PARADIGM pathway analysis of mRNASeq expression and copy number data

Pathway.Name	Avg.Num.Perturbations
BCR signaling pathway	125
IL4-mediated signaling events	120
TCR signaling in naïve CD8+ T cells	105
IL23-mediated signaling events	105
Nephrin/Neph1 signaling in the kidney podocyte	81
IL12-mediated signaling events	76
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	61
Caspase cascade in apoptosis	59
Calcium signaling in the CD4+ TCR pathway	56
E-cadherin signaling events	56

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
BCR signaling pathway	0.3397	125	12407	99	-0.71	0.043	1000	-1000	-0.049	-1000
IL4-mediated signaling events	0.3261	120	10991	91	-1.3	1	1000	-1000	-0.062	-1000
TCR signaling in naïve CD8+ T cells	0.2853	105	9767	93	-0.56	0.12	1000	-1000	-0.034	-1000
IL23-mediated signaling events	0.2853	105	6315	60	-0.76	0.034	1000	-1000	-0.011	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.2201	81	2783	34	-0.15	0.035	1000	-1000	-0.024	-1000
IL12-mediated signaling events	0.2065	76	6689	87	-0.67	0.11	1000	-1000	-0.029	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1658	61	4214	68	-0.57	0.12	1000	-1000	-0.037	-1000
Caspase cascade in apoptosis	0.1603	59	4407	74	-0.16	0.12	1000	-1000	-0.022	-1000
Calcium signaling in the CD4+ TCR pathway	0.1522	56	1761	31	-0.35	0.035	1000	-1000	-0.038	-1000
E-cadherin signaling events	0.1522	56	282	5	-0.082	0.035	1000	-1000	0.017	-1000
IL27-mediated signaling events	0.1495	55	2841	51	-0.26	0.17	1000	-1000	-0.02	-1000
JNK signaling in the CD4+ TCR pathway	0.1467	54	934	17	-0.22	0.033	1000	-1000	-0.02	-1000
Ras signaling in the CD4+ TCR pathway	0.1386	51	876	17	-0.14	0.063	1000	-1000	-0.008	-1000
FAS signaling pathway (CD95)	0.1359	50	2395	47	-0.094	0.076	1000	-1000	-0.025	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.1277	47	3484	74	-0.082	0.08	1000	-1000	-0.039	-1000
E-cadherin signaling in the nascent adherens junction	0.1250	46	3531	76	-0.095	0.051	1000	-1000	-0.034	-1000
a4b1 and a4b7 Integrin signaling	0.1141	42	210	5	-0.031	0.01	1000	-1000	0.016	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.1087	40	1825	45	-0.17	0.072	1000	-1000	-0.017	-1000
Thromboxane A2 receptor signaling	0.1060	39	4147	105	-0.12	0.057	1000	-1000	-0.025	-1000
IL2 signaling events mediated by PI3K	0.1060	39	2303	58	-0.15	0.06	1000	-1000	-0.028	-1000
amb2 Integrin signaling	0.1033	38	3163	82	-0.18	0.044	1000	-1000	-0.013	-1000
Glucocorticoid receptor regulatory network	0.1033	38	4378	114	-0.42	0.23	1000	-1000	-0.032	-1000
Signaling events regulated by Ret tyrosine kinase	0.1033	38	3187	82	-0.068	0.035	1000	-1000	-0.027	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.1005	37	1375	37	-0.22	0.049	1000	-1000	-0.018	-1000
Class I PI3K signaling events	0.1005	37	2736	73	-0.38	0.069	1000	-1000	-0.021	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1005	37	3280	88	-0.21	0.046	1000	-1000	-0.052	-1000
IL2 signaling events mediated by STAT5	0.0978	36	799	22	-0.16	0.036	1000	-1000	-0.018	-1000
S1P4 pathway	0.0951	35	892	25	-0.11	0.045	1000	-1000	-0.009	-1000
IFN-gamma pathway	0.0924	34	2379	68	-0.12	0.045	1000	-1000	-0.033	-1000
Endothelins	0.0897	33	3185	96	-0.15	0.036	1000	-1000	-0.035	-1000
E-cadherin signaling in keratinocytes	0.0897	33	1454	43	-0.082	0.037	1000	-1000	-0.012	-1000
ceramide signaling pathway	0.0870	32	1590	49	-0.1	0.05	1000	-1000	-0.023	-1000
Syndecan-1-mediated signaling events	0.0842	31	1083	34	-0.095	0.035	1000	-1000	-0.014	-1000
Fc-epsilon receptor I signaling in mast cells	0.0842	31	3050	97	-0.1	0.06	1000	-1000	-0.032	-1000
HIF-1-alpha transcription factor network	0.0761	28	2190	76	-0.082	0.11	1000	-1000	-0.001	-1000
LPA receptor mediated events	0.0761	28	2916	102	-0.072	0.045	1000	-1000	-0.06	-1000
Syndecan-4-mediated signaling events	0.0761	28	1922	67	-0.17	0.046	1000	-1000	-0.026	-1000
Visual signal transduction: Cones	0.0707	26	988	38	-0.14	0.043	1000	-1000	-0.007	-1000
FOXA2 and FOXA3 transcription factor networks	0.0679	25	1189	46	-0.42	0.04	1000	-1000	-0.032	-1000
Atypical NF-kappaB pathway	0.0679	25	801	31	-0.14	0.049	1000	-1000	-0.007	-1000
Glypican 1 network	0.0652	24	1175	48	-0.22	0.038	1000	-1000	-0.023	-1000
Osteopontin-mediated events	0.0625	23	892	38	-0.036	0.049	1000	-1000	-0.013	-1000
TRAIL signaling pathway	0.0625	23	1116	48	-0.031	0.052	1000	-1000	-0.015	-1000
Regulation of p38-alpha and p38-beta	0.0625	23	1265	54	-0.23	0.072	1000	-1000	-0.036	-1000
Visual signal transduction: Rods	0.0625	23	1227	52	-0.14	0.047	1000	-1000	-0.012	-1000
Aurora C signaling	0.0571	21	149	7	-0.056	0.032	1000	-1000	-0.005	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0571	21	1105	52	-0.18	0.079	1000	-1000	-0.016	-1000
Ephrin A reverse signaling	0.0543	20	141	7	0	0.025	1000	-1000	0	-1000
Ceramide signaling pathway	0.0543	20	1525	76	-0.1	0.079	1000	-1000	-0.028	-1000
Paxillin-dependent events mediated by a4b1	0.0543	20	732	36	-0.04	0.059	1000	-1000	-0.026	-1000
Arf6 signaling events	0.0516	19	1194	62	-0.1	0.073	1000	-1000	-0.037	-1000
EPO signaling pathway	0.0489	18	1018	55	-0.038	0.053	1000	-1000	-0.014	-1000
IL6-mediated signaling events	0.0489	18	1424	75	-0.19	0.056	1000	-1000	-0.027	-1000
Plasma membrane estrogen receptor signaling	0.0489	18	1602	86	-0.055	0.062	1000	-1000	-0.026	-1000
Signaling events mediated by PTP1B	0.0462	17	1316	76	-0.24	0.063	1000	-1000	-0.036	-1000
Nectin adhesion pathway	0.0462	17	1096	63	-0.17	0.072	1000	-1000	-0.025	-1000
EPHB forward signaling	0.0462	17	1522	85	-0.053	0.067	1000	-1000	-0.038	-1000
Integrins in angiogenesis	0.0435	16	1409	84	-0.14	0.076	1000	-1000	-0.025	-1000
PDGFR-beta signaling pathway	0.0408	15	1483	97	-0.3	0.087	1000	-1000	-0.024	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0380	14	1098	78	-0.074	0.09	1000	-1000	-0.032	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0353	13	376	28	-0.11	0.065	1000	-1000	-0.009	-1000
Signaling events mediated by the Hedgehog family	0.0353	13	709	52	-0.2	0.058	1000	-1000	-0.018	-1000
Cellular roles of Anthrax toxin	0.0353	13	544	39	-0.12	0.041	1000	-1000	-0.015	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0353	13	1179	85	-0.037	0.073	1000	-1000	-0.042	-1000
p75(NTR)-mediated signaling	0.0353	13	1673	125	-0.1	0.088	1000	-1000	-0.031	-1000
BMP receptor signaling	0.0353	13	1128	81	-0.14	0.074	1000	-1000	-0.02	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0353	13	1089	83	-0.097	0.066	1000	-1000	-0.011	-1000
LPA4-mediated signaling events	0.0326	12	144	12	-0.048	0.01	1000	-1000	-0.011	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0326	12	1480	120	-0.074	0.084	1000	-1000	-0.031	-1000
Syndecan-2-mediated signaling events	0.0299	11	821	69	-0.17	0.058	1000	-1000	-0.028	-1000
Ephrin B reverse signaling	0.0299	11	549	48	-0.1	0.048	1000	-1000	-0.029	-1000
Noncanonical Wnt signaling pathway	0.0272	10	277	26	-0.001	0.052	1000	-1000	-0.025	-1000
IL1-mediated signaling events	0.0272	10	673	62	-0.032	0.089	1000	-1000	-0.021	-1000
Canonical Wnt signaling pathway	0.0272	10	518	51	-0.027	0.073	1000	-1000	-0.022	-1000
EGFR-dependent Endothelin signaling events	0.0272	10	225	21	-0.02	0.055	1000	-1000	-0.029	-1000
ErbB2/ErbB3 signaling events	0.0245	9	640	65	-0.023	0.06	1000	-1000	-0.043	-1000
Presenilin action in Notch and Wnt signaling	0.0245	9	606	61	-0.067	0.088	1000	-1000	-0.038	-1000
Signaling events mediated by HDAC Class I	0.0217	8	836	104	-0.064	0.081	1000	-1000	-0.036	-1000
TCGA08_retinoblastoma	0.0217	8	68	8	-0.002	0.027	1000	-1000	-0.001	-1000
Aurora B signaling	0.0217	8	544	67	-0.097	0.089	1000	-1000	-0.025	-1000
Canonical NF-kappaB pathway	0.0190	7	300	39	-0.054	0.073	1000	-1000	-0.009	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0190	7	392	54	-0.078	0.065	1000	-1000	-0.017	-1000
Signaling mediated by p38-gamma and p38-delta	0.0190	7	114	15	-0.004	0.034	1000	-1000	-0.019	-1000
Effects of Botulinum toxin	0.0190	7	187	26	-0.026	0.045	1000	-1000	-0.001	-1000
mTOR signaling pathway	0.0163	6	326	53	-0.022	0.057	1000	-1000	-0.025	-1000
HIF-2-alpha transcription factor network	0.0163	6	276	43	-0.16	0.17	1000	-1000	-0.052	-1000
Glypican 2 network	0.0163	6	27	4	0.025	0.036	1000	-1000	0.017	-1000
TCGA08_rtk_signaling	0.0163	6	172	26	-0.039	0.082	1000	-1000	-0.02	-1000
Insulin Pathway	0.0163	6	458	74	-0.06	0.083	1000	-1000	-0.021	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0163	6	207	33	-0.009	0.077	1000	-1000	-0.026	-1000
Class IB PI3K non-lipid kinase events	0.0163	6	18	3	-0.027	0.027	1000	-1000	-0.02	-1000
PLK1 signaling events	0.0136	5	466	85	-0.007	0.068	1000	-1000	-0.025	-1000
S1P1 pathway	0.0136	5	180	36	0	0.051	1000	-1000	-0.011	-1000
FoxO family signaling	0.0136	5	351	64	-0.41	0.095	1000	-1000	-0.031	-1000
Signaling mediated by p38-alpha and p38-beta	0.0136	5	232	44	-0.006	0.061	1000	-1000	-0.013	-1000
Wnt signaling	0.0136	5	41	7	0.007	0.033	1000	-1000	-0.001	-1000
Regulation of Telomerase	0.0136	5	585	102	-0.11	0.077	1000	-1000	-0.024	-1000
VEGFR1 specific signals	0.0136	5	289	56	-0.047	0.083	1000	-1000	-0.023	-1000
S1P3 pathway	0.0136	5	235	42	-0.036	0.054	1000	-1000	-0.009	-1000
Regulation of Androgen receptor activity	0.0136	5	416	70	-0.058	0.056	1000	-1000	-0.03	-1000
Arf6 downstream pathway	0.0109	4	173	43	-0.051	0.063	1000	-1000	-0.032	-1000
Signaling events mediated by PRL	0.0109	4	141	34	-0.054	0.077	1000	-1000	-0.022	-1000
p38 MAPK signaling pathway	0.0109	4	185	44	-0.011	0.057	1000	-1000	-0.009	-1000
Regulation of nuclear SMAD2/3 signaling	0.0082	3	528	136	-0.11	0.13	1000	-1000	-0.028	-1000
ErbB4 signaling events	0.0082	3	275	69	-0.031	0.055	1000	-1000	-0.022	-1000
Hedgehog signaling events mediated by Gli proteins	0.0082	3	200	65	0	0.081	1000	-1000	-0.032	-1000
Class I PI3K signaling events mediated by Akt	0.0082	3	218	68	-0.054	0.065	1000	-1000	-0.023	-1000
Reelin signaling pathway	0.0082	3	176	56	-0.002	0.078	1000	-1000	-0.014	-1000
Retinoic acid receptors-mediated signaling	0.0082	3	209	58	-0.033	0.067	1000	-1000	-0.021	-1000
Syndecan-3-mediated signaling events	0.0082	3	134	35	-0.017	0.088	1000	-1000	-0.011	-1000
Nongenotropic Androgen signaling	0.0082	3	161	52	-0.041	0.056	1000	-1000	-0.013	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0082	3	497	125	-0.074	0.087	1000	-1000	-0.015	-1000
Arf6 trafficking events	0.0082	3	218	71	-0.052	0.064	1000	-1000	-0.034	-1000
IGF1 pathway	0.0082	3	180	57	-0.024	0.085	1000	-1000	-0.02	-1000
Arf1 pathway	0.0082	3	204	54	-0.008	0.05	1000	-1000	-0.012	-1000
Coregulation of Androgen receptor activity	0.0054	2	176	76	-0.015	0.06	1000	-1000	-0.009	-1000
Signaling events mediated by HDAC Class II	0.0054	2	173	75	-0.039	0.089	1000	-1000	-0.017	-1000
PDGFR-alpha signaling pathway	0.0054	2	118	44	-0.019	0.071	1000	-1000	-0.029	-1000
Signaling events mediated by HDAC Class III	0.0054	2	91	40	-0.056	0.057	1000	-1000	-0.028	-1000
FOXM1 transcription factor network	0.0054	2	121	51	0.008	0.26	1000	-1000	-0.023	-1000
Aurora A signaling	0.0027	1	95	60	0	0.074	1000	-1000	-0.007	-1000
Insulin-mediated glucose transport	0.0027	1	48	32	0	0.064	1000	-1000	-0.017	-1000
S1P5 pathway	0.0027	1	17	17	-0.039	0.041	1000	-1000	-0.009	-1000
Rapid glucocorticoid signaling	0.0027	1	36	20	-0.009	0.041	1000	-1000	-0.002	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	5	23	0.007	0.069	1000	-1000	-0.012	-1000
BARD1 signaling events	0.0000	0	56	57	-0.077	0.089	1000	-1000	-0.042	-1000
PLK2 and PLK4 events	0.0000	0	2	3	0.018	-1000	1000	-1000	-0.003	-1000
Circadian rhythm pathway	0.0000	0	6	22	-0.012	0.08	1000	-1000	-0.017	-1000
TCGA08_p53	0.0000	0	1	7	0	0.031	1000	-1000	-0.002	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	5	27	0	0.082	1000	-1000	-0.019	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.089	1000	-1000	0	-1000
Total	NA	2740	171008	7203	-16	-990	131000	-131000	-2.8	-131000

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.29	0.26	-10000	0	-0.49	216	216
IKBKB	-0.12	0.14	-10000	0	-0.29	91	91
AKT1	-0.17	0.13	0.25	1	-0.27	227	228
IKBKG	-0.12	0.14	-10000	0	-0.28	114	114
CALM1	-0.32	0.33	-10000	0	-0.58	194	194
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
MAP3K1	-0.44	0.38	-10000	0	-0.72	227	227
MAP3K7	0.032	0.011	-10000	0	-10000	0	0
mol:Ca2+	-0.34	0.36	-10000	0	-0.62	194	194
DOK1	0.035	0.003	-10000	0	-10000	0	0
AP-1	-0.15	0.14	-10000	0	-0.27	189	189
LYN	0.016	0.084	-10000	0	-0.42	13	13
BLNK	-0.11	0.21	-10000	0	-0.42	116	116
SHC1	0.032	0.011	-10000	0	-10000	0	0
BCR complex	-0.27	0.27	-10000	0	-0.47	225	225
CD22	-0.47	0.42	-10000	0	-0.77	225	225
CAMK2G	-0.29	0.3	-10000	0	-0.53	194	194
CSNK2A1	0.033	0.008	-10000	0	-10000	0	0
INPP5D	-0.038	0.16	-10000	0	-0.42	58	58
SHC/GRB2/SOS1	-0.24	0.26	-10000	0	-0.42	216	216
GO:0007205	-0.35	0.37	-10000	0	-0.64	194	194
SYK	-0.012	0.13	-10000	0	-0.42	36	36
ELK1	-0.32	0.34	-10000	0	-0.59	194	194
NFATC1	-0.37	0.32	0.32	1	-0.6	225	226
B-cell antigen/BCR complex	-0.27	0.27	-10000	0	-0.47	225	225
PAG1/CSK	0.043	0.031	-10000	0	-0.3	2	2
NFKBIB	-0.024	0.053	0.13	1	-0.13	18	19
HRAS	-0.3	0.31	-10000	0	-0.54	196	196
NFKBIA	-0.024	0.053	0.13	1	-0.13	18	19
NF-kappa-B/RelA/I kappa B beta	-0.013	0.045	0.13	1	-10000	0	1
RasGAP/Csk	-0.17	0.23	-10000	0	-0.34	218	218
mol:GDP	-0.33	0.35	-10000	0	-0.6	195	195
PTEN	0.03	0.012	-10000	0	-10000	0	0
CD79B	-0.2	0.22	-10000	0	-0.42	187	187
NF-kappa-B/RelA/I kappa B alpha	-0.013	0.045	0.13	1	-10000	0	1
GRB2	0.034	0.007	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.42	0.34	-10000	0	-0.66	235	235
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
mol:IP3	-0.35	0.38	-10000	0	-0.64	194	194
CSK	0.034	0.006	-10000	0	-10000	0	0
FOS	-0.3	0.3	-10000	0	-0.54	193	193
CHUK	-0.14	0.15	-10000	0	-0.32	107	107
IBTK	0.032	0.011	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.27	0.32	0.25	1	-0.53	191	192
PTPN6	-0.48	0.42	-10000	0	-0.78	223	223
RELA	0.034	0.007	-10000	0	-10000	0	0
BCL2A1	-0.011	0.037	-10000	0	-0.11	3	3
VAV2	-0.54	0.45	-10000	0	-0.86	229	229
ubiquitin-dependent protein catabolic process	-0.02	0.052	0.13	1	-0.12	18	19
BTK	-0.15	0.41	-10000	0	-1	65	65
CD19	-0.5	0.43	-10000	0	-0.8	228	228
MAP4K1	-0.044	0.17	-10000	0	-0.42	64	64
CD72	-0.066	0.18	-10000	0	-0.42	79	79
PAG1	0.029	0.035	-10000	0	-0.42	2	2
MAPK14	-0.34	0.31	0.24	1	-0.58	219	220
SH3BP5	0.034	0.005	-10000	0	-10000	0	0
PIK3AP1	-0.38	0.42	-10000	0	-0.67	209	209
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.51	0.58	-10000	0	-0.91	208	208
RAF1	-0.28	0.29	-10000	0	-0.51	193	193
RasGAP/p62DOK/SHIP	-0.2	0.25	-10000	0	-0.38	222	222
CD79A	-0.22	0.22	-10000	0	-0.42	210	210
re-entry into mitotic cell cycle	-0.15	0.14	-10000	0	-0.27	189	189
RASA1	0.032	0.025	-10000	0	-0.42	1	1
MAPK3	-0.22	0.23	0.24	1	-0.42	186	187
MAPK1	-0.22	0.23	0.24	1	-0.42	183	184
CD72/SHP1	-0.47	0.42	0.26	1	-0.77	225	226
NFKB1	0.034	0.006	-10000	0	-10000	0	0
MAPK8	-0.36	0.31	-10000	0	-0.59	222	222
actin cytoskeleton organization	-0.42	0.35	-10000	0	-0.67	229	229
NF-kappa-B/RelA	-0.019	0.087	0.24	1	-0.2	6	7
Calcineurin	-0.25	0.28	-10000	0	-0.48	193	193
PI3K	-0.39	0.31	-10000	0	-0.6	240	240
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.4	0.44	-10000	0	-0.7	211	211
SOS1	0.035	0.003	-10000	0	-10000	0	0
Bam32/HPK1	-0.59	0.52	-10000	0	-0.97	227	227
DAPP1	-0.71	0.62	-10000	0	-1.2	227	227
cytokine secretion	-0.34	0.29	0.32	1	-0.55	225	226
mol:DAG	-0.35	0.38	-10000	0	-0.64	194	194
PLCG2	-0.001	0.12	-10000	0	-0.42	28	28
MAP2K1	-0.25	0.26	0.25	1	-0.47	187	188
B-cell antigen/BCR complex/FcgammaRIIB	-0.22	0.24	-10000	0	-0.4	221	221
mol:PI-3-4-5-P3	-0.26	0.19	-10000	0	-0.39	235	235
ETS1	-0.26	0.26	-10000	0	-0.48	191	191
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.26	0.31	-10000	0	-0.48	225	225
B-cell antigen/BCR complex/LYN	-0.42	0.4	-10000	0	-0.71	220	220
MALT1	0.033	0.024	-10000	0	-0.42	1	1
TRAF6	0.035	0.006	-10000	0	-10000	0	0
RAC1	-0.46	0.39	-10000	0	-0.74	228	228
B-cell antigen/BCR complex/LYN/SYK	-0.45	0.43	-10000	0	-0.74	227	227
CARD11	-0.34	0.38	0.26	1	-0.65	190	191
FCGR2B	0.013	0.089	-10000	0	-0.42	15	15
PPP3CA	0.034	0.006	-10000	0	-10000	0	0
BCL10	0.035	0.005	-10000	0	-10000	0	0
IKK complex	-0.042	0.055	0.16	1	-0.12	18	19
PTPRC	-0.098	0.2	-10000	0	-0.42	105	105
PDPK1	-0.17	0.12	-10000	0	-0.26	232	232
PPP3CB	0.032	0.01	-10000	0	-10000	0	0
PPP3CC	0.033	0.008	-10000	0	-10000	0	0
POU2F2	-0.015	0.045	-10000	0	-0.11	10	10

×

IL4-mediated signaling events

Figure S2. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S2. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.85	0.61	-10000	0	-1.3	197	197
STAT6 (cleaved dimer)	-0.92	0.66	-10000	0	-1.4	222	222
IGHG1	-0.23	0.17	-10000	0	-0.37	131	131
IGHG3	-0.82	0.58	-10000	0	-1.2	213	213
AKT1	-0.52	0.47	-10000	0	-1.1	133	133
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.55	0.62	-10000	0	-1.3	125	125
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.58	0.57	-10000	0	-1.2	131	131
THY1	-0.86	0.61	-10000	0	-1.3	198	198
MYB	0.015	0.084	-10000	0	-0.42	13	13
HMGA1	0.029	0.035	-10000	0	-0.42	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.62	0.54	-10000	0	-0.97	209	209
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.62	0.61	-10000	0	-1.3	135	135
SP1	0.036	0.012	-10000	0	-10000	0	0
INPP5D	-0.037	0.16	-10000	0	-0.42	58	58
SOCS5	0.048	0.023	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.9	0.66	-10000	0	-1.4	217	217
SOCS1	-0.53	0.36	-10000	0	-0.79	206	206
SOCS3	-0.48	0.4	-10000	0	-0.94	127	127
FCER2	-1.3	0.68	-10000	0	-1.6	292	292
PARP14	0.013	0.049	-10000	0	-0.42	3	3
CCL17	-0.89	0.64	-10000	0	-1.4	199	199
GRB2	0.034	0.007	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.45	0.45	-10000	0	-0.98	125	125
T cell proliferation	-0.9	0.66	-10000	0	-1.4	209	209
IL4R/JAK1	-0.86	0.62	-10000	0	-1.3	203	203
EGR2	-0.97	0.63	-10000	0	-1.4	215	215
JAK2	-0.043	0.069	-10000	0	-0.44	6	6
JAK3	0.007	0.11	-10000	0	-0.39	25	25
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
JAK1	0.001	0.027	-10000	0	-10000	0	0
COL1A2	-0.22	0.21	-10000	0	-1.2	8	8
CCL26	-0.85	0.61	-10000	0	-1.3	198	198
IL4R	-0.92	0.67	-10000	0	-1.5	199	199
PTPN6	-0.06	0.19	-10000	0	-0.4	88	88
IL13RA2	-0.88	0.62	-10000	0	-1.4	208	208
IL13RA1	-0.04	0.045	-10000	0	-10000	0	0
IRF4	-0.66	0.6	-10000	0	-1.1	201	201
ARG1	-0.24	0.27	-10000	0	-0.79	46	46
CBL	-0.58	0.49	-10000	0	-0.91	206	206
GTF3A	0.034	0.015	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.048	0.072	-10000	0	-0.31	6	6
IRF4/BCL6	-0.57	0.56	-10000	0	-1	201	201
CD40LG	-0.22	0.22	-10000	0	-0.42	196	196
MAPK14	-0.56	0.49	-10000	0	-0.96	178	178
mitosis	-0.47	0.42	-10000	0	-0.96	134	134
STAT6	-1.1	0.89	-10000	0	-1.7	210	210
SPI1	0.008	0.11	-10000	0	-0.42	23	23
RPS6KB1	-0.45	0.4	-10000	0	-0.92	133	133
STAT6 (dimer)	-1.1	0.88	-10000	0	-1.7	210	210
STAT6 (dimer)/PARP14	-1	0.74	-10000	0	-1.5	244	244
mast cell activation	0.017	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.6	0.6	-10000	0	-1.3	135	135
FRAP1	-0.52	0.47	-10000	0	-1.1	133	133
LTA	-1	0.74	-10000	0	-1.6	215	215
FES	0.024	0.066	-10000	0	-0.42	8	8
T-helper 1 cell differentiation	1	0.76	1.5	210	-10000	0	210
CCL11	-0.83	0.58	-10000	0	-1.3	201	201
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.58	0.59	-10000	0	-1.3	130	130
IL2RG	-0.099	0.2	-10000	0	-0.4	112	112
IL10	-0.87	0.63	-10000	0	-1.4	202	202
IRS1	0.032	0.011	-10000	0	-10000	0	0
IRS2	0.034	0.007	-10000	0	-10000	0	0
IL4	-0.19	0.26	-10000	0	-1.3	17	17
IL5	-0.86	0.61	-10000	0	-1.3	201	201
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.68	0.52	-10000	0	-1	207	207
COL1A1	-0.25	0.25	-10000	0	-1.2	14	14
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.9	0.66	-10000	0	-1.4	198	198
IL2R gamma/JAK3	-0.071	0.18	-10000	0	-0.34	111	111
TFF3	-0.93	0.66	-10000	0	-1.4	210	210
ALOX15	-0.86	0.62	-10000	0	-1.4	198	198
MYBL1	0.029	0.035	-10000	0	-0.42	2	2
T-helper 2 cell differentiation	-0.8	0.62	-10000	0	-1.2	212	212
SHC1	0.032	0.011	-10000	0	-10000	0	0
CEBPB	0.033	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.57	0.56	-10000	0	-1.2	133	133
mol:PI-3-4-5-P3	-0.52	0.47	-10000	0	-1.1	133	133
PI3K	-0.57	0.55	-10000	0	-1.2	133	133
DOK2	-0.01	0.13	-10000	0	-0.42	35	35
ETS1	0.045	0.023	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.41	0.41	-10000	0	-0.9	124	124
ITGB3	-0.88	0.62	-10000	0	-1.4	205	205
PIGR	-0.93	0.68	-10000	0	-1.5	205	205
IGHE	0.055	0.059	0.19	33	-10000	0	33
MAPKKK cascade	-0.4	0.39	-10000	0	-0.87	124	124
BCL6	0.04	0.011	-10000	0	-10000	0	0
OPRM1	-0.86	0.61	-10000	0	-1.3	198	198
RETNLB	-0.86	0.61	-10000	0	-1.3	202	202
SELP	-0.97	0.71	-10000	0	-1.5	209	209
AICDA	-1.1	0.67	-10000	0	-1.5	258	258

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.26	0.39	0.3	9	-0.7	158	167
FYN	-0.43	0.56	0.27	2	-1	164	166
LAT/GRAP2/SLP76	-0.28	0.4	-10000	0	-0.72	160	160
IKBKB	0.034	0.007	-10000	0	-10000	0	0
AKT1	-0.22	0.3	-10000	0	-0.54	160	160
B2M	0.026	0.043	-10000	0	-0.43	3	3
IKBKG	-0.05	0.089	0.11	10	-0.15	147	157
MAP3K8	0.02	0.074	-10000	0	-0.42	10	10
mol:Ca2+	-0.018	0.035	0.089	24	-0.054	110	134
integrin-mediated signaling pathway	0.013	0.084	-10000	0	-0.25	34	34
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.36	0.47	-10000	0	-0.87	161	161
TRPV6	0.12	0.37	1.2	40	-10000	0	40
CD28	-0.038	0.17	-10000	0	-0.42	58	58
SHC1	-0.4	0.52	0.31	9	-0.94	163	172
receptor internalization	-0.47	0.61	-10000	0	-1.1	167	167
PRF1	-0.51	0.67	-10000	0	-1.3	154	154
KRAS	0.034	0.006	-10000	0	-10000	0	0
GRB2	0.034	0.007	-10000	0	-10000	0	0
COT/AKT1	-0.16	0.24	-10000	0	-0.42	158	158
LAT	-0.41	0.53	-10000	0	-0.98	162	162
EntrezGene:6955	-0.003	0.004	-10000	0	-10000	0	0
CD3D	-0.12	0.22	-10000	0	-0.43	123	123
CD3E	-0.1	0.21	-10000	0	-0.43	105	105
CD3G	-0.097	0.2	-10000	0	-0.42	102	102
RASGRP2	-0.088	0.097	-10000	0	-0.18	184	184
RASGRP1	-0.23	0.32	0.22	3	-0.58	162	165
HLA-A	-0.004	0.007	-10000	0	-10000	0	0
RASSF5	-0.013	0.13	-10000	0	-0.42	36	36
RAP1A/GTP/RAPL	0.014	0.085	-10000	0	-0.25	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.047	0.091	0.15	8	-0.14	154	162
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.11	0.14	-10000	0	-0.26	155	155
PRKCA	-0.12	0.17	-10000	0	-0.31	155	155
GRAP2	-0.014	0.14	-10000	0	-0.42	38	38
mol:IP3	-0.21	0.28	-10000	0	-0.52	160	160
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.48	0.64	-10000	0	-1.2	157	157
ORAI1	-0.11	0.31	0.36	1	-1	40	41
CSK	-0.42	0.54	0.24	2	-1	162	164
B7 family/CD28	-0.41	0.59	-10000	0	-1.1	159	159
CHUK	0.032	0.01	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.53	0.68	0.21	1	-1.2	163	164
PTPN6	-0.44	0.58	0.2	1	-1.1	162	163
VAV1	-0.42	0.54	-10000	0	-0.99	163	163
Monovalent TCR/CD3	-0.31	0.43	-10000	0	-0.74	162	162
CBL	0.032	0.011	-10000	0	-10000	0	0
LCK	-0.49	0.63	0.25	2	-1.2	160	162
PAG1	-0.41	0.54	0.29	3	-0.98	163	166
RAP1A	0.034	0.007	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.53	0.68	0.2	1	-1.2	166	167
CD80	-0.061	0.18	-10000	0	-0.42	75	75
CD86	-0.022	0.15	-10000	0	-0.42	44	44
PDK1/CARD11/BCL10/MALT1	-0.12	0.18	-10000	0	-0.32	155	155
HRAS	0.034	0.006	-10000	0	-10000	0	0
GO:0035030	-0.32	0.42	-10000	0	-0.78	160	160
CD8A	-0.13	0.22	-10000	0	-0.43	133	133
CD8B	-0.14	0.22	-10000	0	-0.43	135	135
PTPRC	-0.1	0.2	-10000	0	-0.42	105	105
PDK1/PKC theta	-0.28	0.37	0.23	1	-0.69	159	160
CSK/PAG1	-0.39	0.52	0.26	5	-0.97	159	164
SOS1	0.035	0.003	-10000	0	-10000	0	0
peptide-MHC class I	0.008	0.036	-10000	0	-0.31	3	3
GRAP2/SLP76	-0.36	0.49	-10000	0	-0.88	163	163
STIM1	-0.021	0.061	-10000	0	-10000	0	0
RAS family/GTP	-0.05	0.12	0.18	11	-0.19	149	160
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.56	0.72	-10000	0	-1.3	167	167
mol:DAG	-0.2	0.24	-10000	0	-0.45	162	162
RAP1A/GDP	-0.017	0.043	0.077	7	-0.066	136	143
PLCG1	0.033	0.01	-10000	0	-10000	0	0
CD247	-0.1	0.21	-10000	0	-0.42	107	107
cytotoxic T cell degranulation	-0.47	0.61	-10000	0	-1.1	157	157
RAP1A/GTP	-0.031	0.036	-10000	0	-0.068	180	180
mol:PI-3-4-5-P3	-0.27	0.36	-10000	0	-0.67	160	160
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.28	0.38	-10000	0	-0.7	159	159
NRAS	0.034	0.008	-10000	0	-10000	0	0
ZAP70	-0.12	0.22	-10000	0	-0.42	126	126
GRB2/SOS1	0.05	0.011	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.29	0.38	-10000	0	-0.71	159	159
MALT1	0.033	0.024	-10000	0	-0.42	1	1
TRAF6	0.034	0.006	-10000	0	-10000	0	0
CD8 heterodimer	-0.17	0.28	-10000	0	-0.51	147	147
CARD11	-0.074	0.19	-10000	0	-0.42	85	85
PRKCB	-0.15	0.2	0.2	1	-0.36	163	164
PRKCE	-0.12	0.17	0.2	1	-0.31	158	159
PRKCQ	-0.34	0.44	0.24	1	-0.82	160	161
LCP2	0.015	0.09	-10000	0	-0.42	15	15
BCL10	0.034	0.005	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.18	0.25	0.18	1	-0.45	158	159
IKK complex	-0.034	0.08	0.14	13	-0.12	146	159
RAS family/GDP	-0.014	0.021	-10000	0	-0.04	112	112
MAP3K14	-0.12	0.18	0.15	1	-0.31	158	159
PDPK1	-0.2	0.28	-10000	0	-0.51	158	158
TCR/CD3/MHC I/CD8/Fyn	-0.55	0.71	-10000	0	-1.3	161	161

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.5	0.67	-9999	-1.2	158	158
IL23A	-0.53	0.7	-9999	-1.3	159	159
NF kappa B1 p50/RelA/I kappa B alpha	-0.54	0.73	-9999	-1.3	157	157
positive regulation of T cell mediated cytotoxicity	-0.64	0.85	-9999	-1.5	162	162
ITGA3	-0.51	0.67	-9999	-1.2	156	156
IL17F	-0.31	0.41	-9999	-0.74	159	159
IL12B	-0.011	0.087	-9999	-0.45	8	8
STAT1 (dimer)	-0.6	0.8	-9999	-1.4	161	161
CD4	-0.52	0.68	-9999	-1.2	156	156
IL23	-0.51	0.67	-9999	-1.2	158	158
IL23R	-0.038	0.13	-9999	-1.3	2	2
IL1B	-0.56	0.73	-9999	-1.3	155	155
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.59	0.72	-9999	-1.3	180	180
TYK2	-0.001	0.046	-9999	-10000	0	0
STAT4	-0.08	0.2	-9999	-0.42	93	93
STAT3	0.034	0.005	-9999	-10000	0	0
IL18RAP	-0.12	0.21	-9999	-0.42	117	117
IL12RB1	-0.11	0.21	-9999	-0.45	96	96
PIK3CA	0.034	0.006	-9999	-10000	0	0
IL12Rbeta1/TYK2	-0.072	0.16	-9999	-0.34	96	96
IL23R/JAK2	-0.032	0.16	-9999	-1.3	2	2
positive regulation of chronic inflammatory response	-0.64	0.85	-9999	-1.5	162	162
natural killer cell activation	0.006	0.009	-9999	-10000	0	0
JAK2	-0.004	0.078	-9999	-0.45	6	6
PIK3R1	0.034	0.007	-9999	-10000	0	0
NFKB1	0.033	0.007	-9999	-10000	0	0
RELA	0.032	0.008	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.47	0.62	-9999	-1.1	159	159
ALOX12B	-0.5	0.66	-9999	-1.2	156	156
CXCL1	-0.51	0.66	-9999	-1.2	159	159
T cell proliferation	-0.64	0.85	-9999	-1.5	162	162
NFKBIA	0.033	0.006	-9999	-10000	0	0
IL17A	-0.22	0.33	-9999	-0.57	157	157
PI3K	-0.56	0.75	-9999	-1.3	159	159
IFNG	-0.049	0.068	-9999	-0.12	168	168
STAT3 (dimer)	-0.51	0.7	-9999	-1.2	159	159
IL18R1	-0.046	0.16	-9999	-0.42	58	58
IL23/IL23R/JAK2/TYK2/SOCS3	-0.31	0.47	-9999	-0.79	154	154
IL18/IL18R	-0.14	0.25	-9999	-0.43	144	144
macrophage activation	-0.02	0.024	-9999	-0.044	159	159
TNF	-0.57	0.75	-9999	-1.4	157	157
STAT3/STAT4	-0.58	0.77	-9999	-1.4	164	164
STAT4 (dimer)	-0.63	0.82	-9999	-1.5	164	164
IL18	-0.067	0.18	-9999	-0.42	72	72
IL19	-0.5	0.66	-9999	-1.2	156	156
STAT5A (dimer)	-0.6	0.8	-9999	-1.4	161	161
STAT1	0.033	0.033	-9999	-0.42	2	2
SOCS3	0.03	0.041	-9999	-0.42	3	3
CXCL9	-0.66	0.78	-9999	-1.4	178	178
MPO	-0.53	0.68	-9999	-1.2	161	161
positive regulation of humoral immune response	-0.64	0.85	-9999	-1.5	162	162
IL23/IL23R/JAK2/TYK2	-0.76	1	-9999	-1.8	161	161
IL6	-0.51	0.68	-9999	-1.2	156	156
STAT5A	0.033	0.024	-9999	-0.42	1	1
IL2	0.003	0.031	-9999	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.006	0.009	-9999	-10000	0	0
CD3E	-0.61	0.76	-9999	-1.4	162	162
keratinocyte proliferation	-0.64	0.85	-9999	-1.5	162	162
NOS2	-0.5	0.66	-9999	-1.2	156	156

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.087	0.17	0.3	135	-10000	0	135
KIRREL	0.001	0.051	-10000	0	-0.42	2	2
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.088	0.17	-10000	0	-0.3	135	135
PLCG1	0.033	0.01	-10000	0	-10000	0	0
ARRB2	0.033	0.009	-10000	0	-10000	0	0
WASL	0.031	0.011	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.039	0.14	-10000	0	-0.23	122	122
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.06	0.12	-10000	0	-0.23	119	119
FYN	-0.055	0.13	0.27	15	-0.22	134	149
mol:Ca2+	-0.041	0.14	-10000	0	-0.22	124	124
mol:DAG	-0.041	0.14	-10000	0	-0.22	124	124
NPHS2	-0.01	0.038	-10000	0	-10000	0	0
mol:IP3	-0.041	0.14	-10000	0	-0.22	124	124
regulation of endocytosis	-0.045	0.12	-10000	0	-0.2	133	133
Nephrin/NEPH1/podocin/Cholesterol	-0.054	0.13	-10000	0	-0.22	134	134
establishment of cell polarity	-0.087	0.17	-10000	0	-0.3	135	135
Nephrin/NEPH1/podocin/NCK1-2	-0.029	0.14	-10000	0	-0.21	132	132
Nephrin/NEPH1/beta Arrestin2	-0.044	0.12	-10000	0	-0.2	133	133
NPHS1	-0.15	0.22	-10000	0	-0.42	146	146
Nephrin/NEPH1/podocin	-0.053	0.12	-10000	0	-0.22	134	134
TJP1	0.034	0.007	-10000	0	-10000	0	0
NCK1	0.034	0.006	-10000	0	-10000	0	0
NCK2	0.035	0.003	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.04	0.14	-10000	0	-0.23	124	124
CD2AP	0.031	0.026	-10000	0	-0.42	1	1
Nephrin/NEPH1/podocin/GRB2	-0.043	0.14	-10000	0	-0.23	131	131
GRB2	0.034	0.007	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.058	0.13	0.25	23	-0.2	132	155
cytoskeleton organization	-0.081	0.14	0.2	5	-0.28	117	122
Nephrin/NEPH1	-0.056	0.12	-10000	0	-0.21	135	135
Nephrin/NEPH1/ZO-1	-0.055	0.14	-10000	0	-0.24	134	134

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.11	0.25	-10000	0	-0.44	117	117
TBX21	-0.48	0.77	-10000	0	-1.4	135	135
B2M	0.03	0.042	-10000	0	-0.42	3	3
TYK2	0.01	0.048	-10000	0	-10000	0	0
IL12RB1	-0.098	0.22	-10000	0	-0.45	96	96
GADD45B	-0.38	0.66	-10000	0	-1.2	131	131
IL12RB2	-0.005	0.076	-10000	0	-0.43	8	8
GADD45G	-0.42	0.69	-10000	0	-1.3	134	134
natural killer cell activation	-0.005	0.026	0.049	2	-0.042	82	84
RELB	0.035	0.004	-10000	0	-10000	0	0
RELA	0.034	0.007	-10000	0	-10000	0	0
IL18	-0.057	0.18	-10000	0	-0.43	72	72
IL2RA	-0.063	0.18	-10000	0	-0.42	77	77
IFNG	-0.12	0.21	-10000	0	-0.42	121	121
STAT3 (dimer)	-0.31	0.55	-10000	0	-1	137	137
HLA-DRB5	0.001	0.001	-10000	0	-10000	0	0
FASLG	-0.49	0.79	-10000	0	-1.5	138	138
NF kappa B2 p52/RelB	-0.43	0.74	-10000	0	-1.3	136	136
CD4	-0.007	0.13	-10000	0	-0.42	34	34
SOCS1	0.011	0.1	-10000	0	-0.42	19	19
EntrezGene:6955	0.001	0.003	-10000	0	-0.019	2	2
CD3D	-0.12	0.21	-10000	0	-0.42	123	123
CD3E	-0.097	0.2	-10000	0	-0.42	105	105
CD3G	-0.094	0.2	-10000	0	-0.42	102	102
IL12Rbeta2/JAK2	0.003	0.087	-10000	0	-0.32	14	14
CCL3	-0.42	0.71	-10000	0	-1.3	131	131
CCL4	-0.46	0.76	-10000	0	-1.4	131	131
HLA-A	0	0.003	-10000	0	-0.02	2	2
IL18/IL18R	-0.11	0.28	-10000	0	-0.42	144	144
NOS2	-0.44	0.73	-10000	0	-1.4	132	132
IL12/IL12R/TYK2/JAK2/SPHK2	-0.1	0.23	-10000	0	-0.41	114	114
IL1R1	-0.42	0.7	-10000	0	-1.3	131	131
IL4	0.004	0.041	-10000	0	-10000	0	0
JAK2	0.006	0.073	-10000	0	-0.45	6	6
EntrezGene:6957	0.001	0.003	-10000	0	-0.026	1	1
TCR/CD3/MHC I/CD8	-0.51	0.7	-10000	0	-1.2	155	155
RAB7A	-0.27	0.5	-10000	0	-0.91	129	129
lysosomal transport	-0.25	0.47	-10000	0	-0.84	130	130
FOS	-0.3	0.51	-10000	0	-0.95	131	131
STAT4 (dimer)	-0.39	0.68	-10000	0	-1.2	139	139
STAT5A (dimer)	-0.47	0.74	-10000	0	-1.3	151	151
GZMA	-0.49	0.78	-10000	0	-1.5	131	131
GZMB	-0.51	0.79	-10000	0	-1.5	143	143
HLX	0.031	0.011	-10000	0	-10000	0	0
LCK	-0.55	0.88	-10000	0	-1.6	145	145
TCR/CD3/MHC II/CD4	-0.28	0.39	-10000	0	-0.67	165	165
IL2/IL2R	-0.097	0.25	-10000	0	-0.41	130	130
MAPK14	-0.4	0.69	-10000	0	-1.2	139	139
CCR5	-0.42	0.7	-10000	0	-1.3	126	126
IL1B	-0.03	0.14	-10000	0	-0.45	34	34
STAT6	-0.054	0.19	-10000	0	-0.68	8	8
STAT4	-0.08	0.2	-10000	0	-0.42	93	93
STAT3	0.034	0.005	-10000	0	-10000	0	0
STAT1	0.033	0.033	-10000	0	-0.42	2	2
NFKB1	0.034	0.006	-10000	0	-10000	0	0
NFKB2	0.032	0.01	-10000	0	-10000	0	0
IL12B	0.003	0.08	-10000	0	-0.44	8	8
CD8A	-0.13	0.22	-10000	0	-0.42	133	133
CD8B	-0.13	0.22	-10000	0	-0.42	135	135
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.11	0.25	0.44	116	-10000	0	116
IL2RB	-0.042	0.17	-10000	0	-0.42	61	61
proteasomal ubiquitin-dependent protein catabolic process	-0.32	0.58	-10000	0	-1	139	139
IL2RG	-0.1	0.21	-10000	0	-0.42	112	112
IL12	-0.001	0.11	-10000	0	-0.33	27	27
STAT5A	0.033	0.024	-10000	0	-0.42	1	1
CD247	-0.1	0.2	-10000	0	-0.42	107	107
IL2	0.022	0.009	-10000	0	-10000	0	0
SPHK2	0.035	0.004	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.013	0.11	-10000	0	-0.45	19	19
IL12/IL12R/TYK2/JAK2	-0.67	1.1	-10000	0	-2	136	136
MAP2K3	-0.42	0.71	-10000	0	-1.3	141	141
RIPK2	0.032	0.011	-10000	0	-10000	0	0
MAP2K6	-0.42	0.71	-10000	0	-1.3	138	138
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.001	0.001	-10000	0	-10000	0	0
IL18RAP	-0.11	0.22	-10000	0	-0.42	117	117
IL12Rbeta1/TYK2	-0.059	0.18	-10000	0	-0.35	96	96
EOMES	-0.14	0.4	-10000	0	-1.3	35	35
STAT1 (dimer)	-0.38	0.57	-10000	0	-0.98	161	161
T cell proliferation	-0.24	0.44	-10000	0	-0.77	139	139
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.037	0.17	-10000	0	-0.43	58	58
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.27	0.48	-10000	0	-0.84	140	140
ATF2	-0.34	0.6	-10000	0	-1.1	139	139

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.062	0.19	-10000	0	-0.39	81	81
NFATC2	-0.14	0.34	-10000	0	-0.63	101	101
NFATC3	-0.009	0.079	-10000	0	-0.21	10	10
CD40LG	-0.42	0.49	-10000	0	-0.91	156	156
ITCH	0.031	0.019	-10000	0	-0.21	1	1
CBLB	0.033	0.017	-10000	0	-0.21	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.45	0.62	-10000	0	-1.1	151	151
JUNB	0.035	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.039	0.026	-10000	0	-0.25	1	1
T cell anergy	0.003	0.063	-10000	0	-0.32	1	1
TLE4	-0.11	0.28	-10000	0	-0.58	75	75
Jun/NFAT1-c-4/p21SNFT	-0.21	0.41	-10000	0	-0.81	88	88
AP-1/NFAT1-c-4	-0.34	0.53	-10000	0	-0.97	129	129
IKZF1	-0.16	0.35	-10000	0	-0.75	87	87
T-helper 2 cell differentiation	-0.24	0.39	-10000	0	-0.84	97	97
AP-1/NFAT1	-0.1	0.26	-10000	0	-0.46	98	98
CALM1	0.041	0.014	-10000	0	-0.16	1	1
EGR2	-0.16	0.34	-10000	0	-0.83	47	47
EGR3	-0.17	0.37	-10000	0	-0.91	46	46
NFAT1/FOXP3	-0.14	0.34	-10000	0	-0.61	111	111
EGR1	0.026	0.022	-10000	0	-10000	0	0
JUN	-0.008	0.042	-10000	0	-10000	0	0
EGR4	0.024	0.024	-10000	0	-10000	0	0
mol:Ca2+	0.008	0.01	-10000	0	-0.15	1	1
GBP3	-0.12	0.29	-10000	0	-0.57	86	86
FOSL1	0.015	0.09	-10000	0	-0.42	15	15
NFAT1-c-4/MAF/IRF4	-0.17	0.38	-10000	0	-0.77	75	75
DGKA	-0.11	0.28	-10000	0	-0.53	88	88
CREM	0.032	0.01	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.17	0.39	-10000	0	-0.8	76	76
CTLA4	-0.16	0.34	-10000	0	-0.61	114	114
NFAT1-c-4 (dimer)/EGR1	-0.18	0.4	-10000	0	-0.82	77	77
NFAT1-c-4 (dimer)/EGR4	-0.18	0.4	-10000	0	-0.82	79	79
FOS	-0.007	0.042	-10000	0	-10000	0	0
IFNG	-0.57	0.7	-10000	0	-1.2	179	179
T cell activation	-0.13	0.24	-10000	0	-0.64	36	36
MAF	0.034	0.007	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.12	0.29	1	19	-10000	0	19
TNF	-0.22	0.41	-10000	0	-0.85	91	91
FASLG	-0.55	0.8	-10000	0	-1.6	126	126
TBX21	-0.12	0.2	-10000	0	-0.34	144	144
BATF3	0.025	0.053	-10000	0	-0.42	5	5
PRKCQ	-0.1	0.21	-10000	0	-0.42	104	104
PTPN1	-0.099	0.25	-10000	0	-0.5	83	83
NFAT1-c-4/ICER1	-0.17	0.39	-10000	0	-0.79	75	75
GATA3	-0.047	0.17	-10000	0	-0.42	64	64
T-helper 1 cell differentiation	-0.55	0.66	-10000	0	-1.2	179	179
IL2RA	-0.4	0.58	-10000	0	-1	148	148
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.099	0.25	-10000	0	-0.5	83	83
E2F1	0.038	0.011	-10000	0	-10000	0	0
PPARG	0.03	0.047	-10000	0	-0.42	4	4
SLC3A2	-0.097	0.24	-10000	0	-0.49	83	83
IRF4	-0.005	0.12	-10000	0	-0.42	29	29
PTGS2	-0.32	0.42	-10000	0	-0.83	129	129
CSF2	-0.32	0.43	-10000	0	-0.84	131	131
JunB/Fra1/NFAT1-c-4	-0.16	0.38	-10000	0	-0.77	75	75
IL4	-0.25	0.42	-10000	0	-0.9	94	94
IL5	-0.33	0.43	-10000	0	-0.84	131	131
IL2	-0.13	0.24	-10000	0	-0.66	34	34
IL3	-0.068	0.2	-10000	0	-0.92	16	16
RNF128	0.024	0.035	-10000	0	-0.52	1	1
NFATC1	-0.12	0.29	-10000	0	-1	19	19
CDK4	0.1	0.2	0.61	19	-10000	0	19
PTPRK	-0.095	0.25	-10000	0	-0.48	89	89
IL8	-0.34	0.42	-10000	0	-0.84	131	131
POU2F1	0.032	0.011	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.11	0.23	0.29	1	-0.45	101	102
ACTA1	-0.14	0.25	0.23	5	-0.48	116	121
NUMA1	-0.11	0.24	0.26	1	-0.47	101	102
SPTAN1	-0.14	0.25	0.3	1	-0.49	116	117
LIMK1	-0.13	0.26	0.33	5	-0.47	115	120
BIRC3	-0.1	0.2	-10000	0	-0.42	109	109
BIRC2	0.028	0.042	-10000	0	-0.42	3	3
BAX	0.035	0.004	-10000	0	-10000	0	0
CASP10	-0.12	0.2	-10000	0	-0.4	111	111
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.035	0.002	-10000	0	-10000	0	0
PTK2	-0.11	0.23	0.29	1	-0.46	100	101
DIABLO	0.034	0.006	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.14	0.25	0.3	1	-0.48	116	117
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.034	0.006	-10000	0	-10000	0	0
GSN	-0.15	0.26	0.3	1	-0.49	116	117
MADD	0.034	0.005	-10000	0	-10000	0	0
TFAP2A	-0.14	0.33	-10000	0	-0.74	80	80
BID	-0.075	0.13	-10000	0	-0.25	119	119
MAP3K1	-0.042	0.13	-10000	0	-0.51	12	12
TRADD	0.034	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.051	0.011	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.16	0.28	0.51	1	-0.53	117	118
CASP9	0.035	0.005	-10000	0	-10000	0	0
DNA repair	-0.008	0.081	0.21	12	-0.17	25	37
neuron apoptosis	-0.005	0.13	-10000	0	-0.7	10	10
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.13	0.26	0.31	2	-0.48	119	121
APAF1	0.035	0.006	-10000	0	-10000	0	0
CASP6	-0.081	0.24	-10000	0	-0.62	33	33
TRAF2	0.033	0.009	-10000	0	-10000	0	0
ICAD/CAD	-0.14	0.25	0.39	3	-0.47	116	119
CASP7	0.073	0.15	0.28	100	-0.67	1	101
KRT18	-0.089	0.25	-10000	0	-0.66	53	53
apoptosis	-0.1	0.22	0.31	1	-0.43	95	96
DFFA	-0.14	0.26	0.32	2	-0.49	116	118
DFFB	-0.14	0.26	0.32	2	-0.49	116	118
PARP1	0.008	0.081	0.17	25	-0.21	12	37
actin filament polymerization	0.12	0.24	0.44	115	-0.31	4	119
TNF	-0.054	0.18	-10000	0	-0.42	69	69
CYCS	-0.05	0.089	-10000	0	-0.19	88	88
SATB1	-0.088	0.24	-10000	0	-0.6	41	41
SLK	-0.14	0.25	0.3	1	-0.49	116	117
p15 BID/BAX	-0.061	0.13	-10000	0	-0.26	94	94
CASP2	-0.049	0.15	0.22	13	-0.33	59	72
JNK cascade	0.042	0.13	0.5	12	-10000	0	12
CASP3	-0.15	0.27	0.33	1	-0.51	116	117
LMNB2	-0.035	0.18	0.26	4	-0.41	44	48
RIPK1	0.031	0.012	-10000	0	-10000	0	0
CASP4	0.031	0.026	-10000	0	-0.42	1	1
Mammalian IAPs/DIABLO	-0.015	0.14	-10000	0	-0.23	109	109
negative regulation of DNA binding	-0.13	0.33	-10000	0	-0.73	80	80
stress fiber formation	-0.14	0.25	0.3	1	-0.48	116	117
GZMB	-0.13	0.22	-10000	0	-0.45	112	112
CASP1	0.006	0.066	-10000	0	-0.31	14	14
LMNB1	-0.047	0.2	0.25	5	-0.42	58	63
APP	-0.005	0.13	-10000	0	-0.72	10	10
TNFRSF1A	0.034	0.007	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.01	0.001	-10000	0	-10000	0	0
VIM	-0.099	0.22	0.32	1	-0.42	96	97
LMNA	-0.037	0.17	0.25	4	-0.38	50	54
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.064	0.15	-10000	0	-0.35	65	65
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.14	0.25	0.32	2	-0.49	116	118
APAF-1/Caspase 9	0.038	0.093	0.37	3	-0.55	4	7
nuclear fragmentation during apoptosis	-0.11	0.24	0.26	1	-0.46	101	102
CFL2	-0.13	0.24	0.31	4	-0.45	115	119
GAS2	-0.15	0.25	0.3	1	-0.49	115	116
positive regulation of apoptosis	-0.034	0.19	0.24	8	-0.39	56	64
PRF1	-0.079	0.19	-10000	0	-0.42	90	90

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.035	0.064	-10000	0	-0.25	13	13
NFATC2	-0.04	0.08	-10000	0	-0.29	24	24
NFATC3	-0.028	0.047	-10000	0	-0.12	12	12
CD40LG	-0.35	0.35	0.39	1	-0.62	208	209
PTGS2	-0.24	0.28	0.39	1	-0.53	159	160
JUNB	0.035	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.015	0.036	-10000	0	-10000	0	0
CaM/Ca2+	-0.015	0.036	-10000	0	-10000	0	0
CALM1	0.005	0.034	-10000	0	-10000	0	0
JUN	0.001	0.035	-10000	0	-10000	0	0
mol:Ca2+	-0.015	0.015	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.011	0.017	-10000	0	-10000	0	0
FOSL1	0.015	0.09	-10000	0	-0.42	15	15
CREM	0.032	0.01	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.12	0.19	-10000	0	-0.33	128	128
FOS	0.003	0.034	-10000	0	-10000	0	0
IFNG	-0.31	0.34	0.39	1	-0.61	184	185
AP-1/NFAT1-c-4	-0.28	0.37	-10000	0	-0.63	168	168
FASLG	-0.29	0.34	0.39	1	-0.62	164	165
NFAT1-c-4/ICER1	-0.075	0.13	-10000	0	-0.24	87	87
IL2RA	-0.29	0.33	0.39	1	-0.6	169	170
FKBP12/FK506	0.025	0.006	-10000	0	-10000	0	0
CSF2	-0.25	0.29	0.39	1	-0.53	166	167
JunB/Fra1/NFAT1-c-4	-0.07	0.14	-10000	0	-0.28	65	65
IL4	-0.26	0.29	0.39	1	-0.54	163	164
IL2	-0.008	0.14	-10000	0	-1	7	7
IL3	-0.038	0.18	-10000	0	-0.84	17	17
FKBP1A	0.033	0.008	-10000	0	-10000	0	0
BATF3	0.025	0.053	-10000	0	-0.42	5	5
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.032	0.011	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.018	0.14	-9999	-0.25	94	94
E-cadherin/beta catenin	-0.04	0.15	-9999	-0.3	94	94
CTNNB1	0.035	0.005	-9999	-10000	0	0
JUP	0.033	0.008	-9999	-10000	0	0
CDH1	-0.082	0.2	-9999	-0.42	94	94

