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	160
Angiopoietin receptor Tie2-mediated signaling	159
Aurora B signaling	137
FOXM1 transcription factor network	122
Endothelins	75
Glypican 2 network	61
TCGA08_retinoblastoma	60
amb2 Integrin signaling	58
Thromboxane A2 receptor signaling	52
Visual signal transduction: Cones	51

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	0.3272	160	8321	52	-0.65	0.35	1000	-1000	-0.094	-1000
Angiopoietin receptor Tie2-mediated signaling	0.3252	159	14023	88	-0.77	0.06	1000	-1000	-0.14	-1000
Aurora B signaling	0.2802	137	9214	67	-0.62	0.005	1000	-1000	-0.078	-1000
FOXM1 transcription factor network	0.2495	122	6266	51	-0.71	0.002	1000	-1000	-0.19	-1000
Endothelins	0.1534	75	7219	96	-0.45	0.038	1000	-1000	-0.11	-1000
Glypican 2 network	0.1247	61	245	4	-0.085	-0.07	1000	-1000	-0.054	-1000
TCGA08_retinoblastoma	0.1227	60	480	8	-0.28	0.085	1000	-1000	-0.033	-1000
amb2 Integrin signaling	0.1186	58	4837	82	-0.68	0	1000	-1000	-0.1	-1000
Thromboxane A2 receptor signaling	0.1063	52	5524	105	-0.18	0.039	1000	-1000	-0.082	-1000
Visual signal transduction: Cones	0.1043	51	1965	38	-0.28	0.009	1000	-1000	-0.072	-1000
Aurora C signaling	0.1022	50	355	7	-0.41	0	1000	-1000	-0.051	-1000
Fc-epsilon receptor I signaling in mast cells	0.1022	50	4904	97	-0.25	0.033	1000	-1000	-0.11	-1000
IL4-mediated signaling events	0.1002	49	4470	91	-0.8	0.44	1000	-1000	-0.19	-1000
Glucocorticoid receptor regulatory network	0.1002	49	5604	114	-0.56	0.37	1000	-1000	-0.09	-1000
Signaling events regulated by Ret tyrosine kinase	0.1002	49	4025	82	-0.2	0	1000	-1000	-0.11	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0941	46	2410	52	-0.38	0.057	1000	-1000	-0.071	-1000
PLK1 signaling events	0.0900	44	3781	85	-0.36	0.071	1000	-1000	-0.065	-1000
Arf6 signaling events	0.0818	40	2515	62	-0.3	0.015	1000	-1000	-0.076	-1000
BMP receptor signaling	0.0818	40	3246	81	-0.39	0.033	1000	-1000	-0.1	-1000
Canonical Wnt signaling pathway	0.0777	38	1953	51	-0.47	0.16	1000	-1000	-0.073	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0736	36	2828	78	-0.12	0.035	1000	-1000	-0.091	-1000
Signaling mediated by p38-alpha and p38-beta	0.0716	35	1571	44	-0.13	0	1000	-1000	-0.065	-1000
Presenilin action in Notch and Wnt signaling	0.0695	34	2094	61	-0.47	0.013	1000	-1000	-0.093	-1000
TCGA08_p53	0.0675	33	234	7	-0.19	0.097	1000	-1000	-0.032	-1000
Integrins in angiogenesis	0.0675	33	2795	84	-0.46	0.002	1000	-1000	-0.12	-1000
Nongenotropic Androgen signaling	0.0675	33	1718	52	-0.15	0.046	1000	-1000	-0.072	-1000
Nectin adhesion pathway	0.0654	32	2072	63	-0.28	0	1000	-1000	-0.097	-1000
Glypican 1 network	0.0634	31	1523	48	-0.22	0.03	1000	-1000	-0.059	-1000
FOXA2 and FOXA3 transcription factor networks	0.0593	29	1365	46	-0.78	0.073	1000	-1000	-0.12	-1000
HIF-1-alpha transcription factor network	0.0573	28	2192	76	-0.44	0.016	1000	-1000	-0.22	-1000
Coregulation of Androgen receptor activity	0.0552	27	2067	76	-0.4	0.029	1000	-1000	-0.067	-1000
LPA4-mediated signaling events	0.0532	26	314	12	-0.14	0.017	1000	-1000	-0.035	-1000
Syndecan-3-mediated signaling events	0.0532	26	925	35	-0.34	0	1000	-1000	-0.079	-1000
IL23-mediated signaling events	0.0511	25	1549	60	-0.24	0.018	1000	-1000	-0.2	-1000
IL6-mediated signaling events	0.0491	24	1826	75	-0.47	0.05	1000	-1000	-0.1	-1000
ErbB4 signaling events	0.0470	23	1605	69	-0.39	0.2	1000	-1000	-0.094	-1000
Calcium signaling in the CD4+ TCR pathway	0.0450	22	693	31	-0.21	0.012	1000	-1000	-0.15	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0450	22	1560	68	-0.23	0.015	1000	-1000	-0.17	-1000
Visual signal transduction: Rods	0.0450	22	1175	52	-0.18	0	1000	-1000	-0.095	-1000
Regulation of Androgen receptor activity	0.0450	22	1564	70	-0.42	0.018	1000	-1000	-0.08	-1000
Syndecan-1-mediated signaling events	0.0429	21	746	34	-0.35	0	1000	-1000	-0.076	-1000
Aurora A signaling	0.0429	21	1293	60	-0.49	0.029	1000	-1000	-0.069	-1000
Reelin signaling pathway	0.0429	21	1214	56	-0.13	0.003	1000	-1000	-0.12	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0429	21	2740	125	-0.21	0	1000	-1000	-0.14	-1000
Wnt signaling	0.0429	21	150	7	-0.095	0	1000	-1000	-0.056	-1000
IL12-mediated signaling events	0.0409	20	1772	87	-0.15	0.017	1000	-1000	-0.15	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0409	20	661	33	-0.27	0	1000	-1000	-0.076	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0409	20	2477	120	-0.27	0.13	1000	-1000	-0.1	-1000
Osteopontin-mediated events	0.0368	18	717	38	-0.3	0	1000	-1000	-0.13	-1000
Plasma membrane estrogen receptor signaling	0.0368	18	1571	86	-0.18	0.032	1000	-1000	-0.095	-1000
p75(NTR)-mediated signaling	0.0327	16	2085	125	-0.34	0	1000	-1000	-0.13	-1000
TCR signaling in naïve CD8+ T cells	0.0327	16	1534	93	-0.063	0.036	1000	-1000	-0.098	-1000
PDGFR-alpha signaling pathway	0.0307	15	665	44	-0.21	0.014	1000	-1000	-0.07	-1000
HIF-2-alpha transcription factor network	0.0307	15	659	43	-0.37	0.2	1000	-1000	-0.12	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0286	14	795	54	-0.15	0.02	1000	-1000	-0.12	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0286	14	1210	85	-0.15	0.01	1000	-1000	-0.088	-1000
Effects of Botulinum toxin	0.0286	14	374	26	-0.074	0.005	1000	-1000	-0.068	-1000
Regulation of nuclear SMAD2/3 signaling	0.0266	13	1834	136	-0.33	0.093	1000	-1000	-0.097	-1000
Ephrin A reverse signaling	0.0266	13	91	7	-0.023	0.003	1000	-1000	-0.039	-1000
Caspase cascade in apoptosis	0.0225	11	866	74	-0.069	0.035	1000	-1000	-0.066	-1000
Noncanonical Wnt signaling pathway	0.0225	11	301	26	-0.1	0	1000	-1000	-0.098	-1000
FAS signaling pathway (CD95)	0.0225	11	539	47	-0.2	0.009	1000	-1000	-0.062	-1000
Syndecan-2-mediated signaling events	0.0204	10	705	69	-0.17	0.033	1000	-1000	-0.069	-1000
EGFR-dependent Endothelin signaling events	0.0204	10	217	21	-0.063	0	1000	-1000	-0.094	-1000
S1P4 pathway	0.0204	10	262	25	-0.066	0.002	1000	-1000	-0.064	-1000
Ras signaling in the CD4+ TCR pathway	0.0204	10	179	17	-0.054	0.008	1000	-1000	-0.076	-1000
JNK signaling in the CD4+ TCR pathway	0.0184	9	163	17	-0.039	0.023	1000	-1000	-0.083	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0184	9	699	74	-0.17	0.068	1000	-1000	-0.11	-1000
BCR signaling pathway	0.0184	9	977	99	-0.11	0.039	1000	-1000	-0.11	-1000
Syndecan-4-mediated signaling events	0.0184	9	605	67	-0.17	0.009	1000	-1000	-0.098	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0164	8	305	34	-0.028	0	1000	-1000	-0.075	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0164	8	229	28	-0.18	0.02	1000	-1000	-0.074	-1000
Hedgehog signaling events mediated by Gli proteins	0.0164	8	576	65	-0.6	0.043	1000	-1000	-0.086	-1000
S1P1 pathway	0.0164	8	320	36	-0.061	0.01	1000	-1000	-0.078	-1000
IL2 signaling events mediated by STAT5	0.0164	8	177	22	-0.15	0.059	1000	-1000	-0.066	-1000
Signaling events mediated by HDAC Class III	0.0143	7	293	40	-0.15	0.051	1000	-1000	-0.054	-1000
TRAIL signaling pathway	0.0143	7	353	48	-0.097	0.046	1000	-1000	-0.078	-1000
IL27-mediated signaling events	0.0143	7	387	51	-0.12	0.011	1000	-1000	-0.085	-1000
Cellular roles of Anthrax toxin	0.0123	6	255	39	-0.09	0.017	1000	-1000	-0.037	-1000
Signaling events mediated by PTP1B	0.0123	6	514	76	-0.1	0.033	1000	-1000	-0.099	-1000
Retinoic acid receptors-mediated signaling	0.0123	6	369	58	-0.22	0.034	1000	-1000	-0.079	-1000
S1P3 pathway	0.0123	6	260	42	-0.18	0.042	1000	-1000	-0.063	-1000
BARD1 signaling events	0.0102	5	288	57	-0.13	0.022	1000	-1000	-0.08	-1000
IL1-mediated signaling events	0.0102	5	347	62	-0.058	0.042	1000	-1000	-0.11	-1000
Ephrin B reverse signaling	0.0102	5	275	48	-0.07	0.04	1000	-1000	-0.078	-1000
IL2 signaling events mediated by PI3K	0.0102	5	299	58	-0.22	0.073	1000	-1000	-0.1	-1000
Regulation of p38-alpha and p38-beta	0.0102	5	315	54	-0.095	0.037	1000	-1000	-0.092	-1000
LPA receptor mediated events	0.0102	5	597	102	-0.1	0.034	1000	-1000	-0.1	-1000
IGF1 pathway	0.0102	5	291	57	-0.02	0.04	1000	-1000	-0.12	-1000
Insulin Pathway	0.0102	5	442	74	-0.1	0.031	1000	-1000	-0.12	-1000
Signaling events mediated by PRL	0.0102	5	191	34	-0.13	0.029	1000	-1000	-0.073	-1000
ErbB2/ErbB3 signaling events	0.0082	4	286	65	-0.077	0.054	1000	-1000	-0.084	-1000
Signaling events mediated by HDAC Class II	0.0082	4	328	75	-0.079	0	1000	-1000	-0.07	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0082	4	362	83	-0.07	0.049	1000	-1000	-0.095	-1000
Signaling events mediated by HDAC Class I	0.0082	4	430	104	-0.079	0.041	1000	-1000	-0.08	-1000
EPHB forward signaling	0.0082	4	374	85	-0.07	0.032	1000	-1000	-0.1	-1000
Arf6 trafficking events	0.0082	4	294	71	-0.087	0.032	1000	-1000	-0.091	-1000
a4b1 and a4b7 Integrin signaling	0.0061	3	17	5	-0.008	-0.002	1000	-1000	-0.045	-1000
IFN-gamma pathway	0.0061	3	233	68	-0.068	0.065	1000	-1000	-0.12	-1000
TCGA08_rtk_signaling	0.0061	3	79	26	-0.066	0.038	1000	-1000	-0.036	-1000
Class I PI3K signaling events	0.0061	3	262	73	-0.05	0.026	1000	-1000	-0.093	-1000
Regulation of Telomerase	0.0061	3	385	102	-0.12	0.025	1000	-1000	-0.12	-1000
VEGFR1 specific signals	0.0061	3	208	56	-0.21	0.044	1000	-1000	-0.09	-1000
p38 MAPK signaling pathway	0.0061	3	159	44	-0.068	0.034	1000	-1000	-0.079	-1000
Circadian rhythm pathway	0.0041	2	56	22	-0.03	0.038	1000	-1000	-0.072	-1000
Ceramide signaling pathway	0.0041	2	175	76	-0.025	0.04	1000	-1000	-0.081	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0041	2	90	37	-0.01	0.027	1000	-1000	-0.099	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0041	2	131	45	-0.027	0.061	1000	-1000	-0.11	-1000
PDGFR-beta signaling pathway	0.0041	2	220	97	-0.04	0.054	1000	-1000	-0.1	-1000
Class IB PI3K non-lipid kinase events	0.0041	2	6	3	-0.003	-1000	1000	-1000	-0.034	-1000
PLK2 and PLK4 events	0.0020	1	4	3	-0.002	0.018	1000	-1000	-0.027	-1000
Insulin-mediated glucose transport	0.0020	1	50	32	-0.057	0.034	1000	-1000	-0.079	-1000
S1P5 pathway	0.0020	1	30	17	-0.01	0.006	1000	-1000	-0.059	-1000
FoxO family signaling	0.0020	1	97	64	-0.089	0.08	1000	-1000	-0.11	-1000
Paxillin-dependent events mediated by a4b1	0.0020	1	45	36	-0.008	0.02	1000	-1000	-0.085	-1000
Rapid glucocorticoid signaling	0.0020	1	35	20	-0.008	0.007	1000	-1000	-0.049	-1000
E-cadherin signaling in keratinocytes	0.0020	1	85	43	-0.022	0.042	1000	-1000	-0.094	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	0	23	0	0.036	1000	-1000	-0.073	-1000
Canonical NF-kappaB pathway	0.0000	0	33	39	-0.019	0.071	1000	-1000	-0.1	-1000
Arf6 downstream pathway	0.0000	0	11	43	-0.024	0.025	1000	-1000	-0.052	-1000
EPO signaling pathway	0.0000	0	49	55	-0.008	0.065	1000	-1000	-0.12	-1000
mTOR signaling pathway	0.0000	0	7	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	-0.078	-1000
ceramide signaling pathway	0.0000	0	45	49	-0.013	0.043	1000	-1000	-0.062	-1000
Signaling mediated by p38-gamma and p38-delta	0.0000	0	13	15	-0.001	0.027	1000	-1000	-0.066	-1000
Atypical NF-kappaB pathway	0.0000	0	12	31	-0.002	0.03	1000	-1000	-0.081	-1000
E-cadherin signaling in the nascent adherens junction	0.0000	0	49	76	-0.023	0.053	1000	-1000	-0.1	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	1	27	-0.001	0.025	1000	-1000	-0.063	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0	1000	-1000	-0.051	-1000
Arf1 pathway	0.0000	0	32	54	-0.023	0.022	1000	-1000	-0.058	-1000
Alternative NF-kappaB pathway	0.0000	0	4	13	-0.001	0	1000	-1000	-0.07	-1000
Total	NA	2587	162965	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	0.29	-10000	0	-0.69	228	228
IHH	-0.47	0.38	-10000	0	-0.81	273	273
SHH Np/Cholesterol/GAS1	-0.07	0.16	-10000	0	-0.44	77	77
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.069	0.16	0.44	77	-10000	0	77
SMO/beta Arrestin2	-0.36	0.25	-10000	0	-0.59	235	235
SMO	-0.38	0.27	-10000	0	-0.63	236	236
AKT1	-0.15	0.11	-10000	0	-10000	0	0
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	-0.37	0.27	-10000	0	-0.62	236	236
STIL	-0.33	0.25	-10000	0	-0.53	254	254
DHH N/PTCH2	-0.045	0.15	-10000	0	-0.56	39	39
DHH N/PTCH1	-0.36	0.24	-10000	0	-0.58	236	236
PIK3CA	0	0	-10000	0	-10000	0	0
DHH	-0.051	0.19	-10000	0	-0.74	34	34
PTHLH	-0.58	0.36	-10000	0	-0.92	228	228
determination of left/right symmetry	-0.37	0.27	-10000	0	-0.62	236	236
PIK3R1	0	0	-10000	0	-10000	0	0
skeletal system development	-0.57	0.35	-10000	0	-0.9	228	228
IHH N/Hhip	-0.65	0.38	-10000	0	-0.82	389	389
DHH N/Hhip	-0.41	0.29	-10000	0	-0.59	335	335
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.37	0.27	-10000	0	-0.62	236	236
pancreas development	-0.49	0.35	-10000	0	-0.74	327	327
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	0.094	-10000	0	-0.74	8	8
somite specification	-0.37	0.27	-10000	0	-0.62	236	236
SHH Np/Cholesterol/PTCH1	-0.35	0.25	-10000	0	-0.56	251	251
SHH Np/Cholesterol/PTCH2	-0.068	0.16	-10000	0	-0.43	77	77
SHH Np/Cholesterol/Megalin	-0.29	0.27	-10000	0	-0.5	283	283
SHH	-0.064	0.2	-10000	0	-0.54	72	72
catabolic process	-0.37	0.25	-10000	0	-0.61	223	223
SMO/Vitamin D3	-0.37	0.26	-10000	0	-0.59	251	251
SHH Np/Cholesterol/Hhip	-0.36	0.26	-10000	0	-0.5	347	347
LRP2	-0.38	0.37	-10000	0	-0.74	251	251
receptor-mediated endocytosis	-0.5	0.31	-10000	0	-0.72	285	285
SHH Np/Cholesterol/BOC	-0.066	0.16	-10000	0	-0.44	74	74
SHH Np/Cholesterol/CDO	-0.067	0.16	-10000	0	-0.43	77	77
mesenchymal cell differentiation	0.35	0.26	0.5	347	-10000	0	347
mol:Vitamin D3	-0.35	0.26	-10000	0	-0.56	251	251
IHH N/PTCH2	-0.31	0.27	-10000	0	-0.54	273	273
CDON	-0.008	0.074	-10000	0	-0.74	5	5
IHH N/PTCH1	-0.38	0.26	-10000	0	-0.62	223	223
Megalin/LRPAP1	-0.29	0.28	-10000	0	-0.56	251	251
PTCH2	-0.008	0.076	-10000	0	-0.68	6	6
SHH Np/Cholesterol	-0.064	0.15	-10000	0	-0.43	72	72
PTCH1	-0.37	0.25	-10000	0	-0.61	223	223
HHIP	-0.49	0.35	-10000	0	-0.74	327	327

×

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	266	266
NCK1/PAK1/Dok-R	-0.25	0.23	-10000	0	-0.45	266	266
NCK1/Dok-R	-0.69	0.66	-10000	0	-1.3	266	266
PIK3CA	0.007	0.006	-10000	0	-10000	0	0
mol:beta2-estradiol	0.06	0.1	0.25	105	-10000	0	105
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	-10000	0	-0.57	9	9
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.61	0.58	-10000	0	-1.1	266	266
FN1	-0.017	0.11	-10000	0	-0.74	11	11
PLD2	-0.68	0.71	-10000	0	-1.3	266	266
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.047	0.18	-10000	0	-0.73	31	31
ELK1	-0.58	0.61	-10000	0	-1.1	266	266
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	-0.65	0.62	-10000	0	-1.2	266	266
CDKN1A	-0.36	0.35	-10000	0	-0.68	249	249
ITGA5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.69	0.66	-10000	0	-1.3	266	266
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.36	0.38	-10000	0	-0.71	266	266
PLG	-0.68	0.71	-10000	0	-1.3	266	266
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.51	0.48	-10000	0	-0.95	266	266
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	-0.74	174	174
BMX	-0.75	0.75	-10000	0	-1.4	266	266
ANGPT1	-0.37	0.62	-10000	0	-1.5	115	115
tube development	-0.42	0.4	-10000	0	-0.79	254	254
ANGPT4	-0.33	0.37	-10000	0	-0.74	220	220
response to hypoxia	-0.035	0.036	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.75	0.72	-10000	0	-1.4	266	266
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.017	0.13	-10000	0	-0.74	15	15
STAT5A (dimer)	-0.48	0.47	-10000	0	-0.92	254	254
mol:L-citrulline	-0.36	0.38	-10000	0	-0.71	266	266
AGTR1	-0.29	0.37	-10000	0	-0.74	199	199
MAPK14	-0.7	0.7	-10000	0	-1.3	266	266
Tie2/SHP2	-0.6	0.62	-10000	0	-1.2	232	232
TEK	-0.68	0.69	-10000	0	-1.4	232	232
RPS6KB1	-0.5	0.51	-10000	0	-0.96	266	266
Angiotensin II/AT1	-0.23	0.28	-10000	0	-0.56	199	199
Tie2/Ang1/GRB2	-0.73	0.72	-10000	0	-1.3	266	266
MAPK3	-0.6	0.63	-10000	0	-1.2	266	266
MAPK1	-0.6	0.63	-10000	0	-1.2	266	266
Tie2/Ang1/GRB7	-0.73	0.72	-10000	0	-1.3	266	266
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.68	0.71	-10000	0	-1.3	266	266
PI3K	-0.63	0.63	-10000	0	-1.2	266	266
FES	-0.7	0.7	-10000	0	-1.3	266	266
Crk/Dok-R	-0.69	0.66	-10000	0	-1.3	266	266
Tie2/Ang1/ABIN2	-0.73	0.72	-10000	0	-1.3	266	266
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.46	0.46	-10000	0	-0.88	266	266
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	266	266
Tie2/Ang2	-0.62	0.59	-10000	0	-1.2	254	254
Tie2/Ang1	-0.77	0.82	-10000	0	-1.5	266	266
FOXO1	-0.46	0.47	-10000	0	-0.89	266	266
ELF1	-0.034	0.052	-10000	0	-10000	0	0
ELF2	-0.69	0.72	-10000	0	-1.3	266	266
mol:Choline	-0.63	0.66	-10000	0	-1.2	266	266
cell migration	-0.13	0.12	-10000	0	-0.24	252	252
FYN	-0.49	0.47	-10000	0	-0.92	254	254
DOK2	-0.066	0.21	-10000	0	-0.74	44	44
negative regulation of cell cycle	-0.32	0.32	-10000	0	-0.62	249	249
ETS1	-0.063	0.16	-10000	0	-0.83	13	13
PXN	-0.39	0.41	-10000	0	-0.77	266	266
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.42	0.44	-10000	0	-0.82	266	266
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.062	0.16	-10000	0	-0.81	13	13
MAPKKK cascade	-0.63	0.66	-10000	0	-1.2	266	266
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.72	0.73	-10000	0	-1.4	266	266
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.32	0.34	-10000	0	-0.63	266	266
mol:Phosphatidic acid	-0.63	0.66	-10000	0	-1.2	266	266
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.36	0.38	-10000	0	-0.71	266	266
Rac1/GTP	-0.48	0.44	-10000	0	-0.88	266	266
MMP2	-0.68	0.71	-10000	0	-1.3	266	266

×

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	-0.31	236	236
STMN1	-0.29	0.19	-9999	-0.41	351	351
Aurora B/RasGAP/Survivin	-0.5	0.22	-9999	-0.56	436	436
Chromosomal passenger complex/Cul3 protein complex	-0.2	0.1	-9999	-0.33	128	128
BIRC5	-0.49	0.21	-9999	-0.58	415	415
DES	-0.56	0.38	-9999	-0.83	315	315
Aurora C/Aurora B/INCENP	-0.22	0.15	-9999	-0.42	7	7
Aurora B/TACC1	-0.24	0.16	-9999	-0.34	351	351
Aurora B/PP2A	-0.29	0.19	-9999	-0.4	351	351
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	367	367
Cul3 protein complex	-0.011	0.065	-9999	-0.37	15	15
KIF2C	-0.17	0.086	-9999	-0.22	315	315
PEBP1	-0.002	0.048	-9999	-0.76	2	2
KIF20A	-0.3	0.29	-9999	-0.58	253	253
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.29	0.19	-9999	-0.4	351	351
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	0.066	-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	154	154
AURKB	-0.41	0.26	-9999	-0.57	351	351
AURKC	-0.003	0.042	-9999	-0.66	2	2
CDCA8	-0.16	0.26	-9999	-0.58	134	134
cytokinesis	-0.32	0.16	-9999	-0.46	228	228
Aurora B/Septin1	-0.3	0.16	-9999	-0.46	173	173
AURKA	-0.016	0.12	-9999	-0.58	22	22
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	-0.74	396	396
EVI5	0.005	0.004	-9999	-10000	0	0
RhoA/GTP	-0.27	0.18	-9999	-0.5	150	150
SGOL1	-0.3	0.29	-9999	-0.57	255	255
CENPA	-0.24	0.12	-9999	-0.31	342	342
NCAPG	-0.1	0.22	-9999	-0.57	88	88
Aurora B/HC8 Proteasome	-0.29	0.19	-9999	-0.4	351	351
NCAPD2	-0.001	0.026	-9999	-0.57	1	1
Aurora B/PP1-gamma	-0.29	0.19	-9999	-0.4	351	351
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.29	0.29	-9999	-0.57	249	249
NPM1	-0.13	0.083	-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	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.29	0.19	-9999	-0.4	351	351
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.3	0.2	-9999	-0.51	179	179
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.13	0.083	-9999	-10000	0	0
MYLK	-0.15	0.1	-9999	-0.21	351	351
KIF23	-0.12	0.23	-9999	-0.58	98	98
VIM	-0.3	0.21	-9999	-0.42	351	351
RACGAP1	0.001	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.13	0.083	-9999	-10000	0	0
Chromosomal passenger complex	-0.27	0.14	-9999	-0.35	338	338
Chromosomal passenger complex/EVI5	-0.49	0.25	-9999	-0.63	343	343
TACC1	-0.003	0.047	-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	0.43	-9999	-1	146	146
PLK1	-0.19	0.2	-9999	-10000	0	0
BIRC5	-0.32	0.16	-9999	-10000	0	0
HSPA1B	-0.58	0.43	-9999	-1	162	162
MAP2K1	-0.012	0.023	-9999	-10000	0	0
BRCA2	-0.58	0.43	-9999	-1	149	149
FOXM1	-0.7	0.55	-9999	-1.2	213	213
XRCC1	-0.58	0.43	-9999	-1	145	145
FOXM1B/p19	-0.6	0.43	-9999	-1	185	185
Cyclin D1/CDK4	-0.54	0.4	-9999	-0.97	131	131
CDC2	-0.61	0.45	-9999	-1	210	210
TGFA	-0.52	0.38	-9999	-0.92	132	132
SKP2	-0.58	0.43	-9999	-1	137	137
CCNE1	-0.13	0.24	-9999	-0.58	108	108
CKS1B	-0.58	0.43	-9999	-1	149	149
RB1	-0.26	0.15	-9999	-0.49	15	15
FOXM1C/SP1	-0.65	0.45	-9999	-1.1	213	213
AURKB	-0.28	0.19	-9999	-0.41	1	1
CENPF	-0.64	0.47	-9999	-1.1	211	211
CDK4	0.002	0.028	-9999	-0.59	1	1
MYC	-0.51	0.38	-9999	-0.9	136	136
CHEK2	-0.012	0.023	-9999	-10000	0	0
ONECUT1	-0.57	0.42	-9999	-0.99	171	171
CDKN2A	-0.26	0.29	-9999	-0.56	229	229
LAMA4	-0.58	0.43	-9999	-1	171	171
FOXM1B/HNF6	-0.65	0.5	-9999	-1.1	179	179
FOS	-0.63	0.5	-9999	-1.2	163	163
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.58	0.43	-9999	-1	145	145
response to radiation	-0.024	0.023	-9999	-10000	0	0
CENPB	-0.58	0.43	-9999	-1	149	149
CENPA	-0.71	0.46	-9999	-1.1	255	255
NEK2	-0.69	0.48	-9999	-1.1	225	225
HIST1H2BA	-0.58	0.43	-9999	-1	161	161
CCNA2	-0.15	0.26	-9999	-0.59	126	126
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.66	0.5	-9999	-1.2	162	162
CCNB2	-0.66	0.48	-9999	-1.1	226	226
CCNB1	-0.62	0.46	-9999	-1.1	161	161
ETV5	-0.58	0.44	-9999	-1.1	136	136
ESR1	-0.6	0.45	-9999	-1.1	147	147
CCND1	-0.55	0.41	-9999	-0.98	144	144
GSK3A	-0.004	0.019	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.17	0.24	-9999	-0.44	193	193
CDK2	0.002	0.006	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.03	0.027	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.64	0.42	-9999	-1	220	220
GAS1	-0.58	0.44	-9999	-1	148	148
MMP2	-0.58	0.43	-9999	-1	143	143
RB1/FOXM1C	-0.58	0.44	-9999	-1	168	168
CREBBP	0	0	-9999	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.029	0.23	-10000	0	-0.6	45	45
PTK2B	0.002	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.081	0.29	-10000	0	-0.97	31	31
EDN1	-0.042	0.25	-10000	0	-0.78	42	42
EDN3	-0.089	0.24	-10000	0	-0.7	62	62
EDN2	-0.085	0.21	-10000	0	-0.59	71	71
HRAS/GDP	-0.18	0.3	-10000	0	-0.64	122	122
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.054	0.2	-10000	0	-0.49	60	60
ADCY4	-0.078	0.22	-10000	0	-0.71	33	33
ADCY5	-0.09	0.23	-10000	0	-0.66	44	44
ADCY6	-0.054	0.19	-10000	0	-0.64	26	26
ADCY7	-0.053	0.18	-10000	0	-0.59	31	31
ADCY1	-0.054	0.18	-10000	0	-0.59	30	30
ADCY2	-0.085	0.21	-10000	0	-0.65	35	35
ADCY3	-0.053	0.18	-10000	0	-0.59	31	31
ADCY8	-0.18	0.24	-10000	0	-0.64	56	56
ADCY9	-0.054	0.18	-10000	0	-0.6	31	31
arachidonic acid secretion	-0.15	0.27	-10000	0	-0.61	87	87
ETB receptor/Endothelin-1/Gq/GTP	-0.32	0.35	-10000	0	-0.7	176	176
GNAO1	-0.004	0.049	-10000	0	-0.63	3	3
HRAS	0.002	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.038	0.26	-10000	0	-0.63	31	31
ETA receptor/Endothelin-1/Gs/GTP	0.031	0.25	-10000	0	-0.61	33	33
mol:GTP	0	0.004	-10000	0	-10000	0	0
COL3A1	-0.045	0.25	-10000	0	-0.7	31	31
EDNRB	-0.45	0.36	-10000	0	-0.74	301	301
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.044	0.27	-10000	0	-0.79	36	36
CYSLTR1	-0.092	0.36	-10000	0	-0.87	71	71
SLC9A1	-0.007	0.12	-10000	0	-0.37	16	16
mol:GDP	-0.21	0.33	-10000	0	-0.7	126	126
SLC9A3	-0.37	0.39	-10000	0	-0.73	208	208
RAF1	-0.21	0.32	-10000	0	-0.66	136	136
JUN	-0.058	0.23	-10000	0	-0.7	24	24
JAK2	-0.029	0.23	-10000	0	-0.58	49	49
mol:IP3	-0.21	0.3	-10000	0	-0.68	125	125
ETA receptor/Endothelin-1	0.018	0.32	-10000	0	-0.66	52	52
PLCB1	0.003	0.005	-10000	0	-10000	0	0
PLCB2	-0.005	0.095	-10000	0	-0.74	8	8
ETA receptor/Endothelin-3	-0.056	0.21	-10000	0	-0.54	67	67
FOS	-0.2	0.36	-10000	0	-0.86	86	86
Gai/GDP	-0.007	0.067	-10000	0	-0.5	4	4
CRK	0.002	0.004	-10000	0	-10000	0	0
mol:Ca ++	-0.25	0.36	-10000	0	-0.76	139	139
BCAR1	0.007	0.005	-10000	0	-10000	0	0
PRKCB1	-0.2	0.29	-10000	0	-0.64	126	126
GNAQ	0.008	0.034	-10000	0	-0.74	1	1
GNAZ	-0.009	0.081	-10000	0	-0.74	6	6
GNAL	-0.006	0.067	-10000	0	-0.74	4	4
Gs family/GDP	-0.21	0.27	-10000	0	-0.62	123	123
ETA receptor/Endothelin-1/Gq/GTP	-0.066	0.23	-10000	0	-0.55	59	59
MAPK14	-0.24	0.29	-10000	0	-0.65	129	129
TRPC6	-0.089	0.31	-10000	0	-1.1	29	29
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.033	-10000	0	-0.74	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.26	0.3	-10000	0	-0.66	145	145
ETB receptor/Endothelin-2	-0.4	0.29	-10000	0	-0.58	332	332
ETB receptor/Endothelin-3	-0.4	0.3	-10000	0	-0.6	327	327
ETB receptor/Endothelin-1	-0.38	0.34	-10000	0	-0.61	314	314
MAPK3	-0.22	0.36	-10000	0	-0.78	112	112
MAPK1	-0.22	0.36	-10000	0	-0.79	109	109
Rac1/GDP	-0.18	0.3	-10000	0	-0.64	123	123
cAMP biosynthetic process	-0.077	0.21	-10000	0	-0.59	44	44
MAPK8	-0.08	0.27	-10000	0	-0.7	48	48
SRC	0	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.17	0.17	-10000	0	-0.43	69	69
p130Cas/CRK/Src/PYK2	-0.19	0.32	-10000	0	-0.68	122	122
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.18	0.3	-10000	0	-0.64	122	122
COL1A2	-0.26	0.31	-10000	0	-0.75	95	95
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.049	0.19	-10000	0	-0.46	74	74
mol:DAG	-0.21	0.31	-10000	0	-0.68	125	125
MAP2K2	-0.2	0.32	-10000	0	-0.65	144	144
MAP2K1	-0.2	0.32	-10000	0	-0.65	144	144
EDNRA	0.015	0.14	-10000	0	-0.93	5	5
positive regulation of muscle contraction	-0.031	0.2	-10000	0	-0.6	29	29
Gq family/GDP	-0.2	0.3	-10000	0	-0.7	116	116
HRAS/GTP	-0.22	0.32	-10000	0	-0.69	127	127
PRKCH	-0.2	0.29	-10000	0	-0.66	118	118
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.2	0.29	-10000	0	-0.67	117	117
PRKCB	-0.22	0.32	-10000	0	-0.71	123	123
PRKCE	-0.2	0.29	-10000	0	-0.66	118	118
PRKCD	-0.2	0.29	-10000	0	-0.66	116	116
PRKCG	-0.22	0.3	-10000	0	-0.68	124	124
regulation of vascular smooth muscle contraction	-0.24	0.42	-10000	0	-1	86	86
PRKCQ	-0.23	0.34	-10000	0	-0.73	132	132
PLA2G4A	-0.16	0.3	-10000	0	-0.67	87	87
GNA14	-0.17	0.32	-10000	0	-0.74	117	117
GNA15	0.008	0.005	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
GNA11	0.008	0.005	-10000	0	-10000	0	0
Rac1/GTP	0.038	0.26	-10000	0	-0.61	34	34
MMP1	-0.23	0.24	0.32	1	-0.42	283	284

