PARADIGM pathway analysis of mRNASeq expression data - Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	186
Aurora B signaling	167
Aurora C signaling	132
HIF-1-alpha transcription factor network	124
Signaling events regulated by Ret tyrosine kinase	109
Angiopoietin receptor Tie2-mediated signaling	105
Endothelins	103
PDGFR-alpha signaling pathway	96
p75(NTR)-mediated signaling	88
Signaling events mediated by the Hedgehog family	81

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
FOXM1 transcription factor network	0.3529	186	9504	51	-0.97	0.011	1000	-1000	-0.13	-1000
Aurora B signaling	0.3169	167	11189	67	-0.52	0.011	1000	-1000	-0.038	-1000
Aurora C signaling	0.2505	132	930	7	-0.29	0.01	1000	-1000	-0.017	-1000
HIF-1-alpha transcription factor network	0.2353	124	9435	76	-0.49	0.017	1000	-1000	-0.064	-1000
Signaling events regulated by Ret tyrosine kinase	0.2068	109	9015	82	-0.19	0.011	1000	-1000	-0.052	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1992	105	9267	88	-0.32	0.043	1000	-1000	-0.066	-1000
Endothelins	0.1954	103	9944	96	-0.33	0.011	1000	-1000	-0.042	-1000
PDGFR-alpha signaling pathway	0.1822	96	4251	44	-0.29	0.025	1000	-1000	-0.032	-1000
p75(NTR)-mediated signaling	0.1670	88	11105	125	-0.2	0.03	1000	-1000	-0.056	-1000
Signaling events mediated by the Hedgehog family	0.1537	81	4216	52	-0.26	0.15	1000	-1000	-0.025	-1000
Integrins in angiogenesis	0.1442	76	6428	84	-0.29	0.024	1000	-1000	-0.053	-1000
Cellular roles of Anthrax toxin	0.1290	68	2658	39	-0.13	0.019	1000	-1000	-0.013	-1000
S1P3 pathway	0.1290	68	2863	42	-0.41	0.016	1000	-1000	-0.019	-1000
Nongenotropic Androgen signaling	0.1271	67	3496	52	-0.21	0.1	1000	-1000	-0.027	-1000
Fc-epsilon receptor I signaling in mast cells	0.1176	62	6057	97	-0.12	0.028	1000	-1000	-0.045	-1000
Wnt signaling	0.1120	59	418	7	-0.089	-0.003	1000	-1000	-0.01	-1000
PLK1 signaling events	0.1082	57	4887	85	-0.3	0.044	1000	-1000	-0.027	-1000
Signaling mediated by p38-alpha and p38-beta	0.1082	57	2516	44	-0.08	0.011	1000	-1000	-0.033	-1000
Effects of Botulinum toxin	0.1025	54	1428	26	-0.11	0.018	1000	-1000	-0.036	-1000
Glypican 1 network	0.1006	53	2570	48	-0.22	0.022	1000	-1000	-0.019	-1000
Reelin signaling pathway	0.1006	53	2981	56	-0.16	0.03	1000	-1000	-0.041	-1000
IGF1 pathway	0.0949	50	2878	57	-0.077	0.022	1000	-1000	-0.048	-1000
Aurora A signaling	0.0911	48	2900	60	-0.25	0.022	1000	-1000	-0.019	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0911	48	5789	120	-0.19	0.14	1000	-1000	-0.041	-1000
LPA4-mediated signaling events	0.0873	46	555	12	-0.12	0.015	1000	-1000	-0.01	-1000
Noncanonical Wnt signaling pathway	0.0854	45	1174	26	-0.14	0.011	1000	-1000	-0.016	-1000
S1P5 pathway	0.0854	45	781	17	-0.099	0.032	1000	-1000	-0.012	-1000
Syndecan-1-mediated signaling events	0.0835	44	1505	34	-0.17	0.011	1000	-1000	-0.017	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0835	44	3016	68	-0.2	0.081	1000	-1000	-0.089	-1000
TCGA08_retinoblastoma	0.0835	44	359	8	-0.13	0.024	1000	-1000	-0.009	-1000
S1P4 pathway	0.0816	43	1079	25	-0.099	0.024	1000	-1000	-0.014	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0816	43	3417	78	-0.1	0.044	1000	-1000	-0.038	-1000
Thromboxane A2 receptor signaling	0.0797	42	4446	105	-0.18	0.031	1000	-1000	-0.04	-1000
amb2 Integrin signaling	0.0797	42	3456	82	-0.15	0.022	1000	-1000	-0.046	-1000
BMP receptor signaling	0.0759	40	3290	81	-0.28	0.038	1000	-1000	-0.046	-1000
Plasma membrane estrogen receptor signaling	0.0759	40	3468	86	-0.15	0.066	1000	-1000	-0.045	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0740	39	1351	34	-0.039	0.011	1000	-1000	-0.017	-1000
LPA receptor mediated events	0.0740	39	3993	102	-0.14	0.029	1000	-1000	-0.042	-1000
Ephrin B reverse signaling	0.0721	38	1837	48	-0.094	0.015	1000	-1000	-0.033	-1000
FOXA2 and FOXA3 transcription factor networks	0.0702	37	1714	46	-0.22	0.015	1000	-1000	-0.066	-1000
S1P1 pathway	0.0702	37	1335	36	-0.12	0.011	1000	-1000	-0.034	-1000
Ras signaling in the CD4+ TCR pathway	0.0683	36	617	17	-0.075	0.016	1000	-1000	-0.017	-1000
Ephrin A reverse signaling	0.0664	35	250	7	-0.021	0	1000	-1000	-0.01	-1000
Osteopontin-mediated events	0.0645	34	1299	38	-0.12	0.014	1000	-1000	-0.052	-1000
IL4-mediated signaling events	0.0588	31	2847	91	-0.52	0.26	1000	-1000	-0.13	-1000
TCGA08_p53	0.0588	31	222	7	-0.089	0.047	1000	-1000	-0.008	-1000
FAS signaling pathway (CD95)	0.0569	30	1443	47	-0.074	0.037	1000	-1000	-0.037	-1000
Glypican 2 network	0.0550	29	117	4	-0.014	-0.001	1000	-1000	-0.007	-1000
EGFR-dependent Endothelin signaling events	0.0550	29	612	21	-0.12	0.019	1000	-1000	-0.039	-1000
Arf6 signaling events	0.0531	28	1745	62	-0.085	0.027	1000	-1000	-0.03	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0531	28	2424	85	-0.21	0.012	1000	-1000	-0.041	-1000
Syndecan-4-mediated signaling events	0.0512	27	1815	67	-0.26	0.016	1000	-1000	-0.045	-1000
Visual signal transduction: Rods	0.0512	27	1435	52	-0.11	0.011	1000	-1000	-0.044	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0493	26	1407	54	-0.14	0.022	1000	-1000	-0.058	-1000
Coregulation of Androgen receptor activity	0.0474	25	1943	76	-0.13	0.022	1000	-1000	-0.026	-1000
BCR signaling pathway	0.0455	24	2474	99	-0.06	0.047	1000	-1000	-0.048	-1000
Visual signal transduction: Cones	0.0436	23	890	38	-0.081	0.011	1000	-1000	-0.032	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0436	23	1246	52	-0.079	0.023	1000	-1000	-0.024	-1000
Calcium signaling in the CD4+ TCR pathway	0.0436	23	722	31	-0.12	0.015	1000	-1000	-0.042	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0436	23	2889	125	-0.065	0.029	1000	-1000	-0.059	-1000
TCGA08_rtk_signaling	0.0417	22	590	26	-0.15	0.023	1000	-1000	-0.011	-1000
Regulation of Androgen receptor activity	0.0417	22	1552	70	-0.22	0.023	1000	-1000	-0.039	-1000
Syndecan-2-mediated signaling events	0.0398	21	1495	69	-0.1	0.028	1000	-1000	-0.015	-1000
Hedgehog signaling events mediated by Gli proteins	0.0398	21	1419	65	-0.099	0.038	1000	-1000	-0.038	-1000
Glucocorticoid receptor regulatory network	0.0398	21	2405	114	-0.24	0.045	1000	-1000	-0.045	-1000
EPHB forward signaling	0.0398	21	1837	85	-0.034	0.03	1000	-1000	-0.047	-1000
IL6-mediated signaling events	0.0398	21	1580	75	-0.12	0.061	1000	-1000	-0.043	-1000
IL2 signaling events mediated by STAT5	0.0398	21	480	22	-0.1	0.056	1000	-1000	-0.032	-1000
Insulin Pathway	0.0398	21	1625	74	-0.13	0.03	1000	-1000	-0.053	-1000
Presenilin action in Notch and Wnt signaling	0.0380	20	1256	61	-0.12	0.03	1000	-1000	-0.037	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0361	19	648	33	-0.16	0.034	1000	-1000	-0.024	-1000
Regulation of nuclear SMAD2/3 signaling	0.0342	18	2466	136	-0.16	0.053	1000	-1000	-0.035	-1000
Rapid glucocorticoid signaling	0.0342	18	363	20	-0.051	0.011	1000	-1000	-0.008	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0323	17	478	28	-0.099	0.032	1000	-1000	-0.018	-1000
Signaling events mediated by PTP1B	0.0323	17	1345	76	-0.12	0.024	1000	-1000	-0.048	-1000
Nectin adhesion pathway	0.0323	17	1084	63	-0.065	0.021	1000	-1000	-0.048	-1000
Retinoic acid receptors-mediated signaling	0.0323	17	1006	58	-0.052	0.022	1000	-1000	-0.041	-1000
Canonical Wnt signaling pathway	0.0323	17	868	51	-0.097	0.05	1000	-1000	-0.03	-1000
BARD1 signaling events	0.0304	16	930	57	-0.13	0.028	1000	-1000	-0.039	-1000
Class I PI3K signaling events mediated by Akt	0.0304	16	1116	68	-0.24	0.04	1000	-1000	-0.025	-1000
Regulation of p38-alpha and p38-beta	0.0304	16	912	54	-0.18	0.044	1000	-1000	-0.038	-1000
Regulation of Telomerase	0.0285	15	1582	102	-0.3	0.038	1000	-1000	-0.065	-1000
IL12-mediated signaling events	0.0266	14	1293	87	-0.3	0.044	1000	-1000	-0.093	-1000
IL1-mediated signaling events	0.0266	14	913	62	-0.039	0.041	1000	-1000	-0.049	-1000
Signaling mediated by p38-gamma and p38-delta	0.0266	14	214	15	-0.017	0.021	1000	-1000	-0.012	-1000
TCR signaling in naïve CD8+ T cells	0.0266	14	1348	93	-0.043	0.04	1000	-1000	-0.041	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0247	13	1146	83	-0.24	0.044	1000	-1000	-0.038	-1000
FoxO family signaling	0.0247	13	838	64	-0.24	0.043	1000	-1000	-0.039	-1000
IL2 signaling events mediated by PI3K	0.0247	13	757	58	-0.11	0.042	1000	-1000	-0.056	-1000
Signaling events mediated by PRL	0.0247	13	473	34	-0.13	0.018	1000	-1000	-0.02	-1000
Insulin-mediated glucose transport	0.0228	12	400	32	-0.24	0.025	1000	-1000	-0.03	-1000
IFN-gamma pathway	0.0228	12	865	68	-0.22	0.048	1000	-1000	-0.054	-1000
Signaling events mediated by HDAC Class III	0.0228	12	492	40	-0.077	0.016	1000	-1000	-0.022	-1000
Syndecan-3-mediated signaling events	0.0228	12	441	35	-0.09	0.03	1000	-1000	-0.016	-1000
PDGFR-beta signaling pathway	0.0228	12	1258	97	-0.021	0.039	1000	-1000	-0.046	-1000
ErbB2/ErbB3 signaling events	0.0209	11	755	65	-0.12	0.022	1000	-1000	-0.037	-1000
ErbB4 signaling events	0.0209	11	763	69	-0.074	0.031	1000	-1000	-0.065	-1000
mTOR signaling pathway	0.0209	11	628	53	-0.026	0.018	1000	-1000	-0.033	-1000
HIF-2-alpha transcription factor network	0.0209	11	514	43	-0.14	0.022	1000	-1000	-0.041	-1000
Class IB PI3K non-lipid kinase events	0.0209	11	33	3	-0.003	0.003	1000	-1000	-0.007	-1000
JNK signaling in the CD4+ TCR pathway	0.0190	10	180	17	-0.015	0.034	1000	-1000	-0.019	-1000
EPO signaling pathway	0.0190	10	579	55	-0.026	0.035	1000	-1000	-0.05	-1000
Ceramide signaling pathway	0.0190	10	782	76	-0.069	0.036	1000	-1000	-0.02	-1000
Caspase cascade in apoptosis	0.0152	8	596	74	-0.032	0.035	1000	-1000	-0.018	-1000
IL27-mediated signaling events	0.0152	8	434	51	-0.053	0.014	1000	-1000	-0.038	-1000
Signaling events mediated by HDAC Class II	0.0133	7	588	75	-0.053	0.029	1000	-1000	-0.026	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0133	7	269	37	-0.021	0.027	1000	-1000	-0.022	-1000
IL23-mediated signaling events	0.0133	7	455	60	-0.048	0.042	1000	-1000	-0.12	-1000
p38 MAPK signaling pathway	0.0133	7	321	44	-0.046	0.028	1000	-1000	-0.038	-1000
ceramide signaling pathway	0.0114	6	339	49	-0.032	0.038	1000	-1000	-0.02	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0114	6	274	45	-0.032	0.056	1000	-1000	-0.049	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0095	5	403	74	-0.074	0.062	1000	-1000	-0.05	-1000
Canonical NF-kappaB pathway	0.0076	4	170	39	-0.032	0.059	1000	-1000	-0.044	-1000
PLK2 and PLK4 events	0.0076	4	12	3	0.008	0.015	1000	-1000	-0.008	-1000
Class I PI3K signaling events	0.0076	4	314	73	-0.015	0.053	1000	-1000	-0.036	-1000
Arf6 trafficking events	0.0076	4	344	71	-0.19	0.035	1000	-1000	-0.039	-1000
TRAIL signaling pathway	0.0057	3	183	48	-0.001	0.038	1000	-1000	-0.038	-1000
Signaling events mediated by HDAC Class I	0.0057	3	380	104	-0.032	0.044	1000	-1000	-0.034	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0038	2	49	23	-0.004	0.036	1000	-1000	-0.022	-1000
a4b1 and a4b7 Integrin signaling	0.0038	2	11	5	0.009	0.015	1000	-1000	-0.01	-1000
Paxillin-dependent events mediated by a4b1	0.0038	2	98	36	-0.031	0.032	1000	-1000	-0.038	-1000
VEGFR1 specific signals	0.0038	2	137	56	-0.063	0.052	1000	-1000	-0.023	-1000
Arf6 downstream pathway	0.0019	1	50	43	-0.023	0.023	1000	-1000	-0.016	-1000
Atypical NF-kappaB pathway	0.0019	1	36	31	0	0.04	1000	-1000	-0.019	-1000
E-cadherin signaling in the nascent adherens junction	0.0019	1	97	76	-0.003	0.048	1000	-1000	-0.047	-1000
E-cadherin signaling in keratinocytes	0.0019	1	82	43	-0.034	0.036	1000	-1000	-0.034	-1000
E-cadherin signaling events	0.0019	1	7	5	0.009	0.021	1000	-1000	-0.012	-1000
Circadian rhythm pathway	0.0000	0	15	22	-0.011	0.04	1000	-1000	-0.026	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.028	1000	-1000	-0.031	-1000
Arf1 pathway	0.0000	0	8	54	0	0.028	1000	-1000	-0.019	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	0	0.033	1000	-1000	-0.013	-1000
Total	NA	4014	237281	7203	-17	4.3	131000	-131000	-4.7	-131000

FOXM1 transcription factor network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.63	0.36	-9999	-0.95	232	232
PLK1	-0.15	0.087	-9999	-10000	0	0
BIRC5	-0.16	0.081	-9999	-10000	0	0
HSPA1B	-0.63	0.36	-9999	-0.99	202	202
MAP2K1	-0.022	0.016	-9999	-10000	0	0
BRCA2	-0.63	0.36	-9999	-0.95	234	234
FOXM1	-0.76	0.48	-9999	-1.1	294	294
XRCC1	-0.63	0.36	-9999	-0.94	243	243
FOXM1B/p19	-0.68	0.4	-9999	-0.95	307	307
Cyclin D1/CDK4	-0.58	0.32	-9999	-0.86	242	242
CDC2	-0.67	0.38	-9999	-0.94	293	293
TGFA	-0.57	0.31	-9999	-0.84	236	236
SKP2	-0.63	0.36	-9999	-0.95	236	236
CCNE1	-0.14	0.17	-9999	-0.34	214	214
CKS1B	-0.63	0.36	-9999	-0.94	244	244
RB1	-0.24	0.12	-9999	-0.96	3	3
FOXM1C/SP1	-0.7	0.42	-9999	-1	288	288
AURKB	-0.18	0.067	-9999	-10000	0	0
CENPF	-0.67	0.37	-9999	-0.97	270	270
CDK4	-0.001	0.005	-9999	-10000	0	0
MYC	-0.56	0.32	-9999	-0.81	273	273
CHEK2	-0.022	0.016	-9999	-10000	0	0
ONECUT1	-0.62	0.35	-9999	-0.88	279	279
CDKN2A	-0.13	0.17	-9999	-0.32	219	219
LAMA4	-0.66	0.4	-9999	-1	235	235
FOXM1B/HNF6	-0.7	0.42	-9999	-1	279	279
FOS	-0.77	0.48	-9999	-1.1	279	279
SP1	0.011	0.001	-9999	-10000	0	0
CDC25B	-0.63	0.36	-9999	-0.94	247	247
response to radiation	-0.03	0.014	-9999	-10000	0	0
CENPB	-0.63	0.36	-9999	-0.99	204	204
CENPA	-0.69	0.38	-9999	-0.96	290	290
NEK2	-0.69	0.37	-9999	-0.98	276	276
HIST1H2BA	-0.64	0.36	-9999	-0.95	236	236
CCNA2	-0.07	0.14	-9999	-0.34	111	111
EP300	0.011	0	-9999	-10000	0	0
CCNB1/CDK1	-0.72	0.43	-9999	-1	276	276
CCNB2	-0.69	0.38	-9999	-0.96	294	294
CCNB1	-0.67	0.39	-9999	-0.97	275	275
ETV5	-0.63	0.36	-9999	-0.94	248	248
ESR1	-0.68	0.41	-9999	-1	231	231
CCND1	-0.59	0.33	-9999	-0.88	242	242
GSK3A	-0.014	0.013	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.12	0.14	-9999	-0.25	256	256
CDK2	0.003	0.004	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.038	0.017	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.68	0.38	-9999	-0.94	305	305
GAS1	-0.97	0.48	-9999	-1.2	387	387
MMP2	-0.65	0.38	-9999	-0.94	269	269
RB1/FOXM1C	-0.63	0.36	-9999	-0.93	253	253
CREBBP	0.009	0.026	-9999	-0.41	2	2

×

Aurora B 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
Condensin I complex	-0.12	0.064	-10000	0	-0.16	41	41
STMN1	-0.18	0.076	-10000	0	-0.21	464	464
Aurora B/RasGAP/Survivin	-0.28	0.12	-10000	0	-0.31	479	479
Chromosomal passenger complex/Cul3 protein complex	-0.12	0.092	-10000	0	-0.28	102	102
BIRC5	-0.26	0.14	-10000	0	-0.33	410	410
DES	-0.52	0.24	-10000	0	-0.63	442	442
Aurora C/Aurora B/INCENP	-0.13	0.06	-10000	0	-0.15	444	444
Aurora B/TACC1	-0.19	0.11	-10000	0	-0.22	473	473
Aurora B/PP2A	-0.18	0.076	-10000	0	-0.21	464	464
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.024	0.014	-10000	0	-10000	0	0
mitotic metaphase/anaphase transition	-0.004	0.003	-10000	0	-10000	0	0
NDC80	-0.2	0.095	-10000	0	-0.23	465	465
Cul3 protein complex	-0.026	0.1	-10000	0	-0.23	102	102
KIF2C	-0.068	0.035	-10000	0	-0.1	3	3
PEBP1	0.002	0.004	-10000	0	-10000	0	0
KIF20A	-0.3	0.1	-10000	0	-0.33	477	477
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	-0.18	0.081	-10000	0	-0.21	464	464
SEPT1	0.01	0.018	-10000	0	-0.41	1	1
SMC2	0.01	0.015	-10000	0	-0.33	1	1
SMC4	0.011	0	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.01	0.015	-10000	0	-10000	0	0
PSMA3	0.011	0	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.004	0.001	-10000	0	-10000	0	0
H3F3B	-0.074	0.034	-10000	0	-10000	0	0
AURKB	-0.29	0.11	-10000	0	-0.33	464	464
AURKC	0.01	0.021	-10000	0	-0.33	2	2
CDCA8	-0.19	0.17	-10000	0	-0.34	307	307
cytokinesis	-0.15	0.068	-10000	0	-0.25	20	20
Aurora B/Septin1	-0.13	0.079	-10000	0	-0.23	21	21
AURKA	-0.091	0.16	-10000	0	-0.33	155	155
INCENP	0.004	0.004	-10000	0	-10000	0	0
KLHL13	-0.071	0.17	-10000	0	-0.41	102	102
BUB1	-0.26	0.14	-10000	0	-0.33	413	413
hSgo1/Aurora B/Survivin	-0.37	0.15	-10000	0	-0.4	489	489
EVI5	0.011	0.001	-10000	0	-10000	0	0
RhoA/GTP	-0.11	0.064	-10000	0	-0.28	21	21
SGOL1	-0.25	0.14	-10000	0	-0.33	408	408
CENPA	-0.1	0.05	-10000	0	-0.15	149	149
NCAPG	-0.22	0.16	-10000	0	-0.33	350	350
Aurora B/HC8 Proteasome	-0.18	0.076	-10000	0	-0.21	464	464
NCAPD2	0.011	0	-10000	0	-10000	0	0
Aurora B/PP1-gamma	-0.18	0.076	-10000	0	-0.21	464	464
RHOA	0.011	0	-10000	0	-10000	0	0
NCAPH	-0.25	0.14	-10000	0	-0.33	409	409
NPM1	-0.041	0.018	-10000	0	-10000	0	0
RASA1	0.007	0.041	-10000	0	-0.41	5	5
KLHL9	0.01	0.018	-10000	0	-0.41	1	1
mitotic prometaphase	-0.009	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.18	0.076	-10000	0	-0.21	464	464
PPP1CC	0.011	0	-10000	0	-10000	0	0
Centraspindlin	-0.13	0.071	-10000	0	-0.25	42	42
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
NSUN2	-0.041	0.018	-10000	0	-10000	0	0
MYLK	-0.24	0.15	-10000	0	-0.37	304	304
KIF23	-0.005	0.067	-10000	0	-0.34	21	21
VIM	-0.19	0.083	-10000	0	-0.22	464	464
RACGAP1	0.007	0.021	-10000	0	-0.34	2	2
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.041	0.018	-10000	0	-10000	0	0
Chromosomal passenger complex	-0.14	0.067	-10000	0	-0.18	305	305
Chromosomal passenger complex/EVI5	-0.26	0.19	0.13	4	-0.36	411	415
TACC1	-0.066	0.16	-10000	0	-0.41	96	96
PPP2R5D	0.011	0	-10000	0	-10000	0	0
CUL3	0.011	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Aurora C 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
INCENP	0.011	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.13	0.058	-9999	-0.16	464	464
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.038	0.014	-9999	-10000	0	0
AURKB	-0.29	0.11	-9999	-0.33	464	464
AURKC	0.01	0.021	-9999	-0.33	2	2

×

HIF-1-alpha 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
PKM2	-0.36	0.41	-9999	-0.83	171	171
HDAC7	0.012	0.001	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.3	0.36	-9999	-0.76	144	144
SMAD4	0.011	0.018	-9999	-0.41	1	1
ID2	-0.36	0.41	-9999	-0.83	171	171
AP1	-0.075	0.14	-9999	-0.29	160	160
ABCG2	-0.47	0.47	-9999	-0.9	238	238
HIF1A	-0.048	0.062	-9999	-10000	0	0
TFF3	-0.42	0.44	-9999	-0.88	202	202
GATA2	-0.028	0.12	-9999	-0.41	50	50
AKT1	-0.061	0.084	-9999	-0.22	37	37
response to hypoxia	-0.078	0.087	-9999	-0.2	89	89
MCL1	-0.36	0.41	-9999	-0.83	171	171
NDRG1	-0.36	0.41	-9999	-0.83	171	171
SERPINE1	-0.36	0.41	-9999	-0.83	171	171
FECH	-0.36	0.41	-9999	-0.83	171	171
FURIN	-0.36	0.41	-9999	-0.83	171	171
NCOA2	-0.003	0.077	-9999	-0.41	18	18
EP300	-0.073	0.13	-9999	-0.34	73	73
HMOX1	-0.36	0.41	-9999	-0.83	171	171
BHLHE40	-0.36	0.41	-9999	-0.82	173	173
BHLHE41	-0.38	0.43	-9999	-0.87	177	177
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.041	0.083	-9999	-0.3	5	5
ENG	-0.025	0.085	-9999	-0.29	2	2
JUN	0.006	0.049	-9999	-0.41	7	7
RORA	-0.37	0.42	-9999	-0.84	176	176
ABCB1	-0.35	0.5	-9999	-1.2	136	136
TFRC	-0.36	0.41	-9999	-0.83	171	171
CXCR4	-0.36	0.41	-9999	-0.83	171	171
TF	-0.37	0.42	-9999	-0.85	171	171
CITED2	-0.37	0.41	-9999	-0.84	173	173
HIF1A/ARNT	-0.4	0.47	-9999	-0.9	186	186
LDHA	-0.053	0.048	-9999	-10000	0	0
ETS1	-0.36	0.41	-9999	-0.83	173	173
PGK1	-0.36	0.41	-9999	-0.83	171	171
NOS2	-0.37	0.41	-9999	-0.83	174	174
ITGB2	-0.36	0.41	-9999	-0.83	173	173
ALDOA	-0.36	0.41	-9999	-0.82	173	173
Cbp/p300/CITED2	-0.39	0.46	-9999	-0.94	161	161
FOS	-0.12	0.19	-9999	-0.41	159	159
HK2	-0.37	0.41	-9999	-0.84	174	174
SP1	0.01	0.022	-9999	-10000	0	0
GCK	-0.23	0.47	-9999	-1.4	74	74
HK1	-0.36	0.41	-9999	-0.83	171	171
NPM1	-0.36	0.41	-9999	-0.83	170	170
EGLN1	-0.36	0.41	-9999	-0.83	171	171
CREB1	0.017	0	-9999	-10000	0	0
PGM1	-0.36	0.41	-9999	-0.83	170	170
SMAD3	0.009	0.036	-9999	-0.41	4	4
EDN1	-0.14	0.24	-9999	-0.6	74	74
IGFBP1	-0.4	0.43	-9999	-0.87	181	181
VEGFA	-0.25	0.32	-9999	-0.7	107	107
HIF1A/JAB1	-0.023	0.036	-9999	-10000	0	0
CP	-0.4	0.43	-9999	-0.87	185	185
CXCL12	-0.49	0.46	-9999	-0.91	239	239
COPS5	0.011	0.003	-9999	-10000	0	0
SMAD3/SMAD4	0.015	0.029	-9999	-0.28	5	5
BNIP3	-0.36	0.41	-9999	-0.83	171	171
EGLN3	-0.36	0.41	-9999	-0.83	173	173
CA9	-0.44	0.44	-9999	-0.86	218	218
TERT	-0.41	0.43	-9999	-0.87	192	192
ENO1	-0.36	0.41	-9999	-0.83	171	171
PFKL	-0.36	0.41	-9999	-0.83	171	171
NCOA1	0.01	0.018	-9999	-0.41	1	1
ADM	-0.37	0.41	-9999	-0.83	180	180
ARNT	-0.048	0.062	-9999	-10000	0	0
HNF4A	-0.049	0.12	-9999	-0.34	77	77
ADFP	-0.37	0.4	-9999	-0.81	189	189
SLC2A1	-0.25	0.32	-9999	-0.7	108	108
LEP	-0.37	0.41	-9999	-0.83	171	171
HIF1A/ARNT/Cbp/p300	-0.32	0.37	-9999	-0.77	154	154
EPO	-0.22	0.29	-9999	-0.74	57	57
CREBBP	-0.075	0.14	-9999	-0.34	74	74
HIF1A/ARNT/Cbp/p300/HDAC7	-0.3	0.36	-9999	-0.76	137	137
PFKFB3	-0.36	0.41	-9999	-0.83	171	171
NT5E	-0.4	0.43	-9999	-0.88	183	183

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.032	0.034	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.13	0.13	-9999	-0.34	100	100
JUN	-0.078	0.13	-9999	-0.39	36	36
HRAS	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.1	0.13	-9999	-0.23	256	256
RAP1A	0.011	0	-9999	-10000	0	0
FRS2	0.011	0	-9999	-10000	0	0
RAP1A/GDP	0.008	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.1	0.13	-9999	-0.23	255	255
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.09	0.11	-9999	-0.21	249	249
RHOA	0.011	0	-9999	-10000	0	0
RAP1A/GTP	-0.099	0.11	-9999	-0.36	30	30
GRB7	-0.011	0.084	-9999	-0.34	33	33
RET51/GFRalpha1/GDNF	-0.1	0.13	-9999	-0.23	255	255
MAPKKK cascade	-0.099	0.11	-9999	-0.37	32	32
BCAR1	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.11	0.14	-9999	-0.24	264	264
lamellipodium assembly	-0.13	0.13	-9999	-0.24	257	257
RET51/GFRalpha1/GDNF/SHC	-0.1	0.13	-9999	-0.23	255	255
PIK3CA	0.01	0.018	-9999	-0.41	1	1
RET9/GFRalpha1/GDNF/SHC	-0.09	0.11	-9999	-0.21	250	250
RET9/GFRalpha1/GDNF/Shank3	-0.09	0.11	-9999	-0.21	249	249
MAPK3	-0.076	0.11	-9999	-0.34	30	30
DOK1	0.011	0	-9999	-10000	0	0
DOK6	-0.072	0.17	-9999	-0.41	104	104
PXN	0.011	0	-9999	-10000	0	0
neurite development	-0.083	0.12	-9999	-0.27	94	94
DOK5	-0.03	0.12	-9999	-0.41	51	51
GFRA1	-0.19	0.21	-9999	-0.41	250	250
MAPK8	-0.085	0.13	-9999	-0.4	33	33
HRAS/GTP	-0.11	0.12	-9999	-0.23	255	255
tube development	-0.079	0.11	-9999	-0.19	249	249
MAPK1	-0.076	0.11	-9999	-0.34	30	30
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.082	0.11	-9999	-0.2	248	248
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
PDLIM7	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.13	0.16	-9999	-0.39	101	101
SHC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.1	0.13	-9999	-0.23	255	255
RET51/GFRalpha1/GDNF/Dok5	-0.12	0.16	-9999	-0.26	267	267
PRKCA	-0.016	0.1	-9999	-0.41	34	34
HRAS/GDP	0.008	0	-9999	-10000	0	0
CREB1	-0.1	0.14	-9999	-0.25	248	248
PIK3R1	0.007	0.041	-9999	-0.41	5	5
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.084	0.12	-9999	-0.2	248	248
RET51/GFRalpha1/GDNF/Grb7	-0.11	0.14	-9999	-0.24	258	258
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.025	0.11	-9999	-0.37	49	49
DOK4	0.011	0	-9999	-10000	0	0
JNK cascade	-0.076	0.13	-9999	-0.38	36	36
RET9/GFRalpha1/GDNF/FRS2	-0.09	0.11	-9999	-0.21	250	250
SHANK3	0.011	0	-9999	-10000	0	0
RASA1	0.007	0.041	-9999	-0.41	5	5
NCK1	0.009	0.026	-9999	-0.41	2	2
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.083	0.11	-9999	-0.2	248	248
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.091	0.13	-9999	-0.21	254	254
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.095	0.14	-9999	-0.22	255	255
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.095	0.14	-9999	-0.24	168	168
PI3K	-0.17	0.21	-9999	-0.36	257	257
SOS1	0.011	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.079	0.11	-9999	-0.19	249	249
GRB10	0.01	0.018	-9999	-0.41	1	1
activation of MAPKK activity	-0.083	0.11	-9999	-0.31	29	29
RET51/GFRalpha1/GDNF/FRS2	-0.1	0.13	-9999	-0.23	255	255
GAB1	0.008	0.037	-9999	-0.41	4	4
IRS1	-0.031	0.13	-9999	-0.41	53	53
IRS2	-0.045	0.14	-9999	-0.41	70	70
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.098	0.14	-9999	-0.23	254	254
RET51/GFRalpha1/GDNF/PKC alpha	-0.12	0.15	-9999	-0.24	265	265
GRB2	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GDNF	0.003	0.026	-9999	-0.33	3	3
RAC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.16	-9999	-0.26	269	269
Rac1/GTP	-0.15	0.15	-9999	-0.29	257	257
RET9/GFRalpha1/GDNF	-0.11	0.13	-9999	-0.24	250	250
GFRalpha1/GDNF	-0.13	0.15	-9999	-0.29	250	250

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.2	0.44	-10000	0	-0.83	165	165
NCK1/PAK1/Dok-R	-0.12	0.19	-10000	0	-0.4	165	165
NCK1/Dok-R	-0.27	0.51	-10000	0	-0.99	165	165
PIK3CA	0.011	0.018	-10000	0	-0.41	1	1
mol:beta2-estradiol	0.043	0.095	0.23	106	-10000	0	106
RELA	0.011	0	-10000	0	-10000	0	0
SHC1	0.011	0.002	-10000	0	-10000	0	0
Rac/GDP	0.008	0	-10000	0	-10000	0	0
F2	0.025	0.14	0.25	106	-0.34	39	145
TNIP2	0.011	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.29	0.44	-10000	0	-0.92	165	165
FN1	0.007	0.041	-10000	0	-0.41	5	5
PLD2	-0.28	0.53	-10000	0	-1	165	165
PTPN11	0.011	0	-10000	0	-10000	0	0
GRB14	-0.11	0.16	-10000	0	-0.33	191	191
ELK1	-0.24	0.47	-10000	0	-0.93	165	165
GRB7	-0.011	0.084	-10000	0	-0.34	33	33
PAK1	0.011	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.3	0.47	-10000	0	-0.97	165	165
CDKN1A	-0.11	0.3	-10000	0	-0.59	123	123
ITGA5	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.27	0.51	-10000	0	-0.99	165	165
CRK	0.011	0	-10000	0	-10000	0	0
mol:NO	-0.13	0.33	-10000	0	-0.62	165	165
PLG	-0.3	0.53	-10000	0	-1	165	165
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.22	0.4	-10000	0	-0.8	165	165
GRB2	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
ANGPT2	-0.06	0.2	-10000	0	-0.56	35	35
BMX	-0.3	0.54	-10000	0	-1.1	165	165
ANGPT1	-0.23	0.48	-10000	0	-1.2	106	106
tube development	-0.13	0.34	-10000	0	-0.61	164	164
ANGPT4	0.001	0.042	-10000	0	-0.38	6	6
response to hypoxia	-0.018	0.032	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.32	0.56	-10000	0	-1.1	165	165
alpha5/beta1 Integrin	0.016	0	-10000	0	-10000	0	0
FGF2	-0.22	0.21	-10000	0	-0.41	284	284
STAT5A (dimer)	-0.15	0.38	-10000	0	-0.71	150	150
mol:L-citrulline	-0.13	0.33	-10000	0	-0.62	165	165
AGTR1	-0.083	0.17	-10000	0	-0.41	116	116
MAPK14	-0.28	0.54	-10000	0	-1	165	165
Tie2/SHP2	-0.21	0.4	-10000	0	-1.1	91	91
TEK	-0.21	0.46	-10000	0	-1.2	91	91
RPS6KB1	-0.19	0.42	-10000	0	-0.8	165	165
Angiotensin II/AT1	-0.056	0.12	-10000	0	-0.28	116	116
Tie2/Ang1/GRB2	-0.29	0.55	-10000	0	-1.1	165	165
MAPK3	-0.25	0.48	-10000	0	-0.94	165	165
MAPK1	-0.25	0.48	-10000	0	-0.94	165	165
Tie2/Ang1/GRB7	-0.3	0.55	-10000	0	-1.1	165	165
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
MAPK8	-0.28	0.53	-10000	0	-1	165	165
PI3K	-0.24	0.5	-10000	0	-0.96	165	165
FES	-0.28	0.54	-10000	0	-1	165	165
Crk/Dok-R	-0.27	0.51	-10000	0	-0.99	165	165
Tie2/Ang1/ABIN2	-0.29	0.55	-10000	0	-1.1	165	165
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.17	0.39	-10000	0	-0.74	165	165
STAT5A	0.01	0.018	-10000	0	-0.41	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.19	0.42	-10000	0	-0.8	165	165
Tie2/Ang2	-0.2	0.45	-10000	0	-0.83	162	162
Tie2/Ang1	-0.31	0.58	-10000	0	-1.1	165	165
FOXO1	-0.17	0.4	-10000	0	-0.75	165	165
ELF1	-0.005	0.051	-10000	0	-0.43	3	3
ELF2	-0.28	0.53	-10000	0	-1	165	165
mol:Choline	-0.27	0.5	-10000	0	-0.98	165	165
cell migration	-0.071	0.1	-10000	0	-0.22	165	165
FYN	-0.16	0.38	-10000	0	-0.69	164	164
DOK2	0.008	0.031	-10000	0	-0.35	4	4
negative regulation of cell cycle	-0.096	0.28	-10000	0	-0.54	124	124
ETS1	-0.031	0.095	-10000	0	-0.22	106	106
PXN	-0.15	0.35	-10000	0	-0.66	165	165
ITGB1	0.011	0	-10000	0	-10000	0	0
NOS3	-0.16	0.37	-10000	0	-0.7	165	165
RAC1	0.011	0	-10000	0	-10000	0	0
TNF	-0.074	0.15	-10000	0	-0.28	162	162
MAPKKK cascade	-0.27	0.5	-10000	0	-0.98	165	165
RASA1	0.007	0.041	-10000	0	-0.41	5	5
Tie2/Ang1/Shc	-0.29	0.55	-10000	0	-1.1	165	165
NCK1	0.009	0.026	-10000	0	-0.41	2	2
vasculogenesis	-0.11	0.3	-10000	0	-0.55	165	165
mol:Phosphatidic acid	-0.27	0.5	-10000	0	-0.98	165	165
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.13	0.33	-10000	0	-0.62	165	165
Rac1/GTP	-0.23	0.35	-10000	0	-0.75	165	165
MMP2	-0.29	0.54	-10000	0	-1	165	165

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.091	0.2	-10000	0	-0.39	113	113
PTK2B	0.011	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.12	0.31	-10000	0	-0.8	78	78
EDN1	-0.002	0.09	-10000	0	-0.39	11	11
EDN3	-0.098	0.17	-10000	0	-0.36	153	153
EDN2	-0.044	0.12	-10000	0	-0.33	84	84
HRAS/GDP	-0.12	0.21	-10000	0	-0.41	136	136
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.085	0.18	-10000	0	-0.36	124	124
ADCY4	-0.11	0.2	-10000	0	-0.4	129	129
ADCY5	-0.14	0.2	-10000	0	-0.4	155	155
ADCY6	-0.11	0.18	-10000	0	-0.37	131	131
ADCY7	-0.11	0.18	-10000	0	-0.41	107	107
ADCY1	-0.12	0.2	-10000	0	-0.39	133	133
ADCY2	-0.22	0.23	-10000	0	-0.46	202	202
ADCY3	-0.11	0.19	-10000	0	-0.38	124	124
ADCY8	-0.11	0.18	-10000	0	-0.38	130	130
ADCY9	-0.13	0.22	-10000	0	-0.42	153	153
arachidonic acid secretion	-0.17	0.28	-10000	0	-0.46	210	210
ETB receptor/Endothelin-1/Gq/GTP	-0.068	0.15	-10000	0	-0.29	131	131
GNAO1	-0.099	0.18	-10000	0	-0.41	138	138
HRAS	0.009	0.004	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.059	0.21	-10000	0	-0.36	113	113
ETA receptor/Endothelin-1/Gs/GTP	-0.089	0.22	-10000	0	-0.4	131	131
mol:GTP	-0.002	0.005	-10000	0	-10000	0	0
COL3A1	-0.099	0.22	-10000	0	-0.54	69	69
EDNRB	-0.085	0.18	-10000	0	-0.41	122	122
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.13	0.26	-10000	0	-0.53	126	126
CYSLTR1	-0.096	0.21	-10000	0	-0.46	88	88
SLC9A1	-0.059	0.11	-10000	0	-0.24	89	89
mol:GDP	-0.13	0.23	-10000	0	-0.44	140	140
SLC9A3	-0.14	0.31	-10000	0	-0.62	131	131
RAF1	-0.16	0.24	-10000	0	-0.42	199	199
JUN	-0.1	0.26	-10000	0	-0.66	75	75
JAK2	-0.095	0.2	-10000	0	-0.4	118	118
mol:IP3	-0.09	0.18	-10000	0	-0.39	95	95
ETA receptor/Endothelin-1	-0.087	0.26	-10000	0	-0.44	129	129
PLCB1	0.006	0.032	-10000	0	-0.41	3	3
PLCB2	0.008	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.16	0.19	-10000	0	-0.33	274	274
FOS	-0.28	0.42	-10000	0	-0.85	176	176
Gai/GDP	-0.18	0.34	-10000	0	-0.73	139	139
CRK	0.011	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.14	0.25	-10000	0	-0.47	151	151
BCAR1	0.011	0	-10000	0	-10000	0	0
PRKCB1	-0.091	0.17	-10000	0	-0.38	101	101
GNAQ	0.007	0.027	-10000	0	-0.41	2	2
GNAZ	-0.001	0.07	-10000	0	-0.41	15	15
GNAL	-0.051	0.15	-10000	0	-0.41	77	77
Gs family/GDP	-0.16	0.2	-10000	0	-0.41	165	165
ETA receptor/Endothelin-1/Gq/GTP	-0.098	0.21	-10000	0	-0.41	124	124
MAPK14	-0.051	0.13	-10000	0	-0.31	75	75
TRPC6	-0.14	0.34	-10000	0	-0.86	78	78
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.052	-10000	0	-0.41	8	8
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.06	0.14	-10000	0	-0.3	93	93
ETB receptor/Endothelin-2	-0.086	0.15	-10000	0	-0.29	180	180
ETB receptor/Endothelin-3	-0.12	0.16	-10000	0	-0.28	246	246
ETB receptor/Endothelin-1	-0.057	0.15	-10000	0	-0.3	129	129
MAPK3	-0.25	0.38	-10000	0	-0.74	183	183
MAPK1	-0.25	0.38	-10000	0	-0.74	183	183
Rac1/GDP	-0.12	0.21	-10000	0	-0.41	136	136
cAMP biosynthetic process	-0.19	0.24	-10000	0	-0.45	203	203
MAPK8	-0.13	0.3	-10000	0	-0.73	83	83
SRC	0.011	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.087	0.17	-10000	0	-0.26	202	202
p130Cas/CRK/Src/PYK2	-0.11	0.23	-10000	0	-0.53	98	98
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.12	0.21	-10000	0	-0.41	136	136
COL1A2	-0.13	0.25	-10000	0	-0.52	120	120
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.13	0.18	-10000	0	-0.32	219	219
mol:DAG	-0.09	0.18	-10000	0	-0.39	95	95
MAP2K2	-0.2	0.3	-10000	0	-0.55	193	193
MAP2K1	-0.2	0.3	-10000	0	-0.55	191	191
EDNRA	-0.13	0.24	-10000	0	-0.47	162	162
positive regulation of muscle contraction	-0.072	0.17	-10000	0	-0.34	106	106
Gq family/GDP	-0.13	0.19	-10000	0	-0.43	113	113
HRAS/GTP	-0.12	0.21	-10000	0	-0.4	141	141
PRKCH	-0.086	0.18	-10000	0	-0.41	83	83
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.098	0.19	-10000	0	-0.42	97	97
PRKCB	-0.097	0.19	-10000	0	-0.41	104	104
PRKCE	-0.084	0.17	-10000	0	-0.39	89	89
PRKCD	-0.086	0.17	-10000	0	-0.39	89	89
PRKCG	-0.11	0.18	-10000	0	-0.38	117	117
regulation of vascular smooth muscle contraction	-0.33	0.5	-10000	0	-1	175	175
PRKCQ	-0.1	0.18	-10000	0	-0.38	122	122
PLA2G4A	-0.19	0.31	-10000	0	-0.51	209	209
GNA14	-0.034	0.13	-10000	0	-0.41	53	53
GNA15	0.004	0.04	-10000	0	-0.34	7	7
GNA12	0.011	0	-10000	0	-10000	0	0
GNA11	0	0.061	-10000	0	-0.41	11	11
Rac1/GTP	-0.059	0.21	-10000	0	-0.36	113	113
MMP1	-0.05	0.15	0.27	8	-10000	0	8

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.12	0.19	-9999	-0.43	145	145
PDGF/PDGFRA/CRKL	-0.07	0.13	-9999	-0.28	145	145
positive regulation of JUN kinase activity	-0.037	0.099	-9999	-0.2	145	145
CRKL	0.011	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.077	0.13	-9999	-0.29	146	146
AP1	-0.29	0.39	-9999	-0.87	159	159
mol:IP3	-0.08	0.14	-9999	-0.3	145	145
PLCG1	-0.08	0.14	-9999	-0.3	145	145
PDGF/PDGFRA/alphaV Integrin	-0.07	0.13	-9999	-0.28	145	145
RAPGEF1	0.011	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
mol:Ca2+	-0.08	0.14	-9999	-0.3	145	145
CAV3	0.002	0.015	-9999	-0.33	1	1
CAV1	-0.063	0.16	-9999	-0.41	93	93
SHC/Grb2/SOS1	-0.036	0.099	-9999	-0.2	145	145
PDGF/PDGFRA/Shf	-0.073	0.14	-9999	-0.29	147	147
FOS	-0.27	0.4	-9999	-0.86	159	159
JUN	-0.025	0.045	-9999	-0.34	7	7
oligodendrocyte development	-0.07	0.13	-9999	-0.28	145	145
GRB2	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.041	-9999	-0.41	5	5
mol:DAG	-0.08	0.14	-9999	-0.3	145	145
PDGF/PDGFRA	-0.12	0.19	-9999	-0.43	145	145
actin cytoskeleton reorganization	-0.07	0.13	-9999	-0.28	145	145
SRF	0.025	0.011	-9999	-10000	0	0
SHC1	0.011	0	-9999	-10000	0	0
PI3K	-0.052	0.11	-9999	-0.23	148	148
PDGF/PDGFRA/Crk/C3G	-0.049	0.11	-9999	-0.23	145	145
JAK1	-0.069	0.14	-9999	-0.29	145	145
ELK1/SRF	-0.042	0.11	-9999	-0.22	145	145
SHB	0.011	0	-9999	-10000	0	0
SHF	0.005	0.048	-9999	-0.41	7	7
CSNK2A1	0.021	0.024	-9999	-10000	0	0
GO:0007205	-0.09	0.16	-9999	-0.34	145	145
SOS1	0.011	0	-9999	-10000	0	0
Ras protein signal transduction	-0.037	0.099	-9999	-0.2	145	145
PDGF/PDGFRA/SHB	-0.07	0.13	-9999	-0.28	145	145
PDGF/PDGFRA/Caveolin-1	-0.12	0.19	-9999	-0.36	186	186
ITGAV	0.011	0	-9999	-10000	0	0
ELK1	-0.081	0.14	-9999	-0.3	145	145
PIK3CA	0.01	0.018	-9999	-0.41	1	1
PDGF/PDGFRA/Crk	-0.07	0.13	-9999	-0.28	145	145
JAK-STAT cascade	-0.069	0.14	-9999	-0.29	145	145
cell proliferation	-0.073	0.14	-9999	-0.29	147	147

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.016	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.17	0.18	-10000	0	-0.31	294	294
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.085	0.15	-10000	0	-0.38	64	64
NGF (dimer)/p75(NTR)/BEX1	-0.16	0.2	-10000	0	-0.33	271	271
NT-4/5 (dimer)/p75(NTR)	-0.094	0.14	-10000	0	-0.28	195	195
IKBKB	0.011	0	-10000	0	-10000	0	0
AKT1	-0.085	0.14	-10000	0	-0.38	64	64
IKBKG	0.011	0	-10000	0	-10000	0	0
BDNF	-0.043	0.12	-10000	0	-0.33	83	83
MGDIs/NGR/p75(NTR)/LINGO1	-0.064	0.12	-10000	0	-0.23	176	176
FURIN	0.011	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.091	0.12	-10000	0	-0.24	175	175
LINGO1	0.006	0.04	-10000	0	-0.34	7	7
Sortilin/TRAF6/NRIF	-0.002	0.017	-10000	0	-10000	0	0
proBDNF (dimer)	-0.043	0.12	-10000	0	-0.33	83	83
NTRK1	0.001	0.059	-10000	0	-0.37	13	13
RTN4R	0.01	0.018	-10000	0	-0.41	1	1
neuron apoptosis	-0.092	0.14	-10000	0	-0.35	69	69
IRAK1	0.011	0	-10000	0	-10000	0	0
SHC1	-0.11	0.17	-10000	0	-0.29	227	227
ARHGDIA	0.011	0	-10000	0	-10000	0	0
RhoA/GTP	0.008	0	-10000	0	-10000	0	0
Gamma Secretase	0.03	0.024	-10000	0	-0.18	7	7
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.15	0.19	-10000	0	-0.29	287	287
MAGEH1	-0.092	0.18	-10000	0	-0.41	129	129
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.2	0.2	-10000	0	-0.32	347	347
Mammalian IAPs/DIABLO	0.024	0.03	-10000	0	-0.2	8	8
proNGF (dimer)	-0.08	0.17	-10000	0	-0.41	114	114
MAGED1	0.009	0.026	-10000	0	-0.41	2	2
APP	0.011	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.006	0.07	-10000	0	-0.33	23	23
ZNF274	0.011	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.089	0.14	-10000	0	-0.24	227	227
NGF	-0.08	0.17	-10000	0	-0.41	114	114
cell cycle arrest	-0.079	0.13	0.14	41	-0.36	62	103
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.09	0.15	-10000	0	-0.25	227	227
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.071	0.12	-10000	0	-0.23	195	195
NCSTN	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.12	0.17	-10000	0	-0.29	231	231
PSENEN	0.011	0	-10000	0	-10000	0	0
mol:ceramide	-0.095	0.15	-10000	0	-0.25	227	227
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.071	0.13	-10000	0	-0.34	62	62
p75(NTR)/beta APP	-0.083	0.14	-10000	0	-0.28	176	176
BEX1	-0.074	0.17	-10000	0	-0.41	107	107
mol:GDP	-0.12	0.17	-10000	0	-0.29	228	228
NGF (dimer)	-0.077	0.14	-10000	0	-0.25	170	170
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.05	0.11	-10000	0	-0.2	176	176
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
RAC1/GTP	-0.095	0.14	-10000	0	-0.25	227	227
MYD88	0.011	0	-10000	0	-10000	0	0
CHUK	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.12	0.17	-10000	0	-0.29	231	231
RHOB	0.009	0.026	-10000	0	-0.41	2	2
RHOA	0.011	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.028	0.092	-10000	0	-0.22	100	100
NT3 (dimer)	-0.017	0.1	-10000	0	-0.4	36	36
TP53	-0.056	0.1	-10000	0	-0.31	11	11
PRDM4	-0.095	0.15	-10000	0	-0.26	227	227
BDNF (dimer)	-0.087	0.14	-10000	0	-0.3	109	109
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
SORT1	0.011	0	-10000	0	-10000	0	0
activation of caspase activity	-0.1	0.13	-10000	0	-0.38	64	64
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.095	0.15	-10000	0	-0.26	227	227
RHOC	0.011	0	-10000	0	-10000	0	0
XIAP	0.011	0	-10000	0	-10000	0	0
MAPK10	-0.13	0.18	-10000	0	-0.4	125	125
DIABLO	0.011	0	-10000	0	-10000	0	0
SMPD2	-0.095	0.15	-10000	0	-0.26	227	227
APH1B	0.005	0.048	-10000	0	-0.41	7	7
APH1A	0.011	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.11	0.17	-10000	0	-0.29	227	227
PSEN1	0.011	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.1	0.16	-10000	0	-0.3	198	198
MAPK8	-0.094	0.15	-10000	0	-0.36	76	76
MAPK9	-0.092	0.15	-10000	0	-0.36	74	74
APAF1	0.011	0	-10000	0	-10000	0	0
NTF3	-0.017	0.1	-10000	0	-0.4	36	36
NTF4	-0.006	0.07	-10000	0	-0.33	23	23
NDN	-0.19	0.21	-10000	0	-0.41	257	257
RAC1/GDP	0.008	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.094	0.12	-10000	0	-0.35	64	64
p75 CTF/Sortilin/TRAF6/NRIF	0.028	0	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.11	0.17	-10000	0	-0.29	231	231
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.064	0.11	-10000	0	-0.34	11	11
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.075	0.11	-10000	0	-0.21	175	175
PRKACB	0.006	0.045	-10000	0	-0.41	6	6
proBDNF (dimer)/p75 ECD	-0.021	0.085	-10000	0	-0.22	83	83
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.003	0.055	-10000	0	-0.39	10	10
BIRC2	0.011	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.19	0.2	0.15	18	-0.36	255	273
BAD	-0.11	0.16	-10000	0	-0.35	118	118
RIPK2	0.011	0	-10000	0	-10000	0	0
NGFR	-0.13	0.2	-10000	0	-0.41	176	176
CYCS	-0.084	0.14	-10000	0	-0.38	62	62
ADAM17	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.095	0.15	-10000	0	-0.26	227	227
BCL2L11	-0.11	0.16	-10000	0	-0.35	118	118
BDNF (dimer)/p75(NTR)	-0.12	0.15	-10000	0	-0.27	248	248
PI3K	-0.097	0.15	-10000	0	-0.26	231	231
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.095	0.15	-10000	0	-0.26	227	227
NDNL2	0.011	0	-10000	0	-10000	0	0
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.14	0.19	-10000	0	-0.35	228	228
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.095	0.15	-10000	0	-0.26	229	229
TRAF6	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.024	-10000	0	-0.37	2	2
PLG	-0.03	0.12	-10000	0	-0.4	50	50
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.12	0.16	-10000	0	-0.3	180	180
SQSTM1	0.011	0	-10000	0	-10000	0	0
NGFRAP1	0.006	0.045	-10000	0	-0.41	6	6
CASP3	-0.1	0.16	-10000	0	-0.33	118	118
E2F1	-0.054	0.13	-10000	0	-0.33	100	100
CASP9	0.011	0	-10000	0	-10000	0	0
IKK complex	-0.094	0.13	-10000	0	-0.3	120	120
NGF (dimer)/TRKA	-0.055	0.13	-10000	0	-0.28	125	125
MMP7	-0.057	0.14	-10000	0	-0.36	96	96
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.083	0.14	-10000	0	-0.38	62	62
MMP3	-0.051	0.13	-10000	0	-0.33	94	94
APAF-1/Caspase 9	-0.072	0.094	-10000	0	-0.28	63	63

