PARADIGM pathway analysis of mRNA expression data - Glioblastoma Multiforme (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
HIF-1-alpha transcription factor network	225
Glypican 2 network	224
FOXM1 transcription factor network	202
TCGA08_retinoblastoma	152
Endothelins	136
Syndecan-1-mediated signaling events	127
Osteopontin-mediated events	127
EGFR-dependent Endothelin signaling events	118
LPA receptor mediated events	115
amb2 Integrin signaling	111

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
HIF-1-alpha transcription factor network	0.4261	225	17124	76	-0.55	0.023	1000	-1000	-0.008	-1000
Glypican 2 network	0.4242	224	897	4	-0.23	0	1000	-1000	0	-1000
FOXM1 transcription factor network	0.3826	202	10319	51	-0.75	0.017	1000	-1000	-0.048	-1000
TCGA08_retinoblastoma	0.2879	152	1221	8	-0.23	0.073	1000	-1000	-0.002	-1000
Endothelins	0.2576	136	13116	96	-0.47	0.084	1000	-1000	-0.006	-1000
Syndecan-1-mediated signaling events	0.2405	127	4332	34	-0.29	0.018	1000	-1000	0	-1000
Osteopontin-mediated events	0.2405	127	4843	38	-0.32	0.017	1000	-1000	-0.004	-1000
EGFR-dependent Endothelin signaling events	0.2235	118	2483	21	-0.14	0.017	1000	-1000	-0.002	-1000
LPA receptor mediated events	0.2178	115	11808	102	-0.18	0.017	1000	-1000	-0.036	-1000
amb2 Integrin signaling	0.2102	111	9173	82	-0.25	0.022	1000	-1000	0	-1000
PLK1 signaling events	0.1667	88	7524	85	-0.25	0.022	1000	-1000	-0.007	-1000
BARD1 signaling events	0.1591	84	4842	57	-0.26	0.049	1000	-1000	-0.013	-1000
Syndecan-4-mediated signaling events	0.1515	80	5370	67	-0.39	0.021	1000	-1000	-0.01	-1000
HIF-2-alpha transcription factor network	0.1496	79	3432	43	-0.21	0.11	1000	-1000	-0.042	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.1364	72	9030	125	-0.25	0.026	1000	-1000	-0.034	-1000
Fc-epsilon receptor I signaling in mast cells	0.1326	70	6811	97	-0.19	0.032	1000	-1000	-0.026	-1000
Wnt signaling	0.1326	70	495	7	-0.12	0.017	1000	-1000	0.004	-1000
Aurora B signaling	0.1269	67	4513	67	-0.31	0.023	1000	-1000	-0.011	-1000
VEGFR1 specific signals	0.1212	64	3610	56	-0.25	0.039	1000	-1000	-0.007	-1000
Regulation of nuclear SMAD2/3 signaling	0.1155	61	8302	136	-0.28	0.16	1000	-1000	-0.01	-1000
PDGFR-alpha signaling pathway	0.1042	55	2457	44	-0.25	0.023	1000	-1000	-0.005	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.1004	53	3941	74	-0.35	0.033	1000	-1000	-0.031	-1000
Noncanonical Wnt signaling pathway	0.0966	51	1336	26	-0.12	0.017	1000	-1000	-0.029	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0966	51	1905	37	-0.27	0.042	1000	-1000	-0.008	-1000
S1P1 pathway	0.0947	50	1809	36	-0.21	0.022	1000	-1000	-0.031	-1000
TCGA08_p53	0.0947	50	353	7	-0.025	0.009	1000	-1000	0	-1000
FAS signaling pathway (CD95)	0.0947	50	2390	47	-0.045	0.031	1000	-1000	-0.01	-1000
Circadian rhythm pathway	0.0909	48	1065	22	-0.046	0.026	1000	-1000	-0.013	-1000
IL1-mediated signaling events	0.0909	48	2977	62	-0.12	0.049	1000	-1000	-0.009	-1000
Class I PI3K signaling events	0.0890	47	3496	73	-0.093	0.035	1000	-1000	-0.005	-1000
Ras signaling in the CD4+ TCR pathway	0.0871	46	785	17	-0.094	0.016	1000	-1000	-0.003	-1000
Aurora A signaling	0.0833	44	2661	60	-0.16	0.042	1000	-1000	0	-1000
E-cadherin signaling in keratinocytes	0.0833	44	1921	43	-0.14	0.028	1000	-1000	-0.003	-1000
Integrins in angiogenesis	0.0777	41	3468	84	-0.22	0.04	1000	-1000	-0.014	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0701	37	1959	52	-0.24	0.051	1000	-1000	0	-1000
BCR signaling pathway	0.0701	37	3714	99	-0.087	0.048	1000	-1000	-0.033	-1000
Signaling events mediated by HDAC Class I	0.0682	36	3800	104	-0.13	0.034	1000	-1000	-0.018	-1000
Syndecan-2-mediated signaling events	0.0663	35	2462	69	-0.19	0.034	1000	-1000	0	-1000
Syndecan-3-mediated signaling events	0.0663	35	1251	35	-0.14	0.032	1000	-1000	-0.002	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0663	35	3095	88	-0.2	0.037	1000	-1000	-0.046	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0625	33	2610	78	-0.047	0.033	1000	-1000	-0.024	-1000
Glypican 1 network	0.0606	32	1562	48	-0.22	0.028	1000	-1000	-0.005	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0587	31	731	23	-0.085	0.018	1000	-1000	0	-1000
TCGA08_rtk_signaling	0.0587	31	806	26	-0.14	0.021	1000	-1000	-0.002	-1000
Plasma membrane estrogen receptor signaling	0.0568	30	2623	86	-0.42	0.13	1000	-1000	-0.03	-1000
Visual signal transduction: Cones	0.0549	29	1104	38	-0.13	0.04	1000	-1000	0	-1000
Signaling mediated by p38-alpha and p38-beta	0.0530	28	1274	44	-0.043	0.033	1000	-1000	-0.001	-1000
Nongenotropic Androgen signaling	0.0530	28	1479	52	-0.059	0.027	1000	-1000	-0.016	-1000
S1P3 pathway	0.0530	28	1209	42	-0.22	0.022	1000	-1000	0	-1000
Paxillin-dependent events mediated by a4b1	0.0511	27	994	36	-0.27	0.042	1000	-1000	-0.009	-1000
Arf6 downstream pathway	0.0492	26	1139	43	-0.016	0.025	1000	-1000	-0.011	-1000
IL6-mediated signaling events	0.0492	26	1994	75	-0.2	0.034	1000	-1000	-0.009	-1000
ErbB2/ErbB3 signaling events	0.0473	25	1630	65	-0.094	0.022	1000	-1000	-0.025	-1000
IL23-mediated signaling events	0.0473	25	1544	60	-0.026	0.046	1000	-1000	-0.012	-1000
Signaling events mediated by PRL	0.0473	25	870	34	-0.038	0.025	1000	-1000	-0.006	-1000
Signaling events mediated by PTP1B	0.0455	24	1848	76	-0.2	0.033	1000	-1000	-0.005	-1000
TRAIL signaling pathway	0.0455	24	1193	48	-0.02	0.022	1000	-1000	-0.01	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0455	24	1107	45	-0.13	0.026	1000	-1000	-0.015	-1000
Canonical Wnt signaling pathway	0.0455	24	1274	51	-0.11	0.1	1000	-1000	-0.011	-1000
E-cadherin signaling in the nascent adherens junction	0.0436	23	1761	76	-0.086	0.039	1000	-1000	-0.031	-1000
Caspase cascade in apoptosis	0.0417	22	1666	74	-0.13	0.024	1000	-1000	-0.011	-1000
Presenilin action in Notch and Wnt signaling	0.0417	22	1379	61	-0.092	0.035	1000	-1000	-0.006	-1000
Glucocorticoid receptor regulatory network	0.0417	22	2537	114	-0.099	0.075	1000	-1000	-0.02	-1000
Ceramide signaling pathway	0.0417	22	1681	76	-0.13	0.039	1000	-1000	-0.006	-1000
Regulation of Telomerase	0.0417	22	2321	102	-0.14	0.044	1000	-1000	-0.029	-1000
FoxO family signaling	0.0398	21	1403	64	-0.2	0.022	1000	-1000	-0.016	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0398	21	1480	68	-0.19	0.084	1000	-1000	-0.032	-1000
Cellular roles of Anthrax toxin	0.0379	20	818	39	-0.084	0.016	1000	-1000	-0.005	-1000
EPO signaling pathway	0.0379	20	1120	55	-0.033	0.053	1000	-1000	-0.009	-1000
IL2 signaling events mediated by STAT5	0.0379	20	450	22	-0.096	0.042	1000	-1000	0	-1000
Coregulation of Androgen receptor activity	0.0360	19	1483	76	-0.34	0.047	1000	-1000	-0.006	-1000
BMP receptor signaling	0.0360	19	1578	81	-0.085	0.047	1000	-1000	-0.03	-1000
IFN-gamma pathway	0.0360	19	1329	68	-0.064	0.043	1000	-1000	-0.032	-1000
ceramide signaling pathway	0.0360	19	938	49	-0.13	0.025	1000	-1000	-0.012	-1000
IL2 signaling events mediated by PI3K	0.0360	19	1152	58	-0.043	0.037	1000	-1000	-0.016	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0360	19	2312	120	-0.12	0.05	1000	-1000	-0.022	-1000
Regulation of p38-alpha and p38-beta	0.0341	18	1007	54	-0.053	0.033	1000	-1000	0	-1000
IL12-mediated signaling events	0.0322	17	1510	87	-0.22	0.048	1000	-1000	-0.052	-1000
Retinoic acid receptors-mediated signaling	0.0322	17	1028	58	-0.18	0.069	1000	-1000	-0.008	-1000
TCR signaling in naïve CD8+ T cells	0.0322	17	1582	93	-0.094	0.033	1000	-1000	-0.027	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0303	16	889	54	-0.086	0.026	1000	-1000	-0.012	-1000
p75(NTR)-mediated signaling	0.0284	15	1877	125	-0.12	0.082	1000	-1000	-0.03	-1000
IL4-mediated signaling events	0.0284	15	1424	91	-0.15	0.051	1000	-1000	-0.097	-1000
PDGFR-beta signaling pathway	0.0284	15	1486	97	-0.067	0.04	1000	-1000	-0.028	-1000
ErbB4 signaling events	0.0265	14	1004	69	-0.14	0.051	1000	-1000	-0.012	-1000
Canonical NF-kappaB pathway	0.0246	13	545	39	-0.13	0.061	1000	-1000	-0.003	-1000
Signaling mediated by p38-gamma and p38-delta	0.0246	13	209	15	-0.013	0.025	1000	-1000	-0.001	-1000
Insulin Pathway	0.0246	13	1007	74	-0.11	0.048	1000	-1000	-0.023	-1000
Arf6 signaling events	0.0227	12	751	62	-0.14	0.044	1000	-1000	-0.001	-1000
IGF1 pathway	0.0227	12	737	57	-0.032	0.034	1000	-1000	-0.008	-1000
Nectin adhesion pathway	0.0208	11	695	63	-0.086	0.054	1000	-1000	-0.029	-1000
Ephrin B reverse signaling	0.0208	11	571	48	-0.016	0.026	1000	-1000	-0.01	-1000
Signaling events mediated by the Hedgehog family	0.0189	10	552	52	-0.03	0.045	1000	-1000	-0.007	-1000
JNK signaling in the CD4+ TCR pathway	0.0189	10	186	17	-0.017	0.027	1000	-1000	-0.006	-1000
Thromboxane A2 receptor signaling	0.0189	10	1113	105	-0.14	0.035	1000	-1000	-0.036	-1000
Class I PI3K signaling events mediated by Akt	0.0189	10	702	68	-0.026	0.036	1000	-1000	-0.005	-1000
Calcium signaling in the CD4+ TCR pathway	0.0189	10	311	31	-0.082	0.055	1000	-1000	-0.021	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0189	10	356	33	-0.039	0.041	1000	-1000	-0.007	-1000
E-cadherin signaling events	0.0189	10	51	5	0.004	0.023	1000	-1000	0.003	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0170	9	771	85	-0.085	0.049	1000	-1000	-0.023	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0170	9	255	27	-0.036	0.036	1000	-1000	-0.02	-1000
Hedgehog signaling events mediated by Gli proteins	0.0152	8	535	65	-0.064	0.042	1000	-1000	-0.005	-1000
Aurora C signaling	0.0152	8	58	7	-0.005	0.02	1000	-1000	0	-1000
EPHB forward signaling	0.0152	8	684	85	-0.094	0.048	1000	-1000	-0.032	-1000
Arf6 trafficking events	0.0152	8	583	71	-0.026	0.028	1000	-1000	-0.007	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0133	7	210	28	-0.036	0.024	1000	-1000	0	-1000
Signaling events mediated by HDAC Class III	0.0133	7	294	40	-0.034	0.038	1000	-1000	-0.014	-1000
Signaling events regulated by Ret tyrosine kinase	0.0133	7	607	82	-0.02	0.043	1000	-1000	-0.025	-1000
mTOR signaling pathway	0.0114	6	365	53	-0.1	0.034	1000	-1000	-0.027	-1000
S1P5 pathway	0.0114	6	104	17	-0.036	0.017	1000	-1000	-0.003	-1000
Atypical NF-kappaB pathway	0.0114	6	197	31	-0.012	0.033	1000	-1000	0	-1000
IL27-mediated signaling events	0.0114	6	338	51	-0.025	0.044	1000	-1000	-0.015	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0095	5	177	34	-0.027	0.047	1000	-1000	-0.009	-1000
FOXA2 and FOXA3 transcription factor networks	0.0095	5	261	46	-0.018	0.19	1000	-1000	-0.002	-1000
p38 MAPK signaling pathway	0.0095	5	247	44	-0.02	0.048	1000	-1000	-0.011	-1000
Regulation of Androgen receptor activity	0.0095	5	382	70	-0.027	0.068	1000	-1000	-0.015	-1000
Insulin-mediated glucose transport	0.0076	4	132	32	-0.01	0.021	1000	-1000	-0.003	-1000
Reelin signaling pathway	0.0076	4	279	56	-0.003	0.08	1000	-1000	-0.007	-1000
S1P4 pathway	0.0076	4	124	25	-0.036	0.022	1000	-1000	-0.001	-1000
Signaling events mediated by HDAC Class II	0.0057	3	237	75	-0.029	0.043	1000	-1000	-0.018	-1000
a4b1 and a4b7 Integrin signaling	0.0057	3	17	5	0.013	0.023	1000	-1000	0.004	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0057	3	270	83	-0.062	0.047	1000	-1000	-0.007	-1000
LPA4-mediated signaling events	0.0019	1	12	12	0	0.014	1000	-1000	-0.002	-1000
Effects of Botulinum toxin	0.0019	1	42	26	0	0.035	1000	-1000	0	-1000
Arf1 pathway	0.0019	1	75	54	0	0.027	1000	-1000	-0.002	-1000
Alternative NF-kappaB pathway	0.0019	1	22	13	0	0.049	1000	-1000	0	-1000
PLK2 and PLK4 events	0.0000	0	0	3	0.012	0.017	1000	-1000	0.003	-1000
Ephrin A reverse signaling	0.0000	0	2	7	0	0.023	1000	-1000	0	-1000
Rapid glucocorticoid signaling	0.0000	0	4	20	0	0.017	1000	-1000	0	-1000
Visual signal transduction: Rods	0.0000	0	5	52	0	0.042	1000	-1000	-0.003	-1000
Class IB PI3K non-lipid kinase events	0.0000	0	0	3	-0.017	0.017	1000	-1000	-0.004	-1000
Total	NA	4473	255371	7203	-16	5.2	131000	-131000	-1.7	-131000

HIF-1-alpha 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.45	0.47	-10000	0	-0.79	301	301
HDAC7	-0.006	0.012	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.34	0.37	0.36	28	-0.63	285	313
SMAD4	-0.085	0.18	-10000	0	-0.41	126	126
ID2	-0.45	0.47	0.28	28	-0.79	301	329
AP1	-0.047	0.13	-10000	0	-0.29	125	125
ABCG2	-0.45	0.47	-10000	0	-0.79	301	301
HIF1A	-0.062	0.08	-10000	0	-0.14	142	142
TFF3	-0.45	0.47	-10000	0	-0.79	303	303
GATA2	0.017	0.019	-10000	0	-0.41	1	1
AKT1	-0.055	0.082	0.26	2	-0.13	189	191
response to hypoxia	-0.068	0.069	0.31	1	-0.13	227	228
MCL1	-0.45	0.47	-10000	0	-0.8	301	301
NDRG1	-0.45	0.47	-10000	0	-0.79	301	301
SERPINE1	-0.52	0.53	0.28	28	-0.88	313	341
FECH	-0.45	0.47	-10000	0	-0.79	301	301
FURIN	-0.45	0.47	-10000	0	-0.79	301	301
NCOA2	0.019	0.001	-10000	0	-10000	0	0
EP300	-0.026	0.12	0.44	6	-0.18	9	15
HMOX1	-0.55	0.53	-10000	0	-0.9	329	329
BHLHE40	-0.45	0.47	0.26	28	-0.8	302	330
BHLHE41	-0.45	0.47	0.26	28	-0.8	302	330
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.1	0.13	-10000	0	-0.28	117	117
ENG	-0.07	0.15	0.35	3	-0.3	90	93
JUN	0.017	0.019	-10000	0	-0.41	1	1
RORA	-0.45	0.47	-10000	0	-0.8	300	300
ABCB1	-0.093	0.087	-10000	0	-0.18	233	233
TFRC	-0.45	0.47	-10000	0	-0.79	302	302
CXCR4	-0.54	0.53	-10000	0	-0.88	324	324
TF	-0.42	0.47	-10000	0	-0.78	286	286
CITED2	-0.45	0.48	-10000	0	-0.8	301	301
HIF1A/ARNT	-0.49	0.57	0.48	28	-0.9	300	328
LDHA	-0.052	0.054	-10000	0	-10000	0	0
ETS1	-0.45	0.47	-10000	0	-0.8	300	300
PGK1	-0.45	0.47	-10000	0	-0.79	301	301
NOS2	-0.45	0.47	0.26	28	-0.8	302	330
ITGB2	-0.52	0.53	-10000	0	-0.89	310	310
ALDOA	-0.45	0.47	0.28	28	-0.79	301	329
Cbp/p300/CITED2	-0.45	0.48	0.31	28	-0.8	301	329
FOS	-0.084	0.18	-10000	0	-0.41	125	125
HK2	-0.45	0.47	-10000	0	-0.79	301	301
SP1	0.023	0.008	-10000	0	-10000	0	0
GCK	-0.037	0.17	0.56	6	-0.2	91	97
HK1	-0.45	0.47	0.28	28	-0.79	300	328
NPM1	-0.45	0.47	-10000	0	-0.79	302	302
EGLN1	-0.45	0.47	-10000	0	-0.79	301	301
CREB1	0.023	0.002	-10000	0	-10000	0	0
PGM1	-0.45	0.47	-10000	0	-0.79	301	301
SMAD3	0.017	0.003	-10000	0	-10000	0	0
EDN1	-0.036	0.15	0.51	1	-0.24	88	89
IGFBP1	-0.45	0.48	-10000	0	-0.8	302	302
VEGFA	-0.41	0.42	0.38	15	-0.7	321	336
HIF1A/JAB1	-0.033	0.054	-10000	0	-0.3	3	3
CP	-0.5	0.51	0.28	20	-0.86	307	327
CXCL12	-0.45	0.48	-10000	0	-0.8	301	301
COPS5	0.018	0.001	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.048	0.13	-10000	0	-0.28	126	126
BNIP3	-0.45	0.47	-10000	0	-0.79	301	301
EGLN3	-0.45	0.47	0.28	28	-0.79	302	330
CA9	-0.46	0.48	-10000	0	-0.81	302	302
TERT	-0.45	0.47	-10000	0	-0.79	301	301
ENO1	-0.45	0.47	-10000	0	-0.79	301	301
PFKL	-0.45	0.47	-10000	0	-0.79	301	301
NCOA1	0.017	0.003	-10000	0	-10000	0	0
ADM	-0.55	0.52	0.28	20	-0.87	334	354
ARNT	-0.063	0.07	-10000	0	-0.14	159	159
HNF4A	0.021	0	-10000	0	-10000	0	0
ADFP	-0.52	0.53	-10000	0	-0.88	316	316
SLC2A1	-0.32	0.36	-10000	0	-0.61	296	296
LEP	-0.45	0.47	-10000	0	-0.79	301	301
HIF1A/ARNT/Cbp/p300	-0.35	0.38	0.36	28	-0.64	301	329
EPO	-0.18	0.28	0.52	6	-0.44	230	236
CREBBP	-0.026	0.12	0.44	6	-0.17	12	18
HIF1A/ARNT/Cbp/p300/HDAC7	-0.39	0.4	0.36	28	-0.67	313	341
PFKFB3	-0.45	0.47	-10000	0	-0.79	301	301
NT5E	-0.47	0.48	-10000	0	-0.82	305	305

×

Glypican 2 network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.23	0.21	-9999	-0.41	299	299
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	-0.16	0.15	-9999	-0.29	299	299
neuron projection morphogenesis	-0.16	0.15	-9999	-0.29	299	299

×

FOXM1 transcription factor network

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
NFATC3	-0.55	0.55	-9999	-1	269	269
PLK1	-0.031	0.098	-9999	-0.46	22	22
BIRC5	-0.18	0.23	-9999	-0.46	211	211
HSPA1B	-0.56	0.55	-9999	-1	274	274
MAP2K1	-0.013	0.036	-9999	-10000	0	0
BRCA2	-0.55	0.55	-9999	-1	269	269
FOXM1	-0.75	0.8	-9999	-1.3	293	293
XRCC1	-0.55	0.55	-9999	-1	270	270
FOXM1B/p19	-0.64	0.6	-9999	-1.1	274	274
Cyclin D1/CDK4	-0.6	0.55	-9999	-1.1	285	285
CDC2	-0.63	0.63	-9999	-1.2	272	272
TGFA	-0.49	0.48	-9999	-0.92	267	267
SKP2	-0.55	0.55	-9999	-1	269	269
CCNE1	0.005	0.05	-9999	-0.42	7	7
CKS1B	-0.59	0.58	-9999	-1.1	273	273
RB1	-0.26	0.23	-9999	-0.46	238	238
FOXM1C/SP1	-0.68	0.68	-9999	-1.2	274	274
AURKB	-0.034	0.11	-9999	-0.46	27	27
CENPF	-0.6	0.59	-9999	-1.1	276	276
CDK4	-0.27	0.21	-9999	-0.43	342	342
MYC	-0.53	0.5	-9999	-0.94	281	281
CHEK2	-0.026	0.086	-9999	-0.46	16	16
ONECUT1	-0.55	0.54	-9999	-1	270	270
CDKN2A	-0.032	0.14	-9999	-0.41	59	59
LAMA4	-0.55	0.55	-9999	-1	270	270
FOXM1B/HNF6	-0.68	0.68	-9999	-1.3	271	271
FOS	-0.59	0.56	-9999	-1	281	281
SP1	0.016	0.006	-9999	-10000	0	0
CDC25B	-0.56	0.56	-9999	-1	270	270
response to radiation	-0.02	0.026	-9999	-10000	0	0
CENPB	-0.56	0.55	-9999	-1	270	270
CENPA	-0.57	0.58	-9999	-1.1	269	269
NEK2	-0.56	0.56	-9999	-1	270	270
HIST1H2BA	-0.56	0.55	-9999	-1	274	274
CCNA2	-0.1	0.19	-9999	-0.43	139	139
EP300	0.017	0	-9999	-10000	0	0
CCNB1/CDK1	-0.71	0.71	-9999	-1.3	281	281
CCNB2	-0.65	0.6	-9999	-1.1	296	296
CCNB1	-0.64	0.63	-9999	-1.2	281	281
ETV5	-0.55	0.55	-9999	-1	272	272
ESR1	-0.55	0.55	-9999	-1	269	269
CCND1	-0.56	0.53	-9999	-1	271	271
GSK3A	-0.009	0.029	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.075	0.16	-9999	-0.31	146	146
CDK2	-0.011	0.097	-9999	-0.43	27	27
G2/M transition of mitotic cell cycle	-0.024	0.033	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.61	0.62	-9999	-1.1	270	270
GAS1	-0.57	0.56	-9999	-1	279	279
MMP2	-0.63	0.57	-9999	-1.1	301	301
RB1/FOXM1C	-0.59	0.55	-9999	-1.1	274	274
CREBBP	0.017	0	-9999	-10000	0	0

×

TCGA08_retinoblastoma

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0	0.018	-10000	0	-10000	0	0
CDKN2C	-0.23	0.21	-10000	0	-0.41	310	310
CDKN2A	-0.014	0.13	-10000	0	-0.38	59	59
CCND2	0.044	0.062	0.13	113	-10000	0	113
RB1	-0.048	0.068	-10000	0	-0.14	113	113
CDK4	0.031	0.071	0.14	116	-0.081	86	202
CDK6	0.073	0.074	0.13	311	-10000	0	311
G1/S progression	0.048	0.068	0.14	113	-10000	0	113

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.26	0.22	-10000	0	-0.35	397	397
PTK2B	0.017	0	-10000	0	-10000	0	0
mol:Ca2+	-0.039	0.099	-10000	0	-0.48	5	5
EDN1	-0.11	0.11	-10000	0	-0.23	145	145
EDN3	0.014	0.037	-10000	0	-0.41	4	4
EDN2	0.016	0.019	-10000	0	-0.41	1	1
HRAS/GDP	-0.023	0.11	0.18	1	-0.22	53	54
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.087	0.1	-10000	0	-0.2	183	183
ADCY4	-0.22	0.18	-10000	0	-0.29	396	396
ADCY5	-0.22	0.18	-10000	0	-0.29	396	396
ADCY6	-0.21	0.18	-10000	0	-0.34	291	291
ADCY7	-0.21	0.18	-10000	0	-0.35	291	291
ADCY1	-0.21	0.18	-10000	0	-0.34	291	291
ADCY2	-0.21	0.18	-10000	0	-0.34	291	291
ADCY3	-0.22	0.18	-10000	0	-0.29	396	396
ADCY8	-0.21	0.18	-10000	0	-0.35	293	293
ADCY9	-0.21	0.18	-10000	0	-0.34	291	291
arachidonic acid secretion	-0.067	0.14	-10000	0	-0.3	104	104
ETB receptor/Endothelin-1/Gq/GTP	-0.032	0.062	-10000	0	-0.17	43	43
GNAO1	0.002	0.005	-10000	0	-10000	0	0
HRAS	0.016	0.019	-10000	0	-0.41	1	1
ETA receptor/Endothelin-1/G12/GTP	-0.23	0.21	0.25	1	-0.37	315	316
ETA receptor/Endothelin-1/Gs/GTP	-0.22	0.2	0.24	1	-0.34	321	322
mol:GTP	0	0.003	-10000	0	-10000	0	0
COL3A1	-0.41	0.28	-10000	0	-0.55	400	400
EDNRB	-0.047	0.12	-10000	0	-0.42	41	41
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.26	0.21	-10000	0	-0.4	312	312
CYSLTR1	-0.26	0.21	-10000	0	-0.35	397	397
SLC9A1	-0.13	0.11	-10000	0	-0.21	291	291
mol:GDP	-0.03	0.11	0.18	1	-0.22	62	63
SLC9A3	-0.084	0.12	-10000	0	-0.35	38	38
RAF1	-0.05	0.12	-10000	0	-0.26	96	96
JUN	-0.041	0.098	-10000	0	-0.38	8	8
JAK2	-0.26	0.22	-10000	0	-0.35	396	396
mol:IP3	-0.077	0.09	-10000	0	-0.18	170	170
ETA receptor/Endothelin-1	-0.3	0.25	0.28	1	-0.41	397	398
PLCB1	0.017	0.002	-10000	0	-10000	0	0
PLCB2	0.016	0.003	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.17	0.18	-10000	0	-0.42	157	157
FOS	-0.075	0.18	-10000	0	-0.38	125	125
Gai/GDP	-0.47	0.17	-10000	0	-0.52	481	481
CRK	0.017	0	-10000	0	-10000	0	0
mol:Ca ++	-0.23	0.21	-10000	0	-0.37	319	319
BCAR1	0	0	-10000	0	-10000	0	0
PRKCB1	-0.015	0.046	-10000	0	-0.19	18	18
GNAQ	0.018	0.004	-10000	0	-10000	0	0
GNAZ	0.015	0.006	-10000	0	-10000	0	0
GNAL	0.017	0	-10000	0	-10000	0	0
Gs family/GDP	-0.023	0.1	0.17	1	-0.21	55	56
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.12	-10000	0	-0.21	265	265
MAPK14	-0.018	0.052	-10000	0	-0.16	27	27
TRPC6	-0.041	0.1	-10000	0	-0.38	10	10
GNAI2	0.017	0.001	-10000	0	-10000	0	0
GNAI3	-0.036	0.14	-10000	0	-0.41	65	65
GNAI1	0.014	0.02	-10000	0	-0.41	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.022	0.055	-10000	0	-0.16	33	33
ETB receptor/Endothelin-2	-0.022	0.083	-10000	0	-0.29	41	41
ETB receptor/Endothelin-3	-0.024	0.086	-10000	0	-0.29	45	45
ETB receptor/Endothelin-1	-0.11	0.12	-10000	0	-0.25	169	169
MAPK3	-0.069	0.17	-10000	0	-0.35	127	127
MAPK1	-0.073	0.17	-10000	0	-0.35	127	127
Rac1/GDP	-0.023	0.1	0.18	1	-0.22	53	54
cAMP biosynthetic process	-0.17	0.16	-10000	0	-0.3	279	279
MAPK8	-0.054	0.11	-10000	0	-0.35	14	14
SRC	0.017	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.033	0.078	-10000	0	-0.2	88	88
p130Cas/CRK/Src/PYK2	0.005	0.098	-10000	0	-0.28	12	12
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.024	0.1	0.18	1	-0.22	55	56
COL1A2	-0.35	0.29	-10000	0	-0.57	305	305
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.16	0.18	-10000	0	-0.42	155	155
mol:DAG	-0.077	0.09	-10000	0	-0.18	170	170
MAP2K2	-0.061	0.14	-10000	0	-0.3	117	117
MAP2K1	-0.059	0.15	-10000	0	-0.3	117	117
EDNRA	-0.24	0.23	-10000	0	-0.4	288	288
positive regulation of muscle contraction	-0.22	0.19	-10000	0	-0.36	293	293
Gq family/GDP	0.033	0.098	-10000	0	-0.24	18	18
HRAS/GTP	-0.04	0.1	-10000	0	-0.2	92	92
PRKCH	-0.072	0.09	-10000	0	-0.18	158	158
RAC1	0.017	0	-10000	0	-10000	0	0
PRKCA	-0.071	0.088	-10000	0	-0.18	164	164
PRKCB	-0.076	0.088	-10000	0	-0.18	167	167
PRKCE	-0.072	0.088	-10000	0	-0.18	164	164
PRKCD	-0.072	0.089	-10000	0	-0.18	164	164
PRKCG	-0.072	0.089	-10000	0	-0.18	158	158
regulation of vascular smooth muscle contraction	-0.081	0.19	-10000	0	-0.4	127	127
PRKCQ	-0.072	0.088	-10000	0	-0.18	164	164
PLA2G4A	-0.071	0.15	-10000	0	-0.31	104	104
GNA14	0.016	0.027	-10000	0	-0.41	2	2
GNA15	0.012	0.049	-10000	0	-0.41	7	7
GNA12	0.014	0.037	-10000	0	-0.41	4	4
GNA11	0.017	0.003	-10000	0	-10000	0	0
Rac1/GTP	-0.23	0.21	0.25	1	-0.37	312	313
MMP1	0.084	0.15	0.22	132	-0.34	43	175

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.005	0.095	-9999	-0.41	27	27
CCL5	-0.006	0.096	-9999	-0.41	28	28
SDCBP	0.017	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.077	0.14	-9999	-0.21	218	218
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.072	0.14	-9999	-0.31	109	109
Syndecan-1/Syntenin	-0.067	0.14	-9999	-0.3	100	100
MAPK3	-0.19	0.16	-9999	-0.25	394	394
HGF/MET	0.018	0.046	-9999	-0.28	12	12
TGFB1/TGF beta receptor Type II	-0.005	0.095	-9999	-0.41	27	27
BSG	0.017	0	-9999	-10000	0	0
keratinocyte migration	-0.071	0.14	-9999	-0.3	109	109
Syndecan-1/RANTES	-0.077	0.16	-9999	-0.33	107	107
Syndecan-1/CD147	-0.2	0.17	-9999	-0.27	394	394
Syndecan-1/Syntenin/PIP2	-0.065	0.13	-9999	-0.29	100	100
LAMA5	0.006	0.069	-9999	-0.41	14	14
positive regulation of cell-cell adhesion	-0.064	0.13	-9999	-0.28	100	100
MMP7	-0.046	0.15	-9999	-0.41	78	78
HGF	0.015	0.026	-9999	-0.41	2	2
Syndecan-1/CASK	-0.075	0.13	-9999	-0.3	100	100
Syndecan-1/HGF/MET	-0.062	0.14	-9999	-0.29	108	108
regulation of cell adhesion	-0.18	0.15	-9999	-0.24	392	392
HPSE	-0.019	0.12	-9999	-0.41	44	44
positive regulation of cell migration	-0.077	0.14	-9999	-0.21	218	218
SDC1	-0.078	0.14	-9999	-0.21	218	218
Syndecan-1/Collagen	-0.077	0.14	-9999	-0.21	218	218
PPIB	-0.29	0.2	-9999	-0.41	373	373
MET	0.009	0.059	-9999	-0.41	10	10
PRKACA	0.017	0	-9999	-10000	0	0
MMP9	-0.13	0.2	-9999	-0.41	179	179
MAPK1	-0.19	0.16	-9999	-0.25	392	392
homophilic cell adhesion	-0.077	0.14	-9999	-0.21	218	218
MMP1	-0.018	0.12	-9999	-0.41	43	43

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.066	0.13	-9999	-0.23	186	186
NF kappa B1 p50/RelA/I kappa B alpha	-0.056	0.14	-9999	-0.3	83	83
alphaV/beta3 Integrin/Osteopontin/Src	-0.098	0.16	-9999	-0.32	185	185
AP1	-0.2	0.22	-9999	-0.43	203	203
ILK	-0.08	0.13	-9999	-0.24	185	185
bone resorption	-0.21	0.16	-9999	-0.31	305	305
PTK2B	0.017	0	-9999	-10000	0	0
PYK2/p130Cas	-0.066	0.14	-9999	-0.23	199	199
ITGAV	0	0.075	-9999	-0.42	16	16
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.22	0.13	-9999	-0.28	415	415
alphaV/beta3 Integrin/Osteopontin	-0.076	0.15	-9999	-0.27	185	185
MAP3K1	-0.082	0.13	-9999	-0.25	186	186
JUN	0.014	0.019	-9999	-0.41	1	1
MAPK3	-0.08	0.14	-9999	-0.25	185	185
MAPK1	-0.081	0.14	-9999	-0.25	185	185
Rac1/GDP	0.013	0	-9999	-10000	0	0
NFKB1	0.014	0.037	-9999	-0.41	4	4
MAPK8	-0.084	0.12	-9999	-0.24	186	186
ITGB3	0.013	0.011	-9999	-10000	0	0
NFKBIA	-0.076	0.14	-9999	-0.27	129	129
FOS	-0.088	0.18	-9999	-0.42	125	125
CD44	-0.32	0.18	-9999	-0.41	415	415
CHUK	0.016	0.019	-9999	-0.41	1	1
PLAU	-0.13	0.22	-9999	-0.48	131	131
NF kappa B1 p50/RelA	-0.06	0.15	-9999	-0.33	83	83
BCAR1	0	0	-9999	-10000	0	0
RELA	0.017	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.009	0.057	-9999	-0.29	16	16
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.087	0.15	-9999	-0.26	199	199
VAV3	-0.094	0.15	-9999	-0.25	221	221
MAP3K14	-0.079	0.14	-9999	-0.25	185	185
ROCK2	0.017	0	-9999	-10000	0	0
SPP1	-0.14	0.21	-9999	-0.42	181	181
RAC1	0.017	0	-9999	-10000	0	0
Rac1/GTP	-0.08	0.14	-9999	-0.25	165	165
MMP2	-0.24	0.24	-9999	-0.45	283	283

×

EGFR-dependent Endothelin signaling events

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
HRAS	0.016	0.019	-9999	-0.41	1	1
EGFR	-0.14	0.21	-9999	-0.41	194	194
EGF/EGFR	-0.11	0.14	-9999	-0.22	304	304
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.067	0.12	-9999	-0.2	236	236
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.11	0.2	-9999	-0.41	154	154
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	0.015	0.026	-9999	-0.41	2	2
EGF/EGFR dimer/SHC	-0.088	0.14	-9999	-0.24	237	237
mol:GDP	-0.068	0.12	-9999	-0.2	236	236
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.01	0.056	-9999	-0.41	9	9
GRB2/SOS1	0.013	0.001	-9999	-10000	0	0
HRAS/GTP	-0.066	0.1	-9999	-0.18	237	237
SHC1	-0.02	0.12	-9999	-0.41	46	46
HRAS/GDP	-0.062	0.11	-9999	-0.18	237	237
FRAP1	-0.07	0.11	-9999	-0.19	236	236
EGF/EGFR dimer	-0.09	0.15	-9999	-0.28	196	196
SOS1	0	0	-9999	-10000	0	0
GRB2	0.017	0.002	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.07	0.15	-9999	-0.29	158	158

×

LPA receptor mediated events

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
GNB1/GNG2	-0.069	0.091	-10000	0	-0.17	250	250
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.053	-10000	0	-0.21	5	5
AP1	-0.1	0.12	-10000	0	-0.2	302	302
mol:PIP3	-0.12	0.11	-10000	0	-0.2	324	324
AKT1	-0.032	0.073	0.17	3	-0.21	9	12
PTK2B	-0.041	0.059	-10000	0	-0.1	250	250
RHOA	-0.035	0.049	-10000	0	-0.15	6	6
PIK3CB	0.017	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.008	0.029	-10000	0	-10000	0	0
MAGI3	0	0.001	-10000	0	-0.003	13	13
RELA	0.017	0	-10000	0	-10000	0	0
apoptosis	-0.098	0.12	-10000	0	-0.19	285	285
HRAS/GDP	0.012	0.013	-10000	0	-0.29	1	1
positive regulation of microtubule depolymerization	-0.006	0.07	0.22	4	-10000	0	4
NF kappa B1 p50/RelA	-0.055	0.06	-10000	0	-0.16	23	23
endothelial cell migration	-0.18	0.21	-10000	0	-0.41	250	250
ADCY4	-0.015	0.054	-10000	0	-0.19	45	45
ADCY5	-0.015	0.054	-10000	0	-0.19	45	45
ADCY6	-0.015	0.053	-10000	0	-0.18	45	45
ADCY7	-0.016	0.056	-10000	0	-0.19	48	48
ADCY1	-0.015	0.053	-10000	0	-0.18	45	45
ADCY2	-0.015	0.053	-10000	0	-0.18	45	45
ADCY3	-0.015	0.054	-10000	0	-0.19	45	45
ADCY8	-0.015	0.054	-10000	0	-0.18	46	46
ADCY9	-0.015	0.053	-10000	0	-0.18	45	45
GSK3B	-0.035	0.056	-10000	0	-0.094	250	250
arachidonic acid secretion	-0.048	0.069	-10000	0	-0.13	197	197
GNG2	0	0.001	-10000	0	-0.004	23	23
TRIP6	-0.11	0.11	-10000	0	-0.21	284	284
GNAO1	-0.005	0.032	-10000	0	-0.18	16	16
HRAS	0.016	0.019	-10000	0	-0.41	1	1
NFKBIA	-0.02	0.047	-10000	0	-0.13	8	8
GAB1	0.014	0.037	-10000	0	-0.41	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.002	0.14	-10000	0	-0.7	21	21
JUN	0.016	0.019	-10000	0	-0.41	1	1
LPA/LPA2/NHERF2	-0.024	0.04	-10000	0	-10000	0	0
TIAM1	-0.008	0.16	-10000	0	-0.8	21	21
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
mol:IP3	-0.009	0.03	-10000	0	-10000	0	0
PLCB3	-0.017	0.035	-10000	0	-10000	0	0
FOS	-0.085	0.18	-10000	0	-0.41	125	125
positive regulation of mitosis	-0.048	0.069	-10000	0	-0.13	197	197
LPA/LPA1-2-3	-0.077	0.088	-10000	0	-0.17	250	250
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
stress fiber formation	-0.041	0.065	-10000	0	-0.11	250	250
GNAZ	-0.068	0.097	-10000	0	-0.18	215	215
EGFR/PI3K-beta/Gab1	-0.12	0.12	-10000	0	-0.2	324	324
positive regulation of dendritic cell cytokine production	-0.076	0.087	-10000	0	-0.17	250	250
LPA/LPA2/MAGI-3	-0.032	0.036	-10000	0	-0.07	250	250
ARHGEF1	-0.06	0.089	-10000	0	-0.15	251	251
GNAI2	-0.079	0.1	-10000	0	-0.18	250	250
GNAI3	-0.11	0.13	-10000	0	-0.22	281	281
GNAI1	-0.071	0.098	-10000	0	-0.19	222	222
LPA/LPA3	-0.04	0.045	-10000	0	-0.087	250	250
LPA/LPA2	-0.04	0.045	-10000	0	-0.087	250	250
LPA/LPA1	-0.1	0.12	-10000	0	-0.23	250	250
HB-EGF/EGFR	-0.16	0.16	-10000	0	-0.27	320	320
HBEGF	-0.086	0.15	-10000	0	-0.29	179	179
mol:DAG	-0.009	0.03	-10000	0	-10000	0	0
cAMP biosynthetic process	0.001	0.09	0.15	9	-0.16	50	59
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
SRC	0.017	0	-10000	0	-10000	0	0
GNB1	0.017	0.002	-10000	0	-10000	0	0
LYN	-0.039	0.073	-10000	0	-0.19	65	65
GNAQ	-0.023	0.035	-10000	0	-0.06	250	250
LPAR2	0	0.001	-10000	0	-0.003	15	15
LPAR3	0	0	-10000	0	-10000	0	0
LPAR1	-0.063	0.07	-10000	0	-0.14	250	250
IL8	-0.16	0.15	-10000	0	-0.28	295	295
PTK2	-0.065	0.084	-10000	0	-0.15	250	250
Rac1/GDP	0.013	0	-10000	0	-10000	0	0
CASP3	-0.099	0.12	-10000	0	-0.19	285	285
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
PLCG1	-0.016	0.033	-10000	0	-0.05	252	252
PLD2	-0.065	0.084	-10000	0	-0.15	250	250
G12/G13	-0.064	0.1	-10000	0	-0.17	251	251
PI3K-beta	-0.054	0.06	-10000	0	-0.2	5	5
cell migration	-0.046	0.059	-10000	0	-0.21	21	21
SLC9A3R2	0.017	0	-10000	0	-10000	0	0
PXN	-0.041	0.066	-10000	0	-0.11	250	250
HRAS/GTP	-0.049	0.07	-10000	0	-0.14	195	195
RAC1	0.017	0	-10000	0	-10000	0	0
MMP9	-0.13	0.2	-10000	0	-0.41	179	179
PRKCE	0.017	0.001	-10000	0	-10000	0	0
PRKCD	-0.005	0.028	-10000	0	-10000	0	0
Gi(beta/gamma)	-0.017	0.057	-10000	0	-0.19	50	50
mol:LPA	-0.063	0.07	-10000	0	-0.14	250	250
TRIP6/p130 Cas/FAK1/Paxillin	-0.11	0.1	-10000	0	-0.16	380	380
MAPKKK cascade	-0.048	0.069	-10000	0	-0.13	197	197
contractile ring contraction involved in cytokinesis	-0.035	0.049	-10000	0	-0.16	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.024	0.036	-10000	0	-0.061	252	252
GNA15	-0.026	0.043	-10000	0	-0.065	250	250
GNA12	0.014	0.037	-10000	0	-0.41	4	4
GNA13	0.016	0.026	-10000	0	-0.41	2	2
MAPT	-0.022	0.048	-10000	0	-10000	0	0
GNA11	-0.023	0.035	-10000	0	-0.064	1	1
Rac1/GTP	0.002	0.15	-10000	0	-0.73	21	21
MMP2	-0.18	0.21	-10000	0	-0.41	250	250

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.2	0.18	-9999	-0.31	356	356
alphaM/beta2 Integrin/GPIbA	-0.079	0.14	-9999	-0.24	220	220
alphaM/beta2 Integrin/proMMP-9	-0.16	0.19	-9999	-0.31	298	298
PLAUR	-0.021	0.12	-9999	-0.41	47	47
HMGB1	0.015	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.1	0.16	-9999	-0.26	241	241
AGER	0.012	0.04	-9999	-0.43	4	4
RAP1A	0.017	0	-9999	-10000	0	0
SELPLG	0.017	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.065	0.14	-9999	-0.22	222	222
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.2	-9999	-0.41	179	179
CYR61	-0.12	0.2	-9999	-0.41	163	163
TLN1	-0.02	0.12	-9999	-0.41	46	46
Rap1/GTP	-0.037	0.09	-9999	-0.19	109	109
RHOA	0.017	0.001	-9999	-10000	0	0
P-selectin oligomer	0.016	0.019	-9999	-0.41	1	1
MYH2	-0.024	0.096	-9999	-0.2	83	83
MST1R	0.015	0.026	-9999	-0.41	2	2
leukocyte activation during inflammatory response	-0.062	0.12	-9999	-0.2	223	223
APOB	0.015	0.032	-9999	-0.41	3	3
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.19	0.22	-9999	-0.41	250	250
JAM3	0.016	0.019	-9999	-0.41	1	1
GP1BA	0.017	0	-9999	-10000	0	0
alphaM/beta2 Integrin/CTGF	-0.096	0.15	-9999	-0.26	236	236
alphaM/beta2 Integrin	-0.046	0.11	-9999	-0.22	110	110
JAM3 homodimer	0.016	0.019	-9999	-0.41	1	1
ICAM2	0.015	0.032	-9999	-0.41	3	3
ICAM1	0.003	0.076	-9999	-0.41	17	17
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.046	0.1	-9999	-0.22	110	110
cell adhesion	-0.079	0.14	-9999	-0.24	220	220
NFKB1	-0.07	0.15	-9999	-0.22	236	236
THY1	0.013	0.008	-9999	-10000	0	0
RhoA/GDP	0.013	0.001	-9999	-10000	0	0
Lipoprotein(a)	0.022	0.02	-9999	-0.24	3	3
alphaM/beta2 Integrin/LRP/tPA	-0.18	0.18	-9999	-0.28	353	353
IL6	-0.08	0.18	-9999	-0.5	56	56
ITGB2	-0.16	0.21	-9999	-0.42	220	220
elevation of cytosolic calcium ion concentration	-0.13	0.21	-9999	-0.32	255	255
alphaM/beta2 Integrin/JAM2/JAM3	-0.097	0.14	-9999	-0.23	266	266
JAM2	-0.044	0.15	-9999	-0.41	75	75
alphaM/beta2 Integrin/ICAM1	-0.061	0.13	-9999	-0.21	230	230
alphaM/beta2 Integrin/uPA/Plg	-0.11	0.18	-9999	-0.28	254	254
RhoA/GTP	-0.029	0.1	-9999	-0.2	109	109
positive regulation of phagocytosis	-0.089	0.16	-9999	-0.25	223	223
Ron/MSP	0.021	0.038	-9999	-0.28	8	8
alphaM/beta2 Integrin/uPAR/uPA	-0.13	0.21	-9999	-0.32	255	255
alphaM/beta2 Integrin/uPAR	-0.099	0.17	-9999	-0.28	226	226
PLAU	-0.083	0.18	-9999	-0.41	123	123
PLAT	-0.18	0.21	-9999	-0.41	244	244
actin filament polymerization	-0.023	0.093	-9999	-0.2	83	83
MST1	0.012	0.046	-9999	-0.41	6	6
alphaM/beta2 Integrin/lipoprotein(a)	-0.06	0.12	-9999	-0.2	223	223
TNF	-0.062	0.14	-9999	-0.34	56	56
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.13	0.19	-9999	-0.32	254	254
fibrinolysis	-0.11	0.18	-9999	-0.28	254	254
HCK	-0.053	0.16	-9999	-0.41	86	86
dendritic cell antigen processing and presentation	-0.046	0.1	-9999	-0.22	110	110
VTN	0.015	0.026	-9999	-0.41	2	2
alphaM/beta2 Integrin/CYR61	-0.15	0.19	-9999	-0.31	285	285
LPA	0.017	0	-9999	-10000	0	0
LRP1	0.002	0.078	-9999	-0.41	18	18
cell migration	-0.25	0.22	-9999	-0.35	388	388
FN1	-0.065	0.17	-9999	-0.41	101	101
alphaM/beta2 Integrin/Thy1	-0.077	0.12	-9999	-0.24	188	188
MPO	0.017	0	-9999	-10000	0	0
KNG1	0.016	0.019	-9999	-0.41	1	1
RAP1/GDP	0.012	0	-9999	-10000	0	0
ROCK1	-0.024	0.096	-9999	-0.25	49	49
ELA2	0.017	0	-9999	-10000	0	0
PLG	0.017	0	-9999	-10000	0	0
CTGF	-0.014	0.11	-9999	-0.41	38	38
alphaM/beta2 Integrin/Hck	-0.12	0.19	-9999	-0.32	223	223
ITGAM	0.015	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.063	0.13	-9999	-0.21	220	220
HP	-0.051	0.16	-9999	-0.41	84	84
leukocyte adhesion	-0.074	0.12	-9999	-0.2	222	222
SELP	0.016	0.019	-9999	-0.41	1	1

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.006	0.012	0.042	36	-10000	0	36
BUB1B	-0.099	0.12	-10000	0	-0.23	212	212
PLK1	-0.012	0.035	-10000	0	-0.12	37	37
PLK1S1	-0.008	0.02	-10000	0	-0.066	37	37
KIF2A	-0.006	0.033	0.14	2	-0.14	19	21
regulation of mitotic centrosome separation	-0.012	0.035	-10000	0	-0.12	37	37
GOLGA2	0.017	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.073	0.12	-10000	0	-0.23	184	184
WEE1	-0.1	0.11	-10000	0	-0.22	218	218
cytokinesis	-0.1	0.14	-10000	0	-0.28	188	188
PP2A-alpha B56	0.004	0.038	-10000	0	-0.22	2	2
AURKA	-0.008	0.036	-10000	0	-0.15	25	25
PICH/PLK1	-0.2	0.2	-10000	0	-0.33	307	307
CENPE	-0.034	0.094	-10000	0	-0.26	70	70
RhoA/GTP	0.013	0.001	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.006	0.033	0.14	2	-0.14	19	21
PPP2CA	0.017	0.001	-10000	0	-10000	0	0
FZR1	0.017	0	-10000	0	-10000	0	0
TPX2	-0.065	0.067	-10000	0	-0.12	296	296
PAK1	0.015	0.001	-10000	0	-10000	0	0
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.017	0	-10000	0	-10000	0	0
CLSPN	-0.001	0.019	-10000	0	-0.099	8	8
GORASP1	0.017	0	-10000	0	-10000	0	0
metaphase	-0.001	0.002	-10000	0	-0.01	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.008	0.02	-10000	0	-0.066	37	37
G2 phase of mitotic cell cycle	-0.002	0.002	-10000	0	-0.012	16	16
STAG2	-0.005	0.095	-10000	0	-0.41	27	27
GRASP65/GM130/RAB1/GTP	-0.011	0.028	-10000	0	-10000	0	0
spindle elongation	-0.012	0.035	-10000	0	-0.12	37	37
ODF2	0.015	0.002	-10000	0	-10000	0	0
BUB1	-0.013	0.036	-10000	0	-0.24	4	4
TPT1	-0.003	0.02	-10000	0	-0.095	13	13
CDC25C	0.001	0.019	-10000	0	-0.1	6	6
CDC25B	-0.006	0.072	-10000	0	-0.42	15	15
SGOL1	-0.006	0.012	-10000	0	-0.042	36	36
RHOA	0.017	0.001	-10000	0	-10000	0	0
CCNB1/CDK1	-0.2	0.2	-10000	0	-0.31	367	367
CDC14B	0.008	0.002	-10000	0	-10000	0	0
CDC20	-0.23	0.21	-10000	0	-0.41	303	303
PLK1/PBIP1	-0.18	0.083	-10000	0	-0.21	449	449
mitosis	-0.003	0.005	0.016	9	-0.021	21	30
FBXO5	-0.085	0.11	-10000	0	-0.22	195	195
CDC2	-0.15	0.21	-10000	0	-0.42	193	193
NDC80	-0.13	0.2	-10000	0	-0.41	183	183
metaphase plate congression	-0.002	0.021	-10000	0	-0.093	15	15
ERCC6L	-0.2	0.19	-10000	0	-0.33	307	307
NLP/gamma Tubulin	-0.008	0.025	-10000	0	-0.089	31	31
microtubule cytoskeleton organization	-0.003	0.02	-10000	0	-0.094	13	13
G2/M transition DNA damage checkpoint	-0.002	0.002	-10000	0	-0.009	11	11
PPP1R12A	0.016	0.019	-10000	0	-0.41	1	1
interphase	-0.002	0.002	-10000	0	-0.009	11	11
PLK1/PRC1-2	-0.15	0.2	-10000	0	-0.35	249	249
GRASP65/GM130/RAB1/GTP/PLK1	0.019	0.032	-10000	0	-0.15	7	7
RAB1A	0.017	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.014	0.055	-10000	0	-0.23	27	27
mitotic prometaphase	-0.001	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.028	0.048	-10000	0	-0.1	23	23
microtubule-based process	-0.078	0.12	-10000	0	-0.24	186	186
Golgi organization	-0.012	0.035	-10000	0	-0.12	37	37
Cohesin/SA2	-0.014	0.059	-10000	0	-0.2	43	43
PPP1CB/MYPT1	0.022	0.023	-10000	0	-0.29	3	3
KIF20A	-0.13	0.2	-10000	0	-0.41	186	186
APC/C/CDC20	-0.13	0.13	-10000	0	-0.24	303	303
PPP2R1A	0.017	0.003	-10000	0	-10000	0	0
chromosome segregation	-0.17	0.082	-10000	0	-0.21	449	449
PRC1	-0.16	0.21	-10000	0	-0.41	224	224
ECT2	-0.082	0.12	-10000	0	-0.24	183	183
C13orf34	-0.014	0.055	-10000	0	-0.25	24	24
NUDC	-0.002	0.021	-10000	0	-0.094	15	15
regulation of attachment of spindle microtubules to kinetochore	-0.098	0.12	-10000	0	-0.23	212	212
spindle assembly	-0.01	0.032	-10000	0	-0.11	33	33
spindle stabilization	-0.008	0.02	-10000	0	-0.066	37	37
APC/C/HCDH1	0.018	0.001	-10000	0	-10000	0	0
MKLP2/PLK1	-0.079	0.12	-10000	0	-0.24	186	186
CCNB1	-0.23	0.22	-10000	0	-0.42	296	296
PPP1CB	0.015	0.026	-10000	0	-0.41	2	2
BTRC	0.017	0	-10000	0	-10000	0	0
ROCK2	0.003	0.024	-10000	0	-0.12	7	7
TUBG1	-0.003	0.024	-10000	0	-0.12	15	15
G2/M transition of mitotic cell cycle	-0.21	0.19	-10000	0	-0.34	307	307
MLF1IP	-0.25	0.11	-10000	0	-0.3	449	449
INCENP	0.016	0.001	-10000	0	-10000	0	0