×

IL27-mediated signaling events

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
TGFB1	0.032	0.033	-10000	0	-0.42	2	2
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.17	0.3	0.58	100	-10000	0	100
IL27/IL27R/JAK1	-0.12	0.32	-10000	0	-0.77	48	48
TBX21	-0.18	0.27	-10000	0	-0.55	108	108
IL12B	0.008	0.068	-10000	0	-0.42	8	8
IL12A	-0.013	0.067	-10000	0	-0.3	19	19
IL6ST	0.004	0.07	-10000	0	-0.43	8	8
IL27RA/JAK1	-0.064	0.28	-10000	0	-1.2	20	20
IL27	-0.037	0.14	-10000	0	-0.43	40	40
TYK2	0.012	0.033	-10000	0	-10000	0	0
T-helper cell lineage commitment	0.033	0.1	0.42	7	-0.57	1	8
T-helper 2 cell differentiation	0.17	0.3	0.58	100	-10000	0	100
T cell proliferation during immune response	0.17	0.3	0.58	100	-10000	0	100
MAPKKK cascade	-0.17	0.3	-10000	0	-0.58	100	100
STAT3	0.034	0.005	-10000	0	-10000	0	0
STAT2	0.034	0.005	-10000	0	-10000	0	0
STAT1	0.033	0.033	-10000	0	-0.42	2	2
IL12RB1	-0.086	0.2	-10000	0	-0.42	96	96
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.15	0.23	0.36	1	-0.52	82	83
IL27/IL27R/JAK2/TYK2	-0.18	0.31	-10000	0	-0.59	100	100
positive regulation of T cell mediated cytotoxicity	-0.17	0.3	-10000	0	-0.58	100	100
STAT1 (dimer)	-0.16	0.35	0.51	1	-0.69	82	83
JAK2	0.01	0.062	-10000	0	-0.42	6	6
JAK1	0.035	0.005	-10000	0	-10000	0	0
STAT2 (dimer)	-0.16	0.3	-10000	0	-0.56	99	99
T cell proliferation	-0.16	0.3	-10000	0	-0.58	92	92
IL12/IL12R/TYK2/JAK2	-0.18	0.34	-10000	0	-0.76	65	65
IL17A	0.033	0.1	0.42	7	-0.57	1	8
mast cell activation	0.17	0.3	0.58	100	-10000	0	100
IFNG	-0.046	0.068	-10000	0	-0.12	157	157
T cell differentiation	-0.009	0.011	-10000	0	-0.022	142	142
STAT3 (dimer)	-0.16	0.3	-10000	0	-0.56	100	100
STAT5A (dimer)	-0.16	0.3	-10000	0	-0.55	101	101
STAT4 (dimer)	-0.21	0.34	-10000	0	-0.61	121	121
STAT4	-0.08	0.2	-10000	0	-0.42	93	93
T cell activation	-0.003	0.029	0.12	18	-10000	0	18
IL27R/JAK2/TYK2	-0.069	0.29	-10000	0	-1.1	24	24
GATA3	-0.26	0.53	-10000	0	-1.3	80	80
IL18	-0.054	0.12	-10000	0	-0.3	72	72
positive regulation of mast cell cytokine production	-0.15	0.29	-10000	0	-0.54	100	100
IL27/EBI3	-0.075	0.18	-10000	0	-0.36	98	98
IL27RA	-0.081	0.3	-10000	0	-1.3	20	20
IL6	0.014	0.084	-10000	0	-0.42	13	13
STAT5A	0.033	0.024	-10000	0	-0.42	1	1
monocyte differentiation	-0.002	0.004	-10000	0	-0.012	2	2
IL2	0.023	0.11	0.48	20	-10000	0	20
IL1B	-0.023	0.087	-10000	0	-0.3	34	34
EBI3	-0.077	0.18	-10000	0	-0.42	81	81
TNF	-0.052	0.12	-10000	0	-0.3	69	69

×

JNK 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.032	0.21	-10000	0	-0.36	91	91
MAP4K1	-0.044	0.17	-10000	0	-0.42	64	64
MAP3K8	0.02	0.074	-10000	0	-0.42	10	10
PRKCB	-0.097	0.2	-10000	0	-0.42	107	107
DBNL	0.031	0.011	-10000	0	-10000	0	0
CRKL	0.033	0.01	-10000	0	-10000	0	0
MAP3K1	-0.06	0.19	-10000	0	-0.49	50	50
JUN	-0.21	0.37	-10000	0	-0.71	119	119
MAP3K7	-0.056	0.19	-10000	0	-0.49	49	49
GRAP2	-0.014	0.14	-10000	0	-0.42	38	38
CRK	0.033	0.009	-10000	0	-10000	0	0
MAP2K4	-0.064	0.22	0.22	8	-0.49	58	66
LAT	-0.021	0.15	-10000	0	-0.42	45	45
LCP2	0.015	0.09	-10000	0	-0.42	15	15
MAPK8	-0.22	0.39	-10000	0	-0.74	123	123
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.06	0.21	-10000	0	-0.43	69	69
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.02	0.2	-10000	0	-0.34	88	88

×

Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1	-0.11	0.3	-9999	-0.59	96	96
MAP3K8	0.02	0.074	-9999	-0.42	10	10
FOS	-0.13	0.3	-9999	-0.6	98	98
PRKCA	0.033	0.025	-9999	-0.42	1	1
PTPN7	-0.062	0.18	-9999	-0.42	76	76
HRAS	0.034	0.006	-9999	-10000	0	0
PRKCB	-0.096	0.21	-9999	-0.42	107	107
NRAS	0.034	0.008	-9999	-10000	0	0
RAS family/GTP	0.063	0.02	-9999	-10000	0	0
MAPK3	-0.14	0.31	-9999	-0.63	96	96
MAP2K1	-0.074	0.2	-9999	-0.37	103	103
ELK1	0.036	0.003	-9999	-10000	0	0
BRAF	-0.065	0.17	-9999	-0.36	88	88
mol:GTP	0	0	-9999	-10000	0	0
MAPK1	-0.14	0.31	-9999	-0.63	97	97
RAF1	-0.075	0.18	-9999	-0.35	104	104
KRAS	0.034	0.006	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.033	0.073	0.17	82	-0.18	1	83
RFC1	0.037	0.077	0.17	88	-0.18	2	90
PRKDC	0.05	0.1	0.21	96	-10000	0	96
RIPK1	0.031	0.012	-10000	0	-10000	0	0
CASP7	0.004	0.19	-10000	0	-0.57	29	29
FASLG/FAS/FADD/FAF1	-0.002	0.12	0.2	43	-0.25	48	91
MAP2K4	-0.037	0.18	0.23	4	-0.43	44	48
mol:ceramide	-0.045	0.16	-10000	0	-0.3	91	91
GSN	0.032	0.072	0.17	80	-0.18	2	82
FASLG/FAS/FADD/FAF1/Caspase 8	-0.026	0.14	0.23	1	-0.29	59	60
FAS	0.024	0.059	-10000	0	-0.42	6	6
BID	0.065	0.14	0.29	98	-10000	0	98
MAP3K1	-0.004	0.16	0.25	7	-0.48	24	31
MAP3K7	0.031	0.011	-10000	0	-10000	0	0
RB1	0.038	0.077	0.17	92	-0.18	1	93
CFLAR	0.035	0.004	-10000	0	-10000	0	0
HGF/MET	0.033	0.09	-10000	0	-0.26	27	27
ARHGDIB	0.027	0.1	0.18	85	-0.23	18	103
FADD	0.032	0.012	-10000	0	-10000	0	0
actin filament polymerization	-0.032	0.072	0.18	1	-0.17	80	81
NFKB1	-0.02	0.15	-10000	0	-0.67	14	14
MAPK8	-0.038	0.19	-10000	0	-0.46	42	42
DFFA	0.037	0.076	0.17	89	-0.18	1	90
DNA fragmentation during apoptosis	0.037	0.077	0.17	89	-0.18	1	90
FAS/FADD/MET	0.032	0.082	-10000	0	-0.25	24	24
CFLAR/RIP1	0.045	0.018	-10000	0	-10000	0	0
FAIM3	-0.094	0.2	-10000	0	-0.42	102	102
FAF1	0.034	0.012	-10000	0	-10000	0	0
PARP1	0.038	0.076	0.17	91	-0.18	2	93
DFFB	0.037	0.078	0.17	89	-0.18	1	90
CHUK	-0.021	0.13	-10000	0	-0.62	13	13
FASLG	-0.091	0.2	-10000	0	-0.42	99	99
FAS/FADD	0.039	0.045	-10000	0	-0.3	5	5
HGF	0.024	0.058	-10000	0	-0.42	6	6
LMNA	0.033	0.068	0.2	5	-10000	0	5
CASP6	0.036	0.074	0.17	87	-0.17	1	88
CASP10	0.027	0.058	-10000	0	-0.42	6	6
CASP3	0.047	0.089	0.2	88	-10000	0	88
PTPN13	0.029	0.047	-10000	0	-0.42	4	4
CASP8	0.076	0.16	0.34	99	-10000	0	99
IL6	-0.055	0.29	-10000	0	-1.1	23	23
MET	0.006	0.1	-10000	0	-0.42	20	20
ICAD/CAD	0.033	0.07	0.23	4	-10000	0	4
FASLG/FAS/FADD/FAF1/Caspase 10	-0.046	0.16	-10000	0	-0.3	91	91
activation of caspase activity by cytochrome c	0.065	0.14	0.29	98	-10000	0	98
PAK2	0.038	0.078	0.17	90	-0.18	2	92
BCL2	0.035	0.005	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.03	0.1	-10000	0	-0.21	94	94
epithelial cell differentiation	-0.004	0.12	-10000	0	-0.21	93	93
CYFIP2	0.015	0.09	-10000	0	-0.42	15	15
ENAH	-0.033	0.075	0.32	2	-0.26	1	3
EGFR	0.027	0.035	-10000	0	-0.42	2	2
EPHA2	0.03	0.047	-10000	0	-0.42	4	4
MYO6	-0.034	0.1	0.21	7	-0.2	93	100
CTNNB1	0.035	0.005	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.05	0.065	-10000	0	-0.24	15	15
AQP5	-0.03	0.088	-10000	0	-0.35	2	2
CTNND1	0.035	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.032	0.1	0.21	6	-0.2	91	97
regulation of calcium-dependent cell-cell adhesion	-0.038	0.11	0.21	6	-0.2	98	104
EGF	0.001	0.11	-10000	0	-0.42	25	25
NCKAP1	0.035	0.003	-10000	0	-10000	0	0
AQP3	-0.08	0.16	0.4	1	-0.42	47	48
cortical microtubule organization	-0.004	0.12	-10000	0	-0.21	93	93
GO:0000145	-0.048	0.088	0.19	7	-0.19	91	98
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0.13	-10000	0	-0.21	93	93
MLLT4	0.029	0.014	-10000	0	-10000	0	0
ARF6/GDP	-0.051	0.074	-10000	0	-0.19	79	79
ARF6	0.035	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.073	0.044	-10000	0	-0.23	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.032	0.088	0.23	4	-0.24	3	7
PVRL2	0.035	0.004	-10000	0	-10000	0	0
ZYX	-0.029	0.098	0.22	5	-0.2	82	87
ARF6/GTP	0.08	0.047	-10000	0	-0.21	3	3
CDH1	-0.082	0.2	-10000	0	-0.42	94	94
EGFR/EGFR/EGF/EGF	-0.026	0.12	-10000	0	-0.21	104	104
RhoA/GDP	-0.001	0.12	-10000	0	-0.2	93	93
actin cytoskeleton organization	-0.04	0.098	0.2	7	-0.2	93	100
IGF-1R heterotetramer	0.034	0.006	-10000	0	-10000	0	0
GIT1	0.034	0.006	-10000	0	-10000	0	0
IGF1R	0.034	0.006	-10000	0	-10000	0	0
IGF1	0.03	0.041	-10000	0	-0.42	3	3
DIAPH1	-0.017	0.22	-10000	0	-0.57	36	36
Wnt receptor signaling pathway	0.004	0.12	0.21	93	-10000	0	93
RHOA	0.035	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.052	0.075	-10000	0	-0.19	79	79
CTNNA1	0.033	0.008	-10000	0	-10000	0	0
VCL	-0.041	0.099	0.2	7	-0.2	93	100
EFNA1	0.032	0.011	-10000	0	-10000	0	0
LPP	-0.051	0.09	0.21	6	-0.2	89	95
Ephrin A1/EPHA2	-0.006	0.11	-10000	0	-0.2	83	83
SEC6/SEC8	-0.032	0.083	-10000	0	-0.19	78	78
MGAT3	-0.039	0.11	0.22	6	-0.21	98	104
HGF/MET	-0.019	0.13	-10000	0	-0.22	94	94
HGF	0.024	0.058	-10000	0	-0.42	6	6
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.03	0.11	-10000	0	-0.21	94	94
actin cable formation	0.003	0.11	0.28	17	-0.26	7	24
KIAA1543	-0.056	0.095	0.19	9	-0.2	104	113
KIFC3	-0.035	0.1	0.22	6	-0.2	93	99
NCK1	0.034	0.006	-10000	0	-10000	0	0
EXOC3	0.032	0.01	-10000	0	-10000	0	0
ACTN1	-0.034	0.1	0.24	4	-0.2	94	98
NCK1/GIT1	0.049	0.012	-10000	0	-10000	0	0
mol:GDP	-0.004	0.12	-10000	0	-0.21	93	93
EXOC4	0.031	0.012	-10000	0	-10000	0	0
STX4	-0.033	0.1	0.21	7	-0.2	93	100
PIP5K1C	-0.032	0.1	0.22	6	-0.2	91	97
LIMA1	0.035	0.005	-10000	0	-10000	0	0
ABI1	0.032	0.01	-10000	0	-10000	0	0
ROCK1	-0.026	0.1	0.52	3	-0.3	1	4
adherens junction assembly	-0.042	0.1	0.3	3	-0.37	6	9
IGF-1R heterotetramer/IGF1	-0.008	0.11	-10000	0	-0.2	94	94
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.041	0.023	-10000	0	-10000	0	0
MET	0.006	0.1	-10000	0	-0.42	20	20
PLEKHA7	-0.042	0.11	0.22	6	-0.21	104	110
mol:GTP	0.071	0.043	-10000	0	-0.23	3	3
establishment of epithelial cell apical/basal polarity	-0.013	0.12	0.32	11	-10000	0	11
cortical actin cytoskeleton stabilization	-0.03	0.1	-10000	0	-0.21	94	94
regulation of cell-cell adhesion	-0.04	0.098	0.2	7	-0.2	93	100
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.03	0.11	-10000	0	-0.21	94	94

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.09	0.2	-10000	0	-0.4	102	102
KLHL20	-0.014	0.096	0.21	7	-0.21	25	32
CYFIP2	0.015	0.09	-10000	0	-0.42	15	15
Rac1/GDP	-0.033	0.13	0.26	1	-0.25	77	78
ENAH	-0.086	0.19	-10000	0	-0.39	99	99
AP1M1	0.035	0.004	-10000	0	-10000	0	0
RAP1B	0.034	0.007	-10000	0	-10000	0	0
RAP1A	0.034	0.007	-10000	0	-10000	0	0
CTNNB1	0.035	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.012	0.092	-10000	0	-0.18	69	69
ABI1/Sra1/Nap1	-0.037	0.052	-10000	0	-0.15	31	31
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.033	0.16	-10000	0	-0.25	125	125
RAPGEF1	-0.069	0.17	0.24	3	-0.36	91	94
CTNND1	0.035	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.087	0.21	-10000	0	-0.41	104	104
CRK	-0.078	0.18	-10000	0	-0.38	93	93
E-cadherin/gamma catenin/alpha catenin	-0.018	0.14	-10000	0	-0.25	93	93
alphaE/beta7 Integrin	0.004	0.12	-10000	0	-0.29	48	48
IQGAP1	0.034	0.006	-10000	0	-10000	0	0
NCKAP1	0.035	0.003	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.051	0.03	-10000	0	-10000	0	0
DLG1	-0.089	0.2	-10000	0	-0.4	101	101
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.025	0.059	-10000	0	-0.13	71	71
MLLT4	0.029	0.014	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.047	0.069	-10000	0	-0.22	21	21
PI3K	-0.027	0.077	-10000	0	-0.17	70	70
ARF6	0.035	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	-0.041	0.15	-10000	0	-0.3	94	94
TIAM1	0.008	0.1	-10000	0	-0.42	21	21
E-cadherin(dimer)/Ca2+	0	0.13	-10000	0	-0.21	93	93
AKT1	-0.008	0.057	0.16	4	-10000	0	4
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
CDH1	-0.082	0.2	-10000	0	-0.42	94	94
RhoA/GDP	-0.029	0.14	0.28	4	-0.25	81	85
actin cytoskeleton organization	-0.008	0.075	0.18	8	-0.16	24	32
CDC42/GDP	-0.03	0.14	0.28	4	-0.25	82	86
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.037	0.1	-10000	0	-0.21	96	96
ITGB7	-0.026	0.15	-10000	0	-0.42	49	49
RAC1	0.031	0.012	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.001	0.14	-10000	0	-0.23	93	93
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.013	0.12	-10000	0	-0.21	93	93
mol:GDP	-0.05	0.14	0.28	4	-0.28	83	87
CDC42/GTP/IQGAP1	0.045	0.011	-10000	0	-10000	0	0
JUP	0.033	0.008	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	-0.022	0.14	0.27	3	-0.25	79	82
RAC1/GTP/IQGAP1	0.041	0.017	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.051	0.007	-10000	0	-10000	0	0
RHOA	0.035	0.005	-10000	0	-10000	0	0
CDC42	0.035	0.005	-10000	0	-10000	0	0
CTNNA1	0.033	0.008	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.001	0.056	0.14	11	-0.11	18	29
NME1	0.034	0.006	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.09	0.2	-10000	0	-0.4	101	101
regulation of cell-cell adhesion	-0.019	0.076	-10000	0	-0.16	76	76
WASF2	-0.005	0.043	0.1	5	-0.093	10	15
Rap1/GTP	-0.014	0.1	-10000	0	-0.19	71	71
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.022	0.16	-10000	0	-0.23	126	126
CCND1	0	0.066	0.16	11	-0.13	18	29
VAV2	-0.095	0.24	0.37	1	-0.45	101	102
RAP1/GDP	-0.013	0.12	0.3	3	-0.21	79	82
adherens junction assembly	-0.086	0.19	-10000	0	-0.39	101	101
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.032	0.01	-10000	0	-10000	0	0
PIP5K1C	0.035	0.004	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.03	0.15	-10000	0	-0.23	123	123
E-cadherin/beta catenin	-0.07	0.14	-10000	0	-0.31	97	97
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.087	0.19	-10000	0	-0.39	100	100
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
Rac1/GTP	-0.059	0.12	-10000	0	-0.34	28	28
E-cadherin/beta catenin/alpha catenin	-0.017	0.14	-10000	0	-0.25	93	93
ITGAE	0.033	0.009	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.088	0.21	-10000	0	-0.42	103	103

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.032	0.011	-9999	-10000	0	0
ITGB7	-0.026	0.15	-9999	-0.42	49	49
ITGA4	-0.014	0.14	-9999	-0.42	40	40
alpha4/beta7 Integrin	-0.031	0.16	-9999	-0.32	81	81
alpha4/beta1 Integrin	0.01	0.11	-9999	-0.29	40	40

×

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

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
BAG4	0.033	0.008	-10000	0	-10000	0	0
Caspase 8 (4 units)	-0.019	0.13	-10000	0	-0.3	30	30
NEF	-0.035	0.066	-10000	0	-0.2	35	35
NFKBIA	-0.007	0.062	-10000	0	-0.12	5	5
BIRC3	-0.12	0.22	-10000	0	-0.46	109	109
CYCS	-0.034	0.12	0.19	17	-0.25	73	90
RIPK1	0.031	0.012	-10000	0	-10000	0	0
CD247	-0.14	0.25	-10000	0	-0.48	123	123
MAP2K7	-0.035	0.17	0.3	1	-0.44	28	29
protein ubiquitination	-0.021	0.14	0.25	6	-0.37	28	34
CRADD	0.034	0.006	-10000	0	-10000	0	0
DAXX	0.031	0.011	-10000	0	-10000	0	0
FAS	0.025	0.058	-10000	0	-0.42	6	6
BID	-0.046	0.13	0.19	8	-0.26	83	91
NF-kappa-B/RelA/I kappa B alpha	-0.028	0.15	-10000	0	-0.25	110	110
TRADD	0.034	0.007	-10000	0	-10000	0	0
MAP3K5	0.03	0.026	-10000	0	-0.42	1	1
CFLAR	0.035	0.003	-10000	0	-10000	0	0
FADD	0.033	0.008	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.029	0.15	-10000	0	-0.25	110	110
MAPK8	-0.031	0.16	0.28	1	-0.42	26	27
APAF1	0.034	0.006	-10000	0	-10000	0	0
TRAF1	0.025	0.058	-10000	0	-0.42	6	6
TRAF2	0.033	0.009	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.05	0.14	0.2	9	-0.27	89	98
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.046	0.17	-10000	0	-0.39	50	50
CHUK	-0.024	0.15	0.25	6	-0.4	27	33
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.072	0.058	-10000	0	-0.21	5	5
TCRz/NEF	-0.13	0.23	-10000	0	-0.44	123	123
TNF	-0.054	0.18	-10000	0	-0.42	69	69
FASLG	-0.17	0.29	-10000	0	-0.56	122	122
NFKB1	-0.006	0.061	-10000	0	-0.14	2	2
TNFR1A/BAG4/TNF-alpha	0.002	0.12	-10000	0	-0.25	66	66
CASP6	-0.004	0.15	-10000	0	-0.56	13	13
CASP7	-0.15	0.26	0.31	6	-0.48	134	140
RELA	-0.007	0.061	-10000	0	-0.12	2	2
CASP2	0.031	0.011	-10000	0	-10000	0	0
CASP3	-0.14	0.26	0.31	6	-0.47	131	137
TNFRSF1A	0.034	0.007	-10000	0	-10000	0	0
TNFR1A/BAG4	0.048	0.015	-10000	0	-10000	0	0
CASP8	0.035	0.004	-10000	0	-10000	0	0
CASP9	0.035	0.005	-10000	0	-10000	0	0
MAP3K14	-0.038	0.16	0.27	2	-0.43	32	34
APAF-1/Caspase 9	-0.094	0.19	-10000	0	-0.37	101	101
BCL2	-0.028	0.14	0.27	1	-0.4	23	24

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.031	0.026	-10000	0	-0.42	1	1
GNB1/GNG2	-0.055	0.083	-10000	0	-0.2	91	91
AKT1	-0.017	0.12	0.34	1	-0.23	54	55
EGF	0.001	0.11	-10000	0	-0.42	25	25
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.004	0.089	0.24	6	-0.21	37	43
mol:Ca2+	-0.042	0.16	-10000	0	-0.3	95	95
LYN	0.011	0.07	0.23	4	-0.21	18	22
RhoA/GTP	-0.014	0.072	-10000	0	-0.13	80	80
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.066	0.19	-10000	0	-0.37	96	96
GNG2	0.027	0.058	-10000	0	-0.42	6	6
ARRB2	0.033	0.009	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.016	0.11	-10000	0	-0.41	18	18
G beta5/gamma2	-0.067	0.11	-10000	0	-0.25	90	90
PRKCH	-0.053	0.18	-10000	0	-0.34	94	94
DNM1	0.029	0.013	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3	0.013	0.019	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.021	0.074	-10000	0	-0.42	10	10
G12 family/GTP	-0.051	0.15	-10000	0	-0.31	88	88
ADRBK1	0.034	0.007	-10000	0	-10000	0	0
ADRBK2	0.029	0.042	-10000	0	-0.42	3	3
RhoA/GTP/ROCK1	0.046	0.01	-10000	0	-10000	0	0
mol:GDP	0.017	0.13	0.35	23	-10000	0	23
mol:NADP	0.03	0.026	-10000	0	-0.42	1	1
RAB11A	0.034	0.005	-10000	0	-10000	0	0
PRKG1	0.018	0.018	-10000	0	-10000	0	0
mol:IP3	-0.06	0.2	-10000	0	-0.38	95	95
cell morphogenesis	0.045	0.009	-10000	0	-10000	0	0
PLCB2	-0.095	0.27	-10000	0	-0.53	94	94
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.091	0.1	-10000	0	-0.18	195	195
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.005	0.083	0.39	2	-0.21	31	33
RHOA	0.035	0.005	-10000	0	-10000	0	0
PTGIR	0.031	0.041	-10000	0	-0.42	3	3
PRKCB1	-0.059	0.19	-10000	0	-0.37	94	94
GNAQ	0.033	0.009	-10000	0	-10000	0	0
mol:L-citrulline	0.03	0.026	-10000	0	-0.42	1	1
TXA2/TXA2-R family	-0.1	0.27	-10000	0	-0.54	95	95
LCK	-0.046	0.11	0.17	4	-0.2	119	123
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.032	0.049	-10000	0	-0.19	14	14
TXA2-R family/G12 family/GDP/G beta/gamma	0.02	0.087	-10000	0	-0.41	12	12
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.037	0.049	0.18	1	-0.19	13	14
MAPK14	-0.026	0.14	0.21	10	-0.25	85	95
TGM2/GTP	-0.07	0.22	-10000	0	-0.43	92	92
MAPK11	-0.034	0.13	0.24	2	-0.24	90	92
ARHGEF1	-0.018	0.1	0.17	5	-0.18	83	88
GNAI2	0.035	0.005	-10000	0	-10000	0	0
JNK cascade	-0.065	0.2	-10000	0	-0.4	95	95
RAB11/GDP	0.034	0.006	-10000	0	-10000	0	0
ICAM1	-0.042	0.15	-10000	0	-0.29	93	93
cAMP biosynthetic process	-0.059	0.19	-10000	0	-0.36	94	94
Gq family/GTP/EBP50	-0.02	0.092	-10000	0	-0.27	20	20
actin cytoskeleton reorganization	0.045	0.009	-10000	0	-10000	0	0
SRC	0.018	0.062	0.21	12	-0.18	9	21
GNB5	0.033	0.024	-10000	0	-0.42	1	1
GNB1	0.034	0.007	-10000	0	-10000	0	0
EGF/EGFR	-0.094	0.14	0.25	5	-0.27	103	108
VCAM1	-0.061	0.18	-10000	0	-0.36	93	93
TP beta/Gq family/GDP/G beta5/gamma2	-0.016	0.11	-10000	0	-0.41	18	18
platelet activation	-0.036	0.18	0.26	4	-0.31	93	97
PGI2/IP	0.023	0.029	-10000	0	-0.29	3	3
PRKACA	0.017	0.047	-10000	0	-0.22	13	13
Gq family/GDP/G beta5/gamma2	-0.014	0.11	-10000	0	-0.39	19	19
TXA2/TP beta/beta Arrestin2	0.003	0.065	-10000	0	-0.34	10	10
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.008	0.045	-10000	0	-0.21	14	14
mol:DAG	-0.067	0.22	-10000	0	-0.42	94	94
EGFR	0.027	0.035	-10000	0	-0.42	2	2
TXA2/TP alpha	-0.088	0.25	-10000	0	-0.5	94	94
Gq family/GTP	-0.022	0.091	0.23	2	-0.21	62	64
YES1	0.018	0.058	0.22	3	-0.18	10	13
GNAI2/GTP	0.025	0.049	-10000	0	-0.18	16	16
PGD2/DP	0.016	0.052	-10000	0	-0.29	10	10
SLC9A3R1	0.034	0.007	-10000	0	-10000	0	0
FYN	0.02	0.061	0.26	5	-0.18	8	13
mol:NO	0.03	0.026	-10000	0	-0.42	1	1
GNA15	0.021	0.077	-10000	0	-0.42	11	11
PGK/cGMP	0.018	0.031	-10000	0	-0.26	1	1
RhoA/GDP	0.034	0.005	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.051	0.062	-10000	0	-0.19	16	16
NOS3	0.03	0.026	-10000	0	-0.42	1	1
RAC1	0.031	0.012	-10000	0	-10000	0	0
PRKCA	-0.049	0.18	0.28	1	-0.35	90	91
PRKCB	-0.082	0.21	-10000	0	-0.41	97	97
PRKCE	-0.046	0.18	-10000	0	-0.34	94	94
PRKCD	-0.06	0.2	-10000	0	-0.38	95	95
PRKCG	-0.062	0.2	-10000	0	-0.39	93	93
muscle contraction	-0.096	0.26	-10000	0	-0.51	95	95
PRKCZ	-0.056	0.18	0.35	1	-0.35	93	94
ARR3	0.021	0.007	-10000	0	-10000	0	0
TXA2/TP beta	0.037	0.056	0.19	2	-0.19	16	18
PRKCQ	-0.083	0.2	-10000	0	-0.4	97	97
MAPKKK cascade	-0.089	0.24	-10000	0	-0.48	95	95
SELE	-0.058	0.18	-10000	0	-0.35	94	94
TP beta/GNAI2/GDP/G beta/gamma	0.057	0.062	0.21	2	-0.19	16	18
ROCK1	0.035	0.005	-10000	0	-10000	0	0
GNA14	-0.036	0.16	-10000	0	-0.42	56	56
chemotaxis	-0.12	0.31	-10000	0	-0.63	94	94
GNA12	0.031	0.011	-10000	0	-10000	0	0
GNA13	0.034	0.006	-10000	0	-10000	0	0
GNA11	0.035	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.023	0.009	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.13	0.28	-10000	0	-0.63	69	69
UGCG	-0.054	0.23	-10000	0	-0.85	26	26
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.066	0.24	0.27	2	-0.42	86	88
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.053	0.23	-10000	0	-0.84	26	26
mol:DAG	-0.084	0.28	-10000	0	-0.89	38	38
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.087	0.25	0.3	2	-0.44	108	110
FRAP1	-0.11	0.29	0.31	2	-0.51	109	111
FOXO3	-0.12	0.28	0.31	2	-0.5	111	113
AKT1	-0.13	0.31	0.32	2	-0.54	115	117
GAB2	0.033	0.009	-10000	0	-10000	0	0
SMPD1	-0.017	0.15	-10000	0	-0.98	8	8
SGMS1	-0.078	0.26	-10000	0	-0.82	38	38
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	0.011	0.004	-10000	0	-10000	0	0
CALM1	0.034	0.006	-10000	0	-10000	0	0
cell proliferation	-0.084	0.26	0.24	2	-0.69	47	49
EIF3A	0.032	0.01	-10000	0	-10000	0	0
PI3K	0.053	0.015	-10000	0	-10000	0	0
RPS6KB1	-0.001	0.13	-10000	0	-0.98	5	5
mol:sphingomyelin	-0.084	0.28	-10000	0	-0.89	38	38
natural killer cell activation	0.001	0	-10000	0	-10000	0	0
JAK3	0.006	0.11	-10000	0	-0.42	25	25
PIK3R1	0.036	0.008	-10000	0	-10000	0	0
JAK1	0.037	0.005	-10000	0	-10000	0	0
NFKB1	0.034	0.006	-10000	0	-10000	0	0
MYC	-0.08	0.25	0.38	2	-0.48	84	86
MYB	-0.031	0.28	-10000	0	-1.2	19	19
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.15	0.32	-10000	0	-0.58	119	119
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.034	0.13	-10000	0	-0.89	5	5
mol:PI-3-4-5-P3	-0.14	0.31	-10000	0	-0.55	120	120
Rac1/GDP	0.029	0.014	-10000	0	-10000	0	0
T cell proliferation	-0.13	0.29	-10000	0	-0.52	116	116
SHC1	0.032	0.011	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.001	0.016	-10000	0	-0.066	19	19
PRKCZ	-0.14	0.3	-10000	0	-0.55	116	116
NF kappa B1 p50/RelA	-0.077	0.26	0.32	2	-0.45	106	108
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.15	0.3	-10000	0	-0.56	112	112
HSP90AA1	0.033	0.024	-10000	0	-0.42	1	1
RELA	0.034	0.007	-10000	0	-10000	0	0
IL2RA	-0.062	0.18	-10000	0	-0.42	77	77
IL2RB	-0.04	0.17	-10000	0	-0.42	61	61
TERT	0.029	0.013	-10000	0	-10000	0	0
E2F1	0.008	0.11	-10000	0	-0.44	19	19
SOS1	0.036	0.003	-10000	0	-10000	0	0
RPS6	0.031	0.012	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.007	0.032	18	-10000	0	18
PTPN11	0.035	0.006	-10000	0	-10000	0	0
IL2RG	-0.1	0.21	-10000	0	-0.42	112	112
actin cytoskeleton organization	-0.13	0.29	-10000	0	-0.52	116	116
GRB2	0.035	0.007	-10000	0	-10000	0	0
IL2	0.024	0.01	-10000	0	-10000	0	0
PIK3CA	0.036	0.007	-10000	0	-10000	0	0
Rac1/GTP	0.06	0.029	-10000	0	-10000	0	0
LCK	-0.13	0.22	-10000	0	-0.42	138	138
BCL2	-0.077	0.22	-10000	0	-0.43	80	80

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.005	0.14	-10000	0	-0.34	45	45
alphaM/beta2 Integrin/GPIbA	-0.13	0.2	-10000	0	-0.31	189	189
alphaM/beta2 Integrin/proMMP-9	-0.035	0.19	-10000	0	-0.37	74	74
PLAUR	0.033	0.024	-10000	0	-0.42	1	1
HMGB1	0.018	0.037	-10000	0	-0.11	4	4
alphaM/beta2 Integrin/Talin	0.003	0.14	-10000	0	-0.33	44	44
AGER	0.017	0.034	-10000	0	-10000	0	0
RAP1A	0.034	0.007	-10000	0	-10000	0	0
SELPLG	-0.004	0.13	-10000	0	-0.42	31	31
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.007	0.18	-10000	0	-0.29	90	90
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.036	0.16	-10000	0	-0.42	55	55
CYR61	0.031	0.034	-10000	0	-0.42	2	2
TLN1	0.032	0.011	-10000	0	-10000	0	0
Rap1/GTP	-0.071	0.19	-10000	0	-0.41	63	63
RHOA	0.035	0.005	-10000	0	-10000	0	0
P-selectin oligomer	-0.096	0.2	-10000	0	-0.42	103	103
MYH2	-0.1	0.2	-10000	0	-0.44	65	65
MST1R	0.013	0.095	-10000	0	-0.42	17	17
leukocyte activation during inflammatory response	-0.003	0.12	-10000	0	-0.3	42	42
APOB	0.023	0.011	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.027	0.035	-10000	0	-0.42	2	2
JAM3	0.029	0.014	-10000	0	-10000	0	0
GP1BA	-0.18	0.22	-10000	0	-0.42	175	175
alphaM/beta2 Integrin/CTGF	-0.001	0.14	-10000	0	-0.33	44	44
alphaM/beta2 Integrin	-0.1	0.21	-10000	0	-0.47	65	65
JAM3 homodimer	0.029	0.014	-10000	0	-10000	0	0
ICAM2	0.006	0.11	-10000	0	-0.42	23	23
ICAM1	0.026	0.062	-10000	0	-0.42	7	7
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.1	0.21	-10000	0	-0.47	65	65
cell adhesion	-0.13	0.2	-10000	0	-0.31	189	189
NFKB1	-0.053	0.23	0.4	3	-0.43	84	87
THY1	0.029	0.035	-10000	0	-0.42	2	2
RhoA/GDP	0.026	0.004	-10000	0	-10000	0	0
Lipoprotein(a)	0.022	0.015	-10000	0	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	0.018	0.14	-10000	0	-0.32	40	40
IL6	-0.063	0.22	0.38	3	-0.43	78	81
ITGB2	-0.032	0.15	-10000	0	-0.44	42	42
elevation of cytosolic calcium ion concentration	0.014	0.14	-10000	0	-0.32	42	42
alphaM/beta2 Integrin/JAM2/JAM3	0.015	0.14	-10000	0	-0.33	42	42
JAM2	0.032	0.034	-10000	0	-0.42	2	2
alphaM/beta2 Integrin/ICAM1	0.026	0.16	-10000	0	-0.3	60	60
alphaM/beta2 Integrin/uPA/Plg	0.007	0.13	-10000	0	-0.32	42	42
RhoA/GTP	-0.11	0.21	-10000	0	-0.43	78	78
positive regulation of phagocytosis	-0.076	0.22	-10000	0	-0.49	58	58
Ron/MSP	0.033	0.075	-10000	0	-0.3	18	18
alphaM/beta2 Integrin/uPAR/uPA	0.016	0.14	-10000	0	-0.33	42	42
alphaM/beta2 Integrin/uPAR	0.001	0.14	-10000	0	-0.34	45	45
PLAU	0.03	0.026	-10000	0	-0.42	1	1
PLAT	0.032	0.025	-10000	0	-0.42	1	1
actin filament polymerization	-0.099	0.19	-10000	0	-0.42	65	65
MST1	0.033	0.024	-10000	0	-0.42	1	1
alphaM/beta2 Integrin/lipoprotein(a)	0.001	0.12	-10000	0	-0.3	42	42
TNF	-0.13	0.31	-10000	0	-0.69	80	80
RAP1B	0.034	0.007	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0	0.14	-10000	0	-0.34	45	45
fibrinolysis	0.006	0.13	-10000	0	-0.32	42	42
HCK	-0.002	0.12	-10000	0	-0.42	28	28
dendritic cell antigen processing and presentation	-0.1	0.21	-10000	0	-0.47	65	65
VTN	-0.019	0.14	-10000	0	-0.42	43	43
alphaM/beta2 Integrin/CYR61	0.001	0.14	-10000	0	-0.35	43	43
LPA	0.015	0.006	-10000	0	-10000	0	0
LRP1	0.034	0.007	-10000	0	-10000	0	0
cell migration	-0.038	0.17	-10000	0	-0.34	75	75
FN1	0.021	0.077	-10000	0	-0.42	11	11
alphaM/beta2 Integrin/Thy1	0	0.14	-10000	0	-0.34	44	44
MPO	-0.004	0.12	-10000	0	-0.42	30	30
KNG1	0.021	0.01	-10000	0	-10000	0	0
RAP1/GDP	0.044	0.013	-10000	0	-10000	0	0
ROCK1	-0.1	0.2	0.28	1	-0.44	65	66
ELA2	0	0	-10000	0	-10000	0	0
PLG	0.015	0.006	-10000	0	-10000	0	0
CTGF	0.03	0.013	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Hck	-0.012	0.18	-10000	0	-0.45	45	45
ITGAM	0.004	0.086	-10000	0	-0.41	12	12
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.068	0.22	-10000	0	-0.34	118	118
HP	-0.068	0.18	-10000	0	-0.42	80	80
leukocyte adhesion	-0.015	0.16	-10000	0	-0.37	47	47
SELP	-0.096	0.2	-10000	0	-0.42	103	103

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.082	0.097	0.29	21	-10000	0	21
SMARCC2	0.036	0.005	-10000	0	-10000	0	0
SMARCC1	0.036	0.005	-10000	0	-10000	0	0
TBX21	-0.21	0.32	-10000	0	-0.7	104	104
SUMO2	0.036	0.011	-10000	0	-10000	0	0
STAT1 (dimer)	0.003	0.11	-10000	0	-0.29	43	43
FKBP4	0.034	0.006	-10000	0	-10000	0	0
FKBP5	0.003	0.11	-10000	0	-0.42	23	23
GR alpha/HSP90/FKBP51/HSP90	0.095	0.12	0.29	66	-0.21	7	73
PRL	-0.045	0.11	-10000	0	-0.49	1	1
cortisol/GR alpha (dimer)/TIF2	0.19	0.26	0.54	110	-10000	0	110
RELA	0.014	0.073	-10000	0	-0.19	24	24
FGG	0.15	0.21	0.44	109	-10000	0	109
GR beta/TIF2	0.11	0.13	0.3	91	-10000	0	91
IFNG	-0.42	0.53	-10000	0	-1	144	144
apoptosis	0.085	0.15	0.5	33	-10000	0	33
CREB1	0.036	0.009	-10000	0	-10000	0	0
histone acetylation	-0.071	0.15	-10000	0	-0.35	58	58
BGLAP	-0.062	0.14	-10000	0	-0.46	15	15
GR/PKAc	0.13	0.11	0.31	67	-10000	0	67
NF kappa B1 p50/RelA	0.021	0.13	-10000	0	-0.3	36	36
SMARCD1	0.036	0.006	-10000	0	-10000	0	0
MDM2	0.086	0.11	0.23	106	-10000	0	106
GATA3	-0.045	0.17	-10000	0	-0.42	64	64
AKT1	0.028	0.005	-10000	0	-10000	0	0
CSF2	-0.087	0.16	-10000	0	-0.5	24	24
GSK3B	0.037	0.011	-10000	0	-10000	0	0
NR1I3	0.11	0.16	0.53	28	-10000	0	28
CSN2	0.12	0.18	0.36	108	-10000	0	108
BRG1/BAF155/BAF170/BAF60A	0.092	0.023	-10000	0	-10000	0	0
NFATC1	0.024	0.07	-10000	0	-0.42	9	9
POU2F1	0.029	0.02	-10000	0	-10000	0	0
CDKN1A	0.022	0.057	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.003	0.009	-10000	0	-10000	0	0
SFN	0.027	0.015	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.095	0.12	0.31	48	-0.2	5	53
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.096	0.14	0.48	27	-10000	0	27
JUN	-0.14	0.19	-10000	0	-0.42	84	84
IL4	-0.097	0.16	-10000	0	-0.5	25	25
CDK5R1	0.034	0.025	-10000	0	-0.42	1	1
PRKACA	0.035	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.052	0.11	0.22	17	-0.3	28	45
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.12	0.3	59	-0.19	7	66
cortisol/GR alpha (monomer)	0.23	0.32	0.63	118	-10000	0	118
NCOA2	0.032	0.011	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.02	0.074	-10000	0	-0.16	6	6
AP-1/NFAT1-c-4	-0.2	0.27	-10000	0	-0.51	139	139
AFP	-0.11	0.14	-10000	0	-0.56	1	1
SUV420H1	0.033	0.008	-10000	0	-10000	0	0
IRF1	0.06	0.27	0.42	48	-0.66	33	81
TP53	0.05	0.015	-10000	0	-10000	0	0
PPP5C	0.035	0.004	-10000	0	-10000	0	0
KRT17	-0.19	0.27	-10000	0	-0.58	93	93
KRT14	-0.1	0.14	-10000	0	-0.49	12	12
TBP	0.039	0.015	-10000	0	-10000	0	0
CREBBP	0.041	0.012	-10000	0	-10000	0	0
HDAC1	0.033	0.024	-10000	0	-0.42	1	1
HDAC2	0.03	0.012	-10000	0	-10000	0	0
AP-1	-0.2	0.28	-10000	0	-0.51	139	139
MAPK14	0.033	0.014	-10000	0	-10000	0	0
MAPK10	0.029	0.018	-10000	0	-10000	0	0
MAPK11	0.035	0.013	-10000	0	-10000	0	0
KRT5	-0.25	0.38	-10000	0	-0.84	84	84
interleukin-1 receptor activity	-0.001	0.004	-10000	0	-10000	0	0
NCOA1	0.037	0.006	-10000	0	-10000	0	0
STAT1	0.004	0.11	-10000	0	-0.29	43	43
CGA	-0.085	0.15	-10000	0	-0.4	45	45
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.1	0.13	0.33	61	-10000	0	61
MAPK3	0.037	0.01	-10000	0	-10000	0	0
MAPK1	0.035	0.012	-10000	0	-10000	0	0
ICAM1	-0.12	0.23	-10000	0	-0.58	51	51
NFKB1	0.013	0.076	-10000	0	-0.22	13	13
MAPK8	-0.12	0.18	-10000	0	-0.38	90	90
MAPK9	0.035	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.082	0.15	0.51	31	-10000	0	31
BAX	0.013	0.044	-10000	0	-10000	0	0
POMC	-0.25	0.5	-10000	0	-1.6	43	43
EP300	0.037	0.016	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.2	0.26	0.56	103	-10000	0	103
proteasomal ubiquitin-dependent protein catabolic process	0.053	0.091	0.2	70	-10000	0	70
SGK1	0.056	0.074	-10000	0	-10000	0	0
IL13	-0.23	0.32	-10000	0	-0.77	78	78
IL6	-0.12	0.26	-10000	0	-0.55	72	72
PRKACG	0.019	0.009	-10000	0	-10000	0	0
IL5	-0.21	0.28	-10000	0	-0.69	73	73
IL2	-0.2	0.27	-10000	0	-0.61	81	81
CDK5	0.032	0.012	-10000	0	-10000	0	0
PRKACB	0.035	0.005	-10000	0	-10000	0	0
HSP90AA1	0.033	0.024	-10000	0	-0.42	1	1
IL8	-0.12	0.22	-10000	0	-0.58	45	45
CDK5R1/CDK5	0.046	0.028	-10000	0	-0.3	1	1
NF kappa B1 p50/RelA/PKAc	0.056	0.12	-10000	0	-0.28	13	13
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.2	0.25	0.51	121	-10000	0	121
SMARCA4	0.037	0.003	-10000	0	-10000	0	0
chromatin remodeling	0.14	0.16	0.36	104	-10000	0	104
NF kappa B1 p50/RelA/Cbp	0.061	0.11	0.34	1	-0.3	6	7
JUN (dimer)	-0.14	0.19	-10000	0	-0.42	84	84
YWHAH	0.034	0.008	-10000	0	-10000	0	0
VIPR1	-0.2	0.32	0.32	1	-0.68	103	104
NR3C1	0.15	0.21	0.42	109	-10000	0	109
NR4A1	-0.016	0.16	-10000	0	-0.45	42	42
TIF2/SUV420H1	0.045	0.019	-10000	0	-10000	0	0
MAPKKK cascade	0.085	0.15	0.5	33	-10000	0	33
cortisol/GR alpha (dimer)/Src-1	0.21	0.27	0.53	127	-10000	0	127
PBX1	0.028	0.019	-10000	0	-10000	0	0
POU1F1	0.017	0.019	-10000	0	-10000	0	0
SELE	-0.16	0.33	-10000	0	-0.73	76	76
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.16	0.36	104	-10000	0	104
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.2	0.25	0.51	121	-10000	0	121
mol:cortisol	0.14	0.19	0.36	124	-10000	0	124
MMP1	-0.14	0.33	-10000	0	-1	42	42

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0.058	-10000	0	-0.36	6	6
Crk/p130 Cas/Paxillin	-0.049	0.1	-10000	0	-0.23	74	74
JUN	-0.029	0.092	0.2	1	-0.27	10	11
HRAS	0.034	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.004	0.12	-10000	0	-0.23	78	78
RAP1A	0.034	0.007	-10000	0	-10000	0	0
FRS2	0.034	0.007	-10000	0	-10000	0	0
RAP1A/GDP	0.025	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.002	0.13	-10000	0	-0.23	82	82
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.034	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.033	0.009	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.017	0.12	-10000	0	-0.23	81	81
RHOA	0.035	0.005	-10000	0	-10000	0	0
RAP1A/GTP	0.002	0.11	-10000	0	-0.2	79	79
GRB7	0.029	0.012	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF	-0.002	0.13	-10000	0	-0.23	82	82
MAPKKK cascade	-0.023	0.11	-10000	0	-0.22	74	74
BCAR1	0.034	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.019	0.12	-10000	0	-0.23	80	80
lamellipodium assembly	-0.034	0.11	-10000	0	-0.22	74	74
RET51/GFRalpha1/GDNF/SHC	-0.001	0.12	-10000	0	-0.23	72	72
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.014	0.11	-10000	0	-0.23	71	71
RET9/GFRalpha1/GDNF/Shank3	-0.017	0.12	-10000	0	-0.23	78	78
MAPK3	-0.027	0.1	0.19	18	-0.2	76	94
DOK1	0.035	0.003	-10000	0	-10000	0	0
DOK6	0.023	0.062	-10000	0	-0.42	7	7
PXN	0.034	0.006	-10000	0	-10000	0	0
neurite development	-0.018	0.095	0.26	3	-0.28	5	8
DOK5	0.021	0.043	-10000	0	-0.42	3	3
GFRA1	-0.068	0.19	-10000	0	-0.42	81	81
MAPK8	-0.027	0.096	-10000	0	-0.2	80	80
HRAS/GTP	-0.013	0.13	-10000	0	-0.24	80	80
tube development	-0.012	0.11	0.22	5	-0.22	74	79
MAPK1	-0.025	0.098	0.19	17	-0.2	68	85
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.031	0.1	-10000	0	-0.21	77	77
Rac1/GDP	0.023	0.009	-10000	0	-10000	0	0
SRC	0.033	0.009	-10000	0	-10000	0	0
PDLIM7	0.033	0.009	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	0.006	0.13	-10000	0	-0.23	73	73
SHC1	0.032	0.011	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.002	0.13	-10000	0	-0.23	82	82
RET51/GFRalpha1/GDNF/Dok5	-0.01	0.12	-10000	0	-0.23	74	74
PRKCA	0.032	0.025	-10000	0	-0.42	1	1
HRAS/GDP	0.025	0.004	-10000	0	-10000	0	0
CREB1	-0.032	0.11	-10000	0	-0.23	76	76
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.027	0.097	-10000	0	-0.21	71	71
RET51/GFRalpha1/GDNF/Grb7	-0.007	0.12	-10000	0	-0.23	81	81
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.03	0.026	-10000	0	-0.42	1	1
DOK4	0.034	0.007	-10000	0	-10000	0	0
JNK cascade	-0.029	0.091	0.2	1	-0.26	10	11
RET9/GFRalpha1/GDNF/FRS2	-0.017	0.12	-10000	0	-0.23	80	80
SHANK3	0.032	0.01	-10000	0	-10000	0	0
RASA1	0.032	0.025	-10000	0	-0.42	1	1
NCK1	0.034	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.028	0.097	-10000	0	-0.21	72	72
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.03	0.11	-10000	0	-0.21	84	84
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.03	0.11	-10000	0	-0.21	91	91
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.023	0.097	-10000	0	-0.21	70	70
PI3K	-0.043	0.16	0.23	3	-0.31	77	80
SOS1	0.035	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.002	0.11	-10000	0	-0.22	74	74
GRB10	0.031	0.011	-10000	0	-10000	0	0
activation of MAPKK activity	-0.023	0.1	-10000	0	-0.21	81	81
RET51/GFRalpha1/GDNF/FRS2	-0.002	0.13	-10000	0	-0.23	81	81
GAB1	0.035	0.004	-10000	0	-10000	0	0
IRS1	0.032	0.011	-10000	0	-10000	0	0
IRS2	0.034	0.007	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.022	0.097	-10000	0	-0.21	69	69
RET51/GFRalpha1/GDNF/PKC alpha	-0.003	0.13	-10000	0	-0.23	78	78
GRB2	0.034	0.007	-10000	0	-10000	0	0
PRKACA	0.035	0.003	-10000	0	-10000	0	0
GDNF	0.019	0.058	-10000	0	-0.42	6	6
RAC1	0.031	0.012	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.004	0.12	-10000	0	-0.23	81	81
Rac1/GTP	-0.035	0.13	-10000	0	-0.26	71	71
RET9/GFRalpha1/GDNF	-0.031	0.12	-10000	0	-0.25	81	81
GFRalpha1/GDNF	-0.039	0.14	-10000	0	-0.3	81	81

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.03	0.13	-10000	0	-0.29	65	65
CRKL	0.033	0.01	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.009	-10000	0	-10000	0	0
DOCK1	0.032	0.01	-10000	0	-10000	0	0
ITGA4	-0.014	0.14	-10000	0	-0.42	40	40
alpha4/beta7 Integrin/MAdCAM1	-0.15	0.19	-10000	0	-0.28	235	235
EPO	0.026	0.012	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.031	0.16	-10000	0	-0.32	81	81
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.033	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.01	0.11	-10000	0	-0.29	40	40
EPO/EPOR (dimer)	0.042	0.017	-10000	0	-10000	0	0
lamellipodium assembly	0.018	0.076	-10000	0	-0.55	5	5
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
PI3K	0.049	0.013	-10000	0	-10000	0	0
ARF6	0.035	0.004	-10000	0	-10000	0	0
JAK2	-0.004	0.1	-10000	0	-0.28	38	38
PXN	0.034	0.006	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
MADCAM1	-0.22	0.22	-10000	0	-0.42	204	204
cell adhesion	-0.15	0.19	-10000	0	-0.27	235	235
CRKL/CBL	0.044	0.02	-10000	0	-10000	0	0
ITGB1	0.032	0.011	-10000	0	-10000	0	0
SRC	-0.038	0.13	0.19	3	-0.3	68	71
ITGB7	-0.026	0.15	-10000	0	-0.42	49	49
RAC1	0.031	0.012	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.015	0.16	-10000	0	-0.32	74	74
p130Cas/Crk/Dock1	-0.005	0.13	-10000	0	-0.27	62	62
VCAM1	-0.04	0.17	-10000	0	-0.42	60	60
RHOA	0.035	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.047	0.098	-10000	0	-0.22	40	40
BCAR1	-0.055	0.12	0.18	4	-0.28	67	71
EPOR	0.035	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.032	0.011	-10000	0	-10000	0	0
GIT1	0.034	0.006	-10000	0	-10000	0	0
Rac1/GTP	0.018	0.079	-10000	0	-0.57	5	5

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.027	0.046	0.3	5	-10000	0	5
DAPP1	-0.29	0.38	0.34	1	-0.64	158	159
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.38	0.44	0.4	1	-0.8	165	166
mol:DAG	-0.12	0.15	0.23	6	-0.3	141	147
HRAS	0.037	0.009	-10000	0	-10000	0	0
RAP1A	0.036	0.009	-10000	0	-10000	0	0
ARF5/GDP	0.007	0.12	0.21	2	-0.35	26	28
PLCG2	-0.001	0.12	-10000	0	-0.42	28	28
PLCG1	0.033	0.01	-10000	0	-10000	0	0
ARF5	0.031	0.011	-10000	0	-10000	0	0
mol:GTP	-0.002	0.058	0.22	20	-10000	0	20
ARF1/GTP	0.012	0.054	0.3	8	-10000	0	8
RHOA	0.035	0.005	-10000	0	-10000	0	0
YES1	0.034	0.008	-10000	0	-10000	0	0
RAP1A/GTP	0.021	0.03	0.18	11	-10000	0	11
ADAP1	-0.011	0.053	0.26	6	-0.2	10	16
ARAP3	-0.002	0.057	0.22	20	-10000	0	20
INPPL1	0.033	0.009	-10000	0	-10000	0	0
PREX1	0.03	0.035	-10000	0	-0.42	2	2
ARHGEF6	0.015	0.092	-10000	0	-0.42	16	16
ARHGEF7	0.034	0.007	-10000	0	-10000	0	0
ARF1	0.032	0.011	-10000	0	-10000	0	0
NRAS	0.036	0.01	-10000	0	-10000	0	0
FYN	0.031	0.012	-10000	0	-10000	0	0
ARF6	0.035	0.004	-10000	0	-10000	0	0
FGR	-0.01	0.13	-10000	0	-0.42	36	36
mol:Ca2+	-0.054	0.076	0.16	9	-0.14	124	133
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.008	0.1	-10000	0	-0.42	21	21
ZAP70	-0.12	0.22	-10000	0	-0.42	126	126
mol:IP3	-0.081	0.1	0.18	7	-0.2	134	141
LYN	0.016	0.084	-10000	0	-0.42	13	13
ARF1/GDP	0.01	0.12	0.22	1	-0.35	23	24
RhoA/GDP	0.043	0.082	0.25	9	-0.26	5	14
PDK1/Src/Hsp90	0.064	0.022	-10000	0	-10000	0	0
BLNK	-0.11	0.21	-10000	0	-0.42	116	116
actin cytoskeleton reorganization	0.021	0.12	0.26	19	-0.32	15	34
SRC	0.033	0.009	-10000	0	-10000	0	0
PLEKHA2	-0.029	0.091	-10000	0	-0.26	49	49
RAC1	0.031	0.012	-10000	0	-10000	0	0
PTEN	0.027	0.018	-10000	0	-10000	0	0
HSP90AA1	0.033	0.024	-10000	0	-0.42	1	1
ARF6/GTP	0.03	0.052	0.3	10	-10000	0	10
RhoA/GTP	-0.002	0.059	0.24	19	-10000	0	19
Src family/SYK family/BLNK-LAT	-0.38	0.46	-10000	0	-0.79	168	168
BLK	-0.23	0.22	-10000	0	-0.42	216	216
PDPK1	0.035	0.003	-10000	0	-10000	0	0
CYTH1	-0.003	0.055	0.28	10	-10000	0	10
HCK	-0.002	0.12	-10000	0	-0.42	28	28
CYTH3	-0.006	0.043	0.26	6	-10000	0	6
CYTH2	-0.002	0.057	0.27	12	-10000	0	12
KRAS	0.037	0.009	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.026	0.047	0.22	7	-0.29	3	10
SGK1	0.015	0.085	0.23	7	-0.31	19	26
INPP5D	-0.037	0.16	-10000	0	-0.42	58	58
mol:GDP	-0.007	0.13	0.22	4	-0.33	32	36
SOS1	0.035	0.003	-10000	0	-10000	0	0
SYK	-0.012	0.13	-10000	0	-0.42	36	36
ARF6/GDP	0.023	0.082	0.28	15	-0.26	5	20
mol:PI-3-4-5-P3	-0.003	0.055	0.27	11	-10000	0	11
ARAP3/RAP1A/GTP	0.021	0.03	0.18	11	-10000	0	11
VAV1	-0.051	0.18	-10000	0	-0.42	70	70
mol:PI-3-4-P2	-0.029	0.11	-10000	0	-0.3	54	54
RAS family/GTP/PI3K Class I	0.069	0.057	0.21	45	-10000	0	45
PLEKHA1	-0.024	0.082	-10000	0	-0.25	43	43
Rac1/GDP	0.005	0.12	0.21	2	-0.35	24	26
LAT	-0.021	0.15	-10000	0	-0.42	45	45
Rac1/GTP	-0.018	0.15	-10000	0	-0.41	33	33
ITK	-0.043	0.088	0.28	5	-0.21	67	72
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.18	0.22	0.23	3	-0.43	145	148
LCK	-0.14	0.22	-10000	0	-0.42	138	138
BTK	-0.029	0.083	0.27	9	-0.21	42	51

