATA2/HDAC3	0.044	0.012	-9999	-10000	0	0
GATA1/HDAC1	0	0	-9999	-10000	0	0
GATA1/HDAC3	0.041	0.003	-9999	-10000	0	0
CHD4	0.016	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.002	0.012	-9999	-10000	0	0
SIN3/HDAC complex/Mad/Max	0.061	0.003	-9999	-10000	0	0
NuRD Complex	0.071	0.003	-9999	-10000	0	0
positive regulation of chromatin silencing	0.002	0.011	-9999	-10000	0	0
SIN3B	0.015	0.016	-9999	-10000	0	0
MTA2	0.016	0.007	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
SUMO1/HDAC1	0.038	0.002	-9999	-10000	0	0
HDAC complex	0.003	0.017	-9999	-10000	0	0
GATA1/Fog1	0	0.003	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0.001	0.009	-9999	-10000	0	0
TNF	0.012	0.025	-9999	-10000	0	0
negative regulation of cell growth	0.061	0.003	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.06	0.003	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.001	0.006	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0	0.014	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.058	0.011	-9999	-10000	0	0
TFCP2	0.012	0.056	-9999	-0.72	3	3
NR2C1	0.015	0.032	-9999	-0.72	1	1
MBD3	0.016	0	-9999	-10000	0	0
MBD2	0.016	0.01	-9999	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.021	0.048	-9999	-0.47	5	5
ADCY5	0.023	0.024	-9999	-0.47	1	1
ADCY6	0.025	0	-9999	-10000	0	0
ADCY7	0.023	0.014	-9999	-10000	0	0
ADCY1	0.025	0.007	-9999	-10000	0	0
ADCY2	0.017	0.058	-9999	-0.47	7	7
ADCY3	0.025	0.005	-9999	-10000	0	0
ADCY8	0.024	0.013	-9999	-10000	0	0
PRKCE	0.015	0	-9999	-10000	0	0
ADCY9	0.024	0.012	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	0.042	0.03	-9999	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.004	0.019	-9999	-10000	0	0
KIRREL	0.018	0.003	-9999	-10000	0	0
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.004	0.019	-9999	-10000	0	0
PLCG1	0.016	0.007	-9999	-10000	0	0
ARRB2	0.016	0	-9999	-10000	0	0
WASL	0.015	0.032	-9999	-0.72	1	1
Nephrin/NEPH1/podocin/CD2AP	0.005	0.021	-9999	-10000	0	0
ChemicalAbstracts:57-88-5	0	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.048	0.015	-9999	-0.28	1	1
FYN	0.031	0.025	-9999	-0.34	2	2
mol:Ca2+	0.004	0.02	-9999	-10000	0	0
mol:DAG	0.004	0.02	-9999	-10000	0	0
NPHS2	0.018	0.003	-9999	-10000	0	0
mol:IP3	0.004	0.02	-9999	-10000	0	0
regulation of endocytosis	0.003	0.027	-9999	-0.3	2	2
Nephrin/NEPH1/podocin/Cholesterol	0.004	0.018	-9999	-10000	0	0
establishment of cell polarity	0.004	0.019	-9999	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2	0.005	0.022	-9999	-10000	0	0
Nephrin/NEPH1/beta Arrestin2	0.045	0.024	-9999	-0.31	2	2
NPHS1	0.011	0.032	-9999	-10000	0	0
Nephrin/NEPH1/podocin	0.003	0.028	-9999	-0.33	2	2
TJP1	0.013	0.045	-9999	-0.72	2	2
NCK1	0.016	0	-9999	-10000	0	0
NCK2	0.016	0.01	-9999	-10000	0	0
heterophilic cell adhesion	0	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.004	0.021	-9999	-10000	0	0
CD2AP	0.016	0.01	-9999	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.006	0.023	-9999	-10000	0	0
GRB2	0.013	0.022	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
TRPC6	0.015	0.099	-9999	-0.42	26	26
cytoskeleton organization	0.057	0.016	-9999	-10000	0	0
Nephrin/NEPH1	0.003	0.016	-9999	-10000	0	0
Nephrin/NEPH1/ZO-1	0.002	0.036	-9999	-0.49	2	2

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0	0.021	-9999	-0.47	1	1
EFNA5	0.014	0.034	-9999	-0.72	1	1
FYN	0.03	0.035	-9999	-0.42	3	3
neuron projection morphogenesis	0	0.021	-9999	-0.47	1	1
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	0	0.021	-9999	-0.47	1	1