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.012	0.081	-9999	-0.57	10	10
GPC2	-0.085	0.2	-9999	-0.57	73	73
GPC2/Midkine	-0.07	0.16	-9999	-0.42	81	81
neuron projection morphogenesis	-0.07	0.16	-9999	-0.42	81	81

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.06	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	229	229
CCND2	0.073	0.081	0.26	42	-10000	0	42
RB1	-0.079	0.084	-10000	0	-0.26	42	42
CDK4	0.085	0.087	0.26	42	-10000	0	42
CDK6	0.081	0.089	0.29	42	-10000	0	42
G1/S progression	0.072	0.091	0.26	42	-10000	0	42

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.062	0.22	-9999	-0.72	42	42
alphaM/beta2 Integrin/GPIbA	-0.063	0.21	-9999	-0.7	43	43
alphaM/beta2 Integrin/proMMP-9	-0.076	0.21	-9999	-0.69	41	41
PLAUR	0	0	-9999	-10000	0	0
HMGB1	0	0.003	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.058	0.2	-9999	-0.69	41	41
AGER	-0.68	0.2	-9999	-0.74	449	449
RAP1A	0	0	-9999	-10000	0	0
SELPLG	-0.048	0.18	-9999	-0.74	32	32
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.48	0.26	-9999	-0.52	449	449
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.03	0.13	-9999	-0.57	26	26
CYR61	-0.039	0.17	-9999	-0.74	26	26
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.21	0.29	-9999	-0.63	115	115
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.19	0.32	-9999	-0.74	124	124
MYH2	-0.32	0.36	-9999	-0.71	173	173
MST1R	-0.045	0.18	-9999	-0.74	30	30
leukocyte activation during inflammatory response	-0.087	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	0.071	-9999	-0.71	5	5
alphaM/beta2 Integrin/CTGF	-0.075	0.24	-9999	-0.73	50	50
alphaM/beta2 Integrin	-0.26	0.38	-9999	-0.77	119	119
JAM3 homodimer	0	0	-9999	-10000	0	0
ICAM2	-0.05	0.18	-9999	-0.74	33	33
ICAM1	-0.065	0.21	-9999	-0.74	43	43
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.24	0.37	-9999	-0.74	119	119
cell adhesion	-0.062	0.21	-9999	-0.7	43	43
NFKB1	-0.46	0.3	-9999	-0.92	112	112
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	-0.057	0.19	-9999	-0.64	41	41
IL6	-0.49	0.38	-9999	-1.1	114	114
ITGB2	-0.031	0.15	-9999	-0.74	20	20
elevation of cytosolic calcium ion concentration	-0.072	0.2	-9999	-0.64	41	41
alphaM/beta2 Integrin/JAM2/JAM3	-0.12	0.28	-9999	-0.63	92	92
JAM2	-0.11	0.26	-9999	-0.74	74	74
alphaM/beta2 Integrin/ICAM1	-0.11	0.28	-9999	-0.64	84	84
alphaM/beta2 Integrin/uPA/Plg	-0.075	0.2	-9999	-0.65	41	41
RhoA/GTP	-0.3	0.37	-9999	-0.86	117	117
positive regulation of phagocytosis	-0.18	0.27	-9999	-0.75	70	70
Ron/MSP	-0.035	0.14	-9999	-0.55	31	31
alphaM/beta2 Integrin/uPAR/uPA	-0.072	0.2	-9999	-0.64	41	41
alphaM/beta2 Integrin/uPAR	-0.058	0.2	-9999	-0.69	41	41
PLAU	-0.035	0.14	-9999	-0.57	30	30
PLAT	-0.007	0.063	-9999	-0.57	6	6
actin filament polymerization	-0.3	0.32	-9999	-0.66	173	173
MST1	-0.001	0.026	-9999	-0.57	1	1
alphaM/beta2 Integrin/lipoprotein(a)	-0.089	0.22	-9999	-0.59	65	65
TNF	-0.42	0.28	-9999	-0.84	112	112
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.079	0.21	-9999	-0.7	41	41
fibrinolysis	-0.074	0.2	-9999	-0.64	41	41
HCK	-0.008	0.074	-9999	-0.74	5	5
dendritic cell antigen processing and presentation	-0.24	0.37	-9999	-0.74	119	119
VTN	-0.29	0.36	-9999	-0.74	192	192
alphaM/beta2 Integrin/CYR61	-0.082	0.25	-9999	-0.72	56	56
LPA	-0.021	0.11	-9999	-0.57	18	18
LRP1	0	0	-9999	-10000	0	0
cell migration	-0.073	0.21	-9999	-0.66	42	42
FN1	-0.017	0.11	-9999	-0.74	11	11
alphaM/beta2 Integrin/Thy1	-0.058	0.2	-9999	-0.69	41	41
MPO	-0.033	0.15	-9999	-0.74	22	22
KNG1	-0.014	0.089	-9999	-0.57	12	12
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.26	0.34	-9999	-0.79	111	111
ELA2	0	0	-9999	-10000	0	0
PLG	-0.004	0.045	-9999	-0.57	3	3
CTGF	-0.027	0.14	-9999	-0.74	18	18
alphaM/beta2 Integrin/Hck	-0.063	0.22	-9999	-0.71	43	43
ITGAM	-0.061	0.2	-9999	-0.74	40	40
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.19	0.36	-9999	-0.66	139	139
HP	-0.23	0.34	-9999	-0.74	153	153
leukocyte adhesion	-0.44	0.3	-9999	-0.8	147	147
SELP	-0.19	0.32	-9999	-0.74	124	124

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.059	0.21	-10000	0	-0.74	43	43
GNB1/GNG2	-0.07	0.09	-10000	0	-0.22	62	62
AKT1	-0.035	0.13	-10000	0	-0.22	38	38
EGF	-0.014	0.098	-10000	0	-0.69	10	10
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.037	0.13	-10000	0	-0.61	16	16
mol:Ca2+	-0.074	0.18	-10000	0	-0.31	171	171
LYN	-0.017	0.076	-10000	0	-0.53	7	7
RhoA/GTP	-0.047	0.059	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.082	0.2	-10000	0	-0.35	166	166
GNG2	-0.008	0.074	-10000	0	-0.74	5	5
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.018	0.1	-10000	0	-0.57	5	5
G beta5/gamma2	-0.091	0.12	-10000	0	-0.29	71	71
PRKCH	-0.088	0.21	-10000	0	-0.36	165	165
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	-0.023	0.13	-10000	0	-0.74	15	15
G12 family/GTP	-0.12	0.14	-10000	0	-0.31	167	167
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	-0.002	0.033	-10000	0	-0.74	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.039	0.13	0.41	20	-10000	0	20
mol:NADP	-0.006	0.067	-10000	0	-0.74	4	4
RAB11A	0	0	-10000	0	-10000	0	0
PRKG1	-0.06	0.2	-10000	0	-0.74	40	40
mol:IP3	-0.1	0.22	-10000	0	-0.39	173	173
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.15	0.3	-10000	0	-0.53	173	173
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	-0.019	0.085	-10000	0	-0.56	8	8
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.02	0.12	-10000	0	-0.74	13	13
PRKCB1	-0.1	0.22	-10000	0	-0.39	168	168
GNAQ	-0.002	0.033	-10000	0	-0.74	1	1
mol:L-citrulline	-0.006	0.067	-10000	0	-0.74	4	4
TXA2/TXA2-R family	-0.15	0.3	-10000	0	-0.55	167	167
LCK	-0.016	0.075	-10000	0	-0.52	7	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.019	0.09	-10000	0	-0.71	5	5
TXA2-R family/G12 family/GDP/G beta/gamma	0.019	0.044	-10000	0	-0.42	2	2
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.019	0.089	-10000	0	-0.65	6	6
MAPK14	-0.043	0.14	-10000	0	-0.25	67	67
TGM2/GTP	-0.12	0.26	-10000	0	-0.46	177	177
MAPK11	-0.043	0.14	-10000	0	-0.25	44	44
ARHGEF1	-0.035	0.11	-10000	0	-0.2	38	38
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	-0.099	0.23	-10000	0	-0.4	167	167
RAB11/GDP	0	0	-10000	0	-10000	0	0
ICAM1	-0.076	0.19	-10000	0	-0.32	165	165
cAMP biosynthetic process	-0.095	0.21	-10000	0	-0.36	177	177
Gq family/GTP/EBP50	-0.036	0.11	-10000	0	-0.53	3	3
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.015	0.072	-10000	0	-0.52	6	6
GNB5	0	0	-10000	0	-10000	0	0
GNB1	-0.002	0.033	-10000	0	-0.74	1	1
EGF/EGFR	0.023	0.095	-10000	0	-0.42	10	10
VCAM1	-0.069	0.17	-10000	0	-0.3	166	166
TP beta/Gq family/GDP/G beta5/gamma2	-0.018	0.1	-10000	0	-0.57	5	5
platelet activation	-0.06	0.19	-10000	0	-0.31	166	166
PGI2/IP	-0.015	0.091	-10000	0	-0.57	13	13
PRKACA	-0.022	0.1	-10000	0	-0.44	24	24
Gq family/GDP/G beta5/gamma2	-0.021	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	-0.007	0.11	-10000	0	-0.43	25	25
mol:DAG	-0.11	0.25	-10000	0	-0.44	168	168
EGFR	-0.022	0.12	-10000	0	-0.63	17	17
TXA2/TP alpha	-0.14	0.28	-10000	0	-0.5	177	177
Gq family/GTP	-0.066	0.12	-10000	0	-0.28	117	117
YES1	-0.015	0.072	-10000	0	-0.52	6	6
GNAI2/GTP	-0.018	0.084	-10000	0	-0.62	6	6
PGD2/DP	-0.017	0.098	-10000	0	-0.57	15	15
SLC9A3R1	-0.005	0.052	-10000	0	-0.57	4	4
FYN	-0.016	0.076	-10000	0	-0.56	6	6
mol:NO	-0.006	0.067	-10000	0	-0.74	4	4
GNA15	0	0	-10000	0	-10000	0	0
PGK/cGMP	-0.044	0.14	-10000	0	-0.51	42	42
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.054	0.17	-10000	0	-0.76	17	17
NOS3	-0.006	0.067	-10000	0	-0.74	4	4
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.089	0.21	-10000	0	-0.36	157	157
PRKCB	-0.098	0.22	-10000	0	-0.39	159	159
PRKCE	-0.088	0.21	-10000	0	-0.37	156	156
PRKCD	-0.097	0.22	-10000	0	-0.39	164	164
PRKCG	-0.11	0.23	-10000	0	-0.41	166	166
muscle contraction	-0.13	0.28	-10000	0	-0.5	169	169
PRKCZ	-0.081	0.2	-10000	0	-0.35	166	166
ARR3	0	0	-10000	0	-10000	0	0
TXA2/TP beta	-0.02	0.096	-10000	0	-0.67	7	7
PRKCQ	-0.11	0.23	-10000	0	-0.4	171	171
MAPKKK cascade	-0.13	0.27	-10000	0	-0.48	170	170
SELE	-0.11	0.23	-10000	0	-0.42	165	165
TP beta/GNAI2/GDP/G beta/gamma	-0.023	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	117	117
chemotaxis	-0.17	0.34	-10000	0	-0.62	166	166
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 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
Cone Metarhodopsin II/Cone Transducin	-0.021	0.086	-9999	-0.42	17	17
RGS9BP	-0.015	0.1	-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	242	242
mol:ADP	-0.009	0.093	-9999	-0.42	24	24
GNAT2	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.061	0.16	-9999	-0.49	61	61
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	-0.026	0.12	-9999	-0.57	22	22
CNGB3	-0.28	0.29	-9999	-0.57	240	240
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.21	0.2	-9999	-0.36	292	292
Cone PDE6	-0.053	0.14	-9999	-0.42	61	61
Cone Metarhodopsin II	-0.016	0.07	-9999	-0.32	24	24
Na + (4 Units)	-0.22	0.2	-9999	-0.36	292	292
GNAT2/GDP	-0.053	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	-0.022	0.091	-9999	-0.44	17	17
SLC24A2	-0.11	0.23	-9999	-0.57	94	94
GNB3/GNGT2	-0.028	0.12	-9999	-0.5	27	27
GNB3	-0.012	0.081	-9999	-0.57	10	10
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	242	242
mol:Pi	-0.061	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	94	94
RGS9	-0.08	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

×

Aurora C 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	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	-0.68	2	2
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	351	351
AURKC	-0.003	0.042	-9999	-0.66	2	2

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0	0	-9999	-10000	0	0
LAT2	-0.16	0.25	-9999	-0.67	71	71
AP1	-0.19	0.26	-9999	-0.64	104	104
mol:PIP3	-0.16	0.29	-9999	-0.66	83	83
IKBKB	-0.07	0.16	-9999	-0.34	76	76
AKT1	-0.17	0.24	-9999	-0.67	68	68
IKBKG	-0.069	0.16	-9999	-0.34	75	75
MS4A2	-0.17	0.31	-9999	-0.74	110	110
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.002	-9999	-10000	0	0
MAP3K1	-0.099	0.23	-9999	-0.54	78	78
mol:Ca2+	-0.11	0.21	-9999	-0.46	83	83
LYN	0.005	0.05	-9999	-0.77	2	2
CBLB	-0.16	0.24	-9999	-0.64	70	70
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.057	0.15	-9999	-0.44	63	63
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.002	0.033	-9999	-0.74	1	1
PLD2	-0.21	0.28	-9999	-0.77	70	70
PTPN13	-0.12	0.24	-9999	-0.6	71	71
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	71	71
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	-0.69	84	84
LAT	-0.16	0.24	-9999	-0.64	70	70
PAK2	-0.12	0.26	-9999	-0.61	82	82
NFATC2	-0.18	0.32	-9999	-0.94	67	67
HRAS	-0.14	0.29	-9999	-0.68	84	84
GAB2	-0.02	0.12	-9999	-0.74	13	13
PLA2G1B	-0.002	0.037	-9999	-10000	0	0
Fc epsilon R1	-0.25	0.34	-9999	-0.63	196	196
Antigen/IgE/Fc epsilon R1	-0.24	0.32	-9999	-0.59	196	196
mol:GDP	-0.16	0.31	-9999	-0.75	84	84
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	56	56
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.17	0.25	-9999	-0.54	117	117
CHUK	-0.069	0.16	-9999	-0.34	75	75
KLRG1	-0.15	0.23	-9999	-0.63	71	71
VAV1	-0.16	0.25	-9999	-0.67	71	71
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.16	0.24	-9999	-0.64	70	70
negative regulation of mast cell degranulation	-0.14	0.22	-9999	-0.58	71	71
BTK	-0.2	0.33	-9999	-0.8	88	88
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.2	0.31	-9999	-0.85	72	72
GAB2/PI3K/SHP2	-0.19	0.27	-9999	-0.75	68	68
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	-0.22	0.32	-9999	-0.61	151	151
FCER1G	-0.016	0.13	-9999	-0.76	14	14
FCER1A	-0.22	0.35	-9999	-0.75	144	144
Antigen/IgE/Fc epsilon R1/Fyn	-0.22	0.3	-9999	-0.55	196	196
MAPK3	0.033	0.023	-9999	-10000	0	0
MAPK1	0.033	0.023	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.021	0.07	-9999	-10000	0	0
DUSP1	-0.095	0.25	-9999	-0.74	63	63
NF-kappa-B/RelA	-0.059	0.075	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.13	0.24	-9999	-0.62	70	70
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.15	0.24	-9999	-0.63	78	78
FER	-0.16	0.24	-9999	-0.64	70	70
RELA	0	0	-9999	-10000	0	0
ITK	-0.077	0.18	-9999	-0.66	37	37
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.16	0.31	-9999	-0.74	85	85
cytokine secretion	-0.043	0.054	-9999	-10000	0	0
SPHK1	-0.16	0.24	-9999	-0.64	70	70
PTK2	-0.14	0.26	-9999	-0.66	70	70
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.21	0.28	-9999	-0.73	84	84
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.15	0.28	-9999	-0.64	84	84
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	-0.58	71	71
MAP2K4	0.009	0.013	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.24	0.33	-9999	-0.59	197	197
mol:Choline	-0.2	0.28	-9999	-0.75	70	70
SHC/Grb2/SOS1	-0.14	0.22	-9999	-0.6	69	69
FYN	-0.002	0.033	-9999	-0.74	1	1
DOK1	0	0	-9999	-10000	0	0
PXN	-0.12	0.24	-9999	-0.6	69	69
HCLS1	-0.16	0.24	-9999	-0.64	70	70
PRKCB	-0.11	0.22	-9999	-0.49	84	84
FCGR2B	-0.014	0.099	-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	0.088	-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	-0.75	70	70
IKK complex	-0.038	0.12	-9999	-0.28	24	24
WIPF1	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	105	105
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	125	125
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	-0.68	53	53
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	0.033	-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	-1.2	111	111
SOCS1	-0.23	0.35	-10000	0	-0.78	68	68
SOCS3	-0.16	0.27	-10000	0	-1.1	7	7
FCER2	-0.34	0.5	-10000	0	-1.2	76	76
PARP14	0.007	0.006	-10000	0	-10000	0	0
CCL17	-0.46	0.62	-10000	0	-1.4	125	125
GRB2	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.12	0.22	-10000	0	-0.9	7	7
T cell proliferation	-0.38	0.54	-10000	0	-1.2	107	107
IL4R/JAK1	-0.39	0.53	-10000	0	-1.2	105	105
EGR2	-0.41	0.56	-10000	0	-1.2	109	109
JAK2	-0.004	0.034	-10000	0	-10000	0	0
JAK3	0.013	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	-0.65	2	2
CCL26	-0.42	0.55	-10000	0	-1.2	117	117
IL4R	-0.42	0.57	-10000	0	-1.3	105	105
PTPN6	0.019	0.014	-10000	0	-10000	0	0
IL13RA2	-0.42	0.57	-10000	0	-1.2	117	117
IL13RA1	-0.004	0.034	-10000	0	-10000	0	0
IRF4	-0.17	0.36	-10000	0	-0.91	77	77
ARG1	-0.12	0.24	-10000	0	-0.8	30	30
CBL	-0.18	0.29	-10000	0	-0.76	23	23
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	-0.86	72	72
CD40LG	-0.12	0.29	-10000	0	-0.74	86	86
MAPK14	-0.18	0.3	-10000	0	-0.94	12	12
mitosis	-0.14	0.25	-10000	0	-0.84	9	9
STAT6	-0.46	0.63	-10000	0	-1.4	117	117
SPI1	-0.044	0.19	-10000	0	-0.74	35	35
RPS6KB1	-0.13	0.24	-10000	0	-0.88	7	7
STAT6 (dimer)	-0.46	0.63	-10000	0	-1.4	117	117
STAT6 (dimer)/PARP14	-0.43	0.58	-10000	0	-1.3	108	108
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	-0.84	31	31
FRAP1	-0.14	0.26	-10000	0	-0.92	9	9
LTA	-0.39	0.54	-10000	0	-1.2	100	100
FES	-0.002	0.033	-10000	0	-0.74	1	1
T-helper 1 cell differentiation	0.44	0.61	1.3	118	-10000	0	118
CCL11	-0.39	0.52	-10000	0	-1.2	107	107
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.15	0.26	-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	106	106
IRS1	0	0	-10000	0	-10000	0	0
IRS2	-0.005	0.058	-10000	0	-0.74	3	3
IL4	-0.079	0.14	-10000	0	-10000	0	0
IL5	-0.4	0.53	-10000	0	-1.2	105	105
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.31	0.42	-10000	0	-0.9	105	105
COL1A1	-0.14	0.23	-10000	0	-0.69	17	17
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.4	0.55	-10000	0	-1.3	100	100
IL2R gamma/JAK3	-0.004	0.071	-10000	0	-0.55	8	8
TFF3	-0.44	0.62	-10000	0	-1.4	108	108
ALOX15	-0.63	0.76	-10000	0	-1.5	180	180
MYBL1	-0.001	0.026	-10000	0	-0.57	1	1
T-helper 2 cell differentiation	-0.32	0.43	-10000	0	-0.93	107	107
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	44	44
ETS1	-0.001	0.12	-10000	0	-0.7	13	13
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	-1.3	101	101
PIGR	-0.8	0.83	-10000	0	-1.6	259	259
IGHE	0.029	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	0.53	-10000	0	-1.2	102	102
RETNLB	-0.4	0.53	-10000	0	-1.2	103	103
SELP	-0.57	0.74	-10000	0	-1.6	151	151
AICDA	-0.38	0.51	-10000	0	-1.2	105	105

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.06	0.099	0.36	2	-10000	0	2
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	64	64
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	0.33	48	-10000	0	48
PRL	-0.085	0.12	-10000	0	-0.54	3	3
cortisol/GR alpha (dimer)/TIF2	0.31	0.25	0.59	158	-10000	0	158
RELA	-0.046	0.1	-10000	0	-0.33	1	1
FGG	-0.13	0.47	0.54	56	-0.62	227	283
GR beta/TIF2	0.14	0.12	0.36	54	-0.39	1	55
IFNG	-0.35	0.24	-10000	0	-0.76	67	67
apoptosis	0.028	0.12	0.46	2	-0.51	2	4
CREB1	0.001	0.028	-10000	0	-10000	0	0
histone acetylation	-0.012	0.15	0.36	2	-0.39	22	24
BGLAP	-0.096	0.14	-10000	0	-0.53	10	10
GR/PKAc	0.12	0.099	0.34	28	-10000	0	28
NF kappa B1 p50/RelA	-0.083	0.18	-10000	0	-0.49	34	34
SMARCD1	0.011	0	-10000	0	-10000	0	0
MDM2	0.11	0.098	0.29	60	-0.31	1	61
GATA3	-0.013	0.13	-10000	0	-0.71	17	17
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.18	0.42	-10000	0	-1.3	55	55
GSK3B	0.002	0.006	-10000	0	-10000	0	0
NR1I3	0.047	0.11	0.47	1	-10000	0	1
CSN2	0.17	0.16	0.44	44	-10000	0	44
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	-0.58	48	48
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.095	0.14	0.33	39	-10000	0	39
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.035	0.16	0.46	1	-0.9	9	10
JUN	-0.29	0.16	-10000	0	-0.52	97	97
IL4	-0.11	0.15	-10000	0	-0.53	13	13
CDK5R1	-0.01	0.081	-10000	0	-0.57	10	10
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.44	0.23	-10000	0	-0.59	277	277
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.099	0.33	36	-10000	0	36
cortisol/GR alpha (monomer)	0.37	0.32	0.72	166	-10000	0	166
NCOA2	-0.002	0.033	-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	56	56
AP-1/NFAT1-c-4	-0.53	0.24	-10000	0	-0.69	262	262
AFP	-0.19	0.15	-10000	0	-0.66	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	-0.7	271	271
KRT14	-0.37	0.22	-10000	0	-0.64	107	107
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	0.011	0.031	-10000	0	-10000	0	0
AP-1	-0.53	0.25	-10000	0	-0.69	266	266
MAPK14	0.002	0.005	-10000	0	-10000	0	0
MAPK10	-0.01	0.094	-10000	0	-0.74	8	8
MAPK11	0.002	0.006	-10000	0	-10000	0	0
KRT5	-0.56	0.26	-10000	0	-0.72	267	267
interleukin-1 receptor activity	0.008	0.029	-10000	0	-10000	0	0
NCOA1	0.013	0.002	-10000	0	-10000	0	0
STAT1	0.017	0	-10000	0	-10000	0	0
CGA	-0.12	0.16	-10000	0	-0.53	30	30
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.2	0.19	0.48	109	-10000	0	109
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	-1.2	73	73
NFKB1	-0.046	0.1	-10000	0	-10000	0	0
MAPK8	-0.24	0.17	-10000	0	-0.46	121	121
MAPK9	0.002	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.026	0.12	0.46	2	-0.54	2	4
BAX	0.026	0.015	-10000	0	-10000	0	0
POMC	-0.21	0.24	-10000	0	-0.78	36	36
EP300	0.11	0.067	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	0.077	0.074	0.26	15	-0.27	1	16
SGK1	0.17	0.076	-10000	0	-10000	0	0
IL13	-0.27	0.2	-10000	0	-0.71	51	51
IL6	-0.34	0.53	-10000	0	-1.3	103	103
PRKACG	-0.001	0.026	-10000	0	-0.57	1	1
IL5	-0.24	0.17	-10000	0	-0.68	34	34
IL2	-0.34	0.2	-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	0.28	-10000	0	-0.76	63	63
CDK5R1/CDK5	-0.007	0.059	-10000	0	-0.41	10	10
NF kappa B1 p50/RelA/PKAc	-0.058	0.12	-10000	0	-0.48	4	4
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.3	0.23	0.57	150	-10000	0	150
SMARCA4	0.011	0	-10000	0	-10000	0	0
chromatin remodeling	0.19	0.14	0.4	104	-10000	0	104
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	-0.52	97	97
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.42	0.51	-10000	0	-1.1	180	180
NR3C1	0.2	0.2	0.51	96	-10000	0	96
NR4A1	-0.098	0.26	-10000	0	-0.73	67	67
TIF2/SUV420H1	-0.001	0.025	-10000	0	-0.56	1	1
MAPKKK cascade	0.028	0.12	0.46	2	-0.51	2	4
cortisol/GR alpha (dimer)/Src-1	0.32	0.25	0.6	159	-10000	0	159
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	157	157
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.19	0.14	0.4	104	-10000	0	104
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.3	0.23	0.57	150	-10000	0	150
mol:cortisol	0.2	0.2	0.41	175	-0.23	3	178
MMP1	-0.33	0.19	-10000	0	-0.48	295	295

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.044	0.056	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.099	0.14	-9999	-0.43	21	21
JUN	-0.063	0.14	-9999	-0.41	18	18
HRAS	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.17	0.22	-9999	-0.48	126	126
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	126	126
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	-0.42	185	185
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.15	0.2	-9999	-0.66	22	22
GRB7	-0.005	0.052	-9999	-0.57	4	4
RET51/GFRalpha1/GDNF	-0.17	0.22	-9999	-0.48	126	126
MAPKKK cascade	-0.13	0.18	-9999	-0.59	20	20
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.16	0.22	-9999	-0.48	121	121
lamellipodium assembly	-0.095	0.13	-9999	-0.4	21	21
RET51/GFRalpha1/GDNF/SHC	-0.17	0.22	-9999	-0.48	126	126
PIK3CA	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.16	0.22	-9999	-0.48	121	121
RET9/GFRalpha1/GDNF/Shank3	-0.16	0.22	-9999	-0.49	121	121
MAPK3	-0.14	0.19	-9999	-0.62	22	22
DOK1	0	0	-9999	-10000	0	0
DOK6	-0.065	0.21	-9999	-0.74	43	43
PXN	0	0	-9999	-10000	0	0
neurite development	-0.14	0.18	-9999	-0.55	41	41
DOK5	-0.005	0.06	-9999	-0.66	4	4
GFRA1	-0.18	0.32	-9999	-0.74	121	121
MAPK8	-0.096	0.13	-9999	-0.44	18	18
HRAS/GTP	-0.14	0.2	-9999	-0.5	53	53
tube development	-0.15	0.21	-9999	-0.46	121	121
MAPK1	-0.14	0.19	-9999	-0.62	22	22
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.1	0.14	-9999	-0.33	121	121
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	146	146
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.22	-9999	-0.48	126	126
RET51/GFRalpha1/GDNF/Dok5	-0.17	0.23	-9999	-0.49	126	126
PRKCA	-0.003	0.047	-9999	-0.74	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.11	0.16	-9999	-0.36	121	121
PIK3R1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.14	-9999	-0.33	121	121
RET51/GFRalpha1/GDNF/Grb7	-0.17	0.22	-9999	-0.49	127	127
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.02	0.11	-9999	-0.58	17	17
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.062	0.14	-9999	-0.41	18	18
RET9/GFRalpha1/GDNF/FRS2	-0.16	0.22	-9999	-0.42	185	185
SHANK3	-0.003	0.047	-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	121	121
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.1	0.14	-9999	-0.47	18	18
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.1	0.14	-9999	-0.33	122	122
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.48	18	18
PI3K	-0.14	0.2	-9999	-0.64	21	21
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.15	0.21	-9999	-0.46	121	121
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.1	0.14	-9999	-0.47	18	18
RET51/GFRalpha1/GDNF/FRS2	-0.17	0.22	-9999	-0.48	126	126
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	18	18
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.22	-9999	-0.49	127	127
GRB2	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.094	0.21	-9999	-0.57	80	80
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.22	-9999	-0.48	126	126
Rac1/GTP	-0.11	0.16	-9999	-0.48	21	21
RET9/GFRalpha1/GDNF	-0.18	0.24	-9999	-0.47	185	185
GFRalpha1/GDNF	-0.2	0.27	-9999	-0.54	185	185