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.094	0.34	-10000	0	-0.82	63	63
NCK1/PAK1/Dok-R	-0.083	0.15	-10000	0	-0.41	62	62
NCK1/Dok-R	-0.14	0.42	-10000	0	-1	63	63
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
mol:beta2-estradiol	0.03	0.088	0.22	62	-10000	0	62
RELA	0.034	0.007	-10000	0	-10000	0	0
SHC1	0.031	0.011	-10000	0	-10000	0	0
Rac/GDP	0.023	0.009	-10000	0	-10000	0	0
F2	0.026	0.1	0.25	58	-10000	0	58
TNIP2	0.034	0.007	-10000	0	-10000	0	0
NF kappa B/RelA	-0.11	0.39	-10000	0	-0.94	63	63
FN1	0.021	0.077	-10000	0	-0.42	11	11
PLD2	-0.15	0.4	-10000	0	-1	63	63
PTPN11	0.034	0.006	-10000	0	-10000	0	0
GRB14	0.027	0.013	-10000	0	-10000	0	0
ELK1	-0.13	0.37	-10000	0	-0.93	63	63
GRB7	0.029	0.012	-10000	0	-10000	0	0
PAK1	0.033	0.009	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.12	0.41	-10000	0	-0.99	63	63
CDKN1A	-0.036	0.23	-10000	0	-0.57	24	24
ITGA5	0.034	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.14	0.42	-10000	0	-1	62	62
CRK	0.033	0.009	-10000	0	-10000	0	0
mol:NO	-0.047	0.27	0.38	1	-0.61	63	64
PLG	-0.15	0.4	-10000	0	-1	63	63
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.088	0.33	-10000	0	-0.79	63	63
GRB2	0.034	0.007	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
ANGPT2	-0.04	0.18	-10000	0	-0.66	4	4
BMX	-0.18	0.42	-10000	0	-1.1	63	63
ANGPT1	-0.21	0.47	-10000	0	-1.2	61	61
tube development	-0.057	0.24	-10000	0	-0.57	62	62
ANGPT4	0.009	0.015	-10000	0	-10000	0	0
response to hypoxia	-0.012	0.026	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.16	0.42	-10000	0	-1.1	63	63
alpha5/beta1 Integrin	0.046	0.018	-10000	0	-10000	0	0
FGF2	0.029	0.034	-10000	0	-0.42	2	2
STAT5A (dimer)	-0.052	0.28	-10000	0	-0.65	52	52
mol:L-citrulline	-0.047	0.27	0.38	1	-0.61	63	64
AGTR1	0.017	0.008	-10000	0	-10000	0	0
MAPK14	-0.14	0.39	-10000	0	-0.98	63	63
Tie2/SHP2	-0.045	0.22	-10000	0	-0.94	13	13
TEK	-0.05	0.23	-10000	0	-0.92	16	16
RPS6KB1	-0.087	0.33	-10000	0	-0.78	63	63
Angiotensin II/AT1	0.015	0.007	-10000	0	-10000	0	0
Tie2/Ang1/GRB2	-0.15	0.42	-10000	0	-1	63	63
MAPK3	-0.14	0.38	-10000	0	-0.95	63	63
MAPK1	-0.14	0.38	-10000	0	-0.95	63	63
Tie2/Ang1/GRB7	-0.15	0.42	-10000	0	-1.1	63	63
NFKB1	0.034	0.006	-10000	0	-10000	0	0
MAPK8	-0.15	0.4	-10000	0	-1	63	63
PI3K	-0.11	0.38	-10000	0	-0.92	63	63
FES	-0.14	0.4	-10000	0	-0.98	63	63
Crk/Dok-R	-0.15	0.42	-10000	0	-1	63	63
Tie2/Ang1/ABIN2	-0.15	0.42	-10000	0	-1.1	63	63
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.08	0.31	-10000	0	-0.73	63	63
STAT5A	0.033	0.024	-10000	0	-0.42	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.076	0.34	-10000	0	-0.78	62	62
Tie2/Ang2	-0.081	0.31	-10000	0	-0.76	52	52
Tie2/Ang1	-0.16	0.43	-10000	0	-1.1	63	63
FOXO1	-0.081	0.31	-10000	0	-0.74	63	63
ELF1	0.04	0.019	-10000	0	-0.12	2	2
ELF2	-0.15	0.4	-10000	0	-1	63	63
mol:Choline	-0.15	0.39	-10000	0	-0.98	63	63
cell migration	-0.047	0.087	-10000	0	-0.23	63	63
FYN	-0.069	0.27	-10000	0	-0.64	60	60
DOK2	-0.01	0.13	-10000	0	-0.42	35	35
negative regulation of cell cycle	-0.03	0.21	-10000	0	-0.52	26	26
ETS1	0	0.096	-10000	0	-0.24	50	50
PXN	-0.055	0.29	-10000	0	-0.65	62	62
ITGB1	0.032	0.011	-10000	0	-10000	0	0
NOS3	-0.062	0.3	-10000	0	-0.7	63	63
RAC1	0.031	0.012	-10000	0	-10000	0	0
TNF	-0.085	0.2	-10000	0	-0.39	105	105
MAPKKK cascade	-0.15	0.39	-10000	0	-0.98	63	63
RASA1	0.032	0.025	-10000	0	-0.42	1	1
Tie2/Ang1/Shc	-0.15	0.42	-10000	0	-1	63	63
NCK1	0.034	0.006	-10000	0	-10000	0	0
vasculogenesis	-0.037	0.25	0.37	1	-0.55	63	64
mol:Phosphatidic acid	-0.15	0.39	-10000	0	-0.98	63	63
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.047	0.27	0.38	1	-0.61	63	64
Rac1/GTP	-0.081	0.31	-10000	0	-0.73	63	63
MMP2	-0.16	0.4	-10000	0	-1	63	63

×

IL2 signaling events mediated by STAT5

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
GAB2	0.033	0.009	-10000	0	-10000	0	0
ELF1	-0.04	0.15	-10000	0	-0.31	85	85
CCNA2	0.033	0.024	-10000	0	-0.42	1	1
PIK3CA	0.035	0.006	-10000	0	-10000	0	0
JAK3	0.005	0.11	-10000	0	-0.42	25	25
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
JAK1	0.035	0.005	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.16	0.33	-10000	0	-0.6	119	119
SHC1	0.032	0.011	-10000	0	-10000	0	0
SP1	0.019	0.094	-10000	0	-0.33	24	24
IL2RA	-0.13	0.29	-10000	0	-0.63	89	89
IL2RB	-0.042	0.17	-10000	0	-0.42	61	61
SOS1	0.036	0.003	-10000	0	-10000	0	0
IL2RG	-0.1	0.21	-10000	0	-0.42	112	112
G1/S transition of mitotic cell cycle	-0.031	0.22	0.28	1	-0.7	32	33
PTPN11	0.035	0.006	-10000	0	-10000	0	0
CCND2	-0.019	0.18	-10000	0	-0.68	24	24
LCK	-0.14	0.22	-10000	0	-0.42	138	138
GRB2	0.034	0.007	-10000	0	-10000	0	0
IL2	0.023	0.009	-10000	0	-10000	0	0
CDK6	0.028	0.042	-10000	0	-0.42	3	3
CCND3	-0.12	0.28	-10000	0	-0.56	85	85

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.018	0.029	-10000	0	-0.42	1	1
CDC42/GTP	-0.032	0.12	-10000	0	-0.22	96	96
PLCG1	-0.039	0.11	-10000	0	-0.22	83	83
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.035	0.005	-10000	0	-10000	0	0
GNAI3	0.034	0.007	-10000	0	-10000	0	0
G12/G13	0.045	0.018	-10000	0	-10000	0	0
cell migration	-0.032	0.12	-10000	0	-0.21	96	96
S1PR5	0.034	0.008	-10000	0	-10000	0	0
S1PR4	-0.11	0.21	-10000	0	-0.42	118	118
MAPK3	-0.044	0.11	-10000	0	-0.22	89	89
MAPK1	-0.042	0.11	-10000	0	-0.22	89	89
S1P/S1P5/Gi	0.022	0.037	-10000	0	-0.18	4	4
GNAI1	0.031	0.012	-10000	0	-10000	0	0
CDC42/GDP	0.026	0.004	-10000	0	-10000	0	0
S1P/S1P5/G12	0.039	0.019	-10000	0	-10000	0	0
RHOA	-0.027	0.12	0.22	28	-0.21	97	125
S1P/S1P4/Gi	-0.047	0.12	-10000	0	-0.23	91	91
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.027	0.035	-10000	0	-0.42	2	2
S1P/S1P4/G12/G13	-0.022	0.13	-10000	0	-0.22	98	98
GNA12	0.031	0.011	-10000	0	-10000	0	0
GNA13	0.034	0.006	-10000	0	-10000	0	0
CDC42	0.035	0.005	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.025	0.14	0.23	1	-0.2	121	122
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.033	0.01	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.03	0.14	0.28	2	-0.33	30	32
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.021	0.068	-10000	0	-0.28	6	6
antigen processing and presentation of peptide antigen via MHC class I	-0.023	0.086	-10000	0	-0.22	25	25
CaM/Ca2+	-0.02	0.13	-10000	0	-0.2	107	107
RAP1A	0.034	0.007	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.044	0.12	0.28	1	-0.21	106	107
AKT1	-0.042	0.11	0.29	4	-0.26	14	18
MAP2K1	-0.05	0.1	0.24	2	-0.2	86	88
MAP3K11	-0.047	0.11	0.26	3	-0.2	102	105
IFNGR1	0.014	0.031	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.025	0.12	-10000	0	-0.37	25	25
Rap1/GTP	-0.034	0.087	-10000	0	-0.23	12	12
CRKL/C3G	0.045	0.018	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.014	0.14	-10000	0	-0.21	119	119
CEBPB	-0.002	0.11	0.41	2	-0.33	3	5
STAT3	0.034	0.005	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.06	0.29	-10000	0	-1.2	20	20
STAT1	-0.052	0.12	0.31	2	-0.22	90	92
CALM1	0.034	0.006	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.12	0.21	-10000	0	-0.42	121	121
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	-0.037	0.12	0.34	1	-0.21	87	88
CEBPB/PTGES2/Cbp/p300	0.009	0.083	-10000	0	-0.23	2	2
mol:Ca2+	-0.027	0.13	0.22	1	-0.2	121	122
MAPK3	-0.019	0.11	0.4	1	-0.69	2	3
STAT1 (dimer)	-0.023	0.12	-10000	0	-0.31	25	25
MAPK1	-0.026	0.13	0.4	1	-0.72	5	6
JAK2	0.005	0.064	-10000	0	-0.43	6	6
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
JAK1	0.013	0.033	-10000	0	-10000	0	0
CAMK2D	0.034	0.005	-10000	0	-10000	0	0
DAPK1	0.008	0.081	0.36	2	-10000	0	2
SMAD7	-0.004	0.054	0.18	4	-0.15	8	12
CBL/CRKL/C3G	-0.02	0.12	0.31	2	-0.2	75	77
PI3K	-0.019	0.13	-10000	0	-0.2	100	100
IFNG	-0.12	0.21	-10000	0	-0.42	121	121
apoptosis	0.006	0.075	0.3	2	-0.32	1	3
CAMK2G	0.032	0.01	-10000	0	-10000	0	0
STAT3 (dimer)	0.034	0.005	-10000	0	-10000	0	0
CAMK2A	0.024	0.048	-10000	0	-0.42	4	4
CAMK2B	0.021	0.062	-10000	0	-0.42	7	7
FRAP1	-0.052	0.094	0.27	4	-0.24	14	18
PRKCD	-0.04	0.11	0.29	4	-0.24	18	22
RAP1B	0.034	0.007	-10000	0	-10000	0	0
negative regulation of cell growth	-0.023	0.086	-10000	0	-0.22	25	25
PTPN2	0.034	0.007	-10000	0	-10000	0	0
EP300	0.031	0.011	-10000	0	-10000	0	0
IRF1	-0.07	0.17	0.26	2	-0.44	46	48
STAT1 (dimer)/PIASy	-0.036	0.12	0.35	2	-0.21	84	86
SOCS1	-0.038	0.31	-10000	0	-1.3	20	20
mol:GDP	-0.021	0.11	0.29	2	-0.19	76	78
CASP1	-0.009	0.071	0.17	5	-0.24	18	23
PTGES2	0.033	0.009	-10000	0	-10000	0	0
IRF9	0.018	0.052	0.16	7	-10000	0	7
mol:PI-3-4-5-P3	-0.029	0.12	-10000	0	-0.19	109	109
RAP1/GDP	-0.019	0.1	-10000	0	-0.23	12	12
CBL	-0.043	0.11	0.26	3	-0.2	96	99
MAP3K1	-0.047	0.11	0.26	3	-0.2	103	106
PIAS1	0.035	0.005	-10000	0	-10000	0	0
PIAS4	0.035	0.005	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.023	0.086	-10000	0	-0.22	25	25
PTPN11	-0.052	0.11	0.3	1	-0.2	118	119
CREBBP	0.034	0.007	-10000	0	-10000	0	0
RAPGEF1	0.033	0.009	-10000	0	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.006	0.13	0.29	22	-0.26	47	69
PTK2B	0.028	0.048	-10000	0	-0.42	4	4
mol:Ca2+	-0.031	0.22	0.65	1	-0.59	26	27
EDN1	0.016	0.1	0.23	22	-0.32	12	34
EDN3	0	0.093	-10000	0	-0.42	17	17
EDN2	0.017	0.002	-10000	0	-10000	0	0
HRAS/GDP	-0.049	0.2	0.34	2	-0.43	54	56
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.014	0.16	0.2	11	-0.43	32	43
ADCY4	0.025	0.13	0.22	37	-0.27	27	64
ADCY5	-0.017	0.15	0.22	23	-0.26	67	90
ADCY6	0.027	0.12	0.25	13	-0.33	13	26
ADCY7	0.024	0.12	0.22	35	-0.27	22	57
ADCY1	-0.006	0.13	0.26	10	-0.26	39	49
ADCY2	0.005	0.11	0.21	19	-0.3	16	35
ADCY3	0.026	0.12	0.22	31	-0.28	19	50
ADCY8	0.018	0.11	0.22	23	-0.25	21	44
ADCY9	0.028	0.12	0.22	31	-0.3	16	47
arachidonic acid secretion	-0.031	0.18	0.36	3	-0.41	41	44
ETB receptor/Endothelin-1/Gq/GTP	-0.002	0.11	-10000	0	-0.29	32	32
GNAO1	0.018	0.029	-10000	0	-0.42	1	1
HRAS	0.035	0.006	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.036	0.14	0.37	18	-0.25	36	54
ETA receptor/Endothelin-1/Gs/GTP	0.031	0.13	0.34	21	-0.23	46	67
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
COL3A1	0.006	0.13	0.29	23	-0.33	20	43
EDNRB	0.03	0.028	-10000	0	-0.42	1	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.014	0.18	0.29	18	-0.52	28	46
CYSLTR1	-0.021	0.2	0.29	23	-0.53	39	62
SLC9A1	0.011	0.078	0.2	21	-0.24	9	30
mol:GDP	-0.066	0.2	0.3	3	-0.46	55	58
SLC9A3	-0.15	0.3	0.43	1	-0.57	105	106
RAF1	-0.056	0.19	0.36	1	-0.43	51	52
JUN	-0.042	0.23	0.48	1	-0.66	24	25
JAK2	0.004	0.13	0.29	20	-0.28	43	63
mol:IP3	-0.025	0.17	0.23	2	-0.44	36	38
ETA receptor/Endothelin-1	0.024	0.17	0.42	22	-0.3	50	72
PLCB1	0.018	0.084	-10000	0	-0.42	13	13
PLCB2	0.022	0.074	-10000	0	-0.42	10	10
ETA receptor/Endothelin-3	0.004	0.098	0.19	9	-0.23	33	42
FOS	-0.029	0.16	0.46	1	-0.44	20	21
Gai/GDP	-0.015	0.18	-10000	0	-0.75	19	19
CRK	0.033	0.009	-10000	0	-10000	0	0
mol:Ca ++	-0.017	0.19	0.27	11	-0.47	37	48
BCAR1	0.034	0.008	-10000	0	-10000	0	0
PRKCB1	-0.026	0.17	0.22	2	-0.4	41	43
GNAQ	0.035	0.01	-10000	0	-10000	0	0
GNAZ	0.027	0.035	-10000	0	-0.42	2	2
GNAL	0.024	0.053	-10000	0	-0.42	5	5
Gs family/GDP	-0.055	0.19	0.32	2	-0.42	53	55
ETA receptor/Endothelin-1/Gq/GTP	-0.003	0.14	0.22	12	-0.37	32	44
MAPK14	-0.015	0.13	0.3	1	-0.4	25	26
TRPC6	-0.034	0.22	0.66	1	-0.62	26	27
GNAI2	0.035	0.005	-10000	0	-10000	0	0
GNAI3	0.034	0.007	-10000	0	-10000	0	0
GNAI1	0.031	0.012	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.011	0.14	-10000	0	-0.42	25	25
ETB receptor/Endothelin-2	0.03	0.027	-10000	0	-0.3	1	1
ETB receptor/Endothelin-3	0.011	0.075	-10000	0	-0.29	18	18
ETB receptor/Endothelin-1	0.027	0.083	-10000	0	-0.27	9	9
MAPK3	-0.039	0.17	0.38	2	-0.48	27	29
MAPK1	-0.04	0.18	0.38	2	-0.48	27	29
Rac1/GDP	-0.046	0.19	0.39	1	-0.44	51	52
cAMP biosynthetic process	-0.017	0.15	0.26	17	-0.35	33	50
MAPK8	-0.055	0.26	0.51	1	-0.64	47	48
SRC	0.033	0.009	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.013	0.05	-10000	0	-0.26	5	5
p130Cas/CRK/Src/PYK2	-0.053	0.21	0.44	2	-0.48	45	47
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.046	0.19	0.39	1	-0.44	51	52
COL1A2	0.013	0.12	0.3	17	-0.42	9	26
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.02	0.079	0.28	1	-0.18	19	20
mol:DAG	-0.025	0.17	0.23	2	-0.44	36	38
MAP2K2	-0.048	0.18	0.41	2	-0.42	44	46
MAP2K1	-0.048	0.18	0.33	3	-0.44	38	41
EDNRA	0.015	0.11	0.24	23	-0.19	56	79
positive regulation of muscle contraction	0.02	0.12	0.25	40	-0.3	17	57
Gq family/GDP	-0.046	0.22	-10000	0	-0.47	54	54
HRAS/GTP	-0.063	0.2	0.37	1	-0.43	59	60
PRKCH	-0.027	0.17	0.22	1	-0.42	37	38
RAC1	0.031	0.012	-10000	0	-10000	0	0
PRKCA	-0.025	0.17	0.25	6	-0.41	39	45
PRKCB	-0.081	0.22	-10000	0	-0.47	66	66
PRKCE	-0.025	0.17	0.23	4	-0.41	39	43
PRKCD	-0.026	0.17	0.23	3	-0.42	38	41
PRKCG	-0.029	0.17	0.22	1	-0.42	38	39
regulation of vascular smooth muscle contraction	-0.038	0.18	0.49	1	-0.52	21	22
PRKCQ	-0.071	0.2	-10000	0	-0.48	54	54
PLA2G4A	-0.035	0.18	0.37	3	-0.44	41	44
GNA14	-0.035	0.16	-10000	0	-0.42	56	56
GNA15	0.022	0.078	-10000	0	-0.42	11	11
GNA12	0.031	0.011	-10000	0	-10000	0	0
GNA11	0.036	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.036	0.14	0.37	18	-0.25	35	53
MMP1	-0.04	0.2	0.56	4	-0.78	22	26

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.009	0.069	0.23	2	-0.25	4	6
adherens junction organization	-0.042	0.12	-10000	0	-0.22	95	95
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.003	0.073	0.25	1	-0.22	2	3
FMN1	-0.041	0.12	-10000	0	-0.23	91	91
mol:IP3	-0.012	0.067	0.22	1	-0.2	5	6
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.036	0.12	-10000	0	-0.23	92	92
CTNNB1	0.037	0.007	-10000	0	-10000	0	0
AKT1	-0.009	0.085	0.2	2	-0.24	5	7
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.06	0.18	-10000	0	-0.34	97	97
CTNND1	0.035	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.031	0.1	-10000	0	-0.22	78	78
VASP	-0.037	0.11	-10000	0	-0.22	91	91
ZYX	-0.033	0.1	-10000	0	-0.22	78	78
JUB	-0.037	0.11	-10000	0	-0.22	92	92
EGFR(dimer)	-0.025	0.12	-10000	0	-0.22	85	85
E-cadherin/beta catenin-gamma catenin	-0.014	0.13	-10000	0	-0.23	94	94
mol:PI-3-4-5-P3	0.008	0.099	0.23	1	-0.25	5	6
PIK3CA	0.035	0.007	-10000	0	-10000	0	0
PI3K	0.008	0.1	0.23	1	-0.25	5	6
FYN	-0.016	0.075	0.22	2	-0.24	20	22
mol:Ca2+	-0.011	0.066	0.22	1	-0.19	5	6
JUP	0.036	0.009	-10000	0	-10000	0	0
PIK3R1	0.035	0.008	-10000	0	-10000	0	0
mol:DAG	-0.012	0.067	0.22	1	-0.2	5	6
CDH1	-0.082	0.2	-10000	0	-0.42	94	94
RhoA/GDP	0.009	0.085	0.26	4	-0.21	2	6
establishment of polarity of embryonic epithelium	-0.036	0.11	-10000	0	-0.22	91	91
SRC	0.033	0.009	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
RHOA	0.035	0.005	-10000	0	-10000	0	0
EGFR	0.027	0.035	-10000	0	-0.42	2	2
CASR	-0.017	0.062	0.19	4	-0.19	3	7
RhoA/GTP	0.003	0.073	0.22	2	-0.18	4	6
AKT2	-0.01	0.086	0.2	2	-0.23	5	7
actin cable formation	-0.039	0.12	0.19	6	-0.22	88	94
apoptosis	0.008	0.084	0.25	6	-0.22	4	10
CTNNA1	0.034	0.009	-10000	0	-10000	0	0
mol:GDP	-0.014	0.068	0.2	4	-0.21	4	8
PIP5K1A	-0.031	0.11	-10000	0	-0.22	78	78
PLCG1	-0.012	0.068	0.22	1	-0.2	5	6
Rac1/GTP	-0.015	0.12	-10000	0	-0.21	84	84
homophilic cell adhesion	0	0.002	-10000	0	-10000	0	0

×

ceramide signaling pathway

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
MAP4K4	-0.083	0.19	0.23	1	-0.43	64	65
BAG4	0.033	0.008	-10000	0	-10000	0	0
BAD	-0.018	0.068	0.15	7	-0.14	50	57
NFKBIA	0.035	0.004	-10000	0	-10000	0	0
BIRC3	-0.1	0.2	-10000	0	-0.42	109	109
BAX	-0.019	0.068	0.15	5	-0.14	50	55
EnzymeConsortium:3.1.4.12	-0.016	0.048	0.077	5	-0.097	65	70
IKBKB	-0.077	0.18	0.34	1	-0.4	63	64
MAP2K2	-0.015	0.073	0.21	7	-0.19	15	22
MAP2K1	-0.014	0.073	0.21	7	-0.19	15	22
SMPD1	-0.014	0.052	0.093	2	-0.14	23	25
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.07	0.19	0.33	6	-0.42	60	66
MAP2K4	-0.014	0.064	0.18	2	-0.17	15	17
protein ubiquitination	-0.079	0.19	0.24	1	-0.41	63	64
EnzymeConsortium:2.7.1.37	-0.014	0.078	0.22	6	-0.21	15	21
response to UV	0	0.001	0.003	9	-0.002	36	45
RAF1	-0.016	0.07	0.16	6	-0.18	19	25
CRADD	0.034	0.006	-10000	0	-10000	0	0
mol:ceramide	-0.02	0.07	0.13	5	-0.14	63	68
I-kappa-B-alpha/RELA/p50/ubiquitin	0.045	0.011	-10000	0	-10000	0	0
MADD	0.035	0.006	-10000	0	-10000	0	0
MAP3K1	-0.018	0.069	0.15	5	-0.15	48	53
TRADD	0.034	0.007	-10000	0	-10000	0	0
RELA/p50	0.034	0.007	-10000	0	-10000	0	0
MAPK3	-0.01	0.074	0.21	7	-0.19	12	19
MAPK1	-0.011	0.075	0.21	7	-0.2	14	21
p50/RELA/I-kappa-B-alpha	0.05	0.012	-10000	0	-10000	0	0
FADD	-0.08	0.19	0.26	5	-0.43	60	65
KSR1	-0.017	0.07	0.16	6	-0.15	49	55
MAPK8	-0.013	0.059	0.17	2	-0.18	7	9
TRAF2	0.033	0.009	-10000	0	-10000	0	0
response to radiation	0	0.001	0.003	4	-0.002	3	7
CHUK	-0.078	0.18	-10000	0	-0.4	64	64
TNF R/SODD	0.048	0.015	-10000	0	-10000	0	0
TNF	-0.054	0.18	-10000	0	-0.42	69	69
CYCS	-0.013	0.069	0.14	9	-0.15	40	49
IKBKG	-0.079	0.18	-10000	0	-0.4	64	64
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.093	0.2	-10000	0	-0.44	65	65
RELA	0.034	0.007	-10000	0	-10000	0	0
RIPK1	0.031	0.012	-10000	0	-10000	0	0
AIFM1	-0.02	0.067	0.14	7	-0.14	50	57
TNF/TNF R/SODD	0.002	0.12	-10000	0	-0.25	66	66
TNFRSF1A	0.034	0.007	-10000	0	-10000	0	0
response to heat	0	0.001	0.003	4	-0.002	3	7
CASP8	0.002	0.13	-10000	0	-0.69	10	10
NSMAF	-0.072	0.19	0.23	9	-0.42	61	70
response to hydrogen peroxide	0	0.001	0.003	9	-0.002	36	45
BCL2	0.035	0.005	-10000	0	-10000	0	0

×

Syndecan-1-mediated 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
TGFB1	0.032	0.033	-10000	0	-0.42	2	2
CCL5	-0.095	0.2	-10000	0	-0.42	105	105
SDCBP	0.032	0.01	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.028	0.14	0.21	8	-0.28	68	76
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.021	0.15	0.22	9	-0.42	28	37
Syndecan-1/Syntenin	-0.017	0.14	0.21	6	-0.38	28	34
MAPK3	-0.017	0.14	0.22	8	-0.41	24	32
HGF/MET	0.019	0.091	-10000	0	-0.3	25	25
TGFB1/TGF beta receptor Type II	0.032	0.033	-10000	0	-0.42	2	2
BSG	0.035	0.005	-10000	0	-10000	0	0
keratinocyte migration	-0.021	0.14	0.22	9	-0.41	28	37
Syndecan-1/RANTES	-0.073	0.19	0.24	8	-0.45	53	61
Syndecan-1/CD147	0	0.15	0.32	2	-0.43	24	26
Syndecan-1/Syntenin/PIP2	-0.017	0.13	0.2	6	-0.37	28	34
LAMA5	0.031	0.025	-10000	0	-0.42	1	1
positive regulation of cell-cell adhesion	-0.017	0.13	0.19	6	-0.36	28	34
MMP7	0.017	0.07	-10000	0	-0.42	9	9
HGF	0.024	0.058	-10000	0	-0.42	6	6
Syndecan-1/CASK	-0.04	0.13	-10000	0	-0.27	72	72
Syndecan-1/HGF/MET	-0.02	0.16	0.24	5	-0.45	31	36
regulation of cell adhesion	-0.024	0.13	0.29	2	-0.39	23	25
HPSE	0.035	0.004	-10000	0	-10000	0	0
positive regulation of cell migration	-0.028	0.14	0.21	8	-0.28	68	76
SDC1	-0.032	0.14	-10000	0	-0.28	71	71
Syndecan-1/Collagen	-0.028	0.14	0.21	8	-0.28	68	76
PPIB	0.035	0.004	-10000	0	-10000	0	0
MET	0.006	0.1	-10000	0	-0.42	20	20
PRKACA	0.035	0.003	-10000	0	-10000	0	0
MMP9	-0.036	0.16	-10000	0	-0.42	55	55
MAPK1	-0.017	0.13	0.22	8	-0.39	24	32
homophilic cell adhesion	-0.026	0.14	0.23	10	-0.28	68	78
MMP1	0.002	0.1	-10000	0	-0.42	21	21

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.034	0.007	-10000	0	-10000	0	0
LAT2	-0.034	0.17	0.2	4	-0.43	44	48
AP1	-0.069	0.28	-10000	0	-0.57	76	76
mol:PIP3	-0.051	0.24	0.36	12	-0.52	61	73
IKBKB	-0.027	0.14	0.25	20	-0.28	58	78
AKT1	0.023	0.12	0.32	40	-0.23	1	41
IKBKG	-0.029	0.14	0.25	16	-0.28	59	75
MS4A2	0.026	0.021	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
MAP3K1	-0.05	0.2	0.26	9	-0.45	64	73
mol:Ca2+	-0.03	0.18	0.28	20	-0.38	59	79
LYN	0.017	0.086	-10000	0	-0.43	13	13
CBLB	-0.019	0.13	0.2	3	-0.37	35	38
SHC1	0.032	0.011	-10000	0	-10000	0	0
RasGAP/p62DOK	0.06	0.026	-10000	0	-0.22	1	1
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	-0.037	0.16	-10000	0	-0.42	58	58
PLD2	0.024	0.11	0.32	33	-0.2	19	52
PTPN13	-0.008	0.16	-10000	0	-0.49	21	21
PTPN11	0.031	0.02	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.014	0.11	0.29	14	-0.29	12	26
SYK	-0.011	0.14	-10000	0	-0.43	36	36
GRB2	0.034	0.007	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.064	0.22	-10000	0	-0.52	62	62
LAT	-0.039	0.16	0.18	1	-0.43	45	46
PAK2	-0.059	0.23	0.28	7	-0.5	65	72
NFATC2	-0.019	0.12	-10000	0	-0.5	20	20
HRAS	-0.065	0.25	0.28	7	-0.55	65	72
GAB2	0.033	0.009	-10000	0	-10000	0	0
PLA2G1B	0.011	0.13	-10000	0	-0.9	7	7
Fc epsilon R1	0.034	0.081	-10000	0	-0.25	24	24
Antigen/IgE/Fc epsilon R1	0.033	0.074	-10000	0	-0.22	24	24
mol:GDP	-0.091	0.27	0.35	1	-0.6	71	72
JUN	0.031	0.011	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
FOS	0.033	0.008	-10000	0	-10000	0	0
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.015	0.14	0.21	1	-0.38	37	38
CHUK	-0.029	0.14	0.26	14	-0.28	57	71
KLRG1	-0.021	0.12	-10000	0	-0.33	39	39
VAV1	-0.047	0.18	0.2	2	-0.44	52	54
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.014	0.12	0.21	1	-0.39	28	29
negative regulation of mast cell degranulation	-0.023	0.18	0.22	8	-0.37	62	70
BTK	-0.1	0.31	-10000	0	-0.67	74	74
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.026	0.15	-10000	0	-0.36	45	45
GAB2/PI3K/SHP2	-0.002	0.051	-10000	0	-0.2	14	14
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.018	0.14	-10000	0	-0.36	41	41
RAF1	0.005	0.14	-10000	0	-0.99	7	7
Fc epsilon R1/FcgammaRIIB/SHIP	0.021	0.15	-10000	0	-0.3	59	59
FCER1G	0.002	0.11	-10000	0	-0.42	23	23
FCER1A	0.026	0.029	-10000	0	-0.43	1	1
Antigen/IgE/Fc epsilon R1/Fyn	0.044	0.073	-10000	0	-0.2	24	24
MAPK3	0.011	0.13	-10000	0	-0.91	7	7
MAPK1	0.009	0.13	-10000	0	-0.91	7	7
NFKB1	0.034	0.006	-10000	0	-10000	0	0
MAPK8	-0.057	0.28	-10000	0	-0.73	46	46
DUSP1	0.032	0.01	-10000	0	-10000	0	0
NF-kappa-B/RelA	-0.008	0.088	0.16	10	-0.18	55	65
actin cytoskeleton reorganization	-0.005	0.16	-10000	0	-0.49	23	23
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.031	0.22	0.36	1	-0.47	61	62
FER	-0.016	0.13	0.2	3	-0.36	34	37
RELA	0.034	0.007	-10000	0	-10000	0	0
ITK	-0.097	0.18	-10000	0	-0.37	106	106
SOS1	0.035	0.003	-10000	0	-10000	0	0
PLCG1	-0.071	0.27	0.3	11	-0.59	66	77
cytokine secretion	-0.012	0.057	-10000	0	-0.14	35	35
SPHK1	-0.02	0.13	0.2	3	-0.37	36	39
PTK2	-0.007	0.17	-10000	0	-0.52	22	22
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.055	0.22	0.26	1	-0.51	62	63
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.039	0.22	0.32	17	-0.48	60	77
MAP2K2	0.004	0.14	-10000	0	-0.93	7	7
MAP2K1	0.005	0.14	-10000	0	-0.93	7	7
MAP2K7	0.035	0.004	-10000	0	-10000	0	0
KLRG1/SHP2	-0.006	0.12	0.23	6	-0.34	32	38
MAP2K4	-0.013	0.23	-10000	0	-0.88	24	24
Fc epsilon R1/FcgammaRIIB	0.042	0.1	-10000	0	-0.27	32	32
mol:Choline	0.024	0.11	0.32	33	-0.2	19	52
SHC/Grb2/SOS1	0.029	0.14	-10000	0	-0.36	32	32
FYN	0.031	0.012	-10000	0	-10000	0	0
DOK1	0.035	0.003	-10000	0	-10000	0	0
PXN	-0.006	0.16	-10000	0	-0.48	22	22
HCLS1	-0.044	0.18	0.2	3	-0.44	53	56
PRKCB	-0.049	0.18	0.29	14	-0.39	63	77
FCGR2B	0.013	0.089	-10000	0	-0.42	15	15
IGHE	0	0.008	-10000	0	-10000	0	0
KLRG1/SHIP	-0.023	0.18	0.23	6	-0.38	62	68
LCP2	0.015	0.09	-10000	0	-0.42	15	15
PLA2G4A	-0.018	0.13	0.19	2	-0.38	33	35
RASA1	0.032	0.025	-10000	0	-0.42	1	1
mol:Phosphatidic acid	0.024	0.11	0.32	33	-0.2	19	52
IKK complex	-0.014	0.11	0.24	17	-0.21	53	70
WIPF1	0.029	0.052	-10000	0	-0.42	5	5

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	0.006	0.28	-10000	0	-0.6	41	41
HDAC7	0.036	0.006	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0.039	0.34	-10000	0	-0.66	39	39
SMAD4	0.036	0.005	-10000	0	-10000	0	0
ID2	0.03	0.3	-10000	0	-0.61	39	39
AP1	0.045	0.024	-10000	0	-10000	0	0
ABCG2	0.016	0.32	-10000	0	-0.67	40	40
HIF1A	0.029	0.077	-10000	0	-0.18	4	4
TFF3	-0.014	0.33	-10000	0	-0.6	60	60
GATA2	0.035	0.011	-10000	0	-10000	0	0
AKT1	0.017	0.099	-10000	0	-0.22	19	19
response to hypoxia	-0.004	0.082	-10000	0	-0.16	54	54
MCL1	0.021	0.28	-10000	0	-0.6	38	38
NDRG1	0.031	0.28	-10000	0	-0.62	35	35
SERPINE1	0.018	0.28	-10000	0	-0.6	39	39
FECH	0.03	0.29	-10000	0	-0.64	35	35
FURIN	0.028	0.29	-10000	0	-0.61	38	38
NCOA2	0.033	0.011	-10000	0	-10000	0	0
EP300	0.014	0.14	-10000	0	-0.31	40	40
HMOX1	0.029	0.29	-10000	0	-0.62	38	38
BHLHE40	0.032	0.3	-10000	0	-0.62	38	38
BHLHE41	0.025	0.3	-10000	0	-0.62	41	41
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.11	0.11	-10000	0	-10000	0	0
ENG	0.055	0.088	0.33	3	-10000	0	3
JUN	0.032	0.013	-10000	0	-10000	0	0
RORA	0.029	0.29	-10000	0	-0.61	39	39
ABCB1	-0.042	0.32	-10000	0	-1	30	30
TFRC	0.032	0.29	-10000	0	-0.62	37	37
CXCR4	0.016	0.32	-10000	0	-0.68	41	41
TF	-0.029	0.32	-10000	0	-0.64	49	49
CITED2	0.028	0.29	-10000	0	-0.62	38	38
HIF1A/ARNT	0.061	0.37	-10000	0	-0.76	29	29
LDHA	0.041	0.12	-10000	0	-0.83	4	4
ETS1	0.027	0.29	-10000	0	-0.63	35	35
PGK1	0.031	0.3	-10000	0	-0.61	39	39
NOS2	0.02	0.29	-10000	0	-0.62	37	37
ITGB2	0.004	0.33	-10000	0	-0.69	44	44
ALDOA	0.03	0.3	-10000	0	-0.61	40	40
Cbp/p300/CITED2	0.006	0.36	-10000	0	-0.74	43	43
FOS	0.034	0.011	-10000	0	-10000	0	0
HK2	0.032	0.3	-10000	0	-0.62	38	38
SP1	0.03	0.042	-10000	0	-0.13	12	12
GCK	-0.082	0.46	-10000	0	-1.3	43	43
HK1	0.027	0.29	-10000	0	-0.64	34	34
NPM1	0.029	0.29	-10000	0	-0.62	38	38
EGLN1	0.024	0.28	-10000	0	-0.59	39	39
CREB1	0.042	0.009	-10000	0	-10000	0	0
PGM1	0.027	0.29	-10000	0	-0.62	38	38
SMAD3	0.036	0.005	-10000	0	-10000	0	0
EDN1	0.022	0.21	-10000	0	-0.67	14	14
IGFBP1	0.014	0.28	-10000	0	-0.61	38	38
VEGFA	0.022	0.27	-10000	0	-0.58	34	34
HIF1A/JAB1	0.048	0.058	-10000	0	-0.13	2	2
CP	-0.045	0.35	-10000	0	-0.66	57	57
CXCL12	0.02	0.3	-10000	0	-0.64	39	39
COPS5	0.033	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4	0.052	0.01	-10000	0	-10000	0	0
BNIP3	0.025	0.29	-10000	0	-0.64	35	35
EGLN3	0.028	0.3	-10000	0	-0.62	38	38
CA9	-0.004	0.28	-10000	0	-0.64	35	35
TERT	0.023	0.29	-10000	0	-0.63	34	34
ENO1	0.026	0.29	-10000	0	-0.61	39	39
PFKL	0.028	0.29	-10000	0	-0.63	36	36
NCOA1	0.035	0.005	-10000	0	-10000	0	0
ADM	-0.004	0.28	-10000	0	-0.62	37	37
ARNT	0.032	0.068	-10000	0	-0.14	3	3
HNF4A	0.009	0.045	-10000	0	-0.12	37	37
ADFP	0.006	0.28	-10000	0	-0.6	41	41
SLC2A1	0.03	0.28	-10000	0	-0.57	39	39
LEP	-0.003	0.27	-10000	0	-0.61	37	37
HIF1A/ARNT/Cbp/p300	0.03	0.34	-10000	0	-0.68	40	40
EPO	0.051	0.2	-10000	0	-0.5	9	9
CREBBP	0.013	0.14	-10000	0	-0.3	44	44
HIF1A/ARNT/Cbp/p300/HDAC7	0.047	0.34	-10000	0	-0.67	38	38
PFKFB3	0.024	0.29	-10000	0	-0.62	38	38
NT5E	0.006	0.28	-10000	0	-0.62	38	38

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.017	0.11	-10000	0	-0.23	56	56
NF kappa B1 p50/RelA/I kappa B alpha	0.012	0.092	0.24	1	-0.28	11	12
AP1	0.006	0.089	-10000	0	-0.2	53	53
mol:PIP3	-0.016	0.074	-10000	0	-0.19	50	50
AKT1	0.013	0.089	0.25	6	-0.28	8	14
PTK2B	-0.028	0.11	0.18	1	-0.23	60	61
RHOA	0.014	0.065	0.2	6	-0.29	7	13
PIK3CB	0.034	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.002	0.064	0.22	6	-0.27	9	15
MAGI3	0.034	0.007	-10000	0	-10000	0	0
RELA	0.034	0.007	-10000	0	-10000	0	0
apoptosis	-0.019	0.09	-10000	0	-0.23	54	54
HRAS/GDP	0.025	0.004	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.026	0.097	0.2	3	-0.28	25	28
NF kappa B1 p50/RelA	-0.008	0.097	-10000	0	-0.27	25	25
endothelial cell migration	-0.018	0.097	-10000	0	-0.25	51	51
ADCY4	-0.036	0.13	-10000	0	-0.32	59	59
ADCY5	-0.072	0.16	-10000	0	-0.36	74	74
ADCY6	-0.035	0.13	-10000	0	-0.31	60	60
ADCY7	-0.035	0.13	-10000	0	-0.31	59	59
ADCY1	-0.062	0.15	-10000	0	-0.35	63	63
ADCY2	-0.043	0.12	-10000	0	-0.31	62	62
ADCY3	-0.035	0.13	-10000	0	-0.31	60	60
ADCY8	-0.034	0.12	-10000	0	-0.3	56	56
ADCY9	-0.036	0.13	-10000	0	-0.31	61	61
GSK3B	-0.026	0.1	0.19	4	-0.27	33	37
arachidonic acid secretion	-0.037	0.13	-10000	0	-0.3	65	65
GNG2	0.027	0.057	-10000	0	-0.42	6	6
TRIP6	0.024	0.02	-10000	0	-0.15	3	3
GNAO1	-0.025	0.09	-10000	0	-0.24	52	52
HRAS	0.034	0.006	-10000	0	-10000	0	0
NFKBIA	-0.015	0.085	0.23	1	-0.3	13	14
GAB1	0.035	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.017	0.25	-10000	0	-0.88	29	29
JUN	0.031	0.011	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.045	0.029	-10000	0	-0.24	3	3
TIAM1	-0.042	0.3	-10000	0	-1.1	29	29
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
mol:IP3	-0.002	0.059	0.2	4	-0.27	9	13
PLCB3	0.023	0.032	0.19	6	-0.22	3	9
FOS	0.033	0.008	-10000	0	-10000	0	0
positive regulation of mitosis	-0.037	0.13	-10000	0	-0.3	65	65
LPA/LPA1-2-3	0.009	0.1	-10000	0	-0.22	54	54
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.034	0.007	-10000	0	-10000	0	0
stress fiber formation	-0.016	0.11	0.2	1	-0.31	26	27
GNAZ	-0.019	0.091	-10000	0	-0.24	51	51
EGFR/PI3K-beta/Gab1	-0.006	0.082	-10000	0	-0.2	50	50
positive regulation of dendritic cell cytokine production	0.008	0.1	-10000	0	-0.22	54	54
LPA/LPA2/MAGI-3	0.044	0.03	-10000	0	-0.2	4	4
ARHGEF1	0.014	0.1	0.21	40	-0.2	47	87
GNAI2	-0.018	0.093	-10000	0	-0.24	53	53
GNAI3	-0.016	0.09	-10000	0	-0.24	50	50
GNAI1	-0.019	0.091	-10000	0	-0.24	51	51
LPA/LPA3	0.019	0.016	-10000	0	-0.11	2	2
LPA/LPA2	0.024	0.03	-10000	0	-0.22	5	5
LPA/LPA1	-0.02	0.11	-10000	0	-0.29	55	55
HB-EGF/EGFR	-0.01	0.098	-10000	0	-0.25	50	50
HBEGF	-0.024	0.1	-10000	0	-0.3	47	47
mol:DAG	-0.002	0.059	0.2	4	-0.27	9	13
cAMP biosynthetic process	-0.04	0.13	0.21	5	-0.3	65	70
NFKB1	0.034	0.006	-10000	0	-10000	0	0
SRC	0.033	0.009	-10000	0	-10000	0	0
GNB1	0.034	0.007	-10000	0	-10000	0	0
LYN	-0.018	0.12	0.24	2	-0.38	22	24
GNAQ	0.016	0.027	-10000	0	-0.25	3	3
LPAR2	0.031	0.041	-10000	0	-0.42	3	3
LPAR3	0.025	0.015	-10000	0	-10000	0	0
LPAR1	-0.031	0.16	-10000	0	-0.4	55	55
IL8	-0.031	0.13	0.33	1	-0.37	26	27
PTK2	-0.005	0.075	0.19	6	-0.21	40	46
Rac1/GDP	0.023	0.009	-10000	0	-10000	0	0
CASP3	-0.019	0.09	-10000	0	-0.23	54	54
EGFR	0.027	0.035	-10000	0	-0.42	2	2
PLCG1	0	0.058	0.16	4	-0.29	7	11
PLD2	-0.012	0.085	0.19	6	-0.21	53	59
G12/G13	0.019	0.097	-10000	0	-0.22	48	48
PI3K-beta	-0.005	0.079	-10000	0	-0.3	10	10
cell migration	0.004	0.09	0.2	1	-0.26	28	29
SLC9A3R2	0.035	0.004	-10000	0	-10000	0	0
PXN	-0.016	0.11	0.2	1	-0.32	26	27
HRAS/GTP	-0.039	0.13	-10000	0	-0.31	63	63
RAC1	0.031	0.012	-10000	0	-10000	0	0
MMP9	-0.036	0.16	-10000	0	-0.42	55	55
PRKCE	0.035	0.004	-10000	0	-10000	0	0
PRKCD	-0.004	0.064	0.2	7	-0.29	6	13
Gi(beta/gamma)	-0.027	0.13	-10000	0	-0.3	60	60
mol:LPA	0.002	0.012	-10000	0	-0.16	2	2
TRIP6/p130 Cas/FAK1/Paxillin	0.017	0.11	-10000	0	-0.24	32	32
MAPKKK cascade	-0.037	0.13	-10000	0	-0.3	65	65
contractile ring contraction involved in cytokinesis	0.015	0.065	0.2	6	-0.28	7	13
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.021	0.094	-10000	0	-0.24	56	56
GNA15	0.01	0.055	-10000	0	-0.26	13	13
GNA12	0.031	0.011	-10000	0	-10000	0	0
GNA13	0.034	0.006	-10000	0	-10000	0	0
MAPT	-0.027	0.1	0.2	3	-0.28	26	29
GNA11	0.017	0.025	-10000	0	-0.23	3	3
Rac1/GTP	-0.02	0.27	-10000	0	-0.93	29	29
MMP2	-0.019	0.097	-10000	0	-0.25	51	51

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	0.11	-10000	0	-0.48	15	15
Syndecan-4/Syndesmos	-0.038	0.21	-10000	0	-0.5	56	56
positive regulation of JNK cascade	-0.039	0.22	-10000	0	-0.49	58	58
Syndecan-4/ADAM12	-0.042	0.21	-10000	0	-0.49	56	56
CCL5	-0.095	0.2	-10000	0	-0.42	105	105
Rac1/GDP	0.023	0.009	-10000	0	-10000	0	0
DNM2	0.035	0.003	-10000	0	-10000	0	0
ITGA5	0.034	0.006	-10000	0	-10000	0	0
SDCBP	0.032	0.01	-10000	0	-10000	0	0
PLG	0.009	0.019	-10000	0	-10000	0	0
ADAM12	0.029	0.013	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.035	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.027	0.016	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.078	0.19	-10000	0	-0.5	55	55
Syndecan-4/CXCL12/CXCR4	-0.042	0.24	-10000	0	-0.52	58	58
Syndecan-4/Laminin alpha3	-0.044	0.22	-10000	0	-0.5	55	55
MDK	0.029	0.041	-10000	0	-0.42	3	3
Syndecan-4/FZD7	-0.037	0.22	-10000	0	-0.5	56	56
Syndecan-4/Midkine	-0.041	0.21	-10000	0	-0.5	56	56
FZD7	0.034	0.024	-10000	0	-0.42	1	1
Syndecan-4/FGFR1/FGF	-0.028	0.2	-10000	0	-0.47	54	54
THBS1	0.03	0.012	-10000	0	-10000	0	0
integrin-mediated signaling pathway	-0.039	0.21	-10000	0	-0.48	58	58
positive regulation of MAPKKK cascade	-0.039	0.22	-10000	0	-0.49	58	58
Syndecan-4/TACI	-0.13	0.23	-10000	0	-0.58	58	58
CXCR4	0.001	0.12	-10000	0	-0.42	28	28
cell adhesion	0.014	0.054	0.2	7	-0.25	10	17
Syndecan-4/Dynamin	-0.037	0.21	-10000	0	-0.49	56	56
Syndecan-4/TSP1	-0.043	0.21	-10000	0	-0.49	56	56
Syndecan-4/GIPC	-0.037	0.21	-10000	0	-0.49	56	56
Syndecan-4/RANTES	-0.091	0.25	-10000	0	-0.6	55	55
ITGB1	0.032	0.011	-10000	0	-10000	0	0
LAMA1	0.006	0.013	-10000	0	-10000	0	0
LAMA3	0.02	0.08	-10000	0	-0.42	12	12
RAC1	0.031	0.012	-10000	0	-10000	0	0
PRKCA	0.023	0.15	0.84	11	-0.39	1	12
Syndecan-4/alpha-Actinin	-0.038	0.21	-10000	0	-0.5	56	56
TFPI	0.033	0.024	-10000	0	-0.42	1	1
F2	0.013	0.027	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.046	0.018	-10000	0	-10000	0	0
positive regulation of cell adhesion	-0.068	0.2	-10000	0	-0.49	55	55
ACTN1	0.033	0.024	-10000	0	-0.42	1	1
TNC	0.02	0.074	-10000	0	-0.42	10	10
Syndecan-4/CXCL12	-0.044	0.22	-10000	0	-0.5	56	56
FGF6	0.017	0.003	-10000	0	-10000	0	0
RHOA	0.035	0.005	-10000	0	-10000	0	0
CXCL12	0.018	0.077	-10000	0	-0.42	11	11
TNFRSF13B	-0.17	0.22	-10000	0	-0.42	164	164
FGF2	0.03	0.035	-10000	0	-0.42	2	2
FGFR1	0.031	0.012	-10000	0	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.063	0.2	-10000	0	-0.49	56	56
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.016	0.076	-10000	0	-0.4	11	11
cell migration	-0.013	0.012	-10000	0	-10000	0	0
PRKCD	0.029	0.022	-10000	0	-10000	0	0
vasculogenesis	-0.041	0.2	-10000	0	-0.48	56	56
SDC4	-0.057	0.21	-10000	0	-0.52	55	55
Syndecan-4/Tenascin C	-0.041	0.22	-10000	0	-0.5	58	58
Syndecan-4/PI-4-5-P2/PKC alpha	-0.022	0.013	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.037	0.21	-10000	0	-0.5	52	52
MMP9	-0.035	0.16	-10000	0	-0.42	55	55
Rac1/GTP	0.014	0.055	0.2	7	-0.26	10	17
cytoskeleton organization	-0.035	0.2	-10000	0	-0.48	56	56
GIPC1	0.035	0.003	-10000	0	-10000	0	0
Syndecan-4/TFPI	-0.038	0.22	-10000	0	-0.5	56	56

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.008	0.1	-10000	0	-0.21	64	64
RGS9BP	0.034	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.017	0.004	-10000	0	-10000	0	0
mol:Na +	0.023	0.012	-10000	0	-10000	0	0
mol:ADP	-0.015	0.006	-10000	0	-10000	0	0
GNAT2	0.032	0.008	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.056	0.15	-10000	0	-0.25	139	139
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.035	0.013	-10000	0	-10000	0	0
GRK7	0.027	0.01	-10000	0	-10000	0	0
CNGB3	0.02	0.011	-10000	0	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.016	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.009	0.035	0.17	13	-10000	0	13
Cone PDE6	-0.038	0.14	-10000	0	-0.22	136	136
Cone Metarhodopsin II	0.026	0.01	-10000	0	-10000	0	0
Na + (4 Units)	0.027	0.018	-10000	0	-10000	0	0
GNAT2/GDP	-0.035	0.14	-10000	0	-0.21	134	134
GNB5	0.033	0.024	-10000	0	-0.42	1	1
mol:GMP (4 units)	0	0.037	0.17	14	-10000	0	14
Cone Transducin	0.009	0.11	-10000	0	-0.22	64	64
SLC24A2	0.015	0.006	-10000	0	-10000	0	0
GNB3/GNGT2	-0.015	0.13	-10000	0	-0.3	68	68
GNB3	0.03	0.041	-10000	0	-0.42	3	3
GNAT2/GTP	0.024	0.006	-10000	0	-10000	0	0
CNGA3	0.017	0.001	-10000	0	-10000	0	0
ARR3	0.021	0.007	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.024	0.012	-10000	0	-10000	0	0
mol:Pi	-0.056	0.15	-10000	0	-0.25	139	139
Cone CNG Channel	0.043	0.026	-10000	0	-10000	0	0
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.015	0.006	-10000	0	-10000	0	0
RGS9	-0.14	0.22	-10000	0	-0.42	145	145
PDE6C	0.016	0.005	-10000	0	-10000	0	0
GNGT2	-0.05	0.18	-10000	0	-0.42	68	68
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.023	0.01	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.15	0.27	-10000	0	-0.77	28	28
PCK1	-0.071	0.14	-10000	0	-0.6	2	2
HNF4A	-0.15	0.27	0.56	1	-0.81	25	26
KCNJ11	-0.2	0.34	-10000	0	-0.8	57	57
AKT1	-0.097	0.17	-10000	0	-0.41	32	32
response to starvation	0.001	0.005	-10000	0	-10000	0	0
DLK1	-0.19	0.32	-10000	0	-0.78	54	54
NKX2-1	-0.077	0.15	0.31	4	-0.32	59	63
ACADM	-0.16	0.27	-10000	0	-0.78	27	27
TAT	-0.081	0.15	-10000	0	-0.59	6	6
CEBPB	0.031	0.016	-10000	0	-10000	0	0
CEBPA	-0.005	0.13	-10000	0	-0.42	31	31
TTR	-0.081	0.27	-10000	0	-0.93	25	25
PKLR	-0.42	0.47	-10000	0	-0.84	195	195
APOA1	-0.18	0.32	-10000	0	-0.91	31	31
CPT1C	-0.17	0.3	-10000	0	-0.87	31	31
ALAS1	-0.067	0.16	-10000	0	-0.66	2	2
TFRC	-0.098	0.2	-10000	0	-0.7	7	7
FOXF1	0.007	0.1	-10000	0	-0.42	21	21
NF1	0.04	0.008	-10000	0	-10000	0	0
HNF1A (dimer)	0.034	0.006	-10000	0	-10000	0	0
CPT1A	-0.15	0.28	-10000	0	-0.7	39	39
HMGCS1	-0.15	0.27	-10000	0	-0.79	26	26
NR3C1	0.033	0.009	-10000	0	-10000	0	0
CPT1B	-0.15	0.28	-10000	0	-0.68	47	47
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.035	0.005	-10000	0	-10000	0	0
GCK	-0.2	0.36	-10000	0	-0.85	64	64
CREB1	0.031	0.017	-10000	0	-10000	0	0
IGFBP1	-0.062	0.14	-10000	0	-0.51	2	2
PDX1	-0.074	0.16	-10000	0	-0.75	2	2
UCP2	-0.2	0.35	-10000	0	-0.81	65	65
ALDOB	-0.17	0.29	-10000	0	-0.81	29	29
AFP	0.002	0.053	-10000	0	-10000	0	0
BDH1	-0.16	0.28	-10000	0	-0.78	33	33
HADH	-0.17	0.3	-10000	0	-0.79	34	34
F2	-0.18	0.32	-10000	0	-0.87	35	35
HNF1A	0.034	0.006	-10000	0	-10000	0	0
G6PC	0.001	0.085	-10000	0	-10000	0	0
SLC2A2	-0.096	0.19	-10000	0	-0.7	5	5
INS	-0.022	0.005	-10000	0	-10000	0	0
FOXA1	0.031	0.021	-10000	0	-10000	0	0
FOXA3	0.016	0.094	-10000	0	-0.41	16	16
FOXA2	-0.19	0.34	-10000	0	-0.72	77	77
ABCC8	-0.18	0.29	-10000	0	-0.63	77	77
ALB	0.005	0.053	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.049	0.021	-10000	0	-0.3	1	1
FBXW11	0.033	0.008	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.038	0.011	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.049	0.16	0.21	1	-0.36	57	58
NFKBIA	-0.068	0.16	-10000	0	-0.29	112	112
MAPK14	0.031	0.011	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.036	0.013	-10000	0	-10000	0	0
ARRB2	0.017	0.008	-10000	0	-10000	0	0
REL	0.035	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.036	0.024	-10000	0	-0.25	2	2
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.036	0.013	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	0.027	0.007	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
NFKB1	0.018	0.005	-10000	0	-10000	0	0
RELA	0.034	0.007	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	-0.067	0.14	-10000	0	-0.26	113	113
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.047	0.16	0.2	1	-0.36	55	56
SRC	0.033	0.009	-10000	0	-10000	0	0
PI3K	0.049	0.013	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.067	0.14	-10000	0	-0.26	113	113
IKBKB	0.034	0.007	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.033	0.008	-10000	0	-10000	0	0
SYK	-0.012	0.13	-10000	0	-0.42	36	36
I kappa B alpha/PIK3R1	-0.056	0.16	0.2	1	-0.28	112	113
cell death	-0.045	0.15	0.2	1	-0.34	56	57
NF kappa B1 p105/c-Rel	0.038	0.011	-10000	0	-10000	0	0
LCK	-0.14	0.22	-10000	0	-0.42	138	138
BCL3	0.032	0.033	-10000	0	-0.42	2	2

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.031	0.047	-10000	0	-0.26	2	2
fibroblast growth factor receptor signaling pathway	0.031	0.046	-10000	0	-0.26	2	2
LAMA1	0.006	0.013	-10000	0	-10000	0	0
PRNP	0.032	0.025	-10000	0	-0.42	1	1
GPC1/SLIT2	0.021	0.045	-10000	0	-0.29	4	4
SMAD2	0.01	0.019	0.19	1	-10000	0	1
GPC1/PrPc/Cu2+	0.025	0.031	-10000	0	-0.25	1	1
GPC1/Laminin alpha1	-0.007	0.022	-10000	0	-10000	0	0
TDGF1	-0.052	0.17	-10000	0	-0.42	63	63
CRIPTO/GPC1	-0.033	0.12	-10000	0	-0.3	63	63
APP/GPC1	0.025	0.042	-10000	0	-0.3	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.035	0.096	-10000	0	-0.25	60	60
FLT1	0.034	0.007	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.038	0.04	-10000	0	-10000	0	0
SERPINC1	0.027	0.013	-10000	0	-10000	0	0
FYN	-0.035	0.094	-10000	0	-0.25	58	58
FGR	-0.059	0.12	-10000	0	-0.26	89	89
positive regulation of MAPKKK cascade	-0.22	0.24	-10000	0	-0.43	160	160
SLIT2	0.026	0.048	-10000	0	-0.42	4	4
GPC1/NRG	0.023	0.042	-10000	0	-0.3	3	3
NRG1	0.026	0.042	-10000	0	-0.42	3	3
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.034	0.04	-10000	0	-10000	0	0
LYN	-0.044	0.11	-10000	0	-0.26	70	70
mol:Spermine	0.007	0.005	-10000	0	-10000	0	0
cell growth	0.031	0.046	-10000	0	-0.26	2	2
BMP signaling pathway	-0.022	0.017	-10000	0	-10000	0	0
SRC	-0.035	0.096	-10000	0	-0.25	60	60
TGFBR1	0.033	0.009	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.005	0.097	-10000	0	-0.42	18	18
GPC1	0.022	0.017	-10000	0	-10000	0	0
TGFBR1 (dimer)	0.033	0.009	-10000	0	-10000	0	0
VEGFA	0.03	0.013	-10000	0	-10000	0	0
BLK	-0.18	0.16	-10000	0	-0.29	228	228
HCK	-0.053	0.11	-10000	0	-0.26	81	81
FGF2	0.03	0.035	-10000	0	-0.42	2	2
FGFR1	0.031	0.012	-10000	0	-10000	0	0
VEGFR1 homodimer	0.034	0.007	-10000	0	-10000	0	0
TGFBR2	0.035	0.005	-10000	0	-10000	0	0
cell death	0.025	0.042	-10000	0	-0.3	3	3
ATIII/GPC1	0.024	0.03	-10000	0	-10000	0	0
PLA2G2A/GPC1	0.004	0.075	-10000	0	-0.29	18	18
LCK	-0.13	0.16	-10000	0	-0.28	169	169
neuron differentiation	0.023	0.042	-10000	0	-0.3	3	3
PrPc/Cu2+	0.024	0.018	-10000	0	-0.29	1	1
APP	0.031	0.041	-10000	0	-0.42	3	3
TGFBR2 (dimer)	0.035	0.005	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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
IKK alpha homodimer	0.013	0.1	0.2	1	-0.23	49	50
NF kappa B1 p50/RelA/I kappa B alpha	0.03	0.1	0.34	3	-0.34	7	10
alphaV/beta3 Integrin/Osteopontin/Src	0.02	0.11	-10000	0	-0.29	38	38
AP1	0.033	0.11	-10000	0	-0.34	8	8
ILK	-0.002	0.098	-10000	0	-0.24	49	49
bone resorption	-0.009	0.12	-10000	0	-0.35	14	14
PTK2B	0.028	0.048	-10000	0	-0.42	4	4
PYK2/p130Cas	0.017	0.14	-10000	0	-0.23	79	79
ITGAV	0.038	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.049	0.021	-10000	0	-0.3	1	1
alphaV/beta3 Integrin/Osteopontin	0.028	0.12	-10000	0	-0.27	50	50
MAP3K1	-0.004	0.099	0.2	4	-0.24	50	54
JUN	0.032	0.011	-10000	0	-10000	0	0
MAPK3	-0.01	0.091	0.2	2	-0.23	48	50
MAPK1	-0.011	0.088	0.2	2	-0.22	49	51
Rac1/GDP	0.023	0.009	-10000	0	-10000	0	0
NFKB1	0.034	0.006	-10000	0	-10000	0	0
MAPK8	-0.013	0.089	0.2	4	-0.23	43	47
ITGB3	0.012	0.098	-10000	0	-0.42	18	18
NFKBIA	-0.011	0.088	0.2	2	-0.33	11	13
FOS	0.034	0.008	-10000	0	-10000	0	0
CD44	0.033	0.024	-10000	0	-0.42	1	1
CHUK	0.032	0.01	-10000	0	-10000	0	0
PLAU	0.002	0.11	0.35	1	-0.62	3	4
NF kappa B1 p50/RelA	0.044	0.1	-10000	0	-0.33	6	6
BCAR1	0.034	0.007	-10000	0	-10000	0	0
RELA	0.034	0.007	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.034	0.077	-10000	0	-0.29	18	18
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.028	0.12	0.2	4	-0.25	78	82
VAV3	-0.036	0.11	0.19	3	-0.24	76	79
MAP3K14	-0.002	0.099	0.2	2	-0.24	49	51
ROCK2	0.035	0.004	-10000	0	-10000	0	0
SPP1	-0.009	0.14	-10000	0	-0.41	38	38
RAC1	0.031	0.012	-10000	0	-10000	0	0
Rac1/GTP	-0.018	0.1	0.19	1	-0.22	65	66
MMP2	0.001	0.085	0.32	2	-0.32	9	11

