PARADIGM pathway analysis of mRNASeq expression data - Lung Squamous Cell Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Signaling events mediated by the Hedgehog family	166
Angiopoietin receptor Tie2-mediated signaling	157
Aurora B signaling	127
FOXM1 transcription factor network	104
Aurora C signaling	99
Endothelins	76
Glypican 2 network	61
TCGA08_retinoblastoma	59
amb2 Integrin signaling	58
Fc-epsilon receptor I signaling in mast cells	54

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
Signaling events mediated by the Hedgehog family	0.3444	166	8659	52	-0.65	0.35	1000	-1000	-0.092	-1000
Angiopoietin receptor Tie2-mediated signaling	0.3257	157	13888	88	-0.78	0.06	1000	-1000	-0.12	-1000
Aurora B signaling	0.2635	127	8534	67	-0.62	0.005	1000	-1000	-0.084	-1000
FOXM1 transcription factor network	0.2158	104	5345	51	-0.71	0.002	1000	-1000	-0.21	-1000
Aurora C signaling	0.2054	99	696	7	-0.41	0	1000	-1000	-0.044	-1000
Endothelins	0.1577	76	7381	96	-0.45	0.038	1000	-1000	-0.097	-1000
Glypican 2 network	0.1266	61	245	4	-0.087	-0.07	1000	-1000	-0.039	-1000
TCGA08_retinoblastoma	0.1224	59	475	8	-0.28	0.084	1000	-1000	-0.026	-1000
amb2 Integrin signaling	0.1203	58	4801	82	-0.69	0	1000	-1000	-0.098	-1000
Fc-epsilon receptor I signaling in mast cells	0.1120	54	5261	97	-0.26	0.033	1000	-1000	-0.1	-1000
Thromboxane A2 receptor signaling	0.1079	52	5485	105	-0.18	0.038	1000	-1000	-0.084	-1000
Visual signal transduction: Cones	0.1037	50	1927	38	-0.28	0.009	1000	-1000	-0.08	-1000
IL4-mediated signaling events	0.1037	50	4583	91	-0.8	0.44	1000	-1000	-0.17	-1000
Signaling events regulated by Ret tyrosine kinase	0.1037	50	4113	82	-0.2	0	1000	-1000	-0.11	-1000
Glucocorticoid receptor regulatory network	0.1017	49	5614	114	-0.56	0.37	1000	-1000	-0.09	-1000
Signaling mediated by p38-alpha and p38-beta	0.0934	45	1995	44	-0.13	0	1000	-1000	-0.056	-1000
Arf6 signaling events	0.0830	40	2497	62	-0.31	0.015	1000	-1000	-0.072	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0830	40	2102	52	-0.38	0.057	1000	-1000	-0.079	-1000
BMP receptor signaling	0.0809	39	3186	81	-0.39	0.033	1000	-1000	-0.12	-1000
PLK1 signaling events	0.0809	39	3373	85	-0.36	0.071	1000	-1000	-0.063	-1000
Nectin adhesion pathway	0.0768	37	2338	63	-0.27	0	1000	-1000	-0.086	-1000
Integrins in angiogenesis	0.0747	36	3079	84	-0.47	0.002	1000	-1000	-0.11	-1000
Glypican 1 network	0.0705	34	1637	48	-0.22	0.03	1000	-1000	-0.058	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0705	34	2694	78	-0.13	0.036	1000	-1000	-0.093	-1000
TCGA08_p53	0.0664	32	229	7	-0.19	0.096	1000	-1000	-0.031	-1000
Nongenotropic Androgen signaling	0.0664	32	1695	52	-0.16	0.046	1000	-1000	-0.069	-1000
FOXA2 and FOXA3 transcription factor networks	0.0643	31	1433	46	-0.79	0.073	1000	-1000	-0.11	-1000
HIF-1-alpha transcription factor network	0.0602	29	2213	76	-0.44	0.016	1000	-1000	-0.22	-1000
Syndecan-3-mediated signaling events	0.0581	28	991	35	-0.34	0	1000	-1000	-0.074	-1000
Calcium signaling in the CD4+ TCR pathway	0.0581	28	881	31	-0.21	0.012	1000	-1000	-0.14	-1000
LPA4-mediated signaling events	0.0539	26	312	12	-0.14	0.017	1000	-1000	-0.033	-1000
Coregulation of Androgen receptor activity	0.0539	26	2021	76	-0.4	0.028	1000	-1000	-0.07	-1000
Canonical Wnt signaling pathway	0.0539	26	1375	51	-0.47	0.16	1000	-1000	-0.069	-1000
IL23-mediated signaling events	0.0539	26	1617	60	-0.24	0.018	1000	-1000	-0.18	-1000
Reelin signaling pathway	0.0519	25	1404	56	-0.13	0.003	1000	-1000	-0.12	-1000
IL6-mediated signaling events	0.0519	25	1936	75	-0.48	0.05	1000	-1000	-0.11	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0519	25	1713	68	-0.23	0.015	1000	-1000	-0.14	-1000
Presenilin action in Notch and Wnt signaling	0.0498	24	1500	61	-0.47	0.013	1000	-1000	-0.089	-1000
Visual signal transduction: Rods	0.0498	24	1253	52	-0.18	0	1000	-1000	-0.1	-1000
ErbB4 signaling events	0.0456	22	1542	69	-0.38	0.2	1000	-1000	-0.11	-1000
Aurora A signaling	0.0436	21	1272	60	-0.49	0.029	1000	-1000	-0.067	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0436	21	2723	125	-0.21	0	1000	-1000	-0.12	-1000
Wnt signaling	0.0436	21	150	7	-0.096	0	1000	-1000	-0.056	-1000
Regulation of Androgen receptor activity	0.0436	21	1532	70	-0.42	0.018	1000	-1000	-0.081	-1000
IL12-mediated signaling events	0.0415	20	1755	87	-0.15	0.018	1000	-1000	-0.15	-1000
Syndecan-1-mediated signaling events	0.0415	20	687	34	-0.35	0	1000	-1000	-0.082	-1000
Osteopontin-mediated events	0.0394	19	758	38	-0.3	0	1000	-1000	-0.12	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0394	19	650	33	-0.27	0	1000	-1000	-0.079	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0394	19	2378	120	-0.27	0.13	1000	-1000	-0.093	-1000
HIF-2-alpha transcription factor network	0.0353	17	756	43	-0.37	0.2	1000	-1000	-0.12	-1000
Plasma membrane estrogen receptor signaling	0.0353	17	1521	86	-0.18	0.033	1000	-1000	-0.097	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0332	16	907	54	-0.15	0.02	1000	-1000	-0.11	-1000
TCR signaling in naïve CD8+ T cells	0.0332	16	1550	93	-0.064	0.036	1000	-1000	-0.1	-1000
Ephrin A reverse signaling	0.0311	15	106	7	-0.023	0.004	1000	-1000	-0.033	-1000
p75(NTR)-mediated signaling	0.0290	14	1781	125	-0.34	0	1000	-1000	-0.14	-1000
PDGFR-alpha signaling pathway	0.0290	14	653	44	-0.21	0.014	1000	-1000	-0.073	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0270	13	1178	85	-0.16	0.009	1000	-1000	-0.091	-1000
Ras signaling in the CD4+ TCR pathway	0.0270	13	230	17	-0.054	0.009	1000	-1000	-0.068	-1000
Caspase cascade in apoptosis	0.0228	11	843	74	-0.069	0.034	1000	-1000	-0.07	-1000
Regulation of nuclear SMAD2/3 signaling	0.0228	11	1521	136	-0.33	0.092	1000	-1000	-0.1	-1000
Noncanonical Wnt signaling pathway	0.0228	11	303	26	-0.1	0	1000	-1000	-0.1	-1000
FAS signaling pathway (CD95)	0.0228	11	533	47	-0.2	0.009	1000	-1000	-0.059	-1000
Syndecan-2-mediated signaling events	0.0207	10	692	69	-0.17	0.032	1000	-1000	-0.073	-1000
Effects of Botulinum toxin	0.0207	10	266	26	-0.073	0.005	1000	-1000	-0.087	-1000
EGFR-dependent Endothelin signaling events	0.0207	10	214	21	-0.063	0	1000	-1000	-0.093	-1000
JNK signaling in the CD4+ TCR pathway	0.0187	9	160	17	-0.04	0.022	1000	-1000	-0.079	-1000
S1P1 pathway	0.0187	9	351	36	-0.061	0.01	1000	-1000	-0.088	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0187	9	696	74	-0.17	0.068	1000	-1000	-0.11	-1000
BCR signaling pathway	0.0187	9	970	99	-0.11	0.039	1000	-1000	-0.1	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0166	8	285	34	-0.028	0	1000	-1000	-0.084	-1000
Hedgehog signaling events mediated by Gli proteins	0.0166	8	569	65	-0.61	0.043	1000	-1000	-0.1	-1000
Syndecan-4-mediated signaling events	0.0166	8	601	67	-0.17	0.009	1000	-1000	-0.1	-1000
S1P4 pathway	0.0166	8	214	25	-0.066	0.002	1000	-1000	-0.066	-1000
Signaling events mediated by HDAC Class III	0.0145	7	289	40	-0.15	0.051	1000	-1000	-0.059	-1000
TRAIL signaling pathway	0.0145	7	343	48	-0.095	0.046	1000	-1000	-0.082	-1000
IL2 signaling events mediated by STAT5	0.0145	7	175	22	-0.15	0.06	1000	-1000	-0.068	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0124	6	182	28	-0.18	0.02	1000	-1000	-0.069	-1000
Cellular roles of Anthrax toxin	0.0124	6	257	39	-0.09	0.017	1000	-1000	-0.032	-1000
Signaling events mediated by PTP1B	0.0124	6	517	76	-0.1	0.033	1000	-1000	-0.092	-1000
Retinoic acid receptors-mediated signaling	0.0124	6	371	58	-0.22	0.034	1000	-1000	-0.075	-1000
IL1-mediated signaling events	0.0104	5	344	62	-0.059	0.042	1000	-1000	-0.12	-1000
IL2 signaling events mediated by PI3K	0.0104	5	296	58	-0.22	0.073	1000	-1000	-0.1	-1000
Regulation of p38-alpha and p38-beta	0.0104	5	315	54	-0.095	0.037	1000	-1000	-0.089	-1000
IL27-mediated signaling events	0.0104	5	305	51	-0.12	0.011	1000	-1000	-0.092	-1000
LPA receptor mediated events	0.0104	5	539	102	-0.1	0.034	1000	-1000	-0.11	-1000
Insulin Pathway	0.0104	5	379	74	-0.12	0.031	1000	-1000	-0.11	-1000
S1P3 pathway	0.0104	5	251	42	-0.18	0.042	1000	-1000	-0.067	-1000
Signaling events mediated by PRL	0.0104	5	190	34	-0.13	0.029	1000	-1000	-0.075	-1000
Signaling events mediated by HDAC Class II	0.0083	4	324	75	-0.08	0	1000	-1000	-0.077	-1000
BARD1 signaling events	0.0083	4	283	57	-0.13	0.022	1000	-1000	-0.083	-1000
Ephrin B reverse signaling	0.0083	4	228	48	-0.07	0.04	1000	-1000	-0.084	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0083	4	354	83	-0.069	0.049	1000	-1000	-0.096	-1000
Signaling events mediated by HDAC Class I	0.0083	4	444	104	-0.08	0.041	1000	-1000	-0.083	-1000
Arf6 trafficking events	0.0083	4	288	71	-0.086	0.032	1000	-1000	-0.093	-1000
IGF1 pathway	0.0083	4	274	57	-0.019	0.041	1000	-1000	-0.11	-1000
p38 MAPK signaling pathway	0.0083	4	212	44	-0.068	0.034	1000	-1000	-0.079	-1000
ErbB2/ErbB3 signaling events	0.0062	3	253	65	-0.078	0.055	1000	-1000	-0.086	-1000
IFN-gamma pathway	0.0062	3	252	68	-0.068	0.065	1000	-1000	-0.11	-1000
Class I PI3K signaling events	0.0062	3	261	73	-0.049	0.027	1000	-1000	-0.084	-1000
Regulation of Telomerase	0.0062	3	381	102	-0.12	0.024	1000	-1000	-0.12	-1000
VEGFR1 specific signals	0.0062	3	209	56	-0.21	0.045	1000	-1000	-0.099	-1000
Circadian rhythm pathway	0.0041	2	56	22	-0.031	0.038	1000	-1000	-0.066	-1000
a4b1 and a4b7 Integrin signaling	0.0041	2	14	5	-0.006	-0.002	1000	-1000	-0.04	-1000
EPO signaling pathway	0.0041	2	111	55	-0.008	0.065	1000	-1000	-0.12	-1000
Ceramide signaling pathway	0.0041	2	171	76	-0.024	0.04	1000	-1000	-0.071	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0041	2	78	37	-0.009	0.028	1000	-1000	-0.09	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0041	2	134	45	-0.028	0.061	1000	-1000	-0.11	-1000
EPHB forward signaling	0.0041	2	249	85	-0.07	0.032	1000	-1000	-0.11	-1000
TCGA08_rtk_signaling	0.0041	2	76	26	-0.065	0.038	1000	-1000	-0.034	-1000
PDGFR-beta signaling pathway	0.0041	2	212	97	-0.04	0.055	1000	-1000	-0.11	-1000
E-cadherin signaling in keratinocytes	0.0041	2	87	43	-0.022	0.042	1000	-1000	-0.086	-1000
Class IB PI3K non-lipid kinase events	0.0041	2	6	3	-0.003	-1000	1000	-1000	-0.036	-1000
PLK2 and PLK4 events	0.0021	1	4	3	-0.002	0.017	1000	-1000	-0.03	-1000
Insulin-mediated glucose transport	0.0021	1	50	32	-0.057	0.034	1000	-1000	-0.078	-1000
S1P5 pathway	0.0021	1	28	17	-0.009	0.006	1000	-1000	-0.067	-1000
FoxO family signaling	0.0021	1	98	64	-0.089	0.08	1000	-1000	-0.1	-1000
Paxillin-dependent events mediated by a4b1	0.0021	1	54	36	-0.008	0.02	1000	-1000	-0.086	-1000
Rapid glucocorticoid signaling	0.0021	1	35	20	-0.009	0.007	1000	-1000	-0.042	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	0	23	0	0.036	1000	-1000	-0.089	-1000
Canonical NF-kappaB pathway	0.0000	0	33	39	-0.02	0.071	1000	-1000	-0.098	-1000
Arf6 downstream pathway	0.0000	0	15	43	-0.024	0.025	1000	-1000	-0.051	-1000
mTOR signaling pathway	0.0000	0	0	53	-0.003	0.03	1000	-1000	-0.072	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	57	68	-0.057	0.043	1000	-1000	-0.088	-1000
ceramide signaling pathway	0.0000	0	47	49	-0.02	0.043	1000	-1000	-0.071	-1000
Signaling mediated by p38-gamma and p38-delta	0.0000	0	13	15	-0.001	0.027	1000	-1000	-0.07	-1000
Atypical NF-kappaB pathway	0.0000	0	14	31	-0.002	0.03	1000	-1000	-0.076	-1000
E-cadherin signaling in the nascent adherens junction	0.0000	0	48	76	-0.023	0.053	1000	-1000	-0.099	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	1	27	-0.001	0.025	1000	-1000	-0.067	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0	1000	-1000	-0.056	-1000
Arf1 pathway	0.0000	0	44	54	-0.022	0.022	1000	-1000	-0.058	-1000
Alternative NF-kappaB pathway	0.0000	0	4	13	-0.001	0	1000	-1000	-0.077	-1000
Total	NA	2603	161083	7203	-25	-990	131000	-131000	-12	-131000

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.43	0.3	-10000	0	-0.69	225	225
IHH	-0.47	0.38	-10000	0	-0.81	269	269
SHH Np/Cholesterol/GAS1	-0.071	0.17	-10000	0	-0.46	71	71
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.071	0.16	0.45	71	-10000	0	71
SMO/beta Arrestin2	-0.36	0.25	-10000	0	-0.59	233	233
SMO	-0.38	0.27	-10000	0	-0.6	274	274
AKT1	-0.15	0.11	-10000	0	-0.32	3	3
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.005	0.06	-10000	0	-0.66	4	4
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.38	0.27	-10000	0	-0.59	274	274
STIL	-0.33	0.25	-10000	0	-0.53	251	251
DHH N/PTCH2	-0.046	0.16	-10000	0	-0.56	39	39
DHH N/PTCH1	-0.36	0.24	-10000	0	-0.54	294	294
PIK3CA	0	0	-10000	0	-10000	0	0
DHH	-0.052	0.19	-10000	0	-0.74	34	34
PTHLH	-0.58	0.36	-10000	0	-0.92	225	225
determination of left/right symmetry	-0.38	0.27	-10000	0	-0.59	274	274
PIK3R1	0	0	-10000	0	-10000	0	0
skeletal system development	-0.57	0.35	-10000	0	-0.9	225	225
IHH N/Hhip	-0.65	0.38	-10000	0	-0.82	383	383
DHH N/Hhip	-0.41	0.3	-10000	0	-0.6	330	330
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.38	0.27	-10000	0	-0.59	274	274
pancreas development	-0.49	0.35	-10000	0	-0.74	322	322
HHAT	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.012	0.095	-10000	0	-0.74	8	8
somite specification	-0.38	0.27	-10000	0	-0.59	274	274
SHH Np/Cholesterol/PTCH1	-0.35	0.25	-10000	0	-0.55	255	255
SHH Np/Cholesterol/PTCH2	-0.069	0.16	-10000	0	-0.43	77	77
SHH Np/Cholesterol/Megalin	-0.29	0.27	-10000	0	-0.5	276	276
SHH	-0.066	0.2	-10000	0	-0.55	72	72
catabolic process	-0.37	0.25	-10000	0	-0.57	282	282
SMO/Vitamin D3	-0.37	0.27	-10000	0	-0.59	248	248
SHH Np/Cholesterol/Hhip	-0.36	0.26	-10000	0	-0.5	340	340
LRP2	-0.38	0.37	-10000	0	-0.74	247	247
receptor-mediated endocytosis	-0.5	0.31	-10000	0	-0.72	281	281
SHH Np/Cholesterol/BOC	-0.067	0.16	-10000	0	-0.44	74	74
SHH Np/Cholesterol/CDO	-0.069	0.16	-10000	0	-0.44	70	70
mesenchymal cell differentiation	0.35	0.26	0.5	340	-10000	0	340
mol:Vitamin D3	-0.35	0.26	-10000	0	-0.56	255	255
IHH N/PTCH2	-0.31	0.27	-10000	0	-0.54	269	269
CDON	-0.008	0.075	-10000	0	-0.74	5	5
IHH N/PTCH1	-0.38	0.26	-10000	0	-0.58	282	282
Megalin/LRPAP1	-0.29	0.28	-10000	0	-0.56	247	247
PTCH2	-0.009	0.076	-10000	0	-0.68	6	6
SHH Np/Cholesterol	-0.065	0.16	-10000	0	-0.44	72	72
PTCH1	-0.37	0.25	-10000	0	-0.57	282	282
HHIP	-0.5	0.35	-10000	0	-0.74	322	322

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.53	0.53	-10000	0	-1	264	264
NCK1/PAK1/Dok-R	-0.25	0.23	-10000	0	-0.45	264	264
NCK1/Dok-R	-0.7	0.66	-10000	0	-1.3	264	264
PIK3CA	0.007	0.006	-10000	0	-10000	0	0
mol:beta2-estradiol	0.06	0.1	0.25	104	-10000	0	104
RELA	0	0	-10000	0	-10000	0	0
SHC1	0.002	0.004	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.053	0.13	0.26	31	-0.57	9	40
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.61	0.58	-10000	0	-1.1	264	264
FN1	-0.017	0.11	-10000	0	-0.74	11	11
PLD2	-0.68	0.71	-10000	0	-1.3	264	264
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.047	0.18	-10000	0	-0.74	31	31
ELK1	-0.58	0.61	-10000	0	-1.1	264	264
GRB7	-0.005	0.052	-10000	0	-0.57	4	4
PAK1	-0.001	0.026	-10000	0	-0.57	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.66	0.62	-10000	0	-1.2	264	264
CDKN1A	-0.36	0.35	-10000	0	-0.68	256	256
ITGA5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.7	0.66	-10000	0	-1.3	264	264
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.37	0.38	-10000	0	-0.71	264	264
PLG	-0.69	0.71	-10000	0	-1.3	264	264
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.51	0.48	-10000	0	-0.95	264	264
GRB2	0	0	-10000	0	-10000	0	0
PIK3R1	0.002	0.004	-10000	0	-10000	0	0
ANGPT2	-0.34	0.34	-10000	0	-0.75	167	167
BMX	-0.76	0.75	-10000	0	-1.4	264	264
ANGPT1	-0.37	0.61	-10000	0	-1.4	124	124
tube development	-0.42	0.4	-10000	0	-0.78	262	262
ANGPT4	-0.33	0.37	-10000	0	-0.74	216	216
response to hypoxia	-0.035	0.036	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.76	0.72	-10000	0	-1.4	264	264
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.017	0.13	-10000	0	-0.74	15	15
STAT5A (dimer)	-0.49	0.47	-10000	0	-0.91	261	261
mol:L-citrulline	-0.37	0.38	-10000	0	-0.71	264	264
AGTR1	-0.3	0.37	-10000	0	-0.74	199	199
MAPK14	-0.7	0.7	-10000	0	-1.3	264	264
Tie2/SHP2	-0.61	0.62	-10000	0	-1.2	231	231
TEK	-0.68	0.69	-10000	0	-1.4	231	231
RPS6KB1	-0.5	0.51	-10000	0	-0.96	264	264
Angiotensin II/AT1	-0.23	0.28	-10000	0	-0.57	199	199
Tie2/Ang1/GRB2	-0.74	0.72	-10000	0	-1.3	264	264
MAPK3	-0.6	0.63	-10000	0	-1.2	264	264
MAPK1	-0.6	0.63	-10000	0	-1.2	264	264
Tie2/Ang1/GRB7	-0.74	0.72	-10000	0	-1.3	264	264
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.68	0.71	-10000	0	-1.3	264	264
PI3K	-0.64	0.63	-10000	0	-1.2	264	264
FES	-0.7	0.7	-10000	0	-1.3	264	264
Crk/Dok-R	-0.7	0.66	-10000	0	-1.3	264	264
Tie2/Ang1/ABIN2	-0.74	0.72	-10000	0	-1.3	264	264
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.46	0.46	-10000	0	-0.88	264	264
STAT5A	0	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.5	0.51	-10000	0	-0.96	264	264
Tie2/Ang2	-0.62	0.59	-10000	0	-1.2	262	262
Tie2/Ang1	-0.78	0.82	-10000	0	-1.5	264	264
FOXO1	-0.46	0.47	-10000	0	-0.89	264	264
ELF1	-0.034	0.052	-10000	0	-10000	0	0
ELF2	-0.69	0.72	-10000	0	-1.3	264	264
mol:Choline	-0.63	0.65	-10000	0	-1.2	264	264
cell migration	-0.14	0.12	-10000	0	-0.25	118	118
FYN	-0.49	0.47	-10000	0	-0.91	262	262
DOK2	-0.066	0.21	-10000	0	-0.74	43	43
negative regulation of cell cycle	-0.32	0.32	-10000	0	-0.61	261	261
ETS1	-0.062	0.16	-10000	0	-0.66	17	17
PXN	-0.4	0.41	-10000	0	-0.77	264	264
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.43	0.44	-10000	0	-0.82	264	264
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.063	0.16	-10000	0	-0.81	13	13
MAPKKK cascade	-0.63	0.65	-10000	0	-1.2	264	264
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.73	0.73	-10000	0	-1.4	264	264
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.32	0.34	-10000	0	-0.63	264	264
mol:Phosphatidic acid	-0.63	0.65	-10000	0	-1.2	264	264
mol:Angiotensin II	0	0.001	-10000	0	-10000	0	0
mol:NADP	-0.37	0.38	-10000	0	-0.71	264	264
Rac1/GTP	-0.48	0.44	-10000	0	-0.88	264	264
MMP2	-0.68	0.71	-10000	0	-1.3	264	264

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.18	0.14	-9999	-0.36	110	110
STMN1	-0.29	0.19	-9999	-0.4	347	347
Aurora B/RasGAP/Survivin	-0.5	0.22	-9999	-0.63	335	335
Chromosomal passenger complex/Cul3 protein complex	-0.2	0.1	-9999	-0.33	125	125
BIRC5	-0.49	0.21	-9999	-0.58	410	410
DES	-0.56	0.38	-9999	-0.83	311	311
Aurora C/Aurora B/INCENP	-0.22	0.15	-9999	-0.31	338	338
Aurora B/TACC1	-0.24	0.16	-9999	-0.34	347	347
Aurora B/PP2A	-0.29	0.19	-9999	-0.4	347	347
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.059	0.044	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.005	0.003	-9999	-10000	0	0
NDC80	-0.41	0.29	-9999	-0.55	362	362
Cul3 protein complex	-0.012	0.065	-9999	-0.37	15	15
KIF2C	-0.16	0.085	-9999	-0.24	248	248
PEBP1	-0.001	0.034	-9999	-0.76	1	1
KIF20A	-0.3	0.29	-9999	-0.58	249	249
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.29	0.19	-9999	-0.4	347	347
SEPT1	-0.001	0.026	-9999	-0.57	1	1
SMC2	0	0	-9999	-10000	0	0
SMC4	0	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.1	0.065	-9999	-10000	0	0
PSMA3	0	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.004	-9999	-10000	0	0
H3F3B	-0.15	0.1	-9999	-0.21	49	49
AURKB	-0.41	0.26	-9999	-0.57	347	347
AURKC	-0.003	0.043	-9999	-0.66	2	2
CDCA8	-0.16	0.26	-9999	-0.58	131	131
cytokinesis	-0.32	0.16	-9999	-0.49	171	171
Aurora B/Septin1	-0.3	0.16	-9999	-0.47	160	160
AURKA	-0.015	0.12	-9999	-0.57	21	21
INCENP	0.001	0.003	-9999	-10000	0	0
KLHL13	-0.014	0.089	-9999	-0.57	12	12
BUB1	-0.049	0.17	-9999	-0.58	45	45
hSgo1/Aurora B/Survivin	-0.62	0.31	-9999	-0.78	352	352
EVI5	0.005	0.004	-9999	-10000	0	0
RhoA/GTP	-0.27	0.18	-9999	-0.52	119	119
SGOL1	-0.3	0.29	-9999	-0.57	251	251
CENPA	-0.24	0.12	-9999	-0.31	338	338
NCAPG	-0.1	0.22	-9999	-0.57	87	87
Aurora B/HC8 Proteasome	-0.29	0.19	-9999	-0.4	347	347
NCAPD2	-0.001	0.026	-9999	-0.57	1	1
Aurora B/PP1-gamma	-0.29	0.19	-9999	-0.4	347	347
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.29	0.29	-9999	-0.57	245	245
NPM1	-0.13	0.082	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	-0.005	0.058	-9999	-0.74	3	3
mitotic prometaphase	-0.012	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.29	0.19	-9999	-0.4	347	347
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.3	0.19	-9999	-0.54	149	149
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.13	0.082	-9999	-10000	0	0
MYLK	-0.15	0.1	-9999	-0.61	2	2
KIF23	-0.12	0.23	-9999	-0.58	96	96
VIM	-0.3	0.21	-9999	-0.42	347	347
RACGAP1	0.001	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.13	0.082	-9999	-10000	0	0
Chromosomal passenger complex	-0.27	0.14	-9999	-0.35	331	331
Chromosomal passenger complex/EVI5	-0.49	0.25	-9999	-0.63	339	339
TACC1	-0.003	0.048	-9999	-0.74	2	2
PPP2R5D	0	0	-9999	-10000	0	0
CUL3	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

FOXM1 transcription factor network

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
NFATC3	-0.58	0.42	-9999	-1	129	129
PLK1	-0.19	0.2	-9999	-10000	0	0
BIRC5	-0.32	0.16	-9999	-10000	0	0
HSPA1B	-0.58	0.42	-9999	-1.1	120	120
MAP2K1	-0.012	0.023	-9999	-10000	0	0
BRCA2	-0.58	0.42	-9999	-1.1	118	118
FOXM1	-0.7	0.54	-9999	-1.2	167	167
XRCC1	-0.58	0.42	-9999	-1	132	132
FOXM1B/p19	-0.6	0.42	-9999	-1	164	164
Cyclin D1/CDK4	-0.54	0.4	-9999	-0.99	112	112
CDC2	-0.61	0.45	-9999	-1.1	166	166
TGFA	-0.52	0.38	-9999	-0.95	105	105
SKP2	-0.58	0.42	-9999	-1	130	130
CCNE1	-0.13	0.24	-9999	-0.58	107	107
CKS1B	-0.58	0.42	-9999	-1.1	120	120
RB1	-0.26	0.15	-9999	-0.49	18	18
FOXM1C/SP1	-0.65	0.45	-9999	-1.1	168	168
AURKB	-0.28	0.19	-9999	-10000	0	0
CENPF	-0.64	0.47	-9999	-1.1	185	185
CDK4	0.001	0.028	-9999	-0.59	1	1
MYC	-0.51	0.37	-9999	-0.91	120	120
CHEK2	-0.012	0.023	-9999	-10000	0	0
ONECUT1	-0.57	0.42	-9999	-1	143	143
CDKN2A	-0.25	0.29	-9999	-0.56	224	224
LAMA4	-0.58	0.43	-9999	-1	133	133
FOXM1B/HNF6	-0.65	0.5	-9999	-1.2	142	142
FOS	-0.63	0.49	-9999	-1.2	148	148
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.58	0.42	-9999	-1.1	120	120
response to radiation	-0.024	0.022	-9999	-10000	0	0
CENPB	-0.58	0.42	-9999	-1	132	132
CENPA	-0.71	0.46	-9999	-1.1	214	214
NEK2	-0.69	0.47	-9999	-1.1	198	198
HIST1H2BA	-0.58	0.42	-9999	-1.1	118	118
CCNA2	-0.15	0.26	-9999	-0.58	125	125
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.66	0.49	-9999	-1.2	136	136
CCNB2	-0.66	0.48	-9999	-1.1	200	200
CCNB1	-0.62	0.46	-9999	-1.1	135	135
ETV5	-0.58	0.43	-9999	-1.1	121	121
ESR1	-0.59	0.45	-9999	-1.1	116	116
CCND1	-0.55	0.41	-9999	-1	115	115
GSK3A	-0.004	0.018	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.17	0.24	-9999	-0.44	187	187
CDK2	0.002	0.006	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.031	0.027	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.64	0.41	-9999	-1.1	168	168
GAS1	-0.58	0.43	-9999	-1.1	135	135
MMP2	-0.58	0.43	-9999	-1	133	133
RB1/FOXM1C	-0.58	0.44	-9999	-1.1	140	140
CREBBP	0	0	-9999	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.23	0.14	-9999	-0.32	347	347
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.064	0.04	-9999	-10000	0	0
AURKB	-0.41	0.26	-9999	-0.57	347	347
AURKC	-0.003	0.043	-9999	-0.66	2	2

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.029	0.23	-9999	-0.58	51	51
PTK2B	0.002	0.004	-9999	-10000	0	0
mol:Ca2+	-0.078	0.28	-9999	-0.88	35	35
EDN1	-0.041	0.25	-9999	-0.78	41	41
EDN3	-0.091	0.24	-9999	-0.7	62	62
EDN2	-0.087	0.21	-9999	-0.59	71	71
HRAS/GDP	-0.18	0.3	-9999	-0.63	122	122
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.053	0.2	-9999	-0.48	60	60
ADCY4	-0.078	0.22	-9999	-0.65	42	42
ADCY5	-0.09	0.23	-9999	-0.65	47	47
ADCY6	-0.054	0.19	-9999	-0.6	32	32
ADCY7	-0.053	0.18	-9999	-0.59	31	31
ADCY1	-0.054	0.19	-9999	-0.58	32	32
ADCY2	-0.086	0.21	-9999	-0.62	41	41
ADCY3	-0.053	0.18	-9999	-0.59	31	31
ADCY8	-0.18	0.25	-9999	-0.65	56	56
ADCY9	-0.054	0.19	-9999	-0.58	34	34
arachidonic acid secretion	-0.15	0.27	-9999	-0.54	117	117
ETB receptor/Endothelin-1/Gq/GTP	-0.32	0.35	-9999	-0.7	173	173
GNAO1	-0.004	0.05	-9999	-0.63	3	3
HRAS	0	0.002	-9999	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.038	0.26	-9999	-0.54	51	51
ETA receptor/Endothelin-1/Gs/GTP	0.03	0.25	-9999	-0.55	46	46
mol:GTP	0	0.004	-9999	-10000	0	0
COL3A1	-0.045	0.25	-9999	-0.7	31	31
EDNRB	-0.45	0.36	-9999	-0.74	296	296
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.045	0.27	-9999	-0.76	40	40
CYSLTR1	-0.092	0.36	-9999	-0.87	70	70
SLC9A1	-0.007	0.12	-9999	-0.36	19	19
mol:GDP	-0.2	0.33	-9999	-0.69	126	126
SLC9A3	-0.37	0.38	-9999	-0.73	204	204
RAF1	-0.21	0.32	-9999	-0.65	137	137
JUN	-0.056	0.22	-9999	-0.62	33	33
JAK2	-0.029	0.23	-9999	-0.58	51	51
mol:IP3	-0.21	0.3	-9999	-0.66	127	127
ETA receptor/Endothelin-1	0.018	0.32	-9999	-0.67	51	51
PLCB1	0.003	0.005	-9999	-10000	0	0
PLCB2	-0.005	0.096	-9999	-0.74	8	8
ETA receptor/Endothelin-3	-0.057	0.21	-9999	-0.55	67	67
FOS	-0.2	0.35	-9999	-0.85	85	85
Gai/GDP	-0.007	0.067	-9999	-0.95	1	1
CRK	0.002	0.004	-9999	-10000	0	0
mol:Ca ++	-0.25	0.36	-9999	-0.75	137	137
BCAR1	0.005	0.005	-9999	-10000	0	0
PRKCB1	-0.2	0.29	-9999	-0.63	128	128
GNAQ	0.008	0.035	-9999	-0.74	1	1
GNAZ	-0.009	0.082	-9999	-0.74	6	6
GNAL	-0.006	0.067	-9999	-0.74	4	4
Gs family/GDP	-0.21	0.26	-9999	-0.62	122	122
ETA receptor/Endothelin-1/Gq/GTP	-0.065	0.23	-9999	-0.52	66	66
MAPK14	-0.24	0.28	-9999	-0.65	128	128
TRPC6	-0.086	0.3	-9999	-0.99	33	33
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.002	0.034	-9999	-0.74	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.26	0.3	-9999	-0.63	153	153
ETB receptor/Endothelin-2	-0.4	0.29	-9999	-0.58	327	327
ETB receptor/Endothelin-3	-0.4	0.31	-9999	-0.61	321	321
ETB receptor/Endothelin-1	-0.38	0.34	-9999	-0.61	309	309
MAPK3	-0.22	0.36	-9999	-0.7	141	141
MAPK1	-0.22	0.36	-9999	-0.75	120	120
Rac1/GDP	-0.18	0.3	-9999	-0.63	123	123
cAMP biosynthetic process	-0.078	0.21	-9999	-0.59	44	44
MAPK8	-0.078	0.26	-9999	-0.61	65	65
SRC	0	0	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.17	0.17	-9999	-0.51	41	41
p130Cas/CRK/Src/PYK2	-0.19	0.32	-9999	-0.66	124	124
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.18	0.3	-9999	-0.63	122	122
COL1A2	-0.26	0.31	-9999	-0.73	101	101
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.05	0.19	-9999	-0.46	74	74
mol:DAG	-0.21	0.3	-9999	-0.66	127	127
MAP2K2	-0.2	0.32	-9999	-0.64	141	141
MAP2K1	-0.2	0.32	-9999	-0.64	142	142
EDNRA	0.015	0.14	-9999	-0.66	9	9
positive regulation of muscle contraction	-0.031	0.2	-9999	-0.59	31	31
Gq family/GDP	-0.2	0.3	-9999	-0.69	115	115
HRAS/GTP	-0.22	0.32	-9999	-0.68	128	128
PRKCH	-0.2	0.29	-9999	-0.65	117	117
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.2	0.29	-9999	-0.66	118	118
PRKCB	-0.22	0.32	-9999	-0.7	124	124
PRKCE	-0.2	0.29	-9999	-0.65	117	117
PRKCD	-0.2	0.29	-9999	-0.65	117	117
PRKCG	-0.22	0.3	-9999	-0.66	130	130
regulation of vascular smooth muscle contraction	-0.24	0.42	-9999	-1	86	86
PRKCQ	-0.23	0.34	-9999	-0.72	132	132
PLA2G4A	-0.16	0.29	-9999	-0.59	117	117
GNA14	-0.17	0.32	-9999	-0.74	114	114
GNA15	0.008	0.005	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA11	0.008	0.005	-9999	-10000	0	0
Rac1/GTP	0.038	0.26	-9999	-0.54	51	51
MMP1	-0.23	0.24	-9999	-0.43	250	250

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.012	0.082	-9999	-0.57	10	10
GPC2	-0.087	0.2	-9999	-0.57	73	73
GPC2/Midkine	-0.071	0.16	-9999	-0.42	81	81
neuron projection morphogenesis	-0.07	0.16	-9999	-0.42	81	81

×

TCGA08_retinoblastoma

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
CDKN2B	-0.061	0.2	-10000	0	-0.71	41	41
CDKN2C	0.03	0.032	-10000	0	-10000	0	0
CDKN2A	-0.28	0.3	-10000	0	-0.59	224	224
CCND2	0.073	0.082	0.26	42	-10000	0	42
RB1	-0.079	0.085	-10000	0	-0.27	42	42
CDK4	0.084	0.088	0.26	42	-10000	0	42
CDK6	0.081	0.09	0.29	42	-10000	0	42
G1/S progression	0.072	0.091	0.26	42	-10000	0	42

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.063	0.22	-9999	-0.72	42	42
alphaM/beta2 Integrin/GPIbA	-0.064	0.21	-9999	-0.7	43	43
alphaM/beta2 Integrin/proMMP-9	-0.077	0.21	-9999	-0.57	64	64
PLAUR	0	0	-9999	-10000	0	0
HMGB1	0	0.003	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.059	0.2	-9999	-0.69	41	41
AGER	-0.69	0.2	-9999	-0.75	443	443
RAP1A	0	0	-9999	-10000	0	0
SELPLG	-0.048	0.18	-9999	-0.74	31	31
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.48	0.26	-9999	-0.52	443	443
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.03	0.13	-9999	-0.57	25	25
CYR61	-0.04	0.17	-9999	-0.74	26	26
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.21	0.29	-9999	-0.63	112	112
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.19	0.32	-9999	-0.74	121	121
MYH2	-0.32	0.35	-9999	-0.7	171	171
MST1R	-0.048	0.18	-9999	-0.74	31	31
leukocyte activation during inflammatory response	-0.089	0.22	-9999	-0.58	65	65
APOB	-0.049	0.18	-9999	-0.72	33	33
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.006	0.067	-9999	-0.74	4	4
JAM3	0	0	-9999	-10000	0	0
GP1BA	-0.007	0.072	-9999	-0.71	5	5
alphaM/beta2 Integrin/CTGF	-0.075	0.24	-9999	-0.72	50	50
alphaM/beta2 Integrin	-0.26	0.37	-9999	-0.76	116	116
JAM3 homodimer	0	0	-9999	-10000	0	0
ICAM2	-0.048	0.18	-9999	-0.74	31	31
ICAM1	-0.065	0.21	-9999	-0.74	42	42
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.24	0.36	-9999	-0.74	116	116
cell adhesion	-0.063	0.21	-9999	-0.7	43	43
NFKB1	-0.47	0.3	-9999	-0.93	110	110
THY1	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.045	0.14	-9999	-0.45	48	48
alphaM/beta2 Integrin/LRP/tPA	-0.058	0.19	-9999	-0.64	41	41
IL6	-0.49	0.39	-9999	-1.1	112	112
ITGB2	-0.031	0.15	-9999	-0.74	20	20
elevation of cytosolic calcium ion concentration	-0.073	0.2	-9999	-0.64	41	41
alphaM/beta2 Integrin/JAM2/JAM3	-0.12	0.28	-9999	-0.64	90	90
JAM2	-0.11	0.26	-9999	-0.74	73	73
alphaM/beta2 Integrin/ICAM1	-0.11	0.28	-9999	-0.64	85	85
alphaM/beta2 Integrin/uPA/Plg	-0.076	0.2	-9999	-0.65	41	41
RhoA/GTP	-0.3	0.36	-9999	-0.85	114	114
positive regulation of phagocytosis	-0.18	0.27	-9999	-0.74	69	69
Ron/MSP	-0.037	0.14	-9999	-0.55	32	32
alphaM/beta2 Integrin/uPAR/uPA	-0.074	0.2	-9999	-0.65	41	41
alphaM/beta2 Integrin/uPAR	-0.059	0.2	-9999	-0.69	41	41
PLAU	-0.036	0.14	-9999	-0.57	30	30
PLAT	-0.007	0.063	-9999	-0.57	6	6
actin filament polymerization	-0.29	0.32	-9999	-0.65	171	171
MST1	-0.001	0.026	-9999	-0.57	1	1
alphaM/beta2 Integrin/lipoprotein(a)	-0.091	0.23	-9999	-0.59	65	65
TNF	-0.42	0.28	-9999	-0.85	110	110
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.081	0.22	-9999	-0.68	43	43
fibrinolysis	-0.076	0.2	-9999	-0.65	41	41
HCK	-0.008	0.075	-9999	-0.74	5	5
dendritic cell antigen processing and presentation	-0.24	0.36	-9999	-0.74	116	116
VTN	-0.29	0.36	-9999	-0.74	189	189
alphaM/beta2 Integrin/CYR61	-0.084	0.25	-9999	-0.73	55	55
LPA	-0.021	0.11	-9999	-0.57	18	18
LRP1	0	0	-9999	-10000	0	0
cell migration	-0.074	0.21	-9999	-0.66	42	42
FN1	-0.017	0.11	-9999	-0.74	11	11
alphaM/beta2 Integrin/Thy1	-0.059	0.2	-9999	-0.69	41	41
MPO	-0.031	0.15	-9999	-0.74	20	20
KNG1	-0.014	0.089	-9999	-0.57	12	12
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.25	0.33	-9999	-0.76	113	113
ELA2	0	0	-9999	-10000	0	0
PLG	-0.004	0.045	-9999	-0.57	3	3
CTGF	-0.026	0.14	-9999	-0.74	17	17
alphaM/beta2 Integrin/Hck	-0.064	0.22	-9999	-0.71	43	43
ITGAM	-0.062	0.21	-9999	-0.75	40	40
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.19	0.36	-9999	-0.66	136	136
HP	-0.23	0.34	-9999	-0.74	151	151
leukocyte adhesion	-0.44	0.3	-9999	-0.81	145	145
SELP	-0.19	0.32	-9999	-0.74	121	121

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0	0	-9999	-10000	0	0
LAT2	-0.16	0.26	-9999	-0.53	116	116
AP1	-0.19	0.26	-9999	-0.64	103	103
mol:PIP3	-0.16	0.29	-9999	-0.66	83	83
IKBKB	-0.07	0.16	-9999	-0.34	76	76
AKT1	-0.18	0.24	-9999	-0.67	67	67
IKBKG	-0.07	0.16	-9999	-0.34	76	76
MS4A2	-0.17	0.31	-9999	-0.75	109	109
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.002	-9999	-10000	0	0
MAP3K1	-0.1	0.23	-9999	-0.53	81	81
mol:Ca2+	-0.11	0.21	-9999	-0.46	83	83
LYN	0.004	0.05	-9999	-0.77	2	2
CBLB	-0.16	0.24	-9999	-0.63	73	73
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.057	0.15	-9999	-0.44	62	62
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.002	0.034	-9999	-0.74	1	1
PLD2	-0.21	0.29	-9999	-0.57	148	148
PTPN13	-0.13	0.24	-9999	-0.59	74	74
PTPN11	0.005	0.01	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.08	0.19	-9999	-0.42	70	70
SYK	0.006	0.036	-9999	-0.77	1	1
GRB2	0	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.2	0.27	-9999	-0.7	83	83
LAT	-0.16	0.24	-9999	-0.63	73	73
PAK2	-0.12	0.26	-9999	-0.61	82	82
NFATC2	-0.18	0.33	-9999	-0.94	66	66
HRAS	-0.14	0.29	-9999	-0.69	83	83
GAB2	-0.018	0.12	-9999	-0.74	12	12
PLA2G1B	-0.003	0.037	-9999	-10000	0	0
Fc epsilon R1	-0.26	0.34	-9999	-0.64	194	194
Antigen/IgE/Fc epsilon R1	-0.24	0.32	-9999	-0.59	194	194
mol:GDP	-0.16	0.31	-9999	-0.73	88	88
JUN	0	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0	0.002	-9999	-10000	0	0
FOS	-0.085	0.24	-9999	-0.74	55	55
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.17	0.26	-9999	-0.54	116	116
CHUK	-0.07	0.16	-9999	-0.34	76	76
KLRG1	-0.16	0.24	-9999	-0.63	71	71
VAV1	-0.16	0.25	-9999	-0.64	78	78
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.16	0.24	-9999	-0.63	73	73
negative regulation of mast cell degranulation	-0.14	0.22	-9999	-0.58	71	71
BTK	-0.2	0.33	-9999	-0.8	87	87
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.2	0.32	-9999	-0.88	68	68
GAB2/PI3K/SHP2	-0.19	0.27	-9999	-0.75	67	67
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.17	0.25	-9999	-0.69	72	72
RAF1	0.025	0.028	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.23	0.32	-9999	-0.61	150	150
FCER1G	-0.016	0.13	-9999	-0.76	14	14
FCER1A	-0.22	0.35	-9999	-0.76	143	143
Antigen/IgE/Fc epsilon R1/Fyn	-0.22	0.31	-9999	-0.55	194	194
MAPK3	0.033	0.024	-9999	-10000	0	0
MAPK1	0.033	0.024	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.021	0.071	-9999	-10000	0	0
DUSP1	-0.095	0.25	-9999	-0.74	62	62
NF-kappa-B/RelA	-0.059	0.076	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.13	0.25	-9999	-0.59	80	80
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.16	0.24	-9999	-0.63	77	77
FER	-0.16	0.24	-9999	-0.63	74	74
RELA	0	0	-9999	-10000	0	0
ITK	-0.078	0.18	-9999	-0.66	37	37
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.16	0.31	-9999	-0.74	84	84
cytokine secretion	-0.043	0.055	-9999	-10000	0	0
SPHK1	-0.16	0.24	-9999	-0.51	116	116
PTK2	-0.14	0.26	-9999	-0.63	77	77
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.21	0.29	-9999	-0.74	83	83
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.15	0.28	-9999	-0.64	83	83
MAP2K2	0.03	0.024	-9999	-10000	0	0
MAP2K1	0.03	0.024	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.14	0.22	-9999	-0.59	71	71
MAP2K4	0.009	0.013	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.24	0.34	-9999	-0.6	195	195
mol:Choline	-0.2	0.28	-9999	-0.56	148	148
SHC/Grb2/SOS1	-0.14	0.22	-9999	-0.6	69	69
FYN	-0.002	0.034	-9999	-0.74	1	1
DOK1	0	0	-9999	-10000	0	0
PXN	-0.12	0.24	-9999	-0.6	70	70
HCLS1	-0.16	0.24	-9999	-0.6	80	80
PRKCB	-0.11	0.22	-9999	-0.49	83	83
FCGR2B	-0.014	0.1	-9999	-0.74	9	9
IGHE	-0.004	0.009	-9999	-10000	0	0
KLRG1/SHIP	-0.14	0.22	-9999	-0.6	71	71
LCP2	-0.011	0.089	-9999	-0.74	7	7
PLA2G4A	-0.16	0.24	-9999	-0.65	72	72
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.2	0.28	-9999	-0.56	148	148
IKK complex	-0.039	0.12	-9999	-0.27	29	29
WIPF1	0	0	-9999	-10000	0	0

