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	157
Angiopoietin receptor Tie2-mediated signaling	157
Aurora B signaling	128
FOXM1 transcription factor network	114
Aurora C signaling	99
Endothelins	74
Glypican 2 network	61
TCGA08_retinoblastoma	59
amb2 Integrin signaling	52
Visual signal transduction: Cones	47

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	0.3257	157	8205	52	-0.65	0.35	1000	-1000	-0.1	-1000
Angiopoietin receptor Tie2-mediated signaling	0.3257	157	13831	88	-0.78	0.06	1000	-1000	-0.13	-1000
Aurora B signaling	0.2656	128	8576	67	-0.62	0.005	1000	-1000	-0.078	-1000
FOXM1 transcription factor network	0.2365	114	5846	51	-0.71	0.002	1000	-1000	-0.2	-1000
Aurora C signaling	0.2054	99	696	7	-0.41	0	1000	-1000	-0.046	-1000
Endothelins	0.1535	74	7161	96	-0.45	0.038	1000	-1000	-0.098	-1000
Glypican 2 network	0.1266	61	245	4	-0.087	-0.07	1000	-1000	-0.035	-1000
TCGA08_retinoblastoma	0.1224	59	475	8	-0.28	0.084	1000	-1000	-0.031	-1000
amb2 Integrin signaling	0.1079	52	4313	82	-0.69	0	1000	-1000	-0.11	-1000
Visual signal transduction: Cones	0.0975	47	1807	38	-0.28	0.009	1000	-1000	-0.084	-1000
Thromboxane A2 receptor signaling	0.0975	47	4966	105	-0.18	0.038	1000	-1000	-0.084	-1000
Fc-epsilon receptor I signaling in mast cells	0.0954	46	4542	97	-0.26	0.033	1000	-1000	-0.12	-1000
Signaling events regulated by Ret tyrosine kinase	0.0954	46	3843	82	-0.2	0	1000	-1000	-0.1	-1000
IL4-mediated signaling events	0.0913	44	4089	91	-0.8	0.44	1000	-1000	-0.2	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0913	44	2339	52	-0.38	0.057	1000	-1000	-0.076	-1000
BMP receptor signaling	0.0871	42	3453	81	-0.39	0.033	1000	-1000	-0.12	-1000
PLK1 signaling events	0.0871	42	3632	85	-0.36	0.071	1000	-1000	-0.065	-1000
Glucocorticoid receptor regulatory network	0.0871	42	4855	114	-0.56	0.37	1000	-1000	-0.089	-1000
Signaling mediated by p38-alpha and p38-beta	0.0871	42	1867	44	-0.13	0	1000	-1000	-0.064	-1000
Arf6 signaling events	0.0768	37	2308	62	-0.31	0.015	1000	-1000	-0.076	-1000
Nectin adhesion pathway	0.0747	36	2279	63	-0.27	0	1000	-1000	-0.084	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0747	36	2819	78	-0.13	0.036	1000	-1000	-0.1	-1000
Integrins in angiogenesis	0.0705	34	2897	84	-0.47	0.002	1000	-1000	-0.11	-1000
Nongenotropic Androgen signaling	0.0705	34	1783	52	-0.16	0.046	1000	-1000	-0.07	-1000
Glypican 1 network	0.0664	32	1552	48	-0.22	0.03	1000	-1000	-0.062	-1000
TCGA08_p53	0.0664	32	229	7	-0.19	0.096	1000	-1000	-0.034	-1000
Canonical Wnt signaling pathway	0.0664	32	1644	51	-0.47	0.16	1000	-1000	-0.077	-1000
Presenilin action in Notch and Wnt signaling	0.0602	29	1805	61	-0.47	0.013	1000	-1000	-0.087	-1000
FOXA2 and FOXA3 transcription factor networks	0.0602	29	1341	46	-0.79	0.073	1000	-1000	-0.12	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0560	27	3457	125	-0.21	0	1000	-1000	-0.11	-1000
LPA4-mediated signaling events	0.0539	26	312	12	-0.14	0.017	1000	-1000	-0.035	-1000
Coregulation of Androgen receptor activity	0.0539	26	2024	76	-0.4	0.028	1000	-1000	-0.057	-1000
HIF-1-alpha transcription factor network	0.0539	26	2048	76	-0.44	0.016	1000	-1000	-0.22	-1000
Syndecan-3-mediated signaling events	0.0539	26	914	35	-0.34	0	1000	-1000	-0.073	-1000
IL23-mediated signaling events	0.0539	26	1573	60	-0.24	0.018	1000	-1000	-0.19	-1000
Calcium signaling in the CD4+ TCR pathway	0.0519	25	802	31	-0.21	0.012	1000	-1000	-0.14	-1000
IL6-mediated signaling events	0.0498	24	1805	75	-0.48	0.05	1000	-1000	-0.12	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0477	23	1616	68	-0.23	0.015	1000	-1000	-0.16	-1000
Regulation of Androgen receptor activity	0.0456	22	1550	70	-0.42	0.018	1000	-1000	-0.076	-1000
Syndecan-1-mediated signaling events	0.0436	21	731	34	-0.35	0	1000	-1000	-0.079	-1000
Aurora A signaling	0.0436	21	1271	60	-0.49	0.029	1000	-1000	-0.072	-1000
Wnt signaling	0.0436	21	150	7	-0.096	0	1000	-1000	-0.058	-1000
IL12-mediated signaling events	0.0415	20	1800	87	-0.15	0.018	1000	-1000	-0.14	-1000
ErbB4 signaling events	0.0415	20	1419	69	-0.38	0.2	1000	-1000	-0.1	-1000
Reelin signaling pathway	0.0415	20	1125	56	-0.13	0.003	1000	-1000	-0.11	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0394	19	650	33	-0.27	0	1000	-1000	-0.078	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0394	19	2314	120	-0.27	0.13	1000	-1000	-0.088	-1000
Osteopontin-mediated events	0.0373	18	708	38	-0.3	0	1000	-1000	-0.12	-1000
Visual signal transduction: Rods	0.0373	18	971	52	-0.18	0	1000	-1000	-0.11	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0353	17	1489	85	-0.16	0.009	1000	-1000	-0.091	-1000
HIF-2-alpha transcription factor network	0.0353	17	744	43	-0.37	0.2	1000	-1000	-0.11	-1000
Plasma membrane estrogen receptor signaling	0.0353	17	1534	86	-0.18	0.033	1000	-1000	-0.094	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0332	16	880	54	-0.15	0.02	1000	-1000	-0.12	-1000
TCR signaling in naïve CD8+ T cells	0.0332	16	1530	93	-0.064	0.036	1000	-1000	-0.1	-1000
p75(NTR)-mediated signaling	0.0311	15	1986	125	-0.34	0	1000	-1000	-0.13	-1000
PDGFR-alpha signaling pathway	0.0290	14	650	44	-0.21	0.014	1000	-1000	-0.083	-1000
Ephrin A reverse signaling	0.0249	12	87	7	-0.023	0.004	1000	-1000	-0.037	-1000
EGFR-dependent Endothelin signaling events	0.0249	12	261	21	-0.063	0	1000	-1000	-0.079	-1000
Caspase cascade in apoptosis	0.0228	11	846	74	-0.069	0.034	1000	-1000	-0.077	-1000
JNK signaling in the CD4+ TCR pathway	0.0228	11	191	17	-0.04	0.022	1000	-1000	-0.072	-1000
FAS signaling pathway (CD95)	0.0228	11	533	47	-0.2	0.009	1000	-1000	-0.055	-1000
Regulation of nuclear SMAD2/3 signaling	0.0207	10	1483	136	-0.33	0.092	1000	-1000	-0.11	-1000
Noncanonical Wnt signaling pathway	0.0207	10	279	26	-0.1	0	1000	-1000	-0.1	-1000
Syndecan-2-mediated signaling events	0.0207	10	692	69	-0.17	0.032	1000	-1000	-0.074	-1000
Effects of Botulinum toxin	0.0207	10	266	26	-0.073	0.005	1000	-1000	-0.076	-1000
Ras signaling in the CD4+ TCR pathway	0.0207	10	174	17	-0.054	0.009	1000	-1000	-0.078	-1000
S1P1 pathway	0.0187	9	357	36	-0.061	0.01	1000	-1000	-0.081	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0187	9	693	74	-0.17	0.068	1000	-1000	-0.11	-1000
BCR signaling pathway	0.0187	9	926	99	-0.11	0.039	1000	-1000	-0.11	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0166	8	298	34	-0.028	0	1000	-1000	-0.076	-1000
Hedgehog signaling events mediated by Gli proteins	0.0166	8	571	65	-0.61	0.043	1000	-1000	-0.1	-1000
Syndecan-4-mediated signaling events	0.0166	8	581	67	-0.17	0.009	1000	-1000	-0.11	-1000
S1P4 pathway	0.0166	8	214	25	-0.066	0.002	1000	-1000	-0.063	-1000
Signaling events mediated by HDAC Class III	0.0145	7	293	40	-0.15	0.051	1000	-1000	-0.049	-1000
TRAIL signaling pathway	0.0145	7	345	48	-0.095	0.046	1000	-1000	-0.074	-1000
IL2 signaling events mediated by STAT5	0.0145	7	175	22	-0.15	0.06	1000	-1000	-0.062	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0124	6	182	28	-0.18	0.02	1000	-1000	-0.064	-1000
Cellular roles of Anthrax toxin	0.0124	6	257	39	-0.09	0.017	1000	-1000	-0.04	-1000
Signaling events mediated by PTP1B	0.0124	6	525	76	-0.1	0.033	1000	-1000	-0.095	-1000
Retinoic acid receptors-mediated signaling	0.0124	6	366	58	-0.22	0.034	1000	-1000	-0.085	-1000
LPA receptor mediated events	0.0124	6	613	102	-0.1	0.034	1000	-1000	-0.1	-1000
S1P3 pathway	0.0124	6	253	42	-0.18	0.042	1000	-1000	-0.064	-1000
IL1-mediated signaling events	0.0104	5	364	62	-0.059	0.042	1000	-1000	-0.12	-1000
IL2 signaling events mediated by PI3K	0.0104	5	296	58	-0.22	0.073	1000	-1000	-0.1	-1000
Regulation of p38-alpha and p38-beta	0.0104	5	311	54	-0.095	0.037	1000	-1000	-0.094	-1000
IL27-mediated signaling events	0.0104	5	289	51	-0.12	0.011	1000	-1000	-0.11	-1000
IGF1 pathway	0.0104	5	319	57	-0.019	0.041	1000	-1000	-0.11	-1000
Insulin Pathway	0.0104	5	440	74	-0.12	0.031	1000	-1000	-0.11	-1000
Signaling events mediated by PRL	0.0104	5	190	34	-0.13	0.029	1000	-1000	-0.076	-1000
Signaling events mediated by HDAC Class II	0.0083	4	324	75	-0.08	0	1000	-1000	-0.074	-1000
BARD1 signaling events	0.0083	4	283	57	-0.13	0.022	1000	-1000	-0.077	-1000
Ephrin B reverse signaling	0.0083	4	205	48	-0.07	0.04	1000	-1000	-0.083	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0083	4	367	83	-0.069	0.049	1000	-1000	-0.095	-1000
Arf6 trafficking events	0.0083	4	288	71	-0.086	0.032	1000	-1000	-0.088	-1000
VEGFR1 specific signals	0.0083	4	233	56	-0.21	0.045	1000	-1000	-0.094	-1000
ErbB2/ErbB3 signaling events	0.0062	3	259	65	-0.078	0.055	1000	-1000	-0.079	-1000
IFN-gamma pathway	0.0062	3	226	68	-0.068	0.065	1000	-1000	-0.12	-1000
Signaling events mediated by HDAC Class I	0.0062	3	375	104	-0.08	0.041	1000	-1000	-0.089	-1000
Class I PI3K signaling events	0.0062	3	248	73	-0.049	0.027	1000	-1000	-0.087	-1000
Regulation of Telomerase	0.0062	3	393	102	-0.12	0.024	1000	-1000	-0.12	-1000
p38 MAPK signaling pathway	0.0062	3	155	44	-0.068	0.034	1000	-1000	-0.076	-1000
Circadian rhythm pathway	0.0041	2	56	22	-0.031	0.038	1000	-1000	-0.09	-1000
a4b1 and a4b7 Integrin signaling	0.0041	2	14	5	-0.006	-0.002	1000	-1000	-0.045	-1000
Ceramide signaling pathway	0.0041	2	165	76	-0.024	0.04	1000	-1000	-0.075	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0041	2	75	37	-0.009	0.028	1000	-1000	-0.1	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0041	2	132	45	-0.028	0.061	1000	-1000	-0.11	-1000
EPHB forward signaling	0.0041	2	225	85	-0.07	0.032	1000	-1000	-0.12	-1000
TCGA08_rtk_signaling	0.0041	2	76	26	-0.065	0.038	1000	-1000	-0.035	-1000
PDGFR-beta signaling pathway	0.0041	2	217	97	-0.04	0.055	1000	-1000	-0.11	-1000
Class IB PI3K non-lipid kinase events	0.0041	2	6	3	-0.003	-1000	1000	-1000	-0.025	-1000
PLK2 and PLK4 events	0.0021	1	4	3	-0.002	0.017	1000	-1000	-0.033	-1000
Insulin-mediated glucose transport	0.0021	1	50	32	-0.057	0.034	1000	-1000	-0.074	-1000
S1P5 pathway	0.0021	1	28	17	-0.009	0.006	1000	-1000	-0.059	-1000
FoxO family signaling	0.0021	1	98	64	-0.089	0.08	1000	-1000	-0.098	-1000
Paxillin-dependent events mediated by a4b1	0.0021	1	54	36	-0.008	0.02	1000	-1000	-0.082	-1000
Rapid glucocorticoid signaling	0.0021	1	35	20	-0.009	0.007	1000	-1000	-0.049	-1000
E-cadherin signaling in keratinocytes	0.0021	1	58	43	-0.022	0.042	1000	-1000	-0.09	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	0	23	0	0.036	1000	-1000	-0.089	-1000
Canonical NF-kappaB pathway	0.0000	0	33	39	-0.02	0.071	1000	-1000	-0.1	-1000
Arf6 downstream pathway	0.0000	0	15	43	-0.024	0.025	1000	-1000	-0.049	-1000
EPO signaling pathway	0.0000	0	50	55	-0.008	0.065	1000	-1000	-0.12	-1000
mTOR signaling pathway	0.0000	0	0	53	-0.003	0.03	1000	-1000	-0.07	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	57	68	-0.057	0.043	1000	-1000	-0.085	-1000
ceramide signaling pathway	0.0000	0	45	49	-0.02	0.043	1000	-1000	-0.072	-1000
Signaling mediated by p38-gamma and p38-delta	0.0000	0	13	15	-0.001	0.027	1000	-1000	-0.063	-1000
Atypical NF-kappaB pathway	0.0000	0	12	31	-0.002	0.03	1000	-1000	-0.08	-1000
E-cadherin signaling in the nascent adherens junction	0.0000	0	47	76	-0.023	0.053	1000	-1000	-0.11	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	1	27	-0.001	0.025	1000	-1000	-0.072	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0	1000	-1000	-0.054	-1000
Arf1 pathway	0.0000	0	30	54	-0.022	0.022	1000	-1000	-0.064	-1000
Alternative NF-kappaB pathway	0.0000	0	4	13	-0.001	0	1000	-1000	-0.075	-1000
Total	NA	2559	158077	7203	-25	-990	131000	-131000	-12	-131000

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.43	0.3	-10000	0	-0.69	225	225
IHH	-0.47	0.38	-10000	0	-0.81	269	269
SHH Np/Cholesterol/GAS1	-0.071	0.17	-10000	0	-0.46	71	71
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.071	0.16	0.45	71	-10000	0	71
SMO/beta Arrestin2	-0.36	0.25	-10000	0	-0.59	232	232
SMO	-0.38	0.27	-10000	0	-0.63	233	233
AKT1	-0.15	0.11	-10000	0	-0.34	1	1
ARRB2	0	0	-10000	0	-10000	0	0
BOC	-0.005	0.06	-10000	0	-0.66	4	4
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	-0.38	0.27	-10000	0	-0.62	233	233
STIL	-0.33	0.25	-10000	0	-0.7	84	84
DHH N/PTCH2	-0.046	0.16	-10000	0	-0.56	39	39
DHH N/PTCH1	-0.36	0.24	-10000	0	-0.58	238	238
PIK3CA	0	0	-10000	0	-10000	0	0
DHH	-0.052	0.19	-10000	0	-0.74	34	34
PTHLH	-0.58	0.36	-10000	0	-0.92	225	225
determination of left/right symmetry	-0.38	0.27	-10000	0	-0.62	233	233
PIK3R1	0	0	-10000	0	-10000	0	0
skeletal system development	-0.57	0.35	-10000	0	-0.9	225	225
IHH N/Hhip	-0.65	0.38	-10000	0	-0.82	383	383
DHH N/Hhip	-0.41	0.3	-10000	0	-0.6	330	330
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.38	0.27	-10000	0	-0.62	233	233
pancreas development	-0.49	0.35	-10000	0	-0.74	322	322
HHAT	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.012	0.095	-10000	0	-0.74	8	8
somite specification	-0.38	0.27	-10000	0	-0.62	233	233
SHH Np/Cholesterol/PTCH1	-0.35	0.25	-10000	0	-0.56	248	248
SHH Np/Cholesterol/PTCH2	-0.069	0.16	-10000	0	-0.43	77	77
SHH Np/Cholesterol/Megalin	-0.29	0.27	-10000	0	-0.5	276	276
SHH	-0.066	0.2	-10000	0	-0.55	72	72
catabolic process	-0.37	0.25	-10000	0	-0.57	278	278
SMO/Vitamin D3	-0.37	0.27	-10000	0	-0.59	248	248
SHH Np/Cholesterol/Hhip	-0.36	0.26	-10000	0	-0.5	342	342
LRP2	-0.38	0.37	-10000	0	-0.74	247	247
receptor-mediated endocytosis	-0.5	0.31	-10000	0	-0.72	281	281
SHH Np/Cholesterol/BOC	-0.067	0.16	-10000	0	-0.45	66	66
SHH Np/Cholesterol/CDO	-0.069	0.16	-10000	0	-0.43	77	77
mesenchymal cell differentiation	0.35	0.26	0.5	342	-10000	0	342
mol:Vitamin D3	-0.35	0.26	-10000	0	-0.56	248	248
IHH N/PTCH2	-0.31	0.27	-10000	0	-0.54	269	269
CDON	-0.008	0.075	-10000	0	-0.74	5	5
IHH N/PTCH1	-0.38	0.26	-10000	0	-0.58	278	278
Megalin/LRPAP1	-0.29	0.28	-10000	0	-0.56	247	247
PTCH2	-0.009	0.076	-10000	0	-0.68	6	6
SHH Np/Cholesterol	-0.065	0.16	-10000	0	-0.44	72	72
PTCH1	-0.37	0.25	-10000	0	-0.57	278	278
HHIP	-0.5	0.35	-10000	0	-0.74	322	322

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.53	0.53	-10000	0	-1	264	264
NCK1/PAK1/Dok-R	-0.25	0.23	-10000	0	-0.45	264	264
NCK1/Dok-R	-0.7	0.66	-10000	0	-1.3	264	264
PIK3CA	0.007	0.006	-10000	0	-10000	0	0
mol:beta2-estradiol	0.06	0.1	0.25	104	-10000	0	104
RELA	0	0	-10000	0	-10000	0	0
SHC1	0.002	0.004	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.053	0.13	-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	264	264
FN1	-0.017	0.11	-10000	0	-0.74	11	11
PLD2	-0.68	0.71	-10000	0	-1.3	264	264
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.047	0.18	-10000	0	-0.74	31	31
ELK1	-0.58	0.61	-10000	0	-1.1	264	264
GRB7	-0.005	0.052	-10000	0	-0.57	4	4
PAK1	-0.001	0.026	-10000	0	-0.57	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.66	0.62	-10000	0	-1.2	264	264
CDKN1A	-0.36	0.35	-10000	0	-0.68	253	253
ITGA5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.7	0.66	-10000	0	-1.3	264	264
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.37	0.38	-10000	0	-0.71	264	264
PLG	-0.69	0.71	-10000	0	-1.3	264	264
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.51	0.48	-10000	0	-0.95	264	264
GRB2	0	0	-10000	0	-10000	0	0
PIK3R1	0.002	0.004	-10000	0	-10000	0	0
ANGPT2	-0.34	0.34	-10000	0	-0.75	173	173
BMX	-0.76	0.75	-10000	0	-1.4	264	264
ANGPT1	-0.37	0.61	-10000	0	-1.5	113	113
tube development	-0.42	0.4	-10000	0	-0.78	262	262
ANGPT4	-0.33	0.37	-10000	0	-0.74	216	216
response to hypoxia	-0.035	0.036	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.76	0.72	-10000	0	-1.4	264	264
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.017	0.13	-10000	0	-0.74	15	15
STAT5A (dimer)	-0.49	0.47	-10000	0	-0.91	261	261
mol:L-citrulline	-0.37	0.38	-10000	0	-0.71	264	264
AGTR1	-0.3	0.37	-10000	0	-0.74	199	199
MAPK14	-0.7	0.7	-10000	0	-1.3	264	264
Tie2/SHP2	-0.61	0.62	-10000	0	-1.2	231	231
TEK	-0.68	0.69	-10000	0	-1.4	231	231
RPS6KB1	-0.5	0.51	-10000	0	-0.96	264	264
Angiotensin II/AT1	-0.23	0.28	-10000	0	-0.57	199	199
Tie2/Ang1/GRB2	-0.74	0.72	-10000	0	-1.3	264	264
MAPK3	-0.6	0.63	-10000	0	-1.2	264	264
MAPK1	-0.6	0.63	-10000	0	-1.2	264	264
Tie2/Ang1/GRB7	-0.74	0.72	-10000	0	-1.3	264	264
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.68	0.71	-10000	0	-1.3	264	264
PI3K	-0.64	0.63	-10000	0	-1.2	264	264
FES	-0.7	0.7	-10000	0	-1.3	264	264
Crk/Dok-R	-0.7	0.66	-10000	0	-1.3	264	264
Tie2/Ang1/ABIN2	-0.74	0.72	-10000	0	-1.3	264	264
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.46	0.46	-10000	0	-0.88	264	264
STAT5A	0	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.5	0.51	-10000	0	-0.96	264	264
Tie2/Ang2	-0.62	0.59	-10000	0	-1.2	262	262
Tie2/Ang1	-0.78	0.82	-10000	0	-1.5	264	264
FOXO1	-0.46	0.47	-10000	0	-0.89	264	264
ELF1	-0.034	0.052	-10000	0	-10000	0	0
ELF2	-0.69	0.72	-10000	0	-1.3	264	264
mol:Choline	-0.63	0.65	-10000	0	-1.2	264	264
cell migration	-0.14	0.12	-10000	0	-0.25	114	114
FYN	-0.49	0.47	-10000	0	-0.91	261	261
DOK2	-0.066	0.21	-10000	0	-0.74	43	43
negative regulation of cell cycle	-0.32	0.32	-10000	0	-0.61	253	253
ETS1	-0.062	0.16	-10000	0	-0.82	12	12
PXN	-0.4	0.41	-10000	0	-0.77	264	264
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.43	0.44	-10000	0	-0.82	264	264
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.063	0.16	-10000	0	-0.81	13	13
MAPKKK cascade	-0.63	0.65	-10000	0	-1.2	264	264
RASA1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.73	0.73	-10000	0	-1.4	264	264
NCK1	0	0	-10000	0	-10000	0	0
vasculogenesis	-0.32	0.34	-10000	0	-0.63	264	264
mol:Phosphatidic acid	-0.63	0.65	-10000	0	-1.2	264	264
mol:Angiotensin II	0	0.001	-10000	0	-10000	0	0
mol:NADP	-0.37	0.38	-10000	0	-0.71	264	264
Rac1/GTP	-0.48	0.44	-10000	0	-0.88	264	264
MMP2	-0.68	0.71	-10000	0	-1.3	264	264

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.18	0.14	-9999	-0.4	76	76
STMN1	-0.29	0.19	-9999	-0.4	347	347
Aurora B/RasGAP/Survivin	-0.5	0.22	-9999	-0.64	326	326
Chromosomal passenger complex/Cul3 protein complex	-0.2	0.1	-9999	-0.33	125	125
BIRC5	-0.49	0.21	-9999	-0.58	410	410
DES	-0.56	0.38	-9999	-0.83	311	311
Aurora C/Aurora B/INCENP	-0.22	0.15	-9999	-0.31	332	332
Aurora B/TACC1	-0.24	0.16	-9999	-0.34	347	347
Aurora B/PP2A	-0.29	0.19	-9999	-0.4	347	347
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.059	0.044	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.005	0.003	-9999	-10000	0	0
NDC80	-0.41	0.29	-9999	-0.55	362	362
Cul3 protein complex	-0.012	0.065	-9999	-0.48	3	3
KIF2C	-0.16	0.085	-9999	-0.24	248	248
PEBP1	-0.001	0.034	-9999	-0.76	1	1
KIF20A	-0.3	0.29	-9999	-0.58	249	249
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.29	0.19	-9999	-0.4	347	347
SEPT1	-0.001	0.026	-9999	-0.57	1	1
SMC2	0	0	-9999	-10000	0	0
SMC4	0	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.1	0.065	-9999	-10000	0	0
PSMA3	0	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.004	-9999	-10000	0	0
H3F3B	-0.15	0.1	-9999	-10000	0	0
AURKB	-0.41	0.26	-9999	-0.57	347	347
AURKC	-0.003	0.043	-9999	-0.66	2	2
CDCA8	-0.16	0.26	-9999	-0.58	131	131
cytokinesis	-0.32	0.16	-9999	-0.45	231	231
Aurora B/Septin1	-0.3	0.16	-9999	-0.46	169	169
AURKA	-0.015	0.12	-9999	-0.57	21	21
INCENP	0.001	0.003	-9999	-10000	0	0
KLHL13	-0.014	0.089	-9999	-0.57	12	12
BUB1	-0.049	0.17	-9999	-0.58	45	45
hSgo1/Aurora B/Survivin	-0.62	0.31	-9999	-0.78	352	352
EVI5	0.005	0.004	-9999	-10000	0	0
RhoA/GTP	-0.27	0.18	-9999	-0.49	149	149
SGOL1	-0.3	0.29	-9999	-0.57	251	251
CENPA	-0.24	0.12	-9999	-0.31	338	338
NCAPG	-0.1	0.22	-9999	-0.57	87	87
Aurora B/HC8 Proteasome	-0.29	0.19	-9999	-0.4	347	347
NCAPD2	-0.001	0.026	-9999	-0.57	1	1
Aurora B/PP1-gamma	-0.29	0.19	-9999	-0.4	347	347
RHOA	0	0	-9999	-10000	0	0
NCAPH	-0.29	0.29	-9999	-0.57	245	245
NPM1	-0.13	0.082	-9999	-10000	0	0
RASA1	0	0	-9999	-10000	0	0
KLHL9	-0.005	0.058	-9999	-0.74	3	3
mitotic prometaphase	-0.012	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.29	0.19	-9999	-0.4	347	347
PPP1CC	0	0	-9999	-10000	0	0
Centraspindlin	-0.3	0.19	-9999	-0.48	202	202
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.13	0.082	-9999	-10000	0	0
MYLK	-0.15	0.1	-9999	-0.61	2	2
KIF23	-0.12	0.23	-9999	-0.58	96	96
VIM	-0.3	0.21	-9999	-0.42	347	347
RACGAP1	0.001	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.13	0.082	-9999	-10000	0	0
Chromosomal passenger complex	-0.27	0.14	-9999	-0.35	331	331
Chromosomal passenger complex/EVI5	-0.49	0.25	-9999	-0.63	339	339
TACC1	-0.003	0.048	-9999	-0.74	2	2
PPP2R5D	0	0	-9999	-10000	0	0
CUL3	0	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.58	0.42	-9999	-1	144	144
PLK1	-0.19	0.2	-9999	-10000	0	0
BIRC5	-0.32	0.16	-9999	-10000	0	0
HSPA1B	-0.58	0.42	-9999	-1	144	144
MAP2K1	-0.012	0.023	-9999	-10000	0	0
BRCA2	-0.58	0.42	-9999	-1	134	134
FOXM1	-0.7	0.54	-9999	-1.2	198	198
XRCC1	-0.58	0.42	-9999	-1	139	139
FOXM1B/p19	-0.6	0.42	-9999	-1	166	166
Cyclin D1/CDK4	-0.54	0.4	-9999	-0.97	129	129
CDC2	-0.61	0.45	-9999	-1	188	188
TGFA	-0.52	0.38	-9999	-0.94	116	116
SKP2	-0.58	0.42	-9999	-1	133	133
CCNE1	-0.13	0.24	-9999	-0.58	107	107
CKS1B	-0.58	0.42	-9999	-1	133	133
RB1	-0.26	0.15	-9999	-0.48	25	25
FOXM1C/SP1	-0.65	0.45	-9999	-1.1	195	195
AURKB	-0.28	0.19	-9999	-10000	0	0
CENPF	-0.64	0.47	-9999	-1.1	200	200
CDK4	0.001	0.028	-9999	-0.59	1	1
MYC	-0.51	0.37	-9999	-0.91	120	120
CHEK2	-0.012	0.023	-9999	-10000	0	0
ONECUT1	-0.57	0.42	-9999	-1	149	149
CDKN2A	-0.25	0.29	-9999	-0.56	224	224
LAMA4	-0.58	0.43	-9999	-1	138	138
FOXM1B/HNF6	-0.65	0.5	-9999	-1.2	151	151
FOS	-0.63	0.49	-9999	-1.2	148	148
SP1	0	0	-9999	-10000	0	0
CDC25B	-0.58	0.42	-9999	-1	134	134
response to radiation	-0.024	0.022	-9999	-10000	0	0
CENPB	-0.58	0.42	-9999	-1	134	134
CENPA	-0.71	0.46	-9999	-1.1	226	226
NEK2	-0.69	0.47	-9999	-1.1	221	221
HIST1H2BA	-0.58	0.42	-9999	-1	144	144
CCNA2	-0.15	0.26	-9999	-0.58	125	125
EP300	0	0	-9999	-10000	0	0
CCNB1/CDK1	-0.66	0.49	-9999	-1.2	158	158
CCNB2	-0.66	0.48	-9999	-1.1	214	214
CCNB1	-0.62	0.46	-9999	-1.1	157	157
ETV5	-0.58	0.43	-9999	-1	138	138
ESR1	-0.59	0.45	-9999	-1.1	142	142
CCND1	-0.55	0.41	-9999	-0.98	139	139
GSK3A	-0.004	0.018	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.17	0.24	-9999	-0.44	186	186
CDK2	0.002	0.006	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.031	0.027	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.64	0.41	-9999	-1	209	209
GAS1	-0.58	0.43	-9999	-1	136	136
MMP2	-0.58	0.43	-9999	-1	135	135
RB1/FOXM1C	-0.58	0.44	-9999	-1	166	166
CREBBP	0	0	-9999	-10000	0	0

×

Aurora C signaling

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

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

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

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.029	0.23	-9999	-0.58	51	51
PTK2B	0.002	0.004	-9999	-10000	0	0
mol:Ca2+	-0.078	0.28	-9999	-0.85	38	38
EDN1	-0.041	0.25	-9999	-0.78	41	41
EDN3	-0.091	0.24	-9999	-0.7	62	62
EDN2	-0.087	0.21	-9999	-0.59	71	71
HRAS/GDP	-0.18	0.3	-9999	-0.63	122	122
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.053	0.2	-9999	-0.48	61	61
ADCY4	-0.078	0.22	-9999	-0.61	48	48
ADCY5	-0.09	0.23	-9999	-0.55	72	72
ADCY6	-0.054	0.19	-9999	-0.6	32	32
ADCY7	-0.053	0.18	-9999	-0.58	33	33
ADCY1	-0.054	0.19	-9999	-0.58	32	32
ADCY2	-0.086	0.21	-9999	-0.62	41	41
ADCY3	-0.053	0.18	-9999	-0.58	33	33
ADCY8	-0.18	0.25	-9999	-0.6	69	69
ADCY9	-0.054	0.19	-9999	-0.58	34	34
arachidonic acid secretion	-0.15	0.27	-9999	-0.54	116	116
ETB receptor/Endothelin-1/Gq/GTP	-0.32	0.35	-9999	-0.7	173	173
GNAO1	-0.004	0.05	-9999	-0.63	3	3
HRAS	0	0.002	-9999	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.038	0.26	-9999	-0.54	51	51
ETA receptor/Endothelin-1/Gs/GTP	0.03	0.25	-9999	-0.52	54	54
mol:GTP	0	0.004	-9999	-10000	0	0
COL3A1	-0.045	0.25	-9999	-0.69	33	33
EDNRB	-0.45	0.36	-9999	-0.74	296	296
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.045	0.27	-9999	-0.79	36	36
CYSLTR1	-0.092	0.36	-9999	-0.84	76	76
SLC9A1	-0.007	0.12	-9999	-0.36	19	19
mol:GDP	-0.2	0.33	-9999	-0.69	126	126
SLC9A3	-0.37	0.38	-9999	-0.74	200	200
RAF1	-0.21	0.32	-9999	-0.65	137	137
JUN	-0.056	0.22	-9999	-0.62	33	33
JAK2	-0.029	0.23	-9999	-0.58	51	51
mol:IP3	-0.21	0.3	-9999	-0.66	127	127
ETA receptor/Endothelin-1	0.018	0.32	-9999	-0.67	51	51
PLCB1	0.003	0.005	-9999	-10000	0	0
PLCB2	-0.005	0.096	-9999	-0.74	8	8
ETA receptor/Endothelin-3	-0.057	0.21	-9999	-0.55	67	67
FOS	-0.2	0.35	-9999	-0.86	83	83
Gai/GDP	-0.007	0.067	-9999	-0.95	1	1
CRK	0.002	0.004	-9999	-10000	0	0
mol:Ca ++	-0.25	0.36	-9999	-0.75	137	137
BCAR1	0.005	0.005	-9999	-10000	0	0
PRKCB1	-0.2	0.29	-9999	-0.63	129	129
GNAQ	0.008	0.035	-9999	-0.74	1	1
GNAZ	-0.009	0.082	-9999	-0.74	6	6
GNAL	-0.006	0.067	-9999	-0.74	4	4
Gs family/GDP	-0.21	0.26	-9999	-0.62	123	123
ETA receptor/Endothelin-1/Gq/GTP	-0.065	0.23	-9999	-0.52	66	66
MAPK14	-0.24	0.28	-9999	-0.64	129	129
TRPC6	-0.086	0.3	-9999	-0.95	36	36
GNAI2	0	0	-9999	-10000	0	0
GNAI3	0	0	-9999	-10000	0	0
GNAI1	-0.002	0.034	-9999	-0.74	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.26	0.3	-9999	-0.63	154	154
ETB receptor/Endothelin-2	-0.4	0.29	-9999	-0.58	327	327
ETB receptor/Endothelin-3	-0.4	0.31	-9999	-0.61	321	321
ETB receptor/Endothelin-1	-0.38	0.34	-9999	-0.61	309	309
MAPK3	-0.22	0.36	-9999	-0.79	107	107
MAPK1	-0.22	0.36	-9999	-0.79	107	107
Rac1/GDP	-0.18	0.3	-9999	-0.63	122	122
cAMP biosynthetic process	-0.078	0.21	-9999	-0.59	44	44
MAPK8	-0.078	0.26	-9999	-0.61	66	66
SRC	0	0	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.17	0.17	-9999	-0.43	67	67
p130Cas/CRK/Src/PYK2	-0.19	0.32	-9999	-0.66	124	124
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.18	0.3	-9999	-0.63	122	122
COL1A2	-0.26	0.31	-9999	-0.75	92	92
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.05	0.19	-9999	-0.46	74	74
mol:DAG	-0.21	0.3	-9999	-0.66	127	127
MAP2K2	-0.2	0.32	-9999	-0.64	141	141
MAP2K1	-0.2	0.32	-9999	-0.64	141	141
EDNRA	0.015	0.14	-9999	-0.93	5	5
positive regulation of muscle contraction	-0.031	0.2	-9999	-0.58	33	33
Gq family/GDP	-0.2	0.3	-9999	-0.69	116	116
HRAS/GTP	-0.22	0.32	-9999	-0.68	128	128
PRKCH	-0.2	0.29	-9999	-0.65	117	117
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.2	0.29	-9999	-0.66	118	118
PRKCB	-0.22	0.32	-9999	-0.7	124	124
PRKCE	-0.2	0.29	-9999	-0.65	117	117
PRKCD	-0.2	0.29	-9999	-0.65	117	117
PRKCG	-0.22	0.3	-9999	-0.66	130	130
regulation of vascular smooth muscle contraction	-0.24	0.42	-9999	-1	84	84
PRKCQ	-0.23	0.34	-9999	-0.72	132	132
PLA2G4A	-0.16	0.29	-9999	-0.59	117	117
GNA14	-0.17	0.32	-9999	-0.74	114	114
GNA15	0.008	0.005	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
GNA11	0.008	0.005	-9999	-10000	0	0
Rac1/GTP	0.038	0.26	-9999	-0.54	51	51
MMP1	-0.23	0.24	-9999	-10000	0	0