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.009	0.13	-10000	0	-0.42	35	35
positive regulation of NF-kappaB transcription factor activity	0.011	0.1	-10000	0	-0.3	35	35
MAP2K4	0.003	0.1	-10000	0	-0.34	20	20
IKBKB	0.034	0.007	-10000	0	-10000	0	0
TNFRSF10B	0.026	0.058	-10000	0	-0.42	6	6
TNFRSF10A	-0.017	0.14	-10000	0	-0.42	41	41
SMPD1	-0.002	0.066	-10000	0	-0.19	38	38
IKBKG	0.035	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.029	0.026	-10000	0	-0.42	1	1
TRAIL/TRAILR2	0.011	0.11	-10000	0	-0.31	38	38
TRAIL/TRAILR3	-0.001	0.13	-10000	0	-0.31	50	50
TRAIL/TRAILR1	-0.017	0.15	-10000	0	-0.35	60	60
TRAIL/TRAILR4	0.011	0.1	-10000	0	-0.3	35	35
TRAIL/TRAILR1/DAP3/GTP	0.01	0.12	-10000	0	-0.27	51	51
IKK complex	0.014	0.088	-10000	0	-0.34	9	9
RIPK1	0.031	0.012	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.024	0.008	-10000	0	-10000	0	0
MAPK3	-0.011	0.092	-10000	0	-0.3	35	35
MAP3K1	-0.008	0.12	-10000	0	-0.37	25	25
TRAILR4 (trimer)	0.029	0.026	-10000	0	-0.42	1	1
TRADD	0.034	0.007	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.017	0.14	-10000	0	-0.42	41	41
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.015	0.12	-10000	0	-0.29	52	52
CFLAR	0.035	0.003	-10000	0	-10000	0	0
MAPK1	-0.01	0.088	-10000	0	-0.3	32	32
TRAIL/TRAILR1/FADD/TRADD/RIP	0.031	0.13	-10000	0	-0.25	52	52
mol:ceramide	-0.002	0.066	-10000	0	-0.19	38	38
FADD	0.033	0.008	-10000	0	-10000	0	0
MAPK8	0.002	0.1	-10000	0	-0.33	20	20
TRAF2	0.033	0.009	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.008	0.1	-10000	0	-0.42	20	20
CHUK	0.032	0.01	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.006	0.14	-10000	0	-0.3	57	57
DAP3	0.032	0.011	-10000	0	-10000	0	0
CASP10	-0.031	0.14	0.21	1	-0.36	39	40
JNK cascade	0.011	0.1	-10000	0	-0.3	35	35
TRAIL (trimer)	-0.009	0.13	-10000	0	-0.42	35	35
TNFRSF10C	0.008	0.1	-10000	0	-0.42	20	20
TRAIL/TRAILR1/DAP3/GTP/FADD	0.023	0.12	-10000	0	-0.26	48	48
TRAIL/TRAILR2/FADD	0.031	0.099	-10000	0	-0.26	35	35
cell death	-0.002	0.066	-10000	0	-0.19	38	38
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.007	0.083	-10000	0	-0.24	32	32
TRAILR2 (trimer)	0.026	0.058	-10000	0	-0.42	6	6
CASP8	0.013	0.085	-10000	0	-0.73	3	3
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.052	0.095	-10000	0	-0.22	32	32

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.04	0.018	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.031	0.012	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.027	0.058	-10000	0	-0.42	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.033	0.009	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.019	0.011	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.034	0.008	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.034	0.007	-10000	0	-10000	0	0
FYN	0.031	0.012	-10000	0	-10000	0	0
MAP3K12	0.035	0.005	-10000	0	-10000	0	0
FGR	-0.01	0.13	-10000	0	-0.42	36	36
p38 alpha/TAB1	-0.12	0.17	-10000	0	-0.33	100	100
PRKG1	0.018	0.018	-10000	0	-10000	0	0
DUSP8	0.028	0.014	-10000	0	-10000	0	0
PGK/cGMP/p38 alpha	-0.095	0.18	0.2	2	-0.37	75	77
apoptosis	-0.11	0.16	-10000	0	-0.32	100	100
RAL/GTP	0.042	0.016	-10000	0	-10000	0	0
LYN	0.016	0.084	-10000	0	-0.42	13	13
DUSP1	0.032	0.01	-10000	0	-10000	0	0
PAK1	0.033	0.009	-10000	0	-10000	0	0
SRC	0.033	0.009	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.072	0.037	-10000	0	-10000	0	0
TRAF6	0.034	0.006	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.031	0.011	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.041	0.017	-10000	0	-10000	0	0
MAPK11	-0.13	0.21	0.28	4	-0.42	87	91
BLK	-0.23	0.22	-10000	0	-0.42	216	216
HCK	-0.002	0.12	-10000	0	-0.42	28	28
MAP2K3	0.033	0.008	-10000	0	-10000	0	0
DUSP16	0.034	0.006	-10000	0	-10000	0	0
DUSP10	0.027	0.048	-10000	0	-0.42	4	4
TRAF6/MEKK3	0.043	0.011	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	-0.1	0.2	0.23	6	-0.38	92	98
positive regulation of innate immune response	-0.14	0.24	0.31	4	-0.46	89	93
LCK	-0.14	0.22	-10000	0	-0.42	138	138
p38alpha-beta/MKP7	-0.12	0.22	0.31	2	-0.44	88	90
p38alpha-beta/MKP5	-0.12	0.22	0.32	3	-0.45	83	86
PGK/cGMP	0.01	0.017	-10000	0	-10000	0	0
PAK2	0.035	0.005	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.12	0.23	0.32	4	-0.45	85	89
CDC42	0.035	0.005	-10000	0	-10000	0	0
RALB	0.035	0.003	-10000	0	-10000	0	0
RALA	0.031	0.011	-10000	0	-10000	0	0
PAK3	0.027	0.012	-10000	0	-10000	0	0

×

Visual signal transduction: Rods

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
mol:K +	0.035	0.005	-10000	0	-10000	0	0
GNAT1/GTP	0.013	0.002	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.022	0.006	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	-0.009	0.1	-10000	0	-0.25	54	54
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.017	0.003	-10000	0	-10000	0	0
GRK1	0.017	0.004	-10000	0	-10000	0	0
CNG Channel	-0.022	0.14	-10000	0	-0.26	84	84
mol:Na +	0.03	0.051	-10000	0	-0.21	10	10
mol:ADP	0.017	0.004	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.056	0.15	-10000	0	-0.25	139	139
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.041	0.055	-10000	0	-0.21	10	10
CNGB1	0.026	0.01	-10000	0	-10000	0	0
RDH5	0.029	0.047	-10000	0	-0.42	4	4
SAG	0.017	0.003	-10000	0	-10000	0	0
mol:Ca2+	0.012	0.11	0.32	36	-10000	0	36
Na + (4 Units)	0.028	0.047	-10000	0	-0.2	10	10
RGS9	-0.14	0.22	-10000	0	-0.42	145	145
GNB1/GNGT1	0.029	0.025	-10000	0	-10000	0	0
GNAT1/GDP	-0.044	0.14	-10000	0	-0.22	139	139
GUCY2D	0.029	0.011	-10000	0	-10000	0	0
GNGT1	0.018	0.013	-10000	0	-10000	0	0
GUCY2F	0.018	0	-10000	0	-10000	0	0
GNB5	0.033	0.024	-10000	0	-0.42	1	1
mol:GMP (4 units)	-0.04	0.13	-10000	0	-0.28	81	81
mol:11-cis-retinal	0.029	0.047	-10000	0	-0.42	4	4
mol:cGMP	0.031	0.045	-10000	0	-0.22	5	5
GNB1	0.034	0.007	-10000	0	-10000	0	0
Rhodopsin	0.033	0.037	-10000	0	-0.3	4	4
SLC24A1	0.035	0.005	-10000	0	-10000	0	0
CNGA1	0.026	0.053	-10000	0	-0.42	5	5
Metarhodopsin II	0.021	0.006	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.047	0.047	-10000	0	-0.23	5	5
RGS9BP	0.034	0.005	-10000	0	-10000	0	0
Metarhodopsin II/Transducin	0.008	0.009	-10000	0	-10000	0	0
GCAP Family/Ca ++	0.033	0.042	-10000	0	-0.23	5	5
PDE6A/B	-0.008	0.12	-10000	0	-0.29	57	57
mol:Pi	-0.056	0.15	-10000	0	-0.25	139	139
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.032	0.028	-10000	0	-10000	0	0
PDE6B	-0.037	0.16	-10000	0	-0.42	57	57
PDE6A	0.03	0.011	-10000	0	-10000	0	0
PDE6G	-0.033	0.16	-10000	0	-0.42	54	54
RHO	0.017	0.003	-10000	0	-10000	0	0
PDE6	-0.091	0.2	-10000	0	-0.29	169	169
GUCA1A	0.023	0.015	-10000	0	-10000	0	0
GC2/GCAP Family	0.04	0.048	-10000	0	-0.24	5	5
GUCA1C	0.017	0.003	-10000	0	-10000	0	0
GUCA1B	0.025	0.053	-10000	0	-0.42	5	5

×

Aurora C signaling

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
INCENP	0.034	0.006	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.003	0.12	-9999	-0.22	74	74
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.002	0.035	-9999	-0.29	1	1
AURKB	0.032	0.025	-9999	-0.42	1	1
AURKC	-0.056	0.18	-9999	-0.42	73	73

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.012	0.1	-10000	0	-1.2	2	2
VDR	0.032	0.034	-10000	0	-0.42	2	2
FAM120B	0.031	0.012	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.045	0.15	-10000	0	-0.3	62	62
RXRs/LXRs/DNA/Oxysterols	-0.069	0.2	-10000	0	-0.42	76	76
MED1	0.034	0.006	-10000	0	-10000	0	0
mol:9cRA	-0.005	0.024	-10000	0	-0.11	5	5
RARs/THRs/DNA/Src-1	0.028	0.051	-10000	0	-0.21	14	14
RXRs/NUR77	0.003	0.13	-10000	0	-0.24	62	62
RXRs/PPAR	-0.02	0.1	-10000	0	-0.22	67	67
NCOR2	0.034	0.006	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.024	0.024	-10000	0	-0.29	2	2
RARs/VDR/DNA/Vit D3	0.067	0.061	-10000	0	-0.21	15	15
RARA	0.034	0.006	-10000	0	-10000	0	0
NCOA1	0.035	0.005	-10000	0	-10000	0	0
VDR/VDR/DNA	0.032	0.034	-10000	0	-0.42	2	2
RARs/RARs/DNA/9cRA	0.046	0.056	-10000	0	-0.22	13	13
RARG	0.035	0.005	-10000	0	-10000	0	0
RPS6KB1	0.03	0.086	0.54	8	-0.42	2	10
RARs/THRs/DNA/SMRT	0.028	0.051	-10000	0	-0.21	14	14
THRA	0.034	0.006	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.024	0.024	-10000	0	-0.29	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.011	0.13	0.31	1	-0.24	62	63
NR1H4	0.017	0.003	-10000	0	-10000	0	0
RXRs/LXRs/DNA	0.005	0.15	-10000	0	-0.24	60	60
NR1H2	0.022	0.037	-10000	0	-10000	0	0
NR1H3	0.02	0.051	-10000	0	-0.22	6	6
RXRs/VDR/DNA/Vit D3	0.001	0.12	-10000	0	-0.22	63	63
NR4A1	0.033	0.024	-10000	0	-0.42	1	1
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.029	0.096	-10000	0	-0.2	70	70
RXRG	-0.065	0.18	-10000	0	-0.42	73	73
RXR alpha/CCPG	0.036	0.034	-10000	0	-10000	0	0
RXRA	0.022	0.036	-10000	0	-10000	0	0
RXRB	0.019	0.036	-10000	0	-10000	0	0
THRB	0.027	0.035	-10000	0	-0.42	2	2
PPARG	0.03	0.047	-10000	0	-0.42	4	4
PPARD	0.031	0.011	-10000	0	-10000	0	0
TNF	-0.18	0.41	-10000	0	-1	70	70
mol:Oxysterols	-0.004	0.021	-10000	0	-0.092	4	4
cholesterol transport	-0.068	0.2	-10000	0	-0.41	76	76
PPARA	0.032	0.01	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.019	0.084	-10000	0	-0.42	13	13
RXRs/NUR77/BCL2	-0.023	0.098	-10000	0	-0.22	64	64
SREBF1	-0.061	0.18	-10000	0	-0.49	28	28
RXRs/RXRs/DNA/9cRA	-0.011	0.13	0.31	1	-0.24	62	63
ABCA1	-0.062	0.18	-10000	0	-0.52	21	21
RARs/THRs	0.079	0.068	-10000	0	-0.23	14	14
RXRs/FXR	-0.004	0.12	-10000	0	-0.24	62	62
BCL2	0.035	0.005	-10000	0	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.011	0.075	-10000	0	-0.25	26	26
EFNA5	0.025	0.062	-10000	0	-0.42	7	7
FYN	0	0.07	0.19	11	-0.22	26	37
neuron projection morphogenesis	0.011	0.075	-10000	0	-0.25	26	26
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.011	0.075	-10000	0	-0.25	26	26
EPHA5	0.002	0.099	-10000	0	-0.42	19	19

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.012	0.04	-10000	0	-0.3	6	6
MAP4K4	-0.076	0.17	-10000	0	-0.41	63	63
BAG4	0.033	0.008	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.002	0.072	-10000	0	-0.19	41	41
NFKBIA	0.035	0.004	-10000	0	-10000	0	0
BIRC3	-0.1	0.2	-10000	0	-0.42	109	109
BAX	0.003	0.043	-10000	0	-0.34	3	3
RIPK1	0.031	0.012	-10000	0	-10000	0	0
AKT1	-0.003	0.012	-10000	0	-10000	0	0
BAD	-0.02	0.068	0.22	5	-0.19	41	46
SMPD1	-0.016	0.11	0.18	25	-0.21	66	91
RB1	-0.02	0.067	0.19	4	-0.19	40	44
FADD/Caspase 8	-0.065	0.18	0.25	4	-0.43	57	61
MAP2K4	-0.02	0.061	0.17	3	-0.18	32	35
NSMAF	0.032	0.01	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.02	0.062	0.18	4	-0.18	38	42
EGF	0.001	0.11	-10000	0	-0.42	25	25
mol:ceramide	-0.022	0.067	0.14	2	-0.2	42	44
MADD	0.034	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.013	0.033	-10000	0	-0.3	4	4
ASAH1	0.033	0.009	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.02	0.066	0.19	4	-0.18	40	44
cell proliferation	0.014	0.069	-10000	0	-0.21	3	3
BID	-0.05	0.18	-10000	0	-0.58	21	21
MAP3K1	-0.021	0.064	0.19	2	-0.19	39	41
EIF2A	-0.021	0.06	0.17	4	-0.22	3	7
TRADD	0.034	0.007	-10000	0	-10000	0	0
CRADD	0.034	0.006	-10000	0	-10000	0	0
MAPK3	-0.012	0.06	0.17	4	-0.22	2	6
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.014	0.061	0.17	4	-0.21	3	7
Cathepsin D/ceramide	-0.002	0.071	-10000	0	-0.18	42	42
FADD	-0.072	0.17	0.22	2	-0.41	61	63
KSR1	-0.02	0.065	0.19	3	-0.19	40	43
MAPK8	-0.024	0.08	-10000	0	-0.27	13	13
PRKRA	-0.022	0.062	0.15	1	-0.18	40	41
PDGFA	0.023	0.058	-10000	0	-0.42	6	6
TRAF2	0.033	0.009	-10000	0	-10000	0	0
IGF1	0.03	0.041	-10000	0	-0.42	3	3
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.022	0.067	0.14	2	-0.19	42	44
CTSD	0.034	0.007	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.049	0.013	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.016	0.073	-10000	0	-0.22	3	3
PRKCD	0.034	0.006	-10000	0	-10000	0	0
PRKCZ	0.031	0.034	-10000	0	-0.42	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.013	0.033	-10000	0	-0.3	4	4
RelA/NF kappa B1	0.049	0.013	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.016	0.09	-10000	0	-0.42	15	15
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.074	0.18	-10000	0	-0.43	63	63
TNFR1A/BAG4/TNF-alpha	0.002	0.12	-10000	0	-0.25	66	66
mol:Sphingosine-1-phosphate	0.012	0.04	-10000	0	-0.3	6	6
MAP2K1	-0.018	0.062	0.17	7	-0.19	8	15
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.034	0.007	-10000	0	-10000	0	0
CYCS	0.001	0.035	0.19	1	-0.17	2	3
TNFRSF1A	0.034	0.007	-10000	0	-10000	0	0
NFKB1	0.034	0.006	-10000	0	-10000	0	0
TNFR1A/BAG4	0.048	0.015	-10000	0	-10000	0	0
EIF2AK2	-0.022	0.059	-10000	0	-0.18	32	32
TNF-alpha/TNFR1A/FAN	0.003	0.12	-10000	0	-0.25	63	63
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.028	0.13	-10000	0	-0.44	20	20
MAP2K2	-0.019	0.061	0.17	6	-0.19	10	16
SMPD3	-0.034	0.14	0.23	1	-0.29	58	59
TNF	-0.054	0.18	-10000	0	-0.42	69	69
PKC zeta/PAR4	0.033	0.073	-10000	0	-0.3	17	17
mol:PHOSPHOCHOLINE	-0.005	0.071	0.18	25	-0.15	27	52
NF kappa B1/RelA/I kappa B alpha	0.079	0.072	-10000	0	-0.21	17	17
AIFM1	-0.007	0.048	0.18	2	-0.17	3	5
BCL2	0.035	0.005	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.033	0.01	-10000	0	-10000	0	0
Rac1/GDP	0.033	0.016	-10000	0	-10000	0	0
DOCK1	0.032	0.01	-10000	0	-10000	0	0
ITGA4	-0.014	0.14	-10000	0	-0.42	40	40
RAC1	0.031	0.012	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.031	0.16	-10000	0	-0.32	81	81
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.033	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.03	0.099	-10000	0	-0.25	40	40
alpha4/beta7 Integrin/Paxillin	-0.008	0.13	-10000	0	-0.25	80	80
lamellipodium assembly	0.017	0.097	-10000	0	-0.4	15	15
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
PI3K	0.049	0.013	-10000	0	-10000	0	0
ARF6	0.035	0.004	-10000	0	-10000	0	0
TLN1	0.032	0.011	-10000	0	-10000	0	0
PXN	0.019	0.003	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
ARF6/GTP	0.04	0.085	-10000	0	-0.19	39	39
cell adhesion	0.038	0.089	-10000	0	-0.2	40	40
CRKL/CBL	0.044	0.02	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.024	0.088	-10000	0	-0.22	40	40
ITGB1	0.032	0.011	-10000	0	-10000	0	0
ITGB7	-0.026	0.15	-10000	0	-0.42	49	49
ARF6/GDP	0.036	0.012	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.001	0.15	-10000	0	-0.28	73	73
p130Cas/Crk/Dock1	0.059	0.027	-10000	0	-10000	0	0
VCAM1	-0.04	0.17	-10000	0	-0.42	60	60
alpha4/beta1 Integrin/Paxillin/Talin	0.04	0.09	-10000	0	-0.2	40	40
alpha4/beta1 Integrin/Paxillin/GIT1	0.041	0.091	-10000	0	-0.21	40	40
BCAR1	0.034	0.007	-10000	0	-10000	0	0
mol:GDP	-0.039	0.09	0.21	40	-10000	0	40
CBL	0.032	0.011	-10000	0	-10000	0	0
PRKACA	0.035	0.003	-10000	0	-10000	0	0
GIT1	0.034	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.04	0.09	-10000	0	-0.2	40	40
Rac1/GTP	0.016	0.11	-10000	0	-0.45	15	15

×

Arf6 signaling events

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
CENTA1/KIF3B	0.031	0.052	-10000	0	-0.25	11	11
ARNO/beta Arrestin1-2	0.043	0.083	-10000	0	-0.81	3	3
EGFR	0.027	0.035	-10000	0	-0.42	2	2
EPHA2	0.03	0.047	-10000	0	-0.42	4	4
USP6	0.033	0.009	-10000	0	-10000	0	0
IQSEC1	0.035	0.005	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.015	0.089	-10000	0	-0.3	26	26
ARRB2	0.011	0.003	-10000	0	-10000	0	0
mol:GTP	-0.02	0.066	0.23	1	-0.17	35	36
ARRB1	0.033	0.009	-10000	0	-10000	0	0
FBXO8	0.034	0.005	-10000	0	-10000	0	0
TSHR	-0.003	0.12	-10000	0	-0.42	29	29
EGF	0.001	0.11	-10000	0	-0.42	25	25
somatostatin receptor activity	0	0	0.001	19	-0.001	41	60
ARAP2	0.025	0.066	-10000	0	-0.42	8	8
mol:GDP	0.007	0.1	0.19	18	-0.27	26	44
mol:PI-3-4-5-P3	0	0	0.001	14	-0.001	17	31
ITGA2B	0.03	0.012	-10000	0	-10000	0	0
ARF6	0.035	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.073	0.044	-10000	0	-0.23	3	3
ADAP1	0.018	0.077	-10000	0	-0.42	11	11
KIF13B	0.033	0.008	-10000	0	-10000	0	0
HGF/MET	0.019	0.091	-10000	0	-0.3	25	25
PXN	0.034	0.006	-10000	0	-10000	0	0
ARF6/GTP	-0.006	0.12	0.25	19	-0.26	42	61
EGFR/EGFR/EGF/EGF/ARFGEP100	0.031	0.084	-10000	0	-0.25	26	26
ADRB2	0.031	0.034	-10000	0	-0.42	2	2
receptor agonist activity	0	0	0	9	0	40	49
actin filament binding	0	0	0.001	19	0	41	60
SRC	0.033	0.009	-10000	0	-10000	0	0
ITGB3	0.009	0.097	-10000	0	-0.42	18	18
GNAQ	0.033	0.009	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.002	24	-0.001	26	50
ARF6/GDP	-0.066	0.19	0.23	4	-0.35	83	87
ARF6/GDP/GULP/ACAP1	-0.028	0.17	0.23	7	-0.31	65	72
alphaIIb/beta3 Integrin/paxillin/GIT1	0.061	0.071	-10000	0	-0.22	18	18
ACAP1	-0.1	0.21	-10000	0	-0.42	111	111
ACAP2	0.035	0.005	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.015	0.017	-10000	0	-10000	0	0
EFNA1	0.032	0.011	-10000	0	-10000	0	0
HGF	0.024	0.058	-10000	0	-0.42	6	6
CYTH3	0.009	0.003	-10000	0	-10000	0	0
CYTH2	0.017	0.094	-10000	0	-1	3	3
NCK1	0.034	0.006	-10000	0	-10000	0	0
fibronectin binding	0	0	0.001	20	0	40	60
endosomal lumen acidification	0	0	0.001	20	0	32	52
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	0.014	0.095	-10000	0	-0.42	17	17
GNAQ/ARNO	0.036	0.089	-10000	0	-0.93	3	3
mol:Phosphatidic acid	0	0	0	2	-10000	0	2
PIP3-E	0	0	0	15	0	3	18
MET	0.006	0.1	-10000	0	-0.42	20	20
GNA14	-0.036	0.16	-10000	0	-0.42	56	56
GNA15	0.021	0.077	-10000	0	-0.42	11	11
GIT1	0.034	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	20	-0.001	33	53
GNA11	0.035	0.004	-10000	0	-10000	0	0
LHCGR	0.014	0.01	-10000	0	-10000	0	0
AGTR1	0.016	0.007	-10000	0	-10000	0	0
desensitization of G-protein coupled receptor protein signaling pathway	0.015	0.017	-10000	0	-10000	0	0
IPCEF1/ARNO	0.024	0.1	-10000	0	-0.86	3	3
alphaIIb/beta3 Integrin	0.023	0.077	-10000	0	-0.3	18	18

×

EPO 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
BCL2L1	0.031	0.1	0.38	1	-0.41	6	7
CRKL	-0.004	0.092	0.22	6	-0.2	19	25
mol:DAG	0.002	0.092	-10000	0	-0.35	15	15
HRAS	0.016	0.1	0.32	9	-0.32	1	10
MAPK8	0.028	0.083	0.2	35	-0.25	13	48
RAP1A	-0.003	0.096	0.25	5	-0.23	8	13
GAB1	-0.004	0.098	0.24	6	-0.2	20	26
MAPK14	0.021	0.076	0.19	32	-0.25	13	45
EPO	0.016	0.028	-10000	0	-10000	0	0
PLCG1	0.002	0.094	-10000	0	-0.36	15	15
EPOR/TRPC2/IP3 Receptors	0.024	0.029	-10000	0	-10000	0	0
RAPGEF1	0.033	0.009	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.053	0.043	-10000	0	-0.28	3	3
GAB1/SHC/GRB2/SOS1	0.028	0.097	0.29	2	-0.26	2	4
EPO/EPOR (dimer)	0.035	0.035	-10000	0	-10000	0	0
IRS2	-0.002	0.096	0.22	8	-0.2	18	26
STAT1	0.014	0.11	-10000	0	-0.38	16	16
STAT5B	0.009	0.1	-10000	0	-0.35	17	17
cell proliferation	0.008	0.073	0.18	34	-0.23	13	47
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.006	0.13	-10000	0	-0.31	40	40
TEC	-0.009	0.1	0.23	5	-0.28	12	17
SOCS3	0.03	0.041	-10000	0	-0.42	3	3
STAT1 (dimer)	0.014	0.11	-10000	0	-0.37	16	16
JAK2	0.017	0.062	-10000	0	-0.42	6	6
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.027	0.12	0.24	4	-0.18	80	84
EPO/EPOR	0.035	0.035	-10000	0	-10000	0	0
LYN	0.018	0.084	-10000	0	-0.42	13	13
TEC/VAV2	0.003	0.11	0.23	3	-0.27	15	18
elevation of cytosolic calcium ion concentration	0.024	0.029	-10000	0	-10000	0	0
SHC1	0.032	0.011	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.048	0.071	-10000	0	-0.28	13	13
mol:IP3	0.002	0.092	-10000	0	-0.35	15	15
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.004	0.15	0.31	2	-0.32	55	57
SH2B3	0.024	0.028	-10000	0	-10000	0	0
NFKB1	0.031	0.087	0.22	27	-0.25	13	40
EPO/EPOR (dimer)/JAK2/SOCS3	0.016	0.038	-10000	0	-0.25	5	5
PTPN6	-0.01	0.096	0.17	4	-0.18	80	84
TEC/VAV2/GRB2	0.015	0.11	0.3	1	-0.25	13	14
EPOR	0.025	0.029	-10000	0	-10000	0	0
INPP5D	-0.037	0.16	-10000	0	-0.42	58	58
mol:GDP	0.027	0.097	0.29	2	-0.26	2	4
SOS1	0.035	0.003	-10000	0	-10000	0	0
PLCG2	-0.001	0.12	-10000	0	-0.42	28	28
CRKL/CBL/C3G	0.02	0.097	0.3	1	-0.26	4	5
VAV2	-0.001	0.097	0.24	6	-0.22	14	20
CBL	0.002	0.089	0.27	4	-0.23	7	11
SHC/Grb2/SOS1	0.009	0.087	-10000	0	-0.23	4	4
STAT5A	0.008	0.1	-10000	0	-0.34	18	18
GRB2	0.034	0.007	-10000	0	-10000	0	0
STAT5 (dimer)	0.025	0.11	-10000	0	-0.35	14	14
LYN/PLCgamma2	0.014	0.11	-10000	0	-0.32	32	32
PTPN11	0.034	0.006	-10000	0	-10000	0	0
BTK	-0.038	0.15	0.24	6	-0.32	64	70
BCL2	0.035	0.11	0.35	1	-0.38	11	12

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.054	0.26	0.6	2	-0.68	25	27
CRP	-0.052	0.26	0.69	2	-0.68	27	29
cell cycle arrest	-0.079	0.29	0.54	2	-0.7	42	44
TIMP1	-0.028	0.22	0.56	1	-0.61	15	16
IL6ST	0.018	0.07	-10000	0	-0.42	8	8
Rac1/GDP	-0.012	0.15	-10000	0	-0.36	38	38
AP1	0.042	0.14	-10000	0	-0.56	10	10
GAB2	0.033	0.009	-10000	0	-10000	0	0
TNFSF11	-0.19	0.46	0.57	1	-1	83	84
HSP90B1	0.013	0.16	-10000	0	-0.86	10	10
GAB1	0.035	0.005	-10000	0	-10000	0	0
MAPK14	0.024	0.11	0.26	3	-0.54	6	9
AKT1	0.035	0.09	-10000	0	-0.5	7	7
FOXO1	0.037	0.089	-10000	0	-0.47	7	7
MAP2K6	0.015	0.099	0.23	3	-0.33	16	19
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
MAP2K4	-0.03	0.17	0.38	1	-0.42	40	41
MITF	0.006	0.1	-10000	0	-0.28	23	23
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.035	0.003	-10000	0	-10000	0	0
A2M	0.009	0.15	-10000	0	-1.1	6	6
CEBPB	0.034	0.016	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.028	0.11	-10000	0	-0.49	9	9
STAT3	-0.085	0.3	0.61	1	-0.74	42	43
STAT1	0.015	0.097	-10000	0	-0.89	4	4
CEBPD	-0.057	0.26	0.57	1	-0.7	26	27
PIK3CA	0.035	0.007	-10000	0	-10000	0	0
PI3K	0.051	0.014	-10000	0	-10000	0	0
JUN	0.031	0.011	-10000	0	-10000	0	0
PIAS3/MITF	0.027	0.11	0.24	7	-0.3	16	23
MAPK11	0.023	0.1	0.26	2	-0.53	6	8
STAT3 (dimer)/FOXO1	-0.034	0.23	-10000	0	-0.55	29	29
GRB2/SOS1/GAB family	0.054	0.13	-10000	0	-0.37	15	15
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.003	0.12	-10000	0	-0.31	38	38
GRB2	0.034	0.007	-10000	0	-10000	0	0
JAK2	0.023	0.058	-10000	0	-0.42	6	6
LBP	-0.18	0.42	0.58	2	-0.86	91	93
PIK3R1	0.035	0.007	-10000	0	-10000	0	0
JAK1	0.031	0.018	-10000	0	-10000	0	0
MYC	-0.047	0.25	0.57	1	-0.65	27	28
FGG	-0.069	0.26	0.56	1	-0.65	33	34
macrophage differentiation	-0.079	0.29	0.54	2	-0.7	42	44
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.049	0.1	-10000	0	-0.29	20	20
JUNB	-0.062	0.25	0.55	1	-0.64	28	29
FOS	0.033	0.008	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.007	0.097	-10000	0	-0.32	20	20
STAT1/PIAS1	0.019	0.12	-10000	0	-0.32	19	19
GRB2/SOS1/GAB family/SHP2/PI3K	0.037	0.094	-10000	0	-0.5	8	8
STAT3 (dimer)	-0.084	0.3	0.61	1	-0.74	42	43
PRKCD	-0.032	0.22	0.37	13	-0.49	43	56
IL6R	0.025	0.052	-10000	0	-0.44	4	4
SOCS3	0.05	0.15	0.42	1	-1.1	3	4
gp130 (dimer)/JAK1/JAK1/LMO4	0.049	0.068	-10000	0	-0.25	9	9
Rac1/GTP	-0.02	0.16	-10000	0	-0.38	39	39
HCK	-0.002	0.12	-10000	0	-0.42	28	28
MAPKKK cascade	0.035	0.12	0.35	1	-0.56	11	12
bone resorption	-0.17	0.43	0.57	1	-0.92	83	84
IRF1	-0.13	0.39	0.57	1	-1	48	49
mol:GDP	-0.017	0.14	-10000	0	-0.33	46	46
SOS1	0.035	0.003	-10000	0	-10000	0	0
VAV1	-0.018	0.14	-10000	0	-0.34	46	46
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.037	0.11	0.28	1	-0.62	5	6
PTPN11	0.009	0.12	-10000	0	-0.81	7	7
IL6/IL6RA	0.025	0.077	-10000	0	-0.34	13	13
gp130 (dimer)/TYK2/TYK2/LMO4	0.056	0.057	-10000	0	-0.25	9	9
gp130 (dimer)/JAK2/JAK2/LMO4	0.047	0.075	-10000	0	-0.31	12	12
IL6	0.009	0.087	-10000	0	-0.43	13	13
PIAS3	0.031	0.011	-10000	0	-10000	0	0
PTPRE	0.025	0.053	-10000	0	-0.4	5	5
PIAS1	0.035	0.005	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.007	0.073	0.17	1	-0.25	20	21
LMO4	0.027	0.034	-10000	0	-0.42	1	1
STAT3 (dimer)/PIAS3	-0.071	0.28	-10000	0	-0.7	39	39
MCL1	0.056	0.1	-10000	0	-0.6	3	3

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.053	0.075	-10000	0	-0.22	21	21
ER alpha/Gai/GDP/Gbeta gamma	-0.019	0.15	-10000	0	-0.43	30	30
AKT1	-0.055	0.27	-10000	0	-0.69	53	53
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.053	0.27	-10000	0	-0.7	53	53
mol:Ca2+	-0.049	0.16	-10000	0	-0.37	60	60
IGF1R	0.034	0.006	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.037	0.04	-10000	0	-0.25	6	6
SHC1	0.032	0.011	-10000	0	-10000	0	0
apoptosis	0.051	0.26	0.66	53	-10000	0	53
RhoA/GTP	0.025	0.032	-10000	0	-0.19	6	6
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	0.025	0.14	0.25	4	-0.38	22	26
regulation of stress fiber formation	-0.007	0.056	-10000	0	-0.21	7	7
E2/ERA-ERB (dimer)	0.027	0.063	-10000	0	-0.25	17	17
KRAS	0.034	0.006	-10000	0	-10000	0	0
G13/GTP	0.034	0.037	-10000	0	-0.22	6	6
pseudopodium formation	0.007	0.056	0.21	7	-10000	0	7
E2/ER alpha (dimer)/PELP1	0.036	0.038	-10000	0	-0.25	5	5
GRB2	0.034	0.007	-10000	0	-10000	0	0
GNG2	0.027	0.058	-10000	0	-0.42	6	6
GNAO1	0.018	0.029	-10000	0	-0.42	1	1
HRAS	0.034	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.013	0.18	0.27	1	-0.42	49	50
E2/ER beta (dimer)	0.016	0.055	-10000	0	-0.29	11	11
mol:GDP	-0.001	0.082	-10000	0	-0.29	17	17
mol:NADP	-0.013	0.18	0.27	1	-0.42	49	50
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
mol:IP3	-0.054	0.16	-10000	0	-0.39	60	60
IGF-1R heterotetramer	0.034	0.006	-10000	0	-10000	0	0
PLCB1	-0.044	0.16	-10000	0	-0.38	58	58
PLCB2	-0.046	0.16	-10000	0	-0.38	61	61
IGF1	0.03	0.041	-10000	0	-0.42	3	3
mol:L-citrulline	-0.013	0.18	0.27	1	-0.42	49	50
RHOA	0.035	0.005	-10000	0	-10000	0	0
Gai/GDP	-0.005	0.15	-10000	0	-0.61	19	19
JNK cascade	0.016	0.054	-10000	0	-0.29	11	11
BCAR1	0.034	0.007	-10000	0	-10000	0	0
ESR2	0.021	0.077	-10000	0	-0.42	11	11
GNAQ	0.033	0.009	-10000	0	-10000	0	0
ESR1	0.023	0.058	-10000	0	-0.42	6	6
Gq family/GDP/Gbeta gamma	-0.009	0.14	-10000	0	-0.51	18	18
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.041	0.077	-10000	0	-0.52	4	4
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.024	0.13	0.25	3	-0.38	19	22
GNAZ	0.027	0.035	-10000	0	-0.42	2	2
E2/ER alpha (dimer)	0.017	0.041	-10000	0	-0.29	6	6
STRN	0.035	0.003	-10000	0	-10000	0	0
GNAL	0.024	0.053	-10000	0	-0.42	5	5
PELP1	0.033	0.009	-10000	0	-10000	0	0
MAPK11	0.011	0.041	-10000	0	-0.25	9	9
GNAI2	0.035	0.005	-10000	0	-10000	0	0
GNAI3	0.034	0.007	-10000	0	-10000	0	0
GNAI1	0.031	0.012	-10000	0	-10000	0	0
HBEGF	-0.008	0.18	0.34	21	-0.42	38	59
cAMP biosynthetic process	0.017	0.058	-10000	0	-0.21	20	20
SRC	-0.012	0.14	0.24	5	-0.42	27	32
PI3K	0.049	0.013	-10000	0	-10000	0	0
GNB1	0.034	0.007	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.028	0.094	-10000	0	-0.27	17	17
SOS1	0.035	0.003	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.006	0.091	-10000	0	-0.31	19	19
Gs family/GTP	0.024	0.062	-10000	0	-0.21	20	20
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.062	0.02	-10000	0	-10000	0	0
vasodilation	-0.011	0.17	0.26	1	-0.4	49	50
mol:DAG	-0.054	0.16	-10000	0	-0.39	60	60
Gs family/GDP/Gbeta gamma	0.001	0.085	-10000	0	-0.27	17	17
MSN	0.006	0.058	0.22	7	-10000	0	7
Gq family/GTP	-0.036	0.16	-10000	0	-0.38	60	60
mol:PI-3-4-5-P3	-0.05	0.26	-10000	0	-0.67	53	53
NRAS	0.034	0.008	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.011	0.17	0.4	49	-0.26	1	50
GRB2/SOS1	0.05	0.011	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.09	-10000	0	-0.27	17	17
NOS3	-0.015	0.19	0.27	1	-0.44	49	50
GNA11	0.035	0.004	-10000	0	-10000	0	0
MAPKKK cascade	0.001	0.19	0.3	5	-0.46	45	50
E2/ER alpha (dimer)/PELP1/Src	0.023	0.14	0.28	8	-0.4	23	31
ruffle organization	0.007	0.056	0.21	7	-10000	0	7
ROCK2	0.028	0.057	0.23	7	-10000	0	7
GNA14	-0.036	0.16	-10000	0	-0.42	56	56
GNA15	0.021	0.077	-10000	0	-0.42	11	11
GNA13	0.034	0.006	-10000	0	-10000	0	0
MMP9	-0.028	0.17	0.37	9	-0.44	35	44
MMP2	0.001	0.14	0.31	8	-0.39	27	35

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.032	0.01	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.005	0.15	-10000	0	-0.38	44	44
PTP1B/AKT1	0.03	0.077	0.24	2	-0.29	9	11
FYN	0.031	0.012	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.014	0.077	0.25	2	-0.28	12	14
EGFR	0.026	0.037	-10000	0	-0.42	2	2
EGF/EGFR	0.013	0.093	-10000	0	-0.24	29	29
CSF1	0.029	0.047	-10000	0	-0.42	4	4
AKT1	0.035	0.006	-10000	0	-10000	0	0
INSR	0.035	0.004	-10000	0	-10000	0	0
PTP1B/N-cadherin	0.002	0.1	0.29	1	-0.26	30	31
Insulin Receptor/Insulin	0.047	0.077	0.28	1	-0.3	7	8
HCK	-0.002	0.12	-10000	0	-0.42	28	28
CRK	0.033	0.009	-10000	0	-10000	0	0
TYK2	0.012	0.074	0.23	4	-0.28	10	14
EGF	0.002	0.12	-10000	0	-0.42	25	25
YES1	0.034	0.008	-10000	0	-10000	0	0
CAV1	0.028	0.092	0.22	20	-0.28	11	31
TXN	0.033	0.009	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.038	0.081	0.21	1	-0.27	10	11
cell migration	-0.014	0.077	0.28	12	-0.25	2	14
STAT3	0.035	0.006	-10000	0	-10000	0	0
PRLR	0.024	0.016	-10000	0	-10000	0	0
ITGA2B	0.03	0.013	-10000	0	-10000	0	0
CSF1R	0.015	0.09	-10000	0	-0.42	15	15
Prolactin Receptor/Prolactin	0.02	0.028	-10000	0	-10000	0	0
FGR	-0.01	0.13	-10000	0	-0.42	36	36
PTP1B/p130 Cas	0.03	0.076	0.24	2	-0.27	11	13
Crk/p130 Cas	0.043	0.081	0.25	2	-0.26	10	12
DOK1	0.017	0.083	0.23	2	-0.3	12	14
JAK2	-0.019	0.15	0.3	1	-0.39	44	45
Jak2/Leptin Receptor/Leptin	0.023	0.12	-10000	0	-0.34	17	17
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
PTPN1	0.014	0.077	0.26	2	-0.28	12	14
LYN	0.016	0.084	-10000	0	-0.42	13	13
CDH2	-0.017	0.14	-10000	0	-0.42	40	40
SRC	0.039	0.048	-10000	0	-0.67	1	1
ITGB3	0.009	0.098	-10000	0	-0.42	18	18
CAT1/PTP1B	-0.12	0.24	0.26	5	-0.46	91	96
CAPN1	0.034	0.007	-10000	0	-10000	0	0
CSK	0.034	0.006	-10000	0	-10000	0	0
PI3K	0.063	0.075	0.26	1	-0.31	5	6
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	0.024	0.11	-10000	0	-0.33	15	15
negative regulation of transcription	-0.018	0.15	0.3	1	-0.39	44	45
FCGR2A	0.027	0.048	-10000	0	-0.42	4	4
FER	0.034	0.008	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.022	0.077	-10000	0	-0.3	18	18
BLK	-0.23	0.22	-10000	0	-0.42	216	216
Insulin Receptor/Insulin/Shc	0.052	0.021	-10000	0	-10000	0	0
RHOA	0.035	0.005	-10000	0	-10000	0	0
LEPR	0.033	0.024	-10000	0	-0.41	1	1
BCAR1	0.034	0.007	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.034	0.007	-10000	0	-10000	0	0
mol:NADPH	0	0.003	-10000	0	-10000	0	0
TRPV6	-0.24	0.3	0.36	1	-0.56	138	139
PRL	0.009	0.022	-10000	0	-10000	0	0
SOCS3	0.008	0.17	-10000	0	-1.2	7	7
SPRY2	0.034	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.051	0.024	-10000	0	-10000	0	0
CSF1/CSF1R	0.033	0.099	-10000	0	-0.28	19	19
Ras protein signal transduction	0.006	0.089	0.49	11	-10000	0	11
IRS1	0.032	0.011	-10000	0	-10000	0	0
INS	0.015	0.012	-10000	0	-10000	0	0
LEP	0.02	0.018	-10000	0	-10000	0	0
STAT5B	0.007	0.11	0.23	3	-0.36	17	20
STAT5A	0.006	0.11	0.23	3	-0.36	17	20
GRB2	0.034	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.031	0.075	0.24	2	-0.27	10	12
CSN2	0.009	0.047	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
LAT	-0.026	0.18	-10000	0	-0.5	43	43
YBX1	0.045	0.007	-10000	0	-10000	0	0
LCK	-0.14	0.22	-10000	0	-0.42	138	138
SHC1	0.032	0.011	-10000	0	-10000	0	0
NOX4	0.024	0.037	-10000	0	-0.42	2	2

×

Nectin adhesion pathway

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
PDGFRB	0.032	0.01	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.028	0.076	-10000	0	-0.3	18	18
PTK2	0.001	0.1	-10000	0	-0.35	13	13
positive regulation of JNK cascade	0.003	0.11	-10000	0	-0.3	20	20
CDC42/GDP	0.011	0.16	-10000	0	-0.38	32	32
Rac1/GDP	0.008	0.15	-10000	0	-0.38	31	31
RAP1B	0.034	0.007	-10000	0	-10000	0	0
RAP1A	0.034	0.007	-10000	0	-10000	0	0
CTNNB1	0.035	0.005	-10000	0	-10000	0	0
CDC42/GTP	0.008	0.14	-10000	0	-0.36	20	20
nectin-3/I-afadin	0.03	0.055	-10000	0	-0.29	8	8
RAPGEF1	0	0.13	-10000	0	-0.38	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.006	0.14	-10000	0	-0.38	34	34
PDGFB-D/PDGFRB	0.032	0.01	-10000	0	-10000	0	0
TLN1	0.003	0.021	-10000	0	-0.14	7	7
Rap1/GTP	0.004	0.1	-10000	0	-0.28	19	19
IQGAP1	0.034	0.006	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.051	0.03	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.03	0.055	-10000	0	-0.29	8	8
PVR	0.034	0.024	-10000	0	-0.42	1	1
Necl-5(dimer)	0.034	0.024	-10000	0	-0.42	1	1
mol:GDP	-0.01	0.18	-10000	0	-0.47	32	32
MLLT4	0.029	0.014	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
PI3K	0.072	0.059	-10000	0	-0.2	8	8
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.039	0.024	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	-0.002	0.13	-10000	0	-0.33	34	34
PVRL1	0.031	0.011	-10000	0	-10000	0	0
PVRL3	0.022	0.066	-10000	0	-0.42	8	8
PVRL2	0.035	0.004	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
CDH1	-0.082	0.2	-10000	0	-0.42	94	94
CLDN1	-0.17	0.22	-10000	0	-0.42	169	169
JAM-A/CLDN1	-0.065	0.15	-10000	0	-0.24	151	151
SRC	-0.01	0.15	-10000	0	-0.4	42	42
ITGB3	0.009	0.097	-10000	0	-0.42	18	18
nectin-1(dimer)/I-afadin/I-afadin	0.039	0.024	-10000	0	-10000	0	0
FARP2	-0.007	0.18	-10000	0	-0.49	24	24
RAC1	0.031	0.012	-10000	0	-10000	0	0
CTNNA1	0.033	0.008	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.044	0.057	-10000	0	-0.25	9	9
nectin-1/I-afadin	0.039	0.024	-10000	0	-10000	0	0
nectin-2/I-afadin	0.041	0.023	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.041	0.017	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.042	0.055	-10000	0	-0.24	8	8
CDC42/GTP/IQGAP1/filamentous actin	0.045	0.011	-10000	0	-10000	0	0
F11R	0.024	0.058	-10000	0	-0.42	6	6
positive regulation of filopodium formation	0.003	0.11	-10000	0	-0.3	20	20
alphaV/beta3 Integrin/Talin	0.027	0.068	0.24	3	-0.2	15	18
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.041	0.023	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.041	0.023	-10000	0	-10000	0	0
PIP5K1C	0.007	0.024	-10000	0	-0.15	8	8
VAV2	-0.02	0.21	-10000	0	-0.56	35	35
RAP1/GDP	0.017	0.14	-10000	0	-0.35	29	29
ITGAV	0.035	0.004	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.044	0.055	-10000	0	-0.25	8	8
nectin-3(dimer)/I-afadin/I-afadin	0.03	0.055	-10000	0	-0.29	8	8
Rac1/GTP	-0.001	0.15	-10000	0	-0.4	34	34
PTPRM	0.012	0.028	-10000	0	-0.16	8	8
E-cadherin/beta catenin/alpha catenin	0.004	0.13	-10000	0	-0.2	93	93
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.035	0.005	-10000	0	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.027	0.069	-10000	0	-0.24	22	22
cell-cell adhesion	0.01	0.06	0.19	32	-10000	0	32
Ephrin B/EPHB2/RasGAP	0.057	0.094	-10000	0	-0.21	34	34
ITSN1	0.034	0.005	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
SHC1	0.032	0.011	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.04	0.019	-10000	0	-10000	0	0
Ephrin B1/EPHB1	0.036	0.043	-10000	0	-0.25	7	7
HRAS/GDP	0.019	0.083	-10000	0	-0.23	22	22
Ephrin B/EPHB1/GRB7	0.059	0.085	-10000	0	-0.21	26	26
Endophilin/SYNJ1	0.001	0.069	0.18	10	-0.2	33	43
KRAS	0.034	0.006	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.06	0.085	-10000	0	-0.21	25	25
endothelial cell migration	0.061	0.03	-10000	0	-10000	0	0
GRB2	0.034	0.007	-10000	0	-10000	0	0
GRB7	0.029	0.012	-10000	0	-10000	0	0
PAK1	0.001	0.073	0.19	1	-0.21	26	27
HRAS	0.034	0.006	-10000	0	-10000	0	0
RRAS	0.002	0.071	0.19	12	-0.2	33	45
DNM1	0.029	0.013	-10000	0	-10000	0	0
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.004	0.064	0.18	9	-0.2	27	36
lamellipodium assembly	-0.01	0.06	-10000	0	-0.19	32	32
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.019	0.061	-10000	0	-0.22	9	9
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
EPHB2	0.016	0.09	-10000	0	-0.42	15	15
EPHB3	0.032	0.011	-10000	0	-10000	0	0
EPHB1	0.024	0.062	-10000	0	-0.42	7	7
EPHB4	0.032	0.01	-10000	0	-10000	0	0
mol:GDP	-0.004	0.07	0.22	3	-0.24	21	24
Ephrin B/EPHB2	0.044	0.086	-10000	0	-0.21	33	33
Ephrin B/EPHB3	0.05	0.071	-10000	0	-0.21	20	20
JNK cascade	0.01	0.071	0.24	10	-0.23	19	29
Ephrin B/EPHB1	0.047	0.079	-10000	0	-0.21	27	27
RAP1/GDP	0.034	0.098	0.23	24	-0.22	24	48
EFNB2	0.033	0.009	-10000	0	-10000	0	0
EFNB3	0.008	0.1	-10000	0	-0.42	20	20
EFNB1	0.034	0.007	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.04	0.074	-10000	0	-0.24	20	20
RAP1B	0.034	0.007	-10000	0	-10000	0	0
RAP1A	0.034	0.007	-10000	0	-10000	0	0
CDC42/GTP	0.034	0.1	-10000	0	-0.24	32	32
Rap1/GTP	0.01	0.071	-10000	0	-0.2	32	32
axon guidance	0.026	0.069	-10000	0	-0.24	22	22
MAPK3	0.01	0.058	0.2	4	-0.24	3	7
MAPK1	0.015	0.064	0.2	14	-0.24	3	17
Rac1/GDP	0.01	0.084	0.23	10	-0.23	21	31
actin cytoskeleton reorganization	-0.01	0.063	-10000	0	-0.2	22	22
CDC42/GDP	0.022	0.098	0.23	26	-0.23	24	50
PI3K	0.067	0.033	-10000	0	-10000	0	0
EFNA5	0.025	0.062	-10000	0	-0.42	7	7
Ephrin B2/EPHB4	0.04	0.018	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.009	0.076	-10000	0	-0.22	33	33
CDC42	0.035	0.005	-10000	0	-10000	0	0
RAS family/GTP	0.006	0.068	-10000	0	-0.2	30	30
PTK2	0.059	0.18	0.54	42	-10000	0	42
MAP4K4	0.01	0.071	0.24	10	-0.23	19	29
SRC	0.033	0.009	-10000	0	-10000	0	0
KALRN	0.032	0.034	-10000	0	-0.42	2	2
Intersectin/N-WASP	0.045	0.018	-10000	0	-10000	0	0
neuron projection morphogenesis	0.031	0.12	0.31	34	-0.29	5	39
MAP2K1	0.012	0.058	-10000	0	-0.21	8	8
WASL	0.031	0.011	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.063	0.08	-10000	0	-0.24	20	20
cell migration	0.023	0.092	0.26	6	-0.26	7	13
NRAS	0.034	0.008	-10000	0	-10000	0	0
SYNJ1	0.001	0.07	0.18	10	-0.2	33	43
PXN	0.034	0.006	-10000	0	-10000	0	0
TF	-0.053	0.098	0.18	8	-0.22	75	83
HRAS/GTP	0.033	0.085	-10000	0	-0.2	35	35
Ephrin B1/EPHB1-2	0.042	0.074	-10000	0	-0.24	20	20
cell adhesion mediated by integrin	0.012	0.055	0.21	20	-0.19	7	27
RAC1	0.031	0.012	-10000	0	-10000	0	0
mol:GTP	0.035	0.09	-10000	0	-0.2	39	39
RAC1-CDC42/GTP	-0.006	0.064	-10000	0	-0.2	29	29
RASA1	0.032	0.025	-10000	0	-0.42	1	1
RAC1-CDC42/GDP	0.023	0.087	0.23	9	-0.22	21	30
ruffle organization	0.012	0.12	0.34	23	-0.33	2	25
NCK1	0.034	0.006	-10000	0	-10000	0	0
receptor internalization	-0.021	0.061	0.17	8	-0.2	26	34
Ephrin B/EPHB2/KALRN	0.057	0.097	-10000	0	-0.22	34	34
ROCK1	0.02	0.021	0.19	4	-10000	0	4
RAS family/GDP	-0.016	0.062	-10000	0	-0.21	22	22
Rac1/GTP	-0.001	0.067	-10000	0	-0.2	32	32
Ephrin B/EPHB1/Src/Paxillin	0.016	0.066	-10000	0	-0.21	25	25

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.042	0.022	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.039	0.076	-10000	0	-0.25	20	20
PTK2	-0.01	0.14	0.34	11	-0.35	21	32
IGF1R	0.034	0.006	-10000	0	-10000	0	0
PI4KB	0.032	0.011	-10000	0	-10000	0	0
MFGE8	0.033	0.009	-10000	0	-10000	0	0
SRC	0.033	0.009	-10000	0	-10000	0	0
CDKN1B	-0.03	0.15	-10000	0	-0.41	47	47
VEGFA	0.03	0.013	-10000	0	-10000	0	0
ILK	-0.031	0.15	-10000	0	-0.41	48	48
ROCK1	0.035	0.005	-10000	0	-10000	0	0
AKT1	-0.034	0.14	-10000	0	-0.39	47	47
PTK2B	0.022	0.079	0.2	37	-0.21	17	54
alphaV/beta3 Integrin/JAM-A	0.026	0.12	-10000	0	-0.23	57	57
CBL	0.032	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.034	0.07	-10000	0	-0.25	18	18
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.076	0.04	-10000	0	-0.23	3	3
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.007	0.084	-10000	0	-0.23	15	15
alphaV/beta3 Integrin/Syndecan-1	0.039	0.086	-10000	0	-0.27	23	23
PI4KA	0.033	0.01	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.045	0.086	-10000	0	-0.24	26	26
PI4 Kinase	0.043	0.02	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.013	0.12	-10000	0	-0.28	50	50
RPS6KB1	-0.02	0.072	0.34	1	-0.37	5	6
TLN1	0.032	0.011	-10000	0	-10000	0	0
MAPK3	-0.017	0.12	-10000	0	-0.42	22	22
GPR124	0.033	0.008	-10000	0	-10000	0	0
MAPK1	-0.018	0.12	-10000	0	-0.42	22	22
PXN	0.034	0.006	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.068	0.16	-10000	0	-0.26	143	143
cell adhesion	0.033	0.071	-10000	0	-0.26	18	18
ANGPTL3	0.017	0.003	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.053	0.032	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.034	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.009	-10000	0	-10000	0	0
TGFBR2	0.035	0.005	-10000	0	-10000	0	0
ITGB3	0.009	0.097	-10000	0	-0.42	18	18
IGF1	0.03	0.041	-10000	0	-0.42	3	3
RAC1	0.031	0.012	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.043	0.07	-10000	0	-0.25	17	17
apoptosis	0.035	0.004	-10000	0	-10000	0	0
CD47	0.034	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.044	0.072	-10000	0	-0.25	18	18
VCL	0.032	0.01	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.025	0.074	-10000	0	-0.25	18	18
CSF1	0.029	0.047	-10000	0	-0.42	4	4
PIK3C2A	-0.031	0.15	-10000	0	-0.41	48	48
PI4 Kinase/Pyk2	0.004	0.085	-10000	0	-0.2	47	47
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.056	0.068	-10000	0	-0.23	14	14
FAK1/Vinculin	0.007	0.12	0.32	13	-0.29	18	31
alphaV beta3/Integrin/ppsTEM5	0.043	0.071	-10000	0	-0.25	17	17
RHOA	0.035	0.005	-10000	0	-10000	0	0
VTN	-0.019	0.14	-10000	0	-0.42	43	43
BCAR1	0.034	0.007	-10000	0	-10000	0	0
FGF2	0.03	0.035	-10000	0	-0.42	2	2
F11R	0.008	0.047	-10000	0	-0.3	8	8
alphaV/beta3 Integrin/Lactadherin	0.041	0.073	-10000	0	-0.25	18	18
alphaV/beta3 Integrin/TGFBR2	0.045	0.072	-10000	0	-0.25	18	18
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.073	0.045	-10000	0	-0.22	4	4
HSP90AA1	0.033	0.024	-10000	0	-0.42	1	1
alphaV/beta3 Integrin/Talin	0.039	0.066	-10000	0	-0.22	18	18
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.021	0.077	-10000	0	-0.42	11	11
alphaV/beta3 Integrin/Pyk2	0.047	0.075	0.2	23	-0.21	17	40
SDC1	0.026	0.062	-10000	0	-0.42	7	7
VAV3	0.017	0.041	0.19	6	-0.24	6	12
PTPN11	0.034	0.006	-10000	0	-10000	0	0
IRS1	0.032	0.011	-10000	0	-10000	0	0
FAK1/Paxillin	0.007	0.13	0.32	13	-0.29	18	31
cell migration	0.004	0.12	0.29	15	-0.27	16	31
ITGAV	0.035	0.004	-10000	0	-10000	0	0
PI3K	0.041	0.12	-10000	0	-0.21	52	52
SPP1	-0.013	0.14	-10000	0	-0.42	38	38
KDR	0.034	0.008	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.035	0.004	-10000	0	-10000	0	0
COL4A3	-0.14	0.22	-10000	0	-0.42	137	137
angiogenesis	-0.017	0.15	0.27	1	-0.44	24	25
Rac1/GTP	0.03	0.039	0.19	3	-0.22	6	9
EDIL3	0.023	0.017	-10000	0	-10000	0	0
cell proliferation	0.044	0.072	-10000	0	-0.25	18	18