×

Thromboxane A2 receptor signaling

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
TGM2	-0.057	0.21	-10000	0	-0.74	41	41
GNB1/GNG2	-0.069	0.089	-10000	0	-0.21	69	69
AKT1	-0.035	0.13	-10000	0	-0.22	40	40
EGF	-0.014	0.099	-10000	0	-0.69	10	10
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.036	0.13	-10000	0	-0.61	15	15
mol:Ca2+	-0.073	0.18	-10000	0	-0.31	170	170
LYN	-0.016	0.076	-10000	0	-0.53	7	7
RhoA/GTP	-0.046	0.059	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.081	0.2	-10000	0	-0.35	164	164
GNG2	-0.008	0.075	-10000	0	-0.74	5	5
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.017	0.1	-10000	0	-0.57	5	5
G beta5/gamma2	-0.091	0.12	-10000	0	-0.29	69	69
PRKCH	-0.088	0.21	-10000	0	-0.36	162	162
DNM1	-0.002	0.037	-10000	0	-0.57	2	2
TXA2/TP beta/beta Arrestin3	-0.002	0.014	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.022	0.12	-10000	0	-0.74	14	14
G12 family/GTP	-0.11	0.14	-10000	0	-0.31	164	164
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	-0.002	0.034	-10000	0	-0.74	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.038	0.13	0.41	19	-10000	0	19
mol:NADP	-0.005	0.058	-10000	0	-0.74	3	3
RAB11A	0	0	-10000	0	-10000	0	0
PRKG1	-0.058	0.2	-10000	0	-0.74	38	38
mol:IP3	-0.099	0.22	-10000	0	-0.39	170	170
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.15	0.3	-10000	0	-0.53	170	170
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.03	0.1	-10000	0	-0.6	7	7
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.018	0.085	-10000	0	-0.56	8	8
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.018	0.12	-10000	0	-0.74	12	12
PRKCB1	-0.099	0.22	-10000	0	-0.39	165	165
GNAQ	-0.002	0.034	-10000	0	-0.74	1	1
mol:L-citrulline	-0.005	0.058	-10000	0	-0.74	3	3
TXA2/TXA2-R family	-0.15	0.3	-10000	0	-0.55	164	164
LCK	-0.015	0.075	-10000	0	-0.53	7	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.018	0.089	-10000	0	-0.71	5	5
TXA2-R family/G12 family/GDP/G beta/gamma	0.019	0.044	-10000	0	-0.35	4	4
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.018	0.088	-10000	0	-0.71	5	5
MAPK14	-0.043	0.14	-10000	0	-0.24	79	79
TGM2/GTP	-0.12	0.26	-10000	0	-0.45	174	174
MAPK11	-0.043	0.14	-10000	0	-0.24	89	89
ARHGEF1	-0.034	0.11	-10000	0	-0.2	37	37
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	-0.098	0.23	-10000	0	-0.4	164	164
RAB11/GDP	0	0	-10000	0	-10000	0	0
ICAM1	-0.075	0.19	-10000	0	-0.32	162	162
cAMP biosynthetic process	-0.094	0.21	-10000	0	-0.36	174	174
Gq family/GTP/EBP50	-0.035	0.11	-10000	0	-0.54	3	3
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.015	0.071	-10000	0	-0.52	6	6
GNB5	0	0	-10000	0	-10000	0	0
GNB1	-0.002	0.034	-10000	0	-0.74	1	1
EGF/EGFR	0.024	0.095	-10000	0	-0.42	10	10
VCAM1	-0.068	0.17	-10000	0	-0.3	163	163
TP beta/Gq family/GDP/G beta5/gamma2	-0.017	0.1	-10000	0	-0.57	5	5
platelet activation	-0.059	0.19	-10000	0	-0.3	164	164
PGI2/IP	-0.014	0.088	-10000	0	-0.57	12	12
PRKACA	-0.021	0.1	-10000	0	-0.45	22	22
Gq family/GDP/G beta5/gamma2	-0.02	0.1	-10000	0	-0.59	5	5
TXA2/TP beta/beta Arrestin2	-0.002	0.011	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.006	0.11	-10000	0	-0.76	6	6
mol:DAG	-0.11	0.25	-10000	0	-0.44	165	165
EGFR	-0.022	0.12	-10000	0	-0.63	17	17
TXA2/TP alpha	-0.14	0.28	-10000	0	-0.5	174	174
Gq family/GTP	-0.066	0.12	-10000	0	-0.28	114	114
YES1	-0.015	0.071	-10000	0	-0.52	6	6
GNAI2/GTP	-0.017	0.084	-10000	0	-0.62	6	6
PGD2/DP	-0.016	0.095	-10000	0	-0.57	14	14
SLC9A3R1	-0.005	0.052	-10000	0	-0.57	4	4
FYN	-0.015	0.076	-10000	0	-0.57	6	6
mol:NO	-0.005	0.058	-10000	0	-0.74	3	3
GNA15	0	0	-10000	0	-10000	0	0
PGK/cGMP	-0.041	0.14	-10000	0	-0.5	40	40
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.052	0.16	-10000	0	-0.78	16	16
NOS3	-0.005	0.058	-10000	0	-0.74	3	3
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.088	0.21	-10000	0	-0.36	163	163
PRKCB	-0.097	0.22	-10000	0	-0.38	165	165
PRKCE	-0.087	0.21	-10000	0	-0.37	153	153
PRKCD	-0.096	0.22	-10000	0	-0.39	162	162
PRKCG	-0.11	0.23	-10000	0	-0.41	163	163
muscle contraction	-0.13	0.28	-10000	0	-0.5	166	166
PRKCZ	-0.081	0.2	-10000	0	-0.35	163	163
ARR3	0	0	-10000	0	-10000	0	0
TXA2/TP beta	-0.019	0.095	-10000	0	-0.72	6	6
PRKCQ	-0.11	0.23	-10000	0	-0.4	168	168
MAPKKK cascade	-0.13	0.27	-10000	0	-0.48	167	167
SELE	-0.11	0.23	-10000	0	-0.42	162	162
TP beta/GNAI2/GDP/G beta/gamma	-0.022	0.1	-10000	0	-0.73	7	7
ROCK1	0	0	-10000	0	-10000	0	0
GNA14	-0.18	0.32	-10000	0	-0.74	114	114
chemotaxis	-0.17	0.34	-10000	0	-0.62	163	163
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	0	0	-10000	0	-10000	0	0
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.02	0.086	-9999	-0.42	17	17
RGS9BP	-0.015	0.11	-9999	-0.74	10	10
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.002	0.037	-9999	-0.57	2	2
mol:Na +	-0.18	0.18	-9999	-0.35	241	241
mol:ADP	-0.008	0.092	-9999	-0.42	23	23
GNAT2	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.062	0.17	-9999	-0.49	61	61
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	-0.025	0.12	-9999	-0.57	21	21
CNGB3	-0.28	0.29	-9999	-0.57	239	239
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.21	0.2	-9999	-0.36	289	289
Cone PDE6	-0.054	0.14	-9999	-0.44	41	41
Cone Metarhodopsin II	-0.015	0.069	-9999	-0.32	23	23
Na + (4 Units)	-0.22	0.2	-9999	-0.36	289	289
GNAT2/GDP	-0.054	0.14	-9999	-0.42	61	61
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0.009	0.005	-9999	-10000	0	0
Cone Transducin	-0.021	0.091	-9999	-0.44	17	17
SLC24A2	-0.11	0.22	-9999	-0.57	92	92
GNB3/GNGT2	-0.027	0.12	-9999	-0.51	26	26
GNB3	-0.011	0.077	-9999	-0.57	9	9
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	-0.002	0.037	-9999	-0.57	2	2
ARR3	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.18	0.18	-9999	-0.35	241	241
mol:Pi	-0.062	0.16	-9999	-0.49	61	61
Cone CNG Channel	-0.14	0.14	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.11	0.22	-9999	-0.57	92	92
RGS9	-0.081	0.23	-9999	-0.74	53	53
PDE6C	0	0	-9999	-10000	0	0
GNGT2	-0.026	0.14	-9999	-0.74	17	17
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0	0	-9999	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.39	0.54	-10000	0	-1.2	103	103
STAT6 (cleaved dimer)	-0.45	0.48	-10000	0	-1.1	135	135
IGHG1	-0.12	0.19	-10000	0	-0.41	4	4
IGHG3	-0.38	0.51	-10000	0	-1.1	132	132
AKT1	-0.14	0.26	-10000	0	-0.92	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.1	0.22	-10000	0	-1.1	7	7
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.16	0.27	-10000	0	-1	9	9
THY1	-0.39	0.54	-10000	0	-1.2	102	102
MYB	-0.021	0.11	-10000	0	-0.59	17	17
HMGA1	-0.004	0.045	-10000	0	-0.57	3	3
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.2	0.31	-10000	0	-0.67	61	61
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.16	0.27	-10000	0	-1	9	9
SP1	0.017	0.002	-10000	0	-10000	0	0
INPP5D	-0.002	0.034	-10000	0	-0.74	1	1
SOCS5	0.019	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.44	0.48	-10000	0	-1.1	135	135
SOCS1	-0.23	0.35	-10000	0	-0.74	95	95
SOCS3	-0.16	0.27	-10000	0	-1	8	8
FCER2	-0.34	0.5	-10000	0	-1.2	72	72
PARP14	0.007	0.006	-10000	0	-10000	0	0
CCL17	-0.46	0.62	-10000	0	-1.4	123	123
GRB2	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.12	0.23	-10000	0	-0.9	7	7
T cell proliferation	-0.38	0.54	-10000	0	-1.2	105	105
IL4R/JAK1	-0.39	0.53	-10000	0	-1.2	103	103
EGR2	-0.41	0.56	-10000	0	-1.2	108	108
JAK2	-0.003	0.034	-10000	0	-10000	0	0
JAK3	0.012	0.007	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
JAK1	0.009	0.014	-10000	0	-10000	0	0
COL1A2	-0.1	0.18	-10000	0	-0.59	3	3
CCL26	-0.42	0.55	-10000	0	-1.2	116	116
IL4R	-0.42	0.57	-10000	0	-1.3	103	103
PTPN6	0.019	0.014	-10000	0	-10000	0	0
IL13RA2	-0.42	0.57	-10000	0	-1.3	109	109
IL13RA1	-0.003	0.034	-10000	0	-10000	0	0
IRF4	-0.17	0.36	-10000	0	-0.88	82	82
ARG1	-0.12	0.24	-10000	0	-0.84	25	25
CBL	-0.18	0.29	-10000	0	-0.7	33	33
GTF3A	0.013	0.013	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.003	0.05	-10000	0	-10000	0	0
IRF4/BCL6	-0.18	0.31	-10000	0	-0.84	77	77
CD40LG	-0.12	0.29	-10000	0	-0.74	85	85
MAPK14	-0.18	0.3	-10000	0	-0.79	20	20
mitosis	-0.14	0.25	-10000	0	-0.84	9	9
STAT6	-0.46	0.63	-10000	0	-1.3	128	128
SPI1	-0.043	0.19	-10000	0	-0.74	34	34
RPS6KB1	-0.13	0.24	-10000	0	-0.88	7	7
STAT6 (dimer)	-0.46	0.63	-10000	0	-1.3	128	128
STAT6 (dimer)/PARP14	-0.42	0.58	-10000	0	-1.2	120	120
mast cell activation	0.008	0.015	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.17	0.3	-10000	0	-0.81	34	34
FRAP1	-0.14	0.26	-10000	0	-0.92	9	9
LTA	-0.39	0.54	-10000	0	-1.2	103	103
FES	-0.002	0.034	-10000	0	-0.74	1	1
T-helper 1 cell differentiation	0.44	0.61	1.3	128	-10000	0	128
CCL11	-0.38	0.52	-10000	0	-1.2	106	106
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.15	0.27	-10000	0	-1.1	9	9
IL2RG	0	0.095	-10000	0	-0.73	8	8
IL10	-0.39	0.54	-10000	0	-1.2	104	104
IRS1	0	0	-10000	0	-10000	0	0
IRS2	-0.005	0.058	-10000	0	-0.74	3	3
IL4	-0.078	0.14	-10000	0	-10000	0	0
IL5	-0.39	0.54	-10000	0	-1.2	102	102
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.31	0.42	-10000	0	-0.9	103	103
COL1A1	-0.14	0.23	-10000	0	-0.64	28	28
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.4	0.55	-10000	0	-1.2	102	102
IL2R gamma/JAK3	-0.004	0.072	-10000	0	-0.55	8	8
TFF3	-0.44	0.62	-10000	0	-1.4	110	110
ALOX15	-0.62	0.76	-10000	0	-1.5	178	178
MYBL1	-0.001	0.026	-10000	0	-0.57	1	1
T-helper 2 cell differentiation	-0.31	0.43	-10000	0	-0.93	105	105
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	0.01	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.15	0.26	-10000	0	-1	9	9
mol:PI-3-4-5-P3	-0.14	0.26	-10000	0	-0.92	9	9
PI3K	-0.15	0.28	-10000	0	-1	9	9
DOK2	-0.066	0.21	-10000	0	-0.74	43	43
ETS1	0	0.11	-10000	0	-0.71	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.11	0.22	-10000	0	-0.87	7	7
ITGB3	-0.4	0.55	-10000	0	-1.2	104	104
PIGR	-0.8	0.83	-10000	0	-1.6	255	255
IGHE	0.028	0.044	-10000	0	-10000	0	0
MAPKKK cascade	-0.11	0.21	-10000	0	-0.85	7	7
BCL6	0.001	0.004	-10000	0	-10000	0	0
OPRM1	-0.4	0.54	-10000	0	-1.2	103	103
RETNLB	-0.4	0.54	-10000	0	-1.2	102	102
SELP	-0.56	0.74	-10000	0	-1.6	150	150
AICDA	-0.38	0.51	-10000	0	-1.2	104	104

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.043	0.056	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.099	0.14	-9999	-0.43	20	20
JUN	-0.063	0.14	-9999	-0.42	17	17
HRAS	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.17	0.22	-9999	-0.48	124	124
RAP1A	0	0	-9999	-10000	0	0
FRS2	0	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.17	0.22	-9999	-0.48	124	124
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.16	0.22	-9999	-0.48	119	119
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.15	0.2	-9999	-0.43	124	124
GRB7	-0.005	0.052	-9999	-0.57	4	4
RET51/GFRalpha1/GDNF	-0.17	0.22	-9999	-0.48	124	124
MAPKKK cascade	-0.13	0.18	-9999	-0.59	19	19
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.16	0.22	-9999	-0.42	182	182
lamellipodium assembly	-0.095	0.13	-9999	-0.4	20	20
RET51/GFRalpha1/GDNF/SHC	-0.17	0.22	-9999	-0.48	124	124
PIK3CA	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.16	0.22	-9999	-0.48	119	119
RET9/GFRalpha1/GDNF/Shank3	-0.16	0.22	-9999	-0.43	182	182
MAPK3	-0.14	0.18	-9999	-0.62	21	21
DOK1	0	0	-9999	-10000	0	0
DOK6	-0.065	0.21	-9999	-0.74	42	42
PXN	0	0	-9999	-10000	0	0
neurite development	-0.14	0.18	-9999	-0.55	39	39
DOK5	-0.007	0.069	-9999	-0.67	5	5
GFRA1	-0.18	0.32	-9999	-0.74	119	119
MAPK8	-0.096	0.13	-9999	-0.44	17	17
HRAS/GTP	-0.14	0.2	-9999	-0.62	21	21
tube development	-0.15	0.21	-9999	-0.46	119	119
MAPK1	-0.14	0.18	-9999	-0.62	21	21
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.1	0.14	-9999	-0.33	119	119
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.19	0.25	-9999	-0.51	144	144
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.22	-9999	-0.48	124	124
RET51/GFRalpha1/GDNF/Dok5	-0.17	0.23	-9999	-0.49	125	125
PRKCA	-0.003	0.048	-9999	-0.74	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.11	0.15	-9999	-0.36	119	119
PIK3R1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.14	-9999	-0.37	47	47
RET51/GFRalpha1/GDNF/Grb7	-0.17	0.22	-9999	-0.49	125	125
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.021	0.11	-9999	-0.58	17	17
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.061	0.14	-9999	-0.41	17	17
RET9/GFRalpha1/GDNF/FRS2	-0.16	0.22	-9999	-0.42	182	182
SHANK3	-0.003	0.048	-9999	-0.74	2	2
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.34	119	119
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.1	0.14	-9999	-0.33	120	120
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.1	0.14	-9999	-0.47	17	17
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.48	17	17
PI3K	-0.14	0.2	-9999	-0.48	120	120
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.15	0.21	-9999	-0.46	119	119
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.1	0.14	-9999	-0.47	17	17
RET51/GFRalpha1/GDNF/FRS2	-0.17	0.22	-9999	-0.48	124	124
GAB1	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
IRS2	-0.005	0.058	-9999	-0.74	3	3
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.14	-9999	-0.48	17	17
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.22	-9999	-0.49	125	125
GRB2	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.093	0.21	-9999	-0.57	78	78
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.22	-9999	-0.48	124	124
Rac1/GTP	-0.11	0.16	-9999	-0.48	20	20
RET9/GFRalpha1/GDNF	-0.18	0.24	-9999	-0.47	182	182
GFRalpha1/GDNF	-0.2	0.27	-9999	-0.54	182	182

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.06	0.099	0.35	3	-10000	0	3
SMARCC2	0.011	0	-10000	0	-10000	0	0
SMARCC1	0.011	0	-10000	0	-10000	0	0
TBX21	-0.2	0.35	-10000	0	-1	62	62
SUMO2	0.002	0.006	-10000	0	-10000	0	0
STAT1 (dimer)	0.017	0	-10000	0	-10000	0	0
FKBP4	-0.001	0.026	-10000	0	-0.57	1	1
FKBP5	0	0	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90	0.13	0.1	0.34	42	-10000	0	42
PRL	-0.085	0.12	-10000	0	-0.63	1	1
cortisol/GR alpha (dimer)/TIF2	0.31	0.25	0.6	150	-10000	0	150
RELA	-0.046	0.1	-10000	0	-10000	0	0
FGG	-0.13	0.47	0.55	51	-0.62	222	273
GR beta/TIF2	0.14	0.12	0.37	49	-0.39	1	50
IFNG	-0.34	0.24	-10000	0	-0.68	98	98
apoptosis	0.028	0.12	0.46	2	-0.55	1	3
CREB1	0.001	0.028	-10000	0	-10000	0	0
histone acetylation	-0.012	0.15	0.36	2	-0.42	16	18
BGLAP	-0.096	0.14	-10000	0	-0.59	5	5
GR/PKAc	0.12	0.1	0.33	32	-10000	0	32
NF kappa B1 p50/RelA	-0.083	0.18	-10000	0	-0.48	37	37
SMARCD1	0.011	0	-10000	0	-10000	0	0
MDM2	0.11	0.098	0.29	59	-0.31	1	60
GATA3	-0.014	0.13	-10000	0	-0.71	17	17
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.17	0.42	-10000	0	-1.3	51	51
GSK3B	0.002	0.006	-10000	0	-10000	0	0
NR1I3	0.047	0.11	0.47	1	-10000	0	1
CSN2	0.16	0.16	0.44	42	-10000	0	42
BRG1/BAF155/BAF170/BAF60A	0	0	-10000	0	-10000	0	0
NFATC1	0.001	0.034	-10000	0	-0.74	1	1
POU2F1	0.005	0.014	-10000	0	-10000	0	0
CDKN1A	0.026	0.015	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.004	-10000	0	-10000	0	0
SFN	-0.057	0.17	-10000	0	-0.57	48	48
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.095	0.14	0.33	38	-10000	0	38
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.034	0.16	0.46	1	-0.9	9	10
JUN	-0.29	0.16	-10000	0	-0.51	108	108
IL4	-0.11	0.15	-10000	0	-0.52	16	16
CDK5R1	-0.009	0.078	-10000	0	-0.57	9	9
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.44	0.24	-10000	0	-0.59	276	276
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.099	0.33	37	-10000	0	37
cortisol/GR alpha (monomer)	0.37	0.32	0.72	162	-10000	0	162
NCOA2	-0.002	0.034	-10000	0	-0.74	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.17	0.24	-10000	0	-0.83	55	55
AP-1/NFAT1-c-4	-0.53	0.24	-10000	0	-0.68	271	271
AFP	-0.19	0.15	-10000	0	-0.65	16	16
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.18	0.15	0.49	36	-10000	0	36
TP53	0.029	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.54	0.25	-10000	0	-0.69	285	285
KRT14	-0.37	0.22	-10000	0	-0.61	136	136
TBP	0.017	0	-10000	0	-10000	0	0
CREBBP	0.11	0.066	0.34	1	-10000	0	1
HDAC1	0	0.004	-10000	0	-10000	0	0
HDAC2	0.01	0.03	-10000	0	-10000	0	0
AP-1	-0.53	0.25	-10000	0	-0.68	274	274
MAPK14	0.002	0.005	-10000	0	-10000	0	0
MAPK10	-0.011	0.095	-10000	0	-0.74	8	8
MAPK11	0.002	0.006	-10000	0	-10000	0	0
KRT5	-0.56	0.25	-10000	0	-0.68	322	322
interleukin-1 receptor activity	0.008	0.028	-10000	0	-10000	0	0
NCOA1	0.012	0.002	-10000	0	-10000	0	0
STAT1	0.017	0	-10000	0	-10000	0	0
CGA	-0.12	0.17	-10000	0	-0.63	11	11
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.2	0.19	0.51	88	-10000	0	88
MAPK3	0.002	0.006	-10000	0	-10000	0	0
MAPK1	0.002	0.005	-10000	0	-10000	0	0
ICAM1	-0.27	0.45	-10000	0	-1.1	75	75
NFKB1	-0.046	0.1	-10000	0	-0.33	1	1
MAPK8	-0.24	0.17	-10000	0	-0.48	109	109
MAPK9	0.002	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.025	0.12	0.46	2	-0.58	1	3
BAX	0.026	0.015	-10000	0	-10000	0	0
POMC	-0.21	0.24	-10000	0	-0.7	52	52
EP300	0.11	0.066	0.34	1	-10000	0	1
cortisol/GR alpha (dimer)/p53	0.33	0.25	0.61	159	-10000	0	159
proteasomal ubiquitin-dependent protein catabolic process	0.076	0.074	0.26	14	-0.27	1	15
SGK1	0.17	0.076	-10000	0	-10000	0	0
IL13	-0.27	0.2	-10000	0	-0.87	25	25
IL6	-0.34	0.53	-10000	0	-1.3	102	102
PRKACG	-0.001	0.026	-10000	0	-0.57	1	1
IL5	-0.24	0.17	-10000	0	-0.78	21	21
IL2	-0.34	0.21	-10000	0	-0.68	78	78
CDK5	0.001	0.004	-10000	0	-10000	0	0
PRKACB	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.2	0.29	-10000	0	-0.72	73	73
CDK5R1/CDK5	-0.006	0.056	-10000	0	-0.41	9	9
NF kappa B1 p50/RelA/PKAc	-0.059	0.12	-10000	0	-0.47	5	5
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.3	0.23	0.57	148	-10000	0	148
SMARCA4	0.011	0	-10000	0	-10000	0	0
chromatin remodeling	0.19	0.14	0.4	101	-10000	0	101
NF kappa B1 p50/RelA/Cbp	0.036	0.18	0.38	13	-0.53	2	15
JUN (dimer)	-0.29	0.16	-10000	0	-0.51	108	108
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.42	0.51	-10000	0	-1	185	185
NR3C1	0.2	0.2	0.52	93	-10000	0	93
NR4A1	-0.1	0.26	-10000	0	-0.72	68	68
TIF2/SUV420H1	-0.001	0.025	-10000	0	-0.56	1	1
MAPKKK cascade	0.028	0.12	0.46	2	-0.55	1	3
cortisol/GR alpha (dimer)/Src-1	0.32	0.25	0.6	157	-10000	0	157
PBX1	0	0.06	-10000	0	-0.74	3	3
POU1F1	-0.002	0.047	-10000	0	-0.57	3	3
SELE	-0.47	0.61	-10000	0	-1.3	155	155
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.19	0.14	0.4	101	-10000	0	101
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.3	0.23	0.57	148	-10000	0	148
mol:cortisol	0.2	0.2	0.42	164	-0.23	3	167
MMP1	-0.32	0.19	-10000	0	-0.48	274	274

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.12	0.39	-9999	-1.2	49	49
MKNK1	0	0	-9999	-10000	0	0
MAPK14	-0.036	0.12	-9999	-0.43	8	8
ATF2/c-Jun	-0.01	0.098	-9999	-0.43	3	3
MAPK11	-0.036	0.12	-9999	-0.31	72	72
MITF	-0.041	0.16	-9999	-0.37	82	82
MAPKAPK5	-0.032	0.15	-9999	-0.36	72	72
KRT8	-0.032	0.15	-9999	-0.36	72	72
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.054	0.18	-9999	-0.46	72	72
CEBPB	-0.032	0.15	-9999	-0.36	72	72
SLC9A1	-0.032	0.15	-9999	-0.36	72	72
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.026	0.15	-9999	-0.35	72	72
p38alpha-beta/MNK1	-0.065	0.13	-9999	-0.58	8	8
JUN	-0.009	0.098	-9999	-0.42	3	3
PPARGC1A	-0.13	0.28	-9999	-0.51	142	142
USF1	-0.032	0.15	-9999	-0.36	72	72
RAB5/GDP/GDI1	-0.045	0.095	-9999	-0.4	8	8
NOS2	-0.098	0.32	-9999	-1.2	31	31
DDIT3	-0.032	0.15	-9999	-0.36	72	72
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.018	0.12	-9999	-0.43	9	9
p38alpha-beta/HBP1	-0.065	0.13	-9999	-0.58	8	8
CREB1	-0.03	0.16	-9999	-0.38	72	72
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.021	0.13	-9999	-0.52	8	8
RPS6KA4	-0.032	0.15	-9999	-0.36	72	72
PLA2G4A	-0.025	0.14	-9999	-0.53	13	13
GDI1	-0.032	0.15	-9999	-0.36	72	72
TP53	-0.044	0.18	-9999	-0.45	72	72
RPS6KA5	-0.032	0.15	-9999	-0.36	72	72
ESR1	-0.053	0.19	-9999	-0.42	86	86
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.041	0.17	-9999	-0.39	79	79
MEF2A	-0.032	0.15	-9999	-0.36	72	72
EIF4EBP1	-0.032	0.16	-9999	-0.38	72	72
KRT19	-0.039	0.18	-9999	-0.4	74	74
ELK4	-0.032	0.15	-9999	-0.36	72	72
ATF6	-0.032	0.15	-9999	-0.36	72	72
ATF1	-0.03	0.16	-9999	-0.38	72	72
p38alpha-beta/MAPKAPK2	-0.065	0.13	-9999	-0.58	8	8
p38alpha-beta/MAPKAPK3	-0.065	0.13	-9999	-0.58	8	8

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.017	0.094	-9999	0	-0.51	16	16
ARNO/beta Arrestin1-2	-0.17	0.24	-9999	0	-0.45	181	181
EGFR	-0.022	0.12	-9999	0	-0.63	17	17
EPHA2	-0.005	0.058	-9999	0	-0.74	3	3
USP6	0	0	-9999	0	-10000	0	0
IQSEC1	0	0	-9999	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.027	0.12	-9999	0	-0.5	26	26
ARRB2	0.007	0.011	-9999	0	-10000	0	0
mol:GTP	0.015	0.026	-9999	0	-0.15	8	8
ARRB1	-0.14	0.29	-9999	0	-0.74	91	91
FBXO8	0	0	-9999	0	-10000	0	0
TSHR	-0.019	0.1	-9999	0	-0.57	16	16
EGF	-0.014	0.099	-9999	0	-0.69	10	10
somatostatin receptor activity	0	0	-9999	0	-0.001	141	141
ARAP2	-0.002	0.034	-9999	0	-0.74	1	1
mol:GDP	-0.12	0.16	-9999	0	-0.33	134	134
mol:PI-3-4-5-P3	0	0	-9999	0	-0.001	116	116
ITGA2B	-0.023	0.13	-9999	0	-0.74	15	15
ARF6	0	0	-9999	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.034	-9999	0	-0.43	3	3
ADAP1	-0.014	0.1	-9999	0	-0.74	9	9
KIF13B	-0.012	0.095	-9999	0	-0.74	8	8
HGF/MET	-0.12	0.23	-9999	0	-0.56	104	104
PXN	0	0	-9999	0	-10000	0	0
ARF6/GTP	-0.11	0.15	-9999	0	-0.31	141	141
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.023	0.1	-9999	0	-0.42	26	26
ADRB2	-0.21	0.33	-9999	0	-0.74	137	137
receptor agonist activity	0	0	-9999	0	0	145	145
actin filament binding	0	0	-9999	0	-0.001	141	141
SRC	0	0	-9999	0	-10000	0	0
ITGB3	-0.012	0.095	-9999	0	-0.74	8	8
GNAQ	-0.002	0.034	-9999	0	-0.74	1	1
EFA6/PI-4-5-P2	0	0.001	-9999	0	-0.001	116	116
ARF6/GDP	-0.013	0.071	-9999	0	-0.34	4	4
ARF6/GDP/GULP/ACAP1	-0.12	0.14	-9999	0	-0.43	47	47
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.021	0.092	-9999	0	-0.43	23	23
ACAP1	-0.003	0.043	-9999	0	-0.66	2	2
ACAP2	0	0	-9999	0	-10000	0	0
LHCGR/beta Arrestin2	-0.001	0.014	-9999	0	-0.31	1	1
EFNA1	0	0	-9999	0	-10000	0	0
HGF	-0.16	0.3	-9999	0	-0.74	101	101
CYTH3	0.009	0	-9999	0	-10000	0	0
CYTH2	0.005	0.002	-9999	0	-10000	0	0
NCK1	0	0	-9999	0	-10000	0	0
fibronectin binding	0	0	-9999	0	0	101	101
endosomal lumen acidification	0	0	0	1	-0.001	90	91
microtubule-based process	0	0	-9999	0	-10000	0	0
GULP1	-0.014	0.1	-9999	0	-0.74	9	9
GNAQ/ARNO	0.004	0.02	-9999	0	-0.41	1	1
mol:Phosphatidic acid	0	0	-9999	0	-10000	0	0
PIP3-E	0	0	-9999	0	0	10	10
MET	-0.004	0.054	-9999	0	-0.68	3	3
GNA14	-0.18	0.32	-9999	0	-0.74	114	114
GNA15	0	0	-9999	0	-10000	0	0
GIT1	0	0	-9999	0	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	0	-0.001	140	140
GNA11	0	0	-9999	0	-10000	0	0
LHCGR	-0.001	0.026	-9999	0	-0.57	1	1
AGTR1	-0.31	0.36	-9999	0	-0.74	199	199
desensitization of G-protein coupled receptor protein signaling pathway	-0.001	0.014	-9999	0	-0.31	1	1
IPCEF1/ARNO	-0.018	0.079	-9999	0	-0.41	12	12
alphaIIb/beta3 Integrin	-0.027	0.12	-9999	0	-0.56	23	23

×

RXR and RAR heterodimerization with other nuclear receptor

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.032	0.03	-9999	-10000	0	0
VDR	-0.002	0.034	-9999	-0.74	1	1
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.13	0.18	-9999	-0.54	10	10
RXRs/LXRs/DNA/Oxysterols	-0.098	0.16	-9999	-0.64	10	10
MED1	0	0	-9999	-10000	0	0
mol:9cRA	0.004	0.007	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.012	0.06	-9999	-10000	0	0
RXRs/NUR77	-0.28	0.27	-9999	-0.49	277	277
RXRs/PPAR	-0.18	0.2	-9999	-0.57	43	43
NCOR2	-0.002	0.034	-9999	-0.74	1	1
VDR/VDR/Vit D3	-0.001	0.026	-9999	-0.57	1	1
RARs/VDR/DNA/Vit D3	-0.003	0.032	-9999	-0.41	3	3
RARA	0	0	-9999	-10000	0	0
NCOA1	0	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.002	0.034	-9999	-0.74	1	1
RARs/RARs/DNA/9cRA	-0.002	0.027	-9999	-0.42	2	2
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.057	0.053	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.013	0.061	-9999	-10000	0	0
THRA	0	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.001	0.026	-9999	-0.57	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	-0.23	0.22	-9999	-0.43	253	253
NR1H4	-0.005	0.052	-9999	-0.57	4	4
RXRs/LXRs/DNA	-0.21	0.2	-9999	-0.56	10	10
NR1H2	0.015	0.004	-9999	-10000	0	0
NR1H3	0.014	0.005	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.21	0.2	-9999	-0.4	254	254
NR4A1	-0.1	0.25	-9999	-0.74	65	65
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.12	0.14	-9999	-0.34	11	11
RXRG	-0.38	0.37	-9999	-0.74	253	253
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.015	0.004	-9999	-10000	0	0
RXRB	0.014	0.005	-9999	-10000	0	0
THRB	-0.026	0.14	-9999	-0.74	17	17
PPARG	-0.089	0.24	-9999	-0.74	58	58
PPARD	0	0	-9999	-10000	0	0
TNF	-0.1	0.23	-9999	-1.2	13	13
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	-0.097	0.16	-9999	-0.64	10	10
PPARA	0	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.003	0.048	-9999	-0.74	2	2
RXRs/NUR77/BCL2	-0.2	0.2	-9999	-0.36	277	277
SREBF1	-0.082	0.15	-9999	-0.6	9	9
RXRs/RXRs/DNA/9cRA	-0.23	0.22	-9999	-0.43	253	253
ABCA1	-0.082	0.15	-9999	-0.6	9	9
RARs/THRs	-0.016	0.079	-9999	-10000	0	0
RXRs/FXR	-0.23	0.22	-9999	-0.43	253	253
BCL2	-0.001	0.026	-9999	-0.57	1	1

×

BMP 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.18	0.21	-9999	-0.56	73	73
SMAD6-7/SMURF1	-0.053	0.15	-9999	-0.48	53	53
NOG	-0.027	0.14	-9999	-0.73	18	18
SMAD9	-0.1	0.22	-9999	-0.59	72	72
SMAD4	0	0	-9999	-10000	0	0
SMAD5	-0.023	0.13	-9999	-0.47	23	23
BMP7/USAG1	-0.25	0.27	-9999	-0.5	238	238
SMAD5/SKI	-0.05	0.11	-9999	-0.46	19	19
SMAD1	0.033	0.027	-9999	-10000	0	0
BMP2	-0.098	0.25	-9999	-0.74	64	64
SMAD1/SMAD1/SMAD4	-0.035	0.096	-9999	-10000	0	0
BMPR1A	0	0	-9999	-10000	0	0
BMPR1B	-0.057	0.2	-9999	-0.74	37	37
BMPR1A-1B/BAMBI	-0.04	0.13	-9999	-0.48	39	39
AHSG	-0.018	0.099	-9999	-0.57	15	15
CER1	-0.002	0.037	-9999	-0.57	2	2
BMP2-4/CER1	-0.075	0.18	-9999	-0.5	70	70
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.067	0.14	-9999	-0.5	29	29
BMP2-4 (homodimer)	-0.085	0.21	-9999	-0.58	71	71
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.045	0.14	-9999	-0.45	48	48
RGMA	-0.062	0.18	-9999	-0.57	52	52
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.062	0.13	-9999	-0.45	29	29
BMP2-4/USAG1	-0.16	0.27	-9999	-0.55	142	142
SMAD6/SMURF1/SMAD5	-0.05	0.11	-9999	-0.46	19	19
SOSTDC1	-0.14	0.29	-9999	-0.74	93	93
BMP7/BMPR2/BMPR1A-1B	-0.14	0.19	-9999	-0.53	43	43
SKI	0	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.02	0.12	-9999	-0.74	13	13
HFE2	-0.002	0.037	-9999	-0.57	2	2
ZFYVE16	0	0	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.076	0.18	-9999	-0.5	71	71
SMAD5/SMAD5/SMAD4	-0.05	0.11	-9999	-0.47	18	18
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.05	0.1	-9999	-0.45	17	17
BMP7 (homodimer)	-0.2	0.28	-9999	-0.58	169	169
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.028	0.11	-9999	-0.48	28	28
SMAD1/SKI	-0.004	0.012	-9999	-10000	0	0
SMAD6	-0.08	0.23	-9999	-0.74	52	52
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.084	0.19	-9999	-0.5	70	70
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.34	0.28	-9999	-0.57	288	288
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.043	0.15	-9999	-0.56	37	37
CHRDL1	-0.39	0.37	-9999	-0.74	251	251
ENDOFIN/SMAD1	-0.004	0.012	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.04	0.11	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.005	0.06	-9999	-0.66	4	4
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.32	0.3	-9999	-0.55	277	277
BMP2-4/GREM1	-0.28	0.22	-9999	-0.62	70	70
SMAD7	-0.002	0.034	-9999	-0.74	1	1
SMAD8A/SMAD8A/SMAD4	-0.096	0.2	-9999	-0.55	72	72
SMAD1/SMAD6	-0.004	0.012	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.2	0.28	-9999	-0.58	169	169
BMP6	-0.02	0.12	-9999	-0.74	13	13
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.058	0.12	-9999	-0.41	30	30
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	-0.004	0.012	-9999	-10000	0	0
SMAD7/SMURF1	-0.001	0.025	-9999	-0.56	1	1
CTDSPL	0	0	-9999	-10000	0	0
PPP1CA	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.084	0.14	-9999	-0.46	41	41
CHRD	-0.004	0.054	-9999	-0.68	3	3
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.071	0.14	-9999	-0.5	29	29
BMP4	-0.015	0.1	-9999	-0.72	10	10
FST	-0.092	0.21	-9999	-0.57	77	77
BMP2-4/NOG	-0.09	0.21	-9999	-0.53	81	81
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.13	0.18	-9999	-0.5	43	43

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	0.071	0.074	0.15	169	-10000	0	169
BUB1B	-0.13	0.098	-10000	0	-0.22	194	194
PLK1	-0.013	0.036	-10000	0	-0.13	8	8
PLK1S1	-0.003	0.02	-10000	0	-10000	0	0
KIF2A	-0.004	0.033	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	-0.013	0.036	-10000	0	-0.13	8	8
GOLGA2	0	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.2	0.23	-10000	0	-0.41	236	236
WEE1	-0.006	0.038	-10000	0	-10000	0	0
cytokinesis	-0.11	0.12	-10000	0	-0.27	82	82
PP2A-alpha B56	-0.007	0.022	-10000	0	-10000	0	0
AURKA	-0.006	0.029	-10000	0	-0.12	8	8
PICH/PLK1	-0.11	0.17	-10000	0	-0.46	53	53
CENPE	-0.041	0.11	-10000	0	-0.35	54	54
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.004	0.032	-10000	0	-10000	0	0
PPP2CA	0	0	-10000	0	-10000	0	0
FZR1	0	0	-10000	0	-10000	0	0
TPX2	-0.06	0.048	-10000	0	-0.12	4	4
PAK1	0.002	0.026	-10000	0	-0.57	1	1
SPC24	-0.17	0.26	-10000	0	-0.57	144	144
FBXW11	0	0	-10000	0	-10000	0	0
CLSPN	-0.013	0.039	-10000	0	-0.15	5	5
GORASP1	0	0	-10000	0	-10000	0	0
metaphase	0	0.003	-10000	0	-0.012	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.007	0.02	-10000	0	-0.066	4	4
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-10000	0	0
STAG2	0	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.001	0.008	-10000	0	-10000	0	0
spindle elongation	-0.013	0.036	-10000	0	-0.13	8	8
ODF2	0.004	0.005	-10000	0	-10000	0	0
BUB1	-0.005	0.032	-10000	0	-10000	0	0
TPT1	-0.003	0.02	-10000	0	-10000	0	0
CDC25C	-0.077	0.057	-10000	0	-10000	0	0
CDC25B	0.009	0.003	-10000	0	-10000	0	0
SGOL1	-0.071	0.074	-10000	0	-0.15	169	169
RHOA	0	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.029	0.079	-10000	0	-10000	0	0
CDC14B	0.01	0.002	-10000	0	-10000	0	0
CDC20	-0.36	0.28	-10000	0	-0.57	308	308
PLK1/PBIP1	-0.03	0.063	-10000	0	-0.33	18	18
mitosis	-0.001	0.005	0.022	13	-10000	0	13
FBXO5	-0.004	0.031	-10000	0	-10000	0	0
CDC2	-0.001	0.004	-10000	0	-0.013	4	4
NDC80	-0.2	0.27	-10000	0	-0.57	167	167
metaphase plate congression	-0.007	0.025	-10000	0	-10000	0	0
ERCC6L	-0.11	0.16	-10000	0	-0.49	36	36
NLP/gamma Tubulin	-0.005	0.021	-10000	0	-10000	0	0
microtubule cytoskeleton organization	-0.003	0.02	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-10000	0	0
PPP1R12A	0	0	-10000	0	-10000	0	0
interphase	0	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.2	0.2	-10000	0	-0.37	256	256
GRASP65/GM130/RAB1/GTP/PLK1	-0.008	0.015	-10000	0	-10000	0	0
RAB1A	0	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.001	0.028	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.043	0.035	-10000	0	-10000	0	0
microtubule-based process	-0.18	0.17	-10000	0	-0.34	249	249
Golgi organization	-0.013	0.036	-10000	0	-0.13	8	8
Cohesin/SA2	-0.019	0.024	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.3	0.29	-10000	0	-0.57	249	249
APC/C/CDC20	-0.22	0.16	-10000	0	-0.34	308	308
PPP2R1A	0	0	-10000	0	-10000	0	0
chromosome segregation	-0.029	0.062	-10000	0	-0.32	18	18
PRC1	-0.057	0.17	-10000	0	-0.57	48	48
ECT2	-0.016	0.073	-10000	0	-0.35	18	18
C13orf34	-0.003	0.028	-10000	0	-10000	0	0
NUDC	-0.007	0.025	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.13	0.097	-10000	0	-0.22	194	194
spindle assembly	-0.008	0.029	-10000	0	-10000	0	0
spindle stabilization	-0.003	0.02	-10000	0	-10000	0	0
APC/C/HCDH1	0	0	-10000	0	-10000	0	0
MKLP2/PLK1	-0.18	0.17	-10000	0	-0.34	249	249
CCNB1	-0.058	0.19	-10000	0	-0.57	57	57
PPP1CB	0	0	-10000	0	-10000	0	0
BTRC	0	0	-10000	0	-10000	0	0
ROCK2	0.001	0.025	-10000	0	-10000	0	0
TUBG1	-0.003	0.02	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.03	0.076	-10000	0	-10000	0	0
MLF1IP	-0.011	0.083	-10000	0	-0.43	18	18
INCENP	0.004	0.006	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.034	-9999	-0.74	1	1
alphaV beta3 Integrin	-0.009	0.071	-9999	-0.56	8	8
PTK2	-0.1	0.16	-9999	-0.57	40	40
positive regulation of JNK cascade	-0.034	0.09	-9999	-0.34	37	37
CDC42/GDP	-0.022	0.13	-9999	-0.46	37	37
Rac1/GDP	-0.02	0.13	-9999	-0.46	37	37
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.041	0.11	-9999	-0.42	37	37
nectin-3/I-afadin	-0.043	0.15	-9999	-0.56	37	37
RAPGEF1	-0.033	0.15	-9999	-0.53	37	37
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.046	0.17	-9999	-0.62	37	37
PDGFB-D/PDGFRB	-0.002	0.034	-9999	-0.74	1	1
TLN1	-0.02	0.15	-9999	-0.51	31	31
Rap1/GTP	-0.034	0.097	-9999	-0.37	37	37
IQGAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.043	0.15	-9999	-0.56	37	37
PVR	0	0	-9999	-10000	0	0
Necl-5(dimer)	0	0	-9999	-10000	0	0
mol:GDP	-0.033	0.16	-9999	-0.58	37	37
MLLT4	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	-0.032	0.11	-9999	-0.4	38	38
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.2	0.21	-9999	-0.41	231	231
positive regulation of lamellipodium assembly	-0.037	0.096	-9999	-0.35	40	40
PVRL1	-0.27	0.29	-9999	-0.57	231	231
PVRL3	-0.057	0.2	-9999	-0.74	37	37
PVRL2	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
CLDN1	-0.1	0.22	-9999	-0.58	87	87
JAM-A/CLDN1	-0.089	0.17	-9999	-0.49	38	38
SRC	-0.077	0.18	-9999	-0.7	37	37
ITGB3	-0.012	0.095	-9999	-0.74	8	8
nectin-1(dimer)/I-afadin/I-afadin	-0.2	0.21	-9999	-0.41	231	231
FARP2	-0.037	0.16	-9999	-0.57	37	37
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.037	0.13	-9999	-0.48	37	37
nectin-1/I-afadin	-0.2	0.21	-9999	-0.41	231	231
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.2	0.21	-9999	-0.39	249	249
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.034	0.09	-9999	-0.34	37	37
alphaV/beta3 Integrin/Talin	-0.047	0.14	-9999	-0.49	35	35
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	-0.05	0.15	-9999	-0.54	31	31
VAV2	-0.041	0.17	-9999	-0.58	40	40
RAP1/GDP	-0.039	0.11	-9999	-0.43	37	37
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.037	0.13	-9999	-0.48	37	37
nectin-3(dimer)/I-afadin/I-afadin	-0.043	0.15	-9999	-0.56	37	37
Rac1/GTP	-0.045	0.12	-9999	-0.43	40	40
PTPRM	-0.055	0.16	-9999	-0.43	61	61
E-cadherin/beta catenin/alpha catenin	-0.13	0.13	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.029	0.12	-9999	-0.56	25	25
alphaV beta3 Integrin	-0.023	0.11	-9999	-0.5	22	22
PTK2	-0.19	0.23	-9999	-0.69	39	39
IGF1R	0	0	-9999	-10000	0	0
PI4KB	0	0	-9999	-10000	0	0
MFGE8	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
CDKN1B	-0.23	0.29	-9999	-0.58	187	187
VEGFA	0	0	-9999	-10000	0	0
ILK	-0.23	0.29	-9999	-0.58	187	187
ROCK1	0	0	-9999	-10000	0	0
AKT1	-0.21	0.27	-9999	-0.54	187	187
PTK2B	-0.027	0.12	-9999	-0.47	28	28
alphaV/beta3 Integrin/JAM-A	-0.18	0.22	-9999	-0.43	196	196
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.011	0.069	-9999	-0.48	8	8
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.014	0.076	-9999	-0.43	15	15
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.12	0.16	-9999	-0.65	19	19
alphaV/beta3 Integrin/Syndecan-1	-0.009	0.065	-9999	-0.48	9	9
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.038	0.14	-9999	-0.78	10	10
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.19	0.18	-9999	-0.35	260	260
RPS6KB1	-0.035	0.13	-9999	-0.72	10	10
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.1	0.18	-9999	-0.77	22	22
GPR124	0	0	-9999	-10000	0	0
MAPK1	-0.1	0.18	-9999	-0.77	22	22
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.31	0.24	-9999	-0.49	305	305
cell adhesion	-0.012	0.067	-9999	-0.42	11	11
ANGPTL3	-0.005	0.052	-9999	-0.57	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	-0.025	0.11	-9999	-0.48	25	25
IGF-1R heterotetramer	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.058	0.2	-9999	-0.74	38	38
ITGB3	-0.012	0.095	-9999	-0.74	8	8
IGF1	-0.024	0.13	-9999	-0.73	16	16
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.008	0.061	-9999	-0.48	8	8
apoptosis	0	0	-9999	-10000	0	0
CD47	-0.005	0.058	-9999	-0.74	3	3
alphaV/beta3 Integrin/CD47	-0.011	0.072	-9999	-0.48	11	11
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.034	0.13	-9999	-0.51	32	32
CSF1	-0.006	0.067	-9999	-0.74	4	4
PIK3C2A	-0.23	0.29	-9999	-0.58	187	187
PI4 Kinase/Pyk2	-0.16	0.21	-9999	-0.75	25	25
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.03	0.12	-9999	-0.51	28	28
FAK1/Vinculin	-0.15	0.18	-9999	-0.51	39	39
alphaV beta3/Integrin/ppsTEM5	-0.008	0.061	-9999	-0.48	8	8
RHOA	0	0	-9999	-10000	0	0
VTN	-0.29	0.36	-9999	-0.74	189	189
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.023	0.13	-9999	-0.74	15	15
F11R	0.002	0.1	-9999	-0.56	15	15
alphaV/beta3 Integrin/Lactadherin	-0.008	0.061	-9999	-0.48	8	8
alphaV/beta3 Integrin/TGFBR2	-0.045	0.16	-9999	-0.54	40	40
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.004	0.039	-9999	-0.43	4	4
HSP90AA1	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.007	0.056	-9999	-0.44	8	8
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.017	0.11	-9999	-0.74	11	11
alphaV/beta3 Integrin/Pyk2	-0.028	0.12	-9999	-0.47	28	28
SDC1	-0.002	0.034	-9999	-0.74	1	1
VAV3	-0.004	0.041	-9999	-0.4	5	5
PTPN11	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
FAK1/Paxillin	-0.15	0.18	-9999	-0.51	39	39
cell migration	-0.13	0.16	-9999	-0.48	30	30
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.16	0.2	-9999	-0.76	13	13
SPP1	-0.3	0.28	-9999	-0.57	255	255
KDR	-0.038	0.16	-9999	-0.74	25	25
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.47	0.36	-9999	-0.74	305	305
angiogenesis	-0.11	0.22	-9999	-0.76	24	24
Rac1/GTP	-0.004	0.037	-9999	-10000	0	0
EDIL3	-0.04	0.17	-9999	-0.74	26	26
cell proliferation	-0.045	0.16	-9999	-0.54	40	40