EPHA5	0.016	0	-9999	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.012	0.017	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.005	0.02	-9999	-10000	0	0
STXBP1	0.016	0	-9999	-10000	0	0
ACh/CHRNA1	0.019	0.012	-9999	-10000	0	0
RAB3GAP2/RIMS1/UNC13B	0.006	0.021	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	0.006	0.039	-9999	-10000	0	0
mol:ACh	0.01	0.016	-9999	-0.14	5	5
RAB3GAP2	0.016	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	0.003	0.025	-9999	-10000	0	0
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	0.019	0.012	-9999	-10000	0	0
UNC13B	0.015	0.014	-9999	-10000	0	0
CHRNA1	0.015	0.012	-9999	-10000	0	0
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	0.024	0.075	-9999	-0.41	11	11
SNAP25	0.005	0.036	-9999	-0.35	5	5
VAMP2	0.009	0	-9999	-10000	0	0
SYT1	-0.046	0.11	-9999	-0.72	8	8
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.021	0.014	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.003	0.025	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.013	0.045	-9999	-0.72	2	2
SMAD2	0.018	0.022	-9999	-0.28	2	2
SMAD3	0.052	0.021	-9999	-10000	0	0
SMAD3/SMAD4	0.063	0.022	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	-0.001	0.029	-9999	-0.46	2	2
SMAD2/SMAD2/SMAD4	0.023	0.048	-9999	-0.34	2	2
PPM1A	0.016	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
SMAD2/SMAD4	0.025	0.033	-9999	-0.41	2	2
MAP3K1	0.005	0.071	-9999	-0.72	4	4
TRAP-1/SMAD4	-0.002	0.033	-9999	-0.54	2	2
MAPK3	0.016	0	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
NUP214	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
CTDSPL	0.013	0.045	-9999	-0.72	2	2
KPNB1	0.016	0.007	-9999	-10000	0	0
TGFBRAP1	0.016	0.007	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
NUP153	0.015	0.012	-9999	-10000	0	0
KPNA2	-0.029	0.072	-9999	-10000	0	0
PIAS4	0.015	0.016	-9999	-10000	0	0

×

Canonical 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.02	0.005	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.11	0.021	-9999	-10000	0	0
ERC1	0.013	0.022	-9999	-10000	0	0
RIP2/NOD2	-0.018	0.035	-9999	-10000	0	0
NFKBIA	0.058	0.034	-9999	-0.73	1	1
BIRC2	0.016	0	-9999	-10000	0	0
IKBKB	0.014	0.02	-9999	-10000	0	0
RIPK2	0.014	0.02	-9999	-10000	0	0
IKBKG	0.009	0.017	-9999	-10000	0	0
IKK complex/A20	0.005	0.023	-9999	-10000	0	0
NEMO/A20/RIP2	0.014	0.02	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
NEMO/ATM	0.062	0.007	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.003	0.022	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0.005	-9999	-10000	0	0
NOD2	-0.018	0.066	-9999	-10000	0	0
NFKB1	0.02	0.005	-9999	-10000	0	0
RELA	0.02	0.005	-9999	-10000	0	0
MALT1	0.016	0.007	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.016	0	-9999	-10000	0	0
TNF/TNFR1A	-0.002	0.012	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
PRKCA	0.016	0.01	-9999	-10000	0	0
CHUK	0.015	0.032	-9999	-0.72	1	1
UBE2D3	0.016	0	-9999	-10000	0	0
TNF	0.012	0.025	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.001	0.014	-9999	-0.31	1	1
BCL10	0.016	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.058	0.034	-9999	-0.72	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.02	0.005	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
IKK complex	0.013	0.03	-9999	-10000	0	0
CYLD	0.016	0.007	-9999	-10000	0	0
IKK complex/PKC alpha	0.002	0.021	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.003	0.014	-9999	-10000	0	0