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.032	0.03	-9999	-10000	0	0
VDR	-0.002	0.033	-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	-0.58	13	13
MED1	0	0	-9999	-10000	0	0
mol:9cRA	0.004	0.007	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.012	0.059	-9999	-10000	0	0
RXRs/NUR77	-0.28	0.26	-9999	-0.49	282	282
RXRs/PPAR	-0.18	0.2	-9999	-0.56	44	44
NCOR2	-0.002	0.033	-9999	-0.74	1	1
VDR/VDR/Vit D3	-0.001	0.026	-9999	-0.56	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	0.033	-9999	-0.74	1	1
RARs/RARs/DNA/9cRA	-0.002	0.026	-9999	-0.41	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	-0.56	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	-0.23	0.21	-9999	-0.43	258	258
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	259	259
NR4A1	-0.098	0.25	-9999	-0.74	65	65
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.12	0.14	-9999	-0.26	258	258
RXRG	-0.38	0.37	-9999	-0.74	258	258
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	-0.088	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	-0.58	13	13
PPARA	0	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.003	0.047	-9999	-0.74	2	2
RXRs/NUR77/BCL2	-0.2	0.2	-9999	-0.36	282	282
SREBF1	-0.082	0.15	-9999	-0.6	9	9
RXRs/RXRs/DNA/9cRA	-0.23	0.21	-9999	-0.43	258	258
ABCA1	-0.082	0.15	-9999	-0.6	9	9
RARs/THRs	-0.016	0.078	-9999	-0.4	19	19
RXRs/FXR	-0.23	0.22	-9999	-0.43	258	258
BCL2	-0.001	0.026	-9999	-0.57	1	1

×

PLK1 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
regulation of centriole-centriole cohesion	0.071	0.074	0.14	255	-10000	0	255
BUB1B	-0.13	0.098	-10000	0	-0.22	197	197
PLK1	-0.014	0.036	-10000	0	-0.12	13	13
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	-0.014	0.036	-10000	0	-0.12	13	13
GOLGA2	0	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.21	0.23	-10000	0	-0.42	241	241
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	4	4
PICH/PLK1	-0.11	0.17	-10000	0	-0.45	56	56
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	0.033	-10000	0	-10000	0	0
PPP2CA	0	0	-10000	0	-10000	0	0
FZR1	0	0	-10000	0	-10000	0	0
TPX2	-0.06	0.049	-10000	0	-0.11	75	75
PAK1	0.002	0.026	-10000	0	-0.57	1	1
SPC24	-0.17	0.26	-10000	0	-0.57	147	147
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	-0.001	0.003	-10000	0	-0.011	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.007	0.02	-10000	0	-0.063	8	8
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.009	10	10
STAG2	0	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.001	0.008	-10000	0	-10000	0	0
spindle elongation	-0.014	0.036	-10000	0	-0.12	13	13
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	-0.16	19	19
CDC25B	0.009	0.003	-10000	0	-10000	0	0
SGOL1	-0.071	0.074	-10000	0	-0.14	255	255
RHOA	0	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.028	0.079	-10000	0	-0.29	4	4
CDC14B	0.01	0.002	-10000	0	-10000	0	0
CDC20	-0.36	0.28	-10000	0	-0.57	312	312
PLK1/PBIP1	-0.03	0.063	-10000	0	-0.33	18	18
mitosis	-0.001	0.005	0.022	14	-0.018	8	22
FBXO5	-0.004	0.031	-10000	0	-10000	0	0
CDC2	-0.001	0.004	-10000	0	-0.012	14	14
NDC80	-0.2	0.27	-10000	0	-0.57	172	172
metaphase plate congression	-0.007	0.025	-10000	0	-10000	0	0
ERCC6L	-0.11	0.16	-10000	0	-0.43	54	54
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	260	260
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	-0.009	4	4
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	253	253
Golgi organization	-0.014	0.036	-10000	0	-0.12	13	13
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	253	253
APC/C/CDC20	-0.22	0.16	-10000	0	-0.34	312	312
PPP2R1A	0	0	-10000	0	-10000	0	0
chromosome segregation	-0.029	0.062	-10000	0	-0.32	18	18
PRC1	-0.056	0.17	-10000	0	-0.57	48	48
ECT2	-0.016	0.072	-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	0.098	-10000	0	-0.22	197	197
spindle assembly	-0.008	0.03	-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	253	253
CCNB1	-0.057	0.18	-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	-0.29	4	4
MLF1IP	-0.01	0.082	-10000	0	-0.43	18	18
INCENP	0.004	0.006	-10000	0	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.017	0.093	-9999	0	-0.51	16	16
ARNO/beta Arrestin1-2	-0.17	0.24	-9999	0	-0.45	184	184
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	-0.026	0.12	-9999	0	-0.5	26	26
ARRB2	0.007	0.011	-9999	0	-0.21	1	1
mol:GTP	0.015	0.025	-9999	0	-0.15	8	8
ARRB1	-0.14	0.29	-9999	0	-0.74	93	93
FBXO8	0	0	-9999	0	-10000	0	0
TSHR	-0.019	0.1	-9999	0	-0.57	16	16
EGF	-0.014	0.098	-9999	0	-0.69	10	10
somatostatin receptor activity	0	0	-9999	0	-0.001	144	144
ARAP2	-0.002	0.033	-9999	0	-0.74	1	1
mol:GDP	-0.12	0.15	-9999	0	-0.32	151	151
mol:PI-3-4-5-P3	0	0	-9999	0	-0.001	89	89
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	0.099	-9999	0	-0.74	9	9
KIF13B	-0.012	0.094	-9999	0	-0.74	8	8
HGF/MET	-0.12	0.23	-9999	0	-0.56	105	105
PXN	0	0	-9999	0	-10000	0	0
ARF6/GTP	-0.11	0.15	-9999	0	-0.31	144	144
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.022	0.099	-9999	0	-0.51	12	12
ADRB2	-0.21	0.34	-9999	0	-0.74	141	141
receptor agonist activity	0	0	-9999	0	0	146	146
actin filament binding	0	0	-9999	0	-0.001	144	144
SRC	0	0	-9999	0	-10000	0	0
ITGB3	-0.012	0.094	-9999	0	-0.74	8	8
GNAQ	-0.002	0.033	-9999	0	-0.74	1	1
EFA6/PI-4-5-P2	0	0.001	-9999	0	-0.001	118	118
ARF6/GDP	-0.013	0.071	-9999	0	-0.35	3	3
ARF6/GDP/GULP/ACAP1	-0.11	0.14	-9999	0	-0.43	46	46
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.02	0.092	-9999	0	-0.43	23	23
ACAP1	-0.003	0.042	-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	-0.15	0.3	-9999	0	-0.74	102	102
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	104	104
endosomal lumen acidification	0	0	0	9	-0.001	92	101
microtubule-based process	0	0	-9999	0	-10000	0	0
GULP1	-0.014	0.099	-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	11	11
MET	-0.004	0.054	-9999	0	-0.68	3	3
GNA14	-0.18	0.32	-9999	0	-0.74	117	117
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	143	143
GNA11	0	0	-9999	0	-10000	0	0
LHCGR	-0.001	0.026	-9999	0	-0.57	1	1
AGTR1	-0.3	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	-0.017	0.078	-9999	0	-0.41	12	12
alphaIIb/beta3 Integrin	-0.026	0.12	-9999	0	-0.56	23	23

×

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	-0.052	0.15	-9999	-0.48	53	53
NOG	-0.028	0.14	-9999	-0.73	19	19
SMAD9	-0.1	0.22	-9999	-0.59	73	73
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	240	240
SMAD5/SKI	-0.049	0.11	-9999	-0.44	23	23
SMAD1	0.033	0.026	-9999	-10000	0	0
BMP2	-0.098	0.25	-9999	-0.74	65	65
SMAD1/SMAD1/SMAD4	-0.034	0.095	-9999	-10000	0	0
BMPR1A	0	0	-9999	-10000	0	0
BMPR1B	-0.056	0.2	-9999	-0.74	37	37
BMPR1A-1B/BAMBI	-0.04	0.13	-9999	-0.47	42	42
AHSG	-0.019	0.1	-9999	-0.57	16	16
CER1	-0.002	0.037	-9999	-0.57	2	2
BMP2-4/CER1	-0.075	0.18	-9999	-0.5	71	71
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.067	0.14	-9999	-0.49	30	30
BMP2-4 (homodimer)	-0.085	0.21	-9999	-0.57	72	72
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.044	0.14	-9999	-0.45	48	48
RGMA	-0.063	0.18	-9999	-0.57	54	54
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.062	0.13	-9999	-0.45	30	30
BMP2-4/USAG1	-0.16	0.27	-9999	-0.55	143	143
SMAD6/SMURF1/SMAD5	-0.049	0.11	-9999	-0.44	23	23
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	-0.075	0.18	-9999	-0.5	72	72
SMAD5/SMAD5/SMAD4	-0.049	0.11	-9999	-0.44	23	23
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	171	171
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.028	0.12	-9999	-0.48	29	29
SMAD1/SKI	-0.004	0.012	-9999	-10000	0	0
SMAD6	-0.079	0.23	-9999	-0.74	52	52
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.084	0.19	-9999	-0.51	71	71
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.34	0.28	-9999	-0.57	293	293
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.042	0.15	-9999	-0.56	37	37
CHRDL1	-0.39	0.37	-9999	-0.74	256	256
ENDOFIN/SMAD1	-0.004	0.012	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.039	0.11	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.007	0.068	-9999	-0.67	5	5
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.32	0.3	-9999	-0.55	282	282
BMP2-4/GREM1	-0.28	0.22	-9999	-0.62	71	71
SMAD7	-0.002	0.033	-9999	-0.74	1	1
SMAD8A/SMAD8A/SMAD4	-0.096	0.2	-9999	-0.55	73	73
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	171	171
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	31	31
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	42	42
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	-0.49	30	30
BMP4	-0.015	0.1	-9999	-0.72	10	10
FST	-0.093	0.21	-9999	-0.57	79	79
BMP2-4/NOG	-0.09	0.21	-9999	-0.53	82	82
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.13	0.18	-9999	-0.5	43	43

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.004	0.019	-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	87	87
TLE1	0.002	0.031	-10000	0	-0.61	1	1
MACF1	0.004	0.048	-10000	0	-0.74	2	2
CTNNB1	0.068	0.098	0.29	10	-10000	0	10
WIF1	-0.47	0.36	-10000	0	-0.74	311	311
beta catenin/RanBP3	0.003	0.093	0.39	22	-10000	0	22
KREMEN2	-0.37	0.27	-10000	0	-0.57	318	318
DKK1	-0.038	0.15	-10000	0	-0.62	30	30
beta catenin/beta TrCP1	0.069	0.092	0.28	10	-10000	0	10
FZD1	0.001	0.003	-10000	0	-10000	0	0
AXIN2	-0.04	0.29	-10000	0	-1.5	18	18
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	0.094	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	0.05	-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	-0.44	339	339
NKD1	-0.071	0.22	-10000	0	-0.72	48	48
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	0.019	0.098	0.45	23	-10000	0	23
LEF1	0.003	0.031	-10000	0	-0.58	1	1
DVL1	0.08	0.061	0.21	1	-10000	0	1
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	-0.37	327	327
LRP6	0.003	0.005	-10000	0	-10000	0	0
CSNK1A1	0.004	0.019	-10000	0	-10000	0	0
NLK	0.01	0.002	-10000	0	-10000	0	0
CCND1	-0.009	0.17	-10000	0	-1.5	6	6
WNT1	0.004	0.037	-10000	0	-0.57	2	2
GSK3A	0.008	0.005	-10000	0	-10000	0	0
GSK3B	0.001	0.003	-10000	0	-10000	0	0
FRAT1	-0.001	0.033	-10000	0	-0.74	1	1
PPP2R5D	0.076	0.1	0.37	48	-10000	0	48
APC	0	0.019	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.16	0.12	0.26	309	-10000	0	309
CREBBP	0.004	0.018	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.008	0.14	-10000	0	-0.38	64	64
CRKL	-0.013	0.15	-10000	0	-0.41	60	60
HRAS	-0.057	0.14	-10000	0	-0.62	11	11
mol:PIP3	-0.024	0.14	-10000	0	-0.39	59	59
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.021	0.15	-10000	0	-0.43	60	60
FOXO3	-0.006	0.14	-10000	0	-0.37	59	59
AKT1	-0.015	0.14	-10000	0	-0.4	60	60
BAD	-0.006	0.14	-10000	0	-0.37	59	59
megakaryocyte differentiation	-0.047	0.2	-10000	0	-0.48	79	79
GSK3B	-0.006	0.14	-10000	0	-0.37	59	59
RAF1	0.007	0.13	-10000	0	-0.48	11	11
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.021	0.15	-10000	0	-0.43	60	60
STAT1	-0.072	0.35	-10000	0	-1	60	60
HRAS/SPRED1	-0.046	0.11	-10000	0	-0.48	11	11
cell proliferation	-0.02	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	-0.021	0.15	-10000	0	-0.43	60	60
HRAS/SPRED2	-0.046	0.11	-10000	0	-0.48	11	11
LYN/TEC/p62DOK	-0.052	0.14	-10000	0	-0.42	61	61
MAPK3	0.019	0.098	-10000	0	-0.32	11	11
STAP1	-0.044	0.2	-10000	0	-0.49	74	74
GRAP2	-0.039	0.17	-10000	0	-0.74	26	26
JAK2	-0.1	0.28	-10000	0	-0.85	60	60
STAT1 (dimer)	-0.069	0.34	-10000	0	-0.99	60	60
mol:Gleevec	-0.001	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.053	0.14	-10000	0	-0.4	60	60
actin filament polymerization	-0.02	0.15	-10000	0	-0.42	60	60
LYN	-0.003	0.047	-10000	0	-0.74	2	2
STAP1/STAT5A (dimer)	-0.048	0.25	-10000	0	-0.67	60	60
PIK3R1	0	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.044	0.12	-10000	0	-10000	0	0
PI3K	-0.049	0.13	-10000	0	-0.4	60	60
PTEN	-0.002	0.033	-10000	0	-0.74	1	1
SCF/KIT/EPO/EPOR	-0.099	0.44	-10000	0	-1.3	60	60
MAPK8	-0.021	0.15	-10000	0	-0.43	60	60
STAT3 (dimer)	-0.02	0.15	-10000	0	-0.42	60	60
positive regulation of transcription	0.021	0.083	-10000	0	-0.26	10	10
mol:GDP	-0.061	0.15	-10000	0	-0.66	11	11
PIK3C2B	-0.021	0.15	-10000	0	-0.43	60	60
CBL/CRKL	-0.006	0.14	-10000	0	-0.38	60	60
FER	-0.021	0.15	-10000	0	-0.43	60	60
SH2B3	-0.022	0.16	-10000	0	-0.43	62	62
PDPK1	-0.015	0.13	-10000	0	-0.36	59	59
SNAI2	-0.021	0.15	-10000	0	-0.43	60	60
positive regulation of cell proliferation	-0.043	0.26	-10000	0	-0.74	60	60
KITLG	0.013	0.005	-10000	0	-10000	0	0
cell motility	-0.043	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)	-0.031	0.22	-10000	0	-0.61	60	60
SOCS1	-0.002	0.033	-10000	0	-0.74	1	1
cell migration	0.035	0.18	0.45	73	-10000	0	73
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.002	0.064	-10000	0	-0.57	6	6
VAV1	-0.008	0.074	-10000	0	-0.74	5	5
GRB10	-0.021	0.15	-10000	0	-0.43	60	60
PTPN11	0.003	0.008	-10000	0	-10000	0	0
SCF/KIT	-0.057	0.15	-10000	0	-0.46	60	60
GO:0007205	0	0.008	-10000	0	-10000	0	0
MAP2K1	0.016	0.11	-10000	0	-0.36	11	11
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.12	0.46	-10000	0	-1.4	60	60
MAP2K2	0.016	0.11	-10000	0	-0.36	11	11
SHC/Grb2/SOS1	-0.049	0.13	-10000	0	-0.4	60	60
STAT5A	-0.033	0.22	-10000	0	-0.63	60	60
GRB2	0	0	-10000	0	-10000	0	0
response to radiation	-0.02	0.15	-10000	0	-0.42	60	60
SHC/GRAP2	-0.03	0.12	-10000	0	-0.56	26	26
PTPRO	-0.049	0.21	-10000	0	-0.5	79	79
SH2B2	-0.021	0.15	-10000	0	-0.43	60	60
DOK1	0	0	-10000	0	-10000	0	0
MATK	-0.037	0.18	-10000	0	-0.46	73	73
CREBBP	0.028	0.011	-10000	0	-10000	0	0
BCL2	0.011	0.1	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.12	0.39	-9999	-1.2	50	50
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	-0.43	8	8
MITF	-0.041	0.16	-9999	-0.37	83	83
MAPKAPK5	-0.032	0.15	-9999	-0.53	8	8
KRT8	-0.032	0.15	-9999	-0.36	73	73
MAPKAPK3	0	0	-9999	-10000	0	0
MAPKAPK2	0	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.054	0.18	-9999	-0.46	73	73
CEBPB	-0.032	0.15	-9999	-0.36	73	73
SLC9A1	-0.032	0.15	-9999	-0.53	8	8
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.026	0.15	-9999	-0.52	8	8
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	-0.5	146	146
USF1	-0.032	0.15	-9999	-0.36	73	73
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	73	73
RAB5A	0	0	-9999	-10000	0	0
HSPB1	-0.018	0.12	-9999	-0.44	8	8
p38alpha-beta/HBP1	-0.065	0.13	-9999	-0.58	8	8
CREB1	-0.03	0.15	-9999	-0.38	73	73
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.021	0.13	-9999	-0.52	8	8
RPS6KA4	-0.032	0.15	-9999	-0.53	8	8
PLA2G4A	-0.025	0.14	-9999	-0.53	13	13
GDI1	-0.032	0.15	-9999	-0.36	73	73
TP53	-0.044	0.18	-9999	-0.45	73	73
RPS6KA5	-0.032	0.15	-9999	-0.36	73	73
ESR1	-0.054	0.19	-9999	-0.42	88	88
HBP1	0	0	-9999	-10000	0	0
MEF2C	-0.042	0.17	-9999	-0.53	18	18
MEF2A	-0.032	0.15	-9999	-0.36	73	73
EIF4EBP1	-0.032	0.16	-9999	-0.38	73	73
KRT19	-0.039	0.18	-9999	-0.4	75	75
ELK4	-0.032	0.15	-9999	-0.53	8	8
ATF6	-0.032	0.15	-9999	-0.36	73	73
ATF1	-0.03	0.15	-9999	-0.38	73	73
p38alpha-beta/MAPKAPK2	-0.065	0.13	-9999	-0.58	8	8
p38alpha-beta/MAPKAPK3	-0.065	0.13	-9999	-0.58	8	8

×

Presenilin action in Notch and Wnt signaling

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
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	-0.077	0.18	-10000	0	-0.42	88	88
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	0.002	0.042	-10000	0	-0.55	1	1
NICD/RBPSUH	0	0	-10000	0	-10000	0	0
WIF1	-0.47	0.36	-10000	0	-0.74	311	311
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	318	318
DKK1	-0.038	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	56	56
JUN	0	0	-10000	0	-10000	0	0
MAP3K7	0	0.003	-10000	0	-10000	0	0
CTNNB1	0.01	0.065	0.22	16	-10000	0	16
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.3	0.25	-10000	0	-0.44	339	339
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	-0.72	48	48
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	88	88
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	0.043	-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	-0.37	327	327
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	-0.015	0.16	-10000	0	-1.4	6	6
WNT1	-0.002	0.037	-10000	0	-0.57	2	2
Axin1/APC/beta catenin	0.011	0.045	0.27	1	-0.36	1	2
DKK2	-0.13	0.28	-10000	0	-0.74	87	87
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	0.033	-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	48	-0.25	1	49
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.28	0.21	-10000	0	-0.43	310	310
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.013	0.002	-10000	0	-10000	0	0

×

TCGA08_p53

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
CDKN2A	-0.19	0.22	-10000	0	-0.42	229	229
TP53	-0.051	0.056	-10000	0	-10000	0	0
Senescence	-0.051	0.056	-10000	0	-10000	0	0
Apoptosis	-0.051	0.056	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.097	0.11	0.31	4	-0.43	1	5
MDM4	0	0	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.03	0.12	-9999	-0.56	26	26
alphaV beta3 Integrin	-0.022	0.1	-9999	-0.5	22	22
PTK2	-0.19	0.23	-9999	-0.7	40	40
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	190	190
VEGFA	0	0	-9999	-10000	0	0
ILK	-0.23	0.29	-9999	-0.58	190	190
ROCK1	0	0	-9999	-10000	0	0
AKT1	-0.21	0.27	-9999	-0.54	190	190
PTK2B	-0.028	0.12	-9999	-0.8	5	5
alphaV/beta3 Integrin/JAM-A	-0.18	0.22	-9999	-0.43	193	193
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.011	0.068	-9999	-0.48	8	8
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.015	0.078	-9999	-0.43	16	16
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.12	0.16	-9999	-0.65	20	20
alphaV/beta3 Integrin/Syndecan-1	-0.009	0.064	-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	-0.6	8	8
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	308	308
cell adhesion	-0.011	0.066	-9999	-0.44	8	8
ANGPTL3	-0.005	0.052	-9999	-0.57	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	-0.025	0.11	-9999	-0.48	26	26
IGF-1R heterotetramer	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.059	0.2	-9999	-0.74	39	39
ITGB3	-0.012	0.094	-9999	-0.74	8	8
IGF1	-0.025	0.13	-9999	-0.73	17	17
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.008	0.06	-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	0.071	-9999	-0.48	11	11
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.034	0.13	-9999	-0.5	33	33
CSF1	-0.006	0.067	-9999	-0.74	4	4
PIK3C2A	-0.23	0.29	-9999	-0.58	190	190
PI4 Kinase/Pyk2	-0.16	0.21	-9999	-0.74	26	26
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.03	0.12	-9999	-0.5	29	29
FAK1/Vinculin	-0.15	0.18	-9999	-0.55	31	31
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	192	192
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.023	0.13	-9999	-0.74	15	15
F11R	0.002	0.099	-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	41	41
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	-0.81	5	5
SDC1	-0.002	0.033	-9999	-0.74	1	1
VAV3	-0.004	0.04	-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	-0.55	31	31
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	0.29	-9999	-0.57	256	256
KDR	-0.039	0.17	-9999	-0.74	26	26
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.46	0.36	-9999	-0.74	308	308
angiogenesis	-0.11	0.22	-9999	-0.76	24	24
Rac1/GTP	-0.004	0.037	-9999	-10000	0	0
EDIL3	-0.041	0.17	-9999	-0.74	27	27
cell proliferation	-0.045	0.16	-9999	-0.54	41	41

×

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	-0.097	0.18	-10000	0	-0.44	108	108
regulation of S phase of mitotic cell cycle	-0.064	0.13	-10000	0	-0.31	102	102
GNAO1	-0.004	0.049	-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	-0.05	0.16	-10000	0	-0.46	17	17
T-DHT/AR	-0.12	0.23	-10000	0	-0.57	102	102
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.007	56	56
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.033	-10000	0	-0.74	1	1
mol:GDP	-0.12	0.22	-10000	0	-0.55	102	102
cell proliferation	-0.056	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	56	56
mol:Ca2+	-0.012	0.022	-10000	0	-0.069	25	25
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	56	56
cAMP biosynthetic process	0.011	0.021	-10000	0	-10000	0	0
GNG2	-0.008	0.074	-10000	0	-0.74	5	5
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	56	56
HRAS/GTP	-0.086	0.16	-10000	0	-0.4	102	102
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	56	56
PI3K	0	0	-10000	0	-10000	0	0
apoptosis	0.046	0.17	0.45	56	-10000	0	56
T-DHT/AR/PELP1	-0.1	0.2	-10000	0	-0.49	102	102
HRAS/GDP	-0.11	0.21	-10000	0	-0.52	102	102
CREB1	-0.051	0.19	-10000	0	-0.48	56	56
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.15	0.3	-10000	0	-0.74	102	102
GNB1	-0.002	0.033	-10000	0	-0.74	1	1
RAF1	-0.057	0.17	-10000	0	-0.46	17	17
RAC1-CDC42/GDP	-0.1	0.2	-10000	0	-0.5	102	102
T-DHT/AR/PELP1/Src	-0.092	0.18	-10000	0	-0.44	102	102
MAP2K2	-0.05	0.16	-10000	0	-0.46	17	17
T-DHT/AR/PELP1/Src/PI3K	-0.064	0.13	-10000	0	-0.31	102	102
GNAZ	-0.009	0.081	-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	-10000	0	-0.003	39	39
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	-0.36	8	8
CDC42	0	0	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.033	-9999	-0.74	1	1
alphaV beta3 Integrin	-0.009	0.071	-9999	-0.56	8	8
PTK2	-0.1	0.16	-9999	-0.59	37	37
positive regulation of JNK cascade	-0.034	0.089	-9999	-0.34	37	37
CDC42/GDP	-0.021	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	-0.042	0.15	-9999	-0.56	37	37
RAPGEF1	-0.032	0.15	-9999	-0.53	37	37
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.045	0.17	-9999	-0.62	37	37
PDGFB-D/PDGFRB	-0.002	0.033	-9999	-0.74	1	1
TLN1	-0.019	0.15	-9999	-0.5	31	31
Rap1/GTP	-0.034	0.096	-9999	-0.39	21	21
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	-0.042	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	-0.031	0.11	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.2	0.21	-9999	-0.41	237	237
positive regulation of lamellipodium assembly	-0.037	0.096	-9999	-0.35	40	40
PVRL1	-0.28	0.29	-9999	-0.57	237	237
PVRL3	-0.056	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	-0.11	0.22	-9999	-0.58	91	91
JAM-A/CLDN1	-0.09	0.17	-9999	-0.49	38	38
SRC	-0.076	0.18	-9999	-0.7	37	37
ITGB3	-0.012	0.094	-9999	-0.74	8	8
nectin-1(dimer)/I-afadin/I-afadin	-0.2	0.21	-9999	-0.41	237	237
FARP2	-0.036	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)	-0.036	0.13	-9999	-0.48	37	37
nectin-1/I-afadin	-0.2	0.21	-9999	-0.41	237	237
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	-0.64	37	37
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	0.089	-9999	-0.34	37	37
alphaV/beta3 Integrin/Talin	-0.046	0.14	-9999	-0.76	11	11
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	-0.049	0.15	-9999	-0.54	31	31
VAV2	-0.04	0.17	-9999	-0.58	40	40
RAP1/GDP	-0.038	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	-0.036	0.13	-9999	-0.48	37	37
nectin-3(dimer)/I-afadin/I-afadin	-0.042	0.15	-9999	-0.56	37	37
Rac1/GTP	-0.044	0.12	-9999	-0.44	39	39
PTPRM	-0.054	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

×

Glypican 1 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	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	-0.4	42	42
fibroblast growth factor receptor signaling pathway	-0.034	0.11	-10000	0	-0.39	42	42
LAMA1	-0.17	0.26	-10000	0	-0.57	143	143
PRNP	0	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.15	0.25	-10000	0	-0.55	129	129
SMAD2	-0.025	0.14	-10000	0	-0.43	39	39
GPC1/PrPc/Cu2+	-0.019	0.079	-10000	0	-0.35	26	26
GPC1/Laminin alpha1	-0.14	0.22	-10000	0	-0.45	154	154
TDGF1	-0.004	0.045	-10000	0	-0.57	3	3
CRIPTO/GPC1	-0.025	0.098	-10000	0	-0.41	29	29
APP/GPC1	-0.022	0.093	-10000	0	-0.41	26	26
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0	0.087	-10000	0	-10000	0	0
FLT1	0	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.056	0.15	-10000	0	-0.48	39	39
SERPINC1	-0.007	0.063	-10000	0	-0.57	6	6
FYN	-0.001	0.09	-10000	0	-0.49	1	1
FGR	-0.033	0.15	-10000	0	-0.49	33	33
positive regulation of MAPKKK cascade	0.001	0.11	-10000	0	-0.55	6	6
SLIT2	-0.17	0.31	-10000	0	-0.74	110	110
GPC1/NRG	-0.038	0.13	-10000	0	-0.46	40	40
NRG1	-0.021	0.12	-10000	0	-0.74	14	14
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.018	0.077	-10000	0	-10000	0	0
LYN	-0.002	0.092	-10000	0	-0.49	2	2
mol:Spermine	-0.013	0.097	-10000	0	-0.42	26	26
cell growth	-0.034	0.11	-10000	0	-0.39	42	42
BMP signaling pathway	0.03	0.13	0.57	26	-10000	0	26
SRC	0	0.087	-10000	0	-10000	0	0
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	145	145
GPC1	-0.03	0.13	-10000	0	-0.57	26	26
TGFBR1 (dimer)	0	0	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.023	0.13	-10000	0	-0.5	14	14
HCK	-0.005	0.099	-10000	0	-0.48	5	5
FGF2	-0.023	0.13	-10000	0	-0.74	15	15
FGFR1	-0.002	0.033	-10000	0	-0.74	1	1
VEGFR1 homodimer	0	0	-10000	0	-10000	0	0
TGFBR2	-0.059	0.2	-10000	0	-0.74	39	39
cell death	-0.022	0.092	-10000	0	-0.41	26	26
ATIII/GPC1	-0.027	0.1	-10000	0	-0.41	32	32
PLA2G2A/GPC1	-0.18	0.27	-10000	0	-0.56	162	162
LCK	-0.001	0.09	-10000	0	-0.49	1	1
neuron differentiation	-0.038	0.13	-10000	0	-0.46	40	40
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.059	0.2	-10000	0	-0.74	39	39