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.034	0.11	-10000	0	-0.48	16	16
fibroblast growth factor receptor signaling pathway	-0.034	0.11	-10000	0	-0.48	16	16
LAMA1	-0.17	0.26	-10000	0	-0.57	141	141
PRNP	0	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.15	0.25	-10000	0	-0.56	128	128
SMAD2	-0.024	0.14	-10000	0	-0.43	38	38
GPC1/PrPc/Cu2+	-0.018	0.078	-10000	0	-0.35	25	25
GPC1/Laminin alpha1	-0.14	0.22	-10000	0	-0.45	151	151
TDGF1	-0.004	0.045	-10000	0	-0.57	3	3
CRIPTO/GPC1	-0.024	0.097	-10000	0	-0.41	28	28
APP/GPC1	-0.021	0.091	-10000	0	-0.41	25	25
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.001	0.086	-10000	0	-0.35	6	6
FLT1	0	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.056	0.14	-10000	0	-0.42	63	63
SERPINC1	-0.007	0.063	-10000	0	-0.57	6	6
FYN	0	0.089	-10000	0	-0.35	29	29
FGR	-0.033	0.15	-10000	0	-0.48	32	32
positive regulation of MAPKKK cascade	0.002	0.11	-10000	0	-0.46	13	13
SLIT2	-0.17	0.31	-10000	0	-0.74	110	110
GPC1/NRG	-0.036	0.13	-10000	0	-0.46	38	38
NRG1	-0.02	0.12	-10000	0	-0.74	13	13
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.018	0.076	-10000	0	-0.34	25	25
LYN	-0.001	0.091	-10000	0	-0.38	8	8
mol:Spermine	-0.013	0.095	-10000	0	-0.42	25	25
cell growth	-0.034	0.11	-10000	0	-0.48	16	16
BMP signaling pathway	0.03	0.13	0.57	25	-10000	0	25
SRC	0.001	0.086	-10000	0	-0.34	28	28
TGFBR1	0	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.22	0.34	-10000	0	-0.74	143	143
GPC1	-0.03	0.13	-10000	0	-0.57	25	25
TGFBR1 (dimer)	0	0	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.023	0.13	-10000	0	-0.39	53	53
HCK	-0.004	0.099	-10000	0	-0.36	33	33
FGF2	-0.023	0.13	-10000	0	-0.74	15	15
FGFR1	-0.002	0.034	-10000	0	-0.74	1	1
VEGFR1 homodimer	0	0	-10000	0	-10000	0	0
TGFBR2	-0.058	0.2	-10000	0	-0.74	38	38
cell death	-0.021	0.091	-10000	0	-0.41	25	25
ATIII/GPC1	-0.027	0.1	-10000	0	-0.41	31	31
PLA2G2A/GPC1	-0.18	0.27	-10000	0	-0.56	160	160
LCK	0	0.089	-10000	0	-0.35	29	29
neuron differentiation	-0.036	0.13	-10000	0	-0.46	38	38
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.058	0.2	-10000	0	-0.74	38	38

×

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

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
MAP4K1	-0.009	0.14	-10000	0	-10000	0	0
CRKL	-0.013	0.15	-10000	0	-0.41	60	60
HRAS	-0.058	0.14	-10000	0	-0.62	11	11
mol:PIP3	-0.025	0.14	-10000	0	-0.39	60	60
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.022	0.16	-10000	0	-0.43	60	60
FOXO3	-0.007	0.14	-10000	0	-0.37	60	60
AKT1	-0.016	0.14	-10000	0	-0.4	60	60
BAD	-0.007	0.14	-10000	0	-0.37	60	60
megakaryocyte differentiation	-0.049	0.2	-10000	0	-0.49	78	78
GSK3B	-0.007	0.14	-10000	0	-0.37	60	60
RAF1	0.006	0.13	-10000	0	-0.48	11	11
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.022	0.16	-10000	0	-0.43	60	60
STAT1	-0.074	0.36	-10000	0	-1	60	60
HRAS/SPRED1	-0.047	0.11	-10000	0	-0.48	11	11
cell proliferation	-0.021	0.15	-10000	0	-0.42	60	60
PIK3CA	0	0	-10000	0	-10000	0	0
TEC	-0.005	0.058	-10000	0	-0.74	3	3
RPS6KB1	-0.022	0.15	-10000	0	-0.43	60	60
HRAS/SPRED2	-0.047	0.11	-10000	0	-0.48	11	11
LYN/TEC/p62DOK	-0.053	0.14	-10000	0	-0.42	60	60
MAPK3	0.018	0.099	-10000	0	-0.32	11	11
STAP1	-0.045	0.2	-10000	0	-0.49	74	74
GRAP2	-0.04	0.17	-10000	0	-0.74	26	26
JAK2	-0.11	0.28	-10000	0	-0.85	60	60
STAT1 (dimer)	-0.071	0.35	-10000	0	-0.99	60	60
mol:Gleevec	0	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.054	0.14	-10000	0	-0.4	60	60
actin filament polymerization	-0.021	0.15	-10000	0	-0.42	60	60
LYN	-0.003	0.048	-10000	0	-0.74	2	2
STAP1/STAT5A (dimer)	-0.049	0.25	-10000	0	-0.67	60	60
PIK3R1	0	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.045	0.12	-10000	0	-10000	0	0
PI3K	-0.05	0.13	-10000	0	-0.4	60	60
PTEN	0	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.1	0.44	-10000	0	-1.3	60	60
MAPK8	-0.022	0.16	-10000	0	-0.43	60	60
STAT3 (dimer)	-0.021	0.15	-10000	0	-0.42	60	60
positive regulation of transcription	0.02	0.084	-10000	0	-0.3	1	1
mol:GDP	-0.062	0.15	-10000	0	-0.67	11	11
PIK3C2B	-0.021	0.16	-10000	0	-0.43	60	60
CBL/CRKL	-0.007	0.14	-10000	0	-10000	0	0
FER	-0.022	0.16	-10000	0	-0.43	60	60
SH2B3	-0.023	0.16	-10000	0	-0.43	62	62
PDPK1	-0.016	0.13	-10000	0	-0.36	60	60
SNAI2	-0.022	0.16	-10000	0	-0.43	60	60
positive regulation of cell proliferation	-0.044	0.26	-10000	0	-0.74	60	60
KITLG	0.013	0.005	-10000	0	-10000	0	0
cell motility	-0.044	0.26	-10000	0	-0.74	60	60
PTPN6	0.004	0.01	-10000	0	-10000	0	0
EPOR	0.01	0.1	-10000	0	-10000	0	0
STAT5A (dimer)	-0.032	0.22	-10000	0	-0.61	60	60
SOCS1	-0.002	0.034	-10000	0	-0.74	1	1
cell migration	0.036	0.18	0.45	72	-10000	0	72
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.002	0.064	-10000	0	-0.57	6	6
VAV1	-0.008	0.075	-10000	0	-0.74	5	5
GRB10	-0.022	0.16	-10000	0	-0.43	60	60
PTPN11	0.003	0.008	-10000	0	-10000	0	0
SCF/KIT	-0.058	0.15	-10000	0	-0.46	60	60
GO:0007205	0	0.008	-10000	0	-10000	0	0
MAP2K1	0.015	0.11	-10000	0	-0.36	11	11
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.13	0.47	-10000	0	-1.4	60	60
MAP2K2	0.015	0.11	-10000	0	-0.36	11	11
SHC/Grb2/SOS1	-0.049	0.13	-10000	0	-0.4	60	60
STAT5A	-0.034	0.22	-10000	0	-0.63	60	60
GRB2	0	0	-10000	0	-10000	0	0
response to radiation	-0.021	0.15	-10000	0	-0.42	60	60
SHC/GRAP2	-0.03	0.13	-10000	0	-0.56	26	26
PTPRO	-0.05	0.21	-10000	0	-0.5	78	78
SH2B2	-0.022	0.16	-10000	0	-0.43	60	60
DOK1	0	0	-10000	0	-10000	0	0
MATK	-0.037	0.18	-10000	0	-0.46	72	72
CREBBP	0.028	0.011	-10000	0	-10000	0	0
BCL2	0.01	0.1	-10000	0	-10000	0	0

×

TCGA08_p53

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
CDKN2A	-0.19	0.22	-10000	0	-0.42	224	224
TP53	-0.05	0.056	-10000	0	-10000	0	0
Senescence	-0.05	0.056	-10000	0	-10000	0	0
Apoptosis	-0.05	0.056	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.096	0.11	0.31	4	-0.42	1	5
MDM4	0	0	-10000	0	-10000	0	0

×

Nongenotropic Androgen 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
PTK2	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.098	0.18	-10000	0	-0.44	107	107
regulation of S phase of mitotic cell cycle	-0.064	0.13	-10000	0	-0.31	101	101
GNAO1	-0.004	0.05	-10000	0	-0.63	3	3
HRAS	0	0	-10000	0	-10000	0	0
SHBG/T-DHT	0	0	-10000	0	-10000	0	0
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
MAP2K1	-0.051	0.16	-10000	0	-0.46	17	17
T-DHT/AR	-0.12	0.23	-10000	0	-0.57	101	101
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.007	55	55
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.034	-10000	0	-0.74	1	1
mol:GDP	-0.12	0.23	-10000	0	-0.56	101	101
cell proliferation	-0.057	0.2	-10000	0	-0.65	17	17
PIK3CA	0	0	-10000	0	-10000	0	0
FOS	-0.085	0.29	-10000	0	-0.86	55	55
mol:Ca2+	-0.013	0.022	-10000	0	-0.085	8	8
MAPK3	-0.052	0.18	-10000	0	-0.58	17	17
MAPK1	-0.021	0.096	-10000	0	-0.3	17	17
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.004	55	55
cAMP biosynthetic process	0.011	0.021	-10000	0	-10000	0	0
GNG2	-0.008	0.075	-10000	0	-0.74	5	5
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	55	55
HRAS/GTP	-0.086	0.16	-10000	0	-0.4	101	101
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0	0	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	55	55
PI3K	0	0	-10000	0	-10000	0	0
apoptosis	0.046	0.18	0.45	55	-10000	0	55
T-DHT/AR/PELP1	-0.1	0.2	-10000	0	-0.49	101	101
HRAS/GDP	-0.11	0.21	-10000	0	-0.52	101	101
CREB1	-0.051	0.19	-10000	0	-0.49	55	55
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.16	0.3	-10000	0	-0.74	101	101
GNB1	-0.002	0.034	-10000	0	-0.74	1	1
RAF1	-0.058	0.17	-10000	0	-0.46	17	17
RAC1-CDC42/GDP	-0.1	0.2	-10000	0	-0.5	101	101
T-DHT/AR/PELP1/Src	-0.093	0.18	-10000	0	-0.44	101	101
MAP2K2	-0.051	0.16	-10000	0	-0.46	17	17
T-DHT/AR/PELP1/Src/PI3K	-0.064	0.13	-10000	0	-0.31	101	101
GNAZ	-0.009	0.082	-10000	0	-0.74	6	6
SHBG	0	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.024	0.065	-10000	0	-0.48	6	6
mol:T-DHT	0	0.001	0.001	17	-0.003	38	55
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.007	0.037	-10000	0	-0.57	2	2
Gi family/GTP	-0.043	0.085	-10000	0	-0.48	4	4
CDC42	0	0	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.27	0.34	-10000	0	-0.83	53	53
PCK1	-0.14	0.21	-10000	0	-0.74	19	19
HNF4A	-0.32	0.4	-10000	0	-1	51	51
KCNJ11	-0.28	0.39	-10000	0	-1	39	39
AKT1	-0.002	0.086	-10000	0	-10000	0	0
response to starvation	-0.009	0.033	-10000	0	-10000	0	0
DLK1	-0.3	0.38	-10000	0	-0.94	49	49
NKX2-1	-0.79	0.79	-10000	0	-1.5	256	256
ACADM	-0.27	0.34	-10000	0	-0.84	50	50
TAT	-0.12	0.2	-10000	0	-0.79	8	8
CEBPB	0.003	0.006	-10000	0	-10000	0	0
CEBPA	0.002	0.035	-10000	0	-0.75	1	1
TTR	-0.053	0.19	-10000	0	-0.81	14	14
PKLR	-0.28	0.34	-10000	0	-0.85	54	54
APOA1	-0.43	0.55	-10000	0	-1.4	79	79
CPT1C	-0.27	0.34	-10000	0	-0.83	53	53
ALAS1	-0.12	0.18	-10000	0	-10000	0	0
TFRC	-0.17	0.25	-10000	0	-0.92	11	11
FOXF1	0.007	0.24	0.28	6	-0.62	52	58
NF1	0.016	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.014	0.083	-10000	0	-0.6	8	8
CPT1A	-0.27	0.34	-10000	0	-0.83	53	53
HMGCS1	-0.27	0.34	-10000	0	-0.84	50	50
NR3C1	0.017	0.012	-10000	0	-10000	0	0
CPT1B	-0.27	0.34	-10000	0	-0.83	54	54
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.007	0.03	-10000	0	-10000	0	0
GCK	-0.27	0.34	-10000	0	-0.84	53	53
CREB1	0.007	0.016	-10000	0	-10000	0	0
IGFBP1	-0.12	0.17	-10000	0	-0.69	2	2
PDX1	-0.19	0.24	-10000	0	-0.75	4	4
UCP2	-0.27	0.34	-10000	0	-0.84	47	47
ALDOB	-0.27	0.36	-10000	0	-0.9	36	36
AFP	0.018	0.13	-10000	0	-0.76	3	3
BDH1	-0.27	0.34	-10000	0	-0.84	52	52
HADH	-0.27	0.36	-10000	0	-0.94	23	23
F2	-0.35	0.42	-10000	0	-1	63	63
HNF1A	-0.014	0.083	-10000	0	-0.6	8	8
G6PC	0.009	0.086	-10000	0	-0.73	1	1
SLC2A2	-0.18	0.23	-10000	0	-0.86	2	2
INS	-0.009	0.011	-10000	0	-10000	0	0
FOXA1	0.073	0.14	0.3	30	-0.57	11	41
FOXA3	-0.011	0.15	-10000	0	-0.74	17	17
FOXA2	-0.32	0.41	-10000	0	-0.9	75	75
ABCC8	-0.29	0.39	-10000	0	-1	42	42
ALB	0.026	0.12	-10000	0	-0.67	4	4

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.2	0.43	-9999	-1.2	36	36
HDAC7	-0.007	0.013	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.19	0.33	-9999	-0.9	34	34
SMAD4	0	0.002	-9999	-10000	0	0
ID2	-0.2	0.43	-9999	-1.2	36	36
AP1	-0.066	0.18	-9999	-0.56	55	55
ABCG2	-0.24	0.5	-9999	-1.3	56	56
HIF1A	-0.022	0.07	-9999	-10000	0	0
TFF3	-0.23	0.47	-9999	-1.3	43	43
GATA2	-0.072	0.23	-9999	-0.74	52	52
AKT1	-0.032	0.058	-9999	-10000	0	0
response to hypoxia	-0.046	0.064	-9999	-10000	0	0
MCL1	-0.2	0.43	-9999	-1.2	36	36
NDRG1	-0.2	0.43	-9999	-1.2	34	34
SERPINE1	-0.2	0.43	-9999	-1.2	34	34
FECH	-0.2	0.43	-9999	-1.2	33	33
FURIN	-0.2	0.43	-9999	-1.2	36	36
NCOA2	0.007	0.034	-9999	-0.74	1	1
EP300	-0.023	0.088	-9999	-10000	0	0
HMOX1	-0.2	0.43	-9999	-1.2	37	37
BHLHE40	-0.2	0.43	-9999	-1.2	36	36
BHLHE41	-0.2	0.44	-9999	-1.3	38	38
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.03	0.077	-9999	-0.51	4	4
ENG	0.005	0.13	-9999	-0.83	6	6
JUN	0.008	0.005	-9999	-10000	0	0
RORA	-0.2	0.43	-9999	-1.2	36	36
ABCB1	-0.2	0.45	-9999	-1.4	60	60
TFRC	-0.2	0.43	-9999	-1.2	36	36
CXCR4	-0.2	0.43	-9999	-1.2	36	36
TF	-0.22	0.45	-9999	-1.2	42	42
CITED2	-0.2	0.44	-9999	-1.2	37	37
HIF1A/ARNT	-0.24	0.49	-9999	-1.4	41	41
LDHA	-0.033	0.047	-9999	-10000	0	0
ETS1	-0.2	0.45	-9999	-1.3	37	37
PGK1	-0.2	0.43	-9999	-1.2	37	37
NOS2	-0.24	0.48	-9999	-1.2	51	51
ITGB2	-0.21	0.46	-9999	-1.3	39	39
ALDOA	-0.2	0.43	-9999	-1.2	35	35
Cbp/p300/CITED2	-0.24	0.43	-9999	-1.2	42	42
FOS	-0.077	0.24	-9999	-0.74	55	55
HK2	-0.2	0.43	-9999	-1.2	37	37
SP1	0.011	0.024	-9999	-10000	0	0
GCK	-0.029	0.14	-9999	-0.73	1	1
HK1	-0.2	0.43	-9999	-1.2	34	34
NPM1	-0.2	0.43	-9999	-1.2	34	34
EGLN1	-0.2	0.43	-9999	-1.2	37	37
CREB1	0.016	0	-9999	-10000	0	0
PGM1	-0.2	0.43	-9999	-1.2	36	36
SMAD3	0	0.002	-9999	-10000	0	0
EDN1	-0.16	0.39	-9999	-1.2	47	47
IGFBP1	-0.2	0.44	-9999	-1.2	37	37
VEGFA	-0.23	0.31	-9999	-0.84	31	31
HIF1A/JAB1	-0.017	0.029	-9999	-10000	0	0
CP	-0.22	0.46	-9999	-1.3	37	37
CXCL12	-0.22	0.48	-9999	-1.3	44	44
COPS5	0.009	0.005	-9999	-10000	0	0
SMAD3/SMAD4	0	0.004	-9999	-10000	0	0
BNIP3	-0.2	0.43	-9999	-1.2	33	33
EGLN3	-0.24	0.46	-9999	-1.2	47	47
CA9	-0.42	0.47	-9999	-1.3	63	63
TERT	-0.3	0.48	-9999	-1.3	50	50
ENO1	-0.2	0.43	-9999	-1.2	34	34
PFKL	-0.2	0.43	-9999	-1.2	36	36
NCOA1	0	0.001	-9999	-10000	0	0
ADM	-0.2	0.43	-9999	-1.2	38	38
ARNT	-0.023	0.069	-9999	-10000	0	0
HNF4A	0.002	0.075	-9999	-0.57	8	8
ADFP	-0.2	0.43	-9999	-1.2	40	40
SLC2A1	-0.44	0.35	-9999	-0.94	88	88
LEP	-0.24	0.47	-9999	-1.2	49	49
HIF1A/ARNT/Cbp/p300	-0.2	0.34	-9999	-0.92	39	39
EPO	-0.08	0.25	-9999	-0.83	3	3
CREBBP	-0.023	0.088	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/HDAC7	-0.25	0.37	-9999	-0.97	47	47
PFKFB3	-0.2	0.43	-9999	-1.2	36	36
NT5E	-0.2	0.43	-9999	-1.2	36	36

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.01	0.058	-9999	-0.37	11	11
Syndecan-3/Neurocan	-0.02	0.073	-9999	-0.28	34	34
POMC	-0.054	0.17	-9999	-0.58	45	45
EGFR	-0.022	0.12	-9999	-0.63	17	17
Syndecan-3/EGFR	-0.012	0.061	-9999	-0.33	17	17
AGRP	-0.34	0.37	-9999	-0.74	223	223
NCSTN	0	0	-9999	-10000	0	0
PSENEN	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.04	0.15	-9999	-0.57	34	34
long-term memory	-0.001	0.017	-9999	-0.38	1	1
Syndecan-3/IL8	-0.013	0.062	-9999	-0.31	20	20
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	-0.002	0.034	-9999	-0.74	1	1
limb bud formation	0	0	-9999	-10000	0	0
MC4R	-0.025	0.12	-9999	-0.57	21	21
SRC	0	0	-9999	-10000	0	0
PTN	-0.02	0.12	-9999	-0.7	14	14
FGFR/FGF/Syndecan-3	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.027	0.081	-9999	-10000	0	0
Syndecan-3/AgRP	-0.19	0.2	-9999	-0.4	223	223
Syndecan-3/AgRP/MC4R	-0.19	0.2	-9999	-0.4	223	223
Fyn/Cortactin	-0.001	0.025	-9999	-0.56	1	1
SDC3	0	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.013	0.062	-9999	-0.3	20	20
IL8	-0.025	0.12	-9999	-0.61	20	20
Syndecan-3/Fyn/Cortactin	-0.001	0.018	-9999	-0.39	1	1
Syndecan-3/CASK	0	0	-9999	-10000	0	0
alpha-MSH/MC4R	-0.057	0.15	-9999	-0.42	65	65
Gamma Secretase	0	0	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.011	0.037	-9999	-0.54	1	1
NFATC2	-0.06	0.18	-9999	-0.52	66	66
NFATC3	0.012	0.028	-9999	-10000	0	0
CD40LG	-0.17	0.38	-9999	-0.79	108	108
PTGS2	-0.14	0.34	-9999	-0.73	94	94
JUNB	-0.002	0.034	-9999	-0.74	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.011	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.011	-9999	-10000	0	0
CALM1	-0.001	0.003	-9999	-10000	0	0
JUN	-0.001	0.003	-9999	-10000	0	0
mol:Ca2+	-0.006	0.01	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.002	-9999	-10000	0	0
FOSL1	-0.002	0.037	-9999	-0.57	2	2
CREM	0	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.1	0.18	-9999	-0.56	46	46
FOS	-0.086	0.24	-9999	-0.74	55	55
IFNG	-0.11	0.3	-9999	-0.64	79	79
AP-1/NFAT1-c-4	-0.21	0.31	-9999	-0.76	90	90
FASLG	-0.12	0.32	-9999	-0.7	77	77
NFAT1-c-4/ICER1	-0.083	0.16	-9999	-0.51	46	46
IL2RA	-0.11	0.3	-9999	-0.77	36	36
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.15	0.34	-9999	-0.8	65	65
JunB/Fra1/NFAT1-c-4	-0.08	0.16	-9999	-0.49	46	46
IL4	-0.12	0.29	-9999	-0.65	69	69
IL2	-0.004	0.014	-9999	-10000	0	0
IL3	-0.019	0.023	-9999	-10000	0	0
FKBP1A	0	0	-9999	-10000	0	0
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0	0.003	-9999	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.016	0.13	-9999	-0.5	31	31
ADCY5	-0.029	0.15	-9999	-0.5	44	44
ADCY6	0.016	0.032	-9999	-0.49	2	2
ADCY7	0.017	0.023	-9999	-0.49	1	1
ADCY1	0.015	0.04	-9999	-0.49	3	3
ADCY2	-0.026	0.13	-9999	-0.4	49	49
ADCY3	0.017	0.023	-9999	-0.49	1	1
ADCY8	-0.14	0.23	-9999	-0.48	153	153
PRKCE	0.009	0.026	-9999	-0.57	1	1
ADCY9	0.016	0.032	-9999	-0.49	2	2
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.069	0.13	-9999	-0.44	25	25

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.002	0.004	-9999	-10000	0	0
SVIL	0.002	0.004	-9999	-10000	0	0
ZNF318	0	0.005	-9999	-10000	0	0
JMJD2C	-0.004	0.026	-9999	-0.082	46	46
T-DHT/AR/Ubc9	-0.13	0.21	-9999	-0.53	101	101
CARM1	0	0	-9999	-10000	0	0
PRDX1	0	0.001	-9999	-10000	0	0
PELP1	0	0.001	-9999	-10000	0	0
CTNNB1	0.001	0.004	-9999	-10000	0	0
AKT1	0	0.002	-9999	-10000	0	0
PTK2B	0.001	0.004	-9999	-10000	0	0
MED1	0	0.002	-9999	-10000	0	0
MAK	-0.052	0.19	-9999	-0.74	34	34
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.002	0.004	-9999	-10000	0	0
GSN	0.002	0.004	-9999	-10000	0	0
NCOA2	-0.002	0.034	-9999	-0.74	1	1
NCOA6	0.002	0.004	-9999	-10000	0	0
DNA-PK	0	0.006	-9999	-10000	0	0
NCOA4	0	0	-9999	-10000	0	0
PIAS3	0.001	0.004	-9999	-10000	0	0
cell proliferation	-0.093	0.24	-9999	-0.94	34	34
XRCC5	0	0.002	-9999	-10000	0	0
UBE3A	0.001	0.004	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.15	0.23	-9999	-0.54	111	111
FHL2	-0.055	0.081	-9999	-0.55	2	2
RANBP9	0.002	0.004	-9999	-10000	0	0
JMJD1A	-0.035	0.07	-9999	-0.13	157	157
CDK6	-0.002	0.037	-9999	-0.57	2	2
TGFB1I1	0.002	0.004	-9999	-10000	0	0
T-DHT/AR/CyclinD1	-0.14	0.22	-9999	-0.53	106	106
XRCC6	0	0.002	-9999	-10000	0	0
T-DHT/AR	-0.14	0.24	-9999	-0.56	102	102
CTDSP1	0	0	-9999	-10000	0	0
CTDSP2	0	0.004	-9999	-10000	0	0
BRCA1	0.002	0.004	-9999	-10000	0	0
TCF4	-0.001	0.034	-9999	-0.74	1	1
CDKN2A	-0.27	0.29	-9999	-0.57	224	224
SRF	0.016	0.007	-9999	-10000	0	0
NKX3-1	-0.11	0.14	-9999	-0.95	2	2
KLK3	0.028	0.051	-9999	-10000	0	0
TMF1	0	0.001	-9999	-10000	0	0
HNRNPA1	0	0.002	-9999	-10000	0	0
AOF2	0	0.002	-9999	-10000	0	0
APPL1	0.02	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.13	0.21	-9999	-0.53	101	101
AR	-0.17	0.31	-9999	-0.77	101	101
UBA3	0	0	-9999	-10000	0	0
PATZ1	0	0.002	-9999	-10000	0	0
PAWR	0	0.001	-9999	-10000	0	0
PRKDC	0	0.002	-9999	-10000	0	0
PA2G4	0	0.003	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.12	0.19	-9999	-0.48	101	101
RPS6KA3	0.002	0.004	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.13	0.21	-9999	-0.53	101	101
LATS2	-0.001	0.034	-9999	-0.74	1	1
T-DHT/AR/PRX1	-0.12	0.19	-9999	-0.48	101	101
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	0	0.034	-9999	-0.74	1	1
KLK2	-0.095	0.14	-9999	-0.5	28	28
CASP8	0	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.12	0.19	-9999	-0.48	102	102
TMPRSS2	-0.4	0.54	-9999	-1.2	156	156
CCND1	-0.01	0.086	-9999	-0.72	7	7
PIAS1	0.001	0.004	-9999	-10000	0	0
mol:T-DHT	-0.019	0.036	-9999	-0.078	115	115
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.001	0.005	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.13	0.21	-9999	-0.52	103	103
CMTM2	-0.097	0.25	-9999	-0.74	63	63
SNURF	-0.023	0.13	-9999	-0.74	15	15
ZMIZ1	-0.008	0.048	-9999	-0.8	1	1
CCND3	0	0.001	-9999	-10000	0	0
TGIF1	0	0.002	-9999	-10000	0	0
FKBP4	0	0.026	-9999	-0.57	1	1

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.004	0.018	-10000	0	-10000	0	0
AES	0.003	0.015	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0	0	-10000	0	-10000	0	0
DKK2	-0.13	0.28	-10000	0	-0.74	86	86
TLE1	0.002	0.031	-10000	0	-0.61	1	1
MACF1	0.004	0.048	-10000	0	-0.74	2	2
CTNNB1	0.067	0.099	0.29	10	-10000	0	10
WIF1	-0.47	0.36	-10000	0	-0.74	306	306
beta catenin/RanBP3	0.003	0.092	0.4	20	-10000	0	20
KREMEN2	-0.37	0.27	-10000	0	-0.57	314	314
DKK1	-0.039	0.15	-10000	0	-0.62	30	30
beta catenin/beta TrCP1	0.069	0.093	0.28	10	-10000	0	10
FZD1	0.001	0.003	-10000	0	-10000	0	0
AXIN2	-0.038	0.28	-10000	0	-1.5	17	17
AXIN1	0.008	0.005	-10000	0	-10000	0	0
RAN	0.001	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.005	0.021	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.093	0.052	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.02	0.063	0.24	29	-10000	0	29
Axin1/APC/GSK3/beta catenin/Macf1	0.065	0.041	-10000	0	-10000	0	0
HNF1A	-0.006	0.076	-10000	0	-0.58	8	8
CTBP1	0.004	0.018	-10000	0	-10000	0	0
MYC	0.007	0.049	-10000	0	-10000	0	0
RANBP3	0.001	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.3	0.25	-10000	0	-0.72	86	86
NKD1	-0.071	0.22	-10000	0	-0.73	47	47
TCF4	0.002	0.038	-10000	0	-0.74	1	1
TCF3	0.004	0.018	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.001	0.019	-10000	0	-10000	0	0
Ran/GTP	0	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.018	0.097	0.45	22	-10000	0	22
LEF1	0.002	0.031	-10000	0	-0.58	1	1
DVL1	0.08	0.061	-10000	0	-10000	0	0
CSNK2A1	0.001	0.003	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.097	0.068	-10000	0	-0.56	1	1
DKK1/LRP6/Kremen 2	-0.25	0.19	-10000	0	-0.67	24	24
LRP6	0.001	0.004	-10000	0	-10000	0	0
CSNK1A1	0.004	0.018	-10000	0	-10000	0	0
NLK	0.01	0.002	-10000	0	-10000	0	0
CCND1	-0.009	0.18	-10000	0	-1.5	6	6
WNT1	0.004	0.037	-10000	0	-0.57	2	2
GSK3A	0.007	0.005	-10000	0	-10000	0	0
GSK3B	0	0.002	-10000	0	-10000	0	0
FRAT1	-0.001	0.034	-10000	0	-0.74	1	1
PPP2R5D	0.076	0.1	0.37	47	-10000	0	47
APC	0	0.019	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.16	0.12	0.26	304	-10000	0	304
CREBBP	0.004	0.018	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.13	0.44	-10000	0	-1.2	44	44
IL23A	-0.14	0.43	-10000	0	-1.2	38	38
NF kappa B1 p50/RelA/I kappa B alpha	-0.2	0.36	-10000	0	-1.1	47	47
positive regulation of T cell mediated cytotoxicity	-0.14	0.46	-10000	0	-1.2	47	47
ITGA3	-0.13	0.42	-10000	0	-1.2	41	41
IL17F	-0.063	0.28	-10000	0	-0.74	29	29
IL12B	0.016	0.025	-10000	0	-10000	0	0
STAT1 (dimer)	-0.21	0.38	-10000	0	-1.2	47	47
CD4	-0.13	0.43	-10000	0	-1.2	39	39
IL23	-0.14	0.41	-10000	0	-1.1	38	38
IL23R	0.003	0.085	-10000	0	-10000	0	0
IL1B	-0.14	0.44	-10000	0	-1.2	39	39
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.13	0.4	-10000	0	-1.1	35	35
TYK2	0.011	0.019	-10000	0	-10000	0	0
STAT4	-0.012	0.095	-10000	0	-0.74	8	8
STAT3	0	0	-10000	0	-10000	0	0
IL18RAP	-0.027	0.16	-10000	0	-0.74	22	22
IL12RB1	-0.038	0.19	-10000	0	-0.77	31	31
PIK3CA	0	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.027	0.15	-10000	0	-0.59	31	31
IL23R/JAK2	0.003	0.1	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.14	0.46	-10000	0	-1.2	47	47
natural killer cell activation	0	0.007	-10000	0	-10000	0	0
JAK2	0.018	0.023	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
NFKB1	0.004	0.006	-10000	0	-10000	0	0
RELA	0.004	0.006	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.14	0.39	-10000	0	-1.1	38	38
ALOX12B	-0.17	0.42	-10000	0	-1.2	38	38
CXCL1	-0.14	0.46	-10000	0	-1.3	45	45
T cell proliferation	-0.14	0.46	-10000	0	-1.2	47	47
NFKBIA	0.004	0.006	-10000	0	-10000	0	0
IL17A	-0.042	0.24	-10000	0	-0.59	21	21
PI3K	-0.21	0.36	-10000	0	-1.1	47	47
IFNG	-0.001	0.029	0.098	1	-0.13	8	9
STAT3 (dimer)	-0.2	0.34	-10000	0	-1	47	47
IL18R1	-0.001	0.076	-10000	0	-0.74	5	5
IL23/IL23R/JAK2/TYK2/SOCS3	-0.061	0.28	-10000	0	-0.83	23	23
IL18/IL18R	-0.029	0.13	-10000	0	-0.56	25	25
macrophage activation	-0.012	0.017	-10000	0	-0.044	37	37
TNF	-0.14	0.45	-10000	0	-1.2	47	47
STAT3/STAT4	-0.21	0.37	-10000	0	-1.1	48	48
STAT4 (dimer)	-0.22	0.39	-10000	0	-1.2	48	48
IL18	0.002	0.059	-10000	0	-0.74	3	3
IL19	-0.13	0.4	-10000	0	-1.1	37	37
STAT5A (dimer)	-0.21	0.38	-10000	0	-1.2	47	47
STAT1	0	0	-10000	0	-10000	0	0
SOCS3	-0.003	0.048	-10000	0	-0.74	2	2
CXCL9	-0.13	0.43	-10000	0	-1.2	40	40
MPO	-0.15	0.45	-10000	0	-1.2	50	50
positive regulation of humoral immune response	-0.14	0.46	-10000	0	-1.2	47	47
IL23/IL23R/JAK2/TYK2	-0.16	0.52	-10000	0	-1.4	47	47
IL6	-0.24	0.58	-10000	0	-1.3	95	95
STAT5A	0	0	-10000	0	-10000	0	0
IL2	0.006	0.008	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0.007	-10000	0	-10000	0	0
CD3E	-0.12	0.42	-10000	0	-1.2	32	32
keratinocyte proliferation	-0.14	0.46	-10000	0	-1.2	47	47
NOS2	-0.17	0.48	-10000	0	-1.2	62	62

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.008	0.056	-9999	-0.41	9	9
VLDLR	-0.003	0.048	-9999	-0.74	2	2
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.002	0.034	-9999	-0.74	1	1
ITGA3	-0.008	0.075	-9999	-0.74	5	5
RELN/VLDLR/Fyn	-0.086	0.19	-9999	-0.48	86	86
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.001	0.022	-9999	-0.4	1	1
AKT1	-0.055	0.12	-9999	-0.52	2	2
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.036	0.14	-9999	-0.57	30	30
RELN/LRP8/DAB1	-0.099	0.18	-9999	-0.41	115	115
LRPAP1/LRP8	-0.003	0.032	-9999	-0.41	3	3
RELN/LRP8/DAB1/Fyn	-0.093	0.17	-9999	-0.43	84	84
DAB1/alpha3/beta1 Integrin	-0.087	0.16	-9999	-0.69	5	5
long-term memory	-0.12	0.19	-9999	-0.45	82	82
DAB1/LIS1	-0.086	0.16	-9999	-0.63	4	4
DAB1/CRLK/C3G	-0.083	0.15	-9999	-0.61	4	4
PIK3CA	0	0	-9999	-10000	0	0
DAB1/NCK2	-0.087	0.16	-9999	-0.64	4	4
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.065	0.2	-9999	-0.66	48	48
CDK5R1	-0.011	0.077	-9999	-0.57	9	9
RELN	-0.13	0.28	-9999	-0.74	85	85
PIK3R1	0	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.087	0.18	-9999	-0.48	88	88
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.12	0.2	-9999	-0.46	101	101
MAPK8	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.099	0.18	-9999	-0.46	85	85
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.093	0.17	-9999	-0.42	86	86
RELN/LRP8	-0.086	0.18	-9999	-0.47	88	88
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.094	0.17	-9999	-0.43	85	85
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.006	0.057	-9999	-0.56	5	5
RAP1A	-0.077	0.14	-9999	-0.57	4	4
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.003	0.043	-9999	-0.66	2	2
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.005	0.052	-9999	-0.57	4	4
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.014	0.096	-9999	-0.43	2	2
neuron adhesion	-0.075	0.14	-9999	-0.64	4	4
LRP8	-0.004	0.045	-9999	-0.57	3	3
GSK3B	-0.027	0.12	-9999	-0.48	2	2
RELN/VLDLR/DAB1/Fyn	-0.093	0.17	-9999	-0.43	85	85
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.065	0.12	-9999	-0.32	85	85
CDK5	0	0	-9999	-10000	0	0
MAPT	0.003	0.085	-9999	-0.67	7	7
neuron migration	-0.031	0.17	-9999	-0.56	4	4
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.043	0.081	-9999	-0.44	2	2
RELN/VLDLR	-0.079	0.17	-9999	-0.44	83	83