ATM	0.016	0	-9999	-10000	0	0
UBE2D3	0.016	0	-9999	-10000	0	0
PRKDC	0.01	0.03	-9999	-10000	0	0
ATR	0.016	0	-9999	-10000	0	0
UBE2L3	0.016	0	-9999	-10000	0	0
FANCD2	0.033	0.002	-9999	-10000	0	0
protein ubiquitination	0.022	0.039	-9999	-10000	0	0
XRCC5	0.016	0	-9999	-10000	0	0
XRCC6	0.016	0	-9999	-10000	0	0
M/R/N Complex	0	0.004	-9999	-10000	0	0
MRE11A	0.016	0	-9999	-10000	0	0
DNA-PK	0.003	0.015	-9999	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.016	0.031	-9999	-0.41	1	1
FANCF	0.015	0.032	-9999	-0.72	1	1
BRCA1	0.012	0.025	-9999	-10000	0	0
CCNE1	-0.018	0.066	-9999	-10000	0	0
CDK2/Cyclin E1	-0.019	0.038	-9999	-10000	0	0
FANCG	0.014	0.017	-9999	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.016	-9999	-10000	0	0
FANCE	0.015	0.033	-9999	-0.72	1	1
FANCC	0.014	0.017	-9999	-10000	0	0
NBN	0.016	0.007	-9999	-10000	0	0
FANCA	-0.024	0.07	-9999	-10000	0	0
DNA repair	0.046	0.05	-9999	-10000	0	0
BRCA1/BARD1/ubiquitin	-0.004	0.016	-9999	-10000	0	0
BARD1/DNA-PK	0.005	0.021	-9999	-10000	0	0
FANCL	0.016	0	-9999	-10000	0	0
mRNA polyadenylation	0.003	0.014	-9999	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.05	0.02	-9999	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0.004	0.018	-9999	-10000	0	0
BRCA1/BARD1/P53	0.004	0.019	-9999	-10000	0	0
BARD1/CSTF1/BRCA1	0.005	0.019	-9999	-10000	0	0
BRCA1/BACH1	0.012	0.025	-9999	-10000	0	0
BARD1	0.013	0.024	-9999	-10000	0	0
PCNA	0.01	0.031	-9999	-10000	0	0
BRCA1/BARD1/UbcH5C	0.004	0.017	-9999	-10000	0	0
BRCA1/BARD1/UbcH7	0.004	0.017	-9999	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.052	0.051	-9999	-10000	0	0
BARD1/DNA-PK/P53	0.006	0.022	-9999	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.016	-9999	-10000	0	0
BRCA1/BARD1/CTIP	0.001	0.041	-9999	-0.41	4	4
FA complex	0.048	0.02	-9999	-0.28	1	1
BARD1/EWS	-0.002	0.012	-9999	-10000	0	0
RBBP8	0.025	0.05	-9999	-0.54	4	4
TP53	0.016	0.01	-9999	-10000	0	0
TOPBP1	0.015	0.012	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	-0.004	0.019	-9999	-10000	0	0
BRCA1/BARD1	0.024	0.042	-9999	-10000	0	0
CSTF1	0.015	0.016	-9999	-10000	0	0
BARD1/EWS-Fli1	-0.002	0.014	-9999	-10000	0	0
CDK2	0.013	0.024	-9999	-10000	0	0
UniProt:Q9BZD1	0	0	-9999	-10000	0	0
RAD51	-0.078	0.08	-9999	-10000	0	0
RAD50	0.016	0	-9999	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.004	0.016	-9999	-10000	0	0
EWSR1	0.016	0	-9999	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.044	0.051	-9999	-10000	0	0
CLOCK	0.02	0.002	-9999	-10000	0	0
TIMELESS/CRY2	0.051	0.016	-9999	-10000	0	0
DEC1/BMAL1	-0.001	0.024	-9999	-0.53	1	1
ATR	0.016	0	-9999	-10000	0	0
NR1D1	0.052	0.012	-9999	-10000	0	0
ARNTL	0.019	0.032	-9999	-0.72	1	1
TIMELESS	0.049	0.021	-9999	-10000	0	0
NPAS2	0.017	0.022	-9999	-10000	0	0
CRY2	0.016	0	-9999	-10000	0	0
mol:CO	-0.016	0.006	-9999	-10000	0	0
CHEK1	-0.053	0.08	-9999	-10000	0	0
mol:HEME	0.016	0.006	-9999	-10000	0	0
PER1	0.002	0.1	-9999	-0.72	10	10
BMAL/CLOCK/NPAS2	0.05	0.028	-9999	-0.44	1	1
BMAL1/CLOCK	0.065	0.032	-9999	-10000	0	0
S phase of mitotic cell cycle	0.044	0.051	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.044	0.052	-9999	-10000	0	0
mol:NADPH	0.016	0.006	-9999	-10000	0	0
PER1/TIMELESS	0.043	0.063	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.015	0.012	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
ITGB1	0.016	0	-9999	-9999
ITGB7	0.016	0	-9999	-9999
ITGA4	0.01	0.032	-9999	-9999
alpha4/beta7 Integrin	-0.003	0.015	-9999	-9999