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.27	0.34	-10000	0	-0.85	45	45
PCK1	-0.14	0.21	-10000	0	-0.79	13	13
HNF4A	-0.31	0.4	-10000	0	-1.1	47	47
KCNJ11	-0.28	0.39	-10000	0	-1	39	39
AKT1	-0.001	0.086	-10000	0	-10000	0	0
response to starvation	-0.009	0.034	-10000	0	-10000	0	0
DLK1	-0.3	0.38	-10000	0	-0.94	49	49
NKX2-1	-0.78	0.79	0.47	1	-1.5	258	259
ACADM	-0.27	0.34	-10000	0	-0.85	45	45
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	-0.051	0.19	-10000	0	-0.81	14	14
PKLR	-0.27	0.34	-10000	0	-0.85	53	53
APOA1	-0.43	0.55	-10000	0	-1.4	74	74
CPT1C	-0.27	0.34	-10000	0	-0.83	53	53
ALAS1	-0.11	0.18	-10000	0	-10000	0	0
TFRC	-0.16	0.25	-10000	0	-0.94	10	10
FOXF1	0.005	0.24	0.28	4	-0.62	54	58
NF1	0.016	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.014	0.082	-10000	0	-0.6	8	8
CPT1A	-0.27	0.34	-10000	0	-0.84	47	47
HMGCS1	-0.27	0.34	-10000	0	-0.89	30	30
NR3C1	0.017	0.012	-10000	0	-10000	0	0
CPT1B	-0.27	0.34	-10000	0	-0.86	39	39
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.006	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	-0.65	4	4
PDX1	-0.18	0.24	-10000	0	-0.69	18	18
UCP2	-0.27	0.34	-10000	0	-0.84	51	51
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	-0.89	35	35
F2	-0.34	0.42	-10000	0	-1	61	61
HNF1A	-0.014	0.083	-10000	0	-0.6	8	8
G6PC	0.009	0.086	-10000	0	-0.74	1	1
SLC2A2	-0.17	0.23	-10000	0	-0.86	2	2
INS	-0.009	0.011	-10000	0	-10000	0	0
FOXA1	0.073	0.14	0.36	9	-0.57	11	20
FOXA3	-0.01	0.15	-10000	0	-0.74	17	17
FOXA2	-0.32	0.41	-10000	0	-0.92	67	67
ABCC8	-0.29	0.39	-10000	0	-1	42	42
ALB	0.026	0.12	-10000	0	-0.74	3	3

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.2	0.43	-9999	-1.2	35	35
HDAC7	-0.007	0.013	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.19	0.33	-9999	-0.9	36	36
SMAD4	0	0.002	-9999	-10000	0	0
ID2	-0.2	0.43	-9999	-1.2	35	35
AP1	-0.066	0.18	-9999	-0.56	56	56
ABCG2	-0.24	0.5	-9999	-1.3	57	57
HIF1A	-0.023	0.07	-9999	-10000	0	0
TFF3	-0.24	0.47	-9999	-1.3	43	43
GATA2	-0.07	0.23	-9999	-0.74	52	52
AKT1	-0.033	0.058	-9999	-10000	0	0
response to hypoxia	-0.047	0.064	-9999	-10000	0	0
MCL1	-0.2	0.43	-9999	-1.2	35	35
NDRG1	-0.2	0.44	-9999	-1.2	34	34
SERPINE1	-0.2	0.43	-9999	-1.2	34	34
FECH	-0.2	0.43	-9999	-1.2	34	34
FURIN	-0.2	0.43	-9999	-1.2	35	35
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	36	36
BHLHE40	-0.2	0.43	-9999	-1.2	35	35
BHLHE41	-0.2	0.45	-9999	-1.3	36	36
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.031	0.079	-9999	-0.51	5	5
ENG	0.003	0.13	-9999	-0.83	7	7
JUN	0.008	0.005	-9999	-10000	0	0
RORA	-0.2	0.43	-9999	-1.2	35	35
ABCB1	-0.2	0.45	-9999	-1.4	61	61
TFRC	-0.2	0.43	-9999	-1.2	35	35
CXCR4	-0.2	0.43	-9999	-1.2	35	35
TF	-0.22	0.45	-9999	-1.3	36	36
CITED2	-0.2	0.44	-9999	-1.2	36	36
HIF1A/ARNT	-0.24	0.49	-9999	-1.4	42	42
LDHA	-0.034	0.047	-9999	-10000	0	0
ETS1	-0.21	0.45	-9999	-1.3	35	35
PGK1	-0.2	0.43	-9999	-1.2	35	35
NOS2	-0.24	0.48	-9999	-1.3	49	49
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	41	41
FOS	-0.077	0.24	-9999	-0.74	56	56
HK2	-0.2	0.43	-9999	-1.2	35	35
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	36	36
NPM1	-0.2	0.43	-9999	-1.2	35	35
EGLN1	-0.2	0.43	-9999	-1.2	35	35
CREB1	0.016	0	-9999	-10000	0	0
PGM1	-0.2	0.43	-9999	-1.2	35	35
SMAD3	0	0.002	-9999	-10000	0	0
EDN1	-0.16	0.4	-9999	-1.3	48	48
IGFBP1	-0.2	0.44	-9999	-1.2	39	39
VEGFA	-0.23	0.31	-9999	-0.86	26	26
HIF1A/JAB1	-0.017	0.029	-9999	-10000	0	0
CP	-0.22	0.46	-9999	-1.3	39	39
CXCL12	-0.23	0.48	-9999	-1.3	46	46
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	35	35
EGLN3	-0.24	0.47	-9999	-1.3	43	43
CA9	-0.42	0.47	-9999	-1.3	60	60
TERT	-0.3	0.49	-9999	-1.3	50	50
ENO1	-0.2	0.43	-9999	-1.2	36	36
PFKL	-0.2	0.43	-9999	-1.2	35	35
NCOA1	0	0.001	-9999	-10000	0	0
ADM	-0.2	0.43	-9999	-1.2	36	36
ARNT	-0.023	0.07	-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	-0.95	87	87
LEP	-0.25	0.47	-9999	-1.2	46	46
HIF1A/ARNT/Cbp/p300	-0.2	0.34	-9999	-0.92	41	41
EPO	-0.081	0.25	-9999	-0.83	3	3
CREBBP	-0.023	0.088	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/HDAC7	-0.26	0.37	-9999	-0.97	48	48
PFKFB3	-0.2	0.43	-9999	-1.2	38	38
NT5E	-0.2	0.44	-9999	-1.2	35	35

×

Coregulation of Androgen receptor activity

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
NRIP1	0.002	0.004	-9999	-10000	0	0
SVIL	0.001	0.004	-9999	-10000	0	0
ZNF318	0	0.005	-9999	-10000	0	0
JMJD2C	-0.004	0.026	-9999	-0.08	49	49
T-DHT/AR/Ubc9	-0.13	0.21	-9999	-0.52	102	102
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	35	35
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.001	0.004	-9999	-10000	0	0
GSN	0.002	0.004	-9999	-10000	0	0
NCOA2	-0.002	0.033	-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	-0.094	0.24	-9999	-0.94	35	35
XRCC5	0	0.002	-9999	-10000	0	0
UBE3A	0.001	0.004	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.14	0.22	-9999	-0.54	112	112
FHL2	-0.055	0.081	-9999	-0.55	2	2
RANBP9	0.002	0.004	-9999	-10000	0	0
JMJD1A	-0.034	0.07	-9999	-0.13	158	158
CDK6	-0.002	0.037	-9999	-0.57	2	2
TGFB1I1	0.001	0.004	-9999	-10000	0	0
T-DHT/AR/CyclinD1	-0.14	0.22	-9999	-0.53	107	107
XRCC6	0	0.002	-9999	-10000	0	0
T-DHT/AR	-0.14	0.24	-9999	-0.55	103	103
CTDSP1	0.001	0.003	-9999	-10000	0	0
CTDSP2	0	0.004	-9999	-10000	0	0
BRCA1	0.001	0.004	-9999	-10000	0	0
TCF4	-0.001	0.034	-9999	-0.74	1	1
CDKN2A	-0.27	0.29	-9999	-0.57	229	229
SRF	0.016	0.007	-9999	-10000	0	0
NKX3-1	-0.11	0.14	-9999	-0.95	2	2
KLK3	0.029	0.051	-9999	-10000	0	0
TMF1	0.001	0.003	-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	-0.52	102	102
AR	-0.17	0.31	-9999	-0.77	102	102
UBA3	0.001	0.003	-9999	-10000	0	0
PATZ1	0	0.002	-9999	-10000	0	0
PAWR	0.001	0.003	-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	102	102
RPS6KA3	0.002	0.004	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.13	0.21	-9999	-0.52	102	102
LATS2	-0.001	0.033	-9999	-0.74	1	1
T-DHT/AR/PRX1	-0.12	0.19	-9999	-0.48	102	102
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	0	0.034	-9999	-0.74	1	1
KLK2	-0.094	0.14	-9999	-0.45	49	49
CASP8	0	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.12	0.19	-9999	-0.48	103	103
TMPRSS2	-0.4	0.54	-9999	-1.2	157	157
CCND1	-0.01	0.085	-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	104	104
CMTM2	-0.098	0.25	-9999	-0.74	65	65
SNURF	-0.023	0.13	-9999	-0.74	15	15
ZMIZ1	-0.008	0.047	-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

×

LPA4-mediated signaling events

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
ADCY4	-0.015	0.13	-9999	-0.5	31	31
ADCY5	-0.029	0.15	-9999	-0.5	44	44
ADCY6	0.016	0.032	-9999	-0.48	2	2
ADCY7	0.017	0.023	-9999	-0.48	1	1
ADCY1	0.015	0.039	-9999	-0.49	3	3
ADCY2	-0.025	0.13	-9999	-0.4	49	49
ADCY3	0.017	0.023	-9999	-0.48	1	1
ADCY8	-0.14	0.23	-9999	-0.48	155	155
PRKCE	0.009	0.026	-9999	-0.57	1	1
ADCY9	0.016	0.032	-9999	-0.48	2	2
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.068	0.13	-9999	-0.44	25	25

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.072	-9999	-10000	0	0
POMC	-0.055	0.17	-9999	-0.58	46	46
EGFR	-0.022	0.12	-9999	-0.63	17	17
Syndecan-3/EGFR	-0.011	0.061	-9999	-0.4	6	6
AGRP	-0.34	0.37	-9999	-0.74	226	226
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	-0.4	4	4
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	-0.002	0.033	-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	-0.026	0.081	-9999	-10000	0	0
Syndecan-3/AgRP	-0.19	0.2	-9999	-0.4	226	226
Syndecan-3/AgRP/MC4R	-0.19	0.2	-9999	-0.4	226	226
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	-0.012	0.061	-9999	-0.4	4	4
IL8	-0.025	0.12	-9999	-0.61	20	20
Syndecan-3/Fyn/Cortactin	-0.001	0.017	-9999	-0.38	1	1
Syndecan-3/CASK	0	0	-9999	-10000	0	0
alpha-MSH/MC4R	-0.057	0.15	-9999	-0.42	66	66
Gamma Secretase	0	0	-9999	-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	0.43	-10000	0	-1.3	38	38
IL23A	-0.14	0.43	-10000	0	-1.2	36	36
NF kappa B1 p50/RelA/I kappa B alpha	-0.2	0.35	-10000	0	-1.1	46	46
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	37	37
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	-1.3	38	38
IL23	-0.14	0.4	-10000	0	-1.2	36	36
IL23R	0.003	0.085	-10000	0	-10000	0	0
IL1B	-0.14	0.44	-10000	0	-1.3	37	37
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.13	0.4	-10000	0	-1.2	32	32
TYK2	0.011	0.019	-10000	0	-10000	0	0
STAT4	-0.012	0.094	-10000	0	-0.74	8	8
STAT3	0	0	-10000	0	-10000	0	0
IL18RAP	-0.027	0.15	-10000	0	-0.74	22	22
IL12RB1	-0.037	0.19	-10000	0	-0.77	31	31
PIK3CA	0	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.026	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	0.005	0.006	-10000	0	-10000	0	0
RELA	0.005	0.006	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.14	0.38	-10000	0	-1.1	36	36
ALOX12B	-0.17	0.42	-10000	0	-1.2	38	38
CXCL1	-0.14	0.46	-10000	0	-1.3	44	44
T cell proliferation	-0.14	0.46	-10000	0	-1.2	47	47
NFKBIA	0.005	0.006	-10000	0	-10000	0	0
IL17A	-0.042	0.24	-10000	0	-0.6	18	18
PI3K	-0.21	0.36	-10000	0	-1.1	47	47
IFNG	0	0.029	0.098	1	-0.13	8	9
STAT3 (dimer)	-0.2	0.34	-10000	0	-1	47	47
IL18R1	-0.001	0.075	-10000	0	-0.74	5	5
IL23/IL23R/JAK2/TYK2/SOCS3	-0.06	0.28	-10000	0	-0.85	21	21
IL18/IL18R	-0.028	0.13	-10000	0	-0.56	25	25
macrophage activation	-0.012	0.017	-10000	0	-0.045	21	21
TNF	-0.14	0.44	-10000	0	-1.3	39	39
STAT3/STAT4	-0.21	0.36	-10000	0	-1.1	47	47
STAT4 (dimer)	-0.22	0.39	-10000	0	-1.2	47	47
IL18	0.003	0.058	-10000	0	-0.74	3	3
IL19	-0.13	0.4	-10000	0	-1.1	39	39
STAT5A (dimer)	-0.21	0.38	-10000	0	-1.2	47	47
STAT1	0	0	-10000	0	-10000	0	0
SOCS3	-0.003	0.047	-10000	0	-0.74	2	2
CXCL9	-0.13	0.43	-10000	0	-1.3	36	36
MPO	-0.15	0.46	-10000	0	-1.2	49	49
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	96	96
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	0.41	-10000	0	-1.2	33	33
keratinocyte proliferation	-0.14	0.46	-10000	0	-1.2	47	47
NOS2	-0.17	0.48	-10000	0	-1.3	50	50

×

IL6-mediated signaling events

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
BCL2L1	-0.14	0.25	-9999	-0.73	13	13
CRP	-0.15	0.25	-9999	-0.76	12	12
cell cycle arrest	-0.17	0.27	-9999	-0.65	55	55
TIMP1	-0.1	0.21	-9999	-0.65	7	7
IL6ST	-0.016	0.13	-9999	-0.74	16	16
Rac1/GDP	-0.065	0.18	-9999	-0.69	19	19
AP1	-0.004	0.16	-9999	-0.52	13	13
GAB2	-0.003	0.12	-9999	-0.73	13	13
TNFSF11	-0.16	0.26	-9999	-0.67	34	34
HSP90B1	0	0.049	-9999	-10000	0	0
GAB1	0.014	0.008	-9999	-10000	0	0
MAPK14	-0.029	0.17	-9999	-0.73	15	15
AKT1	0.042	0.055	-9999	-10000	0	0
FOXO1	0.049	0.051	-9999	-10000	0	0
MAP2K6	-0.052	0.18	-9999	-0.73	16	16
mol:GTP	-0.002	0.003	-9999	-10000	0	0
MAP2K4	-0.075	0.2	-9999	-0.74	15	15
MITF	-0.069	0.19	-9999	-0.53	43	43
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0	0	-9999	-10000	0	0
A2M	-0.46	0.69	-9999	-1.5	159	159
CEBPB	0.016	0.004	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.029	0.11	-9999	-0.53	6	6
STAT3	-0.18	0.29	-9999	-0.69	55	55
STAT1	-0.008	0.016	-9999	-10000	0	0
CEBPD	-0.14	0.25	-9999	-0.8	13	13
PIK3CA	0.01	0.003	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
JUN	0	0.002	-9999	-10000	0	0
PIAS3/MITF	-0.087	0.16	-9999	-0.64	23	23
MAPK11	-0.029	0.17	-9999	-0.73	15	15
STAT3 (dimer)/FOXO1	-0.19	0.31	-9999	-0.76	55	55
GRB2/SOS1/GAB family	-0.031	0.17	-9999	-0.63	19	19
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.052	0.19	-9999	-0.54	38	38
GRB2	0.014	0.008	-9999	-10000	0	0
JAK2	0	0	-9999	-10000	0	0
LBP	-0.11	0.21	-9999	-0.64	6	6
PIK3R1	0.008	0.005	-9999	-10000	0	0
JAK1	0.01	0.005	-9999	-10000	0	0
MYC	-0.14	0.25	-9999	-0.73	13	13
FGG	-0.47	0.57	-9999	-1.1	228	228
macrophage differentiation	-0.17	0.27	-9999	-0.65	55	55
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.093	0.2	-9999	-0.52	64	64
JUNB	-0.14	0.24	-9999	-0.72	14	14
FOS	-0.084	0.24	-9999	-0.74	56	56
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.072	0.19	-9999	-0.48	61	61
STAT1/PIAS1	-0.085	0.17	-9999	-0.47	55	55
GRB2/SOS1/GAB family/SHP2/PI3K	0.014	0.059	-9999	-10000	0	0
STAT3 (dimer)	-0.18	0.28	-9999	-0.68	55	55
PRKCD	-0.09	0.22	-9999	-0.77	13	13
IL6R	-0.008	0.12	-9999	-0.74	12	12
SOCS3	-0.015	0.17	-9999	-0.9	8	8
gp130 (dimer)/JAK1/JAK1/LMO4	-0.01	0.089	-9999	-0.47	17	17
Rac1/GTP	-0.11	0.17	-9999	-0.71	19	19
HCK	-0.003	0.075	-9999	-0.74	5	5
MAPKKK cascade	0.044	0.12	-9999	-0.54	13	13
bone resorption	-0.15	0.25	-9999	-0.63	34	34
IRF1	-0.14	0.25	-9999	-0.73	13	13
mol:GDP	-0.068	0.19	-9999	-0.55	38	38
SOS1	0.01	0.015	-9999	-10000	0	0
VAV1	-0.069	0.2	-9999	-0.56	38	38
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.047	0.18	-9999	-0.81	16	16
PTPN11	-0.006	0.013	-9999	-10000	0	0
IL6/IL6RA	-0.1	0.24	-9999	-0.6	88	88
gp130 (dimer)/TYK2/TYK2/LMO4	-0.012	0.087	-9999	-0.47	17	17
gp130 (dimer)/JAK2/JAK2/LMO4	-0.012	0.087	-9999	-0.47	17	17
IL6	-0.12	0.28	-9999	-0.74	83	83
PIAS3	0	0	-9999	-10000	0	0
PTPRE	0.01	0.049	-9999	-0.73	2	2
PIAS1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.077	0.17	-9999	-0.42	76	76
LMO4	0.007	0.029	-9999	-0.59	1	1
STAT3 (dimer)/PIAS3	-0.21	0.22	-9999	-0.66	55	55
MCL1	0.05	0.049	-9999	-10000	0	0

×

ErbB4 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
ErbB4/ErbB4/HBEGF/HBEGF	-0.08	0.12	-10000	0	-0.51	18	18
epithelial cell differentiation	-0.036	0.1	-10000	0	-0.55	11	11
ITCH	0.023	0.027	-10000	0	-10000	0	0
WWP1	-0.039	0.088	-10000	0	-10000	0	0
FYN	-0.002	0.033	-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	0.001	0.088	-10000	0	-10000	0	0
PTPRZ1	-0.39	0.27	-10000	0	-0.57	328	328
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.043	0.076	-10000	0	-0.48	7	7
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.057	0.096	-10000	0	-0.5	14	14
ADAM17	0.023	0.027	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.059	0.11	-10000	0	-0.49	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.18	0.22	-10000	0	-0.54	125	125
NCOR1	0	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.053	0.091	-10000	0	-0.48	15	15
GRIN2B	-0.028	0.1	-10000	0	-0.52	8	8
ErbB4/ErbB2/betacellulin	-0.074	0.13	-10000	0	-0.48	38	38
STAT1	0	0	-10000	0	-10000	0	0
HBEGF	-0.026	0.14	-10000	0	-0.74	17	17
PRLR	-0.04	0.15	-10000	0	-0.63	31	31
E4ICDs/ETO2	-0.072	0.1	-10000	0	-0.6	8	8
axon guidance	0.053	0.073	-10000	0	-10000	0	0
NEDD4	0.022	0.043	-10000	0	-0.71	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.036	0.13	-10000	0	-0.46	38	38
CBFA2T3	-0.012	0.094	-10000	0	-0.74	8	8
ErbB4/ErbB2/HBEGF	-0.056	0.092	-10000	0	-0.45	17	17
MAPK3	-0.038	0.071	-10000	0	-0.45	7	7
STAT1 (dimer)	-0.064	0.079	-10000	0	-0.43	1	1
MAPK1	-0.038	0.071	-10000	0	-0.45	7	7
JAK2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.053	0.088	-10000	0	-0.46	14	14
NRG1	0.014	0.099	-10000	0	-0.56	14	14
NRG3	-0.19	0.32	-10000	0	-0.74	124	124
NRG2	-0.077	0.23	-10000	0	-0.74	51	51
NRG4	-0.07	0.19	-10000	0	-0.57	60	60
heart development	0.053	0.073	-10000	0	-10000	0	0
neural crest cell migration	-0.053	0.087	-10000	0	-0.46	14	14
ERBB2	0.029	0.032	-10000	0	-0.42	2	2
WWOX/E4ICDs	-0.064	0.079	-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	125	-10000	0	125
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	97	97
ErbB4/ErbB4/betacellulin/betacellulin	-0.1	0.15	-10000	0	-0.55	38	38
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.085	0.14	-10000	0	-0.59	20	20
MDM2	-0.043	0.098	-10000	0	-0.43	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.041	0.081	-10000	0	-0.46	14	14
STAT5A	0.057	0.068	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.064	0.12	-10000	0	-0.54	19	19
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)	-0.038	0.11	-10000	0	-0.6	11	11
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.045	0.068	-10000	0	-10000	0	0
LRIG1	-0.002	0.033	-10000	0	-0.74	1	1
EREG	-0.15	0.29	-10000	0	-0.72	103	103
BTC	-0.057	0.2	-10000	0	-0.74	38	38
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.053	0.073	-10000	0	-10000	0	0
ERBB4	-0.079	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	0.059	0.072	0.4	1	-10000	0	1
WWOX	0	0	-10000	0	-10000	0	0
cell proliferation	-0.021	0.15	-10000	0	-0.58	14	14

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.011	0.037	-9999	-0.53	1	1
NFATC2	-0.06	0.18	-9999	-0.52	67	67
NFATC3	0.012	0.028	-9999	-10000	0	0
CD40LG	-0.17	0.38	-9999	-0.84	89	89
PTGS2	-0.15	0.34	-9999	-0.8	67	67
JUNB	-0.002	0.033	-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	56	56
IFNG	-0.11	0.3	-9999	-0.82	27	27
AP-1/NFAT1-c-4	-0.21	0.3	-9999	-0.76	90	90
FASLG	-0.12	0.32	-9999	-0.91	32	32
NFAT1-c-4/ICER1	-0.083	0.16	-9999	-0.51	47	47
IL2RA	-0.11	0.3	-9999	-0.84	27	27
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.15	0.34	-9999	-0.78	71	71
JunB/Fra1/NFAT1-c-4	-0.08	0.16	-9999	-0.49	46	46
IL4	-0.12	0.29	-9999	-0.83	24	24
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

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.001	0.093	-10000	0	-0.58	12	12
NFATC2	-0.054	0.3	-10000	0	-0.73	69	69
NFATC3	0.013	0.054	-10000	0	-10000	0	0
CD40LG	-0.17	0.45	-10000	0	-1.1	68	68
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	0.033	-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	-0.061	0.18	-10000	0	-0.45	75	75
TLE4	-0.022	0.24	-10000	0	-0.76	26	26
Jun/NFAT1-c-4/p21SNFT	-0.12	0.26	-10000	0	-1.1	19	19
AP-1/NFAT1-c-4	-0.23	0.39	-10000	0	-1.3	36	36
IKZF1	-0.031	0.28	-10000	0	-1	23	23
T-helper 2 cell differentiation	-0.044	0.28	-10000	0	-0.81	43	43
AP-1/NFAT1	-0.14	0.24	-10000	0	-0.68	47	47
CALM1	-0.028	0.065	-10000	0	-10000	0	0
EGR2	-0.017	0.3	-10000	0	-1.6	12	12
EGR3	-0.019	0.31	-10000	0	-1.5	14	14
NFAT1/FOXP3	-0.09	0.21	-10000	0	-0.73	25	25
EGR1	-0.005	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	-0.04	0.28	-10000	0	-0.93	29	29
FOSL1	-0.002	0.037	-10000	0	-0.57	2	2
NFAT1-c-4/MAF/IRF4	-0.097	0.26	-10000	0	-1.1	19	19
DGKA	-0.018	0.22	-10000	0	-0.76	21	21
CREM	0	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.14	0.29	-10000	0	-1.1	24	24
CTLA4	-0.018	0.21	-10000	0	-0.77	16	16
NFAT1-c-4 (dimer)/EGR1	-0.11	0.28	-10000	0	-1.2	21	21
NFAT1-c-4 (dimer)/EGR4	-0.11	0.27	-10000	0	-1.1	19	19
FOS	-0.083	0.24	-10000	0	-0.75	56	56
IFNG	-0.16	0.35	-10000	0	-1.1	48	48
T cell activation	-0.04	0.24	-10000	0	-0.8	19	19
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	-0.004	0.19	0.85	11	-10000	0	11
TNF	-0.037	0.3	-10000	0	-1	23	23
FASLG	-0.086	0.44	-10000	0	-1.5	34	34
TBX21	-0.065	0.23	-10000	0	-0.74	51	51
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	-0.06	0.22	-10000	0	-0.74	46	46
PTPN1	-0.018	0.22	-10000	0	-0.78	20	20
NFAT1-c-4/ICER1	-0.1	0.26	-10000	0	-1.1	19	19
GATA3	-0.023	0.13	-10000	0	-0.71	17	17
T-helper 1 cell differentiation	-0.15	0.34	-10000	0	-1	49	49
IL2RA	-0.14	0.28	-10000	0	-1	30	30
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.018	0.22	-10000	0	-0.74	23	23
E2F1	0.015	0.004	-10000	0	-10000	0	0
PPARG	-0.088	0.24	-10000	0	-0.74	58	58
SLC3A2	-0.018	0.22	-10000	0	-0.78	20	20
IRF4	-0.009	0.081	-10000	0	-0.74	6	6
PTGS2	-0.15	0.41	-10000	0	-1.1	54	54
CSF2	-0.15	0.42	-10000	0	-1.1	48	48
JunB/Fra1/NFAT1-c-4	-0.096	0.25	-10000	0	-1.1	16	16
IL4	-0.049	0.3	-10000	0	-0.87	40	40
IL5	-0.12	0.36	-10000	0	-1	35	35
IL2	-0.041	0.24	-10000	0	-0.82	19	19
IL3	-0.037	0.049	-10000	0	-10000	0	0
RNF128	-0.097	0.31	-10000	0	-0.8	79	79
NFATC1	0.004	0.19	-10000	0	-0.86	11	11
CDK4	0.007	0.16	0.65	6	-10000	0	6
PTPRK	-0.018	0.22	-10000	0	-0.76	21	21
IL8	-0.12	0.38	-10000	0	-1.1	33	33
POU2F1	0	0.003	-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	0.053	-9999	-0.42	8	8
Metarhodopsin II/Arrestin	-0.001	0.023	-9999	-0.36	2	2
PDE6G/GNAT1/GTP	-0.016	0.082	-9999	-0.43	18	18
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	-0.056	0.13	-9999	-0.58	6	6
mol:Na +	-0.094	0.15	-9999	-0.52	23	23
mol:ADP	-0.002	0.036	-9999	-0.57	2	2
RGS9-1/Gbeta5/R9AP	-0.061	0.16	-9999	-0.49	61	61
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.097	0.15	-9999	-0.54	23	23
CNGB1	-0.052	0.16	-9999	-0.57	44	44
RDH5	-0.003	0.047	-9999	-0.74	2	2
SAG	0	0	-9999	-10000	0	0
mol:Ca2+	-0.09	0.14	-9999	-0.5	23	23
Na + (4 Units)	-0.088	0.14	-9999	-0.49	23	23
RGS9	-0.08	0.23	-9999	-0.74	53	53
GNB1/GNGT1	-0.13	0.19	-9999	-0.41	151	151
GNAT1/GDP	-0.058	0.15	-9999	-0.43	61	61
GUCY2D	0	0	-9999	-10000	0	0
GNGT1	-0.18	0.26	-9999	-0.57	150	150
GUCY2F	0	0	-9999	-10000	0	0
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.033	0.11	-9999	-0.42	32	32
mol:11-cis-retinal	-0.003	0.047	-9999	-0.74	2	2
mol:cGMP	-0.079	0.13	-9999	-10000	0	0
GNB1	-0.002	0.033	-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	0.1	-9999	-0.74	10	10
Metarhodopsin II/Transducin	-0.051	0.076	-9999	-0.37	2	2
GCAP Family/Ca ++	-0.086	0.14	-9999	-0.32	131	131
PDE6A/B	-0.026	0.12	-9999	-0.54	24	24
mol:Pi	-0.061	0.16	-9999	-0.49	61	61
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.1	0.15	-9999	-0.33	61	61
PDE6B	-0.015	0.1	-9999	-0.72	10	10
PDE6A	-0.02	0.12	-9999	-0.72	14	14
PDE6G	-0.015	0.1	-9999	-0.74	10	10
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	131	131
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

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.02	0	-9999	-10000	0	0
SMARCC1	0.006	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	-0.002	0.033	-9999	-0.74	1	1
KAT5	0	0.001	-9999	-10000	0	0
MAPK14	0.011	0.026	-9999	-0.45	1	1
FOXO1	0	0	-9999	-10000	0	0
T-DHT/AR	-0.037	0.13	-9999	-0.44	1	1
MAP2K6	0.005	0.028	-9999	-0.6	1	1
BRM/BAF57	-0.001	0.025	-9999	-0.56	1	1
MAP2K4	0.007	0.007	-9999	-10000	0	0
SMARCA2	0	0.034	-9999	-0.74	1	1
PDE9A	-0.11	0.23	-9999	-0.85	28	28
NCOA2	0.004	0.034	-9999	-0.74	1	1
CEBPA	-0.001	0.033	-9999	-0.74	1	1
EHMT2	0.001	0.003	-9999	-10000	0	0
cell proliferation	-0.047	0.17	-9999	-0.52	24	24
NR0B1	-0.18	0.27	-9999	-0.57	156	156
EGR1	-0.012	0.1	-9999	-0.74	9	9
RXRs/9cRA	-0.23	0.22	-9999	-0.44	258	258
AR/RACK1/Src	-0.015	0.074	-9999	-10000	0	0
AR/GR	-0.064	0.12	-9999	-0.34	41	41
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	-0.014	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	-0.56	23	23
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	157	157
RXRG	-0.39	0.37	-9999	-0.74	258	258
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0.006	0.005	-9999	-10000	0	0
NR2C2	0	0	-9999	-10000	0	0
KLK2	-0.02	0.13	-9999	-0.48	3	3
AR	-0.053	0.15	-9999	-0.33	102	102
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	-0.079	0.23	-9999	-0.74	52	52
MYST2	0	0.001	-9999	-10000	0	0
HOXB13	-0.34	0.28	-9999	-0.57	287	287
T-DHT/AR/RACK1/Src	-0.015	0.069	-9999	-10000	0	0
positive regulation of transcription	-0.078	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	-0.097	0.25	-9999	-0.73	66	66
T-DHT/AR/TIF2	0.012	0.057	-9999	-0.37	1	1
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	-0.44	32	32
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	0.001	0.003	-9999	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0	-9999	-10000	0	0
CCL5	-0.014	0.099	-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	-0.092	0.078	-9999	-0.4	5	5
Syndecan-1/Syntenin	-0.091	0.077	-9999	-0.4	4	4
MAPK3	-0.058	0.087	-9999	-0.48	1	1
HGF/MET	-0.12	0.23	-9999	-0.56	105	105
TGFB1/TGF beta receptor Type II	0	0	-9999	-10000	0	0
BSG	0	0	-9999	-10000	0	0
keratinocyte migration	-0.091	0.078	-9999	-0.39	5	5
Syndecan-1/RANTES	-0.098	0.1	-9999	-0.52	12	12
Syndecan-1/CD147	-0.083	0.072	-9999	-0.43	2	2
Syndecan-1/Syntenin/PIP2	-0.087	0.075	-9999	-0.39	4	4
LAMA5	-0.002	0.033	-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	30	30
HGF	-0.15	0.3	-9999	-0.74	102	102
Syndecan-1/CASK	-0.084	0.094	-9999	-0.41	4	4
Syndecan-1/HGF/MET	-0.17	0.17	-9999	-0.46	105	105
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	-0.089	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	26	26
MAPK1	-0.058	0.087	-9999	-0.48	1	1
homophilic cell adhesion	-0.088	0.099	-9999	-0.42	4	4
MMP1	-0.35	0.28	-9999	-0.57	302	302