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.14	0.25	-10000	0	-0.73	13	13
CRP	-0.15	0.25	-10000	0	-0.73	15	15
cell cycle arrest	-0.17	0.28	-10000	0	-0.65	54	54
TIMP1	-0.11	0.21	-10000	0	-0.6	10	10
IL6ST	-0.016	0.13	-10000	0	-0.74	16	16
Rac1/GDP	-0.066	0.19	-10000	0	-0.69	19	19
AP1	-0.003	0.15	-10000	0	-0.5	12	12
GAB2	-0.002	0.12	-10000	0	-0.74	12	12
TNFSF11	-0.16	0.26	-10000	0	-0.67	33	33
HSP90B1	-0.001	0.05	-10000	0	-10000	0	0
GAB1	0.013	0.009	-10000	0	-10000	0	0
MAPK14	-0.03	0.17	-10000	0	-0.73	15	15
AKT1	0.043	0.054	-10000	0	-10000	0	0
FOXO1	0.049	0.05	-10000	0	-10000	0	0
MAP2K6	-0.053	0.18	-10000	0	-0.73	16	16
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
MAP2K4	-0.076	0.2	-10000	0	-0.69	18	18
MITF	-0.07	0.19	-10000	0	-0.48	62	62
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0	0	-10000	0	-10000	0	0
A2M	-0.46	0.69	-10000	0	-1.5	157	157
CEBPB	0.016	0.004	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.03	0.11	0.23	4	-0.53	5	9
STAT3	-0.18	0.29	-10000	0	-0.69	54	54
STAT1	-0.008	0.016	-10000	0	-10000	0	0
CEBPD	-0.14	0.25	-10000	0	-0.8	13	13
PIK3CA	0.01	0.003	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
JUN	0	0	-10000	0	-10000	0	0
PIAS3/MITF	-0.087	0.17	-10000	0	-0.63	24	24
MAPK11	-0.03	0.17	-10000	0	-0.73	15	15
STAT3 (dimer)/FOXO1	-0.19	0.31	-10000	0	-0.75	56	56
GRB2/SOS1/GAB family	-0.031	0.17	-10000	0	-0.64	18	18
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.052	0.19	-10000	0	-0.45	61	61
GRB2	0.013	0.009	-10000	0	-10000	0	0
JAK2	0	0	-10000	0	-10000	0	0
LBP	-0.11	0.21	-10000	0	-0.64	6	6
PIK3R1	0.008	0.005	-10000	0	-10000	0	0
JAK1	0.01	0.005	-10000	0	-10000	0	0
MYC	-0.14	0.25	-10000	0	-0.73	13	13
FGG	-0.48	0.57	-10000	0	-1.1	226	226
macrophage differentiation	-0.17	0.28	-10000	0	-0.65	54	54
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.093	0.2	-10000	0	-0.52	64	64
JUNB	-0.14	0.24	-10000	0	-0.72	14	14
FOS	-0.084	0.24	-10000	0	-0.74	55	55
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.072	0.19	-10000	0	-0.48	60	60
STAT1/PIAS1	-0.086	0.17	-10000	0	-0.47	54	54
GRB2/SOS1/GAB family/SHP2/PI3K	0.014	0.057	-10000	0	-10000	0	0
STAT3 (dimer)	-0.18	0.28	-10000	0	-0.68	54	54
PRKCD	-0.091	0.22	-10000	0	-0.76	14	14
IL6R	-0.008	0.12	-10000	0	-0.74	12	12
SOCS3	-0.016	0.17	-10000	0	-0.86	9	9
gp130 (dimer)/JAK1/JAK1/LMO4	-0.01	0.089	-10000	0	-0.47	17	17
Rac1/GTP	-0.11	0.17	-10000	0	-0.5	51	51
HCK	-0.003	0.076	-10000	0	-0.74	5	5
MAPKKK cascade	0.045	0.12	-10000	0	-0.53	12	12
bone resorption	-0.15	0.25	-10000	0	-0.63	34	34
IRF1	-0.14	0.25	-10000	0	-0.73	13	13
mol:GDP	-0.068	0.19	-10000	0	-0.48	57	57
SOS1	0.01	0.015	-10000	0	-10000	0	0
VAV1	-0.07	0.2	-10000	0	-0.49	57	57
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.047	0.19	-10000	0	-0.76	18	18
PTPN11	-0.006	0.013	-10000	0	-10000	0	0
IL6/IL6RA	-0.1	0.24	-10000	0	-0.6	87	87
gp130 (dimer)/TYK2/TYK2/LMO4	-0.013	0.088	-10000	0	-0.47	17	17
gp130 (dimer)/JAK2/JAK2/LMO4	-0.013	0.088	-10000	0	-0.47	17	17
IL6	-0.12	0.28	-10000	0	-0.74	82	82
PIAS3	0	0	-10000	0	-10000	0	0
PTPRE	0.01	0.05	-10000	0	-0.74	2	2
PIAS1	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.077	0.18	-10000	0	-0.42	75	75
LMO4	0.007	0.029	-10000	0	-0.59	1	1
STAT3 (dimer)/PIAS3	-0.21	0.22	-10000	0	-0.66	54	54
MCL1	0.05	0.048	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.001	0.094	-10000	0	-0.58	12	12
NFATC2	-0.055	0.3	-10000	0	-0.74	68	68
NFATC3	0.013	0.054	-10000	0	-10000	0	0
CD40LG	-0.18	0.45	-10000	0	-1.1	70	70
ITCH	-0.008	0.11	-10000	0	-10000	0	0
CBLB	-0.008	0.11	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.14	0.28	-10000	0	-1.1	27	27
JUNB	-0.002	0.034	-10000	0	-0.74	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.053	0.12	-10000	0	-10000	0	0
T cell anergy	-0.06	0.18	-10000	0	-0.45	77	77
TLE4	-0.022	0.24	-10000	0	-0.81	22	22
Jun/NFAT1-c-4/p21SNFT	-0.12	0.27	-10000	0	-1	26	26
AP-1/NFAT1-c-4	-0.23	0.39	-10000	0	-1.2	43	43
IKZF1	-0.032	0.28	-10000	0	-1	21	21
T-helper 2 cell differentiation	-0.045	0.28	-10000	0	-0.81	43	43
AP-1/NFAT1	-0.14	0.24	-10000	0	-0.65	55	55
CALM1	-0.028	0.064	-10000	0	-10000	0	0
EGR2	-0.018	0.31	-10000	0	-1.2	19	19
EGR3	-0.02	0.31	-10000	0	-1.2	21	21
NFAT1/FOXP3	-0.091	0.21	-10000	0	-0.74	24	24
EGR1	-0.006	0.1	-10000	0	-0.74	9	9
JUN	0.002	0.022	-10000	0	-10000	0	0
EGR4	-0.005	0.087	-10000	0	-0.57	11	11
mol:Ca2+	-0.032	0.073	-10000	0	-10000	0	0
GBP3	-0.041	0.28	-10000	0	-0.9	32	32
FOSL1	-0.002	0.037	-10000	0	-0.57	2	2
NFAT1-c-4/MAF/IRF4	-0.098	0.26	-10000	0	-0.97	28	28
DGKA	-0.019	0.23	-10000	0	-0.81	18	18
CREM	0	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.15	0.3	-10000	0	-0.96	37	37
CTLA4	-0.018	0.21	-10000	0	-0.79	15	15
NFAT1-c-4 (dimer)/EGR1	-0.11	0.28	-10000	0	-1	28	28
NFAT1-c-4 (dimer)/EGR4	-0.11	0.27	-10000	0	-0.96	29	29
FOS	-0.083	0.24	-10000	0	-0.75	55	55
IFNG	-0.16	0.35	-10000	0	-1	52	52
T cell activation	-0.04	0.24	-10000	0	-0.78	21	21
MAF	0	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.003	0.19	0.77	15	-10000	0	15
TNF	-0.038	0.3	-10000	0	-0.95	31	31
FASLG	-0.087	0.45	-10000	0	-1.5	38	38
TBX21	-0.064	0.23	-10000	0	-0.74	50	50
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	-0.06	0.22	-10000	0	-0.75	45	45
PTPN1	-0.019	0.23	-10000	0	-0.81	18	18
NFAT1-c-4/ICER1	-0.1	0.26	-10000	0	-0.97	28	28
GATA3	-0.024	0.13	-10000	0	-0.71	17	17
T-helper 1 cell differentiation	-0.16	0.34	-10000	0	-0.98	53	53
IL2RA	-0.15	0.28	-10000	0	-0.9	40	40
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.019	0.23	-10000	0	-0.78	20	20
E2F1	0.015	0.004	-10000	0	-10000	0	0
PPARG	-0.089	0.24	-10000	0	-0.74	58	58
SLC3A2	-0.019	0.23	-10000	0	-0.77	21	21
IRF4	-0.009	0.082	-10000	0	-0.74	6	6
PTGS2	-0.15	0.42	-10000	0	-1	60	60
CSF2	-0.15	0.42	-10000	0	-1.1	53	53
JunB/Fra1/NFAT1-c-4	-0.096	0.25	-10000	0	-0.91	29	29
IL4	-0.049	0.3	-10000	0	-0.85	43	43
IL5	-0.12	0.36	-10000	0	-1	41	41
IL2	-0.041	0.24	-10000	0	-0.8	21	21
IL3	-0.037	0.049	-10000	0	-10000	0	0
RNF128	-0.096	0.31	-10000	0	-0.8	77	77
NFATC1	0.003	0.19	-10000	0	-0.78	15	15
CDK4	0.007	0.16	0.62	8	-10000	0	8
PTPRK	-0.019	0.23	-10000	0	-0.86	15	15
IL8	-0.12	0.38	-10000	0	-1	45	45
POU2F1	0	0.003	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	0	0	-10000	0	-10000	0	0
HDAC1	0.001	0.005	-10000	0	-10000	0	0
AES	0	0.002	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.002	0.037	-10000	0	-0.57	2	2
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	-0.001	0.033	-10000	0	-0.73	1	1
AP1	-0.076	0.18	-10000	0	-0.42	86	86
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	0	0.001	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.001	0.042	-10000	0	-0.56	1	1
NICD/RBPSUH	0	0	-10000	0	-10000	0	0
WIF1	-0.47	0.36	-10000	0	-0.74	306	306
NOTCH1	0	0	-10000	0	-10000	0	0
PSENEN	0	0	-10000	0	-10000	0	0
KREMEN2	-0.37	0.27	-10000	0	-0.57	314	314
DKK1	-0.039	0.15	-10000	0	-0.62	30	30
beta catenin/beta TrCP1	0.007	0.06	-10000	0	-10000	0	0
APH1B	0	0	-10000	0	-10000	0	0
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	-0.004	0.026	0.3	1	-10000	0	1
CtBP/CBP/TCF1/TLE1/AES	-0.001	0.027	-10000	0	-10000	0	0
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.085	0.24	-10000	0	-0.74	55	55
JUN	0	0	-10000	0	-10000	0	0
MAP3K7	0	0.003	-10000	0	-10000	0	0
CTNNB1	0.01	0.065	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.3	0.25	-10000	0	-0.72	86	86
HNF1A	-0.009	0.073	-10000	0	-0.57	8	8
CTBP1	0	0.002	-10000	0	-10000	0	0
MYC	0.002	0.012	-10000	0	-10000	0	0
NKD1	-0.071	0.22	-10000	0	-0.73	47	47
FZD1	0	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.001	0.018	-10000	0	-10000	0	0
apoptosis	-0.076	0.18	-10000	0	-0.42	86	86
Delta 1/NOTCHprecursor	0	0	-10000	0	-10000	0	0
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.002	0.012	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.004	0.026	0.3	1	-10000	0	1
DVL1	-0.045	0.044	-10000	0	-0.67	1	1
CSNK2A1	0.01	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.25	0.19	-10000	0	-0.68	24	24
LRP6	0	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
NLK	0.001	0.006	-10000	0	-10000	0	0
CCND1	-0.016	0.16	-10000	0	-1.4	6	6
WNT1	-0.002	0.037	-10000	0	-0.57	2	2
Axin1/APC/beta catenin	0.01	0.045	0.27	1	-0.36	1	2
DKK2	-0.13	0.28	-10000	0	-0.74	86	86
NOTCH1 precursor/DVL1	-0.022	0.029	-10000	0	-0.55	1	1
GSK3B	0	0.002	-10000	0	-10000	0	0
FRAT1	-0.001	0.034	-10000	0	-0.74	1	1
NOTCH/Deltex homolog 1	-0.001	0.018	-10000	0	-10000	0	0
PPP2R5D	0.01	0.1	0.31	47	-0.25	1	48
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.28	0.21	-10000	0	-0.44	305	305
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.013	0.002	-10000	0	-10000	0	0

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0	0	-9999	-10000	0	0
GNAT1/GTP	-0.007	0.054	-9999	-0.42	8	8
Metarhodopsin II/Arrestin	-0.001	0.023	-9999	-0.36	2	2
PDE6G/GNAT1/GTP	-0.015	0.079	-9999	-0.42	17	17
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.009	0.073	-9999	-0.57	8	8
GRK1	-0.002	0.037	-9999	-0.57	2	2
CNG Channel	-0.055	0.13	-9999	-0.58	6	6
mol:Na +	-0.094	0.15	-9999	-0.52	22	22
mol:ADP	-0.002	0.037	-9999	-0.57	2	2
RGS9-1/Gbeta5/R9AP	-0.062	0.17	-9999	-0.49	61	61
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.096	0.15	-9999	-0.54	22	22
CNGB1	-0.051	0.16	-9999	-0.57	43	43
RDH5	-0.003	0.048	-9999	-0.74	2	2
SAG	0	0	-9999	-10000	0	0
mol:Ca2+	-0.089	0.14	-9999	-0.5	22	22
Na + (4 Units)	-0.087	0.14	-9999	-0.49	22	22
RGS9	-0.081	0.23	-9999	-0.74	53	53
GNB1/GNGT1	-0.13	0.19	-9999	-0.41	150	150
GNAT1/GDP	-0.059	0.15	-9999	-0.43	61	61
GUCY2D	0	0	-9999	-10000	0	0
GNGT1	-0.18	0.26	-9999	-0.57	149	149
GUCY2F	0	0	-9999	-10000	0	0
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.031	0.11	-9999	-0.42	30	30
mol:11-cis-retinal	-0.003	0.048	-9999	-0.74	2	2
mol:cGMP	-0.078	0.13	-9999	-10000	0	0
GNB1	-0.002	0.034	-9999	-0.74	1	1
Rhodopsin	-0.004	0.045	-9999	-0.49	4	4
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.007	0.063	-9999	-0.57	6	6
Metarhodopsin II	-0.003	0.029	-9999	-0.32	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.084	0.14	-9999	-10000	0	0
RGS9BP	-0.015	0.11	-9999	-0.74	10	10
Metarhodopsin II/Transducin	-0.052	0.076	-9999	-0.37	2	2
GCAP Family/Ca ++	-0.086	0.14	-9999	-0.32	129	129
PDE6A/B	-0.026	0.12	-9999	-0.54	23	23
mol:Pi	-0.062	0.16	-9999	-0.49	61	61
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.1	0.15	-9999	-0.32	156	156
PDE6B	-0.013	0.098	-9999	-0.72	9	9
PDE6A	-0.021	0.12	-9999	-0.72	14	14
PDE6G	-0.014	0.1	-9999	-0.74	9	9
RHO	-0.002	0.037	-9999	-0.57	2	2
PDE6	-0.075	0.17	-9999	-0.8	10	10
GUCA1A	-0.15	0.25	-9999	-0.57	129	129
GC2/GCAP Family	-0.085	0.14	-9999	-10000	0	0
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0	0	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.079	0.11	-10000	0	-0.51	17	17
epithelial cell differentiation	-0.035	0.1	-10000	0	-0.54	10	10
ITCH	0.023	0.027	-10000	0	-10000	0	0
WWP1	-0.039	0.088	-10000	0	-10000	0	0
FYN	-0.002	0.034	-10000	0	-0.74	1	1
EGFR	-0.022	0.12	-10000	0	-0.63	17	17
PRL	-0.009	0.073	-10000	0	-0.57	8	8
neuron projection morphogenesis	0.002	0.087	-10000	0	-10000	0	0
PTPRZ1	-0.38	0.27	-10000	0	-0.57	323	323
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.042	0.074	-10000	0	-0.48	6	6
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.056	0.094	-10000	0	-0.49	13	13
ADAM17	0.023	0.027	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.058	0.11	-10000	0	-0.49	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.18	0.22	-10000	0	-0.54	123	123
NCOR1	0	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.052	0.089	-10000	0	-0.48	14	14
GRIN2B	-0.027	0.1	-10000	0	-0.53	7	7
ErbB4/ErbB2/betacellulin	-0.073	0.13	-10000	0	-0.51	26	26
STAT1	0	0	-10000	0	-10000	0	0
HBEGF	-0.025	0.13	-10000	0	-0.74	16	16
PRLR	-0.039	0.15	-10000	0	-0.63	30	30
E4ICDs/ETO2	-0.072	0.1	-10000	0	-0.6	8	8
axon guidance	0.054	0.072	-10000	0	-10000	0	0
NEDD4	0.021	0.043	-10000	0	-0.71	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.036	0.13	-10000	0	-0.46	37	37
CBFA2T3	-0.012	0.095	-10000	0	-0.74	8	8
ErbB4/ErbB2/HBEGF	-0.055	0.09	-10000	0	-0.45	16	16
MAPK3	-0.037	0.069	-10000	0	-10000	0	0
STAT1 (dimer)	-0.064	0.079	-10000	0	-0.43	1	1
MAPK1	-0.037	0.069	-10000	0	-10000	0	0
JAK2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.052	0.086	-10000	0	-0.46	13	13
NRG1	0.015	0.097	-10000	0	-0.56	13	13
NRG3	-0.19	0.32	-10000	0	-0.74	122	122
NRG2	-0.078	0.23	-10000	0	-0.74	51	51
NRG4	-0.07	0.19	-10000	0	-0.57	59	59
heart development	0.054	0.072	-10000	0	-10000	0	0
neural crest cell migration	-0.052	0.085	-10000	0	-0.46	13	13
ERBB2	0.029	0.032	-10000	0	-0.42	2	2
WWOX/E4ICDs	-0.064	0.08	-10000	0	-0.43	1	1
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.1	0.14	-10000	0	-0.47	35	35
apoptosis	0.2	0.26	0.57	123	-10000	0	123
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.11	0.17	-10000	0	-0.54	51	51
ErbB4/ErbB2/epiregulin	-0.13	0.18	-10000	0	-0.47	96	96
ErbB4/ErbB4/betacellulin/betacellulin	-0.099	0.15	-10000	0	-0.55	37	37
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.084	0.13	-10000	0	-0.55	22	22
MDM2	-0.043	0.098	-10000	0	-0.43	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.04	0.079	-10000	0	-0.46	13	13
STAT5A	0.057	0.067	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.063	0.12	-10000	0	-0.6	13	13
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.059	0.073	-10000	0	-0.4	1	1
STAT5A (dimer)	-0.037	0.11	-10000	0	-0.59	10	10
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.045	0.067	-10000	0	-10000	0	0
LRIG1	-0.002	0.034	-10000	0	-0.74	1	1
EREG	-0.15	0.29	-10000	0	-0.72	102	102
BTC	-0.057	0.2	-10000	0	-0.74	37	37
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.054	0.072	-10000	0	-10000	0	0
ERBB4	-0.078	0.097	-10000	0	-0.49	1	1
STAT5B	0	0	-10000	0	-10000	0	0
YAP1	-0.02	0.025	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.077	0.12	-10000	0	-0.42	29	29
glial cell differentiation	0.058	0.072	0.4	1	-10000	0	1
WWOX	0	0	-10000	0	-10000	0	0
cell proliferation	-0.02	0.15	-10000	0	-0.6	12	12

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.016	0.039	-9999	-10000	0	0
BIRC5	-0.49	0.2	-9999	-0.57	410	410
NFKBIA	0.018	0.04	-9999	-10000	0	0
CPEB1	-0.048	0.18	-9999	-0.74	31	31
AKT1	0.018	0.04	-9999	-10000	0	0
NDEL1	0	0	-9999	-10000	0	0
Aurora A/BRCA1	0.014	0.035	-9999	-10000	0	0
NDEL1/TACC3	0.018	0.039	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GSK3B	0.013	0.006	-9999	-10000	0	0
PAK1/Aurora A	0.015	0.043	-9999	-0.34	1	1
MDM2	-0.001	0.026	-9999	-0.57	1	1
JUB	0	0	-9999	-10000	0	0
TPX2	-0.28	0.2	-9999	-0.41	337	337
TP53	0.019	0.027	-9999	-10000	0	0
DLG7	0.01	0.039	-9999	-10000	0	0
AURKAIP1	0	0	-9999	-10000	0	0
ARHGEF7	0	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.019	0.041	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.014	0.035	-9999	-10000	0	0
AURKA	0.017	0.049	-9999	-10000	0	0
AURKB	-0.086	0.049	-9999	-0.16	20	20
CDC25B	0.02	0.034	-9999	-10000	0	0
G2/M transition checkpoint	0.014	0.035	-9999	-10000	0	0
mRNA polyadenylation	-0.016	0.12	-9999	-0.44	31	31
Aurora A/CPEB	-0.016	0.12	-9999	-0.44	31	31
Aurora A/TACC1/TRAP/chTOG	0.023	0.044	-9999	-0.4	2	2
BRCA1	0	0	-9999	-10000	0	0
centrosome duplication	0.015	0.043	-9999	-0.34	1	1
regulation of centrosome cycle	0.017	0.038	-9999	-10000	0	0
spindle assembly	0.015	0.043	-9999	-0.4	2	2
TDRD7	0	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.24	0.1	-9999	-0.41	21	21
CENPA	-0.074	0.041	-9999	-0.17	20	20
Aurora A/PP2A	0.016	0.039	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.029	0.03	-9999	-10000	0	0
negative regulation of DNA binding	0.019	0.027	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
Ajuba/Aurora A	0.014	0.035	-9999	-10000	0	0
mitotic prometaphase	0.025	0.017	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.049	-9999	-10000	0	0
TACC1	-0.003	0.048	-9999	-0.74	2	2
TACC3	-0.002	0.037	-9999	-0.57	2	2
Aurora A/Antizyme1	0.02	0.036	-9999	-10000	0	0
Aurora A/RasGAP	0.016	0.039	-9999	-10000	0	0
OAZ1	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.006	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.001	0.016	-9999	-0.34	1	1
Importin alpha/Importin beta/TPX2	-0.28	0.2	-9999	-0.41	337	337
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.21	0.16	-9999	-0.46	21	21
PAK1	-0.001	0.026	-9999	-0.57	1	1
CKAP5	0	0	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.009	0.071	-9999	-0.56	8	8
AKT1	-0.01	0.2	-9999	-0.65	25	25
PTK2B	-0.097	0.23	-9999	-0.88	27	27
VEGFR2 homodimer/Frs2	-0.11	0.26	-9999	-0.6	91	91
CAV1	-0.21	0.33	-9999	-0.74	135	135
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.1	0.24	-9999	-0.92	25	25
endothelial cell proliferation	-0.007	0.2	-9999	-0.61	28	28
mol:Ca2+	-0.053	0.24	-9999	-0.84	25	25
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.098	0.23	-9999	-0.88	25	25
RP11-342D11.1	-0.059	0.24	-9999	-0.84	25	25
CDH5	-0.15	0.3	-9999	-0.74	95	95
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.003	0.048	-9999	-0.74	2	2
HRAS/GDP	-0.079	0.18	-9999	-0.71	25	25
SH2D2A	-0.002	0.034	-9999	-0.74	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.075	0.17	-9999	-0.66	26	26
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.1	0.24	-9999	-0.9	26	26
VEGFR1 homodimer	0	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.088	0.21	-9999	-0.81	25	25
GRB10	-0.052	0.24	-9999	-0.83	25	25
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PAK1	-0.001	0.026	-9999	-0.57	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.17	0.31	-9999	-0.94	53	53
HRAS	0	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.055	0.12	-9999	-0.45	27	27
HIF1A	0	0	-9999	-10000	0	0
FRS2	0	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.096	0.22	-9999	-0.86	25	25
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.035	0.16	-9999	-0.74	23	23
Nck/Pak	-0.001	0.019	-9999	-0.41	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.1	0.24	-9999	-0.94	25	25
mol:GDP	-0.085	0.2	-9999	-0.77	25	25
mol:NADP	-0.008	0.17	-9999	-0.54	27	27
eNOS/Hsp90	-0.003	0.16	-9999	-0.5	26	26
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	-0.054	0.24	-9999	-0.85	25	25
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0	0	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFC	-0.003	0.048	-9999	-0.74	2	2
FAK1/Vinculin	-0.042	0.24	-9999	-0.84	27	27
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.1	0.25	-9999	-0.94	27	27
PTPN6	0	0	-9999	-10000	0	0
EPAS1	-0.13	0.29	-9999	-0.71	91	91
mol:L-citrulline	-0.008	0.17	-9999	-0.54	27	27
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.098	0.23	-9999	-0.88	25	25
VEGFR2 homodimer/VEGFA homodimer	-0.1	0.24	-9999	-0.93	25	25
VEGFR2/3 heterodimer	-0.14	0.29	-9999	-0.63	103	103
VEGFB	0	0	-9999	-10000	0	0
MAPK11	-0.051	0.24	-9999	-0.87	25	25
VEGFR2 homodimer	-0.1	0.3	-9999	-0.69	91	91
FLT1	0	0	-9999	-10000	0	0
NEDD4	-0.002	0.034	-9999	-0.74	1	1
MAPK3	-0.046	0.23	-9999	-0.76	28	28
MAPK1	-0.046	0.23	-9999	-0.76	28	28
VEGFA145/NRP2	-0.005	0.051	-9999	-0.56	4	4
VEGFR1/2 heterodimer	-0.11	0.26	-9999	-0.6	91	91
KDR	-0.1	0.3	-9999	-0.69	91	91
VEGFA165/NRP1/VEGFR2 homodimer	-0.097	0.23	-9999	-0.9	25	25
SRC	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.046	0.23	-9999	-0.78	28	28
PI3K	-0.088	0.21	-9999	-0.82	25	25
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.1	0.24	-9999	-0.92	25	25
FES	-0.056	0.25	-9999	-0.88	25	25
GAB1	-0.092	0.22	-9999	-0.84	25	25
VEGFR2 homodimer/VEGFA homodimer/Src	-0.1	0.24	-9999	-0.92	25	25
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.097	0.23	-9999	-0.57	59	59
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.1	0.24	-9999	-0.92	25	25
PI3K/GAB1	-0.012	0.2	-9999	-0.67	25	25
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.094	0.22	-9999	-0.85	25	25
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.13	0.28	-9999	-1.1	28	28
HSP90AA1	0	0	-9999	-10000	0	0
CDC42	-0.055	0.24	-9999	-0.87	25	25
actin cytoskeleton reorganization	-0.1	0.24	-9999	-0.89	26	26
PTK2	-0.053	0.27	-9999	-0.94	27	27
EDG1	-0.059	0.24	-9999	-0.84	25	25
mol:DAG	-0.054	0.24	-9999	-0.85	25	25
CaM/Ca2+	-0.086	0.2	-9999	-0.78	25	25
MAP2K3	-0.044	0.23	-9999	-0.82	25	25
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.098	0.23	-9999	-0.89	25	25
PLCG1	-0.055	0.24	-9999	-0.87	25	25
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.098	0.23	-9999	-0.88	25	25
IQGAP1	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.1	0.24	-9999	-0.92	25	25
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.1	0.24	-9999	-0.55	91	91
cell migration	-0.039	0.23	-9999	-0.75	27	27
mol:PI-3-4-5-P3	-0.081	0.19	-9999	-0.73	25	25
FYN	-0.002	0.034	-9999	-0.74	1	1
VEGFB/NRP1	-0.089	0.21	-9999	-0.79	25	25
mol:NO	-0.008	0.17	-9999	-0.54	27	27
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.079	0.18	-9999	-0.71	25	25
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.098	0.23	-9999	-0.89	25	25
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.012	0.095	-9999	-0.74	8	8
NOS3	-0.015	0.19	-9999	-0.62	27	27
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.11	0.24	-9999	-0.93	26	26
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.043	0.23	-9999	-0.8	26	26
PRKCB	-0.062	0.25	-9999	-0.88	27	27
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.095	0.22	-9999	-0.84	25	25
VEGFR1/2 heterodimer/VEGFA homodimer	-0.1	0.24	-9999	-0.92	25	25
VEGFA165/NRP2	-0.005	0.051	-9999	-0.56	4	4
MAPKKK cascade	-0.078	0.18	-9999	-0.71	25	25
NRP2	-0.006	0.067	-9999	-0.74	4	4
VEGFC homodimer	-0.003	0.048	-9999	-0.74	2	2
NCK1	0	0	-9999	-10000	0	0
ROCK1	0	0	-9999	-10000	0	0
FAK1/Paxillin	-0.042	0.24	-9999	-0.84	27	27
MAP3K13	-0.055	0.24	-9999	-0.87	25	25
PDPK1	-0.013	0.19	-9999	-0.62	25	25

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.044	0.085	-9999	-0.31	24	24
FZD6	0	0	-9999	-10000	0	0
WNT6	-0.096	0.21	-9999	-0.57	81	81
WNT4	-0.011	0.085	-9999	-0.66	8	8
FZD3	0	0	-9999	-10000	0	0
WNT5A	-0.012	0.084	-9999	-0.59	10	10
WNT11	-0.038	0.16	-9999	-0.68	27	27

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.02	0	-9999	-10000	0	0
SMARCC1	0.007	0.008	-9999	-10000	0	0
REL	0	0.002	-9999	-10000	0	0
HDAC7	-0.03	0.12	-9999	-10000	0	0
JUN	0.001	0.003	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
KAT2B	-0.003	0.048	-9999	-0.74	2	2
KAT5	0	0.001	-9999	-10000	0	0
MAPK14	0.011	0.026	-9999	-0.44	1	1
FOXO1	0	0	-9999	-10000	0	0
T-DHT/AR	-0.038	0.13	-9999	-0.44	1	1
MAP2K6	0.005	0.028	-9999	-0.59	1	1
BRM/BAF57	-0.001	0.025	-9999	-0.56	1	1
MAP2K4	0.007	0.007	-9999	-10000	0	0
SMARCA2	-0.001	0.034	-9999	-0.74	1	1
PDE9A	-0.11	0.24	-9999	-0.85	28	28
NCOA2	0.002	0.034	-9999	-0.74	1	1
CEBPA	-0.001	0.034	-9999	-0.74	1	1
EHMT2	0.001	0.003	-9999	-10000	0	0
cell proliferation	-0.048	0.17	-9999	-0.52	24	24
NR0B1	-0.18	0.27	-9999	-0.57	155	155
EGR1	-0.013	0.1	-9999	-0.74	9	9
RXRs/9cRA	-0.23	0.22	-9999	-0.44	253	253
AR/RACK1/Src	-0.016	0.074	-9999	-10000	0	0
AR/GR	-0.064	0.12	-9999	-0.34	40	40
GNB2L1	0	0	-9999	-10000	0	0
PKN1	0	0	-9999	-10000	0	0
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.012	0.016	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.015	0.074	-9999	-0.45	1	1
SRC	0.018	0.041	-9999	-10000	0	0
NR3C1	0	0	-9999	-10000	0	0
KLK3	-0.13	0.15	-9999	-0.58	17	17
APPBP2	0.007	0.006	-9999	-10000	0	0
TRIM24	0.001	0.004	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.037	0.053	-9999	-10000	0	0
TMPRSS2	-0.42	0.57	-9999	-1.2	156	156
RXRG	-0.39	0.37	-9999	-0.74	253	253
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0.004	0.005	-9999	-10000	0	0
NR2C2	0	0	-9999	-10000	0	0
KLK2	-0.021	0.13	-9999	-0.48	3	3
AR	-0.054	0.15	-9999	-0.33	101	101
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
MDM2	-0.001	0.026	-9999	-0.57	1	1
SRY	-0.005	0.052	-9999	-0.57	4	4
GATA2	-0.08	0.23	-9999	-0.74	52	52
MYST2	0	0.001	-9999	-10000	0	0
HOXB13	-0.34	0.28	-9999	-0.57	283	283
T-DHT/AR/RACK1/Src	-0.016	0.069	-9999	-10000	0	0
positive regulation of transcription	-0.08	0.23	-9999	-0.74	52	52
DNAJA1	0.007	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.006	-9999	-10000	0	0
NCOA1	0.014	0.004	-9999	-10000	0	0
SPDEF	-0.096	0.25	-9999	-0.73	64	64
T-DHT/AR/TIF2	0.012	0.059	-9999	-0.37	2	2
T-DHT/AR/Hsp90	-0.037	0.053	-9999	-10000	0	0
GSK3B	0.007	0.005	-9999	-10000	0	0
NR2C1	0	0.001	-9999	-10000	0	0
mol:T-DHT	0.012	0.043	-9999	-0.38	1	1
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0	0.002	-9999	-10000	0	0
POU2F1	-0.001	0.042	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.13	0.15	-9999	-0.46	24	24
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	0	0.002	-9999	-10000	0	0

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	0	0.13	-10000	0	-0.4	24	24
TBX21	-0.095	0.5	-10000	0	-1.4	55	55
B2M	0.008	0.049	-10000	0	-0.74	2	2
TYK2	0.016	0.016	-10000	0	-10000	0	0
IL12RB1	-0.033	0.19	-10000	0	-0.77	31	31
GADD45B	-0.033	0.37	-10000	0	-1.2	36	36
IL12RB2	-0.045	0.18	-10000	0	-0.57	51	51
GADD45G	-0.017	0.33	-10000	0	-1	33	33
natural killer cell activation	0.006	0.019	-10000	0	-10000	0	0
RELB	-0.001	0.026	-10000	0	-0.57	1	1
RELA	0	0	-10000	0	-10000	0	0
IL18	0.008	0.06	-10000	0	-0.75	3	3
IL2RA	-0.008	0.073	-10000	0	-0.66	6	6
IFNG	-0.009	0.076	-10000	0	-0.68	6	6
STAT3 (dimer)	-0.005	0.29	-10000	0	-0.79	41	41
HLA-DRB5	-0.064	0.22	-10000	0	-0.74	47	47
FASLG	-0.05	0.41	-10000	0	-1.2	42	42
NF kappa B2 p52/RelB	-0.13	0.3	-10000	0	-1	39	39
CD4	-0.013	0.13	-10000	0	-0.74	14	14
SOCS1	-0.002	0.034	-10000	0	-0.74	1	1
EntrezGene:6955	-0.001	0.009	-10000	0	-10000	0	0
CD3D	-0.007	0.11	-10000	0	-0.74	11	11
CD3E	-0.004	0.1	-10000	0	-0.74	9	9
CD3G	-0.036	0.18	-10000	0	-0.74	30	30
IL12Rbeta2/JAK2	-0.02	0.14	-10000	0	-0.41	51	51
CCL3	-0.027	0.35	-10000	0	-1.1	30	30
CCL4	-0.03	0.36	-10000	0	-1.1	37	37
HLA-A	0.009	0.034	-10000	0	-0.74	1	1
IL18/IL18R	0.017	0.15	-10000	0	-0.59	25	25
NOS2	-0.079	0.44	-10000	0	-1.2	53	53
IL12/IL12R/TYK2/JAK2/SPHK2	0.001	0.13	-10000	0	-0.4	21	21
IL1R1	-0.026	0.35	-10000	0	-1	36	36
IL4	-0.004	0.019	-10000	0	-10000	0	0
JAK2	0.016	0.016	-10000	0	-10000	0	0
EntrezGene:6957	0	0.008	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.027	0.31	-10000	0	-1.3	22	22
RAB7A	0.007	0.28	-10000	0	-0.82	30	30
lysosomal transport	0.012	0.27	-10000	0	-0.77	30	30
FOS	-0.15	0.49	-10000	0	-1.2	76	76
STAT4 (dimer)	-0.008	0.34	-10000	0	-0.96	40	40
STAT5A (dimer)	-0.13	0.3	-10000	0	-0.96	45	45
GZMA	-0.033	0.37	-10000	0	-1.1	38	38
GZMB	-0.035	0.38	-10000	0	-1.2	36	36
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.037	0.39	-10000	0	-1.1	41	41
TCR/CD3/MHC II/CD4	-0.084	0.33	-10000	0	-0.91	46	46
IL2/IL2R	-0.014	0.1	-10000	0	-0.67	9	9
MAPK14	-0.015	0.34	-10000	0	-1	37	37
CCR5	-0.026	0.36	-10000	0	-1.1	32	32
IL1B	-0.002	0.12	-10000	0	-0.77	11	11
STAT6	0.018	0.1	-10000	0	-0.26	15	15
STAT4	-0.012	0.095	-10000	0	-0.74	8	8
STAT3	0	0	-10000	0	-10000	0	0
STAT1	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0	-10000	0	-10000	0	0
IL12B	0.017	0.016	-10000	0	-10000	0	0
CD8A	0	0.09	-10000	0	-0.74	7	7
CD8B	-0.011	0.12	-10000	0	-0.7	15	15
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0	0.13	0.4	24	-10000	0	24
IL2RB	-0.005	0.058	-10000	0	-0.74	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.001	0.31	-10000	0	-0.84	40	40
IL2RG	-0.012	0.095	-10000	0	-0.74	8	8
IL12	0.016	0.081	-10000	0	-0.57	8	8
STAT5A	0	0	-10000	0	-10000	0	0
CD247	-0.007	0.11	-10000	0	-0.75	11	11
IL2	0	0	-10000	0	-10000	0	0
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.003	0.1	-10000	0	-0.75	8	8
IL12/IL12R/TYK2/JAK2	-0.053	0.45	-10000	0	-1.2	46	46
MAP2K3	-0.019	0.34	-10000	0	-1	38	38
RIPK2	0	0	-10000	0	-10000	0	0
MAP2K6	-0.019	0.34	-10000	0	-1	38	38
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.053	0.21	-10000	0	-0.74	40	40
IL18RAP	-0.021	0.16	-10000	0	-0.75	22	22
IL12Rbeta1/TYK2	-0.016	0.15	-10000	0	-0.6	31	31
EOMES	-0.023	0.22	-10000	0	-1.4	11	11
STAT1 (dimer)	-0.003	0.29	-10000	0	-0.82	36	36
T cell proliferation	0.006	0.26	-10000	0	-0.69	37	37
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.005	0.078	-10000	0	-0.75	5	5
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.1	0.23	-10000	0	-0.77	39	39
ATF2	-0.003	0.31	-10000	0	-0.91	36	36

×

Syndecan-1-mediated signaling events

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
TGFB1	0	0	-9999	-10000	0	0
CCL5	-0.014	0.1	-9999	-0.74	9	9
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.088	0.1	-9999	-0.42	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.091	0.078	-9999	-0.4	5	5
Syndecan-1/Syntenin	-0.09	0.077	-9999	-0.4	4	4
MAPK3	-0.057	0.087	-9999	-0.48	1	1
HGF/MET	-0.12	0.23	-9999	-0.56	104	104
TGFB1/TGF beta receptor Type II	0	0	-9999	-10000	0	0
BSG	0	0	-9999	-10000	0	0
keratinocyte migration	-0.09	0.077	-9999	-0.39	5	5
Syndecan-1/RANTES	-0.098	0.1	-9999	-0.55	10	10
Syndecan-1/CD147	-0.083	0.072	-9999	-0.51	1	1
Syndecan-1/Syntenin/PIP2	-0.087	0.074	-9999	-0.39	4	4
LAMA5	-0.002	0.034	-9999	-0.74	1	1
positive regulation of cell-cell adhesion	-0.086	0.073	-9999	-0.38	4	4
MMP7	-0.038	0.15	-9999	-0.62	29	29
HGF	-0.16	0.3	-9999	-0.74	101	101
Syndecan-1/CASK	-0.084	0.094	-9999	-0.41	4	4
Syndecan-1/HGF/MET	-0.17	0.17	-9999	-0.54	57	57
regulation of cell adhesion	-0.049	0.085	-9999	-0.46	1	1
HPSE	0	0	-9999	-10000	0	0
positive regulation of cell migration	-0.088	0.1	-9999	-0.42	4	4
SDC1	-0.088	0.1	-9999	-0.43	4	4
Syndecan-1/Collagen	-0.088	0.1	-9999	-0.42	4	4
PPIB	0	0	-9999	-10000	0	0
MET	-0.004	0.054	-9999	-0.68	3	3
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.03	0.13	-9999	-0.57	25	25
MAPK1	-0.057	0.087	-9999	-0.48	1	1
homophilic cell adhesion	-0.087	0.099	-9999	-0.42	4	4
MMP1	-0.35	0.28	-9999	-0.57	298	298

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.15	0.14	-9999	-0.56	5	5
NF kappa B1 p50/RelA/I kappa B alpha	-0.12	0.11	-9999	-0.58	3	3
alphaV/beta3 Integrin/Osteopontin/Src	-0.21	0.2	-9999	-0.4	255	255
AP1	-0.16	0.16	-9999	-0.6	31	31
ILK	-0.14	0.17	-9999	-0.53	8	8
bone resorption	-0.12	0.12	-9999	-0.6	4	4
PTK2B	0	0	-9999	-10000	0	0
PYK2/p130Cas	-0.14	0.13	-9999	-0.65	3	3
ITGAV	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.001	0.025	-9999	-0.56	1	1
alphaV/beta3 Integrin/Osteopontin	-0.18	0.17	-9999	-0.44	25	25
MAP3K1	-0.14	0.17	-9999	-0.54	8	8
JUN	0	0	-9999	-10000	0	0
MAPK3	-0.12	0.16	-9999	-0.56	5	5
MAPK1	-0.12	0.16	-9999	-0.56	5	5
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.12	0.16	-9999	-0.58	5	5
ITGB3	-0.012	0.094	-9999	-0.74	8	8
NFKBIA	-0.1	0.16	-9999	-0.54	5	5
FOS	-0.084	0.24	-9999	-0.74	55	55
CD44	-0.002	0.034	-9999	-0.74	1	1
CHUK	0	0	-9999	-10000	0	0
PLAU	-0.1	0.16	-9999	-0.58	4	4
NF kappa B1 p50/RelA	-0.12	0.11	-9999	-0.56	3	3
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.009	0.071	-9999	-0.56	8	8
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.14	0.17	-9999	-0.52	9	9
VAV3	-0.13	0.17	-9999	-0.53	9	9
MAP3K14	-0.14	0.17	-9999	-0.53	8	8
ROCK2	0	0	-9999	-10000	0	0
SPP1	-0.3	0.28	-9999	-0.56	255	255
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.13	0.13	-9999	-0.73	3	3
MMP2	-0.1	0.17	-9999	-0.52	32	32

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.25	0.35	-9999	-0.74	160	160
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0	0	-9999	-10000	0	0
TCEB1	0	0	-9999	-10000	0	0
HIF1A/p53	-0.009	0.022	-9999	-10000	0	0
HIF1A	-0.011	0.025	-9999	-10000	0	0
COPS5	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0	0	-9999	-10000	0	0
FIH (dimer)	0	0	-9999	-10000	0	0
CDKN2A	-0.27	0.29	-9999	-0.57	224	224
ARNT/IPAS	-0.19	0.26	-9999	-0.56	160	160
HIF1AN	0	0	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
HIF1A/ARNT	-0.009	0.022	-9999	-10000	0	0
CUL2	0	0	-9999	-10000	0	0
OS9	0	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.009	0.022	-9999	-10000	0	0
PHD1-3/OS9	-0.045	0.11	-9999	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	-0.007	0.016	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
HIF1A/JAB1	-0.009	0.022	-9999	-10000	0	0
EGLN3	-0.084	0.2	-9999	-0.57	71	71
EGLN2	0	0	-9999	-10000	0	0
EGLN1	0	0	-9999	-10000	0	0
TP53	0	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.13	0.14	-9999	-0.35	35	35

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.064	0.098	-10000	0	-0.32	4	4
NT3 (dimer)/TRKC	-0.17	0.26	-10000	0	-0.57	146	146
NT3 (dimer)/TRKB	-0.12	0.19	-10000	0	-0.53	34	34
SHC/Grb2/SOS1/GAB1/PI3K	0	0	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.095	0.25	-10000	0	-0.74	62	62
PIK3CA	0	0	-10000	0	-10000	0	0
DYNLT1	0	0	-10000	0	-10000	0	0
NTRK1	-0.009	0.082	-10000	0	-0.74	6	6
NTRK2	-0.14	0.26	-10000	0	-0.62	105	105
NTRK3	-0.22	0.34	-10000	0	-0.74	143	143
NT-4/5 (dimer)/TRKB	-0.12	0.19	-10000	0	-0.39	147	147
neuron apoptosis	0.13	0.19	0.47	86	-10000	0	86
SHC 2-3/Grb2	-0.14	0.21	-10000	0	-0.52	86	86
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.054	0.098	-10000	0	-0.55	8	8
SHC3	-0.16	0.26	-10000	0	-0.69	85	85
STAT3 (dimer)	-0.005	0.043	-10000	0	-0.37	6	6
NT3 (dimer)/TRKA	-0.041	0.12	-10000	0	-0.48	11	11
RIN/GDP	-0.046	0.093	-10000	0	-0.28	2	2
GIPC1	0	0	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
DNAJA3	-0.023	0.068	-10000	0	-0.46	2	2
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.013	0.11	-10000	0	-0.88	7	7
MAGED1	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.012	0.094	-10000	0	-0.74	8	8
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.035	0.12	-10000	0	-0.47	36	36
TRKA/NEDD4-2	-0.007	0.062	-10000	0	-0.56	6	6
ELMO1	-0.017	0.11	-10000	0	-0.74	11	11
RhoG/GTP/ELMO1/DOCK1	-0.011	0.073	-10000	0	-0.49	11	11
NGF	-0.017	0.11	-10000	0	-0.7	12	12
HRAS	0	0	-10000	0	-10000	0	0
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.018	0.12	-10000	0	-0.74	12	12
RIT2	0	0	-10000	0	-10000	0	0
RIT1	0	0	-10000	0	-10000	0	0
FRS2	0	0	-10000	0	-10000	0	0
DNM1	-0.002	0.037	-10000	0	-0.57	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.031	0.087	-10000	0	-0.4	13	13
mol:GDP	-0.067	0.13	-10000	0	-0.42	2	2
NGF (dimer)	-0.017	0.11	-10000	0	-0.7	12	12
RhoG/GDP	-0.013	0.085	-10000	0	-0.57	11	11
RIT1/GDP	-0.042	0.093	-10000	0	-0.28	1	1
TIAM1	0	0	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.14	0.23	-10000	0	-0.45	153	153
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.01	0.083	-10000	0	-0.69	7	7
RAP1/GDP	-0.047	0.067	-10000	0	-10000	0	0
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.095	0.25	-10000	0	-0.74	62	62
ubiquitin-dependent protein catabolic process	-0.017	0.087	-10000	0	-0.48	15	15
Schwann cell development	-0.054	0.036	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	-0.006	0.039	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.22	0.27	-10000	0	-0.72	74	74
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.049	0.077	-10000	0	-10000	0	0
STAT3	-0.005	0.043	-10000	0	-0.37	6	6
axon guidance	-0.21	0.25	-10000	0	-0.68	74	74
MAPK3	-0.005	0.12	-10000	0	-0.43	33	33
MAPK1	-0.005	0.12	-10000	0	-0.43	33	33
CDC42/GDP	-0.042	0.093	-10000	0	-0.28	1	1
NTF3	-0.01	0.083	-10000	0	-0.69	7	7
NTF4	-0.012	0.095	-10000	0	-0.74	8	8
NGF (dimer)/TRKA/FAIM	-0.017	0.087	-10000	0	-0.46	18	18
PI3K	0	0	-10000	0	-10000	0	0
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.27	0.2	-10000	0	-0.42	302	302
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.13	0.24	-10000	0	-0.49	144	144
RGS19	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.057	0.08	-10000	0	-10000	0	0
Rac1/GDP	-0.042	0.093	-10000	0	-0.28	1	1
NGF (dimer)/TRKA/GRIT	-0.017	0.088	-10000	0	-0.46	18	18
neuron projection morphogenesis	0.004	0.073	-10000	0	-0.42	3	3
NGF (dimer)/TRKA/NEDD4-2	-0.017	0.087	-10000	0	-0.48	15	15
MAP2K1	0	0	-10000	0	-10000	0	0
NGFR	-0.047	0.16	-10000	0	-0.57	40	40
NGF (dimer)/TRKA/GIPC/GAIP	-0.011	0.055	-10000	0	-10000	0	0
RAS family/GTP/PI3K	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.047	0.12	-10000	0	-0.66	15	15
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.007	0.062	-10000	0	-0.56	6	6
SQSTM1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.13	0.21	-10000	0	-0.5	79	79
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.014	0.073	-10000	0	-0.4	15	15
MATK	-0.028	0.14	-10000	0	-0.74	18	18
NEDD4L	0	0	-10000	0	-10000	0	0
RAS family/GDP	-0.043	0.064	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.025	0.073	-10000	0	-0.33	15	15
Rac1/GTP	-0.18	0.13	-10000	0	-0.32	139	139
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.013	0.029	-10000	0	-10000	0	0
oxygen homeostasis	-0.01	0.013	-10000	0	-10000	0	0
TCEB2	0	0	-10000	0	-10000	0	0
TCEB1	0	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.099	0.12	-10000	0	-0.44	9	9
EPO	-0.15	0.21	-10000	0	-0.66	13	13
FIH (dimer)	0.003	0.009	-10000	0	-10000	0	0
APEX1	0.003	0.012	-10000	0	-10000	0	0
SERPINE1	-0.2	0.24	-10000	0	-0.78	13	13
FLT1	-0.038	0.16	-10000	0	-0.98	12	12
ADORA2A	-0.19	0.23	-10000	0	-0.71	19	19
germ cell development	-0.19	0.24	-10000	0	-0.74	17	17
SLC11A2	-0.2	0.24	-10000	0	-0.73	19	19
BHLHE40	-0.2	0.24	-10000	0	-0.74	18	18
HIF1AN	0.003	0.009	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.14	0.16	-10000	0	-0.48	38	38
ETS1	0.003	0.12	-10000	0	-0.75	12	12
CITED2	-0.033	0.16	-10000	0	-1.3	8	8
KDR	-0.092	0.33	-10000	0	-1.3	32	32
PGK1	-0.2	0.24	-10000	0	-0.73	19	19
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.21	0.29	-10000	0	-0.79	38	38
EPAS1	-0.12	0.16	-10000	0	-0.4	75	75
SP1	0.016	0	-10000	0	-10000	0	0
ABCG2	-0.24	0.32	-10000	0	-0.96	56	56
EFNA1	-0.2	0.24	-10000	0	-0.76	14	14
FXN	-0.19	0.23	-10000	0	-0.75	13	13
POU5F1	-0.2	0.24	-10000	0	-0.78	17	17
neuron apoptosis	0.2	0.28	0.76	38	-10000	0	38
EP300	0	0	-10000	0	-10000	0	0
EGLN3	-0.084	0.21	-10000	0	-0.59	71	71
EGLN2	0.003	0.009	-10000	0	-10000	0	0
EGLN1	0.003	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0	0	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.003	0.012	-10000	0	-10000	0	0
SLC2A1	-0.37	0.28	-10000	0	-0.74	93	93
TWIST1	-0.27	0.3	-10000	0	-0.76	65	65
ELK1	0.016	0.002	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.14	0.15	-10000	0	-0.53	13	13
VEGFA	-0.2	0.24	-10000	0	-0.68	34	34
CREBBP	0	0	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.023	0.1	-10000	0	-0.46	24	24
ER alpha/Gai/GDP/Gbeta gamma	-0.025	0.11	-10000	0	-0.47	22	22
AKT1	-0.004	0.18	-10000	0	-0.82	21	21
PIK3CA	0	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.007	0.18	-10000	0	-0.83	21	21
mol:Ca2+	-0.087	0.23	-10000	0	-0.48	115	115
IGF1R	0	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.021	0.099	-10000	0	-0.49	21	21
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.002	0.17	0.78	21	-10000	0	21
RhoA/GTP	-0.016	0.073	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.027	0.11	-10000	0	-0.52	22	22
regulation of stress fiber formation	-0.032	0.07	0.58	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.021	0.099	-10000	0	-0.49	21	21
KRAS	0	0	-10000	0	-10000	0	0
G13/GTP	-0.019	0.091	-10000	0	-0.45	21	21
pseudopodium formation	0.032	0.07	-10000	0	-0.58	1	1
E2/ER alpha (dimer)/PELP1	-0.021	0.099	-10000	0	-0.49	21	21
GRB2	0	0	-10000	0	-10000	0	0
GNG2	-0.008	0.075	-10000	0	-0.74	5	5
GNAO1	-0.004	0.05	-10000	0	-0.63	3	3
HRAS	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.016	0.13	-10000	0	-0.54	22	22
E2/ER beta (dimer)	0	0	-10000	0	-10000	0	0
mol:GDP	-0.022	0.1	-10000	0	-0.5	21	21
mol:NADP	0.016	0.13	-10000	0	-0.54	22	22
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.093	0.24	-10000	0	-0.5	115	115
IGF-1R heterotetramer	0	0	-10000	0	-10000	0	0
PLCB1	-0.12	0.22	-10000	0	-0.51	114	114
PLCB2	-0.13	0.23	-10000	0	-0.51	119	119
IGF1	-0.024	0.13	-10000	0	-0.73	16	16
mol:L-citrulline	0.016	0.13	-10000	0	-0.54	22	22
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.007	0.046	-10000	0	-0.67	1	1
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0	0	-10000	0	-10000	0	0
GNAQ	-0.002	0.034	-10000	0	-0.74	1	1
ESR1	-0.032	0.15	-10000	0	-0.74	21	21
Gq family/GDP/Gbeta gamma	-0.073	0.14	-10000	0	-0.81	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.019	0.071	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.027	0.11	-10000	0	-0.52	22	22
GNAZ	-0.009	0.082	-10000	0	-0.74	6	6
E2/ER alpha (dimer)	-0.025	0.12	-10000	0	-0.57	21	21
STRN	0	0	-10000	0	-10000	0	0
GNAL	-0.006	0.067	-10000	0	-0.74	4	4
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.016	0	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.034	-10000	0	-0.74	1	1
HBEGF	0.015	0.12	-10000	0	-0.72	5	5
cAMP biosynthetic process	-0.02	0.091	-10000	0	-0.41	24	24
SRC	0.019	0.11	-10000	0	-0.44	22	22
PI3K	0	0	-10000	0	-10000	0	0
GNB1	-0.002	0.034	-10000	0	-0.74	1	1
G13/GDP/Gbeta gamma	-0.023	0.11	-10000	0	-0.49	21	21
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.03	0.11	-10000	0	-0.46	23	23
Gs family/GTP	-0.021	0.092	-10000	0	-0.42	24	24
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	0.017	0.12	-10000	0	-0.51	22	22
mol:DAG	-0.093	0.24	-10000	0	-0.5	115	115
Gs family/GDP/Gbeta gamma	-0.024	0.1	-10000	0	-0.46	21	21
MSN	0.033	0.076	-10000	0	-0.64	1	1
Gq family/GTP	-0.13	0.24	-10000	0	-0.54	114	114
mol:PI-3-4-5-P3	-0.006	0.17	-10000	0	-0.8	21	21
NRAS	0	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.017	0.12	0.51	22	-10000	0	22
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.02	0.096	-10000	0	-0.47	21	21
NOS3	0.016	0.13	-10000	0	-0.57	22	22
GNA11	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.02	0.14	-10000	0	-0.64	21	21
E2/ER alpha (dimer)/PELP1/Src	-0.028	0.12	-10000	0	-0.55	22	22
ruffle organization	0.032	0.07	-10000	0	-0.58	1	1
ROCK2	-0.014	0.067	-10000	0	-10000	0	0
GNA14	-0.18	0.32	-10000	0	-0.74	114	114
GNA15	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
MMP9	0.011	0.12	-10000	0	-0.59	5	5
MMP2	0.023	0.12	-10000	0	-0.79	5	5