×

BARD1 signaling events

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
BARD1/CSTF1	-0.048	0.13	-10000	0	-0.28	125	125
ATM	-0.003	0.091	-10000	0	-0.41	25	25
UBE2D3	0.017	0.001	-10000	0	-10000	0	0
PRKDC	-0.002	0.088	-10000	0	-0.41	23	23
ATR	0.017	0	-10000	0	-10000	0	0
UBE2L3	0.017	0	-10000	0	-10000	0	0
FANCD2	0.005	0.042	-10000	0	-0.18	25	25
protein ubiquitination	-0.035	0.14	-10000	0	-0.24	148	148
XRCC5	0.017	0	-10000	0	-10000	0	0
XRCC6	0.017	0	-10000	0	-10000	0	0
M/R/N Complex	0.035	0	-10000	0	-10000	0	0
MRE11A	0.017	0	-10000	0	-10000	0	0
DNA-PK	0.023	0.055	-10000	0	-0.24	23	23
FA complex/FANCD2/Ubiquitin	0	0.071	-10000	0	-0.17	68	68
FANCF	0.015	0.026	-10000	0	-0.41	2	2
BRCA1	0.013	0.042	-10000	0	-0.41	5	5
CCNE1	0.011	0.049	-10000	0	-0.41	7	7
CDK2/Cyclin E1	0.006	0.082	-10000	0	-0.32	30	30
FANCG	-0.037	0.14	-10000	0	-0.41	66	66
BRCA1/BACH1/BARD1	-0.051	0.14	-10000	0	-0.29	126	126
FANCE	0.016	0.019	-10000	0	-0.41	1	1
FANCC	0.017	0	-10000	0	-10000	0	0
NBN	0.017	0	-10000	0	-10000	0	0
FANCA	0.017	0	-10000	0	-10000	0	0
DNA repair	-0.14	0.16	-10000	0	-0.34	153	153
BRCA1/BARD1/ubiquitin	-0.051	0.14	-10000	0	-0.29	126	126
BARD1/DNA-PK	-0.026	0.12	-10000	0	-0.22	138	138
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.048	0.13	0.28	125	-10000	0	125
BRCA1/BARD1/CTIP/M/R/N Complex	-0.1	0.1	-10000	0	-0.24	140	140
BRCA1/BACH1/BARD1/TopBP1	-0.032	0.12	-10000	0	-0.24	126	126
BRCA1/BARD1/P53	-0.048	0.15	-10000	0	-0.25	166	166
BARD1/CSTF1/BRCA1	-0.031	0.12	-10000	0	-0.24	126	126
BRCA1/BACH1	0.013	0.042	-10000	0	-0.41	5	5
BARD1	-0.085	0.18	-10000	0	-0.41	125	125
PCNA	-0.26	0.2	-10000	0	-0.41	342	342
BRCA1/BARD1/UbcH5C	-0.031	0.12	-10000	0	-0.24	126	126
BRCA1/BARD1/UbcH7	-0.031	0.12	-10000	0	-0.24	126	126
BRCA1/BARD1/RAD51/PCNA	-0.17	0.17	-10000	0	-0.27	359	359
BARD1/DNA-PK/P53	-0.045	0.15	-10000	0	-0.24	171	171
BRCA1/BARD1/Ubiquitin	-0.051	0.14	-10000	0	-0.29	126	126
BRCA1/BARD1/CTIP	-0.22	0.16	-10000	0	-0.28	423	423
FA complex	0.01	0.051	-10000	0	-0.12	67	67
BARD1/EWS	-0.048	0.13	-10000	0	-0.28	125	125
RBBP8	-0.23	0.14	-10000	0	-0.3	411	411
TP53	-0.039	0.14	-10000	0	-0.41	69	69
TOPBP1	0.016	0.019	-10000	0	-0.41	1	1
G1/S transition of mitotic cell cycle	0.049	0.14	0.25	166	-10000	0	166
BRCA1/BARD1	-0.032	0.15	-10000	0	-0.25	148	148
CSTF1	0.017	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.059	0.13	-10000	0	-0.29	125	125
CDK2	-0.005	0.095	-10000	0	-0.41	27	27
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.017	0	-10000	0	-10000	0	0
RAD50	0.017	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.051	0.14	-10000	0	-0.29	126	126
EWSR1	0.017	0	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.031	0.1	-9999	-0.23	104	104
Syndecan-4/Syndesmos	-0.066	0.12	-9999	-0.3	80	80
positive regulation of JNK cascade	-0.15	0.17	-9999	-0.35	176	176
Syndecan-4/ADAM12	-0.059	0.13	-9999	-0.3	80	80
CCL5	-0.006	0.096	-9999	-0.41	28	28
Rac1/GDP	0.013	0	-9999	-10000	0	0
DNM2	0.017	0	-9999	-10000	0	0
ITGA5	-0.043	0.15	-9999	-0.41	74	74
SDCBP	0.017	0	-9999	-10000	0	0
PLG	0.019	0.005	-9999	-10000	0	0
ADAM12	0.016	0.019	-9999	-0.41	1	1
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.025	0.04	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.066	0.12	-9999	-0.3	80	80
Syndecan-4/CXCL12/CXCR4	-0.15	0.18	-9999	-0.37	176	176
Syndecan-4/Laminin alpha3	-0.064	0.14	-9999	-0.3	89	89
MDK	-0.23	0.21	-9999	-0.41	299	299
Syndecan-4/FZD7	-0.15	0.16	-9999	-0.36	148	148
Syndecan-4/Midkine	-0.17	0.16	-9999	-0.36	173	173
FZD7	-0.18	0.21	-9999	-0.41	244	244
Syndecan-4/FGFR1/FGF	-0.046	0.13	-9999	-0.27	83	83
THBS1	-0.018	0.12	-9999	-0.41	43	43
integrin-mediated signaling pathway	-0.24	0.12	-9999	-0.36	229	229
positive regulation of MAPKKK cascade	-0.15	0.17	-9999	-0.35	176	176
Syndecan-4/TACI	-0.058	0.13	-9999	-0.29	80	80
CXCR4	-0.21	0.22	-9999	-0.41	275	275
cell adhesion	-0.026	0.091	-9999	-0.2	102	102
Syndecan-4/Dynamin	-0.058	0.13	-9999	-0.29	80	80
Syndecan-4/TSP1	-0.073	0.15	-9999	-0.33	96	96
Syndecan-4/GIPC	-0.058	0.13	-9999	-0.29	80	80
Syndecan-4/RANTES	-0.068	0.14	-9999	-0.32	90	90
ITGB1	0.017	0	-9999	-10000	0	0
LAMA1	0	0	-9999	-10000	0	0
LAMA3	0.005	0.071	-9999	-0.41	15	15
RAC1	0.017	0	-9999	-10000	0	0
PRKCA	0.021	0.03	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.074	0.14	-9999	-0.31	95	95
TFPI	-0.078	0.18	-9999	-0.41	117	117
F2	0.01	0.028	-9999	-0.42	2	2
alpha5/beta1 Integrin	-0.018	0.11	-9999	-0.28	74	74
positive regulation of cell adhesion	-0.064	0.13	-9999	-0.29	89	89
ACTN1	-0.017	0.12	-9999	-0.41	42	42
TNC	-0.39	0.09	-9999	-0.41	504	504
Syndecan-4/CXCL12	-0.064	0.14	-9999	-0.31	83	83
FGF6	0.017	0	-9999	-10000	0	0
RHOA	0.017	0.001	-9999	-10000	0	0
CXCL12	0.005	0.071	-9999	-0.41	15	15
TNFRSF13B	0.017	0	-9999	-10000	0	0
FGF2	0.015	0.026	-9999	-0.41	2	2
FGFR1	0.015	0.026	-9999	-0.41	2	2
Syndecan-4/PI-4-5-P2	-0.066	0.12	-9999	-0.3	80	80
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.065	0.17	-9999	-0.41	101	101
cell migration	-0.012	0.012	-9999	-10000	0	0
PRKCD	0.019	0.005	-9999	-10000	0	0
vasculogenesis	-0.071	0.14	-9999	-0.32	96	96
SDC4	-0.064	0.13	-9999	-0.23	181	181
Syndecan-4/Tenascin C	-0.24	0.13	-9999	-0.37	229	229
Syndecan-4/PI-4-5-P2/PKC alpha	-0.024	0.029	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.058	0.13	-9999	-0.29	80	80
MMP9	-0.13	0.2	-9999	-0.41	179	179
Rac1/GTP	-0.026	0.093	-9999	-0.2	101	101
cytoskeleton organization	-0.064	0.12	-9999	-0.29	80	80
GIPC1	0.017	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.1	0.15	-9999	-0.34	117	117

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.008	0.033	-10000	0	-0.41	2	2
oxygen homeostasis	-0.008	0.013	-10000	0	-10000	0	0
TCEB2	0.017	0	-10000	0	-10000	0	0
TCEB1	0.017	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.017	0.075	-10000	0	-0.19	13	13
EPO	-0.078	0.18	-10000	0	-0.29	182	182
FIH (dimer)	0.006	0.016	-10000	0	-10000	0	0
APEX1	0.005	0.021	-10000	0	-10000	0	0
SERPINE1	-0.18	0.28	-10000	0	-0.47	228	228
FLT1	-0.006	0.028	-10000	0	-10000	0	0
ADORA2A	-0.11	0.2	-10000	0	-0.34	182	182
germ cell development	-0.11	0.2	-10000	0	-0.34	189	189
SLC11A2	-0.11	0.21	-10000	0	-0.35	182	182
BHLHE40	-0.12	0.21	-10000	0	-0.35	189	189
HIF1AN	0.006	0.016	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.046	0.13	-10000	0	-0.19	184	184
ETS1	0.027	0.012	-10000	0	-10000	0	0
CITED2	-0.017	0.066	-10000	0	-0.4	14	14
KDR	-0.016	0.077	-10000	0	-0.42	17	17
PGK1	-0.11	0.21	-10000	0	-0.35	182	182
SIRT1	0.017	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	-0.12	0.25	-10000	0	-0.4	182	182
EPAS1	-0.029	0.084	0.29	1	-0.18	33	34
SP1	0.023	0.004	-10000	0	-10000	0	0
ABCG2	-0.11	0.21	-10000	0	-0.35	184	184
EFNA1	-0.12	0.22	-10000	0	-0.36	191	191
FXN	-0.11	0.2	-10000	0	-0.34	182	182
POU5F1	-0.12	0.21	-10000	0	-0.35	189	189
neuron apoptosis	0.11	0.24	0.39	182	-10000	0	182
EP300	0.017	0	-10000	0	-10000	0	0
EGLN3	0.003	0.042	-10000	0	-0.44	4	4
EGLN2	0.006	0.016	-10000	0	-10000	0	0
EGLN1	0.006	0.025	-10000	0	-0.42	1	1
VHL/Elongin B/Elongin C	0.023	0	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.005	0.021	-10000	0	-10000	0	0
SLC2A1	-0.11	0.2	-10000	0	-0.34	183	183
TWIST1	-0.12	0.22	-10000	0	-0.37	192	192
ELK1	0.021	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.045	0.13	-10000	0	-0.26	45	45
VEGFA	-0.21	0.28	-10000	0	-0.42	299	299
CREBBP	0.017	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.016	0.053	-10000	0	-0.28	16	16
AKT1	-0.049	0.11	-10000	0	-0.28	48	48
PTK2B	-0.089	0.13	-10000	0	-0.36	40	40
VEGFR2 homodimer/Frs2	0.021	0.072	-10000	0	-0.33	20	20
CAV1	-0.25	0.21	-10000	0	-0.41	324	324
CALM1	0.016	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.098	0.14	-10000	0	-0.22	290	290
endothelial cell proliferation	-0.04	0.1	-10000	0	-0.25	52	52
mol:Ca2+	-0.091	0.14	-10000	0	-0.4	39	39
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.13	0.18	-10000	0	-0.25	326	326
RP11-342D11.1	-0.097	0.13	-10000	0	-0.4	39	39
CDH5	-0.006	0.098	-10000	0	-0.41	29	29
VEGFA homodimer	-0.099	0.12	-10000	0	-0.21	289	289
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
SHC2	0.017	0	-10000	0	-10000	0	0
HRAS/GDP	-0.093	0.13	-10000	0	-0.37	55	55
SH2D2A	0.017	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.047	0.11	-10000	0	-0.31	36	36
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.096	0.14	-10000	0	-0.22	290	290
VEGFR1 homodimer	0.017	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.093	0.15	-10000	0	-0.41	55	55
GRB10	-0.096	0.15	-10000	0	-0.48	39	39
PTPN11	0.017	0	-10000	0	-10000	0	0
GRB2	0.017	0.002	-10000	0	-10000	0	0
PAK1	0.017	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.13	0.19	-10000	0	-0.4	122	122
HRAS	0.016	0.019	-10000	0	-0.41	1	1
VEGF/Rho/ROCK1/Integrin Complex	-0.034	0.077	-10000	0	-0.2	40	40
HIF1A	0.015	0.026	-10000	0	-0.41	2	2
FRS2	0.015	0.032	-10000	0	-0.41	3	3
oxygen and reactive oxygen species metabolic process	-0.13	0.18	-10000	0	-0.25	326	326
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.017	0	-10000	0	-10000	0	0
Nck/Pak	0.019	0.044	-10000	0	-0.28	11	11
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.098	0.14	-10000	0	-0.22	289	289
mol:GDP	-0.095	0.14	-10000	0	-0.4	55	55
mol:NADP	-0.041	0.098	-10000	0	-0.27	35	35
eNOS/Hsp90	-0.034	0.096	-10000	0	-0.26	35	35
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
mol:IP3	-0.092	0.14	-10000	0	-0.4	39	39
HIF1A/ARNT	0.024	0.019	-10000	0	-0.28	2	2
SHB	0.017	0	-10000	0	-10000	0	0
VEGFA	-0.21	0.22	-10000	0	-0.41	287	287
VEGFC	0.007	0.067	-10000	0	-0.41	13	13
FAK1/Vinculin	-0.059	0.12	-10000	0	-0.3	40	40
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.017	0.001	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.09	0.14	-10000	0	-0.2	296	296
PTPN6	0.008	0.061	-10000	0	-0.41	11	11
EPAS1	0.018	0.051	-10000	0	-0.24	17	17
mol:L-citrulline	-0.041	0.098	-10000	0	-0.27	35	35
ITGAV	0.004	0.074	-10000	0	-0.41	16	16
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.085	0.14	-10000	0	-0.2	290	290
VEGFR2 homodimer/VEGFA homodimer	-0.096	0.16	-10000	0	-0.44	39	39
VEGFR2/3 heterodimer	0.022	0.07	-10000	0	-0.35	17	17
VEGFB	0.017	0	-10000	0	-10000	0	0
MAPK11	-0.089	0.13	-10000	0	-0.39	39	39
VEGFR2 homodimer	0.016	0.08	-10000	0	-0.41	17	17
FLT1	0.017	0	-10000	0	-10000	0	0
NEDD4	0.007	0.067	-10000	0	-0.39	14	14
MAPK3	-0.087	0.12	-10000	0	-0.37	39	39
MAPK1	-0.087	0.12	-10000	0	-0.37	39	39
VEGFA145/NRP2	-0.14	0.16	-10000	0	-0.28	288	288
VEGFR1/2 heterodimer	0.022	0.07	-10000	0	-0.35	17	17
KDR	0.016	0.08	-10000	0	-0.42	17	17
VEGFA165/NRP1/VEGFR2 homodimer	-0.082	0.14	-10000	0	-0.4	39	39
SRC	0.017	0	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.084	0.13	-10000	0	-0.37	39	39
PI3K	-0.066	0.13	-10000	0	-0.33	51	51
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.1	0.14	-10000	0	-0.22	299	299
FES	-0.093	0.14	-10000	0	-0.41	39	39
GAB1	-0.077	0.13	-10000	0	-0.32	58	58
VEGFR2 homodimer/VEGFA homodimer/Src	-0.096	0.14	-10000	0	-0.22	290	290
CTNNB1	0.017	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
ARNT	0.017	0	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.14	0.14	-10000	0	-0.27	223	223
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.13	0.16	-10000	0	-0.24	325	325
PI3K/GAB1	-0.053	0.12	-10000	0	-0.3	51	51
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.08	0.14	-10000	0	-0.36	37	37
PRKACA	0.017	0	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.026	0.078	-10000	0	-0.29	27	27
HSP90AA1	0.017	0	-10000	0	-10000	0	0
CDC42	-0.093	0.14	-10000	0	-0.41	39	39
actin cytoskeleton reorganization	-0.096	0.14	-10000	0	-0.22	290	290
PTK2	-0.069	0.12	-10000	0	-0.32	40	40
EDG1	-0.09	0.14	-10000	0	-0.4	39	39
mol:DAG	-0.092	0.14	-10000	0	-0.4	39	39
CaM/Ca2+	-0.08	0.13	-10000	0	-0.37	39	39
MAP2K3	-0.086	0.13	-10000	0	-0.39	39	39
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.09	0.16	-10000	0	-0.49	39	39
PLCG1	-0.093	0.14	-10000	0	-0.41	39	39
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.083	0.14	-10000	0	-0.37	32	32
IQGAP1	-0.086	0.18	-10000	0	-0.41	127	127
YES1	-0.047	0.15	-10000	0	-0.41	79	79
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.096	0.14	-10000	0	-0.22	290	290
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.1	0.15	-10000	0	-0.22	298	298
cell migration	-0.077	0.14	-10000	0	-0.28	122	122
mol:PI-3-4-5-P3	-0.063	0.12	-10000	0	-0.32	51	51
FYN	0.015	0.027	-10000	0	-0.41	2	2
VEGFB/NRP1	-0.085	0.13	-10000	0	-0.38	39	39
mol:NO	-0.041	0.098	-10000	0	-0.27	35	35
PXN	0.017	0	-10000	0	-10000	0	0
HRAS/GTP	-0.11	0.12	-10000	0	-0.37	55	55
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.092	0.16	-10000	0	-0.49	39	39
VHL	0	0	-10000	0	-10000	0	0
ITGB3	0.017	0	-10000	0	-10000	0	0
NOS3	-0.046	0.11	-10000	0	-0.3	35	35
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.096	0.14	-10000	0	-0.22	290	290
RAC1	0.017	0	-10000	0	-10000	0	0
PRKCA	-0.084	0.13	-10000	0	-0.38	39	39
PRKCB	-0.089	0.13	-10000	0	-0.38	39	39
VCL	0.017	0	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.095	0.14	-10000	0	-0.41	39	39
VEGFR1/2 heterodimer/VEGFA homodimer	-0.096	0.14	-10000	0	-0.22	290	290
VEGFA165/NRP2	-0.14	0.16	-10000	0	-0.28	288	288
MAPKKK cascade	-0.084	0.15	0.25	1	-0.41	55	56
NRP2	0.016	0.019	-10000	0	-0.41	1	1
VEGFC homodimer	0.007	0.067	-10000	0	-0.41	13	13
NCK1	0.008	0.061	-10000	0	-0.41	11	11
ROCK1	0.017	0	-10000	0	-10000	0	0
FAK1/Paxillin	-0.059	0.12	-10000	0	-0.3	40	40
MAP3K13	-0.093	0.14	-10000	0	-0.41	39	39
PDPK1	-0.057	0.11	-10000	0	-0.28	51	51

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.016	0.019	-10000	0	-0.41	1	1
LAT2	-0.058	0.1	-10000	0	-0.24	77	77
AP1	-0.063	0.12	-10000	0	-0.27	99	99
mol:PIP3	-0.054	0.12	-10000	0	-0.27	65	65
IKBKB	-0.026	0.07	-10000	0	-0.19	41	41
AKT1	-0.056	0.11	0.23	12	-0.24	38	50
IKBKG	-0.026	0.07	-10000	0	-0.19	41	41
MS4A2	0.021	0.005	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	-0.004	0.091	-10000	0	-0.41	25	25
MAP3K1	-0.041	0.096	-10000	0	-0.24	59	59
mol:Ca2+	-0.041	0.092	-10000	0	-0.21	65	65
LYN	-0.038	0.14	-10000	0	-0.42	64	64
CBLB	-0.057	0.1	-10000	0	-0.26	66	66
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
RasGAP/p62DOK	0.024	0.044	-10000	0	-0.21	18	18
positive regulation of cell migration	0.009	0.001	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.078	0.1	-10000	0	-0.18	259	259
PTPN13	-0.049	0.1	-10000	0	-0.31	37	37
PTPN11	0.013	0.01	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.027	0.09	0.21	9	-0.2	40	49
SYK	-0.015	0.11	-10000	0	-0.42	36	36
GRB2	0.017	0.002	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.078	0.1	-10000	0	-0.28	65	65
LAT	-0.058	0.1	-10000	0	-0.26	67	67
PAK2	-0.048	0.1	-10000	0	-0.23	87	87
NFATC2	-0.039	0.04	-10000	0	-0.079	259	259
HRAS	-0.046	0.099	-10000	0	-0.24	71	71
GAB2	0.016	0.019	-10000	0	-0.41	1	1
PLA2G1B	0.031	0.021	-10000	0	-10000	0	0
Fc epsilon R1	-0.1	0.14	-10000	0	-0.24	259	259
Antigen/IgE/Fc epsilon R1	-0.09	0.13	-10000	0	-0.22	259	259
mol:GDP	-0.045	0.096	-10000	0	-0.23	69	69
JUN	0.016	0.019	-10000	0	-0.41	1	1
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.015	0.004	-10000	0	-10000	0	0
FOS	-0.085	0.18	-10000	0	-0.41	125	125
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.063	0.11	-10000	0	-0.16	259	259
CHUK	-0.026	0.07	-10000	0	-0.18	42	42
KLRG1	-0.06	0.1	-10000	0	-0.15	252	252
VAV1	-0.059	0.1	-10000	0	-0.24	76	76
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.057	0.1	-10000	0	-0.24	76	76
negative regulation of mast cell degranulation	-0.057	0.095	-10000	0	-0.22	79	79
BTK	-0.047	0.094	-10000	0	-0.23	69	69
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.07	0.11	-10000	0	-0.22	135	135
GAB2/PI3K/SHP2	-0.086	0.09	-10000	0	-0.22	73	73
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.077	0.13	-10000	0	-0.18	267	267
RAF1	0.025	0.019	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.13	0.17	-10000	0	-0.27	282	282
FCER1G	-0.19	0.22	-10000	0	-0.42	255	255
FCER1A	0.005	0.059	-10000	0	-0.42	10	10
Antigen/IgE/Fc epsilon R1/Fyn	-0.078	0.12	-10000	0	-0.2	259	259
MAPK3	0.032	0.02	-10000	0	-10000	0	0
MAPK1	0.028	0.027	-10000	0	-10000	0	0
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
MAPK8	-0.004	0.076	-10000	0	-0.34	21	21
DUSP1	0.002	0.078	-10000	0	-0.41	18	18
NF-kappa-B/RelA	-0.014	0.047	-10000	0	-0.12	40	40
actin cytoskeleton reorganization	-0.043	0.099	-10000	0	-0.32	28	28
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.044	0.1	-10000	0	-0.24	76	76
FER	-0.057	0.1	-10000	0	-0.23	79	79
RELA	0.017	0	-10000	0	-10000	0	0
ITK	-0.011	0.032	-10000	0	-0.093	31	31
SOS1	0	0	-10000	0	-10000	0	0
PLCG1	-0.044	0.099	-10000	0	-0.24	66	66
cytokine secretion	-0.02	0.026	-10000	0	-0.095	33	33
SPHK1	-0.064	0.11	-10000	0	-0.25	90	90
PTK2	-0.045	0.1	-10000	0	-0.33	28	28
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.081	0.1	-10000	0	-0.3	65	65
EDG1	0.009	0.001	-10000	0	-10000	0	0
mol:DAG	-0.05	0.11	-10000	0	-0.26	66	66
MAP2K2	0.026	0.016	-10000	0	-10000	0	0
MAP2K1	0.029	0.025	-10000	0	-10000	0	0
MAP2K7	0.017	0	-10000	0	-10000	0	0
KLRG1/SHP2	-0.055	0.1	-10000	0	-0.24	76	76
MAP2K4	-0.008	0.14	-10000	0	-0.72	21	21
Fc epsilon R1/FcgammaRIIB	-0.14	0.18	-10000	0	-0.29	282	282
mol:Choline	-0.077	0.1	-10000	0	-0.18	259	259
SHC/Grb2/SOS1	-0.063	0.12	-10000	0	-0.27	95	95
FYN	0.015	0.027	-10000	0	-0.41	2	2
DOK1	0.017	0	-10000	0	-10000	0	0
PXN	-0.039	0.097	-10000	0	-0.31	28	28
HCLS1	-0.094	0.16	-10000	0	-0.35	121	121
PRKCB	-0.04	0.09	-10000	0	-0.21	66	66
FCGR2B	-0.087	0.18	-10000	0	-0.41	128	128
IGHE	-0.004	0.006	-10000	0	-10000	0	0
KLRG1/SHIP	-0.057	0.096	-10000	0	-0.23	79	79
LCP2	-0.008	0.1	-10000	0	-0.41	30	30
PLA2G4A	-0.11	0.14	-10000	0	-0.27	179	179
RASA1	0.017	0.002	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.077	0.1	-10000	0	-0.18	259	259
IKK complex	-0.014	0.057	-10000	0	-0.14	35	35
WIPF1	0.008	0.061	-10000	0	-0.41	11	11

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.047	0.1	-9999	-0.16	220	220
FZD6	-0.064	0.17	-9999	-0.41	100	100
WNT6	0.017	0	-9999	-10000	0	0
WNT4	0.015	0.026	-9999	-0.41	2	2
FZD3	0.014	0.032	-9999	-0.41	3	3
WNT5A	-0.12	0.2	-9999	-0.41	168	168
WNT11	0.015	0.026	-9999	-0.41	2	2

×

Aurora B signaling

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
Condensin I complex	-0.16	0.18	-9999	-0.22	405	405
STMN1	0.001	0.067	-9999	-0.29	27	27
Aurora B/RasGAP/Survivin	-0.083	0.15	-9999	-0.26	207	207
Chromosomal passenger complex/Cul3 protein complex	-0.038	0.085	-9999	-0.13	211	211
BIRC5	-0.16	0.21	-9999	-0.42	211	211
DES	-0.004	0.058	-9999	-0.24	12	12
Aurora C/Aurora B/INCENP	0.017	0.057	-9999	-0.22	29	29
Aurora B/TACC1	0.009	0.057	-9999	-0.23	27	27
Aurora B/PP2A	0.009	0.069	-9999	-0.29	27	27
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.007	0.021	-9999	-0.082	27	27
mitotic metaphase/anaphase transition	0	0.003	-9999	-10000	0	0
NDC80	-0.1	0.17	-9999	-0.33	184	184
Cul3 protein complex	0.023	0.003	-9999	-10000	0	0
KIF2C	-0.046	0.1	-9999	-0.18	157	157
PEBP1	0.014	0.005	-9999	-10000	0	0
KIF20A	-0.14	0.21	-9999	-0.42	186	186
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.008	0.069	-9999	-0.29	27	27
SEPT1	0	0	-9999	-10000	0	0
SMC2	-0.033	0.14	-9999	-0.41	61	61
SMC4	-0.31	0.18	-9999	-0.41	401	401
NSUN2/NPM1/Nucleolin	-0.023	0.078	-9999	-0.28	31	31
PSMA3	0.017	0.001	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.003	-9999	-10000	0	0
H3F3B	0.004	0.044	-9999	-0.19	27	27
AURKB	-0.006	0.097	-9999	-0.42	27	27
AURKC	0.015	0.026	-9999	-0.41	2	2
CDCA8	0	0.079	-9999	-0.43	17	17
cytokinesis	-0.11	0.2	-9999	-0.34	187	187
Aurora B/Septin1	-0.1	0.19	-9999	-0.33	187	187
AURKA	0.001	0.08	-9999	-0.42	19	19
INCENP	0.013	0.008	-9999	-10000	0	0
KLHL13	0	0	-9999	-10000	0	0
BUB1	0.014	0.038	-9999	-0.42	4	4
hSgo1/Aurora B/Survivin	-0.084	0.14	-9999	-0.24	211	211
EVI5	0.016	0.002	-9999	-10000	0	0
RhoA/GTP	-0.12	0.22	-9999	-0.38	180	180
SGOL1	0	0	-9999	-10000	0	0
CENPA	-0.039	0.11	-9999	-0.26	86	86
NCAPG	-0.077	0.18	-9999	-0.41	116	116
Aurora B/HC8 Proteasome	0.009	0.069	-9999	-0.29	27	27
NCAPD2	-0.068	0.17	-9999	-0.41	105	105
Aurora B/PP1-gamma	0.009	0.069	-9999	-0.29	27	27
RHOA	0.017	0.001	-9999	-10000	0	0
NCAPH	0.004	0.074	-9999	-0.41	16	16
NPM1	-0.009	0.064	-9999	-0.25	32	32
RASA1	0.017	0.002	-9999	-10000	0	0
KLHL9	0.017	0.003	-9999	-10000	0	0
mitotic prometaphase	-0.003	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.069	-9999	-0.29	27	27
PPP1CC	0.017	0.001	-9999	-10000	0	0
Centraspindlin	-0.13	0.23	-9999	-0.38	204	204
RhoA/GDP	0.013	0.001	-9999	-10000	0	0
NSUN2	-0.013	0.055	-9999	-0.24	27	27
MYLK	-0.003	0.059	-9999	-0.2	42	42
KIF23	-0.05	0.16	-9999	-0.42	79	79
VIM	-0.01	0.085	-9999	-0.29	45	45
RACGAP1	-0.12	0.2	-9999	-0.42	166	166
mitosis	0	0	-9999	-10000	0	0
NCL	-0.006	0.055	-9999	-0.23	27	27
Chromosomal passenger complex	-0.066	0.13	-9999	-0.21	185	185
Chromosomal passenger complex/EVI5	-0.069	0.16	-9999	-0.24	211	211
TACC1	0.017	0.001	-9999	-10000	0	0
PPP2R5D	0.017	0	-9999	-10000	0	0
CUL3	0.017	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.031	0.016	-9999	-0.22	2	2
VEGFR1 homodimer/NRP1	0.019	0.015	-9999	-0.23	2	2
mol:DAG	0.019	0.047	-9999	-0.2	23	23
VEGFR1 homodimer/NRP1/VEGFR 121	-0.1	0.12	-9999	-0.21	289	289
CaM/Ca2+	0.026	0.045	-9999	-0.18	22	22
HIF1A	0.024	0.026	-9999	-0.4	2	2
GAB1	0.014	0.037	-9999	-0.41	4	4
AKT1	0.016	0.059	-9999	-0.31	3	3
PLCG1	0.019	0.047	-9999	-0.2	23	23
NOS3	0.03	0.043	-9999	-0.19	3	3
CBL	0.017	0	-9999	-10000	0	0
mol:NO	0.03	0.042	-9999	-0.19	3	3
FLT1	0.025	0.019	-9999	-0.28	2	2
PGF	0	0.084	-9999	-0.41	21	21
VEGFR1 homodimer/NRP2/VEGFR121	-0.093	0.12	-9999	-0.2	290	290
CALM1	0.016	0.004	-9999	-10000	0	0
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
eNOS/Hsp90	0.039	0.042	-9999	-0.2	2	2
endothelial cell proliferation	0.021	0.04	-9999	-0.17	23	23
mol:Ca2+	0.018	0.047	-9999	-0.2	23	23
MAPK3	0.019	0.04	-9999	-0.17	23	23
MAPK1	0.018	0.04	-9999	-0.17	23	23
PIK3R1	0.016	0.004	-9999	-10000	0	0
PLGF homodimer	0	0.084	-9999	-0.41	21	21
PRKACA	0.017	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.25	0.21	-9999	-0.41	324	324
VEGFA homodimer	-0.22	0.21	-9999	-0.41	287	287
VEGFR1 homodimer/VEGFA homodimer	-0.11	0.13	-9999	-0.23	289	289
platelet activating factor biosynthetic process	0.02	0.039	-9999	-10000	0	0
PI3K	0.026	0.069	-9999	-0.2	43	43
PRKCA	0.018	0.043	-9999	-0.18	23	23
PRKCB	0.013	0.042	-9999	-0.19	23	23
VEGFR1 homodimer/PLGF homodimer	0.021	0.053	-9999	-0.23	23	23
VEGFA	-0.22	0.21	-9999	-0.41	287	287
VEGFB	0.017	0	-9999	-10000	0	0
mol:IP3	0.019	0.047	-9999	-0.2	23	23
RASA1	0.027	0.014	-9999	-0.2	2	2
NRP2	0.016	0.019	-9999	-0.41	1	1
VEGFR1 homodimer	0.025	0.018	-9999	-0.27	2	2
VEGFB homodimer	0.017	0	-9999	-10000	0	0
NCK1	0.008	0.061	-9999	-0.41	11	11
eNOS/Caveolin-1	-0.079	0.1	-9999	-0.24	40	40
PTPN11	0.017	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.025	0.068	-9999	-0.19	43	43
mol:L-citrulline	0.03	0.042	-9999	-0.19	3	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.1	0.13	-9999	-0.2	314	314
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.097	0.12	-9999	-0.2	298	298
CD2AP	-0.023	0.12	-9999	-0.41	49	49
PI3K/GAB1	0.031	0.071	-9999	-0.19	46	46
PDPK1	0.014	0.06	-9999	-0.18	41	41
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.092	0.12	-9999	-0.2	289	289
mol:NADP	0.03	0.042	-9999	-0.19	3	3
HSP90AA1	0.017	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.099	0.13	-9999	-0.2	314	314
VEGFR1 homodimer/NRP2	0.031	0.019	-9999	-0.23	3	3

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.008	0.012	-10000	0	-10000	0	0
HSPA8	0.019	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.017	0.16	0.18	26	-0.26	120	146
AKT1	0.016	0.037	-10000	0	-0.41	4	4
GSC	0.017	0.037	0.11	9	-10000	0	9
NKX2-5	0.016	0.007	-10000	0	-10000	0	0
muscle cell differentiation	0.025	0.098	0.23	65	-10000	0	65
SMAD2-3/SMAD4/SP1	-0.083	0.15	-10000	0	-0.3	109	109
SMAD4	-0.11	0.2	-10000	0	-0.43	133	133
CBFB	0.014	0.037	-10000	0	-0.41	4	4
SAP18	0.018	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.007	0.059	-10000	0	-0.24	25	25
SMAD3/SMAD4/VDR	-0.034	0.11	-10000	0	-0.25	76	76
MYC	-0.097	0.19	-10000	0	-0.42	137	137
CDKN2B	0.044	0.053	-10000	0	-10000	0	0
AP1	-0.074	0.14	-10000	0	-0.29	121	121
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.013	0.094	-10000	0	-0.19	87	87
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.001	0.065	-10000	0	-0.2	13	13
SP3	-0.045	0.15	-10000	0	-0.41	77	77
CREB1	0.017	0	-10000	0	-10000	0	0
FOXH1	0.016	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	-0.036	0.14	-10000	0	-0.27	118	118
GATA3	0.018	0.042	-10000	0	-0.41	5	5
SKI/SIN3/HDAC complex/NCoR1	0.006	0.058	-10000	0	-0.17	20	20
MEF2C/TIF2	-0.016	0.083	-10000	0	-0.2	52	52
endothelial cell migration	0.16	0.2	0.4	215	-10000	0	215
MAX	0.025	0.012	-10000	0	-10000	0	0
RBBP7	0.018	0.001	-10000	0	-10000	0	0
RBBP4	-0.064	0.17	-10000	0	-0.41	100	100
RUNX2	0.017	0	-10000	0	-10000	0	0
RUNX3	0.015	0.032	-10000	0	-0.41	3	3
RUNX1	0.017	0	-10000	0	-10000	0	0
CTBP1	0.017	0.002	-10000	0	-10000	0	0
NR3C1	0.025	0.012	-10000	0	-10000	0	0
VDR	0.017	0	-10000	0	-10000	0	0
CDKN1A	-0.098	0.17	-10000	0	-0.38	111	111
KAT2B	-0.003	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.033	0.11	-10000	0	-0.23	112	112
DCP1A	0.017	0	-10000	0	-10000	0	0
SKI	0.018	0.001	-10000	0	-10000	0	0
SERPINE1	-0.16	0.2	-10000	0	-0.4	215	215
SMAD3/SMAD4/ATF2	-0.057	0.14	-10000	0	-0.26	132	132
SMAD3/SMAD4/ATF3	-0.11	0.18	-10000	0	-0.31	204	204
SAP30	0.018	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.016	0.029	-10000	0	-0.24	2	2
JUN	-0.077	0.14	-10000	0	-0.29	118	118
SMAD3/SMAD4/IRF7	-0.058	0.15	-10000	0	-0.28	126	126
TFE3	-0.032	0.06	-10000	0	-0.14	51	51
COL1A2	-0.2	0.21	-10000	0	-0.41	261	261
mesenchymal cell differentiation	0.058	0.14	0.26	130	-10000	0	130
DLX1	0	0	-10000	0	-10000	0	0
TCF3	0.017	0	-10000	0	-10000	0	0
FOS	-0.094	0.18	-10000	0	-0.42	125	125
SMAD3/SMAD4/Max	-0.036	0.14	-10000	0	-0.26	122	122
Cbp/p300/SNIP1	0.029	0.008	-10000	0	-10000	0	0
ZBTB17	0.015	0	-10000	0	-10000	0	0
LAMC1	-0.18	0.24	-10000	0	-0.45	216	216
TGIF2/HDAC complex/SMAD3/SMAD4	-0.061	0.15	-10000	0	-0.27	134	134
IRF7	0.01	0.064	-10000	0	-0.41	12	12
ESR1	0.03	0.017	-10000	0	-10000	0	0
HNF4A	0.017	0	-10000	0	-10000	0	0
MEF2C	-0.024	0.085	-10000	0	-0.22	56	56
SMAD2-3/SMAD4	-0.057	0.14	-10000	0	-0.26	127	127
Cbp/p300/Src-1	0.022	0.017	-10000	0	-10000	0	0
IGHV3OR16-13	-0.012	0.026	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.011	0.052	-10000	0	-0.41	8	8
CREBBP	0.011	0.008	-10000	0	-10000	0	0
SKIL	0.017	0	-10000	0	-10000	0	0
HDAC1	-0.035	0.14	-10000	0	-0.41	65	65
HDAC2	0.014	0.042	-10000	0	-0.41	5	5
SNIP1	0.018	0.002	-10000	0	-10000	0	0
GCN5L2	0.01	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.11	0.18	-10000	0	-0.29	246	246
MSG1/HSC70	0.013	0.066	-10000	0	-0.28	25	25
SMAD2	0.018	0.008	-10000	0	-10000	0	0
SMAD3	-0.022	0.062	-10000	0	-0.18	1	1
SMAD3/E2F4-5/DP1/p107/SMAD4	-0.026	0.085	-10000	0	-0.19	81	81
SMAD2/SMAD2/SMAD4	-0.028	0.076	0.15	1	-0.15	116	117
NCOR1	0.018	0.001	-10000	0	-10000	0	0
NCOA2	0.017	0	-10000	0	-10000	0	0
NCOA1	0.017	0.003	-10000	0	-10000	0	0
MYOD/E2A	0.025	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	-0.068	0.14	-10000	0	-0.29	98	98
IFNB1	-0.054	0.12	-10000	0	-0.28	84	84
SMAD3/SMAD4/MEF2C	-0.024	0.11	-10000	0	-0.26	56	56
CITED1	-0.003	0.091	-10000	0	-0.41	25	25
SMAD2-3/SMAD4/ARC105	-0.04	0.12	-10000	0	-0.26	84	84
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.005	0.07	-10000	0	-0.23	9	9
RUNX1-3/PEBPB2	0.031	0.031	-10000	0	-0.24	7	7
SMAD7	-0.083	0.15	-10000	0	-0.3	134	134
MYC/MIZ-1	-0.06	0.14	-10000	0	-0.29	137	137
SMAD3/SMAD4	-0.17	0.14	-10000	0	-0.27	291	291
IL10	-0.047	0.12	-10000	0	-0.29	67	67
PIASy/HDAC complex	0.022	0.006	-10000	0	-10000	0	0
PIAS3	0.013	0.027	-10000	0	-0.42	2	2
CDK2	-0.01	0.094	-10000	0	-0.42	27	27
IL5	-0.047	0.12	-10000	0	-0.3	65	65
CDK4	-0.27	0.2	-10000	0	-0.42	342	342
PIAS4	0.022	0.006	-10000	0	-10000	0	0
ATF3	-0.071	0.17	-10000	0	-0.41	108	108
SMAD3/SMAD4/SP1	-0.11	0.16	-10000	0	-0.28	192	192
FOXG1	0.016	0.006	-10000	0	-10000	0	0
FOXO3	0.018	0.026	-10000	0	-0.28	4	4
FOXO1	0.012	0.053	-10000	0	-0.3	14	14
FOXO4	0.018	0.026	-10000	0	-0.28	4	4
heart looping	-0.024	0.085	-10000	0	-0.21	56	56
CEBPB	0.009	0.061	-10000	0	-0.41	11	11
SMAD3/SMAD4/DLX1	-0.065	0.14	-10000	0	-0.26	137	137
MYOD1	0.017	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.057	0.14	-10000	0	-0.27	127	127
SMAD3/SMAD4/GATA3	-0.049	0.15	-10000	0	-0.28	119	119
SnoN/SIN3/HDAC complex/NCoR1	0.017	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.03	0.13	-10000	0	-0.26	81	81
SMAD3/SMAD4/SP1-3	-0.12	0.2	-10000	0	-0.37	146	146
MED15	0.017	0	-10000	0	-10000	0	0
SP1	-0.029	0.053	-10000	0	-0.14	12	12
SIN3B	0.018	0.001	-10000	0	-10000	0	0
SIN3A	0.001	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.014	0.1	-10000	0	-0.2	112	112
ITGB5	-0.12	0.18	-10000	0	-0.38	127	127
TGIF/SIN3/HDAC complex/CtBP	-0.073	0.086	-10000	0	-0.19	138	138
SMAD3/SMAD4/AR	-0.061	0.14	-10000	0	-0.28	130	130
AR	0.011	0.052	-10000	0	-0.41	8	8
negative regulation of cell growth	-0.043	0.1	-10000	0	-0.2	119	119
SMAD3/SMAD4/MYOD	-0.057	0.14	-10000	0	-0.26	130	130
E2F5	0.017	0	-10000	0	-10000	0	0
E2F4	0.017	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.016	0.096	-10000	0	-0.19	110	110
SMAD2-3/SMAD4/FOXO1-3a-4	0.001	0.074	-10000	0	-0.2	26	26
TFDP1	0.005	0.071	-10000	0	-0.41	15	15
SMAD3/SMAD4/AP1	-0.066	0.15	-10000	0	-0.29	120	120
SMAD3/SMAD4/RUNX2	-0.057	0.14	-10000	0	-0.27	128	128
TGIF2	0.011	0.052	-10000	0	-0.41	8	8
TGIF1	-0.28	0.2	-10000	0	-0.41	371	371
ATF2	0.017	0	-10000	0	-10000	0	0

×

PDGFR-alpha 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
PDGFRA	-0.032	0.13	-9999	-0.42	51	51
PDGF/PDGFRA/CRKL	-0.007	0.089	-9999	-0.28	51	51
positive regulation of JUN kinase activity	-0.014	0.092	-9999	-0.21	92	92
CRKL	0.017	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.007	0.089	-9999	-0.28	51	51
AP1	-0.09	0.19	-9999	-0.41	125	125
mol:IP3	-0.021	0.091	-9999	-0.29	51	51
PLCG1	-0.021	0.091	-9999	-0.29	51	51
PDGF/PDGFRA/alphaV Integrin	-0.016	0.1	-9999	-0.28	67	67
RAPGEF1	0.017	0	-9999	-10000	0	0
CRK	0.017	0	-9999	-10000	0	0
mol:Ca2+	-0.021	0.091	-9999	-0.29	51	51
CAV3	0.017	0	-9999	-10000	0	0
CAV1	-0.25	0.21	-9999	-0.41	324	324
SHC/Grb2/SOS1	-0.013	0.092	-9999	-0.21	92	92
PDGF/PDGFRA/Shf	-0.021	0.087	-9999	-0.28	51	51
FOS	-0.092	0.18	-9999	-0.41	125	125
JUN	-0.011	0.027	-9999	-0.34	1	1
oligodendrocyte development	-0.016	0.1	-9999	-0.28	67	67
GRB2	0.017	0.002	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
mol:DAG	-0.021	0.091	-9999	-0.29	51	51
PDGF/PDGFRA	-0.032	0.13	-9999	-0.42	51	51
actin cytoskeleton reorganization	-0.007	0.089	-9999	-0.28	51	51
SRF	0.021	0.007	-9999	-10000	0	0
SHC1	-0.02	0.12	-9999	-0.41	46	46
PI3K	-0.006	0.093	-9999	-0.24	69	69
PDGF/PDGFRA/Crk/C3G	0.007	0.077	-9999	-0.23	51	51
JAK1	-0.016	0.087	-9999	-0.28	51	51
ELK1/SRF	-0.004	0.062	-9999	-0.18	51	51
SHB	0.017	0	-9999	-10000	0	0
SHF	0	0	-9999	-10000	0	0
CSNK2A1	0.023	0.014	-9999	-10000	0	0
GO:0007205	-0.022	0.086	-9999	-0.28	51	51
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.014	0.092	-9999	-0.21	92	92
PDGF/PDGFRA/SHB	-0.007	0.089	-9999	-0.28	51	51
PDGF/PDGFRA/Caveolin-1	-0.2	0.17	-9999	-0.31	347	347
ITGAV	0.004	0.074	-9999	-0.41	16	16
ELK1	-0.021	0.077	-9999	-0.24	51	51
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
PDGF/PDGFRA/Crk	-0.007	0.089	-9999	-0.28	51	51
JAK-STAT cascade	-0.016	0.087	-9999	-0.28	51	51
cell proliferation	-0.021	0.086	-9999	-0.28	51	51

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.11	0.059	-10000	0	-0.13	455	455
epithelial cell differentiation	0.029	0.042	-10000	0	-0.19	18	18
CYFIP2	0.01	0.008	-10000	0	-10000	0	0
ENAH	0.008	0.071	-10000	0	-0.26	20	20
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
EPHA2	0.007	0.067	-10000	0	-0.41	13	13
MYO6	0.018	0.037	-10000	0	-0.18	18	18
CTNNB1	0.017	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.02	0.017	-10000	0	-10000	0	0
AQP5	0.027	0.033	-10000	0	-10000	0	0
CTNND1	0.009	0.059	-10000	0	-0.41	10	10
mol:PI-4-5-P2	0.017	0.036	-10000	0	-0.18	17	17
regulation of calcium-dependent cell-cell adhesion	0.018	0.037	-10000	0	-0.18	18	18
EGF	0.015	0.026	-10000	0	-0.41	2	2
NCKAP1	0.017	0	-10000	0	-10000	0	0
AQP3	0.024	0.045	-10000	0	-0.32	3	3
cortical microtubule organization	0.029	0.042	-10000	0	-0.19	18	18
GO:0000145	0.012	0.034	-10000	0	-0.17	17	17
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.033	0.043	-10000	0	-0.19	18	18
MLLT4	0.017	0	-10000	0	-10000	0	0
ARF6/GDP	-0.019	0.068	-10000	0	-0.35	15	15
ARF6	0.017	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.022	0.085	-10000	0	-0.26	38	38
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.015	0.078	-10000	0	-0.22	39	39
PVRL2	0.017	0	-10000	0	-10000	0	0
ZYX	-0.033	0.099	-10000	0	-0.19	140	140
ARF6/GTP	0.028	0.08	-10000	0	-0.24	38	38
CDH1	0.011	0.052	-10000	0	-0.41	8	8
EGFR/EGFR/EGF/EGF	-0.05	0.11	-10000	0	-0.18	207	207
RhoA/GDP	0.03	0.039	-10000	0	-0.18	18	18
actin cytoskeleton organization	0.019	0.035	-10000	0	-0.17	18	18
IGF-1R heterotetramer	0.017	0	-10000	0	-10000	0	0
GIT1	0.017	0	-10000	0	-10000	0	0
IGF1R	0.017	0	-10000	0	-10000	0	0
IGF1	0.014	0.037	-10000	0	-0.41	4	4
DIAPH1	-0.13	0.2	-10000	0	-0.36	225	225
Wnt receptor signaling pathway	-0.029	0.042	0.19	18	-10000	0	18
RHOA	0.017	0.001	-10000	0	-10000	0	0
RhoA/GTP	-0.019	0.068	-10000	0	-0.35	15	15
CTNNA1	0.017	0	-10000	0	-10000	0	0
VCL	0.019	0.036	-10000	0	-0.17	18	18
EFNA1	-0.002	0.09	-10000	0	-0.41	24	24
LPP	0.003	0.069	-10000	0	-0.19	55	55
Ephrin A1/EPHA2	0.012	0.071	-10000	0	-0.2	47	47
SEC6/SEC8	-0.005	0.029	-10000	0	-10000	0	0
MGAT3	0.018	0.037	-10000	0	-0.18	18	18
HGF/MET	0.022	0.052	-10000	0	-0.19	27	27
HGF	0.015	0.026	-10000	0	-0.41	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.11	0.059	-10000	0	-0.13	455	455
actin cable formation	-0.006	0.07	-10000	0	-0.23	26	26
KIAA1543	0.007	0.034	-10000	0	-0.18	18	18
KIFC3	0.018	0.037	-10000	0	-0.18	18	18
NCK1	0.008	0.061	-10000	0	-0.41	11	11
EXOC3	0.017	0	-10000	0	-10000	0	0
ACTN1	0.002	0.072	-10000	0	-0.2	54	54
NCK1/GIT1	0.019	0.044	-10000	0	-0.28	11	11
mol:GDP	0.029	0.042	-10000	0	-0.19	18	18
EXOC4	0	0	-10000	0	-10000	0	0
STX4	0.018	0.037	-10000	0	-0.18	18	18
PIP5K1C	0.018	0.037	-10000	0	-0.18	17	17
LIMA1	-0.35	0.15	-10000	0	-0.41	453	453
ABI1	0.017	0	-10000	0	-10000	0	0
ROCK1	0.015	0.069	-10000	0	-0.31	15	15
adherens junction assembly	0.015	0.037	-10000	0	-0.16	18	18
IGF-1R heterotetramer/IGF1	0.025	0.044	-10000	0	-0.19	20	20
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.025	0	-10000	0	-10000	0	0
MET	0.009	0.059	-10000	0	-0.41	10	10
PLEKHA7	0.007	0.036	-10000	0	-0.18	18	18
mol:GTP	0.021	0.084	-10000	0	-0.26	38	38
establishment of epithelial cell apical/basal polarity	0.026	0.034	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	-0.11	0.059	-10000	0	-0.13	455	455
regulation of cell-cell adhesion	0.019	0.035	-10000	0	-0.17	18	18
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.11	0.059	-10000	0	-0.13	455	455

×

Noncanonical Wnt signaling pathway

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
NFATC2	0	0	-9999	-10000	0	0
GNB1/GNG2	-0.035	0.096	-9999	-0.25	51	51
mol:DAG	-0.031	0.088	-9999	-0.23	51	51
PLCG1	-0.032	0.09	-9999	-0.24	51	51
YES1	-0.072	0.13	-9999	-0.28	115	115
FZD3	0.014	0.032	-9999	-0.41	3	3
FZD6	-0.064	0.17	-9999	-0.41	100	100
G protein	-0.031	0.092	-9999	-0.24	51	51
MAP3K7	-0.02	0.074	-9999	-0.19	48	48
mol:Ca2+	-0.031	0.086	-9999	-0.22	51	51
mol:IP3	-0.031	0.088	-9999	-0.23	51	51
NLK	0.017	0.056	-9999	-0.71	3	3
GNB1	0.017	0.002	-9999	-10000	0	0
CAMK2A	-0.024	0.079	-9999	-0.21	47	47
MAP3K7IP1	0.017	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.047	0.1	-9999	-0.16	220	220
CSNK1A1	0.017	0	-9999	-10000	0	0
GNAS	-0.041	0.096	-9999	-0.26	51	51
GO:0007205	-0.032	0.085	-9999	-0.22	51	51
WNT6	0.017	0	-9999	-10000	0	0
WNT4	0.015	0.026	-9999	-0.41	2	2
NFAT1/CK1 alpha	-0.055	0.12	-9999	-0.25	110	110
GNG2	0	0	-9999	-10000	0	0
WNT5A	-0.12	0.2	-9999	-0.41	168	168
WNT11	0.015	0.026	-9999	-0.41	2	2
CDC42	-0.065	0.13	-9999	-0.27	110	110

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.023	0.031	-9999	-0.28	5	5
CRKL	0.017	0	-9999	-10000	0	0
Rac1/GDP	0.013	0	-9999	-10000	0	0
DOCK1	0.017	0	-9999	-10000	0	0
ITGA4	0.013	0.042	-9999	-0.41	5	5
alpha4/beta7 Integrin/MAdCAM1	0.041	0.034	-9999	-0.29	5	5
EPO	0.017	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.022	0.041	-9999	-0.38	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.017	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.023	0.03	-9999	-0.28	5	5
EPO/EPOR (dimer)	0.025	0	-9999	-10000	0	0
lamellipodium assembly	0.01	0.037	-9999	-0.15	25	25
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
PI3K	0.009	0.065	-9999	-0.28	25	25
ARF6	0.017	0	-9999	-10000	0	0
JAK2	0.028	0.016	-9999	-0.14	5	5
PXN	0.017	0	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
MADCAM1	0.017	0	-9999	-10000	0	0
cell adhesion	0.039	0.034	-9999	-0.29	5	5
CRKL/CBL	0.025	0	-9999	-10000	0	0
ITGB1	0.017	0	-9999	-10000	0	0
SRC	-0.13	0.11	-9999	-0.21	353	353
ITGB7	0.015	0.026	-9999	-0.41	2	2
RAC1	0.017	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.15	0.13	-9999	-0.24	353	353
p130Cas/Crk/Dock1	-0.1	0.099	-9999	-0.17	353	353
VCAM1	-0.27	0.2	-9999	-0.41	351	351
RHOA	0.017	0.001	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.042	0.024	-9999	-0.21	5	5
BCAR1	-0.12	0.1	-9999	-0.19	353	353
EPOR	0.017	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.017	0	-9999	-10000	0	0
GIT1	0.017	0	-9999	-10000	0	0
Rac1/GTP	0.01	0.038	-9999	-0.16	25	25