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.056	0.18	-10000	0	-0.59	37	37
IHH	-0.13	0.2	-10000	0	-0.39	184	184
SHH Np/Cholesterol/GAS1	-0.15	0.13	-10000	0	-0.23	340	340
LRPAP1	0.011	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.15	0.13	0.23	340	-10000	0	340
SMO/beta Arrestin2	-0.052	0.16	-10000	0	-0.42	27	27
SMO	-0.061	0.16	-10000	0	-0.32	133	133
AKT1	-0.018	0.096	-10000	0	-0.52	5	5
ARRB2	0.011	0	-10000	0	-10000	0	0
BOC	-0.003	0.077	-10000	0	-0.41	18	18
ADRBK1	0.011	0	-10000	0	-10000	0	0
heart looping	-0.06	0.16	-10000	0	-0.32	133	133
STIL	-0.049	0.12	-10000	0	-0.34	32	32
DHH N/PTCH2	-0.023	0.1	-10000	0	-0.3	66	66
DHH N/PTCH1	-0.06	0.14	-10000	0	-0.35	52	52
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
DHH	-0.023	0.11	-10000	0	-0.41	41	41
PTHLH	-0.07	0.21	-10000	0	-0.65	37	37
determination of left/right symmetry	-0.06	0.16	-10000	0	-0.32	133	133
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
skeletal system development	-0.07	0.21	-10000	0	-0.64	37	37
IHH N/Hhip	-0.08	0.13	-10000	0	-0.24	204	204
DHH N/Hhip	-0.024	0.098	-10000	0	-0.26	74	74
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.06	0.16	-10000	0	-0.32	133	133
pancreas development	-0.013	0.088	-10000	0	-0.34	35	35
HHAT	0.008	0.037	-10000	0	-0.41	4	4
PI3K	0.013	0.031	-10000	0	-0.28	6	6
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.26	0.2	-10000	0	-0.41	338	338
somite specification	-0.06	0.16	-10000	0	-0.32	133	133
SHH Np/Cholesterol/PTCH1	-0.052	0.12	-10000	0	-0.36	26	26
SHH Np/Cholesterol/PTCH2	-0.017	0.08	-10000	0	-0.23	33	33
SHH Np/Cholesterol/Megalin	-0.068	0.1	-10000	0	-0.18	232	232
SHH	-0.015	0.082	-10000	0	-0.22	71	71
catabolic process	-0.055	0.14	-10000	0	-0.36	37	37
SMO/Vitamin D3	-0.049	0.14	-10000	0	-0.4	27	27
SHH Np/Cholesterol/Hhip	-0.018	0.075	-10000	0	-0.17	102	102
LRP2	-0.11	0.16	-10000	0	-0.33	188	188
receptor-mediated endocytosis	-0.076	0.14	-10000	0	-0.33	76	76
SHH Np/Cholesterol/BOC	-0.012	0.074	-10000	0	-0.17	86	86
SHH Np/Cholesterol/CDO	-0.03	0.097	-10000	0	-0.24	63	63
mesenchymal cell differentiation	0.018	0.075	0.17	102	-10000	0	102
mol:Vitamin D3	-0.042	0.12	-10000	0	-0.36	26	26
IHH N/PTCH2	-0.079	0.14	-10000	0	-0.28	143	143
CDON	-0.036	0.13	-10000	0	-0.41	59	59
IHH N/PTCH1	-0.035	0.15	-10000	0	-0.36	37	37
Megalin/LRPAP1	-0.068	0.11	-10000	0	-0.22	188	188
PTCH2	-0.012	0.096	-10000	0	-0.41	29	29
SHH Np/Cholesterol	-0.012	0.061	-10000	0	-0.16	71	71
PTCH1	-0.055	0.14	-10000	0	-0.36	37	37
HHIP	-0.013	0.089	-10000	0	-0.34	35	35

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.001	0.07	-9999	-0.28	31	31
alphaV beta3 Integrin	-0.15	0.16	-9999	-0.28	309	309
PTK2	-0.13	0.19	-9999	-0.42	119	119
IGF1R	-0.006	0.082	-9999	-0.41	21	21
PI4KB	0.011	0	-9999	-10000	0	0
MFGE8	0.009	0.026	-9999	-0.41	2	2
SRC	0.011	0	-9999	-10000	0	0
CDKN1B	-0.14	0.21	-9999	-0.58	86	86
VEGFA	0.011	0	-9999	-10000	0	0
ILK	-0.12	0.18	-9999	-0.55	69	69
ROCK1	0.011	0	-9999	-10000	0	0
AKT1	-0.1	0.17	-9999	-0.51	69	69
PTK2B	-0.019	0.1	-9999	-0.38	16	16
alphaV/beta3 Integrin/JAM-A	-0.15	0.16	-9999	-0.36	140	140
CBL	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.027	0.097	-9999	-0.23	97	97
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.045	0.14	-9999	-0.26	134	134
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.038	0.11	-9999	-0.36	29	29
alphaV/beta3 Integrin/Syndecan-1	-0.078	0.12	-9999	-0.21	231	231
PI4KA	0.011	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.18	0.18	-9999	-0.42	151	151
PI4 Kinase	0.016	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
alphaV/beta3 Integrin/Osteopontin	-0.077	0.12	-9999	-0.21	230	230
RPS6KB1	-0.15	0.18	-9999	-0.39	151	151
TLN1	0.011	0	-9999	-10000	0	0
MAPK3	-0.29	0.28	-9999	-0.5	308	308
GPR124	-0.09	0.18	-9999	-0.41	126	126
MAPK1	-0.29	0.28	-9999	-0.5	308	308
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.041	-9999	-0.41	5	5
alphaV/beta3 Integrin/Tumstatin	-0.051	0.12	-9999	-0.26	124	124
cell adhesion	-0.032	0.094	-9999	-0.23	94	94
ANGPTL3	0.004	0.021	-9999	-0.33	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.008	0.059	-9999	-0.23	31	31
IGF-1R heterotetramer	-0.006	0.082	-9999	-0.41	21	21
Rac1/GDP	0.008	0	-9999	-10000	0	0
TGFBR2	0.001	0.065	-9999	-0.41	13	13
ITGB3	-0.065	0.16	-9999	-0.41	96	96
IGF1	-0.069	0.16	-9999	-0.41	100	100
RAC1	0.011	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.081	0.15	-9999	-0.27	183	183
apoptosis	0.011	0	-9999	-10000	0	0
CD47	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.023	0.096	-9999	-0.23	96	96
VCL	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.07	0.15	-9999	-0.28	159	159
CSF1	0.003	0.057	-9999	-0.41	10	10
PIK3C2A	-0.12	0.18	-9999	-0.55	69	69
PI4 Kinase/Pyk2	-0.14	0.14	-9999	-0.35	125	125
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.026	0.11	-9999	-0.23	110	110
FAK1/Vinculin	-0.097	0.15	-9999	-0.34	114	114
alphaV beta3/Integrin/ppsTEM5	-0.081	0.15	-9999	-0.28	183	183
RHOA	0.011	0	-9999	-10000	0	0
VTN	-0.047	0.14	-9999	-0.41	72	72
BCAR1	0.011	0	-9999	-10000	0	0
FGF2	-0.22	0.21	-9999	-0.41	284	284
F11R	-0.14	0.15	-9999	-0.28	285	285
alphaV/beta3 Integrin/Lactadherin	-0.024	0.099	-9999	-0.23	96	96
alphaV/beta3 Integrin/TGFBR2	-0.029	0.11	-9999	-0.25	99	99
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.024	0.031	-9999	-0.2	10	10
HSP90AA1	0.011	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.02	0.087	-9999	-0.2	96	96
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.007	0.041	-9999	-0.41	5	5
alphaV/beta3 Integrin/Pyk2	-0.018	0.1	-9999	-0.38	16	16
SDC1	-0.086	0.15	-9999	-0.33	150	150
VAV3	-0.012	0.074	-9999	-0.34	1	1
PTPN11	0.011	0	-9999	-10000	0	0
IRS1	-0.031	0.13	-9999	-0.41	53	53
FAK1/Paxillin	-0.097	0.15	-9999	-0.34	115	115
cell migration	-0.084	0.14	-9999	-0.31	114	114
ITGAV	0.011	0	-9999	-10000	0	0
PI3K	-0.14	0.14	-9999	-0.36	116	116
SPP1	-0.085	0.15	-9999	-0.33	148	148
KDR	-0.014	0.099	-9999	-0.41	31	31
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.011	0	-9999	-10000	0	0
COL4A3	-0.038	0.13	-9999	-0.39	63	63
angiogenesis	-0.29	0.28	-9999	-0.5	309	309
Rac1/GTP	-0.005	0.068	-9999	-0.3	1	1
EDIL3	-0.071	0.17	-9999	-0.41	102	102
cell proliferation	-0.029	0.11	-9999	-0.25	99	99

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.004	0.079	-10000	0	-0.41	19	19
ANTXR2	-0.13	0.2	-10000	0	-0.41	173	173
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.019	0.028	-10000	0	-0.058	177	177
monocyte activation	-0.029	0.11	-10000	0	-0.41	41	41
MAP2K2	-0.007	0.011	-10000	0	-10000	0	0
MAP2K1	-0.016	0.023	-10000	0	-10000	0	0
MAP2K7	-0.016	0.023	-10000	0	-10000	0	0
MAP2K6	-0.035	0.054	-10000	0	-0.17	66	66
CYAA	-0.064	0.11	-10000	0	-0.21	177	177
MAP2K4	-0.016	0.025	-10000	0	-0.25	1	1
IL1B	-0.011	0.042	-10000	0	-0.16	22	22
Channel	-0.067	0.12	-10000	0	-0.23	177	177
NLRP1	-0.026	0.053	-10000	0	-0.24	25	25
CALM1	0.011	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.021	0.03	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.019	0.028	0.058	177	-10000	0	177
MAPK3	-0.016	0.023	-10000	0	-10000	0	0
MAPK1	-0.016	0.023	-10000	0	-10000	0	0
PGR	-0.078	0.1	-10000	0	-0.23	159	159
PA/Cellular Receptors	-0.075	0.13	-10000	0	-0.25	177	177
apoptosis	-0.019	0.028	-10000	0	-0.058	177	177
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.064	0.11	-10000	0	-0.22	177	177
macrophage activation	-0.003	0.026	-10000	0	-10000	0	0
TNF	-0.032	0.11	-10000	0	-0.33	66	66
VCAM1	-0.029	0.11	-10000	0	-0.41	41	41
platelet activation	-0.021	0.03	-10000	0	-10000	0	0
MAPKKK cascade	0.013	0.031	0.085	31	-10000	0	31
IL18	-0.012	0.042	-10000	0	-0.15	27	27
negative regulation of macrophage activation	-0.019	0.028	-10000	0	-0.058	177	177
LEF	-0.019	0.028	-10000	0	-0.058	177	177
CASP1	-0.021	0.036	-10000	0	-0.12	40	40
mol:cAMP	-0.021	0.03	-10000	0	-10000	0	0
necrosis	-0.019	0.028	-10000	0	-0.058	177	177
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.063	0.11	-10000	0	-0.21	177	177
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.007	0.084	-9999	-0.41	22	22
mol:S1P	-0.009	0.014	-9999	-10000	0	0
S1P1/S1P/Gi	-0.072	0.12	-9999	-0.24	150	150
GNAO1	-0.11	0.19	-9999	-0.42	138	138
S1P/S1P3/G12/G13	0.003	0.046	-9999	-0.22	19	19
AKT1	-0.063	0.16	-9999	-0.55	33	33
AKT3	-0.41	0.55	-9999	-1.1	199	199
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.007	0.084	-9999	-0.41	22	22
GNAI2	0.002	0.014	-9999	-10000	0	0
GNAI3	0.004	0.011	-9999	-10000	0	0
GNAI1	-0.002	0.053	-9999	-0.42	8	8
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.014	0.081	-9999	-0.42	19	19
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.13	0.2	-9999	-0.31	254	254
MAPK3	-0.12	0.19	-9999	-0.32	205	205
MAPK1	-0.12	0.19	-9999	-0.32	205	205
JAK2	-0.12	0.2	-9999	-0.33	205	205
CXCR4	-0.12	0.19	-9999	-0.32	205	205
FLT1	0.003	0.016	-9999	-10000	0	0
RhoA/GDP	0.008	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	-0.12	0.19	-9999	-0.32	205	205
S1P/S1P3/Gi	-0.13	0.2	-9999	-0.31	254	254
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.12	0.18	-9999	-0.31	205	205
VEGFA	0.003	0.016	-9999	-10000	0	0
S1P/S1P2/Gi	-0.084	0.14	-9999	-0.27	150	150
VEGFR1 homodimer/VEGFA homodimer	-0.001	0.031	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.021	0.1	-9999	-0.26	72	72
GNAQ	0.009	0.026	-9999	-0.41	2	2
GNAZ	-0.008	0.07	-9999	-0.41	15	15
G12/G13	0.016	0	-9999	-10000	0	0
GNA14	-0.031	0.13	-9999	-0.41	53	53
GNA15	0.006	0.039	-9999	-0.33	7	7
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
GNA11	0.002	0.06	-9999	-0.41	11	11
Rac1/GTP	-0.12	0.18	-9999	-0.31	205	205

×

Nongenotropic Androgen signaling

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
PTK2	0.009	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.023	0.09	-10000	0	-0.21	98	98
regulation of S phase of mitotic cell cycle	-0.018	0.088	-10000	0	-0.2	93	93
GNAO1	-0.1	0.18	-10000	0	-0.41	138	138
HRAS	0.01	0.002	-10000	0	-10000	0	0
SHBG/T-DHT	0.005	0.024	-10000	0	-0.24	5	5
PELP1	0.01	0.002	-10000	0	-10000	0	0
AKT1	0.009	0.001	-10000	0	-10000	0	0
MAP2K1	-0.031	0.092	-10000	0	-0.27	31	31
T-DHT/AR	-0.044	0.11	-10000	0	-0.29	90	90
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.007	159	159
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.004	0.051	-10000	0	-0.41	8	8
mol:GDP	-0.059	0.14	-10000	0	-0.35	91	91
cell proliferation	-0.1	0.2	-10000	0	-0.38	159	159
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
FOS	-0.21	0.37	-10000	0	-0.77	159	159
mol:Ca2+	-0.024	0.03	-10000	0	-0.061	168	168
MAPK3	-0.069	0.14	-10000	0	-0.26	159	159
MAPK1	-0.049	0.1	-10000	0	-0.2	159	159
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
mol:IP3	-0.001	0.002	-10000	0	-0.004	159	159
cAMP biosynthetic process	0.008	0.031	0.094	5	-0.2	5	10
GNG2	0.003	0.056	-10000	0	-0.4	10	10
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	159	159
HRAS/GTP	-0.041	0.072	-10000	0	-0.19	90	90
actin cytoskeleton reorganization	-0.002	0.019	-10000	0	-0.18	6	6
SRC	0.01	0.002	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	159	159
PI3K	0.012	0.026	-10000	0	-0.23	6	6
apoptosis	0.1	0.2	0.4	159	-10000	0	159
T-DHT/AR/PELP1	-0.031	0.095	-10000	0	-0.24	90	90
HRAS/GDP	-0.056	0.13	-10000	0	-0.33	90	90
CREB1	-0.11	0.21	-10000	0	-0.43	159	159
RAC1-CDC42/GTP	-0.002	0.019	-10000	0	-0.18	6	6
AR	-0.062	0.16	-10000	0	-0.41	90	90
GNB1	0.011	0	-10000	0	-10000	0	0
RAF1	-0.028	0.085	-10000	0	-0.25	31	31
RAC1-CDC42/GDP	-0.049	0.12	-10000	0	-0.31	90	90
T-DHT/AR/PELP1/Src	-0.024	0.086	-10000	0	-0.21	90	90
MAP2K2	-0.031	0.092	-10000	0	-0.27	31	31
T-DHT/AR/PELP1/Src/PI3K	-0.018	0.089	-10000	0	-0.21	93	93
GNAZ	-0.001	0.07	-10000	0	-0.41	15	15
SHBG	0.007	0.041	-10000	0	-0.41	5	5
Gi family/GNB1/GNG2/GDP	-0.072	0.16	-10000	0	-0.32	141	141
mol:T-DHT	-0.001	0.001	-10000	0	-0.003	128	128
RAC1	0.011	0	-10000	0	-10000	0	0
GNRH1	0.005	0.032	-10000	0	-0.29	6	6
Gi family/GTP	-0.058	0.12	-10000	0	-0.21	150	150
CDC42	0.011	0	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.009	0.032	-9999	-0.41	3	3
LAT2	-0.065	0.13	-9999	-0.23	163	163
AP1	-0.12	0.14	-9999	-0.35	99	99
mol:PIP3	-0.066	0.15	-9999	-0.26	165	165
IKBKB	-0.035	0.097	-9999	-0.22	50	50
AKT1	-0.03	0.1	-9999	-0.28	37	37
IKBKG	-0.035	0.097	-9999	-0.22	50	50
MS4A2	-0.12	0.19	-9999	-0.4	162	162
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
MAP3K1	-0.041	0.12	-9999	-0.31	34	34
mol:Ca2+	-0.049	0.12	-9999	-0.2	165	165
LYN	0.01	0.003	-9999	-10000	0	0
CBLB	-0.064	0.12	-9999	-0.23	163	163
SHC1	0.011	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.036	0.1	-9999	-0.21	130	130
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.01	0.018	-9999	-0.41	1	1
PLD2	-0.056	0.11	-9999	-0.24	84	84
PTPN13	-0.09	0.15	-9999	-0.38	62	62
PTPN11	0.01	0.005	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.029	0.11	-9999	-0.26	37	37
SYK	0.01	0.015	-9999	-0.33	1	1
GRB2	0.011	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.097	0.13	-9999	-0.26	165	165
LAT	-0.064	0.12	-9999	-0.23	163	163
PAK2	-0.051	0.13	-9999	-0.34	34	34
NFATC2	-0.081	0.16	-9999	-0.52	54	54
HRAS	-0.061	0.14	-9999	-0.24	162	162
GAB2	0.008	0.037	-9999	-0.41	4	4
PLA2G1B	0.028	0.015	-9999	-10000	0	0
Fc epsilon R1	-0.1	0.13	-9999	-0.25	215	215
Antigen/IgE/Fc epsilon R1	-0.089	0.12	-9999	-0.22	215	215
mol:GDP	-0.069	0.14	-9999	-0.25	163	163
JUN	0.005	0.048	-9999	-0.41	7	7
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.006	0.041	-9999	-0.41	5	5
FOS	-0.12	0.19	-9999	-0.41	159	159
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.074	0.13	-9999	-0.24	165	165
CHUK	-0.035	0.097	-9999	-0.22	50	50
KLRG1	-0.055	0.11	-9999	-0.32	35	35
VAV1	-0.066	0.13	-9999	-0.23	164	164
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.064	0.12	-9999	-0.23	163	163
negative regulation of mast cell degranulation	-0.046	0.1	-9999	-0.3	33	33
BTK	-0.074	0.14	-9999	-0.26	163	163
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.075	0.15	-9999	-0.29	100	100
GAB2/PI3K/SHP2	-0.063	0.088	-9999	-0.31	37	37
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.063	0.12	-9999	-0.26	86	86
RAF1	0.019	0.018	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.08	0.11	-9999	-0.26	87	87
FCER1G	0.016	0.024	-9999	-0.34	2	2
FCER1A	-0.059	0.16	-9999	-0.42	84	84
Antigen/IgE/Fc epsilon R1/Fyn	-0.08	0.11	-9999	-0.26	84	84
MAPK3	0.027	0.015	-9999	-10000	0	0
MAPK1	0.027	0.015	-9999	-10000	0	0
NFKB1	0.01	0.018	-9999	-0.41	1	1
MAPK8	-0.01	0.075	-9999	-0.56	6	6
DUSP1	-0.092	0.18	-9999	-0.41	129	129
NF-kappa-B/RelA	-0.036	0.046	-9999	-0.18	6	6
actin cytoskeleton reorganization	-0.075	0.14	-9999	-0.4	32	32
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.08	0.11	-9999	-0.34	37	37
FER	-0.064	0.12	-9999	-0.23	163	163
RELA	0.011	0	-9999	-10000	0	0
ITK	-0.032	0.062	-9999	-0.36	14	14
SOS1	0.011	0	-9999	-10000	0	0
PLCG1	-0.066	0.14	-9999	-0.25	165	165
cytokine secretion	-0.027	0.034	-9999	-10000	0	0
SPHK1	-0.065	0.13	-9999	-0.23	163	163
PTK2	-0.078	0.15	-9999	-0.41	32	32
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.1	0.13	-9999	-0.27	165	165
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.063	0.15	-9999	-0.25	165	165
MAP2K2	0.023	0.015	-9999	-10000	0	0
MAP2K1	0.023	0.015	-9999	-10000	0	0
MAP2K7	0.011	0	-9999	-10000	0	0
KLRG1/SHP2	-0.057	0.086	-9999	-0.29	33	33
MAP2K4	0.012	0.038	-9999	-0.84	1	1
Fc epsilon R1/FcgammaRIIB	-0.089	0.12	-9999	-0.22	214	214
mol:Choline	-0.056	0.11	-9999	-0.24	84	84
SHC/Grb2/SOS1	-0.068	0.11	-9999	-0.33	32	32
FYN	0.011	0	-9999	-10000	0	0
DOK1	0.011	0	-9999	-10000	0	0
PXN	-0.068	0.14	-9999	-0.38	32	32
HCLS1	-0.064	0.13	-9999	-0.23	164	164
PRKCB	-0.056	0.13	-9999	-0.29	62	62
FCGR2B	0.008	0.035	-9999	-0.39	4	4
IGHE	-0.001	0.004	-9999	-10000	0	0
KLRG1/SHIP	-0.047	0.11	-9999	-0.31	33	33
LCP2	0.01	0.015	-9999	-0.33	1	1
PLA2G4A	-0.075	0.14	-9999	-0.24	173	173
RASA1	0.007	0.041	-9999	-0.41	5	5
mol:Phosphatidic acid	-0.056	0.11	-9999	-0.24	84	84
IKK complex	-0.016	0.078	-9999	-0.16	49	49
WIPF1	0.009	0.026	-9999	-0.41	2	2

×

Wnt 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
Noncanonical Wnts/FZD	-0.063	0.15	-9999	-0.25	158	158
FZD6	0.01	0.018	-9999	-0.41	1	1
WNT6	-0.031	0.12	-9999	-0.38	57	57
WNT4	-0.089	0.18	-9999	-0.41	125	125
FZD3	0.011	0	-9999	-10000	0	0
WNT5A	-0.003	0.074	-9999	-0.41	17	17
WNT11	-0.03	0.12	-9999	-0.35	60	60

×

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	0.044	0.028	0.068	148	-10000	0	148
BUB1B	-0.061	0.051	-10000	0	-0.13	70	70
PLK1	-0.013	0.023	-10000	0	-10000	0	0
PLK1S1	-0.003	0.017	-10000	0	-0.26	1	1
KIF2A	-0.005	0.02	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	-0.013	0.023	-10000	0	-10000	0	0
GOLGA2	0.011	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.11	0.1	-10000	0	-0.18	334	334
WEE1	-0.008	0.023	-10000	0	-10000	0	0
cytokinesis	-0.079	0.042	-10000	0	-0.22	13	13
PP2A-alpha B56	0.037	0.005	-10000	0	-10000	0	0
AURKA	-0.005	0.014	-10000	0	-10000	0	0
PICH/PLK1	-0.079	0.11	-10000	0	-0.2	204	204
CENPE	-0.055	0.089	-10000	0	-0.19	156	156
RhoA/GTP	0.008	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.005	0.02	-10000	0	-10000	0	0
PPP2CA	0.011	0	-10000	0	-10000	0	0
FZR1	0.011	0	-10000	0	-10000	0	0
TPX2	-0.016	0.015	-10000	0	-10000	0	0
PAK1	0.01	0.001	-10000	0	-10000	0	0
SPC24	-0.2	0.17	-10000	0	-0.33	324	324
FBXW11	0.011	0	-10000	0	-10000	0	0
CLSPN	-0.014	0.019	-10000	0	-10000	0	0
GORASP1	0.011	0	-10000	0	-10000	0	0
metaphase	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.008	0.013	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	-0.001	0.002	-10000	0	-10000	0	0
STAG2	0.011	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.012	0.007	-10000	0	-10000	0	0
spindle elongation	-0.013	0.023	-10000	0	-10000	0	0
ODF2	0.01	0.001	-10000	0	-10000	0	0
BUB1	0.023	0.011	-10000	0	-10000	0	0
TPT1	-0.003	0.013	-10000	0	-10000	0	0
CDC25C	-0.018	0.014	-10000	0	-10000	0	0
CDC25B	0.01	0.001	-10000	0	-10000	0	0
SGOL1	-0.044	0.028	-10000	0	-0.068	148	148
RHOA	0.011	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.018	0.048	-10000	0	-10000	0	0
CDC14B	0.008	0.013	-10000	0	-0.3	1	1
CDC20	-0.29	0.11	-10000	0	-0.33	467	467
PLK1/PBIP1	-0.016	0.045	-10000	0	-0.18	32	32
mitosis	-0.004	0.007	-10000	0	-0.015	151	151
FBXO5	-0.005	0.02	-10000	0	-10000	0	0
CDC2	-0.001	0.002	-10000	0	-10000	0	0
NDC80	-0.013	0.087	-10000	0	-0.33	37	37
metaphase plate congression	-0.006	0.015	-10000	0	-10000	0	0
ERCC6L	-0.069	0.1	-10000	0	-0.21	128	128
NLP/gamma Tubulin	-0.005	0.012	-10000	0	-10000	0	0
microtubule cytoskeleton organization	-0.003	0.013	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-10000	0	-10000	0	0
PPP1R12A	0.01	0.018	-10000	0	-0.41	1	1
interphase	-0.001	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.15	0.068	-10000	0	-0.17	477	477
GRASP65/GM130/RAB1/GTP/PLK1	0.008	0.018	-10000	0	-10000	0	0
RAB1A	0.011	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.006	0.022	-10000	0	-10000	0	0
mitotic prometaphase	-0.002	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.013	0.018	-10000	0	-0.19	1	1
microtubule-based process	-0.16	0.059	-10000	0	-0.18	477	477
Golgi organization	-0.013	0.023	-10000	0	-10000	0	0
Cohesin/SA2	-0.013	0.014	-10000	0	-10000	0	0
PPP1CB/MYPT1	0.015	0.013	-10000	0	-0.28	1	1
KIF20A	-0.3	0.1	-10000	0	-0.33	477	477
APC/C/CDC20	-0.16	0.065	-10000	0	-0.18	467	467
PPP2R1A	0.011	0	-10000	0	-10000	0	0
chromosome segregation	-0.019	0.042	-10000	0	-0.18	32	32
PRC1	-0.003	0.068	-10000	0	-0.33	22	22
ECT2	-0.016	0.05	-10000	0	-0.19	33	33
C13orf34	-0.005	0.02	-10000	0	-10000	0	0
NUDC	-0.006	0.015	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.06	0.05	-10000	0	-0.13	70	70
spindle assembly	-0.008	0.018	-10000	0	-10000	0	0
spindle stabilization	-0.003	0.017	-10000	0	-0.26	1	1
APC/C/HCDH1	0.014	0.011	-10000	0	-0.24	1	1
MKLP2/PLK1	-0.16	0.06	-10000	0	-0.18	477	477
CCNB1	-0.048	0.13	-10000	0	-0.33	91	91
PPP1CB	0.011	0.001	-10000	0	-10000	0	0
BTRC	0.011	0	-10000	0	-10000	0	0
ROCK2	-0.009	0.064	-10000	0	-0.4	13	13
TUBG1	-0.003	0.013	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.026	0.043	-10000	0	-10000	0	0
MLF1IP	-0.011	0.056	-10000	0	-0.23	32	32
INCENP	0.01	0.001	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.08	0.31	-9999	-0.95	58	58
MKNK1	0.011	0	-9999	-10000	0	0
MAPK14	-0.014	0.097	-9999	-0.27	65	65
ATF2/c-Jun	-0.004	0.11	-9999	-0.51	10	10
MAPK11	-0.015	0.1	-9999	-0.27	67	67
MITF	-0.041	0.16	-9999	-0.34	107	107
MAPKAPK5	-0.01	0.12	-9999	-0.32	67	67
KRT8	-0.026	0.13	-9999	-0.34	69	69
MAPKAPK3	0.011	0	-9999	-10000	0	0
MAPKAPK2	0.011	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.021	0.14	-9999	-0.39	67	67
CEBPB	-0.01	0.12	-9999	-0.32	67	67
SLC9A1	-0.01	0.12	-9999	-0.32	67	67
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.008	0.12	-9999	-0.31	70	70
p38alpha-beta/MNK1	-0.006	0.11	-9999	-0.3	65	65
JUN	-0.004	0.1	-9999	-0.5	10	10
PPARGC1A	-0.072	0.18	-9999	-0.32	156	156
USF1	-0.01	0.12	-9999	-0.32	67	67
RAB5/GDP/GDI1	-0.029	0.074	-9999	-0.22	65	65
NOS2	-0.019	0.16	-9999	-0.78	11	11
DDIT3	-0.01	0.12	-9999	-0.32	67	67
RAB5A	0.011	0	-9999	-10000	0	0
HSPB1	-0.001	0.097	-9999	-0.25	65	65
p38alpha-beta/HBP1	-0.006	0.11	-9999	-0.3	65	65
CREB1	-0.011	0.13	-9999	-0.34	67	67
RAB5/GDP	0.008	0	-9999	-10000	0	0
EIF4E	-0.001	0.099	-9999	-0.26	65	65
RPS6KA4	-0.01	0.12	-9999	-0.32	67	67
PLA2G4A	-0.013	0.12	-9999	-0.3	68	68
GDI1	-0.01	0.12	-9999	-0.32	67	67
TP53	-0.017	0.14	-9999	-0.39	67	67
RPS6KA5	-0.013	0.12	-9999	-0.32	72	72
ESR1	-0.045	0.17	-9999	-0.35	111	111
HBP1	0.011	0	-9999	-10000	0	0
MEF2C	-0.04	0.16	-9999	-0.34	106	106
MEF2A	-0.014	0.13	-9999	-0.33	72	72
EIF4EBP1	-0.011	0.13	-9999	-0.34	67	67
KRT19	-0.014	0.12	-9999	-0.32	71	71
ELK4	-0.01	0.12	-9999	-0.32	67	67
ATF6	-0.01	0.12	-9999	-0.32	67	67
ATF1	-0.011	0.13	-9999	-0.34	67	67
p38alpha-beta/MAPKAPK2	-0.006	0.11	-9999	-0.3	65	65
p38alpha-beta/MAPKAPK3	-0.006	0.11	-9999	-0.3	65	65

×

Effects of Botulinum toxin

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
STX1A	0.009	0.01	-9999	-0.23	1	1
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.011	0.023	-9999	-0.22	5	5
STXBP1	-0.017	0.1	-9999	-0.41	35	35
ACh/CHRNA1	-0.099	0.1	-9999	-0.23	189	189
RAB3GAP2/RIMS1/UNC13B	0.018	0.019	-9999	-0.17	5	5
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	0.003	0.033	-9999	-0.33	5	5
mol:ACh	-0.044	0.056	-9999	-0.1	242	242
RAB3GAP2	0.011	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.063	0.075	-9999	-0.28	28	28
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.098	0.1	-9999	-0.23	189	189
UNC13B	0.011	0	-9999	-10000	0	0
CHRNA1	-0.11	0.16	-9999	-0.33	189	189
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.082	0.12	-9999	-0.3	117	117
SNAP25	-0.11	0.13	-9999	-0.25	242	242
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.083	0.18	-9999	-0.41	117	117
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.002	0.063	-9999	-0.23	36	36
STX1A/SNAP25 fragment 1/VAMP2	-0.063	0.075	-9999	-0.28	28	28

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.11	0.12	-9999	-0.23	284	284
fibroblast growth factor receptor signaling pathway	-0.11	0.12	-9999	-0.23	284	284
LAMA1	-0.1	0.16	-9999	-0.33	175	175
PRNP	-0.047	0.15	-9999	-0.41	73	73
GPC1/SLIT2	-0.023	0.1	-9999	-0.28	69	69
SMAD2	0.021	0.035	-9999	-0.2	13	13
GPC1/PrPc/Cu2+	-0.02	0.086	-9999	-0.23	73	73
GPC1/Laminin alpha1	-0.062	0.11	-9999	-0.22	175	175
TDGF1	-0.02	0.11	-9999	-0.38	42	42
CRIPTO/GPC1	-0.005	0.074	-9999	-0.26	42	42
APP/GPC1	0.016	0	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
YES1	0.004	0.062	-9999	-0.2	42	42
FLT1	0.011	0	-9999	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.016	0.039	-9999	-0.23	13	13
SERPINC1	0.004	0.039	-9999	-0.33	7	7
FYN	0.004	0.062	-9999	-0.2	42	42
FGR	-0.001	0.073	-9999	-0.22	51	51
positive regulation of MAPKKK cascade	0.014	0.074	-9999	-0.27	26	26
SLIT2	-0.044	0.14	-9999	-0.41	69	69
GPC1/NRG	0.005	0.055	-9999	-0.28	19	19
NRG1	-0.005	0.078	-9999	-0.41	19	19
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.022	0	-9999	-10000	0	0
LYN	0.004	0.062	-9999	-0.2	42	42
mol:Spermine	0.009	0	-9999	-10000	0	0
cell growth	-0.11	0.12	-9999	-0.23	284	284
BMP signaling pathway	-0.011	0	-9999	-10000	0	0
SRC	0.004	0.062	-9999	-0.2	42	42
TGFBR1	0.011	0	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	-0.031	0.12	-9999	-0.39	51	51
GPC1	0.011	0	-9999	-10000	0	0
TGFBR1 (dimer)	0.011	0	-9999	-10000	0	0
VEGFA	0.011	0	-9999	-10000	0	0
BLK	-0.011	0.078	-9999	-0.2	77	77
HCK	0.001	0.065	-9999	-0.2	49	49
FGF2	-0.22	0.21	-9999	-0.41	284	284
FGFR1	0.01	0.018	-9999	-0.41	1	1
VEGFR1 homodimer	0.011	0	-9999	-10000	0	0
TGFBR2	0.001	0.065	-9999	-0.41	13	13
cell death	0.016	0	-9999	-10000	0	0
ATIII/GPC1	0.012	0.027	-9999	-0.22	7	7
PLA2G2A/GPC1	-0.013	0.084	-9999	-0.27	51	51
LCK	0.002	0.066	-9999	-0.21	46	46
neuron differentiation	0.005	0.055	-9999	-0.28	19	19
PrPc/Cu2+	-0.033	0.1	-9999	-0.29	73	73
APP	0.011	0	-9999	-10000	0	0
TGFBR2 (dimer)	0.001	0.065	-9999	-0.41	13	13

×

Reelin signaling 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
CDK5R1/CDK5	0.016	0.01	-9999	-0.22	1	1
VLDLR	0.009	0.026	-9999	-0.41	2	2
CRKL	0.011	0	-9999	-10000	0	0
LRPAP1	0.011	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
ITGA3	0.01	0.018	-9999	-0.41	1	1
RELN/VLDLR/Fyn	-0.069	0.12	-9999	-0.23	192	192
MAPK8IP1/MKK7/MAP3K11/JNK1	0.03	0.024	-9999	-10000	0	0
AKT1	-0.051	0.1	-9999	-0.18	192	192
MAP2K7	0.011	0	-9999	-10000	0	0
RAPGEF1	0.011	0	-9999	-10000	0	0
DAB1	-0.001	0.053	-9999	-0.33	13	13
RELN/LRP8/DAB1	-0.069	0.11	-9999	-0.2	205	205
LRPAP1/LRP8	0.014	0.023	-9999	-0.22	5	5
RELN/LRP8/DAB1/Fyn	-0.058	0.1	-9999	-0.19	187	187
DAB1/alpha3/beta1 Integrin	-0.062	0.08	-9999	-0.33	5	5
long-term memory	-0.13	0.15	-9999	-0.36	103	103
DAB1/LIS1	-0.065	0.083	-9999	-0.31	5	5
DAB1/CRLK/C3G	-0.061	0.078	-9999	-0.3	5	5
PIK3CA	0.01	0.018	-9999	-0.41	1	1
DAB1/NCK2	-0.066	0.084	-9999	-0.31	5	5
ARHGEF2	0.011	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.16	0.2	-9999	-0.41	207	207
CDK5R1	0.01	0.015	-9999	-0.33	1	1
RELN	-0.14	0.2	-9999	-0.41	191	191
PIK3R1	0.007	0.041	-9999	-0.41	5	5
RELN/LRP8/Fyn	-0.07	0.12	-9999	-0.23	193	193
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.13	0.15	-9999	-0.38	96	96
MAPK8	0.007	0.041	-9999	-0.41	5	5
RELN/VLDLR/DAB1	-0.068	0.11	-9999	-0.2	204	204
ITGB1	0.011	0	-9999	-10000	0	0
MAP1B	-0.068	0.12	-9999	-0.2	197	197
RELN/LRP8	-0.07	0.12	-9999	-0.23	193	193
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.061	0.11	-9999	-0.22	53	53
PI3K	0.013	0.031	-9999	-0.28	6	6
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.016	0.013	-9999	-0.28	1	1
RAP1A	-0.031	0.092	-9999	-0.28	5	5
PAFAH1B1	0.011	0	-9999	-10000	0	0
MAPK8IP1	0.01	0.024	-9999	-0.37	2	2
CRLK/C3G	0.016	0	-9999	-10000	0	0
GRIN2B	-0.008	0.066	-9999	-0.33	21	21
NCK2	0.011	0	-9999	-10000	0	0
neuron differentiation	-0.03	0.083	-9999	-0.25	3	3
neuron adhesion	-0.02	0.091	-9999	-0.29	5	5
LRP8	0.008	0.033	-9999	-0.33	5	5
GSK3B	-0.043	0.096	-9999	-0.36	1	1
RELN/VLDLR/DAB1/Fyn	-0.058	0.1	-9999	-0.19	187	187
MAP3K11	0.011	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.061	0.11	-9999	-0.2	192	192
CDK5	0.011	0	-9999	-10000	0	0
MAPT	0.002	0.077	-9999	-0.37	20	20
neuron migration	-0.05	0.13	-9999	-0.23	76	76
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.03	0.083	-9999	-0.25	3	3
RELN/VLDLR	-0.056	0.11	-9999	-0.2	187	187

×

IGF1 pathway

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
NCK2	0.011	0	-10000	0	-10000	0	0
PTK2	0.011	0	-10000	0	-10000	0	0
CRKL	-0.042	0.12	-10000	0	-0.25	110	110
GRB2/SOS1/SHC	0.022	0	-10000	0	-10000	0	0
HRAS	0.011	0	-10000	0	-10000	0	0
IRS1/Crk	-0.042	0.12	-10000	0	-0.26	110	110
IGF-1R heterotetramer/IGF1/PTP1B	-0.036	0.12	-10000	0	-0.25	110	110
AKT1	-0.022	0.11	-10000	0	-0.32	38	38
BAD	-0.015	0.1	-10000	0	-0.3	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.042	0.12	-10000	0	-0.25	110	110
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.042	0.12	-10000	0	-0.26	110	110
RAF1	-0.01	0.1	-10000	0	-0.28	38	38
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.033	0.12	-10000	0	-0.24	110	110
YWHAZ	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.053	0.13	-10000	0	-0.28	110	110
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
RPS6KB1	-0.022	0.11	-10000	0	-0.32	38	38
GNB2L1	0.011	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.01	0.088	-10000	0	-0.25	38	38
PXN	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
HRAS/GTP	-0.047	0.092	-10000	0	-0.32	37	37
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.013	0.092	-10000	0	-0.24	37	37
IGF-1R heterotetramer	-0.02	0.094	-10000	0	-0.46	21	21
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.041	0.12	-10000	0	-0.26	110	110
Crk/p130 Cas/Paxillin	-0.026	0.11	-10000	0	-0.34	37	37
IGF1R	-0.02	0.094	-10000	0	-0.47	21	21
IGF1	-0.077	0.18	-10000	0	-0.44	100	100
IRS2/Crk	-0.061	0.14	-10000	0	-0.25	161	161
PI3K	-0.035	0.12	-10000	0	-0.24	113	113
apoptosis	0.007	0.092	0.26	38	-10000	0	38
HRAS/GDP	0.008	0	-10000	0	-10000	0	0
PRKCD	-0.048	0.16	-10000	0	-0.34	110	110
RAF1/14-3-3 E	-0.002	0.09	-10000	0	-0.25	38	38
BAD/14-3-3	-0.008	0.097	-10000	0	-0.28	38	38
PRKCZ	-0.022	0.11	-10000	0	-0.32	38	38
Crk/p130 Cas/Paxillin/FAK1	-0.038	0.078	-10000	0	-0.27	38	38
PTPN1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.056	0.16	-10000	0	-0.36	110	110
BCAR1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.023	0.1	-10000	0	-0.21	111	111
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.011	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.042	0.12	-10000	0	-0.25	110	110
GRB10	0.01	0.018	-10000	0	-0.41	1	1
PTPN11	-0.042	0.12	-10000	0	-0.25	110	110
IRS1	-0.047	0.13	-10000	0	-0.28	110	110
IRS2	-0.07	0.15	-10000	0	-0.27	161	161
IGF-1R heterotetramer/IGF1	-0.061	0.15	-10000	0	-0.34	110	110
GRB2	0.011	0	-10000	0	-10000	0	0
PDPK1	-0.029	0.11	-10000	0	-0.34	38	38
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKD1	-0.061	0.17	-10000	0	-0.36	114	114
SHC1	0.011	0	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.012	0.043	-9999	-10000	0	0
BIRC5	-0.25	0.14	-9999	-0.33	410	410
NFKBIA	-0.013	0.042	-9999	-10000	0	0
CPEB1	-0.17	0.21	-9999	-0.41	229	229
AKT1	-0.013	0.042	-9999	-10000	0	0
NDEL1	0.011	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.011	0.038	-9999	-10000	0	0
NDEL1/TACC3	-0.04	0.09	-9999	-0.22	82	82
GADD45A	0.011	0	-9999	-10000	0	0
GSK3B	0.007	0.001	-9999	-10000	0	0
PAK1/Aurora A	-0.012	0.043	-9999	-10000	0	0
MDM2	0.011	0	-9999	-10000	0	0
JUB	0.011	0	-9999	-10000	0	0
TPX2	-0.17	0.093	-9999	-0.22	427	427
TP53	0	0.029	-9999	-0.28	1	1
DLG7	-0.02	0.042	-9999	-10000	0	0
AURKAIP1	0.011	0	-9999	-10000	0	0
ARHGEF7	0.011	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.043	0.096	-9999	-0.23	82	82
G2/M transition of mitotic cell cycle	-0.011	0.038	-9999	-10000	0	0
AURKA	-0.024	0.053	-9999	-10000	0	0
AURKB	-0.014	0.013	-9999	-10000	0	0
CDC25B	-0.005	0.032	-9999	-10000	0	0
G2/M transition checkpoint	-0.011	0.038	-9999	-10000	0	0
mRNA polyadenylation	-0.11	0.12	-9999	-0.23	229	229
Aurora A/CPEB	-0.11	0.12	-9999	-0.23	229	229
Aurora A/TACC1/TRAP/chTOG	-0.034	0.091	-9999	-0.22	79	79
BRCA1	0.011	0	-9999	-10000	0	0
centrosome duplication	-0.012	0.043	-9999	-10000	0	0
regulation of centrosome cycle	-0.04	0.089	-9999	-0.22	82	82
spindle assembly	-0.035	0.09	-9999	-0.22	79	79
TDRD7	0.011	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.12	0.086	-9999	-0.21	160	160
CENPA	-0.003	0.016	-9999	-10000	0	0
Aurora A/PP2A	-0.012	0.043	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.003	0.028	-9999	-10000	0	0
negative regulation of DNA binding	0	0.029	-9999	-0.28	1	1
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.016	0	-9999	-10000	0	0
RASA1	0.007	0.041	-9999	-0.41	5	5
Ajuba/Aurora A	-0.011	0.038	-9999	-10000	0	0
mitotic prometaphase	-0.02	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.024	0.053	-9999	-10000	0	0
TACC1	-0.066	0.16	-9999	-0.41	96	96
TACC3	-0.068	0.14	-9999	-0.33	122	122
Aurora A/Antizyme1	-0.003	0.038	-9999	-10000	0	0
Aurora A/RasGAP	-0.014	0.048	-9999	-0.24	5	5
OAZ1	0.011	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.007	0.001	-9999	-10000	0	0
GIT1	0.011	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.022	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.17	0.092	-9999	-0.22	427	427
PPP2R5D	0.011	0	-9999	-10000	0	0
Aurora A/TPX2	-0.15	0.088	-9999	-0.23	155	155
PAK1	0.011	0	-9999	-10000	0	0
CKAP5	0.011	0	-9999	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor 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
CRKL	0.011	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.054	0.09	-10000	0	-0.25	37	37
NT3 (dimer)/TRKC	-0.14	0.17	-10000	0	-0.3	260	260
NT3 (dimer)/TRKB	-0.11	0.16	-10000	0	-0.28	218	218
SHC/Grb2/SOS1/GAB1/PI3K	0.026	0.03	-10000	0	-0.19	10	10
RAPGEF1	0.011	0	-10000	0	-10000	0	0
BDNF	-0.043	0.12	-10000	0	-0.33	83	83
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
DYNLT1	0.011	0	-10000	0	-10000	0	0
NTRK1	0.001	0.059	-10000	0	-0.37	13	13
NTRK2	-0.041	0.14	-10000	0	-0.4	67	67
NTRK3	-0.19	0.21	-10000	0	-0.41	249	249
NT-4/5 (dimer)/TRKB	-0.1	0.15	-10000	0	-0.27	206	206
neuron apoptosis	0.14	0.19	0.4	145	-10000	0	145
SHC 2-3/Grb2	-0.15	0.21	-10000	0	-0.44	144	144
SHC1	0.011	0	-10000	0	-10000	0	0
SHC2	-0.18	0.24	0.17	1	-0.52	147	148
SHC3	-0.12	0.16	0.17	1	-0.4	95	96
STAT3 (dimer)	0.017	0.009	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.083	0.14	-10000	0	-0.25	195	195
RIN/GDP	-0.044	0.08	-10000	0	-0.2	26	26
GIPC1	0.011	0	-10000	0	-10000	0	0
KRAS	0.01	0.015	-10000	0	-0.33	1	1
DNAJA3	-0.13	0.16	0.2	2	-0.29	230	232
RIN/GTP	0.002	0.003	-10000	0	-10000	0	0
CCND1	0.024	0.015	-10000	0	-10000	0	0
MAGED1	0.009	0.026	-10000	0	-0.41	2	2
PTPN11	0.011	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.006	0.07	-10000	0	-0.33	23	23
SHC/GRB2/SOS1	0.022	0	-10000	0	-10000	0	0
GRB2	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.043	0.11	-10000	0	-0.24	134	134
TRKA/NEDD4-2	0.009	0.043	-10000	0	-0.25	14	14
ELMO1	0.008	0.037	-10000	0	-0.41	4	4
RhoG/GTP/ELMO1/DOCK1	0.01	0.037	-10000	0	-0.26	9	9
NGF	-0.08	0.17	-10000	0	-0.41	114	114
HRAS	0.011	0	-10000	0	-10000	0	0
DOCK1	0.006	0.045	-10000	0	-0.41	6	6
GAB2	0.008	0.037	-10000	0	-0.41	4	4
RIT2	0.002	0.004	-10000	0	-10000	0	0
RIT1	0.011	0	-10000	0	-10000	0	0
FRS2	0.011	0	-10000	0	-10000	0	0
DNM1	0.006	0.045	-10000	0	-0.41	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.011	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.12	0.16	0.19	2	-0.31	185	187
mol:GDP	-0.064	0.11	-10000	0	-0.26	46	46
NGF (dimer)	-0.08	0.17	-10000	0	-0.41	114	114
RhoG/GDP	0.006	0.026	-10000	0	-0.29	4	4
RIT1/GDP	-0.04	0.081	-10000	0	-0.2	22	22
TIAM1	0	0.068	-10000	0	-0.41	14	14
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
BDNF (dimer)/TRKB	-0.039	0.1	-10000	0	-0.2	146	146
KIDINS220/CRKL/C3G	0.016	0	-10000	0	-10000	0	0
SHC/RasGAP	0.014	0.029	-10000	0	-0.28	5	5
FRS2 family/SHP2	0.022	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.027	0.02	-10000	0	-0.2	4	4
RIT1/GTP	0.008	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.017	0.1	-10000	0	-0.4	36	36
RAP1/GDP	-0.048	0.053	-10000	0	-0.18	13	13
KIDINS220/CRKL	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.043	0.12	-10000	0	-0.33	83	83
ubiquitin-dependent protein catabolic process	-0.038	0.11	-10000	0	-0.23	125	125
Schwann cell development	-0.037	0.03	-10000	0	-10000	0	0
EHD4	0.011	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.031	0.017	-10000	0	-10000	0	0
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
CDC42/GTP	-0.12	0.12	-10000	0	-0.34	101	101
ABL1	0.009	0.026	-10000	0	-0.41	2	2
SH2B family/GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
Rap1/GTP	0.015	0.046	-10000	0	-10000	0	0
STAT3	0.017	0.009	-10000	0	-10000	0	0
axon guidance	-0.12	0.12	-10000	0	-0.32	101	101
MAPK3	-0.033	0.1	-10000	0	-0.21	128	128
MAPK1	-0.033	0.1	-10000	0	-0.21	128	128
CDC42/GDP	-0.04	0.081	-10000	0	-0.19	26	26
NTF3	-0.017	0.1	-10000	0	-0.4	36	36
NTF4	-0.006	0.07	-10000	0	-0.33	23	23
NGF (dimer)/TRKA/FAIM	-0.038	0.11	-10000	0	-0.23	126	126
PI3K	0.013	0.031	-10000	0	-0.28	6	6
FRS3	0.011	0	-10000	0	-10000	0	0
FAIM	0.01	0.018	-10000	0	-0.41	1	1
GAB1	0.008	0.037	-10000	0	-0.41	4	4
RASGRF1	-0.15	0.17	0.2	2	-0.34	191	193
SOS1	0.011	0	-10000	0	-10000	0	0
MCF2L	-0.11	0.14	-10000	0	-0.25	261	261
RGS19	0.011	0	-10000	0	-10000	0	0
CDC42	0.011	0	-10000	0	-10000	0	0
RAS family/GTP	-0.017	0.07	-10000	0	-10000	0	0
Rac1/GDP	-0.04	0.081	-10000	0	-0.19	27	27
NGF (dimer)/TRKA/GRIT	-0.045	0.11	-10000	0	-0.24	125	125
neuron projection morphogenesis	-0.11	0.17	-10000	0	-0.42	70	70
NGF (dimer)/TRKA/NEDD4-2	-0.038	0.11	-10000	0	-0.23	125	125
MAP2K1	0.029	0.018	-10000	0	-10000	0	0
NGFR	-0.13	0.2	-10000	0	-0.41	176	176
NGF (dimer)/TRKA/GIPC/GAIP	-0.024	0.096	-10000	0	-0.2	124	124
RAS family/GTP/PI3K	0.022	0.024	-10000	0	-0.2	6	6
FRS2 family/SHP2/GRB2/SOS1	0.033	0	-10000	0	-10000	0	0
NRAS	0.011	0	-10000	0	-10000	0	0
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.024	-10000	0	-0.37	2	2
MAPKKK cascade	-0.15	0.25	-10000	0	-0.6	121	121
RASA1	0.007	0.041	-10000	0	-0.41	5	5
TRKA/c-Abl	0.008	0.045	-10000	0	-0.25	15	15
SQSTM1	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.028	0.093	-10000	0	-0.21	59	59
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.019	0.092	-10000	0	-0.18	121	121
MATK	0.001	0.064	-10000	0	-0.4	13	13
NEDD4L	0.01	0.018	-10000	0	-0.41	1	1
RAS family/GDP	-0.044	0.05	-10000	0	-0.17	13	13
NGF (dimer)/TRKA	-0.14	0.17	0.21	2	-0.31	230	232
Rac1/GTP	-0.11	0.11	-10000	0	-0.26	167	167
FRS2 family/SHP2/CRK family	0.033	0	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.005	0.05	-9999	-0.24	22	22
ADCY5	-0.031	0.097	-9999	-0.24	97	97
ADCY6	0.015	0	-9999	-10000	0	0
ADCY7	0.015	0	-9999	-10000	0	0
ADCY1	0.002	0.053	-9999	-0.22	29	29
ADCY2	-0.12	0.12	-9999	-0.24	289	289
ADCY3	0.014	0.015	-9999	-0.24	2	2
ADCY8	0.008	0.017	-9999	-0.18	4	4
PRKCE	0.009	0	-9999	-10000	0	0
ADCY9	-0.017	0.084	-9999	-0.24	69	69
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.06	0.079	-9999	-0.23	43	43

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.032	0.13	-9999	-0.41	53	53
GNB1/GNG2	-0.049	0.14	-9999	-0.41	39	39
mol:DAG	-0.04	0.13	-9999	-0.37	39	39
PLCG1	-0.041	0.13	-9999	-0.39	39	39
YES1	-0.054	0.14	-9999	-0.4	41	41
FZD3	0.011	0	-9999	-10000	0	0
FZD6	0.01	0.018	-9999	-0.41	1	1
G protein	-0.041	0.13	-9999	-0.39	39	39
MAP3K7	-0.12	0.14	-9999	-0.33	120	120
mol:Ca2+	-0.039	0.12	-9999	-0.36	39	39
mol:IP3	-0.04	0.13	-9999	-0.37	39	39
NLK	-0.005	0.009	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CAMK2A	-0.14	0.15	-9999	-0.34	138	138
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.063	0.15	-9999	-0.25	158	158
CSNK1A1	0.011	0	-9999	-10000	0	0
GNAS	-0.054	0.14	-9999	-0.4	41	41
GO:0007205	-0.04	0.13	-9999	-0.37	39	39
WNT6	-0.031	0.12	-9999	-0.38	57	57
WNT4	-0.089	0.18	-9999	-0.41	125	125
NFAT1/CK1 alpha	-0.051	0.14	-9999	-0.41	44	44
GNG2	0.003	0.056	-9999	-0.4	10	10
WNT5A	-0.003	0.074	-9999	-0.41	17	17
WNT11	-0.03	0.12	-9999	-0.35	60	60
CDC42	-0.045	0.14	-9999	-0.41	36	36

×

S1P5 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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.032	0.1	0.18	141	-10000	0	141
GNAI2	0.011	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.008	0.037	-10000	0	-0.19	17	17
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.099	0.18	-10000	0	-0.41	138	138
RhoA/GTP	-0.033	0.1	-10000	0	-0.19	141	141
negative regulation of cAMP metabolic process	-0.042	0.11	-10000	0	-0.21	152	152
GNAZ	-0.001	0.07	-10000	0	-0.41	15	15
GNAI3	0.011	0	-10000	0	-10000	0	0
GNA12	0.011	0	-10000	0	-10000	0	0
S1PR5	-0.001	0.064	-10000	0	-0.35	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.042	0.11	-10000	0	-0.21	152	152
RhoA/GDP	0.008	0	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.052	-10000	0	-0.41	8	8