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.016	0.04	-9999	-10000	0	0
BIRC5	-0.49	0.2	-9999	-0.57	415	415
NFKBIA	0.018	0.041	-9999	-10000	0	0
CPEB1	-0.05	0.18	-9999	-0.74	33	33
AKT1	0.018	0.041	-9999	-10000	0	0
NDEL1	0	0	-9999	-10000	0	0
Aurora A/BRCA1	0.014	0.036	-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	-0.35	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	340	340
TP53	0.019	0.028	-9999	-10000	0	0
DLG7	0.01	0.04	-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	0.042	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.014	0.036	-9999	-10000	0	0
AURKA	0.016	0.05	-9999	-10000	0	0
AURKB	-0.087	0.05	-9999	-0.16	21	21
CDC25B	0.02	0.034	-9999	-10000	0	0
G2/M transition checkpoint	0.014	0.036	-9999	-10000	0	0
mRNA polyadenylation	-0.017	0.12	-9999	-0.44	33	33
Aurora A/CPEB	-0.017	0.12	-9999	-0.44	33	33
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	0.039	-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	22	22
CENPA	-0.075	0.041	-9999	-0.17	21	21
Aurora A/PP2A	0.016	0.04	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.029	0.031	-9999	-10000	0	0
negative regulation of DNA binding	0.019	0.028	-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	0.036	-9999	-10000	0	0
mitotic prometaphase	0.025	0.017	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.05	-9999	-10000	0	0
TACC1	-0.003	0.047	-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	0.04	-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	340	340
PPP2R5D	0	0	-9999	-10000	0	0
Aurora A/TPX2	-0.21	0.16	-9999	-0.46	22	22
PAK1	-0.001	0.026	-9999	-0.57	1	1
CKAP5	0	0	-9999	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.008	0.058	-9999	-0.41	10	10
VLDLR	-0.003	0.047	-9999	-0.74	2	2
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.002	0.033	-9999	-0.74	1	1
ITGA3	-0.008	0.074	-9999	-0.74	5	5
RELN/VLDLR/Fyn	-0.087	0.19	-9999	-0.49	85	85
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.001	0.022	-9999	-10000	0	0
AKT1	-0.056	0.12	-9999	-0.51	2	2
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.036	0.14	-9999	-0.57	31	31
RELN/LRP8/DAB1	-0.1	0.18	-9999	-0.45	86	86
LRPAP1/LRP8	-0.003	0.032	-9999	-0.41	3	3
RELN/LRP8/DAB1/Fyn	-0.093	0.17	-9999	-0.42	86	86
DAB1/alpha3/beta1 Integrin	-0.087	0.16	-9999	-0.69	5	5
long-term memory	-0.12	0.19	-9999	-0.73	15	15
DAB1/LIS1	-0.087	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	-0.088	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	-0.066	0.2	-9999	-0.65	49	49
CDK5R1	-0.012	0.081	-9999	-0.57	10	10
RELN	-0.13	0.28	-9999	-0.73	87	87
PIK3R1	0	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.087	0.18	-9999	-0.48	84	84
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.13	0.2	-9999	-0.74	15	15
MAPK8	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.099	0.18	-9999	-0.45	87	87
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.094	0.17	-9999	-0.42	87	87
RELN/LRP8	-0.086	0.18	-9999	-0.48	84	84
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.095	0.17	-9999	-0.43	69	69
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.006	0.056	-9999	-0.56	5	5
RAP1A	-0.078	0.14	-9999	-0.57	4	4
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.003	0.042	-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	-0.015	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	87	87
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.066	0.12	-9999	-0.32	87	87
CDK5	0	0	-9999	-10000	0	0
MAPT	0.003	0.084	-9999	-0.67	7	7
neuron migration	-0.032	0.17	-9999	-0.55	5	5
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.043	0.082	-9999	-0.44	2	2
RELN/VLDLR	-0.08	0.17	-9999	-0.44	85	85

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.009	0.071	-9999	-0.56	8	8
AKT1	-0.011	0.2	-9999	-0.65	26	26
PTK2B	-0.056	0.25	-9999	-0.88	28	28
VEGFR2 homodimer/Frs2	-0.11	0.26	-9999	-0.61	92	92
CAV1	-0.21	0.33	-9999	-0.74	137	137
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.1	0.24	-9999	-0.93	26	26
endothelial cell proliferation	-0.007	0.2	-9999	-0.62	29	29
mol:Ca2+	-0.053	0.24	-9999	-0.84	26	26
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.098	0.23	-9999	-0.88	26	26
RP11-342D11.1	-0.06	0.24	-9999	-0.84	26	26
CDH5	-0.15	0.3	-9999	-0.74	97	97
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.005	0.058	-9999	-0.74	3	3
HRAS/GDP	-0.079	0.18	-9999	-0.71	26	26
SH2D2A	-0.002	0.033	-9999	-0.74	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.075	0.18	-9999	-0.67	27	27
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.1	0.24	-9999	-0.93	26	26
VEGFR1 homodimer	0	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.088	0.21	-9999	-0.81	26	26
GRB10	-0.053	0.24	-9999	-0.84	26	26
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	0.32	-9999	-0.95	54	54
HRAS	0	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.055	0.12	-9999	-0.45	28	28
HIF1A	0	0	-9999	-10000	0	0
FRS2	0	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.097	0.22	-9999	-0.86	26	26
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.036	0.16	-9999	-0.74	24	24
Nck/Pak	-0.001	0.019	-9999	-0.41	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.1	0.25	-9999	-0.94	26	26
mol:GDP	-0.085	0.2	-9999	-0.77	26	26
mol:NADP	-0.009	0.17	-9999	-0.55	27	27
eNOS/Hsp90	-0.003	0.16	-9999	-0.51	27	27
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	-0.054	0.24	-9999	-0.86	26	26
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	0.047	-9999	-0.74	2	2
FAK1/Vinculin	-0.042	0.24	-9999	-0.84	28	28
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	28	28
PTPN6	0	0	-9999	-10000	0	0
EPAS1	-0.13	0.29	-9999	-0.71	92	92
mol:L-citrulline	-0.009	0.17	-9999	-0.55	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	26	26
VEGFR2 homodimer/VEGFA homodimer	-0.1	0.24	-9999	-0.94	26	26
VEGFR2/3 heterodimer	-0.14	0.3	-9999	-0.64	104	104
VEGFB	0	0	-9999	-10000	0	0
MAPK11	-0.052	0.25	-9999	-0.87	26	26
VEGFR2 homodimer	-0.1	0.31	-9999	-0.69	92	92
FLT1	0	0	-9999	-10000	0	0
NEDD4	-0.002	0.033	-9999	-0.74	1	1
MAPK3	-0.047	0.23	-9999	-0.76	29	29
MAPK1	-0.047	0.23	-9999	-0.76	29	29
VEGFA145/NRP2	-0.005	0.05	-9999	-0.56	4	4
VEGFR1/2 heterodimer	-0.11	0.26	-9999	-0.61	92	92
KDR	-0.11	0.31	-9999	-0.7	92	92
VEGFA165/NRP1/VEGFR2 homodimer	-0.097	0.23	-9999	-0.9	26	26
SRC	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.047	0.23	-9999	-0.82	26	26
PI3K	-0.089	0.21	-9999	-0.82	26	26
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.1	0.24	-9999	-0.93	26	26
FES	-0.056	0.25	-9999	-0.89	26	26
GAB1	-0.092	0.22	-9999	-0.84	26	26
VEGFR2 homodimer/VEGFA homodimer/Src	-0.1	0.24	-9999	-0.93	26	26
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	60	60
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.1	0.24	-9999	-0.93	26	26
PI3K/GAB1	-0.012	0.2	-9999	-0.67	26	26
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.094	0.22	-9999	-0.86	26	26
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.13	0.28	-9999	-0.88	41	41
HSP90AA1	0	0	-9999	-10000	0	0
CDC42	-0.056	0.25	-9999	-0.88	26	26
actin cytoskeleton reorganization	-0.1	0.24	-9999	-0.91	26	26
PTK2	-0.053	0.27	-9999	-0.94	28	28
EDG1	-0.06	0.24	-9999	-0.84	26	26
mol:DAG	-0.054	0.24	-9999	-0.86	26	26
CaM/Ca2+	-0.087	0.2	-9999	-0.78	26	26
MAP2K3	-0.044	0.23	-9999	-0.82	26	26
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.098	0.23	-9999	-0.89	26	26
PLCG1	-0.056	0.25	-9999	-0.88	26	26
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.098	0.23	-9999	-0.88	26	26
IQGAP1	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.1	0.24	-9999	-0.93	26	26
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.1	0.24	-9999	-0.93	26	26
cell migration	-0.039	0.23	-9999	-0.75	28	28
mol:PI-3-4-5-P3	-0.082	0.19	-9999	-0.73	26	26
FYN	-0.002	0.033	-9999	-0.74	1	1
VEGFB/NRP1	-0.089	0.21	-9999	-0.79	26	26
mol:NO	-0.009	0.17	-9999	-0.55	27	27
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.079	0.18	-9999	-0.71	26	26
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.098	0.23	-9999	-0.89	26	26
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.012	0.094	-9999	-0.74	8	8
NOS3	-0.015	0.2	-9999	-0.64	27	27
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.11	0.25	-9999	-0.94	27	27
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.043	0.23	-9999	-0.8	27	27
PRKCB	-0.063	0.26	-9999	-0.88	28	28
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.095	0.22	-9999	-0.85	26	26
VEGFR1/2 heterodimer/VEGFA homodimer	-0.1	0.24	-9999	-0.93	26	26
VEGFA165/NRP2	-0.005	0.05	-9999	-0.56	4	4
MAPKKK cascade	-0.078	0.18	-9999	-0.71	26	26
NRP2	-0.006	0.067	-9999	-0.74	4	4
VEGFC homodimer	-0.003	0.047	-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	28	28
MAP3K13	-0.056	0.25	-9999	-0.88	26	26
PDPK1	-0.013	0.19	-9999	-0.63	26	26

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.044	0.084	-9999	-0.31	24	24
FZD6	0	0	-9999	-10000	0	0
WNT6	-0.095	0.21	-9999	-0.57	81	81
WNT4	-0.011	0.084	-9999	-0.66	8	8
FZD3	0	0	-9999	-10000	0	0
WNT5A	-0.012	0.084	-9999	-0.59	10	10
WNT11	-0.037	0.16	-9999	-0.68	27	27

×

IL12-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	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	22	22
TBX21	-0.095	0.5	-10000	0	-1.4	57	57
B2M	0.008	0.048	-10000	0	-0.74	2	2
TYK2	0.016	0.016	-10000	0	-10000	0	0
IL12RB1	-0.032	0.19	-10000	0	-0.77	31	31
GADD45B	-0.034	0.37	-10000	0	-1.1	40	40
IL12RB2	-0.045	0.18	-10000	0	-0.57	52	52
GADD45G	-0.017	0.33	-10000	0	-1	31	31
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	0.009	0.06	-10000	0	-0.75	3	3
IL2RA	-0.008	0.073	-10000	0	-0.66	6	6
IFNG	-0.008	0.076	-10000	0	-0.68	6	6
STAT3 (dimer)	-0.005	0.29	-10000	0	-0.79	42	42
HLA-DRB5	-0.063	0.22	-10000	0	-0.74	47	47
FASLG	-0.049	0.41	-10000	0	-1.2	41	41
NF kappa B2 p52/RelB	-0.13	0.3	-10000	0	-0.96	44	44
CD4	-0.014	0.13	-10000	0	-0.74	15	15
SOCS1	-0.002	0.033	-10000	0	-0.74	1	1
EntrezGene:6955	-0.001	0.009	-10000	0	-10000	0	0
CD3D	-0.006	0.11	-10000	0	-0.74	11	11
CD3E	-0.003	0.1	-10000	0	-0.74	9	9
CD3G	-0.035	0.18	-10000	0	-0.74	30	30
IL12Rbeta2/JAK2	-0.02	0.14	-10000	0	-0.41	52	52
CCL3	-0.028	0.35	-10000	0	-1.1	37	37
CCL4	-0.03	0.36	-10000	0	-1.1	38	38
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	-0.078	0.44	-10000	0	-1.2	52	52
IL12/IL12R/TYK2/JAK2/SPHK2	0.001	0.13	-10000	0	-0.4	21	21
IL1R1	-0.026	0.35	-10000	0	-1	38	38
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	-0.026	0.31	-10000	0	-1.3	22	22
RAB7A	0.007	0.28	-10000	0	-0.82	31	31
lysosomal transport	0.011	0.27	-10000	0	-0.77	31	31
FOS	-0.15	0.49	-10000	0	-1.2	79	79
STAT4 (dimer)	-0.009	0.34	-10000	0	-0.95	41	41
STAT5A (dimer)	-0.13	0.3	-10000	0	-0.99	42	42
GZMA	-0.033	0.37	-10000	0	-1.1	37	37
GZMB	-0.035	0.37	-10000	0	-1.1	37	37
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.037	0.39	-10000	0	-1.1	40	40
TCR/CD3/MHC II/CD4	-0.084	0.32	-10000	0	-0.89	48	48
IL2/IL2R	-0.014	0.1	-10000	0	-0.66	9	9
MAPK14	-0.016	0.34	-10000	0	-0.99	39	39
CCR5	-0.025	0.36	-10000	0	-1.2	27	27
IL1B	0	0.11	-10000	0	-0.77	10	10
STAT6	0.017	0.1	-10000	0	-0.26	5	5
STAT4	-0.012	0.094	-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	0.016	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	22	-10000	0	22
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	41	41
IL2RG	-0.012	0.094	-10000	0	-0.74	8	8
IL12	0.017	0.081	-10000	0	-0.57	8	8
STAT5A	0	0	-10000	0	-10000	0	0
CD247	-0.006	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	0.099	-10000	0	-0.75	8	8
IL12/IL12R/TYK2/JAK2	-0.052	0.45	-10000	0	-1.2	47	47
MAP2K3	-0.02	0.34	-10000	0	-1	39	39
RIPK2	0	0	-10000	0	-10000	0	0
MAP2K6	-0.02	0.34	-10000	0	-1	39	39
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.055	0.21	-10000	0	-0.74	42	42
IL18RAP	-0.021	0.16	-10000	0	-0.75	22	22
IL12Rbeta1/TYK2	-0.015	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	-0.81	37	37
T cell proliferation	0.006	0.26	-10000	0	-0.69	38	38
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.005	0.077	-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	-0.76	40	40
ATF2	-0.003	0.31	-10000	0	-0.9	37	37

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.24	0.35	-9999	-0.74	162	162
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	229	229
ARNT/IPAS	-0.18	0.26	-9999	-0.56	162	162
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	72	72
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	-0.14	0.14	-9999	-0.35	36	36

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.064	0.1	-10000	0	-0.37	4	4
NT3 (dimer)/TRKC	-0.17	0.26	-10000	0	-0.57	146	146
NT3 (dimer)/TRKB	-0.12	0.19	-10000	0	-0.39	150	150
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	63	63
PIK3CA	0	0	-10000	0	-10000	0	0
DYNLT1	0	0	-10000	0	-10000	0	0
NTRK1	-0.008	0.074	-10000	0	-0.74	5	5
NTRK2	-0.14	0.26	-10000	0	-0.62	108	108
NTRK3	-0.22	0.34	-10000	0	-0.74	143	143
NT-4/5 (dimer)/TRKB	-0.12	0.19	-10000	0	-0.39	151	151
neuron apoptosis	0.13	0.19	0.47	87	-10000	0	87
SHC 2-3/Grb2	-0.14	0.21	-10000	0	-0.52	87	87
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.056	0.1	-10000	0	-0.44	16	16
SHC3	-0.16	0.26	-10000	0	-0.69	86	86
STAT3 (dimer)	-0.005	0.042	-10000	0	-0.37	6	6
NT3 (dimer)/TRKA	-0.041	0.12	-10000	0	-0.37	54	54
RIN/GDP	-0.045	0.092	-10000	0	-0.27	2	2
GIPC1	0	0	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
DNAJA3	-0.023	0.067	-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	-0.034	0.12	-10000	0	-0.48	33	33
TRKA/NEDD4-2	-0.006	0.056	-10000	0	-0.56	5	5
ELMO1	-0.017	0.11	-10000	0	-0.74	11	11
RhoG/GTP/ELMO1/DOCK1	-0.011	0.072	-10000	0	-0.48	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	-0.02	0.12	-10000	0	-0.74	13	13
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	0.086	-10000	0	-0.4	13	13
mol:GDP	-0.066	0.13	-10000	0	-0.38	5	5
NGF (dimer)	-0.017	0.11	-10000	0	-0.7	12	12
RhoG/GDP	-0.013	0.084	-10000	0	-0.56	11	11
RIT1/GDP	-0.041	0.092	-10000	0	-0.28	1	1
TIAM1	-0.002	0.033	-10000	0	-0.74	1	1
PIK3R1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.14	0.23	-10000	0	-0.56	81	81
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	0.082	-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	63	63
ubiquitin-dependent protein catabolic process	-0.016	0.083	-10000	0	-0.48	14	14
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	-0.007	0.04	-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	75	75
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	-0.38	1	1
STAT3	-0.005	0.042	-10000	0	-0.37	6	6
axon guidance	-0.21	0.25	-10000	0	-0.68	75	75
MAPK3	-0.004	0.12	-10000	0	-0.43	33	33
MAPK1	-0.004	0.12	-10000	0	-0.43	33	33
CDC42/GDP	-0.041	0.092	-10000	0	-0.28	1	1
NTF3	-0.01	0.083	-10000	0	-0.69	7	7
NTF4	-0.012	0.094	-10000	0	-0.74	8	8
NGF (dimer)/TRKA/FAIM	-0.016	0.084	-10000	0	-0.48	14	14
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	307	307
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	-0.041	0.092	-10000	0	-0.28	1	1
NGF (dimer)/TRKA/GRIT	-0.016	0.085	-10000	0	-0.46	17	17
neuron projection morphogenesis	0.004	0.072	-10000	0	-0.42	3	3
NGF (dimer)/TRKA/NEDD4-2	-0.016	0.084	-10000	0	-0.48	14	14
MAP2K1	0	0	-10000	0	-10000	0	0
NGFR	-0.049	0.16	-10000	0	-0.57	42	42
NGF (dimer)/TRKA/GIPC/GAIP	-0.01	0.053	-10000	0	-0.31	14	14
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	-0.046	0.12	-10000	0	-0.67	14	14
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.006	0.056	-10000	0	-0.56	5	5
SQSTM1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.13	0.21	-10000	0	-0.51	81	81
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.013	0.07	-10000	0	-10000	0	0
MATK	-0.029	0.14	-10000	0	-0.74	19	19
NEDD4L	0	0	-10000	0	-10000	0	0
RAS family/GDP	-0.042	0.064	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.025	0.073	-10000	0	-0.33	14	14
Rac1/GTP	-0.18	0.13	-10000	0	-0.33	129	129
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.14	0.14	-9999	-0.66	3	3
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	256	256
AP1	-0.16	0.16	-9999	-0.6	31	31
ILK	-0.14	0.17	-9999	-0.6	5	5
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	-0.58	8	8
MAP3K1	-0.14	0.17	-9999	-0.61	5	5
JUN	0	0	-9999	-10000	0	0
MAPK3	-0.12	0.17	-9999	-0.56	5	5
MAPK1	-0.12	0.17	-9999	-0.66	3	3
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	0.093	-9999	-0.74	8	8
NFKBIA	-0.1	0.16	-9999	-0.64	3	3
FOS	-0.085	0.24	-9999	-0.74	56	56
CD44	-0.002	0.033	-9999	-0.74	1	1
CHUK	0	0	-9999	-10000	0	0
PLAU	-0.099	0.16	-9999	-0.55	19	19
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	0.07	-9999	-0.55	8	8
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.14	0.17	-9999	-0.52	9	9
VAV3	-0.12	0.17	-9999	-0.8	3	3
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	256	256
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.13	0.13	-9999	-0.73	3	3
MMP2	-0.1	0.17	-9999	-0.65	8	8

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.023	0.1	-10000	0	-0.46	25	25
ER alpha/Gai/GDP/Gbeta gamma	-0.026	0.11	-10000	0	-0.46	23	23
AKT1	-0.005	0.18	-10000	0	-0.82	22	22
PIK3CA	0	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.008	0.18	-10000	0	-0.83	22	22
mol:Ca2+	-0.089	0.23	-10000	0	-0.48	118	118
IGF1R	0	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.022	0.1	-10000	0	-0.48	22	22
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.003	0.17	0.78	22	-10000	0	22
RhoA/GTP	-0.016	0.074	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.027	0.11	-10000	0	-0.52	23	23
regulation of stress fiber formation	-0.032	0.071	0.58	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.022	0.1	-10000	0	-0.48	22	22
KRAS	0	0	-10000	0	-10000	0	0
G13/GTP	-0.02	0.092	-10000	0	-0.44	22	22
pseudopodium formation	0.032	0.071	-10000	0	-0.58	1	1
E2/ER alpha (dimer)/PELP1	-0.022	0.1	-10000	0	-0.48	22	22
GRB2	0	0	-10000	0	-10000	0	0
GNG2	-0.008	0.074	-10000	0	-0.74	5	5
GNAO1	-0.004	0.049	-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	0.015	0.13	-10000	0	-0.54	23	23
E2/ER beta (dimer)	0	0	-10000	0	-10000	0	0
mol:GDP	-0.023	0.1	-10000	0	-0.5	22	22
mol:NADP	0.015	0.13	-10000	0	-0.54	23	23
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.094	0.24	-10000	0	-0.5	118	118
IGF-1R heterotetramer	0	0	-10000	0	-10000	0	0
PLCB1	-0.12	0.22	-10000	0	-0.51	117	117
PLCB2	-0.13	0.23	-10000	0	-0.52	118	118
IGF1	-0.025	0.13	-10000	0	-0.73	17	17
mol:L-citrulline	0.015	0.13	-10000	0	-0.54	23	23
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.007	0.046	-10000	0	-0.51	2	2
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	0.033	-10000	0	-0.74	1	1
ESR1	-0.033	0.15	-10000	0	-0.74	22	22
Gq family/GDP/Gbeta gamma	-0.074	0.14	-10000	0	-0.81	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.019	0.072	-10000	0	-0.36	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.027	0.11	-10000	0	-0.52	23	23
GNAZ	-0.009	0.081	-10000	0	-0.74	6	6
E2/ER alpha (dimer)	-0.025	0.12	-10000	0	-0.56	22	22
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	0.033	-10000	0	-0.74	1	1
HBEGF	0.014	0.12	-10000	0	-0.72	5	5
cAMP biosynthetic process	-0.021	0.091	-10000	0	-0.41	25	25
SRC	0.019	0.11	-10000	0	-0.44	23	23
PI3K	0	0	-10000	0	-10000	0	0
GNB1	-0.002	0.033	-10000	0	-0.74	1	1
G13/GDP/Gbeta gamma	-0.024	0.11	-10000	0	-0.48	22	22
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.031	0.11	-10000	0	-0.46	24	24
Gs family/GTP	-0.021	0.093	-10000	0	-0.42	25	25
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	0.016	0.12	-10000	0	-0.51	23	23
mol:DAG	-0.094	0.24	-10000	0	-0.5	118	118
Gs family/GDP/Gbeta gamma	-0.024	0.1	-10000	0	-0.45	22	22
MSN	0.032	0.076	-10000	0	-0.64	1	1
Gq family/GTP	-0.13	0.24	-10000	0	-0.54	117	117
mol:PI-3-4-5-P3	-0.007	0.17	-10000	0	-0.79	22	22
NRAS	0	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.016	0.12	0.51	23	-10000	0	23
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.021	0.097	-10000	0	-0.47	22	22
NOS3	0.014	0.14	-10000	0	-0.56	23	23
GNA11	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.019	0.14	-10000	0	-0.63	22	22
E2/ER alpha (dimer)/PELP1/Src	-0.029	0.12	-10000	0	-0.55	23	23
ruffle organization	0.032	0.071	-10000	0	-0.58	1	1
ROCK2	-0.015	0.068	-10000	0	-10000	0	0
GNA14	-0.18	0.32	-10000	0	-0.74	117	117
GNA15	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
MMP9	0.01	0.12	-10000	0	-0.59	5	5
MMP2	0.022	0.12	-10000	0	-0.79	5	5

×

p75(NTR)-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.007	0.061	-9999	-0.56	6	6
Necdin/E2F1	-0.008	0.066	-9999	-0.56	7	7
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.038	0.11	-9999	-0.7	2	2
NGF (dimer)/p75(NTR)/BEX1	-0.097	0.19	-9999	-0.54	55	55
NT-4/5 (dimer)/p75(NTR)	-0.045	0.13	-9999	-0.44	50	50
IKBKB	-0.001	0.026	-9999	-0.57	1	1
AKT1	-0.033	0.1	-9999	-0.46	9	9
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.095	0.25	-9999	-0.74	63	63
MGDIs/NGR/p75(NTR)/LINGO1	-0.062	0.14	-9999	-0.37	81	81
FURIN	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.096	0.19	-9999	-0.45	104	104
LINGO1	-0.052	0.16	-9999	-0.57	44	44
Sortilin/TRAF6/NRIF	-0.004	0.038	-9999	-10000	0	0
proBDNF (dimer)	-0.095	0.25	-9999	-0.74	63	63
NTRK1	-0.008	0.074	-9999	-0.74	5	5
RTN4R	-0.003	0.042	-9999	-0.66	2	2
neuron apoptosis	-0.031	0.16	-9999	-0.57	12	12
IRAK1	0	0	-9999	-10000	0	0
SHC1	-0.019	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	-0.47	15	15
MAGEH1	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.048	0.13	-9999	-0.48	21	21
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	-0.034	0.1	-9999	-0.47	9	9
NGF	-0.017	0.11	-9999	-0.7	12	12
cell cycle arrest	-0.022	0.13	-9999	-0.44	15	15
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.019	0.06	-9999	-0.46	2	2
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.037	0.11	-9999	-0.37	50	50
NCSTN	0	0	-9999	-10000	0	0
mol:GTP	-0.04	0.12	-9999	-0.54	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	-0.014	0.046	-9999	-0.37	2	2
p75(NTR)/beta APP	-0.035	0.12	-9999	-0.41	42	42
BEX1	-0.09	0.23	-9999	-0.68	64	64
mol:GDP	-0.027	0.13	-9999	-0.39	52	52
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	-0.035	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	-0.04	0.12	-9999	-0.55	9	9
RHOB	-0.002	0.033	-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	0.082	-9999	-0.69	7	7
TP53	-0.076	0.15	-9999	-0.67	7	7
PRDM4	-0.016	0.13	-9999	-0.47	15	15
BDNF (dimer)	-0.27	0.24	-9999	-0.65	86	86
PIK3CA	0	0	-9999	-10000	0	0
SORT1	-0.009	0.081	-9999	-0.74	6	6
activation of caspase activity	-0.038	0.11	-9999	-0.68	2	2
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.041	0.12	-9999	-0.47	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	-0.016	0.13	-9999	-0.47	15	15
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.046	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)	-0.043	0.13	-9999	-0.43	49	49
MAPK8	-0.01	0.14	-9999	-0.56	6	6
MAPK9	-0.01	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	0.094	-9999	-0.74	8	8
NDN	-0.011	0.088	-9999	-0.74	7	7
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.031	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	-0.04	0.12	-9999	-0.54	9	9
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.081	0.16	-9999	-0.43	68	68
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.087	0.18	-9999	-0.46	68	68
PRKACB	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.072	0.19	-9999	-0.56	63	63
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.009	0.081	-9999	-0.74	6	6
BIRC2	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.014	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	-0.049	0.16	-9999	-0.57	42	42
CYCS	-0.038	0.11	-9999	-0.55	4	4
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.036	0.11	-9999	-0.5	9	9
BCL2L11	-0.003	0.14	-9999	-0.55	6	6
BDNF (dimer)/p75(NTR)	-0.11	0.22	-9999	-0.52	99	99
PI3K	-0.036	0.11	-9999	-0.5	9	9
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.041	0.12	-9999	-0.47	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)	-0.048	0.14	-9999	-0.45	52	52
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.041	0.12	-9999	-0.47	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	-0.43	74	74
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	0.07	-9999	-0.51	2	2
NGF (dimer)/TRKA	-0.018	0.098	-9999	-0.53	17	17
MMP7	-0.038	0.15	-9999	-0.62	30	30
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.038	0.11	-9999	-0.44	15	15
MMP3	-0.34	0.28	-9999	-0.57	294	294
APAF-1/Caspase 9	-0.03	0.084	-9999	-0.54	3	3