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.14	0.16	-9999	-0.29	290	290
PDGFRB	0.014	0.032	-9999	-0.42	3	3
SPHK1	-0.005	0.04	-9999	-0.21	12	12
mol:S1P	-0.005	0.05	-9999	-0.22	20	20
S1P1/S1P/Gi	-0.08	0.1	-9999	-0.27	84	84
GNAO1	0.002	0.005	-9999	-10000	0	0
PDGFB-D/PDGFRB/PLCgamma1	-0.064	0.088	-9999	-0.24	72	72
PLCG1	-0.068	0.093	-9999	-0.25	77	77
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.014	0.032	-9999	-0.41	3	3
GNAI2	0.022	0.004	-9999	-10000	0	0
GNAI3	-0.036	0.14	-9999	-0.41	65	65
GNAI1	0.013	0.02	-9999	-0.41	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.11	0.14	-9999	-0.23	290	290
S1P1/S1P	-0.074	0.11	-9999	-0.29	38	38
negative regulation of cAMP metabolic process	-0.079	0.099	-9999	-0.26	84	84
MAPK3	-0.076	0.11	-9999	-0.3	71	71
calcium-dependent phospholipase C activity	0	0.002	-9999	-10000	0	0
Rac1/GDP	0.013	0	-9999	-10000	0	0
RhoA/GDP	0.013	0.001	-9999	-10000	0	0
KDR	0.007	0.076	-9999	-0.41	17	17
PLCB2	-0.067	0.1	-9999	-0.26	38	38
RAC1	0.017	0	-9999	-10000	0	0
RhoA/GTP	-0.069	0.092	-9999	-0.25	38	38
receptor internalization	-0.071	0.1	-9999	-0.28	38	38
PTGS2	-0.084	0.12	-9999	-0.43	40	40
Rac1/GTP	-0.069	0.092	-9999	-0.25	38	38
RHOA	0.017	0.001	-9999	-10000	0	0
VEGFA	-0.21	0.21	-9999	-0.4	287	287
negative regulation of T cell proliferation	-0.079	0.099	-9999	-0.26	84	84
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.015	0.006	-9999	-10000	0	0
MAPK1	-0.075	0.11	-9999	-0.3	69	69
S1P1/S1P/PDGFB-D/PDGFRB	-0.07	0.12	-9999	-0.3	41	41
ABCC1	0.01	0.056	-9999	-0.41	9	9

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.025	0.094	-10000	0	-0.29	59	59
TP53	-0.02	0.067	0.17	13	-0.17	57	70
Senescence	-0.02	0.067	0.17	13	-0.17	57	70
Apoptosis	-0.02	0.067	0.17	13	-0.17	57	70
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.009	0.071	0.16	53	-0.26	18	71
MDM4	0.007	0.067	-10000	0	-0.41	13	13

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.025	0.057	-10000	0	-0.14	103	103
RFC1	-0.025	0.058	-10000	0	-0.14	105	105
PRKDC	-0.035	0.077	-10000	0	-0.17	119	119
RIPK1	0.01	0.056	-10000	0	-0.41	9	9
CASP7	-0.009	0.072	-10000	0	-0.23	31	31
FASLG/FAS/FADD/FAF1	-0.002	0.062	0.14	25	-0.15	65	90
MAP2K4	0.001	0.078	-10000	0	-0.23	30	30
mol:ceramide	0.01	0.069	-10000	0	-0.22	23	23
GSN	-0.031	0.069	-10000	0	-0.16	117	117
FASLG/FAS/FADD/FAF1/Caspase 8	0.006	0.064	0.13	24	-0.19	25	49
FAS	-0.039	0.14	-10000	0	-0.42	68	68
BID	-0.004	0.045	0.14	1	-0.25	17	18
MAP3K1	-0.014	0.079	-10000	0	-0.23	39	39
MAP3K7	0.016	0.019	-10000	0	-0.41	1	1
RB1	-0.025	0.058	-10000	0	-0.14	105	105
CFLAR	0.013	0.041	-10000	0	-0.41	5	5
HGF/MET	0.014	0.074	-10000	0	-0.24	41	41
ARHGDIB	-0.045	0.089	-10000	0	-0.18	140	140
FADD	0.015	0.027	-10000	0	-0.41	2	2
actin filament polymerization	0.031	0.069	0.15	117	-10000	0	117
NFKB1	0.007	0.045	-10000	0	-0.24	2	2
MAPK8	0	0.094	-10000	0	-0.24	53	53
DFFA	-0.025	0.058	-10000	0	-0.14	105	105
DNA fragmentation during apoptosis	-0.025	0.058	-10000	0	-0.14	105	105
FAS/FADD/MET	-0.007	0.099	-10000	0	-0.24	79	79
CFLAR/RIP1	0.018	0.05	-10000	0	-0.28	14	14
FAIM3	0.016	0.019	-10000	0	-0.41	1	1
FAF1	0.016	0.007	-10000	0	-10000	0	0
PARP1	-0.025	0.058	-10000	0	-0.14	105	105
DFFB	-0.025	0.058	-10000	0	-0.14	105	105
CHUK	0.009	0.042	-10000	0	-0.21	3	3
FASLG	0.016	0.007	-10000	0	-10000	0	0
FAS/FADD	-0.017	0.11	-10000	0	-0.29	70	70
HGF	0.015	0.026	-10000	0	-0.41	2	2
LMNA	-0.033	0.081	-10000	0	-0.27	34	34
CASP6	-0.037	0.08	-10000	0	-0.17	121	121
CASP10	0.017	0.004	-10000	0	-10000	0	0
CASP3	-0.033	0.066	-10000	0	-0.16	105	105
PTPN13	-0.007	0.099	-10000	0	-0.41	30	30
CASP8	-0.01	0.041	0.22	1	-0.3	10	11
IL6	-0.011	0.13	-10000	0	-0.39	52	52
MET	0.009	0.059	-10000	0	-0.41	10	10
ICAD/CAD	-0.019	0.054	-10000	0	-0.14	12	12
FASLG/FAS/FADD/FAF1/Caspase 10	0.01	0.069	-10000	0	-0.22	23	23
activation of caspase activity by cytochrome c	-0.004	0.044	0.14	1	-0.25	17	18
PAK2	-0.035	0.08	-10000	0	-0.17	118	118
BCL2	0.017	0	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.046	0.19	-10000	0	-0.42	99	99
CLOCK	0.009	0.038	-10000	0	-0.44	3	3
TIMELESS/CRY2	-0.035	0.15	-10000	0	-0.35	99	99
DEC1/BMAL1	0.024	0.007	-10000	0	-10000	0	0
ATR	0.017	0	-10000	0	-10000	0	0
NR1D1	-0.006	0.08	-10000	0	-0.17	98	98
ARNTL	0.012	0.016	-10000	0	-10000	0	0
TIMELESS	-0.046	0.16	-10000	0	-0.38	99	99
NPAS2	0.011	0.024	-10000	0	-0.41	1	1
CRY2	0.017	0	-10000	0	-10000	0	0
mol:CO	0.005	0.034	0.077	99	-10000	0	99
CHEK1	-0.033	0.14	-10000	0	-0.41	61	61
mol:HEME	-0.005	0.034	-10000	0	-0.077	99	99
PER1	0.015	0.032	-10000	0	-0.41	3	3
BMAL/CLOCK/NPAS2	0.026	0.05	-10000	0	-0.29	4	4
BMAL1/CLOCK	-0.003	0.1	-10000	0	-0.34	4	4
S phase of mitotic cell cycle	-0.046	0.19	-10000	0	-0.42	99	99
TIMELESS/CHEK1/ATR	-0.046	0.19	-10000	0	-0.43	99	99
mol:NADPH	-0.005	0.034	-10000	0	-0.077	99	99
PER1/TIMELESS	-0.036	0.15	-10000	0	-0.35	99	99
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.017	0	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.013	0.001	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
MAP3K7IP2	0.017	0	-9999	-10000	0	0
ERC1	0.016	0.019	-9999	-0.41	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.047	0.1	-9999	-0.23	94	94
IRAK/TOLLIP	0.025	0.002	-9999	-10000	0	0
IKBKB	0.017	0	-9999	-10000	0	0
IKBKG	0.017	0	-9999	-10000	0	0
IL1 alpha/IL1R2	0	0.085	-9999	-0.28	43	43
IL1A	0.015	0.032	-9999	-0.41	3	3
IL1B	-0.089	0.15	-9999	-0.3	179	179
IRAK/TRAF6/p62/Atypical PKCs	0.038	0.013	-9999	-0.18	2	2
IL1R2	-0.015	0.11	-9999	-0.41	40	40
IL1R1	0.015	0.032	-9999	-0.41	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.035	0.09	-9999	-0.22	71	71
TOLLIP	0.017	0	-9999	-10000	0	0
TICAM2	0	0	-9999	-10000	0	0
MAP3K3	0.017	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.034	0.012	-9999	-0.24	1	1
IKK complex/ELKS	0.049	0.015	-9999	-0.25	1	1
JUN	0.027	0.012	-9999	-0.16	1	1
MAP3K7	0.016	0.019	-9999	-0.41	1	1
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.057	0.14	-9999	-0.22	197	197
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.013	0.12	-9999	-0.23	111	111
PIK3R1	0.016	0.004	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.004	0.11	-9999	-0.21	112	112
IL1 beta fragment/IL1R1/IL1RAP	-0.07	0.15	-9999	-0.24	199	199
NFKB1	0.014	0.037	-9999	-0.41	4	4
MAPK8	0.027	0.009	-9999	-0.16	1	1
IRAK1	0.016	0.001	-9999	-10000	0	0
IL1RN/IL1R1	0.024	0.023	-9999	-0.28	3	3
IRAK4	0.016	0.019	-9999	-0.41	1	1
PRKCI	0.016	0.019	-9999	-0.41	1	1
TRAF6	0.017	0	-9999	-10000	0	0
PI3K	0.009	0.065	-9999	-0.28	25	25
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.043	0.1	-9999	-0.26	72	72
CHUK	0.016	0.019	-9999	-0.41	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.07	0.15	-9999	-0.24	199	199
IL1 beta/IL1R2	-0.083	0.15	-9999	-0.26	202	202
IRAK/TRAF6/TAK1/TAB1/TAB2	0.048	0.01	-9999	-0.17	1	1
NF kappa B1 p50/RelA	-0.056	0.13	-9999	-0.2	197	197
IRAK3	0.015	0.026	-9999	-0.41	2	2
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.057	0.14	-9999	-0.22	199	199
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.003	0.071	-9999	-0.13	112	112
IL1 alpha/IL1R1/IL1RAP	0.009	0.081	-9999	-0.24	50	50
RELA	0.017	0	-9999	-10000	0	0
MAP3K7IP1	0.017	0	-9999	-10000	0	0
SQSTM1	0.016	0.019	-9999	-0.41	1	1
MYD88	-0.041	0.15	-9999	-0.41	71	71
IRAK/TRAF6/MEKK3	0.035	0.002	-9999	-10000	0	0
IL1RAP	-0.02	0.12	-9999	-0.41	45	45
UBE2N	0.017	0.001	-9999	-10000	0	0
IRAK/TRAF6	-0.053	0.11	-9999	-0.18	198	198
CASP1	-0.12	0.2	-9999	-0.41	173	173
IL1RN/IL1R2	0.002	0.082	-9999	-0.28	40	40
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.086	0.17	-9999	-0.27	221	221
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.004	0.063	-9999	-0.13	72	72
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
IL1RN	0.017	0	-9999	-10000	0	0
TRAF6/TAK1/TAB1/TAB2	0.042	0.01	-9999	-0.18	1	1
MAP2K6	0.027	0.01	-9999	-0.17	1	1

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.028	0.078	-9999	-0.16	131	131
DAPP1	-0.015	0.088	-9999	-0.2	75	75
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.035	0.14	-9999	-0.3	86	86
mol:DAG	-0.019	0.078	-9999	-0.17	78	78
HRAS	0.01	0.022	-9999	-0.41	1	1
RAP1A	0.015	0.004	-9999	-10000	0	0
ARF5/GDP	0.003	0.053	-9999	-0.19	25	25
PLCG2	0.009	0.059	-9999	-0.41	10	10
PLCG1	0.017	0	-9999	-10000	0	0
ARF5	0.017	0	-9999	-10000	0	0
mol:GTP	-0.039	0.078	-9999	-0.17	131	131
ARF1/GTP	-0.033	0.073	-9999	-0.16	131	131
RHOA	0.017	0.001	-9999	-10000	0	0
YES1	-0.047	0.15	-9999	-0.41	79	79
RAP1A/GTP	-0.032	0.082	-9999	-0.17	131	131
ADAP1	-0.037	0.075	-9999	-0.17	131	131
ARAP3	-0.038	0.077	-9999	-0.17	131	131
INPPL1	0.017	0	-9999	-10000	0	0
PREX1	0	0	-9999	-10000	0	0
ARHGEF6	0.01	0.053	-9999	-0.41	8	8
ARHGEF7	0.016	0.019	-9999	-0.41	1	1
ARF1	0.017	0.001	-9999	-10000	0	0
NRAS	-0.093	0.19	-9999	-0.41	136	136
FYN	0.015	0.027	-9999	-0.41	2	2
ARF6	0.017	0	-9999	-10000	0	0
FGR	0.003	0.076	-9999	-0.41	17	17
mol:Ca2+	-0.006	0.042	-9999	-0.12	17	17
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.016	0.003	-9999	-10000	0	0
ZAP70	0.017	0	-9999	-10000	0	0
mol:IP3	-0.01	0.057	-9999	-0.14	45	45
LYN	-0.035	0.14	-9999	-0.41	64	64
ARF1/GDP	0.003	0.053	-9999	-0.19	25	25
RhoA/GDP	-0.018	0.08	-9999	-0.15	131	131
PDK1/Src/Hsp90	0.035	0	-9999	-10000	0	0
BLNK	-0.038	0.14	-9999	-0.41	68	68
actin cytoskeleton reorganization	-0.012	0.069	-9999	-0.18	11	11
SRC	0.017	0	-9999	-10000	0	0
PLEKHA2	0.011	0.011	-9999	-0.24	1	1
RAC1	0.017	0	-9999	-10000	0	0
PTEN	0.019	0.027	-9999	-0.41	2	2
HSP90AA1	0.017	0	-9999	-10000	0	0
ARF6/GTP	-0.028	0.078	-9999	-0.16	131	131
RhoA/GTP	-0.027	0.079	-9999	-0.16	131	131
Src family/SYK family/BLNK-LAT	-0.032	0.13	-9999	-0.29	90	90
BLK	0.017	0	-9999	-10000	0	0
PDPK1	0.017	0	-9999	-10000	0	0
CYTH1	-0.037	0.075	-9999	-0.17	131	131
HCK	-0.053	0.16	-9999	-0.41	86	86
CYTH3	-0.037	0.075	-9999	-0.17	131	131
CYTH2	-0.037	0.075	-9999	-0.17	131	131
KRAS	0.011	0.011	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.004	0.044	-9999	-10000	0	0
SGK1	-0.008	0.047	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.006	0.053	-9999	-0.21	25	25
SOS1	0	0	-9999	-10000	0	0
SYK	-0.012	0.11	-9999	-0.41	36	36
ARF6/GDP	-0.021	0.076	-9999	-0.15	131	131
mol:PI-3-4-5-P3	-0.038	0.079	-9999	-0.17	131	131
ARAP3/RAP1A/GTP	-0.032	0.083	-9999	-0.17	131	131
VAV1	0.016	0.019	-9999	-0.41	1	1
mol:PI-3-4-P2	0.009	0	-9999	-10000	0	0
RAS family/GTP/PI3K Class I	-0.024	0.089	-9999	-0.18	131	131
PLEKHA1	0.01	0.004	-9999	-10000	0	0
Rac1/GDP	0.003	0.053	-9999	-0.19	25	25
LAT	0.016	0.019	-9999	-0.41	1	1
Rac1/GTP	0.011	0.041	-9999	-0.15	24	24
ITK	-0.034	0.08	-9999	-0.17	133	133
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.03	0.1	-9999	-0.21	92	92
LCK	0.014	0.037	-9999	-0.41	4	4
BTK	-0.032	0.077	-9999	-0.16	132	132

×

Ras signaling in the CD4+ TCR 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.021	0.11	-10000	0	-0.21	127	127
MAP3K8	-0.018	0.12	-10000	0	-0.42	42	42
FOS	-0.012	0.069	-10000	0	-0.18	20	20
PRKCA	0.013	0.009	-10000	0	-10000	0	0
PTPN7	0.011	0.022	-10000	0	-0.41	1	1
HRAS	0.016	0.019	-10000	0	-0.41	1	1
PRKCB	-0.002	0.006	0.01	2	-0.012	125	127
NRAS	-0.094	0.19	-10000	0	-0.41	136	136
RAS family/GTP	-0.034	0.1	-10000	0	-0.21	133	133
MAPK3	0.004	0.038	-10000	0	-0.19	1	1
MAP2K1	-0.009	0.048	-10000	0	-0.12	52	52
ELK1	0.011	0.013	-10000	0	-10000	0	0
BRAF	-0.003	0.028	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	0.002	1	-0.004	125	126
MAPK1	-0.005	0.062	-10000	0	-0.27	18	18
RAF1	-0.003	0.029	-10000	0	-0.17	1	1
KRAS	0.016	0.002	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.002	0.077	-9999	-0.2	62	62
BIRC5	-0.16	0.21	-9999	-0.41	211	211
NFKBIA	0.017	0.031	-9999	-0.13	17	17
CPEB1	0.013	0.007	-9999	-10000	0	0
AKT1	0.016	0.036	-9999	-0.14	20	20
NDEL1	0.016	0.004	-9999	-10000	0	0
Aurora A/BRCA1	0.02	0.036	-9999	-0.22	6	6
NDEL1/TACC3	-0.009	0.093	-9999	-0.2	92	92
GADD45A	-0.02	0.12	-9999	-0.41	46	46
GSK3B	0.019	0.007	-9999	-10000	0	0
PAK1/Aurora A	0.024	0.03	-9999	-0.14	1	1
MDM2	0.002	0.078	-9999	-0.41	18	18
JUB	0	0	-9999	-10000	0	0
TPX2	-0.15	0.15	-9999	-0.29	295	295
TP53	-0.001	0.065	-9999	-0.14	80	80
DLG7	-0.092	0.13	-9999	-0.24	230	230
AURKAIP1	0.017	0	-9999	-10000	0	0
ARHGEF7	0.016	0.019	-9999	-0.41	1	1
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.01	0.099	-9999	-0.22	92	92
G2/M transition of mitotic cell cycle	0.02	0.036	-9999	-0.22	6	6
AURKA	0.018	0.036	-9999	-0.15	19	19
AURKB	-0.002	0.047	-9999	-0.18	30	30
CDC25B	0.015	0.039	-9999	-0.16	16	16
G2/M transition checkpoint	0.01	0.025	-9999	-0.11	19	19
mRNA polyadenylation	0.017	0.022	-9999	-10000	0	0
Aurora A/CPEB	0.017	0.022	-9999	-10000	0	0
Aurora A/TACC1/TRAP/chTOG	0.042	0.027	-9999	-10000	0	0
BRCA1	0.013	0.042	-9999	-0.41	5	5
centrosome duplication	0.024	0.03	-9999	-0.14	1	1
regulation of centrosome cycle	-0.009	0.092	-9999	-0.2	92	92
spindle assembly	0.041	0.027	-9999	-10000	0	0
TDRD7	0.017	0.001	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.05	0.12	-9999	-0.19	207	207
CENPA	-0.003	0.054	-9999	-0.12	82	82
Aurora A/PP2A	0.024	0.03	-9999	-0.12	16	16
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	-0.051	0.091	-9999	-0.16	190	190
negative regulation of DNA binding	-0.001	0.065	-9999	-0.14	80	80
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.025	0.014	-9999	-0.28	1	1
RASA1	0.017	0.002	-9999	-10000	0	0
Ajuba/Aurora A	0.011	0.025	-9999	-0.11	19	19
mitotic prometaphase	0	0.009	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.036	-9999	-0.15	19	19
TACC1	0.017	0.001	-9999	-10000	0	0
TACC3	-0.061	0.17	-9999	-0.41	96	96
Aurora A/Antizyme1	0.033	0.028	-9999	-10000	0	0
Aurora A/RasGAP	0.024	0.03	-9999	-0.14	1	1
OAZ1	0.017	0	-9999	-10000	0	0
RAN	0.017	0.001	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.019	0.007	-9999	-10000	0	0
GIT1	0.017	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.034	0.012	-9999	-0.24	1	1
Importin alpha/Importin beta/TPX2	-0.15	0.15	-9999	-0.28	295	295
PPP2R5D	0.017	0	-9999	-10000	0	0
Aurora A/TPX2	-0.1	0.12	-9999	-0.21	295	295
PAK1	0.017	0	-9999	-10000	0	0
CKAP5	0.017	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.02	0.048	-10000	0	-0.16	31	31
adherens junction organization	0.02	0.038	-10000	0	-0.18	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.042	0.1	-10000	0	-0.16	207	207
FMN1	0.019	0.038	-10000	0	-0.14	20	20
mol:IP3	0.017	0.048	-10000	0	-0.17	26	26
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.02	0.04	-10000	0	-0.15	20	20
CTNNB1	0.017	0.002	-10000	0	-10000	0	0
AKT1	0.02	0.051	-10000	0	-0.16	30	30
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.028	0.041	-10000	0	-0.23	7	7
CTNND1	0.009	0.059	-10000	0	-0.41	10	10
mol:PI-4-5-P2	0.022	0.04	-10000	0	-0.19	11	11
VASP	0.022	0.04	-10000	0	-0.19	11	11
ZYX	-0.026	0.094	-10000	0	-0.18	137	137
JUB	0.019	0.038	-10000	0	-0.14	20	20
EGFR(dimer)	-0.046	0.11	-10000	0	-0.18	202	202
E-cadherin/beta catenin-gamma catenin	0.022	0.063	-10000	0	-0.29	19	19
mol:PI-3-4-5-P3	0.024	0.052	-10000	0	-0.17	27	27
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
PI3K	0.024	0.053	-10000	0	-0.18	27	27
FYN	0.023	0.044	-10000	0	-0.14	27	27
mol:Ca2+	0.017	0.047	-10000	0	-0.16	26	26
JUP	0.004	0.073	-10000	0	-0.41	16	16
PIK3R1	0.016	0.005	-10000	0	-10000	0	0
mol:DAG	0.017	0.048	-10000	0	-0.17	26	26
CDH1	0.011	0.052	-10000	0	-0.41	8	8
RhoA/GDP	-0.042	0.1	-10000	0	-0.16	207	207
establishment of polarity of embryonic epithelium	0.022	0.039	-10000	0	-0.19	11	11
SRC	0.017	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
RHOA	0.017	0.001	-10000	0	-10000	0	0
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
CASR	0.018	0.045	-10000	0	-0.15	26	26
RhoA/GTP	0.023	0.045	-10000	0	-0.15	26	26
AKT2	0.022	0.048	-10000	0	-0.16	26	26
actin cable formation	0.021	0.039	-10000	0	-0.18	11	11
apoptosis	-0.019	0.048	0.16	31	-10000	0	31
CTNNA1	0.018	0.002	-10000	0	-10000	0	0
mol:GDP	-0.051	0.1	-10000	0	-0.17	207	207
PIP5K1A	0.022	0.04	-10000	0	-0.19	11	11
PLCG1	0.017	0.048	-10000	0	-0.17	26	26
Rac1/GTP	-0.038	0.1	-10000	0	-0.16	201	201
homophilic cell adhesion	0	0.002	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.15	0.16	-9999	-0.3	292	292
alphaV beta3 Integrin	0.026	0.049	-9999	-0.24	18	18
PTK2	-0.059	0.096	-9999	-0.28	29	29
IGF1R	0.017	0	-9999	-10000	0	0
PI4KB	0.016	0.019	-9999	-0.41	1	1
MFGE8	0.015	0.032	-9999	-0.41	3	3
SRC	0.017	0	-9999	-10000	0	0
CDKN1B	0.022	0.023	-9999	-0.19	2	2
VEGFA	-0.22	0.21	-9999	-0.41	287	287
ILK	0.022	0.023	-9999	-0.19	2	2
ROCK1	0.017	0	-9999	-10000	0	0
AKT1	0.021	0.028	-9999	-0.18	6	6
PTK2B	-0.1	0.12	-9999	-0.2	298	298
alphaV/beta3 Integrin/JAM-A	0.021	0.071	-9999	-0.19	54	54
CBL	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.027	0.046	-9999	-0.24	16	16
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.04	0.033	-9999	-0.21	9	9
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.041	0.07	-9999	-0.21	21	21
alphaV/beta3 Integrin/Syndecan-1	0.003	0.092	-9999	-0.25	59	59
PI4KA	0.006	0.008	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.011	0.1	-9999	-0.19	114	114
PI4 Kinase	0.009	0.014	-9999	-0.14	1	1
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
alphaV/beta3 Integrin/Osteopontin	-0.065	0.14	-9999	-0.25	185	185
RPS6KB1	-0.013	0.095	-9999	-0.36	13	13
TLN1	-0.02	0.12	-9999	-0.41	46	46
MAPK3	0.002	0.07	-9999	-0.18	50	50
GPR124	0.014	0.037	-9999	-0.41	4	4
MAPK1	0.003	0.069	-9999	-0.19	46	46
PXN	0.017	0	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.027	0.046	-9999	-0.24	16	16
cell adhesion	0.029	0.045	-9999	-0.2	20	20
ANGPTL3	0.017	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.12	0.14	-9999	-0.24	292	292
IGF-1R heterotetramer	0.017	0	-9999	-10000	0	0
Rac1/GDP	0.013	0	-9999	-10000	0	0
TGFBR2	0.011	0.052	-9999	-0.41	8	8
ITGB3	0.017	0	-9999	-10000	0	0
IGF1	0.014	0.037	-9999	-0.41	4	4
RAC1	0.017	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.024	0.051	-9999	-0.23	20	20
apoptosis	0.004	0.073	-9999	-0.41	16	16
CD47	0.015	0.026	-9999	-0.41	2	2
alphaV/beta3 Integrin/CD47	0.026	0.049	-9999	-0.24	18	18
VCL	0.017	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	0.027	0.046	-9999	-0.24	16	16
CSF1	0.017	0	-9999	-10000	0	0
PIK3C2A	0.012	0.023	-9999	-0.2	2	2
PI4 Kinase/Pyk2	-0.055	0.079	-9999	-0.28	23	23
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.11	0.14	-9999	-0.22	298	298
FAK1/Vinculin	-0.045	0.085	-9999	-0.23	29	29
alphaV beta3/Integrin/ppsTEM5	0.025	0.051	-9999	-0.24	20	20
RHOA	0.017	0.001	-9999	-10000	0	0
VTN	0.015	0.026	-9999	-0.41	2	2
BCAR1	0	0	-9999	-10000	0	0
FGF2	0.015	0.026	-9999	-0.41	2	2
F11R	-0.003	0.077	-9999	-0.29	36	36
alphaV/beta3 Integrin/Lactadherin	0.025	0.05	-9999	-0.24	19	19
alphaV/beta3 Integrin/TGFBR2	0.023	0.056	-9999	-0.24	24	24
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.026	0.042	-9999	-0.21	16	16
HSP90AA1	0.017	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	0.005	0.084	-9999	-0.23	57	57
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.065	0.17	-9999	-0.41	101	101
alphaV/beta3 Integrin/Pyk2	-0.098	0.13	-9999	-0.2	298	298
SDC1	-0.021	0.12	-9999	-0.41	47	47
VAV3	0.001	0.069	-9999	-0.21	48	48
PTPN11	0.017	0	-9999	-10000	0	0
IRS1	0.013	0.042	-9999	-0.41	5	5
FAK1/Paxillin	-0.045	0.085	-9999	-0.23	29	29
cell migration	-0.039	0.079	-9999	-0.21	29	29
ITGAV	0.004	0.074	-9999	-0.41	16	16
PI3K	0.021	0.073	-9999	-0.18	52	52
SPP1	-0.13	0.2	-9999	-0.41	181	181
KDR	0.003	0.076	-9999	-0.41	17	17
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.004	0.074	-9999	-0.41	16	16
COL4A3	0.017	0	-9999	-10000	0	0
angiogenesis	0.008	0.065	-9999	-0.19	36	36
Rac1/GTP	0.011	0.066	-9999	-0.19	48	48
EDIL3	0.017	0	-9999	-10000	0	0
cell proliferation	0.022	0.056	-9999	-0.23	24	24

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.005	0.093	-9999	-0.39	28	28
VDR	0.017	0	-9999	-10000	0	0
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.074	0.079	-9999	-0.26	5	5
RXRs/LXRs/DNA/Oxysterols	-0.12	0.11	-9999	-0.18	381	381
MED1	0.017	0	-9999	-10000	0	0
mol:9cRA	-0.021	0.016	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.031	0.005	-9999	-10000	0	0
RXRs/NUR77	-0.008	0.044	-9999	-0.26	3	3
RXRs/PPAR	0.002	0.028	-9999	-0.16	5	5
NCOR2	0.017	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0.013	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	0.041	0	-9999	-10000	0	0
RARA	0.017	0	-9999	-10000	0	0
NCOA1	0.017	0.003	-9999	-10000	0	0
VDR/VDR/DNA	0.017	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	0.02	0.009	-9999	-10000	0	0
RARG	0.017	0	-9999	-10000	0	0
RPS6KB1	0.017	0.057	-9999	-0.22	28	28
RARs/THRs/DNA/SMRT	0.032	0	-9999	-10000	0	0
THRA	0.017	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0.013	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.035	0.056	-9999	-0.29	3	3
NR1H4	0.017	0	-9999	-10000	0	0
RXRs/LXRs/DNA	-0.041	0.075	-9999	-0.26	7	7
NR1H2	-0.006	0.017	-9999	-10000	0	0
NR1H3	-0.012	0.041	-9999	-0.42	4	4
RXRs/VDR/DNA/Vit D3	-0.008	0.041	-9999	-0.24	3	3
NR4A1	0.017	0	-9999	-10000	0	0
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.015	0.032	-9999	-0.15	3	3
RXRG	-0.009	0.037	-9999	-0.44	3	3
RXR alpha/CCPG	-0.003	0.012	-9999	-10000	0	0
RXRA	-0.006	0.017	-9999	-10000	0	0
RXRB	-0.009	0.02	-9999	-10000	0	0
THRB	0.017	0	-9999	-10000	0	0
PPARG	0.013	0.042	-9999	-0.41	5	5
PPARD	0.017	0	-9999	-10000	0	0
TNF	-0.1	0.1	-9999	-0.16	355	355
mol:Oxysterols	-0.017	0.014	-9999	-10000	0	0
cholesterol transport	-0.11	0.11	-9999	-0.18	381	381
PPARA	0.017	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.017	0	-9999	-10000	0	0
RXRs/NUR77/BCL2	0.013	0.016	-9999	-0.15	3	3
SREBF1	-0.1	0.099	-9999	-0.16	355	355
RXRs/RXRs/DNA/9cRA	-0.035	0.056	-9999	-0.29	3	3
ABCA1	-0.24	0.18	-9999	-0.35	381	381
RARs/THRs	0.051	0	-9999	-10000	0	0
RXRs/FXR	-0.008	0.044	-9999	-0.26	3	3
BCL2	0.017	0	-9999	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0	0.078	-10000	0	-0.21	36	36
IKBKB	0.007	0.051	-10000	0	-0.18	12	12
AKT1	-0.013	0.069	0.18	1	-0.17	58	59
IKBKG	0.007	0.053	-10000	0	-0.17	17	17
CALM1	-0.011	0.079	-10000	0	-0.25	38	38
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
MAP3K1	-0.01	0.095	-10000	0	-0.24	49	49
MAP3K7	0.016	0.019	-10000	0	-0.41	1	1
mol:Ca2+	-0.016	0.087	-10000	0	-0.27	40	40
DOK1	0.017	0	-10000	0	-10000	0	0
AP-1	-0.011	0.071	-10000	0	-0.17	43	43
LYN	-0.035	0.14	-10000	0	-0.41	64	64
BLNK	-0.038	0.14	-10000	0	-0.41	68	68
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
BCR complex	0.024	0.028	-10000	0	-0.41	2	2
CD22	-0.038	0.11	-10000	0	-0.24	93	93
CAMK2G	-0.006	0.058	-10000	0	-0.23	25	25
CSNK2A1	0.017	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.07	0.14	-10000	0	-0.46	49	49
GO:0007205	-0.016	0.087	-10000	0	-0.28	40	40
SYK	-0.012	0.11	-10000	0	-0.41	36	36
ELK1	-0.012	0.083	-10000	0	-0.26	40	40
NFATC1	-0.019	0.093	-10000	0	-0.24	63	63
B-cell antigen/BCR complex	0.024	0.028	-10000	0	-0.41	2	2
PAG1/CSK	0.013	0	-10000	0	-10000	0	0
NFKBIB	0.013	0.021	-10000	0	-0.085	2	2
HRAS	-0.016	0.094	-10000	0	-0.28	46	46
NFKBIA	0.013	0.021	-10000	0	-0.087	2	2
NF-kappa-B/RelA/I kappa B beta	0.017	0.02	-10000	0	-0.091	4	4
RasGAP/Csk	-0.009	0.11	-10000	0	-0.2	125	125
mol:GDP	-0.013	0.084	-10000	0	-0.26	40	40
PTEN	0.015	0.026	-10000	0	-0.41	2	2
CD79B	0.016	0.019	-10000	0	-0.41	1	1
NF-kappa-B/RelA/I kappa B alpha	0.017	0.02	-10000	0	-0.092	4	4
GRB2	0.017	0.002	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.024	0.11	-10000	0	-0.29	60	60
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
mol:IP3	-0.016	0.088	-10000	0	-0.28	40	40
CSK	0.017	0	-10000	0	-10000	0	0
FOS	-0.051	0.12	-10000	0	-0.22	147	147
CHUK	0.007	0.053	-10000	0	-0.17	22	22
IBTK	0.017	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.006	0.093	-10000	0	-0.23	59	59
PTPN6	-0.037	0.11	-10000	0	-0.25	93	93
RELA	0.017	0	-10000	0	-10000	0	0
BCL2A1	-0.001	0.037	-10000	0	-0.064	129	129
VAV2	-0.034	0.12	-10000	0	-0.29	66	66
ubiquitin-dependent protein catabolic process	0.016	0.021	-10000	0	-0.091	1	1
BTK	0.011	0.009	-10000	0	-10000	0	0
CD19	-0.039	0.11	-10000	0	-0.25	93	93
MAP4K1	0.016	0.019	-10000	0	-0.41	1	1
CD72	0.017	0	-10000	0	-10000	0	0
PAG1	0	0	-10000	0	-10000	0	0
MAPK14	-0.005	0.086	-10000	0	-0.22	51	51
SH3BP5	0.016	0.005	-10000	0	-10000	0	0
PIK3AP1	-0.018	0.09	-10000	0	-0.23	61	61
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.009	0.11	-10000	0	-0.34	40	40
RAF1	-0.012	0.089	-10000	0	-0.26	46	46
RasGAP/p62DOK/SHIP	-0.013	0.099	-10000	0	-0.19	125	125
CD79A	0.015	0.026	-10000	0	-0.41	2	2
re-entry into mitotic cell cycle	-0.011	0.071	-10000	0	-0.17	43	43
RASA1	0.017	0.002	-10000	0	-10000	0	0
MAPK3	-0.001	0.079	0.16	2	-0.23	40	42
MAPK1	-0.002	0.079	0.26	1	-0.23	40	41
CD72/SHP1	-0.027	0.11	-10000	0	-0.28	59	59
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
MAPK8	-0.004	0.085	-10000	0	-0.22	49	49
actin cytoskeleton organization	-0.027	0.1	-10000	0	-0.26	64	64
NF-kappa-B/RelA	0.037	0.036	-10000	0	-0.15	2	2
Calcineurin	0.005	0.069	-10000	0	-0.22	32	32
PI3K	-0.061	0.11	-10000	0	-0.3	79	79
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.019	0.095	-10000	0	-0.24	62	62
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.012	0.094	-10000	0	-0.68	1	1
DAPP1	-0.022	0.095	-10000	0	-0.57	1	1
cytokine secretion	-0.017	0.088	0.14	1	-0.22	63	64
mol:DAG	-0.016	0.088	-10000	0	-0.28	40	40
PLCG2	0.009	0.059	-10000	0	-0.41	10	10
MAP2K1	-0.008	0.083	0.17	1	-0.25	41	42
B-cell antigen/BCR complex/FcgammaRIIB	-0.032	0.12	-10000	0	-0.24	128	128
mol:PI-3-4-5-P3	-0.046	0.084	0.27	1	-0.24	66	67
ETS1	0.048	0.091	0.22	18	-0.2	30	48
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.023	0.16	-10000	0	-0.3	111	111
B-cell antigen/BCR complex/LYN	-0.043	0.11	-10000	0	-0.26	93	93
MALT1	-0.002	0.09	-10000	0	-0.41	24	24
TRAF6	0.017	0	-10000	0	-10000	0	0
RAC1	-0.029	0.11	-10000	0	-0.28	64	64
B-cell antigen/BCR complex/LYN/SYK	-0.042	0.16	-10000	0	-0.4	66	66
CARD11	-0.015	0.083	-10000	0	-0.26	40	40
FCGR2B	-0.087	0.18	-10000	0	-0.41	128	128
PPP3CA	0.014	0.007	-10000	0	-10000	0	0
BCL10	0.014	0.037	-10000	0	-0.41	4	4
IKK complex	0.011	0.025	-10000	0	-0.072	8	8
PTPRC	-0.086	0.18	-10000	0	-0.41	127	127
PDPK1	-0.016	0.069	0.17	1	-0.17	58	59
PPP3CB	0.017	0.002	-10000	0	-10000	0	0
PPP3CC	0.017	0	-10000	0	-10000	0	0
POU2F2	0.016	0.013	-10000	0	-0.052	2	2

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.032	0.11	-9999	-0.18	187	187
Ran/GTP/Exportin 1/HDAC1	-0.021	0.058	-9999	-0.17	65	65
NF kappa B1 p50/RelA/I kappa B alpha	-0.02	0.086	-9999	-0.14	188	188
SUMO1	0.017	0	-9999	-10000	0	0
ZFPM1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.018	0.005	-9999	-0.11	1	1
FKBP3	0.017	0.001	-9999	-10000	0	0
Histones	-0.032	0.092	-9999	-0.22	68	68
YY1/LSF	0.026	0	-9999	-10000	0	0
SMG5	0.017	0	-9999	-10000	0	0
RAN	0.017	0.001	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.03	0.081	-9999	-0.14	186	186
I kappa B alpha/HDAC1	-0.042	0.096	-9999	-0.24	66	66
SAP18	0.017	0	-9999	-10000	0	0
RELA	-0.02	0.07	-9999	-0.12	185	185
HDAC1/Smad7	0.001	0.09	-9999	-0.24	65	65
RANGAP1	0.017	0	-9999	-10000	0	0
HDAC3/TR2	-0.014	0.064	-9999	-0.1	185	185
NuRD/MBD3 Complex	-0.009	0.068	-9999	-0.18	40	40
NF kappa B1 p50/RelA	-0.013	0.07	-9999	-0.25	4	4
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.016	0.019	-9999	-0.41	1	1
GATA1	0.017	0	-9999	-10000	0	0
Mad/Max	0.025	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.007	0.072	-9999	-0.19	40	40
RBBP7	0.017	0	-9999	-10000	0	0
NPC	0.01	0.009	-9999	-0.2	1	1
RBBP4	-0.064	0.17	-9999	-0.41	100	100
MAX	0.017	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.017	0	-9999	-10000	0	0
NFKBIA	-0.025	0.068	-9999	-0.12	186	186
KAT2B	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	-0.009	0.069	-9999	-0.23	20	20
SIN3 complex	0.033	0	-9999	-10000	0	0
SMURF1	0.017	0	-9999	-10000	0	0
CHD3	0.017	0	-9999	-10000	0	0
SAP30	0.017	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.017	0	-9999	-10000	0	0
YY1/HDAC3	-0.008	0.056	-9999	-10000	0	0
YY1/HDAC2	0.024	0.024	-9999	-0.22	5	5
YY1/HDAC1	-0.004	0.081	-9999	-0.22	65	65
NuRD/MBD2 Complex (MeCP1)	-0.009	0.068	-9999	-0.18	40	40
PPARG	-0.034	0.088	-9999	-0.15	189	189
HDAC8/hEST1B	0.023	0	-9999	-10000	0	0
UBE2I	0.017	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
TNFRSF1A	-0.13	0.2	-9999	-0.41	183	183
HDAC3/SMRT (N-CoR2)	-0.014	0.064	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.001	0.09	-9999	-0.24	65	65
CREBBP	0.017	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	-0.011	0.076	-9999	-0.2	40	40
HDAC1	-0.036	0.14	-9999	-0.41	65	65
HDAC3	-0.025	0.068	-9999	-0.12	185	185
HDAC2	0.013	0.042	-9999	-0.41	5	5
YY1	0.018	0	-9999	-10000	0	0
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0.016	0.019	-9999	-0.41	1	1
NCOR2	0.017	0	-9999	-10000	0	0
MXD1	0.017	0	-9999	-10000	0	0
STAT3	0.019	0.027	-9999	-0.18	10	10
NFKB1	0.014	0.037	-9999	-0.41	4	4
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0.019	-9999	-0.41	1	1
YY1/LSF/HDAC1	0.006	0.077	-9999	-0.2	65	65
YY1/SAP30/HDAC1	0.006	0.077	-9999	-0.2	65	65
EP300	0.017	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.019	0.027	-9999	-0.18	10	10
proteasomal ubiquitin-dependent protein catabolic process	-0.025	0.068	-9999	-0.12	186	186
histone deacetylation	-0.008	0.067	-9999	-0.18	40	40
STAT3 (dimer non-phopshorylated)/HDAC3	-0.009	0.063	-9999	-0.22	10	10
nuclear export	-0.023	0	-9999	-10000	0	0
PRKACA	0.017	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	-0.023	0.12	-9999	-0.41	49	49
GATA2/HDAC3	-0.015	0.064	-9999	-0.2	1	1
GATA1/HDAC1	-0.013	0.1	-9999	-0.28	65	65
GATA1/HDAC3	-0.014	0.064	-9999	-10000	0	0
CHD4	0.017	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.083	0.15	-9999	-0.28	185	185
SIN3/HDAC complex/Mad/Max	0.001	0.058	-9999	-0.18	20	20
NuRD Complex	-0.007	0.076	-9999	-0.2	40	40
positive regulation of chromatin silencing	-0.033	0.09	-9999	-0.21	68	68
SIN3B	0.017	0	-9999	-10000	0	0
MTA2	0.017	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0.017	0	-9999	-10000	0	0
SUMO1/HDAC1	0.006	0.071	-9999	-0.18	65	65
HDAC complex	-0.035	0.13	-9999	-0.24	149	149
GATA1/Fog1	0.013	0	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	-0.001	0.093	-9999	-0.24	68	68
TNF	0.015	0.026	-9999	-0.41	2	2
negative regulation of cell growth	0.001	0.058	-9999	-0.18	20	20
NuRD/MBD2/PRMT5 Complex	-0.009	0.068	-9999	-0.18	40	40
Ran/GTP/Exportin 1	0.034	0.006	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.027	0.084	-9999	-0.14	186	186
SIN3/HDAC complex/NCoR1	-0.005	0.064	-9999	-0.2	20	20
TFCP2	0.017	0	-9999	-10000	0	0
NR2C1	0.017	0	-9999	-10000	0	0
MBD3	0.017	0	-9999	-10000	0	0
MBD2	0.017	0	-9999	-10000	0	0

×

Syndecan-2-mediated signaling 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
Syndecan-2/Fibronectin	-0.03	0.11	-9999	-0.24	105	105
EPHB2	0.015	0.026	-9999	-0.41	2	2
Syndecan-2/TACI	0.019	0.036	-9999	-0.19	13	13
LAMA1	0	0	-9999	-10000	0	0
Syndecan-2/alpha2 ITGB1	-0.009	0.1	-9999	-0.21	106	106
HRAS	0.016	0.019	-9999	-0.41	1	1
Syndecan-2/CASK	0.007	0.034	-9999	-0.2	13	13
ITGA5	-0.043	0.15	-9999	-0.41	74	74
BAX	0.018	0.056	-9999	-0.3	14	14
EPB41	0.017	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.017	0.032	-9999	-0.17	13	13
LAMA3	0.005	0.071	-9999	-0.41	15	15
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.041	0.15	-9999	-0.41	72	72
Syndecan-2/MMP2	-0.1	0.13	-9999	-0.24	254	254
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.029	0.12	-9999	-0.28	93	93
dendrite morphogenesis	0.018	0.039	-9999	-0.24	10	10
Syndecan-2/GM-CSF	0.019	0.036	-9999	-0.25	8	8
determination of left/right symmetry	0.01	0.041	-9999	-0.24	13	13
Syndecan-2/PKC delta	0.019	0.036	-9999	-0.25	8	8
GNB2L1	0.017	0	-9999	-10000	0	0
MAPK3	0.019	0.032	-9999	-0.22	8	8
MAPK1	0.018	0.032	-9999	-0.22	8	8
Syndecan-2/RACK1	0.027	0.033	-9999	-0.2	9	9
NF1	0.017	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.01	0.041	-9999	-0.24	13	13
ITGA2	-0.059	0.16	-9999	-0.41	93	93
MAPK8	0.017	0.042	-9999	-0.24	13	13
Syndecan-2/alpha2/beta1 Integrin	-0.012	0.091	-9999	-0.2	99	99
Syndecan-2/Kininogen	0.019	0.037	-9999	-0.25	9	9
ITGB1	0.017	0	-9999	-10000	0	0
SRC	0.021	0.03	-9999	-0.19	9	9
Syndecan-2/CASK/Protein 4.1	0.017	0.032	-9999	-0.22	8	8
extracellular matrix organization	0.006	0.067	-9999	-0.24	34	34
actin cytoskeleton reorganization	-0.03	0.11	-9999	-0.24	105	105
Syndecan-2/Caveolin-2/Ras	-0.004	0.091	-9999	-0.22	76	76
Syndecan-2/Laminin alpha3	0.012	0.056	-9999	-0.24	23	23
Syndecan-2/RasGAP	0.034	0.033	-9999	-0.19	9	9
alpha5/beta1 Integrin	-0.018	0.11	-9999	-0.28	74	74
PRKCD	0.017	0	-9999	-10000	0	0
Syndecan-2 dimer	0.018	0.039	-9999	-0.24	10	10
GO:0007205	0.002	0.01	-9999	-0.11	1	1
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.033	0.031	-9999	-0.18	9	9
RHOA	0.017	0.001	-9999	-10000	0	0
SDCBP	0.017	0	-9999	-10000	0	0
TNFRSF13B	0.017	0	-9999	-10000	0	0
RASA1	0.017	0.002	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.029	0.12	-9999	-0.28	93	93
Syndecan-2/Synbindin	0.019	0.036	-9999	-0.25	8	8
TGFB1	-0.005	0.095	-9999	-0.41	27	27
CASP3	-0.024	0.094	-9999	-0.21	104	104
FN1	-0.065	0.17	-9999	-0.41	101	101
Syndecan-2/IL8	-0.037	0.11	-9999	-0.24	121	121
SDC2	0.01	0.041	-9999	-0.24	13	13
KNG1	0.016	0.019	-9999	-0.41	1	1
Syndecan-2/Neurofibromin	0.019	0.036	-9999	-0.25	8	8
TRAPPC4	0.017	0.001	-9999	-10000	0	0
CSF2	0.017	0	-9999	-10000	0	0
Syndecan-2/TGFB1	0.006	0.067	-9999	-0.24	34	34
Syndecan-2/Syntenin/PI-4-5-P2	0.017	0.032	-9999	-0.17	13	13
Syndecan-2/Ezrin	0.017	0.032	-9999	-0.22	8	8
PRKACA	0.019	0.032	-9999	-0.22	8	8
angiogenesis	-0.037	0.11	-9999	-0.24	121	121
MMP2	-0.19	0.22	-9999	-0.41	250	250
IL8	-0.076	0.18	-9999	-0.41	115	115
calcineurin-NFAT signaling pathway	0.019	0.036	-9999	-0.19	13	13

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.017	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.023	0.063	-9999	-0.19	36	36
Syndecan-3/Neurocan	0.003	0.062	-9999	-0.2	37	37
POMC	0.017	0	-9999	-10000	0	0
EGFR	-0.14	0.21	-9999	-0.41	194	194
Syndecan-3/EGFR	-0.073	0.12	-9999	-0.21	219	219
AGRP	0.017	0	-9999	-10000	0	0
NCSTN	-0.007	0.099	-9999	-0.41	30	30
PSENEN	0.017	0.001	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.017	0	-9999	-10000	0	0
APH1A	0.009	0.059	-9999	-0.41	10	10
NCAN	0.013	0.027	-9999	-0.41	2	2
long-term memory	0.014	0.065	-9999	-0.21	37	37
Syndecan-3/IL8	-0.042	0.11	-9999	-0.21	145	145
PSEN1	0.016	0.019	-9999	-0.41	1	1
Src/Cortactin	0.025	0	-9999	-10000	0	0
FYN	0.015	0.027	-9999	-0.41	2	2
limb bud formation	0.001	0.058	-9999	-0.25	22	22
MC4R	0.016	0.019	-9999	-0.41	1	1
SRC	0.017	0	-9999	-10000	0	0
PTN	0.016	0.004	-9999	-10000	0	0
FGFR/FGF/Syndecan-3	0.001	0.059	-9999	-0.25	22	22
neuron projection morphogenesis	0.016	0.05	-9999	-0.19	23	23
Syndecan-3/AgRP	0.004	0.073	-9999	-0.25	36	36
Syndecan-3/AgRP/MC4R	0.013	0.073	-9999	-0.24	37	37
Fyn/Cortactin	0.023	0.02	-9999	-0.28	2	2
SDC3	0.001	0.059	-9999	-0.26	22	22
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.042	0.11	-9999	-0.21	145	145
IL8	-0.076	0.18	-9999	-0.41	115	115
Syndecan-3/Fyn/Cortactin	0.014	0.066	-9999	-0.21	37	37
Syndecan-3/CASK	-0.007	0.071	-9999	-0.25	36	36
alpha-MSH/MC4R	0.025	0.014	-9999	-0.28	1	1
Gamma Secretase	0.032	0.067	-9999	-0.2	39	39

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.13	0.17	-10000	0	-0.44	52	52
NCK1/PAK1/Dok-R	-0.083	0.075	-10000	0	-0.24	44	44
NCK1/Dok-R	-0.011	0.11	-10000	0	-0.29	17	17
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
mol:beta2-estradiol	0.013	0.044	0.12	78	-10000	0	78
RELA	0.017	0	-10000	0	-10000	0	0
SHC1	-0.022	0.12	-10000	0	-0.41	46	46
Rac/GDP	0.013	0	-10000	0	-10000	0	0
F2	0.037	0.054	-10000	0	-0.42	2	2
TNIP2	0.008	0.061	-10000	0	-0.41	11	11
NF kappa B/RelA	0.005	0.11	-10000	0	-0.35	6	6
FN1	-0.065	0.17	-10000	0	-0.41	101	101
PLD2	-0.013	0.1	-10000	0	-0.27	41	41
PTPN11	0.017	0	-10000	0	-10000	0	0
GRB14	0.002	0.078	-10000	0	-0.41	18	18
ELK1	-0.003	0.098	-10000	0	-0.28	2	2
GRB7	0.016	0.019	-10000	0	-0.41	1	1
PAK1	0.017	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.055	0.17	-10000	0	-0.4	60	60
CDKN1A	-0.16	0.2	-10000	0	-0.47	93	93
ITGA5	-0.043	0.15	-10000	0	-0.41	74	74
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.007	0.1	-10000	0	-0.28	6	6
CRK	0.017	0	-10000	0	-10000	0	0
mol:NO	-0.1	0.14	-10000	0	-0.36	52	52
PLG	-0.013	0.1	-10000	0	-0.27	46	46
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.1	0.15	-10000	0	-0.4	50	50
GRB2	0.017	0.002	-10000	0	-10000	0	0
PIK3R1	0.015	0.004	-10000	0	-10000	0	0
ANGPT2	-0.2	0.21	-10000	0	-0.39	280	280
BMX	-0.013	0.1	-10000	0	-0.27	46	46
ANGPT1	-0.038	0.13	0.14	1	-0.34	78	79
tube development	-0.16	0.19	0.28	1	-0.41	102	103
ANGPT4	0.012	0.005	-10000	0	-10000	0	0
response to hypoxia	-0.006	0.012	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.014	0.11	-10000	0	-0.28	41	41
alpha5/beta1 Integrin	-0.018	0.11	-10000	0	-0.28	74	74
FGF2	0.02	0.027	-10000	0	-0.41	2	2
STAT5A (dimer)	-0.17	0.22	-10000	0	-0.51	87	87
mol:L-citrulline	-0.1	0.14	-10000	0	-0.36	52	52
AGTR1	0.002	0.029	-10000	0	-0.41	2	2
MAPK14	-0.048	0.12	-10000	0	-0.33	38	38
Tie2/SHP2	0.016	0.046	-10000	0	-10000	0	0
TEK	0.009	0.05	-10000	0	-0.24	1	1
RPS6KB1	-0.1	0.15	-10000	0	-0.4	43	43
Angiotensin II/AT1	-0.006	0.026	-10000	0	-0.29	2	2
Tie2/Ang1/GRB2	-0.006	0.11	-10000	0	-0.28	11	11
MAPK3	-0.009	0.099	-10000	0	-0.26	15	15
MAPK1	-0.01	0.097	-10000	0	-0.26	15	15
Tie2/Ang1/GRB7	-0.007	0.11	-10000	0	-0.29	6	6
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
MAPK8	-0.013	0.1	-10000	0	-0.27	46	46
PI3K	-0.12	0.16	-10000	0	-0.42	57	57
FES	-0.049	0.12	-10000	0	-0.33	39	39
Crk/Dok-R	-0.007	0.1	-10000	0	-0.27	10	10
Tie2/Ang1/ABIN2	-0.011	0.11	-10000	0	-0.3	16	16
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.12	0.16	-10000	0	-0.41	52	52
STAT5A	0.016	0.019	-10000	0	-0.41	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.1	0.15	-10000	0	-0.4	42	42
Tie2/Ang2	-0.19	0.23	-10000	0	-0.51	100	100
Tie2/Ang1	-0.017	0.11	-10000	0	-0.29	48	48
FOXO1	-0.14	0.18	-10000	0	-0.43	80	80
ELF1	0.016	0.05	-10000	0	-0.41	7	7
ELF2	-0.015	0.11	-10000	0	-0.28	46	46
mol:Choline	-0.013	0.1	-10000	0	-0.27	46	46
cell migration	-0.064	0.058	-10000	0	-0.16	95	95
FYN	-0.17	0.2	-10000	0	-0.45	102	102
DOK2	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.14	0.19	-10000	0	-0.43	93	93
ETS1	0.008	0.047	-10000	0	-10000	0	0
PXN	-0.09	0.14	-10000	0	-0.36	42	42
ITGB1	0.017	0	-10000	0	-10000	0	0
NOS3	-0.11	0.16	-10000	0	-0.4	52	52
RAC1	0.017	0	-10000	0	-10000	0	0
TNF	0.002	0.053	-10000	0	-0.13	41	41
MAPKKK cascade	-0.013	0.1	-10000	0	-0.27	46	46
RASA1	0.017	0.002	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.031	0.12	-10000	0	-0.32	43	43
NCK1	0.008	0.061	-10000	0	-0.41	11	11
vasculogenesis	-0.097	0.14	-10000	0	-0.34	52	52
mol:Phosphatidic acid	-0.013	0.1	-10000	0	-0.27	46	46
mol:Angiotensin II	-0.009	0.01	-10000	0	-10000	0	0
mol:NADP	-0.1	0.14	-10000	0	-0.36	52	52
Rac1/GTP	-0.099	0.14	-10000	0	-0.39	42	42
MMP2	-0.11	0.14	-10000	0	-0.36	62	62