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.018	-9999	-0.41	1	1
CCL5	0.003	0.054	-9999	-0.37	11	11
SDCBP	0.011	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.07	0.07	-9999	-0.22	51	51
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.061	0.066	-9999	-0.24	29	29
Syndecan-1/Syntenin	-0.061	0.066	-9999	-0.24	28	28
MAPK3	-0.045	0.062	-9999	-0.25	14	14
HGF/MET	-0.047	0.12	-9999	-0.28	111	111
TGFB1/TGF beta receptor Type II	0.01	0.018	-9999	-0.41	1	1
BSG	0.011	0	-9999	-10000	0	0
keratinocyte migration	-0.06	0.066	-9999	-0.24	29	29
Syndecan-1/RANTES	-0.064	0.073	-9999	-0.25	37	37
Syndecan-1/CD147	-0.053	0.065	-9999	-0.24	28	28
Syndecan-1/Syntenin/PIP2	-0.058	0.064	-9999	-0.24	28	28
LAMA5	0.01	0.015	-9999	-0.33	1	1
positive regulation of cell-cell adhesion	-0.058	0.062	-9999	-0.23	28	28
MMP7	-0.057	0.14	-9999	-0.36	96	96
HGF	-0.074	0.17	-9999	-0.41	106	106
Syndecan-1/CASK	-0.067	0.066	-9999	-0.23	34	34
Syndecan-1/HGF/MET	-0.094	0.11	-9999	-0.27	120	120
regulation of cell adhesion	-0.038	0.061	-9999	-0.24	14	14
HPSE	0.002	0.058	-9999	-0.4	11	11
positive regulation of cell migration	-0.07	0.07	-9999	-0.22	51	51
SDC1	-0.071	0.07	-9999	-0.22	51	51
Syndecan-1/Collagen	-0.07	0.07	-9999	-0.22	51	51
PPIB	0.01	0.015	-9999	-0.33	1	1
MET	0.005	0.047	-9999	-0.37	8	8
PRKACA	0.011	0	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	215	215
MAPK1	-0.045	0.062	-9999	-0.25	14	14
homophilic cell adhesion	-0.07	0.069	-9999	-0.22	51	51
MMP1	-0.17	0.17	-9999	-0.33	285	285

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.035	0.13	-10000	0	-0.38	62	62
NFATC2	-0.023	0.18	-10000	0	-0.52	41	41
NFATC3	-0.015	0.083	-10000	0	-0.24	44	44
CD40LG	-0.17	0.33	-10000	0	-0.86	77	77
ITCH	0.027	0.036	-10000	0	-10000	0	0
CBLB	0.027	0.036	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.14	0.25	-10000	0	-0.77	44	44
JUNB	0.007	0.041	-10000	0	-0.41	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.01	0.035	-10000	0	-10000	0	0
T cell anergy	0.015	0.058	-10000	0	-0.24	2	2
TLE4	-0.032	0.21	-10000	0	-0.64	51	51
Jun/NFAT1-c-4/p21SNFT	-0.095	0.33	-10000	0	-0.8	83	83
AP-1/NFAT1-c-4	-0.17	0.39	-10000	0	-0.99	76	76
IKZF1	0.002	0.13	-10000	0	-0.44	22	22
T-helper 2 cell differentiation	-0.083	0.23	-10000	0	-0.76	34	34
AP-1/NFAT1	-0.081	0.18	-10000	0	-0.38	92	92
CALM1	0.015	0.025	-10000	0	-10000	0	0
EGR2	-0.11	0.41	-10000	0	-1.1	58	58
EGR3	-0.14	0.46	-10000	0	-1.2	78	78
NFAT1/FOXP3	-0.044	0.16	-10000	0	-0.39	52	52
EGR1	-0.045	0.14	-10000	0	-0.41	68	68
JUN	0	0.05	-10000	0	-0.41	7	7
EGR4	-0.003	0.059	-10000	0	-0.34	15	15
mol:Ca2+	0.004	0.027	-10000	0	-10000	0	0
GBP3	-0.001	0.14	-10000	0	-0.51	21	21
FOSL1	-0.015	0.09	-10000	0	-0.33	40	40
NFAT1-c-4/MAF/IRF4	-0.13	0.35	-10000	0	-0.86	84	84
DGKA	0.004	0.13	-10000	0	-0.43	19	19
CREM	0.011	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.11	0.34	-10000	0	-0.83	84	84
CTLA4	-0.042	0.16	-10000	0	-0.43	43	43
NFAT1-c-4 (dimer)/EGR1	-0.12	0.36	-10000	0	-0.88	84	84
NFAT1-c-4 (dimer)/EGR4	-0.1	0.34	-10000	0	-0.82	84	84
FOS	-0.12	0.19	-10000	0	-0.41	159	159
IFNG	-0.077	0.19	-10000	0	-0.65	30	30
T cell activation	-0.084	0.21	-10000	0	-0.66	34	34
MAF	-0.067	0.16	-10000	0	-0.41	98	98
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.081	0.3	0.74	78	-10000	0	78
TNF	-0.13	0.33	-10000	0	-0.8	86	86
FASLG	-0.17	0.48	-10000	0	-1.2	82	82
TBX21	0.002	0.062	-10000	0	-0.4	12	12
BATF3	0.01	0.015	-10000	0	-0.33	1	1
PRKCQ	-0.024	0.12	-10000	0	-0.41	47	47
PTPN1	0.004	0.13	-10000	0	-0.43	20	20
NFAT1-c-4/ICER1	-0.097	0.33	-10000	0	-0.82	84	84
GATA3	-0.002	0.07	-10000	0	-0.35	20	20
T-helper 1 cell differentiation	-0.064	0.2	-10000	0	-0.64	30	30
IL2RA	-0.13	0.25	-10000	0	-0.69	57	57
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.004	0.13	-10000	0	-0.42	21	21
E2F1	-0.048	0.13	-10000	0	-0.32	100	100
PPARG	-0.012	0.096	-10000	0	-0.41	29	29
SLC3A2	0.004	0.13	-10000	0	-0.45	16	16
IRF4	-0.003	0.072	-10000	0	-0.37	19	19
PTGS2	-0.19	0.35	-10000	0	-0.87	83	83
CSF2	-0.17	0.33	-10000	0	-0.85	77	77
JunB/Fra1/NFAT1-c-4	-0.096	0.33	-10000	0	-0.79	84	84
IL4	-0.087	0.24	-10000	0	-0.81	33	33
IL5	-0.17	0.33	-10000	0	-0.85	76	76
IL2	-0.086	0.21	-10000	0	-0.68	33	33
IL3	-0.037	0.048	-10000	0	-10000	0	0
RNF128	0.013	0.076	-10000	0	-0.25	40	40
NFATC1	-0.082	0.31	-10000	0	-0.74	77	77
CDK4	0.042	0.18	0.56	20	-10000	0	20
PTPRK	0.003	0.13	-10000	0	-0.44	21	21
IL8	-0.2	0.34	-10000	0	-0.87	79	79
POU2F1	0.011	0	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.001	0.049	-10000	0	-0.35	9	9
CDKN2C	0.021	0.056	-10000	0	-0.38	9	9
CDKN2A	-0.13	0.17	-10000	0	-0.34	219	219
CCND2	0.005	0.049	0.16	10	-0.1	43	53
RB1	-0.006	0.048	0.13	5	-0.17	12	17
CDK4	0.024	0.037	0.17	12	-10000	0	12
CDK6	0.016	0.045	0.17	12	-0.18	11	23
G1/S progression	0.006	0.048	0.16	12	-0.13	5	17

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.099	0.18	-9999	-0.41	138	138
CDC42/GTP	-0.03	0.1	-9999	-0.34	14	14
PLCG1	-0.031	0.1	-9999	-0.19	140	140
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.011	0	-9999	-10000	0	0
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.016	0	-9999	-10000	0	0
cell migration	-0.03	0.099	-9999	-0.18	140	140
S1PR5	-0.001	0.064	-9999	-0.35	17	17
S1PR4	0.009	0.03	-9999	-0.38	3	3
MAPK3	-0.031	0.1	-9999	-0.19	140	140
MAPK1	-0.031	0.1	-9999	-0.19	140	140
S1P/S1P5/Gi	-0.042	0.11	-9999	-0.21	152	152
GNAI1	0.005	0.052	-9999	-0.41	8	8
CDC42/GDP	0.008	0	-9999	-10000	0	0
S1P/S1P5/G12	0.008	0.037	-9999	-0.19	17	17
RHOA	0.024	0.015	-9999	-0.18	2	2
S1P/S1P4/Gi	-0.039	0.11	-9999	-0.21	150	150
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.001	0.07	-9999	-0.41	15	15
S1P/S1P4/G12/G13	0.02	0.016	-9999	-0.19	3	3
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.03	0.15	-10000	0	-0.41	51	51
CRKL	-0.034	0.15	-10000	0	-0.44	48	48
HRAS	-0.014	0.14	-10000	0	-0.38	45	45
mol:PIP3	-0.04	0.14	-10000	0	-0.4	53	53
SPRED1	0.011	0	-10000	0	-10000	0	0
SPRED2	0.01	0.018	-10000	0	-0.41	1	1
GAB1	-0.042	0.16	-10000	0	-0.37	78	78
FOXO3	-0.026	0.14	-10000	0	-0.39	48	48
AKT1	-0.034	0.15	-10000	0	-0.43	48	48
BAD	-0.026	0.14	-10000	0	-0.39	48	48
megakaryocyte differentiation	-0.044	0.16	-10000	0	-0.36	81	81
GSK3B	-0.026	0.14	-10000	0	-0.39	48	48
RAF1	-0.003	0.11	-10000	0	-0.3	45	45
SHC1	0.011	0	-10000	0	-10000	0	0
STAT3	-0.041	0.16	-10000	0	-0.36	81	81
STAT1	-0.1	0.34	-10000	0	-0.84	81	81
HRAS/SPRED1	-0.005	0.11	-10000	0	-0.3	45	45
cell proliferation	-0.041	0.16	-10000	0	-0.44	53	53
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
TEC	0.01	0.015	-10000	0	-0.33	1	1
RPS6KB1	-0.042	0.16	-10000	0	-0.44	54	54
HRAS/SPRED2	-0.005	0.11	-10000	0	-0.31	45	45
LYN/TEC/p62DOK	-0.028	0.15	-10000	0	-0.42	49	49
MAPK3	0.009	0.086	-10000	0	-0.21	45	45
STAP1	-0.043	0.16	-10000	0	-0.36	81	81
GRAP2	-0.003	0.074	-10000	0	-0.41	17	17
JAK2	-0.089	0.3	-10000	0	-0.72	81	81
STAT1 (dimer)	-0.099	0.34	-10000	0	-0.82	81	81
mol:Gleevec	0	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.03	0.15	-10000	0	-0.42	51	51
actin filament polymerization	-0.04	0.15	-10000	0	-0.36	79	79
LYN	0.011	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.054	0.21	-10000	0	-0.51	81	81
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
CBL/CRKL/GRB2	-0.02	0.14	-10000	0	-0.39	48	48
PI3K	-0.032	0.16	-10000	0	-0.45	50	50
PTEN	0.006	0.045	-10000	0	-0.41	6	6
SCF/KIT/EPO/EPOR	-0.1	0.37	-10000	0	-1.2	47	47
MAPK8	-0.043	0.16	-10000	0	-0.45	53	53
STAT3 (dimer)	-0.04	0.15	-10000	0	-0.36	81	81
positive regulation of transcription	0.011	0.073	-10000	0	-0.18	45	45
mol:GDP	-0.018	0.14	-10000	0	-0.39	46	46
PIK3C2B	-0.041	0.16	-10000	0	-0.44	53	53
CBL/CRKL	-0.026	0.14	-10000	0	-0.41	48	48
FER	-0.041	0.16	-10000	0	-0.37	79	79
SH2B3	-0.041	0.16	-10000	0	-0.43	56	56
PDPK1	-0.032	0.13	-10000	0	-0.38	50	50
SNAI2	-0.067	0.18	-10000	0	-0.42	89	89
positive regulation of cell proliferation	-0.071	0.26	-10000	0	-0.62	81	81
KITLG	-0.03	0.13	-10000	0	-0.43	50	50
cell motility	-0.071	0.26	-10000	0	-0.62	81	81
PTPN6	0.011	0.017	-10000	0	-0.33	1	1
EPOR	-0.011	0.12	-10000	0	-0.71	2	2
STAT5A (dimer)	-0.057	0.22	-10000	0	-0.52	81	81
SOCS1	0.01	0.018	-10000	0	-0.41	1	1
cell migration	0.044	0.16	0.44	54	-10000	0	54
SOS1	0.011	0	-10000	0	-10000	0	0
EPO	-0.005	0.073	-10000	0	-0.41	16	16
VAV1	0.007	0.038	-10000	0	-0.34	6	6
GRB10	-0.041	0.16	-10000	0	-0.44	54	54
PTPN11	0.012	0.006	-10000	0	-10000	0	0
SCF/KIT	-0.049	0.16	-10000	0	-0.38	82	82
GO:0007205	0.001	0.008	-10000	0	-10000	0	0
MAP2K1	0.006	0.093	-10000	0	-0.24	45	45
CBL	0.011	0	-10000	0	-10000	0	0
KIT	-0.081	0.35	-10000	0	-1.2	40	40
MAP2K2	0.006	0.093	-10000	0	-0.24	45	45
SHC/Grb2/SOS1	-0.028	0.15	-10000	0	-0.43	48	48
STAT5A	-0.06	0.22	-10000	0	-0.53	81	81
GRB2	0.011	0	-10000	0	-10000	0	0
response to radiation	-0.065	0.18	-10000	0	-0.41	89	89
SHC/GRAP2	0.007	0.052	-10000	0	-0.28	17	17
PTPRO	-0.045	0.16	-10000	0	-0.37	81	81
SH2B2	-0.041	0.16	-10000	0	-0.37	79	79
DOK1	0.011	0	-10000	0	-10000	0	0
MATK	-0.046	0.16	-10000	0	-0.44	54	54
CREBBP	0.016	0.045	-10000	0	-0.43	2	2
BCL2	-0.1	0.38	-10000	0	-1.2	51	51

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.032	0.13	-10000	0	-0.41	53	53
GNB1/GNG2	-0.041	0.072	-10000	0	-0.19	93	93
AKT1	-0.016	0.098	-10000	0	-0.2	91	91
EGF	-0.005	0.071	-10000	0	-0.34	23	23
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.017	0.054	-10000	0	-0.3	1	1
mol:Ca2+	-0.046	0.14	-10000	0	-0.3	115	115
LYN	0.021	0.047	-10000	0	-10000	0	0
RhoA/GTP	-0.029	0.05	-10000	0	-0.13	93	93
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.045	0.16	-10000	0	-0.34	96	96
GNG2	0.003	0.057	-10000	0	-0.4	10	10
ARRB2	0.011	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.005	0.071	-10000	0	-0.33	14	14
G beta5/gamma2	-0.054	0.097	-10000	0	-0.25	93	93
PRKCH	-0.053	0.16	-10000	0	-0.36	99	99
DNM1	0.006	0.045	-10000	0	-0.41	6	6
TXA2/TP beta/beta Arrestin3	-0.005	0.021	-10000	0	-0.2	2	2
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.027	0.12	-10000	0	-0.41	47	47
G12 family/GTP	-0.07	0.12	-10000	0	-0.3	106	106
ADRBK1	0.011	0	-10000	0	-10000	0	0
ADRBK2	0.01	0.018	-10000	0	-0.41	1	1
RhoA/GTP/ROCK1	0.012	0.006	-10000	0	-10000	0	0
mol:GDP	0.022	0.094	0.24	35	-10000	0	35
mol:NADP	0.009	0.024	-10000	0	-0.37	2	2
RAB11A	0.011	0	-10000	0	-10000	0	0
PRKG1	-0.18	0.21	-10000	0	-0.41	232	232
mol:IP3	-0.061	0.18	-10000	0	-0.38	108	108
cell morphogenesis	0.012	0.006	-10000	0	-10000	0	0
PLCB2	-0.09	0.24	-10000	0	-0.53	106	106
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.007	0.057	-10000	0	-0.25	2	2
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.019	0.05	-10000	0	-0.26	1	1
RHOA	0.011	0	-10000	0	-10000	0	0
PTGIR	0.01	0.018	-10000	0	-0.41	1	1
PRKCB1	-0.058	0.17	-10000	0	-0.38	106	106
GNAQ	0.009	0.026	-10000	0	-0.41	2	2
mol:L-citrulline	0.009	0.024	-10000	0	-0.37	2	2
TXA2/TXA2-R family	-0.084	0.23	-10000	0	-0.54	96	96
LCK	0.019	0.049	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.015	0.046	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.018	0.028	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.014	0.045	-10000	0	-10000	0	0
MAPK14	-0.022	0.11	-10000	0	-0.23	94	94
TGM2/GTP	-0.079	0.21	-10000	0	-0.45	118	118
MAPK11	-0.023	0.11	-10000	0	-0.23	95	95
ARHGEF1	-0.018	0.085	-10000	0	-0.18	95	95
GNAI2	0.011	0	-10000	0	-10000	0	0
JNK cascade	-0.057	0.18	-10000	0	-0.38	103	103
RAB11/GDP	0.011	0.001	-10000	0	-10000	0	0
ICAM1	-0.035	0.13	-10000	0	-0.28	93	93
cAMP biosynthetic process	-0.063	0.17	-10000	0	-0.36	118	118
Gq family/GTP/EBP50	-0.001	0.068	-10000	0	-0.27	12	12
actin cytoskeleton reorganization	0.012	0.006	-10000	0	-10000	0	0
SRC	0.021	0.047	-10000	0	-10000	0	0
GNB5	0.011	0	-10000	0	-10000	0	0
GNB1	0.011	0	-10000	0	-10000	0	0
EGF/EGFR	0.031	0.047	-10000	0	-0.21	3	3
VCAM1	-0.044	0.15	-10000	0	-0.33	94	94
TP beta/Gq family/GDP/G beta5/gamma2	0.005	0.071	-10000	0	-0.33	14	14
platelet activation	-0.032	0.14	-10000	0	-0.3	101	101
PGI2/IP	0.008	0.013	-10000	0	-0.29	1	1
PRKACA	-0.003	0.064	-10000	0	-0.21	48	48
Gq family/GDP/G beta5/gamma2	0.003	0.07	-10000	0	-0.31	14	14
TXA2/TP beta/beta Arrestin2	-0.006	0.047	-10000	0	-0.44	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.003	0.06	-10000	0	-0.19	48	48
mol:DAG	-0.068	0.19	-10000	0	-0.43	101	101
EGFR	0	0.067	-10000	0	-0.4	14	14
TXA2/TP alpha	-0.089	0.23	-10000	0	-0.49	118	118
Gq family/GTP	-0.023	0.071	-10000	0	-0.21	62	62
YES1	0.021	0.047	-10000	0	-10000	0	0
GNAI2/GTP	-0.013	0.042	-10000	0	-10000	0	0
PGD2/DP	-0.019	0.084	-10000	0	-0.29	47	47
SLC9A3R1	0.009	0.026	-10000	0	-0.33	3	3
FYN	0.021	0.047	-10000	0	-10000	0	0
mol:NO	0.009	0.024	-10000	0	-0.37	2	2
GNA15	0.006	0.039	-10000	0	-0.33	7	7
PGK/cGMP	-0.096	0.12	-10000	0	-0.24	233	233
RhoA/GDP	0.011	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.002	0.091	-10000	0	-0.34	17	17
NOS3	0.009	0.024	-10000	0	-0.37	2	2
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.059	0.17	-10000	0	-0.37	102	102
PRKCB	-0.059	0.17	-10000	0	-0.38	97	97
PRKCE	-0.051	0.16	-10000	0	-0.36	93	93
PRKCD	-0.056	0.17	-10000	0	-0.38	94	94
PRKCG	-0.066	0.18	-10000	0	-0.4	101	101
muscle contraction	-0.077	0.22	-10000	0	-0.5	100	100
PRKCZ	-0.045	0.16	-10000	0	-0.35	96	96
ARR3	0.003	0.015	-10000	0	-0.33	1	1
TXA2/TP beta	0.01	0.056	-10000	0	-10000	0	0
PRKCQ	-0.062	0.17	-10000	0	-0.38	102	102
MAPKKK cascade	-0.077	0.21	-10000	0	-0.47	107	107
SELE	-0.048	0.16	-10000	0	-0.36	94	94
TP beta/GNAI2/GDP/G beta/gamma	0.016	0.061	-10000	0	-0.33	2	2
ROCK1	0.011	0	-10000	0	-10000	0	0
GNA14	-0.031	0.13	-10000	0	-0.41	53	53
chemotaxis	-0.093	0.26	-10000	0	-0.61	94	94
GNA12	0.011	0	-10000	0	-10000	0	0
GNA13	0.011	0	-10000	0	-10000	0	0
GNA11	0.002	0.06	-10000	0	-0.41	11	11
Rac1/GTP	0.006	0.004	-10000	0	-10000	0	0

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	0.005	0.068	-9999	-0.24	34	34
alphaM/beta2 Integrin/GPIbA	0.014	0.041	-9999	-0.23	11	11
alphaM/beta2 Integrin/proMMP-9	-0.062	0.1	-9999	-0.18	218	218
PLAUR	0.01	0.021	-9999	-0.33	2	2
HMGB1	0.009	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	0.017	0.034	-9999	-0.21	9	9
AGER	0.008	0.021	-9999	-0.4	1	1
RAP1A	0.011	0	-9999	-10000	0	0
SELPLG	0.01	0.021	-9999	-0.33	2	2
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.018	0.057	-9999	-0.27	3	3
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	215	215
CYR61	-0.026	0.12	-9999	-0.41	46	46
TLN1	0.011	0	-9999	-10000	0	0
Rap1/GTP	-0.029	0.061	-9999	-0.25	16	16
RHOA	0.011	0	-9999	-10000	0	0
P-selectin oligomer	-0.15	0.2	-9999	-0.41	201	201
MYH2	-0.03	0.11	-9999	-0.29	45	45
MST1R	-0.022	0.1	-9999	-0.33	51	51
leukocyte activation during inflammatory response	-0.015	0.05	-9999	-0.21	16	16
APOB	0	0.049	-9999	-0.39	8	8
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.011	0.093	-9999	-0.41	27	27
JAM3	-0.1	0.19	-9999	-0.41	142	142
GP1BA	0.008	0.03	-9999	-0.38	3	3
alphaM/beta2 Integrin/CTGF	0.011	0.052	-9999	-0.23	21	21
alphaM/beta2 Integrin	-0.022	0.085	-9999	-0.22	45	45
JAM3 homodimer	-0.1	0.19	-9999	-0.41	142	142
ICAM2	0.011	0	-9999	-10000	0	0
ICAM1	0.008	0.03	-9999	-0.33	4	4
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.022	0.085	-9999	-0.22	45	45
cell adhesion	0.014	0.041	-9999	-0.23	11	11
NFKB1	0.018	0.087	-9999	-0.3	19	19
THY1	0.011	0	-9999	-10000	0	0
RhoA/GDP	0.008	0	-9999	-10000	0	0
Lipoprotein(a)	-0.005	0.055	-9999	-0.2	39	39
alphaM/beta2 Integrin/LRP/tPA	-0.001	0.081	-9999	-0.21	61	61
IL6	0.011	0.13	-9999	-0.63	16	16
ITGB2	0.006	0.035	-9999	-0.33	5	5
elevation of cytosolic calcium ion concentration	0.021	0.035	-9999	-0.19	9	9
alphaM/beta2 Integrin/JAM2/JAM3	-0.11	0.17	-9999	-0.28	238	238
JAM2	-0.14	0.2	-9999	-0.41	185	185
alphaM/beta2 Integrin/ICAM1	0.009	0.063	-9999	-0.24	9	9
alphaM/beta2 Integrin/uPA/Plg	0.001	0.075	-9999	-0.21	49	49
RhoA/GTP	-0.034	0.11	-9999	-0.26	73	73
positive regulation of phagocytosis	-0.02	0.055	-9999	-0.21	21	21
Ron/MSP	-0.009	0.073	-9999	-0.22	57	57
alphaM/beta2 Integrin/uPAR/uPA	0.022	0.036	-9999	-0.19	9	9
alphaM/beta2 Integrin/uPAR	0.017	0.036	-9999	-0.2	11	11
PLAU	0.009	0.026	-9999	-0.33	3	3
PLAT	-0.035	0.13	-9999	-0.41	57	57
actin filament polymerization	-0.029	0.1	-9999	-0.28	45	45
MST1	0.007	0.036	-9999	-0.33	6	6
alphaM/beta2 Integrin/lipoprotein(a)	0.004	0.057	-9999	-0.21	16	16
TNF	0.01	0.11	-9999	-0.39	10	10
RAP1B	0.011	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	0.016	0.037	-9999	-0.21	12	12
fibrinolysis	0	0.074	-9999	-0.21	49	49
HCK	0.006	0.039	-9999	-0.33	7	7
dendritic cell antigen processing and presentation	-0.022	0.085	-9999	-0.22	45	45
VTN	-0.047	0.14	-9999	-0.41	72	72
alphaM/beta2 Integrin/CYR61	-0.004	0.079	-9999	-0.23	53	53
LPA	-0.013	0.081	-9999	-0.33	32	32
LRP1	0.009	0.026	-9999	-0.41	2	2
cell migration	-0.06	0.1	-9999	-0.21	78	78
FN1	0.007	0.041	-9999	-0.41	5	5
alphaM/beta2 Integrin/Thy1	0.017	0.034	-9999	-0.21	9	9
MPO	0.005	0.042	-9999	-0.33	8	8
KNG1	-0.01	0.07	-9999	-0.33	24	24
RAP1/GDP	0.015	0	-9999	-10000	0	0
ROCK1	-0.026	0.11	-9999	-0.3	39	39
ELA2	0	0	-9999	-10000	0	0
PLG	-0.03	0.12	-9999	-0.4	50	50
CTGF	0.001	0.065	-9999	-0.41	13	13
alphaM/beta2 Integrin/Hck	0.015	0.045	-9999	-0.22	14	14
ITGAM	0.005	0.039	-9999	-0.37	5	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.063	0.12	-9999	-0.2	205	205
HP	-0.1	0.17	-9999	-0.35	160	160
leukocyte adhesion	-0.11	0.13	-9999	-0.32	117	117
SELP	-0.15	0.2	-9999	-0.41	201	201

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.03	0.11	-9999	-0.22	116	116
SMAD6-7/SMURF1	0.021	0.019	-9999	-0.23	3	3
NOG	-0.018	0.095	-9999	-0.33	44	44
SMAD9	-0.058	0.17	-9999	-0.5	58	58
SMAD4	0.01	0.018	-9999	-0.41	1	1
SMAD5	-0.018	0.095	-9999	-0.3	30	30
BMP7/USAG1	-0.049	0.12	-9999	-0.27	121	121
SMAD5/SKI	-0.012	0.091	-9999	-0.29	28	28
SMAD1	0.033	0.014	-9999	-10000	0	0
BMP2	-0.025	0.12	-9999	-0.41	45	45
SMAD1/SMAD1/SMAD4	-0.001	0.012	-9999	-10000	0	0
BMPR1A	0.011	0	-9999	-10000	0	0
BMPR1B	-0.016	0.1	-9999	-0.41	34	34
BMPR1A-1B/BAMBI	-0.004	0.081	-9999	-0.24	54	54
AHSG	0.001	0.046	-9999	-0.33	10	10
CER1	0.004	0.005	-9999	-10000	0	0
BMP2-4/CER1	-0.018	0.093	-9999	-0.24	73	73
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.037	0.12	-9999	-0.34	39	39
BMP2-4 (homodimer)	-0.026	0.11	-9999	-0.29	73	73
RGMB	0.01	0.018	-9999	-0.41	1	1
BMP6/BMPR2/BMPR1A-1B	0.009	0.064	-9999	-0.2	43	43
RGMA	-0.08	0.17	-9999	-0.41	114	114
SMURF1	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.042	0.12	-9999	-0.34	41	41
BMP2-4/USAG1	-0.043	0.12	-9999	-0.24	133	133
SMAD6/SMURF1/SMAD5	-0.012	0.091	-9999	-0.29	28	28
SOSTDC1	-0.04	0.13	-9999	-0.36	71	71
BMP7/BMPR2/BMPR1A-1B	-0.009	0.088	-9999	-0.22	59	59
SKI	0.011	0	-9999	-10000	0	0
BMP6 (homodimer)	0.002	0.06	-9999	-0.41	11	11
HFE2	0.003	0.021	-9999	-0.33	2	2
ZFYVE16	0.011	0	-9999	-10000	0	0
MAP3K7	0.011	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.056	0.14	-9999	-0.27	136	136
SMAD5/SMAD5/SMAD4	-0.012	0.093	-9999	-0.29	30	30
MAPK1	0.011	0	-9999	-10000	0	0
TAK1/TAB family	-0.051	0.087	-9999	-0.31	35	35
BMP7 (homodimer)	-0.032	0.12	-9999	-0.37	60	60
NUP214	0.011	0	-9999	-10000	0	0
BMP6/FETUA	0.003	0.052	-9999	-0.25	21	21
SMAD1/SKI	0.038	0.014	-9999	-10000	0	0
SMAD6	0.01	0.018	-9999	-0.41	1	1
CTDSP2	0.011	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.02	0.097	-9999	-0.26	64	64
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.095	0.18	-9999	-0.41	132	132
BMPR2 (homodimer)	0.011	0	-9999	-10000	0	0
GADD34/PP1CA	0.022	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.003	0.072	-9999	-0.28	34	34
CHRDL1	-0.28	0.2	-9999	-0.41	359	359
ENDOFIN/SMAD1	0.038	0.014	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0	0.012	-9999	-10000	0	0
SMAD6/SMURF1	0.011	0	-9999	-10000	0	0
BAMBI	-0.007	0.083	-9999	-0.38	24	24
SMURF2	0.011	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.18	0.15	-9999	-0.26	375	375
BMP2-4/GREM1	-0.075	0.14	-9999	-0.26	181	181
SMAD7	0.009	0.026	-9999	-0.41	2	2
SMAD8A/SMAD8A/SMAD4	-0.049	0.16	-9999	-0.47	58	58
SMAD1/SMAD6	0.038	0.014	-9999	-10000	0	0
TAK1/SMAD6	0.016	0	-9999	-10000	0	0
BMP7	-0.032	0.12	-9999	-0.37	60	60
BMP6	0.002	0.06	-9999	-0.41	11	11
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.037	0.12	-9999	-0.32	43	43
PPM1A	0.011	0	-9999	-10000	0	0
SMAD1/SMURF2	0.038	0.014	-9999	-10000	0	0
SMAD7/SMURF1	0.015	0.018	-9999	-0.28	2	2
CTDSPL	0.011	0	-9999	-10000	0	0
PPP1CA	0.011	0	-9999	-10000	0	0
XIAP	0.011	0	-9999	-10000	0	0
CTDSP1	0.011	0	-9999	-10000	0	0
PPP1R15A	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.076	0.16	-9999	-0.42	67	67
CHRD	-0.063	0.16	-9999	-0.41	92	92
BMPR2	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.05	0.13	-9999	-0.37	41	41
BMP4	-0.015	0.098	-9999	-0.39	34	34
FST	-0.044	0.14	-9999	-0.4	69	69
BMP2-4/NOG	-0.03	0.11	-9999	-0.26	68	68
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.002	0.083	-9999	-0.2	59	59

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.002	0.073	-10000	0	-0.19	69	69
ER alpha/Gai/GDP/Gbeta gamma	-0.087	0.19	-10000	0	-0.32	178	178
AKT1	-0.07	0.25	-10000	0	-0.75	61	61
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.075	0.25	-10000	0	-0.76	61	61
mol:Ca2+	-0.015	0.12	-10000	0	-0.34	56	56
IGF1R	-0.006	0.082	-10000	0	-0.41	21	21
E2/ER alpha (dimer)/Striatin	-0.014	0.08	-10000	0	-0.23	62	62
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	0.066	0.24	0.71	61	-10000	0	61
RhoA/GTP	-0.018	0.051	-10000	0	-0.3	1	1
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.087	0.14	-10000	0	-0.4	72	72
regulation of stress fiber formation	-0.017	0.058	0.26	3	-10000	0	3
E2/ERA-ERB (dimer)	-0.014	0.079	-10000	0	-0.23	61	61
KRAS	0.01	0.015	-10000	0	-0.33	1	1
G13/GTP	-0.011	0.071	-10000	0	-0.21	60	60
pseudopodium formation	0.017	0.058	-10000	0	-0.26	3	3
E2/ER alpha (dimer)/PELP1	-0.013	0.079	-10000	0	-0.23	60	60
GRB2	0.011	0	-10000	0	-10000	0	0
GNG2	0.003	0.056	-10000	0	-0.4	10	10
GNAO1	-0.099	0.18	-10000	0	-0.41	138	138
HRAS	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.056	0.18	-10000	0	-0.5	61	61
E2/ER beta (dimer)	0.008	0.01	-10000	0	-0.23	1	1
mol:GDP	-0.035	0.098	-10000	0	-0.31	60	60
mol:NADP	-0.056	0.18	-10000	0	-0.5	61	61
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
mol:IP3	-0.016	0.13	-10000	0	-0.36	56	56
IGF-1R heterotetramer	-0.006	0.082	-10000	0	-0.41	21	21
PLCB1	-0.022	0.13	-10000	0	-0.37	56	56
PLCB2	-0.021	0.13	-10000	0	-0.37	55	55
IGF1	-0.069	0.16	-10000	0	-0.41	100	100
mol:L-citrulline	-0.056	0.18	-10000	0	-0.5	61	61
RHOA	0.011	0	-10000	0	-10000	0	0
Gai/GDP	-0.15	0.29	-10000	0	-0.63	139	139
JNK cascade	0.008	0.01	-10000	0	-0.22	1	1
BCAR1	0.011	0	-10000	0	-10000	0	0
ESR2	0.01	0.015	-10000	0	-0.33	1	1
GNAQ	0.009	0.026	-10000	0	-0.41	2	2
ESR1	-0.037	0.13	-10000	0	-0.41	60	60
Gq family/GDP/Gbeta gamma	-0.002	0.094	-10000	0	-0.4	15	15
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.009	0.082	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.087	0.14	-10000	0	-0.4	72	72
GNAZ	-0.001	0.07	-10000	0	-0.41	15	15
E2/ER alpha (dimer)	-0.026	0.094	-10000	0	-0.29	60	60
STRN	0.009	0.026	-10000	0	-0.41	2	2
GNAL	-0.051	0.15	-10000	0	-0.41	77	77
PELP1	0.011	0	-10000	0	-10000	0	0
MAPK11	0.014	0.018	-10000	0	-0.22	3	3
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	0.005	0.052	-10000	0	-0.41	8	8
HBEGF	-0.1	0.18	-10000	0	-0.37	116	116
cAMP biosynthetic process	-0.047	0.09	-10000	0	-0.2	124	124
SRC	-0.077	0.18	-10000	0	-0.41	73	73
PI3K	0.013	0.031	-10000	0	-0.28	6	6
GNB1	0.011	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.033	0.085	-10000	0	-0.26	60	60
SOS1	0.011	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.1	0.15	-10000	0	-0.36	108	108
Gs family/GTP	-0.048	0.091	-10000	0	-0.2	124	124
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.021	0.008	-10000	0	-0.16	1	1
vasodilation	-0.053	0.17	-10000	0	-0.48	61	61
mol:DAG	-0.016	0.13	-10000	0	-0.36	56	56
Gs family/GDP/Gbeta gamma	-0.052	0.1	-10000	0	-0.29	64	64
MSN	0.017	0.062	-10000	0	-0.28	3	3
Gq family/GTP	-0.029	0.13	-10000	0	-0.39	55	55
mol:PI-3-4-5-P3	-0.071	0.24	-10000	0	-0.73	61	61
NRAS	0.011	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.053	0.17	0.48	61	-10000	0	61
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
RhoA/GDP	-0.033	0.091	-10000	0	-0.29	60	60
NOS3	-0.059	0.19	-10000	0	-0.53	61	61
GNA11	0.002	0.06	-10000	0	-0.41	11	11
MAPKKK cascade	-0.05	0.19	-10000	0	-0.55	61	61
E2/ER alpha (dimer)/PELP1/Src	-0.092	0.15	-10000	0	-0.42	72	72
ruffle organization	0.017	0.058	-10000	0	-0.26	3	3
ROCK2	0.012	0.065	-10000	0	-0.31	3	3
GNA14	-0.031	0.13	-10000	0	-0.41	53	53
GNA15	0.006	0.039	-10000	0	-0.33	7	7
GNA13	0.011	0	-10000	0	-10000	0	0
MMP9	-0.13	0.18	-10000	0	-0.4	114	114
MMP2	-0.076	0.18	-10000	0	-0.41	79	79

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.028	0.1	0.28	75	-10000	0	75
KIRREL	-0.039	0.14	-10000	0	-0.41	62	62
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.028	0.1	-10000	0	-0.28	75	75
PLCG1	0.011	0	-10000	0	-10000	0	0
ARRB2	0.011	0	-10000	0	-10000	0	0
WASL	0.011	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.011	0.076	-10000	0	-0.2	63	63
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.005	0.077	-10000	0	-0.21	62	62
FYN	-0.013	0.072	-10000	0	-0.2	63	63
mol:Ca2+	-0.014	0.074	-10000	0	-0.2	63	63
mol:DAG	-0.011	0.075	-10000	0	-0.2	63	63
NPHS2	-0.004	0.029	-10000	0	-0.33	3	3
mol:IP3	-0.011	0.075	-10000	0	-0.2	63	63
regulation of endocytosis	-0.005	0.068	-10000	0	-0.18	60	60
Nephrin/NEPH1/podocin/Cholesterol	-0.018	0.076	-10000	0	-0.21	63	63
establishment of cell polarity	-0.028	0.1	-10000	0	-0.28	75	75
Nephrin/NEPH1/podocin/NCK1-2	-0.003	0.072	-10000	0	-0.33	4	4
Nephrin/NEPH1/beta Arrestin2	-0.005	0.069	-10000	0	-0.18	60	60
NPHS1	-0.005	0.055	-10000	0	-0.33	14	14
Nephrin/NEPH1/podocin	-0.013	0.072	-10000	0	-0.2	63	63
TJP1	0.01	0.018	-10000	0	-0.41	1	1
NCK1	0.009	0.026	-10000	0	-0.41	2	2
NCK2	0.011	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.011	0.076	-10000	0	-0.2	63	63
CD2AP	0.011	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.011	0.076	-10000	0	-0.2	63	63
GRB2	0.011	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.026	0.096	-10000	0	-0.22	91	91
cytoskeleton organization	-0.001	0.08	-10000	0	-0.21	62	62
Nephrin/NEPH1	-0.017	0.071	-10000	0	-0.19	75	75
Nephrin/NEPH1/ZO-1	-0.013	0.083	-10000	0	-0.22	63	63

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.005	0.075	-9999	-0.23	44	44
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.068	-9999	-0.24	7	7
AP1	-0.08	0.11	-9999	-0.3	67	67
mol:PIP3	-0.03	0.069	-9999	-0.32	15	15
AKT1	0.029	0.057	-9999	-0.27	8	8
PTK2B	0.006	0.059	-9999	-0.2	32	32
RHOA	0.018	0.03	-9999	-10000	0	0
PIK3CB	0.011	0	-9999	-10000	0	0
mol:Ca2+	0.005	0.063	-9999	-0.19	28	28
MAGI3	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
apoptosis	-0.011	0.085	-9999	-0.23	61	61
HRAS/GDP	0.008	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.009	0.066	-9999	-0.23	17	17
NF kappa B1 p50/RelA	-0.026	0.068	-9999	-0.31	12	12
endothelial cell migration	-0.011	0.13	-9999	-0.44	38	38
ADCY4	-0.044	0.14	-9999	-0.37	54	54
ADCY5	-0.071	0.16	-9999	-0.38	76	76
ADCY6	-0.035	0.13	-9999	-0.34	46	46
ADCY7	-0.035	0.13	-9999	-0.34	46	46
ADCY1	-0.044	0.14	-9999	-0.38	55	55
ADCY2	-0.14	0.19	-9999	-0.4	137	137
ADCY3	-0.036	0.13	-9999	-0.35	48	48
ADCY8	-0.038	0.13	-9999	-0.34	47	47
ADCY9	-0.063	0.16	-9999	-0.38	82	82
GSK3B	0.011	0.057	-9999	-0.2	26	26
arachidonic acid secretion	-0.04	0.13	-9999	-0.21	158	158
GNG2	0.003	0.056	-9999	-0.4	10	10
TRIP6	0.014	0.038	-9999	-0.35	5	5
GNAO1	-0.061	0.14	-9999	-0.26	158	158
HRAS	0.011	0	-9999	-10000	0	0
NFKBIA	0.009	0.076	-9999	-0.23	30	30
GAB1	0.008	0.037	-9999	-0.41	4	4
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.002	0.14	-9999	-0.86	14	14
JUN	0.005	0.048	-9999	-0.41	7	7
LPA/LPA2/NHERF2	0.012	0.023	-9999	-0.18	3	3
TIAM1	-0.025	0.16	-9999	-1	14	14
PIK3R1	0.007	0.041	-9999	-0.41	5	5
mol:IP3	0.004	0.064	-9999	-0.19	28	28
PLCB3	0.018	0.02	-9999	-0.15	3	3
FOS	-0.12	0.19	-9999	-0.41	159	159
positive regulation of mitosis	-0.04	0.13	-9999	-0.21	158	158
LPA/LPA1-2-3	-0.013	0.089	-9999	-0.2	84	84
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.011	0	-9999	-10000	0	0
stress fiber formation	0.007	0.068	-9999	-0.26	14	14
GNAZ	-0.004	0.085	-9999	-0.25	51	51
EGFR/PI3K-beta/Gab1	-0.031	0.071	-9999	-0.33	15	15
positive regulation of dendritic cell cytokine production	-0.017	0.087	-9999	-0.21	69	69
LPA/LPA2/MAGI-3	0.012	0.023	-9999	-0.18	3	3
ARHGEF1	0.015	0.061	-9999	-0.24	16	16
GNAI2	0.003	0.073	-9999	-0.25	38	38
GNAI3	0.003	0.073	-9999	-0.25	38	38
GNAI1	-0.001	0.079	-9999	-0.25	45	45
LPA/LPA3	-0.02	0.081	-9999	-0.26	50	50
LPA/LPA2	0.004	0.028	-9999	-0.22	3	3
LPA/LPA1	-0.007	0.085	-9999	-0.3	38	38
HB-EGF/EGFR	-0.064	0.1	-9999	-0.2	98	98
HBEGF	-0.078	0.12	-9999	-0.22	215	215
mol:DAG	0.004	0.064	-9999	-0.19	28	28
cAMP biosynthetic process	-0.067	0.15	-9999	-0.26	161	161
NFKB1	0.01	0.018	-9999	-0.41	1	1
SRC	0.011	0	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
LYN	0.009	0.076	-9999	-0.23	30	30
GNAQ	-0.003	0.06	-9999	-0.22	29	29
LPAR2	0.009	0.026	-9999	-0.33	3	3
LPAR3	-0.026	0.11	-9999	-0.37	50	50
LPAR1	-0.006	0.085	-9999	-0.45	16	16
IL8	-0.072	0.11	-9999	-0.31	50	50
PTK2	-0.004	0.083	-9999	-0.2	61	61
Rac1/GDP	0.008	0	-9999	-10000	0	0
CASP3	-0.011	0.086	-9999	-0.23	61	61
EGFR	0	0.067	-9999	-0.4	14	14
PLCG1	-0.009	0.075	-9999	-0.22	45	45
PLD2	-0.005	0.084	-9999	-0.2	62	62
G12/G13	0.01	0.066	-9999	-0.22	38	38
PI3K-beta	-0.014	0.05	-9999	-0.3	9	9
cell migration	-0.014	0.049	-9999	-0.25	16	16
SLC9A3R2	0.011	0	-9999	-10000	0	0
PXN	0.007	0.069	-9999	-0.27	14	14
HRAS/GTP	-0.041	0.14	-9999	-0.22	158	158
RAC1	0.011	0	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	215	215
PRKCE	0.011	0.002	-9999	-10000	0	0
PRKCD	0.01	0.061	-9999	-0.23	5	5
Gi(beta/gamma)	-0.034	0.12	-9999	-0.33	48	48
mol:LPA	-0.004	0.034	-9999	-0.16	22	22
TRIP6/p130 Cas/FAK1/Paxillin	-0.023	0.072	-9999	-0.39	9	9
MAPKKK cascade	-0.04	0.13	-9999	-0.21	158	158
contractile ring contraction involved in cytokinesis	0.018	0.03	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.025	0.095	-9999	-0.24	77	77
GNA15	-0.003	0.06	-9999	-0.22	27	27
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
MAPT	0.009	0.067	-9999	-0.23	17	17
GNA11	-0.007	0.066	-9999	-0.22	38	38
Rac1/GTP	-0.003	0.15	-9999	-0.91	14	14
MMP2	-0.011	0.13	-9999	-0.44	38	38

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.009	0.032	-10000	0	-0.41	3	3
EPHB2	0.01	0.026	-10000	0	-0.33	3	3
EFNB1	0.015	0.037	-10000	0	-0.32	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.009	0.071	-10000	0	-0.35	4	4
Ephrin B2/EPHB1-2	-0.001	0.068	-10000	0	-0.2	57	57
neuron projection morphogenesis	-0.021	0.056	-10000	0	-0.33	4	4
Ephrin B1/EPHB1-2/Tiam1	0.006	0.076	-10000	0	-0.2	47	47
DNM1	0.007	0.044	-10000	0	-0.41	6	6
cell-cell signaling	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.047	0.18	-10000	0	-0.52	65	65
YES1	-0.092	0.25	-10000	0	-0.76	65	65
Ephrin B1/EPHB1-2/NCK2	0.011	0.067	-10000	0	-0.18	40	40
PI3K	-0.048	0.18	-10000	0	-0.53	65	65
mol:GDP	0.005	0.075	-10000	0	-0.19	47	47
ITGA2B	0.006	0.047	-10000	0	-0.4	7	7
endothelial cell proliferation	0.014	0.022	-10000	0	-0.23	4	4
FYN	-0.092	0.25	-10000	0	-0.76	65	65
MAP3K7	-0.055	0.19	-10000	0	-0.56	65	65
FGR	-0.094	0.25	-10000	0	-0.76	65	65
TIAM1	0	0.068	-10000	0	-0.41	14	14
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
RGS3	0.011	0	-10000	0	-10000	0	0
cell adhesion	-0.07	0.2	-10000	0	-0.56	65	65
LYN	-0.092	0.25	-10000	0	-0.76	65	65
Ephrin B1/EPHB1-2/Src Family Kinases	-0.086	0.23	-10000	0	-0.7	65	65
Ephrin B1/EPHB1-2	-0.075	0.2	-10000	0	-0.6	65	65
SRC	-0.091	0.25	-10000	0	-0.75	65	65
ITGB3	-0.065	0.16	-10000	0	-0.41	96	96
EPHB1	-0.029	0.12	-10000	0	-0.41	51	51
EPHB4	0.01	0.018	-10000	0	-0.41	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.014	0.022	-10000	0	-0.23	4	4
alphaIIb/beta3 Integrin	-0.041	0.12	-10000	0	-0.28	103	103
BLK	-0.092	0.25	-10000	0	-0.75	65	65
HCK	-0.091	0.25	-10000	0	-0.75	65	65
regulation of stress fiber formation	-0.01	0.066	0.18	40	-10000	0	40
MAPK8	-0.041	0.17	-10000	0	-0.5	65	65
Ephrin B1/EPHB1-2/RGS3	0.011	0.067	-10000	0	-0.18	40	40
endothelial cell migration	-0.054	0.16	-10000	0	-0.46	65	65
NCK2	0.011	0	-10000	0	-10000	0	0
PTPN13	-0.057	0.18	-10000	0	-0.52	65	65
regulation of focal adhesion formation	-0.01	0.066	0.18	40	-10000	0	40
chemotaxis	-0.01	0.066	0.18	40	-10000	0	40
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
Rac1/GTP	-0.022	0.057	-10000	0	-0.34	4	4
angiogenesis	-0.074	0.2	-10000	0	-0.6	65	65
LCK	-0.091	0.25	-10000	0	-0.75	65	65

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.099	0.25	-10000	0	-0.68	35	35
PCK1	-0.12	0.32	-10000	0	-1.2	34	34
HNF4A	-0.16	0.34	-10000	0	-0.84	70	70
KCNJ11	-0.088	0.26	-10000	0	-0.71	32	32
AKT1	-0.048	0.14	-10000	0	-0.38	10	10
response to starvation	-0.01	0.032	-10000	0	-10000	0	0
DLK1	-0.15	0.34	-10000	0	-0.82	73	73
NKX2-1	-0.019	0.15	-10000	0	-10000	0	0
ACADM	-0.1	0.26	-10000	0	-0.71	37	37
TAT	-0.098	0.2	-10000	0	-0.61	24	24
CEBPB	0.013	0.002	-10000	0	-10000	0	0
CEBPA	0.01	0.038	-10000	0	-0.38	5	5
TTR	-0.037	0.13	-10000	0	-0.6	8	8
PKLR	-0.11	0.25	-10000	0	-0.69	36	36
APOA1	-0.21	0.44	-10000	0	-1.2	70	70
CPT1C	-0.1	0.26	-10000	0	-0.74	38	38
ALAS1	-0.042	0.16	-10000	0	-10000	0	0
TFRC	-0.056	0.19	-10000	0	-0.64	7	7
FOXF1	0.008	0.046	-10000	0	-0.4	6	6
NF1	0.015	0.026	-10000	0	-0.41	2	2
HNF1A (dimer)	0.003	0.047	-10000	0	-0.35	8	8
CPT1A	-0.099	0.25	-10000	0	-0.68	35	35
HMGCS1	-0.099	0.25	-10000	0	-0.68	37	37
NR3C1	-0.069	0.16	-10000	0	-0.38	99	99
CPT1B	-0.1	0.25	-10000	0	-0.68	36	36
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.007	0.016	-10000	0	-10000	0	0
GCK	-0.17	0.35	-10000	0	-0.79	94	94
CREB1	0.004	0.041	-10000	0	-0.2	5	5
IGFBP1	-0.22	0.44	-10000	0	-1.2	82	82
PDX1	-0.052	0.15	-10000	0	-10000	0	0
UCP2	-0.1	0.25	-10000	0	-0.69	36	36
ALDOB	-0.09	0.26	-10000	0	-0.71	30	30
AFP	-0.056	0.072	-10000	0	-0.4	10	10
BDH1	-0.099	0.25	-10000	0	-0.68	36	36
HADH	-0.087	0.26	-10000	0	-0.71	29	29
F2	-0.14	0.31	-10000	0	-0.85	43	43
HNF1A	0.003	0.047	-10000	0	-0.35	8	8
G6PC	0.008	0.066	-10000	0	-10000	0	0
SLC2A2	-0.055	0.17	-10000	0	-10000	0	0
INS	0.015	0.058	0.21	19	-10000	0	19
FOXA1	-0.21	0.16	-10000	0	-0.32	353	353
FOXA3	-0.056	0.15	-10000	0	-0.33	114	114
FOXA2	-0.11	0.3	-10000	0	-0.76	40	40
ABCC8	-0.18	0.38	-10000	0	-0.85	104	104
ALB	-0.063	0.14	-10000	0	-1	9	9

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	-0.002	0.071	-9999	-0.28	31	31
PDGFRB	-0.008	0.085	-9999	-0.42	22	22
SPHK1	-0.013	0.023	-9999	-10000	0	0
mol:S1P	-0.016	0.03	-9999	-10000	0	0
S1P1/S1P/Gi	-0.079	0.19	-9999	-0.31	177	177
GNAO1	-0.1	0.19	-9999	-0.41	138	138
PDGFB-D/PDGFRB/PLCgamma1	-0.064	0.17	-9999	-0.38	90	90
PLCG1	-0.068	0.18	-9999	-0.39	86	86
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.008	0.085	-9999	-0.42	22	22
GNAI2	0.011	0.004	-9999	-10000	0	0
GNAI3	0.01	0.004	-9999	-10000	0	0
GNAI1	0.004	0.052	-9999	-0.42	8	8
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.001	0.06	-9999	-0.24	31	31
S1P1/S1P	-0.023	0.065	-9999	-0.27	15	15
negative regulation of cAMP metabolic process	-0.076	0.18	-9999	-0.3	177	177
MAPK3	-0.088	0.22	-9999	-0.53	84	84
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
RhoA/GDP	0.008	0	-9999	-10000	0	0
KDR	-0.014	0.1	-9999	-0.41	31	31
PLCB2	0.004	0.068	-9999	-0.24	14	14
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.019	0.055	-9999	-0.23	15	15
receptor internalization	-0.022	0.061	-9999	-0.25	15	15
PTGS2	-0.12	0.33	-9999	-0.97	62	62
Rac1/GTP	-0.019	0.055	-9999	-0.23	15	15
RHOA	0.011	0	-9999	-10000	0	0
VEGFA	0.011	0.002	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.076	0.18	-9999	-0.3	177	177
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.002	0.071	-9999	-0.42	15	15
MAPK1	-0.088	0.22	-9999	-0.53	84	84
S1P1/S1P/PDGFB-D/PDGFRB	-0.005	0.098	-9999	-0.32	26	26
ABCC1	0.01	0.002	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.075	0.17	-9999	-0.31	161	161
MAP3K8	0.006	0.032	-9999	-0.41	3	3
FOS	-0.043	0.12	-9999	-0.38	24	24
PRKCA	-0.019	0.1	-9999	-0.41	34	34
PTPN7	0.005	0.038	-9999	-0.34	6	6
HRAS	0.01	0.001	-9999	-10000	0	0
PRKCB	-0.017	0.1	-9999	-0.41	32	32
NRAS	0.01	0.001	-9999	-10000	0	0
RAS family/GTP	0.016	0.013	-9999	-0.15	1	1
MAPK3	-0.016	0.068	-9999	-0.25	5	5
MAP2K1	-0.038	0.14	-9999	-0.4	62	62
ELK1	0.005	0.01	-9999	-10000	0	0
BRAF	-0.034	0.14	-9999	-0.38	62	62
mol:GTP	-0.001	0.002	-9999	-0.005	159	159
MAPK1	-0.016	0.068	-9999	-0.25	5	5
RAF1	-0.034	0.14	-9999	-0.38	62	62
KRAS	0.01	0.015	-9999	-0.33	1	1

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.013	0.073	-9999	-0.24	50	50
EFNA5	-0.003	0.075	-9999	-0.4	18	18
FYN	-0.005	0.066	-9999	-0.21	49	49
neuron projection morphogenesis	-0.013	0.073	-9999	-0.24	50	50
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.013	0.074	-9999	-0.24	50	50
EPHA5	-0.021	0.1	-9999	-0.41	33	33