×

Glypican 2 network

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

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

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

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.061	0.2	-10000	0	-0.71	41	41
CDKN2C	0.03	0.032	-10000	0	-10000	0	0
CDKN2A	-0.28	0.3	-10000	0	-0.59	224	224
CCND2	0.073	0.082	0.26	42	-10000	0	42
RB1	-0.079	0.085	-10000	0	-0.27	42	42
CDK4	0.084	0.088	0.26	42	-10000	0	42
CDK6	0.081	0.09	0.29	42	-10000	0	42
G1/S progression	0.072	0.091	0.26	42	-10000	0	42

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.063	0.22	-9999	-0.72	42	42
alphaM/beta2 Integrin/GPIbA	-0.064	0.21	-9999	-0.7	43	43
alphaM/beta2 Integrin/proMMP-9	-0.077	0.21	-9999	-0.68	43	43
PLAUR	0	0	-9999	-10000	0	0
HMGB1	0	0.003	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.059	0.2	-9999	-0.69	41	41
AGER	-0.69	0.2	-9999	-0.75	443	443
RAP1A	0	0	-9999	-10000	0	0
SELPLG	-0.048	0.18	-9999	-0.74	31	31
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.48	0.26	-9999	-0.84	110	110
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.03	0.13	-9999	-0.57	25	25
CYR61	-0.04	0.17	-9999	-0.74	26	26
TLN1	0	0	-9999	-10000	0	0
Rap1/GTP	-0.21	0.29	-9999	-0.69	92	92
RHOA	0	0	-9999	-10000	0	0
P-selectin oligomer	-0.19	0.32	-9999	-0.74	121	121
MYH2	-0.32	0.35	-9999	-0.79	138	138
MST1R	-0.048	0.18	-9999	-0.74	31	31
leukocyte activation during inflammatory response	-0.089	0.22	-9999	-0.58	65	65
APOB	-0.049	0.18	-9999	-0.72	33	33
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.006	0.067	-9999	-0.74	4	4
JAM3	0	0	-9999	-10000	0	0
GP1BA	-0.007	0.072	-9999	-0.71	5	5
alphaM/beta2 Integrin/CTGF	-0.075	0.24	-9999	-0.72	50	50
alphaM/beta2 Integrin	-0.26	0.37	-9999	-0.76	116	116
JAM3 homodimer	0	0	-9999	-10000	0	0
ICAM2	-0.048	0.18	-9999	-0.74	31	31
ICAM1	-0.065	0.21	-9999	-0.74	42	42
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.24	0.36	-9999	-0.74	116	116
cell adhesion	-0.063	0.21	-9999	-0.7	43	43
NFKB1	-0.47	0.3	-9999	-0.93	110	110
THY1	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.045	0.14	-9999	-0.45	48	48
alphaM/beta2 Integrin/LRP/tPA	-0.058	0.19	-9999	-0.64	41	41
IL6	-0.49	0.39	-9999	-1.1	112	112
ITGB2	-0.031	0.15	-9999	-0.74	20	20
elevation of cytosolic calcium ion concentration	-0.073	0.2	-9999	-0.64	41	41
alphaM/beta2 Integrin/JAM2/JAM3	-0.12	0.28	-9999	-0.64	90	90
JAM2	-0.11	0.26	-9999	-0.74	73	73
alphaM/beta2 Integrin/ICAM1	-0.11	0.28	-9999	-0.8	50	50
alphaM/beta2 Integrin/uPA/Plg	-0.076	0.2	-9999	-0.65	41	41
RhoA/GTP	-0.3	0.36	-9999	-0.85	114	114
positive regulation of phagocytosis	-0.18	0.27	-9999	-0.77	64	64
Ron/MSP	-0.037	0.14	-9999	-0.55	32	32
alphaM/beta2 Integrin/uPAR/uPA	-0.074	0.2	-9999	-0.65	41	41
alphaM/beta2 Integrin/uPAR	-0.059	0.2	-9999	-0.69	41	41
PLAU	-0.036	0.14	-9999	-0.57	30	30
PLAT	-0.007	0.063	-9999	-0.57	6	6
actin filament polymerization	-0.29	0.32	-9999	-0.73	138	138
MST1	-0.001	0.026	-9999	-0.57	1	1
alphaM/beta2 Integrin/lipoprotein(a)	-0.091	0.23	-9999	-0.59	65	65
TNF	-0.42	0.28	-9999	-0.85	110	110
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.081	0.22	-9999	-0.7	41	41
fibrinolysis	-0.076	0.2	-9999	-0.65	41	41
HCK	-0.008	0.075	-9999	-0.74	5	5
dendritic cell antigen processing and presentation	-0.24	0.36	-9999	-0.74	116	116
VTN	-0.29	0.36	-9999	-0.74	189	189
alphaM/beta2 Integrin/CYR61	-0.084	0.25	-9999	-0.73	55	55
LPA	-0.021	0.11	-9999	-0.57	18	18
LRP1	0	0	-9999	-10000	0	0
cell migration	-0.074	0.21	-9999	-0.66	42	42
FN1	-0.017	0.11	-9999	-0.74	11	11
alphaM/beta2 Integrin/Thy1	-0.059	0.2	-9999	-0.69	41	41
MPO	-0.031	0.15	-9999	-0.74	20	20
KNG1	-0.014	0.089	-9999	-0.57	12	12
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.25	0.33	-9999	-0.78	108	108
ELA2	0	0	-9999	-10000	0	0
PLG	-0.004	0.045	-9999	-0.57	3	3
CTGF	-0.026	0.14	-9999	-0.74	17	17
alphaM/beta2 Integrin/Hck	-0.064	0.22	-9999	-0.71	43	43
ITGAM	-0.062	0.21	-9999	-0.75	40	40
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.19	0.36	-9999	-0.66	136	136
HP	-0.23	0.34	-9999	-0.74	151	151
leukocyte adhesion	-0.44	0.3	-9999	-0.81	144	144
SELP	-0.19	0.32	-9999	-0.74	121	121

×

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	-0.02	0.086	-9999	-0.42	17	17
RGS9BP	-0.015	0.11	-9999	-0.74	10	10
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.002	0.037	-9999	-0.57	2	2
mol:Na +	-0.18	0.18	-9999	-0.35	241	241
mol:ADP	-0.008	0.092	-9999	-0.42	23	23
GNAT2	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.062	0.17	-9999	-0.49	61	61
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	-0.025	0.12	-9999	-0.57	21	21
CNGB3	-0.28	0.29	-9999	-0.57	239	239
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.21	0.2	-9999	-0.36	289	289
Cone PDE6	-0.054	0.14	-9999	-0.44	41	41
Cone Metarhodopsin II	-0.015	0.069	-9999	-0.32	23	23
Na + (4 Units)	-0.22	0.2	-9999	-0.4	168	168
GNAT2/GDP	-0.054	0.14	-9999	-0.42	61	61
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	0.009	0.005	-9999	-10000	0	0
Cone Transducin	-0.021	0.091	-9999	-0.44	18	18
SLC24A2	-0.11	0.22	-9999	-0.57	92	92
GNB3/GNGT2	-0.027	0.12	-9999	-0.51	26	26
GNB3	-0.011	0.077	-9999	-0.57	9	9
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	-0.002	0.037	-9999	-0.57	2	2
ARR3	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.18	0.18	-9999	-0.35	241	241
mol:Pi	-0.062	0.16	-9999	-0.49	61	61
Cone CNG Channel	-0.14	0.14	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.11	0.22	-9999	-0.57	92	92
RGS9	-0.081	0.23	-9999	-0.74	53	53
PDE6C	0	0	-9999	-10000	0	0
GNGT2	-0.026	0.14	-9999	-0.74	17	17
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0	0	-9999	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.057	0.21	-10000	0	-0.74	41	41
GNB1/GNG2	-0.069	0.089	-10000	0	-0.22	47	47
AKT1	-0.035	0.13	-10000	0	-0.22	36	36
EGF	-0.014	0.099	-10000	0	-0.69	10	10
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.036	0.13	-10000	0	-0.6	16	16
mol:Ca2+	-0.073	0.18	-10000	0	-0.31	165	165
LYN	-0.016	0.076	-10000	0	-0.53	7	7
RhoA/GTP	-0.046	0.059	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.081	0.2	-10000	0	-0.35	162	162
GNG2	-0.008	0.075	-10000	0	-0.74	5	5
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.017	0.1	-10000	0	-0.57	5	5
G beta5/gamma2	-0.091	0.12	-10000	0	-0.29	65	65
PRKCH	-0.088	0.21	-10000	0	-0.36	152	152
DNM1	-0.002	0.037	-10000	0	-0.57	2	2
TXA2/TP beta/beta Arrestin3	-0.002	0.014	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.022	0.12	-10000	0	-0.74	14	14
G12 family/GTP	-0.11	0.14	-10000	0	-0.31	163	163
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	-0.002	0.034	-10000	0	-0.74	1	1
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.038	0.13	0.41	19	-10000	0	19
mol:NADP	-0.005	0.058	-10000	0	-0.74	3	3
RAB11A	0	0	-10000	0	-10000	0	0
PRKG1	-0.058	0.2	-10000	0	-0.74	38	38
mol:IP3	-0.099	0.22	-10000	0	-0.39	165	165
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.15	0.3	-10000	0	-0.54	165	165
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.03	0.1	-10000	0	-0.6	7	7
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.018	0.085	-10000	0	-0.52	10	10
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.018	0.12	-10000	0	-0.74	12	12
PRKCB1	-0.099	0.22	-10000	0	-0.39	163	163
GNAQ	-0.002	0.034	-10000	0	-0.74	1	1
mol:L-citrulline	-0.005	0.058	-10000	0	-0.74	3	3
TXA2/TXA2-R family	-0.15	0.3	-10000	0	-0.55	164	164
LCK	-0.015	0.075	-10000	0	-0.53	7	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.018	0.089	-10000	0	-0.71	5	5
TXA2-R family/G12 family/GDP/G beta/gamma	0.019	0.044	-10000	0	-0.42	2	2
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.018	0.088	-10000	0	-0.71	5	5
MAPK14	-0.043	0.14	-10000	0	-0.25	40	40
TGM2/GTP	-0.12	0.26	-10000	0	-0.51	99	99
MAPK11	-0.043	0.14	-10000	0	-0.26	36	36
ARHGEF1	-0.034	0.11	-10000	0	-0.2	3	3
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	-0.098	0.23	-10000	0	-0.4	164	164
RAB11/GDP	0	0	-10000	0	-10000	0	0
ICAM1	-0.075	0.19	-10000	0	-0.32	161	161
cAMP biosynthetic process	-0.094	0.21	-10000	0	-0.4	97	97
Gq family/GTP/EBP50	-0.035	0.11	-10000	0	-0.54	3	3
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.015	0.071	-10000	0	-0.52	6	6
GNB5	0	0	-10000	0	-10000	0	0
GNB1	-0.002	0.034	-10000	0	-0.74	1	1
EGF/EGFR	0.024	0.095	-10000	0	-0.41	11	11
VCAM1	-0.068	0.17	-10000	0	-0.3	159	159
TP beta/Gq family/GDP/G beta5/gamma2	-0.017	0.1	-10000	0	-0.57	5	5
platelet activation	-0.059	0.19	-10000	0	-0.33	79	79
PGI2/IP	-0.014	0.088	-10000	0	-0.57	12	12
PRKACA	-0.021	0.1	-10000	0	-0.45	22	22
Gq family/GDP/G beta5/gamma2	-0.02	0.1	-10000	0	-0.59	5	5
TXA2/TP beta/beta Arrestin2	-0.002	0.011	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.006	0.11	-10000	0	-0.44	23	23
mol:DAG	-0.11	0.25	-10000	0	-0.44	162	162
EGFR	-0.022	0.12	-10000	0	-0.63	17	17
TXA2/TP alpha	-0.14	0.28	-10000	0	-0.55	97	97
Gq family/GTP	-0.066	0.12	-10000	0	-0.28	114	114
YES1	-0.015	0.071	-10000	0	-0.52	6	6
GNAI2/GTP	-0.017	0.084	-10000	0	-0.62	6	6
PGD2/DP	-0.016	0.095	-10000	0	-0.57	14	14
SLC9A3R1	-0.005	0.052	-10000	0	-0.57	4	4
FYN	-0.015	0.076	-10000	0	-0.57	6	6
mol:NO	-0.005	0.058	-10000	0	-0.74	3	3
GNA15	0	0	-10000	0	-10000	0	0
PGK/cGMP	-0.041	0.14	-10000	0	-0.5	40	40
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.052	0.16	-10000	0	-0.78	16	16
NOS3	-0.005	0.058	-10000	0	-0.74	3	3
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.088	0.21	-10000	0	-0.36	153	153
PRKCB	-0.097	0.22	-10000	0	-0.39	156	156
PRKCE	-0.087	0.21	-10000	0	-0.37	152	152
PRKCD	-0.096	0.22	-10000	0	-0.39	161	161
PRKCG	-0.11	0.23	-10000	0	-0.41	161	161
muscle contraction	-0.13	0.28	-10000	0	-0.5	164	164
PRKCZ	-0.081	0.2	-10000	0	-0.35	162	162
ARR3	0	0	-10000	0	-10000	0	0
TXA2/TP beta	-0.019	0.095	-10000	0	-0.67	7	7
PRKCQ	-0.11	0.23	-10000	0	-0.4	168	168
MAPKKK cascade	-0.13	0.27	-10000	0	-0.48	166	166
SELE	-0.11	0.23	-10000	0	-0.42	159	159
TP beta/GNAI2/GDP/G beta/gamma	-0.022	0.1	-10000	0	-0.73	7	7
ROCK1	0	0	-10000	0	-10000	0	0
GNA14	-0.18	0.32	-10000	0	-0.74	114	114
chemotaxis	-0.17	0.34	-10000	0	-0.63	162	162
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

×

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	0.26	-9999	-0.68	71	71
AP1	-0.19	0.26	-9999	-0.65	98	98
mol:PIP3	-0.16	0.29	-9999	-0.67	82	82
IKBKB	-0.07	0.16	-9999	-0.34	76	76
AKT1	-0.18	0.24	-9999	-0.67	67	67
IKBKG	-0.07	0.16	-9999	-0.34	76	76
MS4A2	-0.17	0.31	-9999	-0.75	109	109
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0	0.002	-9999	-10000	0	0
MAP3K1	-0.1	0.23	-9999	-0.54	77	77
mol:Ca2+	-0.11	0.21	-9999	-0.46	82	82
LYN	0.004	0.05	-9999	-0.77	2	2
CBLB	-0.16	0.24	-9999	-0.65	70	70
SHC1	0	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.057	0.15	-9999	-0.44	62	62
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.002	0.034	-9999	-0.74	1	1
PLD2	-0.21	0.29	-9999	-0.8	66	66
PTPN13	-0.13	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	70	70
SYK	0.006	0.036	-9999	-0.77	1	1
GRB2	0	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.2	0.27	-9999	-0.7	83	83
LAT	-0.16	0.24	-9999	-0.65	70	70
PAK2	-0.12	0.26	-9999	-0.61	81	81
NFATC2	-0.18	0.33	-9999	-0.94	66	66
HRAS	-0.14	0.29	-9999	-0.7	81	81
GAB2	-0.018	0.12	-9999	-0.74	12	12
PLA2G1B	-0.003	0.037	-9999	-10000	0	0
Fc epsilon R1	-0.26	0.34	-9999	-0.64	194	194
Antigen/IgE/Fc epsilon R1	-0.24	0.32	-9999	-0.59	194	194
mol:GDP	-0.16	0.31	-9999	-0.75	82	82
JUN	0	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0	0.002	-9999	-10000	0	0
FOS	-0.085	0.24	-9999	-0.74	55	55
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.17	0.26	-9999	-0.67	73	73
CHUK	-0.07	0.16	-9999	-0.34	75	75
KLRG1	-0.16	0.24	-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	-0.65	70	70
negative regulation of mast cell degranulation	-0.14	0.22	-9999	-0.58	70	70
BTK	-0.2	0.33	-9999	-0.81	86	86
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.2	0.32	-9999	-0.89	67	67
GAB2/PI3K/SHP2	-0.19	0.27	-9999	-0.75	67	67
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.17	0.25	-9999	-0.72	66	66
RAF1	0.025	0.028	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.23	0.32	-9999	-0.87	67	67
FCER1G	-0.016	0.13	-9999	-0.76	14	14
FCER1A	-0.22	0.35	-9999	-0.76	143	143
Antigen/IgE/Fc epsilon R1/Fyn	-0.22	0.31	-9999	-0.82	71	71
MAPK3	0.033	0.024	-9999	-10000	0	0
MAPK1	0.033	0.024	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
MAPK8	-0.021	0.071	-9999	-10000	0	0
DUSP1	-0.095	0.25	-9999	-0.74	62	62
NF-kappa-B/RelA	-0.059	0.076	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.13	0.25	-9999	-0.63	69	69
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.16	0.24	-9999	-0.63	77	77
FER	-0.16	0.24	-9999	-0.65	70	70
RELA	0	0	-9999	-10000	0	0
ITK	-0.078	0.18	-9999	-0.66	37	37
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.16	0.31	-9999	-0.75	82	82
cytokine secretion	-0.043	0.055	-9999	-10000	0	0
SPHK1	-0.16	0.24	-9999	-0.65	70	70
PTK2	-0.14	0.26	-9999	-0.67	69	69
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.21	0.29	-9999	-0.74	83	83
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.15	0.28	-9999	-0.64	82	82
MAP2K2	0.03	0.024	-9999	-10000	0	0
MAP2K1	0.03	0.024	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
KLRG1/SHP2	-0.14	0.22	-9999	-0.59	70	70
MAP2K4	0.009	0.013	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.24	0.34	-9999	-0.65	150	150
mol:Choline	-0.2	0.28	-9999	-0.78	66	66
SHC/Grb2/SOS1	-0.14	0.22	-9999	-0.6	69	69
FYN	-0.002	0.034	-9999	-0.74	1	1
DOK1	0	0	-9999	-10000	0	0
PXN	-0.12	0.24	-9999	-0.6	69	69
HCLS1	-0.16	0.24	-9999	-0.65	70	70
PRKCB	-0.11	0.22	-9999	-0.49	83	83
FCGR2B	-0.014	0.1	-9999	-0.74	9	9
IGHE	-0.004	0.009	-9999	-10000	0	0
KLRG1/SHIP	-0.14	0.22	-9999	-0.6	70	70
LCP2	-0.011	0.089	-9999	-0.74	7	7
PLA2G4A	-0.16	0.24	-9999	-0.65	72	72
RASA1	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.2	0.28	-9999	-0.78	66	66
IKK complex	-0.039	0.12	-9999	-0.27	29	29
WIPF1	0	0	-9999	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.043	0.056	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.099	0.14	-9999	-0.43	20	20
JUN	-0.063	0.14	-9999	-0.42	17	17
HRAS	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.17	0.22	-9999	-0.48	124	124
RAP1A	0	0	-9999	-10000	0	0
FRS2	0	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.17	0.22	-9999	-0.48	124	124
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.16	0.22	-9999	-0.48	119	119
RHOA	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.15	0.2	-9999	-0.66	21	21
GRB7	-0.005	0.052	-9999	-0.57	4	4
RET51/GFRalpha1/GDNF	-0.17	0.22	-9999	-0.48	124	124
MAPKKK cascade	-0.13	0.18	-9999	-0.59	19	19
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.16	0.22	-9999	-0.42	182	182
lamellipodium assembly	-0.095	0.13	-9999	-0.4	20	20
RET51/GFRalpha1/GDNF/SHC	-0.17	0.22	-9999	-0.48	124	124
PIK3CA	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.16	0.22	-9999	-0.48	119	119
RET9/GFRalpha1/GDNF/Shank3	-0.16	0.22	-9999	-0.49	119	119
MAPK3	-0.14	0.18	-9999	-0.62	21	21
DOK1	0	0	-9999	-10000	0	0
DOK6	-0.065	0.21	-9999	-0.74	42	42
PXN	0	0	-9999	-10000	0	0
neurite development	-0.14	0.18	-9999	-0.55	39	39
DOK5	-0.007	0.069	-9999	-0.67	5	5
GFRA1	-0.18	0.32	-9999	-0.74	119	119
MAPK8	-0.096	0.13	-9999	-0.44	17	17
HRAS/GTP	-0.14	0.2	-9999	-0.62	21	21
tube development	-0.15	0.21	-9999	-0.46	119	119
MAPK1	-0.14	0.18	-9999	-0.62	21	21
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.1	0.14	-9999	-0.33	119	119
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
PDLIM7	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.19	0.25	-9999	-0.62	71	71
SHC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.22	-9999	-0.48	124	124
RET51/GFRalpha1/GDNF/Dok5	-0.17	0.23	-9999	-0.49	125	125
PRKCA	-0.003	0.048	-9999	-0.74	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.11	0.15	-9999	-0.36	119	119
PIK3R1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.14	-9999	-0.33	119	119
RET51/GFRalpha1/GDNF/Grb7	-0.17	0.22	-9999	-0.49	125	125
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.021	0.11	-9999	-0.58	17	17
DOK4	0	0	-9999	-10000	0	0
JNK cascade	-0.061	0.14	-9999	-0.41	17	17
RET9/GFRalpha1/GDNF/FRS2	-0.16	0.22	-9999	-0.42	182	182
SHANK3	-0.003	0.048	-9999	-0.74	2	2
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.34	119	119
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.1	0.14	-9999	-0.47	17	17
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.1	0.14	-9999	-0.47	17	17
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.48	17	17
PI3K	-0.14	0.2	-9999	-0.48	120	120
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.15	0.21	-9999	-0.46	119	119
GRB10	0	0	-9999	-10000	0	0
activation of MAPKK activity	-0.1	0.14	-9999	-0.47	17	17
RET51/GFRalpha1/GDNF/FRS2	-0.17	0.22	-9999	-0.48	124	124
GAB1	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
IRS2	-0.005	0.058	-9999	-0.74	3	3
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.1	0.14	-9999	-0.48	17	17
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.22	-9999	-0.49	125	125
GRB2	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GDNF	-0.093	0.21	-9999	-0.57	78	78
RAC1	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.17	0.22	-9999	-0.48	124	124
Rac1/GTP	-0.11	0.16	-9999	-0.48	20	20
RET9/GFRalpha1/GDNF	-0.18	0.24	-9999	-0.47	182	182
GFRalpha1/GDNF	-0.2	0.27	-9999	-0.54	182	182

×

IL4-mediated signaling events

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
BCL2L1	-0.39	0.54	-10000	0	-1.2	98	98
STAT6 (cleaved dimer)	-0.45	0.48	-10000	0	-1.2	104	104
IGHG1	-0.12	0.19	-10000	0	-10000	0	0
IGHG3	-0.38	0.51	-10000	0	-1.2	103	103
AKT1	-0.14	0.26	-10000	0	-1	7	7
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	-1.1	8	8
THY1	-0.39	0.54	-10000	0	-1.2	98	98
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	-0.82	22	22
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.16	0.27	-10000	0	-1.1	8	8
SP1	0.017	0.002	-10000	0	-10000	0	0
INPP5D	-0.002	0.034	-10000	0	-0.74	1	1
SOCS5	0.019	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.44	0.48	-10000	0	-1.2	106	106
SOCS1	-0.23	0.35	-10000	0	-0.78	65	65
SOCS3	-0.16	0.27	-10000	0	-1	8	8
FCER2	-0.34	0.5	-10000	0	-1.3	65	65
PARP14	0.007	0.006	-10000	0	-10000	0	0
CCL17	-0.46	0.62	-10000	0	-1.4	120	120
GRB2	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.12	0.23	-10000	0	-0.9	7	7
T cell proliferation	-0.38	0.54	-10000	0	-1.2	99	99
IL4R/JAK1	-0.39	0.53	-10000	0	-1.2	98	98
EGR2	-0.41	0.56	-10000	0	-1.3	106	106
JAK2	-0.003	0.034	-10000	0	-10000	0	0
JAK3	0.012	0.007	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
JAK1	0.009	0.014	-10000	0	-10000	0	0
COL1A2	-0.1	0.18	-10000	0	-0.65	2	2
CCL26	-0.42	0.55	-10000	0	-1.3	100	100
IL4R	-0.42	0.57	-10000	0	-1.3	98	98
PTPN6	0.019	0.014	-10000	0	-10000	0	0
IL13RA2	-0.42	0.57	-10000	0	-1.3	110	110
IL13RA1	-0.003	0.034	-10000	0	-10000	0	0
IRF4	-0.17	0.36	-10000	0	-0.94	71	71
ARG1	-0.12	0.24	-10000	0	-0.81	29	29
CBL	-0.18	0.29	-10000	0	-0.95	11	11
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	71	71
CD40LG	-0.12	0.29	-10000	0	-0.74	85	85
MAPK14	-0.18	0.3	-10000	0	-1	10	10
mitosis	-0.14	0.25	-10000	0	-0.92	7	7
STAT6	-0.46	0.63	-10000	0	-1.4	103	103
SPI1	-0.043	0.19	-10000	0	-0.74	34	34
RPS6KB1	-0.13	0.24	-10000	0	-0.93	6	6
STAT6 (dimer)	-0.46	0.63	-10000	0	-1.4	103	103
STAT6 (dimer)/PARP14	-0.42	0.58	-10000	0	-1.3	103	103
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	-0.87	28	28
FRAP1	-0.14	0.26	-10000	0	-1	7	7
LTA	-0.39	0.54	-10000	0	-1.2	98	98
FES	-0.002	0.034	-10000	0	-0.74	1	1
T-helper 1 cell differentiation	0.44	0.61	1.4	103	-10000	0	103
CCL11	-0.38	0.52	-10000	0	-1.2	102	102
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.15	0.27	-10000	0	-1.2	7	7
IL2RG	0	0.095	-10000	0	-0.73	8	8
IL10	-0.39	0.54	-10000	0	-1.2	98	98
IRS1	0	0	-10000	0	-10000	0	0
IRS2	-0.005	0.058	-10000	0	-0.74	3	3
IL4	-0.078	0.14	-10000	0	-10000	0	0
IL5	-0.39	0.54	-10000	0	-1.2	98	98
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.31	0.42	-10000	0	-0.91	98	98
COL1A1	-0.14	0.23	-10000	0	-0.69	16	16
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.4	0.55	-10000	0	-1.4	68	68
IL2R gamma/JAK3	-0.004	0.072	-10000	0	-0.55	8	8
TFF3	-0.44	0.62	-10000	0	-1.4	103	103
ALOX15	-0.62	0.76	-10000	0	-1.6	174	174
MYBL1	-0.001	0.026	-10000	0	-0.57	1	1
T-helper 2 cell differentiation	-0.31	0.43	-10000	0	-0.94	100	100
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	-1.2	7	7
mol:PI-3-4-5-P3	-0.14	0.26	-10000	0	-1	7	7
PI3K	-0.15	0.28	-10000	0	-1.1	7	7
DOK2	-0.066	0.21	-10000	0	-0.74	43	43
ETS1	0	0.11	-10000	0	-0.71	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.11	0.22	-10000	0	-0.87	7	7
ITGB3	-0.4	0.55	-10000	0	-1.3	90	90
PIGR	-0.8	0.83	-10000	0	-1.6	254	254
IGHE	0.028	0.044	-10000	0	-10000	0	0
MAPKKK cascade	-0.11	0.21	-10000	0	-0.85	7	7
BCL6	0.001	0.004	-10000	0	-10000	0	0
OPRM1	-0.4	0.54	-10000	0	-1.2	98	98
RETNLB	-0.4	0.54	-10000	0	-1.2	98	98
SELP	-0.56	0.74	-10000	0	-1.6	147	147
AICDA	-0.38	0.51	-10000	0	-1.2	98	98

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.032	0.03	-9999	-10000	0	0
VDR	-0.002	0.034	-9999	-0.74	1	1
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.13	0.18	-9999	-0.54	10	10
RXRs/LXRs/DNA/Oxysterols	-0.098	0.16	-9999	-0.58	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	0.06	-9999	-0.31	19	19
RXRs/NUR77	-0.28	0.27	-9999	-0.49	277	277
RXRs/PPAR	-0.18	0.2	-9999	-0.56	44	44
NCOR2	-0.002	0.034	-9999	-0.74	1	1
VDR/VDR/Vit D3	-0.001	0.026	-9999	-0.57	1	1
RARs/VDR/DNA/Vit D3	-0.003	0.032	-9999	-0.41	3	3
RARA	0	0	-9999	-10000	0	0
NCOA1	0	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.002	0.034	-9999	-0.74	1	1
RARs/RARs/DNA/9cRA	-0.002	0.027	-9999	-0.42	2	2
RARG	0	0	-9999	-10000	0	0
RPS6KB1	0.057	0.053	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.013	0.061	-9999	-0.31	20	20
THRA	0	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.001	0.026	-9999	-0.57	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	-0.23	0.22	-9999	-0.43	253	253
NR1H4	-0.005	0.052	-9999	-0.57	4	4
RXRs/LXRs/DNA	-0.21	0.2	-9999	-0.56	10	10
NR1H2	0.015	0.004	-9999	-10000	0	0
NR1H3	0.014	0.005	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.21	0.2	-9999	-0.4	254	254
NR4A1	-0.1	0.25	-9999	-0.74	65	65
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.12	0.14	-9999	-0.26	183	183
RXRG	-0.38	0.37	-9999	-0.74	253	253
RXR alpha/CCPG	0	0	-9999	-10000	0	0
RXRA	0.015	0.004	-9999	-10000	0	0
RXRB	0.014	0.005	-9999	-10000	0	0
THRB	-0.026	0.14	-9999	-0.74	17	17
PPARG	-0.089	0.24	-9999	-0.74	58	58
PPARD	0	0	-9999	-10000	0	0
TNF	-0.1	0.23	-9999	-1.2	13	13
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	-0.097	0.16	-9999	-0.58	13	13
PPARA	0	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.003	0.048	-9999	-0.74	2	2
RXRs/NUR77/BCL2	-0.2	0.2	-9999	-0.36	277	277
SREBF1	-0.082	0.15	-9999	-0.6	9	9
RXRs/RXRs/DNA/9cRA	-0.23	0.22	-9999	-0.43	253	253
ABCA1	-0.082	0.15	-9999	-0.6	9	9
RARs/THRs	-0.016	0.079	-9999	-0.4	19	19
RXRs/FXR	-0.23	0.22	-9999	-0.43	253	253
BCL2	-0.001	0.026	-9999	-0.57	1	1

×

BMP receptor signaling

Figure 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
BMP7/BMPR2/BMPR1A-1B/FS	-0.18	0.21	-9999	-0.56	73	73
SMAD6-7/SMURF1	-0.053	0.15	-9999	-0.48	53	53
NOG	-0.027	0.14	-9999	-0.73	18	18
SMAD9	-0.1	0.22	-9999	-0.59	72	72
SMAD4	0	0	-9999	-10000	0	0
SMAD5	-0.023	0.13	-9999	-0.47	23	23
BMP7/USAG1	-0.25	0.27	-9999	-0.5	238	238
SMAD5/SKI	-0.05	0.11	-9999	-0.47	18	18
SMAD1	0.033	0.027	-9999	-10000	0	0
BMP2	-0.098	0.25	-9999	-0.74	64	64
SMAD1/SMAD1/SMAD4	-0.035	0.096	-9999	-10000	0	0
BMPR1A	0	0	-9999	-10000	0	0
BMPR1B	-0.057	0.2	-9999	-0.74	37	37
BMPR1A-1B/BAMBI	-0.04	0.13	-9999	-0.48	39	39
AHSG	-0.018	0.099	-9999	-0.57	15	15
CER1	-0.002	0.037	-9999	-0.57	2	2
BMP2-4/CER1	-0.075	0.18	-9999	-0.5	70	70
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.067	0.14	-9999	-0.5	29	29
BMP2-4 (homodimer)	-0.085	0.21	-9999	-0.58	71	71
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.045	0.14	-9999	-0.45	48	48
RGMA	-0.062	0.18	-9999	-0.57	52	52
SMURF1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.062	0.13	-9999	-0.45	29	29
BMP2-4/USAG1	-0.16	0.27	-9999	-0.55	143	143
SMAD6/SMURF1/SMAD5	-0.05	0.11	-9999	-0.45	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	-0.076	0.18	-9999	-0.5	73	73
SMAD5/SMAD5/SMAD4	-0.05	0.11	-9999	-0.47	18	18
MAPK1	0	0	-9999	-10000	0	0
TAK1/TAB family	-0.05	0.1	-9999	-0.45	17	17
BMP7 (homodimer)	-0.2	0.28	-9999	-0.58	169	169
NUP214	0	0	-9999	-10000	0	0
BMP6/FETUA	-0.028	0.11	-9999	-0.48	28	28
SMAD1/SKI	-0.004	0.012	-9999	-10000	0	0
SMAD6	-0.08	0.23	-9999	-0.74	52	52
CTDSP2	0	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.084	0.19	-9999	-0.5	70	70
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.34	0.28	-9999	-0.57	288	288
BMPR2 (homodimer)	0	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.043	0.15	-9999	-0.56	37	37
CHRDL1	-0.39	0.37	-9999	-0.74	251	251
ENDOFIN/SMAD1	-0.004	0.012	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.04	0.11	-9999	-10000	0	0
SMAD6/SMURF1	0	0	-9999	-10000	0	0
BAMBI	-0.005	0.06	-9999	-0.66	4	4
SMURF2	0	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.32	0.3	-9999	-0.55	277	277
BMP2-4/GREM1	-0.28	0.22	-9999	-0.4	331	331
SMAD7	-0.002	0.034	-9999	-0.74	1	1
SMAD8A/SMAD8A/SMAD4	-0.096	0.2	-9999	-0.55	72	72
SMAD1/SMAD6	-0.004	0.012	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.2	0.28	-9999	-0.58	169	169
BMP6	-0.02	0.12	-9999	-0.74	13	13
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.058	0.12	-9999	-0.41	30	30
PPM1A	0	0	-9999	-10000	0	0
SMAD1/SMURF2	-0.004	0.012	-9999	-10000	0	0
SMAD7/SMURF1	-0.001	0.025	-9999	-0.56	1	1
CTDSPL	0	0	-9999	-10000	0	0
PPP1CA	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0	0	-9999	-10000	0	0
PPP1R15A	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.084	0.14	-9999	-0.46	41	41
CHRD	-0.004	0.054	-9999	-0.68	3	3
BMPR2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.071	0.14	-9999	-0.5	29	29
BMP4	-0.015	0.1	-9999	-0.72	10	10
FST	-0.092	0.21	-9999	-0.57	77	77
BMP2-4/NOG	-0.09	0.21	-9999	-0.53	81	81
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.13	0.18	-9999	-0.5	43	43