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.004	0.084	-10000	0	-0.23	52	52
CRKL	0.001	0.088	-10000	0	-0.24	52	52
HRAS	0.008	0.096	-10000	0	-0.33	13	13
mol:PIP3	-0.007	0.086	0.18	3	-0.24	51	54
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0.017	0	-10000	0	-10000	0	0
GAB1	-0.002	0.092	-10000	0	-0.26	52	52
FOXO3	0.005	0.089	-10000	0	-0.24	46	46
AKT1	0.001	0.094	-10000	0	-0.26	51	51
BAD	0.005	0.089	-10000	0	-0.24	46	46
megakaryocyte differentiation	0.001	0.087	-10000	0	-0.25	48	48
GSK3B	0.006	0.089	-10000	0	-0.24	46	46
RAF1	0.011	0.082	-10000	0	-0.27	13	13
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
STAT3	-0.004	0.094	-10000	0	-0.26	54	54
STAT1	-0.003	0.16	-10000	0	-0.44	52	52
HRAS/SPRED1	0.007	0.081	-10000	0	-0.27	13	13
cell proliferation	0	0.09	-10000	0	-0.25	52	52
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
TEC	0.017	0	-10000	0	-10000	0	0
RPS6KB1	0.003	0.094	-10000	0	-0.26	52	52
HRAS/SPRED2	0.015	0.084	-10000	0	-0.27	13	13
LYN/TEC/p62DOK	-0.003	0.11	-10000	0	-0.24	56	56
MAPK3	0.018	0.063	-10000	0	-0.2	11	11
STAP1	-0.001	0.093	-10000	0	-0.26	52	52
GRAP2	0.017	0	-10000	0	-10000	0	0
JAK2	0	0.14	-10000	0	-0.4	52	52
STAT1 (dimer)	-0.002	0.15	-10000	0	-0.43	52	52
mol:Gleevec	-0.001	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.021	0.092	-10000	0	-0.24	52	52
actin filament polymerization	-0.004	0.09	-10000	0	-0.25	61	61
LYN	-0.035	0.14	-10000	0	-0.41	64	64
STAP1/STAT5A (dimer)	0.005	0.12	-10000	0	-0.33	52	52
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.018	0.086	-10000	0	-0.22	52	52
PI3K	0.008	0.097	-10000	0	-0.25	45	45
PTEN	0.015	0.026	-10000	0	-0.41	2	2
SCF/KIT/EPO/EPOR	0.009	0.17	-10000	0	-0.47	52	52
MAPK8	0	0.091	-10000	0	-0.26	52	52
STAT3 (dimer)	-0.004	0.093	-10000	0	-0.25	54	54
positive regulation of transcription	0.018	0.055	-10000	0	-0.17	11	11
mol:GDP	0.007	0.1	-10000	0	-0.24	51	51
PIK3C2B	-0.003	0.094	-10000	0	-0.26	55	55
CBL/CRKL	0.011	0.086	-10000	0	-0.23	52	52
FER	0	0.091	-10000	0	-0.26	52	52
SH2B3	-0.004	0.096	-10000	0	-0.27	52	52
PDPK1	-0.004	0.081	0.18	3	-0.22	51	54
SNAI2	-0.047	0.12	-10000	0	-0.3	58	58
positive regulation of cell proliferation	-0.001	0.14	-10000	0	-0.38	52	52
KITLG	0.018	0.011	-10000	0	-10000	0	0
cell motility	-0.001	0.14	-10000	0	-0.38	52	52
PTPN6	0.008	0.062	-10000	0	-0.42	11	11
EPOR	0.024	0.065	-10000	0	-10000	0	0
STAT5A (dimer)	0.004	0.12	-10000	0	-0.33	52	52
SOCS1	0.017	0	-10000	0	-10000	0	0
cell migration	0	0.09	0.25	52	-10000	0	52
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.018	0.005	-10000	0	-10000	0	0
VAV1	0.016	0.019	-10000	0	-0.41	1	1
GRB10	-0.006	0.1	-10000	0	-0.28	52	52
PTPN11	0.017	0.004	-10000	0	-10000	0	0
SCF/KIT	-0.003	0.096	-10000	0	-0.26	61	61
GO:0007205	0	0.006	-10000	0	-10000	0	0
MAP2K1	0.013	0.068	-10000	0	-0.23	11	11
CBL	0.017	0	-10000	0	-10000	0	0
KIT	0.033	0.067	-10000	0	-0.4	11	11
MAP2K2	0.014	0.068	-10000	0	-0.23	11	11
SHC/Grb2/SOS1	-0.005	0.11	-10000	0	-0.28	53	53
STAT5A	0.004	0.12	-10000	0	-0.34	52	52
GRB2	0.017	0.002	-10000	0	-10000	0	0
response to radiation	-0.046	0.12	-10000	0	-0.3	58	58
SHC/GRAP2	-0.002	0.088	-10000	0	-0.28	46	46
PTPRO	0.001	0.089	-10000	0	-0.26	48	48
SH2B2	-0.004	0.091	-10000	0	-0.25	61	61
DOK1	0.017	0	-10000	0	-10000	0	0
MATK	0	0.091	-10000	0	-0.26	52	52
CREBBP	0.026	0.03	-10000	0	-10000	0	0
BCL2	0.025	0.064	-10000	0	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.029	0.04	-10000	0	-0.24	12	12
fibroblast growth factor receptor signaling pathway	0.028	0.04	-10000	0	-0.23	12	12
LAMA1	0	0	-10000	0	-10000	0	0
PRNP	0.016	0.004	-10000	0	-10000	0	0
GPC1/SLIT2	0.012	0.037	-10000	0	-0.22	11	11
SMAD2	0.017	0.04	-10000	0	-0.21	16	16
GPC1/PrPc/Cu2+	0.018	0.032	-10000	0	-0.24	8	8
GPC1/Laminin alpha1	0.008	0.037	-10000	0	-0.29	8	8
TDGF1	0.015	0.026	-10000	0	-0.41	2	2
CRIPTO/GPC1	0.02	0.042	-10000	0	-0.28	10	10
APP/GPC1	0.021	0.038	-10000	0	-0.28	8	8
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.021	0.1	-10000	0	-0.25	85	85
FLT1	0.017	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.027	0.046	-10000	0	-0.24	16	16
SERPINC1	0.016	0.019	-10000	0	-0.41	1	1
FYN	0.015	0.038	-10000	0	-0.23	12	12
FGR	0.009	0.056	-10000	0	-0.24	27	27
positive regulation of MAPKKK cascade	-0.022	0.096	-10000	0	-0.22	77	77
SLIT2	0.009	0.033	-10000	0	-0.41	3	3
GPC1/NRG	0.021	0.038	-10000	0	-0.28	8	8
NRG1	0.017	0	-10000	0	-10000	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.12	0.14	-10000	0	-0.24	290	290
LYN	-0.014	0.09	-10000	0	-0.24	73	73
mol:Spermine	0.004	0.036	-10000	0	-0.29	8	8
cell growth	0.028	0.04	-10000	0	-0.23	12	12
BMP signaling pathway	-0.011	0.052	0.41	8	-10000	0	8
SRC	0.017	0.035	-10000	0	-0.23	10	10
TGFBR1	0.017	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.14	0.21	-10000	0	-0.41	191	191
GPC1	0.011	0.052	-10000	0	-0.41	8	8
TGFBR1 (dimer)	0.017	0	-10000	0	-10000	0	0
VEGFA	-0.22	0.21	-10000	0	-0.41	287	287
BLK	0.017	0.035	-10000	0	-0.23	10	10
HCK	-0.025	0.1	-10000	0	-0.24	95	95
FGF2	0.015	0.026	-10000	0	-0.41	2	2
FGFR1	0.015	0.026	-10000	0	-0.41	2	2
VEGFR1 homodimer	0.017	0	-10000	0	-10000	0	0
TGFBR2	0.011	0.052	-10000	0	-0.41	8	8
cell death	0.021	0.038	-10000	0	-0.28	8	8
ATIII/GPC1	0.02	0.04	-10000	0	-0.28	9	9
PLA2G2A/GPC1	-0.091	0.15	-10000	0	-0.29	196	196
LCK	0.015	0.043	-10000	0	-0.25	13	13
neuron differentiation	0.021	0.038	-10000	0	-0.28	8	8
PrPc/Cu2+	0.012	0.003	-10000	0	-10000	0	0
APP	0.017	0.001	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.011	0.052	-10000	0	-0.41	8	8

×

Regulation of cytoplasmic and nuclear SMAD2/3 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
SMAD4	-0.085	0.18	-9999	-0.41	126	126
SMAD2	0.013	0.02	-9999	-0.12	2	2
SMAD3	0.018	0.04	-9999	-0.12	37	37
SMAD3/SMAD4	0.001	0.069	-9999	-0.25	10	10
SMAD4/Ubc9/PIASy	-0.029	0.12	-9999	-0.24	126	126
SMAD2/SMAD2/SMAD4	-0.01	0.1	-9999	-0.19	122	122
PPM1A	0.017	0	-9999	-10000	0	0
CALM1	0.016	0.004	-9999	-10000	0	0
SMAD2/SMAD4	-0.032	0.097	-9999	-0.2	126	126
MAP3K1	0.016	0.019	-9999	-0.41	1	1
TRAP-1/SMAD4	-0.049	0.13	-9999	-0.28	126	126
MAPK3	0.017	0	-9999	-10000	0	0
MAPK1	0.017	0.003	-9999	-10000	0	0
NUP214	0.017	0	-9999	-10000	0	0
CTDSP1	0.015	0.032	-9999	-0.41	3	3
CTDSP2	-0.013	0.11	-9999	-0.41	37	37
CTDSPL	0.017	0	-9999	-10000	0	0
KPNB1	0.017	0	-9999	-10000	0	0
TGFBRAP1	0.017	0	-9999	-10000	0	0
UBE2I	0.017	0	-9999	-10000	0	0
NUP153	0.015	0.032	-9999	-0.41	3	3
KPNA2	0.007	0.064	-9999	-0.41	12	12
PIAS4	0.017	0	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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
PDGFRA	-0.025	0.13	-9999	-0.41	51	51
HRAS	0.016	0.019	-9999	-0.41	1	1
EGFR	-0.14	0.21	-9999	-0.41	194	194
AKT	0.015	0.035	-9999	-0.27	5	5
FOXO3	0.017	0	-9999	-10000	0	0
AKT1	0.014	0.037	-9999	-0.41	4	4
FOXO1	0.008	0.061	-9999	-0.41	11	11
AKT3	0.016	0.019	-9999	-0.41	1	1
FOXO4	0.017	0	-9999	-10000	0	0
MET	0.009	0.059	-9999	-0.41	10	10
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
PIK3CB	0.017	0	-9999	-10000	0	0
NRAS	-0.094	0.19	-9999	-0.41	136	136
PIK3CG	0.017	0	-9999	-10000	0	0
PIK3R3	0.016	0.019	-9999	-0.41	1	1
PIK3R2	0.017	0	-9999	-10000	0	0
NF1	0.017	0	-9999	-10000	0	0
RAS	-0.047	0.064	-9999	-0.095	284	284
ERBB2	0.017	0	-9999	-10000	0	0
proliferation/survival/translation	-0.041	0.026	-9999	-10000	0	0
PI3K	-0.028	0.056	-9999	-0.12	71	71
PIK3R1	0.016	0.004	-9999	-10000	0	0
KRAS	0.017	0.002	-9999	-10000	0	0
FOXO	0.021	0.034	-9999	-0.12	10	10
AKT2	0.017	0	-9999	-10000	0	0
PTEN	0.015	0.026	-9999	-0.41	2	2

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.03	0.003	-10000	0	-10000	0	0
ER alpha/Gai/GDP/Gbeta gamma	-0.063	0.064	-10000	0	-0.2	63	63
AKT1	0.007	0.03	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.005	0.031	-10000	0	-10000	0	0
mol:Ca2+	0.03	0.018	-10000	0	-0.14	2	2
IGF1R	0.017	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.023	0	-10000	0	-10000	0	0
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
apoptosis	-0.007	0.03	-10000	0	-10000	0	0
RhoA/GTP	-0.044	0.074	-10000	0	-0.17	134	134
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.047	0.046	-10000	0	-0.18	14	14
regulation of stress fiber formation	0.13	0.11	0.3	95	-0.21	1	96
E2/ERA-ERB (dimer)	0.023	0	-10000	0	-10000	0	0
KRAS	0.017	0.002	-10000	0	-10000	0	0
G13/GTP	0.021	0.015	-10000	0	-0.22	2	2
pseudopodium formation	-0.13	0.11	0.21	1	-0.3	95	96
E2/ER alpha (dimer)/PELP1	0.023	0	-10000	0	-10000	0	0
GRB2	0.017	0.002	-10000	0	-10000	0	0
GNG2	0	0	-10000	0	-10000	0	0
GNAO1	0.002	0.005	-10000	0	-10000	0	0
HRAS	0.016	0.019	-10000	0	-0.41	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.03	0.037	-10000	0	-0.16	8	8
E2/ER beta (dimer)	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.006	0.052	-10000	0	-0.2	2	2
mol:NADP	-0.03	0.037	-10000	0	-0.16	8	8
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
mol:IP3	0.03	0.018	-10000	0	-0.14	2	2
IGF-1R heterotetramer	0.017	0	-10000	0	-10000	0	0
PLCB1	0.028	0.019	-10000	0	-0.15	2	2
PLCB2	0.028	0.019	-10000	0	-0.15	2	2
IGF1	0.014	0.037	-10000	0	-0.41	4	4
mol:L-citrulline	-0.03	0.037	-10000	0	-0.16	8	8
RHOA	0.017	0.001	-10000	0	-10000	0	0
Gai/GDP	-0.42	0.15	-10000	0	-0.46	480	480
JNK cascade	0.013	0	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0.017	0	-10000	0	-10000	0	0
GNAQ	0.017	0	-10000	0	-10000	0	0
ESR1	0.017	0	-10000	0	-10000	0	0
Gq family/GDP/Gbeta gamma	0.026	0.026	-10000	0	-0.16	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.008	0.066	-10000	0	-0.48	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.058	0.074	-10000	0	-0.24	54	54
GNAZ	0.015	0.006	-10000	0	-10000	0	0
E2/ER alpha (dimer)	0.013	0	-10000	0	-10000	0	0
STRN	0.017	0	-10000	0	-10000	0	0
GNAL	0.017	0	-10000	0	-10000	0	0
PELP1	0.017	0	-10000	0	-10000	0	0
MAPK11	0.016	0	-10000	0	-10000	0	0
GNAI2	0.017	0.001	-10000	0	-10000	0	0
GNAI3	-0.036	0.14	-10000	0	-0.41	65	65
GNAI1	0.014	0.02	-10000	0	-0.41	1	1
HBEGF	-0.16	0.1	-10000	0	-0.22	321	321
cAMP biosynthetic process	0.02	0	-10000	0	-10000	0	0
SRC	-0.059	0.062	-10000	0	-0.19	66	66
PI3K	0.009	0.065	-10000	0	-0.28	25	25
GNB1	0.017	0.002	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.002	0.05	-10000	0	-0.21	2	2
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.05	0.06	-10000	0	-0.2	54	54
Gs family/GTP	0.025	0	-10000	0	-10000	0	0
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.03	0.11	-10000	0	-0.21	133	133
vasodilation	-0.03	0.036	-10000	0	-0.15	8	8
mol:DAG	0.03	0.018	-10000	0	-0.14	2	2
Gs family/GDP/Gbeta gamma	-0.02	0.034	-10000	0	-0.22	1	1
MSN	-0.14	0.11	0.21	1	-0.32	95	96
Gq family/GTP	0.028	0.02	-10000	0	-0.12	9	9
mol:PI-3-4-5-P3	0.005	0.03	-10000	0	-10000	0	0
NRAS	-0.094	0.19	-10000	0	-0.41	136	136
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.03	0.036	0.15	8	-10000	0	8
GRB2/SOS1	0.013	0.001	-10000	0	-10000	0	0
RhoA/GDP	0.002	0.053	-10000	0	-0.18	2	2
NOS3	-0.031	0.038	-10000	0	-0.16	8	8
GNA11	0.017	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.015	0.047	-10000	0	-0.2	9	9
E2/ER alpha (dimer)/PELP1/Src	-0.048	0.048	-10000	0	-0.19	14	14
ruffle organization	-0.13	0.11	0.21	1	-0.3	95	96
ROCK2	-0.018	0.083	0.22	1	-0.33	1	2
GNA14	0.015	0.026	-10000	0	-0.41	2	2
GNA15	0.011	0.049	-10000	0	-0.41	7	7
GNA13	0.015	0.026	-10000	0	-0.41	2	2
MMP9	-0.13	0.11	-10000	0	-0.25	224	224
MMP2	-0.15	0.12	-10000	0	-0.26	274	274

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.02	0	-9999	-10000	0	0
RGS9BP	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	-0.068	0.12	-9999	-0.24	184	184
mol:ADP	0	0	-9999	-10000	0	0
GNAT2	0.017	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.023	0.003	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.023	0	-9999	-10000	0	0
GRK7	0	0	-9999	-10000	0	0
CNGB3	0.017	0	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.061	0.11	-9999	-0.21	184	184
Cone PDE6	0.04	0.005	-9999	-10000	0	0
Cone Metarhodopsin II	0	0	-9999	-10000	0	0
Na + (4 Units)	-0.052	0.12	-9999	-0.21	184	184
GNAT2/GDP	0.03	0.003	-9999	-10000	0	0
GNB5	0.017	0.002	-9999	-10000	0	0
mol:GMP (4 units)	0.02	0	-9999	-10000	0	0
Cone Transducin	0.022	0	-9999	-10000	0	0
SLC24A2	0.017	0	-9999	-10000	0	0
GNB3/GNGT2	0.013	0	-9999	-10000	0	0
GNB3	0.017	0	-9999	-10000	0	0
GNAT2/GTP	0.013	0	-9999	-10000	0	0
CNGA3	-0.13	0.2	-9999	-0.41	184	184
ARR3	0.017	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.068	0.12	-9999	-0.24	184	184
mol:Pi	0.023	0.003	-9999	-10000	0	0
Cone CNG Channel	-0.036	0.11	-9999	-0.18	184	184
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.017	0	-9999	-10000	0	0
RGS9	0.017	0	-9999	-10000	0	0
PDE6C	0.017	0	-9999	-10000	0	0
GNGT2	0	0	-9999	-10000	0	0
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.017	0	-9999	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	0.011	0.096	-9999	-0.37	31	31
MKNK1	0.017	0	-9999	-10000	0	0
MAPK14	0.015	0.049	-9999	-0.17	31	31
ATF2/c-Jun	0.027	0.034	-9999	-0.39	1	1
MAPK11	0.017	0.042	-9999	-0.16	29	29
MITF	0.021	0.046	-9999	-0.16	33	33
MAPKAPK5	0.022	0.044	-9999	-0.15	31	31
KRT8	0.011	0.069	-9999	-0.19	53	53
MAPKAPK3	0.015	0.026	-9999	-0.41	2	2
MAPKAPK2	0.017	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.022	0.059	-9999	-0.21	31	31
CEBPB	0.018	0.06	-9999	-0.19	36	36
SLC9A1	0.022	0.044	-9999	-0.15	31	31
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.025	0.045	-9999	-0.15	32	32
p38alpha-beta/MNK1	0.033	0.048	-9999	-0.16	31	31
JUN	0.025	0.034	-9999	-0.39	1	1
PPARGC1A	0.021	0.048	-9999	-0.16	33	33
USF1	0.015	0.044	-9999	-0.16	31	31
RAB5/GDP/GDI1	0.021	0.033	-9999	-0.13	10	10
NOS2	0.015	0.044	-9999	-0.16	31	31
DDIT3	0.006	0.074	-9999	-0.18	67	67
RAB5A	0.017	0	-9999	-10000	0	0
HSPB1	0.016	0.05	-9999	-0.24	10	10
p38alpha-beta/HBP1	0.033	0.048	-9999	-0.16	31	31
CREB1	0.026	0.043	-9999	-0.14	31	31
RAB5/GDP	0.013	0	-9999	-10000	0	0
EIF4E	0.019	0.045	-9999	-0.2	7	7
RPS6KA4	0.022	0.044	-9999	-0.15	31	31
PLA2G4A	-0.043	0.12	-9999	-0.23	143	143
GDI1	0.023	0.039	-9999	-0.16	23	23
TP53	-0.005	0.079	-9999	-0.17	95	95
RPS6KA5	0.022	0.044	-9999	-0.15	31	31
ESR1	0.022	0.044	-9999	-0.15	31	31
HBP1	0.017	0	-9999	-10000	0	0
MEF2C	0.02	0.039	-9999	-0.16	22	22
MEF2A	0.022	0.044	-9999	-0.15	31	31
EIF4EBP1	-0.009	0.058	-9999	-0.19	31	31
KRT19	0.011	0.068	-9999	-0.18	55	55
ELK4	0.022	0.044	-9999	-0.15	31	31
ATF6	0.022	0.044	-9999	-0.15	31	31
ATF1	0.022	0.047	-9999	-0.16	31	31
p38alpha-beta/MAPKAPK2	0.033	0.048	-9999	-0.16	31	31
p38alpha-beta/MAPKAPK3	0.032	0.051	-9999	-0.16	33	33

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.009	0.001	-10000	0	-10000	0	0
GNB1/GNG2	0.018	0.029	-10000	0	-0.22	8	8
regulation of S phase of mitotic cell cycle	0.014	0.038	-10000	0	-0.13	32	32
GNAO1	0.002	0.005	-10000	0	-10000	0	0
HRAS	0.016	0.019	-10000	0	-0.41	1	1
SHBG/T-DHT	0.012	0	-10000	0	-10000	0	0
PELP1	0.017	0.001	-10000	0	-10000	0	0
AKT1	0.007	0.026	-10000	0	-0.29	4	4
MAP2K1	0.005	0.044	-10000	0	-0.18	10	10
T-DHT/AR	0.008	0.037	-10000	0	-0.29	8	8
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.005	127	127
GNAI2	0.017	0.001	-10000	0	-10000	0	0
GNAI3	-0.036	0.14	-10000	0	-0.41	65	65
GNAI1	0.014	0.02	-10000	0	-0.41	1	1
mol:GDP	-0.007	0.036	-10000	0	-0.14	31	31
cell proliferation	-0.011	0.096	-10000	0	-0.21	22	22
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
FOS	-0.046	0.15	-10000	0	-0.32	125	125
mol:Ca2+	0	0.006	-10000	0	-0.054	6	6
MAPK3	-0.003	0.073	-10000	0	-0.24	5	5
MAPK1	-0.011	0.07	-10000	0	-0.23	20	20
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
mol:IP3	-0.001	0.001	-10000	0	-0.003	127	127
cAMP biosynthetic process	0.001	0.005	-10000	0	-10000	0	0
GNG2	0	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	-0.001	0.001	-10000	0	-0.003	127	127
HRAS/GTP	0.018	0.037	-10000	0	-0.2	9	9
actin cytoskeleton reorganization	0.015	0.044	-10000	0	-0.18	24	24
SRC	0.017	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.001	-10000	0	-0.003	127	127
PI3K	0.01	0.055	-10000	0	-0.23	25	25
apoptosis	0.018	0.098	0.19	127	-10000	0	127
T-DHT/AR/PELP1	0.018	0.032	-10000	0	-0.24	8	8
HRAS/GDP	0.012	0.04	-10000	0	-0.17	14	14
CREB1	-0.019	0.1	-10000	0	-0.2	125	125
RAC1-CDC42/GTP	0.021	0.046	-10000	0	-0.19	24	24
AR	0.01	0.053	-10000	0	-0.41	8	8
GNB1	0.017	0.002	-10000	0	-10000	0	0
RAF1	0.009	0.04	-10000	0	-0.19	10	10
RAC1-CDC42/GDP	0.023	0.039	-10000	0	-0.19	8	8
T-DHT/AR/PELP1/Src	0.027	0.031	-10000	0	-0.22	8	8
MAP2K2	0.006	0.045	-10000	0	-0.18	10	10
T-DHT/AR/PELP1/Src/PI3K	0.014	0.038	-10000	0	-0.13	32	32
GNAZ	0.015	0.006	-10000	0	-10000	0	0
SHBG	0.017	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.059	0.063	-10000	0	-0.2	65	65
mol:T-DHT	0	0.001	-10000	0	-0.002	106	106
RAC1	0.017	0	-10000	0	-10000	0	0
GNRH1	0.009	0	-10000	0	-10000	0	0
Gi family/GTP	-0.001	0.021	-10000	0	-0.19	5	5
CDC42	0.017	0	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.032	-9999	-0.41	3	3
mol:S1P	0.001	0.001	-9999	-0.015	1	1
S1P1/S1P/Gi	-0.015	0.052	-9999	-0.15	62	62
GNAO1	0.002	0.005	-9999	-10000	0	0
S1P/S1P3/G12/G13	0.021	0.025	-9999	-0.21	6	6
AKT1	0	0.02	-9999	-0.16	7	7
AKT3	-0.059	0.065	-9999	-0.18	38	38
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.032	-9999	-0.41	3	3
GNAI2	0.018	0.002	-9999	-10000	0	0
GNAI3	-0.035	0.14	-9999	-0.41	65	65
GNAI1	0.015	0.02	-9999	-0.41	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.001	0.001	-9999	-0.022	1	1
S1PR2	0	0	-9999	-10000	0	0
EDG1	0.017	0.001	-9999	-10000	0	0
mol:Ca2+	0.002	0.016	-9999	-0.25	1	1
MAPK3	0.002	0.015	-9999	-0.23	1	1
MAPK1	0.002	0.015	-9999	-0.23	1	1
JAK2	-0.074	0.081	-9999	-0.19	114	114
CXCR4	-0.11	0.11	-9999	-0.21	272	272
FLT1	0.019	0.002	-9999	-10000	0	0
RhoA/GDP	0.013	0.001	-9999	-10000	0	0
Rac1/GDP	0.013	0	-9999	-10000	0	0
SRC	0.002	0.015	-9999	-0.23	1	1
S1P/S1P3/Gi	0.002	0.016	-9999	-0.25	1	1
RAC1	0.017	0	-9999	-10000	0	0
RhoA/GTP	-0.011	0.039	-9999	-0.16	13	13
VEGFA	-0.22	0.21	-9999	-0.41	287	287
S1P/S1P2/Gi	0.001	0.014	-9999	-0.19	1	1
VEGFR1 homodimer/VEGFA homodimer	-0.14	0.16	-9999	-0.28	287	287
RHOA	0.017	0.001	-9999	-10000	0	0
S1P/S1P3/Gq	0.02	0.02	-9999	-0.13	9	9
GNAQ	0.017	0	-9999	-10000	0	0
GNAZ	0.016	0.006	-9999	-10000	0	0
G12/G13	0.022	0.033	-9999	-0.28	6	6
GNA14	0.015	0.026	-9999	-0.41	2	2
GNA15	0.011	0.049	-9999	-0.41	7	7
GNA12	0.014	0.037	-9999	-0.41	4	4
GNA13	0.015	0.026	-9999	-0.41	2	2
GNA11	0.017	0	-9999	-10000	0	0
Rac1/GTP	-0.011	0.039	-9999	-0.16	13	13

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.017	0	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.003	-10000	0	-10000	0	0
DOCK1	0.017	0	-10000	0	-10000	0	0
ITGA4	0.013	0.042	-10000	0	-0.41	5	5
RAC1	0.017	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.022	0.041	-10000	0	-0.38	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.017	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.032	0.026	-10000	0	-0.24	5	5
alpha4/beta7 Integrin/Paxillin	0.032	0.033	-10000	0	-0.29	5	5
lamellipodium assembly	0.018	0.05	-10000	0	-0.26	1	1
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
PI3K	0.009	0.065	-10000	0	-0.28	25	25
ARF6	0.017	0	-10000	0	-10000	0	0
TLN1	-0.02	0.12	-10000	0	-0.41	46	46
PXN	0.018	0	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
ARF6/GTP	0.04	0.021	-10000	0	-0.17	5	5
cell adhesion	0.021	0.07	-10000	0	-0.19	50	50
CRKL/CBL	0.025	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.033	0.024	-10000	0	-0.21	5	5
ITGB1	0.017	0	-10000	0	-10000	0	0
ITGB7	0.015	0.026	-10000	0	-0.41	2	2
ARF6/GDP	0.013	0.003	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.11	0.11	-10000	0	-0.19	353	353
p130Cas/Crk/Dock1	0.023	0	-10000	0	-10000	0	0
VCAM1	-0.27	0.2	-10000	0	-0.41	351	351
alpha4/beta1 Integrin/Paxillin/Talin	0.022	0.071	-10000	0	-0.2	50	50
alpha4/beta1 Integrin/Paxillin/GIT1	0.042	0.023	-10000	0	-0.19	5	5
BCAR1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.041	0.023	0.19	5	-10000	0	5
CBL	0.017	0	-10000	0	-10000	0	0
PRKACA	0.017	0	-10000	0	-10000	0	0
GIT1	0.017	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.022	0.071	-10000	0	-0.2	50	50
Rac1/GTP	0.018	0.053	-10000	0	-0.28	1	1

×

Arf6 downstream pathway

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
PLAUR	-0.006	0.12	-10000	0	-0.38	47	47
regulation of axonogenesis	-0.013	0.029	0.13	3	-10000	0	3
myoblast fusion	-0.002	0.062	0.2	47	-10000	0	47
mol:GTP	0.001	0.041	-10000	0	-0.13	47	47
regulation of calcium-dependent cell-cell adhesion	-0.016	0.041	0.12	45	-10000	0	45
ARF1/GTP	0.014	0.033	-10000	0	-10000	0	0
mol:GM1	0	0.03	-10000	0	-0.095	47	47
mol:Choline	0.011	0.03	-10000	0	-0.22	2	2
lamellipodium assembly	0.001	0.063	-10000	0	-0.2	47	47
MAPK3	0.007	0.059	-10000	0	-0.18	47	47
ARF6/GTP/NME1/Tiam1	0.016	0.042	-10000	0	-0.12	45	45
ARF1	0.017	0.001	-10000	0	-10000	0	0
ARF6/GDP	0.002	0.063	-10000	0	-0.2	47	47
ARF1/GDP	0.01	0.058	-10000	0	-0.18	47	47
ARF6	0.011	0.027	-10000	0	-10000	0	0
RAB11A	0.017	0.001	-10000	0	-10000	0	0
TIAM1	0.015	0.008	-10000	0	-10000	0	0
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.007	0.059	-10000	0	-0.18	47	47
actin filament bundle formation	-0.012	0.059	0.18	47	-10000	0	47
KALRN	0.003	0.049	-10000	0	-0.16	47	47
RAB11FIP3/RAB11A	0.025	0.001	-10000	0	-10000	0	0
RhoA/GDP	0.013	0.06	-10000	0	-0.18	47	47
NME1	-0.001	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.06	-10000	0	-0.18	47	47
substrate adhesion-dependent cell spreading	0.001	0.041	-10000	0	-0.13	47	47
cortical actin cytoskeleton organization	0.001	0.064	-10000	0	-0.2	47	47
RAC1	0.017	0	-10000	0	-10000	0	0
liver development	0.001	0.041	-10000	0	-0.13	47	47
ARF6/GTP	0.001	0.041	-10000	0	-0.13	47	47
RhoA/GTP	0.014	0.033	-10000	0	-10000	0	0
mol:GDP	-0.001	0.062	-10000	0	-0.2	47	47
ARF6/GTP/RAB11FIP3/RAB11A	0.025	0.031	-10000	0	-10000	0	0
RHOA	0.017	0.001	-10000	0	-10000	0	0
PLD1	0.009	0.035	-10000	0	-0.097	49	49
RAB11FIP3	0.017	0	-10000	0	-10000	0	0
tube morphogenesis	0.001	0.063	-10000	0	-0.2	47	47
ruffle organization	0.013	0.029	-10000	0	-0.13	3	3
regulation of epithelial cell migration	0.001	0.041	-10000	0	-0.13	47	47
PLD2	0.01	0.031	-10000	0	-10000	0	0
PIP5K1A	0.013	0.029	-10000	0	-0.13	3	3
mol:Phosphatidic acid	0.011	0.03	-10000	0	-0.22	2	2
Rac1/GTP	0.001	0.064	-10000	0	-0.2	47	47

×

IL6-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.038	0.16	-10000	0	-0.42	41	41
CRP	-0.038	0.16	-10000	0	-0.42	41	41
cell cycle arrest	-0.059	0.17	-10000	0	-0.44	56	56
TIMP1	-0.2	0.22	-10000	0	-0.46	147	147
IL6ST	0.016	0.008	-10000	0	-10000	0	0
Rac1/GDP	0.007	0.076	-10000	0	-0.21	26	26
AP1	-0.035	0.1	-10000	0	-0.23	67	67
GAB2	0.017	0.019	-10000	0	-0.41	1	1
TNFSF11	-0.038	0.16	-10000	0	-0.42	41	41
HSP90B1	0.014	0.055	-10000	0	-0.39	2	2
GAB1	0.014	0.037	-10000	0	-0.41	4	4
MAPK14	0.019	0.048	-10000	0	-10000	0	0
AKT1	0.028	0.04	-10000	0	-0.2	7	7
FOXO1	0.025	0.05	-10000	0	-0.24	7	7
MAP2K6	0.012	0.056	-10000	0	-0.17	13	13
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.001	0.097	-10000	0	-0.3	14	14
MITF	0.004	0.067	-10000	0	-0.2	29	29
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.016	0.019	-10000	0	-0.41	1	1
A2M	-0.01	0.11	-10000	0	-0.44	30	30
CEBPB	0.015	0.062	-10000	0	-0.41	11	11
GRB2/SOS1/GAB family/SHP2	0.009	0.052	0.14	1	-0.28	4	5
STAT3	-0.061	0.18	-10000	0	-0.45	56	56
STAT1	0.003	0.046	-10000	0	-0.24	13	13
CEBPD	-0.038	0.16	-10000	0	-0.42	41	41
PIK3CA	-0.002	0.091	-10000	0	-0.41	25	25
PI3K	0.011	0.065	-10000	0	-0.28	25	25
JUN	0.016	0.019	-10000	0	-0.41	1	1
PIAS3/MITF	0.011	0.068	-10000	0	-0.19	28	28
MAPK11	0.02	0.047	-10000	0	-10000	0	0
STAT3 (dimer)/FOXO1	-0.037	0.16	-10000	0	-0.4	44	44
GRB2/SOS1/GAB family	0.007	0.077	-10000	0	-0.21	24	24
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.008	0.085	-10000	0	-0.16	108	108
GRB2	0.017	0.003	-10000	0	-10000	0	0
JAK2	0.017	0	-10000	0	-10000	0	0
LBP	-0.027	0.15	-10000	0	-0.4	36	36
PIK3R1	0.017	0.005	-10000	0	-10000	0	0
JAK1	0.017	0.003	-10000	0	-10000	0	0
MYC	-0.084	0.22	-10000	0	-0.46	100	100
FGG	-0.042	0.17	-10000	0	-0.45	43	43
macrophage differentiation	-0.059	0.17	-10000	0	-0.44	56	56
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.025	0.079	-10000	0	-0.21	52	52
JUNB	-0.04	0.16	-10000	0	-0.44	42	42
FOS	-0.085	0.18	-10000	0	-0.41	125	125
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.002	0.07	-10000	0	-0.2	33	33
STAT1/PIAS1	-0.005	0.086	-10000	0	-0.23	31	31
GRB2/SOS1/GAB family/SHP2/PI3K	0.024	0.033	-10000	0	-0.23	2	2
STAT3 (dimer)	-0.061	0.18	-10000	0	-0.44	57	57
PRKCD	-0.008	0.12	-10000	0	-0.36	15	15
IL6R	0.018	0.003	-10000	0	-10000	0	0
SOCS3	0.027	0.04	-10000	0	-10000	0	0
gp130 (dimer)/JAK1/JAK1/LMO4	0.033	0.018	-10000	0	-10000	0	0
Rac1/GTP	0.003	0.084	-10000	0	-0.23	26	26
HCK	-0.053	0.16	-10000	0	-0.41	86	86
MAPKKK cascade	0.014	0.052	-10000	0	-0.35	4	4
bone resorption	-0.036	0.16	-10000	0	-0.4	41	41
IRF1	-0.061	0.2	-10000	0	-0.47	76	76
mol:GDP	0.003	0.07	-10000	0	-0.2	28	28
SOS1	0.001	0.003	-10000	0	-10000	0	0
VAV1	0.003	0.071	-10000	0	-0.2	28	28
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.025	0.047	-10000	0	-0.25	2	2
PTPN11	0.011	0.017	-10000	0	-10000	0	0
IL6/IL6RA	-0.006	0.096	-10000	0	-0.29	52	52
gp130 (dimer)/TYK2/TYK2/LMO4	0.033	0.016	-10000	0	-0.23	1	1
gp130 (dimer)/JAK2/JAK2/LMO4	0.034	0.012	-10000	0	-10000	0	0
IL6	-0.026	0.13	-10000	0	-0.42	52	52
PIAS3	0.015	0.026	-10000	0	-0.41	2	2
PTPRE	0.017	0.01	-10000	0	-10000	0	0
PIAS1	0.017	0	-10000	0	-10000	0	0
RAC1	0.017	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.004	0.055	-10000	0	-0.15	51	51
LMO4	0.016	0.008	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.044	0.17	-10000	0	-0.46	41	41
MCL1	0.03	0.049	-10000	0	-0.38	4	4

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.01	0.022	-10000	0	-0.24	4	4
RAS family/GTP	-0.034	0.1	-10000	0	-0.19	133	133
NFATC4	0.015	0.04	-10000	0	-0.13	3	3
ERBB2IP	-0.008	0.1	-10000	0	-0.41	31	31
HSP90 (dimer)	0.017	0	-10000	0	-10000	0	0
mammary gland morphogenesis	0.019	0.054	0.15	18	-0.15	34	52
JUN	0.015	0.047	-10000	0	-10000	0	0
HRAS	0.016	0.019	-10000	0	-0.41	1	1
DOCK7	0.009	0.046	-10000	0	-0.14	34	34
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.005	0.085	0.16	17	-0.2	66	83
AKT1	0.007	0.026	-10000	0	-0.29	4	4
BAD	0.01	0.022	-10000	0	-0.24	4	4
MAPK10	0.01	0.026	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.003	1	1
ErbB2/ErbB3/neuregulin 1 beta	0.021	0.058	0.16	18	-0.16	34	52
RAF1	-0.032	0.099	-10000	0	-0.18	134	134
ErbB2/ErbB3/neuregulin 2	0.015	0.066	0.16	30	-0.21	32	62
STAT3	0.019	0.027	-10000	0	-10000	0	0
cell migration	0.011	0.029	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-10000	0	-0.003	34	34
cell proliferation	-0.026	0.12	-10000	0	-0.36	13	13
FOS	-0.039	0.13	-10000	0	-0.24	121	121
NRAS	-0.094	0.19	-10000	0	-0.41	136	136
mol:Ca2+	0.019	0.054	0.15	18	-0.15	34	52
MAPK3	-0.017	0.098	-10000	0	-0.33	8	8
MAPK1	-0.027	0.11	-10000	0	-0.39	15	15
JAK2	0.016	0.047	-10000	0	-0.16	4	4
NF2	0.012	0.007	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.004	0.061	-10000	0	-0.15	75	75
NRG1	0.017	0.001	-10000	0	-10000	0	0
GRB2/SOS1	0.013	0.001	-10000	0	-10000	0	0
MAPK8	0.022	0.042	-10000	0	-0.13	5	5
MAPK9	0.019	0.029	-10000	0	-10000	0	0
ERBB2	0.009	0.052	0.22	31	-10000	0	31
ERBB3	-0.01	0.1	-10000	0	-0.41	32	32
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
RAC1	0.017	0	-10000	0	-10000	0	0
apoptosis	-0.007	0.022	0.23	4	-10000	0	4
STAT3 (dimer)	0.019	0.027	-10000	0	-10000	0	0
RNF41	0.012	0.02	-10000	0	-0.21	4	4
FRAP1	0.01	0.024	-10000	0	-0.24	5	5
RAC1-CDC42/GTP	-0.006	0.027	-10000	0	-0.12	4	4
ErbB2/ErbB2/HSP90 (dimer)	0.022	0.035	0.16	31	-10000	0	31
CHRNA1	-0.011	0.085	-10000	0	-0.25	13	13
myelination	0.021	0.042	-10000	0	-10000	0	0
PPP3CB	0.015	0.045	-10000	0	-0.15	4	4
KRAS	0.017	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.014	0.058	-10000	0	-0.18	9	9
NRG2	0.017	0	-10000	0	-10000	0	0
mol:GDP	-0.003	0.061	-10000	0	-0.15	75	75
SOS1	0	0	-10000	0	-10000	0	0
MAP2K2	-0.026	0.095	-10000	0	-0.23	46	46
SRC	0.017	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.016	0.047	-10000	0	-0.16	4	4
MAP2K1	-0.028	0.12	-10000	0	-0.41	20	20
heart morphogenesis	0.019	0.054	0.15	18	-0.15	34	52
RAS family/GDP	-0.032	0.11	-10000	0	-0.2	133	133
GRB2	0.017	0.002	-10000	0	-10000	0	0
PRKACA	0.01	0.006	-10000	0	-10000	0	0
CHRNE	0.01	0.013	-10000	0	-10000	0	0
HSP90AA1	0.017	0	-10000	0	-10000	0	0
activation of caspase activity	-0.007	0.026	0.29	4	-10000	0	4
nervous system development	0.019	0.054	0.15	18	-0.15	34	52
CDC42	0.017	0	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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
CCL2	-0.026	0.29	-9999	-0.55	87	87
IL23A	0.027	0.23	-9999	-0.57	41	41
NF kappa B1 p50/RelA/I kappa B alpha	0.033	0.23	-9999	-0.56	41	41
positive regulation of T cell mediated cytotoxicity	0.027	0.24	-9999	-0.6	41	41
ITGA3	0.025	0.24	-9999	-0.58	41	41
IL17F	0.025	0.18	-9999	-0.43	34	34
IL12B	0.025	0.029	-9999	-10000	0	0
STAT1 (dimer)	0.017	0.23	-9999	-0.58	41	41
CD4	0.025	0.24	-9999	-0.58	46	46
IL23	0.025	0.23	-9999	-0.68	20	20
IL23R	0.019	0.063	-9999	-0.12	40	40
IL1B	0.026	0.24	-9999	-0.58	44	44
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	0.032	0.22	-9999	-0.55	40	40
TYK2	0.02	0.027	-9999	-0.39	1	1
STAT4	0.01	0.008	-9999	-10000	0	0
STAT3	0.009	0.059	-9999	-0.41	10	10
IL18RAP	0.018	0.002	-9999	-10000	0	0
IL12RB1	0.021	0.021	-9999	-10000	0	0
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
IL12Rbeta1/TYK2	0.028	0.029	-9999	-0.26	1	1
IL23R/JAK2	0.034	0.086	-9999	-0.17	8	8
positive regulation of chronic inflammatory response	0.027	0.24	-9999	-0.6	41	41
natural killer cell activation	-0.001	0.006	-9999	-10000	0	0
JAK2	0.025	0.029	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
NFKB1	0.015	0.038	-9999	-0.42	4	4
RELA	0.018	0.003	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.026	0.22	-9999	-0.65	20	20
ALOX12B	0.032	0.22	-9999	-0.55	40	40
CXCL1	0.022	0.25	-9999	-0.61	47	47
T cell proliferation	0.027	0.24	-9999	-0.6	41	41
NFKBIA	0.017	0.019	-9999	-0.42	1	1
IL17A	0.046	0.16	-9999	-0.38	22	22
PI3K	0.024	0.22	-9999	-0.57	33	33
IFNG	0.012	0.017	-9999	-0.044	17	17
STAT3 (dimer)	0.027	0.22	-9999	-0.56	34	34
IL18R1	0.018	0.002	-9999	-10000	0	0
IL23/IL23R/JAK2/TYK2/SOCS3	0.039	0.16	-9999	-0.4	18	18
IL18/IL18R	0.016	0.075	-9999	-0.23	45	45
macrophage activation	0.001	0.014	-9999	-0.037	19	19
TNF	0.028	0.23	-9999	-0.57	41	41
STAT3/STAT4	-0.017	0.2	-9999	-0.57	37	37
STAT4 (dimer)	-0.019	0.2	-9999	-0.57	38	38
IL18	-0.019	0.12	-9999	-0.41	45	45
IL19	0.032	0.22	-9999	-0.55	40	40
STAT5A (dimer)	0.023	0.23	-9999	-0.58	40	40
STAT1	0.002	0.078	-9999	-0.41	18	18
SOCS3	0.017	0	-9999	-10000	0	0
CXCL9	0.009	0.25	-9999	-0.56	58	58
MPO	0.032	0.22	-9999	-0.55	40	40
positive regulation of humoral immune response	0.027	0.24	-9999	-0.6	41	41
IL23/IL23R/JAK2/TYK2	0.026	0.24	-9999	-0.6	41	41
IL6	0.014	0.26	-9999	-0.68	40	40
STAT5A	0.016	0.019	-9999	-0.41	1	1
IL2	0.019	0.004	-9999	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	-0.001	0.006	-9999	-10000	0	0
CD3E	0.032	0.22	-9999	-0.55	40	40
keratinocyte proliferation	0.027	0.24	-9999	-0.6	41	41
NOS2	0.026	0.22	-9999	-0.55	40	40

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.011	0.049	-10000	0	-0.41	7	7
mol:Halofuginone	0.004	0.015	-10000	0	-0.17	4	4
ITGA1	0	0	-10000	0	-10000	0	0
CDKN1A	0.009	0.052	-10000	0	-0.14	54	54
PRL-3/alpha Tubulin	0.007	0.073	-10000	0	-0.28	31	31
mol:Ca2+	0.009	0.052	0.22	31	-10000	0	31
AGT	0.016	0.005	-10000	0	-10000	0	0
CCNA2	-0.038	0.1	-10000	0	-0.2	148	148
TUBA1B	0.017	0	-10000	0	-10000	0	0
EGR1	0.011	0.051	-10000	0	-0.28	16	16
CDK2/Cyclin E1	0.012	0.076	-10000	0	-0.28	13	13
MAPK3	0	0.071	-10000	0	-0.28	31	31
PRL-2 /Rab GGTase beta	0.025	0.001	-10000	0	-10000	0	0
MAPK1	-0.001	0.071	-10000	0	-0.28	31	31
PTP4A1	0.015	0.044	-10000	0	-0.21	19	19
PTP4A3	-0.008	0.1	-10000	0	-0.41	31	31
PTP4A2	0.017	0.001	-10000	0	-10000	0	0
ITGB1	0	0.071	-10000	0	-0.28	31	31
SRC	0.017	0	-10000	0	-10000	0	0
RAC1	0.015	0.043	-10000	0	-0.14	32	32
Rab GGTase beta/Rab GGTase alpha	0.025	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.024	0.043	-10000	0	-0.19	20	20
RABGGTA	0.017	0	-10000	0	-10000	0	0
BCAR1	0.002	0.051	0.21	31	-10000	0	31
RHOC	-0.032	0.081	-10000	0	-0.14	184	184
RHOA	0.015	0.043	-10000	0	-0.14	32	32
cell motility	-0.004	0.055	-10000	0	-0.21	13	13
PRL-1/alpha Tubulin	0.024	0.043	-10000	0	-0.19	19	19
PRL-3/alpha1 Integrin	-0.005	0.071	-10000	0	-0.29	31	31
ROCK1	-0.004	0.055	-10000	0	-0.2	14	14
RABGGTB	0.017	0	-10000	0	-10000	0	0
CDK2	-0.005	0.095	-10000	0	-0.41	27	27
mitosis	0.015	0.044	-10000	0	-0.21	19	19
ATF5	0.016	0.019	-10000	0	-0.41	1	1

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.032	-10000	0	-0.41	3	3
Jak2/Leptin Receptor	0.017	0.034	-10000	0	-0.16	3	3
PTP1B/AKT1	-0.002	0.048	-10000	0	-0.18	10	10
FYN	0.015	0.027	-10000	0	-0.41	2	2
p210 bcr-abl/PTP1B	-0.01	0.046	-10000	0	-0.13	41	41
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
EGF/EGFR	-0.055	0.1	-10000	0	-0.18	197	197
CSF1	0.017	0	-10000	0	-10000	0	0
AKT1	0.014	0.037	-10000	0	-0.41	4	4
INSR	0.017	0	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.004	0.049	-10000	0	-0.2	6	6
Insulin Receptor/Insulin	0.018	0.041	-10000	0	-0.18	6	6
HCK	-0.053	0.16	-10000	0	-0.41	86	86
CRK	0.017	0	-10000	0	-10000	0	0
TYK2	-0.007	0.044	-10000	0	-0.18	5	5
EGF	0.013	0.027	-10000	0	-0.41	2	2
YES1	-0.047	0.15	-10000	0	-0.41	79	79
CAV1	-0.069	0.068	-10000	0	-0.16	150	150
TXN	0.015	0.002	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.003	0.051	-10000	0	-0.18	7	7
cell migration	0.01	0.046	0.13	41	-10000	0	41
STAT3	0.009	0.059	-10000	0	-0.41	10	10
PRLR	0.02	0	-10000	0	-10000	0	0
ITGA2B	0.016	0	-10000	0	-10000	0	0
CSF1R	-0.016	0.12	-10000	0	-0.41	41	41
Prolactin Receptor/Prolactin	0.029	0.033	-10000	0	-0.28	6	6
FGR	0.003	0.076	-10000	0	-0.41	17	17
PTP1B/p130 Cas	-0.01	0.043	-10000	0	-0.12	42	42
Crk/p130 Cas	-0.003	0.044	-10000	0	-0.14	7	7
DOK1	0.003	0.04	-10000	0	-0.16	4	4
JAK2	0.011	0.03	-10000	0	-10000	0	0
Jak2/Leptin Receptor/Leptin	0.022	0.051	-10000	0	-0.23	6	6
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
PTPN1	-0.01	0.046	-10000	0	-0.13	42	42
LYN	-0.035	0.14	-10000	0	-0.41	64	64
CDH2	0.014	0.032	-10000	0	-0.41	3	3
SRC	0.014	0.019	-10000	0	-10000	0	0
ITGB3	0.016	0	-10000	0	-10000	0	0
CAT1/PTP1B	-0.027	0.094	-10000	0	-0.22	76	76
CAPN1	0.016	0.001	-10000	0	-10000	0	0
CSK	0.017	0	-10000	0	-10000	0	0
PI3K	0.015	0.057	-10000	0	-0.18	28	28
mol:H2O2	-0.002	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	0.022	0.049	-10000	0	-0.21	8	8
negative regulation of transcription	0.011	0.03	-10000	0	-10000	0	0
FCGR2A	-0.2	0.22	-10000	0	-0.41	265	265
FER	0.015	0.002	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.023	0.001	-10000	0	-10000	0	0
BLK	0.017	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.011	0.077	-10000	0	-0.24	46	46
RHOA	0.016	0.001	-10000	0	-10000	0	0
LEPR	0.014	0.032	-10000	0	-0.41	3	3
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.017	0.002	-10000	0	-10000	0	0
mol:NADPH	-0.002	0.002	-10000	0	-10000	0	0
TRPV6	-0.021	0.1	-10000	0	-0.23	75	75
PRL	0.015	0.045	-10000	0	-0.41	6	6
SOCS3	0.009	0.009	-10000	0	-10000	0	0
SPRY2	0.009	0.053	-10000	0	-0.42	8	8
Insulin Receptor/Insulin/IRS1	0.033	0.026	-10000	0	-0.24	5	5
CSF1/CSF1R	-0.011	0.068	-10000	0	-0.18	45	45
Ras protein signal transduction	0.013	0.031	0.29	5	-10000	0	5
IRS1	0.013	0.042	-10000	0	-0.41	5	5
INS	0.017	0	-10000	0	-10000	0	0
LEP	0.017	0	-10000	0	-10000	0	0
STAT5B	0.003	0.039	-10000	0	-0.16	2	2
STAT5A	0.003	0.039	-10000	0	-0.16	2	2
GRB2	0.017	0.002	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.004	0.048	-10000	0	-0.18	7	7
CSN2	0.023	0.015	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
LAT	-0.065	0.081	-10000	0	-0.2	27	27
YBX1	0.015	0.064	-10000	0	-0.4	12	12
LCK	0.014	0.037	-10000	0	-0.41	4	4
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
NOX4	-0.042	0.15	-10000	0	-0.42	70	70