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.039	0.14	-10000	0	-0.6	25	25
FYN	0.002	0.23	-10000	0	-0.87	26	26
LAT/GRAP2/SLP76	-0.053	0.18	-10000	0	-0.68	31	31
IKBKB	-0.001	0.026	-10000	0	-0.57	1	1
AKT1	0.024	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	0.047	-10000	0	-0.74	2	2
mol:Ca2+	-0.006	0.022	-10000	0	-0.13	8	8
integrin-mediated signaling pathway	-0.001	0.022	-10000	0	-0.48	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.011	0.21	-10000	0	-0.75	29	29
TRPV6	-0.018	0.12	-10000	0	-0.69	14	14
CD28	0.002	0.076	-10000	0	-0.75	5	5
SHC1	0.006	0.21	-10000	0	-0.81	25	25
receptor internalization	-0.009	0.23	-10000	0	-0.83	30	30
PRF1	-0.036	0.32	-10000	0	-1.3	30	30
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	0.2	-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	-0.003	0.1	-10000	0	-0.75	9	9
CD3G	-0.036	0.18	-10000	0	-0.75	30	30
RASGRP2	-0.013	0.065	-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	0.033	-10000	0	-0.74	1	1
RAP1A/GTP/RAPL	-0.001	0.022	-10000	0	-0.48	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	-0.31	23	23
GRAP2	-0.039	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	-0.015	0.23	-10000	0	-0.86	26	26
ORAI1	0.01	0.063	0.36	9	-0.57	1	10
CSK	0.004	0.21	-10000	0	-0.82	25	25
B7 family/CD28	-0.063	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	-0.97	26	26
PTPN6	0.002	0.21	-10000	0	-0.86	24	24
VAV1	0.004	0.21	-10000	0	-0.84	25	25
Monovalent TCR/CD3	-0.024	0.21	-10000	0	-0.64	36	36
CBL	0	0	-10000	0	-10000	0	0
LCK	-0.001	0.23	-10000	0	-0.89	26	26
PAG1	0.001	0.22	-10000	0	-0.82	26	26
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	-0.015	0.13	-10000	0	-0.74	16	16
CD86	0	0.083	-10000	0	-0.75	6	6
PDK1/CARD11/BCL10/MALT1	-0.02	0.065	-10000	0	-0.29	19	19
HRAS	0	0	-10000	0	-10000	0	0
GO:0035030	0.007	0.19	-10000	0	-0.67	30	30
CD8A	0	0.09	-10000	0	-0.75	7	7
CD8B	-0.011	0.12	-10000	0	-0.7	15	15
PTPRC	-0.039	0.19	-10000	0	-0.74	32	32
PDK1/PKC theta	0.018	0.18	-10000	0	-0.59	32	32
CSK/PAG1	0.007	0.2	-10000	0	-0.78	26	26
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.003	0.053	-10000	0	-0.8	2	2
GRAP2/SLP76	-0.062	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	-0.014	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	-0.03	0.3	-10000	0	-1.1	31	31
RAP1A/GTP	-0.009	0.022	-10000	0	-0.071	1	1
mol:PI-3-4-5-P3	0.019	0.17	-10000	0	-0.59	29	29
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.044	0.17	0.26	10	-0.66	27	37
NRAS	0	0	-10000	0	-10000	0	0
ZAP70	-0.012	0.094	-10000	0	-0.74	8	8
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.049	0.16	-10000	0	-0.65	29	29
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.023	0.13	-10000	0	-0.66	17	17
CARD11	-0.004	0.049	-10000	0	-0.63	3	3
PRKCB	-0.033	0.1	-10000	0	-0.37	33	33
PRKCE	-0.023	0.074	-10000	0	-0.3	27	27
PRKCQ	0.006	0.21	-10000	0	-0.69	33	33
LCP2	-0.01	0.088	-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	0.087	-10000	0	-0.31	20	20
PDPK1	0.027	0.13	-10000	0	-0.45	29	29
TCR/CD3/MHC I/CD8/Fyn	-0.011	0.24	-10000	0	-0.91	27	27

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.099	0.21	-9999	-0.57	84	84
AP1	-0.13	0.34	-9999	-1.1	56	56
mol:IP3	0.01	0.06	-9999	-0.54	5	5
PLCG1	0.01	0.06	-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	79	79
CAV1	-0.21	0.33	-9999	-0.74	137	137
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	56	56
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	-0.004	0.045	-9999	-0.47	4	4
PDGF/PDGFRA/Crk/C3G	-0.004	0.045	-9999	-0.47	4	4
JAK1	0.013	0.055	-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	140	140
ITGAV	0	0	-9999	-10000	0	0
ELK1	0.014	0.061	-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

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	10	10
EPO	-0.15	0.21	-10000	0	-0.66	14	14
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	-0.79	13	13
FLT1	-0.039	0.16	-10000	0	-0.96	13	13
ADORA2A	-0.19	0.23	-10000	0	-0.75	14	14
germ cell development	-0.19	0.24	-10000	0	-0.74	18	18
SLC11A2	-0.2	0.24	-10000	0	-0.78	14	14
BHLHE40	-0.2	0.24	-10000	0	-0.78	14	14
HIF1AN	0.003	0.009	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.14	0.16	-10000	0	-0.48	39	39
ETS1	0.002	0.12	-10000	0	-0.75	13	13
CITED2	-0.032	0.16	-10000	0	-1.3	8	8
KDR	-0.095	0.33	-10000	0	-1.3	34	34
PGK1	-0.2	0.24	-10000	0	-0.78	14	14
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	-0.8	36	36
EPAS1	-0.12	0.16	-10000	0	-0.46	38	38
SP1	0.016	0	-10000	0	-10000	0	0
ABCG2	-0.24	0.32	-10000	0	-0.96	57	57
EFNA1	-0.2	0.24	-10000	0	-0.78	14	14
FXN	-0.19	0.23	-10000	0	-0.75	14	14
POU5F1	-0.2	0.24	-10000	0	-0.78	18	18
neuron apoptosis	0.2	0.28	0.78	36	-10000	0	36
EP300	0	0	-10000	0	-10000	0	0
EGLN3	-0.084	0.21	-10000	0	-0.59	72	72
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	-0.78	77	77
TWIST1	-0.27	0.3	-10000	0	-0.8	51	51
ELK1	0.016	0.002	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.14	0.16	-10000	0	-0.52	15	15
VEGFA	-0.2	0.24	-10000	0	-0.79	13	13
CREBBP	0	0	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.003	0.047	-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	-0.48	84	84
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.054	0.18	-9999	-0.43	84	84
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.036	0.14	-9999	-0.57	31	31
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	-0.012	0.081	-9999	-0.57	10	10
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.15	0.25	-9999	-0.57	126	126
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.11	0.2	-9999	-0.49	87	87
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.092	0.14	-9999	-0.48	28	28
MAP1B	-0.002	0.019	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.073	0.15	-9999	-0.62	3	3
RELN	-0.13	0.28	-9999	-0.73	87	87
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	-0.069	0.11	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.063	0.12	-9999	-0.33	35	35
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.1	0.15	-9999	-0.51	28	28
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.02	0	-9999	-10000	0	0
PAFAH1B3	-0.006	0.061	-9999	-0.61	5	5
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	-0.087	0.14	-9999	-0.46	28	28
LRP8	-0.004	0.045	-9999	-0.57	3	3
NDEL1/Katanin 60	-0.092	0.14	-9999	-0.48	28	28
P39/CDK5	-0.14	0.19	-9999	-0.65	26	26
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.042	0.16	-9999	-10000	0	0
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	-0.091	0.17	-9999	-0.67	4	4
RELN/VLDLR	-0.08	0.17	-9999	-0.44	85	85
CDC42	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.003	0.04	-10000	0	-0.51	3	3
CRKL	-0.025	0.12	-10000	0	-0.37	4	4
mol:PIP3	-0.015	0.03	0.63	1	-10000	0	1
AKT1	0.003	0.02	0.42	1	-10000	0	1
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.017	0.11	-10000	0	-0.4	2	2
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
HGF/MET/SHIP2	-0.1	0.2	-10000	0	-0.48	105	105
MAP3K5	-0.009	0.11	-10000	0	-0.44	4	4
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.094	0.18	-10000	0	-0.44	104	104
AP1	-0.057	0.16	-10000	0	-0.5	56	56
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.073	0.24	-10000	0	-0.73	56	56
STAT3 (dimer)	-0.033	0.13	-10000	0	-10000	0	0
GAB1/CRKL/SHP2/PI3K	-0.044	0.086	-10000	0	-10000	0	0
INPP5D	-0.002	0.033	-10000	0	-0.74	1	1
CBL/CRK	-0.018	0.11	-10000	0	-0.4	2	2
PTPN11	0	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.033	-10000	0	-0.74	1	1
ELK1	-0.004	0.022	-10000	0	-0.24	3	3
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.038	0.076	-10000	0	-0.46	2	2
PAK1	0.01	0.022	0.39	1	-10000	0	1
HGF/MET/RANBP10	-0.1	0.2	-10000	0	-0.48	104	104
HRAS	-0.079	0.15	-10000	0	-0.59	4	4
DOCK1	-0.017	0.11	-10000	0	-0.4	2	2
GAB1	-0.033	0.12	-10000	0	-0.39	4	4
CRK	-0.025	0.12	-10000	0	-0.43	2	2
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.12	0.22	-10000	0	-0.54	104	104
JUN	0	0	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.053	0.1	-10000	0	-0.25	104	104
PIK3R1	0	0	-10000	0	-10000	0	0
cell morphogenesis	-0.01	0.14	-10000	0	-10000	0	0
GRB2/SHC	-0.044	0.087	-10000	0	-0.5	2	2
FOS	-0.085	0.24	-10000	0	-0.74	56	56
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.004	0.022	-10000	0	-0.24	3	3
HGF/MET/MUC20	-0.1	0.2	-10000	0	-0.48	105	105
cell migration	-0.044	0.086	-10000	0	-0.49	2	2
GRB2	0	0	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.003	0.04	-10000	0	-0.51	3	3
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.065	0.12	-10000	0	-10000	0	0
MET/MUC20	-0.003	0.041	-10000	0	-0.52	3	3
RAP1B	-0.009	0.1	-10000	0	-0.37	2	2
RAP1A	-0.009	0.1	-10000	0	-0.37	2	2
HGF/MET/RANBP9	-0.1	0.2	-10000	0	-0.48	105	105
RAF1	-0.043	0.16	-10000	0	-0.55	4	4
STAT3	-0.063	0.12	-10000	0	-10000	0	0
cell proliferation	-0.046	0.18	-10000	0	-0.52	4	4
RPS6KB1	-0.018	0.036	-10000	0	-10000	0	0
MAPK3	-0.007	0.019	-10000	0	-0.23	2	2
MAPK1	-0.007	0.019	-10000	0	-0.23	2	2
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	0.009	0.095	-10000	0	-0.37	2	2
SRC	-0.06	0.12	-10000	0	-10000	0	0
PI3K	-0.044	0.087	-10000	0	-0.5	2	2
MET/Glomulin	-0.003	0.036	-10000	0	-0.46	3	3
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.033	0.15	-10000	0	-0.5	4	4
MET	-0.004	0.054	-10000	0	-0.68	3	3
MAP4K1	-0.018	0.12	-10000	0	-0.47	4	4
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.033	0.15	-10000	0	-0.5	4	4
BAD	0.01	0.018	0.39	1	-10000	0	1
MAP2K4	-0.001	0.1	-10000	0	-0.45	2	2
SHP2/GRB2/SOS1/GAB1	-0.046	0.09	-10000	0	-0.45	2	2
INPPL1	0	0	-10000	0	-10000	0	0
PXN	0	0	-10000	0	-10000	0	0
SH3KBP1	-0.003	0.047	-10000	0	-0.74	2	2
HGS	-0.048	0.094	-10000	0	-0.42	4	4
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.15	0.3	-10000	0	-0.74	102	102
RASA1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
PTPRJ	-0.003	0.047	-10000	0	-0.74	2	2
NCK/PLCgamma1	-0.05	0.098	-10000	0	-0.53	2	2
PDPK1	-0.005	0.023	0.48	1	-10000	0	1
HGF/MET/SHIP	-0.1	0.2	-10000	0	-0.48	105	105

×

Effects of Botulinum toxin

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
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	51	51
STXBP1	-0.005	0.058	-9999	-0.74	3	3
ACh/CHRNA1	-0.015	0.073	-9999	-0.42	14	14
RAB3GAP2/RIMS1/UNC13B	-0.05	0.15	-9999	-0.48	51	51
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	-0.074	0.22	-9999	-0.74	49	49
mol:ACh	0.005	0.024	-9999	-0.15	11	11
RAB3GAP2	0	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.043	0.12	-9999	-0.36	55	55
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	0.07	-9999	-0.39	16	16
SNAP25	-0.007	0.049	-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	0.049	-9999	-0.41	7	7
STX1A/SNAP25 fragment 1/VAMP2	-0.043	0.12	-9999	-0.36	55	55

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.025	0.11	-10000	0	-0.52	22	22
AKT1	0.006	0.021	-10000	0	-10000	0	0
GSC	-0.038	0.13	-10000	0	-0.47	2	2
NKX2-5	-0.29	0.28	-10000	0	-0.57	251	251
muscle cell differentiation	0.093	0.098	0.43	8	-10000	0	8
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	0.032	-10000	0	-10000	0	0
MYC	0.007	0.024	-10000	0	-10000	0	0
CDKN2B	-0.091	0.41	-10000	0	-1.4	41	41
AP1	-0.036	0.12	-10000	0	-0.46	1	1
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0	0.005	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.028	0.087	-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	45	45
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	33	33
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	0.033	-10000	0	-0.74	1	1
CDKN1A	0.058	0.042	-10000	0	-10000	0	0
KAT2B	0.002	0.034	-10000	0	-0.74	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.046	0.11	-10000	0	-0.43	21	21
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	-0.002	0.029	-10000	0	-0.54	1	1
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	-0.45	1	1
SMAD3/SMAD4/IRF7	-0.003	0.039	-10000	0	-0.54	2	2
TFE3	0.016	0.001	-10000	0	-10000	0	0
COL1A2	0.006	0.052	-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	282	282
TCF3	0	0	-10000	0	-10000	0	0
FOS	-0.071	0.24	-10000	0	-0.73	56	56
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	0.047	-10000	0	-0.74	2	2
ESR1	-0.033	0.15	-10000	0	-0.74	22	22
HNF4A	-0.009	0.073	-10000	0	-0.57	8	8
MEF2C	-0.16	0.22	-10000	0	-0.71	33	33
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	0.026	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.014	0.023	-10000	0	-0.42	1	1
NCOR1	0	0	-10000	0	-10000	0	0
NCOA2	-0.002	0.033	-10000	0	-0.74	1	1
NCOA1	0	0	-10000	0	-10000	0	0
MYOD/E2A	-0.06	0.14	-10000	0	-0.41	71	71
SMAD2-3/SMAD4/SP1/MIZ-1	0.018	0.053	-10000	0	-10000	0	0
IFNB1	0.035	0.048	-10000	0	-0.48	3	3
SMAD3/SMAD4/MEF2C	-0.17	0.19	-10000	0	-0.68	33	33
CITED1	-0.003	0.042	-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	0.012	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	0.071	0.29	7	-10000	0	7
IL10	0.026	0.11	-10000	0	-0.5	17	17
PIASy/HDAC complex	0.006	0.005	-10000	0	-10000	0	0
PIAS3	0.003	0.007	-10000	0	-10000	0	0
CDK2	0.006	0.01	-10000	0	-10000	0	0
IL5	0.024	0.096	-10000	0	-0.45	16	16
CDK4	0.005	0.028	-10000	0	-0.57	1	1
PIAS4	0.006	0.005	-10000	0	-10000	0	0
ATF3	-0.002	0.033	-10000	0	-0.74	1	1
SMAD3/SMAD4/SP1	0.002	0.027	-10000	0	-10000	0	0
FOXG1	-0.062	0.18	-10000	0	-0.57	52	52
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	33	33
CEBPB	0.008	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.21	0.18	-10000	0	-0.36	282	282
MYOD1	-0.083	0.2	-10000	0	-0.57	71	71
SMAD3/SMAD4/HNF4	-0.007	0.047	-10000	0	-0.35	8	8
SMAD3/SMAD4/GATA3	-0.02	0.093	-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	-0.62	38	38
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	-0.1	0.2	-10000	0	-0.5	102	102
AR	-0.15	0.3	-10000	0	-0.74	102	102
negative regulation of cell growth	0.004	0.024	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.053	0.13	-10000	0	-0.36	66	66
E2F5	0	0	-10000	0	-10000	0	0
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.032	0.088	-10000	0	-0.46	3	3
SMAD2-3/SMAD4/FOXO1-3a-4	-0.018	0.094	-10000	0	-0.36	1	1
TFDP1	-0.004	0.045	-10000	0	-0.57	3	3
SMAD3/SMAD4/AP1	-0.035	0.12	-10000	0	-0.46	1	1
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

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.016	0.076	-9999	-0.36	22	22
EFNA5	-0.003	0.047	-9999	-0.74	2	2
FYN	0.003	0.074	-9999	-0.44	3	3
neuron projection morphogenesis	-0.016	0.076	-9999	-0.36	22	22
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.016	0.076	-9999	-0.36	22	22
EPHA5	-0.023	0.11	-9999	-0.57	20	20

×

Caspase cascade in apoptosis

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
TOP1	0	0.12	-10000	0	-0.48	25	25
ACTA1	-0.012	0.16	-10000	0	-0.64	25	25
NUMA1	0	0.12	-10000	0	-0.48	25	25
SPTAN1	-0.01	0.16	-10000	0	-0.64	25	25
LIMK1	-0.01	0.16	-10000	0	-0.64	25	25
BIRC3	-0.009	0.081	-10000	0	-0.74	6	6
BIRC2	0	0	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
CASP10	-0.011	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	-0.01	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	0.074	-10000	0	-0.3	27	27
MAP3K1	0.004	0.046	-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	-0.011	0.16	-10000	0	-0.63	26	26
CASP9	0.001	0.002	-10000	0	-10000	0	0
DNA repair	-0.002	0.034	0.17	8	-0.21	2	10
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	0.072	-10000	0	-0.43	4	4
TRAF2	0	0	-10000	0	-10000	0	0
ICAD/CAD	-0.003	0.15	-10000	0	-0.61	25	25
CASP7	-0.005	0.042	0.36	6	-10000	0	6
KRT18	0.013	0.02	-10000	0	-10000	0	0
apoptosis	-0.003	0.14	-10000	0	-0.56	25	25
DFFA	-0.01	0.16	-10000	0	-0.64	25	25
DFFB	-0.01	0.16	-10000	0	-0.64	25	25
PARP1	0.002	0.034	0.21	2	-0.17	8	10
actin filament polymerization	0.002	0.14	0.58	25	-10000	0	25
TNF	-0.019	0.12	-10000	0	-0.73	13	13
CYCS	0.007	0.056	-10000	0	-0.26	12	12
SATB1	0.021	0.079	-10000	0	-0.5	4	4
SLK	-0.01	0.16	-10000	0	-0.64	25	25
p15 BID/BAX	-0.014	0.061	-10000	0	-0.34	10	10
CASP2	0.034	0.051	-10000	0	-0.44	1	1
JNK cascade	-0.004	0.046	0.23	10	-10000	0	10
CASP3	-0.018	0.16	-10000	0	-0.66	26	26
LMNB2	0.032	0.049	-10000	0	-0.48	1	1
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.002	0.033	-10000	0	-0.74	1	1
Mammalian IAPs/DIABLO	-0.005	0.048	-10000	0	-0.43	6	6
negative regulation of DNA binding	-0.069	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	0.012	0.051	-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	-0.55	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	0.033	-10000	0	-0.74	1	1
SREBF1	-0.01	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	0.21	-10000	0	-0.52	72	72
positive regulation of apoptosis	0.035	0.049	-10000	0	-0.47	1	1
PRF1	-0.038	0.16	-10000	0	-0.74	25	25

×

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	0.25	-9999	-0.74	67	67
GNB1/GNG2	-0.041	0.086	-9999	-0.47	7	7
mol:DAG	-0.002	0.095	-9999	-0.48	4	4
PLCG1	-0.037	0.079	-9999	-0.5	4	4
YES1	-0.039	0.076	-9999	-0.45	1	1
FZD3	0	0	-9999	-10000	0	0
FZD6	0	0	-9999	-10000	0	0
G protein	-0.038	0.08	-9999	-0.51	4	4
MAP3K7	-0.014	0.13	-9999	-0.54	13	13
mol:Ca2+	-0.001	0.092	-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	0.033	-9999	-0.74	1	1
CAMK2A	-0.024	0.14	-9999	-0.58	14	14
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.044	0.084	-9999	-0.31	24	24
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.039	0.076	-9999	-0.45	1	1
GO:0007205	-0.001	0.094	-9999	-0.48	4	4
WNT6	-0.095	0.21	-9999	-0.57	81	81
WNT4	-0.011	0.084	-9999	-0.66	8	8
NFAT1/CK1 alpha	-0.079	0.14	-9999	-0.54	17	17
GNG2	-0.008	0.074	-9999	-0.74	5	5
WNT5A	-0.012	0.084	-9999	-0.59	10	10
WNT11	-0.037	0.16	-9999	-0.68	27	27
CDC42	-0.003	0.087	-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	0.003	0.022	-10000	0	-10000	0	0
RFC1	0.003	0.022	-10000	0	-10000	0	0
PRKDC	0.003	0.022	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	-0.012	0.039	0.26	2	-10000	0	2
FASLG/FAS/FADD/FAF1	-0.017	0.076	0.24	6	-0.34	20	26
MAP2K4	-0.012	0.13	-10000	0	-0.5	8	8
mol:ceramide	-0.007	0.11	-10000	0	-0.44	21	21
GSN	0.003	0.022	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.027	0.09	-10000	0	-0.42	19	19
FAS	0.007	0.035	-10000	0	-0.76	1	1
BID	0.003	0.032	0.31	5	-10000	0	5
MAP3K1	0.004	0.08	-10000	0	-10000	0	0
MAP3K7	0.008	0.004	-10000	0	-10000	0	0
RB1	0.003	0.022	-10000	0	-10000	0	0
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.11	0.2	-10000	0	-0.48	108	108
ARHGDIB	0.002	0.025	-10000	0	-0.32	1	1
FADD	0.009	0.004	-10000	0	-10000	0	0
actin filament polymerization	-0.003	0.022	-10000	0	-10000	0	0
NFKB1	-0.038	0.08	-10000	0	-0.29	7	7
MAPK8	-0.032	0.19	-10000	0	-0.44	81	81
DFFA	0.003	0.022	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.003	0.022	-10000	0	-10000	0	0
FAS/FADD/MET	-0.004	0.041	-10000	0	-0.48	3	3
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.006	0.079	-10000	0	-0.71	6	6
FAF1	0.009	0.004	-10000	0	-10000	0	0
PARP1	0.003	0.022	-10000	0	-10000	0	0
DFFB	0.003	0.022	-10000	0	-10000	0	0
CHUK	-0.034	0.07	-10000	0	-10000	0	0
FASLG	-0.022	0.15	-10000	0	-0.74	20	20
FAS/FADD	-0.002	0.026	-10000	0	-0.58	1	1
HGF	-0.15	0.3	-10000	0	-0.74	102	102
LMNA	0.002	0.02	-10000	0	-10000	0	0
CASP6	0.003	0.022	-10000	0	-10000	0	0
CASP10	0.007	0.034	-10000	0	-0.74	1	1
CASP3	0.003	0.026	0.23	5	-10000	0	5
PTPN13	-0.006	0.067	-10000	0	-0.74	4	4
CASP8	0.005	0.045	0.43	5	-10000	0	5
IL6	-0.2	0.51	-10000	0	-1.3	83	83
MET	-0.004	0.054	-10000	0	-0.68	3	3
ICAD/CAD	0.002	0.021	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.007	0.11	-10000	0	-0.44	21	21
activation of caspase activity by cytochrome c	0.003	0.032	0.31	5	-10000	0	5
PAK2	0.003	0.021	-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	0.084	-9999	-0.51	13	13
EPHB2	-0.009	0.073	-9999	-0.57	8	8
Syndecan-2/TACI	-0.013	0.071	-9999	-0.41	15	15
LAMA1	-0.17	0.26	-9999	-0.57	143	143
Syndecan-2/alpha2 ITGB1	-0.012	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	0.033	0.035	-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	0.11	-9999	-0.74	12	12
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.021	0.12	-9999	-0.74	14	14
Syndecan-2/MMP2	-0.007	0.063	-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	-0.054	0.15	-9999	-0.48	55	55
determination of left/right symmetry	0.014	0.045	-9999	-0.56	3	3
Syndecan-2/PKC delta	-0.003	0.037	-9999	-0.48	3	3
GNB2L1	0	0	-9999	-10000	0	0
MAPK3	-0.024	0.14	-9999	-0.43	55	55
MAPK1	-0.024	0.14	-9999	-0.43	55	55
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	0.039	-9999	-0.47	3	3
Syndecan-2/alpha2/beta1 Integrin	-0.085	0.13	-9999	-0.5	3	3
Syndecan-2/Kininogen	-0.011	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	0.034	-9999	-0.44	3	3
extracellular matrix organization	-0.003	0.037	-9999	-0.47	3	3
actin cytoskeleton reorganization	-0.014	0.084	-9999	-0.51	13	13
Syndecan-2/Caveolin-2/Ras	-0.015	0.084	-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	0.057	-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	-0.37	3	3
RHOA	0	0	-9999	-10000	0	0
SDCBP	0	0	-9999	-10000	0	0
TNFRSF13B	-0.015	0.098	-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	0.037	-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	0.086	-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	0.037	-9999	-0.48	3	3
TRAPPC4	0	0	-9999	-10000	0	0
CSF2	-0.079	0.23	-9999	-0.74	52	52
Syndecan-2/TGFB1	-0.003	0.037	-9999	-0.48	3	3
Syndecan-2/Syntenin/PI-4-5-P2	-0.003	0.034	-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	-0.012	0.071	-9999	-0.41	15	15

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	53	53
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.019	0.083	-9999	-0.81	1	1
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.008	0.074	-9999	-0.74	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.014	0.098	-9999	-0.69	10	10
EGF/EGFR dimer/SHC	-0.022	0.099	-9999	-0.51	12	12
mol:GDP	-0.019	0.082	-9999	-0.8	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.063	0.21	-9999	-0.74	42	42
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.017	0.075	-9999	-0.74	1	1
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.017	0.077	-9999	-0.75	1	1
FRAP1	-0.018	0.079	-9999	-0.77	1	1
EGF/EGFR dimer	-0.026	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	-0.054	0.16	-9999	-0.56	47	47

×

S1P4 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.004	0.049	-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	-0.029	0.085	-9999	-0.46	3	3
S1PR5	-0.01	0.076	-9999	-0.59	8	8
S1PR4	-0.066	0.21	-9999	-0.74	44	44
MAPK3	0.002	0.1	-9999	-0.3	45	45
MAPK1	0.002	0.1	-9999	-0.48	3	3
S1P/S1P5/Gi	-0.008	0.04	-9999	-0.31	2	2
GNAI1	-0.002	0.033	-9999	-0.74	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.006	0.047	-9999	-0.37	8	8
RHOA	-0.037	0.12	-9999	-0.41	44	44
S1P/S1P4/Gi	-0.033	0.097	-9999	-0.32	45	45
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.009	0.081	-9999	-0.74	6	6
S1P/S1P4/G12/G13	-0.04	0.13	-9999	-0.44	44	44
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

Ras 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
ERK1-2/ELK1	-0.054	0.13	-9999	-0.56	6	6
MAP3K8	0.005	0.048	-9999	-0.74	2	2
FOS	0.002	0.1	-9999	-0.46	6	6
PRKCA	0.006	0.048	-9999	-0.74	2	2
PTPN7	0.008	0.043	-9999	-0.65	2	2
HRAS	0	0	-9999	-10000	0	0
PRKCB	-0.029	0.16	-9999	-0.74	25	25
NRAS	0	0	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.008	0.061	-9999	-0.45	1	1
MAP2K1	-0.002	0.13	-9999	-0.52	26	26
ELK1	-0.001	0.004	-9999	-10000	0	0
BRAF	-0.031	0.12	-9999	-0.52	26	26
mol:GTP	-0.001	0.002	-9999	-0.006	56	56
MAPK1	0.008	0.061	-9999	-0.45	1	1
RAF1	-0.031	0.12	-9999	-0.52	26	26
KRAS	0	0	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR 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
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	0.047	-9999	-0.74	2	2
PRKCB	-0.038	0.16	-9999	-0.74	25	25
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	0.016	0.096	-9999	-0.72	3	3
JUN	-0.005	0.16	-9999	-0.66	25	25
MAP3K7	0.016	0.096	-9999	-0.72	3	3
GRAP2	-0.039	0.17	-9999	-0.74	26	26
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.023	0.098	-9999	-0.76	3	3
LAT	0	0	-9999	-10000	0	0
LCP2	-0.011	0.088	-9999	-0.74	7	7
MAPK8	-0.013	0.16	-9999	-0.7	25	25
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.024	0.094	-9999	-0.76	3	3
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.03	0.12	-9999	-0.81	3	3

×

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	0.082	-9999	-0.48	15	15
AQP5	-0.17	0.25	-9999	-0.55	152	152
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	0.098	-9999	-0.69	10	10
NCKAP1	0	0	-9999	-10000	0	0
AQP3	-0.079	0.19	-9999	-0.55	71	71
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	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.017	0.076	-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	-0.025	0.13	-9999	-0.73	17	17
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	0.17	-9999	-0.39	136	136
HGF/MET	-0.079	0.15	-9999	-10000	0	0
HGF	-0.15	0.3	-9999	-0.74	102	102
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	0.018	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.013	0.067	-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	-0.28	2	2
AKT1	0.003	0.084	-10000	0	-0.28	10	10
IKBKG	0.017	0.053	-10000	0	-0.29	3	3
CALM1	-0.009	0.097	-10000	0	-0.49	12	12
PIK3CA	0	0	-10000	0	-10000	0	0
MAP3K1	0.001	0.14	-10000	0	-0.7	11	11
MAP3K7	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.1	0.23	4	-0.53	12	16
DOK1	0	0	-10000	0	-10000	0	0
AP-1	-0.001	0.08	0.18	3	-0.28	6	9
LYN	-0.003	0.047	-10000	0	-0.74	2	2
BLNK	-0.002	0.033	-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	-0.61	52	52
CAMK2G	-0.002	0.09	-10000	0	-0.64	5	5
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	-0.001	0.033	-10000	0	-0.74	1	1
SHC/GRB2/SOS1	-0.021	0.09	-10000	0	-0.74	3	3
GO:0007205	-0.018	0.1	0.23	4	-0.54	12	16
SYK	-0.002	0.033	-10000	0	-0.74	1	1
ELK1	-0.01	0.099	-10000	0	-0.5	12	12
NFATC1	-0.006	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	-0.008	0.066	-10000	0	-0.56	7	7
NFKBIB	0.014	0.019	0.078	2	-10000	0	2
HRAS	-0.002	0.093	-10000	0	-0.48	12	12
NFKBIA	0.014	0.019	0.078	2	-10000	0	2
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	-0.5	21	21
mol:GDP	-0.019	0.1	-10000	0	-0.52	12	12
PTEN	-0.002	0.033	-10000	0	-0.74	1	1
CD79B	-0.005	0.063	-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	-0.014	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	60	60
CHUK	0.017	0.053	-10000	0	-0.3	2	2
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	-0.77	26	26
RELA	0	0.001	-10000	0	-10000	0	0
BCL2A1	0.015	0.023	-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	46	46
CD19	-0.065	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	-0.011	0.088	-10000	0	-0.74	7	7
MAPK14	0.01	0.12	-10000	0	-0.59	10	10
SH3BP5	-0.011	0.088	-10000	0	-0.74	7	7
PIK3AP1	-0.012	0.13	0.26	4	-0.66	13	17
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.031	0.13	-10000	0	-0.6	18	18
RAF1	0.005	0.088	-10000	0	-0.61	5	5
RasGAP/p62DOK/SHIP	-0.028	0.11	-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	-0.29	6	9
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.019	0.074	-10000	0	-0.48	5	5
MAPK1	0.019	0.074	-10000	0	-0.48	5	5
CD72/SHP1	-0.065	0.18	-10000	0	-0.71	26	26
NFKB1	0	0.001	-10000	0	-10000	0	0
MAPK8	0.01	0.12	-10000	0	-0.59	10	10
actin cytoskeleton organization	-0.013	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	0.072	-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	-0.022	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	0.17	-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	0.081	-10000	0	-0.55	5	5
B-cell antigen/BCR complex/FcgammaRIIB	-0.034	0.14	-10000	0	-0.5	33	33
mol:PI-3-4-5-P3	-0.046	0.098	-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	-0.86	3	3
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	-0.74	26	26
CARD11	-0.012	0.11	-10000	0	-0.55	12	12
FCGR2B	-0.014	0.099	-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	32	32
PDPK1	-0.031	0.067	-10000	0	-0.28	10	10
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