×

PDGFR-beta signaling pathway

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
S1P1/Sphingosine-1-phosphate	-0.005	0.13	0.24	2	-0.43	21	23
PDGFB-D/PDGFRB/SLAP	-0.007	0.12	-10000	0	-0.3	54	54
PDGFB-D/PDGFRB/APS/CBL	0.049	0.051	-10000	0	-0.24	7	7
AKT1	0.023	0.079	0.34	9	-10000	0	9
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	-0.008	0.14	0.29	3	-0.46	23	26
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
FGR	-0.033	0.19	0.33	1	-0.55	38	39
mol:Ca2+	-0.02	0.14	0.25	5	-0.51	22	27
MYC	0.016	0.14	0.38	13	-0.39	15	28
SHC1	0.032	0.011	-10000	0	-10000	0	0
HRAS/GDP	0.052	0.048	0.18	21	-0.21	1	22
LRP1/PDGFRB/PDGFB	0.059	0.028	-10000	0	-10000	0	0
GRB10	0.031	0.011	-10000	0	-10000	0	0
PTPN11	0.034	0.006	-10000	0	-10000	0	0
GO:0007205	-0.021	0.15	0.25	5	-0.52	22	27
PTEN	0.03	0.012	-10000	0	-10000	0	0
GRB2	0.034	0.007	-10000	0	-10000	0	0
GRB7	0.029	0.012	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHP2	0.048	0.016	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.043	0.021	-10000	0	-10000	0	0
cell cycle arrest	-0.007	0.12	-10000	0	-0.3	54	54
HRAS	0.034	0.006	-10000	0	-10000	0	0
HIF1A	0.018	0.074	0.29	11	-10000	0	11
GAB1	-0.036	0.15	0.29	4	-0.51	22	26
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	-0.028	0.14	0.3	6	-0.44	22	28
PDGFB-D/PDGFRB	0.061	0.031	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.047	0.017	-10000	0	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.005	0.12	0.26	1	-0.39	19	20
positive regulation of MAPKKK cascade	0.047	0.016	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
mol:IP3	-0.021	0.15	0.25	5	-0.52	22	27
E5	-0.001	0.002	-10000	0	-10000	0	0
CSK	0.034	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.041	0.022	-10000	0	-10000	0	0
SHB	0.028	0.035	-10000	0	-0.42	2	2
BLK	-0.3	0.27	-10000	0	-0.5	227	227
PTPN2	0.035	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.047	0.018	-10000	0	-10000	0	0
BCAR1	0.034	0.007	-10000	0	-10000	0	0
VAV2	-0.037	0.16	0.33	4	-0.52	24	28
CBL	0.032	0.011	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.047	0.017	-10000	0	-10000	0	0
LCK	-0.18	0.28	-10000	0	-0.52	139	139
PDGFRB	0.033	0.01	-10000	0	-10000	0	0
ACP1	0.035	0.005	-10000	0	-10000	0	0
HCK	-0.02	0.19	0.34	1	-0.58	30	31
ABL1	-0.059	0.16	0.26	4	-0.4	44	48
PDGFB-D/PDGFRB/CBL	-0.052	0.17	-10000	0	-0.57	25	25
PTPN1	0.032	0.011	-10000	0	-10000	0	0
SNX15	0.034	0.007	-10000	0	-10000	0	0
STAT3	0.034	0.005	-10000	0	-10000	0	0
STAT1	0.033	0.033	-10000	0	-0.42	2	2
cell proliferation	0.017	0.14	0.36	14	-0.36	16	30
SLA	-0.035	0.16	-10000	0	-0.42	54	54
actin cytoskeleton reorganization	0.048	0.061	0.33	6	-0.21	2	8
SRC	0.02	0.059	0.3	2	-0.26	1	3
PI3K	0.013	0.015	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.052	0.032	-10000	0	-10000	0	0
SH2B2	0.023	0.062	-10000	0	-0.42	7	7
PLCgamma1/SPHK1	-0.008	0.15	0.29	3	-0.48	23	26
LYN	0.002	0.14	0.3	2	-0.57	14	16
LRP1	0.034	0.007	-10000	0	-10000	0	0
SOS1	0.035	0.003	-10000	0	-10000	0	0
STAT5B	0.034	0.005	-10000	0	-10000	0	0
STAT5A	0.033	0.024	-10000	0	-0.42	1	1
NCK1-2/p130 Cas	0.087	0.047	-10000	0	-10000	0	0
SPHK1	0.03	0.042	-10000	0	-0.42	3	3
EDG1	0	0.003	-10000	0	-10000	0	0
mol:DAG	-0.021	0.15	0.25	5	-0.52	22	27
PLCG1	-0.022	0.15	0.26	5	-0.54	22	27
NHERF/PDGFRB	0.063	0.024	-10000	0	-10000	0	0
YES1	0.016	0.094	0.32	2	-0.53	6	8
cell migration	0.063	0.023	-10000	0	-10000	0	0
SHC/Grb2/SOS1	0.079	0.051	-10000	0	-10000	0	0
SLC9A3R2	0.035	0.004	-10000	0	-10000	0	0
SLC9A3R1	0.034	0.007	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.071	0.038	-10000	0	-10000	0	0
FYN	-0.029	0.18	0.31	2	-0.48	42	44
DOK1	0.037	0.053	0.18	42	-10000	0	42
HRAS/GTP	0.025	0.004	-10000	0	-10000	0	0
PDGFB	0.033	0.009	-10000	0	-10000	0	0
RAC1	-0.013	0.16	0.33	9	-0.5	21	30
PRKCD	0.037	0.055	0.18	42	-10000	0	42
FER	0.037	0.054	0.18	41	-10000	0	41
MAPKKK cascade	0.03	0.089	0.33	14	-10000	0	14
RASA1	0.036	0.056	0.18	42	-0.24	1	43
NCK1	0.034	0.006	-10000	0	-10000	0	0
NCK2	0.035	0.003	-10000	0	-10000	0	0
p62DOK/Csk	0.059	0.049	0.19	33	-10000	0	33
PDGFB-D/PDGFRB/SHB	0.042	0.033	-10000	0	-0.3	2	2
chemotaxis	-0.057	0.15	0.24	5	-0.38	44	49
STAT1-3-5/STAT1-3-5	0.071	0.046	-10000	0	-0.21	3	3
Bovine Papilomavirus E5/PDGFRB	0.023	0.008	-10000	0	-10000	0	0
PTPRJ	0.034	0.006	-10000	0	-10000	0	0

×

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

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
MAP4K1	0.017	0.09	0.29	4	-0.38	7	11
CRKL	0.045	0.091	0.26	16	-0.36	6	22
HRAS	0.014	0.11	0.24	2	-0.34	14	16
mol:PIP3	0.071	0.1	0.28	29	-0.33	7	36
SPRED1	0.033	0.008	-10000	0	-10000	0	0
SPRED2	0.035	0.003	-10000	0	-10000	0	0
GAB1	0.045	0.086	0.21	9	-0.35	7	16
FOXO3	0.065	0.11	0.34	9	-0.33	9	18
AKT1	0.069	0.11	0.35	9	-0.34	11	20
BAD	0.067	0.11	0.34	11	-0.33	9	20
megakaryocyte differentiation	0.031	0.085	0.21	8	-0.34	9	17
GSK3B	0.067	0.11	0.34	12	-0.33	9	21
RAF1	0.023	0.099	0.26	8	-0.3	12	20
SHC1	0.032	0.011	-10000	0	-10000	0	0
STAT3	0.043	0.085	0.21	8	-0.35	7	15
STAT1	0.031	0.16	-10000	0	-0.84	9	9
HRAS/SPRED1	0.032	0.1	0.25	4	-0.29	13	17
cell proliferation	0.038	0.083	0.21	8	-0.36	7	15
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
TEC	0.022	0.074	-10000	0	-0.42	10	10
RPS6KB1	0.064	0.097	0.28	9	-0.36	7	16
HRAS/SPRED2	0.034	0.1	0.25	4	-0.3	12	16
LYN/TEC/p62DOK	0.074	0.099	0.28	1	-0.33	9	10
MAPK3	0.025	0.083	0.24	11	-0.25	5	16
STAP1	-0.068	0.12	0.2	2	-0.38	12	14
GRAP2	-0.014	0.14	-10000	0	-0.42	38	38
JAK2	0.037	0.14	-10000	0	-0.74	9	9
STAT1 (dimer)	0.032	0.16	-10000	0	-0.82	9	9
mol:Gleevec	-0.003	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.04	0.11	-10000	0	-0.31	17	17
actin filament polymerization	0.042	0.096	0.33	10	-0.35	7	17
LYN	0.016	0.084	-10000	0	-0.42	13	13
STAP1/STAT5A (dimer)	-0.074	0.14	0.33	1	-0.5	15	16
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.068	0.092	0.3	7	-0.32	7	14
PI3K	0.09	0.098	0.3	9	-0.35	7	16
PTEN	0.03	0.012	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	0.045	0.18	-10000	0	-1.1	7	7
MAPK8	0.038	0.084	0.21	8	-0.37	7	15
STAT3 (dimer)	0.042	0.084	0.21	8	-0.35	7	15
positive regulation of transcription	0.024	0.074	0.22	11	-0.21	4	15
mol:GDP	0.012	0.11	-10000	0	-0.34	18	18
PIK3C2B	0.047	0.1	0.32	17	-0.37	7	24
CBL/CRKL	0.057	0.091	0.28	10	-0.33	7	17
FER	0.042	0.09	0.25	9	-0.35	8	17
SH2B3	0.044	0.086	0.21	9	-0.35	7	16
PDPK1	0.068	0.1	0.28	27	-0.34	5	32
SNAI2	0.041	0.089	0.23	9	-0.37	7	16
positive regulation of cell proliferation	0.037	0.14	0.31	1	-0.65	9	10
KITLG	0.035	0.028	-10000	0	-0.43	1	1
cell motility	0.037	0.14	0.31	1	-0.65	9	10
PTPN6	-0.074	0.19	-10000	0	-0.41	88	88
EPOR	0.054	0.064	-10000	0	-10000	0	0
STAT5A (dimer)	0.041	0.12	0.32	3	-0.61	7	10
SOCS1	0.011	0.1	-10000	0	-0.42	19	19
cell migration	-0.026	0.091	0.37	8	-0.24	5	13
SOS1	0.035	0.003	-10000	0	-10000	0	0
EPO	0.028	0.015	-10000	0	-10000	0	0
VAV1	-0.051	0.18	-10000	0	-0.42	70	70
GRB10	0.038	0.088	0.26	5	-0.35	8	13
PTPN11	0.032	0.008	-10000	0	-10000	0	0
SCF/KIT	0.049	0.093	0.23	9	-0.36	8	17
GO:0007205	-0.001	0.004	-10000	0	-10000	0	0
MAP2K1	0.022	0.088	0.25	10	-0.26	8	18
CBL	0.032	0.011	-10000	0	-10000	0	0
KIT	0.02	0.19	-10000	0	-1.3	7	7
MAP2K2	0.02	0.087	0.24	11	-0.25	9	20
SHC/Grb2/SOS1	0.081	0.092	0.28	1	-0.35	7	8
STAT5A	0.04	0.13	0.32	3	-0.63	7	10
GRB2	0.034	0.007	-10000	0	-10000	0	0
response to radiation	0.042	0.09	0.24	10	-0.36	7	17
SHC/GRAP2	0.016	0.093	-10000	0	-0.3	29	29
PTPRO	0.031	0.086	0.21	8	-0.34	9	17
SH2B2	0.034	0.084	0.21	3	-0.36	7	10
DOK1	0.035	0.003	-10000	0	-10000	0	0
MATK	0.025	0.09	0.2	4	-0.37	8	12
CREBBP	0.05	0.024	-10000	0	-10000	0	0
BCL2	0.049	0.097	-10000	0	-0.71	3	3

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.035	0.004	-10000	0	-10000	0	0
SPHK1	0.03	0.041	-10000	0	-0.42	3	3
GNAI2	0.035	0.005	-10000	0	-10000	0	0
mol:S1P	0.018	0.028	-10000	0	-0.24	4	4
GNAO1	0.018	0.029	-10000	0	-0.42	1	1
mol:Sphinganine-1-P	0.016	0.029	-10000	0	-0.3	3	3
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.065	0.045	-10000	0	-0.18	4	4
GNAI3	0.034	0.007	-10000	0	-10000	0	0
G12/G13	0.045	0.018	-10000	0	-10000	0	0
S1PR3	0.029	0.042	-10000	0	-0.42	3	3
S1PR2	0.035	0.003	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.01	0.027	-10000	0	-0.2	4	4
S1PR5	0.034	0.008	-10000	0	-10000	0	0
S1PR4	-0.11	0.21	-10000	0	-0.42	118	118
GNAI1	0.031	0.012	-10000	0	-10000	0	0
S1P/S1P5/G12	0.048	0.042	-10000	0	-0.19	4	4
S1P/S1P3/Gq	-0.028	0.15	-10000	0	-0.29	80	80
S1P/S1P4/Gi	-0.029	0.12	0.2	1	-0.22	81	82
GNAQ	0.033	0.009	-10000	0	-10000	0	0
GNAZ	0.027	0.035	-10000	0	-0.42	2	2
GNA14	-0.036	0.16	-10000	0	-0.42	56	56
GNA15	0.021	0.077	-10000	0	-0.42	11	11
GNA12	0.031	0.011	-10000	0	-10000	0	0
GNA13	0.034	0.006	-10000	0	-10000	0	0
GNA11	0.035	0.004	-10000	0	-10000	0	0
ABCC1	0.033	0.024	-10000	0	-0.42	1	1

×

Signaling events mediated by the Hedgehog family

Figure S62. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S62. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.034	0.062	-10000	0	-0.43	4	4
IHH	0.043	0.033	-10000	0	-0.16	4	4
SHH Np/Cholesterol/GAS1	0.022	0.014	-10000	0	-10000	0	0
LRPAP1	0.034	0.007	-10000	0	-10000	0	0
dorsoventral neural tube patterning	-0.022	0.014	-10000	0	-10000	0	0
SMO/beta Arrestin2	0.057	0.083	-10000	0	-0.37	4	4
SMO	0.027	0.07	-10000	0	-0.37	5	5
AKT1	0.032	0.08	-10000	0	-0.34	10	10
ARRB2	0.033	0.009	-10000	0	-10000	0	0
BOC	0.034	0.007	-10000	0	-10000	0	0
ADRBK1	0.034	0.007	-10000	0	-10000	0	0
heart looping	0.027	0.069	-10000	0	-0.36	5	5
STIL	0.046	0.078	0.36	5	-0.3	2	7
DHH N/PTCH2	0.035	0.063	-10000	0	-0.3	12	12
DHH N/PTCH1	0.039	0.073	-10000	0	-0.26	16	16
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
DHH	0.019	0.077	-10000	0	-0.42	11	11
PTHLH	0.026	0.099	-10000	0	-0.63	7	7
determination of left/right symmetry	0.027	0.069	-10000	0	-0.36	5	5
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
skeletal system development	0.026	0.098	-10000	0	-0.63	7	7
IHH N/Hhip	0.04	0.023	-10000	0	-10000	0	0
DHH N/Hhip	0.025	0.059	-10000	0	-0.3	11	11
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.027	0.069	-10000	0	-0.36	5	5
pancreas development	0.017	0.002	-10000	0	-10000	0	0
HHAT	0.03	0.026	-10000	0	-0.42	1	1
PI3K	0.049	0.013	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.031	0.025	-10000	0	-0.42	1	1
somite specification	0.027	0.069	-10000	0	-0.36	5	5
SHH Np/Cholesterol/PTCH1	0.026	0.04	-10000	0	-0.32	2	2
SHH Np/Cholesterol/PTCH2	0.023	0.019	-10000	0	-0.23	1	1
SHH Np/Cholesterol/Megalin	-0.087	0.12	-10000	0	-0.23	157	157
SHH	-0.01	0.005	-10000	0	-10000	0	0
catabolic process	0.034	0.062	-10000	0	-0.42	6	6
SMO/Vitamin D3	0.036	0.064	-10000	0	-0.28	4	4
SHH Np/Cholesterol/Hhip	0.015	0.008	-10000	0	-10000	0	0
LRP2	-0.2	0.22	-10000	0	-0.42	194	194
receptor-mediated endocytosis	-0.058	0.12	-10000	0	-0.37	12	12
SHH Np/Cholesterol/BOC	0.023	0.014	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	0.022	0.014	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.014	0.008	-10000	0	-10000	0	0
mol:Vitamin D3	0.058	0.084	0.38	6	-0.32	2	8
IHH N/PTCH2	0.051	0.033	-10000	0	-0.32	1	1
CDON	0.032	0.011	-10000	0	-10000	0	0
IHH N/PTCH1	0.043	0.067	-10000	0	-0.42	6	6
Megalin/LRPAP1	-0.13	0.17	-10000	0	-0.3	191	191
PTCH2	0.033	0.024	-10000	0	-0.42	1	1
SHH Np/Cholesterol	0.015	0.007	-10000	0	-10000	0	0
PTCH1	0.034	0.063	-10000	0	-0.42	6	6
HHIP	0.017	0.002	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.033	0.008	-10000	0	-10000	0	0
ANTXR2	0.032	0.034	-10000	0	-0.42	2	2
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.004	-10000	0	-0.057	2	2
monocyte activation	-0.12	0.26	-10000	0	-0.5	104	104
MAP2K2	0.019	0.046	-10000	0	-0.6	2	2
MAP2K1	-0.002	0.004	-10000	0	-10000	0	0
MAP2K7	-0.002	0.003	-10000	0	-10000	0	0
MAP2K6	-0.006	0.027	-10000	0	-0.21	6	6
CYAA	-0.005	0.015	-10000	0	-0.21	2	2
MAP2K4	-0.002	0.008	0.14	1	-10000	0	1
IL1B	-0.035	0.095	0.11	2	-0.24	56	58
Channel	0.039	0.024	-10000	0	-0.22	2	2
NLRP1	-0.022	0.061	-10000	0	-0.21	35	35
CALM1	0.034	0.006	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.005	0.069	-10000	0	-0.38	11	11
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.004	0.057	2	-10000	0	2
MAPK3	-0.002	0.004	-10000	0	-10000	0	0
MAPK1	-0.002	0.008	0.14	1	-10000	0	1
PGR	-0.002	0.008	0.14	1	-10000	0	1
PA/Cellular Receptors	0.041	0.026	-10000	0	-0.25	2	2
apoptosis	-0.001	0.004	-10000	0	-0.057	2	2
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.038	0.023	-10000	0	-0.21	2	2
macrophage activation	-0.003	0.007	0.13	1	-10000	0	1
TNF	-0.054	0.18	-10000	0	-0.42	69	69
VCAM1	-0.12	0.26	-10000	0	-0.5	102	102
platelet activation	0.005	0.069	-10000	0	-0.38	11	11
MAPKKK cascade	-0.002	0.017	-10000	0	-0.075	3	3
IL18	-0.048	0.11	0.11	2	-0.25	74	76
negative regulation of macrophage activation	-0.001	0.004	-10000	0	-0.057	2	2
LEF	-0.001	0.004	-10000	0	-0.057	2	2
CASP1	-0.011	0.054	-10000	0	-0.18	28	28
mol:cAMP	0.005	0.069	-10000	0	-0.39	11	11
necrosis	-0.001	0.004	-10000	0	-0.057	2	2
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.039	0.023	-10000	0	-0.21	2	2
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

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

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
MET/RANBP9	0.028	0.068	-10000	0	-0.3	14	14
CRKL	0.036	0.12	0.33	12	-0.4	9	21
mol:PIP3	-0.002	0.012	-10000	0	-10000	0	0
AKT1	-0.006	0.019	-10000	0	-10000	0	0
PTK2B	0.028	0.048	-10000	0	-0.42	4	4
RAPGEF1	0.034	0.11	0.31	12	-0.39	8	20
RANBP10	0.034	0.007	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.034	0.084	-10000	0	-0.26	24	24
MAP3K5	-0.01	0.16	0.32	4	-0.44	25	29
HGF/MET/CIN85/CBL/ENDOPHILINS	0.048	0.085	-10000	0	-0.23	25	25
AP1	0.038	0.05	0.17	7	-10000	0	7
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.032	0.011	-10000	0	-10000	0	0
apoptosis	0.018	0.14	-10000	0	-0.78	9	9
STAT3 (dimer)	0.011	0.085	-10000	0	-0.38	7	7
GAB1/CRKL/SHP2/PI3K	0.073	0.12	0.33	8	-0.39	7	15
INPP5D	-0.037	0.16	-10000	0	-0.42	58	58
CBL/CRK	0.041	0.1	0.32	3	-0.37	10	13
PTPN11	0.034	0.006	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.033	0.01	-10000	0	-10000	0	0
PTEN	0.03	0.012	-10000	0	-10000	0	0
ELK1	0.023	0.13	0.35	42	-10000	0	42
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.01	0.057	-10000	0	-0.24	8	8
PAK1	0.002	0.043	-10000	0	-10000	0	0
HGF/MET/RANBP10	0.036	0.084	-10000	0	-0.26	25	25
HRAS	-0.003	0.14	-10000	0	-0.53	23	23
DOCK1	0.033	0.11	0.31	13	-0.39	8	21
GAB1	0.021	0.11	0.25	2	-0.42	10	12
CRK	0.024	0.11	0.32	3	-0.4	10	13
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.14	-10000	0	-0.48	24	24
JUN	0.031	0.011	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.004	0.065	-10000	0	-0.23	25	25
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
cell morphogenesis	0.041	0.12	0.35	20	-0.41	6	26
GRB2/SHC	0.036	0.075	-10000	0	-0.21	18	18
FOS	0.033	0.008	-10000	0	-10000	0	0
GLMN	0.002	0.026	-10000	0	-0.24	4	4
cell motility	0.023	0.13	0.35	42	-10000	0	42
HGF/MET/MUC20	0.019	0.077	-10000	0	-0.26	25	25
cell migration	0.036	0.073	-10000	0	-0.21	18	18
GRB2	0.034	0.007	-10000	0	-10000	0	0
CBL	0.032	0.011	-10000	0	-10000	0	0
MET/RANBP10	0.025	0.079	-10000	0	-0.29	20	20
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.01	0.074	-10000	0	-0.24	25	25
MET/MUC20	0.005	0.072	-10000	0	-0.29	20	20
RAP1B	0.036	0.11	0.32	13	-0.36	8	21
RAP1A	0.036	0.11	0.32	12	-0.36	8	20
HGF/MET/RANBP9	0.036	0.076	-10000	0	-0.25	20	20
RAF1	0.015	0.14	-10000	0	-0.5	23	23
STAT3	0.011	0.086	-10000	0	-0.38	7	7
cell proliferation	0.032	0.12	0.29	15	-0.36	19	34
RPS6KB1	0.006	0.049	-10000	0	-0.33	5	5
MAPK3	0.009	0.13	0.5	13	-10000	0	13
MAPK1	0.017	0.14	0.55	16	-10000	0	16
RANBP9	0.031	0.012	-10000	0	-10000	0	0
MAPK8	-0.01	0.17	0.32	4	-0.4	33	37
SRC	0.008	0.077	-10000	0	-0.23	25	25
PI3K	0.037	0.081	-10000	0	-0.21	24	24
MET/Glomulin	0.003	0.072	-10000	0	-0.25	23	23
SOS1	0.035	0.003	-10000	0	-10000	0	0
MAP2K1	0.019	0.14	0.33	1	-0.47	23	24
MET	0.006	0.1	-10000	0	-0.42	20	20
MAP4K1	-0.011	0.17	0.31	5	-0.47	25	30
PTK2	0.031	0.012	-10000	0	-10000	0	0
MAP2K2	0.017	0.14	0.36	2	-0.47	22	24
BAD	-0.005	0.027	-10000	0	-10000	0	0
MAP2K4	-0.007	0.14	0.31	4	-0.42	22	26
SHP2/GRB2/SOS1/GAB1	0.034	0.11	-10000	0	-0.32	25	25
INPPL1	0.033	0.009	-10000	0	-10000	0	0
PXN	0.034	0.006	-10000	0	-10000	0	0
SH3KBP1	0.035	0.004	-10000	0	-10000	0	0
HGS	-0.007	0.06	-10000	0	-0.22	25	25
PLCgamma1/PKC	0.024	0.007	-10000	0	-10000	0	0
HGF	0.024	0.058	-10000	0	-0.42	6	6
RASA1	0.032	0.025	-10000	0	-0.42	1	1
NCK1	0.034	0.006	-10000	0	-10000	0	0
PTPRJ	0.034	0.006	-10000	0	-10000	0	0
NCK/PLCgamma1	0.043	0.078	-10000	0	-0.21	24	24
PDPK1	-0.005	0.021	-10000	0	-10000	0	0
HGF/MET/SHIP	-0.009	0.14	-10000	0	-0.28	69	69

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.045	0.038	-10000	0	-0.3	4	4
Necdin/E2F1	0.04	0.052	-10000	0	-0.3	8	8
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.068	0.059	-10000	0	-0.22	8	8
NGF (dimer)/p75(NTR)/BEX1	0.038	0.049	-10000	0	-0.25	4	4
NT-4/5 (dimer)/p75(NTR)	0.025	0.041	-10000	0	-0.3	4	4
IKBKB	0.034	0.007	-10000	0	-10000	0	0
AKT1	0.023	0.055	0.2	23	-0.21	4	27
IKBKG	0.035	0.004	-10000	0	-10000	0	0
BDNF	-0.074	0.19	-10000	0	-0.42	88	88
MGDIs/NGR/p75(NTR)/LINGO1	0.033	0.062	-10000	0	-0.28	8	8
FURIN	0.034	0.007	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.026	0.14	-10000	0	-0.26	92	92
LINGO1	0.027	0.027	-10000	0	-0.42	1	1
Sortilin/TRAF6/NRIF	0.037	0.036	-10000	0	-0.2	6	6
proBDNF (dimer)	-0.074	0.19	-10000	0	-0.42	88	88
NTRK1	0.018	0.077	-10000	0	-0.42	11	11
RTN4R	0.026	0.048	-10000	0	-0.42	4	4
neuron apoptosis	-0.025	0.14	0.33	6	-0.41	14	20
IRAK1	0.035	0.004	-10000	0	-10000	0	0
SHC1	0.011	0.031	-10000	0	-0.25	4	4
ARHGDIA	0.034	0.007	-10000	0	-10000	0	0
RhoA/GTP	0.026	0.004	-10000	0	-10000	0	0
Gamma Secretase	0.088	0.044	-10000	0	-0.2	2	2
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.065	0.055	-10000	0	-0.23	8	8
MAGEH1	0.035	0.002	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.056	0.07	-10000	0	-0.23	16	16
Mammalian IAPs/DIABLO	-0.014	0.14	-10000	0	-0.23	109	109
proNGF (dimer)	0.031	0.011	-10000	0	-10000	0	0
MAGED1	0.035	0.003	-10000	0	-10000	0	0
APP	0.031	0.041	-10000	0	-0.42	3	3
NT-4/5 (dimer)	0.017	0.002	-10000	0	-10000	0	0
ZNF274	0.034	0.005	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	0.046	0.038	0.18	10	-0.21	4	14
NGF	0.031	0.011	-10000	0	-10000	0	0
cell cycle arrest	-0.001	0.082	0.31	18	-0.2	8	26
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.029	0.032	-10000	0	-0.24	3	3
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.042	0.043	-10000	0	-0.26	4	4
NCSTN	0.032	0.011	-10000	0	-10000	0	0
mol:GTP	0.047	0.046	-10000	0	-0.25	4	4
PSENEN	0.035	0.004	-10000	0	-10000	0	0
mol:ceramide	0.012	0.048	0.19	9	-0.22	9	18
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.037	0.043	-10000	0	-0.29	2	2
p75(NTR)/beta APP	0.034	0.052	-10000	0	-0.3	7	7
BEX1	0.027	0.014	-10000	0	-10000	0	0
mol:GDP	0.001	0.027	-10000	0	-0.25	4	4
NGF (dimer)	0.047	0.055	-10000	0	-0.22	9	9
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.053	0.061	-10000	0	-0.25	8	8
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
RAC1/GTP	0.038	0.041	-10000	0	-0.21	4	4
MYD88	0.033	0.024	-10000	0	-0.42	1	1
CHUK	0.032	0.01	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.048	0.047	-10000	0	-0.25	4	4
RHOB	0.035	0.005	-10000	0	-10000	0	0
RHOA	0.035	0.005	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.047	0.016	-10000	0	-10000	0	0
NT3 (dimer)	0.028	0.012	-10000	0	-10000	0	0
TP53	-0.036	0.11	0.36	1	-0.21	83	84
PRDM4	0.014	0.048	0.19	10	-0.23	8	18
BDNF (dimer)	-0.032	0.12	-10000	0	-0.23	92	92
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
SORT1	0.029	0.047	-10000	0	-0.42	4	4
activation of caspase activity	0.061	0.056	-10000	0	-0.21	8	8
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.064	0.055	-10000	0	-0.23	8	8
RHOC	0.034	0.007	-10000	0	-10000	0	0
XIAP	0.035	0.002	-10000	0	-10000	0	0
MAPK10	-0.012	0.11	0.32	11	-0.32	7	18
DIABLO	0.034	0.006	-10000	0	-10000	0	0
SMPD2	0.012	0.048	0.19	9	-0.22	9	18
APH1B	0.031	0.041	-10000	0	-0.42	3	3
APH1A	0.032	0.011	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0.044	0.056	-10000	0	-0.25	8	8
PSEN1	0.034	0.005	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.05	0.011	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	0.031	0.044	-10000	0	-0.3	4	4
MAPK8	-0.01	0.11	0.33	10	-0.29	10	20
MAPK9	-0.009	0.11	0.34	10	-0.31	8	18
APAF1	0.034	0.006	-10000	0	-10000	0	0
NTF3	0.028	0.012	-10000	0	-10000	0	0
NTF4	0.017	0.002	-10000	0	-10000	0	0
NDN	0.022	0.074	-10000	0	-0.42	10	10
RAC1/GDP	0.023	0.009	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.073	0.044	-10000	0	-0.2	4	4
p75 CTF/Sortilin/TRAF6/NRIF	0.079	0.041	-10000	0	-0.23	4	4
RhoA-B-C/GTP	0.046	0.046	-10000	0	-0.25	4	4
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.008	0.14	-10000	0	-0.22	90	90
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.004	0.14	-10000	0	-0.23	91	91
PRKACB	0.035	0.005	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.033	0.15	-10000	0	-0.3	88	88
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.1	0.2	-10000	0	-0.42	109	109
BIRC2	0.028	0.042	-10000	0	-0.42	3	3
neuron projection morphogenesis	-0.005	0.04	0.18	2	-0.22	8	10
BAD	-0.014	0.11	0.33	11	-0.3	10	21
RIPK2	0.032	0.011	-10000	0	-10000	0	0
NGFR	0.024	0.048	-10000	0	-0.42	4	4
CYCS	0.015	0.057	0.24	12	-0.21	8	20
ADAM17	0.035	0.004	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.061	0.049	-10000	0	-0.23	4	4
BCL2L11	-0.015	0.11	0.33	11	-0.3	10	21
BDNF (dimer)/p75(NTR)	-0.045	0.15	-10000	0	-0.3	90	90
PI3K	0.065	0.046	-10000	0	-0.22	4	4
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.063	0.055	-10000	0	-0.23	8	8
NDNL2	0.034	0.007	-10000	0	-10000	0	0
YWHAE	0.033	0.009	-10000	0	-10000	0	0
PRKCI	0.034	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	0.033	0.044	-10000	0	-0.3	4	4
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.065	0.055	-10000	0	-0.23	8	8
TRAF6	0.034	0.006	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
PRKCZ	0.031	0.034	-10000	0	-0.42	2	2
PLG	0.015	0.006	-10000	0	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.034	0.11	-10000	0	-0.22	89	89
SQSTM1	0.033	0.008	-10000	0	-10000	0	0
NGFRAP1	0.031	0.011	-10000	0	-10000	0	0
CASP3	-0.012	0.11	0.32	11	-0.29	10	21
E2F1	0.033	0.009	-10000	0	-10000	0	0
CASP9	0.035	0.005	-10000	0	-10000	0	0
IKK complex	0.055	0.075	-10000	0	-0.26	5	5
NGF (dimer)/TRKA	0.031	0.061	-10000	0	-0.3	11	11
MMP7	0.017	0.07	-10000	0	-0.42	9	9
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.075	0.058	-10000	0	-0.22	8	8
MMP3	0.014	0.016	-10000	0	-10000	0	0
APAF-1/Caspase 9	-0.034	0.093	-10000	0	-0.31	5	5

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.01	0.091	-10000	0	-0.22	40	40
SMAD6-7/SMURF1	0.061	0.026	-10000	0	-10000	0	0
NOG	-0.099	0.2	-10000	0	-0.42	105	105
SMAD9	0.007	0.12	-10000	0	-0.45	22	22
SMAD4	0.035	0.005	-10000	0	-10000	0	0
SMAD5	0.023	0.07	-10000	0	-0.34	7	7
BMP7/USAG1	-0.1	0.16	-10000	0	-0.32	134	134
SMAD5/SKI	0.035	0.096	-10000	0	-0.37	10	10
SMAD1	0.043	0.043	-10000	0	-10000	0	0
BMP2	0.024	0.058	-10000	0	-0.42	6	6
SMAD1/SMAD1/SMAD4	0.048	0.052	-10000	0	-0.35	1	1
BMPR1A	0.032	0.01	-10000	0	-10000	0	0
BMPR1B	0.014	0.017	-10000	0	-10000	0	0
BMPR1A-1B/BAMBI	0.013	0.053	-10000	0	-0.25	7	7
AHSG	0.022	0.011	-10000	0	-10000	0	0
CER1	0.019	0.011	-10000	0	-10000	0	0
BMP2-4/CER1	0.038	0.059	-10000	0	-0.24	12	12
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	0.017	0.073	-10000	0	-0.29	11	11
BMP2-4 (homodimer)	0.033	0.065	-10000	0	-0.29	13	13
RGMB	0.031	0.011	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.042	0.034	-10000	0	-10000	0	0
RGMA	0.029	0.035	-10000	0	-0.42	2	2
SMURF1	0.032	0.01	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	0.01	0.055	-10000	0	-0.29	6	6
BMP2-4/USAG1	-0.075	0.15	-10000	0	-0.26	139	139
SMAD6/SMURF1/SMAD5	0.03	0.095	0.26	1	-0.37	10	11
SOSTDC1	-0.14	0.21	-10000	0	-0.42	133	133
BMP7/BMPR2/BMPR1A-1B	0.019	0.067	-10000	0	-0.23	19	19
SKI	0.034	0.007	-10000	0	-10000	0	0
BMP6 (homodimer)	0.03	0.012	-10000	0	-10000	0	0
HFE2	0.016	0.005	-10000	0	-10000	0	0
ZFYVE16	0.034	0.008	-10000	0	-10000	0	0
MAP3K7	0.031	0.011	-10000	0	-10000	0	0
BMP2-4/CHRD	0.045	0.064	-10000	0	-0.25	13	13
SMAD5/SMAD5/SMAD4	0.037	0.097	0.26	1	-0.37	10	11
MAPK1	0.033	0.009	-10000	0	-10000	0	0
TAK1/TAB family	0.031	0.067	-10000	0	-0.25	7	7
BMP7 (homodimer)	0	0.099	-10000	0	-0.42	19	19
NUP214	0.033	0.009	-10000	0	-10000	0	0
BMP6/FETUA	0.033	0.021	-10000	0	-10000	0	0
SMAD1/SKI	0.056	0.059	-10000	0	-0.35	2	2
SMAD6	0.034	0.007	-10000	0	-10000	0	0
CTDSP2	0.034	0.007	-10000	0	-10000	0	0
BMP2-4/FETUA	0.039	0.063	-10000	0	-0.25	13	13
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.012	0.092	-10000	0	-0.42	16	16
BMPR2 (homodimer)	0.035	0.003	-10000	0	-10000	0	0
GADD34/PP1CA	0.064	0.022	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0.011	0.03	-10000	0	-10000	0	0
CHRDL1	-0.013	0.13	-10000	0	-0.42	36	36
ENDOFIN/SMAD1	0.056	0.059	-10000	0	-0.35	2	2
SMAD6-7/SMURF1/SMAD1	0.074	0.066	-10000	0	-0.41	1	1
SMAD6/SMURF1	0.032	0.01	-10000	0	-10000	0	0
BAMBI	0.023	0.062	-10000	0	-0.42	7	7
SMURF2	0.034	0.006	-10000	0	-10000	0	0
BMP2-4/CHRDL1	0.015	0.12	-10000	0	-0.28	43	43
BMP2-4/GREM1	0.032	0.09	-10000	0	-0.26	27	27
SMAD7	0.034	0.005	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	0.024	0.12	-10000	0	-0.41	24	24
SMAD1/SMAD6	0.05	0.06	-10000	0	-0.35	2	2
TAK1/SMAD6	0.043	0.02	-10000	0	-10000	0	0
BMP7	0	0.099	-10000	0	-0.42	19	19
BMP6	0.03	0.013	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0.014	0.061	-10000	0	-0.3	6	6
PPM1A	0.035	0.005	-10000	0	-10000	0	0
SMAD1/SMURF2	0.056	0.061	-10000	0	-0.35	2	2
SMAD7/SMURF1	0.046	0.017	-10000	0	-10000	0	0
CTDSPL	0.035	0.005	-10000	0	-10000	0	0
PPP1CA	0.034	0.007	-10000	0	-10000	0	0
XIAP	0.035	0.002	-10000	0	-10000	0	0
CTDSP1	0.035	0.004	-10000	0	-10000	0	0
PPP1R15A	0.035	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.004	0.087	-10000	0	-0.26	27	27
CHRD	0.032	0.01	-10000	0	-10000	0	0
BMPR2	0.035	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	0.005	0.055	-10000	0	-0.25	11	11
BMP4	0.025	0.062	-10000	0	-0.42	7	7
FST	0	0.11	-10000	0	-0.42	25	25
BMP2-4/NOG	-0.043	0.15	-10000	0	-0.26	113	113
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.029	0.068	-10000	0	-0.22	17	17

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.033	0.009	-10000	0	-10000	0	0
NFATC1	0.041	0.086	0.28	3	-0.37	4	7
NFATC2	0.009	0.082	0.17	3	-0.26	19	22
NFATC3	0.026	0.028	-10000	0	-0.33	2	2
YWHAE	0.033	0.009	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.089	0.17	0.19	1	-0.35	95	96
Exportin 1/Ran/NUP214	0.066	0.02	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.068	0.19	-10000	0	-0.36	93	93
BCL2/BAX	0.051	0.009	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.026	0.005	-10000	0	-10000	0	0
CaM/Ca2+	0.026	0.005	-10000	0	-10000	0	0
BAX	0.035	0.004	-10000	0	-10000	0	0
MAPK14	0.032	0.011	-10000	0	-10000	0	0
BAD	0.034	0.006	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.066	0.17	-10000	0	-0.34	79	79
Calcineurin A alpha-beta B1/BCL2	0.035	0.005	-10000	0	-10000	0	0
FKBP8	0.035	0.003	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.065	0.16	0.34	79	-10000	0	79
KPNB1	0.034	0.006	-10000	0	-10000	0	0
KPNA2	0.034	0.006	-10000	0	-10000	0	0
XPO1	0.035	0.002	-10000	0	-10000	0	0
SFN	0.027	0.015	-10000	0	-10000	0	0
MAP3K8	0.02	0.074	-10000	0	-0.42	10	10
NFAT4/CK1 alpha	0.041	0.029	0.18	3	-0.18	2	5
MEF2D/NFAT1/Cbp/p300	0.053	0.09	-10000	0	-0.3	9	9
CABIN1	-0.09	0.17	0.19	1	-0.36	95	96
CALM1	0.035	0.006	-10000	0	-10000	0	0
RAN	0.034	0.006	-10000	0	-10000	0	0
MAP3K1	0.034	0.007	-10000	0	-10000	0	0
CAMK4	-0.027	0.15	-10000	0	-0.42	49	49
mol:Ca2+	0.001	0.001	-10000	0	-10000	0	0
MAPK3	0.035	0.004	-10000	0	-10000	0	0
YWHAH	0.034	0.008	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.006	0.13	-10000	0	-0.3	60	60
YWHAB	0.033	0.01	-10000	0	-10000	0	0
MAPK8	0.032	0.01	-10000	0	-10000	0	0
MAPK9	0.033	0.009	-10000	0	-10000	0	0
YWHAG	0.032	0.01	-10000	0	-10000	0	0
FKBP1A	0.033	0.008	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.059	0.099	0.26	1	-0.35	5	6
PRKCH	0.033	0.024	-10000	0	-0.42	1	1
CABIN1/Cbp/p300	0.047	0.017	-10000	0	-10000	0	0
CASP3	0.034	0.006	-10000	0	-10000	0	0
PIM1	0.031	0.011	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.023	0.006	-10000	0	-10000	0	0
apoptosis	0.024	0.02	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.04	0.036	-10000	0	-10000	0	0
PRKCB	-0.097	0.2	-10000	0	-0.42	107	107
PRKCE	0.035	0.004	-10000	0	-10000	0	0
JNK2/NFAT4	0.036	0.046	-10000	0	-0.3	2	2
BAD/BCL-XL	0.047	0.016	-10000	0	-10000	0	0
PRKCD	0.034	0.006	-10000	0	-10000	0	0
NUP214	0.033	0.009	-10000	0	-10000	0	0
PRKCZ	0.032	0.034	-10000	0	-0.42	2	2
PRKCA	0.032	0.025	-10000	0	-0.42	1	1
PRKCG	0.028	0.01	-10000	0	-10000	0	0
PRKCQ	-0.089	0.2	-10000	0	-0.42	98	98
FKBP38/BCL2	0.051	0.008	-10000	0	-10000	0	0
EP300	0.032	0.011	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.033	0.008	-10000	0	-10000	0	0
NFATc/JNK1	0.057	0.084	0.28	3	-0.46	2	5
CaM/Ca2+/FKBP38	0.047	0.009	-10000	0	-10000	0	0
FKBP12/FK506	0.025	0.006	-10000	0	-10000	0	0
CSNK1A1	0.019	0.006	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.006	0.1	-10000	0	-0.25	49	49
NFATc/ERK1	0.059	0.086	0.28	3	-0.39	3	6
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.075	0.2	-10000	0	-0.36	105	105
NR4A1	0.047	0.09	0.23	15	-0.28	9	24
GSK3B	0.034	0.006	-10000	0	-10000	0	0
positive T cell selection	0.026	0.028	-10000	0	-0.33	2	2
NFAT1/CK1 alpha	0.014	0.059	-10000	0	-0.25	9	9
RCH1/ KPNB1	0.05	0.011	-10000	0	-10000	0	0
YWHAQ	0.035	0.004	-10000	0	-10000	0	0
PRKACA	0.035	0.003	-10000	0	-10000	0	0
AKAP5	-0.041	0.17	-10000	0	-0.42	61	61
MEF2D	0.032	0.011	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.032	0.011	-10000	0	-10000	0	0
NFATc/p38 alpha	0.045	0.082	0.28	2	-0.45	2	4
CREBBP	0.035	0.004	-10000	0	-10000	0	0
BCL2	0.035	0.005	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.002	0.026	-10000	0	-0.25	4	4
ADCY5	-0.048	0.1	-10000	0	-0.25	75	75
ADCY6	0.005	0.002	-10000	0	-10000	0	0
ADCY7	0.004	0.013	-10000	0	-0.25	1	1
ADCY1	-0.031	0.087	-10000	0	-0.25	51	51
ADCY2	-0.002	0.007	-10000	0	-10000	0	0
ADCY3	0.005	0.001	-10000	0	-10000	0	0
ADCY8	-0.003	0.007	-10000	0	-10000	0	0
PRKCE	0.01	0.001	-10000	0	-10000	0	0
ADCY9	0.005	0.001	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	0.006	0.063	0.2	13	-10000	0	13

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.033	0.01	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	0.006	0.068	-10000	0	-0.21	22	22
NT3 (dimer)/TRKC	0.018	0.088	-10000	0	-0.3	25	25
NT3 (dimer)/TRKB	0.034	0.056	-10000	0	-0.24	8	8
SHC/Grb2/SOS1/GAB1/PI3K	0.035	0.018	-10000	0	-10000	0	0
RAPGEF1	0.033	0.009	-10000	0	-10000	0	0
BDNF	-0.074	0.19	-10000	0	-0.42	88	88
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
DYNLT1	0.031	0.011	-10000	0	-10000	0	0
NTRK1	0.018	0.077	-10000	0	-0.42	11	11
NTRK2	0.024	0.048	-10000	0	-0.42	4	4
NTRK3	0.002	0.11	-10000	0	-0.42	25	25
NT-4/5 (dimer)/TRKB	0.031	0.054	-10000	0	-0.25	8	8
neuron apoptosis	0.028	0.12	0.36	17	-10000	0	17
SHC 2-3/Grb2	-0.031	0.13	-10000	0	-0.38	17	17
SHC1	0.032	0.011	-10000	0	-10000	0	0
SHC2	-0.036	0.11	-10000	0	-0.41	15	15
SHC3	-0.043	0.13	-10000	0	-0.42	25	25
STAT3 (dimer)	0.041	0.013	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	0.033	0.07	-10000	0	-0.26	14	14
RIN/GDP	0.044	0.089	0.28	14	-0.25	6	20
GIPC1	0.035	0.003	-10000	0	-10000	0	0
KRAS	0.034	0.006	-10000	0	-10000	0	0
DNAJA3	-0.002	0.055	-10000	0	-0.24	14	14
RIN/GTP	0.013	0.002	-10000	0	-10000	0	0
CCND1	0.025	0.011	-10000	0	-10000	0	0
MAGED1	0.035	0.003	-10000	0	-10000	0	0
PTPN11	0.034	0.006	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.017	0.002	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.062	0.025	-10000	0	-10000	0	0
GRB2	0.034	0.007	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.018	0.11	-10000	0	-0.27	42	42
TRKA/NEDD4-2	0.033	0.067	-10000	0	-0.29	14	14
ELMO1	0.014	0.087	-10000	0	-0.42	14	14
RhoG/GTP/ELMO1/DOCK1	0.028	0.057	-10000	0	-0.24	14	14
NGF	0.031	0.011	-10000	0	-10000	0	0
HRAS	0.034	0.006	-10000	0	-10000	0	0
DOCK1	0.032	0.01	-10000	0	-10000	0	0
GAB2	0.033	0.009	-10000	0	-10000	0	0
RIT2	0.017	0.003	-10000	0	-10000	0	0
RIT1	0.032	0.011	-10000	0	-10000	0	0
FRS2	0.034	0.007	-10000	0	-10000	0	0
DNM1	0.029	0.013	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.033	0.009	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.017	0.073	-10000	0	-0.22	23	23
mol:GDP	0.049	0.12	0.33	15	-0.37	7	22
NGF (dimer)	0.031	0.011	-10000	0	-10000	0	0
RhoG/GDP	0.011	0.061	-10000	0	-0.29	14	14
RIT1/GDP	0.036	0.078	0.24	6	-0.25	6	12
TIAM1	0.008	0.1	-10000	0	-0.42	21	21
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.024	0.13	-10000	0	-0.25	91	91
KIDINS220/CRKL/C3G	0.045	0.018	-10000	0	-10000	0	0
SHC/RasGAP	0.044	0.026	-10000	0	-0.3	1	1
FRS2 family/SHP2	0.06	0.027	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.077	0.033	-10000	0	-10000	0	0
RIT1/GTP	0.023	0.008	-10000	0	-10000	0	0
NT3 (dimer)	0.028	0.012	-10000	0	-10000	0	0
RAP1/GDP	0.033	0.065	0.16	5	-0.22	5	10
KIDINS220/CRKL	0.032	0.01	-10000	0	-10000	0	0
BDNF (dimer)	-0.074	0.19	-10000	0	-0.42	88	88
ubiquitin-dependent protein catabolic process	0.044	0.065	-10000	0	-0.25	14	14
Schwann cell development	-0.014	0.022	-10000	0	-10000	0	0
EHD4	0.034	0.008	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.074	0.036	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.03	0.044	-10000	0	-0.25	1	1
RAP1B	0.034	0.007	-10000	0	-10000	0	0
RAP1A	0.034	0.007	-10000	0	-10000	0	0
CDC42/GTP	-0.025	0.12	-10000	0	-0.22	96	96
ABL1	0.033	0.009	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.05	0.011	-10000	0	-10000	0	0
Rap1/GTP	0.01	0.086	-10000	0	-0.37	7	7
STAT3	0.041	0.013	-10000	0	-10000	0	0
axon guidance	-0.034	0.11	-10000	0	-0.21	96	96
MAPK3	0.002	0.1	0.19	29	-0.25	42	71
MAPK1	0.001	0.098	0.19	27	-0.24	42	69
CDC42/GDP	0.052	0.091	0.25	20	-0.25	6	26
NTF3	0.028	0.012	-10000	0	-10000	0	0
NTF4	0.017	0.002	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.044	0.065	-10000	0	-0.25	14	14
PI3K	0.049	0.013	-10000	0	-10000	0	0
FRS3	0.032	0.011	-10000	0	-10000	0	0
FAIM	0.031	0.041	-10000	0	-0.42	3	3
GAB1	0.035	0.004	-10000	0	-10000	0	0
RASGRF1	-0.013	0.074	-10000	0	-0.22	34	34
SOS1	0.035	0.003	-10000	0	-10000	0	0
MCF2L	-0.009	0.065	-10000	0	-0.25	23	23
RGS19	0.032	0.01	-10000	0	-10000	0	0
CDC42	0.035	0.005	-10000	0	-10000	0	0
RAS family/GTP	0.07	0.082	0.31	7	-0.4	4	11
Rac1/GDP	0.042	0.084	0.25	14	-0.26	5	19
NGF (dimer)/TRKA/GRIT	0.029	0.052	-10000	0	-0.25	11	11
neuron projection morphogenesis	0.021	0.14	-10000	0	-0.8	9	9
NGF (dimer)/TRKA/NEDD4-2	0.045	0.065	-10000	0	-0.25	14	14
MAP2K1	0.043	0.061	0.2	46	-10000	0	46
NGFR	0.024	0.048	-10000	0	-0.42	4	4
NGF (dimer)/TRKA/GIPC/GAIP	0.02	0.054	-10000	0	-0.27	9	9
RAS family/GTP/PI3K	0.032	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.084	0.042	-10000	0	-10000	0	0
NRAS	0.034	0.008	-10000	0	-10000	0	0
GRB2/SOS1	0.05	0.011	-10000	0	-10000	0	0
PRKCI	0.034	0.006	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
PRKCZ	0.031	0.034	-10000	0	-0.42	2	2
MAPKKK cascade	-0.011	0.14	-10000	0	-0.54	23	23
RASA1	0.032	0.025	-10000	0	-0.42	1	1
TRKA/c-Abl	0.034	0.059	-10000	0	-0.29	11	11
SQSTM1	0.033	0.008	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.003	0.13	-10000	0	-0.23	89	89
NGF (dimer)/TRKA/p62/Atypical PKCs	0.069	0.067	-10000	0	-0.21	12	12
MATK	-0.018	0.14	-10000	0	-0.42	43	43
NEDD4L	0.031	0.041	-10000	0	-0.42	3	3
RAS family/GDP	-0.011	0.035	-10000	0	-0.18	6	6
NGF (dimer)/TRKA	0.004	0.057	-10000	0	-0.25	14	14
Rac1/GTP	-0.009	0.067	-10000	0	-0.22	20	20
FRS2 family/SHP2/CRK family	0.079	0.046	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.025	0.051	-10000	0	-0.24	12	12
EPHB2	0.016	0.09	-10000	0	-0.42	15	15
Syndecan-2/TACI	-0.079	0.13	-10000	0	-0.24	143	143
LAMA1	0.006	0.013	-10000	0	-10000	0	0
Syndecan-2/alpha2 ITGB1	0.053	0.061	-10000	0	-0.24	10	10
HRAS	0.034	0.006	-10000	0	-10000	0	0
Syndecan-2/CASK	0.01	0.019	-10000	0	-0.24	2	2
ITGA5	0.034	0.006	-10000	0	-10000	0	0
BAX	0.01	0.017	-10000	0	-10000	0	0
EPB41	0.033	0.024	-10000	0	-0.42	1	1
positive regulation of cell-cell adhesion	0.03	0.022	-10000	0	-0.22	2	2
LAMA3	0.02	0.08	-10000	0	-0.42	12	12
EZR	0.027	0.042	-10000	0	-0.42	3	3
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.032	0.011	-10000	0	-10000	0	0
Syndecan-2/MMP2	0.026	0.033	-10000	0	-0.24	4	4
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.044	0.026	-10000	0	-0.3	1	1
dendrite morphogenesis	0.021	0.058	-10000	0	-0.24	16	16
Syndecan-2/GM-CSF	0.027	0.028	-10000	0	-0.24	3	3
determination of left/right symmetry	0.014	0.023	-10000	0	-0.28	2	2
Syndecan-2/PKC delta	0.032	0.024	-10000	0	-0.24	2	2
GNB2L1	0.033	0.008	-10000	0	-10000	0	0
MAPK3	0.032	0.055	0.19	32	-0.22	3	35
MAPK1	0.03	0.053	0.19	29	-0.22	3	32
Syndecan-2/RACK1	0.046	0.028	-10000	0	-0.2	2	2
NF1	0.034	0.007	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.014	0.023	-10000	0	-0.28	2	2
ITGA2	0.032	0.025	-10000	0	-0.42	1	1
MAPK8	0.013	0.02	-10000	0	-0.24	2	2
Syndecan-2/alpha2/beta1 Integrin	0.022	0.029	-10000	0	-0.21	2	2
Syndecan-2/Kininogen	0.023	0.023	-10000	0	-0.24	2	2
ITGB1	0.032	0.011	-10000	0	-10000	0	0
SRC	0.034	0.05	0.19	31	-0.2	2	33
Syndecan-2/CASK/Protein 4.1	0.029	0.025	-10000	0	-0.22	3	3
extracellular matrix organization	0.032	0.028	-10000	0	-0.24	3	3
actin cytoskeleton reorganization	0.025	0.051	-10000	0	-0.24	12	12
Syndecan-2/Caveolin-2/Ras	0.045	0.031	-10000	0	-0.22	2	2
Syndecan-2/Laminin alpha3	0.025	0.056	-10000	0	-0.29	10	10
Syndecan-2/RasGAP	0.058	0.037	-10000	0	-0.2	3	3
alpha5/beta1 Integrin	0.046	0.018	-10000	0	-10000	0	0
PRKCD	0.034	0.006	-10000	0	-10000	0	0
Syndecan-2 dimer	0.021	0.058	-10000	0	-0.24	16	16
GO:0007205	0.003	0.001	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.041	0.034	0.2	4	-0.19	3	7
RHOA	0.035	0.005	-10000	0	-10000	0	0
SDCBP	0.032	0.01	-10000	0	-10000	0	0
TNFRSF13B	-0.17	0.22	-10000	0	-0.42	164	164
RASA1	0.032	0.025	-10000	0	-0.42	1	1
alpha2/beta1 Integrin	0.044	0.026	-10000	0	-0.3	1	1
Syndecan-2/Synbindin	0.03	0.025	-10000	0	-0.24	2	2
TGFB1	0.032	0.033	-10000	0	-0.42	2	2
CASP3	0.037	0.056	0.2	35	-0.22	2	37
FN1	0.021	0.077	-10000	0	-0.42	11	11
Syndecan-2/IL8	0.022	0.036	-10000	0	-0.24	5	5
SDC2	0.014	0.023	-10000	0	-0.29	2	2
KNG1	0.021	0.01	-10000	0	-10000	0	0
Syndecan-2/Neurofibromin	0.032	0.024	-10000	0	-0.24	2	2
TRAPPC4	0.032	0.011	-10000	0	-10000	0	0
CSF2	0.026	0.025	-10000	0	-0.42	1	1
Syndecan-2/TGFB1	0.032	0.028	-10000	0	-0.24	3	3
Syndecan-2/Syntenin/PI-4-5-P2	0.03	0.022	-10000	0	-0.22	2	2
Syndecan-2/Ezrin	0.043	0.039	-10000	0	-0.22	5	5
PRKACA	0.036	0.054	0.2	33	-0.22	2	35
angiogenesis	0.022	0.036	-10000	0	-0.24	5	5
MMP2	0.027	0.035	-10000	0	-0.42	2	2
IL8	0.022	0.043	-10000	0	-0.42	3	3
calcineurin-NFAT signaling pathway	-0.079	0.13	-10000	0	-0.24	143	143