×

TRAIL signaling pathway

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
TNFSF10	-0.02	0.12	-9999	-0.41	46	46
positive regulation of NF-kappaB transcription factor activity	-0.002	0.087	-9999	-0.28	46	46
MAP2K4	0.018	0.043	-9999	-0.19	5	5
IKBKB	0.017	0	-9999	-10000	0	0
TNFRSF10B	0.011	0.052	-9999	-0.41	8	8
TNFRSF10A	0	0	-9999	-10000	0	0
SMPD1	0.002	0.044	-9999	-0.13	52	52
IKBKG	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.017	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.006	0.097	-9999	-0.3	52	52
TRAIL/TRAILR3	-0.002	0.088	-9999	-0.28	46	46
TRAIL/TRAILR1	-0.014	0.085	-9999	-0.29	46	46
TRAIL/TRAILR4	-0.002	0.088	-9999	-0.28	46	46
TRAIL/TRAILR1/DAP3/GTP	0.001	0.067	-9999	-0.22	46	46
IKK complex	0.021	0.037	-9999	-0.15	6	6
RIPK1	0.01	0.056	-9999	-0.41	9	9
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.013	0	-9999	-10000	0	0
MAPK3	-0.009	0.085	-9999	-0.28	46	46
MAP3K1	0.016	0.048	-9999	-0.12	54	54
TRAILR4 (trimer)	0.017	0	-9999	-10000	0	0
TRADD	0.017	0	-9999	-10000	0	0
TRAILR1 (trimer)	0	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.011	0.049	-9999	-0.13	54	54
CFLAR	0.013	0.042	-9999	-0.41	5	5
MAPK1	-0.006	0.081	-9999	-0.28	41	41
TRAIL/TRAILR1/FADD/TRADD/RIP	0.016	0.076	-9999	-0.21	54	54
mol:ceramide	0.002	0.044	-9999	-0.13	52	52
FADD	0.015	0.026	-9999	-0.41	2	2
MAPK8	0.02	0.041	-9999	-0.19	4	4
TRAF2	0.017	0	-9999	-10000	0	0
TRAILR3 (trimer)	0.017	0	-9999	-10000	0	0
CHUK	0.016	0.019	-9999	-0.41	1	1
TRAIL/TRAILR1/FADD	0	0.077	-9999	-0.24	47	47
DAP3	0.017	0	-9999	-10000	0	0
CASP10	-0.006	0.064	-9999	-0.2	47	47
JNK cascade	-0.002	0.087	-9999	-0.28	46	46
TRAIL (trimer)	-0.02	0.12	-9999	-0.41	46	46
TNFRSF10C	0.017	0	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	0.01	0.067	-9999	-0.2	47	47
TRAIL/TRAILR2/FADD	0.007	0.086	-9999	-0.25	53	53
cell death	0.002	0.044	-9999	-0.13	52	52
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.014	0.054	-9999	-0.13	60	60
TRAILR2 (trimer)	0.011	0.052	-9999	-0.41	8	8
CASP8	0.01	0.036	-9999	-0.23	6	6
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.022	0.084	-9999	-0.21	60	60

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.017	0	-9999	-10000	0	0
Caspase 8 (4 units)	0.018	0.068	-9999	-0.27	13	13
NEF	0.004	0	-9999	-10000	0	0
NFKBIA	0.012	0.032	-9999	-0.5	1	1
BIRC3	0.002	0.11	-9999	-0.39	36	36
CYCS	0.012	0.054	-9999	-0.2	13	13
RIPK1	0.01	0.056	-9999	-0.41	9	9
CD247	0.019	0.026	-9999	-0.41	2	2
MAP2K7	0.02	0.044	-9999	-0.22	1	1
protein ubiquitination	0.009	0.056	-9999	-0.18	8	8
CRADD	0.017	0	-9999	-10000	0	0
DAXX	0.016	0.019	-9999	-0.41	1	1
FAS	-0.038	0.14	-9999	-0.41	68	68
BID	0.01	0.057	-9999	-0.21	13	13
NF-kappa-B/RelA/I kappa B alpha	0.026	0.07	-9999	-0.23	36	36
TRADD	0.017	0	-9999	-10000	0	0
MAP3K5	0.017	0.001	-9999	-10000	0	0
CFLAR	0.013	0.042	-9999	-0.41	5	5
FADD	0.015	0.026	-9999	-0.41	2	2
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.026	0.071	-9999	-0.23	36	36
MAPK8	0.023	0.042	-9999	-0.21	1	1
APAF1	0.017	0	-9999	-10000	0	0
TRAF1	0.016	0.019	-9999	-0.41	1	1
TRAF2	0.017	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.011	0.055	-9999	-0.24	6	6
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.004	0.064	-9999	-0.17	24	24
CHUK	0.009	0.058	-9999	-0.19	8	8
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.014	0.092	-9999	-0.21	75	75
TCRz/NEF	0.021	0.019	-9999	-0.28	2	2
TNF	0.015	0.026	-9999	-0.41	2	2
FASLG	0.022	0.015	-9999	-0.23	2	2
NFKB1	0.01	0.045	-9999	-0.43	4	4
TNFR1A/BAG4/TNF-alpha	-0.06	0.13	-9999	-0.24	185	185
CASP6	0.022	0.069	-9999	-0.3	9	9
CASP7	0.007	0.11	-9999	-0.28	51	51
RELA	0.013	0.023	-9999	-10000	0	0
CASP2	0.016	0.019	-9999	-0.41	1	1
CASP3	-0.003	0.11	-9999	-0.28	49	49
TNFRSF1A	-0.13	0.2	-9999	-0.41	183	183
TNFR1A/BAG4	-0.082	0.15	-9999	-0.28	183	183
CASP8	0.009	0.059	-9999	-0.41	10	10
CASP9	0.014	0.037	-9999	-0.41	4	4
MAP3K14	0.006	0.062	-9999	-0.16	26	26
APAF-1/Caspase 9	0.012	0.089	-9999	-0.28	37	37
BCL2	0.025	0.04	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.022	0.14	-10000	0	-0.39	65	65
AES	0.028	0.021	-10000	0	-10000	0	0
FBXW11	0.017	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.019	0.044	-10000	0	-0.28	11	11
SMAD4	-0.085	0.18	-10000	0	-0.41	126	126
DKK2	0.009	0.059	-10000	0	-0.41	10	10
TLE1	0.028	0.02	-10000	0	-10000	0	0
MACF1	0.018	0.001	-10000	0	-10000	0	0
CTNNB1	0.065	0.034	0.22	1	-0.13	3	4
WIF1	0.002	0.006	-10000	0	-10000	0	0
beta catenin/RanBP3	0.092	0.13	0.26	188	-10000	0	188
KREMEN2	0.017	0	-10000	0	-10000	0	0
DKK1	-0.077	0.18	-10000	0	-0.41	116	116
beta catenin/beta TrCP1	0.072	0.033	0.22	1	-0.13	1	2
FZD1	0.009	0.059	-10000	0	-0.41	10	10
AXIN2	-0.043	0.066	-10000	0	-0.13	169	169
AXIN1	0.018	0	-10000	0	-10000	0	0
RAN	0.017	0.002	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.046	0.036	-10000	0	-0.31	4	4
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.042	0.065	-10000	0	-0.18	2	2
Axin1/APC/GSK3	0.059	0.02	0.19	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.056	0.036	-10000	0	-0.14	1	1
HNF1A	0.029	0.021	-10000	0	-10000	0	0
CTBP1	0.029	0.022	-10000	0	-10000	0	0
MYC	-0.11	0.19	-10000	0	-0.43	137	137
RANBP3	0.018	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.03	0.039	-10000	0	-0.24	11	11
NKD1	0	0	-10000	0	-10000	0	0
TCF4	0.028	0.022	-10000	0	-10000	0	0
TCF3	0.029	0.021	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.038	0.036	-10000	0	-0.21	11	11
Ran/GTP	0.014	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.1	0.14	0.28	169	-0.18	1	170
LEF1	0.027	0.039	-10000	0	-0.39	3	3
DVL1	0.004	0.012	-10000	0	-10000	0	0
CSNK2A1	0.017	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.039	0.053	-10000	0	-0.18	2	2
DKK1/LRP6/Kremen 2	-0.024	0.11	-10000	0	-0.23	117	117
LRP6	0.016	0.019	-10000	0	-0.41	1	1
CSNK1A1	0.031	0.024	-10000	0	-10000	0	0
NLK	0.015	0.005	-10000	0	-10000	0	0
CCND1	-0.088	0.18	-10000	0	-0.44	99	99
WNT1	0.017	0.001	-10000	0	-10000	0	0
GSK3A	0.017	0.001	-10000	0	-10000	0	0
GSK3B	0.017	0.002	-10000	0	-10000	0	0
FRAT1	0.016	0.019	-10000	0	-0.41	1	1
PPP2R5D	0.007	0.016	-10000	0	-10000	0	0
APC	0.021	0.031	-10000	0	-0.19	11	11
WNT1/LRP6/FZD1	0.003	0.012	-10000	0	-0.12	2	2
CREBBP	0.029	0.021	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.025	0.029	-9999	-0.15	8	8
KLHL20	0.004	0.065	-9999	-0.13	95	95
CYFIP2	0.01	0.008	-9999	-10000	0	0
Rac1/GDP	0.033	0.027	-9999	-10000	0	0
ENAH	0.016	0.053	-9999	-0.18	33	33
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	0	92	92
RAP1A	0.017	0	-9999	-10000	0	0
CTNNB1	0.017	0	-9999	-10000	0	0
CDC42/GTP	0	0.02	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.015	0.032	-9999	-0.089	76	76
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.039	0.037	-9999	-0.23	9	9
RAPGEF1	0.027	0.026	-9999	-10000	0	0
CTNND1	0.009	0.059	-9999	-0.41	10	10
regulation of calcium-dependent cell-cell adhesion	0.024	0.03	-9999	-0.16	8	8
CRK	0.026	0.028	-9999	-0.15	8	8
E-cadherin/gamma catenin/alpha catenin	0.023	0.064	-9999	-0.29	19	19
alphaE/beta7 Integrin	0.024	0.019	-9999	-0.28	2	2
IQGAP1	-0.086	0.18	-9999	-0.41	127	127
NCKAP1	0.017	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.022	0.001	-9999	-10000	0	0
DLG1	0.025	0.03	-9999	-0.16	9	9
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.006	0.025	-9999	-0.17	4	4
MLLT4	0.017	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.021	0.004	-9999	-10000	0	0
PI3K	-0.008	0.031	-9999	-0.21	4	4
ARF6	0.017	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-0.001	99	99
E-cadherin/gamma catenin	0.012	0.073	-9999	-0.35	19	19
TIAM1	0.016	0.003	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	0.032	0.043	-9999	-0.2	18	18
AKT1	0.016	0.028	-9999	-0.12	8	8
PIK3R1	0.016	0.004	-9999	-10000	0	0
CDH1	0.01	0.053	-9999	-0.41	8	8
RhoA/GDP	0.034	0.025	-9999	-10000	0	0
actin cytoskeleton organization	0.004	0.049	-9999	-0.098	95	95
CDC42/GDP	0.035	0.025	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.012	0.043	-9999	-0.16	28	28
ITGB7	0.015	0.026	-9999	-0.41	2	2
RAC1	0.017	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.035	0.046	-9999	-0.21	18	18
E-cadherin/Ca2+/beta catenin/alpha catenin	0.027	0.028	-9999	-0.2	8	8
mol:GDP	0.027	0.027	-9999	-0.16	2	2
CDC42/GTP/IQGAP1	-0.04	0.11	-9999	-0.24	127	127
JUP	0.004	0.074	-9999	-0.41	16	16
p120 catenin/RhoA/GDP	0.036	0.032	-9999	-10000	0	0
RAC1/GTP/IQGAP1	-0.04	0.11	-9999	-0.24	127	127
PIP5K1C/AP1M1	0.012	0.002	-9999	-10000	0	0
RHOA	0.017	0.001	-9999	-10000	0	0
CDC42	0.017	0	-9999	-10000	0	0
CTNNA1	0.017	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.013	0.074	-9999	-0.17	99	99
NME1	0	0	-9999	-0.001	99	99
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.025	0.029	-9999	-0.15	8	8
regulation of cell-cell adhesion	-0.003	0.016	-9999	-10000	0	0
WASF2	-0.008	0.018	-9999	-0.05	76	76
Rap1/GTP	0.025	0.026	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.039	0.062	-9999	-0.25	20	20
CCND1	-0.017	0.091	-9999	-0.21	99	99
VAV2	0.031	0.03	-9999	-10000	0	0
RAP1/GDP	0.028	0.026	-9999	-0.15	2	2
adherens junction assembly	0.025	0.028	-9999	-0.15	8	8
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.017	0	-9999	-10000	0	0
PIP5K1C	0.016	0.003	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.037	0.058	-9999	-0.24	20	20
E-cadherin/beta catenin	0.019	0.032	-9999	-0.16	8	8
mol:GTP	0	0	-9999	-0.001	99	99
SRC	0.025	0.029	-9999	-0.16	8	8
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
Rac1/GTP	-0.038	0.078	-9999	-0.2	95	95
E-cadherin/beta catenin/alpha catenin	0.03	0.033	-9999	-0.24	8	8
ITGAE	0.017	0.001	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.024	0.03	-9999	-0.16	8	8

×

Caspase cascade in apoptosis

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
TOP1	0.01	0.055	-10000	0	-0.21	9	9
ACTA1	0.004	0.062	0.15	15	-0.19	19	34
NUMA1	0.01	0.055	-10000	0	-0.21	9	9
SPTAN1	0.012	0.064	0.16	30	-0.2	11	41
LIMK1	0.006	0.06	0.15	15	-0.18	17	32
BIRC3	-0.01	0.1	-10000	0	-0.41	33	33
BIRC2	0.017	0	-10000	0	-10000	0	0
BAX	0.011	0.049	-10000	0	-0.41	7	7
CASP10	0.006	0.056	-10000	0	-0.26	22	22
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.009	0.057	-10000	0	-0.2	11	11
DIABLO	0.017	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.014	0.065	0.17	24	-0.22	7	31
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.017	0	-10000	0	-10000	0	0
GSN	0	0.068	0.15	15	-0.2	28	43
MADD	0.017	0.001	-10000	0	-10000	0	0
TFAP2A	0.019	0.026	-10000	0	-0.28	1	1
BID	0.006	0.041	-10000	0	-0.14	36	36
MAP3K1	0.011	0.029	-10000	0	-0.19	1	1
TRADD	0.017	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.023	0.027	-10000	0	-0.28	4	4
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.011	0.087	0.16	13	-0.22	51	64
CASP9	0.014	0.037	-10000	0	-0.41	4	4
DNA repair	-0.006	0.039	0.098	19	-0.13	23	42
neuron apoptosis	0.014	0.037	-10000	0	-0.56	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.011	0.059	-10000	0	-0.22	9	9
APAF1	0.017	0	-10000	0	-10000	0	0
CASP6	0.004	0.056	-10000	0	-0.27	1	1
TRAF2	0.017	0	-10000	0	-10000	0	0
ICAD/CAD	0.009	0.058	-10000	0	-0.24	6	6
CASP7	-0.008	0.07	0.19	26	-0.18	54	80
KRT18	0.001	0.049	-10000	0	-0.2	20	20
apoptosis	0.005	0.071	0.18	6	-0.22	17	23
DFFA	0.006	0.06	0.15	15	-0.18	17	32
DFFB	0.006	0.06	0.15	15	-0.18	17	32
PARP1	0.006	0.039	0.13	23	-0.097	20	43
actin filament polymerization	-0.006	0.057	0.18	16	-0.15	8	24
TNF	0.015	0.026	-10000	0	-0.41	2	2
CYCS	0.011	0.029	-10000	0	-0.11	19	19
SATB1	0.024	0.059	-10000	0	-10000	0	0
SLK	0.006	0.06	0.15	15	-0.2	12	27
p15 BID/BAX	0.012	0.047	-10000	0	-0.14	42	42
CASP2	-0.005	0.058	-10000	0	-0.16	25	25
JNK cascade	-0.011	0.029	0.19	1	-10000	0	1
CASP3	0.003	0.064	0.15	18	-0.19	19	37
LMNB2	0.002	0.051	-10000	0	-0.23	5	5
RIPK1	0.01	0.056	-10000	0	-0.41	9	9
CASP4	-0.07	0.17	-10000	0	-0.41	107	107
Mammalian IAPs/DIABLO	0.018	0.059	-10000	0	-0.21	33	33
negative regulation of DNA binding	0.019	0.026	-10000	0	-0.28	1	1
stress fiber formation	0.006	0.06	0.16	8	-0.2	12	20
GZMB	0.004	0.067	-10000	0	-0.31	22	22
CASP1	-0.088	0.14	-10000	0	-0.26	195	195
LMNB1	-0.014	0.06	-10000	0	-0.21	13	13
APP	0.014	0.037	-10000	0	-0.56	1	1
TNFRSF1A	-0.13	0.2	-10000	0	-0.41	183	183
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.003	0.041	-10000	0	-0.29	10	10
VIM	0.002	0.073	0.17	12	-0.22	23	35
LMNA	0.005	0.048	-10000	0	-0.19	5	5
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.009	0.061	-10000	0	-0.18	24	24
LRDD	0.017	0	-10000	0	-10000	0	0
SREBF1	0.006	0.06	0.15	15	-0.18	17	32
APAF-1/Caspase 9	0.01	0.026	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.01	0.055	-10000	0	-0.2	9	9
CFL2	0.006	0.057	0.15	8	-0.18	16	24
GAS2	-0.009	0.083	0.15	14	-0.2	55	69
positive regulation of apoptosis	-0.003	0.055	-10000	0	-0.21	9	9
PRF1	0.007	0.064	-10000	0	-0.41	12	12

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.007	0.057	-10000	0	-0.2	34	34
HDAC1	-0.029	0.14	-10000	0	-0.4	65	65
AES	0.019	0.005	-10000	0	-10000	0	0
FBXW11	0.017	0	-10000	0	-10000	0	0
DTX1	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.019	0.045	-10000	0	-0.29	11	11
TLE1	0.019	0.004	-10000	0	-10000	0	0
AP1	-0.02	0.068	-10000	0	-0.14	125	125
NCSTN	-0.007	0.1	-10000	0	-0.41	30	30
ADAM10	0.003	0.078	-10000	0	-0.41	18	18
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.016	0.081	-10000	0	-0.22	8	8
NICD/RBPSUH	0.018	0.059	-10000	0	-0.19	34	34
WIF1	0.002	0.006	-10000	0	-10000	0	0
NOTCH1	0.009	0.061	-10000	0	-0.21	34	34
PSENEN	0.017	0.001	-10000	0	-10000	0	0
KREMEN2	0.017	0	-10000	0	-10000	0	0
DKK1	-0.077	0.18	-10000	0	-0.41	116	116
beta catenin/beta TrCP1	0.023	0.03	-10000	0	-10000	0	0
APH1B	0.017	0	-10000	0	-10000	0	0
APH1A	0.009	0.059	-10000	0	-0.41	10	10
AXIN1	0.003	0.028	0.18	5	-10000	0	5
CtBP/CBP/TCF1/TLE1/AES	0.035	0.065	0.17	32	-0.13	31	63
PSEN1	0.016	0.019	-10000	0	-0.41	1	1
FOS	-0.085	0.18	-10000	0	-0.41	125	125
JUN	0.016	0.019	-10000	0	-0.41	1	1
MAP3K7	0.019	0.02	-10000	0	-0.41	1	1
CTNNB1	0.016	0.029	-10000	0	-10000	0	0
MAPK3	0.017	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.029	0.039	-10000	0	-0.24	11	11
HNF1A	0.019	0.004	-10000	0	-10000	0	0
CTBP1	0.019	0.005	-10000	0	-10000	0	0
MYC	-0.092	0.18	-10000	0	-0.4	137	137
NKD1	0.001	0.002	-10000	0	-10000	0	0
FZD1	0.009	0.059	-10000	0	-0.41	10	10
NOTCH1 precursor/Deltex homolog 1	0.007	0.057	-10000	0	-0.2	34	34
apoptosis	-0.02	0.068	-10000	0	-0.14	125	125
Delta 1/NOTCHprecursor	0.007	0.057	-10000	0	-0.2	34	34
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.003	0.031	-10000	0	-10000	0	0
Gamma Secretase	0.031	0.067	-10000	0	-0.2	39	39
APC	-0.01	0.063	0.18	2	-0.29	21	23
DVL1	0.003	0.009	-10000	0	-10000	0	0
CSNK2A1	0.016	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0.02	0.006	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.025	0.11	-10000	0	-0.24	117	117
LRP6	0.016	0.019	-10000	0	-0.41	1	1
CSNK1A1	0.016	0.002	-10000	0	-10000	0	0
NLK	0.028	0.017	-10000	0	-0.18	1	1
CCND1	-0.066	0.17	-10000	0	-0.41	99	99
WNT1	0.017	0	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.024	0.052	0.19	2	-0.2	6	8
DKK2	0.009	0.059	-10000	0	-0.41	10	10
NOTCH1 precursor/DVL1	0.01	0.051	-10000	0	-0.2	12	12
GSK3B	0.017	0.002	-10000	0	-10000	0	0
FRAT1	0.017	0.019	-10000	0	-0.41	1	1
NOTCH/Deltex homolog 1	0.007	0.057	-10000	0	-0.2	34	34
PPP2R5D	0.002	0.007	-10000	0	-10000	0	0
MAPK1	0.017	0.003	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.003	0.023	-10000	0	-0.21	2	2
RBPJ	0.017	0	-10000	0	-10000	0	0
CREBBP	0.013	0.01	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.01	0.052	0.2	5	-0.33	10	15
SMARCC2	0.016	0.019	-10000	0	-0.41	1	1
SMARCC1	0.002	0.078	-10000	0	-0.41	18	18
TBX21	0.016	0.033	0.16	2	-0.19	1	3
SUMO2	0.018	0.004	-10000	0	-10000	0	0
STAT1 (dimer)	-0.012	0.11	-10000	0	-0.25	67	67
FKBP4	0.017	0	-10000	0	-10000	0	0
FKBP5	-0.004	0.093	-10000	0	-0.41	26	26
GR alpha/HSP90/FKBP51/HSP90	-0.009	0.048	0.2	1	-0.27	11	12
PRL	0.014	0.056	-10000	0	-0.42	6	6
cortisol/GR alpha (dimer)/TIF2	-0.015	0.059	0.3	7	-0.33	2	9
RELA	-0.01	0.073	-10000	0	-0.2	40	40
FGG	-0.021	0.061	0.35	1	-0.41	5	6
GR beta/TIF2	-0.005	0.026	0.2	1	-10000	0	1
IFNG	-0.038	0.13	-10000	0	-0.28	92	92
apoptosis	0.022	0.078	0.32	25	-0.27	2	27
CREB1	0.023	0.024	-10000	0	-0.19	7	7
histone acetylation	0.013	0.025	0.15	1	-10000	0	1
BGLAP	0.017	0.034	-10000	0	-0.18	1	1
GR/PKAc	0.006	0.015	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.014	0.14	-10000	0	-0.24	105	105
SMARCD1	0.017	0	-10000	0	-10000	0	0
MDM2	-0.009	0.029	0.16	1	-0.16	6	7
GATA3	0.026	0.042	-10000	0	-0.4	5	5
AKT1	0.01	0.041	0.14	6	-0.42	4	10
CSF2	0.004	0.04	-10000	0	-10000	0	0
GSK3B	0.018	0.004	-10000	0	-10000	0	0
NR1I3	0.075	0.1	0.35	20	-0.25	2	22
CSN2	0	0.086	0.32	28	-0.29	2	30
BRG1/BAF155/BAF170/BAF60A	0.035	0.047	-10000	0	-0.21	19	19
NFATC1	0.026	0	-10000	0	-10000	0	0
POU2F1	0.022	0.015	-10000	0	-10000	0	0
CDKN1A	-0.058	0.15	-10000	0	-0.31	112	112
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.005	-10000	0	-10000	0	0
SFN	-0.01	0.1	-10000	0	-0.41	33	33
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.012	0.063	-10000	0	-0.23	30	30
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.069	0.11	0.34	16	-0.33	6	22
JUN	0.018	0.058	-10000	0	-0.3	9	9
IL4	0.018	0.033	-10000	0	-0.18	1	1
CDK5R1	0.014	0.007	-10000	0	-10000	0	0
PRKACA	0.017	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.021	0.081	0.12	7	-0.25	45	52
GR alpha/HSP90/FKBP51/HSP90/PP5C	0	0.045	0.2	1	-0.24	11	12
cortisol/GR alpha (monomer)	-0.022	0.07	0.33	7	-0.34	3	10
NCOA2	0.017	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.071	0.18	-10000	0	-0.4	125	125
AP-1/NFAT1-c-4	-0.027	0.13	-10000	0	-0.42	22	22
AFP	0.017	0.062	-10000	0	-0.51	2	2
SUV420H1	0.016	0.019	-10000	0	-0.41	1	1
IRF1	-0.043	0.11	0.19	4	-0.3	70	74
TP53	-0.046	0.17	-10000	0	-0.43	71	71
PPP5C	0.017	0	-10000	0	-10000	0	0
KRT17	-0.043	0.14	-10000	0	-0.31	94	94
KRT14	0.003	0.063	-10000	0	-0.48	8	8
TBP	0.025	0.019	-10000	0	-0.4	1	1
CREBBP	0.01	0.018	0.16	7	-10000	0	7
HDAC1	-0.041	0.14	-10000	0	-0.42	65	65
HDAC2	0.011	0.042	-10000	0	-0.42	5	5
AP-1	-0.027	0.13	-10000	0	-0.42	22	22
MAPK14	0.017	0.027	-10000	0	-0.41	2	2
MAPK10	0.01	0.01	-10000	0	-10000	0	0
MAPK11	0.018	0.004	-10000	0	-10000	0	0
KRT5	-0.043	0.14	-10000	0	-0.31	92	92
interleukin-1 receptor activity	-0.002	0	-10000	0	-10000	0	0
NCOA1	0.017	0.01	-10000	0	-10000	0	0
STAT1	-0.012	0.11	-10000	0	-0.25	67	67
CGA	0.012	0.059	0.17	1	-0.38	8	9
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.007	0.034	0.18	5	-0.18	5	10
MAPK3	0.018	0.005	-10000	0	-10000	0	0
MAPK1	0.018	0.005	-10000	0	-10000	0	0
ICAM1	-0.052	0.16	-10000	0	-0.33	105	105
NFKB1	-0.013	0.084	-10000	0	-0.23	43	43
MAPK8	0.019	0.048	0.19	1	-0.23	7	8
MAPK9	0.018	0.004	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.022	0.078	0.32	26	-0.28	2	28
BAX	-0.035	0.1	-10000	0	-0.21	99	99
POMC	-0.045	0.083	0.21	1	-0.21	1	2
EP300	0.01	0.018	0.16	4	-10000	0	4
cortisol/GR alpha (dimer)/p53	-0.029	0.088	0.3	7	-0.31	26	33
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.018	0.12	1	-0.19	1	2
SGK1	0.024	0.029	0.18	8	-10000	0	8
IL13	-0.015	0.092	-10000	0	-0.24	31	31
IL6	-0.069	0.2	-10000	0	-0.4	114	114
PRKACG	0.017	0	-10000	0	-10000	0	0
IL5	-0.004	0.088	0.24	6	-0.24	8	14
IL2	-0.037	0.13	-10000	0	-0.28	92	92
CDK5	0.017	0.005	-10000	0	-10000	0	0
PRKACB	0.016	0.005	-10000	0	-10000	0	0
HSP90AA1	0.017	0	-10000	0	-10000	0	0
IL8	-0.099	0.23	-10000	0	-0.48	127	127
CDK5R1/CDK5	0.021	0.012	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.021	0.1	-10000	0	-0.26	36	36
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.011	0.055	0.3	7	-0.29	2	9
SMARCA4	0.017	0.001	-10000	0	-10000	0	0
chromatin remodeling	-0.007	0.034	0.2	4	-0.17	6	10
NF kappa B1 p50/RelA/Cbp	0.004	0.11	0.22	2	-0.28	41	43
JUN (dimer)	0.018	0.058	-10000	0	-0.3	9	9
YWHAH	0.008	0.009	-10000	0	-10000	0	0
VIPR1	0.016	0.033	0.16	2	-0.19	1	3
NR3C1	-0.013	0.039	0.2	4	-0.21	2	6
NR4A1	0.024	0.001	-10000	0	-10000	0	0
TIF2/SUV420H1	0.025	0.014	-10000	0	-0.28	1	1
MAPKKK cascade	0.022	0.078	0.32	25	-0.27	2	27
cortisol/GR alpha (dimer)/Src-1	-0.015	0.055	0.3	5	-0.28	2	7
PBX1	0.022	0.015	-10000	0	-0.12	3	3
POU1F1	0.022	0.015	-10000	0	-10000	0	0
SELE	-0.045	0.14	-10000	0	-0.3	108	108
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.007	0.034	0.2	4	-0.18	6	10
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.011	0.055	0.3	7	-0.29	2	9
mol:cortisol	-0.017	0.041	0.17	5	-0.16	10	15
MMP1	-0.025	0.13	-10000	0	-0.44	43	43

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.011	0.043	-10000	0	-0.28	11	11
MAP4K4	-0.015	0.068	-10000	0	-0.2	24	24
BAG4	0.017	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.004	0.02	0.1	11	-0.1	8	19
NFKBIA	0.016	0.019	-10000	0	-0.41	1	1
BIRC3	-0.01	0.1	-10000	0	-0.41	33	33
BAX	0.004	0.021	-10000	0	-0.16	7	7
RIPK1	0.01	0.056	-10000	0	-0.41	9	9
AKT1	0.007	0.034	-10000	0	-0.38	4	4
BAD	-0.001	0.021	0.11	11	-0.097	8	19
SMPD1	-0.021	0.057	-10000	0	-0.097	187	187
RB1	-0.001	0.021	0.11	11	-0.097	8	19
FADD/Caspase 8	-0.007	0.069	-10000	0	-0.19	33	33
MAP2K4	0.003	0.021	-10000	0	-0.19	1	1
NSMAF	0.015	0.026	-10000	0	-0.41	2	2
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.002	0.021	0.11	11	-0.19	1	12
EGF	0.015	0.026	-10000	0	-0.41	2	2
mol:ceramide	-0.005	0.022	0.12	11	-0.11	8	19
MADD	0.017	0.001	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.011	0.043	-10000	0	-0.28	11	11
ASAH1	0.017	0.001	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.001	0.02	0.11	11	-0.098	4	15
cell proliferation	0.026	0.026	-10000	0	-0.16	5	5
BID	-0.002	0.053	-10000	0	-0.24	2	2
MAP3K1	-0.001	0.022	0.11	11	-0.21	1	12
EIF2A	0.003	0.02	-10000	0	-10000	0	0
TRADD	0.017	0	-10000	0	-10000	0	0
CRADD	0.017	0	-10000	0	-10000	0	0
MAPK3	0.011	0.022	-10000	0	-0.18	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.008	0.028	-10000	0	-0.18	2	2
Cathepsin D/ceramide	0.001	0.042	0.11	11	-0.19	19	30
FADD	-0.015	0.068	-10000	0	-0.2	26	26
KSR1	-0.001	0.021	0.11	11	-0.097	8	19
MAPK8	0.008	0.024	0.11	11	-0.12	1	12
PRKRA	-0.001	0.021	0.11	11	-0.1	3	14
PDGFA	0.008	0.061	-10000	0	-0.41	11	11
TRAF2	0.017	0	-10000	0	-10000	0	0
IGF1	0.014	0.037	-10000	0	-0.41	4	4
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.004	0.022	0.12	11	-0.11	8	19
CTSD	0.004	0.074	-10000	0	-0.41	16	16
regulation of nitric oxide biosynthetic process	0.023	0.027	-10000	0	-0.28	4	4
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.029	0.028	-10000	0	-0.16	5	5
PRKCD	0.017	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.011	0.043	-10000	0	-0.28	11	11
RelA/NF kappa B1	0.023	0.027	-10000	0	-0.28	4	4
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.017	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.018	0.072	-10000	0	-0.21	24	24
TNFR1A/BAG4/TNF-alpha	-0.06	0.13	-10000	0	-0.24	185	185
mol:Sphingosine-1-phosphate	0.011	0.043	-10000	0	-0.28	11	11
MAP2K1	0.006	0.02	-10000	0	-0.18	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.017	0	-10000	0	-10000	0	0
CYCS	0.002	0.018	0.085	11	-0.095	7	18
TNFRSF1A	-0.13	0.2	-10000	0	-0.41	183	183
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
TNFR1A/BAG4	-0.082	0.15	-10000	0	-0.28	183	183
EIF2AK2	0.003	0.021	0.11	13	-10000	0	13
TNF-alpha/TNFR1A/FAN	-0.061	0.13	-10000	0	-0.24	187	187
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.004	0.052	-10000	0	-0.2	12	12
MAP2K2	0.006	0.02	-10000	0	-0.18	1	1
SMPD3	-0.018	0.058	-10000	0	-0.096	185	185
TNF	0.015	0.026	-10000	0	-0.41	2	2
PKC zeta/PAR4	0.013	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	-0.013	0.023	0.093	13	-0.082	2	15
NF kappa B1/RelA/I kappa B alpha	0.039	0.023	-10000	0	-0.2	5	5
AIFM1	-0.001	0.028	0.085	11	-0.13	16	27
BCL2	0.017	0	-10000	0	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.029	0.11	-9999	-0.3	27	27
RAD9A	0.016	0.019	-9999	-0.41	1	1
AP1	-0.049	0.13	-9999	-0.29	125	125
IFNAR2	0.017	0.005	-9999	-10000	0	0
AKT1	0.018	0.021	-9999	-0.2	4	4
ER alpha/Oestrogen	0.012	0.003	-9999	-10000	0	0
NFX1/SIN3/HDAC complex	-0.006	0.06	-9999	-0.14	48	48
EGF	0.015	0.026	-9999	-0.41	2	2
SMG5	0.017	0	-9999	-10000	0	0
SMG6	0.017	0	-9999	-10000	0	0
SP3/HDAC2	-0.023	0.12	-9999	-0.3	78	78
TERT/c-Abl	-0.024	0.1	-9999	-0.31	17	17
SAP18	0.017	0.001	-9999	-10000	0	0
MRN complex	0.035	0	-9999	-10000	0	0
WT1	0.013	0.042	-9999	-0.42	5	5
WRN	0.013	0.042	-9999	-0.41	5	5
SP1	0.016	0.008	-9999	-10000	0	0
SP3	-0.046	0.15	-9999	-0.41	77	77
TERF2IP	0.016	0.005	-9999	-10000	0	0
Telomerase/Nucleolin	-0.01	0.1	-9999	-0.3	15	15
Mad/Max	0.025	0.006	-9999	-10000	0	0
TERT	-0.03	0.11	-9999	-0.3	30	30
CCND1	-0.054	0.17	-9999	-0.39	99	99
MAX	0.017	0.002	-9999	-10000	0	0
RBBP7	0.017	0.001	-9999	-10000	0	0
RBBP4	-0.064	0.17	-9999	-0.41	100	100
TERF2	0.016	0.01	-9999	-10000	0	0
PTGES3	0.017	0.001	-9999	-10000	0	0
SIN3A	0	0.001	-9999	-10000	0	0
Telomerase/911	0.026	0.034	-9999	-0.2	7	7
CDKN1B	-0.005	0.087	-9999	-0.22	71	71
RAD1	0.015	0.026	-9999	-0.41	2	2
XRCC5	0.017	0	-9999	-10000	0	0
XRCC6	0.017	0	-9999	-10000	0	0
SAP30	0.017	0.001	-9999	-10000	0	0
TRF2/PARP2	0.024	0.01	-9999	-10000	0	0
UBE3A	0.017	0.002	-9999	-10000	0	0
JUN	0.016	0.019	-9999	-0.41	1	1
E6	0	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP	0.012	0.006	-9999	-10000	0	0
FOS	-0.085	0.18	-9999	-0.41	125	125
IFN-gamma/IRF1	-0.008	0.11	-9999	-0.28	71	71
PARP2	0.017	0.001	-9999	-10000	0	0
BLM	-0.084	0.18	-9999	-0.41	124	124
Telomerase	0.013	0.035	-9999	-0.17	7	7
IRF1	-0.036	0.14	-9999	-0.41	70	70
ESR1	0.017	0.001	-9999	-10000	0	0
KU/TER	0.025	0	-9999	-10000	0	0
ATM/TRF2	0.011	0.056	-9999	-0.24	25	25
ubiquitin-dependent protein catabolic process	-0.003	0.063	-9999	-0.19	22	22
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	-0.003	0.064	-9999	-0.19	22	22
HDAC1	-0.036	0.14	-9999	-0.41	65	65
HDAC2	0.012	0.043	-9999	-0.42	5	5
ATM	-0.007	0.056	-9999	-0.26	25	25
SMAD3	0.002	0.067	-9999	-0.28	27	27
ABL1	0.016	0.019	-9999	-0.41	1	1
MXD1	0.017	0.002	-9999	-10000	0	0
MRE11A	0.017	0	-9999	-10000	0	0
HUS1	0.017	0	-9999	-10000	0	0
RPS6KB1	0.016	0.019	-9999	-0.41	1	1
TERT/NF kappa B1/14-3-3	-0.004	0.1	-9999	-0.31	8	8
NR2F2	0.014	0.037	-9999	-0.41	4	4
MAPK3	0.017	0.004	-9999	-10000	0	0
MAPK1	0.017	0.005	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	-0.005	0.094	-9999	-0.41	27	27
NFKB1	0.014	0.037	-9999	-0.41	4	4
HNRNPC	0.017	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.007	0.056	-9999	-0.26	25	25
NBN	0.017	0	-9999	-10000	0	0
EGFR	-0.14	0.21	-9999	-0.41	194	194
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.09	0.15	-9999	-0.28	196	196
MYC	-0.095	0.19	-9999	-0.41	137	137
IL2	0.016	0.009	-9999	-10000	0	0
KU	0.025	0	-9999	-10000	0	0
RAD50	0.017	0	-9999	-10000	0	0
HSP90AA1	0.017	0	-9999	-10000	0	0
TGFB1	-0.005	0.095	-9999	-0.41	27	27
TRF2/BLM	-0.045	0.12	-9999	-0.26	124	124
FRAP1	0.016	0.019	-9999	-0.41	1	1
KU/TERT	-0.014	0.11	-9999	-0.31	12	12
SP1/HDAC2	0.021	0.034	-9999	-0.3	5	5
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.01	0.1	-9999	-0.3	15	15
Smad3/Myc	-0.054	0.13	-9999	-0.25	153	153
911 complex	0.033	0.02	-9999	-0.24	3	3
IFNG	0.02	0.019	-9999	-0.41	1	1
Telomerase/PinX1	-0.033	0.091	-9999	-0.3	15	15
Telomerase/AKT1/mTOR/p70S6K	0.023	0.041	-9999	-0.21	3	3
SIN3B	0.017	0.001	-9999	-10000	0	0
YWHAE	0.017	0.001	-9999	-10000	0	0
Telomerase/EST1B	-0.01	0.1	-9999	-0.31	11	11
response to DNA damage stimulus	0	0.014	-9999	-0.062	25	25
MRN complex/TRF2/Rap1	0.044	0.017	-9999	-10000	0	0
TRF2/WRN	0.021	0.03	-9999	-0.26	5	5
Telomerase/hnRNP C1/C2	-0.01	0.1	-9999	-0.3	15	15
E2F1	0.017	0.005	-9999	-10000	0	0
ZNFX1	0	0.001	-9999	-10000	0	0
PIF1	0	0	-9999	-10000	0	0
NCL	0.017	0	-9999	-10000	0	0
DKC1	0.011	0.049	-9999	-0.41	7	7
telomeric DNA binding	0	0	-9999	-10000	0	0

×

FoxO family 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.016	0.041	-9999	-0.27	1	1
PLK1	-0.078	0.15	-9999	-0.53	23	23
CDKN1B	-0.071	0.1	-9999	-0.27	12	12
FOXO3	-0.083	0.14	-9999	-0.31	54	54
KAT2B	-0.012	0.016	-9999	-0.042	23	23
FOXO1/SIRT1	0.014	0.045	-9999	-0.25	2	2
CAT	-0.071	0.13	-9999	-0.36	25	25
CTNNB1	0.017	0	-9999	-10000	0	0
AKT1	-0.001	0.042	-9999	-0.43	4	4
FOXO1	0.011	0.046	-9999	-0.15	36	36
MAPK10	-0.002	0.045	-9999	-0.21	22	22
mol:GTP	-0.001	0.003	-9999	-10000	0	0
FOXO4	-0.013	0.082	-9999	-0.25	25	25
response to oxidative stress	-0.01	0.016	-9999	-0.039	25	25
FOXO3A/SIRT1	-0.095	0.12	-9999	-0.36	28	28
XPO1	0.017	0.001	-9999	-10000	0	0
EP300	0.018	0.001	-9999	-10000	0	0
BCL2L11	0.006	0.022	-9999	-10000	0	0
FOXO1/SKP2	0.018	0.048	-9999	-0.29	4	4
mol:GDP	-0.01	0.016	-9999	-0.039	25	25
RAN	0.017	0.002	-9999	-10000	0	0
GADD45A	-0.063	0.14	-9999	-0.43	47	47
YWHAQ	0.017	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.012	0.044	-9999	-0.16	5	5
MST1	-0.004	0.05	-9999	-0.43	6	6
CSNK1D	0.015	0.026	-9999	-0.41	2	2
CSNK1E	0.017	0.001	-9999	-10000	0	0
FOXO4/14-3-3 family	-0.035	0.079	-9999	-0.25	28	28
YWHAB	0.017	0.001	-9999	-10000	0	0
MAPK8	-0.008	0.064	-9999	-0.21	46	46
MAPK9	-0.007	0.064	-9999	-0.21	46	46
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0.017	0.001	-9999	-10000	0	0
YWHAZ	0.017	0.002	-9999	-10000	0	0
SIRT1	0.013	0.006	-9999	-10000	0	0
SOD2	-0.2	0.2	-9999	-0.36	288	288
RBL2	-0.051	0.1	-9999	-0.32	2	2
RAL/GDP	-0.01	0.075	-9999	-0.25	46	46
CHUK	0	0.026	-9999	-0.4	1	1
Ran/GTP	0.012	0.005	-9999	-10000	0	0
CSNK1G2	0.017	0	-9999	-10000	0	0
RAL/GTP	-0.008	0.07	-9999	-0.23	46	46
CSNK1G1	0.017	0	-9999	-10000	0	0
FASLG	0.006	0.022	-9999	-10000	0	0
SKP2	0.015	0.026	-9999	-0.41	2	2
USP7	0.017	0.002	-9999	-10000	0	0
IKBKB	0.001	0.02	-9999	-10000	0	0
CCNB1	-0.18	0.21	-9999	-0.36	291	291
FOXO1-3a-4/beta catenin	-0.08	0.13	-9999	-0.32	18	18
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.047	-9999	-0.29	4	4
CSNK1A1	0.017	0	-9999	-10000	0	0
SGK1	-0.012	0.016	-9999	-0.042	23	23
CSNK1G3	0.017	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.022	0.007	-9999	-10000	0	0
ZFAND5	-0.005	0.073	-9999	-0.24	12	12
SFN	-0.01	0.1	-9999	-0.41	33	33
CDK2	-0.003	0.094	-9999	-0.41	27	27
FOXO3A/14-3-3	-0.041	0.072	-9999	-0.24	28	28
CREBBP	0.019	0.002	-9999	-10000	0	0
FBXO32	-0.077	0.12	-9999	-0.35	28	28
BCL6	-0.06	0.12	-9999	-0.43	19	19
RALB	0.016	0.019	-9999	-0.41	1	1
RALA	-0.02	0.12	-9999	-0.41	45	45
YWHAH	0.008	0.009	-9999	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.022	0.005	-10000	0	-10000	0	0
NFATC2	0.041	0.11	-10000	0	-0.28	17	17
NFATC3	0.031	0.086	0.2	2	-0.22	1	3
CD40LG	-0.038	0.18	-10000	0	-0.42	46	46
ITCH	0.026	0.037	-10000	0	-0.17	16	16
CBLB	0.026	0.035	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	0.004	0.12	-10000	0	-0.35	15	15
JUNB	0.011	0.053	-10000	0	-0.41	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	0.03	0.043	-10000	0	-0.21	16	16
T cell anergy	0.012	0.053	-10000	0	-0.22	18	18
TLE4	0.031	0.073	-10000	0	-0.18	13	13
Jun/NFAT1-c-4/p21SNFT	0.028	0.16	-10000	0	-0.33	18	18
AP-1/NFAT1-c-4	-0.022	0.22	-10000	0	-0.49	38	38
IKZF1	0.031	0.073	-10000	0	-0.18	13	13
T-helper 2 cell differentiation	0.02	0.091	-10000	0	-10000	0	0
AP-1/NFAT1	-0.029	0.14	-10000	0	-0.25	101	101
CALM1	0.022	0.026	-10000	0	-10000	0	0
EGR2	0.076	0.14	-10000	0	-0.38	11	11
EGR3	0.084	0.12	0.3	45	-0.38	3	48
NFAT1/FOXP3	0.042	0.082	-10000	0	-0.18	13	13
EGR1	0.006	0.071	-10000	0	-0.41	15	15
JUN	0.013	0.028	-10000	0	-0.41	1	1
EGR4	0.018	0.003	-10000	0	-10000	0	0
mol:Ca2+	0.005	0.029	-10000	0	-0.14	20	20
GBP3	0.024	0.07	-10000	0	-0.18	17	17
FOSL1	0.007	0.067	-10000	0	-0.41	13	13
NFAT1-c-4/MAF/IRF4	0.034	0.15	-10000	0	-0.29	15	15
DGKA	0.031	0.073	-10000	0	-0.22	5	5
CREM	0.016	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	0.023	0.16	-10000	0	-0.32	22	22
CTLA4	0.037	0.056	-10000	0	-0.19	3	3
NFAT1-c-4 (dimer)/EGR1	0.023	0.16	-10000	0	-0.32	26	26
NFAT1-c-4 (dimer)/EGR4	0.029	0.16	-10000	0	-0.3	21	21
FOS	-0.088	0.19	-10000	0	-0.42	125	125
IFNG	0.019	0.08	-10000	0	-0.28	3	3
T cell activation	-0.002	0.11	-10000	0	-0.38	2	2
MAF	0.018	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.083	0.13	0.32	6	-0.3	74	80
TNF	0.017	0.14	-10000	0	-0.32	11	11
FASLG	-0.012	0.21	-10000	0	-0.43	33	33
TBX21	0.023	0.004	-10000	0	-10000	0	0
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.02	0.001	-10000	0	-10000	0	0
PTPN1	0.031	0.073	-10000	0	-0.18	13	13
NFAT1-c-4/ICER1	0.023	0.16	-10000	0	-0.3	21	21
GATA3	0.016	0.042	-10000	0	-0.41	5	5
T-helper 1 cell differentiation	0.019	0.08	-10000	0	-0.27	3	3
IL2RA	0.003	0.13	-10000	0	-0.37	15	15
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.025	0.16	-10000	0	-0.34	99	99
E2F1	-0.059	0.062	-10000	0	-10000	0	0
PPARG	0.013	0.042	-10000	0	-0.41	5	5
SLC3A2	0.025	0.093	-10000	0	-0.39	12	12
IRF4	0.017	0.019	-10000	0	-0.41	1	1
PTGS2	-0.048	0.2	-10000	0	-0.53	43	43
CSF2	-0.038	0.18	-10000	0	-0.44	38	38
JunB/Fra1/NFAT1-c-4	0.023	0.16	-10000	0	-0.31	18	18
IL4	0.02	0.092	-10000	0	-10000	0	0
IL5	-0.038	0.18	-10000	0	-0.44	38	38
IL2	-0.003	0.11	-10000	0	-0.38	2	2
IL3	-0.001	0.03	-10000	0	-10000	0	0
RNF128	0.016	0.076	-10000	0	-0.37	19	19
NFATC1	0.083	0.13	0.3	74	-0.32	6	80
CDK4	-0.19	0.18	0.29	4	-0.44	155	159
PTPRK	0.031	0.073	-10000	0	-0.18	13	13
IL8	-0.08	0.23	-10000	0	-0.5	90	90
POU2F1	0.023	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.014	0.037	-10000	0	-0.41	4	4
ANTXR2	0	0	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.004	-10000	0	-0.051	4	4
monocyte activation	-0.084	0.071	-10000	0	-0.13	353	353
MAP2K2	0.012	0.002	-10000	0	-10000	0	0
MAP2K1	0.004	0.004	-10000	0	-10000	0	0
MAP2K7	0.005	0.004	-10000	0	-10000	0	0
MAP2K6	0.005	0.004	-10000	0	-10000	0	0
CYAA	0.002	0.018	-10000	0	-0.2	4	4
MAP2K4	0.004	0.004	-10000	0	-10000	0	0
IL1B	-0.006	0.036	-10000	0	-0.21	14	14
Channel	0.009	0.02	-10000	0	-0.22	4	4
NLRP1	0.005	0.004	-10000	0	-10000	0	0
CALM1	0.016	0.004	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.01	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.004	0.051	4	-10000	0	4
MAPK3	0.005	0.004	-10000	0	-10000	0	0
MAPK1	0.004	0.004	-10000	0	-10000	0	0
PGR	0.005	0.004	-10000	0	-10000	0	0
PA/Cellular Receptors	0.01	0.022	-10000	0	-0.24	4	4
apoptosis	0	0.004	-10000	0	-0.051	4	4
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.009	0.018	-10000	0	-0.2	4	4
macrophage activation	0.008	0.004	-10000	0	-10000	0	0
TNF	0.015	0.026	-10000	0	-0.41	2	2
VCAM1	-0.084	0.071	-10000	0	-0.14	353	353
platelet activation	0.01	0.006	-10000	0	-10000	0	0
MAPKKK cascade	-0.009	0.009	-10000	0	-10000	0	0
IL18	-0.018	0.062	-10000	0	-0.22	45	45
negative regulation of macrophage activation	0	0.004	-10000	0	-0.051	4	4
LEF	0	0.004	-10000	0	-0.052	4	4
CASP1	-0.005	0.015	-10000	0	-0.07	3	3
mol:cAMP	0.01	0.006	-10000	0	-10000	0	0
necrosis	0	0.004	-10000	0	-0.051	4	4
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.009	0.019	-10000	0	-0.2	4	4
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.033	0.072	-10000	0	-0.24	18	18
CRKL	0.027	0.04	-10000	0	-0.17	19	19
mol:DAG	0.017	0.076	-10000	0	-0.17	64	64
HRAS	0.016	0.068	-10000	0	-0.3	8	8
MAPK8	-0.001	0.08	-10000	0	-0.22	64	64
RAP1A	0.027	0.04	-10000	0	-0.17	19	19
GAB1	0.026	0.043	-10000	0	-0.17	23	23
MAPK14	-0.002	0.081	-10000	0	-0.22	66	66
EPO	0.019	0.007	-10000	0	-10000	0	0
PLCG1	0.017	0.077	-10000	0	-0.18	64	64
EPOR/TRPC2/IP3 Receptors	0.019	0.007	-10000	0	-10000	0	0
RAPGEF1	0.017	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.038	0.006	-10000	0	-10000	0	0
GAB1/SHC/GRB2/SOS1	0.018	0.073	-10000	0	-0.33	8	8
EPO/EPOR (dimer)	0.028	0.011	-10000	0	-10000	0	0
IRS2	0.027	0.039	-10000	0	-0.17	18	18
STAT1	0.019	0.088	-10000	0	-0.31	18	18
STAT5B	0.021	0.077	-10000	0	-0.25	18	18
cell proliferation	-0.001	0.074	-10000	0	-0.2	66	66
GAB1/SHIP/PIK3R1/SHP2/SHC	0.012	0.064	-10000	0	-0.3	8	8
TEC	0.027	0.04	-10000	0	-0.17	19	19
SOCS3	0.017	0	-10000	0	-10000	0	0
STAT1 (dimer)	0.019	0.087	-10000	0	-0.3	18	18
JAK2	0.018	0.007	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.053	0.047	-10000	0	-0.18	19	19
EPO/EPOR	0.028	0.011	-10000	0	-10000	0	0
LYN	-0.033	0.14	-10000	0	-0.41	64	64
TEC/VAV2	0.038	0.04	-10000	0	-0.32	2	2
elevation of cytosolic calcium ion concentration	0.019	0.007	-10000	0	-10000	0	0
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
EPO/EPOR (dimer)/LYN	0.009	0.096	-10000	0	-0.25	64	64
mol:IP3	0.017	0.076	-10000	0	-0.17	64	64
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.032	0.036	-10000	0	-0.3	2	2
SH2B3	0.01	0.059	-10000	0	-0.42	10	10
NFKB1	-0.003	0.084	-10000	0	-0.22	66	66
EPO/EPOR (dimer)/JAK2/SOCS3	0.017	0.02	0.16	10	-10000	0	10
PTPN6	0.024	0.041	-10000	0	-0.18	19	19
TEC/VAV2/GRB2	0.045	0.04	-10000	0	-0.31	2	2
EPOR	0.019	0.007	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.073	-10000	0	-0.33	8	8
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	0.009	0.059	-10000	0	-0.41	10	10
CRKL/CBL/C3G	0.046	0.04	-10000	0	-0.31	2	2
VAV2	0.027	0.04	-10000	0	-0.17	19	19
CBL	0.027	0.04	-10000	0	-0.18	15	15
SHC/Grb2/SOS1	0.009	0.071	-10000	0	-0.19	47	47
STAT5A	0.021	0.078	-10000	0	-0.25	18	18
GRB2	0.017	0.002	-10000	0	-10000	0	0
STAT5 (dimer)	0.038	0.083	-10000	0	-0.3	13	13
LYN/PLCgamma2	-0.016	0.12	-10000	0	-0.32	65	65
PTPN11	0.017	0	-10000	0	-10000	0	0
BTK	0.027	0.042	-10000	0	-0.18	19	19
BCL2	0.033	0.072	-10000	0	-0.24	18	18

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.017	0.019	-9999	-0.41	1	1
ELF1	0.018	0.055	-9999	-0.32	13	13
CCNA2	-0.096	0.19	-9999	-0.41	139	139
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
JAK3	0.018	0	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
JAK1	0.018	0.002	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.039	0.054	-9999	-0.2	12	12
SHC1	-0.02	0.12	-9999	-0.41	46	46
SP1	0.019	0.039	-9999	-0.22	14	14
IL2RA	0.018	0.056	-9999	-0.33	13	13
IL2RB	0.014	0.037	-9999	-0.41	4	4
SOS1	0.001	0	-9999	-10000	0	0
IL2RG	0.01	0.056	-9999	-0.41	9	9
G1/S transition of mitotic cell cycle	-0.027	0.1	-9999	-0.18	151	151
PTPN11	0.018	0	-9999	-10000	0	0
CCND2	0.014	0.068	-9999	-0.4	14	14
LCK	0.014	0.037	-9999	-0.41	4	4
GRB2	0.017	0.002	-9999	-10000	0	0
IL2	0.018	0	-9999	-10000	0	0
CDK6	0.017	0	-9999	-10000	0	0
CCND3	0.042	0.052	-9999	-0.26	5	5