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.038	0.1	-9999	-0.32	14	14
NF kappa B1 p50/RelA/I kappa B alpha	-0.012	0.091	-9999	-0.28	13	13
alphaV/beta3 Integrin/Osteopontin/Src	-0.042	0.1	-9999	-0.21	148	148
AP1	-0.079	0.15	-9999	-0.34	92	92
ILK	-0.049	0.11	-9999	-0.32	17	17
bone resorption	-0.027	0.1	-9999	-0.3	28	28
PTK2B	0.011	0	-9999	-10000	0	0
PYK2/p130Cas	-0.033	0.097	-9999	-0.3	15	15
ITGAV	0.014	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.005	0.057	-9999	-0.28	20	20
alphaV/beta3 Integrin/Osteopontin	-0.064	0.12	-9999	-0.24	95	95
MAP3K1	-0.05	0.11	-9999	-0.32	18	18
JUN	0.006	0.048	-9999	-0.41	7	7
MAPK3	-0.035	0.1	-9999	-0.32	14	14
MAPK1	-0.035	0.1	-9999	-0.32	14	14
Rac1/GDP	0.008	0	-9999	-10000	0	0
NFKB1	0.01	0.018	-9999	-0.41	1	1
MAPK8	-0.041	0.1	-9999	-0.32	21	21
ITGB3	-0.062	0.16	-9999	-0.4	96	96
NFKBIA	-0.024	0.098	-9999	-0.3	14	14
FOS	-0.12	0.19	-9999	-0.41	159	159
CD44	0.005	0.048	-9999	-0.41	7	7
CHUK	0.011	0	-9999	-10000	0	0
PLAU	-0.02	0.095	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.045	0.059	-9999	-0.26	13	13
BCAR1	0.011	0	-9999	-10000	0	0
RELA	0.011	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.031	0.11	-9999	-0.27	96	96
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.051	0.11	-9999	-0.32	19	19
VAV3	-0.079	0.12	-9999	-0.3	65	65
MAP3K14	-0.048	0.11	-9999	-0.32	17	17
ROCK2	0.001	0.065	-9999	-0.41	13	13
SPP1	-0.081	0.15	-9999	-0.32	148	148
RAC1	0.011	0	-9999	-10000	0	0
Rac1/GTP	-0.067	0.11	-9999	-0.27	65	65
MMP2	-0.071	0.15	-9999	-0.37	70	70

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.24	0.38	-10000	0	-1	55	55
STAT6 (cleaved dimer)	-0.27	0.34	-10000	0	-0.95	75	75
IGHG1	-0.085	0.14	-10000	0	-0.36	20	20
IGHG3	-0.24	0.36	-10000	0	-0.92	77	77
AKT1	-0.1	0.2	-10000	0	-0.68	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.064	0.16	-10000	0	-0.65	7	7
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.12	0.23	-10000	0	-0.63	39	39
THY1	-0.24	0.38	-10000	0	-1	56	56
MYB	-0.02	0.098	-10000	0	-0.33	48	48
HMGA1	-0.035	0.12	-10000	0	-0.33	71	71
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.14	0.23	-10000	0	-0.61	39	39
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.1	0.2	-10000	0	-0.67	13	13
SP1	0.017	0.002	-10000	0	-10000	0	0
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
SOCS5	0.017	0.013	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.22	0.37	-10000	0	-1	61	61
SOCS1	-0.14	0.26	-10000	0	-0.7	44	44
SOCS3	-0.1	0.21	-10000	0	-0.94	6	6
FCER2	-0.18	0.3	-10000	0	-0.88	29	29
PARP14	0.012	0.002	-10000	0	-10000	0	0
CCL17	-0.24	0.38	-10000	0	-1	54	54
GRB2	0.011	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.08	0.17	-10000	0	-0.61	6	6
T cell proliferation	-0.24	0.38	-10000	0	-1	59	59
IL4R/JAK1	-0.24	0.38	-10000	0	-1	58	58
EGR2	-0.27	0.46	-10000	0	-1.3	59	59
JAK2	-0.01	0.061	-10000	0	-0.43	9	9
JAK3	0.012	0.031	-10000	0	-0.34	4	4
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
JAK1	0.007	0.028	-10000	0	-0.4	2	2
COL1A2	-0.079	0.18	-10000	0	-1.4	5	5
CCL26	-0.24	0.38	-10000	0	-1	56	56
IL4R	-0.25	0.4	-10000	0	-1.1	59	59
PTPN6	0.017	0.018	-10000	0	-0.31	1	1
IL13RA2	-0.24	0.38	-10000	0	-1	57	57
IL13RA1	-0.002	0.027	-10000	0	-10000	0	0
IRF4	-0.061	0.22	-10000	0	-1.1	18	18
ARG1	-0.054	0.11	-10000	0	-10000	0	0
CBL	-0.12	0.22	-10000	0	-0.58	34	34
GTF3A	0.018	0.001	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
IL13RA1/JAK2	-0.008	0.051	-10000	0	-0.28	9	9
IRF4/BCL6	-0.054	0.21	-10000	0	-1	17	17
CD40LG	0.007	0.063	-10000	0	-0.42	11	11
MAPK14	-0.12	0.22	-10000	0	-0.61	29	29
mitosis	-0.097	0.2	-10000	0	-0.64	12	12
STAT6	-0.27	0.42	-10000	0	-1.1	66	66
SPI1	0.011	0.026	-10000	0	-0.33	3	3
RPS6KB1	-0.089	0.19	-10000	0	-0.64	10	10
STAT6 (dimer)	-0.27	0.42	-10000	0	-1.1	66	66
STAT6 (dimer)/PARP14	-0.25	0.39	-10000	0	-1.1	62	62
mast cell activation	0.006	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.096	0.19	-10000	0	-0.67	9	9
FRAP1	-0.1	0.2	-10000	0	-0.68	12	12
LTA	-0.24	0.38	-10000	0	-1	53	53
FES	0.01	0.018	-10000	0	-0.41	1	1
T-helper 1 cell differentiation	0.26	0.42	1.1	71	-10000	0	71
CCL11	-0.25	0.39	-10000	0	-1.1	63	63
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.095	0.19	-10000	0	-0.7	8	8
IL2RG	0.009	0.049	-10000	0	-0.36	9	9
IL10	-0.24	0.37	-10000	0	-1	58	58
IRS1	-0.031	0.13	-10000	0	-0.41	53	53
IRS2	-0.045	0.14	-10000	0	-0.41	70	70
IL4	-0.058	0.1	-10000	0	-10000	0	0
IL5	-0.24	0.37	-10000	0	-1	58	58
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.21	0.32	-10000	0	-0.84	60	60
COL1A1	-0.075	0.16	-10000	0	-1.5	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.24	0.38	-10000	0	-1.1	48	48
IL2R gamma/JAK3	0.015	0.046	-10000	0	-0.3	10	10
TFF3	-0.3	0.43	-10000	0	-1.1	75	75
ALOX15	-0.25	0.38	-10000	0	-1	62	62
MYBL1	0.011	0	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.21	0.32	-10000	0	-0.83	63	63
SHC1	0.011	0	-10000	0	-10000	0	0
CEBPB	0.013	0.003	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.12	0.21	-10000	0	-0.63	23	23
mol:PI-3-4-5-P3	-0.1	0.2	-10000	0	-0.68	12	12
PI3K	-0.11	0.22	-10000	0	-0.75	11	11
DOK2	0.008	0.031	-10000	0	-0.35	4	4
ETS1	0.017	0.02	-10000	0	-0.38	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.072	0.16	-10000	0	-0.62	5	5
ITGB3	-0.36	0.56	-10000	0	-1.3	113	113
PIGR	-0.33	0.47	-10000	0	-1.2	87	87
IGHE	0.019	0.033	-10000	0	-10000	0	0
MAPKKK cascade	-0.071	0.16	-10000	0	-0.61	5	5
BCL6	0.01	0.018	-10000	0	-0.41	1	1
OPRM1	-0.24	0.38	-10000	0	-1	59	59
RETNLB	-0.24	0.38	-10000	0	-1	56	56
SELP	-0.52	0.66	-10000	0	-1.3	208	208
AICDA	-0.23	0.36	-10000	0	-1	53	53

×

TCGA08_p53

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
CDKN2A	-0.089	0.12	-9999	-0.23	219	219
TP53	-0.023	0.03	-9999	-0.34	1	1
Senescence	-0.023	0.03	-9999	-0.34	1	1
Apoptosis	-0.023	0.03	-9999	-0.34	1	1
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.047	0.055	-9999	-10000	0	0
MDM4	0.011	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.02	0.059	0.2	52	-10000	0	52
RFC1	0.02	0.059	0.2	52	-10000	0	52
PRKDC	0.02	0.059	0.2	52	-10000	0	52
RIPK1	0.011	0.002	-10000	0	-10000	0	0
CASP7	-0.002	0.016	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	0.018	0.064	0.19	57	-0.21	5	62
MAP2K4	0.036	0.057	-10000	0	-0.24	12	12
mol:ceramide	0.027	0.046	-10000	0	-0.24	4	4
GSN	0.017	0.063	0.2	51	-0.22	5	56
FASLG/FAS/FADD/FAF1/Caspase 8	0.037	0.055	0.17	51	-0.25	2	53
FAS	0.007	0.041	-10000	0	-0.41	5	5
BID	0.001	0.017	0.27	2	-10000	0	2
MAP3K1	0.034	0.038	-10000	0	-10000	0	0
MAP3K7	0.011	0.002	-10000	0	-10000	0	0
RB1	0.018	0.061	0.2	51	-0.22	2	53
CFLAR	0.011	0.002	-10000	0	-10000	0	0
HGF/MET	-0.061	0.13	-10000	0	-0.26	158	158
ARHGDIB	0.02	0.059	0.2	52	-10000	0	52
FADD	0.011	0.003	-10000	0	-10000	0	0
actin filament polymerization	-0.017	0.063	0.22	5	-0.2	51	56
NFKB1	-0.009	0.044	-10000	0	-0.65	1	1
MAPK8	0.036	0.087	-10000	0	-0.41	16	16
DFFA	0.02	0.059	0.2	52	-10000	0	52
DNA fragmentation during apoptosis	0.02	0.059	0.2	52	-10000	0	52
FAS/FADD/MET	0.017	0.037	-10000	0	-0.21	13	13
CFLAR/RIP1	0.015	0.003	-10000	0	-10000	0	0
FAIM3	0.009	0.03	-10000	0	-0.38	3	3
FAF1	0.011	0.004	-10000	0	-10000	0	0
PARP1	0.02	0.059	0.2	52	-10000	0	52
DFFB	0.02	0.059	0.2	52	-10000	0	52
CHUK	-0.008	0.04	-10000	0	-0.6	1	1
FASLG	0.003	0.055	-10000	0	-0.36	12	12
FAS/FADD	0.014	0.029	-10000	0	-0.28	5	5
HGF	-0.074	0.17	-10000	0	-0.41	106	106
LMNA	0.018	0.055	0.18	52	-10000	0	52
CASP6	0.02	0.059	0.2	52	-10000	0	52
CASP10	0.01	0.026	-10000	0	-0.41	2	2
CASP3	0.023	0.069	0.23	52	-10000	0	52
PTPN13	-0.041	0.14	-10000	0	-0.41	65	65
CASP8	0.001	0.021	0.33	2	-10000	0	2
IL6	-0.007	0.21	-10000	0	-1.2	16	16
MET	0.005	0.047	-10000	0	-0.37	8	8
ICAD/CAD	0.018	0.055	0.18	52	-10000	0	52
FASLG/FAS/FADD/FAF1/Caspase 10	0.028	0.046	-10000	0	-0.24	4	4
activation of caspase activity by cytochrome c	0.001	0.017	0.27	2	-10000	0	2
PAK2	0.02	0.059	0.2	52	-10000	0	52
BCL2	-0.029	0.12	-10000	0	-0.41	50	50

×

Glypican 2 network

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
MDK	0.01	0.015	-9999	-0.33	1	1
GPC2	-0.014	0.088	-9999	-0.33	38	38
GPC2/Midkine	-0.001	0.061	-9999	-0.22	39	39
neuron projection morphogenesis	-0.001	0.061	-9999	-0.22	39	39

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.011	0	-9999	-10000	0	0
EGFR	0	0.067	-9999	-0.4	14	14
EGF/EGFR	-0.067	0.1	-9999	-0.2	169	169
EGF/EGFR dimer/SHC/GRB2/SOS1	0.019	0.049	-9999	-0.34	1	1
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.12	0.19	-9999	-0.41	159	159
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.005	0.071	-9999	-0.34	23	23
EGF/EGFR dimer/SHC	0.007	0.058	-9999	-0.2	36	36
mol:GDP	-0.011	0.041	-9999	-0.33	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.005	0.048	-9999	-0.41	7	7
GRB2/SOS1	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.009	0.036	-9999	-0.3	1	1
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	-0.01	0.037	-9999	-0.31	1	1
FRAP1	0.016	0.046	-9999	-0.32	1	1
EGF/EGFR dimer	-0.002	0.068	-9999	-0.25	36	36
SOS1	0.011	0	-9999	-10000	0	0
GRB2	0.011	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.077	0.14	-9999	-0.28	163	163

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.015	0	-9999	0	-10000	0	0
ARNO/beta Arrestin1-2	-0.02	0.068	-9999	0	-0.33	1	1
EGFR	0	0.067	-9999	0	-0.4	14	14
EPHA2	0.011	0	-9999	0	-10000	0	0
USP6	0.011	0	-9999	0	-10000	0	0
IQSEC1	0.01	0.018	-9999	0	-0.41	1	1
EGFR/EGFR/EGF/EGF	-0.002	0.068	-9999	0	-0.25	36	36
ARRB2	0.008	0.002	-9999	0	-10000	0	0
mol:GTP	0.015	0.011	-9999	0	-0.14	1	1
ARRB1	0.009	0.026	-9999	0	-0.41	2	2
FBXO8	0.011	0	-9999	0	-10000	0	0
TSHR	-0.006	0.071	-9999	0	-0.34	22	22
EGF	-0.005	0.071	-9999	0	-0.34	23	23
somatostatin receptor activity	0	0	-9999	0	-0.001	77	77
ARAP2	0.009	0.032	-9999	0	-0.41	3	3
mol:GDP	-0.045	0.09	-9999	0	-0.21	80	80
mol:PI-3-4-5-P3	0	0	-9999	0	-0.001	47	47
ITGA2B	0.005	0.047	-9999	0	-0.4	7	7
ARF6	0.011	0	-9999	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.027	0.018	-9999	0	-0.2	2	2
ADAP1	0.011	0	-9999	0	-10000	0	0
KIF13B	0.011	0	-9999	0	-10000	0	0
HGF/MET	-0.047	0.12	-9999	0	-0.28	111	111
PXN	0.011	0	-9999	0	-10000	0	0
ARF6/GTP	-0.04	0.095	-9999	0	-0.22	69	69
EGFR/EGFR/EGF/EGF/ARFGEP100	0.006	0.058	-9999	0	-0.23	18	18
ADRB2	-0.063	0.16	-9999	0	-0.41	92	92
receptor agonist activity	0	0	-9999	0	0	74	74
actin filament binding	0	0	-9999	0	0	73	73
SRC	0.011	0	-9999	0	-10000	0	0
ITGB3	-0.065	0.16	-9999	0	-0.41	96	96
GNAQ	0.009	0.026	-9999	0	-0.41	2	2
EFA6/PI-4-5-P2	0	0	-9999	0	-0.001	62	62
ARF6/GDP	0.018	0.048	-9999	0	-0.28	5	5
ARF6/GDP/GULP/ACAP1	-0.046	0.11	-9999	0	-0.29	62	62
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.016	0.09	-9999	0	-0.2	100	100
ACAP1	0.007	0.036	-9999	0	-0.36	5	5
ACAP2	0.01	0.018	-9999	0	-0.41	1	1
LHCGR/beta Arrestin2	0.001	0.004	-9999	0	-10000	0	0
EFNA1	0.01	0.021	-9999	0	-0.33	2	2
HGF	-0.074	0.17	-9999	0	-0.41	106	106
CYTH3	0.009	0	-9999	0	-10000	0	0
CYTH2	0.007	0.002	-9999	0	-10000	0	0
NCK1	0.009	0.026	-9999	0	-0.41	2	2
fibronectin binding	0	0	-9999	0	0	60	60
endosomal lumen acidification	0	0	0	2	0	45	47
microtubule-based process	0	0	-9999	0	-10000	0	0
GULP1	-0.035	0.13	-9999	0	-0.41	58	58
GNAQ/ARNO	0.012	0.013	-9999	0	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	0	0	3	3
PIP3-E	0	0	-9999	0	0	17	17
MET	0.005	0.047	-9999	0	-0.37	8	8
GNA14	-0.031	0.13	-9999	0	-0.41	53	53
GNA15	0.006	0.039	-9999	0	-0.33	7	7
GIT1	0.011	0	-9999	0	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	0	-0.001	65	65
GNA11	0.002	0.06	-9999	0	-0.41	11	11
LHCGR	0.001	0.003	-9999	0	-10000	0	0
AGTR1	-0.085	0.17	-9999	0	-0.41	116	116
desensitization of G-protein coupled receptor protein signaling pathway	0.001	0.004	-9999	0	-10000	0	0
IPCEF1/ARNO	0.006	0.044	-9999	0	-0.31	1	1
alphaIIb/beta3 Integrin	-0.041	0.12	-9999	0	-0.28	103	103

×

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

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
MET/RANBP9	0.012	0.033	-10000	0	-0.25	8	8
CRKL	-0.013	0.096	-10000	0	-0.41	10	10
mol:PIP3	-0.009	0.043	0.38	6	-10000	0	6
AKT1	0.005	0.03	0.28	6	-10000	0	6
PTK2B	0.011	0	-10000	0	-10000	0	0
RAPGEF1	-0.007	0.091	-10000	0	-0.39	10	10
RANBP10	0.011	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
HGF/MET/SHIP2	-0.031	0.1	-10000	0	-0.23	111	111
MAP3K5	0.001	0.09	-10000	0	-0.39	10	10
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.02	0.096	-10000	0	-0.2	107	107
AP1	-0.066	0.12	-10000	0	-0.25	160	160
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	-0.21	0.34	-10000	0	-0.72	160	160
STAT3 (dimer)	-0.015	0.097	-10000	0	-0.2	110	110
GAB1/CRKL/SHP2/PI3K	-0.034	0.076	-10000	0	-0.4	11	11
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
CBL/CRK	-0.006	0.092	-10000	0	-0.41	9	9
PTPN11	0.011	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.011	0	-10000	0	-10000	0	0
PTEN	0.006	0.045	-10000	0	-0.41	6	6
ELK1	-0.003	0.019	-10000	0	-0.14	8	8
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.025	0.052	-10000	0	-0.26	5	5
PAK1	0.01	0.028	0.27	6	-10000	0	6
HGF/MET/RANBP10	-0.031	0.1	-10000	0	-0.23	111	111
HRAS	-0.024	0.12	-10000	0	-0.55	6	6
DOCK1	-0.009	0.097	-10000	0	-0.41	12	12
GAB1	-0.02	0.1	-10000	0	-0.44	10	10
CRK	-0.013	0.096	-10000	0	-0.41	10	10
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.086	0.17	-10000	0	-0.42	107	107
JUN	0.005	0.048	-10000	0	-0.41	7	7
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.025	0.074	-10000	0	-0.17	107	107
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
cell morphogenesis	0	0.11	-10000	0	-0.4	10	10
GRB2/SHC	-0.009	0.067	-10000	0	-0.29	4	4
FOS	-0.12	0.19	-10000	0	-0.41	159	159
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.003	0.019	-10000	0	-0.14	8	8
HGF/MET/MUC20	-0.039	0.1	-10000	0	-0.24	111	111
cell migration	-0.009	0.066	-10000	0	-0.29	4	4
GRB2	0.011	0	-10000	0	-10000	0	0
CBL	0.011	0	-10000	0	-10000	0	0
MET/RANBP10	0.012	0.033	-10000	0	-0.25	8	8
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.019	0.096	-10000	0	-0.2	110	110
MET/MUC20	0.004	0.033	-10000	0	-0.26	8	8
RAP1B	0	0.087	-10000	0	-0.38	9	9
RAP1A	0	0.087	-10000	0	-0.43	7	7
HGF/MET/RANBP9	-0.031	0.1	-10000	0	-0.23	111	111
RAF1	-0.017	0.11	-10000	0	-0.51	6	6
STAT3	-0.015	0.097	-10000	0	-0.2	110	110
cell proliferation	-0.023	0.13	-10000	0	-0.28	107	107
RPS6KB1	-0.003	0.029	-10000	0	-0.14	3	3
MAPK3	-0.007	0.017	-10000	0	-10000	0	0
MAPK1	-0.007	0.017	-10000	0	-10000	0	0
RANBP9	0.011	0	-10000	0	-10000	0	0
MAPK8	0.012	0.095	-10000	0	-0.42	12	12
SRC	-0.011	0.09	-10000	0	-0.37	5	5
PI3K	-0.011	0.072	-10000	0	-0.3	9	9
MET/Glomulin	0.007	0.028	-10000	0	-0.22	8	8
SOS1	0.011	0	-10000	0	-10000	0	0
MAP2K1	-0.01	0.1	-10000	0	-0.58	4	4
MET	0.005	0.047	-10000	0	-0.37	8	8
MAP4K1	-0.005	0.092	-10000	0	-0.41	9	9
PTK2	0.011	0	-10000	0	-10000	0	0
MAP2K2	-0.01	0.1	-10000	0	-0.58	4	4
BAD	0.01	0.028	0.27	6	-10000	0	6
MAP2K4	0.006	0.084	-10000	0	-0.36	10	10
SHP2/GRB2/SOS1/GAB1	-0.033	0.075	-10000	0	-0.44	8	8
INPPL1	0.011	0	-10000	0	-10000	0	0
PXN	0.011	0	-10000	0	-10000	0	0
SH3KBP1	0.011	0	-10000	0	-10000	0	0
HGS	-0.017	0.069	-10000	0	-0.15	107	107
PLCgamma1/PKC	0.008	0	-10000	0	-10000	0	0
HGF	-0.074	0.17	-10000	0	-0.41	106	106
RASA1	0.007	0.041	-10000	0	-0.41	5	5
NCK1	0.009	0.026	-10000	0	-0.41	2	2
PTPRJ	0.011	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.012	0.076	-10000	0	-0.16	108	108
PDPK1	-0.001	0.034	0.31	6	-10000	0	6
HGF/MET/SHIP	-0.032	0.1	-10000	0	-0.23	112	112

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.014	0.043	-9999	-0.41	5	5
Syndecan-4/Syndesmos	-0.011	0.068	-9999	-10000	0	0
positive regulation of JNK cascade	-0.12	0.11	-9999	-0.33	41	41
Syndecan-4/ADAM12	-0.014	0.071	-9999	-10000	0	0
CCL5	0.003	0.054	-9999	-0.37	11	11
Rac1/GDP	0.008	0	-9999	-10000	0	0
DNM2	0.011	0	-9999	-10000	0	0
ITGA5	0.011	0	-9999	-10000	0	0
SDCBP	0.011	0	-9999	-10000	0	0
PLG	-0.026	0.12	-9999	-0.38	50	50
ADAM12	0.003	0.051	-9999	-0.33	12	12
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.039	0.042	-9999	-0.12	34	34
Syndecan-4/Laminin alpha1	-0.06	0.095	-9999	-0.34	16	16
Syndecan-4/CXCL12/CXCR4	-0.12	0.11	-9999	-0.35	41	41
Syndecan-4/Laminin alpha3	-0.016	0.074	-9999	-10000	0	0
MDK	0.01	0.015	-9999	-0.33	1	1
Syndecan-4/FZD7	-0.041	0.098	-9999	-0.35	10	10
Syndecan-4/Midkine	-0.011	0.068	-9999	-10000	0	0
FZD7	-0.055	0.15	-9999	-0.41	83	83
Syndecan-4/FGFR1/FGF	-0.11	0.1	-9999	-0.36	29	29
THBS1	-0.046	0.14	-9999	-0.41	71	71
integrin-mediated signaling pathway	-0.015	0.073	-9999	-0.37	2	2
positive regulation of MAPKKK cascade	-0.12	0.11	-9999	-0.33	41	41
Syndecan-4/TACI	-0.017	0.074	-9999	-0.34	2	2
CXCR4	0.011	0	-9999	-10000	0	0
cell adhesion	0.013	0.051	-9999	-0.16	38	38
Syndecan-4/Dynamin	-0.011	0.068	-9999	-10000	0	0
Syndecan-4/TSP1	-0.037	0.093	-9999	-0.37	8	8
Syndecan-4/GIPC	-0.011	0.068	-9999	-10000	0	0
Syndecan-4/RANTES	-0.014	0.073	-9999	-0.36	2	2
ITGB1	0.011	0	-9999	-10000	0	0
LAMA1	-0.1	0.16	-9999	-0.33	175	175
LAMA3	0	0.068	-9999	-0.41	14	14
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	-0.007	0.099	-9999	-0.37	34	34
Syndecan-4/alpha-Actinin	-0.011	0.068	-9999	-10000	0	0
TFPI	-0.038	0.14	-9999	-0.41	61	61
F2	-0.024	0.095	-9999	-0.33	46	46
alpha5/beta1 Integrin	0.016	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.058	0.096	-9999	-0.32	20	20
ACTN1	0.011	0	-9999	-10000	0	0
TNC	0.002	0.062	-9999	-0.4	12	12
Syndecan-4/CXCL12	-0.13	0.12	-9999	-0.36	41	41
FGF6	0	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CXCL12	-0.26	0.2	-9999	-0.41	334	334
TNFRSF13B	-0.002	0.058	-9999	-0.33	16	16
FGF2	-0.22	0.21	-9999	-0.41	284	284
FGFR1	0.01	0.018	-9999	-0.41	1	1
Syndecan-4/PI-4-5-P2	-0.018	0.067	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.011	0.04	-9999	-0.39	5	5
cell migration	-0.017	0.019	-9999	-10000	0	0
PRKCD	0.015	0.008	-9999	-10000	0	0
vasculogenesis	-0.036	0.091	-9999	-0.36	8	8
SDC4	-0.018	0.071	-9999	-10000	0	0
Syndecan-4/Tenascin C	-0.015	0.075	-9999	-0.38	2	2
Syndecan-4/PI-4-5-P2/PKC alpha	-0.031	0.034	-9999	-0.11	1	1
Syndecan-4/Syntenin	-0.011	0.068	-9999	-10000	0	0
MMP9	-0.13	0.17	-9999	-0.33	215	215
Rac1/GTP	0.013	0.052	-9999	-0.17	38	38
cytoskeleton organization	-0.011	0.067	-9999	-10000	0	0
GIPC1	0.011	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.033	0.095	-9999	-0.35	11	11

×

Visual signal transduction: Rods

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
mol:K +	0.011	0	-9999	-10000	0	0
GNAT1/GTP	0.002	0.025	-9999	-0.23	6	6
Metarhodopsin II/Arrestin	0.006	0.015	-9999	-0.18	3	3
PDE6G/GNAT1/GTP	-0.007	0.059	-9999	-0.19	50	50
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.002	0.036	-9999	-0.33	6	6
GRK1	0.002	0.015	-9999	-0.33	1	1
CNG Channel	-0.029	0.064	-9999	-0.29	13	13
mol:Na +	-0.018	0.053	-9999	-0.34	6	6
mol:ADP	0.002	0.015	-9999	-0.33	1	1
RGS9-1/Gbeta5/R9AP	-0.042	0.11	-9999	-0.23	115	115
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.018	0.054	-9999	-0.34	6	6
CNGB1	-0.006	0.072	-9999	-0.33	25	25
RDH5	0.009	0.026	-9999	-0.33	3	3
SAG	0.005	0.005	-9999	-10000	0	0
mol:Ca2+	0.011	0.06	-9999	-0.32	6	6
Na + (4 Units)	-0.016	0.049	-9999	-0.31	6	6
RGS9	-0.081	0.17	-9999	-0.41	115	115
GNB1/GNGT1	-0.067	0.11	-9999	-0.22	186	186
GNAT1/GDP	-0.033	0.094	-9999	-0.2	116	116
GUCY2D	0.001	0.049	-9999	-0.33	11	11
GNGT1	-0.11	0.16	-9999	-0.33	186	186
GUCY2F	0.005	0.005	-9999	-10000	0	0
GNB5	0.011	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.003	0.067	-9999	-0.21	23	23
mol:11-cis-retinal	0.009	0.026	-9999	-0.33	3	3
mol:cGMP	0.007	0.045	-9999	-0.22	9	9
GNB1	0.011	0	-9999	-10000	0	0
Rhodopsin	0.009	0.025	-9999	-0.22	6	6
SLC24A1	0.011	0	-9999	-10000	0	0
CNGA1	0.002	0.055	-9999	-0.33	14	14
Metarhodopsin II	0.004	0.015	-9999	-0.16	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.005	0.048	-9999	-0.23	9	9
RGS9BP	-0.006	0.071	-9999	-0.33	24	24
Metarhodopsin II/Transducin	-0.014	0.038	-9999	-10000	0	0
GCAP Family/Ca ++	0.003	0.04	-9999	-0.18	24	24
PDE6A/B	0.001	0.063	-9999	-0.26	28	28
mol:Pi	-0.042	0.11	-9999	-0.23	115	115
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.046	0.087	-9999	-0.16	187	187
PDE6B	-0.008	0.086	-9999	-0.4	24	24
PDE6A	0.008	0.03	-9999	-0.33	4	4
PDE6G	-0.018	0.096	-9999	-0.33	45	45
RHO	0.003	0.026	-9999	-0.33	3	3
PDE6	-0.062	0.09	-9999	-0.33	21	21
GUCA1A	-0.004	0.06	-9999	-0.33	17	17
GC2/GCAP Family	0.006	0.04	-9999	-0.21	7	7
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.005	0.048	-9999	-0.41	7	7

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.011	0	-9999	-10000	0	0
VLDLR	0.009	0.026	-9999	-0.41	2	2
LRPAP1	0.011	0	-9999	-10000	0	0
NUDC	0.011	0	-9999	-10000	0	0
RELN/LRP8	-0.07	0.12	-9999	-0.23	193	193
CaM/Ca2+	0.008	0	-9999	-10000	0	0
KATNA1	0.011	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.057	0.11	-9999	-0.2	188	188
IQGAP1/CaM	0.016	0	-9999	-10000	0	0
DAB1	-0.001	0.053	-9999	-0.33	13	13
IQGAP1	0.011	0	-9999	-10000	0	0
PLA2G7	0.006	0.043	-9999	-0.4	6	6
CALM1	0.011	0	-9999	-10000	0	0
DYNLT1	0.011	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.014	0.023	-9999	-0.22	5	5
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.011	0	-9999	-10000	0	0
CDK5R1	0.01	0.015	-9999	-0.33	1	1
LIS1/Poliovirus Protein 3A	0.013	0	-9999	-10000	0	0
CDK5R2	-0.028	0.1	-9999	-0.33	55	55
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.076	0.12	-9999	-0.23	204	204
YWHAE	0.011	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.032	0.091	-9999	-0.26	3	3
MAP1B	-0.013	0.056	-9999	-0.25	27	27
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.039	0.097	-9999	-0.3	3	3
RELN	-0.14	0.2	-9999	-0.41	191	191
PAFAH/LIS1	0.019	0.026	-9999	-0.22	6	6
LIS1/CLIP170	0.022	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.039	0.054	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.05	0.1	-9999	-0.19	187	187
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.04	0.095	-9999	-0.24	17	17
LIS1/IQGAP1	0.022	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.018	0	-9999	-10000	0	0
PAFAH1B3	0.005	0.044	-9999	-0.33	9	9
PAFAH1B2	0.01	0.018	-9999	-0.41	1	1
MAP1B/LIS1/Dynein heavy chain	0.012	0.037	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.026	0.088	-9999	-0.26	2	2
LRP8	0.008	0.033	-9999	-0.33	5	5
NDEL1/Katanin 60	-0.032	0.091	-9999	-0.26	3	3
P39/CDK5	-0.057	0.1	-9999	-0.31	18	18
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.022	0	-9999	-10000	0	0
CDK5	-0.047	0.1	-9999	-0.26	5	5
PPP2R5D	0.011	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.019	0	-9999	-10000	0	0
CSNK2A1	0.011	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.051	0.1	-9999	-0.19	76	76
RELN/VLDLR	-0.056	0.11	-9999	-0.2	187	187
CDC42	0	0	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

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
NRIP1	0.009	0.032	-9999	-0.41	3	3
SVIL	-0.036	0.13	-9999	-0.41	59	59
ZNF318	0.01	0.005	-9999	-10000	0	0
JMJD2C	-0.003	0.03	-9999	-0.11	34	34
T-DHT/AR/Ubc9	-0.026	0.1	-9999	-0.24	90	90
CARM1	0.011	0	-9999	-10000	0	0
PRDX1	0.011	0	-9999	-10000	0	0
PELP1	0.011	0.001	-9999	-10000	0	0
CTNNB1	0.011	0.002	-9999	-10000	0	0
AKT1	0.011	0.001	-9999	-10000	0	0
PTK2B	0.011	0.002	-9999	-10000	0	0
MED1	0.011	0.001	-9999	-10000	0	0
MAK	-0.011	0.082	-9999	-0.33	32	32
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.007	0.041	-9999	-0.41	5	5
GSN	0.007	0.045	-9999	-0.41	6	6
NCOA2	-0.003	0.076	-9999	-0.41	18	18
NCOA6	0.011	0.002	-9999	-10000	0	0
DNA-PK	0.022	0.005	-9999	-10000	0	0
NCOA4	0.011	0	-9999	-10000	0	0
PIAS3	0.011	0.002	-9999	-10000	0	0
cell proliferation	-0.012	0.024	-9999	-10000	0	0
XRCC5	0.011	0.001	-9999	-10000	0	0
UBE3A	0.012	0.002	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.046	0.12	-9999	-0.25	127	127
FHL2	0.001	0.11	-9999	-0.98	5	5
RANBP9	0.011	0.002	-9999	-10000	0	0
JMJD1A	0.005	0.03	-9999	-0.13	23	23
CDK6	0.001	0.065	-9999	-0.41	13	13
TGFB1I1	-0.12	0.2	-9999	-0.41	171	171
T-DHT/AR/CyclinD1	-0.026	0.11	-9999	-0.25	91	91
XRCC6	0.011	0.001	-9999	-10000	0	0
T-DHT/AR	-0.021	0.12	-9999	-0.26	97	97
CTDSP1	0.011	0.001	-9999	-10000	0	0
CTDSP2	0.01	0.003	-9999	-10000	0	0
BRCA1	0.011	0.002	-9999	-10000	0	0
TCF4	-0.005	0.08	-9999	-0.41	20	20
CDKN2A	-0.13	0.17	-9999	-0.33	219	219
SRF	0.016	0.011	-9999	-10000	0	0
NKX3-1	-0.024	0.17	-9999	-0.94	16	16
KLK3	-0.006	0.043	-9999	-10000	0	0
TMF1	0.011	0.001	-9999	-10000	0	0
HNRNPA1	0.011	0.002	-9999	-10000	0	0
AOF2	0	0.002	-9999	-10000	0	0
APPL1	0.018	0.003	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.026	0.1	-9999	-0.24	90	90
AR	-0.062	0.16	-9999	-0.42	90	90
UBA3	0.011	0.001	-9999	-10000	0	0
PATZ1	0.011	0.002	-9999	-10000	0	0
PAWR	0.011	0.001	-9999	-10000	0	0
PRKDC	0.011	0.001	-9999	-10000	0	0
PA2G4	0.011	0.002	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.022	0.094	-9999	-0.22	92	92
RPS6KA3	0.011	0.018	-9999	-0.41	1	1
T-DHT/AR/ARA70	-0.025	0.1	-9999	-0.24	90	90
LATS2	0.009	0.026	-9999	-0.41	2	2
T-DHT/AR/PRX1	-0.022	0.094	-9999	-0.22	90	90
Cyclin D3/CDK11 p58	0.008	0	-9999	-10000	0	0
VAV3	-0.07	0.14	-9999	-0.33	126	126
KLK2	-0.065	0.19	-9999	-0.87	27	27
CASP8	0.011	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.023	0.11	-9999	-0.23	102	102
TMPRSS2	-0.018	0.14	-9999	-0.64	17	17
CCND1	0.01	0.021	-9999	-0.33	2	2
PIAS1	0.012	0.002	-9999	-10000	0	0
mol:T-DHT	-0.001	0.02	-9999	-0.066	35	35
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.012	0.004	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.032	0.11	-9999	-0.25	104	104
CMTM2	0.008	0.026	-9999	-0.33	3	3
SNURF	-0.024	0.11	-9999	-0.41	40	40
ZMIZ1	0.008	0.037	-9999	-0.42	3	3
CCND3	0.011	0	-9999	-10000	0	0
TGIF1	0.011	0.002	-9999	-10000	0	0
FKBP4	0.011	0.002	-9999	-10000	0	0

×

BCR 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.015	0.086	-10000	0	-0.29	31	31
IKBKB	0.027	0.048	0.16	1	-0.17	3	4
AKT1	0.004	0.066	0.19	4	-0.2	28	32
IKBKG	0.029	0.049	0.16	1	-0.18	3	4
CALM1	0.02	0.08	0.17	65	-0.25	20	85
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
MAP3K1	0.004	0.11	-10000	0	-0.43	26	26
MAP3K7	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0.015	0.083	0.18	65	-0.26	21	86
DOK1	0.011	0	-10000	0	-10000	0	0
AP-1	0	0.077	0.14	40	-0.19	30	70
LYN	0.011	0	-10000	0	-10000	0	0
BLNK	0.009	0.03	-10000	0	-0.38	3	3
SHC1	0.011	0	-10000	0	-10000	0	0
BCR complex	-0.024	0.096	-10000	0	-0.24	81	81
CD22	-0.06	0.13	-10000	0	-0.5	32	32
CAMK2G	0.025	0.076	0.18	4	-0.23	20	24
CSNK2A1	0.011	0	-10000	0	-10000	0	0
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
SHC/GRB2/SOS1	-0.02	0.048	-10000	0	-0.3	3	3
GO:0007205	0.015	0.084	0.18	65	-0.27	21	86
SYK	0.01	0.015	-10000	0	-0.33	1	1
ELK1	0.02	0.08	0.17	65	-0.25	20	85
NFATC1	0.004	0.1	0.18	3	-0.34	31	34
B-cell antigen/BCR complex	-0.024	0.096	-10000	0	-0.24	81	81
PAG1/CSK	0.015	0.022	-10000	0	-0.28	3	3
NFKBIB	0.019	0.021	0.083	1	-0.12	1	2
HRAS	0.02	0.072	0.19	1	-0.23	20	21
NFKBIA	0.019	0.021	0.083	1	-0.12	1	2
NF-kappa-B/RelA/I kappa B beta	0.022	0.02	0.084	1	-0.14	1	2
RasGAP/Csk	0	0.074	-10000	0	-0.2	35	35
mol:GDP	0.014	0.08	0.17	65	-0.25	21	86
PTEN	0.006	0.045	-10000	0	-0.41	6	6
CD79B	-0.009	0.089	-10000	0	-0.41	25	25
NF-kappa-B/RelA/I kappa B alpha	0.022	0.02	0.084	1	-0.14	1	2
GRB2	0.011	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.008	0.12	-10000	0	-0.43	30	30
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
mol:IP3	0.015	0.084	0.18	65	-0.27	21	86
CSK	0.011	0	-10000	0	-10000	0	0
FOS	-0.03	0.12	0.17	33	-0.25	43	76
CHUK	0.029	0.049	0.16	1	-0.18	3	4
IBTK	0.011	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.013	0.047	-10000	0	-0.22	21	21
PTPN6	-0.034	0.14	-10000	0	-0.48	31	31
RELA	0.011	0	-10000	0	-10000	0	0
BCL2A1	0.019	0.016	-10000	0	-10000	0	0
VAV2	-0.009	0.12	-10000	0	-0.44	27	27
ubiquitin-dependent protein catabolic process	0.022	0.021	0.086	1	-0.12	1	2
BTK	-0.005	0.066	-10000	0	-1.1	2	2
CD19	-0.041	0.11	-10000	0	-0.34	50	50
MAP4K1	0.003	0.053	-10000	0	-0.33	13	13
CD72	0.009	0.026	-10000	0	-0.33	3	3
PAG1	0.009	0.032	-10000	0	-0.41	3	3
MAPK14	0.011	0.097	-10000	0	-0.37	26	26
SH3BP5	-0.051	0.15	-10000	0	-0.41	77	77
PIK3AP1	0.022	0.093	0.2	62	-0.3	20	82
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.013	0.055	-10000	0	-0.34	5	5
RAF1	0.025	0.069	0.19	1	-0.22	19	20
RasGAP/p62DOK/SHIP	-0.025	0.058	-10000	0	-0.34	4	4
CD79A	-0.027	0.11	-10000	0	-0.34	58	58
re-entry into mitotic cell cycle	0	0.076	0.14	40	-0.19	30	70
RASA1	0.007	0.041	-10000	0	-0.41	5	5
MAPK3	0.034	0.062	0.18	1	-0.26	3	4
MAPK1	0.034	0.062	0.18	1	-0.26	3	4
CD72/SHP1	-0.026	0.13	-10000	0	-0.45	31	31
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
MAPK8	0.01	0.1	-10000	0	-0.36	29	29
actin cytoskeleton organization	0	0.1	-10000	0	-0.39	26	26
NF-kappa-B/RelA	0.047	0.038	0.16	1	-0.18	1	2
Calcineurin	-0.011	0.045	-10000	0	-0.22	20	20
PI3K	-0.047	0.094	-10000	0	-0.36	32	32
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.019	0.095	0.2	64	-0.31	21	85
SOS1	0.011	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.025	0.17	-10000	0	-0.64	34	34
DAPP1	-0.05	0.18	-10000	0	-0.72	34	34
cytokine secretion	0.005	0.097	0.18	3	-0.32	31	34
mol:DAG	0.015	0.084	0.18	65	-0.27	21	86
PLCG2	0.009	0.024	-10000	0	-0.37	2	2
MAP2K1	0.029	0.066	0.19	1	-0.29	3	4
B-cell antigen/BCR complex/FcgammaRIIB	-0.013	0.085	-10000	0	-0.2	83	83
mol:PI-3-4-5-P3	-0.034	0.073	0.21	5	-0.26	32	37
ETS1	0.029	0.072	0.18	4	-0.21	20	24
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.002	0.071	-10000	0	-0.2	30	30
B-cell antigen/BCR complex/LYN	-0.033	0.11	-10000	0	-0.45	28	28
MALT1	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
RAC1	-0.001	0.11	-10000	0	-0.41	26	26
B-cell antigen/BCR complex/LYN/SYK	-0.055	0.12	-10000	0	-0.48	28	28
CARD11	0.016	0.085	0.17	63	-0.26	21	84
FCGR2B	0.008	0.035	-10000	0	-0.39	4	4
PPP3CA	0.011	0	-10000	0	-10000	0	0
BCL10	0.011	0	-10000	0	-10000	0	0
IKK complex	0.02	0.025	0.11	1	-10000	0	1
PTPRC	0.003	0.056	-10000	0	-0.4	10	10
PDPK1	-0.001	0.062	0.17	4	-0.19	28	32
PPP3CB	0.011	0	-10000	0	-10000	0	0
PPP3CC	0.008	0.037	-10000	0	-0.41	4	4
POU2F2	0.02	0.015	-10000	0	-0.1	1	1

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.004	0.056	-9999	-0.2	36	36
RGS9BP	-0.006	0.071	-9999	-0.33	24	24
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.002	0.015	-9999	-0.33	1	1
mol:Na +	-0.004	0.053	-9999	-0.23	27	27
mol:ADP	0.007	0.015	-9999	-0.22	2	2
GNAT2	0.007	0.026	-9999	-0.33	3	3
RGS9-1/Gbeta5/R9AP	-0.042	0.11	-9999	-0.23	115	115
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.007	0.015	-9999	-0.19	3	3
GRK7	0.006	0.016	-9999	-0.33	1	1
CNGB3	-0.013	0.087	-9999	-0.41	24	24
Cone Metarhodopsin II/X-Arrestin	0.002	0.011	-9999	-0.23	1	1
mol:Ca2+	-0.002	0.048	-9999	-0.2	28	28
Cone PDE6	-0.031	0.092	-9999	-0.2	80	80
Cone Metarhodopsin II	0.006	0.011	-9999	-0.16	2	2
Na + (4 Units)	-0.001	0.048	-9999	-0.2	28	28
GNAT2/GDP	-0.03	0.093	-9999	-0.19	115	115
GNB5	0.011	0	-9999	-10000	0	0
mol:GMP (4 units)	0.008	0.016	-9999	-0.16	4	4
Cone Transducin	0.004	0.06	-9999	-0.21	36	36
SLC24A2	0.004	0.015	-9999	-0.33	1	1
GNB3/GNGT2	-0.003	0.075	-9999	-0.29	34	34
GNB3	-0.015	0.1	-9999	-0.41	32	32
GNAT2/GTP	0.006	0.018	-9999	-0.23	3	3
CNGA3	0.005	0.026	-9999	-0.33	3	3
ARR3	0.003	0.015	-9999	-0.33	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.004	0.053	-9999	-0.23	27	27
mol:Pi	-0.042	0.11	-9999	-0.23	115	115
Cone CNG Channel	-0.01	0.041	-9999	-0.18	24	24
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.004	0.015	-9999	-0.33	1	1
RGS9	-0.081	0.17	-9999	-0.41	115	115
PDE6C	0.003	0.015	-9999	-0.33	1	1
GNGT2	0.009	0.032	-9999	-0.41	3	3
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.004	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.05	-10000	0	-1.1	1	1
VDR	0.003	0.053	-10000	0	-0.33	13	13
FAM120B	0.011	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.011	0.086	-10000	0	-0.26	21	21
RXRs/LXRs/DNA/Oxysterols	0.017	0.086	-10000	0	-0.45	2	2
MED1	0.011	0	-10000	0	-10000	0	0
mol:9cRA	0.003	0.007	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.026	0.11	-10000	0	-0.46	8	8
RXRs/NUR77	-0.01	0.1	-10000	0	-0.21	92	92
RXRs/PPAR	-0.006	0.091	-10000	0	-0.2	90	90
NCOR2	0.011	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.002	0.036	-10000	0	-0.23	13	13
RARs/VDR/DNA/Vit D3	0.018	0.039	-10000	0	-0.19	11	11
RARA	0.011	0	-10000	0	-10000	0	0
NCOA1	0.01	0.018	-10000	0	-0.41	1	1
VDR/VDR/DNA	0.003	0.053	-10000	0	-0.33	13	13
RARs/RARs/DNA/9cRA	0.017	0.031	-10000	0	-0.19	11	11
RARG	0.011	0	-10000	0	-10000	0	0
RPS6KB1	0.012	0.031	-10000	0	-0.4	1	1
RARs/THRs/DNA/SMRT	-0.026	0.1	-10000	0	-0.2	125	125
THRA	0.003	0.057	-10000	0	-0.41	10	10
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.002	0.036	-10000	0	-0.23	13	13
RXRs/PPAR/9cRA/PGJ2/DNA	0	0.084	0.28	1	-0.21	67	68
NR1H4	-0.009	0.062	-10000	0	-0.33	19	19
RXRs/LXRs/DNA	0.018	0.083	-10000	0	-0.23	20	20
NR1H2	0.014	0.006	-10000	0	-10000	0	0
NR1H3	0.014	0.016	-10000	0	-0.32	1	1
RXRs/VDR/DNA/Vit D3	0	0.082	-10000	0	-0.2	66	66
NR4A1	-0.015	0.1	-10000	0	-0.41	33	33
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.003	0.071	-10000	0	-0.18	66	66
RXRG	-0.045	0.14	-10000	0	-0.4	75	75
RXR alpha/CCPG	0.018	0.007	-10000	0	-10000	0	0
RXRA	0.014	0.006	-10000	0	-10000	0	0
RXRB	0.015	0.005	-10000	0	-10000	0	0
THRB	-0.079	0.17	-10000	0	-0.41	112	112
PPARG	-0.012	0.095	-10000	0	-0.41	29	29
PPARD	0.011	0	-10000	0	-10000	0	0
TNF	0.011	0.11	-10000	0	-0.99	2	2
mol:Oxysterols	0.003	0.006	-10000	0	-10000	0	0
cholesterol transport	0.017	0.086	-10000	0	-0.45	2	2
PPARA	0.011	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.002	0.06	-10000	0	-0.41	11	11
RXRs/NUR77/BCL2	-0.039	0.13	-10000	0	-0.25	123	123
SREBF1	0.023	0.08	-10000	0	-0.5	1	1
RXRs/RXRs/DNA/9cRA	0.001	0.084	0.27	1	-0.21	67	68
ABCA1	0.023	0.08	-10000	0	-0.5	1	1
RARs/THRs	-0.021	0.1	-10000	0	-0.41	7	7
RXRs/FXR	-0.007	0.091	-10000	0	-0.22	67	67
BCL2	-0.029	0.12	-10000	0	-0.41	50	50

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.008	0.046	-9999	-0.24	15	15
NFATC2	-0.01	0.079	-9999	-0.24	53	53
NFATC3	0.015	0.018	-9999	-10000	0	0
CD40LG	-0.054	0.18	-9999	-0.51	38	38
PTGS2	-0.074	0.21	-9999	-0.49	73	73
JUNB	0.007	0.041	-9999	-0.41	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.007	-9999	-10000	0	0
CaM/Ca2+	-0.001	0.007	-9999	-10000	0	0
CALM1	0.011	0.005	-9999	-10000	0	0
JUN	0.006	0.049	-9999	-0.41	7	7
mol:Ca2+	-0.002	0.007	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.004	0.004	-9999	-10000	0	0
FOSL1	-0.015	0.09	-9999	-0.33	40	40
CREM	0.011	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.036	0.082	-9999	-0.32	23	23
FOS	-0.12	0.19	-9999	-0.41	159	159
IFNG	-0.066	0.19	-9999	-0.48	56	56
AP-1/NFAT1-c-4	-0.062	0.2	-9999	-0.5	51	51
FASLG	-0.053	0.18	-9999	-0.51	38	38
NFAT1-c-4/ICER1	-0.01	0.082	-9999	-0.27	23	23
IL2RA	-0.055	0.18	-9999	-0.51	40	40
FKBP12/FK506	0.008	0	-9999	-10000	0	0
CSF2	-0.054	0.18	-9999	-0.49	37	37
JunB/Fra1/NFAT1-c-4	-0.022	0.084	-9999	-0.26	28	28
IL4	-0.054	0.17	-9999	-0.49	35	35
IL2	-0.009	0.03	-9999	-10000	0	0
IL3	-0.011	0.015	-9999	-10000	0	0
FKBP1A	0.011	0	-9999	-10000	0	0
BATF3	0.01	0.015	-9999	-0.33	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.011	0	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.037	0.11	-9999	-0.28	96	96
AKT1	0.022	0.15	-9999	-0.51	33	33
PTK2B	-0.02	0.15	-9999	-0.55	31	31
VEGFR2 homodimer/Frs2	-0.005	0.14	-9999	-0.56	31	31
CAV1	-0.063	0.16	-9999	-0.41	93	93
CALM1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.005	0.13	-9999	-0.52	31	31
endothelial cell proliferation	0.018	0.15	-9999	-0.46	38	38
mol:Ca2+	0	0.14	-9999	-0.54	31	31
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.011	0.12	-9999	-0.49	31	31
RP11-342D11.1	-0.007	0.14	-9999	-0.55	31	31
CDH5	0.005	0.048	-9999	-0.41	7	7
VEGFA homodimer	0.029	0.01	-9999	-0.2	1	1
SHC1	0.011	0	-9999	-10000	0	0
SHC2	-0.049	0.15	-9999	-0.41	75	75
HRAS/GDP	-0.034	0.11	-9999	-0.47	31	31
SH2D2A	-0.002	0.065	-9999	-0.33	20	20
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.034	0.11	-9999	-0.46	31	31
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.002	0.14	-9999	-0.53	31	31
VEGFR1 homodimer	0.011	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.037	0.12	-9999	-0.51	31	31
GRB10	0	0.15	-9999	-0.55	31	31
PTPN11	0.011	0	-9999	-10000	0	0
GRB2	0.011	0	-9999	-10000	0	0
PAK1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.013	0.13	-9999	-0.5	31	31
HRAS	0.011	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.012	0.12	-9999	-0.38	31	31
HIF1A	0.011	0	-9999	-10000	0	0
FRS2	0.011	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.01	0.12	-9999	-0.48	31	31
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.006	0.082	-9999	-0.41	21	21
Nck/Pak	0.015	0.018	-9999	-0.28	2	2
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.005	0.13	-9999	-0.52	31	31
mol:GDP	-0.036	0.12	-9999	-0.5	31	31
mol:NADP	0.025	0.12	-9999	-0.4	31	31
eNOS/Hsp90	0.029	0.11	-9999	-0.38	31	31
PIK3R1	0.007	0.041	-9999	-0.41	5	5
mol:IP3	-0.001	0.15	-9999	-0.55	31	31
HIF1A/ARNT	0.016	0	-9999	-10000	0	0
SHB	0.011	0	-9999	-10000	0	0
VEGFA	0.013	0.001	-9999	-10000	0	0
VEGFC	0.004	0.055	-9999	-0.41	9	9
FAK1/Vinculin	-0.008	0.16	-9999	-0.6	31	31
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.026	0.16	-9999	-0.58	31	31
PTPN6	0.01	0.015	-9999	-0.33	1	1
EPAS1	-0.001	0.084	-9999	-0.33	31	31
mol:L-citrulline	0.025	0.12	-9999	-0.4	31	31
ITGAV	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.011	0.12	-9999	-0.49	31	31
VEGFR2 homodimer/VEGFA homodimer	-0.007	0.16	-9999	-0.6	31	31
VEGFR2/3 heterodimer	-0.015	0.15	-9999	-0.58	31	31
VEGFB	0.011	0	-9999	-10000	0	0
MAPK11	-0.002	0.15	-9999	-0.56	32	32
VEGFR2 homodimer	-0.011	0.16	-9999	-0.65	31	31
FLT1	0.011	0	-9999	-10000	0	0
NEDD4	-0.019	0.11	-9999	-0.41	40	40
MAPK3	-0.005	0.14	-9999	-0.51	32	32
MAPK1	-0.005	0.14	-9999	-0.51	32	32
VEGFA145/NRP2	0.004	0.063	-9999	-0.28	25	25
VEGFR1/2 heterodimer	-0.005	0.14	-9999	-0.56	31	31
KDR	-0.011	0.16	-9999	-0.65	31	31
VEGFA165/NRP1/VEGFR2 homodimer	-0.009	0.16	-9999	-0.56	33	33
SRC	0.011	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.005	0.15	-9999	-0.52	32	32
PI3K	0.012	0.16	-9999	-0.57	33	33
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.004	0.13	-9999	-0.52	31	31
FES	-0.001	0.15	-9999	-0.55	32	32
GAB1	-0.039	0.14	-9999	-0.59	31	31
VEGFR2 homodimer/VEGFA homodimer/Src	0.005	0.13	-9999	-0.52	31	31
CTNNB1	0.011	0	-9999	-10000	0	0
SOS1	0.011	0	-9999	-10000	0	0
ARNT	0.011	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.014	0.13	-9999	-0.41	40	40
VEGFR2 homodimer/VEGFA homodimer/Yes	0.005	0.13	-9999	-0.52	31	31
PI3K/GAB1	0.022	0.15	-9999	-0.53	33	33
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.015	0.12	-9999	-0.47	31	31
PRKACA	0.011	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.01	0.15	-9999	-0.57	31	31
HSP90AA1	0.011	0	-9999	-10000	0	0
CDC42	-0.001	0.15	-9999	-0.56	31	31
actin cytoskeleton reorganization	-0.002	0.13	-9999	-0.52	31	31
PTK2	-0.015	0.17	-9999	-0.65	31	31
EDG1	-0.007	0.14	-9999	-0.55	31	31
mol:DAG	-0.001	0.15	-9999	-0.55	31	31
CaM/Ca2+	0.004	0.14	-9999	-0.5	31	31
MAP2K3	0.004	0.14	-9999	-0.53	31	31
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0	0.15	-9999	-0.57	31	31
PLCG1	-0.001	0.15	-9999	-0.56	31	31
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.011	0.12	-9999	-0.49	31	31
IQGAP1	0.011	0	-9999	-10000	0	0
YES1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.005	0.13	-9999	-0.52	31	31
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.004	0.13	-9999	-0.52	31	31
cell migration	0.014	0.15	-9999	-0.53	31	31
mol:PI-3-4-5-P3	0.013	0.15	-9999	-0.52	33	33
FYN	0.011	0	-9999	-10000	0	0
VEGFB/NRP1	-0.001	0.14	-9999	-0.52	31	31
mol:NO	0.025	0.12	-9999	-0.4	31	31
PXN	0.011	0	-9999	-10000	0	0
HRAS/GTP	-0.034	0.11	-9999	-0.46	31	31
VEGFR2 homodimer/VEGFA homodimer/GRB10	0	0.15	-9999	-0.57	31	31
VHL	0.01	0.018	-9999	-0.41	1	1
ITGB3	-0.065	0.16	-9999	-0.41	96	96
NOS3	0.023	0.13	-9999	-0.45	31	31
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.027	0.15	-9999	-0.55	31	31
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	-0.007	0.15	-9999	-0.51	36	36
PRKCB	-0.006	0.15	-9999	-0.52	34	34
VCL	0.011	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.006	0.14	-9999	-0.55	31	31
VEGFR1/2 heterodimer/VEGFA homodimer	0.005	0.13	-9999	-0.52	31	31
VEGFA165/NRP2	0.004	0.063	-9999	-0.28	25	25
MAPKKK cascade	0.021	0.13	-9999	-0.47	31	31
NRP2	-0.009	0.09	-9999	-0.41	25	25
VEGFC homodimer	0.004	0.054	-9999	-0.41	9	9
NCK1	0.009	0.026	-9999	-0.41	2	2
ROCK1	0.011	0	-9999	-10000	0	0
FAK1/Paxillin	-0.008	0.16	-9999	-0.6	31	31
MAP3K13	-0.002	0.15	-9999	-0.56	31	31
PDPK1	0.02	0.14	-9999	-0.46	33	33