×

PLK1 signaling events

Figure 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	251	-10000	0	251
BUB1B	-0.13	0.098	-10000	0	-0.22	194	194
PLK1	-0.013	0.036	-10000	0	-0.13	8	8
PLK1S1	-0.003	0.02	-10000	0	-10000	0	0
KIF2A	-0.004	0.033	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	-0.013	0.036	-10000	0	-0.13	8	8
GOLGA2	0	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.2	0.23	-10000	0	-0.41	236	236
WEE1	-0.006	0.038	-10000	0	-10000	0	0
cytokinesis	-0.11	0.12	-10000	0	-0.25	158	158
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	-0.46	53	53
CENPE	-0.041	0.11	-10000	0	-0.35	54	54
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.004	0.032	-10000	0	-10000	0	0
PPP2CA	0	0	-10000	0	-10000	0	0
FZR1	0	0	-10000	0	-10000	0	0
TPX2	-0.06	0.048	-10000	0	-0.12	4	4
PAK1	0.002	0.026	-10000	0	-0.57	1	1
SPC24	-0.17	0.26	-10000	0	-0.57	144	144
FBXW11	0	0	-10000	0	-10000	0	0
CLSPN	-0.013	0.039	-10000	0	-0.15	5	5
GORASP1	0	0	-10000	0	-10000	0	0
metaphase	0	0.003	-10000	0	-0.012	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.007	0.02	-10000	0	-0.066	4	4
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-10000	0	0
STAG2	0	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.001	0.008	-10000	0	-10000	0	0
spindle elongation	-0.013	0.036	-10000	0	-0.13	8	8
ODF2	0.004	0.005	-10000	0	-10000	0	0
BUB1	-0.005	0.032	-10000	0	-10000	0	0
TPT1	-0.003	0.02	-10000	0	-10000	0	0
CDC25C	-0.077	0.057	-10000	0	-10000	0	0
CDC25B	0.009	0.003	-10000	0	-10000	0	0
SGOL1	-0.071	0.074	-10000	0	-0.14	251	251
RHOA	0	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.029	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	308	308
PLK1/PBIP1	-0.03	0.063	-10000	0	-0.33	18	18
mitosis	-0.001	0.005	0.022	13	-10000	0	13
FBXO5	-0.004	0.031	-10000	0	-10000	0	0
CDC2	-0.001	0.004	-10000	0	-0.012	14	14
NDC80	-0.2	0.27	-10000	0	-0.57	167	167
metaphase plate congression	-0.007	0.025	-10000	0	-10000	0	0
ERCC6L	-0.11	0.16	-10000	0	-0.49	36	36
NLP/gamma Tubulin	-0.005	0.021	-10000	0	-10000	0	0
microtubule cytoskeleton organization	-0.003	0.02	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-10000	0	0
PPP1R12A	0	0	-10000	0	-10000	0	0
interphase	0	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.2	0.2	-10000	0	-0.37	256	256
GRASP65/GM130/RAB1/GTP/PLK1	-0.008	0.015	-10000	0	-10000	0	0
RAB1A	0	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.001	0.028	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.043	0.035	-10000	0	-10000	0	0
microtubule-based process	-0.18	0.17	-10000	0	-0.34	249	249
Golgi organization	-0.013	0.036	-10000	0	-0.13	8	8
Cohesin/SA2	-0.019	0.024	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.3	0.29	-10000	0	-0.57	249	249
APC/C/CDC20	-0.22	0.16	-10000	0	-0.34	308	308
PPP2R1A	0	0	-10000	0	-10000	0	0
chromosome segregation	-0.029	0.062	-10000	0	-0.32	18	18
PRC1	-0.057	0.17	-10000	0	-0.57	48	48
ECT2	-0.016	0.073	-10000	0	-0.35	18	18
C13orf34	-0.003	0.028	-10000	0	-10000	0	0
NUDC	-0.007	0.025	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.13	0.097	-10000	0	-0.22	194	194
spindle assembly	-0.008	0.029	-10000	0	-10000	0	0
spindle stabilization	-0.003	0.02	-10000	0	-10000	0	0
APC/C/HCDH1	0	0	-10000	0	-10000	0	0
MKLP2/PLK1	-0.18	0.17	-10000	0	-0.34	249	249
CCNB1	-0.058	0.19	-10000	0	-0.57	57	57
PPP1CB	0	0	-10000	0	-10000	0	0
BTRC	0	0	-10000	0	-10000	0	0
ROCK2	0.001	0.025	-10000	0	-10000	0	0
TUBG1	-0.003	0.02	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.03	0.076	-10000	0	-0.29	4	4
MLF1IP	-0.011	0.083	-10000	0	-0.43	18	18
INCENP	0.004	0.006	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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
PCK2	0.06	0.099	0.35	3	-10000	0	3
SMARCC2	0.011	0	-10000	0	-10000	0	0
SMARCC1	0.011	0	-10000	0	-10000	0	0
TBX21	-0.2	0.35	-10000	0	-0.88	80	80
SUMO2	0.002	0.006	-10000	0	-10000	0	0
STAT1 (dimer)	0.017	0	-10000	0	-10000	0	0
FKBP4	-0.001	0.026	-10000	0	-0.57	1	1
FKBP5	0	0	-10000	0	-10000	0	0
GR alpha/HSP90/FKBP51/HSP90	0.13	0.1	0.34	37	-10000	0	37
PRL	-0.085	0.12	-10000	0	-0.63	1	1
cortisol/GR alpha (dimer)/TIF2	0.31	0.25	0.6	147	-10000	0	147
RELA	-0.046	0.1	-10000	0	-10000	0	0
FGG	-0.13	0.47	0.54	55	-0.62	226	281
GR beta/TIF2	0.14	0.12	0.38	41	-0.39	1	42
IFNG	-0.34	0.24	-10000	0	-0.76	66	66
apoptosis	0.028	0.12	0.46	2	-0.55	1	3
CREB1	0.001	0.028	-10000	0	-10000	0	0
histone acetylation	-0.012	0.15	0.34	3	-0.38	24	27
BGLAP	-0.096	0.14	-10000	0	-0.51	13	13
GR/PKAc	0.12	0.1	0.35	23	-10000	0	23
NF kappa B1 p50/RelA	-0.083	0.18	-10000	0	-0.48	37	37
SMARCD1	0.011	0	-10000	0	-10000	0	0
MDM2	0.11	0.098	0.3	53	-0.31	1	54
GATA3	-0.014	0.13	-10000	0	-0.71	17	17
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.17	0.42	-10000	0	-1.3	52	52
GSK3B	0.002	0.006	-10000	0	-10000	0	0
NR1I3	0.047	0.11	0.47	1	-10000	0	1
CSN2	0.16	0.16	0.44	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	-0.57	48	48
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.095	0.14	0.34	32	-10000	0	32
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.034	0.16	0.46	1	-0.9	9	10
JUN	-0.29	0.16	-10000	0	-0.52	93	93
IL4	-0.11	0.15	-10000	0	-0.53	13	13
CDK5R1	-0.009	0.078	-10000	0	-0.57	9	9
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.44	0.24	-10000	0	-0.6	258	258
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.099	0.33	35	-10000	0	35
cortisol/GR alpha (monomer)	0.37	0.32	0.72	163	-10000	0	163
NCOA2	-0.002	0.034	-10000	0	-0.74	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.17	0.24	-10000	0	-0.83	55	55
AP-1/NFAT1-c-4	-0.53	0.24	-10000	0	-0.76	172	172
AFP	-0.19	0.15	-10000	0	-0.65	16	16
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.18	0.15	0.45	61	-10000	0	61
TP53	0.029	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.54	0.25	-10000	0	-0.71	263	263
KRT14	-0.37	0.22	-10000	0	-0.6	145	145
TBP	0.017	0	-10000	0	-10000	0	0
CREBBP	0.11	0.066	0.34	1	-10000	0	1
HDAC1	0	0.004	-10000	0	-10000	0	0
HDAC2	0.01	0.03	-10000	0	-10000	0	0
AP-1	-0.53	0.25	-10000	0	-0.76	179	179
MAPK14	0.002	0.005	-10000	0	-10000	0	0
MAPK10	-0.011	0.095	-10000	0	-0.74	8	8
MAPK11	0.002	0.006	-10000	0	-10000	0	0
KRT5	-0.56	0.25	-10000	0	-0.8	158	158
interleukin-1 receptor activity	0.008	0.028	-10000	0	-10000	0	0
NCOA1	0.012	0.002	-10000	0	-10000	0	0
STAT1	0.017	0	-10000	0	-10000	0	0
CGA	-0.12	0.17	-10000	0	-0.56	24	24
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.2	0.19	0.49	102	-10000	0	102
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	69	69
NFKB1	-0.046	0.1	-10000	0	-0.31	3	3
MAPK8	-0.24	0.17	-10000	0	-0.48	108	108
MAPK9	0.002	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.025	0.12	0.46	2	-0.58	1	3
BAX	0.026	0.015	-10000	0	-10000	0	0
POMC	-0.21	0.24	-10000	0	-0.74	42	42
EP300	0.11	0.066	0.34	1	-10000	0	1
cortisol/GR alpha (dimer)/p53	0.33	0.25	0.62	151	-10000	0	151
proteasomal ubiquitin-dependent protein catabolic process	0.076	0.074	0.27	9	-0.27	1	10
SGK1	0.17	0.076	-10000	0	-10000	0	0
IL13	-0.27	0.2	-10000	0	-0.8	34	34
IL6	-0.34	0.53	-10000	0	-1.3	101	101
PRKACG	-0.001	0.026	-10000	0	-0.57	1	1
IL5	-0.24	0.17	-10000	0	-0.78	21	21
IL2	-0.34	0.21	-10000	0	-0.7	67	67
CDK5	0.001	0.004	-10000	0	-10000	0	0
PRKACB	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.2	0.29	-10000	0	-0.75	65	65
CDK5R1/CDK5	-0.006	0.056	-10000	0	-0.41	9	9
NF kappa B1 p50/RelA/PKAc	-0.059	0.12	-10000	0	-0.48	4	4
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.3	0.23	0.57	147	-10000	0	147
SMARCA4	0.011	0	-10000	0	-10000	0	0
chromatin remodeling	0.19	0.14	0.41	90	-10000	0	90
NF kappa B1 p50/RelA/Cbp	0.036	0.18	0.37	14	-0.48	4	18
JUN (dimer)	-0.29	0.16	-10000	0	-0.52	93	93
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.42	0.51	-10000	0	-1.1	176	176
NR3C1	0.2	0.2	0.52	92	-10000	0	92
NR4A1	-0.1	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	-0.55	1	3
cortisol/GR alpha (dimer)/Src-1	0.32	0.25	0.6	158	-10000	0	158
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	153	153
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.19	0.14	0.41	88	-10000	0	88
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.3	0.23	0.57	147	-10000	0	147
mol:cortisol	0.2	0.2	0.44	149	-0.24	2	151
MMP1	-0.32	0.19	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

×

Arf6 signaling events

Figure 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
CENTA1/KIF3B	-0.017	0.094	-9999	0	-0.51	16	16
ARNO/beta Arrestin1-2	-0.17	0.24	-9999	0	-0.7	47	47
EGFR	-0.022	0.12	-9999	0	-0.63	17	17
EPHA2	-0.005	0.058	-9999	0	-0.74	3	3
USP6	0	0	-9999	0	-10000	0	0
IQSEC1	0	0	-9999	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.027	0.12	-9999	0	-0.5	26	26
ARRB2	0.007	0.011	-9999	0	-0.21	1	1
mol:GTP	0.015	0.026	-9999	0	-0.15	8	8
ARRB1	-0.14	0.29	-9999	0	-0.74	91	91
FBXO8	0	0	-9999	0	-10000	0	0
TSHR	-0.019	0.1	-9999	0	-0.57	16	16
EGF	-0.014	0.099	-9999	0	-0.69	10	10
somatostatin receptor activity	0	0	-9999	0	-0.001	141	141
ARAP2	-0.002	0.034	-9999	0	-0.74	1	1
mol:GDP	-0.12	0.16	-9999	0	-0.33	133	133
mol:PI-3-4-5-P3	0	0	-9999	0	-0.001	88	88
ITGA2B	-0.023	0.13	-9999	0	-0.74	15	15
ARF6	0	0	-9999	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.034	-9999	0	-0.43	3	3
ADAP1	-0.014	0.1	-9999	0	-0.74	9	9
KIF13B	-0.012	0.095	-9999	0	-0.74	8	8
HGF/MET	-0.12	0.23	-9999	0	-0.56	104	104
PXN	0	0	-9999	0	-10000	0	0
ARF6/GTP	-0.11	0.15	-9999	0	-0.31	141	141
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.023	0.1	-9999	0	-0.52	12	12
ADRB2	-0.21	0.33	-9999	0	-0.74	137	137
receptor agonist activity	0	0	-9999	0	0	143	143
actin filament binding	0	0	-9999	0	-0.001	141	141
SRC	0	0	-9999	0	-10000	0	0
ITGB3	-0.012	0.095	-9999	0	-0.74	8	8
GNAQ	-0.002	0.034	-9999	0	-0.74	1	1
EFA6/PI-4-5-P2	0	0.001	-9999	0	-0.001	115	115
ARF6/GDP	-0.013	0.071	-9999	0	-0.36	3	3
ARF6/GDP/GULP/ACAP1	-0.12	0.14	-9999	0	-0.43	46	46
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.021	0.092	-9999	0	-0.43	23	23
ACAP1	-0.003	0.043	-9999	0	-0.66	2	2
ACAP2	0	0	-9999	0	-10000	0	0
LHCGR/beta Arrestin2	-0.001	0.014	-9999	0	-0.31	1	1
EFNA1	0	0	-9999	0	-10000	0	0
HGF	-0.16	0.3	-9999	0	-0.74	101	101
CYTH3	0.009	0	-9999	0	-10000	0	0
CYTH2	0.005	0.002	-9999	0	-10000	0	0
NCK1	0	0	-9999	0	-10000	0	0
fibronectin binding	0	0	-9999	0	0	101	101
endosomal lumen acidification	0	0	0	9	-0.001	90	99
microtubule-based process	0	0	-9999	0	-10000	0	0
GULP1	-0.014	0.1	-9999	0	-0.74	9	9
GNAQ/ARNO	0.004	0.02	-9999	0	-0.41	1	1
mol:Phosphatidic acid	0	0	-9999	0	-10000	0	0
PIP3-E	0	0	-9999	0	0	10	10
MET	-0.004	0.054	-9999	0	-0.68	3	3
GNA14	-0.18	0.32	-9999	0	-0.74	114	114
GNA15	0	0	-9999	0	-10000	0	0
GIT1	0	0	-9999	0	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	0	-0.001	135	135
GNA11	0	0	-9999	0	-10000	0	0
LHCGR	-0.001	0.026	-9999	0	-0.57	1	1
AGTR1	-0.31	0.36	-9999	0	-0.74	199	199
desensitization of G-protein coupled receptor protein signaling pathway	-0.001	0.014	-9999	0	-0.31	1	1
IPCEF1/ARNO	-0.018	0.079	-9999	0	-0.75	1	1
alphaIIb/beta3 Integrin	-0.027	0.12	-9999	0	-0.56	23	23

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.034	-9999	-0.74	1	1
alphaV beta3 Integrin	-0.009	0.071	-9999	-0.56	8	8
PTK2	-0.1	0.16	-9999	-0.59	37	37
positive regulation of JNK cascade	-0.034	0.09	-9999	-0.34	37	37
CDC42/GDP	-0.022	0.13	-9999	-0.46	37	37
Rac1/GDP	-0.02	0.13	-9999	-0.46	37	37
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0	0	-9999	-10000	0	0
CTNNB1	0	0	-9999	-10000	0	0
CDC42/GTP	-0.041	0.11	-9999	-0.42	37	37
nectin-3/I-afadin	-0.043	0.15	-9999	-0.56	37	37
RAPGEF1	-0.033	0.15	-9999	-0.53	37	37
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.046	0.17	-9999	-0.62	37	37
PDGFB-D/PDGFRB	-0.002	0.034	-9999	-0.74	1	1
TLN1	-0.02	0.15	-9999	-0.51	31	31
Rap1/GTP	-0.034	0.097	-9999	-0.39	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	-0.043	0.15	-9999	-0.56	37	37
PVR	0	0	-9999	-10000	0	0
Necl-5(dimer)	0	0	-9999	-10000	0	0
mol:GDP	-0.033	0.16	-9999	-0.58	37	37
MLLT4	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	-0.032	0.11	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.2	0.21	-9999	-0.41	231	231
positive regulation of lamellipodium assembly	-0.037	0.096	-9999	-0.36	39	39
PVRL1	-0.27	0.29	-9999	-0.57	231	231
PVRL3	-0.057	0.2	-9999	-0.74	37	37
PVRL2	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
CDH1	0	0	-9999	-10000	0	0
CLDN1	-0.1	0.22	-9999	-0.58	87	87
JAM-A/CLDN1	-0.089	0.17	-9999	-0.49	38	38
SRC	-0.077	0.18	-9999	-0.7	37	37
ITGB3	-0.012	0.095	-9999	-0.74	8	8
nectin-1(dimer)/I-afadin/I-afadin	-0.2	0.21	-9999	-0.41	231	231
FARP2	-0.037	0.16	-9999	-0.57	37	37
RAC1	0	0	-9999	-10000	0	0
CTNNA1	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.037	0.13	-9999	-0.48	37	37
nectin-1/I-afadin	-0.2	0.21	-9999	-0.41	231	231
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.2	0.21	-9999	-0.39	249	249
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.034	0.09	-9999	-0.34	37	37
alphaV/beta3 Integrin/Talin	-0.047	0.14	-9999	-0.49	35	35
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	-0.05	0.15	-9999	-0.54	31	31
VAV2	-0.041	0.17	-9999	-0.58	40	40
RAP1/GDP	-0.039	0.11	-9999	-0.43	37	37
ITGAV	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.037	0.13	-9999	-0.48	37	37
nectin-3(dimer)/I-afadin/I-afadin	-0.043	0.15	-9999	-0.56	37	37
Rac1/GTP	-0.045	0.12	-9999	-0.44	39	39
PTPRM	-0.055	0.16	-9999	-0.43	61	61
E-cadherin/beta catenin/alpha catenin	-0.13	0.13	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.009	0.14	-10000	0	-0.38	60	60
CRKL	-0.013	0.15	-10000	0	-0.41	60	60
HRAS	-0.058	0.14	-10000	0	-0.62	11	11
mol:PIP3	-0.025	0.14	-10000	0	-0.39	60	60
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.022	0.16	-10000	0	-0.43	60	60
FOXO3	-0.007	0.14	-10000	0	-0.37	60	60
AKT1	-0.016	0.14	-10000	0	-0.4	60	60
BAD	-0.007	0.14	-10000	0	-0.37	60	60
megakaryocyte differentiation	-0.049	0.2	-10000	0	-0.49	78	78
GSK3B	-0.007	0.14	-10000	0	-0.37	60	60
RAF1	0.006	0.13	-10000	0	-0.48	11	11
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.022	0.16	-10000	0	-0.43	60	60
STAT1	-0.074	0.36	-10000	0	-1	60	60
HRAS/SPRED1	-0.047	0.11	-10000	0	-0.48	11	11
cell proliferation	-0.021	0.15	-10000	0	-0.42	60	60
PIK3CA	0	0	-10000	0	-10000	0	0
TEC	-0.005	0.058	-10000	0	-0.74	3	3
RPS6KB1	-0.022	0.15	-10000	0	-0.43	60	60
HRAS/SPRED2	-0.047	0.11	-10000	0	-0.48	11	11
LYN/TEC/p62DOK	-0.053	0.14	-10000	0	-0.42	60	60
MAPK3	0.018	0.099	-10000	0	-0.32	11	11
STAP1	-0.045	0.2	-10000	0	-0.49	74	74
GRAP2	-0.04	0.17	-10000	0	-0.74	26	26
JAK2	-0.11	0.28	-10000	0	-0.85	60	60
STAT1 (dimer)	-0.071	0.35	-10000	0	-0.99	60	60
mol:Gleevec	0	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.054	0.14	-10000	0	-0.4	65	65
actin filament polymerization	-0.021	0.15	-10000	0	-0.42	60	60
LYN	-0.003	0.048	-10000	0	-0.74	2	2
STAP1/STAT5A (dimer)	-0.049	0.25	-10000	0	-0.67	60	60
PIK3R1	0	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.045	0.12	-10000	0	-10000	0	0
PI3K	-0.05	0.13	-10000	0	-0.4	60	60
PTEN	0	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.1	0.44	-10000	0	-1.3	60	60
MAPK8	-0.022	0.16	-10000	0	-0.43	60	60
STAT3 (dimer)	-0.021	0.15	-10000	0	-0.42	60	60
positive regulation of transcription	0.02	0.084	-10000	0	-0.3	1	1
mol:GDP	-0.062	0.15	-10000	0	-0.67	11	11
PIK3C2B	-0.021	0.16	-10000	0	-0.43	60	60
CBL/CRKL	-0.007	0.14	-10000	0	-0.38	60	60
FER	-0.022	0.16	-10000	0	-0.43	60	60
SH2B3	-0.023	0.16	-10000	0	-0.43	62	62
PDPK1	-0.016	0.13	-10000	0	-0.36	60	60
SNAI2	-0.022	0.16	-10000	0	-0.43	60	60
positive regulation of cell proliferation	-0.044	0.26	-10000	0	-0.74	60	60
KITLG	0.013	0.005	-10000	0	-10000	0	0
cell motility	-0.044	0.26	-10000	0	-0.74	60	60
PTPN6	0.004	0.01	-10000	0	-10000	0	0
EPOR	0.01	0.1	-10000	0	-10000	0	0
STAT5A (dimer)	-0.032	0.22	-10000	0	-0.61	60	60
SOCS1	-0.002	0.034	-10000	0	-0.74	1	1
cell migration	0.036	0.18	0.45	72	-10000	0	72
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.002	0.064	-10000	0	-0.57	6	6
VAV1	-0.008	0.075	-10000	0	-0.74	5	5
GRB10	-0.022	0.16	-10000	0	-0.43	60	60
PTPN11	0.003	0.008	-10000	0	-10000	0	0
SCF/KIT	-0.058	0.15	-10000	0	-0.46	60	60
GO:0007205	0	0.008	-10000	0	-10000	0	0
MAP2K1	0.015	0.11	-10000	0	-0.36	11	11
CBL	0	0	-10000	0	-10000	0	0
KIT	-0.13	0.47	-10000	0	-1.4	60	60
MAP2K2	0.015	0.11	-10000	0	-0.36	11	11
SHC/Grb2/SOS1	-0.049	0.13	-10000	0	-0.4	60	60
STAT5A	-0.034	0.22	-10000	0	-0.63	60	60
GRB2	0	0	-10000	0	-10000	0	0
response to radiation	-0.021	0.15	-10000	0	-0.42	60	60
SHC/GRAP2	-0.03	0.13	-10000	0	-0.56	26	26
PTPRO	-0.05	0.21	-10000	0	-0.5	78	78
SH2B2	-0.022	0.16	-10000	0	-0.43	60	60
DOK1	0	0	-10000	0	-10000	0	0
MATK	-0.037	0.18	-10000	0	-0.46	72	72
CREBBP	0.028	0.011	-10000	0	-10000	0	0
BCL2	0.01	0.1	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.029	0.12	-9999	-0.56	25	25
alphaV beta3 Integrin	-0.023	0.11	-9999	-0.5	22	22
PTK2	-0.19	0.23	-9999	-0.69	39	39
IGF1R	0	0	-9999	-10000	0	0
PI4KB	0	0	-9999	-10000	0	0
MFGE8	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
CDKN1B	-0.23	0.29	-9999	-0.58	187	187
VEGFA	0	0	-9999	-10000	0	0
ILK	-0.23	0.29	-9999	-0.58	187	187
ROCK1	0	0	-9999	-10000	0	0
AKT1	-0.21	0.27	-9999	-0.54	187	187
PTK2B	-0.027	0.12	-9999	-0.47	28	28
alphaV/beta3 Integrin/JAM-A	-0.18	0.22	-9999	-0.84	13	13
CBL	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.011	0.069	-9999	-0.44	12	12
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.014	0.076	-9999	-0.43	15	15
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.12	0.16	-9999	-0.65	19	19
alphaV/beta3 Integrin/Syndecan-1	-0.009	0.065	-9999	-0.48	9	9
PI4KA	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.038	0.14	-9999	-0.78	10	10
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.19	0.18	-9999	-0.35	260	260
RPS6KB1	-0.035	0.13	-9999	-0.72	10	10
TLN1	0	0	-9999	-10000	0	0
MAPK3	-0.1	0.18	-9999	-0.77	22	22
GPR124	0	0	-9999	-10000	0	0
MAPK1	-0.1	0.18	-9999	-0.77	22	22
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.31	0.24	-9999	-0.49	305	305
cell adhesion	-0.012	0.067	-9999	-0.44	8	8
ANGPTL3	-0.005	0.052	-9999	-0.57	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	-0.025	0.11	-9999	-0.48	25	25
IGF-1R heterotetramer	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	-0.058	0.2	-9999	-0.74	38	38
ITGB3	-0.012	0.095	-9999	-0.74	8	8
IGF1	-0.024	0.13	-9999	-0.73	16	16
RAC1	0	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.008	0.061	-9999	-0.48	8	8
apoptosis	0	0	-9999	-10000	0	0
CD47	-0.005	0.058	-9999	-0.74	3	3
alphaV/beta3 Integrin/CD47	-0.011	0.072	-9999	-0.48	11	11
VCL	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.034	0.13	-9999	-0.51	32	32
CSF1	-0.006	0.067	-9999	-0.74	4	4
PIK3C2A	-0.23	0.29	-9999	-0.58	187	187
PI4 Kinase/Pyk2	-0.16	0.21	-9999	-0.75	25	25
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.03	0.12	-9999	-0.51	28	28
FAK1/Vinculin	-0.15	0.18	-9999	-0.51	39	39
alphaV beta3/Integrin/ppsTEM5	-0.008	0.061	-9999	-0.48	8	8
RHOA	0	0	-9999	-10000	0	0
VTN	-0.29	0.36	-9999	-0.74	189	189
BCAR1	0	0	-9999	-10000	0	0
FGF2	-0.023	0.13	-9999	-0.74	15	15
F11R	0.002	0.1	-9999	-0.56	15	15
alphaV/beta3 Integrin/Lactadherin	-0.008	0.061	-9999	-0.48	8	8
alphaV/beta3 Integrin/TGFBR2	-0.045	0.16	-9999	-0.54	40	40
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.004	0.039	-9999	-0.43	4	4
HSP90AA1	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.007	0.056	-9999	-0.44	8	8
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.017	0.11	-9999	-0.74	11	11
alphaV/beta3 Integrin/Pyk2	-0.028	0.12	-9999	-0.47	28	28
SDC1	-0.002	0.034	-9999	-0.74	1	1
VAV3	-0.004	0.041	-9999	-0.4	5	5
PTPN11	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
FAK1/Paxillin	-0.15	0.18	-9999	-0.51	39	39
cell migration	-0.13	0.16	-9999	-0.48	30	30
ITGAV	0	0	-9999	-10000	0	0
PI3K	-0.16	0.2	-9999	-0.76	13	13
SPP1	-0.3	0.28	-9999	-0.57	255	255
KDR	-0.038	0.16	-9999	-0.74	25	25
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-9999	-10000	0	0
COL4A3	-0.47	0.36	-9999	-0.74	305	305
angiogenesis	-0.11	0.22	-9999	-0.76	24	24
Rac1/GTP	-0.004	0.037	-9999	-10000	0	0
EDIL3	-0.04	0.17	-9999	-0.74	26	26
cell proliferation	-0.045	0.16	-9999	-0.54	40	40

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.098	0.18	-10000	0	-0.44	107	107
regulation of S phase of mitotic cell cycle	-0.064	0.13	-10000	0	-0.31	101	101
GNAO1	-0.004	0.05	-10000	0	-0.63	3	3
HRAS	0	0	-10000	0	-10000	0	0
SHBG/T-DHT	0	0	-10000	0	-10000	0	0
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
MAP2K1	-0.051	0.16	-10000	0	-0.46	17	17
T-DHT/AR	-0.12	0.23	-10000	0	-0.57	101	101
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.007	55	55
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.034	-10000	0	-0.74	1	1
mol:GDP	-0.12	0.23	-10000	0	-0.56	101	101
cell proliferation	-0.057	0.2	-10000	0	-0.65	17	17
PIK3CA	0	0	-10000	0	-10000	0	0
FOS	-0.085	0.29	-10000	0	-0.86	55	55
mol:Ca2+	-0.013	0.022	-10000	0	-0.069	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	55	55
cAMP biosynthetic process	0.011	0.021	-10000	0	-10000	0	0
GNG2	-0.008	0.075	-10000	0	-0.74	5	5
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	55	55
HRAS/GTP	-0.086	0.16	-10000	0	-0.4	101	101
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0	0	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	55	55
PI3K	0	0	-10000	0	-10000	0	0
apoptosis	0.046	0.18	0.45	55	-10000	0	55
T-DHT/AR/PELP1	-0.1	0.2	-10000	0	-0.49	101	101
HRAS/GDP	-0.11	0.21	-10000	0	-0.52	101	101
CREB1	-0.051	0.19	-10000	0	-0.49	55	55
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.16	0.3	-10000	0	-0.74	101	101
GNB1	-0.002	0.034	-10000	0	-0.74	1	1
RAF1	-0.058	0.17	-10000	0	-0.38	101	101
RAC1-CDC42/GDP	-0.1	0.2	-10000	0	-0.5	101	101
T-DHT/AR/PELP1/Src	-0.093	0.18	-10000	0	-0.44	101	101
MAP2K2	-0.051	0.16	-10000	0	-0.46	17	17
T-DHT/AR/PELP1/Src/PI3K	-0.064	0.13	-10000	0	-0.31	101	101
GNAZ	-0.009	0.082	-10000	0	-0.74	6	6
SHBG	0	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.024	0.065	-10000	0	-0.48	6	6
mol:T-DHT	0	0.001	-10000	0	-0.003	38	38
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	-0.37	8	8
CDC42	0	0	-10000	0	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.034	0.11	-10000	0	-0.48	16	16
fibroblast growth factor receptor signaling pathway	-0.034	0.11	-10000	0	-0.48	16	16
LAMA1	-0.17	0.26	-10000	0	-0.57	141	141
PRNP	0	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.15	0.25	-10000	0	-0.56	128	128
SMAD2	-0.024	0.14	-10000	0	-0.43	38	38
GPC1/PrPc/Cu2+	-0.018	0.078	-10000	0	-0.35	25	25
GPC1/Laminin alpha1	-0.14	0.22	-10000	0	-0.45	151	151
TDGF1	-0.004	0.045	-10000	0	-0.57	3	3
CRIPTO/GPC1	-0.024	0.097	-10000	0	-0.41	28	28
APP/GPC1	-0.021	0.091	-10000	0	-0.41	25	25
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.001	0.086	-10000	0	-0.34	28	28
FLT1	0	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.056	0.14	-10000	0	-0.48	38	38
SERPINC1	-0.007	0.063	-10000	0	-0.57	6	6
FYN	0	0.089	-10000	0	-0.49	1	1
FGR	-0.033	0.15	-10000	0	-0.46	38	38
positive regulation of MAPKKK cascade	0.002	0.11	-10000	0	-0.46	13	13
SLIT2	-0.17	0.31	-10000	0	-0.74	110	110
GPC1/NRG	-0.036	0.13	-10000	0	-0.46	38	38
NRG1	-0.02	0.12	-10000	0	-0.74	13	13
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.018	0.076	-10000	0	-0.34	25	25
LYN	-0.001	0.091	-10000	0	-0.38	8	8
mol:Spermine	-0.013	0.095	-10000	0	-0.42	25	25
cell growth	-0.034	0.11	-10000	0	-0.48	16	16
BMP signaling pathway	0.03	0.13	0.57	25	-10000	0	25
SRC	0.001	0.086	-10000	0	-0.35	6	6
TGFBR1	0	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.22	0.34	-10000	0	-0.74	143	143
GPC1	-0.03	0.13	-10000	0	-0.57	25	25
TGFBR1 (dimer)	0	0	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.023	0.13	-10000	0	-0.5	15	15
HCK	-0.004	0.099	-10000	0	-0.36	33	33
FGF2	-0.023	0.13	-10000	0	-0.74	15	15
FGFR1	-0.002	0.034	-10000	0	-0.74	1	1
VEGFR1 homodimer	0	0	-10000	0	-10000	0	0
TGFBR2	-0.058	0.2	-10000	0	-0.74	38	38
cell death	-0.021	0.091	-10000	0	-0.41	25	25
ATIII/GPC1	-0.027	0.1	-10000	0	-0.41	31	31
PLA2G2A/GPC1	-0.18	0.27	-10000	0	-0.56	160	160
LCK	0	0.089	-10000	0	-0.35	29	29
neuron differentiation	-0.036	0.13	-10000	0	-0.46	38	38
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	-0.058	0.2	-10000	0	-0.74	38	38

×

TCGA08_p53

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

×

Canonical Wnt signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.004	0.018	-10000	0	-10000	0	0
AES	0.003	0.015	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0	0	-10000	0	-10000	0	0
DKK2	-0.13	0.28	-10000	0	-0.74	86	86
TLE1	0.002	0.031	-10000	0	-0.61	1	1
MACF1	0.004	0.048	-10000	0	-0.74	2	2
CTNNB1	0.067	0.099	0.29	10	-10000	0	10
WIF1	-0.47	0.36	-10000	0	-0.74	306	306
beta catenin/RanBP3	0.003	0.092	0.4	20	-10000	0	20
KREMEN2	-0.37	0.27	-10000	0	-0.57	314	314
DKK1	-0.039	0.15	-10000	0	-0.62	30	30
beta catenin/beta TrCP1	0.069	0.093	0.28	10	-10000	0	10
FZD1	0.001	0.003	-10000	0	-10000	0	0
AXIN2	-0.038	0.28	-10000	0	-1.5	17	17
AXIN1	0.008	0.005	-10000	0	-10000	0	0
RAN	0.001	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.005	0.021	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.093	0.052	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.02	0.063	0.24	29	-10000	0	29
Axin1/APC/GSK3/beta catenin/Macf1	0.065	0.041	-10000	0	-10000	0	0
HNF1A	-0.006	0.076	-10000	0	-0.58	8	8
CTBP1	0.004	0.018	-10000	0	-10000	0	0
MYC	0.007	0.049	-10000	0	-10000	0	0
RANBP3	0.001	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.3	0.25	-10000	0	-0.72	86	86
NKD1	-0.071	0.22	-10000	0	-0.73	47	47
TCF4	0.002	0.038	-10000	0	-0.74	1	1
TCF3	0.004	0.018	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.001	0.019	-10000	0	-10000	0	0
Ran/GTP	0	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.018	0.097	0.45	22	-10000	0	22
LEF1	0.002	0.031	-10000	0	-0.58	1	1
DVL1	0.08	0.061	-10000	0	-10000	0	0
CSNK2A1	0.001	0.003	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.097	0.068	-10000	0	-0.56	1	1
DKK1/LRP6/Kremen 2	-0.25	0.19	-10000	0	-0.37	293	293
LRP6	0.001	0.004	-10000	0	-10000	0	0
CSNK1A1	0.004	0.018	-10000	0	-10000	0	0
NLK	0.01	0.002	-10000	0	-10000	0	0
CCND1	-0.009	0.18	-10000	0	-1.5	6	6
WNT1	0.004	0.037	-10000	0	-0.57	2	2
GSK3A	0.007	0.005	-10000	0	-10000	0	0
GSK3B	0	0.002	-10000	0	-10000	0	0
FRAT1	-0.001	0.034	-10000	0	-0.74	1	1
PPP2R5D	0.076	0.1	0.37	47	-10000	0	47
APC	0	0.019	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.16	0.12	0.26	304	-10000	0	304
CREBBP	0.004	0.018	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	0	0	-10000	0	-10000	0	0
HDAC1	0.001	0.005	-10000	0	-10000	0	0
AES	0	0.002	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.002	0.037	-10000	0	-0.57	2	2
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	-0.001	0.033	-10000	0	-0.73	1	1
AP1	-0.076	0.18	-10000	0	-0.42	86	86
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	0	0.001	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.001	0.042	-10000	0	-0.56	1	1
NICD/RBPSUH	0	0	-10000	0	-10000	0	0
WIF1	-0.47	0.36	-10000	0	-0.74	306	306
NOTCH1	0	0	-10000	0	-10000	0	0
PSENEN	0	0	-10000	0	-10000	0	0
KREMEN2	-0.37	0.27	-10000	0	-0.57	314	314
DKK1	-0.039	0.15	-10000	0	-0.62	30	30
beta catenin/beta TrCP1	0.007	0.06	-10000	0	-10000	0	0
APH1B	0	0	-10000	0	-10000	0	0
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	-0.004	0.026	0.3	1	-10000	0	1
CtBP/CBP/TCF1/TLE1/AES	-0.001	0.027	-10000	0	-10000	0	0
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.085	0.24	-10000	0	-0.74	55	55
JUN	0	0	-10000	0	-10000	0	0
MAP3K7	0	0.003	-10000	0	-10000	0	0
CTNNB1	0.01	0.065	0.22	6	-10000	0	6
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.3	0.25	-10000	0	-0.72	86	86
HNF1A	-0.009	0.073	-10000	0	-0.57	8	8
CTBP1	0	0.002	-10000	0	-10000	0	0
MYC	0.002	0.012	-10000	0	-10000	0	0
NKD1	-0.071	0.22	-10000	0	-0.73	47	47
FZD1	0	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.001	0.018	-10000	0	-10000	0	0
apoptosis	-0.076	0.18	-10000	0	-0.42	86	86
Delta 1/NOTCHprecursor	0	0	-10000	0	-10000	0	0
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.002	0.012	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.004	0.026	0.3	1	-10000	0	1
DVL1	-0.045	0.044	-10000	0	-0.67	1	1
CSNK2A1	0.01	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.25	0.19	-10000	0	-0.37	323	323
LRP6	0	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
NLK	0.001	0.006	-10000	0	-10000	0	0
CCND1	-0.016	0.16	-10000	0	-1.4	6	6
WNT1	-0.002	0.037	-10000	0	-0.57	2	2
Axin1/APC/beta catenin	0.01	0.045	0.27	1	-0.36	1	2
DKK2	-0.13	0.28	-10000	0	-0.74	86	86
NOTCH1 precursor/DVL1	-0.022	0.029	-10000	0	-0.55	1	1
GSK3B	0	0.002	-10000	0	-10000	0	0
FRAT1	-0.001	0.034	-10000	0	-0.74	1	1
NOTCH/Deltex homolog 1	-0.001	0.018	-10000	0	-10000	0	0
PPP2R5D	0.01	0.1	0.31	47	-0.25	1	48
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.28	0.21	-10000	0	-0.44	305	305
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.013	0.002	-10000	0	-10000	0	0