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.003	0.048	-9999	-0.74	2	2
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.086	0.18	-9999	-0.47	88	88
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.053	0.18	-9999	-0.43	82	82
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.036	0.14	-9999	-0.57	30	30
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.006	0.067	-9999	-0.74	4	4
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.003	0.032	-9999	-0.41	3	3
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.011	0.077	-9999	-0.57	9	9
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.15	0.25	-9999	-0.57	124	124
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.11	0.2	-9999	-0.5	85	85
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.091	0.14	-9999	-0.48	26	26
MAP1B	-0.002	0.019	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.072	0.15	-9999	-0.6	2	2
RELN	-0.13	0.28	-9999	-0.74	85	85
PAFAH/LIS1	-0.004	0.043	-9999	-0.48	4	4
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.068	0.11	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.062	0.12	-9999	-0.56	3	3
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.099	0.15	-9999	-0.51	26	26
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.02	0	-9999	-10000	0	0
PAFAH1B3	-0.005	0.056	-9999	-0.61	4	4
PAFAH1B2	0	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.001	0.012	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.086	0.13	-9999	-0.46	26	26
LRP8	-0.004	0.045	-9999	-0.57	3	3
NDEL1/Katanin 60	-0.091	0.14	-9999	-0.48	26	26
P39/CDK5	-0.14	0.19	-9999	-0.66	25	25
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.042	0.16	-9999	-0.4	82	82
PPP2R5D	0	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.09	0.17	-9999	-0.42	85	85
RELN/VLDLR	-0.079	0.17	-9999	-0.44	83	83
CDC42	0	0	-9999	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.04	0.14	-10000	0	-0.6	25	25
FYN	0.002	0.23	-10000	0	-0.89	25	25
LAT/GRAP2/SLP76	-0.053	0.18	-10000	0	-0.69	31	31
IKBKB	-0.001	0.026	-10000	0	-0.57	1	1
AKT1	0.023	0.14	-10000	0	-0.48	29	29
B2M	0.007	0.049	-10000	0	-0.75	2	2
IKBKG	-0.009	0.03	-10000	0	-0.18	1	1
MAP3K8	-0.003	0.048	-10000	0	-0.74	2	2
mol:Ca2+	-0.006	0.022	-10000	0	-0.12	15	15
integrin-mediated signaling pathway	-0.001	0.022	-10000	0	-0.48	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.01	0.21	-10000	0	-0.75	29	29
TRPV6	-0.019	0.12	-10000	0	-0.69	14	14
CD28	0.001	0.077	-10000	0	-0.75	5	5
SHC1	0.006	0.21	-10000	0	-0.81	25	25
receptor internalization	-0.01	0.23	-10000	0	-0.83	30	30
PRF1	-0.037	0.32	-10000	0	-1.3	29	29
KRAS	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
COT/AKT1	0.027	0.11	-10000	0	-0.4	24	24
LAT	0.006	0.21	-10000	0	-0.81	25	25
EntrezGene:6955	0.001	0.004	-10000	0	-10000	0	0
CD3D	-0.007	0.11	-10000	0	-0.75	11	11
CD3E	-0.004	0.1	-10000	0	-0.75	9	9
CD3G	-0.037	0.18	-10000	0	-0.75	30	30
RASGRP2	-0.013	0.066	-10000	0	-0.18	65	65
RASGRP1	0.025	0.14	-10000	0	-0.46	31	31
HLA-A	0.009	0.035	-10000	0	-0.75	1	1
RASSF5	-0.002	0.034	-10000	0	-0.74	1	1
RAP1A/GTP/RAPL	-0.001	0.022	-10000	0	-0.49	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.023	0.049	-10000	0	-0.13	26	26
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.017	0.054	-10000	0	-0.25	15	15
PRKCA	-0.023	0.076	-10000	0	-0.3	28	28
GRAP2	-0.04	0.17	-10000	0	-0.74	26	26
mol:IP3	-0.033	0.13	0.25	10	-0.49	27	37
EntrezGene:6957	0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.016	0.24	-10000	0	-0.86	26	26
ORAI1	0.01	0.064	0.35	14	-0.57	1	15
CSK	0.004	0.21	-10000	0	-0.82	25	25
B7 family/CD28	-0.064	0.23	-10000	0	-0.87	30	30
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.009	0.25	-10000	0	-1	25	25
PTPN6	0.001	0.21	-10000	0	-0.86	24	24
VAV1	0.004	0.22	-10000	0	-0.84	25	25
Monovalent TCR/CD3	-0.025	0.21	-10000	0	-0.64	36	36
CBL	0	0	-10000	0	-10000	0	0
LCK	-0.001	0.23	-10000	0	-0.91	25	25
PAG1	0.001	0.22	-10000	0	-0.84	25	25
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.01	0.25	-10000	0	-0.97	26	26
CD80	-0.016	0.14	-10000	0	-0.75	16	16
CD86	0	0.084	-10000	0	-0.75	6	6
PDK1/CARD11/BCL10/MALT1	-0.021	0.066	-10000	0	-0.3	16	16
HRAS	0	0	-10000	0	-10000	0	0
GO:0035030	0.006	0.19	-10000	0	-0.68	29	29
CD8A	-0.001	0.091	-10000	0	-0.75	7	7
CD8B	-0.011	0.12	-10000	0	-0.7	15	15
PTPRC	-0.039	0.18	-10000	0	-0.74	31	31
PDK1/PKC theta	0.018	0.18	-10000	0	-0.59	32	32
CSK/PAG1	0.007	0.21	-10000	0	-0.87	21	21
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.003	0.054	-10000	0	-0.8	2	2
GRAP2/SLP76	-0.063	0.21	-10000	0	-0.81	31	31
STIM1	0.007	0.031	-10000	0	-10000	0	0
RAS family/GTP	0.036	0.058	-10000	0	-0.18	16	16
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.015	0.26	-10000	0	-0.92	30	30
mol:DAG	-0.032	0.11	-10000	0	-0.44	27	27
RAP1A/GDP	0.011	0.021	-10000	0	-10000	0	0
PLCG1	0.001	0.003	-10000	0	-10000	0	0
CD247	-0.007	0.11	-10000	0	-0.75	11	11
cytotoxic T cell degranulation	-0.031	0.3	-10000	0	-1.2	30	30
RAP1A/GTP	-0.009	0.022	-10000	0	-0.068	24	24
mol:PI-3-4-5-P3	0.018	0.17	-10000	0	-0.59	29	29
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.045	0.17	0.26	10	-0.66	27	37
NRAS	0	0	-10000	0	-10000	0	0
ZAP70	-0.012	0.095	-10000	0	-0.74	8	8
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.05	0.16	-10000	0	-0.66	28	28
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.024	0.13	-10000	0	-0.67	17	17
CARD11	-0.004	0.05	-10000	0	-0.63	3	3
PRKCB	-0.033	0.1	-10000	0	-0.36	36	36
PRKCE	-0.023	0.074	-10000	0	-0.3	23	23
PRKCQ	0.006	0.21	-10000	0	-0.69	33	33
LCP2	-0.01	0.089	-10000	0	-0.74	7	7
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.026	0.12	-10000	0	-0.4	29	29
IKK complex	0.035	0.046	-10000	0	-0.13	10	10
RAS family/GDP	-0.003	0.007	-10000	0	-10000	0	0
MAP3K14	0.032	0.088	-10000	0	-0.31	20	20
PDPK1	0.027	0.13	-10000	0	-0.46	27	27
TCR/CD3/MHC I/CD8/Fyn	-0.011	0.25	-10000	0	-1	23	23

×

Ephrin A reverse 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.016	0.075	-9999	-0.36	21	21
EFNA5	-0.003	0.048	-9999	-0.74	2	2
FYN	0.004	0.074	-9999	-0.33	22	22
neuron projection morphogenesis	-0.016	0.075	-9999	-0.36	21	21
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.016	0.075	-9999	-0.36	21	21
EPHA5	-0.023	0.11	-9999	-0.57	19	19

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.007	0.062	-9999	-0.56	6	6
Necdin/E2F1	-0.007	0.062	-9999	-0.56	6	6
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.038	0.11	-9999	-0.44	15	15
NGF (dimer)/p75(NTR)/BEX1	-0.096	0.19	-9999	-0.54	54	54
NT-4/5 (dimer)/p75(NTR)	-0.043	0.13	-9999	-0.44	48	48
IKBKB	-0.001	0.026	-9999	-0.57	1	1
AKT1	-0.032	0.099	-9999	-0.69	2	2
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.095	0.25	-9999	-0.74	62	62
MGDIs/NGR/p75(NTR)/LINGO1	-0.061	0.14	-9999	-0.68	7	7
FURIN	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.096	0.19	-9999	-0.51	67	67
LINGO1	-0.052	0.16	-9999	-0.57	44	44
Sortilin/TRAF6/NRIF	-0.004	0.039	-9999	-10000	0	0
proBDNF (dimer)	-0.095	0.25	-9999	-0.74	62	62
NTRK1	-0.009	0.082	-9999	-0.74	6	6
RTN4R	-0.003	0.043	-9999	-0.66	2	2
neuron apoptosis	-0.031	0.16	-9999	-0.6	10	10
IRAK1	0	0	-9999	-10000	0	0
SHC1	-0.018	0.13	-9999	-0.55	9	9
ARHGDIA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.041	0.12	-9999	-0.48	15	15
MAGEH1	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.046	0.13	-9999	-0.48	20	20
Mammalian IAPs/DIABLO	-0.005	0.048	-9999	-0.43	6	6
proNGF (dimer)	-0.017	0.11	-9999	-0.7	12	12
MAGED1	0	0	-9999	-10000	0	0
APP	0	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.012	0.094	-9999	-0.74	8	8
ZNF274	0	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.033	0.1	-9999	-0.47	9	9
NGF	-0.017	0.11	-9999	-0.7	12	12
cell cycle arrest	-0.021	0.13	-9999	-0.51	6	6
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.018	0.06	-9999	-0.47	2	2
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.036	0.11	-9999	-0.48	8	8
NCSTN	0	0	-9999	-10000	0	0
mol:GTP	-0.039	0.12	-9999	-0.55	9	9
PSENEN	0	0	-9999	-10000	0	0
mol:ceramide	-0.015	0.12	-9999	-0.47	15	15
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.013	0.046	-9999	-0.37	2	2
p75(NTR)/beta APP	-0.034	0.11	-9999	-0.41	40	40
BEX1	-0.089	0.23	-9999	-0.68	63	63
mol:GDP	-0.026	0.13	-9999	-0.39	50	50
NGF (dimer)	-0.033	0.11	-9999	-0.5	17	17
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.055	0.13	-9999	-0.63	7	7
PIK3R1	0	0	-9999	-10000	0	0
RAC1/GTP	-0.034	0.1	-9999	-0.48	9	9
MYD88	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.039	0.12	-9999	-0.55	9	9
RHOB	-0.002	0.034	-9999	-0.74	1	1
RHOA	0	0	-9999	-10000	0	0
MAGE-G1/E2F1	0	0	-9999	-10000	0	0
NT3 (dimer)	-0.01	0.083	-9999	-0.69	7	7
TP53	-0.075	0.15	-9999	-0.67	7	7
PRDM4	-0.015	0.12	-9999	-0.47	15	15
BDNF (dimer)	-0.27	0.24	-9999	-0.65	84	84
PIK3CA	0	0	-9999	-10000	0	0
SORT1	-0.009	0.082	-9999	-0.74	6	6
activation of caspase activity	-0.037	0.11	-9999	-0.44	15	15
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.041	0.12	-9999	-0.48	15	15
RHOC	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.014	0.14	-9999	-0.57	8	8
DIABLO	0	0	-9999	-10000	0	0
SMPD2	-0.015	0.12	-9999	-0.47	15	15
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.045	0.13	-9999	-0.52	15	15
PSEN1	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.042	0.13	-9999	-0.43	47	47
MAPK8	-0.009	0.14	-9999	-0.56	6	6
MAPK9	-0.009	0.14	-9999	-0.56	6	6
APAF1	0	0	-9999	-10000	0	0
NTF3	-0.01	0.083	-9999	-0.69	7	7
NTF4	-0.012	0.095	-9999	-0.74	8	8
NDN	-0.009	0.082	-9999	-0.74	6	6
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.03	0.093	-9999	-0.65	2	2
p75 CTF/Sortilin/TRAF6/NRIF	-0.005	0.048	-9999	-0.43	6	6
RhoA-B-C/GTP	-0.039	0.12	-9999	-0.54	9	9
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.08	0.16	-9999	-0.71	7	7
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.086	0.18	-9999	-0.47	67	67
PRKACB	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.072	0.19	-9999	-0.56	62	62
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.009	0.082	-9999	-0.74	6	6
BIRC2	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.013	0.13	-9999	-0.45	13	13
BAD	-0.003	0.14	-9999	-0.55	6	6
RIPK2	0	0	-9999	-10000	0	0
NGFR	-0.047	0.16	-9999	-0.57	40	40
CYCS	-0.037	0.11	-9999	-0.69	2	2
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.035	0.11	-9999	-0.5	9	9
BCL2L11	-0.003	0.14	-9999	-0.55	6	6
BDNF (dimer)/p75(NTR)	-0.1	0.22	-9999	-0.53	96	96
PI3K	-0.035	0.11	-9999	-0.5	9	9
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.041	0.12	-9999	-0.48	15	15
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKCI	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.047	0.14	-9999	-0.45	50	50
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.041	0.12	-9999	-0.48	15	15
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
PLG	-0.004	0.045	-9999	-0.57	3	3
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.084	0.17	-9999	-0.62	17	17
SQSTM1	0	0	-9999	-10000	0	0
NGFRAP1	0	0	-9999	-10000	0	0
CASP3	0	0.13	-9999	-0.5	6	6
E2F1	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
IKK complex	-0.018	0.072	-9999	-0.51	2	2
NGF (dimer)/TRKA	-0.02	0.1	-9999	-0.53	18	18
MMP7	-0.038	0.15	-9999	-0.62	29	29
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.038	0.11	-9999	-0.55	4	4
MMP3	-0.34	0.28	-9999	-0.57	291	291
APAF-1/Caspase 9	-0.03	0.084	-9999	-0.54	3	3

×

PDGFR-alpha signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0	0.074	-9999	-0.71	5	5
PDGF/PDGFRA/CRKL	-0.006	0.053	-9999	-0.52	5	5
positive regulation of JUN kinase activity	-0.004	0.04	-9999	-0.42	4	4
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.097	0.21	-9999	-0.57	81	81
AP1	-0.13	0.34	-9999	-1.1	55	55
mol:IP3	0.01	0.06	-9999	-0.54	5	5
PLCG1	0.01	0.061	-9999	-0.54	5	5
PDGF/PDGFRA/alphaV Integrin	-0.006	0.053	-9999	-0.52	5	5
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.06	-9999	-0.54	5	5
CAV3	-0.12	0.27	-9999	-0.74	76	76
CAV1	-0.21	0.33	-9999	-0.74	135	135
SHC/Grb2/SOS1	-0.004	0.04	-9999	-0.42	4	4
PDGF/PDGFRA/Shf	-0.006	0.053	-9999	-0.52	5	5
FOS	-0.087	0.35	-9999	-1.1	55	55
JUN	-0.007	0.02	-9999	-10000	0	0
oligodendrocyte development	-0.006	0.053	-9999	-0.52	5	5
GRB2	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
mol:DAG	0.01	0.06	-9999	-0.54	5	5
PDGF/PDGFRA	0	0.074	-9999	-0.71	5	5
actin cytoskeleton reorganization	-0.006	0.053	-9999	-0.52	5	5
SRF	0.005	0.014	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.005	0.045	-9999	-0.47	4	4
PDGF/PDGFRA/Crk/C3G	-0.005	0.045	-9999	-0.47	4	4
JAK1	0.013	0.056	-9999	-0.52	5	5
ELK1/SRF	-0.006	0.04	-9999	-0.42	4	4
SHB	0	0	-9999	-10000	0	0
SHF	0	0	-9999	-10000	0	0
CSNK2A1	0.007	0.018	-9999	-10000	0	0
GO:0007205	0.011	0.062	-9999	-0.54	5	5
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.004	0.04	-9999	-0.42	4	4
PDGF/PDGFRA/SHB	-0.006	0.053	-9999	-0.52	5	5
PDGF/PDGFRA/Caveolin-1	-0.16	0.26	-9999	-0.57	138	138
ITGAV	0	0	-9999	-10000	0	0
ELK1	0.014	0.062	-9999	-0.52	4	4
PIK3CA	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.006	0.053	-9999	-0.52	5	5
JAK-STAT cascade	0.013	0.055	-9999	-0.52	5	5
cell proliferation	-0.006	0.053	-9999	-0.52	5	5

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.003	0.04	-9999	-0.51	3	3
CRKL	-0.025	0.12	-9999	-0.43	2	2
mol:PIP3	-0.016	0.006	-9999	-10000	0	0
AKT1	0.003	0.005	-9999	-10000	0	0
PTK2B	0	0	-9999	-10000	0	0
RAPGEF1	-0.017	0.11	-9999	-0.4	2	2
RANBP10	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.1	0.2	-9999	-0.48	103	103
MAP3K5	-0.01	0.11	-9999	-0.44	4	4
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.095	0.18	-9999	-0.44	103	103
AP1	-0.057	0.16	-9999	-0.5	55	55
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
apoptosis	-0.073	0.24	-9999	-0.73	55	55
STAT3 (dimer)	-0.033	0.13	-9999	-10000	0	0
GAB1/CRKL/SHP2/PI3K	-0.045	0.086	-9999	-10000	0	0
INPP5D	-0.002	0.034	-9999	-0.74	1	1
CBL/CRK	-0.018	0.11	-9999	-0.4	2	2
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
ELK1	-0.004	0.022	-9999	-0.24	3	3
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.039	0.076	-9999	-0.46	2	2
PAK1	0.009	0.014	-9999	-10000	0	0
HGF/MET/RANBP10	-0.1	0.2	-9999	-0.48	103	103
HRAS	-0.08	0.15	-9999	-0.59	4	4
DOCK1	-0.017	0.11	-9999	-0.4	2	2
GAB1	-0.034	0.12	-9999	-0.39	4	4
CRK	-0.025	0.12	-9999	-0.43	2	2
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.12	0.22	-9999	-0.54	103	103
JUN	0	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.054	0.1	-9999	-0.25	103	103
PIK3R1	0	0	-9999	-10000	0	0
cell morphogenesis	-0.01	0.14	-9999	-10000	0	0
GRB2/SHC	-0.045	0.088	-9999	-0.5	2	2
FOS	-0.085	0.24	-9999	-0.74	55	55
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.004	0.022	-9999	-0.24	3	3
HGF/MET/MUC20	-0.1	0.2	-9999	-0.48	104	104
cell migration	-0.044	0.087	-9999	-0.5	2	2
GRB2	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
MET/RANBP10	-0.003	0.04	-9999	-0.51	3	3
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.066	0.13	-9999	-10000	0	0
MET/MUC20	-0.003	0.041	-9999	-0.52	3	3
RAP1B	-0.009	0.1	-9999	-10000	0	0
RAP1A	-0.009	0.1	-9999	-10000	0	0
HGF/MET/RANBP9	-0.1	0.2	-9999	-0.48	103	103
RAF1	-0.044	0.16	-9999	-0.55	4	4
STAT3	-0.063	0.12	-9999	-10000	0	0
cell proliferation	-0.047	0.18	-9999	-0.52	4	4
RPS6KB1	-0.019	0.036	-9999	-10000	0	0
MAPK3	-0.007	0.019	-9999	-10000	0	0
MAPK1	-0.007	0.019	-9999	-0.23	2	2
RANBP9	0	0	-9999	-10000	0	0
MAPK8	0.008	0.095	-9999	-0.39	1	1
SRC	-0.061	0.12	-9999	-10000	0	0
PI3K	-0.045	0.088	-9999	-0.5	2	2
MET/Glomulin	-0.003	0.037	-9999	-0.46	3	3
SOS1	0	0	-9999	-10000	0	0
MAP2K1	-0.034	0.15	-9999	-0.5	4	4
MET	-0.004	0.054	-9999	-0.68	3	3
MAP4K1	-0.018	0.12	-9999	-0.47	4	4
PTK2	0	0	-9999	-10000	0	0
MAP2K2	-0.034	0.15	-9999	-0.59	2	2
BAD	0.009	0.005	-9999	-10000	0	0
MAP2K4	-0.002	0.1	-9999	-0.45	2	2
SHP2/GRB2/SOS1/GAB1	-0.047	0.091	-9999	-0.45	2	2
INPPL1	0	0	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
SH3KBP1	-0.003	0.048	-9999	-0.74	2	2
HGS	-0.048	0.095	-9999	-0.42	4	4
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.16	0.3	-9999	-0.74	101	101
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
PTPRJ	-0.003	0.048	-9999	-0.74	2	2
NCK/PLCgamma1	-0.051	0.098	-9999	-0.53	2	2
PDPK1	-0.006	0.006	-9999	-10000	0	0
HGF/MET/SHIP	-0.1	0.2	-9999	-0.48	103	103

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.054	0.13	-9999	-0.37	57	57
MAP3K8	0.005	0.048	-9999	-0.74	2	2
FOS	0.002	0.1	-9999	-0.46	6	6
PRKCA	0.006	0.049	-9999	-0.75	2	2
PTPN7	0.007	0.043	-9999	-0.66	2	2
HRAS	0	0	-9999	-10000	0	0
PRKCB	-0.028	0.16	-9999	-0.74	24	24
NRAS	0	0	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.009	0.061	-9999	-0.45	1	1
MAP2K1	-0.001	0.13	-9999	-0.52	25	25
ELK1	-0.001	0.004	-9999	-10000	0	0
BRAF	-0.03	0.12	-9999	-0.52	25	25
mol:GTP	-0.001	0.002	-9999	-0.006	55	55
MAPK1	0.009	0.061	-9999	-0.28	6	6
RAF1	-0.03	0.12	-9999	-0.52	25	25
KRAS	0	0	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	0	0.12	-10000	0	-0.48	25	25
ACTA1	-0.013	0.16	-10000	0	-0.64	25	25
NUMA1	0	0.12	-10000	0	-0.48	25	25
SPTAN1	-0.011	0.16	-10000	0	-0.64	25	25
LIMK1	-0.011	0.16	-10000	0	-0.64	25	25
BIRC3	-0.009	0.082	-10000	0	-0.74	6	6
BIRC2	0	0	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
CASP10	-0.012	0.16	-10000	0	-0.63	28	28
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0	0.12	-10000	0	-0.48	25	25
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.01	0.15	-10000	0	-0.62	25	25
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	-0.011	0.16	-10000	0	-0.64	25	25
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	-0.069	0.12	-10000	0	-0.78	12	12
BID	0.004	0.075	-10000	0	-0.3	27	27
MAP3K1	0.003	0.047	-10000	0	-0.23	10	10
TRADD	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.012	0.16	-10000	0	-0.63	26	26
CASP9	0.001	0.002	-10000	0	-10000	0	0
DNA repair	-0.002	0.034	-10000	0	-0.21	2	2
neuron apoptosis	0.019	0.016	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.004	0.15	-10000	0	-0.61	25	25
APAF1	0.001	0.003	-10000	0	-10000	0	0
CASP6	0.017	0.073	-10000	0	-0.51	2	2
TRAF2	0	0	-10000	0	-10000	0	0
ICAD/CAD	-0.004	0.15	-10000	0	-0.61	25	25
CASP7	-0.005	0.043	0.36	6	-10000	0	6
KRT18	0.013	0.02	-10000	0	-10000	0	0
apoptosis	-0.003	0.15	-10000	0	-0.57	25	25
DFFA	-0.011	0.16	-10000	0	-0.64	25	25
DFFB	-0.011	0.16	-10000	0	-0.64	25	25
PARP1	0.002	0.035	0.21	2	-10000	0	2
actin filament polymerization	0.002	0.14	0.58	25	-10000	0	25
TNF	-0.02	0.12	-10000	0	-0.73	13	13
CYCS	0.007	0.056	-10000	0	-0.27	11	11
SATB1	0.02	0.079	-10000	0	-0.62	2	2
SLK	-0.011	0.16	-10000	0	-0.64	25	25
p15 BID/BAX	-0.015	0.062	-10000	0	-0.34	10	10
CASP2	0.034	0.052	-10000	0	-0.44	1	1
JNK cascade	-0.003	0.047	0.23	10	-10000	0	10
CASP3	-0.019	0.17	-10000	0	-0.68	25	25
LMNB2	0.032	0.049	-10000	0	-0.48	1	1
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.002	0.034	-10000	0	-0.74	1	1
Mammalian IAPs/DIABLO	-0.005	0.048	-10000	0	-0.43	6	6
negative regulation of DNA binding	-0.068	0.12	-10000	0	-0.77	12	12
stress fiber formation	-0.01	0.15	-10000	0	-0.62	25	25
GZMB	-0.022	0.18	-10000	0	-0.73	27	27
CASP1	0.011	0.052	-10000	0	-0.73	2	2
LMNB1	0.032	0.049	-10000	0	-0.48	1	1
APP	0.019	0.016	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.01	0	-10000	0	-10000	0	0
VIM	-0.008	0.14	-10000	0	-0.56	25	25
LMNA	0.032	0.049	-10000	0	-0.48	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.009	0.047	-10000	0	-0.47	1	1
LRDD	-0.002	0.034	-10000	0	-0.74	1	1
SREBF1	-0.011	0.16	-10000	0	-0.64	25	25
APAF-1/Caspase 9	-0.003	0.022	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0	0.12	-10000	0	-0.47	25	25
CFL2	-0.003	0.15	-10000	0	-0.6	25	25
GAS2	-0.063	0.22	-10000	0	-0.52	71	71
positive regulation of apoptosis	0.034	0.049	-10000	0	-0.47	1	1
PRF1	-0.038	0.16	-10000	0	-0.74	25	25

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.007	0.013	-10000	0	-10000	0	0
HSPA8	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.024	0.11	-10000	0	-0.52	21	21
AKT1	0.006	0.021	-10000	0	-10000	0	0
GSC	-0.038	0.13	-10000	0	-0.44	9	9
NKX2-5	-0.29	0.28	-10000	0	-0.57	247	247
muscle cell differentiation	0.092	0.097	0.44	6	-10000	0	6
SMAD2-3/SMAD4/SP1	-0.009	0.034	-10000	0	-10000	0	0
SMAD4	0.017	0.026	-10000	0	-10000	0	0
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0	0	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.01	0.035	-10000	0	-0.46	1	1
SMAD3/SMAD4/VDR	0.009	0.033	-10000	0	-10000	0	0
MYC	0.007	0.024	-10000	0	-10000	0	0
CDKN2B	-0.093	0.41	-10000	0	-1.4	41	41
AP1	-0.036	0.12	-10000	0	-0.41	11	11
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0	0.005	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.029	0.088	-10000	0	-0.42	4	4
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.048	0.17	-10000	0	-0.58	44	44
SMAD3/SMAD4/GR	-0.003	0.014	-10000	0	-10000	0	0
GATA3	-0.026	0.13	-10000	0	-0.71	17	17
SKI/SIN3/HDAC complex/NCoR1	0	0	-10000	0	-10000	0	0
MEF2C/TIF2	-0.17	0.19	-10000	0	-0.68	31	31
endothelial cell migration	-0.013	0.023	-10000	0	-10000	0	0
MAX	0	0	-10000	0	-10000	0	0
RBBP7	0	0	-10000	0	-10000	0	0
RBBP4	0	0	-10000	0	-10000	0	0
RUNX2	0	0	-10000	0	-10000	0	0
RUNX3	0	0	-10000	0	-10000	0	0
RUNX1	0	0	-10000	0	-10000	0	0
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	0	0	-10000	0	-10000	0	0
VDR	-0.002	0.034	-10000	0	-0.74	1	1
CDKN1A	0.058	0.042	-10000	0	-10000	0	0
KAT2B	0	0.048	-10000	0	-0.74	2	2
SMAD2/SMAD2/SMAD4/FOXH1	-0.046	0.11	-10000	0	-0.47	13	13
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0	-10000	0	-10000	0	0
SERPINE1	0.013	0.023	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	-0.001	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.001	0.017	-10000	0	-10000	0	0
SAP30	0	0	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.016	0.031	-10000	0	-10000	0	0
JUN	0.007	0.13	-10000	0	-0.4	10	10
SMAD3/SMAD4/IRF7	-0.004	0.039	-10000	0	-0.54	2	2
TFE3	0.016	0.001	-10000	0	-10000	0	0
COL1A2	0.005	0.051	-10000	0	-0.4	4	4
mesenchymal cell differentiation	0.001	0.017	-10000	0	-10000	0	0
DLX1	-0.33	0.28	-10000	0	-0.57	276	276
TCF3	0	0	-10000	0	-10000	0	0
FOS	-0.071	0.24	-10000	0	-0.73	55	55
SMAD3/SMAD4/Max	-0.003	0.014	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0	0.016	-10000	0	-10000	0	0
ZBTB17	0.006	0.019	-10000	0	-10000	0	0
LAMC1	0.048	0.028	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.017	-10000	0	-10000	0	0
IRF7	-0.003	0.048	-10000	0	-0.74	2	2
ESR1	-0.032	0.15	-10000	0	-0.74	21	21
HNF4A	-0.009	0.073	-10000	0	-0.57	8	8
MEF2C	-0.16	0.22	-10000	0	-0.71	31	31
SMAD2-3/SMAD4	-0.009	0.029	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.011	0.021	-10000	0	-10000	0	0
IGHV3OR16-13	0	0.001	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	0.005	0.01	-10000	0	-10000	0	0
SKIL	0	0	-10000	0	-10000	0	0
HDAC1	0	0	-10000	0	-10000	0	0
HDAC2	0	0	-10000	0	-10000	0	0
SNIP1	-0.001	0.026	-10000	0	-0.58	1	1
GCN5L2	0.003	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.004	0.022	-10000	0	-10000	0	0
MSG1/HSC70	-0.002	0.032	-10000	0	-0.49	2	2
SMAD2	0.004	0.027	-10000	0	-10000	0	0
SMAD3	0.019	0.022	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.039	0.027	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.013	0.029	-10000	0	-0.4	2	2
NCOR1	0	0	-10000	0	-10000	0	0
NCOA2	-0.002	0.034	-10000	0	-0.74	1	1
NCOA1	0	0	-10000	0	-10000	0	0
MYOD/E2A	-0.059	0.14	-10000	0	-0.41	69	69
SMAD2-3/SMAD4/SP1/MIZ-1	0.016	0.052	-10000	0	-10000	0	0
IFNB1	0.035	0.049	-10000	0	-0.48	3	3
SMAD3/SMAD4/MEF2C	-0.17	0.19	-10000	0	-0.69	31	31
CITED1	-0.003	0.043	-10000	0	-0.66	2	2
SMAD2-3/SMAD4/ARC105	-0.007	0.023	-10000	0	-10000	0	0
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.011	0.15	-10000	0	-0.48	41	41
RUNX1-3/PEBPB2	0	0	-10000	0	-10000	0	0
SMAD7	-0.024	0.1	-10000	0	-1.1	1	1
MYC/MIZ-1	0.013	0.042	-10000	0	-10000	0	0
SMAD3/SMAD4	0.035	0.072	0.29	6	-10000	0	6
IL10	0.026	0.11	-10000	0	-0.71	5	5
PIASy/HDAC complex	0.005	0.005	-10000	0	-10000	0	0
PIAS3	0.004	0.007	-10000	0	-10000	0	0
CDK2	0.005	0.01	-10000	0	-10000	0	0
IL5	0.023	0.096	-10000	0	-0.5	6	6
CDK4	0.005	0.028	-10000	0	-0.57	1	1
PIAS4	0.006	0.005	-10000	0	-10000	0	0
ATF3	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1	0.002	0.027	-10000	0	-10000	0	0
FOXG1	-0.061	0.18	-10000	0	-0.57	51	51
FOXO3	0.015	0.028	-10000	0	-10000	0	0
FOXO1	0.015	0.028	-10000	0	-10000	0	0
FOXO4	0.015	0.028	-10000	0	-10000	0	0
heart looping	-0.16	0.22	-10000	0	-0.7	31	31
CEBPB	0.008	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.2	0.18	-10000	0	-0.4	56	56
MYOD1	-0.082	0.2	-10000	0	-0.57	69	69
SMAD3/SMAD4/HNF4	-0.007	0.048	-10000	0	-0.38	1	1
SMAD3/SMAD4/GATA3	-0.02	0.094	-10000	0	-0.51	15	15
SnoN/SIN3/HDAC complex/NCoR1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.001	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.004	0.025	-10000	0	-10000	0	0
MED15	0	0	-10000	0	-10000	0	0
SP1	0.017	0.011	-10000	0	-10000	0	0
SIN3B	0	0	-10000	0	-10000	0	0
SIN3A	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.2	0.19	-10000	0	-0.65	33	33
ITGB5	0.056	0.034	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.11	0.2	-10000	0	-0.5	101	101
AR	-0.16	0.3	-10000	0	-0.74	101	101
negative regulation of cell growth	0.004	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.052	0.13	-10000	0	-0.41	14	14
E2F5	0	0	-10000	0	-10000	0	0
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.031	0.088	-10000	0	-0.55	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	-0.019	0.095	-10000	0	-0.35	8	8
TFDP1	-0.004	0.045	-10000	0	-0.57	3	3
SMAD3/SMAD4/AP1	-0.035	0.12	-10000	0	-0.41	9	9
SMAD3/SMAD4/RUNX2	-0.001	0.017	-10000	0	-10000	0	0
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0	0	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.1	0.26	-9999	-0.74	66	66
GNB1/GNG2	-0.042	0.086	-9999	-0.47	7	7
mol:DAG	-0.002	0.095	-9999	-0.48	4	4
PLCG1	-0.038	0.08	-9999	-0.5	4	4
YES1	-0.04	0.077	-9999	-0.45	1	1
FZD3	0	0	-9999	-10000	0	0
FZD6	0	0	-9999	-10000	0	0
G protein	-0.038	0.081	-9999	-0.51	4	4
MAP3K7	-0.015	0.14	-9999	-0.54	13	13
mol:Ca2+	-0.002	0.093	-9999	-0.47	4	4
mol:IP3	-0.002	0.095	-9999	-0.48	4	4
NLK	-0.003	0.007	-9999	-10000	0	0
GNB1	-0.002	0.034	-9999	-0.74	1	1
CAMK2A	-0.025	0.15	-9999	-0.58	14	14
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.044	0.085	-9999	-0.31	24	24
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.04	0.077	-9999	-0.45	1	1
GO:0007205	-0.001	0.094	-9999	-0.42	7	7
WNT6	-0.096	0.21	-9999	-0.57	81	81
WNT4	-0.011	0.085	-9999	-0.66	8	8
NFAT1/CK1 alpha	-0.08	0.14	-9999	-0.54	17	17
GNG2	-0.008	0.075	-9999	-0.74	5	5
WNT5A	-0.012	0.084	-9999	-0.59	10	10
WNT11	-0.038	0.16	-9999	-0.68	27	27
CDC42	-0.004	0.088	-9999	-0.43	1	1

×

FAS signaling pathway (CD95)

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
SPTAN1	0.002	0.02	-10000	0	-10000	0	0
RFC1	0.002	0.02	-10000	0	-10000	0	0
PRKDC	0.002	0.02	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	-0.012	0.037	0.26	1	-10000	0	1
FASLG/FAS/FADD/FAF1	-0.018	0.075	0.24	5	-0.34	20	25
MAP2K4	-0.012	0.13	-10000	0	-0.5	8	8
mol:ceramide	-0.007	0.11	-10000	0	-0.44	21	21
GSN	0.002	0.02	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.027	0.09	0.22	3	-0.41	21	24
FAS	0.007	0.035	-10000	0	-0.76	1	1
BID	0.003	0.029	0.31	4	-10000	0	4
MAP3K1	0.003	0.079	-10000	0	-10000	0	0
MAP3K7	0	0	-10000	0	-10000	0	0
RB1	0.002	0.02	-10000	0	-10000	0	0
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.11	0.2	-10000	0	-0.48	107	107
ARHGDIB	0.001	0.023	-10000	0	-0.32	1	1
FADD	0.009	0.004	-10000	0	-10000	0	0
actin filament polymerization	-0.002	0.02	-10000	0	-10000	0	0
NFKB1	-0.039	0.08	-10000	0	-0.29	7	7
MAPK8	-0.033	0.19	-10000	0	-0.44	80	80
DFFA	0.002	0.02	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.002	0.02	-10000	0	-10000	0	0
FAS/FADD/MET	-0.004	0.041	-10000	0	-0.49	3	3
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.005	0.072	-10000	0	-0.7	5	5
FAF1	0.009	0.004	-10000	0	-10000	0	0
PARP1	0.002	0.02	-10000	0	-10000	0	0
DFFB	0.002	0.02	-10000	0	-10000	0	0
CHUK	-0.034	0.07	-10000	0	-10000	0	0
FASLG	-0.022	0.15	-10000	0	-0.75	20	20
FAS/FADD	-0.002	0.027	-10000	0	-0.58	1	1
HGF	-0.16	0.3	-10000	0	-0.74	101	101
LMNA	0.002	0.018	-10000	0	-10000	0	0
CASP6	0.002	0.02	-10000	0	-10000	0	0
CASP10	0.007	0.034	-10000	0	-0.74	1	1
CASP3	0.003	0.023	0.23	4	-10000	0	4
PTPN13	-0.006	0.067	-10000	0	-0.74	4	4
CASP8	0.004	0.041	0.43	4	-10000	0	4
IL6	-0.2	0.51	-10000	0	-1.3	82	82
MET	-0.004	0.054	-10000	0	-0.68	3	3
ICAD/CAD	0.002	0.019	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.008	0.12	-10000	0	-0.44	21	21
activation of caspase activity by cytochrome c	0.003	0.029	0.31	4	-10000	0	4
PAK2	0.002	0.02	-10000	0	-10000	0	0
BCL2	0.001	0.026	-10000	0	-0.57	1	1

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.014	0.085	-9999	-0.51	13	13
EPHB2	-0.009	0.073	-9999	-0.57	8	8
Syndecan-2/TACI	-0.013	0.072	-9999	-0.41	15	15
LAMA1	-0.17	0.26	-9999	-0.57	141	141
Syndecan-2/alpha2 ITGB1	-0.013	0.07	-9999	-0.4	15	15
HRAS	0	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.003	0.038	-9999	-0.48	3	3
ITGA5	0	0	-9999	-10000	0	0
BAX	0.032	0.036	-9999	-10000	0	0
EPB41	0	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.003	0.034	-9999	-0.44	3	3
LAMA3	-0.018	0.12	-9999	-0.74	12	12
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.022	0.12	-9999	-0.74	14	14
Syndecan-2/MMP2	-0.007	0.064	-9999	-0.55	6	6
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0	0	-9999	-10000	0	0
dendrite morphogenesis	-0.009	0.057	-9999	-0.38	11	11
Syndecan-2/GM-CSF	-0.053	0.15	-9999	-0.48	53	53
determination of left/right symmetry	0.014	0.045	-9999	-0.56	3	3
Syndecan-2/PKC delta	-0.003	0.038	-9999	-0.48	3	3
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	-0.023	0.14	-9999	-0.43	53	53
MAPK1	-0.023	0.14	-9999	-0.43	53	53
Syndecan-2/RACK1	-0.003	0.032	-9999	-0.41	3	3
NF1	0	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.014	0.045	-9999	-0.56	3	3
ITGA2	0	0	-9999	-10000	0	0
MAPK8	0.027	0.04	-9999	-0.47	3	3
Syndecan-2/alpha2/beta1 Integrin	-0.085	0.13	-9999	-0.5	3	3
Syndecan-2/Kininogen	-0.012	0.065	-9999	-0.37	15	15
ITGB1	0	0	-9999	-10000	0	0
SRC	-0.002	0.03	-9999	-0.38	3	3
Syndecan-2/CASK/Protein 4.1	-0.003	0.035	-9999	-0.44	3	3
extracellular matrix organization	-0.003	0.037	-9999	-0.48	3	3
actin cytoskeleton reorganization	-0.014	0.085	-9999	-0.51	13	13
Syndecan-2/Caveolin-2/Ras	-0.015	0.085	-9999	-0.46	16	16
Syndecan-2/Laminin alpha3	-0.015	0.083	-9999	-0.48	15	15
Syndecan-2/RasGAP	-0.002	0.03	-9999	-0.39	3	3
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.009	0.058	-9999	-0.38	11	11
GO:0007205	0	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.029	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.016	0.099	-9999	-0.63	12	12
RASA1	0	0	-9999	-10000	0	0
alpha2/beta1 Integrin	0	0	-9999	-10000	0	0
Syndecan-2/Synbindin	-0.003	0.038	-9999	-0.48	3	3
TGFB1	0	0	-9999	-10000	0	0
CASP3	0.025	0.036	-9999	-0.43	3	3
FN1	-0.017	0.11	-9999	-0.74	11	11
Syndecan-2/IL8	-0.018	0.087	-9999	-0.4	22	22
SDC2	0.014	0.045	-9999	-0.56	3	3
KNG1	-0.014	0.089	-9999	-0.57	12	12
Syndecan-2/Neurofibromin	-0.003	0.038	-9999	-0.48	3	3
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.077	0.23	-9999	-0.74	50	50
Syndecan-2/TGFB1	-0.003	0.038	-9999	-0.48	3	3
Syndecan-2/Syntenin/PI-4-5-P2	-0.003	0.035	-9999	-0.44	3	3
Syndecan-2/Ezrin	-0.003	0.034	-9999	-0.43	3	3
PRKACA	0.025	0.036	-9999	-0.43	3	3
angiogenesis	-0.018	0.086	-9999	-0.4	22	22
MMP2	-0.006	0.067	-9999	-0.74	4	4
IL8	-0.025	0.12	-9999	-0.61	20	20
calcineurin-NFAT signaling pathway	-0.013	0.072	-9999	-0.41	15	15

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.006	0.039	-9999	-0.42	4	4
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.059	0.17	-9999	-0.56	50	50
STXBP1	-0.005	0.058	-9999	-0.74	3	3
ACh/CHRNA1	-0.015	0.074	-9999	-0.42	14	14
RAB3GAP2/RIMS1/UNC13B	-0.05	0.15	-9999	-0.49	49	49
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.073	0.22	-9999	-0.74	48	48
mol:ACh	0.005	0.025	-9999	-0.15	11	11
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.043	0.12	-9999	-0.65	3	3
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.015	0.073	-9999	-0.42	14	14
UNC13B	-0.005	0.058	-9999	-0.74	3	3
CHRNA1	-0.018	0.11	-9999	-0.63	14	14
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.015	0.071	-9999	-0.39	16	16
SNAP25	-0.007	0.05	-9999	-0.32	11	11
VAMP2	0	0	-9999	-10000	0	0
SYT1	-0.019	0.1	-9999	-0.57	16	16
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.006	0.05	-9999	-0.41	7	7
STX1A/SNAP25 fragment 1/VAMP2	-0.043	0.12	-9999	-0.65	3	3

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0	0	-9999	-10000	0	0
EGFR	-0.022	0.12	-9999	-0.63	17	17
EGF/EGFR	-0.056	0.15	-9999	-0.45	52	52
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.019	0.084	-9999	-0.81	1	1
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.008	0.075	-9999	-0.74	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.014	0.099	-9999	-0.69	10	10
EGF/EGFR dimer/SHC	-0.023	0.099	-9999	-0.52	12	12
mol:GDP	-0.019	0.083	-9999	-0.8	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.063	0.21	-9999	-0.74	41	41
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.017	0.076	-9999	-0.74	1	1
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.018	0.077	-9999	-0.75	1	1
FRAP1	-0.018	0.08	-9999	-0.77	1	1
EGF/EGFR dimer	-0.027	0.12	-9999	-0.5	26	26
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.053	0.16	-9999	-0.56	46	46