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.1	0.19	-10000	0	-0.41	145	145
HRAS	0.011	0	-10000	0	-10000	0	0
EGFR	0	0.067	-10000	0	-0.4	14	14
AKT	-0.069	0.13	-10000	0	-0.28	108	108
FOXO3	0.011	0	-10000	0	-10000	0	0
AKT1	0.011	0	-10000	0	-10000	0	0
FOXO1	0.009	0.032	-10000	0	-0.41	3	3
AKT3	-0.15	0.2	-10000	0	-0.41	199	199
FOXO4	0.009	0.026	-10000	0	-0.41	2	2
MET	0.005	0.047	-10000	0	-0.37	8	8
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
PIK3CB	0.011	0	-10000	0	-10000	0	0
NRAS	0.011	0	-10000	0	-10000	0	0
PIK3CG	-0.002	0.071	-10000	0	-0.4	16	16
PIK3R3	0.01	0.015	-10000	0	-0.33	1	1
PIK3R2	0.011	0	-10000	0	-10000	0	0
NF1	0.009	0.026	-10000	0	-0.41	2	2
RAS	-0.023	0.074	0.18	1	-0.26	14	15
ERBB2	0.002	0.055	-10000	0	-0.33	14	14
proliferation/survival/translation	0.011	0.066	0.22	21	-10000	0	21
PI3K	-0.014	0.074	0.15	2	-0.21	27	29
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
KRAS	0.01	0.015	-10000	0	-0.33	1	1
FOXO	0.023	0.022	-10000	0	-10000	0	0
AKT2	0.011	0	-10000	0	-10000	0	0
PTEN	0.006	0.045	-10000	0	-0.41	6	6

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.001	-9999	-10000	0	0
SMARCC1	0.006	0.016	-9999	-10000	0	0
REL	0.011	0.001	-9999	-10000	0	0
HDAC7	0.021	0.066	-9999	-0.31	2	2
JUN	0.006	0.048	-9999	-0.41	7	7
EP300	0.011	0	-9999	-10000	0	0
KAT2B	0.004	0.055	-9999	-0.41	9	9
KAT5	0.011	0	-9999	-10000	0	0
MAPK14	-0.009	0.078	-9999	-0.21	66	66
FOXO1	0.009	0.032	-9999	-0.41	3	3
T-DHT/AR	0.019	0.071	-9999	-0.3	3	3
MAP2K6	-0.031	0.11	-9999	-0.33	66	66
BRM/BAF57	0.008	0.051	-9999	-0.28	16	16
MAP2K4	0.011	0.019	-9999	-0.41	1	1
SMARCA2	-0.002	0.072	-9999	-0.41	16	16
PDE9A	-0.02	0.1	-9999	-0.96	4	4
NCOA2	-0.004	0.077	-9999	-0.41	18	18
CEBPA	0.007	0.038	-9999	-0.38	5	5
EHMT2	0.011	0.001	-9999	-10000	0	0
cell proliferation	0.012	0.12	-9999	-0.39	16	16
NR0B1	-0.014	0.076	-9999	-0.33	29	29
EGR1	-0.043	0.14	-9999	-0.41	68	68
RXRs/9cRA	-0.01	0.077	-9999	-0.2	75	75
AR/RACK1/Src	0.009	0.069	-9999	-0.29	5	5
AR/GR	-0.049	0.12	-9999	-0.22	151	151
GNB2L1	0.011	0.002	-9999	-10000	0	0
PKN1	0.011	0	-9999	-10000	0	0
RCHY1	0.011	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.016	0.032	-9999	-0.28	6	6
T-DHT/AR/TIF2/CARM1	0.005	0.082	-9999	-0.32	13	13
SRC	0.012	0.06	-9999	-0.28	2	2
NR3C1	-0.053	0.15	-9999	-0.41	80	80
KLK3	-0.048	0.092	-9999	-0.45	3	3
APPBP2	0.012	0.002	-9999	-10000	0	0
TRIM24	0.011	0.002	-9999	-10000	0	0
T-DHT/AR/TIP60	0.005	0.062	-9999	-0.36	2	2
TMPRSS2	-0.031	0.14	-9999	-1	8	8
RXRG	-0.048	0.14	-9999	-0.4	75	75
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.011	0	-9999	-10000	0	0
RXRB	0.011	0	-9999	-10000	0	0
CARM1	0.011	0.002	-9999	-10000	0	0
NR2C2	0.003	0.057	-9999	-0.41	10	10
KLK2	-0.01	0.15	-9999	-0.57	31	31
AR	-0.022	0.099	-9999	-0.22	90	90
SENP1	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
MDM2	0.011	0.002	-9999	-10000	0	0
SRY	0	0.002	-9999	-10000	0	0
GATA2	-0.029	0.12	-9999	-0.41	50	50
MYST2	0.011	0	-9999	-10000	0	0
HOXB13	-0.22	0.16	-9999	-0.33	354	354
T-DHT/AR/RACK1/Src	0.01	0.064	-9999	-0.31	3	3
positive regulation of transcription	-0.029	0.12	-9999	-0.41	50	50
DNAJA1	0.012	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.001	-9999	-10000	0	0
NCOA1	0.013	0.02	-9999	-0.44	1	1
SPDEF	-0.11	0.17	-9999	-0.34	182	182
T-DHT/AR/TIF2	0.011	0.072	-9999	-0.29	15	15
T-DHT/AR/Hsp90	0.005	0.062	-9999	-0.36	2	2
GSK3B	0.012	0.002	-9999	-10000	0	0
NR2C1	0.011	0	-9999	-10000	0	0
mol:T-DHT	0.007	0.064	-9999	-0.23	6	6
SIRT1	0.009	0.026	-9999	-0.41	2	2
ZMIZ2	0.011	0.002	-9999	-10000	0	0
POU2F1	0.021	0.011	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.008	0.071	-9999	-0.31	5	5
CREBBP	0.009	0.026	-9999	-0.41	2	2
SMARCE1	0.011	0.001	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.012	0.045	-9999	-0.23	18	18
EPHB2	0.009	0.026	-9999	-0.33	3	3
Syndecan-2/TACI	0.006	0.051	-9999	-0.21	28	28
LAMA1	-0.1	0.16	-9999	-0.33	175	175
Syndecan-2/alpha2 ITGB1	0.016	0.061	-9999	-0.2	35	35
HRAS	0.011	0	-9999	-10000	0	0
Syndecan-2/CASK	0.006	0.038	-9999	-0.23	13	13
ITGA5	0.011	0	-9999	-10000	0	0
BAX	0.024	0.04	-9999	-10000	0	0
EPB41	0.01	0.018	-9999	-0.41	1	1
positive regulation of cell-cell adhesion	0.013	0.034	-9999	-0.2	13	13
LAMA3	0	0.068	-9999	-0.41	14	14
EZR	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.025	0.12	-9999	-0.41	45	45
Syndecan-2/MMP2	0.001	0.069	-9999	-0.24	38	38
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.01	0.044	-9999	-0.28	12	12
dendrite morphogenesis	0.013	0.041	-9999	-0.22	16	16
Syndecan-2/GM-CSF	0.008	0.046	-9999	-0.22	20	20
determination of left/right symmetry	0.009	0.046	-9999	-0.28	13	13
Syndecan-2/PKC delta	0.014	0.038	-9999	-0.23	13	13
GNB2L1	0.011	0	-9999	-10000	0	0
MAPK3	0.015	0.042	-9999	-0.21	13	13
MAPK1	0.015	0.042	-9999	-0.21	13	13
Syndecan-2/RACK1	0.019	0.033	-9999	-0.18	13	13
NF1	0.009	0.026	-9999	-0.41	2	2
FGFR/FGF/Syndecan-2	0.009	0.046	-9999	-0.28	13	13
ITGA2	0.001	0.063	-9999	-0.41	12	12
MAPK8	0.018	0.045	-9999	-0.22	18	18
Syndecan-2/alpha2/beta1 Integrin	-0.033	0.089	-9999	-0.22	28	28
Syndecan-2/Kininogen	0.001	0.054	-9999	-0.19	37	37
ITGB1	0.011	0	-9999	-10000	0	0
SRC	0.024	0.031	-9999	-0.17	13	13
Syndecan-2/CASK/Protein 4.1	0.012	0.036	-9999	-0.2	14	14
extracellular matrix organization	0.013	0.04	-9999	-0.23	14	14
actin cytoskeleton reorganization	0.012	0.045	-9999	-0.23	18	18
Syndecan-2/Caveolin-2/Ras	0.001	0.073	-9999	-0.21	56	56
Syndecan-2/Laminin alpha3	0.007	0.056	-9999	-0.24	26	26
Syndecan-2/RasGAP	0.022	0.037	-9999	-0.17	5	5
alpha5/beta1 Integrin	0.016	0	-9999	-10000	0	0
PRKCD	0.011	0	-9999	-10000	0	0
Syndecan-2 dimer	0.013	0.041	-9999	-0.22	16	16
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.028	0.036	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
SDCBP	0.011	0	-9999	-10000	0	0
TNFRSF13B	-0.002	0.058	-9999	-0.33	16	16
RASA1	0.007	0.041	-9999	-0.41	5	5
alpha2/beta1 Integrin	0.01	0.044	-9999	-0.28	12	12
Syndecan-2/Synbindin	0.014	0.038	-9999	-0.23	13	13
TGFB1	0.01	0.018	-9999	-0.41	1	1
CASP3	0.02	0.035	-9999	-0.2	13	13
FN1	0.007	0.041	-9999	-0.41	5	5
Syndecan-2/IL8	-0.043	0.094	-9999	-0.18	168	168
SDC2	0.009	0.046	-9999	-0.28	13	13
KNG1	-0.01	0.07	-9999	-0.33	24	24
Syndecan-2/Neurofibromin	0.013	0.041	-9999	-0.23	15	15
TRAPPC4	0.011	0	-9999	-10000	0	0
CSF2	0.001	0.041	-9999	-0.33	8	8
Syndecan-2/TGFB1	0.014	0.04	-9999	-0.23	14	14
Syndecan-2/Syntenin/PI-4-5-P2	0.013	0.035	-9999	-0.2	13	13
Syndecan-2/Ezrin	0.02	0.035	-9999	-0.2	13	13
PRKACA	0.019	0.037	-9999	-0.2	15	15
angiogenesis	-0.043	0.093	-9999	-0.18	168	168
MMP2	-0.011	0.093	-9999	-0.41	27	27
IL8	-0.09	0.16	-9999	-0.33	156	156
calcineurin-NFAT signaling pathway	0.006	0.051	-9999	-0.2	28	28

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.011	0	-9999	-10000	0	0
HDAC2	0.011	0.001	-9999	-10000	0	0
GNB1/GNG2	0.014	0.041	-9999	-0.22	15	15
forebrain development	-0.066	0.2	-9999	-0.44	100	100
GNAO1	-0.099	0.18	-9999	-0.41	138	138
SMO/beta Arrestin2	0.015	0.029	-9999	-0.28	5	5
SMO	0.007	0.041	-9999	-0.41	5	5
ARRB2	0.011	0.003	-9999	-10000	0	0
GLI3/SPOP	-0.03	0.11	-9999	-0.46	4	4
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0.011	0	-9999	-10000	0	0
GNAI2	0.011	0.002	-9999	-10000	0	0
SIN3/HDAC complex	0.028	0.002	-9999	-10000	0	0
GNAI1	0.005	0.052	-9999	-0.41	8	8
XPO1	0.012	0.004	-9999	-10000	0	0
GLI1/Su(fu)	-0.065	0.13	-9999	-0.44	30	30
SAP30	0.011	0.001	-9999	-10000	0	0
mol:GDP	0.007	0.041	-9999	-0.41	5	5
MIM/GLI2A	0.014	0.017	-9999	-10000	0	0
IFT88	0.011	0	-9999	-10000	0	0
GNAI3	0.011	0.002	-9999	-10000	0	0
GLI2	-0.012	0.078	-9999	-10000	0	0
GLI3	-0.037	0.12	-9999	-0.22	147	147
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
SAP18	0.011	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.011	0	-9999	-10000	0	0
GNG2	0.003	0.056	-9999	-0.4	10	10
Gi family/GTP	-0.039	0.11	-9999	-0.21	153	153
SIN3B	0.011	0.001	-9999	-10000	0	0
SIN3A	0.011	0	-9999	-10000	0	0
GLI3/Su(fu)	-0.004	0.087	-9999	-0.39	3	3
GLI2/Su(fu)	0.004	0.07	-9999	-0.23	3	3
FOXA2	-0.095	0.3	-9999	-1.1	45	45
neural tube patterning	-0.066	0.2	-9999	-0.44	100	100
SPOP	0.011	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.025	0.016	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CSNK1G2	0.011	0	-9999	-10000	0	0
CSNK1G3	0.011	0	-9999	-10000	0	0
MTSS1	0.014	0.017	-9999	-10000	0	0
embryonic limb morphogenesis	-0.066	0.2	-9999	-0.44	100	100
SUFU	0.021	0.018	-9999	-10000	0	0
LGALS3	0.009	0.026	-9999	-0.41	2	2
catabolic process	-0.036	0.13	-9999	-0.28	75	75
GLI3A/CBP	-0.043	0.13	-9999	-0.31	99	99
KIF3A	0.01	0.018	-9999	-0.41	1	1
GLI1	-0.068	0.2	-9999	-0.45	100	100
RAB23	0.007	0.041	-9999	-0.41	5	5
CSNK1A1	0.011	0	-9999	-10000	0	0
IFT172	0.011	0	-9999	-10000	0	0
RBBP7	0.011	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	0.024	0.021	-9999	-0.19	2	2
GNAZ	-0.001	0.07	-9999	-0.41	15	15
RBBP4	0.009	0.032	-9999	-0.41	3	3
CSNK1G1	0.011	0	-9999	-10000	0	0
PIAS1	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GLI2/SPOP	-0.006	0.073	-9999	-10000	0	0
STK36	0.012	0.004	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.03	0.1	-9999	-0.27	32	32
PTCH1	-0.053	0.18	-9999	-0.53	30	30
MIM/GLI1	-0.072	0.23	-9999	-0.53	85	85
CREBBP	-0.043	0.13	-9999	-0.31	99	99
Su(fu)/SIN3/HDAC complex	0.038	0.016	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.01	0.04	-10000	0	-10000	0	0
SMARCC2	0.012	0.002	-10000	0	-10000	0	0
SMARCC1	0.012	0.003	-10000	0	-10000	0	0
TBX21	0.007	0.12	-10000	0	-0.72	9	9
SUMO2	0.01	0.005	-10000	0	-10000	0	0
STAT1 (dimer)	0.017	0.015	-10000	0	-0.32	1	1
FKBP4	0.011	0	-10000	0	-10000	0	0
FKBP5	0.005	0.052	-10000	0	-0.41	8	8
GR alpha/HSP90/FKBP51/HSP90	0	0.1	0.21	11	-0.25	54	65
PRL	-0.025	0.24	-10000	0	-1.3	17	17
cortisol/GR alpha (dimer)/TIF2	0.025	0.16	0.44	20	-0.43	8	28
RELA	-0.016	0.062	-10000	0	-0.23	9	9
FGG	0.003	0.14	0.37	13	-0.45	5	18
GR beta/TIF2	-0.016	0.13	0.23	11	-0.31	65	76
IFNG	-0.092	0.14	-10000	0	-0.49	13	13
apoptosis	-0.077	0.19	0.47	8	-0.56	34	42
CREB1	0.008	0.023	-10000	0	-10000	0	0
histone acetylation	0.039	0.075	0.23	14	-0.24	9	23
BGLAP	0.025	0.065	-10000	0	-10000	0	0
GR/PKAc	0.004	0.093	0.21	8	-0.24	38	46
NF kappa B1 p50/RelA	-0.025	0.11	-10000	0	-0.33	27	27
SMARCD1	0.012	0.003	-10000	0	-10000	0	0
MDM2	0.022	0.041	0.18	14	-10000	0	14
GATA3	0.001	0.07	-10000	0	-0.35	20	20
AKT1	0.005	0.002	-10000	0	-10000	0	0
CSF2	0.018	0.067	-10000	0	-10000	0	0
GSK3B	0.01	0.005	-10000	0	-10000	0	0
NR1I3	-0.055	0.17	0.46	7	-0.55	22	29
CSN2	0.002	0.11	0.32	9	-0.37	4	13
BRG1/BAF155/BAF170/BAF60A	0.035	0.009	-10000	0	-10000	0	0
NFATC1	0.001	0.07	-10000	0	-0.41	15	15
POU2F1	0.008	0.042	-10000	0	-0.23	15	15
CDKN1A	0.032	0.061	-10000	0	-1.3	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.006	-10000	0	-10000	0	0
SFN	-0.24	0.15	-10000	0	-0.33	388	388
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.11	0.14	0.22	15	-0.34	77	92
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.11	0.29	0.44	7	-0.81	68	75
JUN	-0.039	0.1	-10000	0	-0.36	14	14
IL4	0.007	0.081	-10000	0	-0.46	2	2
CDK5R1	0.01	0.015	-10000	0	-0.33	1	1
PRKACA	0.011	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.18	0.17	-10000	0	-0.37	181	181
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.007	0.096	0.21	11	-0.24	40	51
cortisol/GR alpha (monomer)	0.027	0.18	0.51	21	-0.47	4	25
NCOA2	-0.003	0.077	-10000	0	-0.41	18	18
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.15	0.2	-10000	0	-0.44	159	159
AP-1/NFAT1-c-4	-0.16	0.18	-10000	0	-0.49	56	56
AFP	-0.015	0.079	-10000	0	-0.45	1	1
SUV420H1	0.011	0	-10000	0	-10000	0	0
IRF1	0.025	0.089	0.32	2	-10000	0	2
TP53	0.027	0.028	-10000	0	-0.42	2	2
PPP5C	0.011	0	-10000	0	-10000	0	0
KRT17	-0.12	0.19	-10000	0	-0.73	18	18
KRT14	-0.051	0.11	0.43	1	-0.39	1	2
TBP	0.019	0	-10000	0	-10000	0	0
CREBBP	0.031	0.046	-10000	0	-0.32	4	4
HDAC1	0.01	0.003	-10000	0	-10000	0	0
HDAC2	0.01	0.002	-10000	0	-10000	0	0
AP-1	-0.16	0.18	-10000	0	-0.49	56	56
MAPK14	0.01	0.005	-10000	0	-10000	0	0
MAPK10	-0.079	0.17	-10000	0	-0.41	111	111
MAPK11	0.008	0.026	-10000	0	-0.41	2	2
KRT5	-0.14	0.21	-10000	0	-0.78	23	23
interleukin-1 receptor activity	-0.001	0.002	-10000	0	-10000	0	0
NCOA1	0.012	0.018	-10000	0	-0.41	1	1
STAT1	0.017	0.015	-10000	0	-0.32	1	1
CGA	0.006	0.083	-10000	0	-0.37	3	3
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.008	0.099	0.29	2	-0.48	2	4
MAPK3	0.01	0.006	-10000	0	-10000	0	0
MAPK1	0.01	0.005	-10000	0	-10000	0	0
ICAM1	-0.014	0.11	-10000	0	-0.44	4	4
NFKB1	-0.017	0.065	-10000	0	-0.25	9	9
MAPK8	-0.015	0.097	0.26	1	-0.32	14	15
MAPK9	0.01	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.084	0.2	0.47	8	-0.58	36	44
BAX	0.034	0.025	-10000	0	-10000	0	0
POMC	-0.018	0.21	-10000	0	-1.3	10	10
EP300	0.032	0.038	-10000	0	-0.23	2	2
cortisol/GR alpha (dimer)/p53	0.044	0.16	0.46	20	-0.46	2	22
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.033	0.16	1	-10000	0	1
SGK1	0.045	0.094	-10000	0	-1.3	2	2
IL13	-0.057	0.11	-10000	0	-0.6	3	3
IL6	-0.037	0.19	-10000	0	-0.86	19	19
PRKACG	0.003	0.005	-10000	0	-10000	0	0
IL5	-0.055	0.098	-10000	0	-0.54	3	3
IL2	-0.087	0.13	-10000	0	-0.52	7	7
CDK5	0.01	0.003	-10000	0	-10000	0	0
PRKACB	0.006	0.045	-10000	0	-0.41	6	6
HSP90AA1	0.011	0	-10000	0	-10000	0	0
IL8	-0.051	0.14	-10000	0	-0.41	17	17
CDK5R1/CDK5	0.014	0.013	-10000	0	-0.22	1	1
NF kappa B1 p50/RelA/PKAc	-0.002	0.085	-10000	0	-0.33	9	9
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.041	0.14	0.42	21	-0.42	2	23
SMARCA4	0.012	0.002	-10000	0	-10000	0	0
chromatin remodeling	0.025	0.11	0.31	11	-0.43	4	15
NF kappa B1 p50/RelA/Cbp	0.021	0.1	-10000	0	-0.35	8	8
JUN (dimer)	-0.039	0.1	-10000	0	-0.36	14	14
YWHAH	0.011	0	-10000	0	-10000	0	0
VIPR1	0.013	0.09	-10000	0	-0.35	11	11
NR3C1	-0.017	0.16	0.32	14	-0.4	65	79
NR4A1	-0.022	0.12	-10000	0	-0.43	42	42
TIF2/SUV420H1	0.006	0.054	-10000	0	-0.28	18	18
MAPKKK cascade	-0.077	0.19	0.47	8	-0.56	34	42
cortisol/GR alpha (dimer)/Src-1	0.038	0.15	0.45	21	-0.4	4	25
PBX1	-0.009	0.095	-10000	0	-0.35	35	35
POU1F1	-0.002	0.047	-10000	0	-0.25	18	18
SELE	-0.098	0.32	-10000	0	-0.93	63	63
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.025	0.11	0.31	11	-0.43	4	15
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.041	0.14	0.42	21	-0.42	2	23
mol:cortisol	0.023	0.076	0.28	19	-10000	0	19
MMP1	-0.12	0.11	-10000	0	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.006	0.046	-10000	0	-0.22	21	21
cell-cell adhesion	0.03	0.063	0.3	9	-10000	0	9
Ephrin B/EPHB2/RasGAP	0.008	0.069	-10000	0	-0.18	58	58
ITSN1	0.011	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
SHC1	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.006	0.045	-10000	0	-0.21	21	21
Ephrin B1/EPHB1	-0.01	0.074	-10000	0	-0.23	52	52
HRAS/GDP	-0.03	0.067	-10000	0	-0.3	10	10
Ephrin B/EPHB1/GRB7	-0.02	0.098	-10000	0	-0.2	97	97
Endophilin/SYNJ1	0.008	0.062	-10000	0	-0.17	53	53
KRAS	0.01	0.015	-10000	0	-0.33	1	1
Ephrin B/EPHB1/Src	-0.009	0.092	-10000	0	-0.2	96	96
endothelial cell migration	-0.003	0.025	-10000	0	-0.18	10	10
GRB2	0.011	0	-10000	0	-10000	0	0
GRB7	-0.011	0.084	-10000	0	-0.34	33	33
PAK1	0.012	0.067	-10000	0	-0.36	3	3
HRAS	0.011	0	-10000	0	-10000	0	0
RRAS	0.008	0.063	-10000	0	-0.17	53	53
DNM1	0.006	0.045	-10000	0	-0.41	6	6
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.01	0.087	-10000	0	-0.36	8	8
lamellipodium assembly	-0.03	0.063	-10000	0	-0.3	9	9
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.009	0.09	-10000	0	-0.22	53	53
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
EPHB2	0.009	0.026	-10000	0	-0.33	3	3
EPHB3	-0.004	0.072	-10000	0	-0.35	21	21
EPHB1	-0.03	0.12	-10000	0	-0.41	51	51
EPHB4	0.01	0.018	-10000	0	-0.41	1	1
mol:GDP	-0.001	0.084	-10000	0	-0.22	44	44
Ephrin B/EPHB2	0.004	0.066	-10000	0	-0.19	53	53
Ephrin B/EPHB3	-0.002	0.082	-10000	0	-0.22	56	56
JNK cascade	0.009	0.065	-10000	0	-0.18	52	52
Ephrin B/EPHB1	-0.016	0.092	-10000	0	-0.2	96	96
RAP1/GDP	0.01	0.076	-10000	0	-0.28	10	10
EFNB2	0.009	0.032	-10000	0	-0.41	3	3
EFNB3	-0.029	0.12	-10000	0	-0.41	50	50
EFNB1	0.01	0.018	-10000	0	-0.41	1	1
Ephrin B2/EPHB1-2	-0.003	0.069	-10000	0	-0.2	57	57
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
CDC42/GTP	-0.034	0.073	-10000	0	-0.35	9	9
Rap1/GTP	-0.029	0.062	-10000	0	-0.31	9	9
axon guidance	0.005	0.046	-10000	0	-0.22	21	21
MAPK3	0.004	0.081	-10000	0	-0.32	8	8
MAPK1	0.004	0.081	-10000	0	-0.32	8	8
Rac1/GDP	0.006	0.079	-10000	0	-0.29	10	10
actin cytoskeleton reorganization	-0.023	0.051	-10000	0	-0.25	9	9
CDC42/GDP	0.006	0.079	-10000	0	-0.29	10	10
PI3K	0.022	0.029	-10000	0	-0.19	10	10
EFNA5	-0.003	0.075	-10000	0	-0.4	18	18
Ephrin B2/EPHB4	0.013	0.022	-10000	0	-0.23	4	4
Ephrin B/EPHB2/Intersectin/N-WASP	0.007	0.068	-10000	0	-0.2	53	53
CDC42	0.011	0	-10000	0	-10000	0	0
RAS family/GTP	-0.028	0.061	-10000	0	-0.3	9	9
PTK2	0.006	0.018	-10000	0	-10000	0	0
MAP4K4	0.009	0.065	-10000	0	-0.18	52	52
SRC	0.011	0	-10000	0	-10000	0	0
KALRN	0.007	0.041	-10000	0	-0.41	5	5
Intersectin/N-WASP	0.016	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.018	0.081	-10000	0	-0.28	11	11
MAP2K1	-0.002	0.085	-10000	0	-0.35	8	8
WASL	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.004	0.071	-10000	0	-0.2	52	52
cell migration	-0.003	0.099	-10000	0	-0.38	9	9
NRAS	0.011	0	-10000	0	-10000	0	0
SYNJ1	0.008	0.063	-10000	0	-0.17	53	53
PXN	0.011	0	-10000	0	-10000	0	0
TF	0.005	0.072	-10000	0	-0.32	5	5
HRAS/GTP	-0.032	0.068	-10000	0	-0.33	9	9
Ephrin B1/EPHB1-2	-0.002	0.068	-10000	0	-0.2	55	55
cell adhesion mediated by integrin	0.017	0.067	0.2	53	-10000	0	53
RAC1	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.007	0.087	-10000	0	-0.35	9	9
RAC1-CDC42/GTP	-0.034	0.072	-10000	0	-0.3	19	19
RASA1	0.007	0.041	-10000	0	-0.41	5	5
RAC1-CDC42/GDP	0.01	0.076	-10000	0	-0.28	10	10
ruffle organization	0.009	0.081	-10000	0	-0.31	9	9
NCK1	0.009	0.026	-10000	0	-0.41	2	2
receptor internalization	0.012	0.067	-10000	0	-0.35	5	5
Ephrin B/EPHB2/KALRN	0.008	0.071	-10000	0	-0.19	56	56
ROCK1	0.012	0.04	-10000	0	-0.18	21	21
RAS family/GDP	-0.023	0.05	-10000	0	-0.24	9	9
Rac1/GTP	-0.031	0.066	-10000	0	-0.32	9	9
Ephrin B/EPHB1/Src/Paxillin	-0.013	0.095	-10000	0	-0.21	96	96

×

IL6-mediated signaling events

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
BCL2L1	0.032	0.13	-9999	-0.55	3	3
CRP	0.027	0.13	-9999	-0.57	3	3
cell cycle arrest	0.026	0.14	-9999	-0.53	10	10
TIMP1	0.028	0.12	-9999	-0.51	7	7
IL6ST	-0.049	0.15	-9999	-0.41	80	80
Rac1/GDP	-0.001	0.12	-9999	-0.35	37	37
AP1	-0.02	0.12	-9999	-0.52	10	10
GAB2	0.009	0.037	-9999	-0.41	4	4
TNFSF11	0.013	0.14	-9999	-0.56	4	4
HSP90B1	0.032	0.03	-9999	-10000	0	0
GAB1	0.008	0.037	-9999	-0.41	4	4
MAPK14	-0.026	0.13	-9999	-0.38	39	39
AKT1	0.042	0.04	-9999	-0.39	2	2
FOXO1	0.045	0.041	-9999	-0.37	2	2
MAP2K6	-0.031	0.14	-9999	-0.38	44	44
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	0.015	0.12	-9999	-0.39	20	20
MITF	-0.03	0.15	-9999	-0.4	54	54
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.011	0	-9999	-10000	0	0
A2M	0.012	0.079	-9999	-1.3	2	2
CEBPB	0.017	0.002	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.013	0.086	-9999	-0.63	5	5
STAT3	0.028	0.14	-9999	-0.56	10	10
STAT1	0.002	0.014	-9999	-10000	0	0
CEBPD	0.031	0.13	-9999	-0.67	4	4
PIK3CA	0.012	0.018	-9999	-0.41	1	1
PI3K	0.015	0.032	-9999	-0.28	6	6
JUN	0.005	0.048	-9999	-0.41	7	7
PIAS3/MITF	-0.024	0.14	-9999	-0.37	54	54
MAPK11	-0.026	0.13	-9999	-0.38	39	39
STAT3 (dimer)/FOXO1	0.061	0.13	-9999	-0.47	6	6
GRB2/SOS1/GAB family	-0.042	0.1	-9999	-0.37	33	33
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.02	0.13	-9999	-0.35	48	48
GRB2	0.012	0.001	-9999	-10000	0	0
JAK2	0.004	0.055	-9999	-0.41	9	9
LBP	0.019	0.12	-9999	-0.52	2	2
PIK3R1	0.008	0.041	-9999	-0.41	5	5
JAK1	0.012	0.026	-9999	-0.4	2	2
MYC	0.021	0.18	-9999	-0.86	13	13
FGG	0.026	0.13	-9999	-0.57	3	3
macrophage differentiation	0.026	0.14	-9999	-0.53	10	10
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.041	0.12	-9999	-0.38	37	37
JUNB	0.025	0.15	-9999	-0.76	8	8
FOS	-0.12	0.19	-9999	-0.41	159	159
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.017	0.13	-9999	-0.39	40	40
STAT1/PIAS1	0.002	0.12	-9999	-0.33	35	35
GRB2/SOS1/GAB family/SHP2/PI3K	0.033	0.042	-9999	-0.33	4	4
STAT3 (dimer)	0.029	0.14	-9999	-0.55	10	10
PRKCD	0.03	0.12	-9999	-0.44	11	11
IL6R	-0.023	0.12	-9999	-0.41	45	45
SOCS3	-0.026	0.14	-9999	-0.61	11	11
gp130 (dimer)/JAK1/JAK1/LMO4	-0.007	0.092	-9999	-0.22	82	82
Rac1/GTP	0.003	0.12	-9999	-0.35	36	36
HCK	0.006	0.039	-9999	-0.33	7	7
MAPKKK cascade	0.026	0.082	-9999	-0.77	4	4
bone resorption	0.014	0.13	-9999	-0.54	4	4
IRF1	0.032	0.13	-9999	-0.5	6	6
mol:GDP	-0.009	0.13	-9999	-0.37	37	37
SOS1	0.011	0.001	-9999	-10000	0	0
VAV1	-0.01	0.13	-9999	-0.38	37	37
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.038	0.16	-9999	-0.46	49	49
PTPN11	0.002	0.014	-9999	-10000	0	0
IL6/IL6RA	-0.016	0.11	-9999	-0.29	64	64
gp130 (dimer)/TYK2/TYK2/LMO4	-0.01	0.091	-9999	-0.22	80	80
gp130 (dimer)/JAK2/JAK2/LMO4	-0.014	0.097	-9999	-0.23	87	87
IL6	-0.004	0.084	-9999	-0.38	25	25
PIAS3	0.011	0	-9999	-10000	0	0
PTPRE	0.003	0.024	-9999	-0.37	2	2
PIAS1	0.011	0	-9999	-10000	0	0
RAC1	0.011	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.029	0.13	-9999	-0.26	108	108
LMO4	0.015	0.005	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	0.019	0.14	-9999	-0.54	10	10
MCL1	0.046	0.037	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0.008	0.037	-9999	-0.41	4	4
ELF1	0.01	0.043	-9999	-0.38	4	4
CCNA2	-0.061	0.14	-9999	-0.33	111	111
PIK3CA	0.011	0.018	-9999	-0.41	1	1
JAK3	0.009	0.03	-9999	-0.33	4	4
PIK3R1	0.008	0.041	-9999	-0.41	5	5
JAK1	0.01	0.026	-9999	-0.41	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.053	0.045	-9999	-0.51	1	1
SHC1	0.012	0	-9999	-10000	0	0
SP1	-0.043	0.13	-9999	-0.3	100	100
IL2RA	0.013	0.059	-9999	-0.65	1	1
IL2RB	0.011	0.018	-9999	-0.41	1	1
SOS1	0.012	0	-9999	-10000	0	0
IL2RG	0.005	0.048	-9999	-0.36	9	9
G1/S transition of mitotic cell cycle	-0.1	0.27	-9999	-0.64	101	101
PTPN11	0.012	0	-9999	-10000	0	0
CCND2	-0.1	0.26	-9999	-0.65	100	100
LCK	0.008	0.035	-9999	-0.34	5	5
GRB2	0.012	0	-9999	-10000	0	0
IL2	-0.006	0.059	-9999	-0.33	17	17
CDK6	0.001	0.065	-9999	-0.41	13	13
CCND3	0.056	0.041	-9999	-0.43	1	1

×

Insulin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.076	0.11	-9999	-0.36	37	37
TC10/GTP	-0.055	0.076	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.001	0.07	-9999	-0.21	53	53
HRAS	0.011	0	-9999	-10000	0	0
APS homodimer	0.011	0	-9999	-10000	0	0
GRB14	-0.11	0.16	-9999	-0.33	191	191
FOXO3	-0.01	0.037	-9999	-0.57	2	2
AKT1	-0.032	0.092	-9999	-0.28	28	28
INSR	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.03	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.01	0.018	-9999	-0.41	1	1
SORBS1	-0.13	0.2	-9999	-0.41	182	182
CRK	0.011	0	-9999	-10000	0	0
PTPN1	0.027	0.001	-9999	-10000	0	0
CAV1	-0.037	0.11	-9999	-0.23	124	124
CBL/APS/CAP/Crk-II/C3G	-0.041	0.1	-9999	-0.18	182	182
Insulin Receptor/Insulin/IRS1/NCK2	0.001	0.07	-9999	-0.21	53	53
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.02	0.058	-9999	-0.18	49	49
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.013	0.055	-9999	-10000	0	0
RPS6KB1	-0.024	0.086	-9999	-0.25	28	28
PARD6A	0.011	0	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.003	-9999	-10000	0	0
PIK3R1	0.007	0.041	-9999	-0.41	5	5
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.047	0.067	-9999	-0.26	28	28
HRAS/GTP	-0.015	0.043	-9999	-10000	0	0
Insulin Receptor	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.007	0.065	-9999	-10000	0	0
PRKCI	-0.012	0.018	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.06	0.081	-9999	-0.3	28	28
SHC1	0.011	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	-0.002	0.028	-9999	-0.39	2	2
PI3K	-0.02	0.058	-9999	-0.19	49	49
NCK2	0.011	0	-9999	-10000	0	0
RHOQ	0.011	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.008	0	-9999	-10000	0	0
AKT2	-0.032	0.092	-9999	-0.28	28	28
PRKCZ	-0.013	0.029	-9999	-0.52	1	1
SH2B2	0.011	0	-9999	-10000	0	0
SHC/SHIP	0.007	0.062	-9999	-10000	0	0
F2RL2	-0.017	0.1	-9999	-0.4	35	35
TRIP10	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0.017	0.002	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.029	0.001	-9999	-10000	0	0
RAPGEF1	0.011	0	-9999	-10000	0	0
RASA1	0.007	0.041	-9999	-0.41	5	5
NCK1	0.009	0.026	-9999	-0.41	2	2
CBL/APS/CAP/Crk-II	-0.05	0.11	-9999	-0.2	182	182
TC10/GDP	0.008	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.024	0.01	-9999	-0.21	1	1
INPP5D	0	0.065	-9999	-0.19	54	54
SOS1	0.011	0	-9999	-10000	0	0
SGK1	-0.006	0.05	-9999	-0.82	2	2
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.011	0	-9999	-10000	0	0
IRS1	-0.031	0.13	-9999	-0.41	53	53
p62DOK/RasGAP	-0.002	0.028	-9999	-0.4	2	2
INS	0.003	0.002	-9999	-10000	0	0
mol:PI-3-4-P2	0	0.064	-9999	-0.19	54	54
GRB2	0.011	0	-9999	-10000	0	0
EIF4EBP1	-0.027	0.09	-9999	-0.26	32	32
PTPRA	0.012	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
TC10/GTP/CIP4	0.015	0	-9999	-10000	0	0
PDPK1	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.006	0.065	-9999	-0.19	46	46
Insulin Receptor/Insulin/IRS1	-0.006	0.07	-9999	-0.21	53	53
Insulin Receptor/Insulin/IRS3	0.012	0.002	-9999	-10000	0	0
Par3/Par6	0.012	0.052	-9999	-0.19	32	32

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	-0.01	0.064	-10000	0	-0.65	4	4
HDAC1	0.008	0.005	-10000	0	-10000	0	0
AES	0.01	0.001	-10000	0	-10000	0	0
FBXW11	0.011	0	-10000	0	-10000	0	0
DTX1	0.006	0.045	-10000	0	-0.41	6	6
LRP6/FZD1	0.015	0.022	-10000	0	-0.28	3	3
TLE1	0.01	0.018	-10000	0	-0.41	1	1
AP1	-0.063	0.12	-10000	0	-0.24	164	164
NCSTN	0.011	0	-10000	0	-10000	0	0
ADAM10	0.008	0.037	-10000	0	-0.41	4	4
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.03	0.053	-10000	0	-0.56	2	2
NICD/RBPSUH	0.023	0.046	-10000	0	-0.5	4	4
WIF1	-0.097	0.16	-10000	0	-0.35	158	158
NOTCH1	-0.004	0.046	-10000	0	-0.53	4	4
PSENEN	0.011	0	-10000	0	-10000	0	0
KREMEN2	-0.021	0.1	-10000	0	-0.33	50	50
DKK1	-0.063	0.14	-10000	0	-0.33	112	112
beta catenin/beta TrCP1	0.026	0.027	-10000	0	-10000	0	0
APH1B	0.005	0.048	-10000	0	-0.41	7	7
APH1A	0.011	0	-10000	0	-10000	0	0
AXIN1	0.001	0.019	-10000	0	-0.18	4	4
CtBP/CBP/TCF1/TLE1/AES	0.017	0.027	-10000	0	-0.21	3	3
PSEN1	0.011	0	-10000	0	-10000	0	0
FOS	-0.12	0.19	-10000	0	-0.41	159	159
JUN	0.005	0.048	-10000	0	-0.41	7	7
MAP3K7	0.01	0.002	-10000	0	-10000	0	0
CTNNB1	0.02	0.029	0.16	5	-10000	0	5
MAPK3	0.011	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.012	0.084	-10000	0	-0.25	35	35
HNF1A	0.005	0.042	-10000	0	-0.33	8	8
CTBP1	0.01	0.001	-10000	0	-10000	0	0
MYC	-0.004	0.18	-10000	0	-1.3	10	10
NKD1	-0.02	0.1	-10000	0	-0.34	46	46
FZD1	0.009	0.032	-10000	0	-0.41	3	3
NOTCH1 precursor/Deltex homolog 1	0.021	0.051	-10000	0	-0.5	4	4
apoptosis	-0.063	0.12	-10000	0	-0.24	164	164
Delta 1/NOTCHprecursor	0.017	0.067	-10000	0	-0.64	4	4
DLL1	-0.003	0.074	-10000	0	-0.41	17	17
PPARD	0.018	0.013	-10000	0	-10000	0	0
Gamma Secretase	0.03	0.025	-10000	0	-0.18	7	7
APC	0.001	0.019	-10000	0	-0.18	4	4
DVL1	0	0.015	-10000	0	-10000	0	0
CSNK2A1	0.011	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.038	0.096	-10000	0	-0.18	155	155
LRP6	0.011	0	-10000	0	-10000	0	0
CSNK1A1	0.011	0.001	-10000	0	-10000	0	0
NLK	0.011	0.006	-10000	0	-10000	0	0
CCND1	0.018	0.017	-10000	0	-10000	0	0
WNT1	0.004	0.042	-10000	0	-0.33	8	8
Axin1/APC/beta catenin	0.029	0.025	-10000	0	-0.2	1	1
DKK2	-0.016	0.1	-10000	0	-0.4	34	34
NOTCH1 precursor/DVL1	0	0.041	-10000	0	-0.46	4	4
GSK3B	0.011	0	-10000	0	-10000	0	0
FRAT1	0.01	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.006	0.048	-10000	0	-0.51	4	4
PPP2R5D	0.012	0.046	0.21	11	-10000	0	11
MAPK1	0.011	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.033	0.089	-10000	0	-0.21	38	38
RBPJ	0.011	0	-10000	0	-10000	0	0
CREBBP	0.012	0.026	-10000	0	-0.41	2	2

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.16	0.21	-9999	-0.41	210	210
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.011	0	-9999	-10000	0	0
TCEB1	0.011	0	-9999	-10000	0	0
HIF1A/p53	0.025	0.01	-9999	-10000	0	0
HIF1A	0.02	0.005	-9999	-10000	0	0
COPS5	0.011	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.032	0.009	-9999	-10000	0	0
FIH (dimer)	0.011	0	-9999	-10000	0	0
CDKN2A	-0.13	0.17	-9999	-0.33	219	219
ARNT/IPAS	-0.1	0.14	-9999	-0.28	210	210
HIF1AN	0.011	0	-9999	-10000	0	0
GNB2L1	0.011	0	-9999	-10000	0	0
HIF1A/ARNT	0.026	0.005	-9999	-10000	0	0
CUL2	0.011	0	-9999	-10000	0	0
OS9	0.011	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.022	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.026	0.005	-9999	-10000	0	0
PHD1-3/OS9	0.027	0.017	-9999	-0.2	1	1
HIF1A/RACK1/Elongin B/Elongin C	0.034	0.005	-9999	-10000	0	0
VHL	0.01	0.018	-9999	-0.41	1	1
HSP90AA1	0.011	0	-9999	-10000	0	0
HIF1A/JAB1	0.026	0.005	-9999	-10000	0	0
EGLN3	0.008	0.031	-9999	-0.35	4	4
EGLN2	0.011	0	-9999	-10000	0	0
EGLN1	0.011	0	-9999	-10000	0	0
TP53	0.01	0.018	-9999	-0.41	1	1
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.03	0.023	-9999	-0.5	1	1
ARNT	0.011	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.011	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.037	0.074	-9999	-0.19	1	1

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.012	0.005	-10000	0	-10000	0	0
HSPA8	0.011	0.001	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.03	0.089	0.15	3	-0.26	63	66
AKT1	0.013	0.002	-10000	0	-10000	0	0
GSC	-0.029	0.077	-10000	0	-10000	0	0
NKX2-5	-0.049	0.12	-10000	0	-0.34	80	80
muscle cell differentiation	0.044	0.098	0.33	29	-10000	0	29
SMAD2-3/SMAD4/SP1	0.038	0.052	-10000	0	-0.26	3	3
SMAD4	0.007	0.036	-10000	0	-0.42	1	1
CBFB	0.011	0	-10000	0	-10000	0	0
SAP18	0.011	0	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.016	0.045	-10000	0	-0.26	5	5
SMAD3/SMAD4/VDR	0.004	0.041	-10000	0	-0.22	4	4
MYC	0.001	0.058	-10000	0	-0.41	10	10
CDKN2B	0.025	0.032	-10000	0	-10000	0	0
AP1	-0.024	0.12	-10000	0	-0.34	25	25
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.044	0.02	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.011	0.045	-10000	0	-0.34	3	3
SP3	0.013	0	-10000	0	-10000	0	0
CREB1	0.011	0	-10000	0	-10000	0	0
FOXH1	-0.08	0.15	-10000	0	-0.34	130	130
SMAD3/SMAD4/GR	-0.038	0.098	-10000	0	-0.25	83	83
GATA3	-0.004	0.072	-10000	0	-0.35	20	20
SKI/SIN3/HDAC complex/NCoR1	0.036	0.013	-10000	0	-10000	0	0
MEF2C/TIF2	-0.07	0.18	-10000	0	-0.41	82	82
endothelial cell migration	-0.015	0.12	1.2	4	-10000	0	4
MAX	0.01	0.004	-10000	0	-10000	0	0
RBBP7	0.011	0	-10000	0	-10000	0	0
RBBP4	0.008	0.032	-10000	0	-0.41	3	3
RUNX2	0.001	0.058	-10000	0	-0.34	15	15
RUNX3	0.002	0.055	-10000	0	-0.33	14	14
RUNX1	0.011	0	-10000	0	-10000	0	0
CTBP1	0.011	0	-10000	0	-10000	0	0
NR3C1	-0.054	0.15	-10000	0	-0.41	80	80
VDR	0.003	0.053	-10000	0	-0.33	13	13
CDKN1A	0.053	0.067	-10000	0	-1.2	1	1
KAT2B	0.004	0.054	-10000	0	-0.41	9	9
SMAD2/SMAD2/SMAD4/FOXH1	-0.036	0.1	-10000	0	-0.25	46	46
DCP1A	0.011	0	-10000	0	-10000	0	0
SKI	0.011	0	-10000	0	-10000	0	0
SERPINE1	0.015	0.12	-10000	0	-1.3	4	4
SMAD3/SMAD4/ATF2	0.011	0.048	-10000	0	-0.3	7	7
SMAD3/SMAD4/ATF3	-0.011	0.09	-10000	0	-0.27	50	50
SAP30	0.011	0	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.026	0.019	-10000	0	-0.22	2	2
JUN	-0.024	0.12	-10000	0	-0.35	23	23
SMAD3/SMAD4/IRF7	0.006	0.055	-10000	0	-0.28	9	9
TFE3	0.016	0.005	-10000	0	-10000	0	0
COL1A2	0.008	0.087	-10000	0	-0.79	5	5
mesenchymal cell differentiation	-0.005	0.059	0.27	17	-10000	0	17
DLX1	-0.032	0.11	-10000	0	-0.33	61	61
TCF3	0.011	0	-10000	0	-10000	0	0
FOS	-0.11	0.2	-10000	0	-0.41	159	159
SMAD3/SMAD4/Max	0.001	0.036	-10000	0	-0.26	5	5
Cbp/p300/SNIP1	0.023	0.016	-10000	0	-0.23	2	2
ZBTB17	0.009	0.002	-10000	0	-10000	0	0
LAMC1	0.033	0.036	-10000	0	-0.26	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	0.012	0.041	-10000	0	-0.25	5	5
IRF7	0.004	0.051	-10000	0	-0.35	10	10
ESR1	-0.038	0.13	-10000	0	-0.41	60	60
HNF4A	-0.041	0.12	-10000	0	-0.33	77	77
MEF2C	-0.074	0.17	-10000	0	-0.43	77	77
SMAD2-3/SMAD4	0.017	0.048	-10000	0	-0.28	4	4
Cbp/p300/Src-1	0.023	0.02	-10000	0	-0.22	3	3
IGHV3OR16-13	-0.001	0.008	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.011	0	-10000	0	-10000	0	0
CREBBP	0.01	0.026	-10000	0	-0.41	2	2
SKIL	0.011	0	-10000	0	-10000	0	0
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC2	0.011	0	-10000	0	-10000	0	0
SNIP1	0.011	0.001	-10000	0	-10000	0	0
GCN5L2	0.001	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.03	0.045	-10000	0	-0.26	4	4
MSG1/HSC70	0.004	0.047	-10000	0	-0.23	20	20
SMAD2	0.008	0.018	-10000	0	-10000	0	0
SMAD3	0.009	0.047	-10000	0	-0.45	4	4
SMAD3/E2F4-5/DP1/p107/SMAD4	0.026	0.033	-10000	0	-0.22	4	4
SMAD2/SMAD2/SMAD4	0.002	0.043	-10000	0	-0.28	10	10
NCOR1	0.011	0	-10000	0	-10000	0	0
NCOA2	-0.003	0.077	-10000	0	-0.41	18	18
NCOA1	0.01	0.018	-10000	0	-0.41	1	1
MYOD/E2A	-0.01	0.067	-10000	0	-0.22	50	50
SMAD2-3/SMAD4/SP1/MIZ-1	0.044	0.049	-10000	0	-0.24	3	3
IFNB1	0.013	0.064	-10000	0	-0.31	13	13
SMAD3/SMAD4/MEF2C	-0.065	0.17	-10000	0	-0.44	69	69
CITED1	-0.003	0.068	-10000	0	-0.34	20	20
SMAD2-3/SMAD4/ARC105	0.024	0.044	-10000	0	-0.28	2	2
RBL1	0.011	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.041	0.037	-10000	0	-0.34	2	2
RUNX1-3/PEBPB2	0.017	0.031	-10000	0	-0.17	14	14
SMAD7	0.001	0.13	-10000	0	-0.48	12	12
MYC/MIZ-1	0.007	0.041	-10000	0	-0.28	10	10
SMAD3/SMAD4	0.012	0.056	-10000	0	-0.4	4	4
IL10	0.009	0.092	-10000	0	-0.29	34	34
PIASy/HDAC complex	0.01	0.003	-10000	0	-10000	0	0
PIAS3	0.011	0.002	-10000	0	-10000	0	0
CDK2	0.012	0.003	-10000	0	-10000	0	0
IL5	0.011	0.065	-10000	0	-0.31	5	5
CDK4	0.012	0.003	-10000	0	-10000	0	0
PIAS4	0.01	0.003	-10000	0	-10000	0	0
ATF3	-0.027	0.12	-10000	0	-0.41	47	47
SMAD3/SMAD4/SP1	0.033	0.049	-10000	0	-0.25	5	5
FOXG1	-0.16	0.17	-10000	0	-0.33	252	252
FOXO3	0.022	0.003	-10000	0	-10000	0	0
FOXO1	0.02	0.023	-10000	0	-0.28	3	3
FOXO4	0.021	0.019	-10000	0	-0.28	2	2
heart looping	-0.073	0.17	-10000	0	-0.43	77	77
CEBPB	0.012	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.012	0.081	-10000	0	-0.24	38	38
MYOD1	-0.028	0.098	-10000	0	-0.33	50	50
SMAD3/SMAD4/HNF4	-0.017	0.08	-10000	0	-0.22	33	33
SMAD3/SMAD4/GATA3	0	0.071	-10000	0	-0.28	11	11
SnoN/SIN3/HDAC complex/NCoR1	0.011	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.027	0.046	-10000	0	-0.22	3	3
SMAD3/SMAD4/SP1-3	0.041	0.046	-10000	0	-0.25	2	2
MED15	0.011	0	-10000	0	-10000	0	0
SP1	0.018	0.013	-10000	0	-10000	0	0
SIN3B	0.011	0	-10000	0	-10000	0	0
SIN3A	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.061	0.14	-10000	0	-0.35	61	61
ITGB5	0.043	0.036	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.037	0.013	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.032	0.11	-10000	0	-0.25	93	93
AR	-0.061	0.16	-10000	0	-0.41	90	90
negative regulation of cell growth	0.019	0.062	-10000	0	-0.3	5	5
SMAD3/SMAD4/MYOD	-0.009	0.069	-10000	0	-0.22	25	25
E2F5	0.011	0	-10000	0	-10000	0	0
E2F4	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.016	0.085	-10000	0	-0.25	13	13
SMAD2-3/SMAD4/FOXO1-3a-4	0.038	0.038	-10000	0	-0.35	2	2
TFDP1	0.011	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.018	0.12	-10000	0	-0.34	25	25
SMAD3/SMAD4/RUNX2	0.007	0.06	-10000	0	-0.27	17	17
TGIF2	0.011	0	-10000	0	-10000	0	0
TGIF1	0.011	0	-10000	0	-10000	0	0
ATF2	0.009	0.032	-10000	0	-0.41	3	3

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.015	0.082	-10000	0	-0.2	83	83
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.003	0.033	-10000	0	-0.23	11	11
GNB1/GNG2	0.01	0.033	-10000	0	-0.23	10	10
GNB1	0.011	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.026	0.079	-10000	0	-0.22	77	77
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	0.009	0.021	0.061	77	-10000	0	77
GNAL	-0.051	0.15	-10000	0	-0.41	77	77
GNG2	0.003	0.056	-10000	0	-0.4	10	10
CRH	-0.005	0.048	-10000	0	-0.33	11	11
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.028	-10000	0	-0.28	5	5
MAPK11	0.006	0.018	-10000	0	-0.28	2	2