×

Coregulation of Androgen receptor activity

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
NRIP1	0.016	0.032	-9999	-0.41	3	3
SVIL	0.004	0.078	-9999	-0.41	18	18
ZNF318	0.014	0	-9999	-10000	0	0
JMJD2C	0.023	0	-9999	-10000	0	0
T-DHT/AR/Ubc9	0.03	0.034	-9999	-0.23	8	8
CARM1	0.017	0	-9999	-10000	0	0
PRDX1	0.017	0.001	-9999	-10000	0	0
PELP1	0.017	0	-9999	-10000	0	0
CTNNB1	0.018	0	-9999	-10000	0	0
AKT1	0.013	0.037	-9999	-0.41	4	4
PTK2B	0.018	0	-9999	-10000	0	0
MED1	0.016	0	-9999	-10000	0	0
MAK	0.008	0.052	-9999	-0.42	8	8
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	-0.026	0.13	-9999	-0.41	54	54
GSN	0.006	0.071	-9999	-0.41	15	15
NCOA2	0.017	0	-9999	-10000	0	0
NCOA6	0.018	0.001	-9999	-10000	0	0
DNA-PK	0.02	0.055	-9999	-0.24	23	23
NCOA4	0.017	0.001	-9999	-10000	0	0
PIAS3	0.016	0.026	-9999	-0.41	2	2
cell proliferation	0.012	0.033	-9999	-0.24	8	8
XRCC5	0.017	0	-9999	-10000	0	0
UBE3A	0.019	0	-9999	-10000	0	0
T-DHT/AR/SNURF	0.019	0.033	-9999	-0.23	8	8
FHL2	0.028	0.039	-9999	-0.37	4	4
RANBP9	0.018	0.001	-9999	-10000	0	0
JMJD1A	0.021	0.065	-9999	-0.4	12	12
CDK6	0.017	0	-9999	-10000	0	0
TGFB1I1	-0.34	0.16	-9999	-0.41	441	441
T-DHT/AR/CyclinD1	-0.018	0.11	-9999	-0.24	104	104
XRCC6	0.017	0	-9999	-10000	0	0
T-DHT/AR	0.047	0.04	-9999	-0.22	8	8
CTDSP1	0.015	0.032	-9999	-0.41	3	3
CTDSP2	-0.015	0.11	-9999	-0.42	37	37
BRCA1	0.014	0.042	-9999	-0.41	5	5
TCF4	0.016	0.002	-9999	-10000	0	0
CDKN2A	-0.032	0.14	-9999	-0.41	59	59
SRF	0.021	0.011	-9999	-10000	0	0
NKX3-1	0.032	0.038	-9999	-0.18	12	12
KLK3	0.017	0.029	-9999	-10000	0	0
TMF1	0.014	0.037	-9999	-0.41	4	4
HNRNPA1	0.016	0	-9999	-10000	0	0
AOF2	0.013	0.049	-9999	-0.41	7	7
APPL1	0.014	0.026	-9999	-0.29	4	4
T-DHT/AR/Caspase 8	0.024	0.05	-9999	-0.24	18	18
AR	0.015	0.053	-9999	-0.4	8	8
UBA3	0	0	-9999	-10000	0	0
PATZ1	0.016	0	-9999	-10000	0	0
PAWR	0.017	0	-9999	-10000	0	0
PRKDC	-0.002	0.088	-9999	-0.41	23	23
PA2G4	0.015	0.019	-9999	-0.41	1	1
UBE2I	0.017	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.028	0.032	-9999	-0.2	9	9
RPS6KA3	0.018	0.019	-9999	-0.41	1	1
T-DHT/AR/ARA70	0.03	0.034	-9999	-0.23	8	8
LATS2	-0.001	0	-9999	-10000	0	0
T-DHT/AR/PRX1	0.027	0.031	-9999	-0.2	8	8
Cyclin D3/CDK11 p58	0.012	0.013	-9999	-0.29	1	1
VAV3	-0.011	0.11	-9999	-0.41	36	36
KLK2	0.033	0.017	-9999	-10000	0	0
CASP8	0.009	0.059	-9999	-0.41	10	10
T-DHT/AR/TIF2/CARM1	0.04	0.033	-9999	-0.2	8	8
TMPRSS2	0.031	0.047	-9999	-0.22	15	15
CCND1	-0.063	0.17	-9999	-0.41	99	99
PIAS1	0.019	0	-9999	-10000	0	0
mol:T-DHT	0.005	0.006	-9999	-0.045	7	7
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.02	0	-9999	-10000	0	0
T-DHT/AR/CDK6	0.029	0.034	-9999	-0.23	8	8
CMTM2	0	0	-9999	-10000	0	0
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	0.021	0.009	-9999	-10000	0	0
CCND3	0.016	0.019	-9999	-0.41	1	1
TGIF1	-0.29	0.2	-9999	-0.41	371	371
FKBP4	0.018	0	-9999	-10000	0	0

×

BMP receptor 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.04	0.051	-9999	-0.19	25	25
SMAD6-7/SMURF1	0.034	0.012	-9999	-0.24	1	1
NOG	0	0	-9999	-10000	0	0
SMAD9	0.02	0.019	-9999	-10000	0	0
SMAD4	-0.085	0.18	-9999	-0.41	126	126
SMAD5	0.02	0.034	-9999	-0.16	10	10
BMP7/USAG1	0.02	0.04	-9999	-0.28	9	9
SMAD5/SKI	0.029	0.035	-9999	-0.19	5	5
SMAD1	-0.004	0.074	-9999	-0.14	114	114
BMP2	-0.027	0.13	-9999	-0.41	54	54
SMAD1/SMAD1/SMAD4	-0.058	0.084	-9999	-0.26	49	49
BMPR1A	0.012	0.046	-9999	-0.41	6	6
BMPR1B	0.016	0.019	-9999	-0.41	1	1
BMPR1A-1B/BAMBI	0.014	0.075	-9999	-0.25	39	39
AHSG	0.015	0.026	-9999	-0.41	2	2
CER1	0.017	0	-9999	-10000	0	0
BMP2-4/CER1	0.003	0.087	-9999	-0.24	62	62
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	0.016	0.046	-9999	-0.2	9	9
BMP2-4 (homodimer)	-0.011	0.1	-9999	-0.28	62	62
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.04	0.033	-9999	-0.21	9	9
RGMA	0	0	-9999	-10000	0	0
SMURF1	0.017	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	0.007	0.04	-9999	-0.15	11	11
BMP2-4/USAG1	0	0.094	-9999	-0.24	66	66
SMAD6/SMURF1/SMAD5	0.029	0.035	-9999	-0.19	5	5
SOSTDC1	0.011	0.049	-9999	-0.41	7	7
BMP7/BMPR2/BMPR1A-1B	0.04	0.033	-9999	-0.21	9	9
SKI	0.017	0	-9999	-10000	0	0
BMP6 (homodimer)	0.015	0.026	-9999	-0.41	2	2
HFE2	0	0	-9999	-10000	0	0
ZFYVE16	0.013	0.042	-9999	-0.41	5	5
MAP3K7	0.016	0.019	-9999	-0.41	1	1
BMP2-4/CHRD	0.003	0.087	-9999	-0.24	62	62
SMAD5/SMAD5/SMAD4	-0.019	0.098	-9999	-0.18	127	127
MAPK1	0.017	0.003	-9999	-10000	0	0
TAK1/TAB family	0.035	0.041	-9999	-0.16	6	6
BMP7 (homodimer)	0.015	0.026	-9999	-0.41	2	2
NUP214	0.017	0	-9999	-10000	0	0
BMP6/FETUA	0.023	0.027	-9999	-0.28	4	4
SMAD1/SKI	0.002	0.075	-9999	-0.25	8	8
SMAD6	0.017	0	-9999	-10000	0	0
CTDSP2	-0.013	0.11	-9999	-0.41	37	37
BMP2-4/FETUA	0.002	0.089	-9999	-0.24	63	63
MAP3K7IP1	0.017	0	-9999	-10000	0	0
GREM1	-0.002	0.088	-9999	-0.41	23	23
BMPR2 (homodimer)	0.017	0	-9999	-10000	0	0
GADD34/PP1CA	0.032	0.029	-9999	-0.24	6	6
BMPR1A-1B (homodimer)	0.021	0.036	-9999	-0.28	7	7
CHRDL1	0	0	-9999	-10000	0	0
ENDOFIN/SMAD1	0.001	0.077	-9999	-0.23	13	13
SMAD6-7/SMURF1/SMAD1	0.016	0.075	-9999	-0.26	6	6
SMAD6/SMURF1	0.017	0	-9999	-10000	0	0
BAMBI	-0.011	0.1	-9999	-0.41	34	34
SMURF2	0.015	0.026	-9999	-0.41	2	2
BMP2-4/CHRDL1	-0.007	0.084	-9999	-0.24	62	62
BMP2-4/GREM1	-0.008	0.1	-9999	-0.24	82	82
SMAD7	0.016	0.019	-9999	-0.41	1	1
SMAD8A/SMAD8A/SMAD4	-0.023	0.096	-9999	-0.19	126	126
SMAD1/SMAD6	0.002	0.075	-9999	-0.25	8	8
TAK1/SMAD6	0.025	0.014	-9999	-0.28	1	1
BMP7	0.015	0.026	-9999	-0.41	2	2
BMP6	0.015	0.026	-9999	-0.41	2	2
MAP3K7IP2	0.017	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0.013	0.038	-9999	-0.19	5	5
PPM1A	0.017	0	-9999	-10000	0	0
SMAD1/SMURF2	0.002	0.075	-9999	-0.23	10	10
SMAD7/SMURF1	0.025	0.014	-9999	-0.28	1	1
CTDSPL	0.017	0	-9999	-10000	0	0
PPP1CA	0.017	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.015	0.032	-9999	-0.41	3	3
PPP1R15A	0.016	0.019	-9999	-0.41	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	0.007	0.047	-9999	-0.14	26	26
CHRD	0.017	0	-9999	-10000	0	0
BMPR2	0.017	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	0.006	0.045	-9999	-0.11	64	64
BMP4	0.011	0.052	-9999	-0.41	8	8
FST	0.004	0.074	-9999	-0.41	16	16
BMP2-4/NOG	-0.007	0.084	-9999	-0.24	62	62
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.047	0.031	-9999	-0.19	9	9

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.028	0.046	-10000	0	-0.18	14	14
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.017	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.01	0.11	-10000	0	-0.24	76	76
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.027	0.043	-10000	0	-0.24	13	13
antigen processing and presentation of peptide antigen via MHC class I	-0.051	0.077	-10000	0	-0.18	113	113
CaM/Ca2+	0.028	0.042	-10000	0	-0.17	12	12
RAP1A	0.017	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.009	0.068	-10000	0	-0.22	32	32
AKT1	0.008	0.054	-10000	0	-0.16	36	36
MAP2K1	0.017	0.036	-10000	0	-0.2	4	4
MAP3K11	0.016	0.038	-10000	0	-0.17	14	14
IFNGR1	0.007	0.067	-10000	0	-0.41	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.003	0.033	-10000	0	-0.19	10	10
Rap1/GTP	-0.006	0.022	-10000	0	-0.17	3	3
CRKL/C3G	0.025	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.042	0.041	-10000	0	-0.19	15	15
CEBPB	0.037	0.056	-10000	0	-0.26	5	5
STAT3	0.009	0.059	-10000	0	-0.41	10	10
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.043	0.036	-10000	0	-10000	0	0
STAT1	0.003	0.066	-10000	0	-0.22	32	32
CALM1	0.016	0.004	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.016	0.019	-10000	0	-0.41	1	1
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
STAT1 (dimer)/PIAS1	0.012	0.065	-10000	0	-0.2	32	32
CEBPB/PTGES2/Cbp/p300	-0.002	0.041	-10000	0	-0.23	4	4
mol:Ca2+	0.026	0.045	-10000	0	-0.18	14	14
MAPK3	0.03	0.035	-10000	0	-10000	0	0
STAT1 (dimer)	-0.064	0.11	-10000	0	-0.24	113	113
MAPK1	0.013	0.11	-10000	0	-0.58	15	15
JAK2	0.017	0.006	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
JAK1	0.017	0.006	-10000	0	-10000	0	0
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	0.038	0.042	-10000	0	-0.19	3	3
SMAD7	-0.002	0.06	-10000	0	-0.13	29	29
CBL/CRKL/C3G	0.031	0.039	-10000	0	-0.18	4	4
PI3K	0.016	0.059	-10000	0	-0.18	35	35
IFNG	0.016	0.019	-10000	0	-0.41	1	1
apoptosis	0.026	0.043	0.22	4	-0.21	1	5
CAMK2G	0.008	0.009	-10000	0	-10000	0	0
STAT3 (dimer)	0.009	0.058	-10000	0	-0.41	10	10
CAMK2A	0.016	0.004	-10000	0	-10000	0	0
CAMK2B	0.002	0.006	-10000	0	-10000	0	0
FRAP1	0.016	0.058	0.19	3	-0.2	11	14
PRKCD	0.015	0.059	0.2	2	-0.17	32	34
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.051	0.077	-10000	0	-0.18	113	113
PTPN2	0.016	0.019	-10000	0	-0.41	1	1
EP300	0.017	0.002	-10000	0	-10000	0	0
IRF1	-0.016	0.14	-10000	0	-0.36	70	70
STAT1 (dimer)/PIASy	0.009	0.065	-10000	0	-0.21	32	32
SOCS1	0.017	0.003	-10000	0	-10000	0	0
mol:GDP	0.028	0.037	-10000	0	-0.18	4	4
CASP1	-0.045	0.12	-10000	0	-0.21	173	173
PTGES2	0.017	0	-10000	0	-10000	0	0
IRF9	0.029	0.028	-10000	0	-0.12	1	1
mol:PI-3-4-5-P3	0.008	0.054	-10000	0	-0.17	35	35
RAP1/GDP	0.02	0.031	-10000	0	-0.17	3	3
CBL	0.015	0.038	-10000	0	-0.17	14	14
MAP3K1	0.016	0.039	-10000	0	-0.17	15	15
PIAS1	0.017	0	-10000	0	-10000	0	0
PIAS4	0.017	0	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.051	0.077	-10000	0	-0.18	113	113
PTPN11	0.011	0.039	-10000	0	-0.18	14	14
CREBBP	0.017	0.002	-10000	0	-10000	0	0
RAPGEF1	0.017	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.013	0.074	-10000	0	-0.21	24	24
BAG4	0.017	0	-10000	0	-10000	0	0
BAD	0.003	0.027	-10000	0	-10000	0	0
NFKBIA	0.016	0.019	-10000	0	-0.41	1	1
BIRC3	-0.009	0.1	-10000	0	-0.41	33	33
BAX	0.001	0.037	-10000	0	-0.21	7	7
EnzymeConsortium:3.1.4.12	-0.002	0.021	-10000	0	-0.055	24	24
IKBKB	-0.009	0.071	-10000	0	-0.2	24	24
MAP2K2	0.01	0.026	-10000	0	-0.15	1	1
MAP2K1	0.009	0.025	-10000	0	-0.15	1	1
SMPD1	0.002	0.021	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.009	0.074	-10000	0	-0.19	31	31
MAP2K4	0.006	0.026	-10000	0	-0.16	1	1
protein ubiquitination	-0.009	0.072	0.15	1	-0.2	24	25
EnzymeConsortium:2.7.1.37	0.015	0.03	0.13	5	-0.15	1	6
response to UV	0	0	0.001	5	-0.001	1	6
RAF1	0.008	0.027	-10000	0	-0.16	1	1
CRADD	0.017	0	-10000	0	-10000	0	0
mol:ceramide	0	0.028	-10000	0	-0.074	24	24
I-kappa-B-alpha/RELA/p50/ubiquitin	0.023	0.011	-10000	0	-0.24	1	1
MADD	0.017	0.002	-10000	0	-10000	0	0
MAP3K1	0.003	0.028	-10000	0	-0.17	1	1
TRADD	0.017	0	-10000	0	-10000	0	0
RELA/p50	0.017	0	-10000	0	-10000	0	0
MAPK3	0.014	0.028	-10000	0	-0.14	1	1
MAPK1	0.012	0.029	-10000	0	-0.14	1	1
p50/RELA/I-kappa-B-alpha	0.025	0.014	-10000	0	-0.28	1	1
FADD	-0.014	0.074	-10000	0	-0.21	26	26
KSR1	0.004	0.027	-10000	0	-10000	0	0
MAPK8	0.013	0.033	0.13	15	-0.14	1	16
TRAF2	0.017	0.001	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	-0.01	0.071	-10000	0	-0.2	24	24
TNF R/SODD	-0.082	0.15	-10000	0	-0.28	183	183
TNF	0.016	0.026	-10000	0	-0.41	2	2
CYCS	0.002	0.03	-10000	0	-0.12	7	7
IKBKG	-0.009	0.071	-10000	0	-0.2	24	24
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.017	0.077	-10000	0	-0.22	24	24
RELA	0.017	0	-10000	0	-10000	0	0
RIPK1	0.01	0.056	-10000	0	-0.41	9	9
AIFM1	0	0.033	-10000	0	-0.14	9	9
TNF/TNF R/SODD	-0.059	0.13	-10000	0	-0.24	185	185
TNFRSF1A	-0.13	0.2	-10000	0	-0.41	183	183
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.013	0.033	-10000	0	-10000	0	0
NSMAF	-0.013	0.073	-10000	0	-0.2	26	26
response to hydrogen peroxide	0	0	0.001	5	-0.001	1	6
BCL2	0.017	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.034	0.044	-10000	0	-0.26	5	5
UGCG	0.012	0.026	-10000	0	-0.22	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.017	0.092	-10000	0	-0.24	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.012	0.026	-10000	0	-0.22	1	1
mol:DAG	0.006	0.01	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.1	-10000	0	-0.24	36	36
FRAP1	0.002	0.12	-10000	0	-0.26	51	51
FOXO3	-0.003	0.12	-10000	0	-0.26	50	50
AKT1	-0.008	0.13	-10000	0	-0.28	50	50
GAB2	0.015	0.019	-10000	0	-0.41	1	1
SMPD1	0.013	0.024	-10000	0	-10000	0	0
SGMS1	0.012	0.027	-10000	0	-0.26	1	1
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	-0.001	0.053	-10000	0	-0.24	25	25
CALM1	0.016	0.004	-10000	0	-10000	0	0
cell proliferation	-0.001	0.077	-10000	0	-0.2	13	13
EIF3A	0.017	0	-10000	0	-10000	0	0
PI3K	0.011	0.066	-10000	0	-0.28	25	25
RPS6KB1	0.017	0.027	-10000	0	-0.34	1	1
mol:sphingomyelin	0.006	0.01	-10000	0	-10000	0	0
natural killer cell activation	-0.001	0.003	-10000	0	-0.006	133	133
JAK3	0.018	0.003	-10000	0	-10000	0	0
PIK3R1	0.017	0.006	-10000	0	-10000	0	0
JAK1	0.018	0.004	-10000	0	-10000	0	0
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
MYC	-0.043	0.18	-10000	0	-0.35	137	137
MYB	0.023	0.05	-10000	0	-0.38	8	8
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.008	0.092	-10000	0	-0.22	41	41
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.037	0.026	-10000	0	-0.31	1	1
mol:PI-3-4-5-P3	0.009	0.091	-10000	0	-0.21	41	41
Rac1/GDP	0.01	0.049	-10000	0	-0.21	24	24
T cell proliferation	0.008	0.086	-10000	0	-0.2	40	40
SHC1	-0.021	0.12	-10000	0	-0.42	46	46
RAC1	0.017	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.005	-10000	0	-0.039	8	8
PRKCZ	0.007	0.088	-10000	0	-0.21	40	40
NF kappa B1 p50/RelA	0.014	0.12	-10000	0	-0.25	43	43
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.03	0.047	-10000	0	-0.24	7	7
HSP90AA1	0.017	0	-10000	0	-10000	0	0
RELA	0.017	0	-10000	0	-10000	0	0
IL2RA	0.011	0.046	-10000	0	-0.41	6	6
IL2RB	0.015	0.038	-10000	0	-0.42	4	4
TERT	0.017	0	-10000	0	-10000	0	0
E2F1	0.023	0.032	-10000	0	-0.23	8	8
SOS1	-0.001	0.003	-10000	0	-0.006	130	130
RPS6	0.017	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.002	0.018	8	-10000	0	8
PTPN11	0.016	0.003	-10000	0	-10000	0	0
IL2RG	0.01	0.056	-10000	0	-0.42	9	9
actin cytoskeleton organization	0.008	0.086	-10000	0	-0.2	40	40
GRB2	0.016	0.003	-10000	0	-10000	0	0
IL2	0.018	0.004	-10000	0	-10000	0	0
PIK3CA	-0.003	0.092	-10000	0	-0.41	25	25
Rac1/GTP	0.019	0.052	-10000	0	-0.2	24	24
LCK	0.014	0.038	-10000	0	-0.42	4	4
BCL2	0.012	0.1	-10000	0	-0.22	44	44

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.017	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.01	0.065	-10000	0	-0.12	131	131
NT3 (dimer)/TRKC	0.025	0.004	-10000	0	-10000	0	0
NT3 (dimer)/TRKB	0.021	0.052	-10000	0	-0.24	20	20
SHC/Grb2/SOS1/GAB1/PI3K	0.004	0.057	-10000	0	-0.14	70	70
RAPGEF1	0.017	0	-10000	0	-10000	0	0
BDNF	0.005	0.008	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
DYNLT1	-0.044	0.15	-10000	0	-0.41	75	75
NTRK1	0.015	0.026	-10000	0	-0.41	2	2
NTRK2	0.015	0.005	-10000	0	-10000	0	0
NTRK3	0.017	0.003	-10000	0	-10000	0	0
NT-4/5 (dimer)/TRKB	0.011	0.051	-10000	0	-0.24	20	20
neuron apoptosis	0.01	0.048	0.19	17	-10000	0	17
SHC 2-3/Grb2	-0.011	0.051	-10000	0	-0.2	17	17
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
SHC2	-0.012	0.05	-10000	0	-0.17	36	36
SHC3	-0.014	0.06	-10000	0	-0.19	40	40
STAT3 (dimer)	-0.028	0.11	-10000	0	-0.24	105	105
NT3 (dimer)/TRKA	0.023	0.058	-10000	0	-0.24	23	23
RIN/GDP	0.015	0.028	-10000	0	-0.12	6	6
GIPC1	0.017	0	-10000	0	-10000	0	0
KRAS	0.017	0.002	-10000	0	-10000	0	0
DNAJA3	0.002	0.043	-10000	0	-0.17	23	23
RIN/GTP	0.005	0.023	-10000	0	-0.29	3	3
CCND1	-0.059	0.17	-10000	0	-0.4	105	105
MAGED1	0.017	0.001	-10000	0	-10000	0	0
PTPN11	0.017	0	-10000	0	-10000	0	0
RICS	0.013	0.008	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0	0.074	-10000	0	-0.24	46	46
GRB2	0.017	0.002	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.022	0.016	-10000	0	-0.24	2	2
TRKA/NEDD4-2	0.024	0.019	-10000	0	-0.28	2	2
ELMO1	0.011	0.008	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.015	0.011	-10000	0	-10000	0	0
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.016	0.019	-10000	0	-0.41	1	1
DOCK1	0.017	0	-10000	0	-10000	0	0
GAB2	0.016	0.019	-10000	0	-0.41	1	1
RIT2	0.007	0.033	-10000	0	-0.41	3	3
RIT1	-0.12	0.2	-10000	0	-0.41	163	163
FRS2	0.015	0.032	-10000	0	-0.41	3	3
DNM1	0.003	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.017	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.004	0.04	-10000	0	-0.17	19	19
mol:GDP	0.017	0.047	-10000	0	-0.14	12	12
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.008	0.006	-10000	0	-10000	0	0
RIT1/GDP	-0.023	0.08	-10000	0	-0.13	159	159
TIAM1	0.016	0.003	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.001	0.044	-10000	0	-0.24	12	12
KIDINS220/CRKL/C3G	0.025	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.002	0.088	-10000	0	-0.28	46	46
FRS2 family/SHP2	0.033	0.02	-10000	0	-0.24	3	3
SHC/GRB2/SOS1/GAB1	0.01	0.072	-10000	0	-0.21	50	50
RIT1/GTP	-0.081	0.14	-10000	0	-0.29	163	163
NT3 (dimer)	0.017	0	-10000	0	-10000	0	0
RAP1/GDP	-0.005	0.021	-10000	0	-10000	0	0
KIDINS220/CRKL	0.017	0	-10000	0	-10000	0	0
BDNF (dimer)	0.005	0.008	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.022	0.016	-10000	0	-0.24	2	2
Schwann cell development	-0.002	0.007	-10000	0	-10000	0	0
EHD4	-0.011	0.1	-10000	0	-0.41	34	34
FRS2 family/GRB2/SOS1	0.031	0.019	-10000	0	-0.21	3	3
FRS2 family/SHP2/CRK family/C3G/GAB2	0.033	0.011	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.017	0	-10000	0	-10000	0	0
CDC42/GTP	0.002	0.03	-10000	0	-0.16	9	9
ABL1	0.016	0.019	-10000	0	-0.41	1	1
SH2B family/GRB2/SOS1	0.013	0.001	-10000	0	-10000	0	0
Rap1/GTP	0.005	0.021	-10000	0	-10000	0	0
STAT3	-0.028	0.11	-10000	0	-0.24	105	105
axon guidance	0	0.027	-10000	0	-0.16	9	9
MAPK3	0.019	0.014	-10000	0	-0.21	2	2
MAPK1	0.018	0.015	-10000	0	-0.21	2	2
CDC42/GDP	0.02	0.037	-10000	0	-0.1	7	7
NTF3	0.017	0	-10000	0	-10000	0	0
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.013	0.051	-10000	0	-0.24	21	21
PI3K	0.009	0.065	-10000	0	-0.28	25	25
FRS3	0.017	0	-10000	0	-10000	0	0
FAIM	0.002	0.08	-10000	0	-0.41	19	19
GAB1	0.014	0.037	-10000	0	-0.41	4	4
RASGRF1	0.001	0.045	-10000	0	-0.17	25	25
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	0.018	0.008	-10000	0	-10000	0	0
RGS19	0.017	0	-10000	0	-10000	0	0
CDC42	0.017	0	-10000	0	-10000	0	0
RAS family/GTP	0.001	0.061	-10000	0	-0.18	28	28
Rac1/GDP	0.02	0.037	-10000	0	-0.1	3	3
NGF (dimer)/TRKA/GRIT	0.016	0.019	-10000	0	-0.24	2	2
neuron projection morphogenesis	0	0.064	-10000	0	-0.3	7	7
NGF (dimer)/TRKA/NEDD4-2	0.022	0.016	-10000	0	-0.24	2	2
MAP2K1	0.002	0.063	-10000	0	-0.19	50	50
NGFR	-0.001	0.086	-10000	0	-0.41	22	22
NGF (dimer)/TRKA/GIPC/GAIP	-0.015	0.052	-10000	0	-0.14	76	76
RAS family/GTP/PI3K	-0.022	0.076	-10000	0	-0.14	156	156
FRS2 family/SHP2/GRB2/SOS1	0.039	0.018	-10000	0	-0.19	3	3
NRAS	-0.094	0.19	-10000	0	-0.41	136	136
GRB2/SOS1	0.013	0.001	-10000	0	-10000	0	0
PRKCI	0.016	0.019	-10000	0	-0.41	1	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.003	0.031	-10000	0	-10000	0	0
RASA1	0.017	0.002	-10000	0	-10000	0	0
TRKA/c-Abl	0.024	0.023	-10000	0	-0.28	3	3
SQSTM1	0.016	0.019	-10000	0	-0.41	1	1
BDNF (dimer)/TRKB/GIPC	-0.005	0.049	-10000	0	-0.21	15	15
NGF (dimer)/TRKA/p62/Atypical PKCs	0.029	0.02	-10000	0	-0.2	4	4
MATK	0.017	0	-10000	0	-10000	0	0
NEDD4L	0.017	0	-10000	0	-10000	0	0
RAS family/GDP	-0.025	0.041	-10000	0	-0.15	24	24
NGF (dimer)/TRKA	-0.001	0.046	-10000	0	-0.14	44	44
Rac1/GTP	-0.015	0.033	-10000	0	-0.15	15	15
FRS2 family/SHP2/CRK family	0.05	0.018	-10000	0	-0.19	3	3

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.019	0.034	-9999	-0.24	9	9
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.01	0.056	-9999	-0.41	9	9
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.016	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.003	0.028	-9999	-0.13	24	24
response to UV	0	0	-9999	-10000	0	0
YES1	-0.047	0.15	-9999	-0.41	79	79
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.017	0	-9999	-10000	0	0
FYN	0.015	0.027	-9999	-0.41	2	2
MAP3K12	0.017	0	-9999	-10000	0	0
FGR	0.003	0.076	-9999	-0.41	17	17
p38 alpha/TAB1	-0.003	0.067	-9999	-0.16	49	49
PRKG1	0.017	0	-9999	-10000	0	0
DUSP8	0.013	0.007	-9999	-10000	0	0
PGK/cGMP/p38 alpha	-0.005	0.064	-9999	-0.16	46	46
apoptosis	-0.003	0.065	-9999	-0.15	49	49
RAL/GTP	0	0.074	-9999	-0.24	46	46
LYN	-0.035	0.14	-9999	-0.41	64	64
DUSP1	0.002	0.078	-9999	-0.41	18	18
PAK1	0.017	0	-9999	-10000	0	0
SRC	0.017	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.033	0	-9999	-10000	0	0
TRAF6	0.017	0	-9999	-10000	0	0
RAC1	0.017	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.023	0	-9999	-10000	0	0
MAPK11	-0.014	0.076	-9999	-0.16	76	76
BLK	0.017	0	-9999	-10000	0	0
HCK	-0.053	0.16	-9999	-0.41	86	86
MAP2K3	0.017	0	-9999	-10000	0	0
DUSP16	0	0	-9999	-10000	0	0
DUSP10	0.011	0.049	-9999	-0.41	7	7
TRAF6/MEKK3	0.022	0	-9999	-10000	0	0
MAP3K7IP1	0.017	0	-9999	-10000	0	0
MAPK14	-0.01	0.07	-9999	-0.15	77	77
positive regulation of innate immune response	-0.015	0.087	-9999	-0.18	78	78
LCK	0.014	0.037	-9999	-0.41	4	4
p38alpha-beta/MKP7	-0.016	0.083	-9999	-0.18	78	78
p38alpha-beta/MKP5	-0.01	0.09	-9999	-0.21	57	57
PGK/cGMP	0.013	0	-9999	-10000	0	0
PAK2	-0.002	0.09	-9999	-0.41	24	24
p38alpha-beta/MKP1	-0.013	0.097	-9999	-0.22	62	62
CDC42	0.017	0	-9999	-10000	0	0
RALB	0.016	0.019	-9999	-0.41	1	1
RALA	-0.02	0.12	-9999	-0.41	45	45
PAK3	0.003	0.006	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.037	0.043	-10000	0	-0.17	1	1
TBX21	0.045	0.12	-10000	0	-0.35	27	27
B2M	0.017	0	-10000	0	-10000	0	0
TYK2	0.017	0.026	-10000	0	-0.44	1	1
IL12RB1	0.017	0.016	-10000	0	-10000	0	0
GADD45B	0.046	0.12	-10000	0	-0.4	19	19
IL12RB2	0.018	0.017	-10000	0	-10000	0	0
GADD45G	0.044	0.12	-10000	0	-0.34	26	26
natural killer cell activation	0.002	0.014	-10000	0	-10000	0	0
RELB	0.016	0.019	-10000	0	-0.41	1	1
RELA	0.017	0	-10000	0	-10000	0	0
IL18	-0.017	0.12	-10000	0	-0.41	45	45
IL2RA	0.012	0.046	-10000	0	-0.41	6	6
IFNG	0.016	0.019	-10000	0	-0.41	1	1
STAT3 (dimer)	0.042	0.14	-10000	0	-0.38	17	17
HLA-DRB5	-0.002	0.005	-10000	0	-10000	0	0
FASLG	0.045	0.12	-10000	0	-0.37	23	23
NF kappa B2 p52/RelB	0.028	0.14	-10000	0	-0.39	18	18
CD4	-0.002	0.083	-10000	0	-0.42	20	20
SOCS1	0.017	0	-10000	0	-10000	0	0
EntrezGene:6955	-0.003	0.006	-10000	0	-10000	0	0
CD3D	-0.003	0.082	-10000	0	-0.42	20	20
CD3E	0.014	0.02	-10000	0	-0.41	1	1
CD3G	0.012	0.021	-10000	0	-0.41	1	1
IL12Rbeta2/JAK2	0.028	0.027	-10000	0	-10000	0	0
CCL3	0.038	0.12	-10000	0	-0.35	30	30
CCL4	0.045	0.14	-10000	0	-0.44	26	26
HLA-A	0.016	0.019	-10000	0	-0.41	1	1
IL18/IL18R	0.033	0.083	-10000	0	-0.23	45	45
NOS2	0.039	0.12	-10000	0	-0.32	30	30
IL12/IL12R/TYK2/JAK2/SPHK2	0.037	0.043	-10000	0	-0.17	1	1
IL1R1	0.043	0.13	-10000	0	-0.38	25	25
IL4	0.015	0.014	-10000	0	-10000	0	0
JAK2	0.017	0.016	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.016	0.032	-10000	0	-0.16	9	9
RAB7A	0.048	0.12	-10000	0	-0.37	11	11
lysosomal transport	0.048	0.12	-10000	0	-0.37	8	8
FOS	-0.081	0.2	-10000	0	-0.4	131	131
STAT4 (dimer)	0.038	0.13	-10000	0	-0.38	15	15
STAT5A (dimer)	0.027	0.14	-10000	0	-0.38	19	19
GZMA	0.034	0.15	-10000	0	-0.45	29	29
GZMB	0.038	0.14	-10000	0	-0.46	23	23
HLX	0.013	0.042	-10000	0	-0.41	5	5
LCK	0.041	0.13	-10000	0	-0.37	30	30
TCR/CD3/MHC II/CD4	-0.075	0.1	-10000	0	-0.14	320	320
IL2/IL2R	0.035	0.053	-10000	0	-0.26	15	15
MAPK14	0.043	0.13	-10000	0	-0.42	11	11
CCR5	0.043	0.13	-10000	0	-0.44	17	17
IL1B	0.006	0.071	-10000	0	-0.41	14	14
STAT6	0.033	0.048	-10000	0	-0.18	3	3
STAT4	0.01	0.008	-10000	0	-10000	0	0
STAT3	0.009	0.059	-10000	0	-0.41	10	10
STAT1	0.002	0.078	-10000	0	-0.41	18	18
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
NFKB2	0.017	0	-10000	0	-10000	0	0
IL12B	0.018	0.017	-10000	0	-10000	0	0
CD8A	0	0	-10000	0	-10000	0	0
CD8B	0.015	0.026	-10000	0	-0.41	2	2
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.037	0.043	0.17	1	-10000	0	1
IL2RB	0.014	0.037	-10000	0	-0.41	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.039	0.13	-10000	0	-0.36	15	15
IL2RG	0.01	0.056	-10000	0	-0.41	9	9
IL12	0.028	0.027	-10000	0	-10000	0	0
STAT5A	0.016	0.019	-10000	0	-0.41	1	1
CD247	0.013	0.027	-10000	0	-0.42	2	2
IL2	0.017	0	-10000	0	-10000	0	0
SPHK2	0.017	0	-10000	0	-10000	0	0
FRAP1	0.016	0.019	-10000	0	-0.41	1	1
IL12A	0.017	0.016	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	0.047	0.13	-10000	0	-0.39	24	24
MAP2K3	0.039	0.13	-10000	0	-0.42	11	11
RIPK2	0.016	0.019	-10000	0	-0.41	1	1
MAP2K6	0.039	0.13	-10000	0	-0.42	11	11
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.22	0.21	-10000	0	-0.42	292	292
IL18RAP	0.02	0.006	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.025	0.028	-10000	0	-0.32	1	1
EOMES	-0.002	0.019	0.05	3	-10000	0	3
STAT1 (dimer)	0.039	0.13	-10000	0	-0.38	15	15
T cell proliferation	0.024	0.12	-10000	0	-0.34	12	12
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.02	0.006	-10000	0	-10000	0	0
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.028	0.088	-10000	0	-0.36	17	17
ATF2	0.045	0.13	-10000	0	-0.4	11	11

×

Retinoic acid receptors-mediated signaling

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
HDAC1	-0.036	0.14	-10000	0	-0.41	65	65
HDAC3	0.017	0	-10000	0	-10000	0	0
VDR	0.017	0	-10000	0	-10000	0	0
Cbp/p300/PCAF	0.023	0	-10000	0	-10000	0	0
EP300	0.017	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.034	0.011	-10000	0	-10000	0	0
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.015	0.026	-10000	0	-0.41	2	2
AKT1	0.069	0.053	0.13	234	-0.12	3	237
RAR alpha/9cRA/Cyclin H	0.012	0.053	-10000	0	-0.2	6	6
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.031	0.006	-10000	0	-10000	0	0
CDC2	-0.14	0.21	-10000	0	-0.41	193	193
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.025	0.004	-10000	0	-10000	0	0
NCOR2	0.017	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.013	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	0.043	0.034	-10000	0	-0.24	3	3
NCOA2	0.017	0	-10000	0	-10000	0	0
NCOA3	0.015	0.032	-10000	0	-0.41	3	3
NCOA1	0.017	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.017	0	-10000	0	-10000	0	0
RARG	0.018	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.024	0.001	-10000	0	-10000	0	0
MAPK3	0.018	0.001	-10000	0	-10000	0	0
MAPK1	0.017	0.003	-10000	0	-10000	0	0
MAPK8	0.018	0.002	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.012	0.052	-10000	0	-0.23	3	3
RARA	0.025	0.004	-10000	0	-10000	0	0
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.032	0.003	-10000	0	-10000	0	0
PRKCA	0.02	0.003	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.023	0.042	-10000	0	-0.32	3	3
RXRG	0.025	0.016	-10000	0	-0.17	3	3
RXRA	-0.013	0.061	-10000	0	-0.2	3	3
RXRB	0.026	0.004	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.013	0	-10000	0	-10000	0	0
RBP1	-0.18	0.21	-10000	0	-0.41	237	237
CRBP1/9-cic-RA	-0.12	0.15	-10000	0	-0.29	237	237
RARB	0.019	0.001	-10000	0	-10000	0	0
PRKCG	0.02	0.003	-10000	0	-10000	0	0
MNAT1	0.016	0.019	-10000	0	-0.41	1	1
RAR alpha/RXRs	0.057	0.059	-10000	0	-0.23	1	1
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.049	0.027	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.01	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.029	0.036	-10000	0	-0.3	3	3
positive regulation of DNA binding	0.007	0.047	-10000	0	-0.19	6	6
NRIP1	0.032	0.038	-10000	0	-0.4	3	3
RXRs/RARs	0.029	0.03	-10000	0	-0.23	3	3
RXRs/RXRs/DNA/9cRA	0.004	0.05	-10000	0	-0.24	3	3
PRKACA	0.017	0	-10000	0	-10000	0	0
CDK7	0.015	0.026	-10000	0	-0.41	2	2
TFIIH	0.033	0.02	-10000	0	-0.24	3	3
RAR alpha/9cRA	0.045	0.016	-10000	0	-0.16	3	3
CCNH	0.017	0.001	-10000	0	-10000	0	0
CREBBP	0.017	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.032	0.02	-10000	0	-0.17	5	5

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	0.016	0.071	-9999	-0.2	33	33
FYN	0.011	0.079	-9999	-0.25	26	26
LAT/GRAP2/SLP76	0.026	0.074	-9999	-0.22	35	35
IKBKB	0.017	0	-9999	-10000	0	0
AKT1	0.029	0.054	-9999	-0.2	15	15
B2M	0.018	0.004	-9999	-10000	0	0
IKBKG	0.016	0.026	-9999	-0.093	10	10
MAP3K8	-0.017	0.12	-9999	-0.41	42	42
mol:Ca2+	-0.001	0.006	-9999	-10000	0	0
integrin-mediated signaling pathway	0.011	0	-9999	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.029	0.068	-9999	-0.26	16	16
TRPV6	0.002	0.003	-9999	-10000	0	0
CD28	0.017	0.001	-9999	-10000	0	0
SHC1	0.012	0.081	-9999	-0.19	58	58
receptor internalization	0.029	0.046	-9999	-0.24	8	8
PRF1	0.027	0.073	-9999	-0.41	13	13
KRAS	0.017	0.002	-9999	-10000	0	0
GRB2	0.017	0.002	-9999	-10000	0	0
COT/AKT1	0.022	0.076	-9999	-0.2	43	43
LAT	0.027	0.055	-9999	-0.24	11	11
EntrezGene:6955	0.001	0.002	-9999	-10000	0	0
CD3D	0.002	0.083	-9999	-0.42	20	20
CD3E	0.017	0.019	-9999	-0.42	1	1
CD3G	0.017	0.02	-9999	-0.42	1	1
RASGRP2	0.01	0.008	-9999	-10000	0	0
RASGRP1	-0.006	0.076	-9999	-0.23	30	30
HLA-A	0.017	0.019	-9999	-0.41	1	1
RASSF5	0	0	-9999	-10000	0	0
RAP1A/GTP/RAPL	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:GDP	0.004	0.032	-9999	-0.081	27	27
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.01	0.03	-9999	-0.13	20	20
PRKCA	0.021	0.042	-9999	-0.14	24	24
GRAP2	0.017	0	-9999	-10000	0	0
mol:IP3	-0.014	0.048	-9999	-0.2	24	24
EntrezGene:6957	0.001	0.003	-9999	-10000	0	0
TCR/CD3/MHC I/CD8	0.025	0.039	-9999	-0.26	6	6
ORAI1	0	0	-9999	-10000	0	0
CSK	0.026	0.055	-9999	-0.22	14	14
B7 family/CD28	0.033	0.082	-9999	-0.23	37	37
CHUK	0.016	0.019	-9999	-0.41	1	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.025	0.059	-9999	-0.22	18	18
PTPN6	0.02	0.07	-9999	-0.3	17	17
VAV1	0.027	0.056	-9999	-0.22	15	15
Monovalent TCR/CD3	0.017	0.041	-9999	-0.17	20	20
CBL	0.017	0	-9999	-10000	0	0
LCK	0.01	0.079	-9999	-0.25	26	26
PAG1	0.024	0.055	-9999	-0.23	14	14
RAP1A	0.017	0	-9999	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.023	0.062	-9999	-0.23	19	19
CD80	0.017	0.019	-9999	-0.41	1	1
CD86	-0.003	0.092	-9999	-0.41	25	25
PDK1/CARD11/BCL10/MALT1	-0.011	0.037	-9999	-0.15	22	22
HRAS	0.016	0.019	-9999	-0.41	1	1
GO:0035030	0.019	0.07	-9999	-0.2	37	37
CD8A	0.001	0.003	-9999	-10000	0	0
CD8B	0.016	0.027	-9999	-0.42	2	2
PTPRC	-0.086	0.18	-9999	-0.41	127	127
PDK1/PKC theta	0.033	0.063	-9999	-0.24	14	14
CSK/PAG1	0.026	0.053	-9999	-0.22	14	14
SOS1	0	0	-9999	-10000	0	0
peptide-MHC class I	0.026	0.015	-9999	-0.28	1	1
GRAP2/SLP76	0.027	0.081	-9999	-0.24	35	35
STIM1	0.002	0.003	-9999	-10000	0	0
RAS family/GTP	-0.005	0.052	-9999	-0.11	53	53
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.029	0.047	-9999	-0.25	8	8
mol:DAG	-0.013	0.044	-9999	-0.18	25	25
RAP1A/GDP	0.004	0.015	-9999	-0.041	12	12
PLCG1	0.017	0	-9999	-10000	0	0
CD247	0.016	0.027	-9999	-0.42	2	2
cytotoxic T cell degranulation	0.027	0.072	-9999	-0.4	13	13
RAP1A/GTP	0	0.002	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.029	0.061	-9999	-0.23	16	16
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.015	0.058	-9999	-0.24	24	24
NRAS	-0.094	0.19	-9999	-0.41	136	136
ZAP70	0.017	0	-9999	-10000	0	0
GRB2/SOS1	0.013	0.001	-9999	-10000	0	0
LAT/GRAP2/SLP76/VAV1	0.023	0.071	-9999	-0.24	24	24
MALT1	-0.002	0.09	-9999	-0.41	24	24
TRAF6	0.017	0	-9999	-10000	0	0
CD8 heterodimer	0.013	0.019	-9999	-0.29	2	2
CARD11	0	0	-9999	-10000	0	0
PRKCB	-0.01	0.032	-9999	-0.14	25	25
PRKCE	0.021	0.042	-9999	-0.14	24	24
PRKCQ	0.031	0.067	-9999	-0.26	15	15
LCP2	-0.007	0.099	-9999	-0.41	30	30
BCL10	0.014	0.037	-9999	-0.41	4	4
regulation of survival gene product expression	0.028	0.049	-9999	-0.18	14	14
IKK complex	0.025	0.022	-9999	-0.069	6	6
RAS family/GDP	-0.013	0.02	-9999	-0.046	135	135
MAP3K14	0.021	0.061	-9999	-0.16	44	44
PDPK1	0.03	0.053	-9999	-0.2	13	13
TCR/CD3/MHC I/CD8/Fyn	0.028	0.051	-9999	-0.27	9	9

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.017	0.002	-9999	-10000	0	0
VLDLR	0.015	0.032	-9999	-0.41	3	3
LRPAP1	0.017	0	-9999	-10000	0	0
NUDC	0.017	0	-9999	-10000	0	0
RELN/LRP8	0.015	0.026	-9999	-0.24	3	3
CaM/Ca2+	0.012	0.003	-9999	-10000	0	0
KATNA1	0.012	0.046	-9999	-0.41	6	6
GO:0030286	0	0	-9999	-10000	0	0
ABL1	0.01	0.019	-9999	-0.21	2	2
IQGAP1/CaM	-0.048	0.13	-9999	-0.28	127	127
DAB1	0.017	0	-9999	-10000	0	0
IQGAP1	-0.086	0.18	-9999	-0.41	127	127
PLA2G7	0.011	0.052	-9999	-0.41	8	8
CALM1	0.016	0.004	-9999	-10000	0	0
DYNLT1	-0.044	0.15	-9999	-0.41	75	75
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.025	0	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.017	0	-9999	-10000	0	0
CDK5R1	0.014	0.007	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0.013	0.001	-9999	-10000	0	0
CDK5R2	0.007	0.008	-9999	-10000	0	0
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	0.014	0.029	-9999	-0.24	4	4
YWHAE	0.017	0.001	-9999	-10000	0	0
NDEL1/14-3-3 E	0.025	0.045	-9999	-10000	0	0
MAP1B	0.006	0.002	-9999	-10000	0	0
RAC1	-0.01	0.049	-9999	-0.096	127	127
p35/CDK5	0.013	0.019	-9999	-0.18	1	1
RELN	0.006	0.033	-9999	-0.41	3	3
PAFAH/LIS1	0.022	0.032	-9999	-0.24	8	8
LIS1/CLIP170	0.026	0.003	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.004	0.039	-9999	-0.27	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	0.015	0.02	-9999	-10000	0	0
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.023	0.043	-9999	-0.16	1	1
LIS1/IQGAP1	-0.037	0.11	-9999	-0.24	127	127
RHOA	-0.01	0.049	-9999	-0.096	127	127
PAFAH1B1	0.018	0.002	-9999	-10000	0	0
PAFAH1B3	0.016	0.019	-9999	-0.41	1	1
PAFAH1B2	0.017	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.023	0.008	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	0.025	0.048	-9999	-10000	0	0
LRP8	0.017	0	-9999	-10000	0	0
NDEL1/Katanin 60	0.024	0.047	-9999	-10000	0	0
P39/CDK5	0.006	0.016	-9999	-0.18	1	1
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.026	0.003	-9999	-10000	0	0
CDK5	0.009	0.017	-9999	-0.19	2	2
PPP2R5D	0.017	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.022	0.002	-9999	-10000	0	0
CSNK2A1	0.017	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	0.019	0.029	-9999	-0.19	4	4
RELN/VLDLR	0.019	0.03	-9999	-0.21	4	4
CDC42	-0.01	0.049	-9999	-0.096	127	127

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.025	0	-9999	-10000	0	0
Necdin/E2F1	0.016	0.012	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.03	0.047	-9999	-0.19	22	22
NGF (dimer)/p75(NTR)/BEX1	0.007	0.048	-9999	-0.24	17	17
NT-4/5 (dimer)/p75(NTR)	0	0.06	-9999	-0.29	22	22
IKBKB	0.017	0	-9999	-10000	0	0
AKT1	0.001	0.067	-9999	-0.21	47	47
IKBKG	0.017	0	-9999	-10000	0	0
BDNF	0.005	0.008	-9999	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1	0.001	0.051	-9999	-0.24	22	22
FURIN	0.017	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.002	0.04	-9999	-0.24	10	10
LINGO1	0	0	-9999	-10000	0	0
Sortilin/TRAF6/NRIF	-0.014	0.049	-9999	-0.34	2	2
proBDNF (dimer)	0.005	0.008	-9999	-10000	0	0
NTRK1	0.015	0.026	-9999	-0.41	2	2
RTN4R	0	0	-9999	-10000	0	0
neuron apoptosis	0.051	0.072	-9999	-0.21	12	12
IRAK1	0.017	0.001	-9999	-10000	0	0
SHC1	-0.017	0.087	-9999	-0.25	66	66
ARHGDIA	0.017	0	-9999	-10000	0	0
RhoA/GTP	0.013	0.001	-9999	-10000	0	0
Gamma Secretase	0.032	0.067	-9999	-0.2	39	39
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.021	0.048	-9999	-0.21	20	20
MAGEH1	0.016	0.005	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.012	0.043	-9999	-0.21	15	15
Mammalian IAPs/DIABLO	0.018	0.059	-9999	-0.21	33	33
proNGF (dimer)	0	0	-9999	-10000	0	0
MAGED1	0.017	0.001	-9999	-10000	0	0
APP	0.017	0.001	-9999	-10000	0	0
NT-4/5 (dimer)	0	0	-9999	-10000	0	0
ZNF274	0.012	0.046	-9999	-0.41	6	6
RhoA/GDP/RHOGDI	0.018	0.045	-9999	-0.2	22	22
NGF	0	0	-9999	-10000	0	0
cell cycle arrest	0	0.042	-9999	-0.2	22	22
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0	0.059	-9999	-0.13	92	92
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.012	0.052	-9999	-0.24	22	22
NCSTN	-0.007	0.099	-9999	-0.41	30	30
mol:GTP	0.01	0.051	-9999	-0.23	22	22
PSENEN	0.017	0.001	-9999	-10000	0	0
mol:ceramide	0.01	0.046	-9999	-0.21	22	22
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.021	0.026	-9999	-0.098	25	25
p75(NTR)/beta APP	0.012	0.062	-9999	-0.28	22	22
BEX1	0.012	0.008	-9999	-10000	0	0
mol:GDP	-0.004	0.05	-9999	-0.24	22	22
NGF (dimer)	-0.003	0.087	-9999	-0.21	78	78
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.012	0.047	-9999	-0.22	22	22
PIK3R1	0.016	0.004	-9999	-10000	0	0
RAC1/GTP	0.011	0.044	-9999	-0.2	22	22
MYD88	-0.041	0.15	-9999	-0.41	71	71
CHUK	0.016	0.019	-9999	-0.41	1	1
NGF (dimer)/p75(NTR)/PKA	0.011	0.051	-9999	-0.23	22	22
RHOB	0.013	0.037	-9999	-0.41	4	4
RHOA	0.017	0.001	-9999	-10000	0	0
MAGE-G1/E2F1	0.013	0	-9999	-10000	0	0
NT3 (dimer)	0.017	0	-9999	-10000	0	0
TP53	-0.016	0.062	-9999	-0.21	39	39
PRDM4	0.01	0.046	-9999	-0.21	22	22
BDNF (dimer)	-0.012	0.068	-9999	-0.23	32	32
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
SORT1	0.017	0	-9999	-10000	0	0
activation of caspase activity	0.027	0.046	-9999	-0.19	22	22
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.023	0.049	-9999	-0.21	22	22
RHOC	-0.12	0.2	-9999	-0.41	163	163
XIAP	0	0	-9999	-10000	0	0
MAPK10	0.044	0.061	-9999	-10000	0	0
DIABLO	0.017	0	-9999	-10000	0	0
SMPD2	0.01	0.046	-9999	-0.21	22	22
APH1B	0.017	0	-9999	-10000	0	0
APH1A	0.009	0.059	-9999	-0.41	10	10
proNGF (dimer)/p75(NTR)/Sortilin	0.012	0.052	-9999	-0.24	22	22
PSEN1	0.016	0.019	-9999	-0.41	1	1
APAF-1/Pro-Caspase 9	0.023	0.027	-9999	-0.28	4	4
NT3 (dimer)/p75(NTR)	0.013	0.062	-9999	-0.28	22	22
MAPK8	0.081	0.054	-9999	-10000	0	0
MAPK9	0.08	0.054	-9999	-10000	0	0
APAF1	0.017	0	-9999	-10000	0	0
NTF3	0.017	0	-9999	-10000	0	0
NTF4	0	0	-9999	-10000	0	0
NDN	0.011	0.008	-9999	-10000	0	0
RAC1/GDP	0.013	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.04	0.11	-9999	-0.19	170	170
p75 CTF/Sortilin/TRAF6/NRIF	0.039	0.036	-9999	-0.21	11	11
RhoA-B-C/GTP	0.01	0.051	-9999	-0.23	22	22
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.006	0.042	-9999	-0.19	13	13
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.006	0.039	-9999	-0.21	10	10
PRKACB	0.016	0.005	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	0.005	0.026	-9999	-0.23	5	5
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.01	0.1	-9999	-0.41	33	33
BIRC2	0.017	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.007	0.035	-9999	-0.2	15	15
BAD	0.082	0.053	-9999	-10000	0	0
RIPK2	0.016	0.019	-9999	-0.41	1	1
NGFR	-0.001	0.086	-9999	-0.41	22	22
CYCS	0.014	0.043	-9999	-0.19	22	22
ADAM17	0.013	0.042	-9999	-0.41	5	5
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.022	0.05	-9999	-0.21	23	23
BCL2L11	0.082	0.053	-9999	-10000	0	0
BDNF (dimer)/p75(NTR)	-0.002	0.046	-9999	-0.28	10	10
PI3K	0.01	0.072	-9999	-0.23	43	43
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.012	0.047	-9999	-0.22	22	22
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0.017	0.001	-9999	-10000	0	0
PRKCI	0.016	0.019	-9999	-0.41	1	1
NGF (dimer)/p75(NTR)	0	0.06	-9999	-0.29	22	22
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.023	0.049	-9999	-0.21	22	22
TRAF6	0.017	0	-9999	-10000	0	0
RAC1	0.017	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
PLG	0.017	0	-9999	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.007	0.049	-9999	-0.2	19	19
SQSTM1	0.016	0.019	-9999	-0.41	1	1
NGFRAP1	0.017	0.002	-9999	-10000	0	0
CASP3	0.077	0.052	-9999	-10000	0	0
E2F1	0.017	0	-9999	-10000	0	0
CASP9	0.014	0.037	-9999	-0.41	4	4
IKK complex	0.037	0.029	-9999	-0.19	3	3
NGF (dimer)/TRKA	0.012	0.019	-9999	-0.29	2	2
MMP7	-0.046	0.15	-9999	-0.41	78	78
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.028	0.053	-9999	-0.19	28	28
MMP3	0.011	0.049	-9999	-0.41	7	7
APAF-1/Caspase 9	-0.016	0.046	-9999	-0.31	1	1