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0.094	-9999	-0.61	11	11
Syndecan-4/Syndesmos	-0.014	0.062	-9999	-10000	0	0
positive regulation of JNK cascade	-0.045	0.12	-9999	-0.58	8	8
Syndecan-4/ADAM12	-0.087	0.13	-9999	-0.46	9	9
CCL5	-0.014	0.099	-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	-0.58	3	3
ADAM12	-0.16	0.26	-9999	-0.57	134	134
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	-0.091	0.13	-9999	-0.51	2	2
Syndecan-4/CXCL12/CXCR4	-0.047	0.12	-9999	-0.62	8	8
Syndecan-4/Laminin alpha3	-0.024	0.087	-9999	-0.6	2	2
MDK	-0.012	0.081	-9999	-0.57	10	10
Syndecan-4/FZD7	-0.015	0.063	-9999	-10000	0	0
Syndecan-4/Midkine	-0.02	0.074	-9999	-0.57	1	1
FZD7	-0.001	0.026	-9999	-0.57	1	1
Syndecan-4/FGFR1/FGF	-0.028	0.088	-9999	-0.55	5	5
THBS1	-0.011	0.088	-9999	-0.74	7	7
integrin-mediated signaling pathway	-0.023	0.066	-9999	-10000	0	0
positive regulation of MAPKKK cascade	-0.045	0.12	-9999	-0.58	8	8
Syndecan-4/TACI	-0.02	0.077	-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	-0.014	0.062	-9999	-10000	0	0
Syndecan-4/TSP1	-0.02	0.091	-9999	-0.65	6	6
Syndecan-4/GIPC	-0.014	0.062	-9999	-10000	0	0
Syndecan-4/RANTES	-0.021	0.084	-9999	-0.68	2	2
ITGB1	0	0	-9999	-10000	0	0
LAMA1	-0.17	0.26	-9999	-0.57	143	143
LAMA3	-0.018	0.11	-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	-0.014	0.062	-9999	-10000	0	0
TFPI	-0.062	0.2	-9999	-0.74	41	41
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	-0.045	0.13	-9999	-0.64	8	8
FGF6	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
CXCL12	-0.06	0.2	-9999	-0.74	40	40
TNFRSF13B	-0.015	0.098	-9999	-0.63	12	12
FGF2	-0.023	0.13	-9999	-0.74	15	15
FGFR1	-0.002	0.033	-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	0.085	-9999	-0.62	6	6
SDC4	0.008	0.073	-9999	-10000	0	0
Syndecan-4/Tenascin C	-0.019	0.07	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2/PKC alpha	-0.009	0.026	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.014	0.062	-9999	-10000	0	0
MMP9	-0.021	0.13	-9999	-0.57	26	26
Rac1/GTP	-0.007	0.06	-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	-0.046	0.13	-9999	-0.64	8	8

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.028	0.11	0.44	31	-10000	0	31
KIRREL	-0.003	0.091	-10000	0	-0.75	7	7
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.028	0.11	-10000	0	-0.44	31	31
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+	-0.022	0.083	-10000	0	-0.45	8	8
mol:DAG	-0.022	0.084	-10000	0	-0.46	8	8
NPHS2	-0.003	0.047	-10000	0	-0.58	3	3
mol:IP3	-0.022	0.084	-10000	0	-0.46	8	8
regulation of endocytosis	-0.019	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	-0.44	31	31
Nephrin/NEPH1/podocin/NCK1-2	-0.02	0.075	-10000	0	-0.42	8	8
Nephrin/NEPH1/beta Arrestin2	-0.019	0.075	-10000	0	-0.44	8	8
NPHS1	-0.022	0.12	-10000	0	-0.57	24	24
Nephrin/NEPH1/podocin	-0.02	0.081	-10000	0	-0.46	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	-0.022	0.14	-10000	0	-0.5	28	28
cytoskeleton organization	-0.016	0.064	-10000	0	-0.42	8	8
Nephrin/NEPH1	-0.02	0.079	-10000	0	-0.32	31	31
Nephrin/NEPH1/ZO-1	-0.022	0.087	-10000	0	-0.46	8	8

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.019	0.008	-9999	-10000	0	0
GNAO1	-0.004	0.049	-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	-0.01	0.076	-9999	-0.59	8	8
S1PR4	-0.066	0.21	-9999	-0.74	44	44
GNAI1	-0.002	0.033	-9999	-0.74	1	1
S1P/S1P5/G12	-0.005	0.041	-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	-0.31	45	45
GNAQ	-0.002	0.033	-9999	-0.74	1	1
GNAZ	-0.009	0.081	-9999	-0.74	6	6
GNA14	-0.18	0.32	-9999	-0.74	117	117
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

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.006	0.006	-9999	-10000	0	0
HDAC2	0.006	0.006	-9999	-10000	0	0
GNB1/GNG2	-0.007	0.057	-9999	-0.46	7	7
forebrain development	-0.087	0.14	-9999	-0.49	9	9
GNAO1	0.001	0.05	-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	0.034	-9999	-0.74	1	1
XPO1	0.006	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.11	0.11	-9999	-0.53	4	4
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	-0.28	1	1
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	0.074	-9999	-0.74	5	5
Gi family/GTP	0.002	0.05	-9999	-0.32	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	-0.6	0.6	-9999	-1.2	245	245
neural tube patterning	-0.087	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	0.033	-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	-0.087	0.14	-9999	-0.49	9	9
SUFU	0.012	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	-0.089	0.15	-9999	-0.5	9	9
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	0.082	-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	0.055	-9999	-0.51	3	3
PTCH1	-0.08	0.16	-9999	-1	6	6
MIM/GLI1	-0.23	0.29	-9999	-0.52	245	245
CREBBP	0.005	0.033	-9999	-0.38	1	1
Su(fu)/SIN3/HDAC complex	0.029	0.029	-9999	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.03	0.13	-9999	-0.56	26	26
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	-0.012	0.11	-9999	-0.48	26	26
S1P1/S1P	-0.032	0.091	-9999	-0.49	7	7
negative regulation of cAMP metabolic process	0	0.13	-9999	-0.57	7	7
MAPK3	-0.012	0.19	-9999	-0.55	50	50
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	-0.039	0.17	-9999	-0.74	26	26
PLCB2	0.003	0.11	-9999	-0.46	8	8
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.027	0.077	-9999	-0.41	7	7
receptor internalization	-0.03	0.086	-9999	-0.45	7	7
PTGS2	-0.061	0.34	-9999	-1.1	50	50
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	0.083	-9999	-0.74	6	6
MAPK1	-0.012	0.19	-9999	-0.55	50	50
S1P1/S1P/PDGFB-D/PDGFRB	0.006	0.11	-9999	-0.55	7	7
ABCC1	-0.001	0.026	-9999	-0.57	1	1

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	-0.01	0.12	-9999	-0.74	13	13
ELF1	-0.004	0.034	-9999	-0.37	3	3
CCNA2	-0.15	0.25	-9999	-0.57	126	126
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	0.084	-9999	-0.69	6	6
IL2RB	0.006	0.058	-9999	-0.74	3	3
SOS1	0.01	0.001	-9999	-10000	0	0
IL2RG	-0.002	0.095	-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	-0.95	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	0.059	0.064	-9999	-0.56	3	3

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.047	0.41	6	-10000	0	6
CDKN1A	0	0	-10000	0	-10000	0	0
KAT2B	-0.002	0.033	-10000	0	-0.74	1	1
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	0.019	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	72	72
PPARGC1A	-0.15	0.3	-10000	0	-0.74	99	99
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	0.036	-10000	0	-10000	0	0
apoptosis	0	0	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.098	0.2	-10000	0	-0.49	99	99
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	0.004	0.051	-10000	0	-10000	0	0
SIRT1/p300	0	0	-10000	0	-10000	0	0
muscle cell differentiation	0.051	0.12	0.48	1	-10000	0	1
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	0.026	-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	1	1

×

TRAIL signaling 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	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	-0.027	0.12	-10000	0	-0.56	24	24
MAP2K4	0.041	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	0.047	-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	-0.036	0.16	-10000	0	-0.74	24	24
TRAIL/TRAILR2	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR3	-0.073	0.19	-10000	0	-0.56	64	64
TRAIL/TRAILR1	-0.002	0.036	-10000	0	-0.56	2	2
TRAIL/TRAILR4	-0.027	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	0.009	-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)	-0.036	0.16	-10000	0	-0.74	24	24
TRADD	0	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.003	0.047	-10000	0	-0.74	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.001	0.02	-10000	0	-0.31	2	2
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	-0.4	2	2
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)	-0.097	0.25	-10000	0	-0.74	64	64
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.002	0.03	-10000	0	-0.48	2	2
DAP3	0	0	-10000	0	-10000	0	0
CASP10	0.013	0.066	0.29	23	-0.39	1	24
JNK cascade	-0.027	0.12	-10000	0	-0.56	24	24
TRAIL (trimer)	0	0	-10000	0	-10000	0	0
TNFRSF10C	-0.097	0.25	-10000	0	-0.74	64	64
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

×

IL27-mediated signaling events

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
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	0.068	0.36	1	-10000	0	1
IL27/IL27R/JAK1	-0.028	0.093	-10000	0	-0.52	6	6
TBX21	-0.029	0.22	-10000	0	-0.6	52	52
IL12B	0.009	0.004	-10000	0	-10000	0	0
IL12A	0.001	0.073	-10000	0	-0.57	8	8
IL6ST	-0.015	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	0.068	0.36	1	-10000	0	1
T cell proliferation during immune response	-0.003	0.068	0.36	1	-10000	0	1
MAPKKK cascade	0.003	0.068	-10000	0	-0.36	1	1
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	-0.038	0.18	-10000	0	-0.74	31	31
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.019	0.19	-10000	0	-0.63	12	12
IL27/IL27R/JAK2/TYK2	0.002	0.068	-10000	0	-0.36	1	1
positive regulation of T cell mediated cytotoxicity	0.003	0.068	-10000	0	-0.36	1	1
STAT1 (dimer)	-0.058	0.16	0.51	3	-0.67	13	16
JAK2	0.006	0.006	-10000	0	-10000	0	0
JAK1	0.001	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.011	0.057	-10000	0	-10000	0	0
T cell proliferation	-0.051	0.18	-10000	0	-0.42	74	74
IL12/IL12R/TYK2/JAK2	0.008	0.092	-10000	0	-0.59	2	2
IL17A	-0.062	0.14	-10000	0	-0.69	3	3
mast cell activation	-0.003	0.068	0.36	1	-10000	0	1
IFNG	0.006	0.019	-10000	0	-0.13	4	4
T cell differentiation	-0.003	0.005	-10000	0	-0.021	5	5
STAT3 (dimer)	-0.011	0.057	-10000	0	-10000	0	0
STAT5A (dimer)	-0.011	0.057	-10000	0	-10000	0	0
STAT4 (dimer)	-0.018	0.079	-10000	0	-0.46	7	7
STAT4	-0.012	0.094	-10000	0	-0.74	8	8
T cell activation	-0.007	0.003	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.018	0.076	-10000	0	-0.47	4	4
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	-0.011	0.056	-10000	0	-10000	0	0
IL27/EBI3	-0.002	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	83	83
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	-0.002	0.082	-10000	0	-0.57	10	10
EBI3	0.001	0.055	-10000	0	-0.69	3	3
TNF	-0.005	0.091	-10000	0	-0.56	13	13

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.003	0.047	-10000	0	-0.74	2	2
ANTXR2	-0.011	0.088	-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	0.081	-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	-0.53	7	7
MAP2K4	-0.001	0.011	-10000	0	-10000	0	0
IL1B	0.004	0.071	-10000	0	-0.45	11	11
Channel	-0.008	0.071	-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	101	101
PA/Cellular Receptors	-0.009	0.076	-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	-0.019	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	0.045	-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	0.031	-10000	0	-0.28	4	4
mol:cAMP	-0.002	0.015	-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 S80. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.033	-10000	0	-0.74	1	1
Jak2/Leptin Receptor	-0.027	0.099	-10000	0	-0.38	29	29
PTP1B/AKT1	-0.006	0.024	-10000	0	-10000	0	0
FYN	-0.002	0.033	-10000	0	-0.74	1	1
p210 bcr-abl/PTP1B	0.024	0.037	-10000	0	-0.31	1	1
EGFR	-0.012	0.12	-10000	0	-0.63	17	17
EGF/EGFR	-0.02	0.084	-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	0.078	-10000	0	-0.42	8	8
Insulin Receptor/Insulin	-0.004	0.018	-10000	0	-10000	0	0
HCK	-0.008	0.074	-10000	0	-0.74	5	5
CRK	0	0	-10000	0	-10000	0	0
TYK2	0.03	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	-0.54	8	8
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	-0.04	0.15	-10000	0	-0.63	31	31
ITGA2B	-0.023	0.13	-10000	0	-0.74	15	15
CSF1R	-0.014	0.099	-10000	0	-0.74	9	9
Prolactin Receptor/Prolactin	-0.036	0.13	-10000	0	-0.46	38	38
FGR	-0.05	0.18	-10000	0	-0.74	33	33
PTP1B/p130 Cas	-0.006	0.025	-10000	0	-10000	0	0
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	0.047	-10000	0	-0.74	2	2
CDH2	-0.036	0.14	-10000	0	-0.58	30	30
SRC	0.023	0.016	-10000	0	-10000	0	0
ITGB3	-0.012	0.094	-10000	0	-0.74	8	8
CAT1/PTP1B	0.017	0.12	-10000	0	-0.59	10	10
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	-0.026	0.12	-10000	0	-0.56	23	23
BLK	-0.035	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	-0.041	0.18	-10000	0	-0.74	29	29
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	-0.009	0.073	-10000	0	-0.57	8	8
SOCS3	0.002	0.092	-10000	0	-1.4	2	2
SPRY2	-0.004	0.058	-10000	0	-0.74	3	3
Insulin Receptor/Insulin/IRS1	0	0	-10000	0	-10000	0	0
CSF1/CSF1R	-0.015	0.075	-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	86	86
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	-0.47	1	1
CSN2	-0.012	0.04	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
LAT	0.012	0.077	-10000	0	-0.48	11	11
YBX1	0.001	0.004	-10000	0	-10000	0	0
LCK	-0.002	0.033	-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 S81. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-9999	-10000	0	0
HDAC3	0	0	-9999	-10000	0	0
VDR	-0.002	0.033	-9999	-0.74	1	1
Cbp/p300/PCAF	-0.001	0.022	-9999	-0.48	1	1
EP300	0	0	-9999	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.034	0.026	-9999	-0.31	1	1
KAT2B	-0.002	0.033	-9999	-0.74	1	1
MAPK14	0	0	-9999	-10000	0	0
AKT1	0.02	0.033	-9999	-0.31	2	2
RAR alpha/9cRA/Cyclin H	-0.007	0.029	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.032	0.031	-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	0.033	-9999	-0.74	1	1
VDR/VDR/Vit D3	-0.001	0.026	-9999	-0.56	1	1
RXRs/RARs/NRIP1/9cRA	-0.024	0.081	-9999	-0.6	2	2
NCOA2	-0.002	0.033	-9999	-0.74	1	1
NCOA3	0	0	-9999	-10000	0	0
NCOA1	0	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.002	0.033	-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	0.001	-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	-0.66	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	0.033	-9999	-0.41	1	1
PRKCA	0.01	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	259	259
RXRA	0.021	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	-0.56	1	1
RBP1	-0.02	0.1	-9999	-0.57	17	17
CRBP1/9-cic-RA	-0.015	0.077	-9999	-0.42	17	17
RARB	0.009	0.048	-9999	-0.74	2	2
PRKCG	-0.031	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	0.034	0.036	-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	0.027	-9999	-10000	0	0
NRIP1	-0.037	0.084	-9999	-0.69	1	1
RXRs/RARs	-0.048	0.091	-9999	-0.63	2	2
RXRs/RXRs/DNA/9cRA	-0.07	0.075	-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	0.017	-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

×

S1P3 pathway

Figure S82. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S82. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.033	-9999	-0.74	1	1
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	-0.006	0.039	-9999	-0.3	8	8
GNAO1	0.007	0.05	-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	0.033	-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	-0.3	1	1
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	0.04	-9999	-0.3	1	1
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.03	-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	-0.076	0.14	-9999	-0.32	117	117
GNAQ	-0.002	0.033	-9999	-0.74	1	1
GNAZ	0.002	0.082	-9999	-0.74	6	6
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.18	0.32	-9999	-0.74	117	117
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	0.03	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.061	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	108	108
CDK2/Cyclin E1	-0.091	0.17	-9999	-0.41	108	108
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	0.009	0.1	-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	-0.042	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	-0.078	0.2	-9999	-0.57	67	67
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

×

IL1-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
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	0.034	-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	-0.058	0.16	-10000	0	-0.47	61	61
IL1A	-0.052	0.18	-10000	0	-0.65	39	39
IL1B	0.005	0.089	-10000	0	-0.56	12	12
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	0.033	-10000	0	-0.74	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.001	0.041	0.22	9	-0.3	1	10
TOLLIP	0	0	-10000	0	-10000	0	0
TICAM2	-0.009	0.081	-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	-0.01	0.061	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.03	0.11	-10000	0	-0.45	19	19
PIK3R1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.028	0.099	-10000	0	-0.42	19	19
IL1 beta fragment/IL1R1/IL1RAP	-0.011	0.069	-10000	0	-0.43	13	13
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	-0.006	0.039	-10000	0	-10000	0	0
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.011	0.069	-10000	0	-0.43	13	13
IL1 beta/IL1R2	-0.029	0.11	-10000	0	-0.5	12	12
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.009	0.055	-10000	0	-10000	0	0
IRAK3	-0.02	0.12	-10000	0	-0.74	13	13
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.015	0.078	-10000	0	-0.78	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.018	0.069	-10000	0	-0.32	19	19
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	-0.012	0.064	-10000	0	-0.64	1	1
CASP1	-0.003	0.047	-10000	0	-0.74	2	2
IL1RN/IL1R2	-0.026	0.1	-10000	0	-0.43	29	29
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.011	0.065	-10000	0	-10000	0	0
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.013	0.053	-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

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.002	0.033	-10000	0	-0.74	1	1
EPHB2	-0.009	0.072	-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	0.092	-10000	0	-0.53	1	1
Ephrin B2/EPHB1-2	-0.044	0.11	-10000	0	-0.32	68	68
neuron projection morphogenesis	-0.036	0.088	-10000	0	-0.51	1	1
Ephrin B1/EPHB1-2/Tiam1	-0.041	0.1	-10000	0	-0.49	2	2
DNM1	-0.002	0.036	-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	0.087	-10000	0	-0.96	4	4
Ephrin B1/EPHB1-2/NCK2	-0.04	0.099	-10000	0	-0.57	1	1
PI3K	-0.006	0.067	-10000	0	-0.74	4	4
mol:GDP	-0.04	0.1	-10000	0	-0.48	2	2
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	0.087	-10000	0	-0.96	4	4
MAP3K7	-0.007	0.071	-10000	0	-0.78	4	4
FGR	-0.019	0.099	-10000	0	-0.98	4	4
TIAM1	-0.002	0.033	-10000	0	-0.74	1	1
PIK3R1	0	0	-10000	0	-10000	0	0
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.023	0.1	-10000	0	-0.67	4	4
LYN	-0.008	0.088	-10000	0	-0.96	4	4
Ephrin B1/EPHB1-2/Src Family Kinases	-0.007	0.082	-10000	0	-0.9	4	4
Ephrin B1/EPHB1-2	-0.009	0.076	-10000	0	-0.84	4	4
SRC	-0.008	0.086	-10000	0	-0.95	4	4
ITGB3	-0.012	0.094	-10000	0	-0.74	8	8
EPHB1	-0.07	0.19	-10000	0	-0.57	60	60
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	-0.026	0.12	-10000	0	-0.56	23	23
BLK	-0.014	0.095	-10000	0	-1	4	4
HCK	-0.009	0.088	-10000	0	-0.95	4	4
regulation of stress fiber formation	0.04	0.098	0.57	1	-10000	0	1
MAPK8	0.021	0.065	-10000	0	-0.69	4	4
Ephrin B1/EPHB1-2/RGS3	-0.04	0.099	-10000	0	-0.57	1	1
endothelial cell migration	-0.005	0.064	-10000	0	-0.62	5	5
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.003	0.078	-10000	0	-0.85	4	4
regulation of focal adhesion formation	0.04	0.098	0.57	1	-10000	0	1
chemotaxis	0.04	0.098	0.57	1	-10000	0	1
PIK3CA	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.037	0.09	-10000	0	-0.52	1	1
angiogenesis	-0.009	0.075	-10000	0	-0.83	4	4
LCK	-0.008	0.09	-10000	0	-0.98	4	4

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.049	0.058	-10000	0	-0.82	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	-0.01	0.12	-10000	0	-0.74	13	13
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	0.071	0.059	-10000	0	-0.6	1	1
MYB	0.015	0.1	-10000	0	-1.3	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.058	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	0.064	0.07	-10000	0	-0.63	3	3
NF kappa B1 p50/RelA	-0.007	0.042	-10000	0	-0.47	3	3
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.043	0.063	-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	0.074	-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	192	192
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	0.095	-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	0.029	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	-0.53	1	1

×

Regulation of p38-alpha and p38-beta

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
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	0.033	-9999	-0.74	1	1
MAP3K12	0	0	-9999	-10000	0	0
FGR	-0.05	0.18	-9999	-0.74	33	33
p38 alpha/TAB1	-0.012	0.044	-9999	-0.33	2	2
PRKG1	-0.06	0.2	-9999	-0.74	40	40
DUSP8	-0.014	0.099	-9999	-0.74	9	9
PGK/cGMP/p38 alpha	-0.039	0.11	-9999	-0.38	40	40
apoptosis	-0.012	0.042	-9999	-0.32	2	2
RAL/GTP	0	0	-9999	-10000	0	0
LYN	-0.003	0.047	-9999	-0.74	2	2
DUSP1	-0.095	0.25	-9999	-0.74	63	63
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	0.079	-9999	-0.35	11	11
BLK	-0.035	0.15	-9999	-0.66	26	26
HCK	-0.008	0.074	-9999	-0.74	5	5
MAP2K3	0	0	-9999	-10000	0	0
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.002	0.033	-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	0.087	-9999	-0.39	7	7
LCK	-0.002	0.033	-9999	-0.74	1	1
p38alpha-beta/MKP7	-0.019	0.065	-9999	-0.44	2	2
p38alpha-beta/MKP5	-0.019	0.069	-9999	-0.48	3	3
PGK/cGMP	-0.046	0.16	-9999	-0.56	40	40
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.058	0.13	-9999	-0.52	14	14
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.007	0.071	-9999	-0.71	5	5

×

LPA receptor mediated events

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
GNB1/GNG2	-0.009	0.081	-9999	-0.66	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	-0.51	8	8
mol:PIP3	-0.02	0.077	-9999	-0.58	3	3
AKT1	-0.006	0.051	-9999	-0.57	3	3
PTK2B	0.017	0.038	-9999	-0.34	2	2
RHOA	0.027	0.02	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	0	0.081	-9999	-0.45	3	3
MAGI3	-0.002	0.033	-9999	-0.74	1	1
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.011	0.058	-9999	-0.37	8	8
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.024	0.06	-9999	-0.39	8	8
NF kappa B1 p50/RelA	-0.023	0.066	-9999	-0.64	1	1
endothelial cell migration	0.016	0.088	-9999	-0.82	5	5
ADCY4	0.017	0.097	-9999	-0.62	6	6
ADCY5	0.012	0.095	-9999	-0.66	4	4
ADCY6	0.031	0.07	-9999	-0.59	4	4
ADCY7	0.032	0.068	-9999	-0.66	3	3
ADCY1	0.031	0.069	-9999	-0.66	3	3
ADCY2	0.018	0.082	-9999	-0.6	4	4
ADCY3	0.032	0.068	-9999	-0.66	3	3
ADCY8	-0.037	0.12	-9999	-0.65	5	5
ADCY9	0.031	0.073	-9999	-0.65	4	4
GSK3B	0.023	0.036	-9999	-0.38	1	1
arachidonic acid secretion	0.034	0.07	-9999	-0.58	4	4
GNG2	-0.008	0.074	-9999	-0.74	5	5
TRIP6	0	0.004	-9999	-10000	0	0
GNAO1	0.017	0.063	-9999	-0.47	7	7
HRAS	0	0	-9999	-10000	0	0
NFKBIA	0.017	0.074	-9999	-0.38	1	1
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.003	0.059	-9999	-0.92	2	2
JUN	0	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.004	0.038	-9999	-0.48	3	3
TIAM1	-0.004	0.07	-9999	-1.1	2	2
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	0	0.082	-9999	-0.46	3	3
PLCB3	0.021	0.037	-9999	-0.43	3	3
FOS	-0.085	0.24	-9999	-0.74	56	56
positive regulation of mitosis	0.034	0.07	-9999	-0.58	4	4
LPA/LPA1-2-3	-0.014	0.072	-9999	-0.48	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	0.025	0.048	-9999	-0.42	2	2
GNAZ	0.014	0.074	-9999	-0.46	11	11
EGFR/PI3K-beta/Gab1	-0.02	0.081	-9999	-0.61	3	3
positive regulation of dendritic cell cytokine production	-0.014	0.071	-9999	-0.48	6	6
LPA/LPA2/MAGI-3	-0.002	0.023	-9999	-0.48	1	1
ARHGEF1	-0.003	0.041	-9999	-0.54	2	2
GNAI2	0.02	0.05	-9999	-0.43	5	5
GNAI3	0.02	0.05	-9999	-0.47	4	4
GNAI1	0.019	0.065	-9999	-0.51	5	5
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	0.055	-9999	-0.5	5	5
HB-EGF/EGFR	-0.048	0.14	-9999	-0.52	23	23
HBEGF	-0.023	0.14	-9999	-0.48	42	42
mol:DAG	0	0.082	-9999	-0.46	3	3
cAMP biosynthetic process	0.02	0.076	-9999	-0.66	4	4
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
GNB1	-0.002	0.033	-9999	-0.74	1	1
LYN	0.015	0.085	-9999	-0.55	3	3
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	0.055	-9999	-0.83	2	2
IL8	0.001	0.13	-9999	-0.48	12	12
PTK2	-0.012	0.066	-9999	-0.45	6	6
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.011	0.058	-9999	-0.37	8	8
EGFR	-0.022	0.12	-9999	-0.63	17	17
PLCG1	-0.016	0.084	-9999	-0.36	10	10
PLD2	-0.012	0.066	-9999	-0.45	6	6
G12/G13	-0.004	0.044	-9999	-0.58	2	2
PI3K-beta	-0.007	0.062	-9999	-0.69	3	3
cell migration	0.002	0.032	-9999	-0.26	2	2
SLC9A3R2	-0.005	0.058	-9999	-0.74	3	3
PXN	0.025	0.049	-9999	-0.43	2	2
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	26	26
PRKCE	0.008	0.034	-9999	-0.74	1	1
PRKCD	0.007	0.079	-9999	-0.47	2	2
Gi(beta/gamma)	-0.01	0.079	-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	-0.58	4	4
contractile ring contraction involved in cytokinesis	0.027	0.02	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.1	0.17	-9999	-0.4	121	121
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	0.024	0.062	-9999	-0.41	8	8
GNA11	-0.008	0.047	-9999	-0.38	4	4
Rac1/GTP	-0.004	0.063	-9999	-0.98	2	2
MMP2	0.016	0.089	-9999	-0.83	5	5

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0	0	-9999	-10000	0	0
PTK2	0	0	-9999	-10000	0	0
CRKL	0.009	0.073	-9999	-0.38	16	16
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
IRS1/Crk	-0.013	0.069	-9999	-0.39	16	16
IGF-1R heterotetramer/IGF1/PTP1B	-0.015	0.081	-9999	-0.45	16	16
AKT1	0.029	0.064	-9999	-10000	0	0
BAD	0.035	0.061	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.009	0.073	-9999	-0.38	16	16
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.013	0.07	-9999	-0.39	16	16
RAF1	0.038	0.059	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.012	0.065	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.014	0.076	-9999	-0.42	16	16
PIK3CA	0	0	-9999	-10000	0	0
RPS6KB1	0.029	0.064	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.033	0.052	-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	-0.011	0.057	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.012	0.064	-9999	-10000	0	0
IGF-1R heterotetramer	0.007	0.017	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.013	0.07	-9999	-0.39	16	16
Crk/p130 Cas/Paxillin	-0.012	0.061	-9999	-10000	0	0
IGF1R	0.007	0.017	-9999	-10000	0	0
IGF1	-0.016	0.14	-9999	-0.74	17	17
IRS2/Crk	-0.015	0.071	-9999	-0.4	3	3
PI3K	-0.012	0.065	-9999	-0.36	16	16
apoptosis	0.009	0.046	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
PRKCD	0.02	0.088	-9999	-0.46	16	16
RAF1/14-3-3 E	0.04	0.052	-9999	-10000	0	0
BAD/14-3-3	0.039	0.057	-9999	-10000	0	0
PRKCZ	0.029	0.064	-9999	-10000	0	0
Crk/p130 Cas/Paxillin/FAK1	-0.009	0.047	-9999	-10000	0	0
PTPN1	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.016	0.087	-9999	-0.49	16	16
BCAR1	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.013	0.07	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
IRS1/NCK2	-0.013	0.069	-9999	-0.38	16	16
GRB10	0	0	-9999	-10000	0	0
PTPN11	0.009	0.073	-9999	-0.38	16	16
IRS1	0.002	0.079	-9999	-0.42	16	16
IRS2	0.007	0.081	-9999	-0.39	19	19
IGF-1R heterotetramer/IGF1	-0.02	0.1	-9999	-0.56	17	17
GRB2	0	0	-9999	-10000	0	0
PDPK1	-0.011	0.061	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKD1	0.007	0.12	-9999	-0.49	27	27
SHC1	0	0	-9999	-10000	0	0

×

Insulin Pathway

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
CBL/APS/CAP	-0.046	0.12	-9999	-10000	0	0
TC10/GTP	-0.045	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	-0.73	31	31
FOXO3	-0.004	0.014	-9999	-10000	0	0
AKT1	-0.021	0.081	-9999	-10000	0	0
INSR	0.011	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	-0.091	0.24	-9999	-0.74	60	60
CRK	0	0	-9999	-10000	0	0
PTPN1	0.031	0	-9999	-10000	0	0
CAV1	-0.1	0.2	-9999	-0.42	137	137
CBL/APS/CAP/Crk-II/C3G	-0.049	0.13	-9999	-0.4	60	60
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	0.029	0.086	-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	-0.018	0.071	-9999	-10000	0	0
HRAS/GTP	-0.001	0.015	-9999	-10000	0	0
Insulin Receptor	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0	0	-9999	-10000	0	0
PRKCI	-0.006	0.021	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.023	0.087	-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	0.081	-9999	-10000	0	0
PRKCZ	-0.006	0.021	-9999	-10000	0	0
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	-0.001	0.018	-9999	-0.39	1	1
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	-0.053	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	0.023	0.02	-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	0.022	0.02	-9999	-0.42	1	1
GRB2	0	0	-9999	-10000	0	0
EIF4EBP1	0.014	0.1	-9999	-10000	0	0
PTPRA	0.011	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