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.033	0.009	-10000	0	-10000	0	0
EPHB2	0.015	0.091	-10000	0	-0.42	15	15
EFNB1	0.013	0.012	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.038	0.096	-10000	0	-0.24	30	30
Ephrin B2/EPHB1-2	0.038	0.075	-10000	0	-0.25	20	20
neuron projection morphogenesis	0.021	0.084	-10000	0	-0.23	30	30
Ephrin B1/EPHB1-2/Tiam1	0.033	0.1	-10000	0	-0.25	36	36
DNM1	0.029	0.013	-10000	0	-10000	0	0
cell-cell signaling	-0.001	0.003	-10000	0	-10000	0	0
MAP2K4	-0.014	0.087	-10000	0	-0.5	11	11
YES1	-0.003	0.13	-10000	0	-0.75	11	11
Ephrin B1/EPHB1-2/NCK2	0.048	0.075	-10000	0	-0.23	20	20
PI3K	0.03	0.1	-10000	0	-0.52	11	11
mol:GDP	0.031	0.099	-10000	0	-0.24	36	36
ITGA2B	0.03	0.012	-10000	0	-10000	0	0
endothelial cell proliferation	0.039	0.018	-10000	0	-10000	0	0
FYN	-0.015	0.14	-10000	0	-0.76	11	11
MAP3K7	-0.014	0.096	-10000	0	-0.54	11	11
FGR	-0.018	0.14	-10000	0	-0.76	11	11
TIAM1	0.008	0.1	-10000	0	-0.42	21	21
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
RGS3	0.033	0.009	-10000	0	-10000	0	0
cell adhesion	0.004	0.11	-10000	0	-0.49	12	12
LYN	-0.008	0.13	-10000	0	-0.73	11	11
Ephrin B1/EPHB1-2/Src Family Kinases	-0.012	0.12	-10000	0	-0.69	11	11
Ephrin B1/EPHB1-2	-0.016	0.1	-10000	0	-0.59	11	11
SRC	-0.002	0.13	-10000	0	-0.73	11	11
ITGB3	0.009	0.097	-10000	0	-0.42	18	18
EPHB1	0.023	0.062	-10000	0	-0.42	7	7
EPHB4	0.032	0.01	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.039	0.018	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.023	0.077	-10000	0	-0.3	18	18
BLK	-0.1	0.15	-10000	0	-0.79	11	11
HCK	-0.015	0.14	-10000	0	-0.74	11	11
regulation of stress fiber formation	-0.046	0.074	0.23	20	-10000	0	20
MAPK8	-0.014	0.083	-10000	0	-0.47	11	11
Ephrin B1/EPHB1-2/RGS3	0.047	0.074	-10000	0	-0.24	19	19
endothelial cell migration	0.001	0.091	0.21	1	-0.46	9	10
NCK2	0.035	0.003	-10000	0	-10000	0	0
PTPN13	0.036	0.053	-10000	0	-0.54	3	3
regulation of focal adhesion formation	-0.046	0.074	0.23	20	-10000	0	20
chemotaxis	-0.045	0.073	0.24	19	-10000	0	19
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
Rac1/GTP	0.03	0.091	-10000	0	-0.24	30	30
angiogenesis	-0.015	0.1	-10000	0	-0.58	11	11
LCK	-0.063	0.15	-10000	0	-0.78	11	11

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.003	0.11	-10000	0	-0.42	23	23
GNB1/GNG2	0.043	0.084	-10000	0	-0.25	17	17
mol:DAG	0.02	0.071	0.19	5	-0.25	12	17
PLCG1	0.02	0.073	0.19	5	-0.26	12	17
YES1	0.003	0.063	-10000	0	-0.23	19	19
FZD3	0.033	0.009	-10000	0	-10000	0	0
FZD6	0.014	0.087	-10000	0	-0.42	14	14
G protein	0.052	0.088	0.28	4	-0.3	8	12
MAP3K7	0.003	0.058	0.19	3	-0.26	7	10
mol:Ca2+	0.019	0.07	0.18	5	-0.25	12	17
mol:IP3	0.02	0.071	0.19	5	-0.25	12	17
NLK	-0.001	0.12	-10000	0	-0.75	10	10
GNB1	0.034	0.007	-10000	0	-10000	0	0
CAMK2A	0.007	0.066	0.2	4	-0.28	7	11
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	0.007	0.064	-10000	0	-0.25	19	19
CSNK1A1	0.033	0.009	-10000	0	-10000	0	0
GNAS	0.005	0.06	-10000	0	-0.24	16	16
GO:0007205	0.012	0.071	0.21	6	-0.29	7	13
WNT6	0.033	0.008	-10000	0	-10000	0	0
WNT4	0.021	0.017	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.032	0.093	0.28	5	-0.31	8	13
GNG2	0.027	0.058	-10000	0	-0.42	6	6
WNT5A	0.024	0.066	-10000	0	-0.42	8	8
WNT11	0.023	0.017	-10000	0	-10000	0	0
CDC42	0.004	0.064	0.2	3	-0.24	15	18

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.025	0.004	-10000	0	-10000	0	0
PRKCZ	0.031	0.034	-10000	0	-0.42	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.034	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.01	0.076	-10000	0	-0.34	8	8
IRAK/TOLLIP	0.04	0.01	-10000	0	-10000	0	0
IKBKB	0.034	0.007	-10000	0	-10000	0	0
IKBKG	0.035	0.004	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.003	0.12	-10000	0	-0.3	53	53
IL1A	0.03	0.01	-10000	0	-10000	0	0
IL1B	-0.018	0.1	-10000	0	-0.32	37	37
IRAK/TRAF6/p62/Atypical PKCs	0.077	0.039	-10000	0	-0.2	2	2
IL1R2	-0.03	0.16	-10000	0	-0.42	53	53
IL1R1	0.033	0.033	-10000	0	-0.42	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.005	0.084	-10000	0	-0.36	11	11
TOLLIP	0.034	0.006	-10000	0	-10000	0	0
TICAM2	0.028	0.047	-10000	0	-0.42	4	4
MAP3K3	0.034	0.007	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.021	0.007	-10000	0	-10000	0	0
IKK complex/ELKS	0.037	0.063	-10000	0	-0.3	1	1
JUN	-0.008	0.025	0.15	2	-0.18	4	6
MAP3K7	0.031	0.011	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.046	0.11	-10000	0	-0.23	42	42
IL1 alpha/IL1R1/IL1RAP/MYD88	0.077	0.037	-10000	0	-0.23	3	3
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.089	0.04	-10000	0	-0.2	3	3
IL1 beta fragment/IL1R1/IL1RAP	0.015	0.1	-10000	0	-0.25	43	43
NFKB1	0.034	0.006	-10000	0	-10000	0	0
MAPK8	0.007	0.026	0.17	2	-0.19	5	7
IRAK1	0.02	0.004	-10000	0	-10000	0	0
IL1RN/IL1R1	0.04	0.062	-10000	0	-0.3	12	12
IRAK4	0.034	0.006	-10000	0	-10000	0	0
PRKCI	0.034	0.006	-10000	0	-10000	0	0
TRAF6	0.034	0.006	-10000	0	-10000	0	0
PI3K	0.049	0.013	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.011	0.082	-10000	0	-0.32	12	12
CHUK	0.032	0.01	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.015	0.1	-10000	0	-0.25	43	43
IL1 beta/IL1R2	-0.032	0.15	-10000	0	-0.3	82	82
IRAK/TRAF6/TAK1/TAB1/TAB2	0.045	0.018	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.032	0.094	-10000	0	-0.22	39	39
IRAK3	0.028	0.053	-10000	0	-0.42	5	5
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.042	0.11	-10000	0	-0.24	42	42
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.035	0.032	-10000	0	-0.28	3	3
IL1 alpha/IL1R1/IL1RAP	0.057	0.036	-10000	0	-0.25	2	2
RELA	0.034	0.007	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.033	0.008	-10000	0	-10000	0	0
MYD88	0.033	0.024	-10000	0	-0.42	1	1
IRAK/TRAF6/MEKK3	0.057	0.018	-10000	0	-10000	0	0
IL1RAP	0.032	0.01	-10000	0	-10000	0	0
UBE2N	0.034	0.005	-10000	0	-10000	0	0
IRAK/TRAF6	0.014	0.088	-10000	0	-0.3	11	11
CASP1	0.015	0.087	-10000	0	-0.42	14	14
IL1RN/IL1R2	-0.008	0.13	-10000	0	-0.3	61	61
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.033	0.11	-10000	0	-0.24	43	43
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.033	0.06	-10000	0	-0.36	7	7
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
IL1RN	0.022	0.074	-10000	0	-0.42	10	10
TRAF6/TAK1/TAB1/TAB2	0.045	0.018	-10000	0	-10000	0	0
MAP2K6	0.018	0.032	0.18	3	-0.2	6	9

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.029	0.024	-10000	0	-0.42	1	1
AES	0.031	0.005	-10000	0	-10000	0	0
FBXW11	0.033	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.046	0.017	-10000	0	-10000	0	0
SMAD4	0.035	0.005	-10000	0	-10000	0	0
DKK2	0.029	0.042	-10000	0	-0.42	3	3
TLE1	0.028	0.025	-10000	0	-0.42	1	1
MACF1	0.035	0.005	-10000	0	-10000	0	0
CTNNB1	0.013	0.093	0.43	1	-0.36	7	8
WIF1	0.019	0.016	-10000	0	-10000	0	0
beta catenin/RanBP3	-0.004	0.076	0.36	1	-0.34	5	6
KREMEN2	-0.027	0.16	-10000	0	-0.42	50	50
DKK1	-0.023	0.14	-10000	0	-0.42	42	42
beta catenin/beta TrCP1	0.03	0.09	0.42	1	-0.32	7	8
FZD1	0.032	0.011	-10000	0	-10000	0	0
AXIN2	0.018	0.12	0.56	10	-1.4	1	11
AXIN1	0.035	0.003	-10000	0	-10000	0	0
RAN	0.034	0.006	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.029	0.091	-10000	0	-0.52	9	9
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.03	0.11	-10000	0	-0.47	8	8
Axin1/APC/GSK3	0.028	0.063	0.3	3	-0.28	4	7
Axin1/APC/GSK3/beta catenin/Macf1	0.022	0.1	0.37	3	-0.34	9	12
HNF1A	0.031	0.006	-10000	0	-10000	0	0
CTBP1	0.03	0.008	-10000	0	-10000	0	0
MYC	0.073	0.18	0.58	41	-10000	0	41
RANBP3	0.035	0.004	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.019	0.11	-10000	0	-0.25	52	52
NKD1	0.025	0.058	-10000	0	-0.42	6	6
TCF4	0.026	0.041	-10000	0	-0.42	3	3
TCF3	0.031	0.006	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.057	0.08	-10000	0	-0.23	23	23
Ran/GTP	0.025	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.011	0.083	0.43	1	-0.6	2	3
LEF1	0.016	0.08	-10000	0	-0.42	12	12
DVL1	0.02	0.055	-10000	0	-0.41	3	3
CSNK2A1	0.033	0.008	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.04	0.12	0.27	1	-0.55	7	8
DKK1/LRP6/Kremen 2	-0.017	0.14	-10000	0	-0.27	79	79
LRP6	0.034	0.006	-10000	0	-10000	0	0
CSNK1A1	0.029	0.009	-10000	0	-10000	0	0
NLK	0.035	0.007	-10000	0	-10000	0	0
CCND1	0.04	0.14	0.58	19	-10000	0	19
WNT1	-0.002	0.12	-10000	0	-0.42	28	28
GSK3A	0.035	0.004	-10000	0	-10000	0	0
GSK3B	0.034	0.006	-10000	0	-10000	0	0
FRAT1	0.031	0.025	-10000	0	-0.42	1	1
PPP2R5D	0.025	0.042	0.25	5	-0.25	1	6
APC	0.02	0.082	0.21	32	-0.21	22	54
WNT1/LRP6/FZD1	0.013	0.062	-10000	0	-0.22	14	14
CREBBP	0.031	0.005	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin 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
HRAS	0.034	0.006	-9999	-10000	0	0
EGFR	0.027	0.035	-9999	-0.42	2	2
EGF/EGFR	0.028	0.072	-9999	-0.2	27	27
EGF/EGFR dimer/SHC/GRB2/SOS1	0.055	0.083	-9999	-0.21	23	23
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.033	0.009	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	0.001	0.11	-9999	-0.42	25	25
EGF/EGFR dimer/SHC	0.028	0.081	-9999	-0.25	24	24
mol:GDP	0.049	0.079	-9999	-0.21	23	23
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.027	0.042	-9999	-0.42	3	3
GRB2/SOS1	0.05	0.011	-9999	-10000	0	0
HRAS/GTP	0.032	0.067	-9999	-0.2	23	23
SHC1	0.032	0.011	-9999	-10000	0	0
HRAS/GDP	0.049	0.077	-9999	-0.2	23	23
FRAP1	-0.02	0.048	-9999	-0.2	23	23
EGF/EGFR dimer	0.015	0.089	-9999	-0.3	26	26
SOS1	0.035	0.003	-9999	-10000	0	0
GRB2	0.034	0.007	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.039	0.038	-9999	-0.3	3	3

×

ErbB2/ErbB3 signaling events

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
USP8	-0.004	0.005	-10000	0	-10000	0	0
RAS family/GTP	0.052	0.084	-10000	0	-0.24	8	8
NFATC4	-0.014	0.051	0.24	2	-0.2	3	5
ERBB2IP	0.034	0.007	-10000	0	-10000	0	0
HSP90 (dimer)	0.033	0.024	-10000	0	-0.42	1	1
mammary gland morphogenesis	0.023	0.066	-10000	0	-0.23	17	17
JUN	0.037	0.065	0.24	4	-10000	0	4
HRAS	0.034	0.006	-10000	0	-10000	0	0
DOCK7	-0.003	0.059	-10000	0	-0.22	16	16
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.038	0.067	-10000	0	-0.23	16	16
AKT1	0.009	0.005	-10000	0	-10000	0	0
BAD	-0.004	0.004	-10000	0	-10000	0	0
MAPK10	0	0.051	0.2	7	-10000	0	7
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.026	0.071	-10000	0	-0.24	17	17
RAF1	0.031	0.094	0.29	8	-0.3	5	13
ErbB2/ErbB3/neuregulin 2	0.029	0.063	-10000	0	-0.25	16	16
STAT3	0.02	0.13	-10000	0	-0.83	8	8
cell migration	0.013	0.062	0.22	14	-0.16	1	15
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	0	0.24	0.38	2	-0.59	47	49
FOS	0.023	0.15	0.32	2	-0.33	47	49
NRAS	0.033	0.008	-10000	0	-10000	0	0
mol:Ca2+	0.023	0.066	-10000	0	-0.23	17	17
MAPK3	0.009	0.19	0.38	2	-0.46	44	46
MAPK1	0.005	0.2	0.38	2	-0.47	45	47
JAK2	-0.008	0.059	-10000	0	-0.22	15	15
NF2	0.016	0.008	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.011	0.057	-10000	0	-0.23	16	16
NRG1	0.025	0.043	-10000	0	-0.42	3	3
GRB2/SOS1	0.05	0.011	-10000	0	-10000	0	0
MAPK8	0.018	0.068	0.22	3	-0.25	13	16
MAPK9	0.003	0.055	0.2	10	-10000	0	10
ERBB2	-0.023	0.007	-10000	0	-10000	0	0
ERBB3	0.017	0.087	-10000	0	-0.42	14	14
SHC1	0.031	0.011	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
apoptosis	-0.002	0.007	-10000	0	-10000	0	0
STAT3 (dimer)	0.021	0.13	-10000	0	-0.81	8	8
RNF41	-0.006	0.005	-10000	0	-10000	0	0
FRAP1	-0.002	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.005	0.04	-10000	0	-0.17	13	13
ErbB2/ErbB2/HSP90 (dimer)	0.017	0.018	-10000	0	-10000	0	0
CHRNA1	-0.014	0.25	0.36	2	-0.63	48	50
myelination	-0.012	0.054	0.24	3	-10000	0	3
PPP3CB	-0.003	0.055	-10000	0	-0.21	17	17
KRAS	0.034	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.049	0.066	-10000	0	-0.21	13	13
NRG2	0.029	0.042	-10000	0	-0.42	3	3
mol:GDP	0.011	0.057	-10000	0	-0.23	16	16
SOS1	0.035	0.003	-10000	0	-10000	0	0
MAP2K2	0.016	0.1	0.25	12	-0.3	8	20
SRC	0.033	0.009	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.003	0.059	-10000	0	-0.22	17	17
MAP2K1	0.017	0.17	0.35	1	-0.56	9	10
heart morphogenesis	0.023	0.066	-10000	0	-0.23	17	17
RAS family/GDP	0.06	0.081	-10000	0	-0.23	8	8
GRB2	0.034	0.007	-10000	0	-10000	0	0
PRKACA	0.021	0.007	-10000	0	-10000	0	0
CHRNE	0.016	0.019	0.099	2	-10000	0	2
HSP90AA1	0.033	0.024	-10000	0	-0.42	1	1
activation of caspase activity	-0.009	0.005	-10000	0	-10000	0	0
nervous system development	0.023	0.066	-10000	0	-0.23	17	17
CDC42	0.035	0.005	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.024	0.11	-10000	0	-0.37	25	25
HDAC1	0.03	0.024	-10000	0	-0.42	1	1
AES	0.034	0.004	-10000	0	-10000	0	0
FBXW11	0.033	0.008	-10000	0	-10000	0	0
DTX1	-0.067	0.19	-10000	0	-0.42	82	82
LRP6/FZD1	0.046	0.017	-10000	0	-10000	0	0
TLE1	0.031	0.025	-10000	0	-0.42	1	1
AP1	0.02	0.037	-10000	0	-0.22	6	6
NCSTN	0.032	0.011	-10000	0	-10000	0	0
ADAM10	0.034	0.006	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.051	0.053	-10000	0	-0.55	2	2
NICD/RBPSUH	0.032	0.12	-10000	0	-0.38	24	24
WIF1	0.022	0.012	-10000	0	-10000	0	0
NOTCH1	0.007	0.11	-10000	0	-0.4	24	24
PSENEN	0.035	0.004	-10000	0	-10000	0	0
KREMEN2	-0.027	0.16	-10000	0	-0.42	50	50
DKK1	-0.023	0.14	-10000	0	-0.42	42	42
beta catenin/beta TrCP1	0.058	0.058	0.38	2	-10000	0	2
APH1B	0.031	0.041	-10000	0	-0.42	3	3
APH1A	0.032	0.011	-10000	0	-10000	0	0
AXIN1	0.012	0.055	0.3	2	-0.32	1	3
CtBP/CBP/TCF1/TLE1/AES	0.017	0.04	-10000	0	-0.21	2	2
PSEN1	0.035	0.005	-10000	0	-10000	0	0
FOS	0.033	0.008	-10000	0	-10000	0	0
JUN	0.031	0.011	-10000	0	-10000	0	0
MAP3K7	0.03	0.01	-10000	0	-10000	0	0
CTNNB1	0.04	0.062	0.3	5	-10000	0	5
MAPK3	0.035	0.004	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.019	0.11	-10000	0	-0.25	52	52
HNF1A	0.033	0.006	-10000	0	-10000	0	0
CTBP1	0.033	0.007	-10000	0	-10000	0	0
MYC	0.031	0.018	-10000	0	-10000	0	0
NKD1	0.024	0.058	-10000	0	-0.42	6	6
FZD1	0.032	0.011	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.014	0.15	-10000	0	-0.44	27	27
apoptosis	0.02	0.037	-10000	0	-0.22	6	6
Delta 1/NOTCHprecursor	0.027	0.11	-10000	0	-0.37	25	25
DLL1	0.028	0.035	-10000	0	-0.42	2	2
PPARD	0.029	0.041	-10000	0	-0.67	1	1
Gamma Secretase	0.088	0.044	-10000	0	-0.2	2	2
APC	-0.002	0.099	0.3	2	-0.45	11	13
DVL1	0.025	0.046	-10000	0	-0.38	3	3
CSNK2A1	0.034	0.008	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.016	0.14	-10000	0	-0.27	79	79
LRP6	0.034	0.006	-10000	0	-10000	0	0
CSNK1A1	0.033	0.009	-10000	0	-10000	0	0
NLK	0.014	0.006	-10000	0	-10000	0	0
CCND1	0.025	0.085	-10000	0	-0.76	4	4
WNT1	-0.003	0.12	-10000	0	-0.42	28	28
Axin1/APC/beta catenin	0.044	0.11	0.35	7	-0.42	6	13
DKK2	0.029	0.042	-10000	0	-0.42	3	3
NOTCH1 precursor/DVL1	0.017	0.13	-10000	0	-0.48	14	14
GSK3B	0.034	0.006	-10000	0	-10000	0	0
FRAT1	0.03	0.025	-10000	0	-0.42	1	1
NOTCH/Deltex homolog 1	-0.018	0.15	-10000	0	-0.44	27	27
PPP2R5D	0.027	0.033	0.25	5	-10000	0	5
MAPK1	0.033	0.009	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.047	0.078	-10000	0	-0.23	23	23
RBPJ	0.034	0.006	-10000	0	-10000	0	0
CREBBP	0.038	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.008	0.14	-10000	0	-0.27	68	68
Ran/GTP/Exportin 1/HDAC1	0.009	0.011	-10000	0	-0.19	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.001	0.15	0.24	1	-0.3	57	58
SUMO1	0.035	0.003	-10000	0	-10000	0	0
ZFPM1	0.032	0.025	-10000	0	-0.42	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.019	0.007	-10000	0	-10000	0	0
FKBP3	0.035	0.004	-10000	0	-10000	0	0
Histones	0.038	0.11	-10000	0	-0.31	13	13
YY1/LSF	0.04	0.057	0.19	2	-0.22	9	11
SMG5	0.032	0.01	-10000	0	-10000	0	0
RAN	0.034	0.006	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	-0.007	0.089	-10000	0	-0.21	57	57
I kappa B alpha/HDAC1	0.01	0.1	-10000	0	-0.34	12	12
SAP18	0.034	0.007	-10000	0	-10000	0	0
RELA	0.006	0.087	0.28	1	-0.19	44	45
HDAC1/Smad7	0.062	0.024	-10000	0	-10000	0	0
RANGAP1	0.032	0.011	-10000	0	-10000	0	0
HDAC3/TR2	0.011	0.1	-10000	0	-0.35	12	12
NuRD/MBD3 Complex	0.037	0.047	-10000	0	-0.33	1	1
NF kappa B1 p50/RelA	0.015	0.12	0.27	3	-0.34	15	18
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.033	0.008	-10000	0	-10000	0	0
GATA1	0.017	0.002	-10000	0	-10000	0	0
Mad/Max	0.051	0.009	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.033	0.07	-10000	0	-0.28	10	10
RBBP7	0.035	0.003	-10000	0	-10000	0	0
NPC	0.021	0.002	-10000	0	-10000	0	0
RBBP4	0.035	0.005	-10000	0	-10000	0	0
MAX	0.035	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.033	0.008	-10000	0	-10000	0	0
NFKBIA	-0.011	0.089	-10000	0	-0.19	66	66
KAT2B	0.032	0.034	-10000	0	-0.42	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.036	0.031	-10000	0	-0.34	1	1
SIN3 complex	0.081	0.028	-10000	0	-10000	0	0
SMURF1	0.032	0.01	-10000	0	-10000	0	0
CHD3	0.033	0.009	-10000	0	-10000	0	0
SAP30	0.034	0.005	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.033	0.009	-10000	0	-10000	0	0
YY1/HDAC3	0.006	0.078	-10000	0	-0.36	7	7
YY1/HDAC2	0.042	0.04	0.19	2	-0.2	2	4
YY1/HDAC1	0.043	0.046	0.19	2	-0.21	3	5
NuRD/MBD2 Complex (MeCP1)	0.037	0.05	-10000	0	-0.33	2	2
PPARG	-0.022	0.15	-10000	0	-0.3	71	71
HDAC8/hEST1B	0.064	0.022	-10000	0	-10000	0	0
UBE2I	0.035	0.003	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.033	0.008	-10000	0	-10000	0	0
TNFRSF1A	0.034	0.007	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.011	0.1	-10000	0	-0.35	12	12
MBD3L2	0.017	0.002	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.062	0.024	-10000	0	-10000	0	0
CREBBP	0.035	0.004	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.042	0.056	-10000	0	-0.32	1	1
HDAC1	0.033	0.024	-10000	0	-0.42	1	1
HDAC3	-0.003	0.069	-10000	0	-0.38	1	1
HDAC2	0.031	0.012	-10000	0	-10000	0	0
YY1	0.024	0.022	-10000	0	-0.23	2	2
HDAC8	0.035	0	-10000	0	-10000	0	0
SMAD7	0.034	0.005	-10000	0	-10000	0	0
NCOR2	0.034	0.006	-10000	0	-10000	0	0
MXD1	0.035	0.003	-10000	0	-10000	0	0
STAT3	0.027	0.01	-10000	0	-10000	0	0
NFKB1	0.034	0.006	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.035	0.003	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.055	0.06	-10000	0	-0.21	10	10
YY1/SAP30/HDAC1	0.06	0.047	-10000	0	-0.19	3	3
EP300	0.032	0.011	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.027	0.01	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.011	0.089	-10000	0	-0.18	66	66
histone deacetylation	0.034	0.058	-10000	0	-0.26	7	7
STAT3 (dimer non-phopshorylated)/HDAC3	0.02	0.072	-10000	0	-0.34	3	3
nuclear export	-0.064	0.021	-10000	0	-10000	0	0
PRKACA	0.035	0.003	-10000	0	-10000	0	0
GATAD2B	0.032	0.011	-10000	0	-10000	0	0
GATAD2A	0.035	0.004	-10000	0	-10000	0	0
GATA2/HDAC3	0.008	0.1	-10000	0	-0.36	12	12
GATA1/HDAC1	0.037	0.019	-10000	0	-0.3	1	1
GATA1/HDAC3	-0.002	0.1	-10000	0	-0.36	12	12
CHD4	0.034	0.007	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	-0.019	0.13	-10000	0	-0.3	68	68
SIN3/HDAC complex/Mad/Max	0.033	0.044	-10000	0	-0.33	1	1
NuRD Complex	0.044	0.058	-10000	0	-0.3	2	2
positive regulation of chromatin silencing	0.035	0.11	-10000	0	-0.31	13	13
SIN3B	0.035	0.003	-10000	0	-10000	0	0
MTA2	0.034	0.005	-10000	0	-10000	0	0
SIN3A	0.034	0.007	-10000	0	-10000	0	0
XPO1	0.035	0.002	-10000	0	-10000	0	0
SUMO1/HDAC1	0.058	0.033	-10000	0	-0.18	1	1
HDAC complex	0.077	0.035	-10000	0	-0.23	1	1
GATA1/Fog1	0.036	0.02	-10000	0	-0.3	1	1
FKBP25/HDAC1/HDAC2	0.061	0.03	-10000	0	-0.25	1	1
TNF	-0.054	0.18	-10000	0	-0.42	69	69
negative regulation of cell growth	0.031	0.051	-10000	0	-0.25	5	5
NuRD/MBD2/PRMT5 Complex	0.037	0.05	-10000	0	-0.33	2	2
Ran/GTP/Exportin 1	0.06	0.03	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.023	0.13	-10000	0	-0.28	66	66
SIN3/HDAC complex/NCoR1	0.029	0.04	-10000	0	-0.23	1	1
TFCP2	0.026	0.062	-10000	0	-0.42	7	7
NR2C1	0.034	0.006	-10000	0	-10000	0	0
MBD3	0.032	0.034	-10000	0	-0.42	2	2
MBD2	0.035	0.005	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.022	0.022	-10000	0	-10000	0	0
CDKN2C	0.025	0.018	-10000	0	-10000	0	0
CDKN2A	0.01	0.017	-10000	0	-10000	0	0
CCND2	-0.002	0.017	0.1	1	-0.11	2	3
RB1	-0.001	0.019	-10000	0	-0.24	1	1
CDK4	0	0.012	0.12	1	-10000	0	1
CDK6	-0.001	0.018	-10000	0	-0.13	3	3
G1/S progression	0.027	0.067	0.18	59	-0.14	1	60

×

Aurora B signaling

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
Condensin I complex	0.022	0.048	-10000	0	-0.19	11	11
STMN1	0.017	0.024	-10000	0	-0.29	2	2
Aurora B/RasGAP/Survivin	0.061	0.034	-10000	0	-0.25	2	2
Chromosomal passenger complex/Cul3 protein complex	0.002	0.069	-10000	0	-0.28	11	11
BIRC5	0.035	0.007	-10000	0	-10000	0	0
DES	-0.057	0.24	-10000	0	-0.61	55	55
Aurora C/Aurora B/INCENP	0.003	0.12	-10000	0	-0.22	74	74
Aurora B/TACC1	0.042	0.021	-10000	0	-0.24	1	1
Aurora B/PP2A	0.043	0.027	-10000	0	-0.29	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.013	0.009	-10000	0	-0.13	1	1
mitotic metaphase/anaphase transition	0	0.003	-10000	0	-10000	0	0
NDC80	0.015	0.033	-10000	0	-0.3	4	4
Cul3 protein complex	0.038	0.059	-10000	0	-0.24	10	10
KIF2C	0.022	0.022	-10000	0	-10000	0	0
PEBP1	0.035	0.006	-10000	0	-10000	0	0
KIF20A	0.032	0.025	-10000	0	-0.42	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.045	0.03	-10000	0	-0.3	2	2
SEPT1	-0.097	0.2	-10000	0	-0.42	107	107
SMC2	0.032	0.025	-10000	0	-0.42	1	1
SMC4	0.034	0.006	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.002	0.15	0.26	1	-0.52	27	28
PSMA3	0.035	0.005	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.003	-10000	0	-10000	0	0
H3F3B	0.018	0.017	-10000	0	-0.28	1	1
AURKB	0.033	0.026	-10000	0	-0.42	1	1
AURKC	-0.056	0.18	-10000	0	-0.42	73	73
CDCA8	0.036	0.005	-10000	0	-10000	0	0
cytokinesis	0.031	0.054	0.2	2	-0.3	5	7
Aurora B/Septin1	-0.007	0.14	0.31	1	-0.37	17	18
AURKA	0.033	0.01	-10000	0	-10000	0	0
INCENP	0.035	0.006	-10000	0	-10000	0	0
KLHL13	0.017	0.074	-10000	0	-0.42	10	10
BUB1	0.036	0.004	-10000	0	-10000	0	0
hSgo1/Aurora B/Survivin	0.059	0.031	-10000	0	-0.23	2	2
EVI5	0.035	0.007	-10000	0	-10000	0	0
RhoA/GTP	0.064	0.061	-10000	0	-0.25	3	3
SGOL1	0.033	0.024	-10000	0	-0.42	1	1
CENPA	0.021	0.059	-10000	0	-0.24	9	9
NCAPG	0.031	0.034	-10000	0	-0.42	2	2
Aurora B/HC8 Proteasome	0.048	0.023	-10000	0	-0.29	1	1
NCAPD2	0.034	0.007	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.048	0.023	-10000	0	-0.29	1	1
RHOA	0.035	0.005	-10000	0	-10000	0	0
NCAPH	0.034	0.024	-10000	0	-0.42	1	1
NPM1	-0.011	0.13	-10000	0	-0.38	28	28
RASA1	0.032	0.025	-10000	0	-0.42	1	1
KLHL9	0.029	0.014	-10000	0	-10000	0	0
mitotic prometaphase	0	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.047	0.023	-10000	0	-0.29	1	1
PPP1CC	0.034	0.006	-10000	0	-10000	0	0
Centraspindlin	0.054	0.061	-10000	0	-0.23	7	7
RhoA/GDP	0.026	0.004	-10000	0	-10000	0	0
NSUN2	-0.008	0.14	-10000	0	-0.42	25	25
MYLK	0.016	0.032	-10000	0	-0.28	4	4
KIF23	0.034	0.024	-10000	0	-0.42	1	1
VIM	0.017	0.018	-10000	0	-0.29	1	1
RACGAP1	0.036	0.006	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.001	0.092	-10000	0	-0.29	27	27
Chromosomal passenger complex	0.021	0.048	-10000	0	-0.23	7	7
Chromosomal passenger complex/EVI5	0.089	0.044	-10000	0	-0.23	1	1
TACC1	0.034	0.008	-10000	0	-10000	0	0
PPP2R5D	0.032	0.011	-10000	0	-10000	0	0
CUL3	0.035	0.005	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.035	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.051	0.093	0.28	5	-0.3	7	12
ERC1	0.034	0.007	-10000	0	-10000	0	0
RIP2/NOD2	0.031	0.07	-10000	0	-0.3	15	15
NFKBIA	0.023	0.028	0.22	7	-10000	0	7
BIRC2	0.028	0.042	-10000	0	-0.42	3	3
IKBKB	0.034	0.007	-10000	0	-10000	0	0
RIPK2	0.032	0.011	-10000	0	-10000	0	0
IKBKG	0.033	0.067	-10000	0	-0.39	4	4
IKK complex/A20	0.015	0.15	-10000	0	-0.38	25	25
NEMO/A20/RIP2	0.032	0.011	-10000	0	-10000	0	0
XPO1	0.035	0.002	-10000	0	-10000	0	0
NEMO/ATM	0.04	0.099	-10000	0	-0.35	17	17
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.034	0.006	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.046	0.008	-10000	0	-10000	0	0
IKK complex/ELKS	0.044	0.099	-10000	0	-0.32	17	17
BCL10/MALT1/TRAF6	0.066	0.024	-10000	0	-0.25	1	1
NOD2	0.01	0.1	-10000	0	-0.42	19	19
NFKB1	0.037	0.006	-10000	0	-10000	0	0
RELA	0.036	0.007	-10000	0	-10000	0	0
MALT1	0.033	0.024	-10000	0	-0.42	1	1
cIAP1/UbcH5C	0.044	0.035	-10000	0	-0.3	3	3
ATM	0.032	0.011	-10000	0	-10000	0	0
TNF/TNFR1A	-0.019	0.13	-10000	0	-0.3	68	68
TRAF6	0.034	0.006	-10000	0	-10000	0	0
PRKCA	0.032	0.025	-10000	0	-0.42	1	1
CHUK	0.032	0.01	-10000	0	-10000	0	0
UBE2D3	0.034	0.006	-10000	0	-10000	0	0
TNF	-0.054	0.18	-10000	0	-0.42	69	69
NF kappa B1 p50/RelA	0.073	0.027	-10000	0	-10000	0	0
BCL10	0.034	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.028	0.22	7	-10000	0	7
beta TrCP1/SCF ubiquitin ligase complex	0.035	0.009	-10000	0	-10000	0	0
TNFRSF1A	0.034	0.007	-10000	0	-10000	0	0
IKK complex	0.049	0.1	-10000	0	-0.34	17	17
CYLD	0.034	0.007	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.056	0.11	-10000	0	-0.34	14	14

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.034	0.006	-10000	0	-10000	0	0
VLDLR	0.021	0.066	-10000	0	-0.42	8	8
LRPAP1	0.034	0.007	-10000	0	-10000	0	0
NUDC	0.035	0.004	-10000	0	-10000	0	0
RELN/LRP8	0.043	0.038	-10000	0	-10000	0	0
CaM/Ca2+	0.025	0.004	-10000	0	-10000	0	0
KATNA1	0.031	0.012	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	0.032	0.056	0.19	40	-10000	0	40
IQGAP1/CaM	0.049	0.013	-10000	0	-10000	0	0
DAB1	0.021	0.012	-10000	0	-10000	0	0
IQGAP1	0.034	0.006	-10000	0	-10000	0	0
PLA2G7	-0.078	0.19	-10000	0	-0.42	89	89
CALM1	0.034	0.006	-10000	0	-10000	0	0
DYNLT1	0.031	0.011	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.049	0.012	-10000	0	-10000	0	0
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.034	0.006	-10000	0	-10000	0	0
CDK5R1	0.033	0.024	-10000	0	-0.42	1	1
LIS1/Poliovirus Protein 3A	0.013	0.005	-10000	0	-10000	0	0
CDK5R2	0.026	0.015	-10000	0	-10000	0	0
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.024	0.053	-10000	0	-0.25	7	7
YWHAE	0.033	0.009	-10000	0	-10000	0	0
NDEL1/14-3-3 E	0.057	0.086	0.32	28	-10000	0	28
MAP1B	0.007	0.005	-10000	0	-10000	0	0
RAC1	0.016	0.009	-10000	0	-10000	0	0
p35/CDK5	0.028	0.031	0.19	9	-0.21	1	10
RELN	0.024	0.016	-10000	0	-10000	0	0
PAFAH/LIS1	-0.031	0.12	-10000	0	-0.24	84	84
LIS1/CLIP170	0.035	0.014	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0.038	0.036	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	0.003	0.072	-10000	0	-0.22	23	23
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	0.028	0.068	0.28	20	-0.2	1	21
LIS1/IQGAP1	0.035	0.014	-10000	0	-10000	0	0
RHOA	0.018	0.008	-10000	0	-10000	0	0
PAFAH1B1	0.017	0.006	-10000	0	-10000	0	0
PAFAH1B3	0.035	0.004	-10000	0	-10000	0	0
PAFAH1B2	0.032	0.011	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.024	0.035	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	0.065	0.081	0.32	24	-10000	0	24
LRP8	0.035	0.004	-10000	0	-10000	0	0
NDEL1/Katanin 60	0.052	0.082	0.32	24	-10000	0	24
P39/CDK5	0.019	0.033	0.19	9	-10000	0	9
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.036	0.014	-10000	0	-10000	0	0
CDK5	-0.003	0.032	0.19	10	-10000	0	10
PPP2R5D	0.032	0.011	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.031	0.012	-10000	0	-10000	0	0
CSNK2A1	0.033	0.008	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	0.033	0.051	-10000	0	-0.22	7	7
RELN/VLDLR	0.051	0.055	-10000	0	-0.23	7	7
CDC42	0.018	0.008	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0	0.037	-10000	0	-0.25	8	8
SNTA1	0.032	0.01	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	0	0.04	-10000	0	-0.25	9	9
MAPK12	-0.004	0.04	-10000	0	-0.24	10	10
CCND1	0.014	0.044	-10000	0	-0.33	3	3
p38 gamma/SNTA1	0.028	0.063	0.2	23	-0.22	11	34
MAP2K3	0.033	0.008	-10000	0	-10000	0	0
PKN1	0.034	0.024	-10000	0	-0.42	1	1
G2/M transition checkpoint	0	0.049	0.21	7	-0.24	10	17
MAP2K6	0.001	0.033	-10000	0	-0.24	7	7
MAPT	0.008	0.076	0.2	6	-0.3	10	16
MAPK13	0.01	0.046	-10000	0	-0.3	8	8
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.009	0.016	-10000	0	-0.29	1	1

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.009	0.003	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.035	0.027	-10000	0	-0.3	1	1
STXBP1	0.033	0.009	-10000	0	-10000	0	0
ACh/CHRNA1	-0.011	0.096	-10000	0	-0.25	47	47
RAB3GAP2/RIMS1/UNC13B	0.045	0.034	-10000	0	-0.26	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.022	0.012	-10000	0	-10000	0	0
mol:ACh	0.006	0.031	0.089	31	-0.11	2	33
RAB3GAP2	0.032	0.011	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.039	0.041	-10000	0	-0.19	1	1
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.011	0.096	-10000	0	-0.25	47	47
UNC13B	0.03	0.026	-10000	0	-0.42	1	1
CHRNA1	-0.026	0.15	-10000	0	-0.42	48	48
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.022	0.03	0.11	3	-0.14	3	6
SNAP25	0.005	0.004	-10000	0	-10000	0	0
VAMP2	0.006	0.002	-10000	0	-10000	0	0
SYT1	0.027	0.027	-10000	0	-0.42	1	1
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.027	0.014	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.039	0.041	-10000	0	-0.19	1	1

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.035	0.004	-10000	0	-10000	0	0
mol:PIP3	0.007	0.021	-10000	0	-0.17	3	3
FRAP1	0.019	0.068	-10000	0	-0.38	8	8
AKT1	0.021	0.052	0.16	41	-0.19	1	42
INSR	0.035	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.034	0.007	-10000	0	-10000	0	0
mol:GTP	0.052	0.05	0.24	1	-10000	0	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.015	0.025	-10000	0	-0.16	1	1
TSC2	0.035	0.003	-10000	0	-10000	0	0
RHEB/GDP	0.025	0.024	-10000	0	-10000	0	0
TSC1	0.033	0.009	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.027	0.032	-10000	0	-0.19	6	6
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.043	0.04	-10000	0	-0.18	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.032	0.01	-10000	0	-10000	0	0
RPS6KB1	0.04	0.066	0.22	5	-0.27	4	9
MAP3K5	-0.015	0.065	-10000	0	-0.18	46	46
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
apoptosis	-0.015	0.064	-10000	0	-0.18	46	46
mol:LY294002	0	0	-10000	0	-0.001	5	5
EIF4B	0.037	0.061	0.21	5	-0.24	4	9
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.054	0.057	0.22	3	-0.23	3	6
eIF4E/eIF4G1/eIF4A1	0.021	0.041	-10000	0	-0.25	4	4
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.049	0.032	-10000	0	-0.16	6	6
mTOR/RHEB/GTP/Raptor/GBL	0.019	0.042	0.17	8	-10000	0	8
FKBP1A	0.034	0.008	-10000	0	-10000	0	0
RHEB/GTP	0.048	0.044	0.22	1	-10000	0	1
mol:Amino Acids	0	0	-10000	0	-0.001	5	5
FKBP12/Rapamycin	0.025	0.006	-10000	0	-10000	0	0
PDPK1	-0.004	0.027	0.16	5	-0.19	1	6
EIF4E	0.034	0.006	-10000	0	-10000	0	0
ASK1/PP5C	-0.022	0.21	-10000	0	-0.56	47	47
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.018	0.048	-10000	0	-0.25	1	1
TSC1/TSC2	0.057	0.054	0.26	1	-10000	0	1
tumor necrosis factor receptor activity	0	0	0.001	5	-10000	0	5
RPS6	0.031	0.012	-10000	0	-10000	0	0
PPP5C	0.035	0.004	-10000	0	-10000	0	0
EIF4G1	0.034	0.006	-10000	0	-10000	0	0
IRS1	0.007	0.029	-10000	0	-0.2	6	6
INS	0.017	0.003	-10000	0	-10000	0	0
PTEN	0.03	0.012	-10000	0	-10000	0	0
PDK2	-0.004	0.027	0.16	5	-0.19	1	6
EIF4EBP1	0.001	0.18	-10000	0	-1	11	11
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
PPP2R5D	0.034	0.082	0.25	6	-0.35	8	14
peptide biosynthetic process	0.017	0.013	0.18	2	-10000	0	2
RHEB	0.031	0.011	-10000	0	-10000	0	0
EIF4A1	0.033	0.009	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	7	-10000	0	7
EEF2	0.017	0.013	0.18	2	-10000	0	2
eIF4E/4E-BP1	0.018	0.17	-10000	0	-0.97	11	11

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.058	0.08	-10000	0	-0.48	5	5
oxygen homeostasis	0.009	0.008	-10000	0	-10000	0	0
TCEB2	0.034	0.024	-10000	0	-0.42	1	1
TCEB1	0.032	0.011	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.1	0.069	-10000	0	-10000	0	0
EPO	0.11	0.1	-10000	0	-10000	0	0
FIH (dimer)	0.038	0.028	-10000	0	-0.41	1	1
APEX1	0.043	0.017	-10000	0	-10000	0	0
SERPINE1	0.12	0.11	0.37	11	-0.37	1	12
FLT1	0.024	0.16	-10000	0	-0.53	21	21
ADORA2A	0.11	0.13	0.36	18	-0.41	9	27
germ cell development	0.11	0.11	0.37	7	-0.36	1	8
SLC11A2	0.13	0.11	0.37	11	-0.37	1	12
BHLHE40	0.13	0.11	0.37	13	-0.37	1	14
HIF1AN	0.038	0.028	-10000	0	-0.41	1	1
HIF2A/ARNT/SIRT1	0.11	0.086	0.33	1	-10000	0	1
ETS1	0.043	0.016	-10000	0	-10000	0	0
CITED2	0.01	0.16	-10000	0	-0.5	24	24
KDR	0.021	0.16	-10000	0	-0.56	13	13
PGK1	0.13	0.11	0.37	15	-0.37	1	16
SIRT1	0.032	0.01	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.17	0.13	-10000	0	-0.41	1	1
EPAS1	0.068	0.058	0.2	19	-10000	0	19
SP1	0.041	0.006	-10000	0	-10000	0	0
ABCG2	0.12	0.15	0.37	12	-0.41	18	30
EFNA1	0.12	0.1	0.35	1	-0.37	1	2
FXN	0.12	0.11	0.36	18	-0.36	1	19
POU5F1	0.12	0.11	0.37	7	-0.37	1	8
neuron apoptosis	-0.16	0.13	0.4	1	-0.44	1	2
EP300	0.032	0.011	-10000	0	-10000	0	0
EGLN3	0.04	0.035	-10000	0	-0.41	2	2
EGLN2	0.042	0.013	-10000	0	-10000	0	0
EGLN1	0.04	0.015	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.062	0.029	-10000	0	-0.25	1	1
VHL	0.035	0.005	-10000	0	-10000	0	0
ARNT	0.04	0.017	-10000	0	-10000	0	0
SLC2A1	0.12	0.11	0.36	19	-0.36	1	20
TWIST1	0.087	0.1	0.37	6	-0.36	1	7
ELK1	0.041	0.004	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.11	0.093	-10000	0	-10000	0	0
VEGFA	0.12	0.11	0.37	8	-0.37	1	9
CREBBP	0.035	0.004	-10000	0	-10000	0	0

×

Glypican 2 network

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
MDK	0.029	0.041	-9999	-0.42	3	3
GPC2	0.025	0.058	-9999	-0.42	6	6
GPC2/Midkine	0.036	0.056	-9999	-0.3	9	9
neuron projection morphogenesis	0.036	0.056	-9999	-0.3	9	9

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.028	0.048	-10000	0	-0.42	4	4
HRAS	0.034	0.006	-10000	0	-10000	0	0
EGFR	0.027	0.035	-10000	0	-0.42	2	2
AKT	0.062	0.079	0.26	20	-0.19	1	21
FOXO3	0.031	0.012	-10000	0	-10000	0	0
AKT1	0.034	0.005	-10000	0	-10000	0	0
FOXO1	0.034	0.007	-10000	0	-10000	0	0
AKT3	0.031	0.011	-10000	0	-10000	0	0
FOXO4	0.035	0	-10000	0	-10000	0	0
MET	0.006	0.1	-10000	0	-0.42	20	20
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
PIK3CB	0.034	0.006	-10000	0	-10000	0	0
NRAS	0.034	0.008	-10000	0	-10000	0	0
PIK3CG	-0.023	0.15	-10000	0	-0.42	44	44
PIK3R3	0.035	0.005	-10000	0	-10000	0	0
PIK3R2	0.035	0.003	-10000	0	-10000	0	0
NF1	0.034	0.007	-10000	0	-10000	0	0
RAS	0.021	0.044	-10000	0	-10000	0	0
ERBB2	0.034	0.006	-10000	0	-10000	0	0
proliferation/survival/translation	-0.039	0.078	0.23	13	-0.21	1	14
PI3K	0.039	0.082	0.23	31	-0.22	5	36
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
KRAS	0.034	0.006	-10000	0	-10000	0	0
FOXO	0.082	0.069	0.23	31	-10000	0	31
AKT2	0.035	0.004	-10000	0	-10000	0	0
PTEN	0.03	0.012	-10000	0	-10000	0	0

×

Insulin 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.045	0.053	-10000	0	-0.2	11	11
TC10/GTP	0.043	0.051	-10000	0	-0.19	11	11
Insulin Receptor/Insulin/IRS1/Shp2	0.074	0.028	-10000	0	-10000	0	0
HRAS	0.034	0.006	-10000	0	-10000	0	0
APS homodimer	0.023	0.062	-10000	0	-0.42	7	7
GRB14	0.027	0.013	-10000	0	-10000	0	0
FOXO3	-0.042	0.22	-10000	0	-0.61	45	45
AKT1	0	0.042	0.21	2	-10000	0	2
INSR	0.039	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.073	0.039	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.031	0.011	-10000	0	-10000	0	0
SORBS1	0.027	0.048	-10000	0	-0.42	4	4
CRK	0.033	0.009	-10000	0	-10000	0	0
PTPN1	0.01	0.016	-10000	0	-10000	0	0
CAV1	0.02	0.025	0.17	6	-10000	0	6
CBL/APS/CAP/Crk-II/C3G	0.068	0.066	-10000	0	-0.2	11	11
Insulin Receptor/Insulin/IRS1/NCK2	0.076	0.027	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.06	0.025	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.039	0.044	-10000	0	-0.32	3	3
RPS6KB1	-0.003	0.037	0.2	2	-10000	0	2
PARD6A	0.034	0.007	-10000	0	-10000	0	0
CBL	0.032	0.011	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.021	0.045	-10000	0	-0.56	2	2
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.045	0.032	0.19	2	-10000	0	2
HRAS/GTP	-0.002	0.066	-10000	0	-0.19	32	32
Insulin Receptor	0.039	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.078	0.04	-10000	0	-10000	0	0
PRKCI	0.046	0.033	-10000	0	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	0.036	0.018	-10000	0	-10000	0	0
SHC1	0.032	0.011	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.053	0.049	-10000	0	-0.48	2	2
PI3K	0.073	0.03	-10000	0	-10000	0	0
NCK2	0.035	0.003	-10000	0	-10000	0	0
RHOQ	0.035	0.003	-10000	0	-10000	0	0
mol:H2O2	0	0.003	-10000	0	-10000	0	0
HRAS/GDP	0.025	0.004	-10000	0	-10000	0	0
AKT2	0	0.041	0.21	2	-10000	0	2
PRKCZ	0.036	0.067	-10000	0	-0.32	10	10
SH2B2	0.023	0.062	-10000	0	-0.42	7	7
SHC/SHIP	0.01	0.082	0.19	3	-0.2	43	46
F2RL2	-0.014	0.14	-10000	0	-0.42	37	37
TRIP10	0.035	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.053	0.024	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.047	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.083	0.039	-10000	0	-10000	0	0
RAPGEF1	0.033	0.009	-10000	0	-10000	0	0
RASA1	0.032	0.025	-10000	0	-0.42	1	1
NCK1	0.034	0.006	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.058	0.063	-10000	0	-0.22	11	11
TC10/GDP	0.026	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.065	0.036	-10000	0	-10000	0	0
INPP5D	-0.015	0.088	0.18	3	-0.21	57	60
SOS1	0.035	0.003	-10000	0	-10000	0	0
SGK1	-0.06	0.22	-10000	0	-0.65	45	45
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.034	0.006	-10000	0	-10000	0	0
IRS1	0.032	0.011	-10000	0	-10000	0	0
p62DOK/RasGAP	0.053	0.049	-10000	0	-0.48	2	2
INS	0.022	0.009	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.015	0.087	0.18	3	-0.21	57	60
GRB2	0.034	0.007	-10000	0	-10000	0	0
EIF4EBP1	-0.003	0.037	0.2	1	-10000	0	1
PTPRA	0.036	0.01	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.047	0.006	-10000	0	-10000	0	0
PDPK1	0.035	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.032	0.017	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.053	0.025	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.045	0.016	-10000	0	-10000	0	0
Par3/Par6	0.044	0.088	-10000	0	-0.21	36	36

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.02	0.066	-9999	-0.42	8	8
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.034	0.024	-9999	-0.42	1	1
TCEB1	0.032	0.011	-9999	-10000	0	0
HIF1A/p53	0.018	0.085	-9999	-0.26	28	28
HIF1A	0.003	0.078	-9999	-0.27	26	26
COPS5	0.032	0.011	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.077	0.049	-9999	-0.22	1	1
FIH (dimer)	0.031	0.025	-9999	-0.42	1	1
CDKN2A	0.009	0.016	-9999	-10000	0	0
ARNT/IPAS	0.032	0.052	-9999	-0.3	7	7
HIF1AN	0.031	0.025	-9999	-0.42	1	1
GNB2L1	0.033	0.008	-9999	-10000	0	0
HIF1A/ARNT	0.013	0.082	-9999	-0.26	27	27
CUL2	0.032	0.01	-9999	-10000	0	0
OS9	0.034	0.008	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.06	0.031	-9999	-0.25	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.02	0.087	-9999	-0.26	28	28
PHD1-3/OS9	0.074	0.041	-9999	-0.23	2	2
HIF1A/RACK1/Elongin B/Elongin C	0.044	0.084	-9999	-0.25	20	20
VHL	0.035	0.005	-9999	-10000	0	0
HSP90AA1	0.033	0.024	-9999	-0.42	1	1
HIF1A/JAB1	0.019	0.079	-9999	-0.26	21	21
EGLN3	0.032	0.034	-9999	-0.42	2	2
EGLN2	0.035	0.004	-9999	-10000	0	0
EGLN1	0.032	0.011	-9999	-10000	0	0
TP53	0.033	0.009	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.04	0.076	-9999	-0.6	4	4
ARNT	0.032	0.011	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.032	0.01	-9999	-10000	0	0
HIF1A/p19ARF	-0.009	0.073	-9999	-0.25	28	28

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.027	0.057	0.42	6	-10000	0	6
PI3K Class IB/PDE3B	0.027	0.057	-10000	0	-0.42	6	6
PDE3B	0.027	0.057	-10000	0	-0.42	6	6

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.007	0.022	0.14	6	-0.1	1	7
BUB1B	0.012	0.033	0.11	3	-0.18	2	5
PLK1	0.014	0.024	0.079	16	-0.092	4	20
PLK1S1	0.015	0.031	0.094	11	-0.2	5	16
KIF2A	0.013	0.031	0.21	5	-10000	0	5
regulation of mitotic centrosome separation	0.014	0.024	0.079	16	-0.092	4	20
GOLGA2	0.033	0.009	-10000	0	-10000	0	0
Hec1/SPC24	0.049	0.04	0.15	1	-0.18	5	6
WEE1	0.02	0.058	-10000	0	-0.31	9	9
cytokinesis	0.021	0.052	0.17	3	-0.19	11	14
PP2A-alpha B56	0.068	0.087	-10000	0	-0.53	7	7
AURKA	0.016	0.019	0.11	1	-0.17	1	2
PICH/PLK1	0.024	0.027	0.13	1	-0.18	2	3
CENPE	0.006	0.036	-10000	0	-0.19	8	8
RhoA/GTP	0.026	0.004	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.013	0.031	0.21	5	-10000	0	5
PPP2CA	0.033	0.008	-10000	0	-10000	0	0
FZR1	0.035	0.004	-10000	0	-10000	0	0
TPX2	0.018	0.022	0.12	3	-0.14	1	4
PAK1	0.033	0.009	-10000	0	-10000	0	0
SPC24	0.034	0.024	-10000	0	-0.42	1	1
FBXW11	0.033	0.008	-10000	0	-10000	0	0
CLSPN	0.016	0.031	-10000	0	-0.24	4	4
GORASP1	0.035	0.005	-10000	0	-10000	0	0
metaphase	0	0.002	0.016	5	-10000	0	5
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.006	0.013	0.044	16	-0.047	4	20
G2 phase of mitotic cell cycle	0	0.003	0.011	25	-10000	0	25
STAG2	0.035	0.002	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.024	0.067	-10000	0	-0.53	5	5
spindle elongation	0.014	0.024	0.079	16	-0.092	4	20
ODF2	0.033	0.009	-10000	0	-10000	0	0
BUB1	0.032	0.086	-10000	0	-0.57	7	7
TPT1	0.01	0.035	-10000	0	-0.16	12	12
CDC25C	0.006	0.07	-10000	0	-0.28	20	20
CDC25B	0.034	0.009	-10000	0	-10000	0	0
SGOL1	0.007	0.022	0.1	1	-0.14	6	7
RHOA	0.035	0.005	-10000	0	-10000	0	0
CCNB1/CDK1	0.049	0.033	-10000	0	-0.16	1	1
CDC14B	0.009	0.003	-10000	0	-10000	0	0
CDC20	0.035	0.004	-10000	0	-10000	0	0
PLK1/PBIP1	0.012	0.028	0.12	1	-0.17	5	6
mitosis	-0.002	0.003	0.021	2	-10000	0	2
FBXO5	0.004	0.034	0.1	1	-0.12	7	8
CDC2	0.002	0.002	-10000	0	-0.009	6	6
NDC80	0.03	0.041	-10000	0	-0.42	3	3
metaphase plate congression	0.018	0.023	-10000	0	-0.23	2	2
ERCC6L	0.027	0.034	-10000	0	-0.17	3	3
NLP/gamma Tubulin	0.009	0.016	0.082	1	-0.074	4	5
microtubule cytoskeleton organization	0.01	0.035	-10000	0	-0.16	12	12
G2/M transition DNA damage checkpoint	0	0.002	0.012	9	-10000	0	9
PPP1R12A	0.035	0.006	-10000	0	-10000	0	0
interphase	0	0.002	0.012	9	-10000	0	9
PLK1/PRC1-2	0.049	0.033	0.15	1	-0.16	2	3
GRASP65/GM130/RAB1/GTP/PLK1	0.065	0.028	-10000	0	-10000	0	0
RAB1A	0.035	0.003	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.012	0.023	0.071	28	-0.09	1	29
mitotic prometaphase	-0.001	0.002	0.018	2	-10000	0	2
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.052	-10000	0	-0.51	3	3
microtubule-based process	0.033	0.027	0.14	1	-0.23	1	2
Golgi organization	0.014	0.024	0.079	16	-0.092	4	20
Cohesin/SA2	0.029	0.023	-10000	0	-0.12	1	1
PPP1CB/MYPT1	0.05	0.011	-10000	0	-10000	0	0
KIF20A	0.032	0.025	-10000	0	-0.42	1	1
APC/C/CDC20	0.033	0.026	0.14	1	-0.12	1	2
PPP2R1A	0.035	0.004	-10000	0	-10000	0	0
chromosome segregation	0.011	0.027	0.11	1	-0.17	5	6
PRC1	0.034	0.006	-10000	0	-10000	0	0
ECT2	0.012	0.029	0.2	4	-0.12	1	5
C13orf34	0.012	0.021	0.073	16	-0.084	2	18
NUDC	0.018	0.023	-10000	0	-0.23	2	2
regulation of attachment of spindle microtubules to kinetochore	0.012	0.032	0.11	3	-0.18	2	5
spindle assembly	0.011	0.02	0.076	7	-0.081	3	10
spindle stabilization	0.015	0.031	0.093	11	-0.2	5	16
APC/C/HCDH1	0.031	0.009	-10000	0	-10000	0	0
MKLP2/PLK1	0.033	0.027	0.14	1	-0.23	1	2
CCNB1	0.035	0.007	-10000	0	-10000	0	0
PPP1CB	0.035	0.005	-10000	0	-10000	0	0
BTRC	0.032	0.01	-10000	0	-10000	0	0
ROCK2	0.023	0.034	-10000	0	-0.24	3	3
TUBG1	0.012	0.029	-10000	0	-0.16	8	8
G2/M transition of mitotic cell cycle	0.015	0.022	-10000	0	-0.15	1	1
MLF1IP	0.006	0.032	-10000	0	-0.3	4	4
INCENP	0.035	0.006	-10000	0	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.042	0.023	-10000	0	-10000	0	0
PDGFRB	0.034	0.01	-10000	0	-10000	0	0
SPHK1	0.008	0.093	-10000	0	-0.69	6	6
mol:S1P	0.011	0.084	-10000	0	-0.59	6	6
S1P1/S1P/Gi	0.023	0.074	0.24	2	-0.3	11	13
GNAO1	0.019	0.029	-10000	0	-0.42	1	1
PDGFB-D/PDGFRB/PLCgamma1	0.051	0.085	0.27	11	-0.28	7	18
PLCG1	0.015	0.068	0.25	4	-0.27	11	15
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.034	0.01	-10000	0	-10000	0	0
GNAI2	0.035	0.008	-10000	0	-10000	0	0
GNAI3	0.035	0.008	-10000	0	-10000	0	0
GNAI1	0.031	0.013	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.006	0.009	-10000	0	-10000	0	0
S1P1/S1P	0.018	0.068	0.18	1	-0.41	6	7
negative regulation of cAMP metabolic process	0.023	0.073	0.24	2	-0.29	11	13
MAPK3	0.018	0.085	0.31	3	-0.41	7	10
calcium-dependent phospholipase C activity	0	0.001	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.009	-10000	0	-10000	0	0
RhoA/GDP	0.026	0.004	-10000	0	-10000	0	0
KDR	0.034	0.008	-10000	0	-10000	0	0
PLCB2	0.035	0.092	0.24	17	-0.39	7	24
RAC1	0.031	0.012	-10000	0	-10000	0	0
RhoA/GTP	0.018	0.056	-10000	0	-0.35	6	6
receptor internalization	0.016	0.062	-10000	0	-0.39	6	6
PTGS2	0.036	0.13	0.33	9	-0.84	4	13
Rac1/GTP	0.015	0.055	-10000	0	-0.35	6	6
RHOA	0.035	0.005	-10000	0	-10000	0	0
VEGFA	0.03	0.013	-10000	0	-10000	0	0
negative regulation of T cell proliferation	0.023	0.073	0.24	2	-0.29	11	13
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.027	0.036	-10000	0	-0.42	2	2
MAPK1	0.018	0.081	0.23	2	-0.41	7	9
S1P1/S1P/PDGFB-D/PDGFRB	0.04	0.073	0.24	5	-0.36	6	11
ABCC1	0.034	0.024	-10000	0	-0.42	1	1