×

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	-0.84	52	52
PCK1	-0.14	0.21	-10000	0	-0.73	20	20
HNF4A	-0.32	0.4	-10000	0	-1.1	47	47
KCNJ11	-0.28	0.39	-10000	0	-1	39	39
AKT1	-0.002	0.086	-10000	0	-10000	0	0
response to starvation	-0.009	0.033	-10000	0	-10000	0	0
DLK1	-0.3	0.38	-10000	0	-0.94	49	49
NKX2-1	-0.79	0.79	-10000	0	-1.5	256	256
ACADM	-0.27	0.34	-10000	0	-0.86	40	40
TAT	-0.12	0.2	-10000	0	-0.78	9	9
CEBPB	0.003	0.006	-10000	0	-10000	0	0
CEBPA	0.002	0.035	-10000	0	-0.75	1	1
TTR	-0.053	0.19	-10000	0	-0.79	15	15
PKLR	-0.28	0.34	-10000	0	-0.87	46	46
APOA1	-0.43	0.55	-10000	0	-1.4	78	78
CPT1C	-0.27	0.34	-10000	0	-0.89	30	30
ALAS1	-0.12	0.18	-10000	0	-10000	0	0
TFRC	-0.17	0.25	-10000	0	-0.89	12	12
FOXF1	0.007	0.24	0.28	4	-0.62	52	56
NF1	0.016	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.014	0.083	-10000	0	-0.6	8	8
CPT1A	-0.27	0.34	-10000	0	-0.86	39	39
HMGCS1	-0.27	0.34	-10000	0	-0.87	37	37
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	-0.007	0.03	-10000	0	-10000	0	0
GCK	-0.27	0.34	-10000	0	-0.84	54	54
CREB1	0.007	0.016	-10000	0	-10000	0	0
IGFBP1	-0.12	0.17	-10000	0	-0.66	3	3
PDX1	-0.19	0.24	-10000	0	-0.68	21	21
UCP2	-0.27	0.34	-10000	0	-0.86	42	42
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	53	53
HADH	-0.27	0.36	-10000	0	-0.89	35	35
F2	-0.35	0.42	-10000	0	-1.1	50	50
HNF1A	-0.014	0.083	-10000	0	-0.6	8	8
G6PC	0.009	0.086	-10000	0	-0.73	1	1
SLC2A2	-0.18	0.23	-10000	0	-0.86	2	2
INS	-0.009	0.011	-10000	0	-10000	0	0
FOXA1	0.073	0.14	0.33	13	-0.57	11	24
FOXA3	-0.011	0.15	-10000	0	-0.74	17	17
FOXA2	-0.32	0.41	-10000	0	-0.9	74	74
ABCC8	-0.29	0.39	-10000	0	-1	41	41
ALB	0.026	0.12	-10000	0	-0.67	4	4

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.009	0.071	-9999	-0.56	8	8
AKT1	-0.01	0.2	-9999	-0.65	25	25
PTK2B	-0.097	0.23	-9999	-0.88	27	27
VEGFR2 homodimer/Frs2	-0.11	0.26	-9999	-0.6	91	91
CAV1	-0.21	0.33	-9999	-0.74	135	135
CALM1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.1	0.24	-9999	-0.55	91	91
endothelial cell proliferation	-0.007	0.2	-9999	-0.61	28	28
mol:Ca2+	-0.053	0.24	-9999	-0.84	25	25
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.098	0.23	-9999	-0.88	25	25
RP11-342D11.1	-0.059	0.24	-9999	-0.84	25	25
CDH5	-0.15	0.3	-9999	-0.74	95	95
VEGFA homodimer	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
SHC2	-0.003	0.048	-9999	-0.74	2	2
HRAS/GDP	-0.079	0.18	-9999	-0.71	25	25
SH2D2A	-0.002	0.034	-9999	-0.74	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.075	0.17	-9999	-0.66	26	26
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.1	0.24	-9999	-0.55	92	92
VEGFR1 homodimer	0	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.088	0.21	-9999	-0.81	25	25
GRB10	-0.052	0.24	-9999	-0.83	25	25
PTPN11	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PAK1	-0.001	0.026	-9999	-0.57	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.17	0.31	-9999	-0.94	53	53
HRAS	0	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.055	0.12	-9999	-0.45	27	27
HIF1A	0	0	-9999	-10000	0	0
FRS2	0	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.096	0.22	-9999	-0.86	25	25
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.035	0.16	-9999	-0.74	23	23
Nck/Pak	-0.001	0.019	-9999	-0.41	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.1	0.24	-9999	-0.55	91	91
mol:GDP	-0.085	0.2	-9999	-0.77	25	25
mol:NADP	-0.008	0.17	-9999	-0.54	27	27
eNOS/Hsp90	-0.003	0.16	-9999	-0.5	26	26
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	-0.054	0.24	-9999	-0.85	25	25
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0	0	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFC	-0.003	0.048	-9999	-0.74	2	2
FAK1/Vinculin	-0.042	0.24	-9999	-0.84	27	27
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.1	0.25	-9999	-0.94	27	27
PTPN6	0	0	-9999	-10000	0	0
EPAS1	-0.13	0.29	-9999	-0.71	91	91
mol:L-citrulline	-0.008	0.17	-9999	-0.54	27	27
ITGAV	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.098	0.23	-9999	-0.88	25	25
VEGFR2 homodimer/VEGFA homodimer	-0.1	0.24	-9999	-0.93	25	25
VEGFR2/3 heterodimer	-0.14	0.29	-9999	-0.63	103	103
VEGFB	0	0	-9999	-10000	0	0
MAPK11	-0.051	0.24	-9999	-0.87	25	25
VEGFR2 homodimer	-0.1	0.3	-9999	-0.69	91	91
FLT1	0	0	-9999	-10000	0	0
NEDD4	-0.002	0.034	-9999	-0.74	1	1
MAPK3	-0.046	0.23	-9999	-0.76	28	28
MAPK1	-0.046	0.23	-9999	-0.76	28	28
VEGFA145/NRP2	-0.005	0.051	-9999	-0.56	4	4
VEGFR1/2 heterodimer	-0.11	0.26	-9999	-0.6	91	91
KDR	-0.1	0.3	-9999	-0.69	91	91
VEGFA165/NRP1/VEGFR2 homodimer	-0.097	0.23	-9999	-0.9	25	25
SRC	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.046	0.23	-9999	-0.78	28	28
PI3K	-0.088	0.21	-9999	-0.82	25	25
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.1	0.24	-9999	-0.55	91	91
FES	-0.056	0.25	-9999	-0.88	25	25
GAB1	-0.092	0.22	-9999	-0.84	25	25
VEGFR2 homodimer/VEGFA homodimer/Src	-0.1	0.24	-9999	-0.55	91	91
CTNNB1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
ARNT	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.097	0.23	-9999	-0.57	59	59
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.1	0.24	-9999	-0.55	91	91
PI3K/GAB1	-0.012	0.2	-9999	-0.67	25	25
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.094	0.22	-9999	-0.85	25	25
PRKACA	0	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.13	0.28	-9999	-0.59	103	103
HSP90AA1	0	0	-9999	-10000	0	0
CDC42	-0.055	0.24	-9999	-0.87	25	25
actin cytoskeleton reorganization	-0.1	0.24	-9999	-0.54	92	92
PTK2	-0.053	0.27	-9999	-0.94	27	27
EDG1	-0.059	0.24	-9999	-0.84	25	25
mol:DAG	-0.054	0.24	-9999	-0.85	25	25
CaM/Ca2+	-0.086	0.2	-9999	-0.78	25	25
MAP2K3	-0.044	0.23	-9999	-0.82	25	25
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.098	0.23	-9999	-0.89	25	25
PLCG1	-0.055	0.24	-9999	-0.87	25	25
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.098	0.23	-9999	-0.88	25	25
IQGAP1	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.1	0.24	-9999	-0.55	91	91
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.1	0.24	-9999	-0.55	91	91
cell migration	-0.039	0.23	-9999	-0.75	27	27
mol:PI-3-4-5-P3	-0.081	0.19	-9999	-0.73	25	25
FYN	-0.002	0.034	-9999	-0.74	1	1
VEGFB/NRP1	-0.089	0.21	-9999	-0.79	25	25
mol:NO	-0.008	0.17	-9999	-0.54	27	27
PXN	0	0	-9999	-10000	0	0
HRAS/GTP	-0.079	0.18	-9999	-0.71	25	25
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.098	0.23	-9999	-0.89	25	25
VHL	0	0	-9999	-10000	0	0
ITGB3	-0.012	0.095	-9999	-0.74	8	8
NOS3	-0.015	0.19	-9999	-0.62	27	27
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.11	0.24	-9999	-0.56	91	91
RAC1	0	0	-9999	-10000	0	0
PRKCA	-0.043	0.23	-9999	-0.8	26	26
PRKCB	-0.062	0.25	-9999	-0.88	27	27
VCL	0	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.095	0.22	-9999	-0.84	25	25
VEGFR1/2 heterodimer/VEGFA homodimer	-0.1	0.24	-9999	-0.55	91	91
VEGFA165/NRP2	-0.005	0.051	-9999	-0.56	4	4
MAPKKK cascade	-0.078	0.18	-9999	-0.71	25	25
NRP2	-0.006	0.067	-9999	-0.74	4	4
VEGFC homodimer	-0.003	0.048	-9999	-0.74	2	2
NCK1	0	0	-9999	-10000	0	0
ROCK1	0	0	-9999	-10000	0	0
FAK1/Paxillin	-0.042	0.24	-9999	-0.84	27	27
MAP3K13	-0.055	0.24	-9999	-0.87	25	25
PDPK1	-0.013	0.19	-9999	-0.62	25	25

×

LPA4-mediated signaling events

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

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

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

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.002	0.004	-9999	-10000	0	0
SVIL	0.002	0.004	-9999	-10000	0	0
ZNF318	0	0.005	-9999	-10000	0	0
JMJD2C	-0.004	0.026	-9999	-0.08	49	49
T-DHT/AR/Ubc9	-0.13	0.21	-9999	-0.53	101	101
CARM1	0	0	-9999	-10000	0	0
PRDX1	0	0.001	-9999	-10000	0	0
PELP1	0	0.001	-9999	-10000	0	0
CTNNB1	0.001	0.004	-9999	-10000	0	0
AKT1	0	0.002	-9999	-10000	0	0
PTK2B	0.001	0.004	-9999	-10000	0	0
MED1	0	0.002	-9999	-10000	0	0
MAK	-0.052	0.19	-9999	-0.74	34	34
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.002	0.004	-9999	-10000	0	0
GSN	0.002	0.004	-9999	-10000	0	0
NCOA2	-0.002	0.034	-9999	-0.74	1	1
NCOA6	0.002	0.004	-9999	-10000	0	0
DNA-PK	0	0.006	-9999	-10000	0	0
NCOA4	0	0	-9999	-10000	0	0
PIAS3	0.001	0.004	-9999	-10000	0	0
cell proliferation	-0.093	0.24	-9999	-0.94	34	34
XRCC5	0	0.002	-9999	-10000	0	0
UBE3A	0.001	0.004	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.15	0.23	-9999	-0.54	111	111
FHL2	-0.055	0.081	-9999	-0.55	2	2
RANBP9	0.002	0.004	-9999	-10000	0	0
JMJD1A	-0.035	0.07	-9999	-0.13	157	157
CDK6	-0.002	0.037	-9999	-0.57	2	2
TGFB1I1	0.002	0.004	-9999	-10000	0	0
T-DHT/AR/CyclinD1	-0.14	0.22	-9999	-0.53	106	106
XRCC6	0	0.002	-9999	-10000	0	0
T-DHT/AR	-0.14	0.24	-9999	-0.56	102	102
CTDSP1	0	0	-9999	-10000	0	0
CTDSP2	0	0.004	-9999	-10000	0	0
BRCA1	0.002	0.004	-9999	-10000	0	0
TCF4	-0.001	0.034	-9999	-0.74	1	1
CDKN2A	-0.27	0.29	-9999	-0.57	224	224
SRF	0.016	0.007	-9999	-10000	0	0
NKX3-1	-0.11	0.14	-9999	-0.95	2	2
KLK3	0.028	0.051	-9999	-10000	0	0
TMF1	0	0.001	-9999	-10000	0	0
HNRNPA1	0	0.002	-9999	-10000	0	0
AOF2	0	0.002	-9999	-10000	0	0
APPL1	0.02	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.13	0.21	-9999	-0.53	101	101
AR	-0.17	0.31	-9999	-0.77	101	101
UBA3	0	0	-9999	-10000	0	0
PATZ1	0	0.002	-9999	-10000	0	0
PAWR	0	0.001	-9999	-10000	0	0
PRKDC	0	0.002	-9999	-10000	0	0
PA2G4	0	0.003	-9999	-10000	0	0
UBE2I	0	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.12	0.19	-9999	-0.48	101	101
RPS6KA3	0.002	0.004	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.13	0.21	-9999	-0.53	101	101
LATS2	-0.001	0.034	-9999	-0.74	1	1
T-DHT/AR/PRX1	-0.12	0.19	-9999	-0.48	101	101
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	0	0.034	-9999	-0.74	1	1
KLK2	-0.095	0.14	-9999	-0.5	28	28
CASP8	0	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.12	0.19	-9999	-0.48	102	102
TMPRSS2	-0.4	0.54	-9999	-1.2	156	156
CCND1	-0.01	0.086	-9999	-0.72	7	7
PIAS1	0.001	0.004	-9999	-10000	0	0
mol:T-DHT	-0.019	0.036	-9999	-0.078	115	115
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.001	0.005	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.13	0.21	-9999	-0.52	103	103
CMTM2	-0.097	0.25	-9999	-0.74	63	63
SNURF	-0.023	0.13	-9999	-0.74	15	15
ZMIZ1	-0.008	0.048	-9999	-0.8	1	1
CCND3	0	0.001	-9999	-10000	0	0
TGIF1	0	0.002	-9999	-10000	0	0
FKBP4	0	0.026	-9999	-0.57	1	1

×

HIF-1-alpha transcription factor network

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
PKM2	-0.2	0.43	-9999	-1.2	31	31
HDAC7	-0.007	0.013	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.19	0.33	-9999	-0.9	35	35
SMAD4	0	0.002	-9999	-10000	0	0
ID2	-0.2	0.43	-9999	-1.3	30	30
AP1	-0.066	0.18	-9999	-0.56	55	55
ABCG2	-0.24	0.5	-9999	-1.3	55	55
HIF1A	-0.022	0.07	-9999	-10000	0	0
TFF3	-0.23	0.47	-9999	-1.3	40	40
GATA2	-0.072	0.23	-9999	-0.74	52	52
AKT1	-0.032	0.058	-9999	-10000	0	0
response to hypoxia	-0.046	0.064	-9999	-10000	0	0
MCL1	-0.2	0.43	-9999	-1.2	33	33
NDRG1	-0.2	0.43	-9999	-1.2	34	34
SERPINE1	-0.2	0.43	-9999	-1.2	31	31
FECH	-0.2	0.43	-9999	-1.2	33	33
FURIN	-0.2	0.43	-9999	-1.2	33	33
NCOA2	0.007	0.034	-9999	-0.74	1	1
EP300	-0.023	0.088	-9999	-0.29	1	1
HMOX1	-0.2	0.43	-9999	-1.2	33	33
BHLHE40	-0.2	0.43	-9999	-1.2	33	33
BHLHE41	-0.2	0.44	-9999	-1.3	32	32
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.03	0.077	-9999	-0.51	4	4
ENG	0.005	0.13	-9999	-0.83	6	6
JUN	0.008	0.005	-9999	-10000	0	0
RORA	-0.2	0.43	-9999	-1.2	33	33
ABCB1	-0.2	0.45	-9999	-1.4	60	60
TFRC	-0.2	0.43	-9999	-1.2	33	33
CXCR4	-0.2	0.43	-9999	-1.2	31	31
TF	-0.22	0.45	-9999	-1.3	36	36
CITED2	-0.2	0.44	-9999	-1.3	32	32
HIF1A/ARNT	-0.24	0.49	-9999	-1.4	38	38
LDHA	-0.033	0.047	-9999	-10000	0	0
ETS1	-0.2	0.45	-9999	-1.3	32	32
PGK1	-0.2	0.43	-9999	-1.2	31	31
NOS2	-0.24	0.48	-9999	-1.3	45	45
ITGB2	-0.21	0.46	-9999	-1.3	38	38
ALDOA	-0.2	0.43	-9999	-1.2	33	33
Cbp/p300/CITED2	-0.24	0.43	-9999	-1.3	37	37
FOS	-0.077	0.24	-9999	-0.74	55	55
HK2	-0.2	0.43	-9999	-1.3	31	31
SP1	0.011	0.024	-9999	-10000	0	0
GCK	-0.029	0.14	-9999	-0.61	2	2
HK1	-0.2	0.43	-9999	-1.2	33	33
NPM1	-0.2	0.43	-9999	-1.2	33	33
EGLN1	-0.2	0.43	-9999	-1.2	31	31
CREB1	0.016	0	-9999	-10000	0	0
PGM1	-0.2	0.43	-9999	-1.2	31	31
SMAD3	0	0.002	-9999	-10000	0	0
EDN1	-0.16	0.39	-9999	-1.2	47	47
IGFBP1	-0.2	0.44	-9999	-1.2	34	34
VEGFA	-0.23	0.31	-9999	-0.85	28	28
HIF1A/JAB1	-0.017	0.029	-9999	-10000	0	0
CP	-0.22	0.46	-9999	-1.3	35	35
CXCL12	-0.22	0.48	-9999	-1.4	43	43
COPS5	0.009	0.005	-9999	-10000	0	0
SMAD3/SMAD4	0	0.004	-9999	-10000	0	0
BNIP3	-0.2	0.43	-9999	-1.2	33	33
EGLN3	-0.24	0.46	-9999	-1.3	40	40
CA9	-0.42	0.47	-9999	-1.3	58	58
TERT	-0.3	0.48	-9999	-1.3	46	46
ENO1	-0.2	0.43	-9999	-1.2	33	33
PFKL	-0.2	0.43	-9999	-1.2	31	31
NCOA1	0	0.001	-9999	-10000	0	0
ADM	-0.2	0.43	-9999	-1.2	34	34
ARNT	-0.023	0.069	-9999	-10000	0	0
HNF4A	0.002	0.075	-9999	-0.57	8	8
ADFP	-0.2	0.43	-9999	-1.2	37	37
SLC2A1	-0.44	0.35	-9999	-0.95	85	85
LEP	-0.24	0.47	-9999	-1.3	42	42
HIF1A/ARNT/Cbp/p300	-0.2	0.34	-9999	-0.92	39	39
EPO	-0.08	0.25	-9999	-1	1	1
CREBBP	-0.023	0.088	-9999	-0.29	1	1
HIF1A/ARNT/Cbp/p300/HDAC7	-0.25	0.37	-9999	-0.97	46	46
PFKFB3	-0.2	0.43	-9999	-1.3	30	30
NT5E	-0.2	0.43	-9999	-1.3	30	30

×

Syndecan-3-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.01	0.058	-9999	-0.37	11	11
Syndecan-3/Neurocan	-0.02	0.073	-9999	-10000	0	0
POMC	-0.054	0.17	-9999	-0.58	45	45
EGFR	-0.022	0.12	-9999	-0.63	17	17
Syndecan-3/EGFR	-0.012	0.061	-9999	-0.4	6	6
AGRP	-0.34	0.37	-9999	-0.74	223	223
NCSTN	0	0	-9999	-10000	0	0
PSENEN	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
NCAN	-0.04	0.15	-9999	-0.57	34	34
long-term memory	-0.001	0.017	-9999	-0.38	1	1
Syndecan-3/IL8	-0.013	0.062	-9999	-0.4	4	4
PSEN1	0	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	-0.002	0.034	-9999	-0.74	1	1
limb bud formation	0	0	-9999	-10000	0	0
MC4R	-0.025	0.12	-9999	-0.57	21	21
SRC	0	0	-9999	-10000	0	0
PTN	-0.02	0.12	-9999	-0.7	14	14
FGFR/FGF/Syndecan-3	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.027	0.081	-9999	-10000	0	0
Syndecan-3/AgRP	-0.19	0.2	-9999	-0.4	223	223
Syndecan-3/AgRP/MC4R	-0.19	0.2	-9999	-0.4	223	223
Fyn/Cortactin	-0.001	0.025	-9999	-0.56	1	1
SDC3	0	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.013	0.062	-9999	-0.4	4	4
IL8	-0.025	0.12	-9999	-0.61	20	20
Syndecan-3/Fyn/Cortactin	-0.001	0.018	-9999	-0.39	1	1
Syndecan-3/CASK	0	0	-9999	-10000	0	0
alpha-MSH/MC4R	-0.057	0.15	-9999	-0.42	65	65
Gamma Secretase	0	0	-9999	-10000	0	0

×

IL23-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.13	0.44	-10000	0	-1.2	40	40
IL23A	-0.14	0.43	-10000	0	-1.2	37	37
NF kappa B1 p50/RelA/I kappa B alpha	-0.2	0.36	-10000	0	-1.1	47	47
positive regulation of T cell mediated cytotoxicity	-0.14	0.46	-10000	0	-1.2	47	47
ITGA3	-0.13	0.42	-10000	0	-1.2	40	40
IL17F	-0.063	0.28	-10000	0	-0.74	29	29
IL12B	0.016	0.025	-10000	0	-10000	0	0
STAT1 (dimer)	-0.21	0.38	-10000	0	-1.2	47	47
CD4	-0.13	0.43	-10000	0	-1.2	39	39
IL23	-0.14	0.41	-10000	0	-1.2	37	37
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	-1.1	34	34
TYK2	0.011	0.019	-10000	0	-10000	0	0
STAT4	-0.012	0.095	-10000	0	-0.74	8	8
STAT3	0	0	-10000	0	-10000	0	0
IL18RAP	-0.027	0.16	-10000	0	-0.74	22	22
IL12RB1	-0.038	0.19	-10000	0	-0.77	31	31
PIK3CA	0	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.027	0.15	-10000	0	-0.59	31	31
IL23R/JAK2	0.003	0.1	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.14	0.46	-10000	0	-1.2	47	47
natural killer cell activation	0	0.007	-10000	0	-10000	0	0
JAK2	0.018	0.023	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
NFKB1	0.004	0.006	-10000	0	-10000	0	0
RELA	0.004	0.006	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.14	0.39	-10000	0	-1.1	37	37
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	0.004	0.006	-10000	0	-10000	0	0
IL17A	-0.042	0.24	-10000	0	-0.59	22	22
PI3K	-0.21	0.36	-10000	0	-1.1	47	47
IFNG	-0.001	0.029	0.098	1	-0.12	11	12
STAT3 (dimer)	-0.2	0.34	-10000	0	-1.1	45	45
IL18R1	-0.001	0.076	-10000	0	-0.74	5	5
IL23/IL23R/JAK2/TYK2/SOCS3	-0.061	0.28	-10000	0	-0.84	22	22
IL18/IL18R	-0.029	0.13	-10000	0	-0.56	25	25
macrophage activation	-0.012	0.017	-10000	0	-0.045	27	27
TNF	-0.14	0.45	-10000	0	-1.3	41	41
STAT3/STAT4	-0.21	0.37	-10000	0	-1.1	48	48
STAT4 (dimer)	-0.22	0.39	-10000	0	-1.2	48	48
IL18	0.002	0.059	-10000	0	-0.74	3	3
IL19	-0.13	0.4	-10000	0	-1.1	35	35
STAT5A (dimer)	-0.21	0.38	-10000	0	-1.2	47	47
STAT1	0	0	-10000	0	-10000	0	0
SOCS3	-0.003	0.048	-10000	0	-0.74	2	2
CXCL9	-0.13	0.43	-10000	0	-1.2	40	40
MPO	-0.15	0.45	-10000	0	-1.2	47	47
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	94	94
STAT5A	0	0	-10000	0	-10000	0	0
IL2	0.006	0.008	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0.007	-10000	0	-10000	0	0
CD3E	-0.12	0.42	-10000	0	-1.2	32	32
keratinocyte proliferation	-0.14	0.46	-10000	0	-1.2	47	47
NOS2	-0.17	0.48	-10000	0	-1.3	51	51

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.011	0.037	-9999	-0.54	1	1
NFATC2	-0.06	0.18	-9999	-0.52	66	66
NFATC3	0.012	0.028	-9999	-10000	0	0
CD40LG	-0.17	0.38	-9999	-0.83	93	93
PTGS2	-0.14	0.34	-9999	-0.75	84	84
JUNB	-0.002	0.034	-9999	-0.74	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.011	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.011	-9999	-10000	0	0
CALM1	-0.001	0.003	-9999	-10000	0	0
JUN	-0.001	0.003	-9999	-10000	0	0
mol:Ca2+	-0.006	0.01	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.002	-9999	-10000	0	0
FOSL1	-0.002	0.037	-9999	-0.57	2	2
CREM	0	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.1	0.18	-9999	-0.57	45	45
FOS	-0.086	0.24	-9999	-0.74	55	55
IFNG	-0.11	0.3	-9999	-0.77	34	34
AP-1/NFAT1-c-4	-0.21	0.31	-9999	-0.77	88	88
FASLG	-0.12	0.32	-9999	-0.75	58	58
NFAT1-c-4/ICER1	-0.083	0.16	-9999	-0.51	46	46
IL2RA	-0.11	0.3	-9999	-0.7	53	53
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.15	0.34	-9999	-0.79	67	67
JunB/Fra1/NFAT1-c-4	-0.08	0.16	-9999	-0.5	45	45
IL4	-0.12	0.29	-9999	-0.66	64	64
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

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.14	0.25	-10000	0	-0.73	13	13
CRP	-0.15	0.25	-10000	0	-0.76	12	12
cell cycle arrest	-0.17	0.28	-10000	0	-0.65	54	54
TIMP1	-0.11	0.21	-10000	0	-0.63	8	8
IL6ST	-0.016	0.13	-10000	0	-0.74	16	16
Rac1/GDP	-0.066	0.19	-10000	0	-0.69	19	19
AP1	-0.003	0.15	-10000	0	-0.49	13	13
GAB2	-0.002	0.12	-10000	0	-0.74	12	12
TNFSF11	-0.16	0.26	-10000	0	-0.66	34	34
HSP90B1	-0.001	0.05	-10000	0	-10000	0	0
GAB1	0.013	0.009	-10000	0	-10000	0	0
MAPK14	-0.03	0.17	-10000	0	-0.73	15	15
AKT1	0.043	0.054	-10000	0	-10000	0	0
FOXO1	0.049	0.05	-10000	0	-10000	0	0
MAP2K6	-0.053	0.18	-10000	0	-0.76	15	15
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
MAP2K4	-0.076	0.2	-10000	0	-0.74	15	15
MITF	-0.07	0.19	-10000	0	-0.67	24	24
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0	0	-10000	0	-10000	0	0
A2M	-0.46	0.69	-10000	0	-1.5	157	157
CEBPB	0.016	0.004	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.03	0.11	0.22	28	-0.53	5	33
STAT3	-0.18	0.29	-10000	0	-0.69	54	54
STAT1	-0.008	0.016	-10000	0	-10000	0	0
CEBPD	-0.14	0.25	-10000	0	-0.8	13	13
PIK3CA	0.01	0.003	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
JUN	0	0	-10000	0	-10000	0	0
PIAS3/MITF	-0.087	0.17	-10000	0	-0.65	22	22
MAPK11	-0.03	0.17	-10000	0	-0.73	15	15
STAT3 (dimer)/FOXO1	-0.19	0.31	-10000	0	-0.75	56	56
GRB2/SOS1/GAB family	-0.031	0.17	-10000	0	-0.64	18	18
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.052	0.19	-10000	0	-0.55	36	36
GRB2	0.013	0.009	-10000	0	-10000	0	0
JAK2	0	0	-10000	0	-10000	0	0
LBP	-0.11	0.21	-10000	0	-0.64	6	6
PIK3R1	0.008	0.005	-10000	0	-10000	0	0
JAK1	0.01	0.005	-10000	0	-10000	0	0
MYC	-0.14	0.25	-10000	0	-0.73	13	13
FGG	-0.48	0.57	-10000	0	-1.1	226	226
macrophage differentiation	-0.17	0.28	-10000	0	-0.65	54	54
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.093	0.2	-10000	0	-0.53	62	62
JUNB	-0.14	0.24	-10000	0	-0.72	14	14
FOS	-0.084	0.24	-10000	0	-0.74	55	55
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.072	0.19	-10000	0	-0.5	55	55
STAT1/PIAS1	-0.086	0.17	-10000	0	-0.51	37	37
GRB2/SOS1/GAB family/SHP2/PI3K	0.014	0.057	-10000	0	-10000	0	0
STAT3 (dimer)	-0.18	0.28	-10000	0	-0.68	54	54
PRKCD	-0.091	0.22	-10000	0	-0.76	14	14
IL6R	-0.008	0.12	-10000	0	-0.74	12	12
SOCS3	-0.016	0.17	-10000	0	-0.71	15	15
gp130 (dimer)/JAK1/JAK1/LMO4	-0.01	0.089	-10000	0	-0.47	17	17
Rac1/GTP	-0.11	0.17	-10000	0	-0.55	38	38
HCK	-0.003	0.076	-10000	0	-0.74	5	5
MAPKKK cascade	0.045	0.12	-10000	0	-0.53	12	12
bone resorption	-0.15	0.25	-10000	0	-0.63	34	34
IRF1	-0.14	0.25	-10000	0	-0.73	13	13
mol:GDP	-0.068	0.19	-10000	0	-0.55	38	38
SOS1	0.01	0.015	-10000	0	-10000	0	0
VAV1	-0.07	0.2	-10000	0	-0.56	38	38
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.047	0.19	-10000	0	-0.76	18	18
PTPN11	-0.006	0.013	-10000	0	-10000	0	0
IL6/IL6RA	-0.1	0.24	-10000	0	-0.6	87	87
gp130 (dimer)/TYK2/TYK2/LMO4	-0.013	0.088	-10000	0	-0.47	17	17
gp130 (dimer)/JAK2/JAK2/LMO4	-0.013	0.088	-10000	0	-0.47	17	17
IL6	-0.12	0.28	-10000	0	-0.74	82	82
PIAS3	0	0	-10000	0	-10000	0	0
PTPRE	0.01	0.05	-10000	0	-0.74	2	2
PIAS1	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.077	0.18	-10000	0	-0.45	61	61
LMO4	0.007	0.029	-10000	0	-0.59	1	1
STAT3 (dimer)/PIAS3	-0.21	0.22	-10000	0	-0.66	54	54
MCL1	0.05	0.048	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

Figure 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	0.094	-10000	0	-0.58	12	12
NFATC2	-0.055	0.3	-10000	0	-0.74	68	68
NFATC3	0.013	0.054	-10000	0	-10000	0	0
CD40LG	-0.18	0.45	-10000	0	-1.1	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	29	29
JUNB	-0.002	0.034	-10000	0	-0.74	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.053	0.12	-10000	0	-10000	0	0
T cell anergy	-0.06	0.18	-10000	0	-0.48	49	49
TLE4	-0.022	0.24	-10000	0	-0.8	23	23
Jun/NFAT1-c-4/p21SNFT	-0.12	0.27	-10000	0	-1.1	24	24
AP-1/NFAT1-c-4	-0.23	0.39	-10000	0	-1.3	39	39
IKZF1	-0.032	0.28	-10000	0	-1	23	23
T-helper 2 cell differentiation	-0.045	0.28	-10000	0	-0.81	43	43
AP-1/NFAT1	-0.14	0.24	-10000	0	-0.65	55	55
CALM1	-0.028	0.064	-10000	0	-10000	0	0
EGR2	-0.018	0.31	-10000	0	-1.4	15	15
EGR3	-0.02	0.31	-10000	0	-1.3	18	18
NFAT1/FOXP3	-0.091	0.21	-10000	0	-0.7	28	28
EGR1	-0.006	0.1	-10000	0	-0.74	9	9
JUN	0.002	0.022	-10000	0	-10000	0	0
EGR4	-0.005	0.087	-10000	0	-0.57	11	11
mol:Ca2+	-0.032	0.073	-10000	0	-10000	0	0
GBP3	-0.041	0.28	-10000	0	-0.9	32	32
FOSL1	-0.002	0.037	-10000	0	-0.57	2	2
NFAT1-c-4/MAF/IRF4	-0.098	0.26	-10000	0	-1.1	20	20
DGKA	-0.019	0.23	-10000	0	-0.77	21	21
CREM	0	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.15	0.3	-10000	0	-1	31	31
CTLA4	-0.018	0.21	-10000	0	-0.77	16	16
NFAT1-c-4 (dimer)/EGR1	-0.11	0.28	-10000	0	-1.1	23	23
NFAT1-c-4 (dimer)/EGR4	-0.11	0.27	-10000	0	-1	24	24
FOS	-0.083	0.24	-10000	0	-0.75	55	55
IFNG	-0.16	0.35	-10000	0	-1	51	51
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	-0.003	0.19	0.85	11	-10000	0	11
TNF	-0.038	0.3	-10000	0	-1	23	23
FASLG	-0.087	0.45	-10000	0	-1.5	34	34
TBX21	-0.064	0.23	-10000	0	-0.74	50	50
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	-0.06	0.22	-10000	0	-0.75	45	45
PTPN1	-0.019	0.23	-10000	0	-0.7	27	27
NFAT1-c-4/ICER1	-0.1	0.26	-10000	0	-1	24	24
GATA3	-0.024	0.13	-10000	0	-0.71	17	17
T-helper 1 cell differentiation	-0.16	0.34	-10000	0	-1	51	51
IL2RA	-0.15	0.28	-10000	0	-0.84	51	51
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.019	0.23	-10000	0	-0.77	21	21
E2F1	0.015	0.004	-10000	0	-10000	0	0
PPARG	-0.089	0.24	-10000	0	-0.74	58	58
SLC3A2	-0.019	0.23	-10000	0	-0.77	21	21
IRF4	-0.009	0.082	-10000	0	-0.74	6	6
PTGS2	-0.15	0.42	-10000	0	-1.1	54	54
CSF2	-0.15	0.42	-10000	0	-1.1	47	47
JunB/Fra1/NFAT1-c-4	-0.096	0.25	-10000	0	-1.1	19	19
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	-0.096	0.31	-10000	0	-0.8	77	77
NFATC1	0.003	0.19	-10000	0	-0.86	11	11
CDK4	0.007	0.16	0.62	8	-10000	0	8
PTPRK	-0.019	0.23	-10000	0	-0.77	21	21
IL8	-0.12	0.38	-10000	0	-1.1	37	37
POU2F1	0	0.003	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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
HDAC1	0.02	0	-9999	-10000	0	0
SMARCC1	0.007	0.008	-9999	-10000	0	0
REL	0	0.002	-9999	-10000	0	0
HDAC7	-0.03	0.12	-9999	-10000	0	0
JUN	0.001	0.003	-9999	-10000	0	0
EP300	0	0	-9999	-10000	0	0
KAT2B	-0.003	0.048	-9999	-0.74	2	2
KAT5	0	0.001	-9999	-10000	0	0
MAPK14	0.011	0.026	-9999	-0.44	1	1
FOXO1	0	0	-9999	-10000	0	0
T-DHT/AR	-0.038	0.13	-9999	-0.44	1	1
MAP2K6	0.005	0.028	-9999	-0.59	1	1
BRM/BAF57	-0.001	0.025	-9999	-0.56	1	1
MAP2K4	0.007	0.007	-9999	-10000	0	0
SMARCA2	-0.001	0.034	-9999	-0.74	1	1
PDE9A	-0.11	0.24	-9999	-0.85	28	28
NCOA2	0.002	0.034	-9999	-0.74	1	1
CEBPA	-0.001	0.034	-9999	-0.74	1	1
EHMT2	0.001	0.003	-9999	-10000	0	0
cell proliferation	-0.048	0.17	-9999	-0.52	24	24
NR0B1	-0.18	0.27	-9999	-0.57	155	155
EGR1	-0.013	0.1	-9999	-0.74	9	9
RXRs/9cRA	-0.23	0.22	-9999	-0.44	253	253
AR/RACK1/Src	-0.016	0.074	-9999	-10000	0	0
AR/GR	-0.064	0.12	-9999	-0.34	40	40
GNB2L1	0	0	-9999	-10000	0	0
PKN1	0	0	-9999	-10000	0	0
RCHY1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.012	0.016	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.015	0.074	-9999	-0.45	1	1
SRC	0.018	0.041	-9999	-10000	0	0
NR3C1	0	0	-9999	-10000	0	0
KLK3	-0.13	0.15	-9999	-0.6	13	13
APPBP2	0.007	0.006	-9999	-10000	0	0
TRIM24	0.001	0.004	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.037	0.053	-9999	-10000	0	0
TMPRSS2	-0.42	0.57	-9999	-1.2	156	156
RXRG	-0.39	0.37	-9999	-0.74	253	253
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0	0	-9999	-10000	0	0
RXRB	0	0	-9999	-10000	0	0
CARM1	0.004	0.005	-9999	-10000	0	0
NR2C2	0	0	-9999	-10000	0	0
KLK2	-0.021	0.13	-9999	-0.48	3	3
AR	-0.054	0.15	-9999	-0.33	101	101
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
MDM2	-0.001	0.026	-9999	-0.57	1	1
SRY	-0.005	0.052	-9999	-0.57	4	4
GATA2	-0.08	0.23	-9999	-0.74	52	52
MYST2	0	0.001	-9999	-10000	0	0
HOXB13	-0.34	0.28	-9999	-0.57	283	283
T-DHT/AR/RACK1/Src	-0.016	0.069	-9999	-10000	0	0
positive regulation of transcription	-0.08	0.23	-9999	-0.74	52	52
DNAJA1	0.007	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.006	-9999	-10000	0	0
NCOA1	0.014	0.004	-9999	-10000	0	0
SPDEF	-0.096	0.25	-9999	-0.73	64	64
T-DHT/AR/TIF2	0.012	0.059	-9999	-0.37	2	2
T-DHT/AR/Hsp90	-0.037	0.053	-9999	-10000	0	0
GSK3B	0.007	0.005	-9999	-10000	0	0
NR2C1	0	0.001	-9999	-10000	0	0
mol:T-DHT	0.012	0.043	-9999	-0.38	1	1
SIRT1	0	0	-9999	-10000	0	0
ZMIZ2	0	0.002	-9999	-10000	0	0
POU2F1	-0.001	0.042	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.13	0.15	-9999	-0.42	46	46
CREBBP	0	0	-9999	-10000	0	0
SMARCE1	0	0.002	-9999	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0	-9999	-10000	0	0
CCL5	-0.014	0.1	-9999	-0.74	9	9
SDCBP	0	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.088	0.1	-9999	-0.42	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.091	0.078	-9999	-0.4	5	5
Syndecan-1/Syntenin	-0.09	0.077	-9999	-0.46	2	2
MAPK3	-0.057	0.087	-9999	-0.48	1	1
HGF/MET	-0.12	0.23	-9999	-0.56	104	104
TGFB1/TGF beta receptor Type II	0	0	-9999	-10000	0	0
BSG	0	0	-9999	-10000	0	0
keratinocyte migration	-0.09	0.077	-9999	-0.39	5	5
Syndecan-1/RANTES	-0.098	0.1	-9999	-0.52	12	12
Syndecan-1/CD147	-0.083	0.072	-9999	-0.44	2	2
Syndecan-1/Syntenin/PIP2	-0.087	0.074	-9999	-0.44	2	2
LAMA5	-0.002	0.034	-9999	-0.74	1	1
positive regulation of cell-cell adhesion	-0.086	0.073	-9999	-0.43	2	2
MMP7	-0.038	0.15	-9999	-0.62	29	29
HGF	-0.16	0.3	-9999	-0.74	101	101
Syndecan-1/CASK	-0.084	0.094	-9999	-0.41	4	4
Syndecan-1/HGF/MET	-0.17	0.17	-9999	-0.46	104	104
regulation of cell adhesion	-0.049	0.085	-9999	-0.46	1	1
HPSE	0	0	-9999	-10000	0	0
positive regulation of cell migration	-0.088	0.1	-9999	-0.42	4	4
SDC1	-0.088	0.1	-9999	-0.43	4	4
Syndecan-1/Collagen	-0.088	0.1	-9999	-0.42	4	4
PPIB	0	0	-9999	-10000	0	0
MET	-0.004	0.054	-9999	-0.68	3	3
PRKACA	0	0	-9999	-10000	0	0
MMP9	-0.03	0.13	-9999	-0.57	25	25
MAPK1	-0.057	0.087	-9999	-0.48	1	1
homophilic cell adhesion	-0.087	0.099	-9999	-0.42	4	4
MMP1	-0.35	0.28	-9999	-0.57	298	298