×

Signaling events mediated by PRL

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.13	0.24	-9999	-0.57	108	108
mol:Halofuginone	0	0	-9999	-10000	0	0
ITGA1	-0.008	0.074	-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	-0.039	0.16	-9999	-0.73	26	26
CCNA2	-0.052	0.15	-9999	-0.68	3	3
TUBA1B	0	0	-9999	-10000	0	0
EGR1	0.01	0.077	-9999	-0.55	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	0.025	0.061	-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	0.052	-9999	-10000	0	0
PRL-3/alpha1 Integrin	-0.006	0.056	-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	0.025	0.061	-9999	-10000	0	0
ATF5	-0.008	0.068	-9999	-0.57	7	7

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.045	-9999	-10000	0	0
NFATC4	0.032	0.055	-9999	-10000	0	0
ERBB2IP	0.002	0.004	-9999	-10000	0	0
HSP90 (dimer)	0	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.011	0.06	-9999	-0.36	4	4
JUN	0.044	0.058	-9999	-0.49	1	1
HRAS	0	0	-9999	-10000	0	0
DOCK7	0.028	0.066	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.013	0.071	-9999	-0.42	14	14
AKT1	0.01	0.002	-9999	-10000	0	0
BAD	0.018	0.001	-9999	-10000	0	0
MAPK10	-0.009	0.046	-9999	-0.35	3	3
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.012	0.065	-9999	-0.39	3	3
RAF1	0.047	0.058	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.048	0.14	-9999	-0.44	53	53
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	0.038	0.15	-9999	-0.56	8	8
FOS	0.009	0.2	-9999	-0.5	61	61
NRAS	0	0	-9999	-10000	0	0
mol:Ca2+	-0.011	0.06	-9999	-0.36	4	4
MAPK3	0.045	0.11	-9999	-0.47	5	5
MAPK1	0.045	0.11	-9999	-0.47	5	5
JAK2	0.028	0.066	-9999	-10000	0	0
NF2	-0.001	0.018	-9999	-0.4	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.01	0.056	-9999	-0.33	14	14
NRG1	-0.012	0.12	-9999	-0.74	14	14
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	0.031	0.061	-9999	-0.31	5	5
MAPK9	-0.005	0.029	-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	0.001	-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	0.005	-9999	-10000	0	0
FRAP1	0.009	0.002	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.007	0.041	-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	0.036	0.053	-9999	-10000	0	0
PPP3CB	0.026	0.062	-9999	-10000	0	0
KRAS	0	0	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.008	0.047	-9999	-10000	0	0
NRG2	-0.077	0.23	-9999	-0.74	51	51
mol:GDP	0.014	0.06	-9999	-0.33	14	14
SOS1	0	0	-9999	-10000	0	0
MAP2K2	0.054	0.059	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	-0.01	0.057	-9999	-10000	0	0
MAP2K1	0.036	0.11	-9999	-0.48	5	5
heart morphogenesis	-0.011	0.06	-9999	-0.36	4	4
RAS family/GDP	-0.008	0.045	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PRKACA	-0.001	0.005	-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	-0.011	0.06	-9999	-0.36	4	4
CDC42	0	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
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	-0.049	0.16	-9999	-0.56	43	43
GATA1/HDAC5	-0.049	0.16	-9999	-0.56	43	43
GATA2/HDAC5	-0.059	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	-0.079	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	0.061	-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	-0.065	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	0.033	-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	0.037	-9999	-0.48	3	3
HDAC4/ER alpha	-0.025	0.12	-9999	-0.56	22	22
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	-0.033	0.15	-9999	-0.74	22	22
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	-0.015	0.1	-9999	-0.74	10	10
RAN	0	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.009	0.06	-9999	-0.4	11	11
GNG2	-0.008	0.074	-9999	-0.74	5	5
NCOR2	-0.002	0.033	-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

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
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	19	19
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	-0.035	0.1	-10000	0	-0.48	19	19
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	-0.038	0.1	-10000	0	-0.51	17	17
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	17	-10000	0	17
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	-0.58	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	-0.054	0.12	-10000	0	-0.45	13	13
CABIN1	-0.013	0.12	-10000	0	-0.52	19	19
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+	-0.001	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	-0.038	0.16	-10000	0	-0.74	25	25
PRKCE	-0.002	0.033	-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	0.047	-10000	0	-0.74	2	2
PRKCG	-0.041	0.15	-10000	0	-0.57	35	35
PRKCQ	-0.07	0.22	-10000	0	-0.74	46	46
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	0.024	-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	0.038	-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	19	19
NR4A1	-0.052	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	0.044	-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	0.047	-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	0.024	-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 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
NF kappa B/RelA	-0.011	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	-10000	0	0
SUMO1	0	0	-9999	-10000	0	0
ZFPM1	-0.002	0.033	-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	0.013	-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	0.046	-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	-0.079	0.23	-9999	-0.74	52	52
GATA1	-0.065	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	-0.002	0.033	-9999	-0.74	1	1
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	0.033	-9999	-10000	0	0
YY1/HDAC2	-0.001	0.013	-9999	-10000	0	0
YY1/HDAC1	-0.001	0.013	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0	0	-9999	-10000	0	0
PPARG	-0.052	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	0.021	-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	0.025	0.016	-9999	-0.34	1	1
HDAC8	0	0	-9999	-10000	0	0
SMAD7	-0.002	0.033	-9999	-0.74	1	1
NCOR2	-0.002	0.033	-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	0.011	-9999	-10000	0	0
YY1/SAP30/HDAC1	-0.001	0.011	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.022	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	-0.052	0.14	-9999	-0.44	52	52
GATA1/HDAC1	-0.049	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	0.088	-9999	-0.55	13	13
SIN3/HDAC complex/Mad/Max	0	0	-9999	-10000	0	0
NuRD Complex	0	0.009	-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	-0.05	0.16	-9999	-0.56	44	44
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.019	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	0.033	-9999	-0.74	1	1
MBD2	0	0	-9999	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.066	-10000	0	-0.35	18	18
Ephrin B1/EPHB1	-0.043	0.12	-10000	0	-0.35	60	60
HRAS/GDP	-0.031	0.08	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	-0.039	0.097	-10000	0	-0.4	1	1
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	-0.4	1	1
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	-0.01	0.054	-10000	0	-10000	0	0
HRAS	0	0	-10000	0	-10000	0	0
RRAS	-0.006	0.041	-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	-0.38	1	1
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	-0.3	1	1
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	60	60
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	-0.039	0.098	-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	0.033	-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	-0.32	68	68
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	0.018	-10000	0	-0.41	1	1
EFNA5	-0.003	0.047	-10000	0	-0.74	2	2
Ephrin B2/EPHB4	-0.001	0.022	-10000	0	-0.48	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	-0.003	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	-0.46	1	1
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	-0.006	0.067	-10000	0	-0.74	4	4
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.025	0.06	-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	-0.043	0.11	-10000	0	-0.62	1	1
cell migration	0.027	0.056	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
SYNJ1	-0.006	0.041	-10000	0	-0.38	1	1
PXN	0	0	-10000	0	-10000	0	0
TF	0.01	0.092	-10000	0	-10000	0	0
HRAS/GTP	-0.035	0.085	-10000	0	-0.5	1	1
Ephrin B1/EPHB1-2	-0.044	0.11	-10000	0	-0.32	67	67
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	-0.45	2	2
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	0.048	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	-0.01	0.056	-10000	0	-0.4	5	5
ROCK1	0.01	0.063	-10000	0	-10000	0	0
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	0.049	-10000	0	-0.31	1	1

×

Arf6 trafficking 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	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	0.047	-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	-0.04	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	-0.087	0.19	-10000	0	-0.38	141	141
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	115	115
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

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0	0	-9999	-10000	0	0
ITGB7	-0.002	0.033	-9999	-0.74	1	1
ITGA4	-0.008	0.074	-9999	-0.74	5	5
alpha4/beta7 Integrin	-0.007	0.061	-9999	-0.56	6	6
alpha4/beta1 Integrin	-0.006	0.056	-9999	-0.56	5	5

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	3	3
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	0.033	-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	0.038	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.004	0.039	-9999	-10000	0	0
AKT1	-0.004	0.034	-9999	-10000	0	0
MAP2K1	0.042	0.045	-9999	-10000	0	0
MAP3K11	0.033	0.045	-9999	-10000	0	0
IFNGR1	0.009	0.034	-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	0.043	-9999	-10000	0	0
CEBPB	0.041	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	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
IFN-gamma (dimer)	0.002	0.076	-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	0.066	-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	-10000	0	0
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	34	34
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	0.002	0.077	-9999	-0.68	6	6
apoptosis	0.018	0.13	-9999	-0.44	34	34
CAMK2G	0	0	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
CAMK2A	-0.056	0.2	-9999	-0.74	37	37
CAMK2B	-0.068	0.18	-9999	-0.57	58	58
FRAP1	0.044	0.038	-9999	-10000	0	0
PRKCD	-0.004	0.034	-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	0.037	-9999	-10000	0	0
SOCS1	-0.003	0.066	-9999	-1.5	1	1
mol:GDP	-0.004	0.033	-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	0.032	0.045	-9999	-10000	0	0
MAP3K1	0.034	0.045	-9999	-10000	0	0
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	0.025	0.046	-9999	-0.4	2	2
CREBBP	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.007	0.071	-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	0.033	-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	-0.066	0.21	-10000	0	-0.74	44	44
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	-0.002	0.033	-10000	0	-0.74	1	1

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.028	0.28	1	-10000	0	1
DAPP1	0.009	0.12	-10000	0	-0.56	14	14
Src family/SYK family/BLNK-LAT/BTK-ITK	0.005	0.17	-10000	0	-0.72	17	17
mol:DAG	0.026	0.087	-10000	0	-0.28	18	18
HRAS	0.01	0.002	-10000	0	-10000	0	0
RAP1A	0	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.026	0.056	-10000	0	-0.32	7	7
PLCG2	0	0	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.03	0.25	1	-10000	0	1
ARF1/GTP	-0.002	0.029	0.26	1	-10000	0	1
RHOA	0	0	-10000	0	-10000	0	0
YES1	0	0	-10000	0	-10000	0	0
RAP1A/GTP	-0.002	0.029	-10000	0	-10000	0	0
ADAP1	-0.008	0.058	-10000	0	-10000	0	0
ARAP3	-0.002	0.03	0.25	1	-10000	0	1
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	-0.011	0.088	-10000	0	-0.74	7	7
ARHGEF6	-0.027	0.14	-10000	0	-0.74	18	18
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	0.01	0.002	-10000	0	-10000	0	0
FYN	-0.002	0.033	-10000	0	-0.74	1	1
ARF6	0	0	-10000	0	-10000	0	0
FGR	-0.05	0.18	-10000	0	-0.74	33	33
mol:Ca2+	0.023	0.047	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.002	0.033	-10000	0	-0.74	1	1
ZAP70	-0.012	0.094	-10000	0	-0.74	8	8
mol:IP3	0.026	0.064	-10000	0	-10000	0	0
LYN	-0.003	0.047	-10000	0	-0.74	2	2
ARF1/GDP	0.026	0.056	-10000	0	-0.32	7	7
RhoA/GDP	-0.006	0.035	0.26	1	-10000	0	1
PDK1/Src/Hsp90	0	0	-10000	0	-10000	0	0
BLNK	-0.002	0.033	-10000	0	-0.74	1	1
actin cytoskeleton reorganization	0.045	0.066	-10000	0	-0.49	3	3
SRC	0	0	-10000	0	-10000	0	0
PLEKHA2	0.026	0.023	-10000	0	-0.48	1	1
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.001	0.033	-10000	0	-0.72	1	1
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.001	0.028	0.28	1	-10000	0	1
RhoA/GTP	-0.002	0.028	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.032	0.11	-10000	0	-0.52	16	16
BLK	-0.035	0.15	-10000	0	-0.66	26	26
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	-0.002	0.028	-10000	0	-10000	0	0
HCK	-0.008	0.074	-10000	0	-0.74	5	5
CYTH3	-0.002	0.028	-10000	0	-10000	0	0
CYTH2	-0.002	0.028	0.25	1	-10000	0	1
KRAS	0.01	0.002	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.001	0.016	-10000	0	-10000	0	0
SGK1	-0.001	0.017	0.22	1	-10000	0	1
INPP5D	-0.002	0.033	-10000	0	-0.74	1	1
mol:GDP	0.022	0.058	-10000	0	-0.34	7	7
SOS1	0	0	-10000	0	-10000	0	0
SYK	-0.002	0.033	-10000	0	-0.74	1	1
ARF6/GDP	-0.006	0.036	0.27	1	-10000	0	1
mol:PI-3-4-5-P3	-0.001	0.032	0.34	1	-10000	0	1
ARAP3/RAP1A/GTP	-0.002	0.03	-10000	0	-10000	0	0
VAV1	-0.008	0.074	-10000	0	-0.74	5	5
mol:PI-3-4-P2	0.018	0.026	-10000	0	-0.56	1	1
RAS family/GTP/PI3K Class I	-0.002	0.028	-10000	0	-10000	0	0
PLEKHA1	0.026	0.023	-10000	0	-0.48	1	1
Rac1/GDP	0.026	0.056	-10000	0	-0.32	7	7
LAT	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.019	0.1	-10000	0	-0.45	20	20
ITK	-0.03	0.1	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.024	0.12	-10000	0	-0.4	22	22
LCK	-0.002	0.033	-10000	0	-0.74	1	1
BTK	-0.037	0.11	-10000	0	-10000	0	0

×

Regulation of Telomerase

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
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	56	56
IFNAR2	0.007	0.006	-9999	-10000	0	0
AKT1	-0.004	0.063	-9999	-0.3	10	10
ER alpha/Oestrogen	-0.026	0.12	-9999	-0.57	22	22
NFX1/SIN3/HDAC complex	0.025	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	0.006	0.005	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.024	0.13	-9999	-0.58	26	26
WRN	-0.002	0.033	-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	0.2	-9999	-0.79	5	5
CCND1	-0.083	0.21	-9999	-1.2	7	7
MAX	0.006	0.005	-9999	-10000	0	0
RBBP7	0.006	0.005	-9999	-10000	0	0
RBBP4	0.006	0.005	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0.006	0.005	-9999	-10000	0	0
Telomerase/911	0.016	0.032	-9999	-10000	0	0
CDKN1B	0.015	0.052	-9999	-0.47	2	2
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	0.006	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	56	56
IFN-gamma/IRF1	-0.006	0.056	-9999	-0.5	6	6
PARP2	0	0	-9999	-10000	0	0
BLM	-0.012	0.081	-9999	-0.57	10	10
Telomerase	-0.027	0.053	-9999	-10000	0	0
IRF1	0.009	0.007	-9999	-10000	0	0
ESR1	-0.028	0.16	-9999	-0.74	22	22
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	0.006	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	-0.016	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	0.006	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	0.006	0.005	-9999	-10000	0	0
PIF1	-0.055	0.17	-9999	-0.57	47	47
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 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
VEGFR1 homodimer/VEGFB homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	0.018	0.073	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	-0.014	0.06	-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	0.04	0.069	-9999	-0.58	1	1
CBL	0	0	-9999	-10000	0	0
mol:NO	0.04	0.067	-9999	-0.55	1	1
FLT1	0.026	0	-9999	-10000	0	0
PGF	-0.029	0.13	-9999	-0.57	25	25
VEGFR1 homodimer/NRP2/VEGFR121	-0.003	0.039	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
eNOS/Hsp90	0.044	0.065	-9999	-0.53	1	1
endothelial cell proliferation	0.018	0.094	-9999	-0.62	1	1
mol:Ca2+	0.018	0.073	-9999	-10000	0	0
MAPK3	0.03	0.07	-9999	-10000	0	0
MAPK1	0.03	0.07	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
PLGF homodimer	-0.029	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	137	137
VEGFA homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.036	0.068	-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	-0.017	0.075	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.018	0.073	-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	0.19	-9999	-0.59	7	7
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.014	0.06	-9999	-10000	0	0
mol:L-citrulline	0.04	0.067	-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	0.04	0.067	-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

×

p38 MAPK 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	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	0.024	-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	0.081	-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	-0.023	0.13	-9999	-0.74	15	15
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	58	58
CCM2	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.042	0.11	-9999	-0.35	58	58
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	-10000	0	0
OSM/MEKK3	0	0	-9999	-10000	0	0
TAOK1	0.014	0.019	-9999	-0.42	1	1
TAOK2	0.015	0	-9999	-10000	0	0
TAOK3	0.015	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	-0.018	0.087	-9999	-0.43	20	20

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.092	-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	0.032	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.03	0.13	-9999	-0.57	26	26

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	-0.009	0.081	-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	0.02	0.042	-10000	0	-0.23	12	12
RB1	-0.001	0.019	0.19	2	-10000	0	2
FADD/Caspase 8	0.04	0.054	-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	0.098	-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	0.06	-10000	0	-0.33	16	16
BID	0.024	0.039	-10000	0	-0.38	1	1
MAP3K1	-0.001	0.019	-10000	0	-10000	0	0
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	0.17	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	0.18	2	-10000	0	2
PRKRA	-0.001	0.019	0.19	2	-10000	0	2
PDGFA	-0.003	0.047	-10000	0	-0.74	2	2
TRAF2	0	0	-10000	0	-10000	0	0
IGF1	-0.025	0.13	-10000	0	-0.73	17	17
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	0.064	-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	0.053	-10000	0	-0.68	1	1
TNFR1A/BAG4/TNF-alpha	-0.013	0.077	-10000	0	-0.48	12	12
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	-0.012	0.075	-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	-0.3	16	16
TNF	-0.019	0.12	-10000	0	-0.73	13	13
PKC zeta/PAR4	0	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	-0.005	0.039	0.24	9	-10000	0	9
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 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
PTK2	-0.006	0.054	-9999	-0.49	6	6
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.008	0.074	-9999	-0.74	5	5
alpha4/beta7 Integrin/MAdCAM1	-0.008	0.055	-9999	-0.43	6	6
EPO	-0.007	0.063	-9999	-0.57	6	6
alpha4/beta7 Integrin	-0.007	0.061	-9999	-0.56	6	6
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.006	0.056	-9999	-0.56	5	5
EPO/EPOR (dimer)	-0.005	0.045	-9999	-0.41	6	6
lamellipodium assembly	0.001	0.005	-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	-0.006	0.039	-9999	-0.34	5	5
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
MADCAM1	-0.005	0.052	-9999	-0.57	4	4
cell adhesion	-0.008	0.054	-9999	-0.43	6	6
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	0.02	0.074	-9999	-0.57	6	6
ITGB7	-0.002	0.033	-9999	-0.74	1	1
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.01	0.077	-9999	-0.53	9	9
p130Cas/Crk/Dock1	-0.007	0.059	-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	0.043	-9999	-0.43	5	5
BCAR1	0.027	0.07	-9999	-0.53	6	6
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	0.001	0.005	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.03	0.087	-9999	-0.75	6	6
CYCS	0.033	0.064	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.024	0.13	-9999	-0.83	11	11
MAP2K7	0.034	0.05	-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	0.033	-9999	-0.74	1	1
BID	0.027	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	-0.014	0.062	-9999	-0.3	15	15
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	-0.027	0.12	-9999	-0.51	26	26
TNF	-0.019	0.12	-9999	-0.73	13	13
FASLG	-0.02	0.2	-9999	-0.82	26	26
NFKB1	-0.001	0.012	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.077	-9999	-0.48	12	12
CASP6	-0.006	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	0.045	0.047	-9999	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.005	0.04	-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	33	33
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	-10000	0	0
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	0.041	-9999	-0.71	1	1
PTEN	-0.002	0.033	-9999	-0.74	1	1
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	0.054	0.042	-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	0.049	-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	-0.003	0.044	-9999	-0.56	3	3
LCK	-0.002	0.035	-9999	-0.55	2	2
PDGFRB	0.009	0.034	-9999	-0.75	1	1
ACP1	0	0	-9999	-10000	0	0
HCK	-0.006	0.065	-9999	-0.59	6	6
ABL1	0.024	0.052	-9999	-0.65	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	-0.039	0.17	-9999	-0.74	26	26
actin cytoskeleton reorganization	0.002	0.02	-9999	-10000	0	0
SRC	0	0.022	-9999	-0.49	1	1
PI3K	-0.005	0.044	-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	0.058	-9999	-0.47	7	7
YES1	0	0.022	-9999	-0.48	1	1
cell migration	-0.007	0.058	-9999	-0.46	7	7
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	-0.007	0.056	-9999	-0.49	5	5
FYN	-0.001	0.034	-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	-0.66	1	1
PRKCD	0.029	0.021	-9999	-0.44	1	1
FER	0.029	0.021	-9999	-0.44	1	1
MAPKKK cascade	-0.001	0.017	-9999	-10000	0	0
RASA1	0.029	0.021	-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	0.047	-9999	-0.74	2	2

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.047	-10000	0	-0.74	2	2
PDE3B	-0.003	0.047	-10000	0	-0.74	2	2

×

PLK2 and PLK4 events

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
PLK2	-0.002	0.033	-9999	-0.74	1	1
PLK4	-0.001	0.026	-9999	-0.57	1	1
regulation of centriole replication	0.018	0.033	-9999	-0.48	2	2

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.032	-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	-0.58	48	48
LNPEP	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.006	0.047	-9999	-0.37	8	8
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	-0.004	0.049	-9999	-0.63	3	3
RhoA/GTP	-0.007	0.035	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.007	0.04	-9999	-0.3	2	2
GNAZ	-0.009	0.081	-9999	-0.74	6	6
GNAI3	0	0	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
S1PR5	-0.01	0.076	-9999	-0.59	8	8
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.008	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	0.033	-9999	-0.74	1	1

×

FoxO family signaling

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
G6PC	0.024	0.033	-9999	-10000	0	0
PLK1	-0.089	0.21	-9999	-0.73	3	3
CDKN1B	0.051	0.085	-9999	-10000	0	0
FOXO3	-0.022	0.16	-9999	-0.63	3	3
KAT2B	0.007	0.037	-9999	-0.75	1	1
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	0.02	-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	-0.062	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	0.029	-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	-0.043	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	0.029	-9999	-0.56	1	1
CCNB1	-0.032	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	-0.58	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	-0.017	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 S115. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.008	0.074	-10000	0	-0.74	5	5
RAC1	0	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.007	0.061	-10000	0	-0.56	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.005	0.048	-10000	0	-0.48	5	5
alpha4/beta7 Integrin/Paxillin	-0.005	0.048	-10000	0	-0.43	6	6
lamellipodium assembly	0.001	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	-0.004	0.037	-10000	0	-10000	0	0
cell adhesion	-0.004	0.04	-10000	0	-10000	0	0
CRKL/CBL	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.004	0.043	-10000	0	-0.43	5	5
ITGB1	0	0	-10000	0	-10000	0	0
ITGB7	-0.002	0.033	-10000	0	-0.74	1	1
ARF6/GDP	0.001	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.008	0.067	-10000	0	-0.54	6	6
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	-0.004	0.041	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.004	0.041	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
mol:GDP	0.004	0.04	0.4	5	-10000	0	5
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	-0.004	0.041	-10000	0	-10000	0	0
Rac1/GTP	0.001	0.006	-10000	0	-10000	0	0

×

Rapid glucocorticoid 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.008	0.064	-10000	0	-0.46	9	9
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.019	-10000	0	-0.42	1	1
GNB1/GNG2	-0.006	0.053	-10000	0	-0.48	6	6
GNB1	-0.002	0.033	-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	-0.45	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	0.074	-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

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0	0	-9999	-10000	0	0
adherens junction organization	0.032	0.033	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	-0.009	0.049	-9999	-10000	0	0
FMN1	0.012	0.1	-9999	-0.38	31	31
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)	-0.01	0.056	-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	0.01	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	0.01	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	0.019	0.099	-9999	-0.36	31	31
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	0.051	-9999	-10000	0	0
homophilic cell adhesion	0.001	0	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0	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	0.014	-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	0.047	-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	0.088	-9999	-0.55	13	13
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.003	0.047	-9999	-0.74	2	2
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.019	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	0.017	-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 S120. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.037	0.003	-10000	0	-10000	0	0
regulation of axonogenesis	-0.024	0.019	-10000	0	-10000	0	0
myoblast fusion	0.001	0.013	-10000	0	-10000	0	0
mol:GTP	0	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.002	0.025	0.46	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	-10000	0	0
lamellipodium assembly	-0.001	0.015	-10000	0	-10000	0	0
MAPK3	0.025	0.004	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.002	0.025	-10000	0	-0.46	1	1
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.013	-10000	0	-10000	0	0
ARF1/GDP	-0.001	0.012	-10000	0	-10000	0	0
ARF6	0.008	0.002	-10000	0	-10000	0	0
RAB11A	0	0	-10000	0	-10000	0	0
TIAM1	0.01	0.034	-10000	0	-0.74	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.025	0.004	-10000	0	-10000	0	0
actin filament bundle formation	0.001	0.011	-10000	0	-10000	0	0
KALRN	-0.003	0.04	-10000	0	-0.44	4	4
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.001	0.011	-10000	0	-10000	0	0
NME1	0.01	0.026	-10000	0	-0.57	1	1
Rac1/GDP	-0.001	0.011	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.005	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.001	0.015	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
liver development	0	0.005	-10000	0	-10000	0	0
ARF6/GTP	0	0.005	-10000	0	-10000	0	0
RhoA/GTP	0	0.002	-10000	0	-10000	0	0
mol:GDP	-0.001	0.014	-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	0.031	-10000	0	-0.38	3	3
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	-0.001	0.015	-10000	0	-10000	0	0
ruffle organization	0.024	0.019	-10000	0	-10000	0	0
regulation of epithelial cell migration	0	0.005	-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	-10000	0	0
Rac1/GTP	-0.001	0.016	-10000	0	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-10000	0	0
HRAS	-0.003	0.025	-10000	0	-10000	0	0
MAPK8	0.027	0.045	-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	0.045	-10000	0	-0.44	2	2
EPO	0.004	0.063	-10000	0	-0.56	6	6
PLCG1	-0.005	0.034	-10000	0	-10000	0	0
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	0.047	-10000	0	-0.5	2	2
GAB1/SHC/GRB2/SOS1	-0.003	0.027	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.003	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	-10000	0	0
STAT5B	-0.005	0.034	-10000	0	-10000	0	0
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	-0.38	1	1
SOCS3	-0.003	0.047	-10000	0	-0.74	2	2
STAT1 (dimer)	0.051	0.041	-10000	0	-10000	0	0
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	-10000	0	0
EPO/EPOR	-0.003	0.045	-10000	0	-0.4	6	6
LYN	0.008	0.048	-10000	0	-0.74	2	2
TEC/VAV2	0.04	0.067	-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	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.006	0.041	-10000	0	-10000	0	0
SH2B3	0.008	0.048	-10000	0	-0.74	2	2
NFKB1	0.027	0.045	-10000	0	-0.44	2	2
EPO/EPOR (dimer)/JAK2/SOCS3	-0.002	0.031	0.3	2	-10000	0	2
PTPN6	0.033	0.039	-10000	0	-10000	0	0
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	0.033	-10000	0	-0.74	1	1
mol:GDP	-0.003	0.027	-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	0.055	-10000	0	-0.74	1	1
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	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.062	0.043	-10000	0	-10000	0	0
LYN/PLCgamma2	-0.002	0.035	-10000	0	-0.56	2	2
PTPN11	0	0	-10000	0	-10000	0	0
BTK	0	0.13	-10000	0	-0.74	2	2
BCL2	0.065	0.04	-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	0.001	0.014	0.31	1	-10000	0	1
FRAP1	0.013	0.005	-10000	0	-10000	0	0
AKT1	0	0.011	0.23	1	-10000	0	1
INSR	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0	-10000	0	-10000	0	0
TSC2	0	0	-10000	0	-10000	0	0
RHEB/GDP	0	0	-10000	0	-10000	0	0
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0	0	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.025	0.007	-10000	0	-10000	0	0
MAP3K5	0.009	0	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
apoptosis	0.009	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-10000	0	0
EIF4B	0.03	0.007	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.028	0.006	0.17	1	-10000	0	1
FKBP1A	0	0.001	-10000	0	-10000	0	0
RHEB/GTP	0	0	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-10000	0	0
FKBP12/Rapamycin	0	0.001	-10000	0	-10000	0	0
PDPK1	0.001	0.011	0.25	1	-10000	0	1
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	0	0.004	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.014	0.001	-10000	0	-10000	0	0
TSC1/TSC2	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
EIF4G1	0	0	-10000	0	-10000	0	0
IRS1	0.007	0	-10000	0	-10000	0	0
INS	0	0	-10000	0	-10000	0	0
PTEN	-0.002	0.033	-10000	0	-0.74	1	1
PDK2	0.001	0.011	0.25	1	-10000	0	1
EIF4EBP1	0.004	0.021	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
PPP2R5D	0.019	0.005	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
EIF4A1	0	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.004	1	-10000	0	1
EEF2	0.015	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	-0.003	0.014	-10000	0	-10000	0	0

×

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	0.019	-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	0.015	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	0.024	0.041	-9999	-0.43	4	4
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.028	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.024	0.041	-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	-0.58	48	48
G1/S transition of mitotic cell cycle	0.038	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.029	0.038	-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	0.081	-9999	-0.74	6	6
BAX	0.027	0.021	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.012	0.015	-9999	-0.12	1	1
IKBKB	0.041	0.056	-9999	-0.49	1	1
MAP2K2	0.038	0.023	-9999	-10000	0	0
MAP2K1	0.038	0.023	-9999	-10000	0	0
SMPD1	0.017	0.015	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.042	0.055	-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	0.022	-9999	-10000	0	0
CRADD	0.01	0.001	-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	0.01	0.001	-9999	-10000	0	0
MAP3K1	0.027	0.021	-9999	-10000	0	0
TRADD	0.01	0.001	-9999	-10000	0	0
RELA/p50	0	0	-9999	-10000	0	0
MAPK3	0.04	0.022	-9999	-10000	0	0
MAPK1	0.04	0.022	-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	-0.49	1	1
TNF R/SODD	-0.001	0.019	-9999	-0.41	1	1
TNF	-0.01	0.12	-9999	-0.73	13	13
CYCS	0.028	0.02	-9999	-10000	0	0
IKBKG	0.042	0.054	-9999	-0.49	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.03	0.059	-9999	-0.56	1	1
RELA	0	0	-9999	-10000	0	0
RIPK1	0	0.001	-9999	-10000	0	0
AIFM1	0.028	0.02	-9999	-10000	0	0
TNF/TNF R/SODD	-0.013	0.077	-9999	-0.48	12	12
TNFRSF1A	0	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.023	0.015	-9999	-10000	0	0
NSMAF	0.036	0.056	-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	0.045	-9999	-0.37	6	6
MAPK13	0.02	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.015	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	0.017	-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	-10000	0	0
ARRB2	0.015	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	-0.26	1	1
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	0.033	-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	0.033	-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	0.031	-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	-0.002	0.024	-9999	-0.44	1	1
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	-0.002	0.033	-9999	-0.74	1	1
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	0.033	-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	0.052	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	-10000	0	0
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	-0.023	0.13	-9999	-0.74	15	15
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	0.044	-9999	-10000	0	0
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	0.084	-9999	-0.48	15	15

×

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	-0.0053	0.038	0.038	-0.07
84_STAT5A	-0.0053	0.038	0.038	-0.07