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.011	0	-9999	-10000	0	0
SPHK1	0.01	0.021	-9999	-0.33	2	2
GNAI2	0.011	0	-9999	-10000	0	0
mol:S1P	0.018	0.005	-9999	-10000	0	0
GNAO1	-0.099	0.18	-9999	-0.41	138	138
mol:Sphinganine-1-P	0.017	0.014	-9999	-0.22	2	2
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.032	0.004	-9999	-10000	0	0
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.016	0	-9999	-10000	0	0
S1PR3	-0.004	0.079	-9999	-0.41	19	19
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0	0.003	-9999	-10000	0	0
S1PR5	-0.001	0.064	-9999	-0.35	17	17
S1PR4	0.009	0.03	-9999	-0.38	3	3
GNAI1	0.005	0.052	-9999	-0.41	8	8
S1P/S1P5/G12	0.02	0.033	-9999	-0.19	4	4
S1P/S1P3/Gq	-0.008	0.11	-9999	-0.27	57	57
S1P/S1P4/Gi	-0.031	0.11	-9999	-0.2	140	140
GNAQ	0.009	0.026	-9999	-0.41	2	2
GNAZ	-0.001	0.07	-9999	-0.41	15	15
GNA14	-0.031	0.13	-9999	-0.41	53	53
GNA15	0.006	0.039	-9999	-0.33	7	7
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.011	0	-9999	-10000	0	0
GNA11	0.002	0.06	-9999	-0.41	11	11
ABCC1	0.011	0	-9999	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.007	0.084	-10000	0	-0.41	22	22
Jak2/Leptin Receptor	-0.098	0.14	-10000	0	-0.4	60	60
PTP1B/AKT1	0.017	0.04	-10000	0	-0.2	5	5
FYN	0.011	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.013	0.044	-10000	0	-0.23	5	5
EGFR	0	0.068	-10000	0	-0.41	14	14
EGF/EGFR	-0.016	0.05	-10000	0	-0.25	17	17
CSF1	0.003	0.057	-10000	0	-0.41	10	10
AKT1	0.011	0.001	-10000	0	-10000	0	0
INSR	0.011	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.013	0.089	-10000	0	-0.27	27	27
Insulin Receptor/Insulin	-0.008	0.023	-10000	0	-10000	0	0
HCK	0.006	0.039	-10000	0	-0.33	7	7
CRK	0.011	0	-10000	0	-10000	0	0
TYK2	0.018	0.042	-10000	0	-0.22	5	5
EGF	-0.004	0.071	-10000	0	-0.33	23	23
YES1	0.011	0	-10000	0	-10000	0	0
CAV1	-0.002	0.078	-10000	0	-0.3	13	13
TXN	0.011	0.002	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.004	0.079	-10000	0	-0.24	32	32
cell migration	-0.013	0.044	0.23	5	-10000	0	5
STAT3	0.011	0.001	-10000	0	-10000	0	0
PRLR	-0.074	0.17	-10000	0	-0.41	106	106
ITGA2B	0.005	0.047	-10000	0	-0.4	7	7
CSF1R	0.008	0.035	-10000	0	-0.39	4	4
Prolactin Receptor/Prolactin	-0.057	0.13	-10000	0	-0.3	119	119
FGR	0.002	0.06	-10000	0	-0.41	11	11
PTP1B/p130 Cas	0.018	0.041	-10000	0	-0.22	5	5
Crk/p130 Cas	0.024	0.04	-10000	0	-0.2	5	5
DOK1	0.015	0.06	-10000	0	-0.25	14	14
JAK2	-0.037	0.13	-10000	0	-0.32	51	51
Jak2/Leptin Receptor/Leptin	-0.014	0.052	-10000	0	-0.38	7	7
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
PTPN1	0.013	0.044	-10000	0	-0.23	5	5
LYN	0.011	0	-10000	0	-10000	0	0
CDH2	-0.053	0.15	-10000	0	-0.41	80	80
SRC	0.019	0.019	-10000	0	-10000	0	0
ITGB3	-0.066	0.16	-10000	0	-0.41	96	96
CAT1/PTP1B	0.018	0.072	-10000	0	-0.31	7	7
CAPN1	0.012	0.001	-10000	0	-10000	0	0
CSK	0.011	0	-10000	0	-10000	0	0
PI3K	-0.007	0.025	-10000	0	-0.23	2	2
mol:H2O2	0	0.001	-10000	0	-10000	0	0
STAT3 (dimer)	-0.012	0.048	-10000	0	-0.35	7	7
negative regulation of transcription	-0.036	0.12	-10000	0	-0.32	51	51
FCGR2A	0.01	0.015	-10000	0	-0.33	1	1
FER	0.011	0.002	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.042	0.12	-10000	0	-0.28	103	103
BLK	-0.015	0.087	-10000	0	-0.33	37	37
Insulin Receptor/Insulin/Shc	0.016	0.002	-10000	0	-10000	0	0
RHOA	0.012	0.001	-10000	0	-10000	0	0
LEPR	-0.12	0.19	-10000	0	-0.41	160	160
BCAR1	0.011	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.011	0	-10000	0	-10000	0	0
mol:NADPH	0.001	0.001	-10000	0	-10000	0	0
TRPV6	0.013	0.067	-10000	0	-0.37	5	5
PRL	-0.008	0.079	-10000	0	-0.4	21	21
SOCS3	0.005	0.076	-10000	0	-1.2	2	2
SPRY2	0.006	0.045	-10000	0	-0.42	6	6
Insulin Receptor/Insulin/IRS1	-0.009	0.076	-10000	0	-0.24	53	53
CSF1/CSF1R	0.019	0.057	-10000	0	-0.26	12	12
Ras protein signal transduction	0.007	0.014	-10000	0	-10000	0	0
IRS1	-0.031	0.13	-10000	0	-0.41	53	53
INS	0.001	0.003	-10000	0	-10000	0	0
LEP	0.005	0.026	-10000	0	-0.33	3	3
STAT5B	-0.003	0.065	-10000	0	-0.24	17	17
STAT5A	-0.003	0.065	-10000	0	-0.24	16	16
GRB2	0.011	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.064	-10000	0	-0.26	17	17
CSN2	-0.03	0.061	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
LAT	0.019	0.019	-10000	0	-10000	0	0
YBX1	0.017	0.018	-10000	0	-0.4	1	1
LCK	0.008	0.035	-10000	0	-0.35	5	5
SHC1	0.011	0	-10000	0	-10000	0	0
NOX4	0.007	0.04	-10000	0	-0.4	5	5

×

Nectin adhesion pathway

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
PDGFRB	-0.007	0.084	-9999	-0.41	22	22
alphaV beta3 Integrin	-0.037	0.11	-9999	-0.28	96	96
PTK2	-0.036	0.086	-9999	-0.38	22	22
positive regulation of JNK cascade	-0.014	0.057	-9999	-0.28	22	22
CDC42/GDP	0.019	0.087	-9999	-0.38	22	22
Rac1/GDP	0.02	0.087	-9999	-0.38	22	22
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.011	0	-9999	-10000	0	0
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	-0.017	0.07	-9999	-0.35	22	22
nectin-3/I-afadin	0.004	0.059	-9999	-0.28	22	22
RAPGEF1	0.013	0.094	-9999	-0.42	22	22
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.007	0.11	-9999	-0.48	22	22
PDGFB-D/PDGFRB	-0.007	0.084	-9999	-0.41	22	22
TLN1	0.001	0.076	-9999	-0.26	34	34
Rap1/GTP	-0.014	0.06	-9999	-0.3	22	22
IQGAP1	0.011	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.021	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.004	0.059	-9999	-0.28	22	22
PVR	0.011	0	-9999	-10000	0	0
Necl-5(dimer)	0.011	0	-9999	-10000	0	0
mol:GDP	0.015	0.1	-9999	-0.46	22	22
MLLT4	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
PI3K	0.013	0.069	-9999	-0.33	8	8
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.015	0.014	-9999	-0.22	2	2
positive regulation of lamellipodium assembly	-0.015	0.06	-9999	-0.3	22	22
PVRL1	0.01	0.021	-9999	-0.33	2	2
PVRL3	-0.007	0.084	-9999	-0.41	22	22
PVRL2	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.041	-9999	-0.41	5	5
CDH1	0.009	0.026	-9999	-0.41	2	2
CLDN1	-0.043	0.14	-9999	-0.41	68	68
JAM-A/CLDN1	-0.011	0.091	-9999	-0.21	86	86
SRC	0	0.12	-9999	-0.53	22	22
ITGB3	-0.065	0.16	-9999	-0.41	96	96
nectin-1(dimer)/I-afadin/I-afadin	0.015	0.014	-9999	-0.22	2	2
FARP2	0.01	0.1	-9999	-0.46	22	22
RAC1	0.011	0	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.012	0.05	-9999	-0.23	22	22
nectin-1/I-afadin	0.015	0.014	-9999	-0.22	2	2
nectin-2/I-afadin	0.016	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.015	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.011	0.054	-9999	-0.24	22	22
CDC42/GTP/IQGAP1/filamentous actin	0.015	0	-9999	-10000	0	0
F11R	0.01	0.018	-9999	-0.41	1	1
positive regulation of filopodium formation	-0.014	0.057	-9999	-0.28	22	22
alphaV/beta3 Integrin/Talin	-0.022	0.11	-9999	-0.31	40	40
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.016	0	-9999	-10000	0	0
PIP5K1C	-0.005	0.081	-9999	-0.29	34	34
VAV2	0.01	0.1	-9999	-0.46	22	22
RAP1/GDP	-0.016	0.07	-9999	-0.35	22	22
ITGAV	0.011	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.012	0.05	-9999	-0.23	22	22
nectin-3(dimer)/I-afadin/I-afadin	0.004	0.059	-9999	-0.28	22	22
Rac1/GTP	-0.018	0.073	-9999	-0.36	22	22
PTPRM	-0.013	0.089	-9999	-0.26	55	55
E-cadherin/beta catenin/alpha catenin	-0.001	0.013	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC3	0.011	0	-10000	0	-10000	0	0
VDR	0.003	0.053	-10000	0	-0.33	13	13
Cbp/p300/PCAF	0.017	0.036	-10000	0	-0.23	11	11
EP300	0.011	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.02	0.051	-10000	0	-0.28	7	7
KAT2B	0.004	0.055	-10000	0	-0.41	9	9
MAPK14	0.011	0	-10000	0	-10000	0	0
AKT1	0.012	0.06	0.19	20	-0.24	12	32
RAR alpha/9cRA/Cyclin H	-0.02	0.064	-10000	0	-0.24	36	36
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.017	0.056	-10000	0	-0.27	11	11
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.004	0.066	-10000	0	-0.25	18	18
NCOR2	0.011	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.002	0.036	-10000	0	-0.23	13	13
RXRs/RARs/NRIP1/9cRA	-0.002	0.13	-10000	0	-0.4	43	43
NCOA2	-0.003	0.077	-10000	0	-0.41	18	18
NCOA3	0.01	0.015	-10000	0	-0.33	1	1
NCOA1	0.01	0.018	-10000	0	-0.41	1	1
VDR/VDR/DNA	0.003	0.053	-10000	0	-0.33	13	13
RARG	0.012	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.015	0.001	-10000	0	-10000	0	0
MAPK3	0.012	0.001	-10000	0	-10000	0	0
MAPK1	0.011	0	-10000	0	-10000	0	0
MAPK8	0.008	0.041	-10000	0	-0.41	5	5
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.011	0.12	-10000	0	-0.38	42	42
RARA	-0.004	0.072	-10000	0	-0.23	44	44
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.01	0.07	-10000	0	-0.3	16	16
PRKCA	-0.014	0.1	-10000	0	-0.41	34	34
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.012	0.14	-10000	0	-0.42	43	43
RXRG	-0.052	0.13	-10000	0	-0.3	100	100
RXRA	0.003	0.067	-10000	0	-0.2	44	44
RXRB	-0.013	0.087	-10000	0	-0.28	40	40
VDR/Vit D3/DNA	0.002	0.036	-10000	0	-0.23	13	13
RBP1	-0.007	0.084	-10000	0	-0.41	22	22
CRBP1/9-cic-RA	-0.004	0.059	-10000	0	-0.29	22	22
RARB	0.004	0.061	-10000	0	-0.41	11	11
PRKCG	-0.036	0.12	-10000	0	-0.34	73	73
MNAT1	0.011	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.002	0.14	-10000	0	-0.42	42	42
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.003	0.11	-10000	0	-0.34	41	41
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.069	-10000	0	-0.35	8	8
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.012	0.14	-10000	0	-0.42	43	43
positive regulation of DNA binding	-0.019	0.061	-10000	0	-0.23	36	36
NRIP1	-0.012	0.15	-10000	0	-0.78	10	10
RXRs/RARs	-0.017	0.14	-10000	0	-0.41	45	45
RXRs/RXRs/DNA/9cRA	-0.017	0.12	-10000	0	-0.4	42	42
PRKACA	0.011	0	-10000	0	-10000	0	0
CDK7	0.011	0	-10000	0	-10000	0	0
TFIIH	0.022	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.01	0.039	-10000	0	-0.33	2	2
CCNH	0.011	0	-10000	0	-10000	0	0
CREBBP	0.009	0.026	-10000	0	-0.41	2	2
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0.02	0.18	1	-10000	0	1
AES	0.011	0.017	0.16	1	-10000	0	1
FBXW11	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.014	0.023	-10000	0	-0.28	3	3
SMAD4	0.01	0.018	-10000	0	-0.41	1	1
DKK2	-0.016	0.1	-10000	0	-0.4	34	34
TLE1	0.011	0.025	0.16	1	-0.41	1	2
MACF1	0.011	0	-10000	0	-10000	0	0
CTNNB1	0.04	0.048	0.21	6	-10000	0	6
WIF1	-0.097	0.16	-10000	0	-0.35	158	158
beta catenin/RanBP3	0.02	0.091	0.36	33	-10000	0	33
KREMEN2	-0.021	0.1	-10000	0	-0.33	50	50
DKK1	-0.063	0.14	-10000	0	-0.33	112	112
beta catenin/beta TrCP1	0.045	0.045	0.2	6	-10000	0	6
FZD1	0.009	0.032	-10000	0	-0.41	3	3
AXIN2	-0.052	0.28	-10000	0	-1.3	26	26
AXIN1	0.011	0	-10000	0	-10000	0	0
RAN	0.011	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.014	0.023	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.05	0.056	0.22	1	-0.32	5	6
Axin1/APC/GSK3	0.018	0.031	0.16	6	-10000	0	6
Axin1/APC/GSK3/beta catenin/Macf1	0.043	0.028	-10000	0	-10000	0	0
HNF1A	0.006	0.046	0.16	1	-0.34	8	9
CTBP1	0.011	0.017	0.17	1	-10000	0	1
MYC	-0.017	0.19	-10000	0	-1.3	10	10
RANBP3	0.011	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.012	0.084	-10000	0	-0.25	35	35
NKD1	-0.02	0.1	-10000	0	-0.34	46	46
TCF4	-0.005	0.081	0.16	1	-0.4	20	21
TCF3	0.011	0.017	0.16	1	-10000	0	1
WNT1/LRP6/FZD1/Axin1	0.024	0.028	-10000	0	-0.2	3	3
Ran/GTP	0.008	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.019	0.11	0.44	28	-0.4	2	30
LEF1	0.007	0.045	0.16	1	-0.38	6	7
DVL1	0.03	0.019	-10000	0	-10000	0	0
CSNK2A1	0.011	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.047	0.077	-10000	0	-0.34	9	9
DKK1/LRP6/Kremen 2	-0.038	0.096	-10000	0	-0.18	155	155
LRP6	0.011	0	-10000	0	-10000	0	0
CSNK1A1	0.012	0.02	0.18	1	-10000	0	1
NLK	0.011	0.003	-10000	0	-10000	0	0
CCND1	0.003	0.056	-10000	0	-0.51	1	1
WNT1	0.004	0.042	-10000	0	-0.33	8	8
GSK3A	0.011	0	-10000	0	-10000	0	0
GSK3B	0.011	0	-10000	0	-10000	0	0
FRAT1	0.011	0	-10000	0	-10000	0	0
PPP2R5D	0.031	0.047	0.17	43	-10000	0	43
APC	0.027	0.025	-10000	0	-0.18	3	3
WNT1/LRP6/FZD1	0.037	0.059	0.2	32	-0.19	3	35
CREBBP	0.01	0.03	-10000	0	-0.39	2	2

×

BARD1 signaling events

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
BARD1/CSTF1	0.01	0.042	-10000	0	-0.28	11	11
ATM	0.011	0	-10000	0	-10000	0	0
UBE2D3	0.011	0	-10000	0	-10000	0	0
PRKDC	0.011	0	-10000	0	-10000	0	0
ATR	0.011	0	-10000	0	-10000	0	0
UBE2L3	0.011	0	-10000	0	-10000	0	0
FANCD2	0.02	0.007	-10000	0	-10000	0	0
protein ubiquitination	-0.057	0.07	-10000	0	-0.33	5	5
XRCC5	0.011	0	-10000	0	-10000	0	0
XRCC6	0.011	0	-10000	0	-10000	0	0
M/R/N Complex	0.022	0	-10000	0	-10000	0	0
MRE11A	0.011	0	-10000	0	-10000	0	0
DNA-PK	0.022	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.019	0.029	-10000	0	-10000	0	0
FANCF	0.009	0.026	-10000	0	-0.41	2	2
BRCA1	0.011	0	-10000	0	-10000	0	0
CCNE1	-0.13	0.17	-10000	0	-0.33	214	214
CDK2/Cyclin E1	-0.079	0.12	-10000	0	-0.22	214	214
FANCG	0.011	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.01	0.042	-10000	0	-0.28	11	11
FANCE	0.011	0	-10000	0	-10000	0	0
FANCC	0.011	0	-10000	0	-10000	0	0
NBN	0.011	0	-10000	0	-10000	0	0
FANCA	-0.071	0.14	-10000	0	-0.33	126	126
DNA repair	-0.015	0.087	-10000	0	-0.31	7	7
BRCA1/BARD1/ubiquitin	0.01	0.042	-10000	0	-0.28	11	11
BARD1/DNA-PK	0.024	0.032	-10000	0	-0.2	11	11
FANCL	0.011	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.01	0.042	0.28	11	-10000	0	11
BRCA1/BARD1/CTIP/M/R/N Complex	0.028	0.031	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0.017	0.036	-10000	0	-0.23	11	11
BRCA1/BARD1/P53	0.023	0.034	-10000	0	-0.2	12	12
BARD1/CSTF1/BRCA1	0.017	0.036	-10000	0	-0.23	11	11
BRCA1/BACH1	0.011	0	-10000	0	-10000	0	0
BARD1	0.002	0.06	-10000	0	-0.41	11	11
PCNA	0.011	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.017	0.036	-10000	0	-0.23	11	11
BRCA1/BARD1/UbcH7	0.017	0.036	-10000	0	-0.23	11	11
BRCA1/BARD1/RAD51/PCNA	-0.028	0.089	-10000	0	-0.29	11	11
BARD1/DNA-PK/P53	0.028	0.032	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.01	0.042	-10000	0	-0.28	11	11
BRCA1/BARD1/CTIP	0.022	0.032	-10000	0	-0.2	11	11
FA complex	0.013	0.036	-10000	0	-0.24	1	1
BARD1/EWS	0.01	0.042	-10000	0	-0.28	11	11
RBBP8	0.018	0	-10000	0	-10000	0	0
TP53	0.01	0.018	-10000	0	-0.41	1	1
TOPBP1	0.011	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.022	0.034	0.2	12	-10000	0	12
BRCA1/BARD1	-0.039	0.087	-10000	0	-0.34	5	5
CSTF1	0.011	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.002	0.042	-10000	0	-0.29	11	11
CDK2	0.011	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.089	0.16	-10000	0	-0.33	155	155
RAD50	0.011	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.01	0.042	-10000	0	-0.28	11	11
EWSR1	0.011	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.018	0.01	-9999	-0.22	1	1
BAD/BCL-XL/YWHAZ	0.027	0.008	-9999	-10000	0	0
CDKN1B	0.021	0.041	-9999	-0.23	1	1
CDKN1A	0.029	0.009	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.011	0	-9999	-10000	0	0
FOXO3	0.029	0.004	-9999	-10000	0	0
AKT1	0	0.002	-9999	-10000	0	0
BAD	0.011	0	-9999	-10000	0	0
AKT3	-0.096	0.14	-9999	-0.28	199	199
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.029	0.013	-9999	-10000	0	0
AKT1/ASK1	0.027	0.015	-9999	-10000	0	0
BAD/YWHAZ	0.022	0	-9999	-10000	0	0
RICTOR	0.009	0.026	-9999	-0.41	2	2
RAF1	0.011	0	-9999	-10000	0	0
JNK cascade	-0.026	0.015	-9999	-10000	0	0
TSC1	0.029	0.009	-9999	-10000	0	0
YWHAZ	0.011	0	-9999	-10000	0	0
AKT1/RAF1	0.03	0.004	-9999	-10000	0	0
EP300	0.011	0	-9999	-10000	0	0
mol:GDP	0.024	0.004	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.029	0.004	-9999	-10000	0	0
YWHAQ	0.011	0	-9999	-10000	0	0
TBC1D4	0.017	0.021	-9999	-0.22	4	4
MAP3K5	0.009	0.032	-9999	-0.41	3	3
MAPKAP1	0.011	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.01	0.015	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0
AKT1S1	0.029	0.004	-9999	-10000	0	0
CASP9	0.029	0.004	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.026	0.04	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.022	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
AKT2/p21CIP1	0.033	0.009	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0.002	-9999	-10000	0	0
CHUK	0.029	0.004	-9999	-10000	0	0
BAD/BCL-XL	0.04	0.007	-9999	-10000	0	0
mTORC2	0.013	0.014	-9999	-0.21	2	2
AKT2	0.014	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.022	0.018	-9999	-10000	0	0
PDPK1	0.011	0	-9999	-10000	0	0
MDM2	0.029	0.004	-9999	-10000	0	0
MAPKKK cascade	-0.029	0.004	-9999	-10000	0	0
MDM2/Cbp/p300	0.039	0.012	-9999	-10000	0	0
TSC1/TSC2	0.034	0.009	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.012	-9999	-10000	0	0
glucose import	-0.085	0.11	-9999	-0.2	257	257
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.004	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.085	0.11	-9999	-0.2	257	257
GSK3A	0.029	0.004	-9999	-10000	0	0
FOXO1	0.028	0.015	-9999	-10000	0	0
GSK3B	0.029	0.004	-9999	-10000	0	0
SFN	-0.24	0.15	-9999	-0.33	388	388
G1/S transition of mitotic cell cycle	0.034	0.003	-9999	-10000	0	0
p27Kip1/14-3-3 family	-0.002	0.025	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
KPNA1	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
YWHAG	0.011	0	-9999	-10000	0	0
RHEB	0.011	0	-9999	-10000	0	0
CREBBP	0.009	0.026	-9999	-0.41	2	2

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.015	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.011	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.032	0.11	-9999	-0.33	66	66
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.01	0.018	-9999	-0.41	1	1
RAC1-CDC42/GTP/PAK family	-0.007	0.068	-9999	-0.17	74	74
response to UV	0	0	-9999	-10000	0	0
YES1	0.011	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	0.011	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
MAP3K12	0.008	0.037	-9999	-0.41	4	4
FGR	0.002	0.06	-9999	-0.41	11	11
p38 alpha/TAB1	-0.003	0.016	-9999	-0.21	1	1
PRKG1	-0.18	0.21	-9999	-0.41	232	232
DUSP8	0.007	0.041	-9999	-0.41	5	5
PGK/cGMP/p38 alpha	-0.066	0.076	-9999	-0.22	23	23
apoptosis	-0.003	0.015	-9999	-0.2	1	1
RAL/GTP	0.015	0	-9999	-10000	0	0
LYN	0.011	0	-9999	-10000	0	0
DUSP1	-0.092	0.18	-9999	-0.41	129	129
PAK1	0.011	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.028	0	-9999	-10000	0	0
TRAF6	0.011	0	-9999	-10000	0	0
RAC1	0.011	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	0.011	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.015	0	-9999	-10000	0	0
MAPK11	0.032	0.036	-9999	-10000	0	0
BLK	-0.015	0.087	-9999	-0.33	37	37
HCK	0.006	0.039	-9999	-0.33	7	7
MAP2K3	0.011	0	-9999	-10000	0	0
DUSP16	0.011	0	-9999	-10000	0	0
DUSP10	0.011	0	-9999	-10000	0	0
TRAF6/MEKK3	0.014	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.035	0.028	-9999	-0.23	1	1
positive regulation of innate immune response	0.039	0.04	-9999	-10000	0	0
LCK	0.008	0.035	-9999	-0.35	5	5
p38alpha-beta/MKP7	0.044	0.038	-9999	-10000	0	0
p38alpha-beta/MKP5	0.044	0.038	-9999	-10000	0	0
PGK/cGMP	-0.12	0.15	-9999	-0.29	232	232
PAK2	0.011	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.018	0.074	-9999	-0.26	9	9
CDC42	0.011	0	-9999	-10000	0	0
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
PAK3	-0.052	0.14	-9999	-0.41	74	74

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.13	0.12	-9999	-0.44	4	4
RAD9A	0.011	0	-9999	-10000	0	0
AP1	-0.08	0.14	-9999	-0.29	160	160
IFNAR2	0.007	0.019	-9999	-0.41	1	1
AKT1	-0.012	0.058	-9999	-0.18	22	22
ER alpha/Oestrogen	-0.028	0.094	-9999	-0.29	60	60
NFX1/SIN3/HDAC complex	0.032	0.016	-9999	-10000	0	0
EGF	-0.005	0.071	-9999	-0.34	23	23
SMG5	0.011	0	-9999	-10000	0	0
SMG6	0.011	0	-9999	-10000	0	0
SP3/HDAC2	0.012	0.009	-9999	-10000	0	0
TERT/c-Abl	-0.12	0.11	-9999	-0.44	5	5
SAP18	0.011	0.001	-9999	-10000	0	0
MRN complex	0.022	0	-9999	-10000	0	0
WT1	-0.3	0.18	-9999	-0.41	391	391
WRN	0.011	0	-9999	-10000	0	0
SP1	0.009	0.007	-9999	-10000	0	0
SP3	0.01	0.002	-9999	-10000	0	0
TERF2IP	0.011	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.1	0.09	-9999	-0.4	2	2
Mad/Max	0.012	0.009	-9999	-10000	0	0
TERT	-0.13	0.12	-9999	-0.46	3	3
CCND1	-0.11	0.11	-9999	-10000	0	0
MAX	0.01	0.002	-9999	-10000	0	0
RBBP7	0.011	0.001	-9999	-10000	0	0
RBBP4	0.008	0.032	-9999	-0.41	3	3
TERF2	0.01	0	-9999	-10000	0	0
PTGES3	0.011	0	-9999	-10000	0	0
SIN3A	0.011	0.001	-9999	-10000	0	0
Telomerase/911	0.009	0.021	-9999	-10000	0	0
CDKN1B	-0.016	0.12	-9999	-0.5	23	23
RAD1	0.011	0	-9999	-10000	0	0
XRCC5	0.011	0	-9999	-10000	0	0
XRCC6	0.011	0	-9999	-10000	0	0
SAP30	0.011	0.001	-9999	-10000	0	0
TRF2/PARP2	0.016	0	-9999	-10000	0	0
UBE3A	0.01	0.002	-9999	-10000	0	0
JUN	0.005	0.048	-9999	-0.41	7	7
E6	-0.001	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.005	-9999	-10000	0	0
FOS	-0.12	0.19	-9999	-0.41	159	159
IFN-gamma/IRF1	-0.02	0.086	-9999	-0.22	80	80
PARP2	0.011	0	-9999	-10000	0	0
BLM	-0.027	0.11	-9999	-0.33	59	59
Telomerase	-0.013	0.036	-9999	-10000	0	0
IRF1	0.007	0.033	-9999	-10000	0	0
ESR1	-0.037	0.13	-9999	-0.41	60	60
KU/TER	0.016	0	-9999	-10000	0	0
ATM/TRF2	0.017	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.037	0.015	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.038	0.015	-9999	-10000	0	0
HDAC1	0.011	0.001	-9999	-10000	0	0
HDAC2	0.008	0.006	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.016	0.029	-9999	-0.28	5	5
ABL1	0.009	0.026	-9999	-0.41	2	2
MXD1	0.01	0.002	-9999	-10000	0	0
MRE11A	0.011	0	-9999	-10000	0	0
HUS1	0.011	0	-9999	-10000	0	0
RPS6KB1	0.011	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.097	0.096	-9999	-0.4	2	2
NR2F2	-0.008	0.09	-9999	-0.41	25	25
MAPK3	0.003	0.041	-9999	-0.22	17	17
MAPK1	0.003	0.041	-9999	-0.22	17	17
TGFB1/TGF beta receptor Type II	0.01	0.018	-9999	-0.41	1	1
NFKB1	0.01	0.018	-9999	-0.41	1	1
HNRNPC	0.011	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	0.011	0	-9999	-10000	0	0
EGFR	-0.001	0.067	-9999	-0.41	14	14
mol:Oestrogen	-0.001	0.001	-9999	-10000	0	0
EGF/EGFR	-0.006	0.068	-9999	-0.25	36	36
MYC	0.002	0.058	-9999	-0.41	10	10
IL2	-0.008	0.059	-9999	-0.33	17	17
KU	0.016	0	-9999	-10000	0	0
RAD50	0.011	0	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
TGFB1	0.011	0.018	-9999	-0.41	1	1
TRF2/BLM	-0.008	0.068	-9999	-0.2	59	59
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.11	0.11	-9999	-0.44	2	2
SP1/HDAC2	0.014	0.01	-9999	-10000	0	0
PINX1	0.011	0	-9999	-10000	0	0
Telomerase/EST1A	-0.1	0.09	-9999	-0.4	2	2
Smad3/Myc	0.015	0.044	-9999	-0.24	14	14
911 complex	0.022	0	-9999	-10000	0	0
IFNG	-0.032	0.11	-9999	-0.32	57	57
Telomerase/PinX1	-0.1	0.09	-9999	-0.4	2	2
Telomerase/AKT1/mTOR/p70S6K	-0.015	0.041	-9999	-10000	0	0
SIN3B	0.011	0.001	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
Telomerase/EST1B	-0.1	0.09	-9999	-0.4	2	2
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.032	0	-9999	-10000	0	0
TRF2/WRN	0.016	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.1	0.09	-9999	-0.4	2	2
E2F1	-0.056	0.13	-9999	-0.33	100	100
ZNFX1	0.011	0.001	-9999	-10000	0	0
PIF1	-0.074	0.15	-9999	-0.33	132	132
NCL	0.011	0	-9999	-10000	0	0
DKC1	0.011	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

IL12-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
IL12/IL12R/TYK2/JAK2/SOCS1	0.023	0.076	-10000	0	-0.33	8	8
TBX21	0.004	0.25	-10000	0	-1	19	19
B2M	0.012	0.005	-10000	0	-10000	0	0
TYK2	0.014	0.016	-10000	0	-10000	0	0
IL12RB1	0.002	0.072	-10000	0	-0.37	18	18
GADD45B	0.038	0.17	-10000	0	-0.75	9	9
IL12RB2	-0.005	0.082	-10000	0	-0.33	30	30
GADD45G	0.015	0.25	-10000	0	-0.95	24	24
natural killer cell activation	0.003	0.016	-10000	0	-10000	0	0
RELB	0.011	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
IL18	0.01	0.042	-10000	0	-0.33	8	8
IL2RA	-0.003	0.068	-10000	0	-0.33	21	21
IFNG	-0.028	0.1	-10000	0	-0.33	57	57
STAT3 (dimer)	0.028	0.19	-10000	0	-0.62	21	21
HLA-DRB5	-0.005	0.068	-10000	0	-0.38	16	16
FASLG	0.009	0.23	-10000	0	-0.98	15	15
NF kappa B2 p52/RelB	-0.064	0.17	-10000	0	-0.69	25	25
CD4	0.006	0.017	-10000	0	-0.35	1	1
SOCS1	0.01	0.018	-10000	0	-0.41	1	1
EntrezGene:6955	-0.006	0.014	-10000	0	-10000	0	0
CD3D	-0.008	0.074	-10000	0	-0.37	21	21
CD3E	-0.002	0.065	-10000	0	-0.39	14	14
CD3G	0	0.048	-10000	0	-0.35	9	9
IL12Rbeta2/JAK2	0.005	0.074	-10000	0	-0.24	39	39
CCL3	0.013	0.22	-10000	0	-0.89	14	14
CCL4	0.009	0.24	-10000	0	-0.97	16	16
HLA-A	0.011	0.016	-10000	0	-0.33	1	1
IL18/IL18R	0.043	0.054	-10000	0	-0.24	12	12
NOS2	0.018	0.23	-10000	0	-0.89	20	20
IL12/IL12R/TYK2/JAK2/SPHK2	0.023	0.074	-10000	0	-0.3	8	8
IL1R1	0.003	0.26	-10000	0	-1.1	19	19
IL4	0.001	0.017	-10000	0	-10000	0	0
JAK2	0.007	0.058	-10000	0	-0.42	9	9
EntrezGene:6957	-0.005	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.002	0.12	-10000	0	-0.64	14	14
RAB7A	0.044	0.18	-10000	0	-0.69	10	10
lysosomal transport	0.044	0.17	-10000	0	-0.64	11	11
FOS	-0.3	0.56	-10000	0	-1.1	162	162
STAT4 (dimer)	0.04	0.2	-10000	0	-0.66	20	20
STAT5A (dimer)	-0.074	0.18	-10000	0	-0.69	29	29
GZMA	-0.004	0.27	-10000	0	-1.1	21	21
GZMB	0.003	0.23	-10000	0	-0.96	15	15
HLX	0.011	0	-10000	0	-10000	0	0
LCK	0.02	0.23	-10000	0	-0.77	25	25
TCR/CD3/MHC II/CD4	-0.042	0.12	-10000	0	-0.21	131	131
IL2/IL2R	0.008	0.063	-10000	0	-0.3	14	14
MAPK14	0.036	0.2	-10000	0	-0.68	23	23
CCR5	0.03	0.2	-10000	0	-0.9	12	12
IL1B	0.011	0.042	-10000	0	-0.44	4	4
STAT6	0.024	0.078	0.2	1	-0.26	10	11
STAT4	0.01	0.018	-10000	0	-0.41	1	1
STAT3	0.011	0	-10000	0	-10000	0	0
STAT1	0.01	0.015	-10000	0	-0.33	1	1
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
NFKB2	0.011	0	-10000	0	-10000	0	0
IL12B	0.01	0.021	-10000	0	-0.31	1	1
CD8A	0	0.068	-10000	0	-0.39	15	15
CD8B	-0.011	0.088	-10000	0	-0.35	33	33
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.023	0.076	0.33	8	-10000	0	8
IL2RB	0.01	0.018	-10000	0	-0.41	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.041	0.19	-10000	0	-0.61	20	20
IL2RG	0.005	0.048	-10000	0	-0.36	9	9
IL12	0.014	0.05	-10000	0	-0.23	16	16
STAT5A	0.01	0.018	-10000	0	-0.41	1	1
CD247	0.006	0.031	-10000	0	-0.38	3	3
IL2	-0.007	0.059	-10000	0	-0.33	17	17
SPHK2	0.011	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.003	0.062	-10000	0	-0.35	15	15
IL12/IL12R/TYK2/JAK2	0.019	0.24	-10000	0	-0.81	25	25
MAP2K3	0.031	0.2	-10000	0	-0.66	24	24
RIPK2	0.011	0	-10000	0	-10000	0	0
MAP2K6	0.033	0.2	-10000	0	-0.67	23	23
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.004	0.028	-10000	0	-0.42	2	2
IL18RAP	0.01	0.046	-10000	0	-0.38	7	7
IL12Rbeta1/TYK2	0.012	0.056	-10000	0	-0.26	18	18
EOMES	-0.01	0.14	-10000	0	-1.2	7	7
STAT1 (dimer)	0.03	0.18	-10000	0	-0.63	19	19
T cell proliferation	0.038	0.16	-10000	0	-0.5	21	21
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.012	0.038	-10000	0	-0.41	4	4
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.039	0.13	0.24	1	-0.55	21	22
ATF2	0.039	0.19	-10000	0	-0.64	22	22

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.007	0.07	-10000	0	-0.28	32	32
PRKCZ	0.01	0.024	-10000	0	-0.37	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.003	0.023	-10000	0	-0.23	4	4
IRAK/TOLLIP	0.01	0.053	-10000	0	-0.2	32	32
IKBKB	0.011	0	-10000	0	-10000	0	0
IKBKG	0.011	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.015	0.086	-10000	0	-0.24	64	64
IL1A	-0.012	0.084	-10000	0	-0.33	34	34
IL1B	0.015	0.035	-10000	0	-0.33	5	5
IRAK/TRAF6/p62/Atypical PKCs	0.011	0.047	-10000	0	-0.34	1	1
IL1R2	-0.013	0.089	-10000	0	-0.34	36	36
IL1R1	0.004	0.055	-10000	0	-0.41	9	9
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.026	0.057	0.18	23	-0.26	10	33
TOLLIP	0.011	0	-10000	0	-10000	0	0
TICAM2	0.004	0.051	-10000	0	-0.41	8	8
MAP3K3	0.011	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.007	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.041	0.042	-10000	0	-10000	0	0
JUN	0.002	0.069	-10000	0	-0.28	9	9
MAP3K7	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.028	0.05	-10000	0	-0.42	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88	0.011	0.057	-10000	0	-0.23	11	11
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.017	0.053	-10000	0	-0.21	11	11
IL1 beta fragment/IL1R1/IL1RAP	0.02	0.045	-10000	0	-0.22	16	16
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
MAPK8	-0.001	0.068	-10000	0	-0.29	7	7
IRAK1	0.003	0.059	-10000	0	-0.23	32	32
IL1RN/IL1R1	-0.023	0.092	-10000	0	-0.23	85	85
IRAK4	0.011	0	-10000	0	-10000	0	0
PRKCI	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
PI3K	0.013	0.031	-10000	0	-0.28	6	6
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.026	0.04	-10000	0	-0.28	4	4
CHUK	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.02	0.045	-10000	0	-0.22	16	16
IL1 beta/IL1R2	0.005	0.058	-10000	0	-0.19	41	41
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.01	0.039	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.007	0.039	-10000	0	-0.38	3	3
IRAK3	-0.008	0.088	-10000	0	-0.41	24	24
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.027	0.049	-10000	0	-0.36	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.02	0.04	-10000	0	-0.22	11	11
IL1 alpha/IL1R1/IL1RAP	0.004	0.062	-10000	0	-0.2	44	44
RELA	0.011	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.011	0	-10000	0	-10000	0	0
MYD88	0.011	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.016	0.05	-10000	0	-0.18	32	32
IL1RAP	0.009	0.032	-10000	0	-0.41	3	3
UBE2N	0.011	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.015	0.047	-10000	0	-0.3	6	6
CASP1	0.009	0.026	-10000	0	-0.41	2	2
IL1RN/IL1R2	-0.034	0.1	-10000	0	-0.24	105	105
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.026	0.042	-10000	0	-0.21	15	15
TMEM189-UBE2V1	-0.021	0.099	-10000	0	-0.41	32	32
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.018	0.058	-10000	0	-0.34	9	9
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
IL1RN	-0.039	0.12	-10000	0	-0.33	78	78
TRAF6/TAK1/TAB1/TAB2	-0.011	0.042	-10000	0	-0.18	32	32
MAP2K6	-0.005	0.069	-10000	0	-0.31	6	6

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.021	0.021	-9999	-0.17	6	6
SNTA1	0.011	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.021	0.021	-9999	-0.17	6	6
MAPK12	-0.01	0.073	-9999	-0.21	28	28
CCND1	0.003	0.033	-9999	-10000	0	0
p38 gamma/SNTA1	-0.003	0.069	-9999	-0.34	1	1
MAP2K3	0.011	0	-9999	-10000	0	0
PKN1	0.011	0	-9999	-10000	0	0
G2/M transition checkpoint	-0.01	0.073	-9999	-0.21	28	28
MAP2K6	-0.017	0.081	-9999	-0.19	92	92
MAPT	0.001	0.062	-9999	-0.27	20	20
MAPK13	0.015	0.025	-9999	-0.22	6	6
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	-0.001	0.064	-9999	-0.28	27	27

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.012	0.068	-10000	0	-0.35	15	15
FYN	0.033	0.1	-10000	0	-0.44	16	16
LAT/GRAP2/SLP76	-0.013	0.082	-10000	0	-0.39	18	18
IKBKB	0.011	0	-10000	0	-10000	0	0
AKT1	0.038	0.078	-10000	0	-0.32	17	17
B2M	0.012	0.002	-10000	0	-10000	0	0
IKBKG	-0.004	0.019	-10000	0	-0.11	10	10
MAP3K8	0.009	0.032	-10000	0	-0.41	3	3
mol:Ca2+	-0.006	0.017	-10000	0	-0.082	19	19
integrin-mediated signaling pathway	0.015	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.037	0.11	-10000	0	-0.44	18	18
TRPV6	-0.043	0.12	-10000	0	-0.4	57	57
CD28	0.01	0.021	-10000	0	-0.33	2	2
SHC1	0.032	0.097	-10000	0	-0.42	17	17
receptor internalization	0.027	0.09	-10000	0	-0.43	15	15
PRF1	0.021	0.14	-10000	0	-0.99	7	7
KRAS	0.01	0.015	-10000	0	-0.33	1	1
GRB2	0.011	0	-10000	0	-10000	0	0
COT/AKT1	0.039	0.065	-10000	0	-0.27	15	15
LAT	0.032	0.097	-10000	0	-0.43	16	16
EntrezGene:6955	0.001	0.002	-10000	0	-10000	0	0
CD3D	-0.002	0.073	-10000	0	-0.36	21	21
CD3E	0.002	0.065	-10000	0	-0.39	14	14
CD3G	0.005	0.047	-10000	0	-0.35	9	9
RASGRP2	-0.011	0.059	-10000	0	-0.16	73	73
RASGRP1	0.04	0.085	-10000	0	-0.35	17	17
HLA-A	0.012	0.015	-10000	0	-0.33	1	1
RASSF5	0.011	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.035	-10000	0	-0.11	12	12
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.008	0.032	-10000	0	-0.18	13	13
PRKCA	-0.006	0.047	-10000	0	-0.2	19	19
GRAP2	-0.003	0.074	-10000	0	-0.41	17	17
mol:IP3	0.003	0.081	0.18	49	-0.33	14	63
EntrezGene:6957	0.001	0.002	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.018	0.084	-10000	0	-0.41	14	14
ORAI1	0.027	0.074	0.24	57	-10000	0	57
CSK	0.031	0.099	-10000	0	-0.42	17	17
B7 family/CD28	0.032	0.098	-10000	0	-0.43	16	16
CHUK	0.011	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.027	0.11	-10000	0	-0.41	22	22
PTPN6	0.029	0.098	-10000	0	-0.43	16	16
VAV1	0.031	0.1	-10000	0	-0.44	17	17
Monovalent TCR/CD3	0.012	0.064	-10000	0	-0.29	19	19
CBL	0.011	0	-10000	0	-10000	0	0
LCK	0.03	0.1	-10000	0	-0.46	16	16
PAG1	0.03	0.1	-10000	0	-0.43	18	18
RAP1A	0.011	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.027	0.11	-10000	0	-0.48	16	16
CD80	-0.008	0.079	-10000	0	-0.33	30	30
CD86	0.01	0.021	-10000	0	-0.34	2	2
PDK1/CARD11/BCL10/MALT1	-0.01	0.039	-10000	0	-0.21	14	14
HRAS	0.011	0	-10000	0	-10000	0	0
GO:0035030	0.029	0.086	-10000	0	-0.37	16	16
CD8A	0.001	0.068	-10000	0	-0.39	15	15
CD8B	-0.01	0.088	-10000	0	-0.35	33	33
PTPRC	0.003	0.057	-10000	0	-0.4	10	10
PDK1/PKC theta	0.039	0.097	-10000	0	-0.38	19	19
CSK/PAG1	0.033	0.099	-10000	0	-0.41	18	18
SOS1	0.011	0	-10000	0	-10000	0	0
peptide-MHC class I	0.018	0.011	-10000	0	-0.22	1	1
GRAP2/SLP76	-0.015	0.095	-10000	0	-0.44	19	19
STIM1	0.013	0.036	-10000	0	-10000	0	0
RAS family/GTP	0.039	0.036	-10000	0	-0.15	7	7
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.027	0.094	-10000	0	-0.45	15	15
mol:DAG	-0.006	0.059	-10000	0	-0.28	16	16
RAP1A/GDP	0.012	0.015	-10000	0	-0.057	6	6
PLCG1	0.011	0	-10000	0	-10000	0	0
CD247	0.01	0.03	-10000	0	-0.39	3	3
cytotoxic T cell degranulation	0.022	0.13	-10000	0	-0.92	7	7
RAP1A/GTP	-0.008	0.02	-10000	0	-0.057	73	73
mol:PI-3-4-5-P3	0.037	0.09	-10000	0	-0.37	18	18
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0	0.096	0.19	46	-0.42	14	60
NRAS	0.011	0	-10000	0	-10000	0	0
ZAP70	-0.001	0.064	-10000	0	-0.34	18	18
GRB2/SOS1	0.016	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.012	0.081	-10000	0	-0.39	17	17
MALT1	0.011	0	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.004	0.081	-10000	0	-0.26	44	44
CARD11	0.001	0.058	-10000	0	-0.35	14	14
PRKCB	-0.008	0.058	-10000	0	-0.27	20	20
PRKCE	-0.004	0.042	-10000	0	-0.21	14	14
PRKCQ	0.034	0.11	-10000	0	-0.42	20	20
LCP2	0.01	0.015	-10000	0	-0.33	1	1
BCL10	0.011	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.037	0.069	-10000	0	-0.28	17	17
IKK complex	0.03	0.037	-10000	0	-0.095	16	16
RAS family/GDP	-0.001	0.005	-10000	0	-10000	0	0
MAP3K14	0.038	0.052	-10000	0	-0.21	14	14
PDPK1	0.039	0.075	-10000	0	-0.31	17	17
TCR/CD3/MHC I/CD8/Fyn	0.02	0.12	-10000	0	-0.48	21	21

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.01	0.015	-10000	0	-0.33	1	1
NFATC1	0.034	0.051	-10000	0	-0.31	2	2
NFATC2	0.015	0.048	-10000	0	-0.21	8	8
NFATC3	0.018	0.016	-10000	0	-0.31	1	1
YWHAE	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.017	0.1	-10000	0	-0.26	52	52
Exportin 1/Ran/NUP214	0.021	0.006	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.032	0.081	-10000	0	-0.35	22	22
BCL2/BAX	-0.012	0.087	-10000	0	-0.28	50	50
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.004	-10000	0	-10000	0	0
CaM/Ca2+	0.008	0.004	-10000	0	-10000	0	0
BAX	0.011	0	-10000	0	-10000	0	0
MAPK14	0.011	0.003	-10000	0	-10000	0	0
BAD	0.011	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.011	0.1	-10000	0	-0.38	21	21
Calcineurin A alpha-beta B1/BCL2	-0.029	0.12	-10000	0	-0.41	50	50
FKBP8	0.011	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.01	0.099	0.38	21	-10000	0	21
KPNB1	0.011	0	-10000	0	-10000	0	0
KPNA2	-0.004	0.07	-10000	0	-0.33	23	23
XPO1	0.011	0	-10000	0	-10000	0	0
SFN	-0.24	0.15	-10000	0	-0.33	388	388
MAP3K8	0.008	0.032	-10000	0	-0.41	3	3
NFAT4/CK1 alpha	0.026	0.012	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.026	0.076	-10000	0	-0.23	34	34
CABIN1	-0.017	0.11	-10000	0	-0.27	52	52
CALM1	0.011	0.002	-10000	0	-10000	0	0
RAN	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.011	0	-10000	0	-10000	0	0
CAMK4	0.003	0.051	-10000	0	-0.36	10	10
mol:Ca2+	0	0.004	-10000	0	-10000	0	0
MAPK3	0.011	0	-10000	0	-10000	0	0
YWHAH	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.014	0.023	-10000	0	-0.28	3	3
YWHAB	0.011	0	-10000	0	-10000	0	0
MAPK8	0.007	0.041	-10000	0	-0.41	5	5
MAPK9	0.011	0	-10000	0	-10000	0	0
YWHAG	0.011	0	-10000	0	-10000	0	0
FKBP1A	0.011	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.044	0.049	-10000	0	-0.27	1	1
PRKCH	0.009	0.032	-10000	0	-0.41	3	3
CABIN1/Cbp/p300	0.015	0.019	-10000	0	-0.28	2	2
CASP3	0.011	0.003	-10000	0	-10000	0	0
PIM1	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.008	0.002	-10000	0	-10000	0	0
apoptosis	-0.008	0.023	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.02	-10000	0	-10000	0	0
PRKCB	-0.015	0.1	-10000	0	-0.41	32	32
PRKCE	0.011	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.022	0.014	-10000	0	-0.28	1	1
BAD/BCL-XL	0.016	0.01	-10000	0	-0.22	1	1
PRKCD	0.011	0	-10000	0	-10000	0	0
NUP214	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.024	-10000	0	-0.37	2	2
PRKCA	-0.016	0.1	-10000	0	-0.41	34	34
PRKCG	-0.038	0.12	-10000	0	-0.34	73	73
PRKCQ	-0.026	0.12	-10000	0	-0.41	47	47
FKBP38/BCL2	-0.012	0.087	-10000	0	-0.28	50	50
EP300	0.011	0.003	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.011	0	-10000	0	-10000	0	0
NFATc/JNK1	0.036	0.053	-10000	0	-0.29	2	2
CaM/Ca2+/FKBP38	0.015	0.004	-10000	0	-10000	0	0
FKBP12/FK506	0.008	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.011	0.03	-10000	0	-0.2	10	10
NFATc/ERK1	0.039	0.048	-10000	0	-0.28	2	2
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.032	0.081	-10000	0	-0.35	22	22
NR4A1	0.016	0.12	-10000	0	-0.4	34	34
GSK3B	0.011	0.003	-10000	0	-10000	0	0
positive T cell selection	0.018	0.016	-10000	0	-0.31	1	1
NFAT1/CK1 alpha	-0.01	0.029	-10000	0	-0.22	3	3
RCH1/ KPNB1	0.006	0.048	-10000	0	-0.22	23	23
YWHAQ	0.011	0	-10000	0	-10000	0	0
PRKACA	0.011	0.003	-10000	0	-10000	0	0
AKAP5	0.009	0.032	-10000	0	-0.41	3	3
MEF2D	0.011	0.003	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.011	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.038	0.049	-10000	0	-0.29	2	2
CREBBP	0.009	0.026	-10000	0	-0.41	2	2
BCL2	-0.029	0.12	-10000	0	-0.41	50	50

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.027	0.026	-9999	-10000	0	0
PLK1	-0.089	0.18	-9999	-0.61	22	22
CDKN1B	0.001	0.14	-9999	-0.44	27	27
FOXO3	-0.05	0.18	-9999	-0.51	55	55
KAT2B	-0.002	0.057	-9999	-0.42	9	9
FOXO1/SIRT1	0.022	0.03	-9999	-10000	0	0
CAT	-0.04	0.17	-9999	-0.55	21	21
CTNNB1	0.011	0	-9999	-10000	0	0
AKT1	0.007	0.016	-9999	-10000	0	0
FOXO1	0.026	0.026	-9999	-0.22	5	5
MAPK10	-0.019	0.089	-9999	-0.19	111	111
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.038	0.076	-9999	-0.31	3	3
response to oxidative stress	-0.005	0.018	-9999	-10000	0	0
FOXO3A/SIRT1	-0.074	0.15	-9999	-0.47	57	57
XPO1	0.012	0	-9999	-10000	0	0
EP300	0.012	0.001	-9999	-10000	0	0
BCL2L11	0.011	0.025	-9999	-10000	0	0
FOXO1/SKP2	0.029	0.024	-9999	-0.21	2	2
mol:GDP	-0.005	0.018	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
GADD45A	0.012	0.096	-9999	-0.44	1	1
YWHAQ	0.011	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.033	0.017	-9999	-10000	0	0
MST1	0.001	0.04	-9999	-0.34	6	6
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.011	0.021	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
MAPK8	0.024	0.023	-9999	-0.2	5	5
MAPK9	0.026	0.008	-9999	-10000	0	0
YWHAG	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
YWHAZ	0.011	0	-9999	-10000	0	0
SIRT1	0.009	0.026	-9999	-0.41	2	2
SOD2	0.019	0.12	-9999	-0.4	7	7
RBL2	-0.014	0.15	-9999	-0.8	5	5
RAL/GDP	0.016	0.012	-9999	-10000	0	0
CHUK	0.005	0.016	-9999	-10000	0	0
Ran/GTP	0.011	0.001	-9999	-10000	0	0
CSNK1G2	0.011	0	-9999	-10000	0	0
RAL/GTP	0.022	0.012	-9999	-10000	0	0
CSNK1G1	0.011	0	-9999	-10000	0	0
FASLG	-0.001	0.12	-9999	-1.3	4	4
SKP2	0.011	0	-9999	-10000	0	0
USP7	0.012	0	-9999	-10000	0	0
IKBKB	0.005	0.016	-9999	-10000	0	0
CCNB1	-0.052	0.18	-9999	-0.6	22	22
FOXO1-3a-4/beta catenin	0.033	0.11	-9999	-0.37	7	7
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.024	-9999	-0.2	2	2
CSNK1A1	0.011	0	-9999	-10000	0	0
SGK1	0.003	0.032	-9999	-0.44	2	2
CSNK1G3	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.02	0.002	-9999	-10000	0	0
ZFAND5	0.043	0.067	-9999	-10000	0	0
SFN	-0.24	0.15	-9999	-0.33	388	388
CDK2	0.013	0.002	-9999	-10000	0	0
FOXO3A/14-3-3	0.003	0.035	-9999	-10000	0	0
CREBBP	0.011	0.026	-9999	-0.41	2	2
FBXO32	-0.14	0.41	-9999	-1.2	68	68
BCL6	-0.013	0.14	-9999	-0.67	5	5
RALB	0.012	0	-9999	-10000	0	0
RALA	0.012	0	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.039	0.042	-10000	0	-0.54	1	1
UGCG	0.004	0.092	-10000	0	-0.64	10	10
AKT1/mTOR/p70S6K/Hsp90/TERT	0.022	0.1	-10000	0	-0.26	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.006	0.091	-10000	0	-0.63	10	10
mol:DAG	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.04	0.11	-10000	0	-0.34	60	60
FRAP1	0.017	0.15	-10000	0	-0.39	60	60
FOXO3	0.038	0.1	-10000	0	-0.36	17	17
AKT1	0.033	0.1	-10000	0	-0.38	17	17
GAB2	0.007	0.037	-10000	0	-0.41	4	4
SMPD1	0.017	0.02	-10000	0	-10000	0	0
SGMS1	0.017	0.02	-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	0.013	0.027	-10000	0	-0.24	6	6
CALM1	0.011	0	-10000	0	-10000	0	0
cell proliferation	0.02	0.074	-10000	0	-0.29	20	20
EIF3A	0.011	0	-10000	0	-10000	0	0
PI3K	0.016	0.033	-10000	0	-0.28	6	6
RPS6KB1	0.014	0.023	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.001	-10000	0	-10000	0	0
natural killer cell activation	0	0.003	-10000	0	-0.012	10	10
JAK3	0.01	0.03	-10000	0	-0.33	4	4
PIK3R1	0.008	0.041	-10000	0	-0.41	5	5
JAK1	0.011	0.026	-10000	0	-0.41	2	2
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
MYC	0.028	0.15	-10000	0	-0.82	12	12
MYB	0.013	0.046	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.039	0.072	-10000	0	-0.39	3	3
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.025	0.021	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.039	0.071	-10000	0	-0.38	3	3
Rac1/GDP	0.018	0.025	-10000	0	-0.21	6	6
T cell proliferation	0.042	0.069	-10000	0	-0.4	2	2
SHC1	0.011	0.004	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.002	0.007	-10000	0	-0.019	48	48
PRKCZ	0.042	0.07	-10000	0	-0.42	2	2
NF kappa B1 p50/RelA	-0.034	0.11	-10000	0	-0.34	60	60
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.034	0.045	-10000	0	-0.44	2	2
HSP90AA1	0.011	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
IL2RA	-0.003	0.067	-10000	0	-0.33	21	21
IL2RB	0.012	0.019	-10000	0	-0.41	1	1
TERT	-0.11	0.16	-10000	0	-0.33	193	193
E2F1	0.014	0.031	-10000	0	-10000	0	0
SOS1	0.011	0.004	-10000	0	-10000	0	0
RPS6	0.011	0	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.003	0.009	48	-10000	0	48
PTPN11	0.011	0.004	-10000	0	-10000	0	0
IL2RG	0.006	0.048	-10000	0	-0.36	9	9
actin cytoskeleton organization	0.042	0.069	-10000	0	-0.4	2	2
GRB2	0.011	0.004	-10000	0	-10000	0	0
IL2	-0.005	0.059	-10000	0	-0.33	17	17
PIK3CA	0.011	0.019	-10000	0	-0.41	1	1
Rac1/GTP	0.024	0.025	-10000	0	-0.19	6	6
LCK	0.009	0.035	-10000	0	-0.35	5	5
BCL2	-0.021	0.26	-10000	0	-0.81	51	51