×

IL4-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
BCL2L1	-0.053	0.22	-10000	0	-0.71	11	11
STAT6 (cleaved dimer)	-0.11	0.16	-10000	0	-0.69	13	13
IGHG1	-0.015	0.12	-10000	0	-0.39	13	13
IGHG3	-0.059	0.21	-10000	0	-0.69	11	11
AKT1	-0.004	0.15	-10000	0	-0.5	8	8
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.015	0.12	-10000	0	-0.37	13	13
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.008	0.14	-10000	0	-0.45	9	9
THY1	-0.076	0.28	-10000	0	-0.64	73	73
MYB	0.011	0.052	-10000	0	-0.41	8	8
HMGA1	0.016	0.019	-10000	0	-0.41	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.013	0.16	-10000	0	-0.47	13	13
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.011	0.14	-10000	0	-0.42	11	11
SP1	-0.021	0.045	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.015	0.013	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.041	0.21	-10000	0	-0.72	11	11
SOCS1	-0.012	0.18	-10000	0	-0.54	9	9
SOCS3	-0.006	0.14	-10000	0	-0.52	5	5
FCER2	-0.034	0.19	-10000	0	-0.69	6	6
PARP14	0.001	0.001	-10000	0	-10000	0	0
CCL17	-0.053	0.22	-10000	0	-0.69	12	12
GRB2	0.017	0.002	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.015	0.14	-10000	0	-0.38	23	23
T cell proliferation	-0.042	0.22	-10000	0	-0.71	12	12
IL4R/JAK1	-0.056	0.22	-10000	0	-0.69	14	14
EGR2	-0.057	0.24	-10000	0	-0.71	17	17
JAK2	0.013	0.03	-10000	0	-10000	0	0
JAK3	0.021	0.003	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
JAK1	0.017	0.013	-10000	0	-10000	0	0
COL1A2	-0.15	0.23	-10000	0	-0.46	118	118
CCL26	-0.06	0.22	-10000	0	-0.65	16	16
IL4R	-0.06	0.24	-10000	0	-0.72	15	15
PTPN6	0.01	0.061	-10000	0	-0.4	11	11
IL13RA2	-0.13	0.28	-10000	0	-0.64	52	52
IL13RA1	-0.055	0.16	-10000	0	-0.43	80	80
IRF4	0.017	0.075	-10000	0	-0.62	1	1
ARG1	0.002	0.11	-10000	0	-0.38	13	13
CBL	-0.016	0.15	-10000	0	-0.5	9	9
GTF3A	0.014	0.027	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
IL13RA1/JAK2	-0.029	0.12	-10000	0	-0.3	80	80
IRF4/BCL6	0.013	0.078	-10000	0	-0.56	1	1
CD40LG	0.024	0.003	-10000	0	-10000	0	0
MAPK14	-0.012	0.15	-10000	0	-0.49	10	10
mitosis	-0.002	0.15	-10000	0	-0.48	8	8
STAT6	-0.038	0.24	-10000	0	-0.57	40	40
SPI1	0.016	0.053	-10000	0	-0.41	8	8
RPS6KB1	0	0.14	-10000	0	-0.46	9	9
STAT6 (dimer)	-0.038	0.24	-10000	0	-0.57	40	40
STAT6 (dimer)/PARP14	-0.068	0.22	-10000	0	-0.74	11	11
mast cell activation	0	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.001	0.13	-10000	0	-0.42	11	11
FRAP1	-0.004	0.15	-10000	0	-0.5	8	8
LTA	-0.054	0.22	-10000	0	-0.73	11	11
FES	0.017	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.051	0.24	0.66	20	-10000	0	20
CCL11	-0.055	0.22	-10000	0	-0.67	14	14
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	0.002	0.14	-10000	0	-0.41	11	11
IL2RG	0.013	0.056	-10000	0	-0.41	9	9
IL10	-0.053	0.22	-10000	0	-0.71	11	11
IRS1	0.013	0.042	-10000	0	-0.41	5	5
IRS2	0.017	0.002	-10000	0	-10000	0	0
IL4	0.005	0.087	-10000	0	-0.2	3	3
IL5	-0.053	0.22	-10000	0	-0.71	11	11
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.053	0.22	-10000	0	-0.58	19	19
COL1A1	-0.044	0.19	-10000	0	-0.47	66	66
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.056	0.22	-10000	0	-0.71	13	13
IL2R gamma/JAK3	0.026	0.041	-10000	0	-0.29	9	9
TFF3	-0.058	0.23	-10000	0	-0.7	19	19
ALOX15	-0.053	0.22	-10000	0	-0.71	11	11
MYBL1	-0.048	0.15	-10000	0	-0.41	80	80
T-helper 2 cell differentiation	-0.041	0.2	-10000	0	-0.67	9	9
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
CEBPB	0.013	0.062	-10000	0	-0.41	11	11
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.006	0.14	-10000	0	-0.45	8	8
mol:PI-3-4-5-P3	-0.003	0.15	-10000	0	-0.5	8	8
PI3K	-0.005	0.15	-10000	0	-0.52	8	8
DOK2	0	0	-10000	0	-10000	0	0
ETS1	0.016	0.015	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.012	0.14	-10000	0	-0.37	23	23
ITGB3	-0.053	0.22	-10000	0	-0.71	11	11
PIGR	-0.054	0.23	-10000	0	-0.71	12	12
IGHE	0.021	0.05	0.14	29	-0.13	1	30
MAPKKK cascade	-0.012	0.13	-10000	0	-0.37	22	22
BCL6	0.003	0.074	-10000	0	-0.41	16	16
OPRM1	-0.053	0.22	-10000	0	-0.71	11	11
RETNLB	-0.06	0.22	-10000	0	-0.65	16	16
SELP	-0.054	0.22	-10000	0	-0.72	11	11
AICDA	-0.053	0.21	-10000	0	-0.7	11	11

×

PDGFR-beta signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.011	0.06	-9999	-0.24	14	14
PDGFB-D/PDGFRB/SLAP	0.002	0.083	-9999	-0.3	37	37
PDGFB-D/PDGFRB/APS/CBL	0.021	0.02	-9999	-0.24	3	3
AKT1	0.026	0.052	-9999	-0.24	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.007	0.058	-9999	-0.21	21	21
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
FGR	0.004	0.044	-9999	-0.2	17	17
mol:Ca2+	0.008	0.038	-9999	-0.22	4	4
MYC	-0.067	0.17	-9999	-0.34	138	138
SHC1	-0.02	0.12	-9999	-0.41	46	46
HRAS/GDP	0.027	0.022	-9999	-0.19	5	5
LRP1/PDGFRB/PDGFB	0.023	0.053	-9999	-0.24	21	21
GRB10	0.004	0.074	-9999	-0.41	16	16
PTPN11	0.017	0	-9999	-10000	0	0
GO:0007205	0.008	0.039	-9999	-0.22	4	4
PTEN	0.015	0.026	-9999	-0.41	2	2
GRB2	0.017	0.002	-9999	-10000	0	0
GRB7	0.016	0.019	-9999	-0.41	1	1
PDGFB-D/PDGFRB/SHP2	0.023	0.023	-9999	-0.28	3	3
PDGFB-D/PDGFRB/GRB10	0.013	0.058	-9999	-0.29	19	19
cell cycle arrest	0.002	0.082	-9999	-0.3	37	37
HRAS	0.016	0.019	-9999	-0.41	1	1
HIF1A	0.025	0.049	-9999	-0.21	1	1
GAB1	-0.008	0.065	-9999	-0.21	19	19
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.008	0.065	-9999	-0.21	18	18
PDGFB-D/PDGFRB	0.027	0.029	-9999	-0.24	4	4
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.023	0.024	-9999	-0.28	3	3
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.003	0.079	-9999	-0.24	24	24
positive regulation of MAPKKK cascade	0.023	0.023	-9999	-0.28	3	3
PIK3R1	0.016	0.004	-9999	-10000	0	0
mol:IP3	0.008	0.039	-9999	-0.22	4	4
E5	0	0.001	-9999	-10000	0	0
CSK	0.017	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.022	0.027	-9999	-0.29	4	4
SHB	0.017	0	-9999	-10000	0	0
BLK	-0.002	0.022	-9999	-0.21	4	4
PTPN2	0.015	0.019	-9999	-0.42	1	1
PDGFB-D/PDGFRB/SNX15	0.023	0.023	-9999	-0.28	3	3
BCAR1	0	0	-9999	-10000	0	0
VAV2	-0.024	0.093	-9999	-0.23	50	50
CBL	0.017	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.023	0.023	-9999	-0.28	3	3
LCK	-0.005	0.028	-9999	-0.2	8	8
PDGFRB	0.014	0.033	-9999	-0.42	3	3
ACP1	0.017	0.001	-9999	-10000	0	0
HCK	-0.031	0.065	-9999	-0.18	71	71
ABL1	-0.003	0.055	-9999	-0.18	18	18
PDGFB-D/PDGFRB/CBL	-0.006	0.065	-9999	-0.21	17	17
PTPN1	0.016	0.003	-9999	-10000	0	0
SNX15	0.017	0	-9999	-10000	0	0
STAT3	0.009	0.059	-9999	-0.41	10	10
STAT1	0.002	0.078	-9999	-0.41	18	18
cell proliferation	-0.061	0.16	-9999	-0.32	138	138
SLA	-0.011	0.11	-9999	-0.41	35	35
actin cytoskeleton reorganization	0.026	0.036	-9999	-0.18	15	15
SRC	-0.003	0.022	-9999	-0.21	4	4
PI3K	-0.01	0.039	-9999	-0.17	24	24
PDGFB-D/PDGFRB/GRB7/SHC	0.009	0.081	-9999	-0.24	49	49
SH2B2	0	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.007	0.059	-9999	-0.22	21	21
LYN	-0.025	0.06	-9999	-0.2	35	35
LRP1	0.002	0.078	-9999	-0.41	18	18
SOS1	0	0	-9999	-10000	0	0
STAT5B	0.017	0	-9999	-10000	0	0
STAT5A	0.016	0.019	-9999	-0.41	1	1
NCK1-2/p130 Cas	0.032	0.04	-9999	-0.19	15	15
SPHK1	0.001	0.08	-9999	-0.41	19	19
EDG1	0.017	0.002	-9999	-10000	0	0
mol:DAG	0.008	0.039	-9999	-0.22	4	4
PLCG1	0.008	0.039	-9999	-0.23	4	4
NHERF/PDGFRB	0.032	0.026	-9999	-0.24	5	5
YES1	-0.028	0.063	-9999	-0.19	40	40
cell migration	0.031	0.026	-9999	-0.24	5	5
SHC/Grb2/SOS1	0.017	0.07	-9999	-0.2	48	48
SLC9A3R2	0.017	0	-9999	-10000	0	0
SLC9A3R1	0.015	0.026	-9999	-0.41	2	2
NHERF1-2/PDGFRB/PTEN	0.04	0.029	-9999	-0.21	7	7
FYN	-0.014	0.064	-9999	-0.31	22	22
DOK1	0.021	0.021	-9999	-0.21	4	4
HRAS/GTP	0.012	0.013	-9999	-0.29	1	1
PDGFB	0.017	0	-9999	-10000	0	0
RAC1	-0.041	0.12	-9999	-0.23	139	139
PRKCD	0.02	0.022	-9999	-0.22	4	4
FER	0.02	0.022	-9999	-0.22	4	4
MAPKKK cascade	-0.018	0.057	-9999	-0.19	48	48
RASA1	0.02	0.022	-9999	-0.22	4	4
NCK1	0.008	0.061	-9999	-0.41	11	11
NCK2	0.017	0.001	-9999	-10000	0	0
p62DOK/Csk	0.033	0.019	-9999	-0.19	4	4
PDGFB-D/PDGFRB/SHB	0.023	0.023	-9999	-0.28	3	3
chemotaxis	-0.003	0.054	-9999	-0.18	18	18
STAT1-3-5/STAT1-3-5	0.025	0.055	-9999	-0.19	31	31
Bovine Papilomavirus E5/PDGFRB	0.009	0.023	-9999	-0.29	3	3
PTPRJ	0.017	0	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.029	0.029	-10000	0	-0.22	3	3
epithelial cell differentiation	0.032	0.031	-10000	0	-0.21	1	1
ITCH	0.018	0.02	-10000	0	-0.41	1	1
WWP1	0.025	0.025	-10000	0	-0.26	2	2
FYN	0.015	0.027	-10000	0	-0.41	2	2
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
PRL	0.012	0.046	-10000	0	-0.41	6	6
neuron projection morphogenesis	0.022	0.058	-10000	0	-0.2	6	6
PTPRZ1	-0.003	0.088	-10000	0	-0.41	23	23
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.032	0.068	-10000	0	-0.21	8	8
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.026	0.028	-10000	0	-0.21	6	6
ADAM17	0.014	0.041	-10000	0	-0.4	5	5
ErbB4/ErbB4	0.026	0.025	-10000	0	-0.24	2	2
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.017	0.023	-10000	0	-0.26	1	1
NCOR1	0.017	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.034	0.026	-10000	0	-0.2	5	5
GRIN2B	0.033	0.024	-10000	0	-0.21	2	2
ErbB4/ErbB2/betacellulin	0.035	0.027	-10000	0	-0.19	6	6
STAT1	0.002	0.078	-10000	0	-0.41	18	18
HBEGF	0.015	0.026	-10000	0	-0.41	2	2
PRLR	0.017	0	-10000	0	-10000	0	0
E4ICDs/ETO2	0.03	0.025	-10000	0	-0.26	1	1
axon guidance	0.023	0.031	-10000	0	-0.27	1	1
NEDD4	0.007	0.069	-10000	0	-0.41	14	14
Prolactin receptor/Prolactin receptor/Prolactin	0.022	0.033	-10000	0	-0.28	6	6
CBFA2T3	0.017	0	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	0.034	0.03	-10000	0	-0.19	8	8
MAPK3	0.022	0.061	-10000	0	-0.2	7	7
STAT1 (dimer)	0.021	0.051	-10000	0	-0.22	19	19
MAPK1	0.021	0.061	-10000	0	-0.2	7	7
JAK2	0.017	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	0.03	0.027	-10000	0	-0.19	6	6
NRG1	0.016	0.028	-10000	0	-0.27	5	5
NRG3	0	0	-10000	0	-10000	0	0
NRG2	0.017	0	-10000	0	-10000	0	0
NRG4	0	0	-10000	0	-10000	0	0
heart development	0.023	0.031	-10000	0	-0.27	1	1
neural crest cell migration	0.029	0.026	-10000	0	-0.19	6	6
ERBB2	0.016	0.028	-10000	0	-0.27	5	5
WWOX/E4ICDs	0.03	0.025	-10000	0	-0.26	1	1
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
ErbB4/EGFR/neuregulin 4	-0.055	0.11	-10000	0	-0.2	194	194
apoptosis	-0.022	0.026	0.2	2	-10000	0	2
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.03	0.025	-10000	0	-0.26	1	1
ErbB4/ErbB2/epiregulin	0.031	0.043	-10000	0	-0.2	16	16
ErbB4/ErbB4/betacellulin/betacellulin	0.03	0.025	-10000	0	-0.26	1	1
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.051	0.035	-10000	0	-0.21	1	1
MDM2	0.018	0.047	-10000	0	-0.21	20	20
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.03	0.027	-10000	0	-0.19	7	7
STAT5A	0.027	0.032	-10000	0	-0.25	1	1
ErbB4/EGFR/neuregulin 1 beta	-0.046	0.11	-10000	0	-0.19	196	196
DLG4	0.017	0	-10000	0	-10000	0	0
GRB2/SHC	-0.002	0.088	-10000	0	-0.28	46	46
E4ICDs/TAB2/NCoR1	0.038	0.023	-10000	0	-0.24	1	1
STAT5A (dimer)	0.047	0.036	-10000	0	-0.23	1	1
MAP3K7IP2	0.017	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.034	0.031	-10000	0	-0.25	1	1
LRIG1	-0.002	0.088	-10000	0	-0.41	23	23
EREG	0.009	0.059	-10000	0	-0.41	10	10
BTC	0.017	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.023	0.031	-10000	0	-0.27	1	1
ERBB4	0.026	0.025	-10000	0	-0.24	2	2
STAT5B	0.017	0	-10000	0	-10000	0	0
YAP1	-0.001	0.062	-10000	0	-0.2	46	46
GRB2	0.017	0.002	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.023	0.026	-10000	0	-0.2	6	6
glial cell differentiation	-0.038	0.023	0.24	1	-10000	0	1
WWOX	0.017	0	-10000	0	-10000	0	0
cell proliferation	0.033	0.025	-10000	0	-0.2	1	1

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.019	0.004	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.061	0.024	-9999	-0.16	2	2
ERC1	0.016	0.019	-9999	-0.41	1	1
RIP2/NOD2	0.02	0.04	-9999	-0.28	9	9
NFKBIA	0.025	0.027	-9999	-0.24	5	5
BIRC2	0.017	0	-9999	-10000	0	0
IKBKB	0.017	0	-9999	-10000	0	0
RIPK2	0.016	0.019	-9999	-0.41	1	1
IKBKG	0.031	0.025	-9999	-0.17	1	1
IKK complex/A20	-0.017	0.1	-9999	-0.23	25	25
NEMO/A20/RIP2	0.016	0.019	-9999	-0.41	1	1
XPO1	0.017	0	-9999	-10000	0	0
NEMO/ATM	0.03	0.051	-9999	-0.17	26	26
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.017	0.001	-9999	-10000	0	0
Exportin 1/RanGTP	0.023	0.002	-9999	-10000	0	0
IKK complex/ELKS	0.043	0.028	-9999	-0.32	1	1
BCL10/MALT1/TRAF6	0.021	0.062	-9999	-0.24	27	27
NOD2	0.011	0.052	-9999	-0.41	8	8
NFKB1	0.016	0.037	-9999	-0.41	4	4
RELA	0.019	0.004	-9999	-10000	0	0
MALT1	-0.002	0.09	-9999	-0.41	24	24
cIAP1/UbcH5C	0.025	0.001	-9999	-10000	0	0
ATM	-0.003	0.091	-9999	-0.41	25	25
TNF/TNFR1A	-0.083	0.15	-9999	-0.28	185	185
TRAF6	0.017	0	-9999	-10000	0	0
PRKCA	0.017	0	-9999	-10000	0	0
CHUK	0.016	0.019	-9999	-0.41	1	1
UBE2D3	0.017	0.001	-9999	-10000	0	0
TNF	0.015	0.026	-9999	-0.41	2	2
NF kappa B1 p50/RelA	0.042	0.026	-9999	-0.22	5	5
BCL10	0.014	0.037	-9999	-0.41	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.027	-9999	-0.24	5	5
beta TrCP1/SCF ubiquitin ligase complex	0.019	0.004	-9999	-10000	0	0
TNFRSF1A	-0.13	0.2	-9999	-0.41	183	183
IKK complex	0.048	0.028	-9999	-10000	0	0
CYLD	0.017	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.053	0.028	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.005	0.042	-9999	-0.24	15	15
SNTA1	0.017	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.01	0.042	-9999	-0.24	15	15
MAPK12	0.015	0.02	-9999	-0.13	10	10
CCND1	-0.013	0.062	-9999	-0.14	99	99
p38 gamma/SNTA1	0.025	0.02	-9999	-10000	0	0
MAP2K3	0.017	0	-9999	-10000	0	0
PKN1	0.009	0.059	-9999	-0.41	10	10
G2/M transition checkpoint	0.015	0.02	-9999	-0.13	10	10
MAP2K6	0.013	0.023	-9999	-0.15	10	10
MAPT	0.009	0.035	-9999	-0.18	15	15
MAPK13	0.009	0.05	-9999	-0.29	15	15
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.011	0.027	-9999	-0.18	10	10

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.029	0.02	-9999	-0.18	5	5
TC10/GTP	0.027	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.044	0.025	-9999	-0.21	5	5
HRAS	0.016	0.019	-9999	-0.41	1	1
APS homodimer	0	0	-9999	-10000	0	0
GRB14	0.002	0.078	-9999	-0.41	18	18
FOXO3	0.012	0.013	-9999	-10000	0	0
AKT1	0.021	0.062	-9999	-0.19	5	5
INSR	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.048	0.006	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.004	0.074	-9999	-0.41	16	16
SORBS1	0.017	0	-9999	-10000	0	0
CRK	0.017	0	-9999	-10000	0	0
PTPN1	0.024	0.009	-9999	-10000	0	0
CAV1	-0.11	0.11	-9999	-0.2	324	324
CBL/APS/CAP/Crk-II/C3G	0.041	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0.044	0.025	-9999	-0.21	5	5
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.023	0.049	-9999	-0.18	27	27
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.023	0.044	-9999	-0.23	3	3
RPS6KB1	0.022	0.058	-9999	-0.3	1	1
PARD6A	0.017	0	-9999	-10000	0	0
CBL	0.017	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.016	0.011	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.022	0.054	-9999	-0.29	1	1
HRAS/GTP	-0.016	0.051	-9999	-0.17	49	49
Insulin Receptor	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.029	0.076	-9999	-0.21	48	48
PRKCI	0.025	0.028	-9999	-0.17	1	1
Insulin Receptor/Insulin/GRB14/PDK1	-0.014	0.047	-9999	-0.17	43	43
SHC1	-0.02	0.12	-9999	-0.41	46	46
negative regulation of MAPKKK cascade	0.029	0.033	-9999	-0.19	10	10
PI3K	0.03	0.052	-9999	-0.18	27	27
NCK2	0.017	0.001	-9999	-10000	0	0
RHOQ	0.017	0	-9999	-10000	0	0
mol:H2O2	0	0.001	-9999	-10000	0	0
HRAS/GDP	0.012	0.013	-9999	-0.29	1	1
AKT2	0.023	0.059	-9999	-0.33	1	1
PRKCZ	0.015	0.026	-9999	-0.16	6	6
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	0.003	0.066	-9999	-0.2	48	48
F2RL2	0.017	0	-9999	-10000	0	0
TRIP10	0.012	0.046	-9999	-0.41	6	6
Insulin Receptor/Insulin/Shc	0.013	0.071	-9999	-0.22	46	46
TC10/GTP/CIP4/Exocyst	0.02	0.028	-9999	-0.24	6	6
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.022	0.068	-9999	-0.2	46	46
RAPGEF1	0.017	0	-9999	-10000	0	0
RASA1	0.017	0.002	-9999	-10000	0	0
NCK1	0.008	0.061	-9999	-0.41	11	11
CBL/APS/CAP/Crk-II	0.033	0	-9999	-10000	0	0
TC10/GDP	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.016	0.086	-9999	-0.22	59	59
INPP5D	0.011	0.021	-9999	-0.2	5	5
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.002	0.005	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.017	0	-9999	-10000	0	0
IRS1	0.013	0.042	-9999	-0.41	5	5
p62DOK/RasGAP	0.03	0.034	-9999	-0.2	10	10
INS	0.019	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.011	0.021	-9999	-0.2	5	5
GRB2	0.017	0.002	-9999	-10000	0	0
EIF4EBP1	-0.071	0.11	-9999	-0.31	27	27
PTPRA	0.019	0.002	-9999	-10000	0	0
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
TC10/GTP/CIP4	0.02	0.028	-9999	-0.24	6	6
PDPK1	0.017	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.013	0.047	-9999	-0.13	48	48
Insulin Receptor/Insulin/IRS1	0.033	0.024	-9999	-0.22	5	5
Insulin Receptor/Insulin/IRS3	0.028	0	-9999	-10000	0	0
Par3/Par6	0.038	0.025	-9999	-0.19	6	6

×

Arf6 signaling events

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
CENTA1/KIF3B	0.011	0.016	-10000	0	-0.24	2	2
ARNO/beta Arrestin1-2	0.025	0.009	-10000	0	-0.17	1	1
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
EPHA2	0.007	0.067	-10000	0	-0.41	13	13
USP6	0.017	0	-10000	0	-10000	0	0
IQSEC1	0.017	0.002	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.09	0.15	-10000	0	-0.28	196	196
ARRB2	0.015	0	-10000	0	-10000	0	0
mol:GTP	0.002	0.005	0.042	2	-10000	0	2
ARRB1	0.017	0	-10000	0	-10000	0	0
FBXO8	0	0	-10000	0	-10000	0	0
TSHR	0.014	0.037	-10000	0	-0.41	4	4
EGF	0.015	0.026	-10000	0	-0.41	2	2
somatostatin receptor activity	0	0	-10000	0	0	1	1
ARAP2	0	0	-10000	0	0	1	1
mol:GDP	0.019	0.019	-10000	0	-0.089	1	1
mol:PI-3-4-5-P3	0	0	-10000	0	0	1	1
ITGA2B	0.017	0	-10000	0	-10000	0	0
ARF6	0.017	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.022	0.085	-10000	0	-0.26	38	38
ADAP1	0	0	-10000	0	-10000	0	0
KIF13B	0.015	0.026	-10000	0	-0.41	2	2
HGF/MET	0.018	0.046	-10000	0	-0.28	12	12
PXN	0.017	0	-10000	0	-10000	0	0
ARF6/GTP	0.028	0.033	-10000	0	-0.095	1	1
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.065	0.13	-10000	0	-0.24	194	194
ADRB2	0.016	0.019	-10000	0	-0.41	1	1
receptor agonist activity	0	0	0	1	0	1	2
actin filament binding	0	0	-10000	0	0	1	1
SRC	0.017	0	-10000	0	-10000	0	0
ITGB3	0.017	0	-10000	0	-10000	0	0
GNAQ	0.017	0	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0	-10000	0	-10000	0	0
ARF6/GDP	0.021	0.025	-10000	0	-0.11	6	6
ARF6/GDP/GULP/ACAP1	0.033	0.024	-10000	0	-0.17	4	4
alphaIIb/beta3 Integrin/paxillin/GIT1	0.044	0	-10000	0	-10000	0	0
ACAP1	0	0	-10000	0	-10000	0	0
ACAP2	0	0	-10000	0	0	1	1
LHCGR/beta Arrestin2	0.018	0	-10000	0	-10000	0	0
EFNA1	-0.002	0.09	-10000	0	-0.41	24	24
HGF	0.015	0.026	-10000	0	-0.41	2	2
CYTH3	0	0	-10000	0	0	1	1
CYTH2	0	0	-10000	0	-0.002	1	1
NCK1	0.008	0.061	-10000	0	-0.41	11	11
fibronectin binding	0	0	-10000	0	-10000	0	0
endosomal lumen acidification	0	0	-10000	0	-10000	0	0
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	0.014	0.037	-10000	0	-0.41	4	4
GNAQ/ARNO	0.013	0.001	-10000	0	-10000	0	0
mol:Phosphatidic acid	0	0	-10000	0	0	1	1
PIP3-E	0.001	0.004	-10000	0	-10000	0	0
MET	0.009	0.059	-10000	0	-0.41	10	10
GNA14	0.016	0.026	-10000	0	-0.41	2	2
GNA15	0.011	0.049	-10000	0	-0.41	7	7
GIT1	0.017	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
GNA11	0.017	0	-10000	0	-10000	0	0
LHCGR	0.017	0	-10000	0	-10000	0	0
AGTR1	0.016	0.026	-10000	0	-0.41	2	2
desensitization of G-protein coupled receptor protein signaling pathway	0.018	0	-10000	0	-10000	0	0
IPCEF1/ARNO	-0.029	0.042	-10000	0	-0.18	6	6
alphaIIb/beta3 Integrin	0.025	0	-10000	0	-10000	0	0

×

IGF1 pathway

Figure S90. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S90. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.017	0.001	-10000	0	-10000	0	0
PTK2	0.017	0.001	-10000	0	-10000	0	0
CRKL	0.018	0.023	-10000	0	-0.16	9	9
GRB2/SOS1/SHC	0	0.074	-10000	0	-0.24	46	46
HRAS	0.016	0.019	-10000	0	-0.41	1	1
IRS1/Crk	0.022	0.024	-10000	0	-0.16	9	9
IGF-1R heterotetramer/IGF1/PTP1B	0.031	0.022	-10000	0	-0.21	4	4
AKT1	0.012	0.046	-10000	0	-0.17	28	28
BAD	0.021	0.05	-10000	0	-0.16	28	28
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.018	0.023	-10000	0	-0.16	9	9
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.024	0.024	-10000	0	-0.16	9	9
RAF1	0.027	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.029	0.024	-10000	0	-0.15	9	9
YWHAZ	0.017	0.002	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.021	0.026	-10000	0	-0.18	9	9
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
RPS6KB1	0.013	0.044	-10000	0	-0.17	25	25
GNB2L1	0.017	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.02	0.047	0.28	2	-10000	0	2
PXN	0.017	0	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.013	0.001	-10000	0	-10000	0	0
HRAS/GTP	-0.001	0.059	-10000	0	-0.18	47	47
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.017	0.072	-10000	0	-0.21	49	49
IGF-1R heterotetramer	0.017	0.008	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.031	0.025	-10000	0	-0.16	9	9
Crk/p130 Cas/Paxillin	0.031	0.022	-10000	0	-0.14	9	9
IGF1R	0.017	0.008	-10000	0	-10000	0	0
IGF1	0.014	0.038	-10000	0	-0.41	4	4
IRS2/Crk	0.025	0.023	-10000	0	-0.14	9	9
PI3K	0.027	0.053	-10000	0	-0.18	30	30
apoptosis	-0.028	0.047	-10000	0	-10000	0	0
HRAS/GDP	0.012	0.013	-10000	0	-0.29	1	1
PRKCD	0.016	0.035	-10000	0	-0.16	7	7
RAF1/14-3-3 E	0.034	0.045	-10000	0	-10000	0	0
BAD/14-3-3	0.029	0.049	-10000	0	-10000	0	0
PRKCZ	0.009	0.042	-10000	0	-0.16	27	27
Crk/p130 Cas/Paxillin/FAK1	0.021	0.04	-10000	0	-10000	0	0
PTPN1	0.017	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.013	0.037	-10000	0	-0.17	7	7
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.01	0.091	-10000	0	-0.24	62	62
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	0.024	0.024	-10000	0	-0.16	9	9
GRB10	0.004	0.074	-10000	0	-0.41	16	16
PTPN11	0.018	0.023	-10000	0	-0.16	9	9
IRS1	0.014	0.025	-10000	0	-0.18	9	9
IRS2	0.018	0.023	-10000	0	-0.16	9	9
IGF-1R heterotetramer/IGF1	0.021	0.028	-10000	0	-0.28	4	4
GRB2	0.017	0.002	-10000	0	-10000	0	0
PDPK1	0.014	0.046	-10000	0	-0.17	30	30
YWHAE	0.017	0.001	-10000	0	-10000	0	0
PRKD1	-0.032	0.09	-10000	0	-0.18	131	131
SHC1	-0.02	0.12	-10000	0	-0.41	46	46

×

Nectin adhesion pathway

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
PDGFRB	0.015	0.032	-9999	-0.41	3	3
alphaV beta3 Integrin	0.016	0.053	-9999	-0.28	16	16
PTK2	0.026	0.04	-9999	-0.18	7	7
positive regulation of JNK cascade	0	0.007	-9999	-10000	0	0
CDC42/GDP	0.053	0.02	-9999	-10000	0	0
Rac1/GDP	0.054	0.02	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0.017	0	-9999	-10000	0	0
CTNNB1	0.017	0	-9999	-10000	0	0
CDC42/GTP	0.04	0.018	-9999	-10000	0	0
nectin-3/I-afadin	0.024	0.019	-9999	-0.28	2	2
RAPGEF1	0.041	0.022	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.04	0.023	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.032	-9999	-0.41	3	3
TLN1	0	0.059	-9999	-0.19	46	46
Rap1/GTP	0	0.008	-9999	-10000	0	0
IQGAP1	-0.086	0.18	-9999	-0.41	127	127
Rap1/GTP/I-afadin	0.022	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.024	0.019	-9999	-0.28	2	2
PVR	0.017	0	-9999	-10000	0	0
Necl-5(dimer)	0.017	0	-9999	-10000	0	0
mol:GDP	0.049	0.022	-9999	-10000	0	0
MLLT4	0.017	0	-9999	-10000	0	0
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
PI3K	0.034	0.056	-9999	-0.19	29	29
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.025	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	0	0.008	-9999	-10000	0	0
PVRL1	0.017	0	-9999	-10000	0	0
PVRL3	0.015	0.026	-9999	-0.41	2	2
PVRL2	0.017	0	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
CDH1	0.011	0.052	-9999	-0.41	8	8
CLDN1	0.01	0.056	-9999	-0.41	9	9
JAM-A/CLDN1	0.023	0.08	-9999	-0.26	36	36
SRC	0.035	0.025	-9999	-0.19	2	2
ITGB3	0.017	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin	0.025	0	-9999	-10000	0	0
FARP2	0.046	0.021	-9999	-10000	0	0
RAC1	0.017	0	-9999	-10000	0	0
CTNNA1	0.017	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.034	0.017	-9999	-0.24	2	2
nectin-1/I-afadin	0.025	0	-9999	-10000	0	0
nectin-2/I-afadin	0.025	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	-0.04	0.11	-9999	-0.24	127	127
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.034	0.017	-9999	-0.24	2	2
CDC42/GTP/IQGAP1/filamentous actin	-0.04	0.11	-9999	-0.24	127	127
F11R	-0.011	0.1	-9999	-0.41	34	34
positive regulation of filopodium formation	0	0.007	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	0.012	0.073	-9999	-0.19	56	56
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.025	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.025	0	-9999	-10000	0	0
PIP5K1C	0.017	0.009	-9999	-10000	0	0
VAV2	0.047	0.022	-9999	-10000	0	0
RAP1/GDP	0.041	0.019	-9999	-10000	0	0
ITGAV	0.004	0.074	-9999	-0.41	16	16
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.034	0.017	-9999	-0.24	2	2
nectin-3(dimer)/I-afadin/I-afadin	0.024	0.019	-9999	-0.28	2	2
Rac1/GTP	0.045	0.018	-9999	-10000	0	0
PTPRM	0.016	0.009	-9999	-0.12	2	2
E-cadherin/beta catenin/alpha catenin	0.047	0.028	-9999	-0.18	8	8
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.017	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.016	0.003	-10000	0	-10000	0	0
EPHB2	0.016	0.026	-10000	0	-0.41	2	2
EFNB1	0.003	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.006	0.024	-10000	0	-0.18	1	1
Ephrin B2/EPHB1-2	0.026	0.039	-10000	0	-0.21	13	13
neuron projection morphogenesis	0.004	0.019	-10000	0	-0.17	1	1
Ephrin B1/EPHB1-2/Tiam1	0.005	0.024	-10000	0	-0.2	1	1
DNM1	0.003	0.006	-10000	0	-10000	0	0
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.007	0.038	-10000	0	-0.16	10	10
YES1	-0.015	0.053	-10000	0	-0.21	30	30
Ephrin B1/EPHB1-2/NCK2	0.005	0.024	-10000	0	-0.2	1	1
PI3K	0.01	0.063	-10000	0	-0.19	37	37
mol:GDP	0.005	0.023	-10000	0	-0.19	1	1
ITGA2B	0.017	0	-10000	0	-10000	0	0
endothelial cell proliferation	0.022	0.005	-10000	0	-10000	0	0
FYN	-0.006	0.048	-10000	0	-0.19	30	30
MAP3K7	-0.007	0.038	-10000	0	-0.16	31	31
FGR	-0.01	0.046	-10000	0	-0.19	30	30
TIAM1	0.016	0.003	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
RGS3	0.016	0.019	-10000	0	-0.41	1	1
cell adhesion	0.015	0.058	-10000	0	-0.19	24	24
LYN	-0.013	0.05	-10000	0	-0.2	30	30
Ephrin B1/EPHB1-2/Src Family Kinases	-0.008	0.041	-10000	0	-0.17	30	30
Ephrin B1/EPHB1-2	-0.009	0.042	-10000	0	-0.18	30	30
SRC	-0.008	0.045	-10000	0	-0.19	30	30
ITGB3	0.017	0	-10000	0	-10000	0	0
EPHB1	0.007	0.064	-10000	0	-0.41	12	12
EPHB4	0.017	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.022	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.025	0	-10000	0	-10000	0	0
BLK	-0.006	0.045	-10000	0	-0.19	30	30
HCK	-0.016	0.051	-10000	0	-0.2	30	30
regulation of stress fiber formation	-0.005	0.023	0.19	1	-10000	0	1
MAPK8	0.015	0.043	-10000	0	-0.16	2	2
Ephrin B1/EPHB1-2/RGS3	0.005	0.024	-10000	0	-0.2	1	1
endothelial cell migration	-0.001	0.04	0.13	14	-0.14	30	44
NCK2	0.017	0.001	-10000	0	-10000	0	0
PTPN13	-0.009	0.099	-10000	0	-0.41	30	30
regulation of focal adhesion formation	-0.005	0.023	0.19	1	-10000	0	1
chemotaxis	-0.005	0.023	0.19	1	-10000	0	1
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
Rac1/GTP	0.005	0.022	-10000	0	-0.18	1	1
angiogenesis	-0.009	0.042	-10000	0	-0.18	30	30
LCK	-0.008	0.045	-10000	0	-0.19	30	30

×

Signaling events mediated by the Hedgehog family

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
TGFB2	0.033	0.074	-10000	0	-0.32	22	22
IHH	0.024	0.023	-10000	0	-0.13	7	7
SHH Np/Cholesterol/GAS1	-0.002	0.074	-10000	0	-0.21	58	58
LRPAP1	0.017	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.002	0.073	0.21	58	-10000	0	58
SMO/beta Arrestin2	0.045	0.047	-10000	0	-0.27	7	7
SMO	0.038	0.048	-10000	0	-0.28	7	7
AKT1	0.029	0.055	-10000	0	-0.21	19	19
ARRB2	0.017	0	-10000	0	-10000	0	0
BOC	0	0	-10000	0	-10000	0	0
ADRBK1	0.017	0	-10000	0	-10000	0	0
heart looping	0.038	0.048	-10000	0	-0.28	7	7
STIL	0.004	0.084	-10000	0	-0.18	75	75
DHH N/PTCH2	0.013	0	-10000	0	-10000	0	0
DHH N/PTCH1	0.025	0.053	-10000	0	-0.22	22	22
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
DHH	0	0	-10000	0	-10000	0	0
PTHLH	0.033	0.076	-10000	0	-0.33	22	22
determination of left/right symmetry	0.038	0.048	-10000	0	-0.28	7	7
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
skeletal system development	0.033	0.075	-10000	0	-0.33	22	22
IHH N/Hhip	0.016	0.012	-10000	0	-10000	0	0
DHH N/Hhip	0	0	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.038	0.048	-10000	0	-0.28	7	7
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	0.017	0	-10000	0	-10000	0	0
PI3K	0.009	0.065	-10000	0	-0.28	25	25
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.03	0.13	-10000	0	-0.41	58	58
somite specification	0.038	0.048	-10000	0	-0.28	7	7
SHH Np/Cholesterol/PTCH1	0.035	0.048	-10000	0	-0.3	7	7
SHH Np/Cholesterol/PTCH2	0.024	0	-10000	0	-10000	0	0
SHH Np/Cholesterol/Megalin	0.023	0.01	-10000	0	-0.21	1	1
SHH	0.018	0	-10000	0	-10000	0	0
catabolic process	0.03	0.061	-10000	0	-0.25	22	22
SMO/Vitamin D3	0.042	0.047	-10000	0	-0.28	7	7
SHH Np/Cholesterol/Hhip	0.012	0	-10000	0	-10000	0	0
LRP2	0.016	0.019	-10000	0	-0.41	1	1
receptor-mediated endocytosis	0.042	0.044	-10000	0	-0.25	7	7
SHH Np/Cholesterol/BOC	0.012	0	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	0.024	0	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.012	0	-10000	0	-10000	0	0
mol:Vitamin D3	0.037	0.049	-10000	0	-0.3	7	7
IHH N/PTCH2	0.029	0.014	-10000	0	-10000	0	0
CDON	0.017	0	-10000	0	-10000	0	0
IHH N/PTCH1	0.038	0.063	-10000	0	-0.25	22	22
Megalin/LRPAP1	0.025	0.014	-10000	0	-0.28	1	1
PTCH2	0.017	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	0.015	0	-10000	0	-10000	0	0
PTCH1	0.03	0.061	-10000	0	-0.25	22	22
HHIP	0	0	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	0.029	0.06	-9999	-0.21	32	32
MAP4K1	0.016	0.019	-9999	-0.41	1	1
MAP3K8	-0.017	0.12	-9999	-0.41	42	42
PRKCB	0	0	-9999	-10000	0	0
DBNL	0	0	-9999	-10000	0	0
CRKL	0.017	0	-9999	-10000	0	0
MAP3K1	0.021	0.034	-9999	-0.18	1	1
JUN	0.019	0.015	-9999	-0.18	1	1
MAP3K7	0.021	0.034	-9999	-0.18	1	1
GRAP2	0.017	0	-9999	-10000	0	0
CRK	0.017	0	-9999	-10000	0	0
MAP2K4	0.018	0.045	-9999	-0.18	15	15
LAT	0.016	0.019	-9999	-0.41	1	1
LCP2	-0.007	0.099	-9999	-0.41	30	30
MAPK8	0.016	0.014	-9999	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.02	0.035	-9999	-0.12	30	30
LAT/GRAP2/SLP76/HPK1/HIP-55	0.027	0.056	-9999	-0.19	32	32

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.013	0.037	-10000	0	-0.41	4	4
GNB1/GNG2	-0.046	0.035	-10000	0	-0.14	15	15
AKT1	-0.016	0.082	-10000	0	-0.18	3	3
EGF	0.015	0.026	-10000	0	-0.41	2	2
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	0.023	0.033	-10000	0	-0.16	16	16
mol:Ca2+	-0.029	0.11	-10000	0	-0.23	15	15
LYN	0.007	0.06	-10000	0	-0.15	64	64
RhoA/GTP	-0.031	0.027	-10000	0	-0.12	3	3
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.047	0.12	-10000	0	-0.27	36	36
GNG2	0	0	-10000	0	-10000	0	0
ARRB2	0.017	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.027	0.019	-10000	0	-0.13	7	7
G beta5/gamma2	-0.058	0.045	-10000	0	-0.19	15	15
PRKCH	-0.041	0.12	-10000	0	-0.28	16	16
DNM1	0.003	0.007	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3	0.002	0.005	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.002	3	3
PTGDR	0.017	0	-10000	0	-10000	0	0
G12 family/GTP	-0.071	0.055	-10000	0	-0.22	19	19
ADRBK1	0.017	0	-10000	0	-10000	0	0
ADRBK2	0.017	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.023	0.002	-10000	0	-10000	0	0
mol:GDP	0.003	0.065	0.17	1	-10000	0	1
mol:NADP	0.017	0	-10000	0	-10000	0	0
RAB11A	0.017	0.001	-10000	0	-10000	0	0
PRKG1	0.017	0	-10000	0	-10000	0	0
mol:IP3	-0.039	0.12	-10000	0	-0.28	15	15
cell morphogenesis	0.023	0.002	-10000	0	-10000	0	0
PLCB2	-0.054	0.14	-10000	0	-0.36	15	15
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	0.029	0.006	-10000	0	-10000	0	0
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0	0.068	-10000	0	-0.15	86	86
RHOA	0.017	0.001	-10000	0	-10000	0	0
PTGIR	0.017	0	-10000	0	-10000	0	0
PRKCB1	-0.009	0.049	-10000	0	-0.31	3	3
GNAQ	0.017	0	-10000	0	-10000	0	0
mol:L-citrulline	0.017	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.062	0.15	-10000	0	-0.38	15	15
LCK	0.028	0.017	-10000	0	-0.15	4	4
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.033	0.002	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.022	0.039	-10000	0	-0.31	6	6
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.033	0.002	-10000	0	-10000	0	0
MAPK14	-0.028	0.093	-10000	0	-0.18	36	36
TGM2/GTP	-0.035	0.13	-10000	0	-0.3	15	15
MAPK11	-0.028	0.093	-10000	0	-0.18	36	36
ARHGEF1	-0.018	0.07	-10000	0	-0.14	15	15
GNAI2	0.017	0.001	-10000	0	-10000	0	0
JNK cascade	-0.045	0.13	-10000	0	-0.29	15	15
RAB11/GDP	0.017	0.001	-10000	0	-10000	0	0
ICAM1	-0.034	0.11	-10000	0	-0.3	15	15
cAMP biosynthetic process	-0.032	0.11	-10000	0	-0.25	15	15
Gq family/GTP/EBP50	0.02	0.021	-10000	0	-0.12	10	10
actin cytoskeleton reorganization	0.023	0.002	-10000	0	-10000	0	0
SRC	0.029	0.006	-10000	0	-10000	0	0
GNB5	0.017	0.002	-10000	0	-10000	0	0
GNB1	0.017	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.013	0.061	-10000	0	-0.17	33	33
VCAM1	-0.078	0.13	-10000	0	-0.25	30	30
TP beta/Gq family/GDP/G beta5/gamma2	0.027	0.019	-10000	0	-0.13	7	7
platelet activation	-0.03	0.12	-10000	0	-0.24	16	16
PGI2/IP	0.013	0.001	-10000	0	-10000	0	0
PRKACA	0.019	0.001	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.026	0.019	-10000	0	-0.12	7	7
TXA2/TP beta/beta Arrestin2	0.002	0.006	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.019	0.002	-10000	0	-10000	0	0
mol:DAG	-0.049	0.13	-10000	0	-0.32	15	15
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
TXA2/TP alpha	-0.041	0.14	-10000	0	-0.33	15	15
Gq family/GTP	0.016	0.017	-10000	0	-0.11	9	9
YES1	0.002	0.065	-10000	0	-0.15	79	79
GNAI2/GTP	0.023	0.005	-10000	0	-10000	0	0
PGD2/DP	0.013	0.001	-10000	0	-10000	0	0
SLC9A3R1	0.015	0.026	-10000	0	-0.41	2	2
FYN	0.027	0.013	-10000	0	-0.15	2	2
mol:NO	0.017	0	-10000	0	-10000	0	0
GNA15	0.011	0.049	-10000	0	-0.41	7	7
PGK/cGMP	0.023	0.001	-10000	0	-10000	0	0
RhoA/GDP	0.017	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.034	0.018	-10000	0	-0.17	4	4
NOS3	0.017	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
PRKCA	-0.041	0.12	-10000	0	-0.27	15	15
PRKCB	-0.046	0.12	-10000	0	-0.27	15	15
PRKCE	-0.044	0.12	-10000	0	-0.28	15	15
PRKCD	-0.051	0.12	-10000	0	-0.29	15	15
PRKCG	-0.047	0.12	-10000	0	-0.29	15	15
muscle contraction	-0.055	0.14	-10000	0	-0.36	15	15
PRKCZ	-0.041	0.12	-10000	0	-0.26	15	15
ARR3	0.017	0	-10000	0	-10000	0	0
TXA2/TP beta	0.034	0.005	-10000	0	-10000	0	0
PRKCQ	-0.044	0.12	-10000	0	-0.27	15	15
MAPKKK cascade	-0.051	0.13	-10000	0	-0.33	15	15
SELE	-0.038	0.11	-10000	0	-0.24	15	15
TP beta/GNAI2/GDP/G beta/gamma	0.035	0.004	-10000	0	-10000	0	0
ROCK1	0.017	0	-10000	0	-10000	0	0
GNA14	0.015	0.026	-10000	0	-0.41	2	2
chemotaxis	-0.077	0.16	-10000	0	-0.44	15	15
GNA12	0.014	0.037	-10000	0	-0.41	4	4
GNA13	0.015	0.026	-10000	0	-0.41	2	2
GNA11	0.017	0	-10000	0	-10000	0	0
Rac1/GTP	0.013	0.001	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.018	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.035	0.004	-10000	0	-10000	0	0
CDKN1B	0.02	0.037	-10000	0	-0.14	27	27
CDKN1A	-0.001	0.069	-10000	0	-0.16	80	80
FRAP1	0.016	0.019	-10000	0	-0.41	1	1
PRKDC	-0.002	0.088	-10000	0	-0.41	23	23
FOXO3	0.02	0.037	-10000	0	-0.14	27	27
AKT1	0.017	0.039	-10000	0	-0.15	27	27
BAD	0.017	0	-10000	0	-10000	0	0
AKT3	0.015	0.009	-10000	0	-0.18	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.02	0.037	-10000	0	-0.14	27	27
AKT1/ASK1	0.025	0.037	-10000	0	-0.18	1	1
BAD/YWHAZ	0.035	0.004	-10000	0	-10000	0	0
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0.016	0.019	-10000	0	-0.41	1	1
JNK cascade	-0.024	0.036	0.18	1	-10000	0	1
TSC1	0.019	0.037	-10000	0	-0.14	27	27
YWHAZ	0.017	0.002	-10000	0	-10000	0	0
AKT1/RAF1	0.026	0.039	-10000	0	-0.14	28	28
EP300	0.017	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.038	-10000	0	-0.15	27	27
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.02	0.037	-10000	0	-0.19	1	1
YWHAQ	0.017	0	-10000	0	-10000	0	0
TBC1D4	0.016	0	-10000	0	-10000	0	0
MAP3K5	0.017	0.001	-10000	0	-10000	0	0
MAPKAP1	0.017	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.002	0.036	0.15	10	-10000	0	10
YWHAH	0.008	0.009	-10000	0	-10000	0	0
AKT1S1	0.016	0.037	-10000	0	-0.14	27	27
CASP9	0.018	0.045	-10000	0	-0.16	28	28
YWHAB	0.017	0.001	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.029	0.037	-10000	0	-0.18	1	1
GBL	0.017	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.035	0	-10000	0	-10000	0	0
YWHAE	0.017	0.001	-10000	0	-10000	0	0
SRC	0.017	0	-10000	0	-10000	0	0
AKT2/p21CIP1	0.004	0.066	-10000	0	-0.16	55	55
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.026	0.015	-10000	0	-0.17	1	1
CHUK	0.019	0.038	-10000	0	-0.14	28	28
BAD/BCL-XL	0.036	0.037	-10000	0	-0.17	1	1
mTORC2	0.033	0.011	-10000	0	-0.21	1	1
AKT2	0.015	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.005	0.048	-10000	0	-0.2	10	10
PDPK1	0.017	0	-10000	0	-10000	0	0
MDM2	0.013	0.051	-10000	0	-0.16	44	44
MAPKKK cascade	-0.026	0.039	0.14	28	-10000	0	28
MDM2/Cbp/p300	0.031	0.052	-10000	0	-0.16	19	19
TSC1/TSC2	0.022	0.036	-10000	0	-0.17	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.05	-10000	0	-0.16	19	19
glucose import	0.018	0	-10000	0	-10000	0	0
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.027	0.027	-10000	0	-0.22	1	1
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.018	0	-10000	0	-10000	0	0
GSK3A	0.02	0.037	-10000	0	-0.14	27	27
FOXO1	0.016	0.047	-10000	0	-0.15	37	37
GSK3B	0.02	0.036	-10000	0	-0.14	26	26
SFN	-0.01	0.1	-10000	0	-0.41	33	33
G1/S transition of mitotic cell cycle	0.022	0.035	-10000	0	-0.18	1	1
p27Kip1/14-3-3 family	0.012	0.026	-10000	0	-0.15	4	4
PRKACA	0.017	0	-10000	0	-10000	0	0
KPNA1	0.017	0	-10000	0	-10000	0	0
HSP90AA1	0.017	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0.017	0	-10000	0	-10000	0	0
CREBBP	0.017	0	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.021	0.012	-9999	-10000	0	0
NFATC2	0.012	0.01	-9999	-10000	0	0
NFATC3	0.021	0.012	-9999	-10000	0	0
CD40LG	0.019	0.1	-9999	-0.33	15	15
PTGS2	0.009	0.13	-9999	-0.39	31	31
JUNB	0.011	0.052	-9999	-0.41	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.008	-9999	-10000	0	0
CaM/Ca2+	0.015	0.008	-9999	-10000	0	0
CALM1	0.018	0.005	-9999	-10000	0	0
JUN	0.019	0.019	-9999	-0.41	1	1
mol:Ca2+	0.002	0.004	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.012	0.011	-9999	-0.24	1	1
FOSL1	0.007	0.067	-9999	-0.41	13	13
CREM	0.017	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	0.055	0.041	-9999	-0.19	3	3
FOS	-0.082	0.18	-9999	-0.41	125	125
IFNG	0.019	0.1	-9999	-0.33	16	16
AP-1/NFAT1-c-4	0.05	0.13	-9999	-0.37	15	15
FASLG	0.019	0.1	-9999	-0.33	15	15
NFAT1-c-4/ICER1	0.039	0.026	-9999	-10000	0	0
IL2RA	0.017	0.11	-9999	-0.37	17	17
FKBP12/FK506	0.012	0.013	-9999	-0.29	1	1
CSF2	0.019	0.1	-9999	-0.33	15	15
JunB/Fra1/NFAT1-c-4	0.042	0.051	-9999	-0.18	19	19
IL4	0.019	0.1	-9999	-0.33	15	15
IL2	0.001	0.004	-9999	-10000	0	0
IL3	0.004	0.008	-9999	-10000	0	0
FKBP1A	0.016	0.019	-9999	-0.41	1	1
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.023	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.017	0	-9999	-10000	0	0
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.017	0	-9999	-10000	0	0
TCEB1	0.017	0	-9999	-10000	0	0
HIF1A/p53	-0.001	0.073	-9999	-0.18	69	69
HIF1A	0.015	0.021	-9999	-0.11	3	3
COPS5	0.017	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.041	0	-9999	-10000	0	0
FIH (dimer)	0.017	0	-9999	-10000	0	0
CDKN2A	-0.031	0.14	-9999	-0.41	59	59
ARNT/IPAS	0.025	0	-9999	-10000	0	0
HIF1AN	0.017	0	-9999	-10000	0	0
GNB2L1	0.017	0	-9999	-10000	0	0
HIF1A/ARNT	0.024	0.023	-9999	-10000	0	0
CUL2	0.017	0	-9999	-10000	0	0
OS9	-0.018	0.12	-9999	-0.41	43	43
RACK1/Elongin B/Elongin C	0.035	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.024	0.023	-9999	-10000	0	0
PHD1-3/OS9	0.021	0.072	-9999	-0.21	48	48
HIF1A/RACK1/Elongin B/Elongin C	0.038	0.024	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0.017	0	-9999	-10000	0	0
HIF1A/JAB1	0.024	0.023	-9999	-10000	0	0
EGLN3	0.014	0.037	-9999	-0.41	4	4
EGLN2	0.017	0	-9999	-10000	0	0
EGLN1	0.016	0.019	-9999	-0.41	1	1
TP53	-0.039	0.14	-9999	-0.41	69	69
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.028	0.005	-9999	-10000	0	0
ARNT	0.017	0	-9999	-10000	0	0
ARD1A	0.016	0.019	-9999	-0.41	1	1
RBX1	0.017	0	-9999	-10000	0	0
HIF1A/p19ARF	0.003	0.071	-9999	-0.19	59	59