×

Aurora A signaling

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

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

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

×

Wnt 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
Noncanonical Wnts/FZD	-0.044	0.085	-9999	-0.31	24	24
FZD6	0	0	-9999	-10000	0	0
WNT6	-0.096	0.21	-9999	-0.57	81	81
WNT4	-0.011	0.085	-9999	-0.66	8	8
FZD3	0	0	-9999	-10000	0	0
WNT5A	-0.012	0.084	-9999	-0.59	10	10
WNT11	-0.038	0.16	-9999	-0.68	27	27

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0	0.13	-10000	0	-0.38	31	31
TBX21	-0.095	0.5	-10000	0	-1.4	56	56
B2M	0.008	0.049	-10000	0	-0.74	2	2
TYK2	0.016	0.016	-10000	0	-10000	0	0
IL12RB1	-0.033	0.19	-10000	0	-0.77	31	31
GADD45B	-0.033	0.37	-10000	0	-1.1	39	39
IL12RB2	-0.045	0.18	-10000	0	-0.57	51	51
GADD45G	-0.017	0.33	-10000	0	-0.99	35	35
natural killer cell activation	0.006	0.019	-10000	0	-10000	0	0
RELB	-0.001	0.026	-10000	0	-0.57	1	1
RELA	0	0	-10000	0	-10000	0	0
IL18	0.008	0.06	-10000	0	-0.75	3	3
IL2RA	-0.008	0.073	-10000	0	-0.66	6	6
IFNG	-0.009	0.076	-10000	0	-0.68	6	6
STAT3 (dimer)	-0.005	0.29	-10000	0	-0.79	41	41
HLA-DRB5	-0.064	0.22	-10000	0	-0.74	47	47
FASLG	-0.05	0.41	-10000	0	-1.2	41	41
NF kappa B2 p52/RelB	-0.13	0.3	-10000	0	-0.95	44	44
CD4	-0.013	0.13	-10000	0	-0.74	14	14
SOCS1	-0.002	0.034	-10000	0	-0.74	1	1
EntrezGene:6955	-0.001	0.009	-10000	0	-10000	0	0
CD3D	-0.007	0.11	-10000	0	-0.74	11	11
CD3E	-0.004	0.1	-10000	0	-0.74	9	9
CD3G	-0.036	0.18	-10000	0	-0.74	30	30
IL12Rbeta2/JAK2	-0.02	0.14	-10000	0	-0.41	51	51
CCL3	-0.027	0.35	-10000	0	-1	36	36
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	-0.079	0.44	-10000	0	-1.2	51	51
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	-0.027	0.31	-10000	0	-1.3	22	22
RAB7A	0.007	0.28	-10000	0	-0.8	33	33
lysosomal transport	0.012	0.27	-10000	0	-0.74	34	34
FOS	-0.15	0.49	-10000	0	-1.2	75	75
STAT4 (dimer)	-0.008	0.34	-10000	0	-0.94	41	41
STAT5A (dimer)	-0.13	0.3	-10000	0	-0.96	45	45
GZMA	-0.033	0.37	-10000	0	-1.1	36	36
GZMB	-0.035	0.38	-10000	0	-1.2	36	36
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.037	0.39	-10000	0	-1.1	43	43
TCR/CD3/MHC II/CD4	-0.084	0.33	-10000	0	-0.91	46	46
IL2/IL2R	-0.014	0.1	-10000	0	-0.67	9	9
MAPK14	-0.015	0.34	-10000	0	-0.99	38	38
CCR5	-0.026	0.36	-10000	0	-1.2	30	30
IL1B	-0.002	0.12	-10000	0	-0.77	11	11
STAT6	0.018	0.1	-10000	0	-0.26	14	14
STAT4	-0.012	0.095	-10000	0	-0.74	8	8
STAT3	0	0	-10000	0	-10000	0	0
STAT1	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0	-10000	0	-10000	0	0
IL12B	0.017	0.016	-10000	0	-10000	0	0
CD8A	0	0.09	-10000	0	-0.74	7	7
CD8B	-0.011	0.12	-10000	0	-0.7	15	15
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0	0.13	0.38	31	-10000	0	31
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	0.095	-10000	0	-0.74	8	8
IL12	0.016	0.081	-10000	0	-0.57	8	8
STAT5A	0	0	-10000	0	-10000	0	0
CD247	-0.007	0.11	-10000	0	-0.75	11	11
IL2	0	0	-10000	0	-10000	0	0
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.003	0.1	-10000	0	-0.75	8	8
IL12/IL12R/TYK2/JAK2	-0.053	0.45	-10000	0	-1.2	46	46
MAP2K3	-0.019	0.34	-10000	0	-0.99	39	39
RIPK2	0	0	-10000	0	-10000	0	0
MAP2K6	-0.019	0.34	-10000	0	-0.98	40	40
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.053	0.21	-10000	0	-0.74	40	40
IL18RAP	-0.021	0.16	-10000	0	-0.75	22	22
IL12Rbeta1/TYK2	-0.016	0.15	-10000	0	-0.6	31	31
EOMES	-0.023	0.22	-10000	0	-1.4	11	11
STAT1 (dimer)	-0.003	0.29	-10000	0	-0.82	36	36
T cell proliferation	0.006	0.26	-10000	0	-0.68	39	39
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.005	0.078	-10000	0	-0.75	5	5
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.1	0.23	-10000	0	-0.76	40	40
ATF2	-0.003	0.31	-10000	0	-0.89	38	38

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.079	0.11	-10000	0	-0.51	17	17
epithelial cell differentiation	-0.035	0.1	-10000	0	-0.57	8	8
ITCH	0.023	0.027	-10000	0	-10000	0	0
WWP1	-0.039	0.088	-10000	0	-10000	0	0
FYN	-0.002	0.034	-10000	0	-0.74	1	1
EGFR	-0.022	0.12	-10000	0	-0.63	17	17
PRL	-0.009	0.073	-10000	0	-0.57	8	8
neuron projection morphogenesis	0.002	0.087	-10000	0	-10000	0	0
PTPRZ1	-0.38	0.27	-10000	0	-0.57	323	323
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.042	0.074	-10000	0	-0.48	6	6
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.056	0.094	-10000	0	-0.49	13	13
ADAM17	0.023	0.027	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.058	0.11	-10000	0	-0.49	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.18	0.22	-10000	0	-0.54	123	123
NCOR1	0	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.052	0.089	-10000	0	-0.56	7	7
GRIN2B	-0.027	0.1	-10000	0	-0.53	7	7
ErbB4/ErbB2/betacellulin	-0.073	0.13	-10000	0	-0.54	20	20
STAT1	0	0	-10000	0	-10000	0	0
HBEGF	-0.025	0.13	-10000	0	-0.74	16	16
PRLR	-0.039	0.15	-10000	0	-0.63	30	30
E4ICDs/ETO2	-0.072	0.1	-10000	0	-0.6	8	8
axon guidance	0.054	0.072	-10000	0	-10000	0	0
NEDD4	0.021	0.043	-10000	0	-0.71	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.036	0.13	-10000	0	-0.46	37	37
CBFA2T3	-0.012	0.095	-10000	0	-0.74	8	8
ErbB4/ErbB2/HBEGF	-0.055	0.09	-10000	0	-0.53	6	6
MAPK3	-0.037	0.069	-10000	0	-10000	0	0
STAT1 (dimer)	-0.064	0.079	-10000	0	-0.43	1	1
MAPK1	-0.037	0.069	-10000	0	-10000	0	0
JAK2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.052	0.086	-10000	0	-0.53	6	6
NRG1	0.015	0.097	-10000	0	-0.56	13	13
NRG3	-0.19	0.32	-10000	0	-0.74	122	122
NRG2	-0.078	0.23	-10000	0	-0.74	51	51
NRG4	-0.07	0.19	-10000	0	-0.57	59	59
heart development	0.054	0.072	-10000	0	-10000	0	0
neural crest cell migration	-0.052	0.085	-10000	0	-0.52	6	6
ERBB2	0.029	0.032	-10000	0	-0.42	2	2
WWOX/E4ICDs	-0.064	0.08	-10000	0	-0.43	1	1
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.1	0.14	-10000	0	-0.48	32	32
apoptosis	0.2	0.26	0.57	123	-10000	0	123
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.11	0.17	-10000	0	-0.54	51	51
ErbB4/ErbB2/epiregulin	-0.13	0.18	-10000	0	-0.53	50	50
ErbB4/ErbB4/betacellulin/betacellulin	-0.099	0.15	-10000	0	-0.55	37	37
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.084	0.13	-10000	0	-0.62	15	15
MDM2	-0.043	0.098	-10000	0	-0.43	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.04	0.079	-10000	0	-0.46	13	13
STAT5A	0.057	0.067	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.063	0.12	-10000	0	-0.58	14	14
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.059	0.073	-10000	0	-0.4	1	1
STAT5A (dimer)	-0.037	0.11	-10000	0	-0.62	8	8
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.045	0.067	-10000	0	-10000	0	0
LRIG1	-0.002	0.034	-10000	0	-0.74	1	1
EREG	-0.15	0.29	-10000	0	-0.72	102	102
BTC	-0.057	0.2	-10000	0	-0.74	37	37
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.054	0.072	-10000	0	-10000	0	0
ERBB4	-0.078	0.097	-10000	0	-0.49	1	1
STAT5B	0	0	-10000	0	-10000	0	0
YAP1	-0.02	0.025	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.077	0.12	-10000	0	-0.59	2	2
glial cell differentiation	0.058	0.072	0.4	1	-10000	0	1
WWOX	0	0	-10000	0	-10000	0	0
cell proliferation	-0.02	0.15	-10000	0	-0.6	12	12

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.008	0.056	-9999	-0.41	9	9
VLDLR	-0.003	0.048	-9999	-0.74	2	2
CRKL	0	0	-9999	-10000	0	0
LRPAP1	0	0	-9999	-10000	0	0
FYN	-0.002	0.034	-9999	-0.74	1	1
ITGA3	-0.008	0.075	-9999	-0.74	5	5
RELN/VLDLR/Fyn	-0.086	0.19	-9999	-0.49	83	83
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.001	0.022	-9999	-0.4	1	1
AKT1	-0.055	0.12	-9999	-0.52	2	2
MAP2K7	0	0	-9999	-10000	0	0
RAPGEF1	0	0	-9999	-10000	0	0
DAB1	-0.036	0.14	-9999	-0.57	30	30
RELN/LRP8/DAB1	-0.099	0.18	-9999	-0.45	84	84
LRPAP1/LRP8	-0.003	0.032	-9999	-0.41	3	3
RELN/LRP8/DAB1/Fyn	-0.093	0.17	-9999	-0.43	84	84
DAB1/alpha3/beta1 Integrin	-0.087	0.16	-9999	-0.69	5	5
long-term memory	-0.12	0.19	-9999	-0.73	15	15
DAB1/LIS1	-0.086	0.16	-9999	-0.63	4	4
DAB1/CRLK/C3G	-0.083	0.15	-9999	-0.61	4	4
PIK3CA	0	0	-9999	-10000	0	0
DAB1/NCK2	-0.087	0.16	-9999	-0.64	4	4
ARHGEF2	0	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.065	0.2	-9999	-0.66	48	48
CDK5R1	-0.011	0.077	-9999	-0.57	9	9
RELN	-0.13	0.28	-9999	-0.74	85	85
PIK3R1	0	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.087	0.18	-9999	-0.48	82	82
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.12	0.2	-9999	-0.74	15	15
MAPK8	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.099	0.18	-9999	-0.46	85	85
ITGB1	0	0	-9999	-10000	0	0
MAP1B	-0.093	0.17	-9999	-0.42	86	86
RELN/LRP8	-0.086	0.18	-9999	-0.48	82	82
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.094	0.17	-9999	-0.65	5	5
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.006	0.057	-9999	-0.56	5	5
RAP1A	-0.077	0.14	-9999	-0.57	4	4
PAFAH1B1	0	0	-9999	-10000	0	0
MAPK8IP1	-0.003	0.043	-9999	-0.66	2	2
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	-0.005	0.052	-9999	-0.57	4	4
NCK2	0	0	-9999	-10000	0	0
neuron differentiation	-0.014	0.096	-9999	-0.43	2	2
neuron adhesion	-0.075	0.14	-9999	-0.64	4	4
LRP8	-0.004	0.045	-9999	-0.57	3	3
GSK3B	-0.027	0.12	-9999	-0.48	2	2
RELN/VLDLR/DAB1/Fyn	-0.093	0.17	-9999	-0.43	85	85
MAP3K11	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.065	0.12	-9999	-0.32	85	85
CDK5	0	0	-9999	-10000	0	0
MAPT	0.003	0.085	-9999	-0.67	7	7
neuron migration	-0.031	0.17	-9999	-0.56	4	4
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.043	0.081	-9999	-0.44	2	2
RELN/VLDLR	-0.079	0.17	-9999	-0.44	83	83

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

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

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.064	0.098	-10000	0	-0.32	4	4
NT3 (dimer)/TRKC	-0.17	0.26	-10000	0	-0.57	146	146
NT3 (dimer)/TRKB	-0.12	0.19	-10000	0	-0.53	34	34
SHC/Grb2/SOS1/GAB1/PI3K	0	0	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	-0.095	0.25	-10000	0	-0.74	62	62
PIK3CA	0	0	-10000	0	-10000	0	0
DYNLT1	0	0	-10000	0	-10000	0	0
NTRK1	-0.009	0.082	-10000	0	-0.74	6	6
NTRK2	-0.14	0.26	-10000	0	-0.62	105	105
NTRK3	-0.22	0.34	-10000	0	-0.74	143	143
NT-4/5 (dimer)/TRKB	-0.12	0.19	-10000	0	-0.53	36	36
neuron apoptosis	0.13	0.19	0.47	86	-10000	0	86
SHC 2-3/Grb2	-0.14	0.21	-10000	0	-0.52	86	86
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.054	0.098	-10000	0	-0.55	8	8
SHC3	-0.16	0.26	-10000	0	-0.69	85	85
STAT3 (dimer)	-0.005	0.043	-10000	0	-0.37	6	6
NT3 (dimer)/TRKA	-0.041	0.12	-10000	0	-0.37	53	53
RIN/GDP	-0.046	0.093	-10000	0	-0.28	2	2
GIPC1	0	0	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
DNAJA3	-0.023	0.068	-10000	0	-0.46	2	2
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.013	0.11	-10000	0	-0.88	7	7
MAGED1	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.012	0.094	-10000	0	-0.74	8	8
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.035	0.12	-10000	0	-0.48	33	33
TRKA/NEDD4-2	-0.007	0.062	-10000	0	-0.56	6	6
ELMO1	-0.017	0.11	-10000	0	-0.74	11	11
RhoG/GTP/ELMO1/DOCK1	-0.011	0.073	-10000	0	-0.49	11	11
NGF	-0.017	0.11	-10000	0	-0.7	12	12
HRAS	0	0	-10000	0	-10000	0	0
DOCK1	0	0	-10000	0	-10000	0	0
GAB2	-0.018	0.12	-10000	0	-0.74	12	12
RIT2	0	0	-10000	0	-10000	0	0
RIT1	0	0	-10000	0	-10000	0	0
FRS2	0	0	-10000	0	-10000	0	0
DNM1	-0.002	0.037	-10000	0	-0.57	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.031	0.087	-10000	0	-0.4	13	13
mol:GDP	-0.067	0.13	-10000	0	-0.37	7	7
NGF (dimer)	-0.017	0.11	-10000	0	-0.7	12	12
RhoG/GDP	-0.013	0.085	-10000	0	-0.57	11	11
RIT1/GDP	-0.042	0.093	-10000	0	-0.27	2	2
TIAM1	0	0	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.14	0.23	-10000	0	-0.45	153	153
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.01	0.083	-10000	0	-0.69	7	7
RAP1/GDP	-0.047	0.067	-10000	0	-10000	0	0
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.095	0.25	-10000	0	-0.74	62	62
ubiquitin-dependent protein catabolic process	-0.017	0.087	-10000	0	-0.48	15	15
Schwann cell development	-0.054	0.036	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	-0.006	0.039	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.22	0.27	-10000	0	-0.72	74	74
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.049	0.077	-10000	0	-0.38	1	1
STAT3	-0.005	0.043	-10000	0	-0.37	6	6
axon guidance	-0.21	0.25	-10000	0	-0.68	74	74
MAPK3	-0.005	0.12	-10000	0	-0.43	33	33
MAPK1	-0.005	0.12	-10000	0	-0.43	33	33
CDC42/GDP	-0.042	0.093	-10000	0	-0.27	2	2
NTF3	-0.01	0.083	-10000	0	-0.69	7	7
NTF4	-0.012	0.095	-10000	0	-0.74	8	8
NGF (dimer)/TRKA/FAIM	-0.017	0.087	-10000	0	-0.48	15	15
PI3K	0	0	-10000	0	-10000	0	0
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.27	0.2	-10000	0	-0.42	302	302
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.13	0.24	-10000	0	-0.49	148	148
RGS19	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.057	0.08	-10000	0	-10000	0	0
Rac1/GDP	-0.042	0.093	-10000	0	-0.27	2	2
NGF (dimer)/TRKA/GRIT	-0.017	0.088	-10000	0	-0.46	18	18
neuron projection morphogenesis	0.004	0.073	-10000	0	-0.47	1	1
NGF (dimer)/TRKA/NEDD4-2	-0.017	0.087	-10000	0	-0.48	15	15
MAP2K1	0	0	-10000	0	-10000	0	0
NGFR	-0.047	0.16	-10000	0	-0.57	40	40
NGF (dimer)/TRKA/GIPC/GAIP	-0.011	0.055	-10000	0	-0.31	15	15
RAS family/GTP/PI3K	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.047	0.12	-10000	0	-0.66	15	15
RASA1	0	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.007	0.062	-10000	0	-0.56	6	6
SQSTM1	0	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.13	0.21	-10000	0	-0.5	79	79
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.014	0.073	-10000	0	-10000	0	0
MATK	-0.028	0.14	-10000	0	-0.74	18	18
NEDD4L	0	0	-10000	0	-10000	0	0
RAS family/GDP	-0.043	0.064	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.025	0.073	-10000	0	-0.33	15	15
Rac1/GTP	-0.18	0.13	-10000	0	-0.32	139	139
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.15	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	255	255
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	-0.46	20	20
MAP3K1	-0.14	0.17	-9999	-0.54	8	8
JUN	0	0	-9999	-10000	0	0
MAPK3	-0.12	0.16	-9999	-0.66	3	3
MAPK1	-0.12	0.16	-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	0.094	-9999	-0.74	8	8
NFKBIA	-0.1	0.16	-9999	-0.64	3	3
FOS	-0.084	0.24	-9999	-0.74	55	55
CD44	-0.002	0.034	-9999	-0.74	1	1
CHUK	0	0	-9999	-10000	0	0
PLAU	-0.1	0.16	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.12	0.11	-9999	-0.56	3	3
BCAR1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.009	0.071	-9999	-0.56	8	8
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.14	0.17	-9999	-0.52	9	9
VAV3	-0.13	0.17	-9999	-0.8	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	255	255
RAC1	0	0	-9999	-10000	0	0
Rac1/GTP	-0.13	0.13	-9999	-0.73	3	3
MMP2	-0.1	0.17	-9999	-0.66	8	8

×

Visual signal transduction: Rods

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
mol:K +	0	0	-9999	-10000	0	0
GNAT1/GTP	-0.007	0.054	-9999	-0.42	8	8
Metarhodopsin II/Arrestin	-0.001	0.023	-9999	-0.36	2	2
PDE6G/GNAT1/GTP	-0.015	0.079	-9999	-0.42	17	17
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.009	0.073	-9999	-0.57	8	8
GRK1	-0.002	0.037	-9999	-0.57	2	2
CNG Channel	-0.055	0.13	-9999	-0.58	6	6
mol:Na +	-0.094	0.15	-9999	-0.52	22	22
mol:ADP	-0.002	0.037	-9999	-0.57	2	2
RGS9-1/Gbeta5/R9AP	-0.062	0.17	-9999	-0.49	61	61
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.096	0.15	-9999	-0.54	22	22
CNGB1	-0.051	0.16	-9999	-0.57	43	43
RDH5	-0.003	0.048	-9999	-0.74	2	2
SAG	0	0	-9999	-10000	0	0
mol:Ca2+	-0.089	0.14	-9999	-0.5	22	22
Na + (4 Units)	-0.087	0.14	-9999	-0.49	22	22
RGS9	-0.081	0.23	-9999	-0.74	53	53
GNB1/GNGT1	-0.13	0.19	-9999	-0.41	150	150
GNAT1/GDP	-0.059	0.15	-9999	-0.43	61	61
GUCY2D	0	0	-9999	-10000	0	0
GNGT1	-0.18	0.26	-9999	-0.57	149	149
GUCY2F	0	0	-9999	-10000	0	0
GNB5	0	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.031	0.11	-9999	-0.42	30	30
mol:11-cis-retinal	-0.003	0.048	-9999	-0.74	2	2
mol:cGMP	-0.078	0.13	-9999	-10000	0	0
GNB1	-0.002	0.034	-9999	-0.74	1	1
Rhodopsin	-0.004	0.045	-9999	-0.49	4	4
SLC24A1	0	0	-9999	-10000	0	0
CNGA1	-0.007	0.063	-9999	-0.57	6	6
Metarhodopsin II	-0.003	0.029	-9999	-0.32	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.084	0.14	-9999	-10000	0	0
RGS9BP	-0.015	0.11	-9999	-0.74	10	10
Metarhodopsin II/Transducin	-0.052	0.076	-9999	-0.37	2	2
GCAP Family/Ca ++	-0.086	0.14	-9999	-10000	0	0
PDE6A/B	-0.026	0.12	-9999	-0.54	23	23
mol:Pi	-0.062	0.16	-9999	-0.49	61	61
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.1	0.15	-9999	-0.56	3	3
PDE6B	-0.013	0.098	-9999	-0.72	9	9
PDE6A	-0.021	0.12	-9999	-0.72	14	14
PDE6G	-0.014	0.1	-9999	-0.74	9	9
RHO	-0.002	0.037	-9999	-0.57	2	2
PDE6	-0.075	0.17	-9999	-0.8	10	10
GUCA1A	-0.15	0.25	-9999	-0.57	129	129
GC2/GCAP Family	-0.085	0.14	-9999	-10000	0	0
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.003	0.04	-9999	-0.51	3	3
CRKL	-0.025	0.12	-9999	-0.37	4	4
mol:PIP3	-0.016	0.006	-9999	-10000	0	0
AKT1	0.003	0.005	-9999	-10000	0	0
PTK2B	0	0	-9999	-10000	0	0
RAPGEF1	-0.017	0.11	-9999	-0.4	2	2
RANBP10	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.1	0.2	-9999	-0.48	104	104
MAP3K5	-0.01	0.11	-9999	-0.44	4	4
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.095	0.18	-9999	-0.44	103	103
AP1	-0.057	0.16	-9999	-0.5	55	55
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
apoptosis	-0.073	0.24	-9999	-0.73	55	55
STAT3 (dimer)	-0.033	0.13	-9999	-10000	0	0
GAB1/CRKL/SHP2/PI3K	-0.045	0.086	-9999	-10000	0	0
INPP5D	-0.002	0.034	-9999	-0.74	1	1
CBL/CRK	-0.018	0.11	-9999	-0.4	2	2
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
ELK1	-0.004	0.022	-9999	-0.24	3	3
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.039	0.076	-9999	-0.46	2	2
PAK1	0.009	0.014	-9999	-10000	0	0
HGF/MET/RANBP10	-0.1	0.2	-9999	-0.48	104	104
HRAS	-0.08	0.15	-9999	-0.59	4	4
DOCK1	-0.017	0.11	-9999	-0.4	2	2
GAB1	-0.034	0.12	-9999	-0.26	103	103
CRK	-0.025	0.12	-9999	-0.43	2	2
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.12	0.22	-9999	-0.54	103	103
JUN	0	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.054	0.1	-9999	-0.25	103	103
PIK3R1	0	0	-9999	-10000	0	0
cell morphogenesis	-0.01	0.14	-9999	-10000	0	0
GRB2/SHC	-0.045	0.088	-9999	-0.5	2	2
FOS	-0.085	0.24	-9999	-0.74	55	55
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.004	0.022	-9999	-0.24	3	3
HGF/MET/MUC20	-0.1	0.2	-9999	-0.48	104	104
cell migration	-0.044	0.087	-9999	-0.5	2	2
GRB2	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
MET/RANBP10	-0.003	0.04	-9999	-0.51	3	3
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.066	0.13	-9999	-0.31	103	103
MET/MUC20	-0.003	0.041	-9999	-0.52	3	3
RAP1B	-0.009	0.1	-9999	-0.37	2	2
RAP1A	-0.009	0.1	-9999	-0.37	2	2
HGF/MET/RANBP9	-0.1	0.2	-9999	-0.48	104	104
RAF1	-0.044	0.16	-9999	-0.55	4	4
STAT3	-0.063	0.12	-9999	-10000	0	0
cell proliferation	-0.047	0.18	-9999	-0.4	103	103
RPS6KB1	-0.019	0.036	-9999	-10000	0	0
MAPK3	-0.007	0.019	-9999	-10000	0	0
MAPK1	-0.007	0.019	-9999	-10000	0	0
RANBP9	0	0	-9999	-10000	0	0
MAPK8	0.008	0.095	-9999	-0.37	2	2
SRC	-0.061	0.12	-9999	-10000	0	0
PI3K	-0.045	0.088	-9999	-0.5	2	2
MET/Glomulin	-0.003	0.037	-9999	-0.46	3	3
SOS1	0	0	-9999	-10000	0	0
MAP2K1	-0.034	0.15	-9999	-0.5	4	4
MET	-0.004	0.054	-9999	-0.68	3	3
MAP4K1	-0.018	0.12	-9999	-0.47	4	4
PTK2	0	0	-9999	-10000	0	0
MAP2K2	-0.034	0.15	-9999	-0.5	4	4
BAD	0.009	0.005	-9999	-10000	0	0
MAP2K4	-0.002	0.1	-9999	-0.45	2	2
SHP2/GRB2/SOS1/GAB1	-0.047	0.091	-9999	-0.45	2	2
INPPL1	0	0	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
SH3KBP1	-0.003	0.048	-9999	-0.74	2	2
HGS	-0.048	0.095	-9999	-0.42	4	4
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.16	0.3	-9999	-0.74	101	101
RASA1	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
PTPRJ	-0.003	0.048	-9999	-0.74	2	2
NCK/PLCgamma1	-0.051	0.098	-9999	-0.53	2	2
PDPK1	-0.006	0.006	-9999	-10000	0	0
HGF/MET/SHIP	-0.1	0.2	-9999	-0.48	103	103

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	-0.43	14	14
EPO	-0.15	0.21	-10000	0	-0.66	13	13
FIH (dimer)	0.003	0.009	-10000	0	-10000	0	0
APEX1	0.003	0.012	-10000	0	-10000	0	0
SERPINE1	-0.2	0.24	-10000	0	-0.74	18	18
FLT1	-0.038	0.16	-10000	0	-0.98	12	12
ADORA2A	-0.19	0.23	-10000	0	-0.75	13	13
germ cell development	-0.19	0.24	-10000	0	-0.71	22	22
SLC11A2	-0.2	0.24	-10000	0	-0.78	13	13
BHLHE40	-0.2	0.24	-10000	0	-0.74	18	18
HIF1AN	0.003	0.009	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.14	0.16	-10000	0	-0.48	38	38
ETS1	0.003	0.12	-10000	0	-0.75	12	12
CITED2	-0.033	0.16	-10000	0	-1.3	8	8
KDR	-0.092	0.33	-10000	0	-1.3	32	32
PGK1	-0.2	0.24	-10000	0	-0.78	13	13
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.21	0.29	-10000	0	-0.79	37	37
EPAS1	-0.12	0.16	-10000	0	-0.4	75	75
SP1	0.016	0	-10000	0	-10000	0	0
ABCG2	-0.24	0.32	-10000	0	-0.95	57	57
EFNA1	-0.2	0.24	-10000	0	-0.78	13	13
FXN	-0.19	0.23	-10000	0	-0.75	13	13
POU5F1	-0.2	0.24	-10000	0	-0.74	22	22
neuron apoptosis	0.2	0.28	0.76	37	-10000	0	37
EP300	0	0	-10000	0	-10000	0	0
EGLN3	-0.084	0.21	-10000	0	-0.59	71	71
EGLN2	0.003	0.009	-10000	0	-10000	0	0
EGLN1	0.003	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0	0	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.003	0.012	-10000	0	-10000	0	0
SLC2A1	-0.37	0.28	-10000	0	-0.77	76	76
TWIST1	-0.27	0.3	-10000	0	-0.75	69	69
ELK1	0.016	0.002	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.14	0.15	-10000	0	-0.48	30	30
VEGFA	-0.2	0.24	-10000	0	-0.74	18	18
CREBBP	0	0	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.023	0.1	-10000	0	-0.46	24	24
ER alpha/Gai/GDP/Gbeta gamma	-0.025	0.11	-10000	0	-0.47	22	22
AKT1	-0.004	0.18	-10000	0	-0.82	21	21
PIK3CA	0	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.007	0.18	-10000	0	-0.83	21	21
mol:Ca2+	-0.087	0.23	-10000	0	-0.47	119	119
IGF1R	0	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.021	0.099	-10000	0	-0.49	21	21
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.002	0.17	0.78	21	-10000	0	21
RhoA/GTP	-0.016	0.073	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.027	0.11	-10000	0	-0.52	22	22
regulation of stress fiber formation	-0.032	0.07	0.58	1	-10000	0	1
E2/ERA-ERB (dimer)	-0.021	0.099	-10000	0	-0.49	21	21
KRAS	0	0	-10000	0	-10000	0	0
G13/GTP	-0.019	0.091	-10000	0	-0.45	21	21
pseudopodium formation	0.032	0.07	-10000	0	-0.58	1	1
E2/ER alpha (dimer)/PELP1	-0.021	0.099	-10000	0	-0.49	21	21
GRB2	0	0	-10000	0	-10000	0	0
GNG2	-0.008	0.075	-10000	0	-0.74	5	5
GNAO1	-0.004	0.05	-10000	0	-0.63	3	3
HRAS	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.016	0.13	-10000	0	-0.54	22	22
E2/ER beta (dimer)	0	0	-10000	0	-10000	0	0
mol:GDP	-0.022	0.1	-10000	0	-0.5	21	21
mol:NADP	0.016	0.13	-10000	0	-0.54	22	22
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.093	0.24	-10000	0	-0.49	119	119
IGF-1R heterotetramer	0	0	-10000	0	-10000	0	0
PLCB1	-0.12	0.22	-10000	0	-0.51	114	114
PLCB2	-0.13	0.23	-10000	0	-0.51	119	119
IGF1	-0.024	0.13	-10000	0	-0.73	16	16
mol:L-citrulline	0.016	0.13	-10000	0	-0.54	22	22
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.007	0.046	-10000	0	-0.67	1	1
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0	0	-10000	0	-10000	0	0
GNAQ	-0.002	0.034	-10000	0	-0.74	1	1
ESR1	-0.032	0.15	-10000	0	-0.74	21	21
Gq family/GDP/Gbeta gamma	-0.073	0.14	-10000	0	-0.81	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.019	0.071	-10000	0	-0.36	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.027	0.11	-10000	0	-0.52	22	22
GNAZ	-0.009	0.082	-10000	0	-0.74	6	6
E2/ER alpha (dimer)	-0.025	0.12	-10000	0	-0.57	21	21
STRN	0	0	-10000	0	-10000	0	0
GNAL	-0.006	0.067	-10000	0	-0.74	4	4
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.016	0	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.034	-10000	0	-0.74	1	1
HBEGF	0.015	0.12	-10000	0	-0.72	5	5
cAMP biosynthetic process	-0.02	0.091	-10000	0	-0.41	24	24
SRC	0.019	0.11	-10000	0	-0.44	22	22
PI3K	0	0	-10000	0	-10000	0	0
GNB1	-0.002	0.034	-10000	0	-0.74	1	1
G13/GDP/Gbeta gamma	-0.023	0.11	-10000	0	-0.49	21	21
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.03	0.11	-10000	0	-0.46	23	23
Gs family/GTP	-0.021	0.092	-10000	0	-0.42	24	24
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	0.017	0.12	-10000	0	-0.51	22	22
mol:DAG	-0.093	0.24	-10000	0	-0.49	119	119
Gs family/GDP/Gbeta gamma	-0.024	0.1	-10000	0	-0.46	21	21
MSN	0.033	0.076	-10000	0	-0.64	1	1
Gq family/GTP	-0.13	0.24	-10000	0	-0.54	114	114
mol:PI-3-4-5-P3	-0.006	0.17	-10000	0	-0.8	21	21
NRAS	0	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.017	0.12	0.51	22	-10000	0	22
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.02	0.096	-10000	0	-0.47	21	21
NOS3	0.016	0.13	-10000	0	-0.57	22	22
GNA11	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.02	0.14	-10000	0	-0.64	21	21
E2/ER alpha (dimer)/PELP1/Src	-0.028	0.12	-10000	0	-0.55	22	22
ruffle organization	0.032	0.07	-10000	0	-0.58	1	1
ROCK2	-0.014	0.067	-10000	0	-10000	0	0
GNA14	-0.18	0.32	-10000	0	-0.74	114	114
GNA15	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
MMP9	0.011	0.12	-10000	0	-0.59	5	5
MMP2	0.023	0.12	-10000	0	-0.79	5	5

×

Lissencephaly gene (LIS1) in neuronal migration and development

Figure 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
DYNC1H1	0	0	-9999	-10000	0	0
VLDLR	-0.003	0.048	-9999	-0.74	2	2
LRPAP1	0	0	-9999	-10000	0	0
NUDC	0	0	-9999	-10000	0	0
RELN/LRP8	-0.086	0.18	-9999	-0.48	82	82
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.053	0.18	-9999	-0.43	82	82
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.036	0.14	-9999	-0.57	30	30
IQGAP1	0	0	-9999	-10000	0	0
PLA2G7	-0.006	0.067	-9999	-0.74	4	4
CALM1	0	0	-9999	-10000	0	0
DYNLT1	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.003	0.032	-9999	-0.41	3	3
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0	0	-9999	-10000	0	0
CDK5R1	-0.011	0.077	-9999	-0.57	9	9
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.15	0.25	-9999	-0.57	124	124
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.11	0.2	-9999	-0.46	113	113
YWHAE	0	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.091	0.14	-9999	-0.48	26	26
MAP1B	-0.002	0.019	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.072	0.15	-9999	-0.6	2	2
RELN	-0.13	0.28	-9999	-0.74	85	85
PAFAH/LIS1	-0.004	0.043	-9999	-0.48	4	4
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.068	0.11	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.062	0.12	-9999	-0.56	3	3
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.099	0.15	-9999	-0.51	26	26
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.02	0	-9999	-10000	0	0
PAFAH1B3	-0.005	0.056	-9999	-0.61	4	4
PAFAH1B2	0	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.001	0.012	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.086	0.13	-9999	-0.46	26	26
LRP8	-0.004	0.045	-9999	-0.57	3	3
NDEL1/Katanin 60	-0.091	0.14	-9999	-0.48	26	26
P39/CDK5	-0.14	0.19	-9999	-0.66	25	25
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.042	0.16	-9999	-0.4	82	82
PPP2R5D	0	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.09	0.17	-9999	-0.44	36	36
RELN/VLDLR	-0.079	0.17	-9999	-0.44	83	83
CDC42	0	0	-9999	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