alpha4/beta1 Integrin	-0.003	0.015	-9999	-9999

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.002	0.046	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.021	0.038	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.002	0.028	-9999	-0.64	1	1
AURKB	-0.014	0.063	-9999	-10000	0	0
AURKC	0.013	0.022	-9999	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.005	0.011	-9999	-10000	0	0
BUB1B	0.005	0.023	-9999	-10000	0	0
PLK1	0.017	0.011	-9999	-10000	0	0
PLK1S1	0.008	0.007	-9999	-10000	0	0
KIF2A	0.026	0.01	-9999	-10000	0	0
regulation of mitotic centrosome separation	0.017	0.011	-9999	-10000	0	0
GOLGA2	0.016	0.01	-9999	-10000	0	0
Hec1/SPC24	0.031	0.042	-9999	-10000	0	0
WEE1	0.019	0.052	-9999	-0.55	4	4
cytokinesis	0.016	0.023	-9999	-10000	0	0
PP2A-alpha B56	0.067	0.027	-9999	-10000	0	0
AURKA	0.02	0.005	-9999	-10000	0	0
PICH/PLK1	-0.032	0.088	-9999	-0.32	3	3
CENPE	-0.011	0.045	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.026	0.01	-9999	-10000	0	0
PPP2CA	0.016	0	-9999	-10000	0	0
FZR1	0.016	0.007	-9999	-10000	0	0
TPX2	0.019	0.006	-9999	-10000	0	0
PAK1	-0.011	0.058	-9999	-10000	0	0
SPC24	0	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
CLSPN	0.018	0.006	-9999	-10000	0	0
GORASP1	0.016	0	-9999	-10000	0	0
metaphase	-0.001	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	0.008	0.007	-9999	-10000	0	0
G2 phase of mitotic cell cycle	-0.001	0.001	-9999	-10000	0	0
STAG2	0.016	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.015	0.013	-9999	-10000	0	0
spindle elongation	0.017	0.011	-9999	-10000	0	0
ODF2	0.013	0.015	-9999	-10000	0	0
BUB1	0.057	0.027	-9999	-10000	0	0
TPT1	0.015	0.007	-9999	-10000	0	0
CDC25C	0.025	0.005	-9999	-10000	0	0
CDC25B	0.005	0.045	-9999	-10000	0	0
SGOL1	0.005	0.011	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CCNB1/CDK1	0.065	0.071	-9999	-0.32	4	4
CDC14B	0	0.089	-9999	-0.56	13	13
CDC20	-0.04	0.077	-9999	-10000	0	0
PLK1/PBIP1	-0.024	0.027	-9999	-10000	0	0
mitosis	-0.004	0.005	-9999	-10000	0	0
FBXO5	0.017	0.017	-9999	-10000	0	0
CDC2	-0.064	0.08	-9999	-10000	0	0
NDC80	-0.077	0.08	-9999	-10000	0	0
metaphase plate congression	0.016	0.007	-9999	-10000	0	0
ERCC6L	-0.027	0.069	-9999	-0.37	3	3
NLP/gamma Tubulin	0.013	0.007	-9999	-10000	0	0
microtubule cytoskeleton organization	0.015	0.007	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-9999	-10000	0	0
PPP1R12A	0.016	0	-9999	-10000	0	0
interphase	-0.001	0.001	-9999	-10000	0	0
PLK1/PRC1-2	0.061	0.075	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0.002	0.008	-9999	-10000	0	0
RAB1A	0.016	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	0.018	0.012	-9999	-10000	0	0
mitotic prometaphase	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.04	-9999	-10000	0	0
microtubule-based process	0.046	0.042	-9999	-10000	0	0
Golgi organization	0.017	0.011	-9999	-10000	0	0
Cohesin/SA2	0	0.002	-9999	-10000	0	0
PPP1CB/MYPT1	0	0.001	-9999	-10000	0	0
KIF20A	-0.09	0.077	-9999	-10000	0	0
APC/C/CDC20	0.032	0.036	-9999	-10000	0	0
PPP2R1A	0.016	0.007	-9999	-10000	0	0
chromosome segregation	-0.024	0.026	-9999	-10000	0	0
PRC1	-0.065	0.081	-9999	-10000	0	0
ECT2	0.003	0.041	-9999	-10000	0	0
C13orf34	0.02	0.011	-9999	-10000	0	0
NUDC	0.016	0.007	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.005	0.023	-9999	-10000	0	0
spindle assembly	0.016	0.01	-9999	-10000	0	0
spindle stabilization	0.008	0.007	-9999	-10000	0	0
APC/C/HCDH1	0.01	0.077	-9999	-0.47	13	13