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.033	0.12	-9999	-0.47	34	34
MAP4K1	-0.006	0.067	-9999	-0.74	4	4
MAP3K8	-0.003	0.048	-9999	-0.74	2	2
PRKCB	-0.037	0.16	-9999	-0.74	24	24
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	0.015	0.097	-9999	-0.72	3	3
JUN	-0.005	0.16	-9999	-0.66	24	24
MAP3K7	0.015	0.097	-9999	-0.72	3	3
GRAP2	-0.04	0.17	-9999	-0.74	26	26
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.022	0.099	-9999	-0.77	3	3
LAT	0	0	-9999	-10000	0	0
LCP2	-0.011	0.089	-9999	-0.74	7	7
MAPK8	-0.012	0.16	-9999	-0.7	24	24
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.024	0.094	-9999	-0.76	3	3
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.031	0.12	-9999	-0.81	3	3

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.029	0.12	-9999	-0.56	25	25
PDGFRB	0.008	0.034	-9999	-0.74	1	1
SPHK1	-0.008	0.021	-9999	-10000	0	0
mol:S1P	-0.01	0.029	-9999	-10000	0	0
S1P1/S1P/Gi	-0.001	0.14	-9999	-0.59	7	7
GNAO1	0.006	0.051	-9999	-0.64	3	3
PDGFB-D/PDGFRB/PLCgamma1	-0.04	0.1	-9999	-0.5	8	8
PLCG1	0.006	0.13	-9999	-0.54	7	7
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.034	-9999	-0.74	1	1
GNAI2	0.01	0.004	-9999	-10000	0	0
GNAI3	0.009	0.004	-9999	-10000	0	0
GNAI1	0.008	0.035	-9999	-0.75	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.011	0.11	-9999	-0.48	25	25
S1P1/S1P	-0.031	0.091	-9999	-0.38	25	25
negative regulation of cAMP metabolic process	0	0.13	-9999	-0.57	7	7
MAPK3	-0.011	0.19	-9999	-0.55	49	49
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.038	0.16	-9999	-0.74	25	25
PLCB2	0.004	0.11	-9999	-0.45	9	9
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.027	0.077	-9999	-0.41	7	7
receptor internalization	-0.03	0.085	-9999	-0.36	25	25
PTGS2	-0.061	0.34	-9999	-1.1	49	49
Rac1/GTP	-0.027	0.077	-9999	-0.41	7	7
RHOA	0	0	-9999	-10000	0	0
VEGFA	0	0.001	-9999	-10000	0	0
negative regulation of T cell proliferation	0	0.13	-9999	-0.57	7	7
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0	0.084	-9999	-0.74	6	6
MAPK1	-0.011	0.19	-9999	-0.55	49	49
S1P1/S1P/PDGFB-D/PDGFRB	0.006	0.11	-9999	-0.56	7	7
ABCC1	-0.001	0.026	-9999	-0.57	1	1

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0	0	-9999	-10000	0	0
epithelial cell differentiation	0	0	-9999	-10000	0	0
CYFIP2	-0.023	0.13	-9999	-0.74	15	15
ENAH	0.058	0.023	-9999	-10000	0	0
EGFR	-0.022	0.12	-9999	-0.63	17	17
EPHA2	-0.005	0.058	-9999	-0.74	3	3
MYO6	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.015	0.083	-9999	-0.48	15	15
AQP5	-0.17	0.25	-9999	-0.55	149	149
CTNND1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.11	0.17	-9999	-0.38	136	136
EGF	-0.014	0.099	-9999	-0.69	10	10
NCKAP1	0	0	-9999	-10000	0	0
AQP3	-0.08	0.19	-9999	-0.55	70	70
cortical microtubule organization	0	0	-9999	-10000	0	0
GO:0000145	0.033	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
MLLT4	0	0	-9999	-10000	0	0
ARF6/GDP	-0.002	0.025	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.034	-9999	-0.43	3	3
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.044	0	-9999	-10000	0	0
PVRL2	0	0	-9999	-10000	0	0
ZYX	0	0	-9999	-10000	0	0
ARF6/GTP	-0.002	0.031	-9999	-0.4	3	3
CDH1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.017	0.077	-9999	-0.76	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
actin cytoskeleton organization	0.039	0	-9999	-10000	0	0
IGF-1R heterotetramer	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
IGF1R	0	0	-9999	-10000	0	0
IGF1	-0.024	0.13	-9999	-0.73	16	16
DIAPH1	-0.02	0.11	-9999	-0.64	15	15
Wnt receptor signaling pathway	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
RhoA/GTP	-0.002	0.025	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
VCL	0.04	0	-9999	-10000	0	0
EFNA1	0	0	-9999	-10000	0	0
LPP	0.04	0	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.002	0.029	-9999	-10000	0	0
SEC6/SEC8	0	0	-9999	-10000	0	0
MGAT3	-0.11	0.18	-9999	-0.39	136	136
HGF/MET	-0.08	0.15	-9999	-10000	0	0
HGF	-0.16	0.3	-9999	-0.74	101	101
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0	0	-9999	-10000	0	0
actin cable formation	0.068	0.028	-9999	-10000	0	0
KIAA1543	0.039	0.019	-9999	-10000	0	0
KIFC3	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
EXOC3	0	0	-9999	-10000	0	0
ACTN1	0	0	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
EXOC4	0	0	-9999	-10000	0	0
STX4	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
LIMA1	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
ROCK1	-0.002	0.022	-9999	-10000	0	0
adherens junction assembly	0.052	0.019	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.012	0.065	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	-0.004	0.054	-9999	-0.68	3	3
PLEKHA7	0	0	-9999	-10000	0	0
mol:GTP	-0.003	0.034	-9999	-0.43	3	3
establishment of epithelial cell apical/basal polarity	0	0	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0.039	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0	0	-9999	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.014	0.094	-10000	0	-0.47	10	10
IKBKB	0.015	0.051	-10000	0	-0.27	3	3
AKT1	0.003	0.085	-10000	0	-0.27	17	17
IKBKG	0.017	0.053	-10000	0	-0.28	5	5
CALM1	-0.009	0.097	-10000	0	-0.49	12	12
PIK3CA	0	0	-10000	0	-10000	0	0
MAP3K1	0	0.14	-10000	0	-0.7	11	11
MAP3K7	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.1	0.23	2	-0.53	12	14
DOK1	0	0	-10000	0	-10000	0	0
AP-1	-0.001	0.08	0.18	3	-0.26	9	12
LYN	-0.003	0.048	-10000	0	-0.74	2	2
BLNK	-0.002	0.034	-10000	0	-0.74	1	1
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.03	0.12	-10000	0	-0.52	28	28
CD22	-0.076	0.21	-10000	0	-0.62	51	51
CAMK2G	-0.002	0.091	-10000	0	-0.64	5	5
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	-0.001	0.034	-10000	0	-0.74	1	1
SHC/GRB2/SOS1	-0.021	0.091	-10000	0	-0.74	3	3
GO:0007205	-0.018	0.1	-10000	0	-0.54	12	12
SYK	-0.002	0.034	-10000	0	-0.74	1	1
ELK1	-0.01	0.099	-10000	0	-0.5	12	12
NFATC1	-0.007	0.12	-10000	0	-0.54	14	14
B-cell antigen/BCR complex	-0.03	0.12	-10000	0	-0.52	28	28
PAG1/CSK	-0.007	0.062	-10000	0	-0.56	6	6
NFKBIB	0.014	0.019	0.078	2	-10000	0	2
HRAS	-0.002	0.094	-10000	0	-0.48	12	12
NFKBIA	0.014	0.019	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.018	0.016	-10000	0	-10000	0	0
RasGAP/Csk	-0.029	0.12	-10000	0	-0.77	6	6
mol:GDP	-0.019	0.1	-10000	0	-0.52	12	12
PTEN	0	0	-10000	0	-10000	0	0
CD79B	-0.006	0.064	-10000	0	-0.7	4	4
NF-kappa-B/RelA/I kappa B alpha	0.018	0.016	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.015	0.14	-10000	0	-0.56	18	18
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.026	0.1	0.23	4	-0.55	12	16
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.047	0.16	-10000	0	-0.41	64	64
CHUK	0.017	0.053	-10000	0	-0.28	5	5
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.022	0.081	-10000	0	-0.61	6	6
PTPN6	-0.07	0.2	-10000	0	-0.78	25	25
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0.015	0.024	-10000	0	-0.12	11	11
VAV2	-0.059	0.16	-10000	0	-0.83	13	13
ubiquitin-dependent protein catabolic process	0.018	0.019	0.081	2	-10000	0	2
BTK	-0.11	0.33	-10000	0	-1.1	45	45
CD19	-0.066	0.17	-10000	0	-0.66	23	23
MAP4K1	-0.006	0.067	-10000	0	-0.74	4	4
CD72	-0.001	0.026	-10000	0	-0.57	1	1
PAG1	-0.009	0.082	-10000	0	-0.74	6	6
MAPK14	0.01	0.12	-10000	0	-0.59	10	10
SH3BP5	-0.011	0.089	-10000	0	-0.74	7	7
PIK3AP1	-0.012	0.13	-10000	0	-0.68	12	12
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.032	0.13	-10000	0	-0.61	18	18
RAF1	0.005	0.088	-10000	0	-0.62	5	5
RasGAP/p62DOK/SHIP	-0.028	0.12	-10000	0	-0.74	7	7
CD79A	-0.035	0.15	-10000	0	-0.66	26	26
re-entry into mitotic cell cycle	-0.001	0.08	0.18	3	-0.26	9	12
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.018	0.074	-10000	0	-0.49	5	5
MAPK1	0.018	0.074	-10000	0	-0.49	5	5
CD72/SHP1	-0.065	0.18	-10000	0	-0.72	25	25
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.01	0.12	-10000	0	-0.59	10	10
actin cytoskeleton organization	-0.014	0.15	-10000	0	-0.67	13	13
NF-kappa-B/RelA	0.039	0.031	0.16	2	-10000	0	2
Calcineurin	-0.02	0.073	-10000	0	-0.57	5	5
PI3K	-0.064	0.14	-10000	0	-0.6	17	17
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.023	0.1	0.26	4	-0.53	12	16
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.038	0.16	-10000	0	-0.91	12	12
DAPP1	-0.042	0.18	-10000	0	-1.1	11	11
cytokine secretion	-0.005	0.11	-10000	0	-0.5	14	14
mol:DAG	-0.026	0.1	0.23	4	-0.55	12	16
PLCG2	0	0	-10000	0	-10000	0	0
MAP2K1	0.012	0.082	-10000	0	-0.55	5	5
B-cell antigen/BCR complex/FcgammaRIIB	-0.034	0.14	-10000	0	-0.59	21	21
mol:PI-3-4-5-P3	-0.047	0.099	-10000	0	-0.4	17	17
ETS1	-0.004	0.11	-10000	0	-0.51	16	16
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.025	0.11	-10000	0	-0.48	18	18
B-cell antigen/BCR complex/LYN	-0.042	0.16	-10000	0	-0.74	17	17
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0.002	-10000	0	-10000	0	0
RAC1	-0.016	0.16	-10000	0	-0.73	13	13
B-cell antigen/BCR complex/LYN/SYK	-0.068	0.19	-10000	0	-0.75	25	25
CARD11	-0.012	0.11	-10000	0	-0.55	12	12
FCGR2B	-0.014	0.1	-10000	0	-0.74	9	9
PPP3CA	0	0	-10000	0	-10000	0	0
BCL10	0	0	-10000	0	-10000	0	0
IKK complex	0.016	0.026	-10000	0	-10000	0	0
PTPRC	-0.048	0.18	-10000	0	-0.74	31	31
PDPK1	-0.031	0.067	-10000	0	-0.27	14	14
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.018	0.013	-10000	0	-0.1	1	1

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.028	0.11	0.45	30	-10000	0	30
KIRREL	-0.005	0.091	-10000	0	-0.75	7	7
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.028	0.11	-10000	0	-0.45	30	30
PLCG1	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.022	0.084	-10000	0	-0.46	8	8
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.012	0.051	-10000	0	-0.34	7	7
FYN	-0.02	0.08	-10000	0	-0.46	8	8
mol:Ca2+	-0.021	0.083	-10000	0	-0.45	8	8
mol:DAG	-0.022	0.084	-10000	0	-0.46	8	8
NPHS2	-0.003	0.048	-10000	0	-0.58	3	3
mol:IP3	-0.022	0.084	-10000	0	-0.46	8	8
regulation of endocytosis	-0.018	0.074	-10000	0	-0.43	8	8
Nephrin/NEPH1/podocin/Cholesterol	-0.022	0.086	-10000	0	-0.46	8	8
establishment of cell polarity	-0.028	0.11	-10000	0	-0.45	30	30
Nephrin/NEPH1/podocin/NCK1-2	-0.019	0.075	-10000	0	-0.51	2	2
Nephrin/NEPH1/beta Arrestin2	-0.019	0.075	-10000	0	-0.44	8	8
NPHS1	-0.021	0.12	-10000	0	-0.57	23	23
Nephrin/NEPH1/podocin	-0.02	0.081	-10000	0	-0.47	8	8
TJP1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
NCK2	0	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.022	0.084	-10000	0	-0.46	8	8
CD2AP	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.022	0.084	-10000	0	-0.46	8	8
GRB2	0	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.02	0.13	-10000	0	-0.49	26	26
cytoskeleton organization	-0.015	0.064	-10000	0	-0.51	1	1
Nephrin/NEPH1	-0.02	0.079	-10000	0	-0.32	30	30
Nephrin/NEPH1/ZO-1	-0.022	0.087	-10000	0	-0.46	8	8

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.006	0.006	-9999	-10000	0	0
HDAC2	0.006	0.006	-9999	-10000	0	0
GNB1/GNG2	-0.007	0.058	-9999	-0.45	8	8
forebrain development	-0.089	0.14	-9999	-0.49	9	9
GNAO1	0.001	0.051	-9999	-0.63	3	3
SMO/beta Arrestin2	-0.002	0.027	-9999	-0.42	2	2
SMO	0.003	0.038	-9999	-0.58	2	2
ARRB2	0.005	0.005	-9999	-10000	0	0
GLI3/SPOP	0.043	0.015	-9999	-10000	0	0
mol:GTP	-0.003	0.004	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0.005	0.005	-9999	-10000	0	0
SIN3/HDAC complex	0	0.004	-9999	-10000	0	0
GNAI1	0.004	0.035	-9999	-0.75	1	1
XPO1	0.006	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.11	0.11	-9999	-0.58	3	3
SAP30	0.006	0.006	-9999	-10000	0	0
mol:GDP	0.003	0.038	-9999	-0.58	2	2
MIM/GLI2A	-0.033	0.05	-9999	-10000	0	0
IFT88	0	0	-9999	-10000	0	0
GNAI3	0.005	0.005	-9999	-10000	0	0
GLI2	0.037	0.021	-9999	-10000	0	0
GLI3	0.04	0.016	-9999	-10000	0	0
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0.006	0.006	-9999	-10000	0	0
embryonic digit morphogenesis	0	0	-9999	-10000	0	0
GNG2	-0.008	0.075	-9999	-0.74	5	5
Gi family/GTP	0.001	0.05	-9999	-0.33	5	5
SIN3B	0.006	0.006	-9999	-10000	0	0
SIN3A	0.006	0.006	-9999	-10000	0	0
GLI3/Su(fu)	-0.001	0.009	-9999	-10000	0	0
GLI2/Su(fu)	0.023	0.032	-9999	-10000	0	0
FOXA2	-0.61	0.6	-9999	-1.2	244	244
neural tube patterning	-0.089	0.14	-9999	-0.49	9	9
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.001	0.009	-9999	-10000	0	0
GNB1	-0.002	0.034	-9999	-0.74	1	1
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	-0.033	0.05	-9999	-10000	0	0
embryonic limb morphogenesis	-0.089	0.14	-9999	-0.49	9	9
SUFU	0.011	0.017	-9999	-10000	0	0
LGALS3	0	0	-9999	-10000	0	0
catabolic process	-0.001	0.012	-9999	-10000	0	0
GLI3A/CBP	0.005	0.033	-9999	-0.38	1	1
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.091	0.15	-9999	-0.55	6	6
RAB23	0	0	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
IFT172	0	0	-9999	-10000	0	0
RBBP7	0.006	0.006	-9999	-10000	0	0
Su(fu)/Galectin3	-0.001	0.009	-9999	-10000	0	0
GNAZ	-0.004	0.083	-9999	-0.74	6	6
RBBP4	0.006	0.006	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	-0.002	0.014	-9999	-10000	0	0
STK36	0.006	0.006	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.009	0.056	-9999	-0.62	2	2
PTCH1	-0.082	0.17	-9999	-1	6	6
MIM/GLI1	-0.23	0.29	-9999	-0.52	244	244
CREBBP	0.005	0.033	-9999	-0.38	1	1
Su(fu)/SIN3/HDAC complex	0.029	0.029	-9999	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0.095	-9999	-0.61	11	11
Syndecan-4/Syndesmos	-0.019	0.059	-9999	-10000	0	0
positive regulation of JNK cascade	-0.044	0.11	-9999	-0.59	7	7
Syndecan-4/ADAM12	-0.089	0.13	-9999	-0.44	16	16
CCL5	-0.014	0.1	-9999	-0.74	9	9
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0	0	-9999	-10000	0	0
ITGA5	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
PLG	-0.005	0.045	-9999	-0.57	3	3
ADAM12	-0.16	0.25	-9999	-0.57	131	131
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.011	0.033	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.094	0.13	-9999	-0.45	6	6
Syndecan-4/CXCL12/CXCR4	-0.046	0.12	-9999	-0.63	7	7
Syndecan-4/Laminin alpha3	-0.028	0.085	-9999	-0.6	2	2
MDK	-0.012	0.082	-9999	-0.57	10	10
Syndecan-4/FZD7	-0.019	0.06	-9999	-10000	0	0
Syndecan-4/Midkine	-0.024	0.072	-9999	-0.5	2	2
FZD7	-0.001	0.026	-9999	-0.57	1	1
Syndecan-4/FGFR1/FGF	-0.029	0.089	-9999	-0.55	5	5
THBS1	-0.009	0.082	-9999	-0.74	6	6
integrin-mediated signaling pathway	-0.023	0.066	-9999	-10000	0	0
positive regulation of MAPKKK cascade	-0.044	0.11	-9999	-0.59	7	7
Syndecan-4/TACI	-0.025	0.075	-9999	-10000	0	0
CXCR4	0	0	-9999	-10000	0	0
cell adhesion	-0.007	0.059	-9999	-0.36	13	13
Syndecan-4/Dynamin	-0.019	0.059	-9999	-10000	0	0
Syndecan-4/TSP1	-0.023	0.086	-9999	-0.68	5	5
Syndecan-4/GIPC	-0.019	0.059	-9999	-10000	0	0
Syndecan-4/RANTES	-0.026	0.082	-9999	-0.68	2	2
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.17	0.26	-9999	-0.57	141	141
LAMA3	-0.018	0.12	-9999	-0.74	12	12
RAC1	0	0	-9999	-10000	0	0
PRKCA	0.004	0.05	-9999	-0.69	2	2
Syndecan-4/alpha-Actinin	-0.019	0.059	-9999	-10000	0	0
TFPI	-0.061	0.2	-9999	-0.74	40	40
F2	-0.013	0.096	-9999	-0.57	14	14
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.072	0.16	-9999	-0.64	5	5
ACTN1	0	0	-9999	-10000	0	0
TNC	-0.011	0.08	-9999	-0.59	9	9
Syndecan-4/CXCL12	-0.049	0.13	-9999	-0.66	7	7
FGF6	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.06	0.2	-9999	-0.74	39	39
TNFRSF13B	-0.016	0.099	-9999	-0.63	12	12
FGF2	-0.023	0.13	-9999	-0.74	15	15
FGFR1	-0.002	0.034	-9999	-0.74	1	1
Syndecan-4/PI-4-5-P2	0.007	0.069	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.015	0.11	-9999	-0.73	11	11
cell migration	-0.004	0.013	-9999	-10000	0	0
PRKCD	0.002	0.006	-9999	-10000	0	0
vasculogenesis	-0.023	0.083	-9999	-0.65	5	5
SDC4	0.008	0.073	-9999	-10000	0	0
Syndecan-4/Tenascin C	-0.024	0.068	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2/PKC alpha	-0.009	0.026	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.019	0.059	-9999	-10000	0	0
MMP9	-0.02	0.13	-9999	-0.57	25	25
Rac1/GTP	-0.008	0.061	-9999	-0.37	13	13
cytoskeleton organization	-0.018	0.058	-9999	-10000	0	0
GIPC1	0	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.05	0.13	-9999	-0.66	7	7

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.004	0.05	-9999	-0.63	3	3
CDC42/GTP	-0.029	0.087	-9999	-0.47	3	3
PLCG1	0.002	0.1	-9999	-0.48	3	3
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.028	0.085	-9999	-0.46	3	3
S1PR5	-0.009	0.072	-9999	-0.6	7	7
S1PR4	-0.066	0.21	-9999	-0.74	43	43
MAPK3	0.002	0.1	-9999	-0.48	3	3
MAPK1	0.002	0.1	-9999	-0.48	3	3
S1P/S1P5/Gi	-0.007	0.04	-9999	-0.31	2	2
GNAI1	-0.002	0.034	-9999	-0.74	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.005	0.045	-9999	-0.37	7	7
RHOA	-0.036	0.12	-9999	-0.41	43	43
S1P/S1P4/Gi	-0.033	0.097	-9999	-0.32	44	44
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.009	0.082	-9999	-0.74	6	6
S1P/S1P4/G12/G13	-0.039	0.13	-9999	-0.44	43	43
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0	0	-10000	0	-10000	0	0
HDAC4	0	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.012	0.048	0.41	6	-10000	0	6
CDKN1A	0	0	-10000	0	-10000	0	0
KAT2B	-0.003	0.048	-10000	0	-0.74	2	2
BAX	0	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
TAT	-0.002	0.037	-10000	0	-0.57	2	2
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.049	0.15	-10000	0	-0.42	71	71
PPARGC1A	-0.15	0.3	-10000	0	-0.74	96	96
FHL2	-0.005	0.052	-10000	0	-0.57	4	4
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0	-10000	0	-10000	0	0
HIST2H4A	0.012	0.048	-10000	0	-0.41	6	6
SIRT1/FOXO3a	0	0	-10000	0	-10000	0	0
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.011	0.037	-10000	0	-10000	0	0
apoptosis	0	0	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.097	0.2	-10000	0	-0.49	96	96
p53/SIRT1	0	0	-10000	0	-10000	0	0
SIRT1/FOXO4	0	0	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.003	0.028	-10000	0	-10000	0	0
HIST1H1E	-0.014	0.046	-10000	0	-10000	0	0
SIRT1/p300	0	0	-10000	0	-10000	0	0
muscle cell differentiation	0.051	0.12	0.48	2	-10000	0	2
TP53	0	0	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
MEF2D	0	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.002	0.027	-10000	0	-0.41	2	2
ACSS2	0.017	0	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.051	0.12	-10000	0	-0.48	2	2

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0	0	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	-0.028	0.12	-10000	0	-0.56	24	24
MAP2K4	0.04	0.011	-10000	0	-10000	0	0
IKBKB	-0.001	0.026	-10000	0	-0.57	1	1
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.003	0.048	-10000	0	-0.74	2	2
SMPD1	0	0	-10000	0	-10000	0	0
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.037	0.16	-10000	0	-0.74	24	24
TRAIL/TRAILR2	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR3	-0.072	0.19	-10000	0	-0.56	62	62
TRAIL/TRAILR1	-0.002	0.036	-10000	0	-0.56	2	2
TRAIL/TRAILR4	-0.028	0.12	-10000	0	-0.56	24	24
TRAIL/TRAILR1/DAP3/GTP	-0.002	0.028	-10000	0	-0.44	2	2
IKK complex	-0.001	0.01	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.02	0	-10000	0	-10000	0	0
MAP3K1	-0.001	0.009	-10000	0	-10000	0	0
TRAILR4 (trimer)	-0.037	0.16	-10000	0	-0.74	24	24
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.003	0.048	-10000	0	-0.74	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.001	0.02	-10000	0	-10000	0	0
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.002	0.026	-10000	0	-10000	0	0
mol:ceramide	0	0	-10000	0	-10000	0	0
FADD	0	0	-10000	0	-10000	0	0
MAPK8	0.046	0.01	-10000	0	-10000	0	0
TRAF2	0	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.095	0.25	-10000	0	-0.74	62	62
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.002	0.031	-10000	0	-0.48	2	2
DAP3	0	0	-10000	0	-10000	0	0
CASP10	0.013	0.066	0.29	23	-0.4	1	24
JNK cascade	-0.028	0.12	-10000	0	-0.56	24	24
TRAIL (trimer)	0	0	-10000	0	-10000	0	0
TNFRSF10C	-0.095	0.25	-10000	0	-0.74	62	62
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.002	0.026	-10000	0	-0.41	2	2
TRAIL/TRAILR2/FADD	0	0	-10000	0	-10000	0	0
cell death	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0	0	-10000	0	-10000	0	0
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0	0.003	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by STAT5

Figure S76. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S76. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	-0.008	0.12	-9999	-0.74	12	12
ELF1	-0.004	0.034	-9999	-0.37	3	3
CCNA2	-0.15	0.25	-9999	-0.57	125	125
PIK3CA	0.01	0.001	-9999	-10000	0	0
JAK3	0.01	0.001	-9999	-10000	0	0
PIK3R1	0.01	0.001	-9999	-10000	0	0
JAK1	0.01	0.001	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.055	0.074	-9999	-0.68	3	3
SHC1	0.01	0.001	-9999	-10000	0	0
SP1	-0.002	0.029	-9999	-0.37	3	3
IL2RA	0.018	0.085	-9999	-0.69	6	6
IL2RB	0.005	0.059	-9999	-0.74	3	3
SOS1	0.01	0.001	-9999	-10000	0	0
IL2RG	-0.002	0.096	-9999	-0.74	8	8
G1/S transition of mitotic cell cycle	-0.014	0.11	-9999	-0.93	3	3
PTPN11	0.01	0.001	-9999	-10000	0	0
CCND2	0.02	0.077	-9999	-0.96	3	3
LCK	0.009	0.034	-9999	-0.74	1	1
GRB2	0.01	0.001	-9999	-10000	0	0
IL2	0.005	0.005	-9999	-10000	0	0
CDK6	-0.002	0.037	-9999	-0.57	2	2
CCND3	0.06	0.064	-9999	-0.56	3	3

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0	0	-9999	-10000	0	0
SPHK1	0	0	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
mol:S1P	0	0.007	-9999	-10000	0	0
GNAO1	-0.004	0.05	-9999	-0.63	3	3
mol:Sphinganine-1-P	0.02	0	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0	0.004	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0	0.006	-9999	-10000	0	0
S1PR5	-0.009	0.072	-9999	-0.6	7	7
S1PR4	-0.066	0.21	-9999	-0.74	43	43
GNAI1	-0.002	0.034	-9999	-0.74	1	1
S1P/S1P5/G12	-0.005	0.039	-9999	-0.43	1	1
S1P/S1P3/Gq	-0.067	0.12	-9999	-0.64	2	2
S1P/S1P4/Gi	-0.031	0.093	-9999	-0.5	3	3
GNAQ	-0.002	0.034	-9999	-0.74	1	1
GNAZ	-0.009	0.082	-9999	-0.74	6	6
GNA14	-0.18	0.32	-9999	-0.74	114	114
GNA15	0	0	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	0	0	-9999	-10000	0	0
ABCC1	-0.001	0.026	-9999	-0.57	1	1

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.003	0.048	-10000	0	-0.74	2	2
ANTXR2	-0.011	0.089	-10000	0	-0.74	7	7
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.013	-10000	0	-0.1	7	7
monocyte activation	-0.002	0.082	-10000	0	-0.45	15	15
MAP2K2	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	-0.001	0.011	-10000	0	-10000	0	0
MAP2K7	-0.001	0.011	-10000	0	-10000	0	0
MAP2K6	-0.002	0.018	-10000	0	-0.31	1	1
CYAA	0.006	0.069	-10000	0	-0.54	7	7
MAP2K4	-0.001	0.011	-10000	0	-10000	0	0
IL1B	0.003	0.074	-10000	0	-0.41	14	14
Channel	-0.008	0.072	-10000	0	-0.57	7	7
NLRP1	-0.004	0.038	-10000	0	-0.47	3	3
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.002	0.015	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.013	0.1	7	-10000	0	7
MAPK3	-0.001	0.011	-10000	0	-10000	0	0
MAPK1	-0.001	0.011	-10000	0	-10000	0	0
PGR	-0.09	0.18	-10000	0	-0.44	100	100
PA/Cellular Receptors	-0.009	0.077	-10000	0	-0.61	7	7
apoptosis	-0.002	0.013	-10000	0	-0.1	7	7
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.008	0.067	-10000	0	-0.53	7	7
macrophage activation	0.017	0.012	-10000	0	-10000	0	0
TNF	-0.02	0.12	-10000	0	-0.73	13	13
VCAM1	-0.015	0.079	-10000	0	-0.46	15	15
platelet activation	-0.002	0.015	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.013	0.12	2	-10000	0	2
IL18	0.01	0.046	-10000	0	-0.45	4	4
negative regulation of macrophage activation	-0.002	0.013	-10000	0	-0.1	7	7
LEF	-0.002	0.013	-10000	0	-0.11	7	7
CASP1	-0.003	0.032	-10000	0	-0.28	4	4
mol:cAMP	-0.002	0.016	-10000	0	-10000	0	0
necrosis	-0.002	0.013	-10000	0	-0.1	7	7
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.008	0.068	-10000	0	-0.54	7	7
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.002	0.034	-10000	0	-0.74	1	1
Jak2/Leptin Receptor	-0.026	0.098	-10000	0	-0.38	28	28
PTP1B/AKT1	-0.006	0.024	-10000	0	-10000	0	0
FYN	-0.002	0.034	-10000	0	-0.74	1	1
p210 bcr-abl/PTP1B	0.024	0.037	-10000	0	-0.31	1	1
EGFR	-0.013	0.12	-10000	0	-0.63	17	17
EGF/EGFR	-0.021	0.085	-10000	0	-0.48	12	12
CSF1	-0.006	0.067	-10000	0	-0.74	4	4
AKT1	0.007	0.005	-10000	0	-10000	0	0
INSR	0.007	0.005	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.023	0.077	-10000	0	-0.4	9	9
Insulin Receptor/Insulin	-0.004	0.019	-10000	0	-10000	0	0
HCK	-0.008	0.075	-10000	0	-0.74	5	5
CRK	0	0	-10000	0	-10000	0	0
TYK2	0.029	0.035	-10000	0	-0.29	1	1
EGF	-0.005	0.1	-10000	0	-0.69	10	10
YES1	0	0	-10000	0	-10000	0	0
CAV1	-0.026	0.11	-10000	0	-0.47	11	11
TXN	0.007	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.005	0.022	-10000	0	-10000	0	0
cell migration	-0.024	0.037	0.31	1	-10000	0	1
STAT3	0	0	-10000	0	-10000	0	0
PRLR	-0.039	0.15	-10000	0	-0.63	30	30
ITGA2B	-0.023	0.13	-10000	0	-0.74	15	15
CSF1R	-0.014	0.1	-10000	0	-0.74	9	9
Prolactin Receptor/Prolactin	-0.035	0.13	-10000	0	-0.47	37	37
FGR	-0.049	0.18	-10000	0	-0.74	32	32
PTP1B/p130 Cas	-0.006	0.025	-10000	0	-0.29	1	1
Crk/p130 Cas	-0.005	0.022	-10000	0	-10000	0	0
DOK1	0.033	0.036	-10000	0	-0.33	1	1
JAK2	0.014	0.048	-10000	0	-0.32	1	1
Jak2/Leptin Receptor/Leptin	-0.043	0.082	-10000	0	-0.48	3	3
PIK3R1	0	0	-10000	0	-10000	0	0
PTPN1	0.024	0.037	-10000	0	-0.31	1	1
LYN	-0.003	0.048	-10000	0	-0.74	2	2
CDH2	-0.035	0.14	-10000	0	-0.58	29	29
SRC	0.023	0.016	-10000	0	-10000	0	0
ITGB3	-0.012	0.095	-10000	0	-0.74	8	8
CAT1/PTP1B	0.017	0.12	-10000	0	-0.51	15	15
CAPN1	0.007	0.005	-10000	0	-10000	0	0
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.003	0.015	-10000	0	-10000	0	0
mol:H2O2	0	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.039	0.076	-10000	0	-0.54	2	2
negative regulation of transcription	0.014	0.048	-10000	0	-0.32	1	1
FCGR2A	-0.017	0.11	-10000	0	-0.74	11	11
FER	0.007	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.027	0.12	-10000	0	-0.56	23	23
BLK	-0.036	0.15	-10000	0	-0.66	26	26
Insulin Receptor/Insulin/Shc	0	0	-10000	0	-10000	0	0
RHOA	0.007	0.005	-10000	0	-10000	0	0
LEPR	-0.04	0.17	-10000	0	-0.74	28	28
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.001	0.14	-10000	0	-0.61	16	16
PRL	-0.01	0.073	-10000	0	-0.57	8	8
SOCS3	0.002	0.093	-10000	0	-1.4	2	2
SPRY2	-0.005	0.059	-10000	0	-0.75	3	3
Insulin Receptor/Insulin/IRS1	0	0	-10000	0	-10000	0	0
CSF1/CSF1R	-0.016	0.076	-10000	0	-0.46	11	11
Ras protein signal transduction	0.005	0.012	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.1	0.22	-10000	0	-0.57	84	84
STAT5B	0.022	0.037	-10000	0	-0.25	1	1
STAT5A	0.022	0.037	-10000	0	-0.25	1	1
GRB2	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.007	0.033	-10000	0	-0.38	2	2
CSN2	-0.012	0.04	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
LAT	0.011	0.077	-10000	0	-0.48	11	11
YBX1	0.001	0.003	-10000	0	-10000	0	0
LCK	-0.002	0.034	-10000	0	-0.74	1	1
SHC1	0	0	-10000	0	-10000	0	0
NOX4	-0.001	0.026	-10000	0	-0.57	1	1

×

Retinoic acid receptors-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-9999	-10000	0	0
HDAC3	0	0	-9999	-10000	0	0
VDR	-0.002	0.034	-9999	-0.74	1	1
Cbp/p300/PCAF	-0.002	0.031	-9999	-0.48	2	2
EP300	0	0	-9999	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.034	0.029	-9999	-0.31	1	1
KAT2B	-0.003	0.048	-9999	-0.74	2	2
MAPK14	0	0	-9999	-10000	0	0
AKT1	0.02	0.034	-9999	-0.31	2	2
RAR alpha/9cRA/Cyclin H	-0.007	0.029	-9999	-0.35	2	2
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.031	0.033	-9999	-0.41	1	1
CDC2	0.001	0	-9999	-10000	0	0
response to UV	0.001	0	-9999	-10000	0	0
RAR alpha/Jnk1	-0.008	0.03	-9999	-10000	0	0
NCOR2	-0.002	0.034	-9999	-0.74	1	1
VDR/VDR/Vit D3	-0.001	0.026	-9999	-0.57	1	1
RXRs/RARs/NRIP1/9cRA	-0.024	0.082	-9999	-0.6	2	2
NCOA2	-0.002	0.034	-9999	-0.74	1	1
NCOA3	0	0	-9999	-10000	0	0
NCOA1	0	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.002	0.034	-9999	-0.74	1	1
RARG	0.01	0.001	-9999	-10000	0	0
RAR gamma1/9cRA	0	0	-9999	-10000	0	0
MAPK3	0.01	0.002	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
MAPK8	0.011	0.001	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.065	0.072	-9999	-0.67	2	2
RARA	0.013	0.043	-9999	-0.29	2	2
negative regulation of phosphoinositide 3-kinase cascade	0	0	-9999	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.031	0.036	-9999	-0.41	1	1
PRKCA	0.009	0.048	-9999	-0.74	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.041	0.09	-9999	-0.63	2	2
RXRG	-0.22	0.22	-9999	-0.42	254	254
RXRA	0.02	0.041	-9999	-0.31	2	2
RXRB	0.006	0.065	-9999	-0.41	2	2
VDR/Vit D3/DNA	-0.001	0.026	-9999	-0.57	1	1
RBP1	-0.02	0.1	-9999	-0.57	17	17
CRBP1/9-cic-RA	-0.015	0.078	-9999	-0.42	17	17
RARB	0.008	0.048	-9999	-0.74	2	2
PRKCG	-0.032	0.15	-9999	-0.57	35	35
MNAT1	0	0	-9999	-10000	0	0
RAR alpha/RXRs	-0.031	0.081	-9999	-0.66	2	2
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.013	0.07	-9999	-0.5	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.033	0.038	-9999	-0.4	1	1
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.041	0.09	-9999	-0.63	2	2
positive regulation of DNA binding	-0.006	0.028	-9999	-0.33	2	2
NRIP1	-0.037	0.084	-9999	-0.69	1	1
RXRs/RARs	-0.048	0.091	-9999	-0.54	3	3
RXRs/RXRs/DNA/9cRA	-0.07	0.076	-9999	-0.69	2	2
PRKACA	0	0	-9999	-10000	0	0
CDK7	0	0	-9999	-10000	0	0
TFIIH	0	0	-9999	-10000	0	0
RAR alpha/9cRA	-0.005	0.018	-9999	-10000	0	0
CCNH	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0
RAR gamma2/9cRA	0	0	-9999	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.006	0.035	-10000	0	-10000	0	0
IRAK/TOLLIP	0	0	-10000	0	-10000	0	0
IKBKB	-0.001	0.026	-10000	0	-0.57	1	1
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.059	0.16	-10000	0	-0.47	61	61
IL1A	-0.053	0.18	-10000	0	-0.65	39	39
IL1B	0.004	0.094	-10000	0	-0.56	13	13
IRAK/TRAF6/p62/Atypical PKCs	0	0	-10000	0	-10000	0	0
IL1R2	-0.028	0.12	-10000	0	-0.57	24	24
IL1R1	-0.002	0.034	-10000	0	-0.74	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0	0.04	0.22	8	-10000	0	8
TOLLIP	0	0	-10000	0	-10000	0	0
TICAM2	-0.009	0.082	-10000	0	-0.74	6	6
MAP3K3	0	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0	0.004	-10000	0	-10000	0	0
JUN	0.042	0.012	-10000	0	-10000	0	0
MAP3K7	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.011	0.064	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.031	0.11	-10000	0	-0.46	19	19
PIK3R1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.028	0.1	-10000	0	-0.42	19	19
IL1 beta fragment/IL1R1/IL1RAP	-0.013	0.073	-10000	0	-0.43	14	14
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.036	0.013	-10000	0	-10000	0	0
IRAK1	0.022	0.004	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.007	0.064	-10000	0	-0.54	6	6
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.007	0.04	-10000	0	-10000	0	0
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.013	0.073	-10000	0	-0.43	14	14
IL1 beta/IL1R2	-0.03	0.11	-10000	0	-0.5	13	13
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.01	0.057	-10000	0	-10000	0	0
IRAK3	-0.018	0.12	-10000	0	-0.74	12	12
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.016	0.08	-10000	0	-0.78	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.019	0.069	-10000	0	-0.62	1	1
IL1 alpha/IL1R1/IL1RAP	-0.034	0.12	-10000	0	-0.42	39	39
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0	0	-10000	0	-10000	0	0
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0	0	-10000	0	-10000	0	0
IL1RAP	0	0	-10000	0	-10000	0	0
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.013	0.066	-10000	0	-0.64	1	1
CASP1	-0.003	0.048	-10000	0	-0.74	2	2
IL1RN/IL1R2	-0.026	0.1	-10000	0	-0.43	29	29
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.012	0.068	-10000	0	-0.4	14	14
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.013	0.054	-10000	0	-0.61	1	1
PIK3CA	0	0	-10000	0	-10000	0	0
IL1RN	-0.008	0.07	-10000	0	-0.63	6	6
TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
MAP2K6	-0.001	0.012	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.049	0.058	-10000	0	-0.83	1	1
UGCG	-0.002	0.009	-10000	0	-10000	0	0
AKT1/mTOR/p70S6K/Hsp90/TERT	0.034	0.066	-10000	0	-0.46	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.024	0.015	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.007	0.043	-10000	0	-0.48	3	3
FRAP1	0.071	0.067	-10000	0	-0.56	3	3
FOXO3	0.073	0.064	-10000	0	-0.55	3	3
AKT1	0.068	0.068	-10000	0	-0.6	3	3
GAB2	-0.008	0.12	-10000	0	-0.74	12	12
SMPD1	-0.002	0.009	-10000	0	-10000	0	0
SGMS1	-0.002	0.009	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.001	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	0.044	0.029	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
RPS6KB1	0.021	0.026	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.002	-10000	0	-10000	0	0
natural killer cell activation	0.001	0	-10000	0	-10000	0	0
JAK3	0.012	0.001	-10000	0	-10000	0	0
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
JAK1	0.012	0.001	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MYC	0.072	0.059	-10000	0	-0.6	1	1
MYB	0.014	0.1	-10000	0	-1.3	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.059	0.075	-10000	0	-0.68	3	3
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.003	0.017	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.058	0.073	-10000	0	-0.66	3	3
Rac1/GDP	0	0	-10000	0	-10000	0	0
T cell proliferation	0.064	0.068	-10000	0	-0.6	3	3
SHC1	0.01	0.002	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.008	-10000	0	-0.039	17	17
PRKCZ	0.065	0.07	-10000	0	-0.63	3	3
NF kappa B1 p50/RelA	-0.007	0.043	-10000	0	-0.47	3	3
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.043	0.064	-10000	0	-0.64	3	3
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL2RA	0.002	0.075	-10000	0	-0.66	6	6
IL2RB	0.008	0.059	-10000	0	-0.74	3	3
TERT	-0.22	0.28	-10000	0	-0.57	190	190
E2F1	0.018	0.048	-10000	0	-0.45	2	2
SOS1	0.01	0.002	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.004	0.019	17	-10000	0	17
PTPN11	0.01	0.002	-10000	0	-10000	0	0
IL2RG	0	0.096	-10000	0	-0.74	8	8
actin cytoskeleton organization	0.064	0.068	-10000	0	-0.6	3	3
GRB2	0.01	0.002	-10000	0	-10000	0	0
IL2	0.007	0.005	-10000	0	-10000	0	0
PIK3CA	0.013	0.001	-10000	0	-10000	0	0
Rac1/GTP	0.028	0.005	-10000	0	-10000	0	0
LCK	0.011	0.034	-10000	0	-0.74	1	1
BCL2	0.073	0.057	-10000	0	-0.54	1	1

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.001	0.026	-9999	-0.57	1	1
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.003	0.025	-9999	-0.26	4	4
response to UV	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
FYN	-0.002	0.034	-9999	-0.74	1	1
MAP3K12	0	0	-9999	-10000	0	0
FGR	-0.049	0.18	-9999	-0.74	32	32
p38 alpha/TAB1	-0.012	0.044	-9999	-0.33	2	2
PRKG1	-0.058	0.2	-9999	-0.74	38	38
DUSP8	-0.014	0.1	-9999	-0.74	9	9
PGK/cGMP/p38 alpha	-0.038	0.11	-9999	-0.38	38	38
apoptosis	-0.012	0.043	-9999	-0.32	2	2
RAL/GTP	0	0	-9999	-10000	0	0
LYN	-0.003	0.048	-9999	-0.74	2	2
DUSP1	-0.095	0.25	-9999	-0.74	62	62
PAK1	-0.001	0.026	-9999	-0.57	1	1
SRC	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.031	0.08	-9999	-0.35	11	11
BLK	-0.036	0.15	-9999	-0.66	26	26
HCK	-0.008	0.075	-9999	-0.74	5	5
MAP2K3	0	0	-9999	-10000	0	0
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.002	0.034	-9999	-0.74	1	1
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.033	0.061	-9999	-0.36	2	2
positive regulation of innate immune response	0.037	0.088	-9999	-0.38	11	11
LCK	-0.002	0.034	-9999	-0.74	1	1
p38alpha-beta/MKP7	-0.019	0.065	-9999	-0.44	2	2
p38alpha-beta/MKP5	-0.02	0.069	-9999	-0.45	4	4
PGK/cGMP	-0.045	0.15	-9999	-0.57	38	38
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.059	0.13	-9999	-0.49	17	17
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.007	0.072	-9999	-0.71	5	5

×

IL27-mediated signaling events

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
TGFB1	0.003	0.026	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.003	0.069	-10000	0	-10000	0	0
IL27/IL27R/JAK1	-0.028	0.094	-10000	0	-0.58	1	1
TBX21	-0.029	0.22	-10000	0	-0.62	43	43
IL12B	0.009	0.004	-10000	0	-10000	0	0
IL12A	0.001	0.074	-10000	0	-0.57	8	8
IL6ST	-0.016	0.14	-10000	0	-0.75	16	16
IL27RA/JAK1	-0.003	0.013	-10000	0	-10000	0	0
IL27	0.008	0.007	-10000	0	-10000	0	0
TYK2	0.011	0.003	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.062	0.14	-10000	0	-0.69	3	3
T-helper 2 cell differentiation	-0.003	0.069	-10000	0	-10000	0	0
T cell proliferation during immune response	-0.003	0.069	-10000	0	-10000	0	0
MAPKKK cascade	0.003	0.069	-10000	0	-10000	0	0
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	0.001	0.003	-10000	0	-10000	0	0
IL12RB1	-0.039	0.18	-10000	0	-0.74	31	31
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.018	0.19	-10000	0	-0.63	12	12
IL27/IL27R/JAK2/TYK2	0.002	0.069	-10000	0	-10000	0	0
positive regulation of T cell mediated cytotoxicity	0.003	0.069	-10000	0	-10000	0	0
STAT1 (dimer)	-0.058	0.16	0.51	3	-0.77	6	9
JAK2	0.006	0.006	-10000	0	-10000	0	0
JAK1	0.001	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.012	0.057	-10000	0	-10000	0	0
T cell proliferation	-0.052	0.18	-10000	0	-0.51	26	26
IL12/IL12R/TYK2/JAK2	0.007	0.093	-10000	0	-0.59	2	2
IL17A	-0.062	0.14	-10000	0	-0.69	3	3
mast cell activation	-0.003	0.069	-10000	0	-10000	0	0
IFNG	0.006	0.02	-10000	0	-0.13	4	4
T cell differentiation	-0.003	0.005	-10000	0	-0.022	4	4
STAT3 (dimer)	-0.012	0.057	-10000	0	-10000	0	0
STAT5A (dimer)	-0.012	0.057	-10000	0	-10000	0	0
STAT4 (dimer)	-0.018	0.08	-10000	0	-0.48	6	6
STAT4	-0.012	0.095	-10000	0	-0.74	8	8
T cell activation	-0.007	0.003	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.018	0.077	-10000	0	-10000	0	0
GATA3	-0.035	0.24	-10000	0	-1.4	14	14
IL18	0.006	0.045	-10000	0	-0.57	3	3
positive regulation of mast cell cytokine production	-0.012	0.056	-10000	0	-10000	0	0
IL27/EBI3	-0.003	0.042	-10000	0	-0.52	3	3
IL27RA	0.007	0.017	-10000	0	-10000	0	0
IL6	-0.12	0.28	-10000	0	-0.74	82	82
STAT5A	0	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.001	0.006	-10000	0	-10000	0	0
IL1B	-0.003	0.086	-10000	0	-0.57	11	11
EBI3	0.001	0.055	-10000	0	-0.69	3	3
TNF	-0.005	0.092	-10000	0	-0.56	13	13