Figure 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
GRB2/SOS1/SHC	-0.04	0.14	-10000	0	-0.6	25	25
FYN	0.002	0.23	-10000	0	-0.91	24	24
LAT/GRAP2/SLP76	-0.053	0.18	-10000	0	-0.69	31	31
IKBKB	-0.001	0.026	-10000	0	-0.57	1	1
AKT1	0.023	0.14	-10000	0	-0.48	29	29
B2M	0.007	0.049	-10000	0	-0.75	2	2
IKBKG	-0.009	0.03	-10000	0	-0.18	1	1
MAP3K8	-0.003	0.048	-10000	0	-0.74	2	2
mol:Ca2+	-0.006	0.022	-10000	0	-0.12	15	15
integrin-mediated signaling pathway	-0.001	0.022	-10000	0	-0.48	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.01	0.21	-10000	0	-0.75	29	29
TRPV6	-0.019	0.12	-10000	0	-0.69	14	14
CD28	0.001	0.077	-10000	0	-0.75	5	5
SHC1	0.006	0.21	-10000	0	-0.81	25	25
receptor internalization	-0.01	0.23	-10000	0	-0.83	30	30
PRF1	-0.037	0.32	-10000	0	-1.3	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	0.21	-10000	0	-0.81	25	25
EntrezGene:6955	0.001	0.004	-10000	0	-10000	0	0
CD3D	-0.007	0.11	-10000	0	-0.75	11	11
CD3E	-0.004	0.1	-10000	0	-0.75	9	9
CD3G	-0.037	0.18	-10000	0	-0.75	30	30
RASGRP2	-0.013	0.066	-10000	0	-0.18	65	65
RASGRP1	0.025	0.14	-10000	0	-0.46	31	31
HLA-A	0.009	0.035	-10000	0	-0.75	1	1
RASSF5	-0.002	0.034	-10000	0	-0.74	1	1
RAP1A/GTP/RAPL	-0.001	0.022	-10000	0	-0.49	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.023	0.049	-10000	0	-0.13	26	26
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.017	0.054	-10000	0	-0.25	15	15
PRKCA	-0.023	0.076	-10000	0	-0.31	23	23
GRAP2	-0.04	0.17	-10000	0	-0.74	26	26
mol:IP3	-0.033	0.13	0.25	10	-0.49	27	37
EntrezGene:6957	0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.016	0.24	-10000	0	-0.86	26	26
ORAI1	0.01	0.064	0.35	14	-0.57	1	15
CSK	0.004	0.21	-10000	0	-0.82	25	25
B7 family/CD28	-0.064	0.23	-10000	0	-0.87	30	30
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.009	0.25	-10000	0	-1	25	25
PTPN6	0.001	0.21	-10000	0	-0.86	24	24
VAV1	0.004	0.22	-10000	0	-0.84	25	25
Monovalent TCR/CD3	-0.025	0.21	-10000	0	-0.64	36	36
CBL	0	0	-10000	0	-10000	0	0
LCK	-0.001	0.23	-10000	0	-0.93	24	24
PAG1	0.001	0.22	-10000	0	-0.84	25	25
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.01	0.25	-10000	0	-1	25	25
CD80	-0.016	0.14	-10000	0	-0.75	16	16
CD86	0	0.084	-10000	0	-0.75	6	6
PDK1/CARD11/BCL10/MALT1	-0.021	0.066	-10000	0	-0.3	17	17
HRAS	0	0	-10000	0	-10000	0	0
GO:0035030	0.006	0.19	-10000	0	-0.67	30	30
CD8A	-0.001	0.091	-10000	0	-0.75	7	7
CD8B	-0.011	0.12	-10000	0	-0.7	15	15
PTPRC	-0.039	0.18	-10000	0	-0.74	31	31
PDK1/PKC theta	0.018	0.18	-10000	0	-0.59	32	32
CSK/PAG1	0.007	0.21	-10000	0	-0.87	21	21
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.003	0.054	-10000	0	-0.8	2	2
GRAP2/SLP76	-0.063	0.21	-10000	0	-0.81	31	31
STIM1	0.007	0.031	-10000	0	-10000	0	0
RAS family/GTP	0.036	0.058	-10000	0	-0.18	16	16
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.015	0.26	-10000	0	-0.92	30	30
mol:DAG	-0.032	0.11	-10000	0	-0.44	27	27
RAP1A/GDP	0.011	0.021	-10000	0	-10000	0	0
PLCG1	0.001	0.003	-10000	0	-10000	0	0
CD247	-0.007	0.11	-10000	0	-0.75	11	11
cytotoxic T cell degranulation	-0.031	0.3	-10000	0	-1.2	30	30
RAP1A/GTP	-0.009	0.022	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.018	0.17	-10000	0	-0.59	29	29
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.045	0.17	0.26	10	-0.66	27	37
NRAS	0	0	-10000	0	-10000	0	0
ZAP70	-0.012	0.095	-10000	0	-0.74	8	8
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.05	0.16	-10000	0	-0.64	30	30
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.024	0.13	-10000	0	-0.67	17	17
CARD11	-0.004	0.05	-10000	0	-0.63	3	3
PRKCB	-0.033	0.1	-10000	0	-0.34	41	41
PRKCE	-0.023	0.074	-10000	0	-0.29	28	28
PRKCQ	0.006	0.21	-10000	0	-0.69	33	33
LCP2	-0.01	0.089	-10000	0	-0.74	7	7
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.026	0.12	-10000	0	-0.4	29	29
IKK complex	0.035	0.046	-10000	0	-0.13	10	10
RAS family/GDP	-0.003	0.007	-10000	0	-10000	0	0
MAP3K14	0.032	0.088	-10000	0	-0.3	21	21
PDPK1	0.027	0.13	-10000	0	-0.48	24	24
TCR/CD3/MHC I/CD8/Fyn	-0.011	0.25	-10000	0	-1	22	22

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.007	0.062	-9999	-0.56	6	6
Necdin/E2F1	-0.007	0.062	-9999	-0.56	6	6
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.038	0.11	-9999	-0.44	15	15
NGF (dimer)/p75(NTR)/BEX1	-0.096	0.19	-9999	-0.54	54	54
NT-4/5 (dimer)/p75(NTR)	-0.043	0.13	-9999	-0.44	48	48
IKBKB	-0.001	0.026	-9999	-0.57	1	1
AKT1	-0.032	0.099	-9999	-0.69	2	2
IKBKG	0	0	-9999	-10000	0	0
BDNF	-0.095	0.25	-9999	-0.74	62	62
MGDIs/NGR/p75(NTR)/LINGO1	-0.061	0.14	-9999	-0.37	79	79
FURIN	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.096	0.19	-9999	-0.46	101	101
LINGO1	-0.052	0.16	-9999	-0.57	44	44
Sortilin/TRAF6/NRIF	-0.004	0.039	-9999	-10000	0	0
proBDNF (dimer)	-0.095	0.25	-9999	-0.74	62	62
NTRK1	-0.009	0.082	-9999	-0.74	6	6
RTN4R	-0.003	0.043	-9999	-0.66	2	2
neuron apoptosis	-0.031	0.16	-9999	-0.56	13	13
IRAK1	0	0	-9999	-10000	0	0
SHC1	-0.018	0.13	-9999	-0.55	9	9
ARHGDIA	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.041	0.12	-9999	-0.48	15	15
MAGEH1	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.046	0.13	-9999	-0.48	20	20
Mammalian IAPs/DIABLO	-0.005	0.048	-9999	-0.43	6	6
proNGF (dimer)	-0.017	0.11	-9999	-0.7	12	12
MAGED1	0	0	-9999	-10000	0	0
APP	0	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.012	0.094	-9999	-0.74	8	8
ZNF274	0	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.033	0.1	-9999	-0.47	9	9
NGF	-0.017	0.11	-9999	-0.7	12	12
cell cycle arrest	-0.021	0.13	-9999	-0.44	15	15
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.018	0.06	-9999	-0.47	2	2
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.036	0.11	-9999	-0.48	8	8
NCSTN	0	0	-9999	-10000	0	0
mol:GTP	-0.039	0.12	-9999	-0.55	9	9
PSENEN	0	0	-9999	-10000	0	0
mol:ceramide	-0.015	0.12	-9999	-0.47	15	15
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.013	0.046	-9999	-0.37	2	2
p75(NTR)/beta APP	-0.034	0.11	-9999	-0.41	40	40
BEX1	-0.089	0.23	-9999	-0.68	63	63
mol:GDP	-0.026	0.13	-9999	-0.39	50	50
NGF (dimer)	-0.033	0.11	-9999	-0.5	17	17
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.055	0.13	-9999	-0.63	7	7
PIK3R1	0	0	-9999	-10000	0	0
RAC1/GTP	-0.034	0.1	-9999	-0.48	9	9
MYD88	0	0	-9999	-10000	0	0
CHUK	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.039	0.12	-9999	-0.55	9	9
RHOB	-0.002	0.034	-9999	-0.74	1	1
RHOA	0	0	-9999	-10000	0	0
MAGE-G1/E2F1	0	0	-9999	-10000	0	0
NT3 (dimer)	-0.01	0.083	-9999	-0.69	7	7
TP53	-0.075	0.15	-9999	-0.67	7	7
PRDM4	-0.015	0.12	-9999	-0.47	15	15
BDNF (dimer)	-0.27	0.24	-9999	-0.65	84	84
PIK3CA	0	0	-9999	-10000	0	0
SORT1	-0.009	0.082	-9999	-0.74	6	6
activation of caspase activity	-0.037	0.11	-9999	-0.44	15	15
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.041	0.12	-9999	-0.48	15	15
RHOC	0	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
MAPK10	-0.014	0.14	-9999	-0.5	14	14
DIABLO	0	0	-9999	-10000	0	0
SMPD2	-0.015	0.12	-9999	-0.47	15	15
APH1B	0	0	-9999	-10000	0	0
APH1A	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.045	0.13	-9999	-0.52	15	15
PSEN1	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.042	0.13	-9999	-0.43	47	47
MAPK8	-0.009	0.14	-9999	-0.49	12	12
MAPK9	-0.009	0.14	-9999	-0.56	6	6
APAF1	0	0	-9999	-10000	0	0
NTF3	-0.01	0.083	-9999	-0.69	7	7
NTF4	-0.012	0.095	-9999	-0.74	8	8
NDN	-0.009	0.082	-9999	-0.74	6	6
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.03	0.093	-9999	-0.65	2	2
p75 CTF/Sortilin/TRAF6/NRIF	-0.005	0.048	-9999	-0.43	6	6
RhoA-B-C/GTP	-0.039	0.12	-9999	-0.54	9	9
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.08	0.16	-9999	-0.44	67	67
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.086	0.18	-9999	-0.47	67	67
PRKACB	0	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.072	0.19	-9999	-0.56	62	62
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.009	0.082	-9999	-0.74	6	6
BIRC2	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.013	0.13	-9999	-0.44	14	14
BAD	-0.003	0.14	-9999	-0.55	6	6
RIPK2	0	0	-9999	-10000	0	0
NGFR	-0.047	0.16	-9999	-0.57	40	40
CYCS	-0.037	0.11	-9999	-0.55	4	4
ADAM17	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.035	0.11	-9999	-0.5	9	9
BCL2L11	-0.003	0.14	-9999	-0.55	6	6
BDNF (dimer)/p75(NTR)	-0.1	0.22	-9999	-0.53	96	96
PI3K	-0.035	0.11	-9999	-0.5	9	9
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.041	0.12	-9999	-0.48	15	15
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKCI	0	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.047	0.14	-9999	-0.45	50	50
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.041	0.12	-9999	-0.48	15	15
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
PLG	-0.004	0.045	-9999	-0.57	3	3
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.084	0.17	-9999	-0.6	18	18
SQSTM1	0	0	-9999	-10000	0	0
NGFRAP1	0	0	-9999	-10000	0	0
CASP3	0	0.13	-9999	-0.5	6	6
E2F1	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
IKK complex	-0.018	0.072	-9999	-0.51	2	2
NGF (dimer)/TRKA	-0.02	0.1	-9999	-0.53	18	18
MMP7	-0.038	0.15	-9999	-0.62	29	29
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.038	0.11	-9999	-0.44	15	15
MMP3	-0.34	0.28	-9999	-0.57	291	291
APAF-1/Caspase 9	-0.03	0.084	-9999	-0.54	3	3

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0	0.074	-9999	-0.71	5	5
PDGF/PDGFRA/CRKL	-0.006	0.053	-9999	-0.52	5	5
positive regulation of JUN kinase activity	-0.004	0.04	-9999	-0.42	4	4
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.097	0.21	-9999	-0.57	81	81
AP1	-0.13	0.34	-9999	-1.1	55	55
mol:IP3	0.01	0.06	-9999	-0.54	5	5
PLCG1	0.01	0.061	-9999	-0.54	5	5
PDGF/PDGFRA/alphaV Integrin	-0.006	0.053	-9999	-0.52	5	5
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.06	-9999	-0.54	5	5
CAV3	-0.12	0.27	-9999	-0.74	76	76
CAV1	-0.21	0.33	-9999	-0.74	135	135
SHC/Grb2/SOS1	-0.004	0.04	-9999	-0.42	4	4
PDGF/PDGFRA/Shf	-0.006	0.053	-9999	-0.52	5	5
FOS	-0.087	0.35	-9999	-1.1	55	55
JUN	-0.007	0.02	-9999	-10000	0	0
oligodendrocyte development	-0.006	0.053	-9999	-0.52	5	5
GRB2	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
mol:DAG	0.01	0.06	-9999	-0.54	5	5
PDGF/PDGFRA	0	0.074	-9999	-0.71	5	5
actin cytoskeleton reorganization	-0.006	0.053	-9999	-0.52	5	5
SRF	0.005	0.014	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.005	0.045	-9999	-0.47	4	4
PDGF/PDGFRA/Crk/C3G	-0.005	0.045	-9999	-0.47	4	4
JAK1	0.013	0.056	-9999	-0.52	5	5
ELK1/SRF	-0.006	0.04	-9999	-0.48	1	1
SHB	0	0	-9999	-10000	0	0
SHF	0	0	-9999	-10000	0	0
CSNK2A1	0.007	0.018	-9999	-10000	0	0
GO:0007205	0.011	0.062	-9999	-0.54	5	5
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.004	0.04	-9999	-0.42	4	4
PDGF/PDGFRA/SHB	-0.006	0.053	-9999	-0.52	5	5
PDGF/PDGFRA/Caveolin-1	-0.16	0.26	-9999	-0.57	138	138
ITGAV	0	0	-9999	-10000	0	0
ELK1	0.014	0.062	-9999	-0.52	4	4
PIK3CA	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.006	0.053	-9999	-0.52	5	5
JAK-STAT cascade	0.013	0.055	-9999	-0.52	5	5
cell proliferation	-0.006	0.053	-9999	-0.52	5	5

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.016	0.075	-9999	-0.36	21	21
EFNA5	-0.003	0.048	-9999	-0.74	2	2
FYN	0.004	0.074	-9999	-0.44	3	3
neuron projection morphogenesis	-0.016	0.075	-9999	-0.36	21	21
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.016	0.075	-9999	-0.36	21	21
EPHA5	-0.023	0.11	-9999	-0.57	19	19

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0	0	-9999	-10000	0	0
EGFR	-0.022	0.12	-9999	-0.63	17	17
EGF/EGFR	-0.056	0.15	-9999	-0.45	52	52
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.019	0.084	-9999	-0.44	12	12
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.008	0.075	-9999	-0.74	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.014	0.099	-9999	-0.69	10	10
EGF/EGFR dimer/SHC	-0.023	0.099	-9999	-0.42	26	26
mol:GDP	-0.019	0.083	-9999	-0.43	12	12
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.063	0.21	-9999	-0.74	41	41
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.017	0.076	-9999	-0.74	1	1
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.018	0.077	-9999	-0.75	1	1
FRAP1	-0.018	0.08	-9999	-0.42	12	12
EGF/EGFR dimer	-0.027	0.12	-9999	-0.5	26	26
SOS1	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.053	0.16	-9999	-0.56	46	46

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0	0.12	-10000	0	-0.48	25	25
ACTA1	-0.013	0.16	-10000	0	-0.64	25	25
NUMA1	0	0.12	-10000	0	-0.48	25	25
SPTAN1	-0.011	0.16	-10000	0	-0.64	25	25
LIMK1	-0.011	0.16	-10000	0	-0.64	25	25
BIRC3	-0.009	0.082	-10000	0	-0.74	6	6
BIRC2	0	0	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
CASP10	-0.012	0.16	-10000	0	-0.63	28	28
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0	0.12	-10000	0	-0.48	25	25
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.01	0.15	-10000	0	-0.62	25	25
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0	0	-10000	0	-10000	0	0
GSN	-0.011	0.16	-10000	0	-0.64	25	25
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	-0.069	0.12	-10000	0	-0.78	12	12
BID	0.004	0.075	-10000	0	-0.3	27	27
MAP3K1	0.003	0.047	-10000	0	-0.23	10	10
TRADD	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.012	0.16	-10000	0	-0.63	26	26
CASP9	0.001	0.002	-10000	0	-10000	0	0
DNA repair	-0.002	0.034	-10000	0	-0.21	2	2
neuron apoptosis	0.019	0.016	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.004	0.15	-10000	0	-0.61	25	25
APAF1	0.001	0.003	-10000	0	-10000	0	0
CASP6	0.017	0.073	-10000	0	-0.51	2	2
TRAF2	0	0	-10000	0	-10000	0	0
ICAD/CAD	-0.004	0.15	-10000	0	-0.61	25	25
CASP7	-0.005	0.043	0.36	6	-10000	0	6
KRT18	0.013	0.02	-10000	0	-10000	0	0
apoptosis	-0.003	0.15	-10000	0	-0.57	25	25
DFFA	-0.011	0.16	-10000	0	-0.64	25	25
DFFB	-0.011	0.16	-10000	0	-0.64	25	25
PARP1	0.002	0.035	0.21	2	-10000	0	2
actin filament polymerization	0.002	0.14	0.58	25	-10000	0	25
TNF	-0.02	0.12	-10000	0	-0.73	13	13
CYCS	0.007	0.056	-10000	0	-0.26	12	12
SATB1	0.02	0.079	-10000	0	-0.5	4	4
SLK	-0.011	0.16	-10000	0	-0.64	25	25
p15 BID/BAX	-0.015	0.062	-10000	0	-0.34	10	10
CASP2	0.034	0.052	-10000	0	-0.44	1	1
JNK cascade	-0.003	0.047	0.23	10	-10000	0	10
CASP3	-0.019	0.17	-10000	0	-0.68	25	25
LMNB2	0.032	0.049	-10000	0	-0.48	1	1
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.002	0.034	-10000	0	-0.74	1	1
Mammalian IAPs/DIABLO	-0.005	0.048	-10000	0	-0.43	6	6
negative regulation of DNA binding	-0.068	0.12	-10000	0	-0.77	12	12
stress fiber formation	-0.01	0.15	-10000	0	-0.62	25	25
GZMB	-0.022	0.18	-10000	0	-0.73	27	27
CASP1	0.011	0.052	-10000	0	-0.73	2	2
LMNB1	0.032	0.049	-10000	0	-0.48	1	1
APP	0.019	0.016	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.01	0	-10000	0	-10000	0	0
VIM	-0.008	0.14	-10000	0	-0.56	25	25
LMNA	0.032	0.049	-10000	0	-0.48	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.009	0.047	-10000	0	-0.47	1	1
LRDD	-0.002	0.034	-10000	0	-0.74	1	1
SREBF1	-0.011	0.16	-10000	0	-0.64	25	25
APAF-1/Caspase 9	-0.003	0.022	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0	0.12	-10000	0	-0.47	25	25
CFL2	-0.003	0.15	-10000	0	-0.6	25	25
GAS2	-0.063	0.22	-10000	0	-0.52	71	71
positive regulation of apoptosis	0.034	0.049	-10000	0	-0.47	1	1
PRF1	-0.038	0.16	-10000	0	-0.74	25	25

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.033	0.12	-9999	-0.47	34	34
MAP4K1	-0.006	0.067	-9999	-0.74	4	4
MAP3K8	-0.003	0.048	-9999	-0.74	2	2
PRKCB	-0.037	0.16	-9999	-0.74	24	24
DBNL	0	0	-9999	-10000	0	0
CRKL	0	0	-9999	-10000	0	0
MAP3K1	0.015	0.097	-9999	-0.72	3	3
JUN	-0.005	0.16	-9999	-0.66	24	24
MAP3K7	0.015	0.097	-9999	-0.72	3	3
GRAP2	-0.04	0.17	-9999	-0.74	26	26
CRK	0	0	-9999	-10000	0	0
MAP2K4	0.022	0.099	-9999	-0.77	3	3
LAT	0	0	-9999	-10000	0	0
LCP2	-0.011	0.089	-9999	-0.74	7	7
MAPK8	-0.012	0.16	-9999	-0.7	24	24
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.024	0.094	-9999	-0.76	3	3
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.031	0.12	-9999	-0.44	34	34

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.002	0.02	-10000	0	-10000	0	0
RFC1	0.002	0.02	-10000	0	-10000	0	0
PRKDC	0.002	0.02	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	-0.012	0.037	0.26	1	-10000	0	1
FASLG/FAS/FADD/FAF1	-0.018	0.075	0.24	5	-0.34	20	25
MAP2K4	-0.012	0.13	-10000	0	-0.5	8	8
mol:ceramide	-0.007	0.11	-10000	0	-0.44	21	21
GSN	0.002	0.02	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.027	0.09	0.22	4	-0.41	21	25
FAS	0.007	0.035	-10000	0	-0.76	1	1
BID	0.003	0.029	0.31	4	-10000	0	4
MAP3K1	0.003	0.079	-10000	0	-10000	0	0
MAP3K7	0	0	-10000	0	-10000	0	0
RB1	0.002	0.02	-10000	0	-10000	0	0
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.11	0.2	-10000	0	-0.48	106	106
ARHGDIB	0.001	0.023	-10000	0	-0.32	1	1
FADD	0.009	0.004	-10000	0	-10000	0	0
actin filament polymerization	-0.002	0.02	-10000	0	-10000	0	0
NFKB1	-0.039	0.08	-10000	0	-0.28	8	8
MAPK8	-0.033	0.19	-10000	0	-0.44	80	80
DFFA	0.002	0.02	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.002	0.02	-10000	0	-10000	0	0
FAS/FADD/MET	-0.004	0.041	-10000	0	-0.45	4	4
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.005	0.072	-10000	0	-0.7	5	5
FAF1	0.009	0.004	-10000	0	-10000	0	0
PARP1	0.002	0.02	-10000	0	-10000	0	0
DFFB	0.002	0.02	-10000	0	-10000	0	0
CHUK	-0.034	0.07	-10000	0	-10000	0	0
FASLG	-0.022	0.15	-10000	0	-0.75	20	20
FAS/FADD	-0.002	0.027	-10000	0	-0.58	1	1
HGF	-0.16	0.3	-10000	0	-0.74	101	101
LMNA	0.002	0.018	-10000	0	-10000	0	0
CASP6	0.002	0.02	-10000	0	-10000	0	0
CASP10	0.007	0.034	-10000	0	-0.74	1	1
CASP3	0.003	0.023	0.24	2	-10000	0	2
PTPN13	-0.006	0.067	-10000	0	-0.74	4	4
CASP8	0.004	0.041	0.43	4	-10000	0	4
IL6	-0.2	0.51	-10000	0	-1.3	82	82
MET	-0.004	0.054	-10000	0	-0.68	3	3
ICAD/CAD	0.002	0.019	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.008	0.12	-10000	0	-0.44	21	21
activation of caspase activity by cytochrome c	0.003	0.029	0.31	4	-10000	0	4
PAK2	0.002	0.02	-10000	0	-10000	0	0
BCL2	0.001	0.026	-10000	0	-0.57	1	1

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.007	0.013	-10000	0	-10000	0	0
HSPA8	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.024	0.11	-10000	0	-0.52	21	21
AKT1	0.006	0.021	-10000	0	-10000	0	0
GSC	-0.038	0.13	-10000	0	-0.47	2	2
NKX2-5	-0.29	0.28	-10000	0	-0.57	247	247
muscle cell differentiation	0.092	0.097	0.43	7	-10000	0	7
SMAD2-3/SMAD4/SP1	-0.009	0.034	-10000	0	-10000	0	0
SMAD4	0.017	0.026	-10000	0	-10000	0	0
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0	0	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.01	0.035	-10000	0	-0.46	1	1
SMAD3/SMAD4/VDR	0.009	0.033	-10000	0	-10000	0	0
MYC	0.007	0.024	-10000	0	-10000	0	0
CDKN2B	-0.093	0.41	-10000	0	-1.4	41	41
AP1	-0.036	0.12	-10000	0	-0.46	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	-0.029	0.088	-10000	0	-0.42	4	4
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	-0.048	0.17	-10000	0	-0.58	44	44
SMAD3/SMAD4/GR	-0.003	0.014	-10000	0	-10000	0	0
GATA3	-0.026	0.13	-10000	0	-0.71	17	17
SKI/SIN3/HDAC complex/NCoR1	0	0	-10000	0	-10000	0	0
MEF2C/TIF2	-0.17	0.19	-10000	0	-0.68	31	31
endothelial cell migration	-0.013	0.023	-10000	0	-10000	0	0
MAX	0	0	-10000	0	-10000	0	0
RBBP7	0	0	-10000	0	-10000	0	0
RBBP4	0	0	-10000	0	-10000	0	0
RUNX2	0	0	-10000	0	-10000	0	0
RUNX3	0	0	-10000	0	-10000	0	0
RUNX1	0	0	-10000	0	-10000	0	0
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	0	0	-10000	0	-10000	0	0
VDR	-0.002	0.034	-10000	0	-0.74	1	1
CDKN1A	0.058	0.042	-10000	0	-10000	0	0
KAT2B	0	0.048	-10000	0	-0.74	2	2
SMAD2/SMAD2/SMAD4/FOXH1	-0.046	0.11	-10000	0	-0.48	12	12
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0	-10000	0	-10000	0	0
SERPINE1	0.013	0.023	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF2	-0.001	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.001	0.017	-10000	0	-10000	0	0
SAP30	0	0	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.016	0.031	-10000	0	-10000	0	0
JUN	0.007	0.13	-10000	0	-0.45	1	1
SMAD3/SMAD4/IRF7	-0.004	0.039	-10000	0	-0.54	2	2
TFE3	0.016	0.001	-10000	0	-10000	0	0
COL1A2	0.005	0.051	-10000	0	-0.4	4	4
mesenchymal cell differentiation	0.001	0.017	-10000	0	-10000	0	0
DLX1	-0.33	0.28	-10000	0	-0.57	276	276
TCF3	0	0	-10000	0	-10000	0	0
FOS	-0.071	0.24	-10000	0	-0.73	55	55
SMAD3/SMAD4/Max	-0.003	0.014	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0	0.016	-10000	0	-0.34	1	1
ZBTB17	0.006	0.019	-10000	0	-10000	0	0
LAMC1	0.048	0.028	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.017	-10000	0	-10000	0	0
IRF7	-0.003	0.048	-10000	0	-0.74	2	2
ESR1	-0.032	0.15	-10000	0	-0.74	21	21
HNF4A	-0.009	0.073	-10000	0	-0.57	8	8
MEF2C	-0.16	0.22	-10000	0	-0.71	31	31
SMAD2-3/SMAD4	-0.009	0.029	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.011	0.021	-10000	0	-10000	0	0
IGHV3OR16-13	0	0.001	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	0.005	0.01	-10000	0	-10000	0	0
SKIL	0	0	-10000	0	-10000	0	0
HDAC1	0	0	-10000	0	-10000	0	0
HDAC2	0	0	-10000	0	-10000	0	0
SNIP1	-0.001	0.026	-10000	0	-0.58	1	1
GCN5L2	0.003	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.004	0.022	-10000	0	-10000	0	0
MSG1/HSC70	-0.002	0.032	-10000	0	-0.49	2	2
SMAD2	0.004	0.027	-10000	0	-10000	0	0
SMAD3	0.019	0.022	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.039	0.027	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.013	0.029	-10000	0	-0.4	2	2
NCOR1	0	0	-10000	0	-10000	0	0
NCOA2	-0.002	0.034	-10000	0	-0.74	1	1
NCOA1	0	0	-10000	0	-10000	0	0
MYOD/E2A	-0.059	0.14	-10000	0	-0.41	69	69
SMAD2-3/SMAD4/SP1/MIZ-1	0.016	0.052	-10000	0	-10000	0	0
IFNB1	0.035	0.049	-10000	0	-0.48	3	3
SMAD3/SMAD4/MEF2C	-0.17	0.19	-10000	0	-0.69	31	31
CITED1	-0.003	0.043	-10000	0	-0.66	2	2
SMAD2-3/SMAD4/ARC105	-0.007	0.023	-10000	0	-10000	0	0
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.011	0.15	-10000	0	-0.48	41	41
RUNX1-3/PEBPB2	0	0	-10000	0	-10000	0	0
SMAD7	-0.024	0.1	-10000	0	-1.1	1	1
MYC/MIZ-1	0.013	0.042	-10000	0	-10000	0	0
SMAD3/SMAD4	0.035	0.072	0.28	7	-10000	0	7
IL10	0.026	0.11	-10000	0	-0.86	3	3
PIASy/HDAC complex	0.005	0.005	-10000	0	-10000	0	0
PIAS3	0.004	0.007	-10000	0	-10000	0	0
CDK2	0.005	0.01	-10000	0	-10000	0	0
IL5	0.023	0.096	-10000	0	-0.56	2	2
CDK4	0.005	0.028	-10000	0	-0.57	1	1
PIAS4	0.006	0.005	-10000	0	-10000	0	0
ATF3	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1	0.002	0.027	-10000	0	-10000	0	0
FOXG1	-0.061	0.18	-10000	0	-0.57	51	51
FOXO3	0.015	0.028	-10000	0	-10000	0	0
FOXO1	0.015	0.028	-10000	0	-10000	0	0
FOXO4	0.015	0.028	-10000	0	-10000	0	0
heart looping	-0.16	0.22	-10000	0	-0.7	31	31
CEBPB	0.008	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.2	0.18	-10000	0	-0.4	56	56
MYOD1	-0.082	0.2	-10000	0	-0.57	69	69
SMAD3/SMAD4/HNF4	-0.007	0.048	-10000	0	-0.38	1	1
SMAD3/SMAD4/GATA3	-0.02	0.094	-10000	0	-0.51	15	15
SnoN/SIN3/HDAC complex/NCoR1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.001	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.004	0.025	-10000	0	-10000	0	0
MED15	0	0	-10000	0	-10000	0	0
SP1	0.017	0.011	-10000	0	-10000	0	0
SIN3B	0	0	-10000	0	-10000	0	0
SIN3A	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.2	0.19	-10000	0	-0.65	33	33
ITGB5	0.056	0.034	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.11	0.2	-10000	0	-0.5	101	101
AR	-0.16	0.3	-10000	0	-0.74	101	101
negative regulation of cell growth	0.004	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.052	0.13	-10000	0	-0.41	14	14
E2F5	0	0	-10000	0	-10000	0	0
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.031	0.088	-10000	0	-0.55	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	-0.019	0.095	-10000	0	-0.35	8	8
TFDP1	-0.004	0.045	-10000	0	-0.57	3	3
SMAD3/SMAD4/AP1	-0.035	0.12	-10000	0	-0.46	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

×

Noncanonical Wnt signaling pathway

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
NFATC2	-0.1	0.26	-9999	-0.74	66	66
GNB1/GNG2	-0.042	0.086	-9999	-0.47	7	7
mol:DAG	-0.002	0.095	-9999	-0.48	4	4
PLCG1	-0.038	0.08	-9999	-0.5	4	4
YES1	-0.04	0.077	-9999	-0.45	1	1
FZD3	0	0	-9999	-10000	0	0
FZD6	0	0	-9999	-10000	0	0
G protein	-0.038	0.081	-9999	-0.51	4	4
MAP3K7	-0.015	0.14	-9999	-0.54	13	13
mol:Ca2+	-0.002	0.093	-9999	-0.47	4	4
mol:IP3	-0.002	0.095	-9999	-0.48	4	4
NLK	-0.003	0.007	-9999	-10000	0	0
GNB1	-0.002	0.034	-9999	-0.74	1	1
CAMK2A	-0.025	0.15	-9999	-0.58	14	14
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.044	0.085	-9999	-0.37	3	3
CSNK1A1	0	0	-9999	-10000	0	0
GNAS	-0.04	0.077	-9999	-0.45	1	1
GO:0007205	-0.001	0.094	-9999	-0.48	4	4
WNT6	-0.096	0.21	-9999	-0.57	81	81
WNT4	-0.011	0.085	-9999	-0.66	8	8
NFAT1/CK1 alpha	-0.08	0.14	-9999	-0.54	17	17
GNG2	-0.008	0.075	-9999	-0.74	5	5
WNT5A	-0.012	0.084	-9999	-0.59	10	10
WNT11	-0.038	0.16	-9999	-0.68	27	27
CDC42	-0.004	0.088	-9999	-0.43	1	1

×

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

×

Effects of Botulinum toxin

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

×

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	0.049	-9999	-0.75	2	2
PTPN7	0.007	0.043	-9999	-0.66	2	2
HRAS	0	0	-9999	-10000	0	0
PRKCB	-0.028	0.16	-9999	-0.74	24	24
NRAS	0	0	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.009	0.061	-9999	-0.45	1	1
MAP2K1	-0.001	0.13	-9999	-0.52	25	25
ELK1	-0.001	0.004	-9999	-10000	0	0
BRAF	-0.03	0.12	-9999	-0.52	25	25
mol:GTP	-0.001	0.002	-9999	-0.006	55	55
MAPK1	0.009	0.061	-9999	-0.45	1	1
RAF1	-0.03	0.12	-9999	-0.52	25	25
KRAS	0	0	-9999	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.029	0.12	-9999	-0.56	25	25
PDGFRB	0.008	0.034	-9999	-0.74	1	1
SPHK1	-0.008	0.021	-9999	-10000	0	0
mol:S1P	-0.01	0.029	-9999	-10000	0	0
S1P1/S1P/Gi	-0.001	0.14	-9999	-0.59	7	7
GNAO1	0.006	0.051	-9999	-0.64	3	3
PDGFB-D/PDGFRB/PLCgamma1	-0.04	0.1	-9999	-0.5	8	8
PLCG1	0.006	0.13	-9999	-0.54	7	7
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.008	0.034	-9999	-0.74	1	1
GNAI2	0.01	0.004	-9999	-10000	0	0
GNAI3	0.009	0.004	-9999	-10000	0	0
GNAI1	0.008	0.035	-9999	-0.75	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.011	0.11	-9999	-0.48	25	25
S1P1/S1P	-0.031	0.091	-9999	-0.38	25	25
negative regulation of cAMP metabolic process	0	0.13	-9999	-0.57	7	7
MAPK3	-0.011	0.19	-9999	-0.55	49	49
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	-0.038	0.16	-9999	-0.74	25	25
PLCB2	0.004	0.11	-9999	-0.4	15	15
RAC1	0	0	-9999	-10000	0	0
RhoA/GTP	-0.027	0.077	-9999	-0.41	7	7
receptor internalization	-0.03	0.085	-9999	-0.36	25	25
PTGS2	-0.061	0.34	-9999	-1.1	49	49
Rac1/GTP	-0.027	0.077	-9999	-0.41	7	7
RHOA	0	0	-9999	-10000	0	0
VEGFA	0	0.001	-9999	-10000	0	0
negative regulation of T cell proliferation	0	0.13	-9999	-0.57	7	7
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0	0.084	-9999	-0.74	6	6
MAPK1	-0.011	0.19	-9999	-0.55	49	49
S1P1/S1P/PDGFB-D/PDGFRB	0.006	0.11	-9999	-0.56	7	7
ABCC1	-0.001	0.026	-9999	-0.57	1	1