MKLP2/PLK1	0.047	0.042	-9999	-10000	0	0
CCNB1	-0.046	0.078	-9999	-10000	0	0
PPP1CB	0.016	0	-9999	-10000	0	0
BTRC	0.013	0.023	-9999	-10000	0	0
ROCK2	0.026	0.024	-9999	-0.49	1	1
TUBG1	0.015	0.007	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.018	0.034	-9999	-0.32	4	4
MLF1IP	-0.041	0.055	-9999	-10000	0	0
INCENP	0.002	0.046	-9999	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
CDKN2A	-0.004	0.04	-9999	-9999
TP53	-0.003	0.013	-9999	-9999
Senescence	-0.003	0.013	-9999	-9999
Apoptosis	-0.003	0.013	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0.007	0.026	-9999	-9999
MDM4	0.015	0.016	-9999	-9999

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
MDK	0.004	0.043	-9999	-9999
GPC2	0	0	-9999	-9999
GPC2/Midkine	-0.007	0.025	-9999	-9999
neuron projection morphogenesis	-0.007	0.025	-9999	-9999

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.016	0	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	0.001	-9999	-9999
MDM2/SUMO1	0.039	0.008	-9999	-9999
HDAC4	0.016	0	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	0.001	-9999	-9999
SUMO1	0.016	0	-9999	-9999
NPC/RanGAP1/SUMO1	0.022	0.002	-9999	-9999
mol:GTP	0	0	-9999	-9999
XPO1	0.036	0.003	-9999	-9999
EntrezGene:23636	0	0	-9999	-9999
RAN	0.016	0	-9999	-9999
EntrezGene:8021	0	0	-9999	-9999
RANBP2	0.016	0.007	-9999	-9999
SUMO1/HDAC4	0.038	0.002	-9999	-9999
SUMO1/HDAC1	0.038	0.002	-9999	-9999
RANGAP1	0.01	0.031	-9999	-9999
MDM2/SUMO1/SUMO1	0.002	0.014	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.027	0.003	-9999	-9999
Ran/GTP	0.001	0.004	-9999	-9999
EntrezGene:23225	0	0	-9999	-9999
MDM2	0.012	0.025	-9999	-9999
UBE2I	0.016	0	-9999	-9999
Ran/GTP/Exportin 1	0.001	0.006	-9999	-9999
NPC	0	0.003	-9999	-9999
PIAS2	0.016	0	-9999	-9999
PIAS1	0.016	0.007	-9999	-9999
EntrezGene:9972	0	0	-9999	-9999

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.016	0	-9999	-10000	0	0
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.016	0.01	-9999	-10000	0	0
TCEB1	0.014	0.019	-9999	-10000	0	0
HIF1A/p53	0.041	0.029	-9999	-0.26	4	4
HIF1A	0.032	0.03	-9999	-0.28	4	4
COPS5	0.016	0.007	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.004	0.019	-9999	-10000	0	0
FIH (dimer)	0.016	0	-9999	-10000	0	0
CDKN2A	-0.011	0.061	-9999	-10000	0	0
ARNT/IPAS	0	0	-9999	-10000	0	0
HIF1AN	0.016	0	-9999	-10000	0	0
GNB2L1	0.016	0	-9999	-10000	0	0
HIF1A/ARNT	0.041	0.029	-9999	-0.27	2	2
CUL2	0.016	0.007	-9999	-10000	0	0
OS9	0.016	0.01	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.001	0.01	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.041	0.029	-9999	-0.27	2	2
PHD1-3/OS9	0.018	0.041	-9999	-0.41	1	1
HIF1A/RACK1/Elongin B/Elongin C	0.001	0.024	-9999	-10000	0	0
VHL	0.012	0.027	-9999	-10000	0	0
HSP90AA1	0.016	0.01	-9999	-10000	0	0
HIF1A/JAB1	0.041	0.029	-9999	-0.27	2	2
EGLN3	-0.017	0.071	-9999	-0.72	1	1
EGLN2	0.014	0.017	-9999	-10000	0	0
EGLN1	0.015	0.016	-9999	-10000	0	0
TP53	0.016	0.01	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.05	0.009	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
ARD1A	0.015	0.012	-9999	-10000	0	0
RBX1	0.016	0	-9999	-10000	0	0
HIF1A/p19ARF	0.048	0.035	-9999	-0.27	2	2

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.003	0.035	-10000	0	-0.4	4	4
MAPK9	0.011	0.002	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.013	0.015	-10000	0	-10000	0	0
GNB1/GNG2	-0.001	0.021	-10000	0	-0.47	1	1
GNB1	0.016	0.01	-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	0.011	0	-10000	0	-10000	0	0