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.015	0.039	-10000	0	-10000	0	0
PLK1	-0.026	0.19	-10000	0	-0.75	4	4
CDKN1B	0.095	0.14	0.35	2	-0.34	16	18
FOXO3	-0.024	0.21	-10000	0	-0.53	25	25
KAT2B	0.018	0.049	-10000	0	-0.41	2	2
FOXO1/SIRT1	0.055	0.045	0.25	1	-10000	0	1
CAT	-0.025	0.19	-10000	0	-0.75	4	4
CTNNB1	0.034	0.005	-10000	0	-10000	0	0
AKT1	0.023	0.038	-10000	0	-10000	0	0
FOXO1	0.024	0.043	0.23	3	-10000	0	3
MAPK10	0.036	0.046	0.19	26	-10000	0	26
mol:GTP	0.002	0	-10000	0	-10000	0	0
FOXO4	0.068	0.064	0.3	1	-10000	0	1
response to oxidative stress	0.002	0.019	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.072	0.15	-10000	0	-0.59	5	5
XPO1	0.036	0.002	-10000	0	-10000	0	0
EP300	0.032	0.011	-10000	0	-10000	0	0
BCL2L11	0.015	0.1	-10000	0	-1.2	2	2
FOXO1/SKP2	0.039	0.037	-10000	0	-10000	0	0
mol:GDP	0.002	0.019	-10000	0	-10000	0	0
RAN	0.036	0.006	-10000	0	-10000	0	0
GADD45A	0.08	0.13	-10000	0	-0.58	3	3
YWHAQ	0.035	0.004	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.06	0.082	0.25	1	-0.3	7	8
MST1	0.02	0.044	-10000	0	-0.43	1	1
CSNK1D	0.034	0.007	-10000	0	-10000	0	0
CSNK1E	0.032	0.01	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.043	0.063	-10000	0	-0.34	4	4
YWHAB	0.033	0.01	-10000	0	-10000	0	0
MAPK8	0.045	0.05	0.2	34	-10000	0	34
MAPK9	0.045	0.05	0.2	35	-10000	0	35
YWHAG	0.032	0.01	-10000	0	-10000	0	0
YWHAE	0.033	0.009	-10000	0	-10000	0	0
YWHAZ	0.032	0.011	-10000	0	-10000	0	0
SIRT1	0.047	0.032	-10000	0	-10000	0	0
SOD2	0.05	0.16	-10000	0	-0.56	12	12
RBL2	-0.005	0.21	-10000	0	-0.75	15	15
RAL/GDP	0.048	0.021	-10000	0	-10000	0	0
CHUK	0.022	0.035	-10000	0	-10000	0	0
Ran/GTP	0.029	0.005	-10000	0	-10000	0	0
CSNK1G2	0.035	0.004	-10000	0	-10000	0	0
RAL/GTP	0.052	0.022	-10000	0	-10000	0	0
CSNK1G1	0.035	0.004	-10000	0	-10000	0	0
FASLG	-0.41	0.66	-10000	0	-1.4	119	119
SKP2	0.033	0.009	-10000	0	-10000	0	0
USP7	0.036	0.004	-10000	0	-10000	0	0
IKBKB	0.021	0.037	-10000	0	-10000	0	0
CCNB1	-0.024	0.19	-10000	0	-0.66	6	6
FOXO1-3a-4/beta catenin	0.06	0.14	-10000	0	-0.35	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.039	0.036	-10000	0	-10000	0	0
CSNK1A1	0.033	0.009	-10000	0	-10000	0	0
SGK1	0.021	0.035	-10000	0	-10000	0	0
CSNK1G3	0.033	0.008	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.052	0.009	-10000	0	-10000	0	0
ZFAND5	0.065	0.058	-10000	0	-10000	0	0
SFN	0.027	0.015	-10000	0	-10000	0	0
CDK2	0.035	0.005	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.035	0.075	-10000	0	-0.35	4	4
CREBBP	0.035	0.004	-10000	0	-10000	0	0
FBXO32	-0.008	0.2	-10000	0	-0.7	8	8
BCL6	0.008	0.18	-10000	0	-0.68	9	9
RALB	0.036	0.003	-10000	0	-10000	0	0
RALA	0.032	0.012	-10000	0	-10000	0	0
YWHAH	0.034	0.008	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.02	0.093	-10000	0	-0.76	4	4
MKNK1	0.035	0.004	-10000	0	-10000	0	0
MAPK14	0.037	0.046	-10000	0	-0.33	4	4
ATF2/c-Jun	0.032	0.042	-10000	0	-0.32	1	1
MAPK11	0.038	0.046	-10000	0	-0.33	4	4
MITF	0.018	0.073	-10000	0	-0.29	17	17
MAPKAPK5	0.03	0.048	-10000	0	-0.37	4	4
KRT8	-0.006	0.11	-10000	0	-0.29	43	43
MAPKAPK3	0.034	0.005	-10000	0	-10000	0	0
MAPKAPK2	0.031	0.011	-10000	0	-10000	0	0
p38alpha-beta/CK2	0.047	0.07	-10000	0	-0.51	4	4
CEBPB	0.028	0.048	-10000	0	-0.37	4	4
SLC9A1	0.03	0.047	-10000	0	-0.37	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.034	0.05	0.22	1	-0.36	4	5
p38alpha-beta/MNK1	0.06	0.064	-10000	0	-0.42	4	4
JUN	0.033	0.045	-10000	0	-0.32	1	1
PPARGC1A	0.013	0.067	-10000	0	-0.3	14	14
USF1	0.028	0.045	-10000	0	-0.35	4	4
RAB5/GDP/GDI1	0.042	0.042	-10000	0	-0.28	3	3
NOS2	0.027	0.071	-10000	0	-0.74	2	2
DDIT3	0.03	0.048	-10000	0	-0.37	4	4
RAB5A	0.035	0.004	-10000	0	-10000	0	0
HSPB1	0.029	0.067	0.29	16	-0.3	4	20
p38alpha-beta/HBP1	0.056	0.065	-10000	0	-0.41	4	4
CREB1	0.032	0.05	-10000	0	-0.36	4	4
RAB5/GDP	0.026	0.003	-10000	0	-10000	0	0
EIF4E	0.041	0.067	0.25	3	-0.37	4	7
RPS6KA4	0.03	0.044	-10000	0	-0.38	3	3
PLA2G4A	0.033	0.061	0.25	1	-0.29	6	7
GDI1	0.031	0.044	-10000	0	-0.38	3	3
TP53	0.016	0.06	-10000	0	-0.5	4	4
RPS6KA5	0.028	0.053	-10000	0	-0.33	6	6
ESR1	0.02	0.072	-10000	0	-0.37	10	10
HBP1	0.032	0.011	-10000	0	-10000	0	0
MEF2C	0.028	0.05	-10000	0	-0.34	5	5
MEF2A	0.03	0.048	-10000	0	-0.37	4	4
EIF4EBP1	0.03	0.056	-10000	0	-0.41	4	4
KRT19	0.024	0.05	-10000	0	-0.35	5	5
ELK4	0.028	0.046	-10000	0	-0.35	4	4
ATF6	0.028	0.046	-10000	0	-0.35	4	4
ATF1	0.031	0.05	-10000	0	-0.36	4	4
p38alpha-beta/MAPKAPK2	0.057	0.06	-10000	0	-0.37	4	4
p38alpha-beta/MAPKAPK3	0.061	0.064	-10000	0	-0.41	4	4

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	0.007	0.064	-9999	-0.25	19	19
FZD6	0.014	0.087	-9999	-0.42	14	14
WNT6	0.033	0.008	-9999	-10000	0	0
WNT4	0.021	0.017	-9999	-10000	0	0
FZD3	0.033	0.009	-9999	-10000	0	0
WNT5A	0.024	0.066	-9999	-0.42	8	8
WNT11	0.023	0.017	-9999	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0.015	0.13	-10000	0	-0.9	3	3
RAD9A	0.034	0.007	-10000	0	-10000	0	0
AP1	0.045	0.024	-10000	0	-10000	0	0
IFNAR2	0.036	0.007	-10000	0	-10000	0	0
AKT1	0.02	0.027	-10000	0	-0.16	6	6
ER alpha/Oestrogen	0.018	0.041	-10000	0	-0.29	6	6
NFX1/SIN3/HDAC complex	0.042	0.035	-10000	0	-0.23	1	1
EGF	0.002	0.11	-10000	0	-0.42	25	25
SMG5	0.032	0.01	-10000	0	-10000	0	0
SMG6	0.033	0.009	-10000	0	-10000	0	0
SP3/HDAC2	0.048	0.019	-10000	0	-10000	0	0
TERT/c-Abl	0.026	0.13	-10000	0	-0.83	3	3
SAP18	0.034	0.007	-10000	0	-10000	0	0
MRN complex	0.056	0.036	-10000	0	-0.25	2	2
WT1	0.016	0.012	-10000	0	-10000	0	0
WRN	0.033	0.008	-10000	0	-10000	0	0
SP1	0.037	0.008	-10000	0	-10000	0	0
SP3	0.036	0.004	-10000	0	-10000	0	0
TERF2IP	0.034	0.007	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.052	0.12	-10000	0	-0.82	2	2
Mad/Max	0.053	0.011	-10000	0	-10000	0	0
TERT	0.014	0.13	-10000	0	-0.94	3	3
CCND1	0.026	0.12	-10000	0	-0.85	2	2
MAX	0.035	0.006	-10000	0	-10000	0	0
RBBP7	0.035	0.003	-10000	0	-10000	0	0
RBBP4	0.035	0.005	-10000	0	-10000	0	0
TERF2	0.033	0.015	-10000	0	-10000	0	0
PTGES3	0.034	0.006	-10000	0	-10000	0	0
SIN3A	0.034	0.007	-10000	0	-10000	0	0
Telomerase/911	0.052	0.058	-10000	0	-0.28	1	1
CDKN1B	-0.076	0.15	-10000	0	-0.26	132	132
RAD1	0.033	0.009	-10000	0	-10000	0	0
XRCC5	0.035	0.004	-10000	0	-10000	0	0
XRCC6	0.032	0.01	-10000	0	-10000	0	0
SAP30	0.035	0.006	-10000	0	-10000	0	0
TRF2/PARP2	0.051	0.016	-10000	0	-10000	0	0
UBE3A	0.035	0.007	-10000	0	-10000	0	0
JUN	0.032	0.012	-10000	0	-10000	0	0
E6	0.001	0.001	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.027	0.006	-10000	0	-10000	0	0
FOS	0.034	0.009	-10000	0	-10000	0	0
IFN-gamma/IRF1	-0.082	0.18	-10000	0	-0.31	137	137
PARP2	0.035	0.005	-10000	0	-10000	0	0
BLM	0.034	0.007	-10000	0	-10000	0	0
Telomerase	0.056	0.07	-10000	0	-0.35	3	3
IRF1	-0.002	0.13	-10000	0	-0.41	32	32
ESR1	0.024	0.058	-10000	0	-0.42	6	6
KU/TER	0.047	0.016	-10000	0	-10000	0	0
ATM/TRF2	0.046	0.017	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.047	0.042	0.18	2	-0.28	1	3
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.048	0.041	0.18	2	-0.29	1	3
HDAC1	0.034	0.024	-10000	0	-0.42	1	1
HDAC2	0.033	0.013	-10000	0	-10000	0	0
ATM	0.013	0.009	-10000	0	-10000	0	0
SMAD3	0.016	0.023	-10000	0	-0.3	2	2
ABL1	0.033	0.009	-10000	0	-10000	0	0
MXD1	0.036	0.004	-10000	0	-10000	0	0
MRE11A	0.032	0.01	-10000	0	-10000	0	0
HUS1	0.031	0.011	-10000	0	-10000	0	0
RPS6KB1	0.034	0.007	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.052	0.13	-10000	0	-1	2	2
NR2F2	0.033	0.007	-10000	0	-10000	0	0
MAPK3	0.01	0.012	-10000	0	-10000	0	0
MAPK1	0.01	0.012	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.032	0.033	-10000	0	-0.42	2	2
NFKB1	0.034	0.006	-10000	0	-10000	0	0
HNRNPC	0.035	0.005	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.013	0.009	-10000	0	-10000	0	0
NBN	0.032	0.011	-10000	0	-10000	0	0
EGFR	0.027	0.036	-10000	0	-0.42	2	2
mol:Oestrogen	0	0.001	-10000	0	-10000	0	0
EGF/EGFR	0.016	0.089	-10000	0	-0.3	26	26
MYC	0.032	0.012	-10000	0	-10000	0	0
IL2	0.022	0.016	-10000	0	-10000	0	0
KU	0.047	0.016	-10000	0	-10000	0	0
RAD50	0.031	0.034	-10000	0	-0.42	2	2
HSP90AA1	0.033	0.024	-10000	0	-0.42	1	1
TGFB1	0.032	0.034	-10000	0	-0.42	2	2
TRF2/BLM	0.049	0.018	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.043	0.13	-10000	0	-0.84	3	3
SP1/HDAC2	0.05	0.02	-10000	0	-10000	0	0
PINX1	0.033	0.009	-10000	0	-10000	0	0
Telomerase/EST1A	0.052	0.12	-10000	0	-0.82	2	2
Smad3/Myc	0.034	0.014	-10000	0	-10000	0	0
911 complex	0.057	0.029	-10000	0	-10000	0	0
IFNG	-0.11	0.21	-10000	0	-0.41	121	121
Telomerase/PinX1	0.05	0.12	-10000	0	-0.82	2	2
Telomerase/AKT1/mTOR/p70S6K	0.027	0.089	-10000	0	-0.42	8	8
SIN3B	0.035	0.003	-10000	0	-10000	0	0
YWHAE	0.033	0.009	-10000	0	-10000	0	0
Telomerase/EST1B	0.048	0.12	-10000	0	-0.82	2	2
response to DNA damage stimulus	-0.003	0.031	-10000	0	-0.1	30	30
MRN complex/TRF2/Rap1	0.077	0.048	-10000	0	-0.22	2	2
TRF2/WRN	0.049	0.018	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	0.052	0.12	-10000	0	-0.82	2	2
E2F1	0.034	0.011	-10000	0	-10000	0	0
ZNFX1	0.032	0.01	-10000	0	-10000	0	0
PIF1	0.031	0.041	-10000	0	-0.42	3	3
NCL	0.035	0.005	-10000	0	-10000	0	0
DKC1	0.035	0.004	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.043	0.014	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	0.02	0.006	-10000	0	-10000	0	0
mol:DAG	0.017	0.044	0.2	5	-0.22	9	14
VEGFR1 homodimer/NRP1/VEGFR 121	0.034	0.018	-10000	0	-10000	0	0
CaM/Ca2+	0.036	0.045	0.2	5	-0.21	9	14
HIF1A	0.043	0.007	-10000	0	-10000	0	0
GAB1	0.035	0.004	-10000	0	-10000	0	0
AKT1	0.019	0.047	-10000	0	-10000	0	0
PLCG1	0.017	0.044	0.2	5	-0.22	9	14
NOS3	0.039	0.064	0.28	1	-0.52	1	2
CBL	0.032	0.011	-10000	0	-10000	0	0
mol:NO	0.041	0.064	0.28	1	-0.5	1	2
FLT1	0.027	0.008	-10000	0	-10000	0	0
PGF	0.022	0.074	-10000	0	-0.42	10	10
VEGFR1 homodimer/NRP2/VEGFR121	0.053	0.028	-10000	0	-10000	0	0
CALM1	0.034	0.006	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
eNOS/Hsp90	0.059	0.065	0.29	1	-0.49	1	2
endothelial cell proliferation	-0.028	0.11	-10000	0	-0.38	13	13
mol:Ca2+	0.017	0.043	0.2	5	-0.22	9	14
MAPK3	-0.007	0.038	0.18	5	-0.2	9	14
MAPK1	-0.006	0.035	0.18	5	-10000	0	5
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
PLGF homodimer	0.022	0.074	-10000	0	-0.42	10	10
PRKACA	0.035	0.003	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.032	0.011	-10000	0	-10000	0	0
VEGFA homodimer	0.03	0.013	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.038	0.02	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.015	0.068	-10000	0	-10000	0	0
PI3K	0.071	0.053	-10000	0	-0.21	9	9
PRKCA	0.006	0.041	0.19	5	-0.21	9	14
PRKCB	-0.047	0.11	0.19	3	-0.23	90	93
VEGFR1 homodimer/PLGF homodimer	0.037	0.046	-10000	0	-0.24	9	9
VEGFA	0.03	0.013	-10000	0	-10000	0	0
VEGFB	0.034	0.006	-10000	0	-10000	0	0
mol:IP3	0.017	0.044	0.2	5	-0.22	9	14
RASA1	0.024	0.029	0.2	7	-0.22	1	8
NRP2	0.035	0.004	-10000	0	-10000	0	0
VEGFR1 homodimer	0.027	0.008	-10000	0	-10000	0	0
VEGFB homodimer	0.034	0.006	-10000	0	-10000	0	0
NCK1	0.034	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.046	0.066	0.29	1	-0.49	1	2
PTPN11	0.034	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.069	0.052	-10000	0	-0.2	9	9
mol:L-citrulline	0.041	0.064	0.28	1	-0.5	1	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.067	0.041	-10000	0	-0.21	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.052	0.029	-10000	0	-10000	0	0
CD2AP	0.031	0.026	-10000	0	-0.42	1	1
PI3K/GAB1	0.083	0.057	-10000	0	-0.2	9	9
PDPK1	0.021	0.045	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.053	0.028	-10000	0	-10000	0	0
mol:NADP	0.041	0.064	0.28	1	-0.5	1	2
HSP90AA1	0.033	0.024	-10000	0	-0.42	1	1
ubiquitin-dependent protein catabolic process	0.064	0.04	-10000	0	-0.21	1	1
VEGFR1 homodimer/NRP2	0.044	0.013	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.032	0.01	-10000	0	-10000	0	0
mol:S1P	0.001	0	-10000	0	-10000	0	0
S1P1/S1P/Gi	0.017	0.033	-10000	0	-0.18	6	6
GNAO1	0.019	0.029	-10000	0	-0.42	1	1
S1P/S1P3/G12/G13	0.054	0.038	-10000	0	-0.22	3	3
AKT1	0.026	0.089	-10000	0	-0.4	14	14
AKT3	0.041	0.044	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.032	0.01	-10000	0	-10000	0	0
GNAI2	0.036	0.005	-10000	0	-10000	0	0
GNAI3	0.035	0.007	-10000	0	-10000	0	0
GNAI1	0.032	0.012	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.03	0.042	-10000	0	-0.42	3	3
S1PR2	0.035	0.003	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	0.029	0.047	-10000	0	-0.22	7	7
MAPK3	0.027	0.045	-10000	0	-0.22	6	6
MAPK1	0.024	0.043	-10000	0	-0.22	6	6
JAK2	0.021	0.084	0.21	2	-0.32	13	15
CXCR4	0.017	0.069	-10000	0	-0.24	17	17
FLT1	0.036	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.026	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.009	-10000	0	-10000	0	0
SRC	0.025	0.042	-10000	0	-0.22	5	5
S1P/S1P3/Gi	0.029	0.047	-10000	0	-0.22	7	7
RAC1	0.031	0.012	-10000	0	-10000	0	0
RhoA/GTP	0.042	0.059	-10000	0	-0.23	4	4
VEGFA	0.032	0.014	-10000	0	-10000	0	0
S1P/S1P2/Gi	0.029	0.037	-10000	0	-0.18	4	4
VEGFR1 homodimer/VEGFA homodimer	0.048	0.024	-10000	0	-10000	0	0
RHOA	0.035	0.005	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.013	0.11	-10000	0	-0.24	63	63
GNAQ	0.033	0.009	-10000	0	-10000	0	0
GNAZ	0.028	0.036	-10000	0	-0.42	2	2
G12/G13	0.045	0.018	-10000	0	-10000	0	0
GNA14	-0.036	0.16	-10000	0	-0.42	56	56
GNA15	0.021	0.077	-10000	0	-0.42	11	11
GNA12	0.031	0.011	-10000	0	-10000	0	0
GNA13	0.034	0.006	-10000	0	-10000	0	0
GNA11	0.035	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.035	0.056	-10000	0	-0.22	5	5

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.017	-10000	0	-0.3	1	1
SMARCC1	0.02	0.012	-10000	0	-10000	0	0
REL	0.035	0.003	-10000	0	-10000	0	0
HDAC7	0.026	0.071	0.22	1	-0.21	2	3
JUN	0.031	0.011	-10000	0	-10000	0	0
EP300	0.032	0.011	-10000	0	-10000	0	0
KAT2B	0.032	0.034	-10000	0	-0.42	2	2
KAT5	0.034	0.007	-10000	0	-10000	0	0
MAPK14	0.011	0.041	-10000	0	-0.3	6	6
FOXO1	0.034	0.007	-10000	0	-10000	0	0
T-DHT/AR	0.056	0.08	-10000	0	-0.22	5	5
MAP2K6	0.027	0.058	-10000	0	-0.42	6	6
BRM/BAF57	0.045	0.018	-10000	0	-10000	0	0
MAP2K4	0.033	0.012	-10000	0	-10000	0	0
SMARCA2	0.031	0.012	-10000	0	-10000	0	0
PDE9A	0.013	0.12	-10000	0	-0.69	8	8
NCOA2	0.032	0.011	-10000	0	-10000	0	0
CEBPA	-0.004	0.13	-10000	0	-0.42	31	31
EHMT2	0.031	0.011	-10000	0	-10000	0	0
cell proliferation	0.054	0.13	0.34	29	-0.3	6	35
NR0B1	0.017	0.001	-10000	0	-10000	0	0
EGR1	0.03	0.012	-10000	0	-10000	0	0
RXRs/9cRA	0.003	0.11	-10000	0	-0.22	62	62
AR/RACK1/Src	0.043	0.075	0.26	6	-0.21	6	12
AR/GR	0.034	0.051	-10000	0	-0.2	2	2
GNB2L1	0.033	0.008	-10000	0	-10000	0	0
PKN1	0.034	0.024	-10000	0	-0.42	1	1
RCHY1	0.035	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	0.017	0.014	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.048	0.062	0.23	2	-0.22	4	6
SRC	0.019	0.073	0.19	51	-0.21	4	55
NR3C1	0.033	0.009	-10000	0	-10000	0	0
KLK3	-0.002	0.044	-10000	0	-10000	0	0
APPBP2	0.033	0.014	-10000	0	-10000	0	0
TRIM24	0.031	0.011	-10000	0	-10000	0	0
T-DHT/AR/TIP60	0.035	0.066	0.21	5	-0.23	6	11
TMPRSS2	-0.014	0.22	-10000	0	-0.86	21	21
RXRG	-0.058	0.18	-10000	0	-0.42	73	73
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.033	0.009	-10000	0	-10000	0	0
RXRB	0.031	0.011	-10000	0	-10000	0	0
CARM1	0.035	0.003	-10000	0	-10000	0	0
NR2C2	0.034	0.005	-10000	0	-10000	0	0
KLK2	0.033	0.059	0.28	1	-10000	0	1
AR	0.015	0.04	0.17	3	-0.17	2	5
SENP1	0.034	0.006	-10000	0	-10000	0	0
HSP90AA1	0.033	0.024	-10000	0	-0.42	1	1
MDM2	0.033	0.008	-10000	0	-10000	0	0
SRY	0	0	-10000	0	-10000	0	0
GATA2	0.033	0.008	-10000	0	-10000	0	0
MYST2	0	0	-10000	0	-10000	0	0
HOXB13	0.012	0.016	-10000	0	-10000	0	0
T-DHT/AR/RACK1/Src	0.046	0.077	0.24	11	-0.22	6	17
positive regulation of transcription	0.033	0.008	-10000	0	-10000	0	0
DNAJA1	0.03	0.016	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.013	-10000	0	-0.17	1	1
NCOA1	0.039	0.012	-10000	0	-10000	0	0
SPDEF	0.024	0.015	-10000	0	-10000	0	0
T-DHT/AR/TIF2	0.041	0.076	0.24	17	-0.26	4	21
T-DHT/AR/Hsp90	0.036	0.068	0.21	6	-0.22	7	13
GSK3B	0.035	0.007	-10000	0	-10000	0	0
NR2C1	0.034	0.006	-10000	0	-10000	0	0
mol:T-DHT	0	0.04	0.22	6	-0.22	4	10
SIRT1	0.032	0.01	-10000	0	-10000	0	0
ZMIZ2	0.031	0.011	-10000	0	-10000	0	0
POU2F1	0.034	0.034	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	0.023	0.064	0.22	1	-0.23	6	7
CREBBP	0.035	0.004	-10000	0	-10000	0	0
SMARCE1	0.034	0.006	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.026	0.06	-10000	0	-1	1	1
regulation of axonogenesis	-0.014	0.032	0.23	5	-10000	0	5
myoblast fusion	-0.034	0.033	0.39	1	-10000	0	1
mol:GTP	0.024	0.026	-10000	0	-0.16	6	6
regulation of calcium-dependent cell-cell adhesion	-0.051	0.075	0.23	22	-10000	0	22
ARF1/GTP	0.04	0.027	-10000	0	-0.17	1	1
mol:GM1	0.011	0.018	-10000	0	-0.17	1	1
mol:Choline	0.014	0.017	-10000	0	-0.15	1	1
lamellipodium assembly	0.022	0.049	-10000	0	-0.34	5	5
MAPK3	0.03	0.026	-10000	0	-0.34	1	1
ARF6/GTP/NME1/Tiam1	0.052	0.076	-10000	0	-0.23	22	22
ARF1	0.032	0.011	-10000	0	-10000	0	0
ARF6/GDP	0.035	0.033	-10000	0	-0.4	1	1
ARF1/GDP	0.037	0.043	-10000	0	-0.24	3	3
ARF6	0.042	0.012	-10000	0	-0.14	1	1
RAB11A	0.034	0.005	-10000	0	-10000	0	0
TIAM1	0.01	0.1	-10000	0	-0.42	21	21
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.029	0.026	-10000	0	-0.34	1	1
actin filament bundle formation	-0.045	0.04	0.21	6	-10000	0	6
KALRN	0.021	0.029	-10000	0	-0.24	3	3
RAB11FIP3/RAB11A	0.051	0.009	-10000	0	-10000	0	0
RhoA/GDP	0.046	0.04	-10000	0	-0.21	6	6
NME1	0.035	0.008	-10000	0	-10000	0	0
Rac1/GDP	0.041	0.041	-10000	0	-0.22	5	5
substrate adhesion-dependent cell spreading	0.024	0.026	-10000	0	-0.16	6	6
cortical actin cytoskeleton organization	0.022	0.049	-10000	0	-0.34	5	5
RAC1	0.031	0.012	-10000	0	-10000	0	0
liver development	0.024	0.026	-10000	0	-0.16	6	6
ARF6/GTP	0.024	0.026	-10000	0	-0.16	6	6
RhoA/GTP	0.044	0.025	-10000	0	-0.17	1	1
mol:GDP	0.02	0.039	-10000	0	-0.23	6	6
ARF6/GTP/RAB11FIP3/RAB11A	0.063	0.027	-10000	0	-0.15	1	1
RHOA	0.035	0.005	-10000	0	-10000	0	0
PLD1	0.025	0.021	-10000	0	-0.17	1	1
RAB11FIP3	0.035	0.003	-10000	0	-10000	0	0
tube morphogenesis	0.022	0.049	-10000	0	-0.34	5	5
ruffle organization	0.014	0.032	-10000	0	-0.23	5	5
regulation of epithelial cell migration	0.024	0.026	-10000	0	-0.16	6	6
PLD2	0.024	0.021	-10000	0	-0.17	1	1
PIP5K1A	0.014	0.032	-10000	0	-0.23	5	5
mol:Phosphatidic acid	0.014	0.017	-10000	0	-0.15	1	1
Rac1/GTP	0.022	0.049	-10000	0	-0.34	5	5

×

Signaling events mediated by PRL

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
CCNE1	0.035	0.004	-10000	0	-10000	0	0
mol:Halofuginone	0.005	0.003	-10000	0	-10000	0	0
ITGA1	0.033	0.009	-10000	0	-10000	0	0
CDKN1A	0.022	0.038	-10000	0	-0.3	4	4
PRL-3/alpha Tubulin	0.044	0.026	-10000	0	-0.3	1	1
mol:Ca2+	-0.054	0.095	-10000	0	-0.31	44	44
AGT	-0.031	0.15	-10000	0	-0.42	49	49
CCNA2	0.017	0.051	-10000	0	-10000	0	0
TUBA1B	0.034	0.005	-10000	0	-10000	0	0
EGR1	0.018	0.01	-10000	0	-10000	0	0
CDK2/Cyclin E1	0.077	0.053	0.28	1	-10000	0	1
MAPK3	0.016	0.018	-10000	0	-0.3	1	1
PRL-2 /Rab GGTase beta	0.051	0.009	-10000	0	-10000	0	0
MAPK1	0.015	0.018	-10000	0	-0.3	1	1
PTP4A1	0.008	0.006	-10000	0	-10000	0	0
PTP4A3	0.03	0.026	-10000	0	-0.42	1	1
PTP4A2	0.035	0.005	-10000	0	-10000	0	0
ITGB1	0.015	0.018	-10000	0	-0.3	1	1
SRC	0.033	0.009	-10000	0	-10000	0	0
RAC1	0.019	0.046	-10000	0	-0.32	5	5
Rab GGTase beta/Rab GGTase alpha	0.051	0.01	-10000	0	-10000	0	0
PRL-1/ATF-5	0.049	0.058	0.36	4	-10000	0	4
RABGGTA	0.035	0.004	-10000	0	-10000	0	0
BCAR1	-0.019	0.021	0.34	1	-10000	0	1
RHOC	0.023	0.043	-10000	0	-0.33	4	4
RHOA	0.022	0.046	-10000	0	-0.32	5	5
cell motility	0.049	0.065	0.32	5	-0.33	3	8
PRL-1/alpha Tubulin	0.048	0.057	0.36	4	-10000	0	4
PRL-3/alpha1 Integrin	0.041	0.028	-10000	0	-0.3	1	1
ROCK1	0.048	0.059	0.32	4	-0.35	2	6
RABGGTB	0.035	0.005	-10000	0	-10000	0	0
CDK2	0.035	0.004	-10000	0	-10000	0	0
mitosis	0.008	0.006	-10000	0	-10000	0	0
ATF5	0.035	0.004	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.023	0.021	-10000	0	-0.2	1	1
TRAF2/ASK1	0.04	0.023	-10000	0	-0.25	1	1
ATM	0.032	0.011	-10000	0	-10000	0	0
MAP2K3	-0.011	0.11	-10000	0	-0.34	25	25
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.001	0.1	0.25	1	-0.32	23	24
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.011	0.13	-10000	0	-0.42	35	35
TXN	0.01	0.003	-10000	0	-10000	0	0
CALM1	0.034	0.006	-10000	0	-10000	0	0
GADD45A	0.034	0.005	-10000	0	-10000	0	0
GADD45B	0.035	0.004	-10000	0	-10000	0	0
MAP3K1	0.034	0.007	-10000	0	-10000	0	0
MAP3K6	0.035	0.005	-10000	0	-10000	0	0
MAP3K7	0.031	0.011	-10000	0	-10000	0	0
MAP3K4	0.031	0.012	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.044	0.025	-10000	0	-0.3	1	1
TAK1/TAB family	-0.009	0.031	-10000	0	-0.14	16	16
RAC1/OSM/MEKK3	0.057	0.025	-10000	0	-10000	0	0
TRAF2	0.033	0.009	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.015	0.099	-10000	0	-0.28	23	23
TRAF6	0.01	0.002	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.021	0.062	-10000	0	-0.42	7	7
CCM2	0.031	0.011	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.033	0.044	-10000	0	-0.25	7	7
MAPK11	0.032	0.01	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.044	0.05	-10000	0	-0.22	8	8
OSM/MEKK3	0.045	0.019	-10000	0	-10000	0	0
TAOK1	0.018	0.007	-10000	0	-10000	0	0
TAOK2	0.018	0.006	-10000	0	-10000	0	0
TAOK3	0.018	0.007	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.031	0.011	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.03	0.026	-10000	0	-0.42	1	1
MAP3K10	0.035	0.004	-10000	0	-10000	0	0
MAP3K3	0.034	0.007	-10000	0	-10000	0	0
TRX/ASK1	0.027	0.024	-10000	0	-0.24	1	1
GADD45/MTK1/MTK1	0.043	0.087	-10000	0	-0.21	35	35

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.032	0.012	-10000	0	-10000	0	0
HSPA8	0.032	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.064	0.065	-10000	0	-0.27	5	5
AKT1	0.035	0.016	-10000	0	-10000	0	0
GSC	0.008	0.065	-10000	0	-10000	0	0
NKX2-5	0.001	0.005	-10000	0	-10000	0	0
muscle cell differentiation	-0.063	0.06	0.51	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.12	0.054	-10000	0	-10000	0	0
SMAD4	0.042	0.034	-10000	0	-10000	0	0
CBFB	0.034	0.007	-10000	0	-10000	0	0
SAP18	0.034	0.007	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.048	0.067	-10000	0	-0.25	15	15
SMAD3/SMAD4/VDR	0.1	0.059	-10000	0	-0.22	2	2
MYC	0.03	0.012	-10000	0	-10000	0	0
CDKN2B	-0.11	0.25	-10000	0	-0.88	14	14
AP1	0.06	0.039	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.041	0.066	-10000	0	-0.36	4	4
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.031	0.047	-10000	0	-0.32	5	5
SP3	0.037	0.002	-10000	0	-10000	0	0
CREB1	0.035	0.003	-10000	0	-10000	0	0
FOXH1	0.031	0.015	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	0.074	0.048	-10000	0	-10000	0	0
GATA3	-0.052	0.18	-10000	0	-0.44	64	64
SKI/SIN3/HDAC complex/NCoR1	0.028	0.057	-10000	0	-0.37	3	3
MEF2C/TIF2	0.049	0.052	0.36	2	-0.38	2	4
endothelial cell migration	-0.02	0.085	0.74	3	-10000	0	3
MAX	0.033	0.006	-10000	0	-10000	0	0
RBBP7	0.035	0.003	-10000	0	-10000	0	0
RBBP4	0.035	0.005	-10000	0	-10000	0	0
RUNX2	0.029	0.035	-10000	0	-0.42	2	2
RUNX3	0.005	0.11	-10000	0	-0.42	24	24
RUNX1	0.031	0.041	-10000	0	-0.42	3	3
CTBP1	0.034	0.007	-10000	0	-10000	0	0
NR3C1	0.032	0.009	-10000	0	-10000	0	0
VDR	0.032	0.034	-10000	0	-0.42	2	2
CDKN1A	0.037	0.046	-10000	0	-0.54	1	1
KAT2B	0.032	0.034	-10000	0	-0.42	2	2
SMAD2/SMAD2/SMAD4/FOXH1	0.073	0.042	-10000	0	-10000	0	0
DCP1A	0.034	0.006	-10000	0	-10000	0	0
SKI	0.034	0.007	-10000	0	-10000	0	0
SERPINE1	0.02	0.086	-10000	0	-0.75	3	3
SMAD3/SMAD4/ATF2	0.079	0.048	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.07	0.05	-10000	0	-10000	0	0
SAP30	0.034	0.005	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.057	0.03	-10000	0	-10000	0	0
JUN	0.04	0.034	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	0.076	0.06	-10000	0	-0.27	4	4
TFE3	0.04	0.007	-10000	0	-10000	0	0
COL1A2	0.025	0.024	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.069	0.055	0.29	2	-10000	0	2
DLX1	0.008	0.1	-10000	0	-0.42	19	19
TCF3	0.035	0.005	-10000	0	-10000	0	0
FOS	0.039	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/Max	0.075	0.049	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.063	0.024	-10000	0	-10000	0	0
ZBTB17	0.034	0.005	-10000	0	-10000	0	0
LAMC1	0.039	0.034	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.073	0.049	-10000	0	-10000	0	0
IRF7	0.03	0.047	-10000	0	-0.42	4	4
ESR1	0.023	0.058	-10000	0	-0.42	6	6
HNF4A	0.022	0.013	-10000	0	-10000	0	0
MEF2C	0.052	0.075	0.45	4	-0.4	2	6
SMAD2-3/SMAD4	0.086	0.048	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.063	0.025	-10000	0	-10000	0	0
IGHV3OR16-13	0.012	0.045	-10000	0	-0.43	3	3
TGIF2/HDAC complex	0.033	0.009	-10000	0	-10000	0	0
CREBBP	0.035	0.006	-10000	0	-10000	0	0
SKIL	0.034	0.006	-10000	0	-10000	0	0
HDAC1	0.033	0.024	-10000	0	-0.42	1	1
HDAC2	0.031	0.012	-10000	0	-10000	0	0
SNIP1	0.035	0.004	-10000	0	-10000	0	0
GCN5L2	0	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.093	0.046	-10000	0	-10000	0	0
MSG1/HSC70	0.029	0.072	-10000	0	-0.29	16	16
SMAD2	0.037	0.016	-10000	0	-10000	0	0
SMAD3	0.041	0.033	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.036	0.044	-10000	0	-0.22	6	6
SMAD2/SMAD2/SMAD4	0.024	0.046	0.17	8	-0.23	3	11
NCOR1	0.033	0.009	-10000	0	-10000	0	0
NCOA2	0.032	0.011	-10000	0	-10000	0	0
NCOA1	0.035	0.005	-10000	0	-10000	0	0
MYOD/E2A	0.044	0.013	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.13	0.061	-10000	0	-10000	0	0
IFNB1	0.024	0.041	0.22	1	-0.24	3	4
SMAD3/SMAD4/MEF2C	0.092	0.069	-10000	0	-0.38	2	2
CITED1	0.014	0.092	-10000	0	-0.42	16	16
SMAD2-3/SMAD4/ARC105	0.097	0.053	-10000	0	-10000	0	0
RBL1	0.033	0.009	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.04	0.068	-10000	0	-0.48	5	5
RUNX1-3/PEBPB2	0.043	0.087	-10000	0	-0.26	25	25
SMAD7	0.077	0.033	-10000	0	-10000	0	0
MYC/MIZ-1	0.043	0.02	-10000	0	-10000	0	0
SMAD3/SMAD4	0.032	0.044	-10000	0	-0.36	2	2
IL10	-0.025	0.15	-10000	0	-0.44	28	28
PIASy/HDAC complex	0.035	0.005	-10000	0	-10000	0	0
PIAS3	0.032	0.011	-10000	0	-10000	0	0
CDK2	0.035	0.006	-10000	0	-10000	0	0
IL5	-0.023	0.12	-10000	0	-0.25	67	67
CDK4	0.034	0.009	-10000	0	-10000	0	0
PIAS4	0.035	0.005	-10000	0	-10000	0	0
ATF3	0.031	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1	0.092	0.048	-10000	0	-10000	0	0
FOXG1	0.013	0.024	-10000	0	-10000	0	0
FOXO3	0.017	0.018	-10000	0	-10000	0	0
FOXO1	0.018	0.018	-10000	0	-10000	0	0
FOXO4	0.019	0.018	-10000	0	-10000	0	0
heart looping	0.051	0.075	0.45	4	-0.4	2	6
CEBPB	0.032	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.056	0.088	-10000	0	-0.26	19	19
MYOD1	0.026	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.063	0.049	-10000	0	-10000	0	0
SMAD3/SMAD4/GATA3	0.011	0.16	-10000	0	-0.28	75	75
SnoN/SIN3/HDAC complex/NCoR1	0.034	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.082	0.099	-10000	0	-0.23	25	25
SMAD3/SMAD4/SP1-3	0.12	0.05	-10000	0	-10000	0	0
MED15	0.033	0.009	-10000	0	-10000	0	0
SP1	0.041	0.007	-10000	0	-10000	0	0
SIN3B	0.035	0.003	-10000	0	-10000	0	0
SIN3A	0.034	0.007	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.074	0.044	-10000	0	-0.21	2	2
ITGB5	0.043	0.034	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.034	0.052	-10000	0	-0.39	2	2
SMAD3/SMAD4/AR	0.056	0.05	-10000	0	-10000	0	0
AR	0.02	0.017	-10000	0	-10000	0	0
negative regulation of cell growth	0.052	0.052	-10000	0	-0.33	1	1
SMAD3/SMAD4/MYOD	0.072	0.047	-10000	0	-10000	0	0
E2F5	0.023	0.062	-10000	0	-0.42	7	7
E2F4	0.034	0.007	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.091	0.055	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.037	0.053	-10000	0	-0.36	5	5
TFDP1	0.033	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.088	0.047	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.07	0.055	-10000	0	-0.29	2	2
TGIF2	0.033	0.009	-10000	0	-10000	0	0
TGIF1	0.034	0.007	-10000	0	-10000	0	0
ATF2	0.035	0.002	-10000	0	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.032	0.064	-10000	0	-10000	0	0
epithelial cell differentiation	0.026	0.055	-10000	0	-10000	0	0
ITCH	0.039	0.017	-10000	0	-10000	0	0
WWP1	0.023	0.068	-10000	0	-10000	0	0
FYN	0.031	0.012	-10000	0	-10000	0	0
EGFR	0.027	0.035	-10000	0	-0.42	2	2
PRL	0.02	0.013	-10000	0	-10000	0	0
neuron projection morphogenesis	0.036	0.079	0.3	10	-10000	0	10
PTPRZ1	-0.012	0.13	-10000	0	-0.42	34	34
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.055	0.069	-10000	0	-0.27	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.02	0.052	-10000	0	-0.3	1	1
ADAM17	0.041	0.014	-10000	0	-10000	0	0
ErbB4/ErbB4	0.018	0.062	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.009	0.1	-10000	0	-0.33	9	9
NCOR1	0.033	0.009	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.033	0.053	-10000	0	-0.27	1	1
GRIN2B	0.014	0.048	0.26	2	-0.26	1	3
ErbB4/ErbB2/betacellulin	0.031	0.051	-10000	0	-10000	0	0
STAT1	0.033	0.033	-10000	0	-0.42	2	2
HBEGF	0.033	0.009	-10000	0	-10000	0	0
PRLR	0.024	0.016	-10000	0	-10000	0	0
E4ICDs/ETO2	0.017	0.086	-10000	0	-0.32	2	2
axon guidance	0.033	0.067	0.28	3	-10000	0	3
NEDD4	0.039	0.015	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	0.021	0.028	-10000	0	-10000	0	0
CBFA2T3	0.001	0.12	-10000	0	-0.42	26	26
ErbB4/ErbB2/HBEGF	0.038	0.051	-10000	0	-10000	0	0
MAPK3	0.044	0.079	0.28	11	-0.26	1	12
STAT1 (dimer)	0.034	0.068	-10000	0	-10000	0	0
MAPK1	0.039	0.075	0.29	8	-10000	0	8
JAK2	0.023	0.058	-10000	0	-0.42	6	6
ErbB4/ErbB2/neuregulin 1 beta	0.02	0.049	-10000	0	-0.29	1	1
NRG1	0.015	0.032	-10000	0	-0.3	3	3
NRG3	-0.031	0.14	-10000	0	-0.42	44	44
NRG2	0.029	0.042	-10000	0	-0.42	3	3
NRG4	0.018	0.073	-10000	0	-0.42	10	10
heart development	0.033	0.067	0.28	3	-10000	0	3
neural crest cell migration	0.021	0.049	-10000	0	-0.28	1	1
ERBB2	0.023	0.01	-10000	0	-10000	0	0
WWOX/E4ICDs	0.033	0.065	-10000	0	-10000	0	0
SHC1	0.032	0.011	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.032	0.08	-10000	0	-0.32	4	4
apoptosis	0.025	0.13	0.33	46	-10000	0	46
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.029	0.069	-10000	0	-0.34	1	1
ErbB4/ErbB2/epiregulin	0.033	0.051	-10000	0	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	0.024	0.064	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.036	0.073	-10000	0	-10000	0	0
MDM2	0.02	0.069	0.26	12	-10000	0	12
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.03	0.043	-10000	0	-0.27	1	1
STAT5A	0.031	0.065	0.27	1	-10000	0	1
ErbB4/EGFR/neuregulin 1 beta	0.028	0.056	-10000	0	-0.29	1	1
DLG4	0.033	0.009	-10000	0	-10000	0	0
GRB2/SHC	0.045	0.018	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.028	0.059	-10000	0	-10000	0	0
STAT5A (dimer)	0.038	0.067	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.051	0.068	-10000	0	-10000	0	0
LRIG1	0.033	0.024	-10000	0	-0.42	1	1
EREG	0.026	0.012	-10000	0	-10000	0	0
BTC	0.023	0.012	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.029	0.062	0.28	1	-10000	0	1
ERBB4	0.018	0.063	-10000	0	-10000	0	0
STAT5B	0.034	0.005	-10000	0	-10000	0	0
YAP1	0.005	0.086	-10000	0	-0.37	16	16
GRB2	0.034	0.007	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.032	0.065	-10000	0	-0.29	4	4
glial cell differentiation	-0.028	0.058	-10000	0	-10000	0	0
WWOX	0.033	0.008	-10000	0	-10000	0	0
cell proliferation	0.026	0.059	0.28	2	-10000	0	2

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.033	0.024	-10000	0	-0.42	1	1
HDAC2	0.031	0.012	-10000	0	-10000	0	0
GNB1/GNG2	0.049	0.063	-10000	0	-0.25	13	13
forebrain development	0.05	0.07	-10000	0	-0.34	2	2
GNAO1	0.019	0.029	-10000	0	-0.42	1	1
SMO/beta Arrestin2	0.038	0.052	-10000	0	-0.29	8	8
SMO	0.022	0.067	-10000	0	-0.42	8	8
ARRB2	0.033	0.009	-10000	0	-10000	0	0
GLI3/SPOP	0.049	0.074	0.24	1	-0.27	3	4
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.034	0.006	-10000	0	-10000	0	0
GNAI2	0.035	0.006	-10000	0	-10000	0	0
SIN3/HDAC complex	0.081	0.028	-10000	0	-10000	0	0
GNAI1	0.031	0.012	-10000	0	-10000	0	0
XPO1	0.037	0.006	-10000	0	-10000	0	0
GLI1/Su(fu)	0.04	0.073	-10000	0	-0.37	1	1
SAP30	0.034	0.005	-10000	0	-10000	0	0
mol:GDP	0.022	0.066	-10000	0	-0.42	8	8
MIM/GLI2A	0.027	0.042	-10000	0	-0.42	3	3
IFT88	0.032	0.025	-10000	0	-0.42	1	1
GNAI3	0.034	0.008	-10000	0	-10000	0	0
GLI2	0.036	0.058	0.22	6	-0.24	3	9
GLI3	0.033	0.072	0.23	1	-0.26	5	6
CSNK1D	0.034	0.007	-10000	0	-10000	0	0
CSNK1E	0.032	0.01	-10000	0	-10000	0	0
SAP18	0.034	0.007	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.032	0.025	-10000	0	-0.42	1	1
GNG2	0.027	0.058	-10000	0	-0.42	6	6
Gi family/GTP	0.018	0.051	-10000	0	-0.24	10	10
SIN3B	0.035	0.003	-10000	0	-10000	0	0
SIN3A	0.034	0.007	-10000	0	-10000	0	0
GLI3/Su(fu)	0.037	0.086	0.22	1	-0.31	14	15
GLI2/Su(fu)	0.042	0.065	0.24	3	-0.25	8	11
FOXA2	0.026	0.078	-10000	0	-0.65	3	3
neural tube patterning	0.05	0.07	-10000	0	-0.34	2	2
SPOP	0.034	0.006	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.038	0.062	-10000	0	-0.19	1	1
GNB1	0.034	0.007	-10000	0	-10000	0	0
CSNK1G2	0.035	0.004	-10000	0	-10000	0	0
CSNK1G3	0.033	0.008	-10000	0	-10000	0	0
MTSS1	0.027	0.042	-10000	0	-0.42	3	3
embryonic limb morphogenesis	0.05	0.07	-10000	0	-0.34	2	2
SUFU	0.024	0.03	-10000	0	-0.15	8	8
LGALS3	0.016	0.09	-10000	0	-0.42	15	15
catabolic process	0.073	0.09	0.33	3	-0.33	3	6
GLI3A/CBP	0.042	0.029	-10000	0	-0.32	2	2
KIF3A	0.033	0.008	-10000	0	-10000	0	0
GLI1	0.05	0.071	-10000	0	-0.36	1	1
RAB23	0.032	0.01	-10000	0	-10000	0	0
CSNK1A1	0.033	0.009	-10000	0	-10000	0	0
IFT172	0.03	0.047	-10000	0	-0.42	4	4
RBBP7	0.035	0.003	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.03	0.076	-10000	0	-0.24	12	12
GNAZ	0.027	0.036	-10000	0	-0.42	2	2
RBBP4	0.035	0.005	-10000	0	-10000	0	0
CSNK1G1	0.035	0.004	-10000	0	-10000	0	0
PIAS1	0.035	0.005	-10000	0	-10000	0	0
PRKACA	0.035	0.003	-10000	0	-10000	0	0
GLI2/SPOP	0.051	0.057	0.24	3	-0.21	3	6
STK36	0.036	0.007	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.021	0.057	-10000	0	-0.24	12	12
PTCH1	0.046	0.1	-10000	0	-1	2	2
MIM/GLI1	0.06	0.069	-10000	0	-10000	0	0
CREBBP	0.042	0.029	-10000	0	-0.32	2	2
Su(fu)/SIN3/HDAC complex	0.038	0.063	0.22	2	-0.3	7	9

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.018	0.005	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.05	0.024	-10000	0	-10000	0	0
CDKN1B	0.026	0.051	0.27	1	-0.28	6	7
CDKN1A	0.036	0.07	0.27	2	-0.28	7	9
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.033	0.009	-10000	0	-10000	0	0
FOXO3	0.023	0.038	-10000	0	-0.28	3	3
AKT1	0.028	0.042	-10000	0	-0.29	4	4
BAD	0.034	0.006	-10000	0	-10000	0	0
AKT3	0.018	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.024	0.05	-10000	0	-0.28	7	7
AKT1/ASK1	0.042	0.058	-10000	0	-0.27	7	7
BAD/YWHAZ	0.062	0.025	-10000	0	-10000	0	0
RICTOR	0.031	0.025	-10000	0	-0.42	1	1
RAF1	0.035	0.005	-10000	0	-10000	0	0
JNK cascade	-0.041	0.056	0.26	7	-10000	0	7
TSC1	0.023	0.045	-10000	0	-0.28	5	5
YWHAZ	0.032	0.011	-10000	0	-10000	0	0
AKT1/RAF1	0.051	0.059	-10000	0	-0.28	7	7
EP300	0.032	0.011	-10000	0	-10000	0	0
mol:GDP	0.025	0.051	-10000	0	-0.29	7	7
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.023	0.05	-10000	0	-0.28	7	7
YWHAQ	0.035	0.004	-10000	0	-10000	0	0
TBC1D4	0.014	0.035	0.24	6	-0.23	2	8
MAP3K5	0.03	0.026	-10000	0	-0.42	1	1
MAPKAP1	0.033	0.009	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.054	0.057	0.28	1	-0.23	8	9
YWHAH	0.034	0.008	-10000	0	-10000	0	0
AKT1S1	0.024	0.051	-10000	0	-0.28	7	7
CASP9	0.025	0.051	0.27	1	-0.28	6	7
YWHAB	0.033	0.01	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.051	0.064	0.29	5	-0.27	6	11
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.064	0.022	-10000	0	-10000	0	0
YWHAE	0.033	0.009	-10000	0	-10000	0	0
SRC	0.033	0.009	-10000	0	-10000	0	0
AKT2/p21CIP1	0.046	0.073	0.26	9	-10000	0	9
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.032	-10000	0	-0.26	3	3
CHUK	0.025	0.039	-10000	0	-0.28	3	3
BAD/BCL-XL	0.051	0.057	-10000	0	-0.27	7	7
mTORC2	0.038	0.021	-10000	0	-0.22	1	1
AKT2	0.02	0.003	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.059	0.064	0.26	6	-0.28	2	8
PDPK1	0.035	0.003	-10000	0	-10000	0	0
MDM2	0.029	0.053	-10000	0	-0.28	5	5
MAPKKK cascade	-0.05	0.058	0.28	7	-10000	0	7
MDM2/Cbp/p300	0.065	0.066	0.29	4	-0.27	2	6
TSC1/TSC2	0.02	0.042	-10000	0	-0.28	5	5
proteasomal ubiquitin-dependent protein catabolic process	0.062	0.064	0.28	4	-0.26	2	6
glucose import	0.008	0.027	0.21	5	-0.21	1	6
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.028	0.038	0.18	1	-10000	0	1
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.008	0.027	0.21	5	-0.21	1	6
GSK3A	0.024	0.051	-10000	0	-0.28	7	7
FOXO1	0.024	0.05	-10000	0	-0.28	6	6
GSK3B	0.024	0.052	-10000	0	-0.28	7	7
SFN	0.027	0.015	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.028	0.057	0.25	2	-0.28	7	9
p27Kip1/14-3-3 family	0.044	0.042	-10000	0	-0.29	1	1
PRKACA	0.035	0.003	-10000	0	-10000	0	0
KPNA1	0.034	0.006	-10000	0	-10000	0	0
HSP90AA1	0.033	0.024	-10000	0	-0.42	1	1
YWHAG	0.032	0.01	-10000	0	-10000	0	0
RHEB	0.031	0.011	-10000	0	-10000	0	0
CREBBP	0.035	0.004	-10000	0	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.044	0.025	-10000	0	-0.3	1	1
VLDLR	0.021	0.066	-10000	0	-0.42	8	8
CRKL	0.033	0.01	-10000	0	-10000	0	0
LRPAP1	0.034	0.007	-10000	0	-10000	0	0
FYN	0.031	0.012	-10000	0	-10000	0	0
ITGA3	0.032	0.01	-10000	0	-10000	0	0
RELN/VLDLR/Fyn	0.029	0.055	-10000	0	-0.25	7	7
MAPK8IP1/MKK7/MAP3K11/JNK1	0.078	0.047	-10000	0	-0.2	1	1
AKT1	0.002	0.042	-10000	0	-0.2	7	7
MAP2K7	0.035	0.004	-10000	0	-10000	0	0
RAPGEF1	0.033	0.009	-10000	0	-10000	0	0
DAB1	0.021	0.012	-10000	0	-10000	0	0
RELN/LRP8/DAB1	0.034	0.034	-10000	0	-10000	0	0
LRPAP1/LRP8	0.049	0.012	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	0.045	0.035	-10000	0	-10000	0	0
DAB1/alpha3/beta1 Integrin	0.041	0.049	-10000	0	-0.2	7	7
long-term memory	0.048	0.041	-10000	0	-10000	0	0
DAB1/LIS1	0.052	0.058	-10000	0	-0.21	7	7
DAB1/CRLK/C3G	0.043	0.049	-10000	0	-0.2	7	7
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
DAB1/NCK2	0.056	0.058	-10000	0	-0.21	7	7
ARHGEF2	0.031	0.026	-10000	0	-0.42	1	1
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.031	0.01	-10000	0	-10000	0	0
CDK5R1	0.033	0.024	-10000	0	-0.42	1	1
RELN	0.024	0.016	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
RELN/LRP8/Fyn	0.039	0.039	-10000	0	-10000	0	0
GRIN2A/RELN/LRP8/DAB1/Fyn	0.058	0.044	-10000	0	-10000	0	0
MAPK8	0.032	0.01	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.023	0.049	-10000	0	-0.23	7	7
ITGB1	0.032	0.011	-10000	0	-10000	0	0
MAP1B	0.016	0.049	0.16	17	-0.21	7	24
RELN/LRP8	0.043	0.038	-10000	0	-10000	0	0
GRIN2B/RELN/LRP8/DAB1/Fyn	0.052	0.044	-10000	0	-10000	0	0
PI3K	0.049	0.013	-10000	0	-10000	0	0
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.042	0.022	-10000	0	-10000	0	0
RAP1A	0.015	0.08	0.32	8	-10000	0	8
PAFAH1B1	0.033	0.009	-10000	0	-10000	0	0
MAPK8IP1	0.033	0.008	-10000	0	-10000	0	0
CRLK/C3G	0.045	0.018	-10000	0	-10000	0	0
GRIN2B	0.022	0.013	-10000	0	-10000	0	0
NCK2	0.035	0.003	-10000	0	-10000	0	0
neuron differentiation	0.02	0.062	-10000	0	-0.28	6	6
neuron adhesion	0.015	0.08	0.32	7	-10000	0	7
LRP8	0.035	0.004	-10000	0	-10000	0	0
GSK3B	0.004	0.045	-10000	0	-0.19	7	7
RELN/VLDLR/DAB1/Fyn	0.037	0.05	-10000	0	-0.22	7	7
MAP3K11	0.034	0.007	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	0.014	0.036	-10000	0	-0.21	7	7
CDK5	0.031	0.011	-10000	0	-10000	0	0
MAPT	-0.002	0.063	0.68	3	-10000	0	3
neuron migration	0.02	0.078	0.24	27	-0.22	7	34
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.021	0.061	-10000	0	-0.28	5	5
RELN/VLDLR	0.051	0.055	-10000	0	-0.23	7	7