×

Signaling events mediated by PRL

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
CCNE1	-0.13	0.17	-9999	-0.33	214	214
mol:Halofuginone	0.004	0	-9999	-10000	0	0
ITGA1	0.009	0.032	-9999	-0.41	3	3
CDKN1A	0.012	0.04	-9999	-0.36	1	1
PRL-3/alpha Tubulin	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.044	0.1	-9999	-0.29	80	80
AGT	-0.052	0.15	-9999	-0.4	80	80
CCNA2	-0.028	0.098	-9999	-0.33	18	18
TUBA1B	0.011	0	-9999	-10000	0	0
EGR1	-0.019	0.099	-9999	-0.28	68	68
CDK2/Cyclin E1	-0.041	0.088	-9999	-0.46	1	1
MAPK3	0.018	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.016	0	-9999	-10000	0	0
MAPK1	0.018	0	-9999	-10000	0	0
PTP4A1	0	0.075	-9999	-10000	0	0
PTP4A3	0.011	0	-9999	-10000	0	0
PTP4A2	0.011	0	-9999	-10000	0	0
ITGB1	0.018	0	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
RAC1	0.013	0.036	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.016	0	-9999	-10000	0	0
PRL-1/ATF-5	0.005	0.071	-9999	-0.33	1	1
RABGGTA	0.011	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	0.013	0.036	-9999	-10000	0	0
RHOA	0.013	0.036	-9999	-10000	0	0
cell motility	0.016	0.039	-9999	-10000	0	0
PRL-1/alpha Tubulin	0.006	0.069	-9999	-10000	0	0
PRL-3/alpha1 Integrin	0.015	0.022	-9999	-0.28	3	3
ROCK1	0.016	0.039	-9999	-10000	0	0
RABGGTB	0.011	0	-9999	-10000	0	0
CDK2	0.011	0	-9999	-10000	0	0
mitosis	0	0.074	-9999	-10000	0	0
ATF5	0.008	0.03	-9999	-0.33	4	4

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.069	0.088	-9999	-0.28	1	1
CaM/Ca2+	0.008	0	-9999	-10000	0	0
AKT1	0.011	0	-9999	-10000	0	0
AKT2	0.011	0	-9999	-10000	0	0
STXBP4	0.01	0.018	-9999	-0.41	1	1
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.073	0.1	-9999	-0.31	1	1
YWHAZ	0.011	0	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
YWHAQ	0.011	0	-9999	-10000	0	0
TBC1D4	0.016	0.026	-9999	-0.28	4	4
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
SNARE/Synip	0.022	0.011	-9999	-0.23	1	1
YWHAG	0.011	0	-9999	-10000	0	0
ASIP	0.007	0.016	-9999	-0.33	1	1
PRKCI	0.011	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0.008	0	-9999	-10000	0	0
RHOQ	0.011	0	-9999	-10000	0	0
GYS1	0.025	0	-9999	-10000	0	0
PRKCZ	0.01	0.024	-9999	-0.37	2	2
TRIP10	0.011	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.015	0	-9999	-10000	0	0
AS160/14-3-3	-0.006	0.029	-9999	-10000	0	0
VAMP2	0.011	0	-9999	-10000	0	0
SLC2A4	-0.08	0.11	-9999	-0.34	1	1
STX4	0.011	0	-9999	-10000	0	0
GSK3B	0.021	0	-9999	-10000	0	0
SFN	-0.24	0.15	-9999	-0.33	388	388
LNPEP	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.014	0.051	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.011	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.037	0.047	-10000	0	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.015	0.037	-10000	0	-0.23	11	11
antigen processing and presentation of peptide antigen via MHC class I	-0.031	0.043	-10000	0	-0.26	4	4
CaM/Ca2+	-0.013	0.036	-10000	0	-10000	0	0
RAP1A	0.011	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.019	0.049	-10000	0	-0.24	1	1
AKT1	0.024	0.049	-10000	0	-0.28	2	2
MAP2K1	0.024	0.046	-10000	0	-10000	0	0
MAP3K11	0.018	0.048	-10000	0	-10000	0	0
IFNGR1	0.011	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.18	0.16	-10000	0	-0.33	292	292
Rap1/GTP	-0.009	0.023	-10000	0	-10000	0	0
CRKL/C3G	0.016	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.013	0.055	-10000	0	-10000	0	0
CEBPB	0.048	0.048	-10000	0	-0.38	2	2
STAT3	0.011	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.018	0.068	-10000	0	-1	1	1
STAT1	0.018	0.049	-10000	0	-0.24	1	1
CALM1	0.011	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.027	0.1	-10000	0	-0.32	57	57
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
STAT1 (dimer)/PIAS1	0.023	0.047	-10000	0	-0.23	1	1
CEBPB/PTGES2/Cbp/p300	-0.003	0.018	-10000	0	-0.24	1	1
mol:Ca2+	0.012	0.05	-10000	0	-10000	0	0
MAPK3	0.033	0.042	-10000	0	-10000	0	0
STAT1 (dimer)	-0.038	0.057	-10000	0	-0.36	4	4
MAPK1	0.033	0.042	-10000	0	-10000	0	0
JAK2	0.004	0.054	-10000	0	-0.41	9	9
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
JAK1	0.009	0.026	-10000	0	-0.41	2	2
CAMK2D	0.009	0.026	-10000	0	-0.41	2	2
DAPK1	0.046	0.05	-10000	0	-0.58	2	2
SMAD7	0.001	0.041	-10000	0	-0.29	2	2
CBL/CRKL/C3G	0.027	0.044	-10000	0	-10000	0	0
PI3K	-0.014	0.039	-10000	0	-0.31	2	2
IFNG	-0.027	0.1	-10000	0	-0.32	57	57
apoptosis	0.027	0.04	-10000	0	-0.43	2	2
CAMK2G	0.011	0	-10000	0	-10000	0	0
STAT3 (dimer)	0.011	0	-10000	0	-10000	0	0
CAMK2A	-0.22	0.21	-10000	0	-0.41	292	292
CAMK2B	-0.046	0.13	-10000	0	-0.33	88	88
FRAP1	0.023	0.046	-10000	0	-0.27	2	2
PRKCD	0.026	0.05	-10000	0	-0.28	2	2
RAP1B	0.011	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.031	0.043	-10000	0	-0.26	4	4
PTPN2	0.011	0	-10000	0	-10000	0	0
EP300	0.011	0	-10000	0	-10000	0	0
IRF1	0.044	0.042	-10000	0	-10000	0	0
STAT1 (dimer)/PIASy	0.021	0.047	0.18	1	-0.23	1	2
SOCS1	0.001	0.056	-10000	0	-1.3	1	1
mol:GDP	-0.011	0.029	-10000	0	-10000	0	0
CASP1	0.001	0.041	-10000	0	-0.19	4	4
PTGES2	0.01	0.018	-10000	0	-0.41	1	1
IRF9	0.04	0.019	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.014	0.038	-10000	0	-0.3	2	2
RAP1/GDP	-0.009	0.024	-10000	0	-10000	0	0
CBL	0.017	0.048	-10000	0	-10000	0	0
MAP3K1	0.018	0.048	-10000	0	-10000	0	0
PIAS1	0.011	0	-10000	0	-10000	0	0
PIAS4	0.011	0	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.031	0.043	-10000	0	-0.26	4	4
PTPN11	0.011	0.05	-10000	0	-10000	0	0
CREBBP	0.01	0.026	-10000	0	-0.41	2	2
RAPGEF1	0.011	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.011	0	-10000	0	-10000	0	0
HDAC4	0.011	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.011	0.033	0.23	9	-10000	0	9
CDKN1A	-0.001	0.028	-10000	0	-0.61	1	1
KAT2B	0.004	0.055	-10000	0	-0.41	9	9
BAX	0.011	0	-10000	0	-10000	0	0
FOXO3	0	0.006	-10000	0	-10000	0	0
FOXO1	0.009	0.032	-10000	0	-0.41	3	3
FOXO4	0.016	0.022	-10000	0	-0.24	4	4
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.011	0	-10000	0	-10000	0	0
TAT	0.007	0.016	-10000	0	-0.33	1	1
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.014	0.078	-10000	0	-0.23	58	58
PPARGC1A	-0.077	0.17	-10000	0	-0.41	110	110
FHL2	0.007	0.041	-10000	0	-0.41	5	5
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	-0.001	0.018	-10000	0	-0.28	2	2
HIST2H4A	0.011	0.033	-10000	0	-0.23	9	9
SIRT1/FOXO3a	-0.001	0.015	-10000	0	-0.23	2	2
SIRT1	0.006	0.027	0.18	1	-0.41	2	3
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	-0.001	0.015	-10000	0	-0.23	2	2
SIRT1/Histone H1b	0.013	0.026	-10000	0	-0.22	4	4
apoptosis	0.001	0.015	0.23	2	-10000	0	2
SIRT1/PGC1A	-0.05	0.097	0.12	1	-0.24	111	112
p53/SIRT1	-0.001	0.026	0.36	1	-0.28	3	4
SIRT1/FOXO4	0.016	0.024	-10000	0	-0.2	6	6
FOXO1/FHL2/SIRT1	0.015	0.031	-10000	0	-0.21	10	10
HIST1H1E	0.012	0.025	-10000	0	-0.24	2	2
SIRT1/p300	-0.001	0.018	-10000	0	-0.28	2	2
muscle cell differentiation	0.014	0.065	0.19	59	-0.14	1	60
TP53	0.006	0.02	0.18	1	-0.41	1	2
KU70/SIRT1/BAX	-0.001	0.015	-10000	0	-0.23	2	2
CREBBP	0.009	0.026	-10000	0	-0.41	2	2
MEF2D	0.011	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.001	0.021	0.14	1	-0.26	3	4
ACSS2	0.015	0.019	-10000	0	-0.28	2	2
SIRT1/PCAF/MYOD	-0.014	0.065	0.14	1	-0.19	59	60

×

Syndecan-3-mediated signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.011	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.014	0.082	-9999	-0.21	3	3
Syndecan-3/Neurocan	0.007	0.028	-9999	-10000	0	0
POMC	-0.011	0.087	-9999	-0.36	31	31
EGFR	0	0.067	-9999	-0.4	14	14
Syndecan-3/EGFR	0.015	0.033	-9999	-0.18	13	13
AGRP	0.006	0.016	-9999	-0.33	1	1
NCSTN	0.011	0	-9999	-10000	0	0
PSENEN	0.011	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.005	0.048	-9999	-0.41	7	7
APH1A	0.011	0	-9999	-10000	0	0
NCAN	-0.004	0.058	-9999	-0.33	16	16
long-term memory	0.026	0.006	-9999	-10000	0	0
Syndecan-3/IL8	-0.026	0.072	-9999	-0.19	1	1
PSEN1	0.011	0	-9999	-10000	0	0
Src/Cortactin	0.016	0	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
limb bud formation	-0.001	0.005	-9999	-10000	0	0
MC4R	-0.004	0.056	-9999	-0.33	15	15
SRC	0.011	0	-9999	-10000	0	0
PTN	-0.089	0.18	-9999	-0.41	125	125
FGFR/FGF/Syndecan-3	-0.001	0.005	-9999	-10000	0	0
neuron projection morphogenesis	-0.025	0.078	-9999	-0.24	6	6
Syndecan-3/AgRP	0.011	0.013	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.004	0.027	-9999	-0.18	1	1
Fyn/Cortactin	0.016	0	-9999	-10000	0	0
SDC3	-0.001	0.005	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.026	0.071	-9999	-0.19	1	1
IL8	-0.09	0.16	-9999	-0.33	156	156
Syndecan-3/Fyn/Cortactin	0.026	0.006	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.004	-9999	-10000	0	0
alpha-MSH/MC4R	-0.009	0.072	-9999	-0.24	44	44
Gamma Secretase	0.03	0.024	-9999	-0.18	7	7

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.016	0.084	-9999	-0.38	22	22
PDGFB-D/PDGFRB/SLAP	0.004	0.06	-9999	-0.28	23	23
PDGFB-D/PDGFRB/APS/CBL	0.012	0.05	-9999	-0.23	22	22
AKT1	0.035	0.047	-9999	-0.3	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.016	0.091	-9999	-0.41	22	22
PIK3CA	0.01	0.018	-9999	-0.41	1	1
FGR	-0.021	0.1	-9999	-0.38	30	30
mol:Ca2+	0.011	0.096	-9999	-0.44	22	22
MYC	0.021	0.13	-9999	-0.67	13	13
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	0.02	0.047	-9999	-0.2	7	7
LRP1/PDGFRB/PDGFB	0.011	0.054	-9999	-0.24	23	23
GRB10	0.01	0.018	-9999	-0.41	1	1
PTPN11	0.011	0	-9999	-10000	0	0
GO:0007205	0.011	0.097	-9999	-0.45	22	22
PTEN	0.006	0.045	-9999	-0.41	6	6
GRB2	0.011	0	-9999	-10000	0	0
GRB7	-0.011	0.084	-9999	-0.34	33	33
PDGFB-D/PDGFRB/SHP2	0.004	0.059	-9999	-0.28	22	22
PDGFB-D/PDGFRB/GRB10	0.004	0.061	-9999	-0.28	23	23
cell cycle arrest	0.004	0.06	-9999	-0.28	23	23
HRAS	0.011	0	-9999	-10000	0	0
HIF1A	0.039	0.043	-9999	-0.26	2	2
GAB1	0.014	0.093	-9999	-0.41	22	22
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.018	0.086	-9999	-0.37	22	22
PDGFB-D/PDGFRB	0.013	0.052	-9999	-0.23	22	22
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.004	0.059	-9999	-0.28	22	22
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.015	0.072	-9999	-0.34	22	22
positive regulation of MAPKKK cascade	0.004	0.059	-9999	-0.28	22	22
PIK3R1	0.007	0.041	-9999	-0.41	5	5
mol:IP3	0.011	0.098	-9999	-0.45	22	22
E5	0	0.001	-9999	-10000	0	0
CSK	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.01	0.084	-9999	-0.26	52	52
SHB	0.011	0	-9999	-10000	0	0
BLK	-0.011	0.053	-9999	-0.26	22	22
PTPN2	0.011	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.004	0.059	-9999	-0.28	22	22
BCAR1	0.011	0	-9999	-10000	0	0
VAV2	0.017	0.096	-9999	-0.39	23	23
CBL	0.011	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.004	0.059	-9999	-0.28	22	22
LCK	-0.011	0.066	-9999	-0.29	22	22
PDGFRB	-0.006	0.085	-9999	-0.41	22	22
ACP1	0.011	0	-9999	-10000	0	0
HCK	-0.01	0.053	-9999	-0.26	22	22
ABL1	0.016	0.079	-9999	-0.34	22	22
PDGFB-D/PDGFRB/CBL	0.012	0.1	-9999	-0.47	22	22
PTPN1	0.011	0.002	-9999	-10000	0	0
SNX15	0.011	0	-9999	-10000	0	0
STAT3	0.011	0	-9999	-10000	0	0
STAT1	0.01	0.015	-9999	-0.33	1	1
cell proliferation	0.023	0.11	-9999	-0.55	15	15
SLA	0.01	0.015	-9999	-0.33	1	1
actin cytoskeleton reorganization	0.032	0.043	-9999	-0.35	1	1
SRC	-0.01	0.053	-9999	-0.26	22	22
PI3K	-0.01	0.039	-9999	-0.33	2	2
PDGFB-D/PDGFRB/GRB7/SHC	0	0.071	-9999	-0.21	52	52
SH2B2	0.011	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.016	0.093	-9999	-0.42	22	22
LYN	-0.01	0.053	-9999	-0.26	22	22
LRP1	0.009	0.026	-9999	-0.41	2	2
SOS1	0.011	0	-9999	-10000	0	0
STAT5B	0.009	0.026	-9999	-0.41	2	2
STAT5A	0.01	0.018	-9999	-0.41	1	1
NCK1-2/p130 Cas	-0.004	0.039	-9999	-0.37	1	1
SPHK1	0.01	0.021	-9999	-0.33	2	2
EDG1	0.001	0.002	-9999	-10000	0	0
mol:DAG	0.011	0.098	-9999	-0.45	22	22
PLCG1	0.01	0.1	-9999	-0.46	22	22
NHERF/PDGFRB	0.011	0.052	-9999	-0.22	25	25
YES1	-0.011	0.052	-9999	-0.26	22	22
cell migration	0.011	0.051	-9999	-0.22	25	25
SHC/Grb2/SOS1	-0.003	0.036	-9999	-10000	0	0
SLC9A3R2	0.011	0	-9999	-10000	0	0
SLC9A3R1	0.009	0.026	-9999	-0.33	3	3
NHERF1-2/PDGFRB/PTEN	0.016	0.054	-9999	-0.2	27	27
FYN	-0.01	0.053	-9999	-0.26	22	22
DOK1	0.017	0.046	-9999	-0.2	22	22
HRAS/GTP	0.008	0	-9999	-10000	0	0
PDGFB	0.011	0	-9999	-10000	0	0
RAC1	0.023	0.1	-9999	-0.37	32	32
PRKCD	0.018	0.046	-9999	-0.2	22	22
FER	0.018	0.046	-9999	-0.2	22	22
MAPKKK cascade	-0.006	0.034	-9999	-10000	0	0
RASA1	0.016	0.052	-9999	-0.21	26	26
NCK1	0.009	0.026	-9999	-0.41	2	2
NCK2	0.011	0	-9999	-10000	0	0
p62DOK/Csk	0.022	0.042	-9999	-0.18	22	22
PDGFB-D/PDGFRB/SHB	0.004	0.059	-9999	-0.28	22	22
chemotaxis	0.016	0.077	-9999	-0.34	22	22
STAT1-3-5/STAT1-3-5	-0.008	0.036	-9999	-0.35	1	1
Bovine Papilomavirus E5/PDGFRB	-0.003	0.06	-9999	-0.29	22	22
PTPRJ	0.011	0	-9999	-10000	0	0

×

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	0.015	0.002	-9999	-10000	0	0
RAS family/GTP	0.009	0.049	-9999	-0.27	5	5
NFATC4	0.015	0.046	-9999	-0.33	2	2
ERBB2IP	0.011	0.001	-9999	-10000	0	0
HSP90 (dimer)	0.011	0	-9999	-10000	0	0
mammary gland morphogenesis	0.004	0.048	-9999	-0.22	10	10
JUN	-0.005	0.069	-9999	-0.3	5	5
HRAS	0.01	0.001	-9999	-10000	0	0
DOCK7	0.014	0.048	-9999	-0.32	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.003	0.052	-9999	-0.21	20	20
AKT1	0.009	0.001	-9999	-10000	0	0
BAD	0.015	0.001	-9999	-10000	0	0
MAPK10	-0.008	0.067	-9999	-0.22	11	11
mol:GTP	-0.001	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.004	0.051	-9999	-0.23	10	10
RAF1	0.012	0.055	-9999	-0.28	5	5
ErbB2/ErbB3/neuregulin 2	-0.026	0.085	-9999	-0.21	87	87
STAT3	0.001	0.003	-9999	-10000	0	0
cell migration	0.002	0.061	-9999	-0.2	16	16
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	-0.076	0.18	-9999	-0.42	63	63
FOS	-0.12	0.24	-9999	-0.47	160	160
NRAS	0.01	0.001	-9999	-10000	0	0
mol:Ca2+	0.004	0.048	-9999	-0.22	10	10
MAPK3	-0.042	0.13	-9999	-0.42	15	15
MAPK1	-0.042	0.13	-9999	-0.42	15	15
JAK2	0.011	0.052	-9999	-0.32	2	2
NF2	0	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.011	0.051	-9999	-0.23	20	20
NRG1	-0.005	0.078	-9999	-0.41	19	19
GRB2/SOS1	0.016	0.001	-9999	-10000	0	0
MAPK8	0.005	0.056	-9999	-0.22	25	25
MAPK9	0.022	0.028	-9999	-0.16	2	2
ERBB2	-0.006	0.037	-9999	-0.23	14	14
ERBB3	0.008	0.032	-9999	-0.41	3	3
SHC1	0.01	0.001	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
apoptosis	0.001	0.006	-9999	-10000	0	0
STAT3 (dimer)	0.017	0.003	-9999	-10000	0	0
RNF41	0.02	0.003	-9999	-10000	0	0
FRAP1	0.008	0.001	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.007	0.028	-9999	-0.23	2	2
ErbB2/ErbB2/HSP90 (dimer)	-0.005	0.029	-9999	-0.18	14	14
CHRNA1	-0.051	0.13	-9999	-0.3	57	57
myelination	0.02	0.044	-9999	-0.31	2	2
PPP3CB	0.006	0.044	-9999	-0.3	2	2
KRAS	0.01	0.015	-9999	-0.33	1	1
RAC1-CDC42/GDP	0.022	0.045	-9999	-0.21	12	12
NRG2	-0.049	0.15	-9999	-0.41	74	74
mol:GDP	0.011	0.051	-9999	-0.23	20	20
SOS1	0.011	0.001	-9999	-10000	0	0
MAP2K2	0.011	0.061	-9999	-0.3	5	5
SRC	0.011	0	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	0.014	0.047	-9999	-0.31	2	2
MAP2K1	-0.046	0.13	-9999	-0.43	15	15
heart morphogenesis	0.004	0.048	-9999	-0.22	10	10
RAS family/GDP	0.017	0.047	-9999	-0.28	4	4
GRB2	0.011	0.001	-9999	-10000	0	0
PRKACA	-0.001	0.003	-9999	-10000	0	0
CHRNE	0.006	0.023	-9999	-0.18	4	4
HSP90AA1	0.011	0	-9999	-10000	0	0
activation of caspase activity	-0.009	0.001	-9999	-10000	0	0
nervous system development	0.004	0.048	-9999	-0.22	10	10
CDC42	0.011	0	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.008	0.044	-9999	-10000	0	0
epithelial cell differentiation	-0.04	0.077	-9999	-0.38	5	5
ITCH	0.017	0.011	-9999	-10000	0	0
WWP1	0.007	0.041	-9999	-10000	0	0
FYN	0.011	0	-9999	-10000	0	0
EGFR	0	0.067	-9999	-0.4	14	14
PRL	-0.008	0.079	-9999	-0.4	21	21
neuron projection morphogenesis	0.031	0.048	-9999	-10000	0	0
PTPRZ1	-0.013	0.078	-9999	-0.33	30	30
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.022	0.051	-9999	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.006	0.057	-9999	-0.33	1	1
ADAM17	0.017	0.011	-9999	-10000	0	0
ErbB4/ErbB4	0.003	0.053	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.008	0.057	-9999	-10000	0	0
NCOR1	0.011	0	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.012	0.053	-9999	-0.3	1	1
GRIN2B	0.008	0.061	-9999	-0.37	2	2
ErbB4/ErbB2/betacellulin	0.007	0.057	-9999	-0.3	2	2
STAT1	0.01	0.015	-9999	-0.33	1	1
HBEGF	0.011	0	-9999	-10000	0	0
PRLR	-0.074	0.17	-9999	-0.41	106	106
E4ICDs/ETO2	-0.026	0.095	-9999	-0.35	10	10
axon guidance	0.014	0.036	-9999	-10000	0	0
NEDD4	-0.018	0.11	-9999	-0.41	40	40
Prolactin receptor/Prolactin receptor/Prolactin	-0.056	0.13	-9999	-0.3	119	119
CBFA2T3	-0.049	0.15	-9999	-0.41	75	75
ErbB4/ErbB2/HBEGF	0.015	0.042	-9999	-10000	0	0
MAPK3	0.026	0.049	-9999	-10000	0	0
STAT1 (dimer)	0.007	0.046	-9999	-10000	0	0
MAPK1	0.026	0.049	-9999	-10000	0	0
JAK2	0.004	0.055	-9999	-0.41	9	9
ErbB4/ErbB2/neuregulin 1 beta	0.007	0.06	-9999	-0.32	2	2
NRG1	0.01	0.056	-9999	-0.28	19	19
NRG3	-0.008	0.069	-9999	-0.33	23	23
NRG2	-0.049	0.15	-9999	-0.41	74	74
NRG4	-0.02	0.097	-9999	-0.33	47	47
heart development	0.014	0.036	-9999	-10000	0	0
neural crest cell migration	0.007	0.059	-9999	-0.32	2	2
ERBB2	0.015	0.039	-9999	-0.22	14	14
WWOX/E4ICDs	0.008	0.044	-9999	-10000	0	0
SHC1	0.011	0	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.006	0.077	-9999	-0.35	7	7
apoptosis	0.007	0.037	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.026	0.093	-9999	-0.34	10	10
ErbB4/ErbB2/epiregulin	-0.009	0.069	-9999	-0.31	2	2
ErbB4/ErbB4/betacellulin/betacellulin	-0.001	0.062	-9999	-0.36	3	3
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.031	0.11	-9999	-0.39	13	13
MDM2	0.009	0.045	-9999	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.007	0.044	-9999	-0.29	1	1
STAT5A	0.019	0.036	-9999	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	0.007	0.066	-9999	-0.39	4	4
DLG4	0.009	0.032	-9999	-0.41	3	3
GRB2/SHC	0.016	0	-9999	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.011	0.032	-9999	-10000	0	0
STAT5A (dimer)	-0.043	0.081	-9999	-0.41	5	5
MAP3K7IP2	0	0	-9999	-10000	0	0
STAT5B (dimer)	0.018	0.038	-9999	-10000	0	0
LRIG1	0.009	0.032	-9999	-0.41	3	3
EREG	-0.035	0.12	-9999	-0.33	69	69
BTC	-0.004	0.076	-9999	-0.41	18	18
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.017	0.034	-9999	-10000	0	0
ERBB4	0.003	0.053	-9999	-10000	0	0
STAT5B	0.009	0.026	-9999	-0.41	2	2
YAP1	-0.001	0.024	-9999	-0.52	1	1
GRB2	0.011	0	-9999	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0	0.067	-9999	-0.3	5	5
glial cell differentiation	0.011	0.032	-9999	-10000	0	0
WWOX	0.011	0	-9999	-10000	0	0
cell proliferation	0.01	0.069	-9999	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.011	0	-10000	0	-10000	0	0
mol:PIP3	-0.024	0.081	0.23	5	-0.25	56	61
FRAP1	0.008	0.019	-10000	0	-10000	0	0
AKT1	0	0.073	0.2	5	-0.2	56	61
INSR	0.011	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.008	0.002	-10000	0	-10000	0	0
mol:GTP	-0.017	0.049	-10000	0	-0.31	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.005	0.014	-10000	0	-10000	0	0
TSC2	0.011	0	-10000	0	-10000	0	0
RHEB/GDP	-0.014	0.041	-10000	0	-0.27	2	2
TSC1	0.01	0.018	-10000	0	-0.41	1	1
Insulin Receptor/IRS1	-0.018	0.094	-10000	0	-0.3	53	53
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.006	0.017	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.011	0	-10000	0	-10000	0	0
RPS6KB1	0.011	0.041	0.16	5	-0.21	2	7
MAP3K5	0.007	0.025	-10000	0	-0.32	3	3
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
apoptosis	0.007	0.025	-10000	0	-0.32	3	3
mol:LY294002	0	0	-10000	0	-0.001	53	53
EIF4B	0.016	0.038	0.16	5	-0.19	2	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.018	0.034	-10000	0	-0.17	2	2
eIF4E/eIF4G1/eIF4A1	-0.001	0.004	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.01	0.091	-10000	0	-0.27	57	57
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.029	0.15	5	-0.14	3	8
FKBP1A	0.011	0	-10000	0	-10000	0	0
RHEB/GTP	-0.014	0.041	-10000	0	-0.27	2	2
mol:Amino Acids	0	0	-10000	0	-0.001	53	53
FKBP12/Rapamycin	0.008	0.001	-10000	0	-10000	0	0
PDPK1	-0.022	0.073	0.21	5	-0.22	56	61
EIF4E	0.011	0	-10000	0	-10000	0	0
ASK1/PP5C	0.012	0.047	-10000	0	-0.58	3	3
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.014	0.002	-10000	0	-10000	0	0
TSC1/TSC2	0.01	0.062	-10000	0	-0.33	2	2
tumor necrosis factor receptor activity	0	0	0.001	53	-10000	0	53
RPS6	0.011	0	-10000	0	-10000	0	0
PPP5C	0.011	0	-10000	0	-10000	0	0
EIF4G1	0.011	0	-10000	0	-10000	0	0
IRS1	-0.026	0.1	-10000	0	-0.32	53	53
INS	0.001	0.003	-10000	0	-10000	0	0
PTEN	0.006	0.044	-10000	0	-0.41	6	6
PDK2	-0.022	0.073	0.21	5	-0.22	56	61
EIF4EBP1	0.012	0.007	-10000	0	-10000	0	0
PIK3CA	0.01	0.018	-10000	0	-0.41	1	1
PPP2R5D	0.013	0.018	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0.001	-10000	0	-10000	0	0
RHEB	0.011	0	-10000	0	-10000	0	0
EIF4A1	0.011	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	6	-0.002	2	8
EEF2	0.014	0.001	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.017	0.005	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.007	0.049	-10000	0	-1.1	1	1
oxygen homeostasis	-0.002	0.014	-10000	0	-10000	0	0
TCEB2	0.011	0	-10000	0	-10000	0	0
TCEB1	0.011	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.017	0.04	-10000	0	-0.29	4	4
EPO	-0.022	0.21	-10000	0	-0.52	27	27
FIH (dimer)	0.009	0.013	-10000	0	-10000	0	0
APEX1	0.007	0.015	-10000	0	-10000	0	0
SERPINE1	-0.014	0.2	-10000	0	-0.51	19	19
FLT1	-0.012	0.062	-10000	0	-1.1	1	1
ADORA2A	-0.013	0.19	-10000	0	-0.48	17	17
germ cell development	-0.021	0.21	-10000	0	-0.51	28	28
SLC11A2	-0.013	0.2	-10000	0	-0.48	18	18
BHLHE40	-0.013	0.2	-10000	0	-0.48	18	18
HIF1AN	0.009	0.013	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.005	0.12	-10000	0	-0.34	8	8
ETS1	0.021	0.02	-10000	0	-0.42	1	1
CITED2	-0.037	0.18	-10000	0	-1	17	17
KDR	-0.065	0.26	-10000	0	-1.1	31	31
PGK1	-0.013	0.2	-10000	0	-0.49	16	16
SIRT1	0.009	0.026	-10000	0	-0.41	2	2
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	-0.017	0.22	-10000	0	-0.55	18	18
EPAS1	0.011	0.089	-10000	0	-0.37	3	3
SP1	0.017	0.001	-10000	0	-10000	0	0
ABCG2	-0.14	0.3	-10000	0	-0.54	101	101
EFNA1	-0.013	0.2	-10000	0	-0.5	16	16
FXN	-0.013	0.19	-10000	0	-0.48	17	17
POU5F1	-0.023	0.21	-10000	0	-0.53	28	28
neuron apoptosis	0.017	0.22	0.54	18	-10000	0	18
EP300	0.011	0	-10000	0	-10000	0	0
EGLN3	0.006	0.034	-10000	0	-0.35	4	4
EGLN2	0.009	0.013	-10000	0	-10000	0	0
EGLN1	0.009	0.013	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.022	0.011	-10000	0	-0.23	1	1
VHL	0.01	0.018	-10000	0	-0.41	1	1
ARNT	0.007	0.015	-10000	0	-10000	0	0
SLC2A1	-0.013	0.19	-10000	0	-0.48	17	17
TWIST1	-0.04	0.24	-10000	0	-0.54	59	59
ELK1	0.016	0.01	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.001	0.12	-10000	0	-0.43	3	3
VEGFA	-0.013	0.2	-10000	0	-0.48	18	18
CREBBP	0.009	0.026	-10000	0	-0.41	2	2

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.003	0.053	0.36	11	-10000	0	11
PI3K Class IB/PDE3B	0.003	0.053	-10000	0	-0.36	11	11
PDE3B	0.003	0.053	-10000	0	-0.36	11	11

×

JNK signaling in the CD4+ TCR 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
LAT/GRAP2/SLP76/HPK1	0.016	0.051	-9999	-0.21	18	18
MAP4K1	0.003	0.053	-9999	-0.33	13	13
MAP3K8	0.009	0.032	-9999	-0.41	3	3
PRKCB	-0.015	0.1	-9999	-0.41	32	32
DBNL	0.011	0	-9999	-10000	0	0
CRKL	0.011	0	-9999	-10000	0	0
MAP3K1	0.029	0.038	-9999	-0.22	1	1
JUN	-0.01	0.14	-9999	-0.52	37	37
MAP3K7	0.029	0.038	-9999	-0.22	1	1
GRAP2	-0.003	0.074	-9999	-0.41	17	17
CRK	0.011	0	-9999	-10000	0	0
MAP2K4	0.034	0.04	-9999	-0.22	1	1
LAT	0.011	0	-9999	-10000	0	0
LCP2	0.01	0.015	-9999	-0.33	1	1
MAPK8	-0.014	0.15	-9999	-0.55	37	37
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.024	0.041	-9999	-0.24	1	1
LAT/GRAP2/SLP76/HPK1/HIP-55	0.022	0.048	-9999	-0.2	18	18

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.02	0.12	-10000	0	-0.44	6	6
CRKL	0.019	0.054	-10000	0	-0.24	6	6
mol:DAG	0.019	0.066	-10000	0	-0.24	18	18
HRAS	0.035	0.05	-10000	0	-10000	0	0
MAPK8	0.016	0.047	-10000	0	-0.19	20	20
RAP1A	0.019	0.054	-10000	0	-0.24	6	6
GAB1	0.017	0.057	-10000	0	-0.24	8	8
MAPK14	0.018	0.041	-10000	0	-0.19	15	15
EPO	-0.003	0.072	-10000	0	-0.4	16	16
PLCG1	0.019	0.067	-10000	0	-0.24	18	18
EPOR/TRPC2/IP3 Receptors	0.007	0.039	-10000	0	-0.32	7	7
RAPGEF1	0.011	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.012	0.048	-10000	0	-0.2	25	25
GAB1/SHC/GRB2/SOS1	-0.012	0.036	-10000	0	-0.22	2	2
EPO/EPOR (dimer)	0.005	0.057	-10000	0	-0.26	23	23
IRS2	-0.008	0.086	-10000	0	-0.26	19	19
STAT1	0.018	0.089	-10000	0	-0.37	6	6
STAT5B	0.017	0.08	-10000	0	-0.26	19	19
cell proliferation	0.021	0.044	-10000	0	-0.19	8	8
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.013	0.04	-10000	0	-0.23	7	7
TEC	0.018	0.054	-10000	0	-0.24	6	6
SOCS3	0.009	0.026	-10000	0	-0.41	2	2
STAT1 (dimer)	0.018	0.087	-10000	0	-0.37	6	6
JAK2	0.004	0.055	-10000	0	-0.41	9	9
PIK3R1	0.007	0.041	-10000	0	-0.41	5	5
EPO/EPOR (dimer)/JAK2	0.023	0.06	-10000	0	-0.26	6	6
EPO/EPOR	0.005	0.057	-10000	0	-0.26	23	23
LYN	0.011	0.004	-10000	0	-10000	0	0
TEC/VAV2	0.025	0.053	-10000	0	-0.22	6	6
elevation of cytosolic calcium ion concentration	0.007	0.039	-10000	0	-0.32	7	7
SHC1	0.011	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.017	0.048	-10000	0	-0.2	23	23
mol:IP3	0.019	0.066	-10000	0	-0.24	18	18
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.001	0.086	-10000	0	-0.25	22	22
SH2B3	0.01	0.019	-10000	0	-0.41	1	1
NFKB1	0.018	0.042	-10000	0	-0.19	16	16
EPO/EPOR (dimer)/JAK2/SOCS3	-0.01	0.049	0.23	1	-0.22	26	27
PTPN6	0.013	0.056	-10000	0	-0.25	6	6
TEC/VAV2/GRB2	0.029	0.052	-10000	0	-0.22	3	3
EPOR	0.007	0.039	-10000	0	-0.32	7	7
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
mol:GDP	-0.012	0.036	-10000	0	-0.22	2	2
SOS1	0.011	0	-10000	0	-10000	0	0
PLCG2	0.01	0.024	-10000	0	-0.37	2	2
CRKL/CBL/C3G	0.03	0.051	-10000	0	-0.21	6	6
VAV2	0.019	0.054	-10000	0	-0.24	6	6
CBL	0.019	0.054	-10000	0	-0.24	6	6
SHC/Grb2/SOS1	-0.012	0.036	-10000	0	-0.21	6	6
STAT5A	0.018	0.079	-10000	0	-0.26	19	19
GRB2	0.011	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.023	0.11	-10000	0	-0.27	51	51
LYN/PLCgamma2	0.015	0.017	-10000	0	-0.25	2	2
PTPN11	0.011	0	-10000	0	-10000	0	0
BTK	0.017	0.057	-10000	0	-0.27	6	6
BCL2	-0.026	0.25	-10000	0	-0.79	50	50

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0.018	-10000	0	-0.28	2	2
MAP4K4	0.028	0.034	-10000	0	-0.4	1	1
BAG4	0.009	0.032	-10000	0	-0.41	3	3
PKC zeta/ceramide	-0.001	0.016	0.12	2	-0.18	2	4
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	0.003	0.055	-10000	0	-0.39	10	10
BAX	0.002	0.006	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
AKT1	0.014	0.002	-10000	0	-10000	0	0
BAD	-0.002	0.012	0.13	2	-10000	0	2
SMPD1	0.015	0.025	-10000	0	-0.17	2	2
RB1	-0.003	0.02	0.13	2	-0.22	3	5
FADD/Caspase 8	0.036	0.033	-10000	0	-0.39	1	1
MAP2K4	0.003	0.014	0.14	1	-0.19	1	2
NSMAF	0.011	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.003	0.017	0.13	2	-0.19	2	4
EGF	-0.005	0.071	-10000	0	-0.34	23	23
mol:ceramide	-0.009	0.013	0.13	2	-10000	0	2
MADD	0.011	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.017	0.018	-10000	0	-0.28	2	2
ASAH1	0.011	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.003	0.02	0.13	2	-0.22	3	5
cell proliferation	-0.012	0.07	-10000	0	-0.15	99	99
BID	0.024	0.025	-10000	0	-0.29	1	1
MAP3K1	-0.002	0.012	0.13	2	-10000	0	2
EIF2A	0.009	0.011	0.14	1	-10000	0	1
TRADD	0.011	0	-10000	0	-10000	0	0
CRADD	0.011	0	-10000	0	-10000	0	0
MAPK3	0.012	0.016	0.14	1	-0.17	2	3
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.012	0.016	0.14	1	-0.17	2	3
Cathepsin D/ceramide	-0.001	0.014	0.12	2	-0.16	1	3
FADD	0.028	0.034	-10000	0	-0.4	1	1
KSR1	-0.003	0.017	0.13	2	-0.21	2	4
MAPK8	0.005	0.027	0.13	2	-0.22	6	8
PRKRA	-0.002	0.012	0.13	2	-10000	0	2
PDGFA	0.009	0.026	-10000	0	-0.41	2	2
TRAF2	0.011	0	-10000	0	-10000	0	0
IGF1	-0.069	0.16	-10000	0	-0.41	100	100
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.009	0.013	0.13	2	-10000	0	2
CTSD	0.01	0.015	-10000	0	-0.33	1	1
regulation of nitric oxide biosynthetic process	0.016	0.013	-10000	0	-0.28	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.012	0.074	-10000	0	-0.16	99	99
PRKCD	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.024	-10000	0	-0.37	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.017	0.018	-10000	0	-0.28	2	2
RelA/NF kappa B1	0.016	0.013	-10000	0	-0.28	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.011	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.024	0.036	-10000	0	-0.43	1	1
TNFR1A/BAG4/TNF-alpha	-0.004	0.067	-10000	0	-0.18	69	69
mol:Sphingosine-1-phosphate	0.017	0.018	-10000	0	-0.28	2	2
MAP2K1	0.008	0.016	0.14	1	-0.18	2	3
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
CYCS	0.014	0.041	0.14	51	-10000	0	51
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
NFKB1	0.01	0.018	-10000	0	-0.41	1	1
TNFR1A/BAG4	0.015	0.022	-10000	0	-0.28	3	3
EIF2AK2	0.004	0.011	0.14	1	-10000	0	1
TNF-alpha/TNFR1A/FAN	-0.002	0.065	-10000	0	-0.18	66	66
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.03	0.023	-10000	0	-0.22	1	1
MAP2K2	0.008	0.016	0.14	1	-0.18	2	3
SMPD3	0.016	0.033	-10000	0	-0.25	4	4
TNF	-0.032	0.11	-10000	0	-0.33	66	66
PKC zeta/PAR4	0.015	0.016	-10000	0	-0.25	2	2
mol:PHOSPHOCHOLINE	-0.004	0.021	0.16	3	-10000	0	3
NF kappa B1/RelA/I kappa B alpha	0.032	0.015	-10000	0	-10000	0	0
AIFM1	0.014	0.041	0.14	51	-10000	0	51
BCL2	-0.029	0.12	-10000	0	-0.41	50	50

×

Caspase cascade in apoptosis

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
TOP1	0.013	0.049	-10000	0	-0.29	6	6
ACTA1	0.004	0.059	0.16	3	-0.3	10	13
NUMA1	0.013	0.049	-10000	0	-0.29	6	6
SPTAN1	0.007	0.058	0.16	5	-0.3	10	15
LIMK1	0.007	0.058	0.16	5	-0.3	10	15
BIRC3	0.003	0.055	-10000	0	-0.39	10	10
BIRC2	0.011	0	-10000	0	-10000	0	0
BAX	0.011	0	-10000	0	-10000	0	0
CASP10	-0.002	0.075	-10000	0	-0.2	58	58
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.011	0	-10000	0	-10000	0	0
PTK2	0.013	0.049	-10000	0	-0.29	6	6
DIABLO	0.011	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.007	0.058	0.16	5	-0.3	10	15
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.011	0	-10000	0	-10000	0	0
GSN	0.004	0.061	0.16	4	-0.26	15	19
MADD	0.011	0	-10000	0	-10000	0	0
TFAP2A	0.028	0.039	-10000	0	-0.59	2	2
BID	0.008	0.037	-10000	0	-0.18	11	11
MAP3K1	0.008	0.024	-10000	0	-0.2	1	1
TRADD	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.016	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.007	0.058	0.16	5	-0.3	10	15
CASP9	0.011	0	-10000	0	-10000	0	0
DNA repair	-0.005	0.022	0.14	1	-0.16	5	6
neuron apoptosis	0.019	0.008	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.013	0.056	-10000	0	-0.28	10	10
APAF1	0.011	0	-10000	0	-10000	0	0
CASP6	0.022	0.032	-10000	0	-0.28	1	1
TRAF2	0.011	0	-10000	0	-10000	0	0
ICAD/CAD	0.012	0.056	0.17	1	-0.29	10	11
CASP7	-0.004	0.033	0.25	8	-10000	0	8
KRT18	0.013	0.032	-10000	0	-0.7	1	1
apoptosis	0.014	0.054	0.18	5	-0.28	6	11
DFFA	0.007	0.058	0.16	5	-0.3	10	15
DFFB	0.007	0.058	0.16	5	-0.3	10	15
PARP1	0.005	0.022	0.16	5	-0.14	1	6
actin filament polymerization	-0.009	0.058	0.28	11	-0.16	3	14
TNF	-0.032	0.11	-10000	0	-0.33	66	66
CYCS	0.009	0.032	-10000	0	-0.15	8	8
SATB1	-0.006	0.082	-10000	0	-0.35	6	6
SLK	0.007	0.058	0.16	5	-0.3	10	15
p15 BID/BAX	0.013	0.033	-10000	0	-0.26	2	2
CASP2	0.03	0.03	-10000	0	-0.3	1	1
JNK cascade	-0.008	0.024	0.19	1	-10000	0	1
CASP3	0.001	0.062	0.17	5	-0.32	10	15
LMNB2	0.032	0.024	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
CASP4	0.01	0.018	-10000	0	-0.41	1	1
Mammalian IAPs/DIABLO	0.024	0.03	-10000	0	-0.2	8	8
negative regulation of DNA binding	0.028	0.039	-10000	0	-0.58	2	2
stress fiber formation	0.007	0.058	0.16	5	-0.3	10	15
GZMB	-0.011	0.086	-10000	0	-0.25	57	57
CASP1	0.012	0.022	-10000	0	-0.28	3	3
LMNB1	0.032	0.024	-10000	0	-10000	0	0
APP	0.019	0.008	-10000	0	-10000	0	0
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0	-10000	0	-10000	0	0
VIM	0.009	0.053	0.18	5	-0.24	10	15
LMNA	0.032	0.024	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.026	0.032	-10000	0	-0.32	1	1
LRDD	0.011	0	-10000	0	-10000	0	0
SREBF1	0.007	0.058	0.16	5	-0.3	10	15
APAF-1/Caspase 9	-0.001	0.017	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.013	0.048	-10000	0	-0.29	6	6
CFL2	0.009	0.059	0.16	3	-0.28	11	14
GAS2	-0.008	0.081	0.17	4	-0.24	42	46
positive regulation of apoptosis	0.035	0.024	-10000	0	-10000	0	0
PRF1	0.004	0.05	-10000	0	-0.37	9	9

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.011	0.019	-10000	0	-0.4	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.011	0.096	0.46	5	-10000	0	5
IL27/IL27R/JAK1	-0.016	0.11	0.32	1	-0.72	4	5
TBX21	0.001	0.12	-10000	0	-0.43	13	13
IL12B	0.006	0.016	-10000	0	-0.33	1	1
IL12A	0.001	0.042	-10000	0	-0.24	15	15
IL6ST	-0.053	0.15	-10000	0	-0.42	80	80
IL27RA/JAK1	0.012	0.072	-10000	0	-1.1	2	2
IL27	0.001	0.051	-10000	0	-0.33	12	12
TYK2	0.012	0.005	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.001	0.048	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.011	0.096	0.46	5	-10000	0	5
T cell proliferation during immune response	0.011	0.096	0.46	5	-10000	0	5
MAPKKK cascade	-0.011	0.096	-10000	0	-0.46	5	5
STAT3	0.011	0	-10000	0	-10000	0	0
STAT2	0.011	0	-10000	0	-10000	0	0
STAT1	0.011	0.015	-10000	0	-0.34	1	1
IL12RB1	-0.001	0.067	-10000	0	-0.35	18	18
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.002	0.12	-10000	0	-0.45	12	12
IL27/IL27R/JAK2/TYK2	-0.011	0.097	-10000	0	-0.47	5	5
positive regulation of T cell mediated cytotoxicity	-0.011	0.096	-10000	0	-0.46	5	5
STAT1 (dimer)	-0.04	0.12	0.47	4	-0.71	5	9
JAK2	0.003	0.055	-10000	0	-0.41	9	9
JAK1	0.01	0.026	-10000	0	-0.41	2	2
STAT2 (dimer)	-0.004	0.092	-10000	0	-0.44	5	5
T cell proliferation	-0.012	0.1	-10000	0	-0.41	12	12
IL12/IL12R/TYK2/JAK2	0.014	0.053	-10000	0	-0.52	1	1
IL17A	-0.002	0.047	-10000	0	-10000	0	0
mast cell activation	0.011	0.096	0.46	5	-10000	0	5
IFNG	0	0.022	-10000	0	-0.075	4	4
T cell differentiation	-0.002	0.004	-10000	0	-0.015	21	21
STAT3 (dimer)	-0.004	0.092	-10000	0	-0.44	5	5
STAT5A (dimer)	-0.005	0.093	-10000	0	-0.44	5	5
STAT4 (dimer)	-0.005	0.092	-10000	0	-0.44	5	5
STAT4	0.01	0.018	-10000	0	-0.41	1	1
T cell activation	-0.007	0.009	0.12	2	-10000	0	2
IL27R/JAK2/TYK2	-0.014	0.11	-10000	0	-0.71	4	4
GATA3	-0.012	0.13	-10000	0	-1.2	6	6
IL18	0.005	0.029	-10000	0	-0.23	8	8
positive regulation of mast cell cytokine production	-0.004	0.091	-10000	0	-0.44	5	5
IL27/EBI3	0.004	0.056	-10000	0	-0.25	22	22
IL27RA	0.004	0.076	-10000	0	-1.2	2	2
IL6	-0.007	0.084	-10000	0	-0.38	25	25
STAT5A	0.01	0.018	-10000	0	-0.41	1	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	-0.001	0.036	0.46	2	-10000	0	2
IL1B	0.007	0.026	-10000	0	-0.29	4	4
EBI3	0.002	0.054	-10000	0	-0.34	13	13
TNF	-0.021	0.078	-10000	0	-0.23	66	66

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.024	0.03	-9999	-0.2	9	9
HDAC3	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0.013	0.004	-9999	-10000	0	0
GATA1/HDAC5	0.013	0.004	-9999	-10000	0	0
GATA2/HDAC5	-0.012	0.087	-9999	-0.28	50	50
HDAC5/BCL6/BCoR	0.022	0.011	-9999	-0.23	1	1
HDAC9	0.003	0.057	-9999	-0.41	10	10
Glucocorticoid receptor/Hsp90/HDAC6	-0.015	0.09	-9999	-0.23	80	80
HDAC4/ANKRA2	0.016	0.013	-9999	-0.28	1	1
HDAC5/YWHAB	0.016	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
GATA2	-0.029	0.12	-9999	-0.41	50	50
HDAC4/RFXANK	0.015	0.018	-9999	-0.22	3	3
BCOR	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.011	0	-9999	-10000	0	0
HDAC5	0.011	0	-9999	-10000	0	0
GNB1/GNG2	0.011	0.04	-9999	-0.27	10	10
Histones	0.029	0.027	-9999	-10000	0	0
ADRBK1	0.011	0	-9999	-10000	0	0
HDAC4	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.016	0.013	-9999	-0.28	1	1
HDAC4/Ubc9	0.016	0	-9999	-10000	0	0
HDAC7	0.011	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.016	0	-9999	-10000	0	0
TUBA1B	0.011	0	-9999	-10000	0	0
HDAC6	0.011	0	-9999	-10000	0	0
HDAC5/RFXANK	0.015	0.018	-9999	-0.22	3	3
CAMK4	0.003	0.051	-9999	-0.36	10	10
Tubulin/HDAC6	0.02	0.024	-9999	-0.19	7	7
SUMO1	0.011	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.011	0	-9999	-10000	0	0
GATA1	0.006	0.005	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
NR3C1	-0.053	0.15	-9999	-0.41	80	80
SUMO1/HDAC4	0.025	0	-9999	-10000	0	0
SRF	0.011	0	-9999	-10000	0	0
HDAC4/YWHAB	0.016	0	-9999	-10000	0	0
Tubulin	0.013	0.029	-9999	-0.24	7	7
HDAC4/14-3-3 E	0.016	0	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
RANGAP1	0.011	0	-9999	-10000	0	0
BCL6/BCoR	0.016	0.013	-9999	-0.28	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0.022	0	-9999	-10000	0	0
HDAC4/SRF	0.018	0.03	-9999	-0.2	10	10
HDAC4/ER alpha	-0.017	0.094	-9999	-0.28	60	60
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.029	0.027	-9999	-10000	0	0
cell motility	0.019	0.024	-9999	-0.19	7	7
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
HDAC7/HDAC3	0.016	0	-9999	-10000	0	0
BCL6	0.01	0.018	-9999	-0.41	1	1
HDAC4/CaMK II delta B	0.011	0	-9999	-10000	0	0
Hsp90/HDAC6	0.016	0	-9999	-10000	0	0
ESR1	-0.037	0.13	-9999	-0.41	60	60
HDAC6/HDAC11	0.016	0.01	-9999	-0.22	1	1
Ran/GTP/Exportin 1	0.027	0	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
MEF2C	-0.031	0.13	-9999	-0.41	52	52
RAN	0.011	0	-9999	-10000	0	0
HDAC4/MEF2C	0.012	0.063	-9999	-0.18	52	52
GNG2	0.003	0.056	-9999	-0.4	10	10
NCOR2	0.011	0	-9999	-10000	0	0
TUBB2A	0.006	0.042	-9999	-0.35	7	7
HDAC11	0.01	0.015	-9999	-0.33	1	1
HSP90AA1	0.011	0	-9999	-10000	0	0
RANBP2	0.011	0	-9999	-10000	0	0
ANKRA2	0.01	0.018	-9999	-0.41	1	1
RFXANK	0.009	0.026	-9999	-0.33	3	3
nuclear import	-0.024	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.023	0.021	-9999	-0.28	2	2
CRKL	0.011	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
DOCK1	0.006	0.045	-9999	-0.41	6	6
ITGA4	0.009	0.03	-9999	-0.38	3	3
alpha4/beta7 Integrin/MAdCAM1	0.013	0.05	-9999	-0.2	2	2
EPO	-0.004	0.071	-9999	-0.4	16	16
alpha4/beta7 Integrin	0.014	0.023	-9999	-0.25	4	4
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.015	0.021	-9999	-0.26	3	3
EPO/EPOR (dimer)	0.003	0.056	-9999	-0.26	23	23
lamellipodium assembly	0.025	0.029	-9999	-0.24	6	6
PIK3CA	0.01	0.018	-9999	-0.41	1	1
PI3K	0.013	0.031	-9999	-0.28	6	6
ARF6	0.011	0	-9999	-10000	0	0
JAK2	0.013	0.056	-9999	-0.28	9	9
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.007	0.041	-9999	-0.41	5	5
MADCAM1	-0.016	0.09	-9999	-0.33	40	40
cell adhesion	0.012	0.049	-9999	-0.2	2	2
CRKL/CBL	0.016	0	-9999	-10000	0	0
ITGB1	0.011	0	-9999	-10000	0	0
SRC	0.008	0.064	-9999	-0.21	40	40
ITGB7	0.01	0.015	-9999	-0.33	1	1
RAC1	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.002	0.071	-9999	-0.24	41	41
p130Cas/Crk/Dock1	0.023	0.061	-9999	-0.43	2	2
VCAM1	-0.021	0.11	-9999	-0.41	40	40
RHOA	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.027	0.016	-9999	-0.2	2	2
BCAR1	0.014	0.06	-9999	-0.38	2	2
EPOR	0.006	0.039	-9999	-0.33	7	7
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
GIT1	0.011	0	-9999	-10000	0	0
Rac1/GTP	-0.002	0.026	-9999	-0.24	6	6