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

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

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.014	0.094	-10000	0	-0.47	10	10
IKBKB	0.015	0.051	-10000	0	-0.28	2	2
AKT1	0.003	0.085	-10000	0	-0.28	11	11
IKBKG	0.017	0.053	-10000	0	-0.28	5	5
CALM1	-0.009	0.097	-10000	0	-0.49	12	12
PIK3CA	0	0	-10000	0	-10000	0	0
MAP3K1	0	0.14	-10000	0	-0.7	11	11
MAP3K7	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.1	-10000	0	-0.53	12	12
DOK1	0	0	-10000	0	-10000	0	0
AP-1	-0.001	0.08	-10000	0	-0.28	6	6
LYN	-0.003	0.048	-10000	0	-0.74	2	2
BLNK	-0.002	0.034	-10000	0	-0.74	1	1
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.03	0.12	-10000	0	-0.52	28	28
CD22	-0.076	0.21	-10000	0	-0.62	51	51
CAMK2G	-0.002	0.091	-10000	0	-0.64	5	5
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	-0.001	0.034	-10000	0	-0.74	1	1
SHC/GRB2/SOS1	-0.021	0.091	-10000	0	-0.74	3	3
GO:0007205	-0.018	0.1	-10000	0	-0.54	12	12
SYK	-0.002	0.034	-10000	0	-0.74	1	1
ELK1	-0.01	0.099	-10000	0	-0.5	12	12
NFATC1	-0.007	0.12	-10000	0	-0.54	14	14
B-cell antigen/BCR complex	-0.03	0.12	-10000	0	-0.52	28	28
PAG1/CSK	-0.007	0.062	-10000	0	-0.56	6	6
NFKBIB	0.014	0.019	0.078	2	-10000	0	2
HRAS	-0.002	0.094	-10000	0	-0.48	12	12
NFKBIA	0.014	0.019	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	-0.51	21	21
mol:GDP	-0.019	0.1	-10000	0	-0.52	12	12
PTEN	0	0	-10000	0	-10000	0	0
CD79B	-0.006	0.064	-10000	0	-0.7	4	4
NF-kappa-B/RelA/I kappa B alpha	0.018	0.016	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.015	0.14	-10000	0	-0.56	18	18
PIK3R1	0	0	-10000	0	-10000	0	0
mol:IP3	-0.026	0.1	-10000	0	-0.55	12	12
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.047	0.16	-10000	0	-0.41	59	59
CHUK	0.017	0.053	-10000	0	-0.29	3	3
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.022	0.081	-10000	0	-0.61	6	6
PTPN6	-0.07	0.2	-10000	0	-0.78	25	25
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0.015	0.024	-10000	0	-0.12	11	11
VAV2	-0.059	0.16	-10000	0	-0.83	13	13
ubiquitin-dependent protein catabolic process	0.018	0.019	0.081	2	-10000	0	2
BTK	-0.11	0.33	-10000	0	-1.1	45	45
CD19	-0.066	0.17	-10000	0	-0.66	23	23
MAP4K1	-0.006	0.067	-10000	0	-0.74	4	4
CD72	-0.001	0.026	-10000	0	-0.57	1	1
PAG1	-0.009	0.082	-10000	0	-0.74	6	6
MAPK14	0.01	0.12	-10000	0	-0.59	10	10
SH3BP5	-0.011	0.089	-10000	0	-0.74	7	7
PIK3AP1	-0.012	0.13	-10000	0	-0.68	12	12
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.032	0.13	-10000	0	-0.68	14	14
RAF1	0.005	0.088	-10000	0	-0.62	5	5
RasGAP/p62DOK/SHIP	-0.028	0.12	-10000	0	-0.74	7	7
CD79A	-0.035	0.15	-10000	0	-0.66	26	26
re-entry into mitotic cell cycle	-0.001	0.08	-10000	0	-0.29	6	6
RASA1	0	0	-10000	0	-10000	0	0
MAPK3	0.018	0.074	-10000	0	-0.49	5	5
MAPK1	0.018	0.074	-10000	0	-0.49	5	5
CD72/SHP1	-0.065	0.18	-10000	0	-0.72	25	25
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.01	0.12	-10000	0	-0.59	10	10
actin cytoskeleton organization	-0.014	0.15	-10000	0	-0.67	13	13
NF-kappa-B/RelA	0.039	0.031	0.16	2	-10000	0	2
Calcineurin	-0.02	0.073	-10000	0	-0.57	5	5
PI3K	-0.064	0.14	-10000	0	-0.6	17	17
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.023	0.1	0.26	4	-0.53	12	16
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.038	0.16	-10000	0	-0.91	12	12
DAPP1	-0.042	0.18	-10000	0	-1.1	11	11
cytokine secretion	-0.005	0.11	-10000	0	-0.5	14	14
mol:DAG	-0.026	0.1	-10000	0	-0.55	12	12
PLCG2	0	0	-10000	0	-10000	0	0
MAP2K1	0.012	0.082	-10000	0	-0.55	5	5
B-cell antigen/BCR complex/FcgammaRIIB	-0.034	0.14	-10000	0	-0.59	21	21
mol:PI-3-4-5-P3	-0.047	0.099	-10000	0	-0.4	17	17
ETS1	-0.004	0.11	-10000	0	-0.52	15	15
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	-0.75	25	25
CARD11	-0.012	0.11	-10000	0	-0.55	12	12
FCGR2B	-0.014	0.1	-10000	0	-0.74	9	9
PPP3CA	0	0	-10000	0	-10000	0	0
BCL10	0	0	-10000	0	-10000	0	0
IKK complex	0.016	0.026	-10000	0	-10000	0	0
PTPRC	-0.048	0.18	-10000	0	-0.74	31	31
PDPK1	-0.031	0.067	-10000	0	-0.28	9	9
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.018	0.013	-10000	0	-0.1	1	1

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.028	0.11	0.45	30	-10000	0	30
KIRREL	-0.005	0.091	-10000	0	-0.75	7	7
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.028	0.11	-10000	0	-0.45	30	30
PLCG1	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.022	0.084	-10000	0	-0.46	8	8
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.012	0.051	-10000	0	-0.34	7	7
FYN	-0.02	0.08	-10000	0	-0.46	8	8
mol:Ca2+	-0.021	0.083	-10000	0	-0.45	8	8
mol:DAG	-0.022	0.084	-10000	0	-0.46	8	8
NPHS2	-0.003	0.048	-10000	0	-0.58	3	3
mol:IP3	-0.022	0.084	-10000	0	-0.46	8	8
regulation of endocytosis	-0.018	0.074	-10000	0	-0.43	8	8
Nephrin/NEPH1/podocin/Cholesterol	-0.022	0.086	-10000	0	-0.46	8	8
establishment of cell polarity	-0.028	0.11	-10000	0	-0.45	30	30
Nephrin/NEPH1/podocin/NCK1-2	-0.019	0.075	-10000	0	-0.42	8	8
Nephrin/NEPH1/beta Arrestin2	-0.019	0.075	-10000	0	-0.44	8	8
NPHS1	-0.021	0.12	-10000	0	-0.57	23	23
Nephrin/NEPH1/podocin	-0.02	0.081	-10000	0	-0.47	8	8
TJP1	0	0	-10000	0	-10000	0	0
NCK1	0	0	-10000	0	-10000	0	0
NCK2	0	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.022	0.084	-10000	0	-0.46	8	8
CD2AP	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.022	0.084	-10000	0	-0.46	8	8
GRB2	0	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.02	0.13	-10000	0	-0.49	26	26
cytoskeleton organization	-0.015	0.064	-10000	0	-0.42	8	8
Nephrin/NEPH1	-0.02	0.079	-10000	0	-0.32	30	30
Nephrin/NEPH1/ZO-1	-0.022	0.087	-10000	0	-0.46	8	8

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.006	0.006	-9999	-10000	0	0
HDAC2	0.006	0.006	-9999	-10000	0	0
GNB1/GNG2	-0.007	0.058	-9999	-0.48	6	6
forebrain development	-0.089	0.14	-9999	-0.49	9	9
GNAO1	0.001	0.051	-9999	-0.63	3	3
SMO/beta Arrestin2	-0.002	0.027	-9999	-0.42	2	2
SMO	0.003	0.038	-9999	-0.58	2	2
ARRB2	0.005	0.005	-9999	-10000	0	0
GLI3/SPOP	0.043	0.015	-9999	-10000	0	0
mol:GTP	-0.003	0.004	-9999	-10000	0	0
GSK3B	0	0	-9999	-10000	0	0
GNAI2	0.005	0.005	-9999	-10000	0	0
SIN3/HDAC complex	0	0.004	-9999	-10000	0	0
GNAI1	0.004	0.035	-9999	-0.75	1	1
XPO1	0.006	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.11	0.11	-9999	-0.53	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	-10000	0	0
CSNK1D	0	0	-9999	-10000	0	0
CSNK1E	0	0	-9999	-10000	0	0
SAP18	0.006	0.006	-9999	-10000	0	0
embryonic digit morphogenesis	0	0	-9999	-10000	0	0
GNG2	-0.008	0.075	-9999	-0.74	5	5
Gi family/GTP	0.001	0.05	-9999	-0.33	5	5
SIN3B	0.006	0.006	-9999	-10000	0	0
SIN3A	0.006	0.006	-9999	-10000	0	0
GLI3/Su(fu)	-0.001	0.009	-9999	-10000	0	0
GLI2/Su(fu)	0.023	0.032	-9999	-10000	0	0
FOXA2	-0.61	0.6	-9999	-1.2	244	244
neural tube patterning	-0.089	0.14	-9999	-0.49	9	9
SPOP	0	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.001	0.009	-9999	-10000	0	0
GNB1	-0.002	0.034	-9999	-0.74	1	1
CSNK1G2	0	0	-9999	-10000	0	0
CSNK1G3	0	0	-9999	-10000	0	0
MTSS1	-0.033	0.05	-9999	-10000	0	0
embryonic limb morphogenesis	-0.089	0.14	-9999	-0.49	9	9
SUFU	0.011	0.017	-9999	-10000	0	0
LGALS3	0	0	-9999	-10000	0	0
catabolic process	-0.001	0.012	-9999	-10000	0	0
GLI3A/CBP	0.005	0.033	-9999	-0.38	1	1
KIF3A	0	0	-9999	-10000	0	0
GLI1	-0.091	0.15	-9999	-0.5	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	0.083	-9999	-0.74	6	6
RBBP4	0.006	0.006	-9999	-10000	0	0
CSNK1G1	0	0	-9999	-10000	0	0
PIAS1	0	0	-9999	-10000	0	0
PRKACA	0	0	-9999	-10000	0	0
GLI2/SPOP	-0.002	0.014	-9999	-10000	0	0
STK36	0.006	0.006	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.009	0.056	-9999	-0.62	2	2
PTCH1	-0.082	0.17	-9999	-1	6	6
MIM/GLI1	-0.23	0.29	-9999	-0.52	244	244
CREBBP	0.005	0.033	-9999	-0.38	1	1
Su(fu)/SIN3/HDAC complex	0.029	0.029	-9999	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

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

×

S1P4 pathway

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

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

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

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0	0	-10000	0	-10000	0	0
HDAC4	0	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.012	0.048	0.41	6	-10000	0	6
CDKN1A	0	0	-10000	0	-10000	0	0
KAT2B	-0.003	0.048	-10000	0	-0.74	2	2
BAX	0	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
TAT	-0.002	0.037	-10000	0	-0.57	2	2
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.049	0.15	-10000	0	-0.42	71	71
PPARGC1A	-0.15	0.3	-10000	0	-0.74	96	96
FHL2	-0.005	0.052	-10000	0	-0.57	4	4
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0	-10000	0	-10000	0	0
HIST2H4A	0.012	0.048	-10000	0	-0.41	6	6
SIRT1/FOXO3a	0	0	-10000	0	-10000	0	0
SIRT1	0	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.011	0.037	-10000	0	-10000	0	0
apoptosis	0	0	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.097	0.2	-10000	0	-0.49	96	96
p53/SIRT1	0	0	-10000	0	-10000	0	0
SIRT1/FOXO4	0	0	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.003	0.028	-10000	0	-0.31	4	4
HIST1H1E	-0.014	0.046	-10000	0	-10000	0	0
SIRT1/p300	0	0	-10000	0	-10000	0	0
muscle cell differentiation	0.051	0.12	0.48	2	-10000	0	2
TP53	0	0	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
MEF2D	0	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.002	0.027	-10000	0	-0.41	2	2
ACSS2	0.017	0	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.051	0.12	-10000	0	-0.48	2	2

×

TRAIL signaling pathway

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

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

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

×

IL2 signaling events mediated by STAT5

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

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

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

×

Sphingosine 1-phosphate (S1P) pathway

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

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

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

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.003	0.048	-10000	0	-0.74	2	2
ANTXR2	-0.011	0.089	-10000	0	-0.74	7	7
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.013	-10000	0	-0.1	7	7
monocyte activation	-0.002	0.082	-10000	0	-0.45	15	15
MAP2K2	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	-0.001	0.011	-10000	0	-10000	0	0
MAP2K7	-0.001	0.011	-10000	0	-10000	0	0
MAP2K6	-0.002	0.018	-10000	0	-0.31	1	1
CYAA	0.006	0.069	-10000	0	-0.54	7	7
MAP2K4	-0.001	0.011	-10000	0	-10000	0	0
IL1B	0.003	0.074	-10000	0	-0.45	12	12
Channel	-0.008	0.072	-10000	0	-0.57	7	7
NLRP1	-0.004	0.038	-10000	0	-0.47	3	3
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.002	0.015	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.013	0.1	7	-10000	0	7
MAPK3	-0.001	0.011	-10000	0	-10000	0	0
MAPK1	-0.001	0.011	-10000	0	-10000	0	0
PGR	-0.09	0.18	-10000	0	-0.44	100	100
PA/Cellular Receptors	-0.009	0.077	-10000	0	-0.61	7	7
apoptosis	-0.002	0.013	-10000	0	-0.1	7	7
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.008	0.067	-10000	0	-0.53	7	7
macrophage activation	0.017	0.012	-10000	0	-10000	0	0
TNF	-0.02	0.12	-10000	0	-0.73	13	13
VCAM1	-0.015	0.079	-10000	0	-0.46	15	15
platelet activation	-0.002	0.015	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.013	0.12	2	-10000	0	2
IL18	0.01	0.046	-10000	0	-0.36	6	6
negative regulation of macrophage activation	-0.002	0.013	-10000	0	-0.1	7	7
LEF	-0.002	0.013	-10000	0	-0.11	7	7
CASP1	-0.003	0.032	-10000	0	-0.28	4	4
mol:cAMP	-0.002	0.016	-10000	0	-10000	0	0
necrosis	-0.002	0.013	-10000	0	-0.1	7	7
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.008	0.068	-10000	0	-0.54	7	7
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.034	-10000	0	-0.74	1	1
Jak2/Leptin Receptor	-0.026	0.098	0.19	2	-0.38	28	30
PTP1B/AKT1	-0.006	0.024	-10000	0	-10000	0	0
FYN	-0.002	0.034	-10000	0	-0.74	1	1
p210 bcr-abl/PTP1B	0.024	0.037	-10000	0	-0.31	1	1
EGFR	-0.013	0.12	-10000	0	-0.63	17	17
EGF/EGFR	-0.021	0.085	-10000	0	-0.48	12	12
CSF1	-0.006	0.067	-10000	0	-0.74	4	4
AKT1	0.007	0.005	-10000	0	-10000	0	0
INSR	0.007	0.005	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.023	0.077	-10000	0	-0.37	12	12
Insulin Receptor/Insulin	-0.004	0.019	-10000	0	-10000	0	0
HCK	-0.008	0.075	-10000	0	-0.74	5	5
CRK	0	0	-10000	0	-10000	0	0
TYK2	0.029	0.035	-10000	0	-0.29	1	1
EGF	-0.005	0.1	-10000	0	-0.69	10	10
YES1	0	0	-10000	0	-10000	0	0
CAV1	-0.026	0.11	-10000	0	-0.47	11	11
TXN	0.007	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.005	0.022	-10000	0	-10000	0	0
cell migration	-0.024	0.037	0.31	1	-10000	0	1
STAT3	0	0	-10000	0	-10000	0	0
PRLR	-0.039	0.15	-10000	0	-0.63	30	30
ITGA2B	-0.023	0.13	-10000	0	-0.74	15	15
CSF1R	-0.014	0.1	-10000	0	-0.74	9	9
Prolactin Receptor/Prolactin	-0.035	0.13	-10000	0	-0.47	37	37
FGR	-0.049	0.18	-10000	0	-0.74	32	32
PTP1B/p130 Cas	-0.006	0.025	-10000	0	-0.29	1	1
Crk/p130 Cas	-0.005	0.022	-10000	0	-10000	0	0
DOK1	0.033	0.036	-10000	0	-0.33	1	1
JAK2	0.014	0.048	-10000	0	-0.29	2	2
Jak2/Leptin Receptor/Leptin	-0.043	0.082	-10000	0	-0.46	4	4
PIK3R1	0	0	-10000	0	-10000	0	0
PTPN1	0.024	0.037	-10000	0	-0.31	1	1
LYN	-0.003	0.048	-10000	0	-0.74	2	2
CDH2	-0.035	0.14	-10000	0	-0.58	29	29
SRC	0.023	0.016	-10000	0	-10000	0	0
ITGB3	-0.012	0.095	-10000	0	-0.74	8	8
CAT1/PTP1B	0.017	0.12	-10000	0	-0.52	14	14
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	-0.45	4	4
negative regulation of transcription	0.014	0.048	-10000	0	-0.28	2	2
FCGR2A	-0.017	0.11	-10000	0	-0.74	11	11
FER	0.007	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.027	0.12	-10000	0	-0.56	23	23
BLK	-0.036	0.15	-10000	0	-0.66	26	26
Insulin Receptor/Insulin/Shc	0	0	-10000	0	-10000	0	0
RHOA	0.007	0.005	-10000	0	-10000	0	0
LEPR	-0.04	0.17	-10000	0	-0.74	28	28
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.001	0.14	-10000	0	-0.61	16	16
PRL	-0.01	0.073	-10000	0	-0.57	8	8
SOCS3	0.002	0.093	-10000	0	-1.4	2	2
SPRY2	-0.005	0.059	-10000	0	-0.75	3	3
Insulin Receptor/Insulin/IRS1	0	0	-10000	0	-10000	0	0
CSF1/CSF1R	-0.016	0.076	-10000	0	-0.46	11	11
Ras protein signal transduction	0.005	0.012	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.1	0.22	-10000	0	-0.57	84	84
STAT5B	0.022	0.037	-10000	0	-0.25	1	1
STAT5A	0.022	0.037	-10000	0	-0.25	1	1
GRB2	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.007	0.033	-10000	0	-0.47	1	1
CSN2	-0.012	0.04	-10000	0	-10000	0	0
PIK3CA	0	0	-10000	0	-10000	0	0
LAT	0.011	0.077	-10000	0	-0.48	11	11
YBX1	0.001	0.003	-10000	0	-10000	0	0
LCK	-0.002	0.034	-10000	0	-0.74	1	1
SHC1	0	0	-10000	0	-10000	0	0
NOX4	-0.001	0.026	-10000	0	-0.57	1	1

×

Retinoic acid receptors-mediated signaling

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

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

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

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.009	0.081	-9999	-0.67	6	6
NF kappa B1 p50/RelA/I kappa B alpha	-0.017	0.047	-9999	-10000	0	0
AP1	-0.054	0.13	-9999	-0.51	8	8
mol:PIP3	-0.02	0.078	-9999	-0.58	3	3
AKT1	-0.006	0.051	-9999	-0.57	3	3
PTK2B	0.017	0.038	-9999	-0.29	4	4
RHOA	0.028	0.016	-9999	-10000	0	0
PIK3CB	0	0	-9999	-10000	0	0
mol:Ca2+	0	0.082	-9999	-0.42	4	4
MAGI3	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
apoptosis	-0.011	0.059	-9999	-0.41	6	6
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.023	0.061	-9999	-0.4	8	8
NF kappa B1 p50/RelA	-0.024	0.066	-9999	-0.65	1	1
endothelial cell migration	0.015	0.089	-9999	-0.82	5	5
ADCY4	0.017	0.098	-9999	-0.62	6	6
ADCY5	0.011	0.096	-9999	-0.66	4	4
ADCY6	0.031	0.07	-9999	-0.59	4	4
ADCY7	0.031	0.069	-9999	-0.66	3	3
ADCY1	0.031	0.07	-9999	-0.66	3	3
ADCY2	0.018	0.082	-9999	-0.68	3	3
ADCY3	0.031	0.069	-9999	-0.66	3	3
ADCY8	-0.037	0.12	-9999	-0.66	5	5
ADCY9	0.031	0.074	-9999	-0.65	4	4
GSK3B	0.023	0.036	-9999	-0.38	1	1
arachidonic acid secretion	0.034	0.07	-9999	-0.58	4	4
GNG2	-0.008	0.075	-9999	-0.74	5	5
TRIP6	0	0.004	-9999	-10000	0	0
GNAO1	0.017	0.063	-9999	-0.55	5	5
HRAS	0	0	-9999	-10000	0	0
NFKBIA	0.017	0.074	-9999	-0.38	1	1
GAB1	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.002	0.042	-9999	-0.92	1	1
JUN	0	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.004	0.039	-9999	-0.48	3	3
TIAM1	-0.002	0.049	-9999	-1.1	1	1
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	0	0.083	-9999	-0.43	4	4
PLCB3	0.021	0.037	-9999	-0.44	3	3
FOS	-0.085	0.24	-9999	-0.74	55	55
positive regulation of mitosis	0.034	0.07	-9999	-0.58	4	4
LPA/LPA1-2-3	-0.014	0.072	-9999	-0.49	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
stress fiber formation	0.024	0.048	-9999	-0.42	2	2
GNAZ	0.013	0.075	-9999	-0.46	11	11
EGFR/PI3K-beta/Gab1	-0.021	0.081	-9999	-0.62	3	3
positive regulation of dendritic cell cytokine production	-0.014	0.072	-9999	-0.48	6	6
LPA/LPA2/MAGI-3	-0.001	0.007	-9999	-10000	0	0
ARHGEF1	-0.003	0.041	-9999	-0.55	2	2
GNAI2	0.02	0.051	-9999	-0.64	2	2
GNAI3	0.02	0.051	-9999	-0.64	2	2
GNAI1	0.019	0.066	-9999	-0.84	2	2
LPA/LPA3	-0.014	0.078	-9999	-0.46	14	14
LPA/LPA2	-0.001	0.01	-9999	-10000	0	0
LPA/LPA1	-0.005	0.056	-9999	-0.5	5	5
HB-EGF/EGFR	-0.047	0.14	-9999	-0.41	56	56
HBEGF	-0.022	0.14	-9999	-0.47	41	41
mol:DAG	0	0.083	-9999	-0.43	4	4
cAMP biosynthetic process	0.019	0.076	-9999	-0.66	4	4
NFKB1	0	0	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
GNB1	-0.002	0.034	-9999	-0.74	1	1
LYN	0.015	0.085	-9999	-0.56	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	0.056	-9999	-0.83	2	2
IL8	0.001	0.13	-9999	-0.44	17	17
PTK2	-0.013	0.067	-9999	-0.45	6	6
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.011	0.059	-9999	-0.41	6	6
EGFR	-0.022	0.12	-9999	-0.63	17	17
PLCG1	-0.016	0.085	-9999	-0.36	10	10
PLD2	-0.013	0.067	-9999	-0.45	6	6
G12/G13	-0.004	0.044	-9999	-0.59	2	2
PI3K-beta	-0.007	0.062	-9999	-0.69	3	3
cell migration	0.002	0.03	-9999	-0.26	1	1
SLC9A3R2	-0.005	0.058	-9999	-0.74	3	3
PXN	0.025	0.049	-9999	-0.43	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	25	25
PRKCE	0.008	0.034	-9999	-0.74	1	1
PRKCD	0.007	0.079	-9999	-0.47	2	2
Gi(beta/gamma)	-0.011	0.08	-9999	-0.65	5	5
mol:LPA	-0.001	0.017	-9999	-0.21	3	3
TRIP6/p130 Cas/FAK1/Paxillin	-0.002	0.06	-9999	-0.64	1	1
MAPKKK cascade	0.034	0.07	-9999	-0.58	4	4
contractile ring contraction involved in cytokinesis	0.027	0.016	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.1	0.17	-9999	-0.4	118	118
GNA15	-0.008	0.047	-9999	-0.38	4	4
GNA12	0	0	-9999	-10000	0	0
GNA13	0	0	-9999	-10000	0	0
MAPT	0.023	0.063	-9999	-0.41	8	8
GNA11	-0.008	0.047	-9999	-0.38	4	4
Rac1/GTP	-0.002	0.045	-9999	-0.98	1	1
MMP2	0.015	0.09	-9999	-0.83	5	5

×

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

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.006	0.035	-10000	0	-10000	0	0
IRAK/TOLLIP	0	0	-10000	0	-10000	0	0
IKBKB	-0.001	0.026	-10000	0	-0.57	1	1
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.059	0.16	-10000	0	-0.47	61	61
IL1A	-0.053	0.18	-10000	0	-0.65	39	39
IL1B	0.004	0.094	-10000	0	-0.56	13	13
IRAK/TRAF6/p62/Atypical PKCs	0	0	-10000	0	-10000	0	0
IL1R2	-0.028	0.12	-10000	0	-0.57	24	24
IL1R1	-0.002	0.034	-10000	0	-0.74	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0	0.04	0.22	8	-0.31	1	9
TOLLIP	0	0	-10000	0	-10000	0	0
TICAM2	-0.009	0.082	-10000	0	-0.74	6	6
MAP3K3	0	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0	0.004	-10000	0	-10000	0	0
JUN	0.042	0.012	-10000	0	-10000	0	0
MAP3K7	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.011	0.064	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.031	0.11	-10000	0	-0.46	19	19
PIK3R1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.028	0.1	-10000	0	-0.42	19	19
IL1 beta fragment/IL1R1/IL1RAP	-0.013	0.073	-10000	0	-0.43	14	14
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	0.036	0.013	-10000	0	-10000	0	0
IRAK1	0.022	0.004	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.007	0.064	-10000	0	-0.54	6	6
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
TRAF6	0	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.007	0.04	-10000	0	-0.3	1	1
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.013	0.073	-10000	0	-0.43	14	14
IL1 beta/IL1R2	-0.03	0.11	-10000	0	-0.5	13	13
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.01	0.057	-10000	0	-10000	0	0
IRAK3	-0.018	0.12	-10000	0	-0.74	12	12
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.016	0.08	-10000	0	-0.78	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.019	0.069	-10000	0	-0.32	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	-0.013	0.066	-10000	0	-0.64	1	1
CASP1	-0.003	0.048	-10000	0	-0.74	2	2
IL1RN/IL1R2	-0.026	0.1	-10000	0	-0.43	29	29
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.012	0.068	-10000	0	-0.4	14	14
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.013	0.054	-10000	0	-0.61	1	1
PIK3CA	0	0	-10000	0	-10000	0	0
IL1RN	-0.008	0.07	-10000	0	-0.63	6	6
TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
MAP2K6	-0.001	0.012	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.001	0.026	-9999	-0.57	1	1
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.003	0.025	-9999	-0.26	4	4
response to UV	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0	0	-9999	-10000	0	0
FYN	-0.002	0.034	-9999	-0.74	1	1
MAP3K12	0	0	-9999	-10000	0	0
FGR	-0.049	0.18	-9999	-0.74	32	32
p38 alpha/TAB1	-0.012	0.044	-9999	-0.33	2	2
PRKG1	-0.058	0.2	-9999	-0.74	38	38
DUSP8	-0.014	0.1	-9999	-0.74	9	9
PGK/cGMP/p38 alpha	-0.038	0.11	-9999	-0.38	38	38
apoptosis	-0.012	0.043	-9999	-0.38	1	1
RAL/GTP	0	0	-9999	-10000	0	0
LYN	-0.003	0.048	-9999	-0.74	2	2
DUSP1	-0.095	0.25	-9999	-0.74	62	62
PAK1	-0.001	0.026	-9999	-0.57	1	1
SRC	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.031	0.08	-9999	-0.35	11	11
BLK	-0.036	0.15	-9999	-0.66	26	26
HCK	-0.008	0.075	-9999	-0.74	5	5
MAP2K3	0	0	-9999	-10000	0	0
DUSP16	0	0	-9999	-10000	0	0
DUSP10	-0.002	0.034	-9999	-0.74	1	1
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.033	0.061	-9999	-0.36	2	2
positive regulation of innate immune response	0.037	0.088	-9999	-0.38	11	11
LCK	-0.002	0.034	-9999	-0.74	1	1
p38alpha-beta/MKP7	-0.019	0.065	-9999	-0.44	2	2
p38alpha-beta/MKP5	-0.02	0.069	-9999	-0.48	3	3
PGK/cGMP	-0.045	0.15	-9999	-0.57	38	38
PAK2	0	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.059	0.13	-9999	-0.51	15	15
CDC42	0	0	-9999	-10000	0	0
RALB	0	0	-9999	-10000	0	0
RALA	0	0	-9999	-10000	0	0
PAK3	-0.007	0.072	-9999	-0.71	5	5

×

IL27-mediated signaling events

Figure 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
TGFB1	0.003	0.026	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.003	0.069	-10000	0	-10000	0	0
IL27/IL27R/JAK1	-0.028	0.094	-10000	0	-10000	0	0
TBX21	-0.029	0.22	-10000	0	-0.62	42	42
IL12B	0.009	0.004	-10000	0	-10000	0	0
IL12A	0.001	0.074	-10000	0	-0.57	8	8
IL6ST	-0.016	0.14	-10000	0	-0.75	16	16
IL27RA/JAK1	-0.003	0.013	-10000	0	-10000	0	0
IL27	0.008	0.007	-10000	0	-10000	0	0
TYK2	0.011	0.003	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.062	0.14	-10000	0	-0.69	3	3
T-helper 2 cell differentiation	-0.003	0.069	-10000	0	-10000	0	0
T cell proliferation during immune response	-0.003	0.069	-10000	0	-10000	0	0
MAPKKK cascade	0.003	0.069	-10000	0	-10000	0	0
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	0.001	0.003	-10000	0	-10000	0	0
IL12RB1	-0.039	0.18	-10000	0	-0.74	31	31
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.018	0.19	-10000	0	-0.63	12	12
IL27/IL27R/JAK2/TYK2	0.002	0.069	-10000	0	-10000	0	0
positive regulation of T cell mediated cytotoxicity	0.003	0.069	-10000	0	-10000	0	0
STAT1 (dimer)	-0.058	0.16	0.51	3	-0.77	6	9
JAK2	0.006	0.006	-10000	0	-10000	0	0
JAK1	0.001	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.012	0.057	-10000	0	-10000	0	0
T cell proliferation	-0.052	0.18	-10000	0	-0.58	13	13
IL12/IL12R/TYK2/JAK2	0.007	0.093	-10000	0	-0.59	2	2
IL17A	-0.062	0.14	-10000	0	-0.69	3	3
mast cell activation	-0.003	0.069	-10000	0	-10000	0	0
IFNG	0.006	0.02	-10000	0	-0.13	4	4
T cell differentiation	-0.003	0.005	-10000	0	-0.023	3	3
STAT3 (dimer)	-0.012	0.057	-10000	0	-10000	0	0
STAT5A (dimer)	-0.012	0.057	-10000	0	-10000	0	0
STAT4 (dimer)	-0.018	0.08	-10000	0	-0.48	6	6
STAT4	-0.012	0.095	-10000	0	-0.74	8	8
T cell activation	-0.007	0.003	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.018	0.077	-10000	0	-10000	0	0
GATA3	-0.035	0.24	-10000	0	-1.4	14	14
IL18	0.006	0.045	-10000	0	-0.57	3	3
positive regulation of mast cell cytokine production	-0.012	0.056	-10000	0	-10000	0	0
IL27/EBI3	-0.003	0.042	-10000	0	-0.52	3	3
IL27RA	0.007	0.017	-10000	0	-10000	0	0
IL6	-0.12	0.28	-10000	0	-0.74	82	82
STAT5A	0	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.001	0.006	-10000	0	-10000	0	0
IL1B	-0.003	0.086	-10000	0	-0.57	11	11
EBI3	0.001	0.055	-10000	0	-0.69	3	3
TNF	-0.005	0.092	-10000	0	-0.56	13	13

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0	0	-9999	-10000	0	0
PTK2	0	0	-9999	-10000	0	0
CRKL	0.01	0.072	-9999	-0.39	15	15
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
IRS1/Crk	-0.012	0.068	-9999	-0.39	15	15
IGF-1R heterotetramer/IGF1/PTP1B	-0.015	0.079	-9999	-0.45	15	15
AKT1	0.03	0.063	-9999	-10000	0	0
BAD	0.036	0.06	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0.072	-9999	-0.39	15	15
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.013	0.068	-9999	-0.39	15	15
RAF1	0.038	0.058	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.012	0.064	-9999	-0.36	15	15
YWHAZ	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.014	0.074	-9999	-0.42	15	15
PIK3CA	0	0	-9999	-10000	0	0
RPS6KB1	0.03	0.063	-9999	-10000	0	0
GNB2L1	0	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.033	0.051	-9999	-10000	0	0
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.01	0.056	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.011	0.062	-9999	-10000	0	0
IGF-1R heterotetramer	0.007	0.016	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.013	0.068	-9999	-0.39	15	15
Crk/p130 Cas/Paxillin	-0.011	0.06	-9999	-10000	0	0
IGF1R	0.007	0.016	-9999	-10000	0	0
IGF1	-0.015	0.13	-9999	-0.74	16	16
IRS2/Crk	-0.014	0.07	-9999	-0.37	18	18
PI3K	-0.012	0.063	-9999	-0.36	15	15
apoptosis	0.008	0.045	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
PRKCD	0.021	0.086	-9999	-0.46	15	15
RAF1/14-3-3 E	0.041	0.051	-9999	-10000	0	0
BAD/14-3-3	0.04	0.056	-9999	-10000	0	0
PRKCZ	0.03	0.063	-9999	-10000	0	0
Crk/p130 Cas/Paxillin/FAK1	-0.008	0.046	-9999	-10000	0	0
PTPN1	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.015	0.085	-9999	-0.49	15	15
BCAR1	0	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.013	0.069	-9999	-0.39	15	15
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
IRS1/NCK2	-0.012	0.067	-9999	-0.38	15	15
GRB10	0	0	-9999	-10000	0	0
PTPN11	0.01	0.072	-9999	-0.39	15	15
IRS1	0.003	0.077	-9999	-0.42	15	15
IRS2	0.007	0.08	-9999	-0.39	18	18
IGF-1R heterotetramer/IGF1	-0.019	0.1	-9999	-0.56	16	16
GRB2	0	0	-9999	-10000	0	0
PDPK1	-0.011	0.059	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
PRKD1	0.008	0.12	-9999	-0.49	26	26
SHC1	0	0	-9999	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.047	0.12	-9999	-10000	0	0
TC10/GTP	-0.046	0.12	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0	0	-9999	-10000	0	0
HRAS	0	0	-9999	-10000	0	0
APS homodimer	0	0	-9999	-10000	0	0
GRB14	-0.047	0.18	-9999	-0.74	31	31
FOXO3	-0.004	0.014	-9999	-10000	0	0
AKT1	-0.021	0.082	-9999	-10000	0	0
INSR	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0	0	-9999	-10000	0	0
SORBS1	-0.092	0.24	-9999	-0.74	60	60
CRK	0	0	-9999	-10000	0	0
PTPN1	0.031	0	-9999	-10000	0	0
CAV1	-0.12	0.19	-9999	-0.42	135	135
CBL/APS/CAP/Crk-II/C3G	-0.05	0.13	-9999	-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	0.028	0.087	-9999	-10000	0	0
PARD6A	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.019	0.072	-9999	-10000	0	0
HRAS/GTP	-0.001	0.015	-9999	-10000	0	0
Insulin Receptor	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0	0	-9999	-10000	0	0
PRKCI	-0.006	0.022	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.023	0.088	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	-0.021	0.082	-9999	-10000	0	0
PRKCZ	-0.006	0.022	-9999	-10000	0	0
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	-0.001	0.018	-9999	-0.4	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	-0.054	0.14	-9999	-0.43	60	60
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	-0.001	0.019	-9999	-0.42	1	1
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.002	0.007	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
IRS1	0	0	-9999	-10000	0	0
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	-0.001	0.019	-9999	-0.42	1	1
GRB2	0	0	-9999	-10000	0	0
EIF4EBP1	0.013	0.1	-9999	-10000	0	0
PTPRA	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.053	0.11	-9999	-0.41	3	3

×

Signaling events mediated by PRL

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

×

Signaling events mediated by HDAC Class II

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

×

BARD1 signaling events

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

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.002	0.034	-10000	0	-0.74	1	1
EPHB2	-0.009	0.073	-10000	0	-0.57	8	8
EFNB1	0.018	0.028	-10000	0	-0.41	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.037	0.091	-10000	0	-0.53	1	1
Ephrin B2/EPHB1-2	-0.044	0.11	-10000	0	-0.53	2	2
neuron projection morphogenesis	-0.035	0.087	-10000	0	-0.51	1	1
Ephrin B1/EPHB1-2/Tiam1	-0.04	0.099	-10000	0	-0.57	1	1
DNM1	-0.002	0.037	-10000	0	-0.57	2	2
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.015	0.069	-10000	0	-0.73	4	4
YES1	-0.007	0.088	-10000	0	-0.96	4	4
Ephrin B1/EPHB1-2/NCK2	-0.04	0.099	-10000	0	-0.57	1	1
PI3K	-0.006	0.068	-10000	0	-0.74	4	4
mol:GDP	-0.04	0.098	-10000	0	-0.56	1	1
ITGA2B	-0.023	0.13	-10000	0	-0.74	15	15
endothelial cell proliferation	-0.001	0.022	-10000	0	-0.48	1	1
FYN	-0.008	0.088	-10000	0	-0.96	4	4
MAP3K7	-0.007	0.071	-10000	0	-0.78	4	4
FGR	-0.019	0.1	-10000	0	-0.99	4	4
TIAM1	0	0	-10000	0	-10000	0	0
PIK3R1	0	0	-10000	0	-10000	0	0
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.024	0.1	-10000	0	-0.67	4	4
LYN	-0.008	0.088	-10000	0	-0.96	4	4
Ephrin B1/EPHB1-2/Src Family Kinases	-0.007	0.083	-10000	0	-0.91	4	4
Ephrin B1/EPHB1-2	-0.009	0.077	-10000	0	-0.84	4	4
SRC	-0.008	0.087	-10000	0	-0.95	4	4
ITGB3	-0.012	0.095	-10000	0	-0.74	8	8
EPHB1	-0.07	0.19	-10000	0	-0.57	59	59
EPHB4	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.001	0.022	-10000	0	-0.49	1	1
alphaIIb/beta3 Integrin	-0.027	0.12	-10000	0	-0.56	23	23
BLK	-0.014	0.095	-10000	0	-1	4	4
HCK	-0.01	0.089	-10000	0	-0.95	4	4
regulation of stress fiber formation	0.04	0.098	0.56	1	-10000	0	1
MAPK8	0.021	0.066	-10000	0	-0.69	4	4
Ephrin B1/EPHB1-2/RGS3	-0.04	0.099	-10000	0	-0.57	1	1
endothelial cell migration	-0.006	0.065	-10000	0	-0.62	5	5
NCK2	0	0	-10000	0	-10000	0	0
PTPN13	-0.003	0.078	-10000	0	-0.86	4	4
regulation of focal adhesion formation	0.04	0.098	0.56	1	-10000	0	1
chemotaxis	0.04	0.098	0.56	1	-10000	0	1
PIK3CA	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.036	0.089	-10000	0	-0.52	1	1
angiogenesis	-0.009	0.076	-10000	0	-0.83	4	4
LCK	-0.008	0.09	-10000	0	-0.99	4	4