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.033	0.024	-10000	0	-0.42	1	1
HDAC3	0.033	0.008	-10000	0	-10000	0	0
VDR	0.032	0.034	-10000	0	-0.42	2	2
Cbp/p300/PCAF	0.061	0.033	-10000	0	-0.25	2	2
EP300	0.032	0.011	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.036	0.059	0.18	7	-0.38	1	8
KAT2B	0.032	0.034	-10000	0	-0.42	2	2
MAPK14	0.031	0.011	-10000	0	-10000	0	0
AKT1	0.009	0.068	0.23	4	-0.24	18	22
RAR alpha/9cRA/Cyclin H	0.054	0.062	-10000	0	-0.23	2	2
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.02	0.056	-10000	0	-0.21	7	7
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.035	0.03	-10000	0	-0.16	5	5
NCOR2	0.034	0.006	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.024	0.024	-10000	0	-0.29	2	2
RXRs/RARs/NRIP1/9cRA	0.029	0.079	-10000	0	-0.41	2	2
NCOA2	0.032	0.011	-10000	0	-10000	0	0
NCOA3	0.032	0.01	-10000	0	-10000	0	0
NCOA1	0.035	0.005	-10000	0	-10000	0	0
VDR/VDR/DNA	0.032	0.034	-10000	0	-0.42	2	2
RARG	0.035	0.005	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.047	0.007	-10000	0	-10000	0	0
MAPK3	0.036	0.004	-10000	0	-10000	0	0
MAPK1	0.033	0.009	-10000	0	-10000	0	0
MAPK8	0.033	0.011	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.03	0.069	-10000	0	-0.55	1	1
RARA	0.024	0.016	-10000	0	-0.2	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.019	0.053	-10000	0	-0.21	8	8
PRKCA	0.035	0.025	-10000	0	-0.42	1	1
RXRs/RARs/NRIP1/9cRA/HDAC1	0.023	0.085	-10000	0	-0.38	4	4
RXRG	-0.033	0.12	-10000	0	-0.28	71	71
RXRA	0.026	0.024	-10000	0	-0.2	1	1
RXRB	0.025	0.02	-10000	0	-0.28	1	1
VDR/Vit D3/DNA	0.024	0.024	-10000	0	-0.29	2	2
RBP1	0.026	0.058	-10000	0	-0.42	6	6
CRBP1/9-cic-RA	0.019	0.041	-10000	0	-0.29	6	6
RARB	0.021	0.084	-10000	0	-0.42	13	13
PRKCG	0.031	0.01	-10000	0	-10000	0	0
MNAT1	0.035	0.005	-10000	0	-10000	0	0
RAR alpha/RXRs	0.01	0.07	0.25	1	-0.4	3	4
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.029	0.087	0.26	1	-0.4	7	8
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.077	0.26	2	-0.28	6	8
RXRs/RARs/NRIP1/9cRA/HDAC3	0.022	0.086	-10000	0	-0.38	4	4
positive regulation of DNA binding	0.042	0.055	-10000	0	-0.22	2	2
NRIP1	0.025	0.085	-10000	0	-0.49	1	1
RXRs/RARs	0.024	0.088	-10000	0	-0.35	8	8
RXRs/RXRs/DNA/9cRA	0.007	0.054	-10000	0	-0.57	1	1
PRKACA	0.035	0.003	-10000	0	-10000	0	0
CDK7	0.034	0.007	-10000	0	-10000	0	0
TFIIH	0.067	0.018	-10000	0	-10000	0	0
RAR alpha/9cRA	0.066	0.056	-10000	0	-0.16	1	1
CCNH	0.034	0.008	-10000	0	-10000	0	0
CREBBP	0.035	0.004	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.06	0.027	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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
CTTN	0.033	0.008	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.051	0.056	-9999	-0.36	3	3
Syndecan-3/Neurocan	0.035	0.045	-9999	-0.38	3	3
POMC	-0.017	0.14	-9999	-0.42	42	42
EGFR	0.027	0.035	-9999	-0.42	2	2
Syndecan-3/EGFR	0.037	0.045	-9999	-0.37	2	2
AGRP	0.026	0.011	-9999	-10000	0	0
NCSTN	0.032	0.011	-9999	-10000	0	0
PSENEN	0.035	0.004	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.031	0.041	-9999	-0.42	3	3
APH1A	0.032	0.011	-9999	-10000	0	0
NCAN	0.028	0.011	-9999	-10000	0	0
long-term memory	0.053	0.049	-9999	-0.34	3	3
Syndecan-3/IL8	0.032	0.051	-9999	-0.37	3	3
PSEN1	0.034	0.005	-9999	-10000	0	0
Src/Cortactin	0.046	0.017	-9999	-10000	0	0
FYN	0.031	0.012	-9999	-10000	0	0
limb bud formation	0.014	0.037	-9999	-0.39	3	3
MC4R	0.023	0.014	-9999	-10000	0	0
SRC	0.033	0.009	-9999	-10000	0	0
PTN	0.023	0.017	-9999	-10000	0	0
FGFR/FGF/Syndecan-3	0.014	0.038	-9999	-0.39	3	3
neuron projection morphogenesis	0.051	0.067	-9999	-0.35	3	3
Syndecan-3/AgRP	0.033	0.043	-9999	-0.37	3	3
Syndecan-3/AgRP/MC4R	0.043	0.051	-9999	-0.36	3	3
Fyn/Cortactin	0.044	0.02	-9999	-10000	0	0
SDC3	0.014	0.038	-9999	-0.39	3	3
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.032	0.051	-9999	-0.36	3	3
IL8	0.022	0.043	-9999	-0.42	3	3
Syndecan-3/Fyn/Cortactin	0.054	0.05	-9999	-0.35	3	3
Syndecan-3/CASK	0.012	0.036	-9999	-0.37	3	3
alpha-MSH/MC4R	-0.002	0.11	-9999	-0.3	41	41
Gamma Secretase	0.088	0.044	-9999	-0.2	2	2

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.037	0.043	-10000	0	-0.22	5	5
regulation of S phase of mitotic cell cycle	0.023	0.014	-10000	0	-10000	0	0
GNAO1	0.019	0.029	-10000	0	-0.42	1	1
HRAS	0.035	0.006	-10000	0	-10000	0	0
SHBG/T-DHT	0.02	0.01	-10000	0	-10000	0	0
PELP1	0.033	0.009	-10000	0	-10000	0	0
AKT1	0.01	0.002	-10000	0	-10000	0	0
MAP2K1	0.02	0.053	0.19	30	-10000	0	30
T-DHT/AR	0.011	0.017	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.035	0.005	-10000	0	-10000	0	0
GNAI3	0.034	0.007	-10000	0	-10000	0	0
GNAI1	0.031	0.012	-10000	0	-10000	0	0
mol:GDP	-0.001	0.014	-10000	0	-10000	0	0
cell proliferation	0.038	0.06	0.27	9	-10000	0	9
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
FOS	0.039	0.049	0.26	1	-10000	0	1
mol:Ca2+	0.003	0.007	-10000	0	-0.047	3	3
MAPK3	0.028	0.055	0.3	4	-10000	0	4
MAPK1	0.028	0.051	0.21	2	-0.3	5	7
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
mol:IP3	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.003	0.008	-10000	0	-10000	0	0
GNG2	0.027	0.058	-10000	0	-0.42	6	6
potassium channel inhibitor activity	0	0	-10000	0	-10000	0	0
HRAS/GTP	0.045	0.027	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.045	0.022	-10000	0	-10000	0	0
SRC	0.033	0.009	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
PI3K	0.044	0.012	-10000	0	-10000	0	0
apoptosis	-0.041	0.053	0.28	2	-0.26	4	6
T-DHT/AR/PELP1	0.023	0.027	-10000	0	-10000	0	0
HRAS/GDP	0.012	0.025	-10000	0	-10000	0	0
CREB1	0.041	0.055	0.26	4	-0.3	2	6
RAC1-CDC42/GTP	0.056	0.028	-10000	0	-10000	0	0
AR	0.02	0.017	-10000	0	-10000	0	0
GNB1	0.034	0.007	-10000	0	-10000	0	0
RAF1	0.034	0.051	0.2	30	-10000	0	30
RAC1-CDC42/GDP	0.041	0.028	-10000	0	-10000	0	0
T-DHT/AR/PELP1/Src	0.039	0.03	-10000	0	-10000	0	0
MAP2K2	0.019	0.052	0.19	28	-10000	0	28
T-DHT/AR/PELP1/Src/PI3K	0.023	0.014	-10000	0	-10000	0	0
GNAZ	0.027	0.035	-10000	0	-0.42	2	2
SHBG	0.03	0.012	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.009	0.08	-10000	0	-0.34	12	12
mol:T-DHT	0	0	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
GNRH1	0.003	0.042	-10000	0	-0.29	7	7
Gi family/GTP	0.01	0.03	-10000	0	-0.17	4	4
CDC42	0.035	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.028	0.076	-10000	0	-0.3	18	18
AKT1	0.061	0.079	0.41	3	-0.34	1	4
PTK2B	0.031	0.075	0.36	3	-10000	0	3
VEGFR2 homodimer/Frs2	0.045	0.017	-10000	0	-10000	0	0
CAV1	0.032	0.011	-10000	0	-10000	0	0
CALM1	0.034	0.006	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.056	0.031	-10000	0	-10000	0	0
endothelial cell proliferation	0.021	0.13	0.31	15	-0.29	8	23
mol:Ca2+	0.041	0.046	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.071	0.042	-10000	0	-10000	0	0
RP11-342D11.1	0.018	0.026	0.18	8	-10000	0	8
CDH5	0.034	0.007	-10000	0	-10000	0	0
VEGFA homodimer	0.07	0.038	-10000	0	-10000	0	0
SHC1	0.032	0.011	-10000	0	-10000	0	0
SHC2	0.022	0.036	-10000	0	-0.42	2	2
HRAS/GDP	0.053	0.032	-10000	0	-10000	0	0
SH2D2A	-0.003	0.12	-10000	0	-0.42	28	28
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.035	0.1	-10000	0	-0.43	3	3
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.036	0.074	-10000	0	-0.22	24	24
VEGFR1 homodimer	0.034	0.007	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.085	0.049	-10000	0	-10000	0	0
GRB10	0.039	0.042	-10000	0	-10000	0	0
PTPN11	0.034	0.006	-10000	0	-10000	0	0
GRB2	0.034	0.007	-10000	0	-10000	0	0
PAK1	0.033	0.009	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.087	0.045	-10000	0	-10000	0	0
HRAS	0.034	0.006	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.037	0.057	-10000	0	-0.29	3	3
HIF1A	0.035	0.005	-10000	0	-10000	0	0
FRS2	0.034	0.007	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.069	0.04	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.033	0.01	-10000	0	-10000	0	0
Nck/Pak	0.047	0.015	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.051	0.033	-10000	0	-10000	0	0
mol:GDP	0.066	0.039	-10000	0	-10000	0	0
mol:NADP	0.071	0.075	0.33	8	-0.31	2	10
eNOS/Hsp90	0.087	0.072	0.33	8	-0.3	2	10
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
mol:IP3	0.041	0.047	-10000	0	-10000	0	0
HIF1A/ARNT	0.046	0.017	-10000	0	-10000	0	0
SHB	0.028	0.035	-10000	0	-0.42	2	2
VEGFA	0.032	0.013	-10000	0	-10000	0	0
VEGFC	0.034	0.006	-10000	0	-10000	0	0
FAK1/Vinculin	0.065	0.074	0.32	5	-10000	0	5
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.035	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.06	0.066	-10000	0	-0.2	14	14
PTPN6	-0.074	0.19	-10000	0	-0.42	88	88
EPAS1	0.045	0.01	-10000	0	-10000	0	0
mol:L-citrulline	0.071	0.075	0.33	8	-0.31	2	10
ITGAV	0.035	0.004	-10000	0	-10000	0	0
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.073	0.04	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer	0.063	0.031	-10000	0	-10000	0	0
VEGFR2/3 heterodimer	0.044	0.018	-10000	0	-10000	0	0
VEGFB	0.034	0.006	-10000	0	-10000	0	0
MAPK11	0.038	0.067	0.32	7	-10000	0	7
VEGFR2 homodimer	0.03	0.011	-10000	0	-10000	0	0
FLT1	0.034	0.007	-10000	0	-10000	0	0
NEDD4	0.036	0.007	-10000	0	-10000	0	0
MAPK3	0.013	0.087	0.33	8	-10000	0	8
MAPK1	0.017	0.091	0.32	12	-10000	0	12
VEGFA145/NRP2	0.045	0.021	-10000	0	-10000	0	0
VEGFR1/2 heterodimer	0.045	0.017	-10000	0	-10000	0	0
KDR	0.03	0.011	-10000	0	-10000	0	0
VEGFA165/NRP1/VEGFR2 homodimer	0.067	0.034	-10000	0	-10000	0	0
SRC	0.033	0.009	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.023	0.09	0.31	12	-10000	0	12
PI3K	0.054	0.054	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.057	0.03	-10000	0	-10000	0	0
FES	0.038	0.057	-10000	0	-10000	0	0
GAB1	0.051	0.043	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.054	0.032	-10000	0	-10000	0	0
CTNNB1	0.035	0.005	-10000	0	-10000	0	0
SOS1	0.035	0.003	-10000	0	-10000	0	0
ARNT	0.032	0.011	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.074	0.072	0.34	6	-0.29	2	8
VEGFR2 homodimer/VEGFA homodimer/Yes	0.056	0.031	-10000	0	-10000	0	0
PI3K/GAB1	0.062	0.073	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.081	0.047	-10000	0	-10000	0	0
PRKACA	0.035	0.003	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.06	0.025	-10000	0	-10000	0	0
HSP90AA1	0.033	0.024	-10000	0	-0.42	1	1
CDC42	0.045	0.047	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.035	0.073	-10000	0	-0.22	24	24
PTK2	0.04	0.062	0.28	4	-10000	0	4
EDG1	0.018	0.026	0.18	8	-10000	0	8
mol:DAG	0.041	0.047	-10000	0	-10000	0	0
CaM/Ca2+	0.055	0.044	-10000	0	-10000	0	0
MAP2K3	0.036	0.063	0.36	4	-10000	0	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.072	0.051	-10000	0	-10000	0	0
PLCG1	0.042	0.047	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.063	0.049	-10000	0	-0.2	2	2
IQGAP1	0.034	0.006	-10000	0	-10000	0	0
YES1	0.034	0.008	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.057	0.03	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.003	0.12	-10000	0	-0.22	78	78
cell migration	0.077	0.089	0.31	17	-10000	0	17
mol:PI-3-4-5-P3	0.052	0.052	-10000	0	-10000	0	0
FYN	0.031	0.012	-10000	0	-10000	0	0
VEGFB/NRP1	0.036	0.027	-10000	0	-10000	0	0
mol:NO	0.071	0.075	0.33	8	-0.31	2	10
PXN	0.034	0.006	-10000	0	-10000	0	0
HRAS/GTP	0.032	0.02	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.049	0.031	-10000	0	-10000	0	0
VHL	0.035	0.005	-10000	0	-10000	0	0
ITGB3	0.009	0.097	-10000	0	-0.42	18	18
NOS3	0.073	0.078	0.34	8	-0.35	2	10
VEGFR2 homodimer/VEGFA homodimer/Sck	0.043	0.039	-10000	0	-0.22	2	2
RAC1	0.031	0.012	-10000	0	-10000	0	0
PRKCA	0.034	0.061	0.36	4	-10000	0	4
PRKCB	-0.017	0.11	0.36	4	-10000	0	4
VCL	0.032	0.01	-10000	0	-10000	0	0
VEGFA165/NRP1	0.04	0.03	-10000	0	-10000	0	0
VEGFR1/2 heterodimer/VEGFA homodimer	0.057	0.03	-10000	0	-10000	0	0
VEGFA165/NRP2	0.045	0.021	-10000	0	-10000	0	0
MAPKKK cascade	0.049	0.051	0.36	1	-10000	0	1
NRP2	0.035	0.004	-10000	0	-10000	0	0
VEGFC homodimer	0.034	0.006	-10000	0	-10000	0	0
NCK1	0.034	0.006	-10000	0	-10000	0	0
ROCK1	0.035	0.005	-10000	0	-10000	0	0
FAK1/Paxillin	0.067	0.076	0.32	5	-10000	0	5
MAP3K13	0.043	0.049	-10000	0	-10000	0	0
PDPK1	0.046	0.053	0.25	3	-10000	0	3

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.03	0.013	-10000	0	-10000	0	0
CLTC	0.032	0.058	0.22	1	-0.37	6	7
calcium ion-dependent exocytosis	0.026	0.029	-10000	0	-10000	0	0
Dynamin 2/GTP	0.035	0.008	-10000	0	-10000	0	0
EXOC4	0.031	0.012	-10000	0	-10000	0	0
CD59	0.023	0.042	-10000	0	-0.29	5	5
CPE	0.017	0.025	-10000	0	-0.25	3	3
CTNNB1	0.035	0.005	-10000	0	-10000	0	0
membrane fusion	0.025	0.03	-10000	0	-10000	0	0
CTNND1	0.02	0.02	0.19	5	-10000	0	5
DNM2	0.035	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.028	0.038	0.17	3	-0.23	2	5
TSHR	-0.003	0.072	-10000	0	-0.25	29	29
INS	0.006	0.081	-10000	0	-0.46	10	10
BIN1	0.017	0.09	-10000	0	-0.42	15	15
mol:Choline	0.025	0.03	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.004	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.035	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.035	0.008	-10000	0	-10000	0	0
JUP	0.022	0.041	-10000	0	-0.29	5	5
ASAP2/amphiphysin II	0.055	0.058	-10000	0	-0.22	15	15
ARF6/GTP	0.026	0.003	-10000	0	-10000	0	0
CDH1	-0.025	0.092	-10000	0	-0.38	6	6
clathrin-independent pinocytosis	0.026	0.003	-10000	0	-10000	0	0
MAPK8IP3	0.035	0.003	-10000	0	-10000	0	0
positive regulation of endocytosis	0.026	0.003	-10000	0	-10000	0	0
EXOC2	0.031	0.012	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.028	0.045	-10000	0	-0.2	2	2
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.034	0.006	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.014	0.089	0.32	6	-10000	0	6
positive regulation of phagocytosis	0.019	0.004	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.047	0.007	-10000	0	-10000	0	0
ACAP1	-0.005	0.064	-10000	0	-0.19	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.019	0.049	-10000	0	-0.3	6	6
clathrin heavy chain/ACAP1	0.023	0.053	0.24	2	-0.29	6	8
JIP4/KLC1	0.064	0.015	-10000	0	-10000	0	0
EXOC1	0.035	0.005	-10000	0	-10000	0	0
exocyst	0.029	0.044	-10000	0	-0.21	2	2
RALA/GTP	0.023	0.008	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.046	0.009	-10000	0	-10000	0	0
receptor recycling	0.026	0.003	-10000	0	-10000	0	0
CTNNA1	0.019	0.02	0.19	5	-10000	0	5
NME1	0.019	0.004	-10000	0	-10000	0	0
clathrin coat assembly	0.032	0.059	0.22	1	-0.36	6	7
IL2RA	-0.015	0.089	-10000	0	-0.39	7	7
VAMP3	0.019	0.004	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.034	0.051	-10000	0	-0.27	7	7
EXOC6	0.031	0.025	-10000	0	-0.42	1	1
PLD1	0.018	0.011	-10000	0	-10000	0	0
PLD2	0.017	0.011	-10000	0	-10000	0	0
EXOC5	0.035	0.005	-10000	0	-10000	0	0
PIP5K1C	0.023	0.034	-10000	0	-0.23	2	2
SDC1	0.017	0.052	-10000	0	-0.31	6	6
ARF6/GDP	0.032	0.007	-10000	0	-10000	0	0
EXOC7	0.034	0.007	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.016	0.092	-10000	0	-0.33	6	6
mol:Phosphatidic acid	0.025	0.03	-10000	0	-10000	0	0
endocytosis	-0.052	0.057	0.22	15	-10000	0	15
SCAMP2	0.034	0.006	-10000	0	-10000	0	0
ADRB2	0.029	0.059	0.22	2	-0.34	6	8
EXOC3	0.032	0.01	-10000	0	-10000	0	0
ASAP2	0.035	0.004	-10000	0	-10000	0	0
Dynamin 2/GDP	0.04	0.009	-10000	0	-10000	0	0
KLC1	0.034	0.006	-10000	0	-10000	0	0
AVPR2	0.03	0.061	0.21	5	-0.35	6	11
RALA	0.031	0.011	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.014	0.089	0.36	1	-0.31	6	7

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.035	0.003	-10000	0	-10000	0	0
PTK2	0.031	0.012	-10000	0	-10000	0	0
CRKL	0.019	0.027	0.17	3	-0.22	3	6
GRB2/SOS1/SHC	0.062	0.025	-10000	0	-10000	0	0
HRAS	0.034	0.006	-10000	0	-10000	0	0
IRS1/Crk	0.029	0.026	-10000	0	-0.22	3	3
IGF-1R heterotetramer/IGF1/PTP1B	0.056	0.039	-10000	0	-0.24	3	3
AKT1	0.014	0.038	0.19	7	-0.19	3	10
BAD	-0.002	0.038	0.18	7	-0.18	3	10
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0.026	0.17	2	-0.22	3	5
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.04	0.032	0.22	2	-0.22	3	5
RAF1	0.023	0.067	0.28	1	-0.38	7	8
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.075	0.037	-10000	0	-0.21	2	2
YWHAZ	0.032	0.011	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.041	0.03	0.16	1	-0.24	3	4
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
RPS6KB1	0.014	0.035	0.19	6	-0.19	2	8
GNB2L1	0.033	0.008	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.023	0.071	0.28	4	-0.33	6	10
PXN	0.034	0.006	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.05	0.011	-10000	0	-10000	0	0
HRAS/GTP	0.036	0.025	-10000	0	-0.19	1	1
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.085	0.045	-10000	0	-0.19	1	1
IGF-1R heterotetramer	0.035	0.015	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.06	0.036	-10000	0	-0.22	3	3
Crk/p130 Cas/Paxillin	0.072	0.038	0.23	1	-0.2	3	4
IGF1R	0.035	0.015	-10000	0	-10000	0	0
IGF1	0.033	0.044	-10000	0	-0.43	3	3
IRS2/Crk	0.031	0.028	0.17	2	-0.21	3	5
PI3K	0.074	0.039	-10000	0	-0.21	3	3
apoptosis	-0.024	0.038	-10000	0	-0.22	2	2
HRAS/GDP	0.025	0.004	-10000	0	-10000	0	0
PRKCD	0.026	0.056	0.21	2	-0.28	8	10
RAF1/14-3-3 E	0.038	0.065	0.28	1	-0.34	7	8
BAD/14-3-3	0.026	0.039	0.23	2	-10000	0	2
PRKCZ	0.012	0.04	0.19	6	-0.19	5	11
Crk/p130 Cas/Paxillin/FAK1	0.043	0.033	-10000	0	-0.18	1	1
PTPN1	0.032	0.01	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.022	0.053	-10000	0	-0.29	8	8
BCAR1	0.034	0.007	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.068	0.041	-10000	0	-0.19	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.035	0.003	-10000	0	-10000	0	0
IRS1/NCK2	0.038	0.032	-10000	0	-0.22	3	3
GRB10	0.031	0.011	-10000	0	-10000	0	0
PTPN11	0.021	0.027	0.17	3	-0.22	3	6
IRS1	0.019	0.03	0.13	5	-0.23	3	8
IRS2	0.02	0.027	0.17	3	-0.22	3	6
IGF-1R heterotetramer/IGF1	0.046	0.038	-10000	0	-0.32	3	3
GRB2	0.034	0.007	-10000	0	-10000	0	0
PDPK1	0.025	0.038	0.2	7	-0.2	3	10
YWHAE	0.033	0.009	-10000	0	-10000	0	0
PRKD1	0.027	0.051	-10000	0	-0.28	7	7
SHC1	0.032	0.011	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.018	0.033	0.15	19	-10000	0	19
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.022	0.044	0.14	21	-0.2	2	23
AP2	0.05	0.01	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.041	0.018	-10000	0	-10000	0	0
CLTB	0.033	0.008	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.022	0.012	-10000	0	-10000	0	0
CD4	-0.008	0.13	-10000	0	-0.42	34	34
CLTA	0.032	0.011	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ARFGAP1	0.009	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.01	0.011	-10000	0	-10000	0	0
ARF1/GTP	0.038	0.018	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.013	0.009	-10000	0	-10000	0	0
mol:Choline	0.009	0.011	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.033	0.011	-10000	0	-10000	0	0
DDEF1	0.008	0.011	-10000	0	-10000	0	0
ARF1/GDP	0.007	0.014	-10000	0	-0.11	1	1
AP2M1	0.034	0.006	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.015	0.008	-10000	0	-10000	0	0
Rac/GTP	0.025	0.01	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.043	0.021	-10000	0	-10000	0	0
ARFIP2	0.026	0.019	-10000	0	-10000	0	0
COPA	0.032	0.011	-10000	0	-10000	0	0
RAC1	0.031	0.012	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.011	0.047	-10000	0	-0.2	9	9
ARF1/GTP/ARHGAP10	0.022	0.009	-10000	0	-10000	0	0
GGA3	0.034	0.007	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.025	0.043	-10000	0	-0.21	11	11
AP2A1	0.035	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.01	0.044	-10000	0	-0.22	11	11
ARF1/GDP/Membrin	0.025	0.05	-10000	0	-0.24	11	11
Arfaptin 2/Rac/GDP	0.039	0.017	-10000	0	-10000	0	0
CYTH2	0.038	0.009	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.042	0.017	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.023	0.009	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.008	0.074	-10000	0	-0.22	27	27
PLD2	0.009	0.011	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	0.009	0.003	-10000	0	-10000	0	0
PIP5K1A	0.01	0.011	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.022	0.026	-10000	0	-0.12	2	2
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.009	0.011	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.009	0.003	-10000	0	-10000	0	0
GOSR2	0.013	0.036	-10000	0	-0.31	4	4
USO1	0.015	0.026	-10000	0	-0.32	2	2
GBF1	0.002	0.067	-10000	0	-0.31	16	16
ARF1/GTP/Arfaptin 2	0.044	0.018	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.037	0.093	-10000	0	-0.25	34	34

×

Coregulation of Androgen receptor activity

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
NRIP1	0.034	0.006	-9999	-10000	0	0
SVIL	0.032	0.01	-9999	-10000	0	0
ZNF318	0.032	0.011	-9999	-10000	0	0
JMJD2C	0.003	0.006	-9999	-10000	0	0
T-DHT/AR/Ubc9	0.025	0.04	-9999	-0.19	2	2
CARM1	0.035	0.003	-9999	-10000	0	0
PRDX1	0.029	0.053	-9999	-0.42	5	5
PELP1	0.033	0.009	-9999	-10000	0	0
CTNNB1	0.035	0.005	-9999	-10000	0	0
AKT1	0.034	0.005	-9999	-10000	0	0
PTK2B	0.028	0.048	-9999	-0.42	4	4
MED1	0.034	0.006	-9999	-10000	0	0
MAK	0.03	0.012	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.032	0.01	-9999	-10000	0	0
GSN	0.033	0.009	-9999	-10000	0	0
NCOA2	0.032	0.011	-9999	-10000	0	0
NCOA6	0.033	0.009	-9999	-10000	0	0
DNA-PK	0.06	0.027	-9999	-10000	0	0
NCOA4	0.032	0.011	-9999	-10000	0	0
PIAS3	0.031	0.011	-9999	-10000	0	0
cell proliferation	0.019	0.016	-9999	-10000	0	0
XRCC5	0.035	0.004	-9999	-10000	0	0
UBE3A	0.034	0.006	-9999	-10000	0	0
T-DHT/AR/SNURF	0.015	0.061	-9999	-0.24	13	13
FHL2	0.021	0.11	-9999	-0.78	6	6
RANBP9	0.031	0.012	-9999	-10000	0	0
JMJD1A	0.001	0.028	-9999	-0.13	15	15
CDK6	0.028	0.042	-9999	-0.42	3	3
TGFB1I1	0.034	0.024	-9999	-0.42	1	1
T-DHT/AR/CyclinD1	0.022	0.04	-9999	-0.19	2	2
XRCC6	0.032	0.01	-9999	-10000	0	0
T-DHT/AR	0.028	0.061	-9999	-0.19	18	18
CTDSP1	0.035	0.004	-9999	-10000	0	0
CTDSP2	0.034	0.007	-9999	-10000	0	0
BRCA1	0.034	0.005	-9999	-10000	0	0
TCF4	0.03	0.041	-9999	-0.42	3	3
CDKN2A	0.009	0.016	-9999	-10000	0	0
SRF	0.036	0.022	-9999	-0.15	3	3
NKX3-1	-0.002	0.05	-9999	-0.24	15	15
KLK3	0	0.037	-9999	-10000	0	0
TMF1	0.034	0.007	-9999	-10000	0	0
HNRNPA1	0.035	0.004	-9999	-10000	0	0
AOF2	0	0	-9999	-10000	0	0
APPL1	0.019	0.004	-9999	-10000	0	0
T-DHT/AR/Caspase 8	0.025	0.041	-9999	-0.17	3	3
AR	0.017	0.03	-9999	-0.14	2	2
UBA3	0.034	0.007	-9999	-10000	0	0
PATZ1	0.034	0.007	-9999	-10000	0	0
PAWR	0.016	0.09	-9999	-0.42	15	15
PRKDC	0.033	0.009	-9999	-10000	0	0
PA2G4	0.035	0.005	-9999	-10000	0	0
UBE2I	0.035	0.003	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.023	0.034	-9999	-10000	0	0
RPS6KA3	0.035	0.003	-9999	-10000	0	0
T-DHT/AR/ARA70	0.022	0.04	-9999	-0.16	3	3
LATS2	0.034	0.007	-9999	-10000	0	0
T-DHT/AR/PRX1	0.02	0.046	-9999	-0.2	7	7
Cyclin D3/CDK11 p58	0.023	0.008	-9999	-10000	0	0
VAV3	0.029	0.041	-9999	-0.42	3	3
KLK2	0.009	0.03	-9999	-10000	0	0
CASP8	0.035	0.004	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.038	0.044	-9999	-0.17	2	2
TMPRSS2	-0.015	0.18	-9999	-0.88	15	15
CCND1	0.032	0.01	-9999	-10000	0	0
PIAS1	0.035	0.005	-9999	-10000	0	0
mol:T-DHT	0	0.017	-9999	-0.067	19	19
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.035	0.004	-9999	-10000	0	0
T-DHT/AR/CDK6	0.021	0.046	-9999	-0.22	5	5
CMTM2	0.031	0.011	-9999	-10000	0	0
SNURF	0.02	0.077	-9999	-0.42	11	11
ZMIZ1	0.03	0.026	-9999	-0.14	1	1
CCND3	0.032	0.011	-9999	-10000	0	0
TGIF1	0.034	0.007	-9999	-10000	0	0
FKBP4	0.034	0.006	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.077	0.041	-9999	-0.22	3	3
HDAC3	0.033	0.008	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.009	0.003	-9999	-10000	0	0
GATA1/HDAC4	0.037	0.009	-9999	-10000	0	0
GATA1/HDAC5	0.038	0.008	-9999	-10000	0	0
GATA2/HDAC5	0.048	0.015	-9999	-10000	0	0
HDAC5/BCL6/BCoR	0.067	0.018	-9999	-10000	0	0
HDAC9	0.012	0.089	-9999	-0.42	15	15
Glucocorticoid receptor/Hsp90/HDAC6	0.065	0.025	-9999	-0.23	1	1
HDAC4/ANKRA2	0.047	0.023	-9999	-0.3	1	1
HDAC5/YWHAB	0.047	0.016	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.019	0.007	-9999	-10000	0	0
GATA2	0.033	0.008	-9999	-10000	0	0
HDAC4/RFXANK	0.049	0.013	-9999	-10000	0	0
BCOR	0.035	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.032	0.01	-9999	-10000	0	0
HDAC5	0.034	0.006	-9999	-10000	0	0
GNB1/GNG2	0.044	0.041	-9999	-0.29	5	5
Histones	0.032	0.061	-9999	-0.2	16	16
ADRBK1	0.034	0.007	-9999	-10000	0	0
HDAC4	0.033	0.008	-9999	-10000	0	0
XPO1	0.035	0.002	-9999	-10000	0	0
HDAC5/ANKRA2	0.048	0.022	-9999	-0.3	1	1
HDAC4/Ubc9	0.049	0.012	-9999	-10000	0	0
HDAC7	0.034	0.006	-9999	-10000	0	0
HDAC5/14-3-3 E	0.048	0.015	-9999	-10000	0	0
TUBA1B	0.034	0.005	-9999	-10000	0	0
HDAC6	0.035	0.003	-9999	-10000	0	0
HDAC5/RFXANK	0.05	0.011	-9999	-10000	0	0
CAMK4	-0.027	0.15	-9999	-0.42	49	49
Tubulin/HDAC6	0.061	0.026	-9999	-10000	0	0
SUMO1	0.035	0.003	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.033	0.01	-9999	-10000	0	0
GATA1	0.017	0.002	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.033	0.009	-9999	-10000	0	0
NR3C1	0.033	0.009	-9999	-10000	0	0
SUMO1/HDAC4	0.058	0.029	-9999	-10000	0	0
SRF	0.032	0.011	-9999	-10000	0	0
HDAC4/YWHAB	0.046	0.017	-9999	-10000	0	0
Tubulin	0.045	0.019	-9999	-10000	0	0
HDAC4/14-3-3 E	0.046	0.017	-9999	-10000	0	0
GNB1	0.034	0.007	-9999	-10000	0	0
RANGAP1	0.032	0.011	-9999	-10000	0	0
BCL6/BCoR	0.051	0.01	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.063	0.024	-9999	-10000	0	0
HDAC4/SRF	0.022	0.1	-9999	-0.25	41	41
HDAC4/ER alpha	0.038	0.047	-9999	-0.29	6	6
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.032	0.061	-9999	-0.2	16	16
cell motility	0.06	0.025	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.035	0.003	-9999	-10000	0	0
HDAC7/HDAC3	0.048	0.015	-9999	-10000	0	0
BCL6	0.034	0.006	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.033	0.008	-9999	-10000	0	0
Hsp90/HDAC6	0.05	0.02	-9999	-0.3	1	1
ESR1	0.023	0.058	-9999	-0.42	6	6
HDAC6/HDAC11	0.051	0.008	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.06	0.03	-9999	-10000	0	0
NPC	0.021	0.002	-9999	-10000	0	0
MEF2C	0.031	0.034	-9999	-0.42	2	2
RAN	0.034	0.006	-9999	-10000	0	0
HDAC4/MEF2C	0.089	0.041	-9999	-0.19	2	2
GNG2	0.027	0.058	-9999	-0.42	6	6
NCOR2	0.034	0.006	-9999	-10000	0	0
TUBB2A	0.031	0.012	-9999	-10000	0	0
HDAC11	0.035	0.005	-9999	-10000	0	0
HSP90AA1	0.033	0.024	-9999	-0.42	1	1
RANBP2	0.035	0.003	-9999	-10000	0	0
ANKRA2	0.033	0.025	-9999	-0.42	1	1
RFXANK	0.035	0.004	-9999	-10000	0	0
nuclear import	-0.039	0.019	-9999	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.03	0.048	-10000	0	-0.42	4	4
PDGF/PDGFRA/CRKL	0.042	0.039	-10000	0	-0.28	4	4
positive regulation of JUN kinase activity	0.069	0.043	-10000	0	-0.21	3	3
CRKL	0.033	0.01	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	0.033	0.035	-10000	0	-0.28	4	4
AP1	0.015	0.043	-10000	0	-10000	0	0
mol:IP3	0.014	0.03	-10000	0	-0.3	3	3
PLCG1	0.014	0.031	-10000	0	-0.3	3	3
PDGF/PDGFRA/alphaV Integrin	0.045	0.038	-10000	0	-0.28	4	4
RAPGEF1	0.033	0.009	-10000	0	-10000	0	0
CRK	0.033	0.009	-10000	0	-10000	0	0
mol:Ca2+	0.014	0.03	-10000	0	-0.3	3	3
CAV3	0.017	0.002	-10000	0	-10000	0	0
CAV1	0.032	0.011	-10000	0	-10000	0	0
SHC/Grb2/SOS1	0.071	0.044	-10000	0	-0.21	3	3
PDGF/PDGFRA/Shf	0.043	0.039	-10000	0	-0.28	4	4
FOS	0	0.04	0.32	2	-10000	0	2
JUN	-0.019	0.013	-10000	0	-10000	0	0
oligodendrocyte development	0.045	0.038	-10000	0	-0.28	4	4
GRB2	0.034	0.007	-10000	0	-10000	0	0
PIK3R1	0.034	0.007	-10000	0	-10000	0	0
mol:DAG	0.014	0.03	-10000	0	-0.3	3	3
PDGF/PDGFRA	0.03	0.048	-10000	0	-0.42	4	4
actin cytoskeleton reorganization	0.037	0.045	-10000	0	-0.29	5	5
SRF	0.014	0.01	-10000	0	-10000	0	0
SHC1	0.032	0.011	-10000	0	-10000	0	0
PI3K	0.06	0.039	-10000	0	-0.22	4	4
PDGF/PDGFRA/Crk/C3G	0.056	0.042	-10000	0	-0.23	4	4
JAK1	0.015	0.033	-10000	0	-0.28	4	4
ELK1/SRF	0.018	0.038	0.16	19	-0.23	2	21
SHB	0.028	0.035	-10000	0	-0.42	2	2
SHF	0.034	0.007	-10000	0	-10000	0	0
CSNK2A1	0.029	0.015	-10000	0	-10000	0	0
GO:0007205	0.006	0.031	-10000	0	-0.32	3	3
SOS1	0.035	0.003	-10000	0	-10000	0	0
Ras protein signal transduction	0.069	0.043	-10000	0	-0.21	3	3
PDGF/PDGFRA/SHB	0.038	0.045	-10000	0	-0.29	5	5
PDGF/PDGFRA/Caveolin-1	0.04	0.04	-10000	0	-0.28	4	4
ITGAV	0.035	0.004	-10000	0	-10000	0	0
ELK1	0.003	0.026	0.25	1	-0.28	2	3
PIK3CA	0.034	0.006	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	0.042	0.04	-10000	0	-0.28	4	4
JAK-STAT cascade	0.015	0.032	-10000	0	-0.28	4	4
cell proliferation	0.043	0.038	-10000	0	-0.28	4	4

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.032	0.011	-10000	0	-10000	0	0
HDAC4	0.033	0.008	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.005	0.051	0.3	10	-10000	0	10
CDKN1A	-0.006	0.005	-10000	0	-10000	0	0
KAT2B	0.032	0.034	-10000	0	-0.42	2	2
BAX	0.035	0.004	-10000	0	-10000	0	0
FOXO3	-0.005	0.005	-10000	0	-10000	0	0
FOXO1	0.034	0.007	-10000	0	-10000	0	0
FOXO4	0.02	0.007	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.032	0.01	-10000	0	-10000	0	0
TAT	0.017	0.003	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.003	0.027	-10000	0	-0.3	2	2
PPARGC1A	0.009	0.073	-10000	0	-0.42	10	10
FHL2	0.029	0.052	-10000	0	-0.42	5	5
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.041	0.019	-10000	0	-10000	0	0
HIST2H4A	0.005	0.051	-10000	0	-0.3	10	10
SIRT1/FOXO3a	-0.002	0.059	-10000	0	-0.19	31	31
SIRT1	0.028	0.009	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.054	0.028	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.047	0.039	-10000	0	-10000	0	0
apoptosis	-0.056	0.026	-10000	0	-10000	0	0
SIRT1/PGC1A	0.014	0.051	-10000	0	-0.25	10	10
p53/SIRT1	0.035	0.015	-10000	0	-10000	0	0
SIRT1/FOXO4	0.04	0.031	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	0.054	0.039	-10000	0	-0.22	5	5
HIST1H1E	0.018	0.009	-10000	0	-10000	0	0
SIRT1/p300	0.04	0.019	-10000	0	-10000	0	0
muscle cell differentiation	-0.038	0.027	0.25	2	-0.22	1	3
TP53	0.029	0.008	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.057	0.026	-10000	0	-10000	0	0
CREBBP	0.035	0.004	-10000	0	-10000	0	0
MEF2D	0.032	0.011	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.032	0.011	-10000	0	-10000	0	0
ACSS2	0.014	0.007	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.038	0.027	0.23	1	-0.25	2	3

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.24	0.15	-10000	0	-1	2	2
PLK1	0.084	0.062	-10000	0	-0.55	2	2
BIRC5	0.082	0.071	-10000	0	-0.67	2	2
HSPA1B	0.26	0.17	0.7	2	-1	2	4
MAP2K1	0.07	0.027	-10000	0	-10000	0	0
BRCA2	0.24	0.2	0.7	1	-1.1	6	7
FOXM1	0.26	0.17	-10000	0	-1.2	2	2
XRCC1	0.24	0.15	-10000	0	-1	2	2
FOXM1B/p19	0.048	0.15	-10000	0	-1.1	2	2
Cyclin D1/CDK4	0.21	0.16	-10000	0	-0.86	2	2
CDC2	0.25	0.16	-10000	0	-1.1	2	2
TGFA	0.19	0.18	-10000	0	-0.85	3	3
SKP2	0.25	0.16	-10000	0	-0.96	2	2
CCNE1	0.043	0.007	-10000	0	-10000	0	0
CKS1B	0.24	0.15	-10000	0	-1	2	2
RB1	0.16	0.13	-10000	0	-0.87	2	2
FOXM1C/SP1	0.25	0.16	-10000	0	-1.1	2	2
AURKB	0.042	0.18	-10000	0	-0.69	13	13
CENPF	0.26	0.17	0.68	1	-1.2	2	3
CDK4	0.047	0.014	-10000	0	-10000	0	0
MYC	0.21	0.16	-10000	0	-0.88	2	2
CHEK2	0.067	0.03	-10000	0	-10000	0	0
ONECUT1	0.14	0.18	-10000	0	-0.96	2	2
CDKN2A	0.008	0.013	-10000	0	-10000	0	0
LAMA4	0.24	0.15	-10000	0	-1	2	2
FOXM1B/HNF6	0.14	0.19	-10000	0	-1.1	2	2
FOS	0.24	0.15	-10000	0	-1	2	2
SP1	0.036	0.005	-10000	0	-10000	0	0
CDC25B	0.25	0.16	-10000	0	-1	2	2
response to radiation	0.033	0.016	-10000	0	-10000	0	0
CENPB	0.25	0.16	-10000	0	-1	2	2
CENPA	0.24	0.17	-10000	0	-1.4	2	2
NEK2	0.26	0.19	0.68	1	-1.3	3	4
HIST1H2BA	0.26	0.17	0.69	2	-1	2	4
CCNA2	0.042	0.026	-10000	0	-0.43	1	1
EP300	0.032	0.011	-10000	0	-10000	0	0
CCNB1/CDK1	0.25	0.16	-10000	0	-1.2	2	2
CCNB2	0.24	0.2	0.73	2	-0.99	6	8
CCNB1	0.25	0.16	-10000	0	-1.1	2	2
ETV5	0.24	0.16	0.7	1	-1	3	4
ESR1	0.23	0.22	-10000	0	-0.99	9	9
CCND1	0.2	0.16	-10000	0	-0.93	2	2
GSK3A	0.067	0.023	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.1	0.031	-10000	0	-10000	0	0
CDK2	0.043	0.007	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.038	0.018	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	0.23	0.17	-10000	0	-1.1	2	2
GAS1	0.24	0.18	-10000	0	-1	5	5
MMP2	0.24	0.18	-10000	0	-1	4	4
RB1/FOXM1C	0.22	0.17	0.6	1	-0.88	3	4
CREBBP	0.035	0.004	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.046	0.027	-10000	0	-10000	0	0
BIRC5	0.034	0.007	-10000	0	-10000	0	0
NFKBIA	0.013	0.012	-10000	0	-10000	0	0
CPEB1	0.001	0.12	-10000	0	-0.42	27	27
AKT1	0.013	0.012	-10000	0	-10000	0	0
NDEL1	0.033	0.009	-10000	0	-10000	0	0
Aurora A/BRCA1	0.034	0.021	-10000	0	-10000	0	0
NDEL1/TACC3	0.056	0.03	-10000	0	-10000	0	0
GADD45A	0.034	0.005	-10000	0	-10000	0	0
GSK3B	0.033	0.009	-10000	0	-10000	0	0
PAK1/Aurora A	0.044	0.027	-10000	0	-10000	0	0
MDM2	0.033	0.008	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.018	0.006	-10000	0	-10000	0	0
TP53	0.026	0.025	-10000	0	-10000	0	0
DLG7	0.014	0.012	-10000	0	-10000	0	0
AURKAIP1	0.034	0.007	-10000	0	-10000	0	0
ARHGEF7	0.034	0.007	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.059	0.031	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.033	0.021	-10000	0	-10000	0	0
AURKA	0.024	0.016	-10000	0	-10000	0	0
AURKB	0.017	0.025	-10000	0	-0.27	2	2
CDC25B	0.023	0.012	-10000	0	-10000	0	0
G2/M transition checkpoint	0.013	0.016	-10000	0	-10000	0	0
mRNA polyadenylation	0.016	0.066	-10000	0	-0.21	24	24
Aurora A/CPEB	0.016	0.066	-10000	0	-0.21	24	24
Aurora A/TACC1/TRAP/chTOG	0.074	0.041	-10000	0	-0.2	1	1
BRCA1	0.034	0.005	-10000	0	-10000	0	0
centrosome duplication	0.044	0.027	-10000	0	-10000	0	0
regulation of centrosome cycle	0.054	0.029	-10000	0	-10000	0	0
spindle assembly	0.072	0.04	-10000	0	-0.2	1	1
TDRD7	0.032	0.025	-10000	0	-0.42	1	1
Aurora A/RasGAP/Survivin	0.07	0.037	-10000	0	-0.2	1	1
CENPA	0.019	0.036	-10000	0	-0.27	5	5
Aurora A/PP2A	0.042	0.029	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.034	0.04	0.19	7	-10000	0	7
negative regulation of DNA binding	0.018	0.049	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.049	0.014	-10000	0	-10000	0	0
RASA1	0.032	0.025	-10000	0	-0.42	1	1
Ajuba/Aurora A	0.013	0.016	-10000	0	-10000	0	0
mitotic prometaphase	0.001	0.019	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.016	-10000	0	-10000	0	0
TACC1	0.034	0.008	-10000	0	-10000	0	0
TACC3	0.034	0.008	-10000	0	-10000	0	0
Aurora A/Antizyme1	0.063	0.03	-10000	0	-10000	0	0
Aurora A/RasGAP	0.044	0.032	-10000	0	-0.24	1	1
OAZ1	0.035	0.004	-10000	0	-10000	0	0
RAN	0.034	0.006	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.034	0.008	-10000	0	-10000	0	0
GIT1	0.034	0.006	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.062	0.025	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.018	0.006	-10000	0	-10000	0	0
PPP2R5D	0.032	0.011	-10000	0	-10000	0	0
Aurora A/TPX2	0.03	0.021	-10000	0	-10000	0	0
PAK1	0.033	0.009	-10000	0	-10000	0	0
CKAP5	0.034	0.006	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.037	0.11	-9999	-0.34	12	12
CaM/Ca2+	0.025	0.004	-9999	-10000	0	0
AKT1	0.034	0.005	-9999	-10000	0	0
AKT2	0.035	0.004	-9999	-10000	0	0
STXBP4	0.034	0.007	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.012	0.11	-9999	-0.36	14	14
YWHAZ	0.032	0.011	-9999	-10000	0	0
CALM1	0.034	0.006	-9999	-10000	0	0
YWHAQ	0.035	0.004	-9999	-10000	0	0
TBC1D4	0.016	0.024	-9999	-0.3	2	2
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.034	0.008	-9999	-10000	0	0
YWHAB	0.033	0.01	-9999	-10000	0	0
SNARE/Synip	0.064	0.022	-9999	-10000	0	0
YWHAG	0.032	0.01	-9999	-10000	0	0
ASIP	0.027	0.013	-9999	-10000	0	0
PRKCI	0.034	0.006	-9999	-10000	0	0
AS160/CaM/Ca2+	0.025	0.004	-9999	-10000	0	0
RHOQ	0.035	0.003	-9999	-10000	0	0
GYS1	0.018	0.005	-9999	-10000	0	0
PRKCZ	0.031	0.034	-9999	-0.42	2	2
TRIP10	0.035	0.004	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.047	0.006	-9999	-10000	0	0
AS160/14-3-3	0.029	0.044	-9999	-0.22	4	4
VAMP2	0.033	0.009	-9999	-10000	0	0
SLC2A4	0.011	0.12	-9999	-0.4	14	14
STX4	0.035	0.004	-9999	-10000	0	0
GSK3B	0.029	0.008	-9999	-10000	0	0
SFN	0.027	0.015	-9999	-10000	0	0
LNPEP	0.034	0.008	-9999	-10000	0	0
YWHAE	0.033	0.009	-9999	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.039	0.043	0.17	3	-10000	0	3
GNAI2	0.035	0.005	-10000	0	-10000	0	0
S1P/S1P5/G12	0.039	0.019	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.018	0.029	-10000	0	-0.42	1	1
RhoA/GTP	0.041	0.045	-10000	0	-0.17	3	3
negative regulation of cAMP metabolic process	0.022	0.036	-10000	0	-0.18	4	4
GNAZ	0.027	0.035	-10000	0	-0.42	2	2
GNAI3	0.034	0.007	-10000	0	-10000	0	0
GNA12	0.031	0.011	-10000	0	-10000	0	0
S1PR5	0.034	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.022	0.037	-10000	0	-0.18	4	4
RhoA/GDP	0.026	0.004	-10000	0	-10000	0	0
RHOA	0.035	0.005	-10000	0	-10000	0	0
GNAI1	0.031	0.012	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.042	0.05	-10000	0	-0.21	10	10
MAPK9	0.01	0.003	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.009	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.041	0.035	-10000	0	-0.24	5	5
GNB1	0.034	0.007	-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	0.009	0.003	-10000	0	-10000	0	0
Gs family/GTP	0.015	0.03	-10000	0	-0.22	5	5
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	0.002	0.007	0.062	5	-10000	0	5
GNAL	0.024	0.053	-10000	0	-0.42	5	5
GNG2	0.027	0.058	-10000	0	-0.42	6	6
CRH	0.016	0.005	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.009	0.003	-10000	0	-10000	0	0
MAPK11	0.009	0.003	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.035	0.005	-9999	-10000	0	0
SMAD2	0.007	0.035	-9999	-0.2	1	1
SMAD3	0.039	0.031	-9999	-10000	0	0
SMAD3/SMAD4	0.054	0.047	-9999	-0.39	3	3
SMAD4/Ubc9/PIASy	0.069	0.013	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.064	0.047	-9999	-10000	0	0
PPM1A	0.035	0.005	-9999	-10000	0	0
CALM1	0.034	0.006	-9999	-10000	0	0
SMAD2/SMAD4	0.027	0.037	-9999	-0.19	1	1
MAP3K1	0.034	0.007	-9999	-10000	0	0
TRAP-1/SMAD4	0.051	0.008	-9999	-10000	0	0
MAPK3	0.035	0.004	-9999	-10000	0	0
MAPK1	0.033	0.009	-9999	-10000	0	0
NUP214	0.033	0.009	-9999	-10000	0	0
CTDSP1	0.035	0.004	-9999	-10000	0	0
CTDSP2	0.034	0.007	-9999	-10000	0	0
CTDSPL	0.035	0.005	-9999	-10000	0	0
KPNB1	0.034	0.006	-9999	-10000	0	0
TGFBRAP1	0.035	0.003	-9999	-10000	0	0
UBE2I	0.035	0.003	-9999	-10000	0	0
NUP153	0.031	0.012	-9999	-10000	0	0
KPNA2	0.034	0.006	-9999	-10000	0	0
PIAS4	0.035	0.004	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.047	0.023	-10000	0	-0.3	1	1
ATM	0.032	0.011	-10000	0	-10000	0	0
UBE2D3	0.034	0.006	-10000	0	-10000	0	0
PRKDC	0.033	0.009	-10000	0	-10000	0	0
ATR	0.034	0.006	-10000	0	-10000	0	0
UBE2L3	0.033	0.009	-10000	0	-10000	0	0
FANCD2	0.027	0.01	-10000	0	-10000	0	0
protein ubiquitination	0.082	0.037	-10000	0	-0.21	1	1
XRCC5	0.035	0.004	-10000	0	-10000	0	0
XRCC6	0.032	0.01	-10000	0	-10000	0	0
M/R/N Complex	0.056	0.036	-10000	0	-0.25	2	2
MRE11A	0.032	0.01	-10000	0	-10000	0	0
DNA-PK	0.06	0.027	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.006	0.13	-10000	0	-0.47	21	21
FANCF	0.034	0.005	-10000	0	-10000	0	0
BRCA1	0.034	0.005	-10000	0	-10000	0	0
CCNE1	0.035	0.004	-10000	0	-10000	0	0
CDK2/Cyclin E1	0.051	0.009	-10000	0	-10000	0	0
FANCG	0.032	0.011	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.05	0.02	-10000	0	-0.3	1	1
FANCE	0.031	0.011	-10000	0	-10000	0	0
FANCC	0.033	0.009	-10000	0	-10000	0	0
NBN	0.032	0.011	-10000	0	-10000	0	0
FANCA	0.033	0.009	-10000	0	-10000	0	0
DNA repair	0.018	0.072	-10000	0	-0.4	5	5
BRCA1/BARD1/ubiquitin	0.05	0.02	-10000	0	-0.3	1	1
BARD1/DNA-PK	0.075	0.035	-10000	0	-10000	0	0
FANCL	0.035	0.003	-10000	0	-10000	0	0
mRNA polyadenylation	-0.046	0.023	0.3	1	-10000	0	1
BRCA1/BARD1/CTIP/M/R/N Complex	0.023	0.056	-10000	0	-0.23	4	4
BRCA1/BACH1/BARD1/TopBP1	0.067	0.023	-10000	0	-0.25	1	1
BRCA1/BARD1/P53	0.08	0.033	-10000	0	-0.23	1	1
BARD1/CSTF1/BRCA1	0.063	0.028	-10000	0	-0.25	1	1
BRCA1/BACH1	0.034	0.005	-10000	0	-10000	0	0
BARD1	0.034	0.024	-10000	0	-0.42	1	1
PCNA	0.033	0.008	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.067	0.023	-10000	0	-0.25	1	1
BRCA1/BARD1/UbcH7	0.063	0.027	-10000	0	-0.25	1	1
BRCA1/BARD1/RAD51/PCNA	0.079	0.034	-10000	0	-0.23	1	1
BARD1/DNA-PK/P53	0.082	0.044	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.05	0.02	-10000	0	-0.3	1	1
BRCA1/BARD1/CTIP	0.052	0.021	-10000	0	-10000	0	0
FA complex	0.029	0.038	-10000	0	-0.25	4	4
BARD1/EWS	0.048	0.022	-10000	0	-0.3	1	1
RBBP8	0.017	0.006	-10000	0	-10000	0	0
TP53	0.033	0.009	-10000	0	-10000	0	0
TOPBP1	0.034	0.006	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.077	0.032	0.23	1	-10000	0	1
BRCA1/BARD1	0.089	0.04	-10000	0	-0.22	1	1
CSTF1	0.032	0.01	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.025	0.017	-10000	0	-0.29	1	1
CDK2	0.035	0.004	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.034	0.008	-10000	0	-10000	0	0
RAD50	0.031	0.034	-10000	0	-0.42	2	2
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.05	0.02	-10000	0	-0.3	1	1
EWSR1	0.033	0.008	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.034	0.007	-9999	-10000	0	0
PLK4	0.033	0.024	-9999	-0.42	1	1
regulation of centriole replication	0.018	0.017	-9999	-0.3	1	1

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.062	0.031	-9999	-10000	0	0
CLOCK	0.037	0.006	-9999	-10000	0	0
TIMELESS/CRY2	0.05	0.021	-9999	-10000	0	0
DEC1/BMAL1	0.038	0.011	-9999	-10000	0	0
ATR	0.034	0.006	-9999	-10000	0	0
NR1D1	0.031	0.01	-9999	-10000	0	0
ARNTL	0.037	0.006	-9999	-10000	0	0
TIMELESS	0.031	0.01	-9999	-10000	0	0
NPAS2	0.034	0.041	-9999	-0.41	3	3
CRY2	0.034	0.006	-9999	-10000	0	0
mol:CO	-0.012	0	-9999	-10000	0	0
CHEK1	0.032	0.011	-9999	-10000	0	0
mol:HEME	0.012	0	-9999	-10000	0	0
PER1	0.033	0.009	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.08	0.034	-9999	-0.24	3	3
BMAL1/CLOCK	0.042	0.038	-9999	-10000	0	0
S phase of mitotic cell cycle	0.062	0.031	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.063	0.032	-9999	-10000	0	0
mol:NADPH	0.012	0	-9999	-10000	0	0
PER1/TIMELESS	0.049	0.02	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.016	0.004	-9999	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	0.003	0.005	-10000	0	-9999	0
TP53	0.002	0.004	-10000	0	-9999	0
Senescence	0.002	0.004	-10000	0	-9999	0
Apoptosis	0.002	0.004	-10000	0	-9999	0
Activated_Oncogenes	0	0	-10000	0	-9999	0
MDM2	0.003	0.017	0.29	1	-9999	1
MDM4	0.031	0.012	-10000	0	-9999	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.033	0.024	-9999	-0.42	1	1
Ran/GTP/Exportin 1/HDAC4	0.009	0.006	-9999	-10000	0	0
MDM2/SUMO1	0.058	0.032	-9999	-10000	0	0
HDAC4	0.033	0.008	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0.008	0.012	-9999	-0.17	1	1
SUMO1	0.035	0.003	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.016	0.013	-9999	-0.18	1	1
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.015	0.006	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.034	0.006	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.035	0.003	-9999	-10000	0	0
SUMO1/HDAC4	0.058	0.029	-9999	-10000	0	0
SUMO1/HDAC1	0.058	0.033	-9999	-0.18	1	1
RANGAP1	0.032	0.011	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.082	0.027	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.019	0.007	-9999	-10000	0	0
Ran/GTP	0.042	0.026	-9999	-0.16	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.033	0.008	-9999	-10000	0	0
UBE2I	0.035	0.003	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.04	0.026	-9999	-10000	0	0
NPC	0.021	0.002	-9999	-10000	0	0
PIAS2	0.034	0.006	-9999	-10000	0	0
PIAS1	0.035	0.005	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.046	0.017	-9999	-9999
FBXW11	0.033	0.008	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.033	0.008	-9999	-9999
CHUK	0.032	0.01	-9999	-9999
NF kappa B2 p100/RelB	0.089	0.038	-9999	-9999
NFKB1	0.034	0.006	-9999	-9999
MAP3K14	0.034	0.007	-9999	-9999
NF kappa B1 p50/RelB	0.05	0.01	-9999	-9999
RELB	0.035	0.004	-9999	-9999
NFKB2	0.032	0.01	-9999	-9999
NF kappa B2 p52/RelB	0.043	0.014	-9999	-9999
regulation of B cell activation	0.043	0.014	-9999	-9999

pid_entity	TCGA.Z2.AA3V	TCGA.Z2.AA3S	TCGA.Z2.A8RT	TCGA.YG.AA3P
109_MAP3K5	0.045	-0.34	0.045	-0.46
47_PPARGC1A	0.035	0.035	0.035	0.035
105_BMP4	0.035	0.035	0.035	0
105_BMP6	0.035	0.035	0.035	0.035
105_BMP7	0	0.035	0.035	0
105_BMP2	0.035	0.035	0.035	0.035
131_RELN/VLDLR	0.091	0	0	0.091
30_TGFB1/TGF beta receptor Type II	0.035	0.035	0.035	0.035
84_STAT5B	0.045	-0.22	0.027	-0.24
84_STAT5A	0.045	-0.22	0.027	-0.24