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	0.017	0.23	-9999	-1.2	11	11
IL23A	0.018	0.22	-9999	-1	10	10
NF kappa B1 p50/RelA/I kappa B alpha	-0.044	0.16	-9999	-0.95	10	10
positive regulation of T cell mediated cytotoxicity	0.018	0.22	-9999	-1	10	10
ITGA3	0.022	0.2	-9999	-1	8	8
IL17F	0.032	0.16	-9999	-0.64	9	9
IL12B	0.015	0.025	-9999	-0.32	1	1
STAT1 (dimer)	0.018	0.21	-9999	-1	10	10
CD4	0.024	0.2	-9999	-0.99	8	8
IL23	0.014	0.21	-9999	-0.98	10	10
IL23R	0.021	0.053	-9999	-10000	0	0
IL1B	0.016	0.22	-9999	-1.1	11	11
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	0.019	0.2	-9999	-1	8	8
TYK2	0.015	0.013	-9999	-10000	0	0
STAT4	0.01	0.018	-9999	-0.41	1	1
STAT3	0.011	0	-9999	-10000	0	0
IL18RAP	0.005	0.045	-9999	-0.38	7	7
IL12RB1	0.003	0.071	-9999	-0.36	18	18
PIK3CA	0.01	0.018	-9999	-0.41	1	1
IL12Rbeta1/TYK2	0.011	0.053	-9999	-0.25	18	18
IL23R/JAK2	0.028	0.076	-9999	-10000	0	0
positive regulation of chronic inflammatory response	0.018	0.22	-9999	-1	10	10
natural killer cell activation	-0.001	0.005	-9999	-10000	0	0
JAK2	0.012	0.06	-9999	-0.42	9	9
PIK3R1	0.007	0.041	-9999	-0.41	5	5
NFKB1	0.011	0.018	-9999	-0.41	1	1
RELA	0.012	0.002	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.015	0.2	-9999	-0.91	11	11
ALOX12B	0.019	0.2	-9999	-1	8	8
CXCL1	-0.004	0.25	-9999	-1.1	15	15
T cell proliferation	0.018	0.22	-9999	-1	10	10
NFKBIA	0.012	0.002	-9999	-10000	0	0
IL17A	0.042	0.13	-9999	-0.54	6	6
PI3K	-0.027	0.18	-9999	-0.97	10	10
IFNG	0.003	0.019	-9999	-10000	0	0
STAT3 (dimer)	-0.048	0.16	-9999	-0.92	10	10
IL18R1	0.007	0.036	-9999	-0.41	4	4
IL23/IL23R/JAK2/TYK2/SOCS3	0.029	0.14	-9999	-0.64	7	7
IL18/IL18R	0.014	0.045	-9999	-0.22	16	16
macrophage activation	-0.003	0.01	-9999	-0.041	11	11
TNF	0.014	0.22	-9999	-1.1	8	8
STAT3/STAT4	-0.026	0.18	-9999	-0.97	10	10
STAT4 (dimer)	0.018	0.21	-9999	-1	10	10
IL18	0.005	0.042	-9999	-0.34	8	8
IL19	0.005	0.21	-9999	-1	8	8
STAT5A (dimer)	0.018	0.21	-9999	-1	10	10
STAT1	0.01	0.015	-9999	-0.33	1	1
SOCS3	0.009	0.026	-9999	-0.41	2	2
CXCL9	0.005	0.23	-9999	-1.2	9	9
MPO	0.023	0.2	-9999	-0.95	9	9
positive regulation of humoral immune response	0.018	0.22	-9999	-1	10	10
IL23/IL23R/JAK2/TYK2	0.017	0.23	-9999	-1.1	10	10
IL6	0.001	0.27	-9999	-1.1	20	20
STAT5A	0.01	0.018	-9999	-0.41	1	1
IL2	-0.007	0.06	-9999	-0.33	17	17
positive regulation of tyrosine phosphorylation of STAT protein	-0.001	0.005	-9999	-10000	0	0
CD3E	0.013	0.24	-9999	-1.1	14	14
keratinocyte proliferation	0.018	0.22	-9999	-1	10	10
NOS2	0.013	0.23	-9999	-1	14	14

×

p38 MAPK 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.01	0.016	-10000	0	-0.2	3	3
TRAF2/ASK1	0.014	0.019	-10000	0	-0.23	3	3
ATM	0.011	0	-10000	0	-10000	0	0
MAP2K3	0.026	0.02	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.028	0.025	-10000	0	-0.22	3	3
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.001	0.07	-10000	0	-0.41	15	15
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.011	0	-10000	0	-10000	0	0
GADD45A	0.011	0	-10000	0	-10000	0	0
GADD45B	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.011	0	-10000	0	-10000	0	0
MAP3K6	0.011	0	-10000	0	-10000	0	0
MAP3K7	0.011	0	-10000	0	-10000	0	0
MAP3K4	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.015	0.022	-10000	0	-0.28	3	3
TAK1/TAB family	0.001	0.009	0.15	2	-10000	0	2
RAC1/OSM/MEKK3	0.021	0	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.001	0.009	-10000	0	-10000	0	0
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.046	0.13	-10000	0	-0.33	88	88
CCM2	0.011	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.018	0.073	-10000	0	-0.18	88	88
MAPK11	0.009	0.026	-10000	0	-0.41	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.01	0.067	-10000	0	-0.16	91	91
OSM/MEKK3	0.016	0	-10000	0	-10000	0	0
TAOK1	0.013	0.018	-10000	0	-0.28	2	2
TAOK2	0.014	0	-10000	0	-10000	0	0
TAOK3	0.014	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.011	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.009	0.032	-10000	0	-0.41	3	3
MAP3K10	0.011	0	-10000	0	-10000	0	0
MAP3K3	0.011	0	-10000	0	-10000	0	0
TRX/ASK1	0.012	0.018	-10000	0	-0.23	3	3
GADD45/MTK1/MTK1	0.02	0.035	-10000	0	-0.19	15	15

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.032	0.039	-10000	0	-0.38	1	1
BAG4	0.009	0.032	-10000	0	-0.41	3	3
BAD	0.023	0.014	-10000	0	-0.12	1	1
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	0.003	0.055	-10000	0	-0.39	10	10
BAX	0.023	0.014	-10000	0	-0.12	1	1
EnzymeConsortium:3.1.4.12	0.01	0.011	-10000	0	-0.092	1	1
IKBKB	0.036	0.037	-10000	0	-0.36	1	1
MAP2K2	0.031	0.018	-10000	0	-0.16	1	1
MAP2K1	0.031	0.018	-10000	0	-0.16	1	1
SMPD1	0.015	0.011	-10000	0	-0.087	1	1
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.038	0.037	-10000	0	-0.37	1	1
MAP2K4	0.027	0.016	-10000	0	-0.15	1	1
protein ubiquitination	0.038	0.037	-10000	0	-0.36	1	1
EnzymeConsortium:2.7.1.37	0.035	0.019	-10000	0	-0.16	1	1
response to UV	0	0	-10000	0	-0.002	1	1
RAF1	0.027	0.018	-10000	0	-0.16	2	2
CRADD	0.011	0	-10000	0	-10000	0	0
mol:ceramide	0.018	0.015	-10000	0	-0.13	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0.015	0	-10000	0	-10000	0	0
MADD	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.023	0.014	-10000	0	-0.12	1	1
TRADD	0.011	0	-10000	0	-10000	0	0
RELA/p50	0.011	0	-10000	0	-10000	0	0
MAPK3	0.033	0.017	-10000	0	-0.16	1	1
MAPK1	0.033	0.017	-10000	0	-0.16	1	1
p50/RELA/I-kappa-B-alpha	0.016	0	-10000	0	-10000	0	0
FADD	0.032	0.039	-10000	0	-0.24	8	8
KSR1	0.023	0.019	-10000	0	-0.16	3	3
MAPK8	0.03	0.023	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.036	0.037	-10000	0	-0.36	1	1
TNF R/SODD	0.015	0.022	-10000	0	-0.28	3	3
TNF	-0.032	0.11	-10000	0	-0.33	66	66
CYCS	0.033	0.03	0.12	47	-0.11	1	48
IKBKG	0.036	0.037	-10000	0	-0.36	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.027	0.041	-10000	0	-0.25	8	8
RELA	0.011	0	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
AIFM1	0.033	0.03	0.12	47	-0.11	1	48
TNF/TNF R/SODD	-0.003	0.067	-10000	0	-0.18	69	69
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.023	0.011	-10000	0	-10000	0	0
NSMAF	0.032	0.038	-10000	0	-0.37	1	1
response to hydrogen peroxide	0	0	-10000	0	-0.002	1	1
BCL2	-0.029	0.12	-10000	0	-0.41	50	50

×

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

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
BAG4	0.009	0.032	-9999	-0.41	3	3
Caspase 8 (4 units)	0.03	0.035	-9999	-0.36	1	1
NEF	0.001	0.019	-9999	-0.16	4	4
NFKBIA	0.012	0.012	-9999	-10000	0	0
BIRC3	0.027	0.061	-9999	-0.4	10	10
CYCS	0.035	0.037	-9999	-0.25	4	4
RIPK1	0.011	0	-9999	-10000	0	0
CD247	0.01	0.037	-9999	-0.26	7	7
MAP2K7	0.037	0.034	-9999	-0.36	1	1
protein ubiquitination	0.049	0.027	-9999	-10000	0	0
CRADD	0.011	0	-9999	-10000	0	0
DAXX	0.011	0	-9999	-10000	0	0
FAS	0.007	0.041	-9999	-0.41	5	5
BID	0.031	0.038	-9999	-0.26	4	4
NF-kappa-B/RelA/I kappa B alpha	0.026	0.035	-9999	-0.22	9	9
TRADD	0.011	0	-9999	-10000	0	0
MAP3K5	0.009	0.032	-9999	-0.41	3	3
CFLAR	0.011	0	-9999	-10000	0	0
FADD	0.011	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.027	0.035	-9999	-0.22	9	9
MAPK8	0.039	0.038	-9999	-0.34	1	1
APAF1	0.011	0	-9999	-10000	0	0
TRAF1	0.011	0	-9999	-10000	0	0
TRAF2	0.011	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.026	0.04	-9999	-0.26	5	5
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.043	0.03	-9999	-0.24	2	2
CHUK	0.05	0.028	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.03	0.026	-9999	-0.18	8	8
TCRz/NEF	0.01	0.04	-9999	-0.22	14	14
TNF	-0.032	0.11	-9999	-0.33	66	66
FASLG	0.013	0.062	-9999	-0.34	14	14
NFKB1	0.011	0.022	-9999	-0.4	1	1
TNFR1A/BAG4/TNF-alpha	-0.004	0.067	-9999	-0.18	69	69
CASP6	-0.003	0.022	-9999	-10000	0	0
CASP7	0.056	0.069	-9999	-0.44	8	8
RELA	0.012	0.012	-9999	-10000	0	0
CASP2	0.011	0	-9999	-10000	0	0
CASP3	0.056	0.069	-9999	-0.44	8	8
TNFRSF1A	0.011	0	-9999	-10000	0	0
TNFR1A/BAG4	0.015	0.022	-9999	-0.28	3	3
CASP8	0.011	0	-9999	-10000	0	0
CASP9	0.011	0	-9999	-10000	0	0
MAP3K14	0.047	0.029	-9999	-10000	0	0
APAF-1/Caspase 9	-0.007	0.04	-9999	-0.28	9	9
BCL2	0.026	0.068	-9999	-0.29	6	6

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.024	0.013	-10000	0	-0.19	2	2
epithelial cell differentiation	-0.001	0.011	-10000	0	-0.18	2	2
CYFIP2	0.009	0.032	-10000	0	-0.41	3	3
ENAH	0.049	0.016	-10000	0	-10000	0	0
EGFR	0	0.067	-10000	0	-0.4	14	14
EPHA2	0.011	0	-10000	0	-10000	0	0
MYO6	0.029	0.012	-10000	0	-10000	0	0
CTNNB1	0.011	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.021	0.019	-10000	0	-0.23	3	3
AQP5	0.013	0.045	-10000	0	-0.38	6	6
CTNND1	0.011	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.029	0.012	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.023	0.038	-10000	0	-0.18	16	16
EGF	-0.005	0.071	-10000	0	-0.34	23	23
NCKAP1	0.011	0	-10000	0	-10000	0	0
AQP3	-0.004	0.044	-10000	0	-0.45	5	5
cortical microtubule organization	-0.001	0.011	-10000	0	-0.18	2	2
GO:0000145	0.027	0.012	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.025	0.013	-10000	0	-0.19	2	2
MLLT4	0.011	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.013	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.027	0.018	-10000	0	-0.2	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.037	0.012	-10000	0	-10000	0	0
PVRL2	0.011	0	-10000	0	-10000	0	0
ZYX	0.029	0.012	-10000	0	-10000	0	0
ARF6/GTP	0.03	0.016	-10000	0	-0.18	2	2
CDH1	0.009	0.026	-10000	0	-0.41	2	2
EGFR/EGFR/EGF/EGF	-0.01	0.041	-10000	0	-0.32	3	3
RhoA/GDP	-0.001	0.01	-10000	0	-10000	0	0
actin cytoskeleton organization	0.033	0.012	-10000	0	-10000	0	0
IGF-1R heterotetramer	-0.006	0.082	-10000	0	-0.41	21	21
GIT1	0.011	0	-10000	0	-10000	0	0
IGF1R	-0.006	0.082	-10000	0	-0.41	21	21
IGF1	-0.069	0.16	-10000	0	-0.41	100	100
DIAPH1	-0.003	0.04	-10000	0	-0.52	3	3
Wnt receptor signaling pathway	0.001	0.011	0.18	2	-10000	0	2
RHOA	0.011	0	-10000	0	-10000	0	0
RhoA/GTP	-0.001	0.013	-10000	0	-10000	0	0
CTNNA1	0.011	0	-10000	0	-10000	0	0
VCL	0.033	0.012	-10000	0	-10000	0	0
EFNA1	0.01	0.021	-10000	0	-0.33	2	2
LPP	0.034	0.012	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.001	0.012	-10000	0	-10000	0	0
SEC6/SEC8	-0.001	0.009	-10000	0	-10000	0	0
MGAT3	0.023	0.039	-10000	0	-0.18	16	16
HGF/MET	-0.035	0.073	-10000	0	-0.47	3	3
HGF	-0.074	0.17	-10000	0	-0.41	106	106
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.024	0.014	-10000	0	-0.2	2	2
actin cable formation	0.062	0.016	-10000	0	-10000	0	0
KIAA1543	0.033	0.025	-10000	0	-0.35	2	2
KIFC3	0.029	0.012	-10000	0	-0.17	2	2
NCK1	0.009	0.026	-10000	0	-0.41	2	2
EXOC3	0.011	0	-10000	0	-10000	0	0
ACTN1	0.029	0.012	-10000	0	-10000	0	0
NCK1/GIT1	0.015	0.018	-10000	0	-0.28	2	2
mol:GDP	-0.001	0.011	-10000	0	-0.18	2	2
EXOC4	0.011	0	-10000	0	-10000	0	0
STX4	0.029	0.012	-10000	0	-0.17	2	2
PIP5K1C	0.029	0.012	-10000	0	-10000	0	0
LIMA1	0.011	0	-10000	0	-10000	0	0
ABI1	0.011	0	-10000	0	-10000	0	0
ROCK1	0.047	0.016	-10000	0	-10000	0	0
adherens junction assembly	0.045	0.027	-10000	0	-0.36	2	2
IGF-1R heterotetramer/IGF1	-0.038	0.079	-10000	0	-0.35	12	12
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0	-10000	0	-10000	0	0
MET	0.005	0.047	-10000	0	-0.37	8	8
PLEKHA7	0.029	0.015	-10000	0	-10000	0	0
mol:GTP	0.026	0.017	-10000	0	-0.2	2	2
establishment of epithelial cell apical/basal polarity	0.047	0.011	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.024	0.013	-10000	0	-0.19	2	2
regulation of cell-cell adhesion	0.033	0.012	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.024	0.014	-10000	0	-0.2	2	2

×

Canonical NF-kappaB 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
FBXW11	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.059	0.034	-9999	-10000	0	0
ERC1	0.011	0	-9999	-10000	0	0
RIP2/NOD2	0.016	0.01	-9999	-0.22	1	1
NFKBIA	0.036	0.01	-9999	-10000	0	0
BIRC2	0.011	0	-9999	-10000	0	0
IKBKB	0.011	0	-9999	-10000	0	0
RIPK2	0.011	0	-9999	-10000	0	0
IKBKG	0.037	0.003	-9999	-10000	0	0
IKK complex/A20	-0.012	0.032	-9999	-10000	0	0
NEMO/A20/RIP2	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
NEMO/ATM	0.041	0.002	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.015	0	-9999	-10000	0	0
IKK complex/ELKS	0	0	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0.022	0	-9999	-10000	0	0
NOD2	0.01	0.015	-9999	-0.33	1	1
NFKB1	0.013	0.018	-9999	-0.4	1	1
RELA	0.014	0	-9999	-10000	0	0
MALT1	0.011	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.016	0	-9999	-10000	0	0
ATM	0.011	0	-9999	-10000	0	0
TNF/TNFR1A	-0.013	0.078	-9999	-0.22	66	66
TRAF6	0.011	0	-9999	-10000	0	0
PRKCA	-0.016	0.1	-9999	-0.41	34	34
CHUK	0.011	0	-9999	-10000	0	0
UBE2D3	0.011	0	-9999	-10000	0	0
TNF	-0.032	0.11	-9999	-0.33	66	66
NF kappa B1 p50/RelA	0.031	0.011	-9999	-0.22	1	1
BCL10	0.011	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.035	0.01	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
TNFRSF1A	0.011	0	-9999	-10000	0	0
IKK complex	0.046	0.002	-9999	-10000	0	0
CYLD	0.011	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.009	0.034	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.01	0.018	-9999	-0.41	1	1
PLK4	0.008	0.033	-9999	-0.33	5	5
regulation of centriole replication	0.015	0.026	-9999	-0.23	6	6

×

Class I PI3K signaling events

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
ARF5/GTP	0.002	0.024	0.21	6	-10000	0	6
DAPP1	0.028	0.043	-10000	0	-0.3	3	3
Src family/SYK family/BLNK-LAT/BTK-ITK	0.044	0.047	-10000	0	-0.49	1	1
mol:DAG	0.046	0.031	0.16	5	-0.18	1	6
HRAS	0.012	0.001	-10000	0	-10000	0	0
RAP1A	0.012	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.027	0.046	-10000	0	-0.32	3	3
PLCG2	0.01	0.024	-10000	0	-0.37	2	2
PLCG1	0.011	0	-10000	0	-10000	0	0
ARF5	0.011	0	-10000	0	-10000	0	0
mol:GTP	0.002	0.023	0.2	6	-10000	0	6
ARF1/GTP	0.002	0.024	0.21	6	-10000	0	6
RHOA	0.011	0	-10000	0	-10000	0	0
YES1	0.011	0	-10000	0	-10000	0	0
RAP1A/GTP	0.023	0.021	0.2	6	-10000	0	6
ADAP1	0.002	0.023	0.2	6	-10000	0	6
ARAP3	0.002	0.023	0.2	6	-10000	0	6
INPPL1	0.011	0	-10000	0	-10000	0	0
PREX1	0.011	0	-10000	0	-10000	0	0
ARHGEF6	0.001	0.065	-10000	0	-0.41	13	13
ARHGEF7	0.011	0	-10000	0	-10000	0	0
ARF1	0.011	0	-10000	0	-10000	0	0
NRAS	0.012	0.001	-10000	0	-10000	0	0
FYN	0.011	0	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
FGR	0.002	0.06	-10000	0	-0.41	11	11
mol:Ca2+	0.032	0.018	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0	0.068	-10000	0	-0.41	14	14
ZAP70	-0.001	0.064	-10000	0	-0.34	18	18
mol:IP3	0.039	0.024	-10000	0	-10000	0	0
LYN	0.011	0	-10000	0	-10000	0	0
ARF1/GDP	0.027	0.046	-10000	0	-0.32	3	3
RhoA/GDP	0	0.025	0.2	5	-0.2	1	6
PDK1/Src/Hsp90	0.022	0	-10000	0	-10000	0	0
BLNK	0.009	0.03	-10000	0	-0.38	3	3
actin cytoskeleton reorganization	0.046	0.036	0.21	4	-0.23	3	7
SRC	0.011	0	-10000	0	-10000	0	0
PLEKHA2	0.023	0.011	-10000	0	-0.23	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
PTEN	0.003	0.042	-10000	0	-0.39	6	6
HSP90AA1	0.011	0	-10000	0	-10000	0	0
ARF6/GTP	0.002	0.024	0.21	6	-10000	0	6
RhoA/GTP	0.028	0.02	0.2	6	-10000	0	6
Src family/SYK family/BLNK-LAT	0.034	0.04	-10000	0	-0.3	1	1
BLK	-0.015	0.087	-10000	0	-0.33	37	37
PDPK1	0.011	0	-10000	0	-10000	0	0
CYTH1	0.002	0.023	0.2	6	-10000	0	6
HCK	0.006	0.039	-10000	0	-0.33	7	7
CYTH3	0.002	0.023	0.2	6	-10000	0	6
CYTH2	0.002	0.023	0.2	6	-10000	0	6
KRAS	0.011	0.015	-10000	0	-0.33	1	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.035	0.03	-10000	0	-0.38	2	2
SGK1	0	0.031	-10000	0	-0.42	2	2
INPP5D	0.01	0.018	-10000	0	-0.41	1	1
mol:GDP	0.022	0.048	-10000	0	-0.22	13	13
SOS1	0.011	0	-10000	0	-10000	0	0
SYK	0.01	0.015	-10000	0	-0.33	1	1
ARF6/GDP	0	0.026	0.21	5	-0.21	1	6
mol:PI-3-4-5-P3	0.002	0.026	0.23	6	-10000	0	6
ARAP3/RAP1A/GTP	0.023	0.021	0.2	6	-10000	0	6
VAV1	0.007	0.038	-10000	0	-0.34	6	6
mol:PI-3-4-P2	0.018	0.013	-10000	0	-0.28	1	1
RAS family/GTP/PI3K Class I	0.025	0.01	-10000	0	-10000	0	0
PLEKHA1	0.023	0.011	-10000	0	-0.23	1	1
Rac1/GDP	0.027	0.046	-10000	0	-0.2	13	13
LAT	0.011	0	-10000	0	-10000	0	0
Rac1/GTP	0.019	0.067	-10000	0	-0.27	24	24
ITK	-0.003	0.035	0.2	6	-10000	0	6
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.053	0.039	0.18	5	-0.24	1	6
LCK	0.008	0.035	-10000	0	-0.35	5	5
BTK	0.001	0.025	0.2	6	-10000	0	6

×

Arf6 trafficking events

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
SLC2A4	-0.19	0.21	-10000	0	-0.41	255	255
CLTC	0.026	0.001	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.021	0.006	-10000	0	-10000	0	0
Dynamin 2/GTP	0.02	0	-10000	0	-10000	0	0
EXOC4	0.011	0	-10000	0	-10000	0	0
CD59	0.023	0.001	-10000	0	-10000	0	0
CPE	-0.01	0.074	-10000	0	-0.24	52	52
CTNNB1	0.011	0	-10000	0	-10000	0	0
membrane fusion	0.021	0.006	-10000	0	-10000	0	0
CTNND1	0.025	0	-10000	0	-10000	0	0
DNM2	0.011	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.026	0.003	-10000	0	-10000	0	0
TSHR	0.005	0.041	-10000	0	-0.19	22	22
INS	0.01	0.002	-10000	0	-10000	0	0
BIN1	0.008	0.037	-10000	0	-0.41	4	4
mol:Choline	0.021	0.006	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0.02	0	-10000	0	-10000	0	0
JUP	0.023	0.008	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.02	0.02	-10000	0	-0.2	4	4
ARF6/GTP	0.008	0	-10000	0	-10000	0	0
CDH1	0.022	0.011	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.008	0	-10000	0	-10000	0	0
MAPK8IP3	0.011	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0.008	0	-10000	0	-10000	0	0
EXOC2	0.011	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.035	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.011	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0.006	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.015	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.015	0	-10000	0	-10000	0	0
ACAP1	0.02	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.019	0.012	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.03	0.004	-10000	0	-10000	0	0
JIP4/KLC1	0.021	0	-10000	0	-10000	0	0
EXOC1	0.011	0	-10000	0	-10000	0	0
exocyst	0.035	0	-10000	0	-10000	0	0
RALA/GTP	0.008	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.015	0	-10000	0	-10000	0	0
receptor recycling	0.008	0	-10000	0	-10000	0	0
CTNNA1	0.025	0	-10000	0	-10000	0	0
NME1	0.015	0	-10000	0	-10000	0	0
clathrin coat assembly	0.026	0.002	-10000	0	-10000	0	0
IL2RA	0.02	0.016	-10000	0	-10000	0	0
VAMP3	0.015	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.074	0.076	-10000	0	-0.18	1	1
EXOC6	0.011	0	-10000	0	-10000	0	0
PLD1	0.018	0	-10000	0	-10000	0	0
PLD2	0.017	0.011	-10000	0	-0.24	1	1
EXOC5	0.011	0	-10000	0	-10000	0	0
PIP5K1C	0.026	0.001	-10000	0	-10000	0	0
SDC1	0.003	0.032	-10000	0	-10000	0	0
ARF6/GDP	0.015	0	-10000	0	-10000	0	0
EXOC7	0.011	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0	0.006	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.021	0.006	-10000	0	-10000	0	0
endocytosis	-0.019	0.019	0.2	4	-10000	0	4
SCAMP2	0.011	0	-10000	0	-10000	0	0
ADRB2	-0.004	0.075	-10000	0	-10000	0	0
EXOC3	0.011	0	-10000	0	-10000	0	0
ASAP2	0.011	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.021	0	-10000	0	-10000	0	0
KLC1	0.011	0	-10000	0	-10000	0	0
AVPR2	-0.032	0.092	-10000	0	-0.21	1	1
RALA	0.011	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0.005	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.007	0.041	-10000	0	-0.37	6	6
positive regulation of NF-kappaB transcription factor activity	0.007	0.052	-10000	0	-0.27	18	18
MAP2K4	0.035	0.02	-10000	0	-10000	0	0
IKBKB	0.011	0	-10000	0	-10000	0	0
TNFRSF10B	0.011	0	-10000	0	-10000	0	0
TNFRSF10A	0.009	0.026	-10000	0	-0.41	2	2
SMPD1	0.014	0.015	-10000	0	-0.16	3	3
IKBKG	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.001	0.063	-10000	0	-0.41	12	12
TRAIL/TRAILR2	0.013	0.028	-10000	0	-0.25	6	6
TRAIL/TRAILR3	0.013	0.031	-10000	0	-0.25	7	7
TRAIL/TRAILR1	0.012	0.034	-10000	0	-0.26	8	8
TRAIL/TRAILR4	0.007	0.052	-10000	0	-0.27	18	18
TRAIL/TRAILR1/DAP3/GTP	0.018	0.026	-10000	0	-0.19	8	8
IKK complex	-0.001	0.007	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.008	0	-10000	0	-10000	0	0
MAPK3	0.015	0.028	-10000	0	-0.25	6	6
MAP3K1	0.031	0.02	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.001	0.063	-10000	0	-0.41	12	12
TRADD	0.011	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.009	0.026	-10000	0	-0.41	2	2
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.028	0.022	-10000	0	-0.19	5	5
CFLAR	0.011	0	-10000	0	-10000	0	0
MAPK1	0.015	0.028	-10000	0	-0.25	6	6
TRAIL/TRAILR1/FADD/TRADD/RIP	0.03	0.024	-10000	0	-10000	0	0
mol:ceramide	0.014	0.015	-10000	0	-0.16	3	3
FADD	0.011	0	-10000	0	-10000	0	0
MAPK8	0.038	0.027	-10000	0	-10000	0	0
TRAF2	0.011	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.01	0.018	-10000	0	-0.41	1	1
CHUK	0.011	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.019	0.028	-10000	0	-0.21	8	8
DAP3	0.011	0	-10000	0	-10000	0	0
CASP10	0.002	0.046	0.22	12	-0.31	4	16
JNK cascade	0.007	0.052	-10000	0	-0.27	18	18
TRAIL (trimer)	0.007	0.041	-10000	0	-0.37	6	6
TNFRSF10C	0.01	0.018	-10000	0	-0.41	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	0.023	0.024	-10000	0	-0.19	5	5
TRAIL/TRAILR2/FADD	0.02	0.024	-10000	0	-0.23	3	3
cell death	0.014	0.015	-10000	0	-0.16	3	3
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.028	0.018	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.011	0	-10000	0	-10000	0	0
CASP8	0.001	0.009	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.031	0.02	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.012	0.032	-9999	-0.24	2	2
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.027	0.032	-9999	-0.24	2	2
SUMO1	0.011	0	-9999	-10000	0	0
ZFPM1	0.009	0.026	-9999	-0.41	2	2
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
FKBP3	0.011	0	-9999	-10000	0	0
Histones	0.028	0.025	-9999	-10000	0	0
YY1/LSF	0.018	0.04	-9999	-0.2	17	17
SMG5	0.011	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.015	0.035	-9999	-0.19	2	2
I kappa B alpha/HDAC1	0.016	0.028	-9999	-10000	0	0
SAP18	0.011	0	-9999	-10000	0	0
RELA	0.02	0.032	-9999	-0.19	4	4
HDAC1/Smad7	0.022	0.015	-9999	-0.23	2	2
RANGAP1	0.011	0	-9999	-10000	0	0
HDAC3/TR2	0.016	0.028	-9999	-10000	0	0
NuRD/MBD3 Complex	0.037	0.013	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.023	0.03	-9999	-0.18	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.029	0.12	-9999	-0.41	50	50
GATA1	0.006	0.005	-9999	-10000	0	0
Mad/Max	0.016	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.043	0.017	-9999	-10000	0	0
RBBP7	0.011	0	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
RBBP4	0.009	0.032	-9999	-0.41	3	3
MAX	0.011	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.011	0	-9999	-10000	0	0
NFKBIA	0.011	0.031	-9999	-10000	0	0
KAT2B	0.004	0.055	-9999	-0.41	9	9
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.034	0.015	-9999	-10000	0	0
SIN3 complex	0.028	0	-9999	-10000	0	0
SMURF1	0.011	0	-9999	-10000	0	0
CHD3	0.011	0	-9999	-10000	0	0
SAP30	0.011	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.011	0	-9999	-10000	0	0
YY1/HDAC3	0.022	0.036	-9999	-10000	0	0
YY1/HDAC2	0.021	0.031	-9999	-0.19	11	11
YY1/HDAC1	0.021	0.031	-9999	-0.19	11	11
NuRD/MBD2 Complex (MeCP1)	0.037	0.013	-9999	-10000	0	0
PPARG	0.005	0.071	-9999	-0.26	30	30
HDAC8/hEST1B	0.022	0	-9999	-10000	0	0
UBE2I	0.011	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
TNFRSF1A	0.011	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.016	0.028	-9999	-10000	0	0
MBD3L2	0.002	0.004	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.021	0.015	-9999	-0.23	2	2
CREBBP	0.009	0.026	-9999	-0.41	2	2
NuRD/MBD3/MBD3L2 Complex	0.041	0.013	-9999	-10000	0	0
HDAC1	0.011	0	-9999	-10000	0	0
HDAC3	0.011	0.031	-9999	-10000	0	0
HDAC2	0.011	0	-9999	-10000	0	0
YY1	0.019	0.037	-9999	-0.23	11	11
HDAC8	0.011	0	-9999	-10000	0	0
SMAD7	0.009	0.026	-9999	-0.41	2	2
NCOR2	0.011	0	-9999	-10000	0	0
MXD1	0.011	0	-9999	-10000	0	0
STAT3	0.02	0.018	-9999	-0.27	2	2
NFKB1	0.01	0.018	-9999	-0.41	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.011	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.024	0.036	-9999	-0.18	17	17
YY1/SAP30/HDAC1	0.026	0.028	-9999	-10000	0	0
EP300	0.011	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.02	0.018	-9999	-0.27	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.031	-9999	-10000	0	0
histone deacetylation	0.037	0.013	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.023	0.028	-9999	-10000	0	0
nuclear export	-0.022	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GATAD2B	0.011	0	-9999	-10000	0	0
GATAD2A	0.011	0	-9999	-10000	0	0
GATA2/HDAC3	-0.005	0.073	-9999	-0.21	50	50
GATA1/HDAC1	0.013	0.004	-9999	-10000	0	0
GATA1/HDAC3	0.005	0.027	-9999	-10000	0	0
CHD4	0.011	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.013	0.078	-9999	-0.22	66	66
SIN3/HDAC complex/Mad/Max	0.037	0.013	-9999	-10000	0	0
NuRD Complex	0.044	0.013	-9999	-10000	0	0
positive regulation of chromatin silencing	0.027	0.025	-9999	-10000	0	0
SIN3B	0.011	0	-9999	-10000	0	0
MTA2	0.011	0	-9999	-10000	0	0
SIN3A	0.011	0	-9999	-10000	0	0
XPO1	0.011	0	-9999	-10000	0	0
SUMO1/HDAC1	0.025	0	-9999	-10000	0	0
HDAC complex	0.027	0.017	-9999	-0.2	3	3
GATA1/Fog1	0.011	0.019	-9999	-0.28	2	2
FKBP25/HDAC1/HDAC2	0.022	0	-9999	-10000	0	0
TNF	-0.032	0.11	-9999	-0.33	66	66
negative regulation of cell growth	0.037	0.013	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.037	0.013	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.027	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.023	0.033	-9999	-0.25	2	2
SIN3/HDAC complex/NCoR1	0.035	0.015	-9999	-10000	0	0
TFCP2	0.006	0.045	-9999	-0.41	6	6
NR2C1	0.011	0	-9999	-10000	0	0
MBD3	0.011	0	-9999	-10000	0	0
MBD2	0.011	0	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.01	0.018	-9999	-0.41	1	1
SMAD2	0.011	0	-9999	-10000	0	0
SMAD3	0.031	0.017	-9999	-0.16	4	4
SMAD3/SMAD4	0.036	0.019	-9999	-0.33	1	1
SMAD4/Ubc9/PIASy	0.022	0.011	-9999	-0.23	1	1
SMAD2/SMAD2/SMAD4	0.025	0.033	-9999	-10000	0	0
PPM1A	0.011	0	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
SMAD2/SMAD4	0.017	0.009	-9999	-0.2	1	1
MAP3K1	0.011	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.011	0.038	-9999	-0.28	9	9
MAPK3	0.011	0	-9999	-10000	0	0
MAPK1	0.011	0	-9999	-10000	0	0
NUP214	0.011	0	-9999	-10000	0	0
CTDSP1	0.011	0	-9999	-10000	0	0
CTDSP2	0.011	0	-9999	-10000	0	0
CTDSPL	0.011	0	-9999	-10000	0	0
KPNB1	0.011	0	-9999	-10000	0	0
TGFBRAP1	0.005	0.052	-9999	-0.41	8	8
UBE2I	0.011	0	-9999	-10000	0	0
NUP153	0.01	0.018	-9999	-0.41	1	1
KPNA2	-0.004	0.07	-9999	-0.33	23	23
PIAS4	0.011	0	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.011	0	-9999	-10000	0	0
ITGB7	0.01	0.015	-9999	-0.33	1	1
ITGA4	0.009	0.03	-9999	-0.38	3	3
alpha4/beta7 Integrin	0.014	0.023	-9999	-0.25	4	4
alpha4/beta1 Integrin	0.015	0.021	-9999	-0.26	3	3

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.011	0	-9999	-10000	0	0
Rac1/GDP	0	0.003	-9999	-10000	0	0
DOCK1	0.006	0.045	-9999	-0.41	6	6
ITGA4	0.009	0.03	-9999	-0.38	3	3
RAC1	0.011	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.014	0.023	-9999	-0.25	4	4
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.021	0.018	-9999	-0.23	2	2
alpha4/beta7 Integrin/Paxillin	0.026	0.018	-9999	-0.2	2	2
lamellipodium assembly	-0.006	0.047	-9999	-0.4	6	6
PIK3CA	0.01	0.018	-9999	-0.41	1	1
PI3K	0.013	0.031	-9999	-0.28	6	6
ARF6	0.011	0	-9999	-10000	0	0
TLN1	0.011	0	-9999	-10000	0	0
PXN	0.018	0	-9999	-10000	0	0
PIK3R1	0.007	0.041	-9999	-0.41	5	5
ARF6/GTP	-0.001	0.011	-9999	-10000	0	0
cell adhesion	0.031	0.015	-9999	-0.18	2	2
CRKL/CBL	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.026	0.016	-9999	-0.2	2	2
ITGB1	0.011	0	-9999	-10000	0	0
ITGB7	0.01	0.015	-9999	-0.33	1	1
ARF6/GDP	0	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.016	0.061	-9999	-0.38	2	2
p130Cas/Crk/Dock1	0.02	0.027	-9999	-0.23	6	6
VCAM1	-0.021	0.11	-9999	-0.41	40	40
alpha4/beta1 Integrin/Paxillin/Talin	0.032	0.015	-9999	-0.18	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	0.032	0.015	-9999	-10000	0	0
BCAR1	0.011	0	-9999	-10000	0	0
mol:GDP	-0.031	0.015	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GIT1	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.032	0.015	-9999	-0.18	2	2
Rac1/GTP	-0.006	0.053	-9999	-0.44	6	6

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.027	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.018	0	-9999	-10000	0	0
mol:DAG	0.031	0.008	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.024	0	-9999	-10000	0	0
CaM/Ca2+	0.036	0.007	-9999	-10000	0	0
HIF1A	0.018	0	-9999	-10000	0	0
GAB1	0.008	0.037	-9999	-0.41	4	4
AKT1	0.043	0.026	-9999	-10000	0	0
PLCG1	0.031	0.008	-9999	-10000	0	0
NOS3	0.048	0.017	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
mol:NO	0.048	0.017	-9999	-10000	0	0
FLT1	0.025	0	-9999	-10000	0	0
PGF	0.01	0.015	-9999	-0.33	1	1
VEGFR1 homodimer/NRP2/VEGFR121	0.021	0.048	-9999	-10000	0	0
CALM1	0.011	0	-9999	-10000	0	0
PIK3CA	0.01	0.018	-9999	-0.41	1	1
eNOS/Hsp90	0.052	0.017	-9999	-10000	0	0
endothelial cell proliferation	0.019	0.065	-9999	-0.31	4	4
mol:Ca2+	0.031	0.008	-9999	-10000	0	0
MAPK3	0.026	0.05	-9999	-10000	0	0
MAPK1	0.026	0.05	-9999	-10000	0	0
PIK3R1	0.007	0.041	-9999	-0.41	5	5
PLGF homodimer	0.01	0.015	-9999	-0.33	1	1
PRKACA	0.011	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.063	0.16	-9999	-0.41	93	93
VEGFA homodimer	0.011	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.027	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.031	0.048	-9999	-10000	0	0
PI3K	0.034	0.024	-9999	-10000	0	0
PRKCA	0.022	0.053	-9999	-10000	0	0
PRKCB	0.022	0.051	-9999	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	0.026	0.008	-9999	-10000	0	0
VEGFA	0.011	0	-9999	-10000	0	0
VEGFB	0.011	0	-9999	-10000	0	0
mol:IP3	0.031	0.008	-9999	-10000	0	0
RASA1	0.029	0.022	-9999	-10000	0	0
NRP2	-0.009	0.09	-9999	-0.41	25	25
VEGFR1 homodimer	0.025	0	-9999	-10000	0	0
VEGFB homodimer	0.011	0	-9999	-10000	0	0
NCK1	0.009	0.026	-9999	-0.41	2	2
eNOS/Caveolin-1	0.019	0.075	-9999	-0.41	1	1
PTPN11	0.011	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.033	0.023	-9999	-10000	0	0
mol:L-citrulline	0.048	0.017	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.037	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.031	0.014	-9999	-10000	0	0
CD2AP	0.011	0	-9999	-10000	0	0
PI3K/GAB1	0.037	0.029	-9999	-10000	0	0
PDPK1	0.037	0.022	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.032	0	-9999	-10000	0	0
mol:NADP	0.048	0.017	-9999	-10000	0	0
HSP90AA1	0.011	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.036	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.015	0.053	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.033	0.013	-10000	0	-10000	0	0
regulation of axonogenesis	-0.023	0.008	-10000	0	-10000	0	0
myoblast fusion	-0.017	0.013	-10000	0	-10000	0	0
mol:GTP	-0.001	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.022	0.04	0.22	14	-10000	0	14
ARF1/GTP	0	0.003	-10000	0	-10000	0	0
mol:GM1	0.008	0.005	-10000	0	-10000	0	0
mol:Choline	0.022	0.011	-10000	0	-0.22	1	1
lamellipodium assembly	0.001	0.012	-10000	0	-10000	0	0
MAPK3	0.023	0.008	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.023	0.04	-10000	0	-0.22	14	14
ARF1	0.011	0	-10000	0	-10000	0	0
ARF6/GDP	0.017	0.013	-10000	0	-10000	0	0
ARF1/GDP	0.023	0.012	-10000	0	-10000	0	0
ARF6	0.01	0.003	-10000	0	-10000	0	0
RAB11A	0.011	0	-10000	0	-10000	0	0
TIAM1	0.001	0.068	-10000	0	-0.41	14	14
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.023	0.008	-10000	0	-10000	0	0
actin filament bundle formation	-0.021	0.01	-10000	0	-10000	0	0
KALRN	-0.001	0.023	-10000	0	-0.21	5	5
RAB11FIP3/RAB11A	0.016	0	-10000	0	-10000	0	0
RhoA/GDP	0.021	0.01	-10000	0	-10000	0	0
NME1	0.012	0.001	-10000	0	-10000	0	0
Rac1/GDP	0.021	0.01	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.001	0.005	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.001	0.012	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
liver development	-0.001	0.005	-10000	0	-10000	0	0
ARF6/GTP	-0.001	0.005	-10000	0	-10000	0	0
RhoA/GTP	0	0.003	-10000	0	-10000	0	0
mol:GDP	0.002	0.013	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.021	0.005	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
PLD1	0.017	0.004	-10000	0	-10000	0	0
RAB11FIP3	0.011	0	-10000	0	-10000	0	0
tube morphogenesis	0.001	0.012	-10000	0	-10000	0	0
ruffle organization	0.023	0.008	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.001	0.005	-10000	0	-10000	0	0
PLD2	0.017	0.013	-10000	0	-0.26	1	1
PIP5K1A	0.023	0.008	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.022	0.011	-10000	0	-0.22	1	1
Rac1/GTP	0.001	0.012	-10000	0	-10000	0	0

×

Atypical NF-kappaB 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
BCL3/RelA	0.016	0.01	-9999	-0.22	1	1
FBXW11	0.011	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.021	0.011	-9999	-0.23	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.037	0.012	-9999	-10000	0	0
NFKBIA	0.022	0.01	-9999	-0.17	1	1
MAPK14	0.011	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.021	0.011	-9999	-0.23	1	1
ARRB2	0.014	0	-9999	-10000	0	0
REL	0.011	0.001	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.021	0.014	-9999	-0.2	2	2
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.021	0.011	-9999	-0.23	1	1
PIK3CA	0.01	0.018	-9999	-0.41	1	1
NF kappa B1 p50 dimer	0.016	0.013	-9999	-0.28	1	1
PIK3R1	0.007	0.041	-9999	-0.41	5	5
NFKB1	0.018	0.013	-9999	-0.28	1	1
RELA	0.011	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.028	0.012	-9999	-0.18	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.04	0.012	-9999	-10000	0	0
SRC	0.011	0	-9999	-10000	0	0
PI3K	0.013	0.031	-9999	-0.28	6	6
NF kappa B1 p50/RelA	0.028	0.012	-9999	-0.18	1	1
IKBKB	0.011	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
SYK	0.01	0.015	-9999	-0.33	1	1
I kappa B alpha/PIK3R1	0.025	0.022	-9999	-0.18	5	5
cell death	0.039	0.012	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.021	0.011	-9999	-0.23	1	1
LCK	0.008	0.035	-9999	-0.35	5	5
BCL3	0.01	0.015	-9999	-0.33	1	1

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.032	0.025	-9999	-0.38	2	2
KLHL20	-0.002	0.012	-9999	-10000	0	0
CYFIP2	0.009	0.032	-9999	-0.41	3	3
Rac1/GDP	0.048	0.016	-9999	-0.21	2	2
ENAH	0.032	0.027	-9999	-0.38	2	2
AP1M1	0.011	0	-9999	-10000	0	0
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.011	0	-9999	-10000	0	0
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	0	0.008	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.002	0.011	-9999	-0.13	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.027	0.016	-9999	-0.2	2	2
RAPGEF1	0.041	0.023	-9999	-0.32	2	2
CTNND1	0.011	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.027	0.026	-9999	-0.4	2	2
CRK	0.037	0.024	-9999	-0.35	2	2
E-cadherin/gamma catenin/alpha catenin	0.021	0.023	-9999	-0.34	2	2
alphaE/beta7 Integrin	0.016	0.01	-9999	-0.22	1	1
IQGAP1	0.011	0	-9999	-10000	0	0
NCKAP1	0.011	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.021	0	-9999	-10000	0	0
DLG1	0.032	0.025	-9999	-0.38	2	2
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.01	-9999	-10000	0	0
MLLT4	0.011	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.015	0.036	-9999	-0.2	14	14
PI3K	-0.001	0.012	-9999	-10000	0	0
ARF6	0.011	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.015	0.027	-9999	-0.4	2	2
TIAM1	0	0.068	-9999	-0.41	14	14
E-cadherin(dimer)/Ca2+	0.026	0.013	-9999	-0.19	2	2
AKT1	-0.001	0.007	-9999	-10000	0	0
PIK3R1	0.007	0.041	-9999	-0.41	5	5
CDH1	0.009	0.026	-9999	-0.41	2	2
RhoA/GDP	0.048	0.016	-9999	-0.21	2	2
actin cytoskeleton organization	0.034	0.015	-9999	-10000	0	0
CDC42/GDP	0.048	0.016	-9999	-0.21	2	2
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.019	0.021	-9999	-0.31	2	2
ITGB7	0.01	0.015	-9999	-0.33	1	1
RAC1	0.011	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.028	0.014	-9999	-0.2	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin	0.019	0.013	-9999	-0.19	2	2
mol:GDP	0.046	0.018	-9999	-0.24	2	2
CDC42/GTP/IQGAP1	0.015	0	-9999	-10000	0	0
JUP	0.01	0.018	-9999	-0.41	1	1
p120 catenin/RhoA/GDP	0.045	0.017	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0.015	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.016	0	-9999	-10000	0	0
RHOA	0.011	0	-9999	-10000	0	0
CDC42	0.011	0	-9999	-10000	0	0
CTNNA1	0.011	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.027	0.014	-9999	-0.13	2	2
NME1	0.011	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.032	0.027	-9999	-0.38	2	2
regulation of cell-cell adhesion	0	0.007	-9999	-10000	0	0
WASF2	-0.001	0.005	-9999	-10000	0	0
Rap1/GTP	-0.001	0.009	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.031	0.021	-9999	-0.38	1	1
CCND1	0.031	0.016	-9999	-0.15	2	2
VAV2	0.041	0.024	-9999	-0.35	2	2
RAP1/GDP	0.043	0.015	-9999	-10000	0	0
adherens junction assembly	0.032	0.026	-9999	-0.37	2	2
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.011	0	-9999	-10000	0	0
PIP5K1C	0.011	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.036	0.021	-9999	-0.36	1	1
E-cadherin/beta catenin	-0.001	0.018	-9999	-0.3	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.032	0.025	-9999	-0.38	2	2
PIK3CA	0.01	0.018	-9999	-0.41	1	1
Rac1/GTP	-0.003	0.018	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0.022	0.015	-9999	-0.23	2	2
ITGAE	0.011	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.027	0.027	-9999	-0.4	2	2

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.036	0.03	-10000	0	-0.22	7	7
adherens junction organization	0.033	0.028	-10000	0	-0.35	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.036	0.042	-10000	0	-0.38	2	2
FMN1	0.027	0.038	-10000	0	-0.34	2	2
mol:IP3	0.03	0.026	-10000	0	-0.29	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.028	0.027	-10000	0	-0.36	2	2
CTNNB1	0.011	0.001	-10000	0	-10000	0	0
AKT1	0.036	0.027	-10000	0	-0.33	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.032	0.029	-10000	0	-0.42	2	2
CTNND1	0.012	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.033	0.025	-10000	0	-0.33	2	2
VASP	0.033	0.026	-10000	0	-0.34	2	2
ZYX	0.033	0.026	-10000	0	-0.34	2	2
JUB	0.033	0.026	-10000	0	-0.34	2	2
EGFR(dimer)	0.028	0.045	-10000	0	-0.36	3	3
E-cadherin/beta catenin-gamma catenin	-0.001	0.021	-10000	0	-0.31	2	2
mol:PI-3-4-5-P3	0.03	0.028	-10000	0	-0.35	1	1
PIK3CA	0.011	0.018	-10000	0	-0.41	1	1
PI3K	0.031	0.029	-10000	0	-0.36	1	1
FYN	0.031	0.037	-10000	0	-0.24	1	1
mol:Ca2+	0.03	0.026	-10000	0	-0.29	1	1
JUP	0.01	0.018	-10000	0	-0.4	1	1
PIK3R1	0.008	0.041	-10000	0	-0.41	5	5
mol:DAG	0.03	0.026	-10000	0	-0.29	1	1
CDH1	0.009	0.026	-10000	0	-0.41	2	2
RhoA/GDP	0.036	0.042	-10000	0	-0.38	2	2
establishment of polarity of embryonic epithelium	0.033	0.025	-10000	0	-0.33	2	2
SRC	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
RHOA	0.011	0	-10000	0	-10000	0	0
EGFR	0	0.067	-10000	0	-0.4	14	14
CASR	0.023	0.044	-10000	0	-0.27	1	1
RhoA/GTP	-0.002	0.02	-10000	0	-0.26	1	1
AKT2	0.036	0.027	-10000	0	-0.33	1	1
actin cable formation	0.032	0.037	-10000	0	-0.46	1	1
apoptosis	-0.034	0.029	0.2	7	-10000	0	7
CTNNA1	0.012	0.001	-10000	0	-10000	0	0
mol:GDP	0.031	0.044	-10000	0	-0.41	2	2
PIP5K1A	0.033	0.026	-10000	0	-0.34	2	2
PLCG1	0.031	0.026	-10000	0	-0.3	1	1
Rac1/GTP	-0.005	0.036	-10000	0	-0.41	2	2
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.021	0.023	-9999	-0.34	2	2
E-cadherin/beta catenin	0.015	0.018	-9999	-0.28	2	2
CTNNB1	0.011	0	-9999	-10000	0	0
JUP	0.01	0.018	-9999	-0.41	1	1
CDH1	0.009	0.026	-9999	-0.41	2	2

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.039	0.011	-9999	-10000	0	0
CLOCK	0.014	0.001	-9999	-10000	0	0
TIMELESS/CRY2	0.034	0.012	-9999	-10000	0	0
DEC1/BMAL1	0.011	0.013	-9999	-0.28	1	1
ATR	0.011	0	-9999	-10000	0	0
NR1D1	0.033	0.009	-9999	-10000	0	0
ARNTL	0.013	0.018	-9999	-0.41	1	1
TIMELESS	0.033	0.013	-9999	-10000	0	0
NPAS2	0.01	0.041	-9999	-0.41	5	5
CRY2	0.011	0	-9999	-10000	0	0
mol:CO	-0.011	0.003	-9999	-10000	0	0
CHEK1	0.011	0	-9999	-10000	0	0
mol:HEME	0.011	0.003	-9999	-10000	0	0
PER1	0.009	0.026	-9999	-0.41	2	2
BMAL/CLOCK/NPAS2	0.033	0.027	-9999	-0.22	6	6
BMAL1/CLOCK	0.04	0.019	-9999	-10000	0	0
S phase of mitotic cell cycle	0.039	0.011	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.039	0.011	-9999	-10000	0	0
mol:NADPH	0.011	0.003	-9999	-10000	0	0
PER1/TIMELESS	0.034	0.018	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.001	0.004	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.011	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0.025	-9999	-9999
HDAC4	0.011	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.011	-9999	-9999
NPC/RanGAP1/SUMO1	0.014	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.023	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.011	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.011	-9999	-9999
SUMO1/HDAC4	0.025	-9999	-9999
SUMO1/HDAC1	0.025	-9999	-9999
RANGAP1	0.011	-9999	-9999
MDM2/SUMO1/SUMO1	0.028	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	-9999	-9999
Ran/GTP	0.022	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.011	-9999	-9999
UBE2I	0.011	-9999	-9999
Ran/GTP/Exportin 1	0.027	-9999	-9999
NPC	0.007	-9999	-9999
PIAS2	0.011	-9999	-9999
PIAS1	0.011	-9999	-9999
EntrezGene:9972	0	-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	0.016	0.004	-9999	-10000	0	0
AP2	0.016	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.016	0	-9999	-10000	0	0
CLTB	0.011	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.021	0	-9999	-10000	0	0
CD4	0.01	0.015	-9999	-0.33	1	1
CLTA	0.011	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.006	-9999	-0.15	1	1
ARF1/GTP	0	0.003	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.022	0	-9999	-10000	0	0
mol:Choline	0	0.007	-9999	-0.15	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.011	0	-9999	-10000	0	0
DDEF1	0	0.007	-9999	-0.16	1	1
ARF1/GDP	0	0.002	-9999	-10000	0	0
AP2M1	0.011	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.014	0	-9999	-10000	0	0
Rac/GTP	0.009	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.021	0	-9999	-10000	0	0
ARFIP2	0.01	0	-9999	-10000	0	0
COPA	0.011	0	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.021	0.002	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.008	0	-9999	-10000	0	0
GGA3	0.011	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.015	0.003	-9999	-10000	0	0
AP2A1	0.011	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.022	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.015	0.003	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.014	0	-9999	-10000	0	0
CYTH2	0.011	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.016	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.008	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	0.028	0.003	-9999	-10000	0	0
PLD2	0	0.007	-9999	-0.15	1	1
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0	0.006	-9999	-0.15	1	1
ARF1/GTP/Membrin/GBF1/p115	0	0.003	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0.007	-9999	-0.15	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.009	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	0.016	0.001	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.022	0.009	-9999	-0.17	1	1

×

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	0.016	0	-9999	-10000	0	0
FBXW11	0.011	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
CHUK	0.011	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.033	0	-9999	-10000	0	0
NFKB1	0.01	0.018	-9999	-0.41	1	1
MAP3K14	0.011	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	0.016	0.013	-9999	-0.28	1	1
RELB	0.011	0	-9999	-10000	0	0
NFKB2	0.011	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.015	0	-9999	-10000	0	0
regulation of B cell activation	0.015	0	-9999	-10000	0	0

pid_entity	TCGA.SL.A6JA	TCGA.SL.A6J9	TCGA.SJ.A6ZJ	TCGA.SJ.A6ZI
109_MAP3K5	-0.13	0.043	0.043	0.043
47_PPARGC1A	-0.41	0.011	0.011	-0.41
105_BMP4	0.011	-0.41	0.011	0.011
105_BMP6	0.011	0.011	0.011	0.011
105_BMP7	0.011	0.011	0.011	0.011
105_BMP2	0.011	-0.41	0.011	0.011
131_RELN/VLDLR	-0.2	-0.2	0.028	-0.2
30_TGFB1/TGF beta receptor Type II	0.011	0.011	0.013	0.01
84_STAT5B	-0.023	-0.091	-0.024	0.038
84_STAT5A	-0.023	-0.091	-0.024	0.038