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.009	0.081	-9999	-0.67	6	6
NF kappa B1 p50/RelA/I kappa B alpha	-0.017	0.047	-9999	-10000	0	0
AP1	-0.054	0.13	-9999	-0.72	3	3
mol:PIP3	-0.02	0.078	-9999	-0.58	3	3
AKT1	-0.006	0.051	-9999	-0.57	3	3
PTK2B	0.017	0.038	-9999	-0.4	1	1
RHOA	0.028	0.016	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	0	0.082	-9999	-0.49	2	2
MAGI3	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.011	0.059	-9999	-0.41	6	6
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.023	0.061	-9999	-0.4	7	7
NF kappa B1 p50/RelA	-0.024	0.066	-9999	-0.65	1	1
endothelial cell migration	0.015	0.089	-9999	-0.82	5	5
ADCY4	0.017	0.098	-9999	-0.62	6	6
ADCY5	0.011	0.096	-9999	-0.66	4	4
ADCY6	0.031	0.07	-9999	-0.59	4	4
ADCY7	0.031	0.069	-9999	-0.66	3	3
ADCY1	0.031	0.07	-9999	-0.66	3	3
ADCY2	0.018	0.082	-9999	-0.68	3	3
ADCY3	0.031	0.069	-9999	-0.66	3	3
ADCY8	-0.037	0.12	-9999	-0.66	5	5
ADCY9	0.031	0.074	-9999	-0.65	4	4
GSK3B	0.023	0.036	-9999	-0.38	1	1
arachidonic acid secretion	0.034	0.07	-9999	-0.67	3	3
GNG2	-0.008	0.075	-9999	-0.74	5	5
TRIP6	0	0.004	-9999	-10000	0	0
GNAO1	0.017	0.063	-9999	-0.55	5	5
HRAS	0	0	-9999	-10000	0	0
NFKBIA	0.017	0.074	-9999	-10000	0	0
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.002	0.042	-9999	-0.92	1	1
JUN	0	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.004	0.039	-9999	-0.48	3	3
TIAM1	-0.002	0.049	-9999	-1.1	1	1
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	0	0.083	-9999	-0.5	2	2
PLCB3	0.021	0.037	-9999	-0.44	3	3
FOS	-0.085	0.24	-9999	-0.74	55	55
positive regulation of mitosis	0.034	0.07	-9999	-0.67	3	3
LPA/LPA1-2-3	-0.014	0.072	-9999	-0.49	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
stress fiber formation	0.024	0.048	-9999	-0.51	1	1
GNAZ	0.013	0.075	-9999	-0.52	8	8
EGFR/PI3K-beta/Gab1	-0.021	0.081	-9999	-0.62	3	3
positive regulation of dendritic cell cytokine production	-0.014	0.072	-9999	-0.48	6	6
LPA/LPA2/MAGI-3	-0.001	0.007	-9999	-10000	0	0
ARHGEF1	-0.003	0.041	-9999	-0.55	2	2
GNAI2	0.02	0.051	-9999	-0.64	2	2
GNAI3	0.02	0.051	-9999	-0.64	2	2
GNAI1	0.019	0.066	-9999	-0.84	2	2
LPA/LPA3	-0.014	0.078	-9999	-0.46	14	14
LPA/LPA2	-0.001	0.01	-9999	-10000	0	0
LPA/LPA1	-0.005	0.056	-9999	-0.5	5	5
HB-EGF/EGFR	-0.047	0.14	-9999	-0.51	22	22
HBEGF	-0.022	0.14	-9999	-0.47	41	41
mol:DAG	0	0.083	-9999	-0.5	2	2
cAMP biosynthetic process	0.019	0.076	-9999	-0.66	4	4
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
GNB1	-0.002	0.034	-9999	-0.74	1	1
LYN	0.015	0.085	-9999	-0.64	2	2
GNAQ	-0.009	0.05	-9999	-0.38	5	5
LPAR2	0	0	-9999	-10000	0	0
LPAR3	-0.018	0.1	-9999	-0.62	14	14
LPAR1	-0.005	0.056	-9999	-0.83	2	2
IL8	0.001	0.13	-9999	-0.49	11	11
PTK2	-0.013	0.067	-9999	-0.56	2	2
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.011	0.059	-9999	-0.41	6	6
EGFR	-0.022	0.12	-9999	-0.63	17	17
PLCG1	-0.016	0.085	-9999	-0.36	10	10
PLD2	-0.013	0.067	-9999	-0.56	2	2
G12/G13	-0.004	0.044	-9999	-0.59	2	2
PI3K-beta	-0.007	0.062	-9999	-0.69	3	3
cell migration	0.002	0.03	-9999	-0.26	1	1
SLC9A3R2	-0.005	0.058	-9999	-0.74	3	3
PXN	0.025	0.049	-9999	-0.52	1	1
HRAS/GTP	-0.009	0.067	-9999	-0.61	4	4
RAC1	0	0	-9999	-10000	0	0
MMP9	-0.03	0.13	-9999	-0.57	25	25
PRKCE	0.008	0.034	-9999	-0.74	1	1
PRKCD	0.007	0.079	-9999	-0.47	2	2
Gi(beta/gamma)	-0.011	0.08	-9999	-0.65	5	5
mol:LPA	-0.001	0.017	-9999	-0.21	3	3
TRIP6/p130 Cas/FAK1/Paxillin	-0.002	0.06	-9999	-0.64	1	1
MAPKKK cascade	0.034	0.07	-9999	-0.67	3	3
contractile ring contraction involved in cytokinesis	0.027	0.016	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.1	0.17	-9999	-0.4	118	118
GNA15	-0.008	0.047	-9999	-0.38	4	4
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	0.023	0.063	-9999	-0.42	7	7
GNA11	-0.008	0.047	-9999	-0.38	4	4
Rac1/GTP	-0.002	0.045	-9999	-0.98	1	1
MMP2	0.015	0.09	-9999	-0.83	5	5

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.047	0.12	-9999	-10000	0	0
TC10/GTP	-0.046	0.12	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0	0	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
APS homodimer	0	0	-9999	-10000	0	0
GRB14	-0.047	0.18	-9999	-0.74	31	31
FOXO3	-0.004	0.014	-9999	-10000	0	0
AKT1	-0.021	0.082	-9999	-10000	0	0
INSR	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.092	0.24	-9999	-0.74	60	60
CRK	0	0	-9999	-10000	0	0
PTPN1	0.031	0	-9999	-10000	0	0
CAV1	-0.12	0.19	-9999	-0.42	135	135
CBL/APS/CAP/Crk-II/C3G	-0.05	0.13	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0	0	-9999	-10000	0	0
RPS6KB1	0.028	0.087	-9999	-10000	0	0
PARD6A	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.019	0.072	-9999	-10000	0	0
HRAS/GTP	-0.001	0.015	-9999	-10000	0	0
Insulin Receptor	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0	0	-9999	-10000	0	0
PRKCI	-0.006	0.022	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.023	0.088	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	-0.021	0.082	-9999	-10000	0	0
PRKCZ	-0.006	0.022	-9999	-10000	0	0
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	-0.001	0.018	-9999	-10000	0	0
F2RL2	-0.1	0.22	-9999	-0.58	88	88
TRIP10	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.054	0.14	-9999	-0.43	60	60
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	-0.001	0.019	-9999	-0.42	1	1
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.002	0.007	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	-0.001	0.019	-9999	-0.42	1	1
GRB2	0	0	-9999	-10000	0	0
EIF4EBP1	0.013	0.1	-9999	-10000	0	0
PTPRA	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.053	0.11	-9999	-0.41	3	3

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.034	-9999	-0.74	1	1
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	-0.006	0.039	-9999	-0.31	7	7
GNAO1	0.007	0.051	-9999	-0.63	3	3
S1P/S1P3/G12/G13	0	0.001	-9999	-10000	0	0
AKT1	-0.003	0.024	-9999	-0.46	1	1
AKT3	0.041	0.063	-9999	-1.3	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.002	0.034	-9999	-0.74	1	1
GNAI2	0.011	0.001	-9999	-10000	0	0
GNAI3	0.011	0.001	-9999	-10000	0	0
GNAI1	0.009	0.034	-9999	-0.74	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.011	0.001	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.033	0.04	-9999	-10000	0	0
MAPK3	0.039	0.038	-9999	-10000	0	0
MAPK1	0.039	0.038	-9999	-10000	0	0
JAK2	0.042	0.038	-9999	-10000	0	0
CXCR4	0.039	0.038	-9999	-10000	0	0
FLT1	0.012	0.001	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.039	0.038	-9999	-10000	0	0
S1P/S1P3/Gi	0.033	0.041	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.031	-9999	-10000	0	0
VEGFA	0.012	0.001	-9999	-10000	0	0
S1P/S1P2/Gi	0.03	0.039	-9999	-0.3	1	1
VEGFR1 homodimer/VEGFA homodimer	0.022	0.003	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.075	0.14	-9999	-0.32	114	114
GNAQ	-0.002	0.034	-9999	-0.74	1	1
GNAZ	0.002	0.083	-9999	-0.74	6	6
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.18	0.32	-9999	-0.74	114	114
GNA15	0	0	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
GNA11	0	0	-9999	-10000	0	0
Rac1/GTP	-0.005	0.031	-9999	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.13	0.24	-9999	-0.57	107	107
mol:Halofuginone	0	0	-9999	-10000	0	0
ITGA1	-0.008	0.075	-9999	-0.74	5	5
CDKN1A	-0.003	0.022	-9999	-10000	0	0
PRL-3/alpha Tubulin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.03	0.13	-9999	-0.56	26	26
AGT	-0.04	0.17	-9999	-0.73	26	26
CCNA2	-0.053	0.15	-9999	-0.69	3	3
TUBA1B	0	0	-9999	-10000	0	0
EGR1	0.01	0.078	-9999	-0.56	9	9
CDK2/Cyclin E1	-0.062	0.11	-9999	-0.43	2	2
MAPK3	0.02	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-9999	-10000	0	0
MAPK1	0.02	0	-9999	-10000	0	0
PTP4A1	0.024	0.062	-9999	-10000	0	0
PTP4A3	0	0	-9999	-10000	0	0
PTP4A2	0	0	-9999	-10000	0	0
ITGB1	0.02	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
RAC1	-0.003	0.022	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.011	0.062	-9999	-10000	0	0
RABGGTA	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	-0.003	0.022	-9999	-10000	0	0
RHOA	-0.003	0.022	-9999	-10000	0	0
cell motility	0.029	0.028	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.007	0.053	-9999	-10000	0	0
PRL-3/alpha1 Integrin	-0.006	0.057	-9999	-0.56	5	5
ROCK1	0.029	0.028	-9999	-10000	0	0
RABGGTB	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
mitosis	0.024	0.061	-9999	-10000	0	0
ATF5	-0.008	0.068	-9999	-0.57	7	7

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.005	0.048	-9999	-0.43	6	6
HDAC3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.05	0.16	-9999	-0.56	43	43
GATA1/HDAC5	-0.05	0.16	-9999	-0.56	43	43
GATA2/HDAC5	-0.06	0.17	-9999	-0.56	52	52
HDAC5/BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC9	-0.005	0.056	-9999	-0.61	4	4
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
GATA2	-0.08	0.23	-9999	-0.74	52	52
HDAC4/RFXANK	0	0	-9999	-10000	0	0
BCOR	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0	0	-9999	-10000	0	0
HDAC5	0	0	-9999	-10000	0	0
GNB1/GNG2	-0.007	0.062	-9999	-0.56	6	6
Histones	-0.001	0.014	-9999	-10000	0	0
ADRBK1	0	0	-9999	-10000	0	0
HDAC4	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0	0	-9999	-10000	0	0
HDAC6	0	0	-9999	-10000	0	0
HDAC5/RFXANK	0	0	-9999	-10000	0	0
CAMK4	-0.005	0.058	-9999	-0.74	3	3
Tubulin/HDAC6	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
GATA1	-0.066	0.21	-9999	-0.74	43	43
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
NR3C1	0	0	-9999	-10000	0	0
SUMO1/HDAC4	0	0	-9999	-10000	0	0
SRF	0	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	0	0	-9999	-10000	0	0
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	-0.002	0.034	-9999	-0.74	1	1
RANGAP1	0	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	-0.001	0.022	-9999	-0.48	1	1
HDAC4/SRF	-0.003	0.038	-9999	-0.48	3	3
HDAC4/ER alpha	-0.024	0.11	-9999	-0.56	21	21
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.001	0.014	-9999	-10000	0	0
cell motility	0	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.032	0.15	-9999	-0.74	21	21
HDAC6/HDAC11	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	-0.014	0.1	-9999	-0.74	9	9
RAN	0	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.008	0.058	-9999	-0.4	10	10
GNG2	-0.008	0.075	-9999	-0.74	5	5
NCOR2	-0.002	0.034	-9999	-0.74	1	1
TUBB2A	0	0	-9999	-10000	0	0
HDAC11	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
ANKRA2	0	0	-9999	-10000	0	0
RFXANK	0	0	-9999	-10000	0	0
nuclear import	0	0	-9999	-10000	0	0

×

BARD1 signaling events

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
BARD1/CSTF1	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
PRKDC	0	0	-9999	-10000	0	0
ATR	0	0	-9999	-10000	0	0
UBE2L3	0	0	-9999	-10000	0	0
FANCD2	0.022	0	-9999	-10000	0	0
protein ubiquitination	-0.062	0.12	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
M/R/N Complex	0	0	-9999	-10000	0	0
MRE11A	0	0	-9999	-10000	0	0
DNA-PK	0	0	-9999	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.002	0.012	-9999	-10000	0	0
FANCF	0	0	-9999	-10000	0	0
BRCA1	0	0	-9999	-10000	0	0
CCNE1	-0.13	0.24	-9999	-0.57	107	107
CDK2/Cyclin E1	-0.091	0.17	-9999	-0.41	107	107
FANCG	-0.002	0.037	-9999	-0.57	2	2
BRCA1/BACH1/BARD1	0	0	-9999	-10000	0	0
FANCE	0	0	-9999	-10000	0	0
FANCC	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
FANCA	-0.002	0.037	-9999	-0.57	2	2
DNA repair	0.01	0.099	-9999	-10000	0	0
BRCA1/BARD1/ubiquitin	0	0	-9999	-10000	0	0
BARD1/DNA-PK	0	0	-9999	-10000	0	0
FANCL	-0.001	0.026	-9999	-0.57	1	1
mRNA polyadenylation	0	0	-9999	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0	0	-9999	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0	0	-9999	-10000	0	0
BRCA1/BARD1/P53	0	0	-9999	-10000	0	0
BARD1/CSTF1/BRCA1	0	0	-9999	-10000	0	0
BRCA1/BACH1	0	0	-9999	-10000	0	0
BARD1	0	0	-9999	-10000	0	0
PCNA	0	0	-9999	-10000	0	0
BRCA1/BARD1/UbcH5C	0	0	-9999	-10000	0	0
BRCA1/BARD1/UbcH7	0	0	-9999	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	-0.041	0.1	-9999	-10000	0	0
BARD1/DNA-PK/P53	0	0	-9999	-10000	0	0
BRCA1/BARD1/Ubiquitin	0	0	-9999	-10000	0	0
BRCA1/BARD1/CTIP	0	0	-9999	-10000	0	0
FA complex	-0.001	0.016	-9999	-10000	0	0
BARD1/EWS	0	0	-9999	-10000	0	0
RBBP8	0.02	0	-9999	-10000	0	0
TP53	0	0	-9999	-10000	0	0
TOPBP1	0	0	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	0	0	-9999	-10000	0	0
BRCA1/BARD1	-0.062	0.12	-9999	-10000	0	0
CSTF1	0	0	-9999	-10000	0	0
BARD1/EWS-Fli1	0	0	-9999	-10000	0	0
CDK2	0	0	-9999	-10000	0	0
UniProt:Q9BZD1	0	0	-9999	-10000	0	0
RAD51	-0.076	0.19	-9999	-0.57	64	64
RAD50	0	0	-9999	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0	0	-9999	-10000	0	0
EWSR1	0	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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
EFNB2	-0.002	0.034	-10000	0	-0.74	1	1
EPHB2	-0.009	0.073	-10000	0	-0.57	8	8
EFNB1	0.018	0.028	-10000	0	-0.41	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.037	0.091	-10000	0	-0.53	1	1
Ephrin B2/EPHB1-2	-0.044	0.11	-10000	0	-0.53	2	2
neuron projection morphogenesis	-0.035	0.087	-10000	0	-0.51	1	1
Ephrin B1/EPHB1-2/Tiam1	-0.04	0.099	-10000	0	-0.57	1	1
DNM1	-0.002	0.037	-10000	0	-0.57	2	2
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.015	0.069	-10000	0	-0.73	4	4
YES1	-0.007	0.088	-10000	0	-0.96	4	4
Ephrin B1/EPHB1-2/NCK2	-0.04	0.099	-10000	0	-0.57	1	1
PI3K	-0.006	0.068	-10000	0	-0.74	4	4
mol:GDP	-0.04	0.098	-10000	0	-0.56	1	1
ITGA2B	-0.023	0.13	-10000	0	-0.74	15	15
endothelial cell proliferation	-0.001	0.022	-10000	0	-0.48	1	1
FYN	-0.008	0.088	-10000	0	-0.96	4	4
MAP3K7	-0.007	0.071	-10000	0	-0.78	4	4
FGR	-0.019	0.1	-10000	0	-0.99	4	4
TIAM1	0	0	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.024	0.1	-10000	0	-0.42	27	27
LYN	-0.008	0.088	-10000	0	-0.96	4	4
Ephrin B1/EPHB1-2/Src Family Kinases	-0.007	0.083	-10000	0	-0.91	4	4
Ephrin B1/EPHB1-2	-0.009	0.077	-10000	0	-0.84	4	4
SRC	-0.008	0.087	-10000	0	-0.95	4	4
ITGB3	-0.012	0.095	-10000	0	-0.74	8	8
EPHB1	-0.07	0.19	-10000	0	-0.57	59	59
EPHB4	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.001	0.022	-10000	0	-0.49	1	1
alphaIIb/beta3 Integrin	-0.027	0.12	-10000	0	-0.56	23	23
BLK	-0.014	0.095	-10000	0	-1	4	4
HCK	-0.01	0.089	-10000	0	-0.95	4	4
regulation of stress fiber formation	0.04	0.098	0.56	1	-10000	0	1
MAPK8	0.021	0.066	-10000	0	-0.69	4	4
Ephrin B1/EPHB1-2/RGS3	-0.04	0.099	-10000	0	-0.57	1	1
endothelial cell migration	-0.006	0.065	-10000	0	-0.62	5	5
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.003	0.078	-10000	0	-0.86	4	4
regulation of focal adhesion formation	0.04	0.098	0.56	1	-10000	0	1
chemotaxis	0.04	0.098	0.56	1	-10000	0	1
PIK3CA	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.036	0.089	-10000	0	-0.52	1	1
angiogenesis	-0.009	0.076	-10000	0	-0.83	4	4
LCK	-0.008	0.09	-10000	0	-0.99	4	4

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.046	0.019	-10000	0	-10000	0	0
NFATC2	0.002	0.069	-10000	0	-0.31	1	1
NFATC3	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.013	0.12	-10000	0	-0.51	18	18
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.034	0.1	-10000	0	-0.49	18	18
BCL2/BAX	-0.001	0.019	-10000	0	-0.41	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.004	-10000	0	-10000	0	0
CaM/Ca2+	-0.001	0.004	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0.003	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.037	0.1	-10000	0	-0.51	16	16
Calcineurin A alpha-beta B1/BCL2	-0.001	0.026	-10000	0	-0.57	1	1
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.037	0.1	0.5	16	-10000	0	16
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	0	0	-10000	0	-10000	0	0
XPO1	0	0	-10000	0	-10000	0	0
SFN	-0.057	0.17	-10000	0	-0.57	48	48
MAP3K8	0.006	0.048	-10000	0	-0.74	2	2
NFAT4/CK1 alpha	0	0	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.055	0.12	-10000	0	-0.45	13	13
CABIN1	-0.013	0.12	-10000	0	-0.52	18	18
CALM1	0.001	0.003	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	0	0	-10000	0	-10000	0	0
CAMK4	-0.005	0.058	-10000	0	-0.74	3	3
mol:Ca2+	-0.002	0.007	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.002	0.036	-10000	0	-0.56	2	2
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	0.009	0.003	-10000	0	-10000	0	0
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.003	0.017	-10000	0	-10000	0	0
PRKCH	0	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.001	0.004	-10000	0	-10000	0	0
CASP3	0.009	0.003	-10000	0	-10000	0	0
PIM1	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	0	0.007	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.008	0.024	-10000	0	-10000	0	0
PRKCB	-0.037	0.16	-10000	0	-0.74	24	24
PRKCE	-0.002	0.034	-10000	0	-0.74	1	1
JNK2/NFAT4	0	0	-10000	0	-10000	0	0
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0	0	-10000	0	-10000	0	0
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.003	-10000	0	-10000	0	0
PRKCA	-0.003	0.048	-10000	0	-0.74	2	2
PRKCG	-0.042	0.15	-10000	0	-0.57	35	35
PRKCQ	-0.069	0.22	-10000	0	-0.74	45	45
FKBP38/BCL2	-0.001	0.019	-10000	0	-0.41	1	1
EP300	0	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	0.046	0.025	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0.008	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.003	0.039	-10000	0	-0.49	3	3
NFATc/ERK1	0.049	0.018	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.034	0.1	-10000	0	-0.48	18	18
NR4A1	-0.053	0.25	-10000	0	-0.68	65	65
GSK3B	0.009	0.003	-10000	0	-10000	0	0
positive T cell selection	0	0	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.021	0.045	-10000	0	-10000	0	0
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0.009	0.003	-10000	0	-10000	0	0
AKAP5	-0.003	0.048	-10000	0	-0.74	2	2
MEF2D	0	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.046	0.025	-10000	0	-10000	0	0
CREBBP	0	0.001	-10000	0	-10000	0	0
BCL2	-0.001	0.026	-10000	0	-0.57	1	1

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.012	0.07	-9999	-0.45	12	12
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.01	0.06	-9999	-0.38	12	12
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.002	0.034	-9999	-0.74	1	1
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0	0	-9999	-10000	0	0
Histones	-0.005	0.03	-9999	-10000	0	0
YY1/LSF	-0.001	0.018	-9999	-10000	0	0
SMG5	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.009	0.053	-9999	-0.34	12	12
I kappa B alpha/HDAC1	-0.006	0.036	-9999	-10000	0	0
SAP18	0	0	-9999	-10000	0	0
RELA	-0.008	0.047	-9999	-0.3	12	12
HDAC1/Smad7	-0.001	0.022	-9999	-0.48	1	1
RANGAP1	0	0	-9999	-10000	0	0
HDAC3/TR2	-0.006	0.036	-9999	-10000	0	0
NuRD/MBD3 Complex	0	0.009	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.007	0.042	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.08	0.23	-9999	-0.74	52	52
GATA1	-0.066	0.21	-9999	-0.74	43	43
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.019	0.062	-9999	-0.45	1	1
RBBP7	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0	0	-9999	-10000	0	0
MAX	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NFKBIA	-0.007	0.041	-9999	-10000	0	0
KAT2B	-0.003	0.048	-9999	-0.74	2	2
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0	0	-9999	-10000	0	0
SIN3 complex	0	0	-9999	-10000	0	0
SMURF1	0	0	-9999	-10000	0	0
CHD3	0	0	-9999	-10000	0	0
SAP30	0	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0	0	-9999	-10000	0	0
YY1/HDAC3	-0.006	0.035	-9999	-10000	0	0
YY1/HDAC2	-0.001	0.018	-9999	-10000	0	0
YY1/HDAC1	-0.001	0.018	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0	0	-9999	-10000	0	0
PPARG	-0.053	0.13	-9999	-0.37	69	69
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.007	0.041	-9999	-0.43	1	1
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.001	0.022	-9999	-0.48	1	1
CREBBP	0	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.01	-9999	-10000	0	0
HDAC1	0	0	-9999	-10000	0	0
HDAC3	-0.007	0.041	-9999	-10000	0	0
HDAC2	0	0	-9999	-10000	0	0
YY1	-0.001	0.022	-9999	-0.34	2	2
HDAC8	0	0	-9999	-10000	0	0
SMAD7	-0.002	0.034	-9999	-0.74	1	1
NCOR2	-0.002	0.034	-9999	-0.74	1	1
MXD1	0	0	-9999	-10000	0	0
STAT3	0.022	0	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.001	0.016	-9999	-10000	0	0
YY1/SAP30/HDAC1	-0.001	0.016	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.022	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.007	0.041	-9999	-10000	0	0
histone deacetylation	0.041	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.005	0.032	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0	-9999	-10000	0	0
GATA2/HDAC3	-0.053	0.14	-9999	-0.44	52	52
GATA1/HDAC1	-0.05	0.16	-9999	-0.56	43	43
GATA1/HDAC3	-0.044	0.13	-9999	-0.44	43	43
CHD4	0	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.015	0.089	-9999	-0.55	13	13
SIN3/HDAC complex/Mad/Max	0	0	-9999	-10000	0	0
NuRD Complex	0	0.01	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.005	0.03	-9999	-10000	0	0
SIN3B	0	0	-9999	-10000	0	0
MTA2	0	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	-0.051	0.16	-9999	-0.56	44	44
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.02	0.12	-9999	-0.73	13	13
negative regulation of cell growth	0.041	0	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.01	0.063	-9999	-0.4	12	12
SIN3/HDAC complex/NCoR1	0	0	-9999	-10000	0	0
TFCP2	0	0	-9999	-10000	0	0
NR2C1	0	0	-9999	-10000	0	0
MBD3	-0.002	0.034	-9999	-0.74	1	1
MBD2	0	0	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.006	0.067	-10000	0	-0.74	4	4
CLTC	0.027	0.009	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.023	0.008	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.001	0.014	-10000	0	-10000	0	0
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.024	0.007	-10000	0	-10000	0	0
CPE	0.014	0.028	-10000	0	-0.42	2	2
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.001	0.007	-10000	0	-10000	0	0
CTNND1	0.027	0.014	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.028	0.006	-10000	0	-10000	0	0
TSHR	0.003	0.066	-10000	0	-0.35	16	16
INS	0.01	0.002	-10000	0	-10000	0	0
BIN1	-0.003	0.048	-10000	0	-0.74	2	2
mol:Choline	-0.001	0.007	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0.017	-10000	0	-0.35	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.014	-10000	0	-10000	0	0
JUP	0.024	0.007	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.002	0.028	-10000	0	-0.44	2	2
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.024	0.007	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0.01	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.016	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	-0.001	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.039	0.12	-10000	0	-0.36	3	3
clathrin heavy chain/ACAP1	0.032	0.01	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0	0	-10000	0	-10000	0	0
exocyst	0	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.027	0.014	-10000	0	-10000	0	0
NME1	0.015	0.017	-10000	0	-0.35	1	1
clathrin coat assembly	0.027	0.009	-10000	0	-10000	0	0
IL2RA	0.022	0.026	-10000	0	-10000	0	0
VAMP3	0.016	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.003	0.033	-10000	0	-0.36	4	4
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.001	0.01	-10000	0	-10000	0	0
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.028	0.007	-10000	0	-10000	0	0
SDC1	0.024	0.014	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.016	-10000	0	-0.35	1	1
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0	0.01	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.001	0.007	-10000	0	-10000	0	0
endocytosis	0.002	0.028	0.44	2	-10000	0	2
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.086	0.19	-10000	0	-0.38	137	137
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	-0.001	0.014	-10000	0	-10000	0	0
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	-0.065	0.18	-10000	0	-0.38	113	113
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0.009	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0	0	-9999	-10000	0	0
PTK2	0	0	-9999	-10000	0	0
CRKL	0.01	0.072	-9999	-0.39	15	15
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
IRS1/Crk	-0.012	0.068	-9999	-0.39	15	15
IGF-1R heterotetramer/IGF1/PTP1B	-0.015	0.079	-9999	-0.45	15	15
AKT1	0.03	0.063	-9999	-10000	0	0
BAD	0.036	0.06	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0.072	-9999	-0.39	15	15
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.013	0.068	-9999	-0.39	15	15
RAF1	0.038	0.058	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.012	0.064	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.014	0.074	-9999	-0.42	15	15
PIK3CA	0	0	-9999	-10000	0	0
RPS6KB1	0.03	0.063	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.033	0.051	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.01	0.056	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.011	0.062	-9999	-10000	0	0
IGF-1R heterotetramer	0.007	0.016	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.013	0.068	-9999	-0.39	15	15
Crk/p130 Cas/Paxillin	-0.011	0.06	-9999	-10000	0	0
IGF1R	0.007	0.016	-9999	-10000	0	0
IGF1	-0.015	0.13	-9999	-0.74	16	16
IRS2/Crk	-0.014	0.07	-9999	-0.4	3	3
PI3K	-0.012	0.063	-9999	-10000	0	0
apoptosis	0.008	0.045	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
PRKCD	0.021	0.086	-9999	-0.46	15	15
RAF1/14-3-3 E	0.041	0.051	-9999	-10000	0	0
BAD/14-3-3	0.04	0.056	-9999	-10000	0	0
PRKCZ	0.03	0.063	-9999	-10000	0	0
Crk/p130 Cas/Paxillin/FAK1	-0.008	0.046	-9999	-10000	0	0
PTPN1	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.015	0.085	-9999	-0.49	15	15
BCAR1	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.013	0.069	-9999	-0.39	15	15
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
IRS1/NCK2	-0.012	0.067	-9999	-0.38	15	15
GRB10	0	0	-9999	-10000	0	0
PTPN11	0.01	0.072	-9999	-0.39	15	15
IRS1	0.003	0.077	-9999	-0.42	15	15
IRS2	0.007	0.08	-9999	-0.39	18	18
IGF-1R heterotetramer/IGF1	-0.019	0.1	-9999	-0.56	16	16
GRB2	0	0	-9999	-10000	0	0
PDPK1	-0.011	0.059	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKD1	0.008	0.12	-9999	-0.49	26	26
SHC1	0	0	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-9999	-10000	0	0
TRAF2/ASK1	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
MAP2K3	0.027	0.023	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.034	0.022	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.009	0.082	-9999	-0.74	6	6
TXN	0.007	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
GADD45A	0	0	-9999	-10000	0	0
GADD45B	-0.022	0.12	-9999	-0.74	14	14
MAP3K1	0	0	-9999	-10000	0	0
MAP3K6	0	0	-9999	-10000	0	0
MAP3K7	0	0	-9999	-10000	0	0
MAP3K4	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0	0	-9999	-10000	0	0
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0	0	-9999	-10000	0	0
TRAF2	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.002	0.005	-9999	-10000	0	0
TRAF6	0.007	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.068	0.18	-9999	-0.57	57	57
CCM2	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.042	0.11	-9999	-0.35	57	57
MAPK11	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.037	0.1	-9999	-0.31	57	57
OSM/MEKK3	0	0	-9999	-10000	0	0
TAOK1	0.014	0.02	-9999	-0.42	1	1
TAOK2	0.014	0	-9999	-10000	0	0
TAOK3	0.014	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0	0	-9999	-10000	0	0
MAP3K10	-0.001	0.026	-9999	-0.57	1	1
MAP3K3	0	0	-9999	-10000	0	0
TRX/ASK1	0	0	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.017	0.086	-9999	-0.43	19	19

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.018	0.003	-9999	-10000	0	0
RAS family/GTP	-0.008	0.044	-9999	-10000	0	0
NFATC4	0.032	0.054	-9999	-10000	0	0
ERBB2IP	0.001	0.003	-9999	-10000	0	0
HSP90 (dimer)	0	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.01	0.059	-9999	-10000	0	0
JUN	0.044	0.058	-9999	-0.49	1	1
HRAS	0	0	-9999	-10000	0	0
DOCK7	0.029	0.064	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.012	0.07	-9999	-0.42	13	13
AKT1	0.01	0.002	-9999	-10000	0	0
BAD	0.018	0.001	-9999	-10000	0	0
MAPK10	-0.009	0.045	-9999	-0.33	4	4
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.011	0.063	-9999	-10000	0	0
RAF1	0.048	0.057	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.048	0.14	-9999	-0.44	52	52
STAT3	0	0	-9999	-10000	0	0
cell migration	0.04	0.045	-9999	-0.3	2	2
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	0.039	0.15	-9999	-0.56	8	8
FOS	0.01	0.2	-9999	-0.5	60	60
NRAS	0	0	-9999	-10000	0	0
mol:Ca2+	-0.01	0.059	-9999	-10000	0	0
MAPK3	0.046	0.11	-9999	-0.47	5	5
MAPK1	0.046	0.11	-9999	-0.64	1	1
JAK2	0.029	0.064	-9999	-10000	0	0
NF2	-0.001	0.019	-9999	-0.4	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.009	0.054	-9999	-0.33	13	13
NRG1	-0.011	0.12	-9999	-0.74	13	13
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	0.032	0.06	-9999	-10000	0	0
MAPK9	-0.005	0.028	-9999	-10000	0	0
ERBB2	-0.002	0.027	-9999	-0.42	2	2
ERBB3	0.009	0.004	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.003	0.008	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
RNF41	0.025	0.004	-9999	-10000	0	0
FRAP1	0.009	0.002	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.007	0.04	-9999	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	-0.001	0.023	-9999	-0.35	2	2
CHRNA1	0.043	0.12	-9999	-0.63	6	6
myelination	0.037	0.052	-9999	-10000	0	0
PPP3CB	-0.009	0.052	-9999	-10000	0	0
KRAS	0	0	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.008	0.046	-9999	-10000	0	0
NRG2	-0.078	0.23	-9999	-0.74	51	51
mol:GDP	0.015	0.059	-9999	-0.33	13	13
SOS1	0	0	-9999	-10000	0	0
MAP2K2	0.055	0.058	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	-0.01	0.055	-9999	-10000	0	0
MAP2K1	0.036	0.11	-9999	-0.48	5	5
heart morphogenesis	-0.01	0.059	-9999	-10000	0	0
RAS family/GDP	-0.008	0.044	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PRKACA	-0.001	0.004	-9999	-10000	0	0
CHRNE	0.02	0.017	-9999	-0.24	1	1
HSP90AA1	0	0	-9999	-10000	0	0
activation of caspase activity	-0.01	0.002	-9999	-10000	0	0
nervous system development	-0.01	0.059	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.005	0.042	-9999	-0.39	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.004	0.034	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.002	0.023	-9999	-0.49	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.013	0.045	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.039	-9999	-0.38	1	1
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.004	0.039	-9999	-0.38	2	2
AKT1	-0.004	0.034	-9999	-10000	0	0
MAP2K1	0.042	0.045	-9999	-0.39	1	1
MAP3K11	0.033	0.045	-9999	-0.39	2	2
IFNGR1	0.009	0.035	-9999	-0.74	1	1
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.05	0.13	-9999	-0.48	37	37
Rap1/GTP	-0.003	0.029	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.005	0.044	-9999	-0.4	5	5
CEBPB	0.042	0.13	-9999	-0.72	2	2
STAT3	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.007	0.067	-9999	-1.2	1	1
STAT1	-0.004	0.039	-9999	-0.38	2	2
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	0.001	0.077	-9999	-0.68	6	6
PIK3CA	0	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.004	0.037	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	-0.019	0.065	-9999	-0.41	2	2
mol:Ca2+	-0.005	0.041	-9999	-0.38	5	5
MAPK3	0.043	0.062	-9999	-10000	0	0
STAT1 (dimer)	-0.017	0.059	-9999	-10000	0	0
MAPK1	0.043	0.062	-9999	-0.44	1	1
JAK2	0.01	0.005	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
JAK1	0.01	0.005	-9999	-10000	0	0
CAMK2D	0	0	-9999	-10000	0	0
DAPK1	0.02	0.18	-9999	-0.64	33	33
SMAD7	0.038	0.045	-9999	-0.33	1	1
CBL/CRKL/C3G	-0.004	0.035	-9999	-10000	0	0
PI3K	-0.004	0.037	-9999	-10000	0	0
IFNG	0.001	0.077	-9999	-0.68	6	6
apoptosis	0.018	0.13	-9999	-0.44	33	33
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.057	0.2	-9999	-0.74	37	37
CAMK2B	-0.068	0.18	-9999	-0.57	57	57
FRAP1	0.044	0.039	-9999	-10000	0	0
PRKCD	-0.004	0.035	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
negative regulation of cell growth	-0.013	0.045	-9999	-10000	0	0
PTPN2	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
IRF1	0.065	0.038	-9999	-10000	0	0
STAT1 (dimer)/PIASy	-0.004	0.038	-9999	-10000	0	0
SOCS1	-0.003	0.066	-9999	-1.5	1	1
mol:GDP	-0.004	0.034	-9999	-10000	0	0
CASP1	0.037	0.047	-9999	-0.33	2	2
PTGES2	0	0	-9999	-10000	0	0
IRF9	0.044	0.041	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.036	-9999	-10000	0	0
RAP1/GDP	-0.003	0.029	-9999	-10000	0	0
CBL	-0.003	0.04	-9999	-0.38	1	1
MAP3K1	0.034	0.046	-9999	-0.39	2	2
PIAS1	0	0	-9999	-10000	0	0
PIAS4	0	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.013	0.045	-9999	-10000	0	0
PTPN11	-0.005	0.042	-9999	-0.38	5	5
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.002	0.026	-9999	-10000	0	0
DAPP1	0.009	0.12	-9999	-0.56	14	14
Src family/SYK family/BLNK-LAT/BTK-ITK	0.005	0.17	-9999	-0.65	22	22
mol:DAG	0.026	0.087	-9999	-0.28	22	22
HRAS	0	0.001	-9999	-10000	0	0
RAP1A	0	0.001	-9999	-10000	0	0
ARF5/GDP	0.026	0.055	-9999	-0.32	7	7
PLCG2	0	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
ARF5	0	0	-9999	-10000	0	0
mol:GTP	-0.002	0.028	-9999	-10000	0	0
ARF1/GTP	-0.002	0.027	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.002	0.028	-9999	-10000	0	0
ADAP1	-0.009	0.057	-9999	-10000	0	0
ARAP3	-0.002	0.028	-9999	-10000	0	0
INPPL1	0	0	-9999	-10000	0	0
PREX1	-0.011	0.089	-9999	-0.74	7	7
ARHGEF6	-0.028	0.14	-9999	-0.74	18	18
ARHGEF7	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
NRAS	0	0.001	-9999	-10000	0	0
FYN	-0.002	0.034	-9999	-0.74	1	1
ARF6	0	0	-9999	-10000	0	0
FGR	-0.049	0.18	-9999	-0.74	32	32
mol:Ca2+	0.024	0.047	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0	0	-9999	-10000	0	0
ZAP70	-0.012	0.095	-9999	-0.74	8	8
mol:IP3	0.027	0.064	-9999	-10000	0	0
LYN	-0.003	0.048	-9999	-0.74	2	2
ARF1/GDP	0.026	0.055	-9999	-0.32	7	7
RhoA/GDP	-0.006	0.034	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	-0.002	0.034	-9999	-0.74	1	1
actin cytoskeleton reorganization	0.045	0.066	-9999	-0.49	3	3
SRC	0	0	-9999	-10000	0	0
PLEKHA2	0.025	0.023	-9999	-0.48	1	1
RAC1	0	0	-9999	-10000	0	0
PTEN	0	0.003	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
ARF6/GTP	-0.002	0.026	-9999	-10000	0	0
RhoA/GTP	-0.002	0.026	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.033	0.11	-9999	-0.51	17	17
BLK	-0.036	0.15	-9999	-0.66	26	26
PDPK1	0	0	-9999	-10000	0	0
CYTH1	-0.002	0.026	-9999	-10000	0	0
HCK	-0.008	0.075	-9999	-0.74	5	5
CYTH3	-0.002	0.026	-9999	-10000	0	0
CYTH2	-0.002	0.026	-9999	-10000	0	0
KRAS	0	0.001	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.001	0.013	-9999	-10000	0	0
SGK1	-0.001	0.014	-9999	-10000	0	0
INPP5D	-0.002	0.034	-9999	-0.74	1	1
mol:GDP	0.022	0.058	-9999	-0.34	7	7
SOS1	0	0	-9999	-10000	0	0
SYK	-0.002	0.034	-9999	-0.74	1	1
ARF6/GDP	-0.006	0.034	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.002	0.028	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.002	0.028	-9999	-10000	0	0
VAV1	-0.008	0.075	-9999	-0.74	5	5
mol:PI-3-4-P2	0.018	0.026	-9999	-0.56	1	1
RAS family/GTP/PI3K Class I	-0.002	0.028	-9999	-0.36	3	3
PLEKHA1	0.025	0.023	-9999	-0.48	1	1
Rac1/GDP	0.026	0.055	-9999	-0.32	7	7
LAT	0	0	-9999	-10000	0	0
Rac1/GTP	-0.019	0.099	-9999	-0.46	19	19
ITK	-0.031	0.1	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.024	0.12	-9999	-0.4	22	22
LCK	-0.002	0.034	-9999	-0.74	1	1
BTK	-0.037	0.11	-9999	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.09	0.19	-9999	-0.77	5	5
RAD9A	0	0	-9999	-10000	0	0
AP1	-0.064	0.18	-9999	-0.56	55	55
IFNAR2	0.007	0.006	-9999	-10000	0	0
AKT1	-0.004	0.062	-9999	-0.3	10	10
ER alpha/Oestrogen	-0.025	0.12	-9999	-0.57	21	21
NFX1/SIN3/HDAC complex	0.024	0.021	-9999	-10000	0	0
EGF	-0.008	0.1	-9999	-0.69	10	10
SMG5	0	0	-9999	-10000	0	0
SMG6	0	0	-9999	-10000	0	0
SP3/HDAC2	0	0.001	-9999	-10000	0	0
TERT/c-Abl	-0.12	0.15	-9999	-0.72	5	5
SAP18	0.005	0.005	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.025	0.13	-9999	-0.58	26	26
WRN	-0.002	0.034	-9999	-0.74	1	1
SP1	0.008	0.006	-9999	-10000	0	0
SP3	0.006	0.005	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.1	0.13	-9999	-0.64	5	5
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.092	0.19	-9999	-0.79	5	5
CCND1	-0.084	0.21	-9999	-1.2	7	7
MAX	0.006	0.005	-9999	-10000	0	0
RBBP7	0.005	0.005	-9999	-10000	0	0
RBBP4	0.005	0.005	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0.005	0.005	-9999	-10000	0	0
Telomerase/911	0.016	0.032	-9999	-10000	0	0
CDKN1B	0.015	0.052	-9999	-0.46	4	4
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	0.005	0.005	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.006	0.005	-9999	-10000	0	0
JUN	0.006	0.005	-9999	-10000	0	0
E6	-0.003	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0.001	-9999	-10000	0	0
FOS	-0.079	0.24	-9999	-0.74	55	55
IFN-gamma/IRF1	-0.006	0.056	-9999	-0.5	6	6
PARP2	0	0	-9999	-10000	0	0
BLM	-0.012	0.082	-9999	-0.57	10	10
Telomerase	-0.026	0.052	-9999	-10000	0	0
IRF1	0.009	0.007	-9999	-10000	0	0
ESR1	-0.028	0.15	-9999	-0.74	21	21
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0	-9999	-10000	0	0
HDAC1	0.005	0.005	-9999	-10000	0	0
HDAC2	0.007	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.022	0.005	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0.006	0.005	-9999	-10000	0	0
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	0	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.11	0.14	-9999	-0.71	5	5
NR2F2	0.01	0.012	-9999	-10000	0	0
MAPK3	0.01	0.009	-9999	-10000	0	0
MAPK1	0.01	0.009	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.005	0.007	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
EGFR	-0.017	0.12	-9999	-0.64	17	17
mol:Oestrogen	-0.002	0.003	-9999	-10000	0	0
EGF/EGFR	-0.027	0.12	-9999	-0.5	26	26
MYC	0.007	0.005	-9999	-10000	0	0
IL2	0	0.012	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
TGFB1	0.005	0.007	-9999	-10000	0	0
TRF2/BLM	-0.008	0.054	-9999	-0.38	10	10
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.11	0.15	-9999	-0.71	5	5
SP1/HDAC2	0	0.002	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.1	0.13	-9999	-0.64	5	5
Smad3/Myc	0.011	0.014	-9999	-10000	0	0
911 complex	0	0	-9999	-10000	0	0
IFNG	0	0.077	-9999	-0.68	6	6
Telomerase/PinX1	-0.1	0.13	-9999	-0.64	5	5
Telomerase/AKT1/mTOR/p70S6K	-0.003	0.062	-9999	-10000	0	0
SIN3B	0.005	0.005	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.1	0.13	-9999	-0.64	5	5
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	-0.001	0.024	-9999	-0.52	1	1
Telomerase/hnRNP C1/C2	-0.1	0.13	-9999	-0.64	5	5
E2F1	0.007	0.006	-9999	-10000	0	0
ZNFX1	0.005	0.005	-9999	-10000	0	0
PIF1	-0.053	0.17	-9999	-0.57	45	45
NCL	0	0	-9999	-10000	0	0
DKC1	0	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	0.018	0.074	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	-0.014	0.061	-9999	-10000	0	0
HIF1A	0	0	-9999	-10000	0	0
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.011	0.046	-9999	-10000	0	0
PLCG1	0.018	0.074	-9999	-10000	0	0
NOS3	0.041	0.067	-9999	-0.58	1	1
CBL	0	0	-9999	-10000	0	0
mol:NO	0.041	0.065	-9999	-0.55	1	1
FLT1	0.026	0	-9999	-10000	0	0
PGF	-0.03	0.13	-9999	-0.57	25	25
VEGFR1 homodimer/NRP2/VEGFR121	-0.004	0.039	-9999	-0.43	4	4
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
eNOS/Hsp90	0.045	0.063	-9999	-0.53	1	1
endothelial cell proliferation	0.018	0.093	-9999	-0.62	1	1
mol:Ca2+	0.018	0.073	-9999	-10000	0	0
MAPK3	0.029	0.071	-9999	-10000	0	0
MAPK1	0.029	0.071	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
PLGF homodimer	-0.03	0.13	-9999	-0.57	25	25
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.21	0.33	-9999	-0.74	135	135
VEGFA homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.035	0.069	-9999	-10000	0	0
PI3K	-0.014	0.061	-9999	-10000	0	0
PRKCA	0.023	0.074	-9999	-10000	0	0
PRKCB	0.003	0.12	-9999	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	-0.018	0.075	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.018	0.074	-9999	-10000	0	0
RASA1	0.035	0	-9999	-10000	0	0
NRP2	-0.006	0.067	-9999	-0.74	4	4
VEGFR1 homodimer	0.026	0	-9999	-10000	0	0
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.066	0.18	-9999	-0.58	6	6
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.014	0.06	-9999	-10000	0	0
mol:L-citrulline	0.041	0.065	-9999	-0.55	1	1
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0	0	-9999	-10000	0	0
CD2AP	0	0	-9999	-10000	0	0
PI3K/GAB1	-0.013	0.056	-9999	-10000	0	0
PDPK1	-0.013	0.056	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-9999	-10000	0	0
mol:NADP	0.041	0.065	-9999	-0.55	1	1
HSP90AA1	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	-0.004	0.043	-9999	-0.47	4	4