Gs family/GTP	-0.003	0.033	-10000	0	-0.44	3	3
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	0.001	0.008	0.1	3	-10000	0	3
GNAL	0.012	0.056	-10000	0	-0.72	3	3
GNG2	0.015	0.032	-10000	0	-0.72	1	1
CRH	0.013	0.022	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.01	0.019	-10000	0	-0.42	1	1
MAPK11	0.011	0	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.001	0.005	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.022	0.006	-9999	-10000	0	0
AP2	-0.001	0.01	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.008	-9999	-10000	0	0
CLTB	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.032	0.001	-9999	-10000	0	0
CD4	0.016	0	-9999	-10000	0	0
CLTA	0.016	0	-9999	-10000	0	0
mol:GTP	0.001	0.002	-9999	-10000	0	0
ARFGAP1	0.013	0.012	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.011	-9999	-0.23	1	1
ARF1/GTP	-0.001	0.009	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.034	0.006	-9999	-10000	0	0
mol:Choline	0	0.011	-9999	-0.24	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.015	0.01	-9999	-10000	0	0
DDEF1	0	0.011	-9999	-0.24	1	1
ARF1/GDP	0	0.007	-9999	-10000	0	0
AP2M1	0.016	0.01	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0.004	-9999	-10000	0	0
Rac/GTP	0	0.002	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0.009	-9999	-10000	0	0
ARFIP2	0.013	0.017	-9999	-10000	0	0
COPA	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.03	0.004	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.004	-9999	-10000	0	0
GGA3	0.016	0.007	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0.005	-9999	-10000	0	0
AP2A1	0.015	0.014	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.034	0.004	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0.006	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	-0.001	0.007	-9999	-10000	0	0
CYTH2	0.001	0.002	-9999	-10000	0	0
ARF1/GTP/GGA3	0.001	0.006	-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	0.045	0.002	-9999	-10000	0	0
PLD2	0	0.011	-9999	-0.24	1	1
ARF-GAP1/v-SNARE	0.013	0.012	-9999	-10000	0	0
PIP5K1A	0	0.011	-9999	-0.23	1	1
ARF1/GTP/Membrin/GBF1/p115	0	0.007	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0.011	-9999	-0.24	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.013	0.012	-9999	-10000	0	0
GOSR2	0	0.005	-9999	-10000	0	0
USO1	0	0.005	-9999	-10000	0	0
GBF1	0	0.005	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0.01	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0	0.009	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.001	0.023	-9999	-0.54	1	1
FBXW11	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
CHUK	0.015	0.032	-9999	-0.72	1	1
NF kappa B2 p100/RelB	0.002	0.022	-9999	-0.38	1	1
NFKB1	0.016	0	-9999	-10000	0	0
MAP3K14	0.016	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.002	0.012	-9999	-10000	0	0
RELB	0.013	0.024	-9999	-10000	0	0
NFKB2	0.015	0.012	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.001	0.013	-9999	-10000	0	0
regulation of B cell activation	0.001	0.012	-9999	-10000	0	0

pid_entity	TCGA.E2.A1BD	TCGA.E2.A1BC	TCGA.E2.A1B6	TCGA.E2.A1B5
109_MAP3K5	0.07	0.07	0.073	0.073
47_PPARGC1A	0.016	0.016	0.016	-0.15
105_BMP4	0.016	0.016	0.016	0.016
105_BMP6	0.016	0.016	0.016	0.016
105_BMP7	0.016	0.016	0.016	0.016
105_BMP2	0.016	0.016	0.016	0.016
131_RELN/VLDLR	0	0	-0.41	0.087
30_TGFB1/TGF beta receptor Type II	0.016	0.015	0.015	0.016
84_STAT5B	-0.25	-0.045	-0.037	-0.25
84_STAT5A	-0.25	-0.045	-0.037	-0.25