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

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

×

Arf6 trafficking events

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

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

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

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0	0	-9999	-10000	0	0
mol:DAG	0.018	0.074	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-9999	-10000	0	0
CaM/Ca2+	-0.014	0.061	-9999	-10000	0	0
HIF1A	0	0	-9999	-10000	0	0
GAB1	0	0	-9999	-10000	0	0
AKT1	-0.011	0.046	-9999	-10000	0	0
PLCG1	0.018	0.074	-9999	-10000	0	0
NOS3	0.041	0.067	-9999	-0.58	1	1
CBL	0	0	-9999	-10000	0	0
mol:NO	0.041	0.065	-9999	-0.55	1	1
FLT1	0.026	0	-9999	-10000	0	0
PGF	-0.03	0.13	-9999	-0.57	25	25
VEGFR1 homodimer/NRP2/VEGFR121	-0.004	0.039	-9999	-0.43	4	4
CALM1	0	0	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
eNOS/Hsp90	0.045	0.063	-9999	-0.53	1	1
endothelial cell proliferation	0.018	0.093	-9999	-0.62	1	1
mol:Ca2+	0.018	0.073	-9999	-10000	0	0
MAPK3	0.029	0.071	-9999	-10000	0	0
MAPK1	0.029	0.071	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
PLGF homodimer	-0.03	0.13	-9999	-0.57	25	25
PRKACA	0	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.21	0.33	-9999	-0.74	135	135
VEGFA homodimer	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.035	0.069	-9999	-10000	0	0
PI3K	-0.014	0.061	-9999	-10000	0	0
PRKCA	0.023	0.074	-9999	-10000	0	0
PRKCB	0.003	0.12	-9999	-0.4	24	24
VEGFR1 homodimer/PLGF homodimer	-0.018	0.075	-9999	-10000	0	0
VEGFA	0	0	-9999	-10000	0	0
VEGFB	0	0	-9999	-10000	0	0
mol:IP3	0.018	0.074	-9999	-10000	0	0
RASA1	0.035	0	-9999	-10000	0	0
NRP2	-0.006	0.067	-9999	-0.74	4	4
VEGFR1 homodimer	0.026	0	-9999	-10000	0	0
VEGFB homodimer	0	0	-9999	-10000	0	0
NCK1	0	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.066	0.18	-9999	-0.58	6	6
PTPN11	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.014	0.06	-9999	-10000	0	0
mol:L-citrulline	0.041	0.065	-9999	-0.55	1	1
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0	0	-9999	-10000	0	0
CD2AP	0	0	-9999	-10000	0	0
PI3K/GAB1	-0.013	0.056	-9999	-10000	0	0
PDPK1	-0.013	0.056	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-9999	-10000	0	0
mol:NADP	0.041	0.065	-9999	-0.55	1	1
HSP90AA1	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	-0.004	0.043	-9999	-0.47	4	4

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.018	0.003	-9999	-10000	0	0
RAS family/GTP	-0.008	0.044	-9999	-10000	0	0
NFATC4	0.032	0.054	-9999	-10000	0	0
ERBB2IP	0.001	0.003	-9999	-10000	0	0
HSP90 (dimer)	0	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.01	0.059	-9999	-10000	0	0
JUN	0.044	0.058	-9999	-0.49	1	1
HRAS	0	0	-9999	-10000	0	0
DOCK7	0.029	0.064	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.012	0.07	-9999	-0.42	13	13
AKT1	0.01	0.002	-9999	-10000	0	0
BAD	0.018	0.001	-9999	-10000	0	0
MAPK10	-0.009	0.045	-9999	-0.33	4	4
mol:GTP	0	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.011	0.063	-9999	-10000	0	0
RAF1	0.048	0.057	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.048	0.14	-9999	-0.45	51	51
STAT3	0	0	-9999	-10000	0	0
cell migration	0.04	0.045	-9999	-0.3	2	2
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	0.039	0.15	-9999	-0.56	8	8
FOS	0.01	0.2	-9999	-0.5	60	60
NRAS	0	0	-9999	-10000	0	0
mol:Ca2+	-0.01	0.059	-9999	-10000	0	0
MAPK3	0.046	0.11	-9999	-0.47	5	5
MAPK1	0.046	0.11	-9999	-0.47	5	5
JAK2	0.029	0.064	-9999	-10000	0	0
NF2	-0.001	0.019	-9999	-0.4	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.009	0.054	-9999	-0.33	13	13
NRG1	-0.011	0.12	-9999	-0.74	13	13
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	0.032	0.06	-9999	-0.32	3	3
MAPK9	-0.005	0.028	-9999	-10000	0	0
ERBB2	-0.002	0.027	-9999	-0.42	2	2
ERBB3	0.009	0.004	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
apoptosis	0.003	0.008	-9999	-10000	0	0
STAT3 (dimer)	0	0	-9999	-10000	0	0
RNF41	0.025	0.004	-9999	-10000	0	0
FRAP1	0.009	0.002	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.007	0.04	-9999	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	-0.001	0.023	-9999	-0.35	2	2
CHRNA1	0.043	0.12	-9999	-0.63	6	6
myelination	0.037	0.052	-9999	-10000	0	0
PPP3CB	-0.009	0.052	-9999	-10000	0	0
KRAS	0	0	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.008	0.046	-9999	-10000	0	0
NRG2	-0.078	0.23	-9999	-0.74	51	51
mol:GDP	0.015	0.059	-9999	-0.33	13	13
SOS1	0	0	-9999	-10000	0	0
MAP2K2	0.055	0.058	-9999	-10000	0	0
SRC	0	0	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	-0.01	0.055	-9999	-10000	0	0
MAP2K1	0.036	0.11	-9999	-0.48	5	5
heart morphogenesis	-0.01	0.059	-9999	-10000	0	0
RAS family/GDP	-0.008	0.044	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
PRKACA	-0.001	0.004	-9999	-10000	0	0
CHRNE	0.02	0.017	-9999	-0.24	1	1
HSP90AA1	0	0	-9999	-10000	0	0
activation of caspase activity	-0.01	0.002	-9999	-10000	0	0
nervous system development	-0.01	0.059	-9999	-10000	0	0
CDC42	0	0	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

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

×

Signaling events mediated by HDAC Class I

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

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.002	0.026	-9999	-10000	0	0
DAPP1	0.009	0.12	-9999	-0.56	14	14
Src family/SYK family/BLNK-LAT/BTK-ITK	0.005	0.17	-9999	-0.72	17	17
mol:DAG	0.026	0.087	-9999	-0.28	18	18
HRAS	0	0.001	-9999	-10000	0	0
RAP1A	0	0.001	-9999	-10000	0	0
ARF5/GDP	0.026	0.055	-9999	-0.32	7	7
PLCG2	0	0	-9999	-10000	0	0
PLCG1	0	0	-9999	-10000	0	0
ARF5	0	0	-9999	-10000	0	0
mol:GTP	-0.002	0.028	-9999	-10000	0	0
ARF1/GTP	-0.002	0.027	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
YES1	0	0	-9999	-10000	0	0
RAP1A/GTP	-0.002	0.028	-9999	-10000	0	0
ADAP1	-0.009	0.057	-9999	-10000	0	0
ARAP3	-0.002	0.028	-9999	-10000	0	0
INPPL1	0	0	-9999	-10000	0	0
PREX1	-0.011	0.089	-9999	-0.74	7	7
ARHGEF6	-0.028	0.14	-9999	-0.74	18	18
ARHGEF7	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
NRAS	0	0.001	-9999	-10000	0	0
FYN	-0.002	0.034	-9999	-0.74	1	1
ARF6	0	0	-9999	-10000	0	0
FGR	-0.049	0.18	-9999	-0.74	32	32
mol:Ca2+	0.024	0.047	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0	0	-9999	-10000	0	0
ZAP70	-0.012	0.095	-9999	-0.74	8	8
mol:IP3	0.027	0.064	-9999	-10000	0	0
LYN	-0.003	0.048	-9999	-0.74	2	2
ARF1/GDP	0.026	0.055	-9999	-0.32	7	7
RhoA/GDP	-0.006	0.034	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	-0.002	0.034	-9999	-0.74	1	1
actin cytoskeleton reorganization	0.045	0.066	-9999	-0.49	3	3
SRC	0	0	-9999	-10000	0	0
PLEKHA2	0.025	0.023	-9999	-0.48	1	1
RAC1	0	0	-9999	-10000	0	0
PTEN	0	0.003	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
ARF6/GTP	-0.002	0.026	-9999	-10000	0	0
RhoA/GTP	-0.002	0.026	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.033	0.11	-9999	-0.52	16	16
BLK	-0.036	0.15	-9999	-0.66	26	26
PDPK1	0	0	-9999	-10000	0	0
CYTH1	-0.002	0.026	-9999	-10000	0	0
HCK	-0.008	0.075	-9999	-0.74	5	5
CYTH3	-0.002	0.026	-9999	-10000	0	0
CYTH2	-0.002	0.026	-9999	-10000	0	0
KRAS	0	0.001	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.001	0.013	-9999	-10000	0	0
SGK1	-0.001	0.014	-9999	-10000	0	0
INPP5D	-0.002	0.034	-9999	-0.74	1	1
mol:GDP	0.022	0.058	-9999	-0.34	7	7
SOS1	0	0	-9999	-10000	0	0
SYK	-0.002	0.034	-9999	-0.74	1	1
ARF6/GDP	-0.006	0.034	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.002	0.028	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.002	0.028	-9999	-10000	0	0
VAV1	-0.008	0.075	-9999	-0.74	5	5
mol:PI-3-4-P2	0.018	0.026	-9999	-0.56	1	1
RAS family/GTP/PI3K Class I	-0.002	0.028	-9999	-10000	0	0
PLEKHA1	0.025	0.023	-9999	-0.48	1	1
Rac1/GDP	0.026	0.055	-9999	-0.32	7	7
LAT	0	0	-9999	-10000	0	0
Rac1/GTP	-0.019	0.099	-9999	-0.46	19	19
ITK	-0.031	0.1	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.024	0.12	-9999	-0.4	22	22
LCK	-0.002	0.034	-9999	-0.74	1	1
BTK	-0.037	0.11	-9999	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.09	0.19	-9999	-0.77	5	5
RAD9A	0	0	-9999	-10000	0	0
AP1	-0.064	0.18	-9999	-0.56	55	55
IFNAR2	0.007	0.006	-9999	-10000	0	0
AKT1	-0.004	0.062	-9999	-0.28	21	21
ER alpha/Oestrogen	-0.025	0.12	-9999	-0.57	21	21
NFX1/SIN3/HDAC complex	0.024	0.021	-9999	-10000	0	0
EGF	-0.008	0.1	-9999	-0.69	10	10
SMG5	0	0	-9999	-10000	0	0
SMG6	0	0	-9999	-10000	0	0
SP3/HDAC2	0	0.001	-9999	-10000	0	0
TERT/c-Abl	-0.12	0.15	-9999	-0.72	5	5
SAP18	0.005	0.005	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.025	0.13	-9999	-0.58	26	26
WRN	-0.002	0.034	-9999	-0.74	1	1
SP1	0.008	0.006	-9999	-10000	0	0
SP3	0.006	0.005	-9999	-10000	0	0
TERF2IP	0	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.1	0.13	-9999	-0.64	5	5
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.092	0.19	-9999	-0.79	5	5
CCND1	-0.084	0.21	-9999	-1.2	7	7
MAX	0.006	0.005	-9999	-10000	0	0
RBBP7	0.005	0.005	-9999	-10000	0	0
RBBP4	0.005	0.005	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0	0	-9999	-10000	0	0
SIN3A	0.005	0.005	-9999	-10000	0	0
Telomerase/911	0.016	0.032	-9999	-10000	0	0
CDKN1B	0.015	0.052	-9999	-0.46	4	4
RAD1	0	0	-9999	-10000	0	0
XRCC5	0	0	-9999	-10000	0	0
XRCC6	0	0	-9999	-10000	0	0
SAP30	0.005	0.005	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.006	0.005	-9999	-10000	0	0
JUN	0.006	0.005	-9999	-10000	0	0
E6	-0.003	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0.001	-9999	-10000	0	0
FOS	-0.079	0.24	-9999	-0.74	55	55
IFN-gamma/IRF1	-0.006	0.056	-9999	-0.5	6	6
PARP2	0	0	-9999	-10000	0	0
BLM	-0.012	0.082	-9999	-0.57	10	10
Telomerase	-0.026	0.052	-9999	-10000	0	0
IRF1	0.009	0.007	-9999	-10000	0	0
ESR1	-0.028	0.15	-9999	-0.74	21	21
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0	-9999	-10000	0	0
HDAC1	0.005	0.005	-9999	-10000	0	0
HDAC2	0.007	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.022	0.005	-9999	-10000	0	0
ABL1	0	0	-9999	-10000	0	0
MXD1	0.006	0.005	-9999	-10000	0	0
MRE11A	0	0	-9999	-10000	0	0
HUS1	0	0	-9999	-10000	0	0
RPS6KB1	0	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.11	0.14	-9999	-0.68	6	6
NR2F2	0.01	0.012	-9999	-10000	0	0
MAPK3	0.01	0.009	-9999	-10000	0	0
MAPK1	0.01	0.009	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.005	0.007	-9999	-10000	0	0
NFKB1	0	0	-9999	-10000	0	0
HNRNPC	0	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0	0	-9999	-10000	0	0
EGFR	-0.017	0.12	-9999	-0.64	17	17
mol:Oestrogen	-0.002	0.003	-9999	-10000	0	0
EGF/EGFR	-0.027	0.12	-9999	-0.5	26	26
MYC	0.007	0.005	-9999	-10000	0	0
IL2	0	0.012	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0	0	-9999	-10000	0	0
HSP90AA1	0	0	-9999	-10000	0	0
TGFB1	0.005	0.007	-9999	-10000	0	0
TRF2/BLM	-0.008	0.054	-9999	-0.38	10	10
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.11	0.15	-9999	-0.71	5	5
SP1/HDAC2	0	0.002	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.1	0.13	-9999	-0.64	5	5
Smad3/Myc	0.011	0.014	-9999	-10000	0	0
911 complex	0	0	-9999	-10000	0	0
IFNG	0	0.077	-9999	-0.68	6	6
Telomerase/PinX1	-0.1	0.13	-9999	-0.64	5	5
Telomerase/AKT1/mTOR/p70S6K	-0.003	0.062	-9999	-10000	0	0
SIN3B	0.005	0.005	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0
Telomerase/EST1B	-0.1	0.13	-9999	-0.64	5	5
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	-0.001	0.024	-9999	-0.52	1	1
Telomerase/hnRNP C1/C2	-0.1	0.13	-9999	-0.64	5	5
E2F1	0.007	0.006	-9999	-10000	0	0
ZNFX1	0.005	0.005	-9999	-10000	0	0
PIF1	-0.053	0.17	-9999	-0.57	45	45
NCL	0	0	-9999	-10000	0	0
DKC1	0	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

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

×

Circadian rhythm pathway

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

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

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

×

a4b1 and a4b7 Integrin signaling

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

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

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

×

Ceramide signaling pathway

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

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

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

×

Paxillin-independent events mediated by a4b1 and a4b7

Figure 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
PTK2	-0.005	0.05	-9999	-0.49	5	5
CRKL	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0	0	-9999	-10000	0	0
ITGA4	-0.006	0.067	-9999	-0.74	4	4
alpha4/beta7 Integrin/MAdCAM1	-0.006	0.05	-9999	-0.43	5	5
EPO	-0.007	0.063	-9999	-0.57	6	6
alpha4/beta7 Integrin	-0.006	0.057	-9999	-0.56	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.005	0.051	-9999	-0.56	4	4
EPO/EPOR (dimer)	-0.005	0.046	-9999	-0.41	6	6
lamellipodium assembly	0	0.004	-9999	-10000	0	0
PIK3CA	0	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0	0	-9999	-10000	0	0
JAK2	-0.005	0.036	-9999	-0.34	4	4
PXN	0	0	-9999	-10000	0	0
PIK3R1	0	0	-9999	-10000	0	0
MADCAM1	-0.004	0.045	-9999	-0.57	3	3
cell adhesion	-0.006	0.05	-9999	-0.43	5	5
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0	0	-9999	-10000	0	0
SRC	0.021	0.072	-9999	-0.6	5	5
ITGB7	-0.002	0.034	-9999	-0.74	1	1
RAC1	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.009	0.074	-9999	-0.65	5	5
p130Cas/Crk/Dock1	-0.007	0.057	-9999	-0.72	2	2
VCAM1	-0.008	0.073	-9999	-0.66	6	6
RHOA	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.004	0.039	-9999	-0.43	4	4
BCAR1	0.028	0.068	-9999	-0.56	5	5
EPOR	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0	0	-9999	-10000	0	0
GIT1	0	0	-9999	-10000	0	0
Rac1/GTP	0	0.004	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	-0.001	0.026	-9999	-0.57	1	1
Caspase 8 (4 units)	-0.011	0.047	-9999	-10000	0	0
NEF	-0.007	0.037	-9999	-10000	0	0
NFKBIA	-0.001	0.012	-9999	-10000	0	0
BIRC3	0.029	0.088	-9999	-0.75	6	6
CYCS	0.032	0.064	-9999	-10000	0	0
RIPK1	0	0	-9999	-10000	0	0
CD247	-0.025	0.13	-9999	-0.83	11	11
MAP2K7	0.034	0.051	-9999	-10000	0	0
protein ubiquitination	0.056	0.038	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
DAXX	0	0	-9999	-10000	0	0
FAS	-0.002	0.034	-9999	-0.74	1	1
BID	0.026	0.067	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.004	0.036	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
MAP3K5	0	0	-9999	-10000	0	0
CFLAR	0	0	-9999	-10000	0	0
FADD	0	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.004	0.036	-9999	-10000	0	0
MAPK8	0.04	0.048	-9999	-10000	0	0
APAF1	0	0	-9999	-10000	0	0
TRAF1	0	0	-9999	-10000	0	0
TRAF2	0	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.015	0.062	-9999	-0.3	16	16
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.006	0.034	-9999	-10000	0	0
CHUK	0.057	0.04	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.001	0.018	-9999	-0.4	1	1
TCRz/NEF	-0.028	0.13	-9999	-0.51	26	26
TNF	-0.02	0.12	-9999	-0.73	13	13
FASLG	-0.021	0.2	-9999	-0.82	26	26
NFKB1	-0.001	0.012	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.078	-9999	-0.48	12	12
CASP6	-0.007	0.028	-9999	-10000	0	0
CASP7	0.061	0.085	-9999	-0.6	6	6
RELA	-0.001	0.012	-9999	-10000	0	0
CASP2	0	0	-9999	-10000	0	0
CASP3	0.061	0.085	-9999	-0.6	6	6
TNFRSF1A	0	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.019	-9999	-0.41	1	1
CASP8	0	0	-9999	-10000	0	0
CASP9	0	0	-9999	-10000	0	0
MAP3K14	0.053	0.043	-9999	-10000	0	0
APAF-1/Caspase 9	-0.013	0.062	-9999	-0.49	6	6
BCL2	0.044	0.048	-9999	-10000	0	0

×

EPHB forward signaling

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

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

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

×

TCGA08_rtk_signaling

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

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

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

×

PDGFR-beta signaling pathway

Figure 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	-0.004	0.038	-9999	-0.53	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.031	0.04	-9999	-0.66	1	1
PIK3CA	0	0	-9999	-10000	0	0
FGR	-0.04	0.15	-9999	-0.6	32	32
mol:Ca2+	0.027	0.041	-9999	-0.7	1	1
MYC	0.044	0.051	-9999	-0.46	1	1
SHC1	0	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.018	-9999	-0.39	1	1
LRP1/PDGFRB/PDGFB	-0.001	0.022	-9999	-0.48	1	1
GRB10	0	0	-9999	-10000	0	0
PTPN11	0	0	-9999	-10000	0	0
GO:0007205	0.027	0.042	-9999	-0.71	1	1
PTEN	0	0	-9999	-10000	0	0
GRB2	0	0	-9999	-10000	0	0
GRB7	-0.005	0.052	-9999	-0.57	4	4
PDGFB-D/PDGFRB/SHP2	-0.001	0.025	-9999	-0.56	1	1
PDGFB-D/PDGFRB/GRB10	-0.001	0.025	-9999	-0.56	1	1
cell cycle arrest	-0.031	0.13	-9999	-0.58	26	26
HRAS	0	0	-9999	-10000	0	0
HIF1A	0.055	0.04	-9999	-0.46	1	1
GAB1	0.028	0.054	-9999	-0.72	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.033	0.05	-9999	-0.66	1	1
PDGFB-D/PDGFRB	0.001	0.024	-9999	-0.49	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.025	-9999	-0.56	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.005	0.035	-9999	-0.63	1	1
positive regulation of MAPKKK cascade	-0.001	0.025	-9999	-0.56	1	1
PIK3R1	0	0	-9999	-10000	0	0
mol:IP3	0.027	0.042	-9999	-0.72	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.001	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.005	0.045	-9999	-0.44	5	5
SHB	0	0	-9999	-10000	0	0
BLK	-0.02	0.1	-9999	-0.59	15	15
PTPN2	0.001	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.025	-9999	-0.56	1	1
BCAR1	0	0	-9999	-10000	0	0
VAV2	0.029	0.068	-9999	-0.57	2	2
CBL	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.004	0.044	-9999	-0.56	3	3
LCK	-0.002	0.036	-9999	-0.55	2	2
PDGFRB	0.009	0.035	-9999	-0.75	1	1
ACP1	0	0	-9999	-10000	0	0
HCK	-0.006	0.066	-9999	-0.59	6	6
ABL1	0.024	0.053	-9999	-0.66	1	1
PDGFB-D/PDGFRB/CBL	0.026	0.059	-9999	-0.77	1	1
PTPN1	0.001	0.003	-9999	-10000	0	0
SNX15	0	0	-9999	-10000	0	0
STAT3	0	0	-9999	-10000	0	0
STAT1	0	0	-9999	-10000	0	0
cell proliferation	0.043	0.048	-9999	-0.43	1	1
SLA	-0.04	0.17	-9999	-0.74	26	26
actin cytoskeleton reorganization	0.002	0.02	-9999	-10000	0	0
SRC	0	0.023	-9999	-0.49	1	1
PI3K	-0.005	0.042	-9999	-0.6	1	1
PDGFB-D/PDGFRB/GRB7/SHC	-0.004	0.038	-9999	-0.37	5	5
SH2B2	0	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.031	0.041	-9999	-0.69	1	1
LYN	-0.002	0.045	-9999	-0.56	3	3
LRP1	0	0	-9999	-10000	0	0
SOS1	0	0	-9999	-10000	0	0
STAT5B	0	0	-9999	-10000	0	0
STAT5A	0	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0	0.019	-9999	-10000	0	0
SPHK1	0.01	0.003	-9999	-10000	0	0
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.027	0.042	-9999	-0.72	1	1
PLCG1	0.027	0.043	-9999	-0.74	1	1
NHERF/PDGFRB	-0.007	0.059	-9999	-0.56	4	4
YES1	0	0.022	-9999	-0.48	1	1
cell migration	-0.007	0.058	-9999	-0.56	4	4
SHC/Grb2/SOS1	0	0.019	-9999	-10000	0	0
SLC9A3R2	-0.005	0.058	-9999	-0.74	3	3
SLC9A3R1	-0.005	0.052	-9999	-0.57	4	4
NHERF1-2/PDGFRB/PTEN	-0.006	0.053	-9999	-0.51	4	4
FYN	-0.001	0.035	-9999	-0.53	2	2
DOK1	0.029	0.021	-9999	-0.44	1	1
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0	0	-9999	-10000	0	0
RAC1	0.04	0.063	-9999	-0.67	1	1
PRKCD	0.029	0.022	-9999	-0.44	1	1
FER	0.029	0.022	-9999	-0.44	1	1
MAPKKK cascade	-0.001	0.017	-9999	-10000	0	0
RASA1	0.029	0.022	-9999	-0.44	1	1
NCK1	0	0	-9999	-10000	0	0
NCK2	0	0	-9999	-10000	0	0
p62DOK/Csk	0.001	0.02	-9999	-0.4	1	1
PDGFB-D/PDGFRB/SHB	-0.001	0.025	-9999	-0.56	1	1
chemotaxis	0.024	0.051	-9999	-0.63	1	1
STAT1-3-5/STAT1-3-5	-0.001	0.017	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.001	0.026	-9999	-0.57	1	1
PTPRJ	-0.003	0.048	-9999	-0.74	2	2

×

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	0.048	-10000	0	-0.74	2	2
PDE3B	-0.003	0.048	-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	0.034	-9999	-0.74	1	1
PLK4	-0.001	0.026	-9999	-0.57	1	1
regulation of centriole replication	0.017	0.033	-9999	-0.48	2	2

×

Insulin-mediated glucose transport

Figure 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	0.033	-9999	-10000	0	0
YWHAZ	0	0	-9999	-10000	0	0
CALM1	0	0	-9999	-10000	0	0
YWHAQ	0	0	-9999	-10000	0	0
TBC1D4	0.02	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0	0	-9999	-10000	0	0
YWHAB	0	0	-9999	-10000	0	0
SNARE/Synip	0	0	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	-0.002	0.037	-9999	-0.57	2	2
PRKCI	0	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0	0	-9999	-10000	0	0
RHOQ	0	0	-9999	-10000	0	0
GYS1	0.028	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
TRIP10	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	-0.009	0.029	-9999	-10000	0	0
VAMP2	0	0	-9999	-10000	0	0
SLC2A4	0.034	0.035	-9999	-10000	0	0
STX4	0	0	-9999	-10000	0	0
GSK3B	0.022	0	-9999	-10000	0	0
SFN	-0.057	0.17	-9999	-0.57	48	48
LNPEP	0	0	-9999	-10000	0	0
YWHAE	0	0	-9999	-10000	0	0

×

S1P5 pathway

Figure 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	-0.005	0.045	-9999	-0.37	7	7
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	-0.004	0.05	-9999	-0.63	3	3
RhoA/GTP	-0.006	0.035	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.007	0.04	-9999	-0.3	2	2
GNAZ	-0.009	0.082	-9999	-0.74	6	6
GNAI3	0	0	-9999	-10000	0	0
GNA12	0	0	-9999	-10000	0	0
S1PR5	-0.009	0.072	-9999	-0.6	7	7
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.007	0.04	-9999	-0.31	2	2
RhoA/GDP	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
GNAI1	-0.002	0.034	-9999	-0.74	1	1

×

FoxO family signaling

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

×

Paxillin-dependent events mediated by a4b1

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

×

Rapid glucocorticoid signaling

Figure 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	-0.009	0.065	-10000	0	-0.46	9	9
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.02	-10000	0	-0.42	1	1
GNB1/GNG2	-0.006	0.054	-10000	0	-0.49	6	6
GNB1	-0.002	0.034	-10000	0	-0.74	1	1
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.004	0.041	-10000	0	-0.46	4	4
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.001	0.01	0.11	4	-10000	0	4
GNAL	-0.006	0.067	-10000	0	-0.74	4	4
GNG2	-0.008	0.075	-10000	0	-0.74	5	5
CRH	-0.001	0.026	-10000	0	-0.57	1	1
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0	-10000	0	-10000	0	0
MAPK11	0.007	0	-10000	0	-10000	0	0

×

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

×

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	0.015	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.001	0.016	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.003	0.048	-9999	-0.74	2	2
NFKB1	0	0	-9999	-10000	0	0
RELA	0	0	-9999	-10000	0	0
MALT1	0	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
TNF/TNFR1A	-0.015	0.089	-9999	-0.55	13	13
TRAF6	0	0	-9999	-10000	0	0
PRKCA	-0.003	0.048	-9999	-0.74	2	2
CHUK	0	0	-9999	-10000	0	0
UBE2D3	0	0	-9999	-10000	0	0
TNF	-0.02	0.12	-9999	-0.73	13	13
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.041	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
TNFRSF1A	0	0	-9999	-10000	0	0
IKK complex	-0.001	0.018	-9999	-10000	0	0
CYLD	0	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.003	0.027	-9999	-10000	0	0

×

Arf6 downstream pathway

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

×

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	0.046	-10000	0	-0.44	2	2
RAP1A	0.039	0.038	-10000	0	-10000	0	0
GAB1	0.039	0.038	-10000	0	-10000	0	0
MAPK14	0.027	0.046	-10000	0	-0.44	2	2
EPO	0.004	0.064	-10000	0	-0.56	6	6
PLCG1	-0.005	0.035	-10000	0	-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	0.048	-10000	0	-0.5	2	2
GAB1/SHC/GRB2/SOS1	-0.003	0.027	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.005	0.045	-10000	0	-0.4	6	6
IRS2	0.036	0.05	-10000	0	-10000	0	0
STAT1	0.051	0.042	-10000	0	-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	-10000	0	0
SOCS3	-0.003	0.048	-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	-0.005	0.045	-10000	0	-0.4	6	6
LYN	0.008	0.048	-10000	0	-0.74	2	2
TEC/VAV2	0.039	0.068	-10000	0	-0.73	2	2
elevation of cytosolic calcium ion concentration	0.012	0.004	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.001	0.049	-10000	0	-0.49	2	2
mol:IP3	-0.005	0.034	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.006	0.042	-10000	0	-10000	0	0
SH2B3	0.008	0.048	-10000	0	-0.74	2	2
NFKB1	0.027	0.046	-10000	0	-0.44	2	2
EPO/EPOR (dimer)/JAK2/SOCS3	-0.002	0.031	0.3	2	-0.26	2	4
PTPN6	0.033	0.04	-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	0.034	-10000	0	-0.74	1	1
mol:GDP	-0.003	0.028	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	0	0	-10000	0	-10000	0	0
CRKL/CBL/C3G	-0.004	0.029	-10000	0	-10000	0	0
VAV2	0.036	0.056	-10000	0	-0.74	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	0.036	-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	Mean.of.Down.Perturbations
GBL	0	0	-9999	-9999
MKNK1	0	0	-9999	-9999
mol:PIP3	0	0	-9999	-9999
FRAP1	0.013	0	-9999	-9999
AKT1	0	0	-9999	-9999
INSR	0	0	-9999	-9999
Insulin Receptor/Insulin	0	0	-9999	-9999
mol:GTP	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0	-9999	-9999
TSC2	0	0	-9999	-9999
RHEB/GDP	0	0	-9999	-9999
TSC1	0	0	-9999	-9999
Insulin Receptor/IRS1	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0	-9999	-9999
mol:GDP	0	0	-9999	-9999
EIF3A	0	0	-9999	-9999
RPS6KB1	0.025	0	-9999	-9999
MAP3K5	0.009	0	-9999	-9999
PIK3R1	0	0	-9999	-9999
apoptosis	0.009	0	-9999	-9999
mol:LY294002	0	0	-9999	-9999
EIF4B	0.03	0	-9999	-9999
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0	0	-9999	-9999
eIF4E/eIF4G1/eIF4A1	0	0	-9999	-9999
KIAA1303	0	0	-9999	-9999
PI3K	0	0	-9999	-9999
mTOR/RHEB/GTP/Raptor/GBL	0.028	0	-9999	-9999
FKBP1A	0	0	-9999	-9999
RHEB/GTP	0	0	-9999	-9999
mol:Amino Acids	0	0	-9999	-9999
FKBP12/Rapamycin	0	0	-9999	-9999
PDPK1	0	0	-9999	-9999
EIF4E	0	0	-9999	-9999
ASK1/PP5C	0	0	-9999	-9999
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.014	0	-9999	-9999
TSC1/TSC2	0	0	-9999	-9999
tumor necrosis factor receptor activity	0	0	-9999	-9999
RPS6	0	0	-9999	-9999
PPP5C	0	0	-9999	-9999
EIF4G1	0	0	-9999	-9999
IRS1	0.007	0	-9999	-9999
INS	0	0	-9999	-9999
PTEN	0	0	-9999	-9999
PDK2	0	0	-9999	-9999
EIF4EBP1	0.004	0.02	-9999	-9999
PIK3CA	0	0	-9999	-9999
PPP2R5D	0.019	0	-9999	-9999
peptide biosynthetic process	0.014	0	-9999	-9999
RHEB	0	0	-9999	-9999
EIF4A1	0	0	-9999	-9999
mol:Rapamycin	0	0	-9999	-9999
EEF2	0.015	0	-9999	-9999
eIF4E/4E-BP1	-0.003	0.014	-9999	-9999

×

Class I PI3K signaling events mediated by Akt

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

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

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

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.036	0.057	-9999	-0.53	1	1
BAG4	-0.001	0.026	-9999	-0.57	1	1
BAD	0.027	0.021	-9999	-10000	0	0
NFKBIA	0	0	-9999	-10000	0	0
BIRC3	-0.009	0.082	-9999	-0.74	6	6
BAX	0.027	0.021	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.012	0.016	-9999	-0.12	1	1
IKBKB	0.041	0.056	-9999	-0.5	1	1
MAP2K2	0.038	0.023	-9999	-10000	0	0
MAP2K1	0.038	0.023	-9999	-10000	0	0
SMPD1	0.017	0.016	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.042	0.056	-9999	-0.51	1	1
MAP2K4	0.033	0.021	-9999	-10000	0	0
protein ubiquitination	0.043	0.055	-9999	-0.5	1	1
EnzymeConsortium:2.7.1.37	0.042	0.025	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.033	0.023	-9999	-10000	0	0
CRADD	0	0	-9999	-10000	0	0
mol:ceramide	0.021	0.022	-9999	-0.16	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0	0	-9999	-10000	0	0
MAP3K1	0.027	0.021	-9999	-10000	0	0
TRADD	0	0	-9999	-10000	0	0
RELA/p50	0	0	-9999	-10000	0	0
MAPK3	0.04	0.023	-9999	-10000	0	0
MAPK1	0.04	0.023	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.036	0.057	-9999	-0.53	1	1
KSR1	0.027	0.022	-9999	-10000	0	0
MAPK8	0.038	0.02	-9999	-10000	0	0
TRAF2	0	0.001	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.042	0.054	-9999	-0.5	1	1
TNF R/SODD	-0.001	0.019	-9999	-0.41	1	1
TNF	-0.02	0.12	-9999	-0.73	13	13
CYCS	0.028	0.021	-9999	-10000	0	0
IKBKG	0.042	0.054	-9999	-0.5	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.03	0.06	-9999	-0.56	1	1
RELA	0	0	-9999	-10000	0	0
RIPK1	0	0.001	-9999	-10000	0	0
AIFM1	0.028	0.021	-9999	-10000	0	0
TNF/TNF R/SODD	-0.013	0.078	-9999	-0.48	12	12
TNFRSF1A	0	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.023	0.016	-9999	-10000	0	0
NSMAF	0.036	0.057	-9999	-0.52	1	1
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	-0.001	0.026	-9999	-0.57	1	1

×

Signaling mediated by p38-gamma and p38-delta

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

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

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

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0	0	-9999	-10000	0	0
FBXW11	0	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.001	0.016	-9999	-0.34	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.001	0.018	-9999	-10000	0	0
NFKBIA	0.025	0.018	-9999	-0.26	2	2
MAPK14	0	0	-9999	-10000	0	0
NF kappa B1 p105/p50	-0.001	0.016	-9999	-0.34	1	1
ARRB2	0.014	0	-9999	-10000	0	0
REL	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.001	0.016	-9999	-0.34	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	-0.001	0.016	-9999	-0.34	1	1
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	-10000	0	0
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	-10000	0	0
IKBKB	-0.001	0.026	-9999	-0.57	1	1
beta TrCP1/SCF ubiquitin ligase complex	0	0	-9999	-10000	0	0
SYK	-0.002	0.034	-9999	-0.74	1	1
I kappa B alpha/PIK3R1	-0.001	0.015	-9999	-10000	0	0
cell death	-0.001	0.016	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.001	0.016	-9999	-0.34	1	1
LCK	-0.002	0.034	-9999	-0.74	1	1
BCL3	0	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

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

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

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

×

E-cadherin signaling events

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

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

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

×

Arf1 pathway

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

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

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

×

Alternative NF-kappaB pathway

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

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

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

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