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.001	0.012	-9999	-10000	0	0
CLOCK	0.013	0	-9999	-10000	0	0
TIMELESS/CRY2	0	0	-9999	-10000	0	0
DEC1/BMAL1	-0.022	0.093	-9999	-0.41	26	26
ATR	0	0	-9999	-10000	0	0
NR1D1	0.038	0	-9999	-10000	0	0
ARNTL	0.013	0	-9999	-10000	0	0
TIMELESS	0.038	0	-9999	-10000	0	0
NPAS2	0.013	0	-9999	-10000	0	0
CRY2	0	0	-9999	-10000	0	0
mol:CO	-0.012	0	-9999	-10000	0	0
CHEK1	-0.001	0.026	-9999	-0.57	1	1
mol:HEME	0.012	0	-9999	-10000	0	0
PER1	-0.005	0.058	-9999	-0.74	3	3
BMAL/CLOCK/NPAS2	0.035	0	-9999	-10000	0	0
BMAL1/CLOCK	0.037	0.037	-9999	-10000	0	0
S phase of mitotic cell cycle	-0.001	0.012	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.012	-9999	-10000	0	0
mol:NADPH	0.012	0	-9999	-10000	0	0
PER1/TIMELESS	-0.003	0.033	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.031	0.13	-9999	-0.57	26	26

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.002	0.034	-9999	-0.74	1	1
ITGA4	-0.006	0.067	-9999	-0.74	4	4
alpha4/beta7 Integrin	-0.006	0.057	-9999	-0.56	5	5
alpha4/beta1 Integrin	-0.005	0.051	-9999	-0.56	4	4

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.066	0.037	-10000	0	-10000	0	0
CRKL	0.039	0.038	-10000	0	-10000	0	0
mol:DAG	-0.005	0.034	-10000	0	-0.39	2	2
HRAS	-0.003	0.025	-10000	0	-10000	0	0
MAPK8	0.027	0.046	-10000	0	-0.44	2	2
RAP1A	0.039	0.038	-10000	0	-10000	0	0
GAB1	0.039	0.038	-10000	0	-10000	0	0
MAPK14	0.027	0.046	-10000	0	-0.44	2	2
EPO	0.004	0.064	-10000	0	-0.56	6	6
PLCG1	-0.005	0.035	-10000	0	-0.4	2	2
EPOR/TRPC2/IP3 Receptors	0.012	0.004	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.006	0.048	-10000	0	-0.5	2	2
GAB1/SHC/GRB2/SOS1	-0.003	0.027	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.005	0.045	-10000	0	-0.4	6	6
IRS2	0.036	0.05	-10000	0	-10000	0	0
STAT1	0.051	0.042	-10000	0	-0.39	2	2
STAT5B	-0.005	0.034	-10000	0	-0.4	2	2
cell proliferation	0.034	0.043	-10000	0	-0.4	2	2
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.004	0.029	-10000	0	-10000	0	0
TEC	0.036	0.05	-10000	0	-10000	0	0
SOCS3	-0.003	0.048	-10000	0	-0.74	2	2
STAT1 (dimer)	0.051	0.041	-10000	0	-0.38	2	2
JAK2	0.011	0.004	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.041	0.041	-10000	0	-0.37	2	2
EPO/EPOR	-0.005	0.045	-10000	0	-0.4	6	6
LYN	0.008	0.048	-10000	0	-0.74	2	2
TEC/VAV2	0.039	0.068	-10000	0	-0.73	2	2
elevation of cytosolic calcium ion concentration	0.012	0.004	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.001	0.049	-10000	0	-0.49	2	2
mol:IP3	-0.005	0.034	-10000	0	-0.39	2	2
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.006	0.042	-10000	0	-10000	0	0
SH2B3	0.008	0.048	-10000	0	-0.74	2	2
NFKB1	0.027	0.046	-10000	0	-0.44	2	2
EPO/EPOR (dimer)/JAK2/SOCS3	-0.002	0.031	0.3	2	-10000	0	2
PTPN6	0.033	0.04	-10000	0	-0.37	2	2
TEC/VAV2/GRB2	-0.008	0.058	-10000	0	-0.7	2	2
EPOR	0.012	0.004	-10000	0	-10000	0	0
INPP5D	-0.002	0.034	-10000	0	-0.74	1	1
mol:GDP	-0.003	0.028	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	0	0	-10000	0	-10000	0	0
CRKL/CBL/C3G	-0.004	0.029	-10000	0	-10000	0	0
VAV2	0.036	0.056	-10000	0	-0.5	3	3
CBL	0.039	0.038	-10000	0	-10000	0	0
SHC/Grb2/SOS1	-0.004	0.029	-10000	0	-10000	0	0
STAT5A	-0.005	0.034	-10000	0	-0.4	2	2
GRB2	0	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.062	0.043	-10000	0	-10000	0	0
LYN/PLCgamma2	-0.002	0.036	-10000	0	-0.56	2	2
PTPN11	0	0	-10000	0	-10000	0	0
BTK	0	0.13	-10000	0	-0.39	45	45
BCL2	0.065	0.04	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0.037	-10000	0	-0.56	2	2
MAP4K4	0.032	0.057	-10000	0	-0.64	1	1
BAG4	-0.001	0.026	-10000	0	-0.57	1	1
PKC zeta/ceramide	-0.002	0.018	0.18	2	-10000	0	2
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.009	0.082	-10000	0	-0.74	6	6
BAX	0.001	0.01	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.017	0.003	-10000	0	-10000	0	0
BAD	-0.001	0.019	0.19	2	-10000	0	2
SMPD1	0.019	0.042	-10000	0	-0.24	12	12
RB1	-0.001	0.019	0.19	2	-10000	0	2
FADD/Caspase 8	0.04	0.055	-10000	0	-0.61	1	1
MAP2K4	0.005	0.018	-10000	0	-10000	0	0
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.005	0.018	-10000	0	-10000	0	0
EGF	-0.014	0.099	-10000	0	-0.69	10	10
mol:ceramide	-0.01	0.02	0.2	2	-10000	0	2
MADD	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.017	0.037	-10000	0	-0.56	2	2
ASAH1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.001	0.019	0.19	2	-10000	0	2
cell proliferation	-0.012	0.058	-10000	0	-0.33	15	15
BID	0.024	0.039	-10000	0	-0.38	1	1
MAP3K1	-0.001	0.019	0.19	2	-10000	0	2
EIF2A	0.012	0.017	-10000	0	-10000	0	0
TRADD	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
MAPK3	0.015	0.017	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.015	0.017	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.002	0.018	0.18	2	-10000	0	2
FADD	0.032	0.057	-10000	0	-0.64	1	1
KSR1	-0.001	0.019	0.19	2	-10000	0	2
MAPK8	0.009	0.017	0.19	2	-10000	0	2
PRKRA	-0.001	0.019	0.19	2	-10000	0	2
PDGFA	-0.003	0.048	-10000	0	-0.74	2	2
TRAF2	0	0	-10000	0	-10000	0	0
IGF1	-0.024	0.13	-10000	0	-0.73	16	16
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.01	0.02	0.2	2	-10000	0	2
CTSD	0	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.013	0.062	-10000	0	-0.35	15	15
PRKCD	0	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.017	0.037	-10000	0	-0.56	2	2
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.01	0.054	-10000	0	-0.68	1	1
TNFR1A/BAG4/TNF-alpha	-0.013	0.078	-10000	0	-0.46	14	14
mol:Sphingosine-1-phosphate	0.017	0.037	-10000	0	-0.56	2	2
MAP2K1	0.012	0.017	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	0.001	0.014	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.001	0.019	-10000	0	-0.41	1	1
EIF2AK2	0.005	0.018	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.013	0.076	-10000	0	-0.48	12	12
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.005	0.027	-10000	0	-0.32	1	1
MAP2K2	0.012	0.017	-10000	0	-10000	0	0
SMPD3	0.017	0.064	-10000	0	-0.42	6	6
TNF	-0.02	0.12	-10000	0	-0.73	13	13
PKC zeta/PAR4	0	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	-0.005	0.039	0.23	11	-10000	0	11
NF kappa B1/RelA/I kappa B alpha	0	0	-10000	0	-10000	0	0
AIFM1	0.001	0.014	-10000	0	-10000	0	0
BCL2	-0.001	0.026	-10000	0	-0.57	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.005	0.05	-9999	-0.49	5	5
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.006	0.067	-9999	-0.74	4	4
alpha4/beta7 Integrin/MAdCAM1	-0.006	0.05	-9999	-0.43	5	5
EPO	-0.007	0.063	-9999	-0.57	6	6
alpha4/beta7 Integrin	-0.006	0.057	-9999	-0.56	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.005	0.051	-9999	-0.56	4	4
EPO/EPOR (dimer)	-0.005	0.046	-9999	-0.41	6	6
lamellipodium assembly	0	0.004	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.005	0.036	-9999	-0.34	4	4
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
MADCAM1	-0.004	0.045	-9999	-0.57	3	3
cell adhesion	-0.006	0.05	-9999	-0.43	5	5
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	0.021	0.072	-9999	-0.6	5	5
ITGB7	-0.002	0.034	-9999	-0.74	1	1
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.009	0.074	-9999	-0.54	8	8
p130Cas/Crk/Dock1	-0.007	0.057	-9999	-0.72	2	2
VCAM1	-0.008	0.073	-9999	-0.66	6	6
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.004	0.039	-9999	-0.43	4	4
BCAR1	0.028	0.068	-9999	-0.56	5	5
EPOR	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
Rac1/GTP	0	0.004	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	-0.001	0.026	-9999	-0.57	1	1
Caspase 8 (4 units)	-0.011	0.047	-9999	-10000	0	0
NEF	-0.007	0.037	-9999	-10000	0	0
NFKBIA	-0.001	0.012	-9999	-10000	0	0
BIRC3	0.029	0.088	-9999	-0.75	6	6
CYCS	0.032	0.064	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.025	0.13	-9999	-0.83	11	11
MAP2K7	0.034	0.051	-9999	-10000	0	0
protein ubiquitination	0.056	0.038	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.002	0.034	-9999	-0.74	1	1
BID	0.026	0.067	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.036	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
MAP3K5	0	0	-9999	-10000	0	0
CFLAR	0	0	-9999	-10000	0	0
FADD	0	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.036	-9999	-10000	0	0
MAPK8	0.04	0.048	-9999	-10000	0	0
APAF1	0	0	-9999	-10000	0	0
TRAF1	0	0	-9999	-10000	0	0
TRAF2	0	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.015	0.062	-9999	-0.3	16	16
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.006	0.034	-9999	-10000	0	0
CHUK	0.057	0.04	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.001	0.018	-9999	-0.4	1	1
TCRz/NEF	-0.028	0.13	-9999	-0.51	26	26
TNF	-0.02	0.12	-9999	-0.73	13	13
FASLG	-0.021	0.2	-9999	-0.82	26	26
NFKB1	-0.001	0.012	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.078	-9999	-0.46	14	14
CASP6	-0.007	0.028	-9999	-10000	0	0
CASP7	0.061	0.085	-9999	-0.6	6	6
RELA	-0.001	0.012	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.061	0.085	-9999	-0.6	6	6
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.019	-9999	-0.41	1	1
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.053	0.043	-9999	-10000	0	0
APAF-1/Caspase 9	-0.013	0.062	-9999	-0.49	6	6
BCL2	0.044	0.048	-9999	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.008	0.054	-10000	0	-0.38	10	10
cell-cell adhesion	0.032	0.079	0.46	1	-10000	0	1
Ephrin B/EPHB2/RasGAP	-0.007	0.044	-10000	0	-0.4	1	1
ITSN1	0	0	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.013	0.067	-10000	0	-0.35	18	18
Ephrin B1/EPHB1	-0.043	0.12	-10000	0	-0.35	59	59
HRAS/GDP	-0.031	0.08	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	-0.039	0.097	-10000	0	-10000	0	0
Endophilin/SYNJ1	-0.006	0.041	-10000	0	-0.38	1	1
KRAS	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.036	0.095	-10000	0	-10000	0	0
endothelial cell migration	-0.001	0.018	-10000	0	-0.4	1	1
GRB2	0	0	-10000	0	-10000	0	0
GRB7	-0.005	0.052	-10000	0	-0.57	4	4
PAK1	-0.009	0.051	-10000	0	-10000	0	0
HRAS	0	0	-10000	0	-10000	0	0
RRAS	-0.006	0.042	-10000	0	-0.38	1	1
DNM1	-0.002	0.037	-10000	0	-0.57	2	2
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.035	0.09	-10000	0	-10000	0	0
lamellipodium assembly	-0.032	0.079	-10000	0	-0.46	1	1
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.018	0.047	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
EPHB2	-0.009	0.073	-10000	0	-0.57	8	8
EPHB3	-0.021	0.11	-10000	0	-0.57	18	18
EPHB1	-0.07	0.19	-10000	0	-0.57	59	59
EPHB4	0	0	-10000	0	-10000	0	0
mol:GDP	-0.022	0.08	-10000	0	-0.43	1	1
Ephrin B/EPHB2	-0.007	0.045	-10000	0	-0.41	1	1
Ephrin B/EPHB3	-0.013	0.06	-10000	0	-0.41	1	1
JNK cascade	-0.038	0.097	-10000	0	-0.57	1	1
Ephrin B/EPHB1	-0.037	0.097	-10000	0	-0.41	1	1
RAP1/GDP	-0.018	0.069	-10000	0	-10000	0	0
EFNB2	-0.002	0.034	-10000	0	-0.74	1	1
EFNB3	-0.002	0.037	-10000	0	-0.57	2	2
EFNB1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.044	0.11	-10000	0	-0.53	2	2
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.032	0.079	-10000	0	-0.46	1	1
Rap1/GTP	-0.032	0.078	-10000	0	-0.47	1	1
axon guidance	-0.008	0.054	-10000	0	-0.38	10	10
MAPK3	0.026	0.053	-10000	0	-10000	0	0
MAPK1	0.026	0.053	-10000	0	-10000	0	0
Rac1/GDP	-0.02	0.074	-10000	0	-0.39	1	1
actin cytoskeleton reorganization	-0.027	0.066	-10000	0	-10000	0	0
CDC42/GDP	-0.02	0.074	-10000	0	-0.39	1	1
PI3K	-0.001	0.019	-10000	0	-0.41	1	1
EFNA5	-0.003	0.048	-10000	0	-0.74	2	2
Ephrin B2/EPHB4	-0.001	0.022	-10000	0	-0.49	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	-0.004	0.024	-10000	0	-0.31	1	1
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.031	0.076	-10000	0	-10000	0	0
PTK2	0.01	0.026	-10000	0	-10000	0	0
MAP4K4	-0.039	0.098	-10000	0	-0.57	1	1
SRC	0	0	-10000	0	-10000	0	0
KALRN	-0.005	0.058	-10000	0	-0.74	3	3
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.025	0.059	-10000	0	-10000	0	0
MAP2K1	0.019	0.055	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.042	0.11	-10000	0	-0.61	1	1
cell migration	0.027	0.056	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
SYNJ1	-0.006	0.042	-10000	0	-0.38	1	1
PXN	0	0	-10000	0	-10000	0	0
TF	0.011	0.091	-10000	0	-10000	0	0
HRAS/GTP	-0.034	0.085	-10000	0	-0.5	1	1
Ephrin B1/EPHB1-2	-0.043	0.11	-10000	0	-0.62	1	1
cell adhesion mediated by integrin	-0.002	0.041	0.41	1	-10000	0	1
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.037	0.092	-10000	0	-0.54	1	1
RAC1-CDC42/GTP	-0.039	0.086	-10000	0	-0.47	2	2
RASA1	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.018	0.069	-10000	0	-10000	0	0
ruffle organization	-0.032	0.078	-10000	0	-0.47	1	1
NCK1	0	0	-10000	0	-10000	0	0
receptor internalization	0.032	0.049	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	-0.009	0.054	-10000	0	-0.4	4	4
ROCK1	0.009	0.063	-10000	0	-0.31	18	18
RAS family/GDP	-0.023	0.058	-10000	0	-10000	0	0
Rac1/GTP	-0.034	0.083	-10000	0	-0.5	1	1
Ephrin B/EPHB1/Src/Paxillin	-0.018	0.048	-10000	0	-10000	0	0

×

TCGA08_rtk_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
PDGFRA	-0.007	0.072	-10000	0	-0.71	5	5
HRAS	0	0	-10000	0	-10000	0	0
EGFR	-0.022	0.12	-10000	0	-0.63	17	17
AKT	0.032	0.023	-10000	0	-0.38	1	1
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	-0.002	0.034	-10000	0	-0.74	1	1
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.004	0.054	-10000	0	-0.68	3	3
PIK3CA	0	0	-10000	0	-10000	0	0
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
PIK3CG	-0.065	0.21	-10000	0	-0.74	42	42
PIK3R3	0	0	-10000	0	-10000	0	0
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	0	0	-10000	0	-10000	0	0
RAS	0.016	0.034	-10000	0	-10000	0	0
ERBB2	-0.002	0.037	-10000	0	-0.57	2	2
proliferation/survival/translation	-0.018	0.034	0.21	2	-10000	0	2
PI3K	0.014	0.051	-10000	0	-0.26	3	3
PIK3R1	0	0	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
FOXO	0.038	0.015	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
PTEN	0	0	-10000	0	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.004	0.032	-9999	-0.62	1	1
PDGFB-D/PDGFRB/SLAP	-0.031	0.13	-9999	-0.58	26	26
PDGFB-D/PDGFRB/APS/CBL	-0.001	0.022	-9999	-0.48	1	1
AKT1	-0.004	0.038	-9999	-0.53	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.031	0.04	-9999	-0.66	1	1
PIK3CA	0	0	-9999	-10000	0	0
FGR	-0.04	0.15	-9999	-0.6	32	32
mol:Ca2+	0.027	0.041	-9999	-0.7	1	1
MYC	0.044	0.051	-9999	-0.46	1	1
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.018	-9999	-0.39	1	1
LRP1/PDGFRB/PDGFB	-0.001	0.022	-9999	-0.48	1	1
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.027	0.042	-9999	-0.71	1	1
PTEN	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
GRB7	-0.005	0.052	-9999	-0.57	4	4
PDGFB-D/PDGFRB/SHP2	-0.001	0.025	-9999	-0.56	1	1
PDGFB-D/PDGFRB/GRB10	-0.001	0.025	-9999	-0.56	1	1
cell cycle arrest	-0.031	0.13	-9999	-0.58	26	26
HRAS	0	0	-9999	-10000	0	0
HIF1A	0.055	0.04	-9999	-0.46	1	1
GAB1	0.028	0.054	-9999	-0.72	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.033	0.05	-9999	-0.66	1	1
PDGFB-D/PDGFRB	0.001	0.024	-9999	-0.49	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.025	-9999	-0.56	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.005	0.035	-9999	-0.63	1	1
positive regulation of MAPKKK cascade	-0.001	0.025	-9999	-0.56	1	1
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	0.027	0.042	-9999	-0.72	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.001	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.005	0.045	-9999	-0.44	5	5
SHB	0	0	-9999	-10000	0	0
BLK	-0.02	0.1	-9999	-0.59	15	15
PTPN2	0.001	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.025	-9999	-0.56	1	1
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.029	0.068	-9999	-0.57	2	2
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.004	0.044	-9999	-0.56	3	3
LCK	-0.002	0.036	-9999	-0.55	2	2
PDGFRB	0.009	0.035	-9999	-0.75	1	1
ACP1	0	0	-9999	-10000	0	0
HCK	-0.006	0.066	-9999	-0.59	6	6
ABL1	0.024	0.053	-9999	-0.66	1	1
PDGFB-D/PDGFRB/CBL	0.026	0.059	-9999	-0.77	1	1
PTPN1	0.001	0.003	-9999	-10000	0	0
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	0	0	-9999	-10000	0	0
cell proliferation	0.043	0.048	-9999	-0.43	1	1
SLA	-0.04	0.17	-9999	-0.74	26	26
actin cytoskeleton reorganization	0.002	0.02	-9999	-10000	0	0
SRC	0	0.023	-9999	-0.49	1	1
PI3K	-0.005	0.042	-9999	-0.6	1	1
PDGFB-D/PDGFRB/GRB7/SHC	-0.004	0.038	-9999	-0.48	1	1
SH2B2	0	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.031	0.041	-9999	-0.69	1	1
LYN	-0.002	0.045	-9999	-0.56	3	3
LRP1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
STAT5B	0	0	-9999	-10000	0	0
STAT5A	0	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0	0.019	-9999	-10000	0	0
SPHK1	0.01	0.003	-9999	-10000	0	0
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.027	0.042	-9999	-0.72	1	1
PLCG1	0.027	0.043	-9999	-0.74	1	1
NHERF/PDGFRB	-0.007	0.059	-9999	-0.56	4	4
YES1	0	0.022	-9999	-0.48	1	1
cell migration	-0.007	0.058	-9999	-0.56	4	4
SHC/Grb2/SOS1	0	0.019	-9999	-10000	0	0
SLC9A3R2	-0.005	0.058	-9999	-0.74	3	3
SLC9A3R1	-0.005	0.052	-9999	-0.57	4	4
NHERF1-2/PDGFRB/PTEN	-0.006	0.053	-9999	-0.51	4	4
FYN	-0.001	0.035	-9999	-0.53	2	2
DOK1	0.029	0.021	-9999	-0.44	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.04	0.063	-9999	-0.67	1	1
PRKCD	0.029	0.022	-9999	-0.44	1	1
FER	0.029	0.022	-9999	-0.44	1	1
MAPKKK cascade	-0.001	0.017	-9999	-10000	0	0
RASA1	0.029	0.022	-9999	-0.44	1	1
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	0.001	0.02	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.001	0.025	-9999	-0.56	1	1
chemotaxis	0.024	0.051	-9999	-0.63	1	1
STAT1-3-5/STAT1-3-5	-0.001	0.017	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.001	0.026	-9999	-0.57	1	1
PTPRJ	-0.003	0.048	-9999	-0.74	2	2

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0	0	-9999	-10000	0	0
adherens junction organization	0.033	0.032	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	-0.009	0.049	-9999	-10000	0	0
FMN1	0.014	0.099	-9999	-0.38	29	29
mol:IP3	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
CTNND1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.038	0	-9999	-10000	0	0
VASP	0.039	0	-9999	-10000	0	0
ZYX	0.039	0	-9999	-10000	0	0
JUB	0.039	0	-9999	-10000	0	0
EGFR(dimer)	-0.011	0.057	-9999	-0.38	6	6
E-cadherin/beta catenin-gamma catenin	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
FYN	0.042	0.036	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
JUP	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
RhoA/GDP	-0.009	0.049	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.038	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
EGFR	-0.022	0.12	-9999	-0.63	17	17
CASR	0.036	0.039	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
actin cable formation	0.02	0.097	-9999	-0.36	29	29
apoptosis	0	0	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
mol:GDP	-0.01	0.053	-9999	-10000	0	0
PIP5K1A	0.039	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.01	0.052	-9999	-0.34	6	6
homophilic cell adhesion	0.001	0	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	0.003	0.047	0.74	2	-10000	0	2
PI3K Class IB/PDE3B	-0.003	0.048	-10000	0	-0.74	2	2
PDE3B	-0.003	0.048	-10000	0	-0.74	2	2

×

PLK2 and PLK4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.002	0.034	-9999	-0.74	1	1
PLK4	-0.001	0.026	-9999	-0.57	1	1
regulation of centriole replication	0.017	0.033	-9999	-0.48	2	2

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.001	0.022	-9999	-10000	0	0
CaM/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
AKT2	0	0	-9999	-10000	0	0
STXBP4	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.033	0.033	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.02	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
SNARE/Synip	0	0	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	-0.002	0.037	-9999	-0.57	2	2
PRKCI	0	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0.028	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
TRIP10	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	-0.009	0.029	-9999	-10000	0	0
VAMP2	0	0	-9999	-10000	0	0
SLC2A4	0.034	0.035	-9999	-10000	0	0
STX4	0	0	-9999	-10000	0	0
GSK3B	0.022	0	-9999	-10000	0	0
SFN	-0.057	0.17	-9999	-0.57	48	48
LNPEP	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0

×

S1P5 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	0.006	0.035	-9999	-10000	0	0
GNAI2	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.005	0.045	-9999	-0.37	7	7
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	-0.004	0.05	-9999	-0.63	3	3
RhoA/GTP	-0.006	0.035	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.007	0.04	-9999	-0.3	2	2
GNAZ	-0.009	0.082	-9999	-0.74	6	6
GNAI3	0	0	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
S1PR5	-0.009	0.072	-9999	-0.6	7	7
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.007	0.04	-9999	-0.31	2	2
RhoA/GDP	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
GNAI1	-0.002	0.034	-9999	-0.74	1	1

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.024	0.033	-9999	-10000	0	0
PLK1	-0.089	0.21	-9999	-0.73	3	3
CDKN1B	0.05	0.085	-9999	-10000	0	0
FOXO3	-0.023	0.16	-9999	-0.63	3	3
KAT2B	0.005	0.05	-9999	-0.74	2	2
FOXO1/SIRT1	0.018	0.025	-9999	-10000	0	0
CAT	-0.017	0.16	-9999	-1.4	2	2
CTNNB1	0	0	-9999	-10000	0	0
AKT1	0.009	0.016	-9999	-10000	0	0
FOXO1	0.027	0.021	-9999	-10000	0	0
MAPK10	0.022	0.057	-9999	-0.41	8	8
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.079	0.032	-9999	-10000	0	0
response to oxidative stress	-0.003	0.02	-9999	-10000	0	0
FOXO3A/SIRT1	-0.063	0.099	-9999	-0.61	2	2
XPO1	0.01	0	-9999	-10000	0	0
EP300	0.006	0.006	-9999	-10000	0	0
BCL2L11	0.015	0.028	-9999	-10000	0	0
FOXO1/SKP2	-0.003	0.027	-9999	-10000	0	0
mol:GDP	-0.003	0.02	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
GADD45A	0.046	0.073	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.053	0.03	-9999	-10000	0	0
MST1	0.007	0.03	-9999	-0.56	1	1
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.038	0.038	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
MAPK8	0.03	0.008	-9999	-10000	0	0
MAPK9	0.029	0.008	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
SIRT1	0.008	0.013	-9999	-10000	0	0
SOD2	0.054	0.096	-9999	-10000	0	0
RBL2	0.018	0.11	-9999	-10000	0	0
RAL/GDP	0.014	0.014	-9999	-10000	0	0
CHUK	0.008	0.015	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
CSNK1G2	0	0	-9999	-10000	0	0
RAL/GTP	0.017	0.017	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
FASLG	-0.044	0.3	-9999	-1.5	20	20
SKP2	-0.004	0.045	-9999	-0.57	3	3
USP7	0.011	0	-9999	-10000	0	0
IKBKB	0.007	0.03	-9999	-0.56	1	1
CCNB1	-0.033	0.18	-9999	-0.73	3	3
FOXO1-3a-4/beta catenin	-0.015	0.039	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.027	-9999	-10000	0	0
CSNK1A1	0	0	-9999	-10000	0	0
SGK1	0.008	0.014	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
ZFAND5	0.08	0.029	-9999	-10000	0	0
SFN	-0.057	0.17	-9999	-0.57	48	48
CDK2	0.006	0.006	-9999	-10000	0	0
FOXO3A/14-3-3	0.02	0.052	-9999	-10000	0	0
CREBBP	0.006	0.006	-9999	-10000	0	0
FBXO32	-0.018	0.15	-9999	-0.66	2	2
BCL6	0.018	0.11	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.001	0.006	-10000	0	-10000	0	0
DOCK1	0	0	-10000	0	-10000	0	0
ITGA4	-0.006	0.067	-10000	0	-0.74	4	4
RAC1	0	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.006	0.057	-10000	0	-0.56	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.004	0.043	-10000	0	-0.48	4	4
alpha4/beta7 Integrin/Paxillin	-0.004	0.044	-10000	0	-0.43	5	5
lamellipodium assembly	0	0.005	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
TLN1	0	0	-10000	0	-10000	0	0
PXN	0.02	0	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.003	0.033	-10000	0	-10000	0	0
cell adhesion	-0.003	0.036	-10000	0	-0.4	4	4
CRKL/CBL	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.004	0.039	-10000	0	-0.43	4	4
ITGB1	0	0	-10000	0	-10000	0	0
ITGB7	-0.002	0.034	-10000	0	-0.74	1	1
ARF6/GDP	0.001	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.008	0.065	-10000	0	-0.57	5	5
p130Cas/Crk/Dock1	0	0	-10000	0	-10000	0	0
VCAM1	-0.008	0.073	-10000	0	-0.66	6	6
alpha4/beta1 Integrin/Paxillin/Talin	-0.003	0.037	-10000	0	-0.4	4	4
alpha4/beta1 Integrin/Paxillin/GIT1	-0.003	0.037	-10000	0	-0.4	4	4
BCAR1	0	0	-10000	0	-10000	0	0
mol:GDP	0.003	0.036	0.4	4	-10000	0	4
CBL	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
GIT1	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.003	0.037	-10000	0	-0.4	4	4
Rac1/GTP	0	0.005	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.009	0.065	-10000	0	-0.46	9	9
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.02	-10000	0	-0.42	1	1
GNB1/GNG2	-0.006	0.054	-10000	0	-0.49	6	6
GNB1	-0.002	0.034	-10000	0	-0.74	1	1
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	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.004	0.041	-10000	0	-0.46	4	4
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.001	0.01	0.11	4	-10000	0	4
GNAL	-0.006	0.067	-10000	0	-0.74	4	4
GNG2	-0.008	0.075	-10000	0	-0.74	5	5
CRH	-0.001	0.026	-10000	0	-0.57	1	1
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0	-10000	0	-10000	0	0
MAPK11	0.007	0	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
SMAD4	0	-9999	-9999
SMAD2	0.012	-9999	-9999
SMAD3	0.036	-9999	-9999
SMAD3/SMAD4	0	-9999	-9999
SMAD4/Ubc9/PIASy	0	-9999	-9999
SMAD2/SMAD2/SMAD4	0	-9999	-9999
PPM1A	0	-9999	-9999
CALM1	0	-9999	-9999
SMAD2/SMAD4	0	-9999	-9999
MAP3K1	0	-9999	-9999
TRAP-1/SMAD4	0	-9999	-9999
MAPK3	0	-9999	-9999
MAPK1	0	-9999	-9999
NUP214	0	-9999	-9999
CTDSP1	0	-9999	-9999
CTDSP2	0	-9999	-9999
CTDSPL	0	-9999	-9999
KPNB1	0	-9999	-9999
TGFBRAP1	0	-9999	-9999
UBE2I	0	-9999	-9999
NUP153	0	-9999	-9999
KPNA2	0	-9999	-9999
PIAS4	0	-9999	-9999

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.071	0.019	-9999	-10000	0	0
ERC1	0	0	-9999	-10000	0	0
RIP2/NOD2	-0.002	0.036	-9999	-0.56	2	2
NFKBIA	0.041	0	-9999	-10000	0	0
BIRC2	0	0	-9999	-10000	0	0
IKBKB	-0.001	0.026	-9999	-0.57	1	1
RIPK2	0	0	-9999	-10000	0	0
IKBKG	-0.001	0.016	-9999	-10000	0	0
IKK complex/A20	-0.01	0.056	-9999	-10000	0	0
NEMO/A20/RIP2	0	0	-9999	-10000	0	0
XPO1	0	0	-9999	-10000	0	0
NEMO/ATM	-0.001	0.015	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.001	0.016	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.003	0.048	-9999	-0.74	2	2
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
TNF/TNFR1A	-0.015	0.089	-9999	-0.55	13	13
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.003	0.048	-9999	-0.74	2	2
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.02	0.12	-9999	-0.73	13	13
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.041	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
IKK complex	-0.001	0.018	-9999	-10000	0	0
CYLD	0	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.003	0.027	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.038	0.002	-10000	0	-10000	0	0
regulation of axonogenesis	-0.024	0.019	-10000	0	-10000	0	0
myoblast fusion	0.001	0.011	-10000	0	-10000	0	0
mol:GTP	0	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.001	0.015	0.32	1	-10000	0	1
ARF1/GTP	0	0.002	-10000	0	-10000	0	0
mol:GM1	0.009	0.004	-10000	0	-10000	0	0
mol:Choline	0.023	0.028	-10000	0	-0.33	3	3
lamellipodium assembly	-0.001	0.013	-10000	0	-10000	0	0
MAPK3	0.025	0.003	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.001	0.015	-10000	0	-0.32	1	1
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.011	-10000	0	-10000	0	0
ARF1/GDP	-0.001	0.01	-10000	0	-10000	0	0
ARF6	0.008	0.002	-10000	0	-10000	0	0
RAB11A	0	0	-10000	0	-10000	0	0
TIAM1	0.011	0.001	-10000	0	-10000	0	0
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.025	0.003	-10000	0	-10000	0	0
actin filament bundle formation	0.001	0.009	-10000	0	-10000	0	0
KALRN	-0.003	0.035	-10000	0	-0.44	3	3
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.001	0.009	-10000	0	-10000	0	0
NME1	0.01	0.026	-10000	0	-0.57	1	1
Rac1/GDP	-0.001	0.009	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.004	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.001	0.013	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
liver development	0	0.004	-10000	0	-10000	0	0
ARF6/GTP	0	0.004	-10000	0	-10000	0	0
RhoA/GTP	0	0.002	-10000	0	-10000	0	0
mol:GDP	-0.001	0.012	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0	0.001	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PLD1	0.015	0.032	-10000	0	-0.38	3	3
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	-0.001	0.013	-10000	0	-10000	0	0
ruffle organization	0.024	0.019	-10000	0	-10000	0	0
regulation of epithelial cell migration	0	0.004	-10000	0	-10000	0	0
PLD2	0.018	0.004	-10000	0	-10000	0	0
PIP5K1A	-0.001	0.016	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.023	0.028	-10000	0	-0.33	3	3
Rac1/GTP	-0.001	0.013	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
GBL	0	0	-9999	-9999
MKNK1	0	0	-9999	-9999
mol:PIP3	0	0	-9999	-9999
FRAP1	0.013	0	-9999	-9999
AKT1	0	0	-9999	-9999
INSR	0	0	-9999	-9999
Insulin Receptor/Insulin	0	0	-9999	-9999
mol:GTP	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0	-9999	-9999
TSC2	0	0	-9999	-9999
RHEB/GDP	0	0	-9999	-9999
TSC1	0	0	-9999	-9999
Insulin Receptor/IRS1	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0	-9999	-9999
mol:GDP	0	0	-9999	-9999
EIF3A	0	0	-9999	-9999
RPS6KB1	0.025	0	-9999	-9999
MAP3K5	0.009	0	-9999	-9999
PIK3R1	0	0	-9999	-9999
apoptosis	0.009	0	-9999	-9999
mol:LY294002	0	0	-9999	-9999
EIF4B	0.03	0	-9999	-9999
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1	0	0	-9999	-9999
KIAA1303	0	0	-9999	-9999
PI3K	0	0	-9999	-9999
mTOR/RHEB/GTP/Raptor/GBL	0.028	0	-9999	-9999
FKBP1A	0	0	-9999	-9999
RHEB/GTP	0	0	-9999	-9999
mol:Amino Acids	0	0	-9999	-9999
FKBP12/Rapamycin	0	0	-9999	-9999
PDPK1	0	0	-9999	-9999
EIF4E	0	0	-9999	-9999
ASK1/PP5C	0	0	-9999	-9999
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.014	0	-9999	-9999
TSC1/TSC2	0	0	-9999	-9999
tumor necrosis factor receptor activity	0	0	-9999	-9999
RPS6	0	0	-9999	-9999
PPP5C	0	0	-9999	-9999
EIF4G1	0	0	-9999	-9999
IRS1	0.007	0	-9999	-9999
INS	0	0	-9999	-9999
PTEN	0	0	-9999	-9999
PDK2	0	0	-9999	-9999
EIF4EBP1	0.004	0.02	-9999	-9999
PIK3CA	0	0	-9999	-9999
PPP2R5D	0.019	0	-9999	-9999
peptide biosynthetic process	0.014	0	-9999	-9999
RHEB	0	0	-9999	-9999
EIF4A1	0	0	-9999	-9999
mol:Rapamycin	0	0	-9999	-9999
EEF2	0.015	0	-9999	-9999
eIF4E/4E-BP1	-0.003	0.014	-9999	-9999

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.02	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-9999	-10000	0	0
CDKN1B	0.033	0	-9999	-10000	0	0
CDKN1A	0.033	0	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0	0	-9999	-10000	0	0
FOXO3	0.033	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0	0	-9999	-10000	0	0
AKT3	0.014	0.02	-9999	-0.42	1	1
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.033	0	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0	0	-9999	-10000	0	0
RAF1	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.033	0	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
AKT1/RAF1	0	0	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.033	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.021	0	-9999	-10000	0	0
MAP3K5	0	0	-9999	-10000	0	0
MAPKAP1	0	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.03	0.025	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
AKT1S1	0.033	0	-9999	-10000	0	0
CASP9	0.033	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
p27Kip1/KPNA1	0	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
AKT2/p21CIP1	0	0	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0	-9999	-10000	0	0
CHUK	0.033	0	-9999	-10000	0	0
BAD/BCL-XL	0	0	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.014	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.043	0.027	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
MDM2	0.032	0.014	-9999	-10000	0	0
MAPKKK cascade	0	0	-9999	-10000	0	0
MDM2/Cbp/p300	0	0.011	-9999	-10000	0	0
TSC1/TSC2	0.038	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.01	-9999	-10000	0	0
glucose import	0.023	0.041	-9999	-0.43	4	4
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.027	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.023	0.042	-9999	-0.43	4	4
GSK3A	0.033	0	-9999	-10000	0	0
FOXO1	0.033	0	-9999	-10000	0	0
GSK3B	0.033	0	-9999	-10000	0	0
SFN	-0.057	0.17	-9999	-0.57	48	48
G1/S transition of mitotic cell cycle	0.038	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.029	0.039	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
KPNA1	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
RHEB	0	0	-9999	-10000	0	0
CREBBP	0	0	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.036	0.057	-9999	-0.53	1	1
BAG4	-0.001	0.026	-9999	-0.57	1	1
BAD	0.027	0.021	-9999	-10000	0	0
NFKBIA	0	0	-9999	-10000	0	0
BIRC3	-0.009	0.082	-9999	-0.74	6	6
BAX	0.027	0.021	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.012	0.016	-9999	-0.12	1	1
IKBKB	0.041	0.056	-9999	-0.5	1	1
MAP2K2	0.038	0.023	-9999	-10000	0	0
MAP2K1	0.038	0.023	-9999	-10000	0	0
SMPD1	0.017	0.016	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.042	0.056	-9999	-0.51	1	1
MAP2K4	0.033	0.021	-9999	-10000	0	0
protein ubiquitination	0.043	0.055	-9999	-0.5	1	1
EnzymeConsortium:2.7.1.37	0.042	0.025	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.033	0.023	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
mol:ceramide	0.021	0.022	-9999	-0.16	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0	0	-9999	-10000	0	0
MAP3K1	0.027	0.021	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
RELA/p50	0	0	-9999	-10000	0	0
MAPK3	0.04	0.023	-9999	-10000	0	0
MAPK1	0.04	0.023	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.036	0.057	-9999	-0.53	1	1
KSR1	0.027	0.022	-9999	-10000	0	0
MAPK8	0.038	0.02	-9999	-10000	0	0
TRAF2	0	0.001	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.042	0.054	-9999	-0.5	1	1
TNF R/SODD	-0.001	0.019	-9999	-0.41	1	1
TNF	-0.02	0.12	-9999	-0.73	13	13
CYCS	0.028	0.021	-9999	-10000	0	0
IKBKG	0.042	0.054	-9999	-0.5	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.03	0.06	-9999	-0.56	1	1
RELA	0	0	-9999	-10000	0	0
RIPK1	0	0.001	-9999	-10000	0	0
AIFM1	0.028	0.021	-9999	-10000	0	0
TNF/TNF R/SODD	-0.013	0.078	-9999	-0.46	14	14
TNFRSF1A	0	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.023	0.016	-9999	-10000	0	0
NSMAF	0.036	0.057	-9999	-0.52	1	1
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	-0.001	0.026	-9999	-0.57	1	1

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.027	0	-9999	-10000	0	0
SNTA1	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.025	0.024	-9999	-10000	0	0
MAPK12	0.027	0.015	-9999	-10000	0	0
CCND1	0.013	0.052	-9999	-0.44	6	6
p38 gamma/SNTA1	-0.001	0.013	-9999	-10000	0	0
MAP2K3	0	0	-9999	-10000	0	0
PKN1	0	0	-9999	-10000	0	0
G2/M transition checkpoint	0.027	0.015	-9999	-10000	0	0
MAP2K6	0.021	0.016	-9999	-0.34	1	1
MAPT	0.023	0.046	-9999	-0.37	6	6
MAPK13	0.02	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.014	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.001	0.016	-9999	-0.34	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.001	0.018	-9999	-10000	0	0
NFKBIA	0.025	0.018	-9999	-0.26	2	2
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	-0.001	0.016	-9999	-0.34	1	1
ARRB2	0.014	0	-9999	-10000	0	0
REL	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.001	0.016	-9999	-0.34	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	-0.001	0.016	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	-0.001	0.019	-9999	-0.41	1	1
PIK3R1	0	0	-9999	-10000	0	0
NFKB1	0.019	0.02	-9999	-0.41	1	1
RELA	0	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.03	0.019	-9999	-0.25	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.001	0.017	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.001	0.017	-9999	-0.26	1	1
IKBKB	-0.001	0.026	-9999	-0.57	1	1
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	-0.002	0.034	-9999	-0.74	1	1
I kappa B alpha/PIK3R1	-0.001	0.015	-9999	-10000	0	0
cell death	-0.001	0.016	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.001	0.016	-9999	-0.34	1	1
LCK	-0.002	0.034	-9999	-0.74	1	1
BCL3	0	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0	0	-9999	-10000	0	0
KLHL20	-0.004	0.03	-9999	-0.38	1	1
CYFIP2	-0.023	0.13	-9999	-0.74	15	15
Rac1/GDP	0.053	0.011	-9999	-10000	0	0
ENAH	0	0	-9999	-10000	0	0
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	0	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.007	0.034	-9999	-0.25	5	5
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.001	0.02	-9999	-0.43	1	1
RAPGEF1	0.048	0.002	-9999	-10000	0	0
CTNND1	0	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-9999	-10000	0	0
CRK	0.042	0.005	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0	0	-9999	-10000	0	0
alphaE/beta7 Integrin	-0.001	0.025	-9999	-0.56	1	1
IQGAP1	0	0	-9999	-10000	0	0
NCKAP1	0	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0	0	-9999	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
MLLT4	0	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.001	0.014	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0	0	-9999	-10000	0	0
TIAM1	0	0	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	0	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
RhoA/GDP	0.052	0.011	-9999	-10000	0	0
actin cytoskeleton organization	-0.003	0.022	-9999	-0.26	1	1
CDC42/GDP	0.052	0.011	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
ITGB7	-0.002	0.034	-9999	-0.74	1	1
RAC1	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
mol:GDP	0.051	0.012	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	0	0.006	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.004	0.031	-9999	-0.25	7	7
NME1	-0.001	0.026	-9999	-0.57	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0	0	-9999	-10000	0	0
WASF2	-0.003	0.017	-9999	-0.14	1	1
Rap1/GTP	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.001	0.018	-9999	-0.4	1	1
CCND1	-0.005	0.039	-9999	-0.32	7	7
VAV2	0.04	0.062	-9999	-0.74	3	3
RAP1/GDP	0	0.001	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.001	0.017	-9999	-10000	0	0
E-cadherin/beta catenin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
Rac1/GTP	-0.007	0.053	-9999	-0.49	3	3
E-cadherin/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
ITGAE	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	-0.001	0.013	-9999	-10000	0	0
HDAC4	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.025	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0	0	-9999	-10000	0	0
SUMO1/HDAC4	0	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
RANGAP1	0	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.001	0.014	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	0	-9999	-10000	0	0
Ran/GTP	0	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	-0.001	0.026	-9999	-0.57	1	1
UBE2I	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

E-cadherin signaling events

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.of.Up.Perturbations	Mean.of.Down.Perturbations
E-cadherin/beta catenin-gamma catenin	-9999	-9999
E-cadherin/beta catenin	-9999	-9999
CTNNB1	-9999	-9999
JUP	-9999	-9999
CDH1	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.018	0	-9999	-10000	0	0
AP2	-0.001	0.019	-9999	-0.41	1	1
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0	-9999	-10000	0	0
CD4	-0.022	0.12	-9999	-0.74	14	14
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	-0.001	0.026	-9999	-0.57	1	1
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.022	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	-0.008	0.043	-9999	-0.26	14	14
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.01	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.01	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.015	0.082	-9999	-0.48	14	14

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.001	0.013	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAP3K14	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.001	0.019	-9999	-0.41	1	1
RELB	-0.001	0.026	-9999	-0.57	1	1
NFKB2	0	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	-0.001	0.016	-9999	-0.35	1	1
regulation of B cell activation	-0.001	0.016	-9999	-0.35	1	1

pid_entity	TCGA.O2.A5IB	TCGA.O2.A52W	TCGA.O2.A52V	TCGA.O2.A52S
109_MAP3K5	0.047	0.047	0.047	-0.2
47_PPARGC1A	0	0	0	-0.74
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	0	-0.57	-0.57	0
105_BMP2	-0.74	0	0	0
131_RELN/VLDLR	0	0	0	-0.43
30_TGFB1/TGF beta receptor Type II	0.016	0.014	0.014	0.013
84_STAT5B	-0.0052	0.038	0.038	-0.07
84_STAT5A	-0.0052	0.038	0.038	-0.07