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.023	0.064	-9999	-0.29	19	19
E-cadherin/beta catenin	0.021	0.038	-9999	-0.28	8	8
CTNNB1	0.017	0	-9999	-10000	0	0
JUP	0.004	0.074	-9999	-0.41	16	16
CDH1	0.011	0.052	-9999	-0.41	8	8

×

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

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
MET/RANBP9	0.02	0.042	-10000	0	-0.28	10	10
CRKL	0.027	0.022	-10000	0	-10000	0	0
mol:PIP3	-0.011	0.023	0.35	2	-10000	0	2
AKT1	-0.003	0.025	0.26	2	-0.21	4	6
PTK2B	0.017	0	-10000	0	-10000	0	0
RAPGEF1	0.03	0.021	-10000	0	-10000	0	0
RANBP10	0.017	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
HGF/MET/SHIP2	0.029	0.04	-10000	0	-0.24	12	12
MAP3K5	0.038	0.022	-10000	0	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	0.028	0.036	-10000	0	-0.21	12	12
AP1	-0.042	0.12	-10000	0	-0.25	125	125
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
apoptosis	-0.015	0.082	-10000	0	-0.66	2	2
STAT3 (dimer)	0.029	0.021	-10000	0	-10000	0	0
GAB1/CRKL/SHP2/PI3K	0.038	0.047	-10000	0	-0.26	1	1
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.037	0.022	-10000	0	-10000	0	0
PTPN11	0.017	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.017	0	-10000	0	-10000	0	0
PTEN	0.015	0.026	-10000	0	-0.41	2	2
ELK1	-0.001	0.044	0.21	17	-0.16	10	27
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.021	0.015	-10000	0	-10000	0	0
PAK1	0.001	0.023	0.24	2	-0.2	4	6
HGF/MET/RANBP10	0.029	0.04	-10000	0	-0.24	12	12
HRAS	0.028	0.029	-10000	0	-10000	0	0
DOCK1	0.03	0.021	-10000	0	-10000	0	0
GAB1	0.025	0.023	-10000	0	-10000	0	0
CRK	0.027	0.022	-10000	0	-10000	0	0
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.027	0.028	-10000	0	-0.16	10	10
JUN	0.016	0.019	-10000	0	-0.41	1	1
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.01	0.022	-10000	0	-0.14	12	12
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
cell morphogenesis	0.041	0.047	-10000	0	-0.19	1	1
GRB2/SHC	0.011	0.067	-10000	0	-0.18	54	54
FOS	-0.085	0.18	-10000	0	-0.41	125	125
GLMN	0.003	0	-10000	0	-10000	0	0
cell motility	-0.001	0.044	0.21	17	-0.16	10	27
HGF/MET/MUC20	0.017	0.039	-10000	0	-0.24	12	12
cell migration	0.011	0.066	-10000	0	-0.18	54	54
GRB2	0.017	0.002	-10000	0	-10000	0	0
CBL	0.017	0	-10000	0	-10000	0	0
MET/RANBP10	0.02	0.042	-10000	0	-0.28	10	10
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.028	0.023	-10000	0	-0.12	12	12
MET/MUC20	0.007	0.041	-10000	0	-0.29	10	10
RAP1B	0.029	0.02	-10000	0	-10000	0	0
RAP1A	0.032	0.02	-10000	0	-10000	0	0
HGF/MET/RANBP9	0.029	0.04	-10000	0	-0.24	12	12
RAF1	0.03	0.029	-10000	0	-10000	0	0
STAT3	0.029	0.022	-10000	0	-10000	0	0
cell proliferation	0.019	0.06	-10000	0	-0.23	9	9
RPS6KB1	0.012	0.01	-10000	0	-10000	0	0
MAPK3	-0.013	0.02	-10000	0	-10000	0	0
MAPK1	0.006	0.11	0.59	17	-10000	0	17
RANBP9	0.017	0.001	-10000	0	-10000	0	0
MAPK8	0.049	0.027	-10000	0	-10000	0	0
SRC	0.028	0.021	-10000	0	-10000	0	0
PI3K	0.019	0.049	-10000	0	-0.17	31	31
MET/Glomulin	0.01	0.036	-10000	0	-0.25	10	10
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	0.032	0.028	-10000	0	-10000	0	0
MET	0.009	0.059	-10000	0	-0.41	10	10
MAP4K1	0.035	0.022	-10000	0	-10000	0	0
PTK2	0.017	0.001	-10000	0	-10000	0	0
MAP2K2	0.032	0.029	-10000	0	-10000	0	0
BAD	0.001	0.023	0.24	2	-0.2	4	6
MAP2K4	0.038	0.022	-10000	0	-10000	0	0
SHP2/GRB2/SOS1/GAB1	0.028	0.027	-10000	0	-10000	0	0
INPPL1	0.017	0	-10000	0	-10000	0	0
PXN	0.017	0	-10000	0	-10000	0	0
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	0.013	0.021	-10000	0	-0.12	12	12
PLCgamma1/PKC	0.013	0	-10000	0	-10000	0	0
HGF	0.015	0.026	-10000	0	-0.41	2	2
RASA1	0.017	0.002	-10000	0	-10000	0	0
NCK1	0.008	0.061	-10000	0	-0.41	11	11
PTPRJ	0.017	0	-10000	0	-10000	0	0
NCK/PLCgamma1	0.027	0.037	-10000	0	-0.15	21	21
PDPK1	-0.006	0.019	0.29	2	-10000	0	2
HGF/MET/SHIP	0.017	0.039	-10000	0	-0.24	12	12

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	-0.036	0.14	-9999	-0.41	65	65
Ran/GTP/Exportin 1/HDAC4	0	0.007	-9999	-0.16	1	1
MDM2/SUMO1	0.026	0.039	-9999	-0.18	18	18
HDAC4	0.017	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.02	0.053	-9999	-0.16	65	65
SUMO1	0.017	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.014	0.005	-9999	-0.11	1	1
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.02	0.005	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.017	0.001	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0.019	-9999	-0.41	1	1
SUMO1/HDAC4	0.033	0.005	-9999	-10000	0	0
SUMO1/HDAC1	0.006	0.071	-9999	-0.18	65	65
RANGAP1	0.017	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.036	0.046	-9999	-0.21	18	18
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.018	0.005	-9999	-0.11	1	1
Ran/GTP	0.026	0.006	-9999	-0.093	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.002	0.078	-9999	-0.41	18	18
UBE2I	0.017	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.028	0.005	-9999	-10000	0	0
NPC	0.01	0.009	-9999	-0.2	1	1
PIAS2	0.017	0	-9999	-10000	0	0
PIAS1	0.017	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.036	0.14	-9999	-0.41	65	65
HDAC2	0.013	0.042	-9999	-0.41	5	5
GNB1/GNG2	0.023	0.012	-9999	-0.24	1	1
forebrain development	0.02	0.049	-9999	-0.31	8	8
GNAO1	0.002	0.005	-9999	-10000	0	0
SMO/beta Arrestin2	0.027	0.014	-9999	-0.28	1	1
SMO	0.017	0.019	-9999	-0.41	1	1
ARRB2	0.018	0.001	-9999	-10000	0	0
GLI3/SPOP	0.02	0.04	-9999	-0.24	2	2
mol:GTP	0.001	0.001	-9999	-10000	0	0
GSK3B	0.017	0.001	-9999	-10000	0	0
GNAI2	0.018	0.001	-9999	-10000	0	0
SIN3/HDAC complex	0.032	0.001	-9999	-10000	0	0
GNAI1	0.014	0.02	-9999	-0.41	1	1
XPO1	0.019	0.003	-9999	-10000	0	0
GLI1/Su(fu)	-0.001	0.038	-9999	-0.28	7	7
SAP30	0.017	0	-9999	-10000	0	0
mol:GDP	0.017	0.019	-9999	-0.41	1	1
MIM/GLI2A	0.023	0.007	-9999	-10000	0	0
IFT88	0.017	0	-9999	-10000	0	0
GNAI3	-0.035	0.14	-9999	-0.41	65	65
GLI2	0.035	0.008	-9999	-10000	0	0
GLI3	0.011	0.04	-9999	-0.22	3	3
CSNK1D	0.015	0.026	-9999	-0.41	2	2
CSNK1E	0.017	0.001	-9999	-10000	0	0
SAP18	0.017	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.017	0	-9999	-10000	0	0
GNG2	0	0	-9999	-10000	0	0
Gi family/GTP	0.001	0.017	-9999	-0.2	2	2
SIN3B	0.017	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
GLI3/Su(fu)	0.017	0.031	-9999	-0.17	3	3
GLI2/Su(fu)	0.037	0.01	-9999	-10000	0	0
FOXA2	0.03	0.037	-9999	-0.38	4	4
neural tube patterning	0.02	0.049	-9999	-0.31	8	8
SPOP	0.017	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.02	0.006	-9999	-0.11	1	1
GNB1	0.017	0.002	-9999	-10000	0	0
CSNK1G2	0.017	0	-9999	-10000	0	0
CSNK1G3	0.017	0	-9999	-10000	0	0
MTSS1	0.023	0.007	-9999	-10000	0	0
embryonic limb morphogenesis	0.02	0.049	-9999	-0.31	8	8
SUFU	0.009	0.007	-9999	-0.13	1	1
LGALS3	-0.034	0.14	-9999	-0.41	62	62
catabolic process	0.041	0.039	-9999	-0.18	3	3
GLI3A/CBP	0.023	0.03	-9999	-0.22	8	8
KIF3A	0.016	0.005	-9999	-10000	0	0
GLI1	0.021	0.05	-9999	-0.31	8	8
RAB23	0.013	0.042	-9999	-0.41	5	5
CSNK1A1	0.017	0	-9999	-10000	0	0
IFT172	0	0	-9999	-10000	0	0
RBBP7	0.017	0	-9999	-10000	0	0
Su(fu)/Galectin3	-0.007	0.075	-9999	-0.21	62	62
GNAZ	0.015	0.006	-9999	-10000	0	0
RBBP4	-0.064	0.17	-9999	-0.41	100	100
CSNK1G1	0.017	0	-9999	-10000	0	0
PIAS1	0.017	0	-9999	-10000	0	0
PRKACA	0.017	0	-9999	-10000	0	0
GLI2/SPOP	0.042	0.008	-9999	-10000	0	0
STK36	0.002	0.002	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.01	0.039	-9999	-0.12	53	53
PTCH1	0.023	0.064	-9999	-0.47	7	7
MIM/GLI1	0.038	0.055	-9999	-0.3	10	10
CREBBP	0.023	0.03	-9999	-0.22	8	8
Su(fu)/SIN3/HDAC complex	-0.005	0.061	-9999	-0.2	20	20

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.017	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.02	0.056	-9999	-0.21	29	29
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.01	0.017	-9999	-10000	0	0
AURKB	-0.005	0.095	-9999	-0.41	27	27
AURKC	0.015	0.026	-9999	-0.41	2	2

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.022	0.016	-10000	0	-0.24	2	2
cell-cell adhesion	0.004	0.024	-10000	0	-10000	0	0
Ephrin B/EPHB2/RasGAP	0.047	0.019	-10000	0	-0.19	2	2
ITSN1	0.017	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
SHC1	-0.02	0.12	-10000	0	-0.41	46	46
Ephrin B1/EPHB3	0.017	0.041	-10000	0	-0.24	13	13
Ephrin B1/EPHB1	0.017	0.039	-10000	0	-0.24	12	12
HRAS/GDP	0.024	0.029	-10000	0	-0.15	12	12
Ephrin B/EPHB1/GRB7	0.043	0.038	-10000	0	-0.19	12	12
Endophilin/SYNJ1	0.022	0.014	-10000	0	-0.18	2	2
KRAS	0.017	0.002	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.043	0.036	-10000	0	-0.19	11	11
endothelial cell migration	0.023	0.048	-10000	0	-0.19	23	23
GRB2	0.017	0.002	-10000	0	-10000	0	0
GRB7	0.016	0.019	-10000	0	-0.41	1	1
PAK1	0.027	0.014	-10000	0	-0.18	2	2
HRAS	0.016	0.019	-10000	0	-0.41	1	1
RRAS	0.016	0.039	-10000	0	-0.18	19	19
DNM1	0.003	0.007	-10000	0	-10000	0	0
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.02	0.03	-10000	0	-0.18	11	11
lamellipodium assembly	-0.004	0.024	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.015	0.05	-10000	0	-0.12	57	57
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
EPHB2	0.015	0.026	-10000	0	-0.41	2	2
EPHB3	0.007	0.067	-10000	0	-0.41	13	13
EPHB1	0.007	0.064	-10000	0	-0.41	12	12
EPHB4	0.017	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.029	-10000	0	-0.16	1	1
Ephrin B/EPHB2	0.038	0.017	-10000	0	-0.19	2	2
Ephrin B/EPHB3	0.033	0.037	-10000	0	-0.19	13	13
JNK cascade	0.016	0.047	-10000	0	-0.19	26	26
Ephrin B/EPHB1	0.034	0.035	-10000	0	-0.19	11	11
RAP1/GDP	0.03	0.028	-10000	0	-0.14	1	1
EFNB2	0.016	0.003	-10000	0	-10000	0	0
EFNB3	0.017	0.001	-10000	0	-10000	0	0
EFNB1	0.017	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.026	0.039	-10000	0	-0.21	13	13
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.017	0	-10000	0	-10000	0	0
CDC42/GTP	0.037	0.032	-10000	0	-10000	0	0
Rap1/GTP	-0.004	0.024	-10000	0	-10000	0	0
axon guidance	0.022	0.016	-10000	0	-0.24	2	2
MAPK3	0.018	0.044	-10000	0	-0.18	5	5
MAPK1	0.017	0.044	-10000	0	-0.18	5	5
Rac1/GDP	0.033	0.029	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.031	0.053	-10000	0	-0.26	4	4
CDC42/GDP	0.033	0.029	-10000	0	-0.14	1	1
PI3K	0.026	0.049	-10000	0	-0.2	23	23
EFNA5	0.017	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.022	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.03	0.012	-10000	0	-0.12	2	2
CDC42	0.017	0	-10000	0	-10000	0	0
RAS family/GTP	-0.04	0.069	-10000	0	-0.32	4	4
PTK2	0.008	0.007	-10000	0	-10000	0	0
MAP4K4	0.016	0.047	-10000	0	-0.19	26	26
SRC	0.017	0	-10000	0	-10000	0	0
KALRN	0.017	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0.025	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.04	0.028	-10000	0	-10000	0	0
MAP2K1	0.016	0.046	-10000	0	-0.17	7	7
WASL	0.017	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.032	0.054	-10000	0	-0.21	25	25
cell migration	0.024	0.048	0.17	3	-0.18	7	10
NRAS	-0.094	0.19	-10000	0	-0.41	136	136
SYNJ1	0.022	0.015	-10000	0	-0.18	2	2
PXN	0.017	0	-10000	0	-10000	0	0
TF	0.016	0.02	-10000	0	-10000	0	0
HRAS/GTP	0.034	0.034	-10000	0	-0.16	14	14
Ephrin B1/EPHB1-2	0.027	0.039	-10000	0	-0.21	14	14
cell adhesion mediated by integrin	-0.015	0.031	-10000	0	-0.16	4	4
RAC1	0.017	0	-10000	0	-10000	0	0
mol:GTP	0.038	0.036	-10000	0	-0.17	13	13
RAC1-CDC42/GTP	-0.007	0.033	-10000	0	-10000	0	0
RASA1	0.017	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.041	0.028	-10000	0	-10000	0	0
ruffle organization	0.03	0.032	-10000	0	-10000	0	0
NCK1	0.008	0.061	-10000	0	-0.41	11	11
receptor internalization	0.005	0.012	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	0.048	0.018	-10000	0	-0.19	2	2
ROCK1	0.014	0.036	-10000	0	-0.21	13	13
RAS family/GDP	-0.032	0.055	-10000	0	-0.25	4	4
Rac1/GTP	-0.004	0.025	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/Paxillin	0.027	0.024	-10000	0	-0.13	12	12

×

Arf6 trafficking 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.017	0	-9999	-10000	0	0
CLTC	0.018	0.013	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.01	0.033	-9999	-0.097	45	45
Dynamin 2/GTP	0.018	0	-9999	-10000	0	0
EXOC4	0	0	-9999	-10000	0	0
CD59	0.014	0.017	-9999	-10000	0	0
CPE	0.014	0.004	-9999	-10000	0	0
CTNNB1	0.017	0	-9999	-10000	0	0
membrane fusion	0.009	0.036	-9999	-0.11	45	45
CTNND1	0.014	0.03	-9999	-0.2	10	10
DNM2	0.017	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.015	0.023	-9999	-0.094	3	3
TSHR	0.014	0.022	-9999	-0.24	4	4
INS	0.015	0.008	-9999	-10000	0	0
BIN1	0.016	0.005	-9999	-10000	0	0
mol:Choline	0.009	0.036	-9999	-0.11	45	45
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	0.006	0	-9999	-10000	0	0
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.017	0	-9999	-10000	0	0
mol:Ca2+	0.017	0	-9999	-10000	0	0
JUP	0.01	0.029	-9999	-0.12	16	16
ASAP2/amphiphysin II	0.02	0.006	-9999	-10000	0	0
ARF6/GTP	0.013	0	-9999	-10000	0	0
CDH1	0.012	0.023	-9999	-10000	0	0
clathrin-independent pinocytosis	0.013	0	-9999	-10000	0	0
MAPK8IP3	0.017	0	-9999	-10000	0	0
positive regulation of endocytosis	0.013	0	-9999	-10000	0	0
EXOC2	0.017	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0.019	0.024	-9999	-0.092	24	24
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.016	0.019	-9999	-0.41	1	1
regulation of calcium-dependent cell-cell adhesion	-0.026	0.02	-9999	-10000	0	0
positive regulation of phagocytosis	0.015	0.011	-9999	-0.24	1	1
ARF6/GTP/JIP3	0.023	0	-9999	-10000	0	0
ACAP1	0.009	0.031	-9999	-0.092	45	45
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	0.014	0.017	-9999	-10000	0	0
clathrin heavy chain/ACAP1	0.016	0.027	-9999	-0.14	1	1
JIP4/KLC1	0.024	0.018	-9999	-0.21	1	1
EXOC1	0.011	0.049	-9999	-0.41	7	7
exocyst	0.019	0.025	-9999	-0.093	24	24
RALA/GTP	-0.013	0.084	-9999	-0.29	45	45
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.023	0.011	-9999	-0.24	1	1
receptor recycling	0.013	0	-9999	-10000	0	0
CTNNA1	0.018	0	-9999	-10000	0	0
NME1	0.006	0	-9999	-10000	0	0
clathrin coat assembly	0.018	0.013	-9999	-10000	0	0
IL2RA	0.013	0.021	-9999	-0.11	6	6
VAMP3	0.015	0.011	-9999	-0.24	1	1
GLUT4/clathrin heavy chain/ACAP1	0.023	0.027	-9999	-0.13	1	1
EXOC6	0	0	-9999	-10000	0	0
PLD1	0.008	0.032	-9999	-0.094	46	46
PLD2	0.009	0.03	-9999	-0.09	45	45
EXOC5	0.003	0.076	-9999	-0.41	17	17
PIP5K1C	0.015	0.022	-9999	-0.11	1	1
SDC1	0.003	0.041	-9999	-0.12	47	47
ARF6/GDP	0.013	0	-9999	-10000	0	0
EXOC7	0.017	0	-9999	-10000	0	0
E-cadherin/beta catenin	0.028	0.021	-9999	-10000	0	0
mol:Phosphatidic acid	0.009	0.036	-9999	-0.11	45	45
endocytosis	-0.02	0.006	-9999	-10000	0	0
SCAMP2	0.017	0	-9999	-10000	0	0
ADRB2	0.02	0.015	-9999	-0.17	1	1
EXOC3	0.017	0	-9999	-10000	0	0
ASAP2	0	0	-9999	-10000	0	0
Dynamin 2/GDP	0.017	0	-9999	-10000	0	0
KLC1	0.013	0.008	-9999	-10000	0	0
AVPR2	0.02	0.013	-9999	-10000	0	0
RALA	-0.02	0.12	-9999	-0.41	45	45
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.028	0.032	-9999	-0.15	10	10

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0	-9999	-10000	0	0
SPHK1	0.002	0.08	-9999	-0.41	19	19
GNAI2	0.017	0.001	-9999	-10000	0	0
mol:S1P	0.01	0.04	-9999	-0.16	26	26
GNAO1	0.002	0.005	-9999	-10000	0	0
mol:Sphinganine-1-P	0.007	0.056	-9999	-0.28	19	19
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.024	0.04	-9999	-0.21	8	8
GNAI3	-0.036	0.14	-9999	-0.41	65	65
G12/G13	0.022	0.033	-9999	-0.28	6	6
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0.017	0.001	-9999	-10000	0	0
S1P1/S1P	0.018	0.035	-9999	-0.26	2	2
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
GNAI1	0.014	0.02	-9999	-0.41	1	1
S1P/S1P5/G12	0.015	0.037	-9999	-0.13	30	30
S1P/S1P3/Gq	0.023	0.029	-9999	-0.17	7	7
S1P/S1P4/Gi	0	0.027	-9999	-0.32	3	3
GNAQ	0.017	0	-9999	-10000	0	0
GNAZ	0.015	0.006	-9999	-10000	0	0
GNA14	0.015	0.026	-9999	-0.41	2	2
GNA15	0.011	0.049	-9999	-0.41	7	7
GNA12	0.014	0.037	-9999	-0.41	4	4
GNA13	0.015	0.026	-9999	-0.41	2	2
GNA11	0.017	0	-9999	-10000	0	0
ABCC1	0.01	0.056	-9999	-0.41	9	9

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.017	0	-10000	0	-10000	0	0
HDAC4	0.017	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	0.014	-10000	0	-10000	0	0
CDKN1A	-0.019	0.098	-10000	0	-0.3	54	54
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.011	0.049	-10000	0	-0.41	7	7
FOXO3	-0.006	0.003	-10000	0	-10000	0	0
FOXO1	0.008	0.061	-10000	0	-0.41	11	11
FOXO4	0.018	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.017	0	-10000	0	-10000	0	0
TAT	0.017	0	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.009	0	-10000	0	-10000	0	0
PPARGC1A	0.015	0.032	-10000	0	-0.41	3	3
FHL2	0.013	0.037	-10000	0	-0.41	4	4
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.029	0.019	-10000	0	-10000	0	0
HIST2H4A	0.011	0.014	-10000	0	-10000	0	0
SIRT1/FOXO3a	0.012	0.02	-10000	0	-10000	0	0
SIRT1	0.022	0.027	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.038	0.018	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.029	0.021	-10000	0	-0.12	1	1
apoptosis	-0.034	0.035	0.23	7	-10000	0	7
SIRT1/PGC1A	0.025	0.027	-10000	0	-0.24	3	3
p53/SIRT1	-0.004	0.12	0.25	43	-0.28	69	112
SIRT1/FOXO4	0.03	0.02	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	0.028	0.044	-10000	0	-0.21	15	15
HIST1H1E	0.018	0.007	-10000	0	-0.15	1	1
SIRT1/p300	0.029	0.019	-10000	0	-10000	0	0
muscle cell differentiation	-0.019	0.018	-10000	0	-10000	0	0
TP53	-0.034	0.15	-10000	0	-0.41	69	69
KU70/SIRT1/BAX	0.034	0.035	-10000	0	-0.23	7	7
CREBBP	0.017	0	-10000	0	-10000	0	0
MEF2D	0.017	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.029	0.019	-10000	0	-10000	0	0
ACSS2	0.011	0.014	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.019	0.018	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	0.026	0.006	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.007	0.024	-9999	-0.18	5	5
JUN	0.028	0.023	-9999	-0.17	1	1
HRAS	0.016	0.019	-9999	-0.41	1	1
RET51/GFRalpha1/GDNF/GRB10	0.035	0.047	-9999	-0.21	19	19
RAP1A	0.017	0	-9999	-10000	0	0
FRS2	0.015	0.032	-9999	-0.41	3	3
RAP1A/GDP	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.043	0.019	-9999	-0.21	3	3
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.017	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	0.032	0.015	-9999	-0.21	2	2
RHOA	0.017	0.001	-9999	-10000	0	0
RAP1A/GTP	0.04	0.017	-9999	-0.18	3	3
GRB7	0.016	0.019	-9999	-0.41	1	1
RET51/GFRalpha1/GDNF	0.043	0.019	-9999	-0.21	3	3
MAPKKK cascade	0.029	0.023	-9999	-0.15	4	4
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.03	0.028	-9999	-0.21	7	7
lamellipodium assembly	0.02	0.036	-9999	-0.18	5	5
RET51/GFRalpha1/GDNF/SHC	0.021	0.075	-9999	-0.22	47	47
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
RET9/GFRalpha1/GDNF/SHC	0.011	0.073	-9999	-0.22	46	46
RET9/GFRalpha1/GDNF/Shank3	0.021	0.015	-9999	-0.22	2	2
MAPK3	0.026	0.015	-9999	-0.17	3	3
DOK1	0.017	0	-9999	-10000	0	0
DOK6	0	0	-9999	-10000	0	0
PXN	0.017	0	-9999	-10000	0	0
neurite development	0.03	0.015	-9999	-0.15	3	3
DOK5	0.015	0.019	-9999	-0.41	1	1
GFRA1	0.015	0.026	-9999	-0.41	2	2
MAPK8	0.028	0.023	-9999	-10000	0	0
HRAS/GTP	0.037	0.027	-9999	-0.17	4	4
tube development	0.023	0.014	-9999	-0.2	2	2
MAPK1	0.026	0.016	-9999	-0.17	3	3
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.025	0.015	-9999	-0.12	5	5
Rac1/GDP	0.013	0	-9999	-10000	0	0
SRC	0.017	0	-9999	-10000	0	0
PDLIM7	0.017	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	0.039	0.018	-9999	-0.19	3	3
SHC1	-0.02	0.12	-9999	-0.41	46	46
RET51/GFRalpha1/GDNF/Dok4	0.043	0.019	-9999	-0.21	3	3
RET51/GFRalpha1/GDNF/Dok5	0.039	0.024	-9999	-0.21	4	4
PRKCA	0.017	0	-9999	-10000	0	0
HRAS/GDP	0.012	0.013	-9999	-0.29	1	1
CREB1	0.014	0.044	-9999	-0.13	46	46
PIK3R1	0.016	0.004	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.012	0.047	-9999	-0.13	50	50
RET51/GFRalpha1/GDNF/Grb7	0.042	0.022	-9999	-0.21	4	4
mol:GDP	0	0	-9999	-10000	0	0
RET	0.016	0.019	-9999	-0.41	1	1
DOK4	0.017	0	-9999	-10000	0	0
JNK cascade	0.028	0.023	-9999	-0.16	1	1
RET9/GFRalpha1/GDNF/FRS2	0.031	0.024	-9999	-0.21	5	5
SHANK3	0	0	-9999	-10000	0	0
RASA1	0.017	0.002	-9999	-10000	0	0
NCK1	0.008	0.061	-9999	-0.41	11	11
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.008	0.045	-9999	-0.14	46	46
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.03	0.016	-9999	-0.12	6	6
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.028	0.025	-9999	-0.12	14	14
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.013	0.045	-9999	-0.13	47	47
PI3K	0.027	0.047	-9999	-0.2	10	10
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.029	0.014	-9999	-0.2	2	2
GRB10	0.004	0.074	-9999	-0.41	16	16
activation of MAPKK activity	0.029	0.015	-9999	-0.11	5	5
RET51/GFRalpha1/GDNF/FRS2	0.041	0.027	-9999	-0.21	6	6
GAB1	0.014	0.037	-9999	-0.41	4	4
IRS1	0.013	0.042	-9999	-0.41	5	5
IRS2	0.017	0.002	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.017	0.047	-9999	-0.12	51	51
RET51/GFRalpha1/GDNF/PKC alpha	0.043	0.019	-9999	-0.21	3	3
GRB2	0.017	0.002	-9999	-10000	0	0
PRKACA	0.017	0	-9999	-10000	0	0
GDNF	0.017	0	-9999	-10000	0	0
RAC1	0.017	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.04	0.031	-9999	-0.21	8	8
Rac1/GTP	0.025	0.042	-9999	-0.2	5	5
RET9/GFRalpha1/GDNF	0.022	0.016	-9999	-0.24	2	2
GFRalpha1/GDNF	0.024	0.019	-9999	-0.28	2	2

×

mTOR 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
GBL	0.017	0	-10000	0	-10000	0	0
MKNK1	0.017	0	-10000	0	-10000	0	0
mol:PIP3	0.002	0.044	0.22	2	-0.18	27	29
FRAP1	0.018	0.026	-10000	0	-0.37	1	1
AKT1	0.007	0.041	0.16	2	-0.16	24	26
INSR	0.017	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.023	0	-10000	0	-10000	0	0
mol:GTP	0.027	0.042	0.19	1	-0.14	25	26
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.006	0.025	-10000	0	-0.17	7	7
TSC2	0.017	0	-10000	0	-10000	0	0
RHEB/GDP	0.016	0.035	-10000	0	-0.13	25	25
TSC1	0.016	0.019	-10000	0	-0.41	1	1
Insulin Receptor/IRS1	0.018	0.015	-10000	0	-0.14	5	5
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.018	0.036	-10000	0	-0.19	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.017	0	-10000	0	-10000	0	0
RPS6KB1	0.022	0.034	0.17	1	-0.26	1	2
MAP3K5	0.007	0.008	-10000	0	-0.086	4	4
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
apoptosis	0.007	0.008	-10000	0	-0.086	4	4
mol:LY294002	0	0	0.001	1	-0.001	5	6
EIF4B	0.024	0.031	0.16	1	-0.22	1	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.034	0.031	0.16	1	-0.21	1	2
eIF4E/eIF4G1/eIF4A1	-0.005	0.026	-10000	0	-0.18	6	6
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.017	0.047	-10000	0	-0.18	27	27
mTOR/RHEB/GTP/Raptor/GBL	0.027	0.029	0.16	1	-0.2	1	2
FKBP1A	0.016	0.019	-10000	0	-0.42	1	1
RHEB/GTP	0.024	0.037	-10000	0	-0.16	2	2
mol:Amino Acids	0	0	0.001	1	-0.001	5	6
FKBP12/Rapamycin	0.012	0.013	-10000	0	-0.29	1	1
PDPK1	0.005	0.042	0.17	2	-0.17	24	26
EIF4E	0.013	0.042	-10000	0	-0.41	5	5
ASK1/PP5C	0.028	0.05	-10000	0	-0.45	5	5
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.021	0.018	-10000	0	-0.16	5	5
TSC1/TSC2	0.03	0.045	0.2	1	-0.15	25	26
tumor necrosis factor receptor activity	0	0	0.001	5	-0.001	1	6
RPS6	0.017	0	-10000	0	-10000	0	0
PPP5C	0.017	0	-10000	0	-10000	0	0
EIF4G1	0.014	0.037	-10000	0	-0.41	4	4
IRS1	0.007	0.015	-10000	0	-0.15	5	5
INS	0.017	0	-10000	0	-10000	0	0
PTEN	0.015	0.026	-10000	0	-0.41	2	2
PDK2	0.005	0.042	0.17	2	-0.17	24	26
EIF4EBP1	-0.1	0.12	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
PPP2R5D	0.02	0.024	-10000	0	-0.33	1	1
peptide biosynthetic process	0.02	0	-10000	0	-10000	0	0
RHEB	0.017	0	-10000	0	-10000	0	0
EIF4A1	0.009	0.059	-10000	0	-0.41	10	10
mol:Rapamycin	0	0.001	0.003	1	-0.002	24	25
EEF2	0.02	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	-0.088	0.11	-10000	0	-0.41	2	2

×

S1P5 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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.015	0.038	0.16	12	-10000	0	12
GNAI2	0.017	0.001	-10000	0	-10000	0	0
S1P/S1P5/G12	0.01	0.022	-10000	0	-0.24	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.002	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.015	0.039	-10000	0	-0.16	12	12
negative regulation of cAMP metabolic process	0.001	0.01	-10000	0	-0.1	3	3
GNAZ	0.015	0.006	-10000	0	-10000	0	0
GNAI3	-0.036	0.14	-10000	0	-0.41	65	65
GNA12	0.014	0.037	-10000	0	-0.41	4	4
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.001	0.01	-10000	0	-0.1	3	3
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
RHOA	0.017	0.001	-10000	0	-10000	0	0
GNAI1	0.014	0.02	-10000	0	-0.41	1	1

×

Atypical NF-kappaB pathway

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
BCL3/RelA	0.025	0	-9999	-10000	0	0
FBXW11	0.017	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.024	0.023	-9999	-0.24	4	4
NF kappa B1 p50/RelA/I kappa B alpha	0.03	0.043	-9999	-0.25	6	6
NFKBIA	0.012	0.037	-9999	-0.11	40	40
MAPK14	0.015	0.026	-9999	-0.41	2	2
NF kappa B1 p105/p50	0.024	0.023	-9999	-0.24	4	4
ARRB2	0.014	0.012	-9999	-0.18	2	2
REL	0.017	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.024	0.023	-9999	-0.24	4	4
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.024	0.023	-9999	-0.24	4	4
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
NF kappa B1 p50 dimer	0.016	0.026	-9999	-0.28	4	4
PIK3R1	0.016	0.004	-9999	-10000	0	0
NFKB1	0.015	0.026	-9999	-0.29	4	4
RELA	0.017	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.017	0.038	-9999	-0.17	7	7
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.033	0.043	-9999	-0.24	6	6
SRC	0.017	0	-9999	-10000	0	0
PI3K	0.009	0.065	-9999	-0.28	25	25
NF kappa B1 p50/RelA	0.017	0.038	-9999	-0.18	7	7
IKBKB	0.017	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
SYK	-0.012	0.11	-9999	-0.41	36	36
I kappa B alpha/PIK3R1	0.021	0.033	-9999	-0.18	3	3
cell death	0.032	0.041	-9999	-0.24	6	6
NF kappa B1 p105/c-Rel	0.024	0.023	-9999	-0.24	4	4
LCK	0.014	0.037	-9999	-0.41	4	4
BCL3	0.017	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.002	0.094	-10000	0	-0.4	27	27
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.025	0.011	-10000	0	-10000	0	0
IL27/IL27R/JAK1	0.037	0.019	-10000	0	-10000	0	0
TBX21	0.024	0.033	-10000	0	-10000	0	0
IL12B	0.018	0.001	-10000	0	-10000	0	0
IL12A	0.009	0	-10000	0	-10000	0	0
IL6ST	0.018	0.001	-10000	0	-10000	0	0
IL27RA/JAK1	0.022	0.003	-10000	0	-10000	0	0
IL27	0.001	0.001	-10000	0	-10000	0	0
TYK2	0.018	0.019	-10000	0	-0.41	1	1
T-helper cell lineage commitment	0.002	0.071	-10000	0	-0.17	74	74
T-helper 2 cell differentiation	-0.025	0.011	-10000	0	-10000	0	0
T cell proliferation during immune response	-0.025	0.011	-10000	0	-10000	0	0
MAPKKK cascade	0.025	0.011	-10000	0	-10000	0	0
STAT3	0.009	0.059	-10000	0	-0.41	10	10
STAT2	0.017	0	-10000	0	-10000	0	0
STAT1	0.003	0.078	-10000	0	-0.41	18	18
IL12RB1	0.018	0	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.025	0.033	-10000	0	-10000	0	0
IL27/IL27R/JAK2/TYK2	0.025	0.012	-10000	0	-10000	0	0
positive regulation of T cell mediated cytotoxicity	0.025	0.011	-10000	0	-10000	0	0
STAT1 (dimer)	0.037	0.046	0.28	4	-0.34	1	5
JAK2	0.017	0.001	-10000	0	-10000	0	0
JAK1	0.017	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	0.034	0.012	-10000	0	-10000	0	0
T cell proliferation	0.009	0.062	-10000	0	-0.27	2	2
IL12/IL12R/TYK2/JAK2	0.044	0.011	-10000	0	-10000	0	0
IL17A	0.002	0.071	-10000	0	-0.17	74	74
mast cell activation	-0.025	0.011	-10000	0	-10000	0	0
IFNG	0.011	0.004	-10000	0	-0.072	1	1
T cell differentiation	0.001	0.001	-10000	0	-0.013	1	1
STAT3 (dimer)	0.03	0.031	-10000	0	-10000	0	0
STAT5A (dimer)	0.034	0.015	-10000	0	-10000	0	0
STAT4 (dimer)	0.019	0.02	-10000	0	-10000	0	0
STAT4	0.01	0.008	-10000	0	-10000	0	0
T cell activation	-0.006	0	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.041	0.011	-10000	0	-10000	0	0
GATA3	0.003	0.035	-10000	0	-0.35	5	5
IL18	-0.016	0.084	-10000	0	-0.29	45	45
positive regulation of mast cell cytokine production	0.03	0.03	-10000	0	-10000	0	0
IL27/EBI3	0.011	0.023	-10000	0	-0.29	3	3
IL27RA	0.012	0.002	-10000	0	-10000	0	0
IL6	-0.018	0.13	-10000	0	-0.4	52	52
STAT5A	0.016	0.019	-10000	0	-0.41	1	1
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.005	0.002	-10000	0	-10000	0	0
IL1B	0.001	0.048	-10000	0	-0.29	14	14
EBI3	0.014	0.032	-10000	0	-0.41	3	3
TNF	0.008	0.018	-10000	0	-0.29	2	2

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.027	0.022	0.28	2	-10000	0	2
KIRREL	0.018	0.02	-10000	0	-0.41	1	1
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.027	0.022	-10000	0	-0.28	2	2
PLCG1	0.017	0	-10000	0	-10000	0	0
ARRB2	0.017	0	-10000	0	-10000	0	0
WASL	0.017	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.019	0.078	-10000	0	-0.22	51	51
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.029	0.021	-10000	0	-0.12	4	4
FYN	0.019	0.017	-10000	0	-0.17	4	4
mol:Ca2+	0.043	0.023	-10000	0	-0.19	2	2
mol:DAG	0.044	0.024	-10000	0	-0.19	2	2
NPHS2	0.019	0.006	-10000	0	-10000	0	0
mol:IP3	0.044	0.024	-10000	0	-0.19	2	2
regulation of endocytosis	0.037	0.019	-10000	0	-0.16	4	4
Nephrin/NEPH1/podocin/Cholesterol	0.034	0.024	-10000	0	-0.2	2	2
establishment of cell polarity	0.027	0.022	-10000	0	-0.28	2	2
Nephrin/NEPH1/podocin/NCK1-2	0.047	0.037	-10000	0	-0.17	13	13
Nephrin/NEPH1/beta Arrestin2	0.039	0.019	-10000	0	-0.16	4	4
NPHS1	0.018	0.02	-10000	0	-0.41	1	1
Nephrin/NEPH1/podocin	0.032	0.019	-10000	0	-0.17	4	4
TJP1	0.017	0	-10000	0	-10000	0	0
NCK1	0.008	0.061	-10000	0	-0.41	11	11
NCK2	0.017	0.001	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.045	0.024	-10000	0	-0.19	2	2
CD2AP	-0.023	0.12	-10000	0	-0.41	49	49
Nephrin/NEPH1/podocin/GRB2	0.044	0.023	-10000	0	-0.19	2	2
GRB2	0.017	0.002	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.022	0.023	-10000	0	-0.19	5	5
cytoskeleton organization	0.031	0.023	0.19	2	-0.15	2	4
Nephrin/NEPH1	0.023	0.016	-10000	0	-0.19	2	2
Nephrin/NEPH1/ZO-1	0.036	0.018	-10000	0	-0.22	2	2

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	0.12	0.1	-10000	0	-0.44	6	6
PCK1	0.11	0.074	-10000	0	-0.34	7	7
HNF4A	0.14	0.11	-10000	0	-0.58	5	5
KCNJ11	0.14	0.11	-10000	0	-0.46	5	5
AKT1	0.096	0.069	-10000	0	-0.26	7	7
response to starvation	0.005	0.004	-10000	0	-10000	0	0
DLK1	0.12	0.16	-10000	0	-0.47	13	13
NKX2-1	0.1	0.076	0.27	17	-0.31	4	21
ACADM	0.12	0.1	-10000	0	-0.43	7	7
TAT	0.11	0.065	-10000	0	-0.4	2	2
CEBPB	0.013	0.061	-10000	0	-0.41	11	11
CEBPA	0.01	0.074	-10000	0	-0.41	16	16
TTR	0.095	0.083	-10000	0	-0.66	3	3
PKLR	0.12	0.1	-10000	0	-0.46	5	5
APOA1	0.15	0.12	-10000	0	-0.6	5	5
CPT1C	0.12	0.099	-10000	0	-0.47	5	5
ALAS1	0.11	0.068	-10000	0	-0.33	2	2
TFRC	0.13	0.093	-10000	0	-0.37	5	5
FOXF1	-0.018	0.11	-10000	0	-0.41	36	36
NF1	0.023	0.006	-10000	0	-10000	0	0
HNF1A (dimer)	0.033	0.004	-10000	0	-10000	0	0
CPT1A	0.12	0.1	-10000	0	-0.46	5	5
HMGCS1	0.12	0.1	-10000	0	-0.46	5	5
NR3C1	0.026	0.019	-10000	0	-10000	0	0
CPT1B	0.12	0.1	-10000	0	-0.46	5	5
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.023	0	-10000	0	-10000	0	0
GCK	0.12	0.1	-10000	0	-0.46	5	5
CREB1	0.025	0.011	-10000	0	-10000	0	0
IGFBP1	0.09	0.085	-10000	0	-0.31	13	13
PDX1	0.12	0.066	-10000	0	-0.29	2	2
UCP2	0.096	0.16	-10000	0	-0.42	20	20
ALDOB	0.14	0.11	-10000	0	-0.45	5	5
AFP	0.026	0.031	-10000	0	-0.43	2	2
BDH1	0.12	0.1	-10000	0	-0.46	5	5
HADH	0.14	0.11	-10000	0	-0.44	6	6
F2	0.15	0.12	-10000	0	-0.66	4	4
HNF1A	0.033	0.004	-10000	0	-10000	0	0
G6PC	0.048	0.037	-10000	0	-0.23	1	1
SLC2A2	0.13	0.082	-10000	0	-0.5	2	2
INS	0.008	0.019	-10000	0	-10000	0	0
FOXA1	0.012	0.019	0.14	2	-0.19	3	5
FOXA3	0.036	0.025	-10000	0	-0.16	3	3
FOXA2	0.19	0.13	-10000	0	-0.53	5	5
ABCC8	0.14	0.11	-10000	0	-0.45	5	5
ALB	0.026	0.031	-10000	0	-0.43	2	2

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.02	0.002	-10000	0	-10000	0	0
TRAF2/ASK1	0.023	0.002	-10000	0	-10000	0	0
ATM	-0.003	0.091	-10000	0	-0.41	25	25
MAP2K3	0.048	0.035	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.046	0.035	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.007	0.067	-10000	0	-0.41	13	13
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.016	0.004	-10000	0	-10000	0	0
GADD45A	-0.02	0.12	-10000	0	-0.41	46	46
GADD45B	0.01	0.056	-10000	0	-0.41	9	9
MAP3K1	0.016	0.019	-10000	0	-0.41	1	1
MAP3K6	0.015	0.032	-10000	0	-0.41	3	3
MAP3K7	0.016	0.019	-10000	0	-0.41	1	1
MAP3K4	0.017	0.001	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.024	0.023	-10000	0	-0.28	3	3
TAK1/TAB family	0.012	0.009	0.12	2	-0.12	1	3
RAC1/OSM/MEKK3	0.022	0	-10000	0	-10000	0	0
TRAF2	0.017	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.001	0.022	-10000	0	-10000	0	0
TRAF6	0.015	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.002	0.006	-10000	0	-10000	0	0
CCM2	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.003	0.008	-10000	0	-10000	0	0
MAPK11	0.017	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.005	0.012	-10000	0	-10000	0	0
OSM/MEKK3	0.013	0	-10000	0	-10000	0	0
TAOK1	-0.002	0.042	-10000	0	-0.19	25	25
TAOK2	0.005	0.042	-10000	0	-0.18	25	25
TAOK3	0.005	0.042	-10000	0	-0.18	25	25
MAP3K7IP1	0.017	0	-10000	0	-10000	0	0
MAPK14	0.015	0.026	-10000	0	-0.41	2	2
MAP3K7IP2	0.017	0	-10000	0	-10000	0	0
MAP3K5	0.017	0.001	-10000	0	-10000	0	0
MAP3K10	0.017	0	-10000	0	-10000	0	0
MAP3K3	0.017	0	-10000	0	-10000	0	0
TRX/ASK1	0.018	0.002	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.011	0.081	-10000	0	-0.2	66	66

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.027	0.098	-9999	-0.29	65	65
SMARCC1	0.012	0.075	-9999	-0.39	18	18
REL	0.016	0	-9999	-10000	0	0
HDAC7	0.038	0.029	-9999	-10000	0	0
JUN	0.017	0.019	-9999	-0.41	1	1
EP300	0.017	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
KAT5	0	0	-9999	-10000	0	0
MAPK14	0.02	0.019	-9999	-0.28	2	2
FOXO1	0.008	0.061	-9999	-0.41	11	11
T-DHT/AR	0.059	0.034	-9999	-10000	0	0
MAP2K6	0.019	0.002	-9999	-10000	0	0
BRM/BAF57	0.027	0	-9999	-10000	0	0
MAP2K4	0.018	0.004	-9999	-10000	0	0
SMARCA2	0.018	0	-9999	-10000	0	0
PDE9A	0.035	0.041	-9999	-0.4	4	4
NCOA2	0.018	0	-9999	-10000	0	0
CEBPA	0.004	0.074	-9999	-0.41	16	16
EHMT2	0.018	0	-9999	-10000	0	0
cell proliferation	0.068	0.03	-9999	-0.18	1	1
NR0B1	-0.023	0.12	-9999	-0.41	49	49
EGR1	0.005	0.071	-9999	-0.41	15	15
RXRs/9cRA	0.033	0.018	-9999	-0.21	3	3
AR/RACK1/Src	0.043	0.02	-9999	-10000	0	0
AR/GR	0.034	0.02	-9999	-0.12	1	1
GNB2L1	0.017	0	-9999	-10000	0	0
PKN1	0.009	0.059	-9999	-0.41	10	10
RCHY1	0.017	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
MAPK8	0.02	0.006	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.052	0.023	-9999	-10000	0	0
SRC	0.024	0.016	-9999	-0.18	2	2
NR3C1	0.017	0	-9999	-10000	0	0
KLK3	0.025	0.024	-9999	-10000	0	0
APPBP2	0.018	0.002	-9999	-10000	0	0
TRIM24	0.011	0.056	-9999	-0.41	9	9
T-DHT/AR/TIP60	0.023	0.018	-9999	-0.17	2	2
TMPRSS2	0.035	0.035	-9999	-0.33	4	4
RXRG	0.015	0.032	-9999	-0.41	3	3
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.017	0	-9999	-10000	0	0
RXRB	0.017	0	-9999	-10000	0	0
CARM1	0.018	0	-9999	-10000	0	0
NR2C2	0.017	0	-9999	-10000	0	0
KLK2	0.055	0.02	-9999	-10000	0	0
AR	0.026	0.022	-9999	-0.12	10	10
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0.017	0	-9999	-10000	0	0
MDM2	0.001	0.078	-9999	-0.41	18	18
SRY	0.015	0.019	-9999	-0.41	1	1
GATA2	0.016	0.019	-9999	-0.41	1	1
MYST2	0.017	0	-9999	-10000	0	0
HOXB13	0.018	0	-9999	-10000	0	0
T-DHT/AR/RACK1/Src	0.04	0.02	-9999	-10000	0	0
positive regulation of transcription	0.016	0.019	-9999	-0.41	1	1
DNAJA1	0.018	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.007	0.062	-9999	-0.15	80	80
NCOA1	0.017	0.02	-9999	-10000	0	0
SPDEF	0.019	0	-9999	-10000	0	0
T-DHT/AR/TIF2	0.035	0.022	-9999	-0.12	1	1
T-DHT/AR/Hsp90	0.035	0.021	-9999	-0.17	2	2
GSK3B	0.018	0.002	-9999	-10000	0	0
NR2C1	0.017	0	-9999	-10000	0	0
mol:T-DHT	0.023	0.017	-9999	-0.2	2	2
SIRT1	0.017	0	-9999	-10000	0	0
ZMIZ2	0.016	0	-9999	-10000	0	0
POU2F1	0.028	0.009	-9999	-10000	0	0
T-DHT/AR/DAX-1	0.015	0.064	-9999	-0.18	50	50
CREBBP	0.017	0	-9999	-10000	0	0
SMARCE1	0.018	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.01	0.028	-9999	-0.2	1	1
CaM/Ca2+	0.012	0.003	-9999	-10000	0	0
AKT1	0.014	0.037	-9999	-0.41	4	4
AKT2	0.017	0	-9999	-10000	0	0
STXBP4	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.002	0.03	-9999	-0.13	4	4
YWHAZ	0.017	0.002	-9999	-10000	0	0
CALM1	0.016	0.004	-9999	-10000	0	0
YWHAQ	0.017	0	-9999	-10000	0	0
TBC1D4	0.015	0.026	-9999	-0.28	4	4
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.008	0.009	-9999	-10000	0	0
YWHAB	0.017	0.001	-9999	-10000	0	0
SNARE/Synip	0.021	0.007	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	0.017	0	-9999	-10000	0	0
PRKCI	0.016	0.019	-9999	-0.41	1	1
AS160/CaM/Ca2+	0.012	0.003	-9999	-10000	0	0
RHOQ	0.017	0	-9999	-10000	0	0
GYS1	0.004	0.063	-9999	-0.22	40	40
PRKCZ	0	0	-9999	-10000	0	0
TRIP10	0.012	0.046	-9999	-0.41	6	6
TC10/GTP/CIP4/Exocyst	0.02	0.028	-9999	-0.24	6	6
AS160/14-3-3	0.006	0.037	-9999	-0.13	24	24
VAMP2	0.016	0.005	-9999	-10000	0	0
SLC2A4	-0.003	0.031	-9999	-0.14	4	4
STX4	0.017	0	-9999	-10000	0	0
GSK3B	0.021	0.017	-9999	-0.18	4	4
SFN	-0.01	0.1	-9999	-0.41	33	33
LNPEP	0.016	0.019	-9999	-0.41	1	1
YWHAE	0.017	0.001	-9999	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.02	0.011	-10000	0	-10000	0	0
VLDLR	0.015	0.032	-10000	0	-0.41	3	3
CRKL	0.017	0	-10000	0	-10000	0	0
LRPAP1	0.017	0	-10000	0	-10000	0	0
FYN	0.015	0.027	-10000	0	-0.41	2	2
ITGA3	0.002	0.08	-10000	0	-0.41	19	19
RELN/VLDLR/Fyn	0.013	0.03	-10000	0	-0.24	4	4
MAPK8IP1/MKK7/MAP3K11/JNK1	0.051	0	-10000	0	-10000	0	0
AKT1	0.001	0.044	-10000	0	-0.15	33	33
MAP2K7	0.017	0	-10000	0	-10000	0	0
RAPGEF1	0.017	0	-10000	0	-10000	0	0
DAB1	0.017	0	-10000	0	-10000	0	0
RELN/LRP8/DAB1	0.014	0.024	-10000	0	-0.21	3	3
LRPAP1/LRP8	0.025	0	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	0.017	0.027	-10000	0	-0.19	3	3
DAB1/alpha3/beta1 Integrin	0.014	0.035	-10000	0	-0.2	6	6
long-term memory	0.016	0.028	-10000	0	-0.18	2	2
DAB1/LIS1	0.021	0.031	-10000	0	-0.18	4	4
DAB1/CRLK/C3G	0.017	0.026	-10000	0	-0.17	4	4
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
DAB1/NCK2	0.022	0.031	-10000	0	-0.18	4	4
ARHGEF2	0.017	0	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.011	0.008	-10000	0	-10000	0	0
CDK5R1	0.014	0.007	-10000	0	-10000	0	0
RELN	0.006	0.033	-10000	0	-0.41	3	3
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
RELN/LRP8/Fyn	0.014	0.027	-10000	0	-0.24	3	3
GRIN2A/RELN/LRP8/DAB1/Fyn	0.016	0.028	-10000	0	-0.19	2	2
MAPK8	0.017	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.013	0.027	-10000	0	-0.21	4	4
ITGB1	0.017	0	-10000	0	-10000	0	0
MAP1B	0.011	0.018	-10000	0	-0.18	2	2
RELN/LRP8	0.015	0.026	-10000	0	-0.24	3	3
GRIN2B/RELN/LRP8/DAB1/Fyn	0.021	0.031	-10000	0	-0.19	3	3
PI3K	0.009	0.065	-10000	0	-0.28	25	25
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.014	0.058	-10000	0	-0.28	19	19
RAP1A	0.08	0.052	-10000	0	-10000	0	0
PAFAH1B1	0.017	0.002	-10000	0	-10000	0	0
MAPK8IP1	0.017	0	-10000	0	-10000	0	0
CRLK/C3G	0.025	0	-10000	0	-10000	0	0
GRIN2B	0.017	0	-10000	0	-10000	0	0
NCK2	0.017	0.001	-10000	0	-10000	0	0
neuron differentiation	0.016	0.021	-10000	0	-0.12	2	2
neuron adhesion	0.077	0.058	-10000	0	-0.32	1	1
LRP8	0.017	0	-10000	0	-10000	0	0
GSK3B	0.003	0.041	-10000	0	-0.18	17	17
RELN/VLDLR/DAB1/Fyn	0.016	0.029	-10000	0	-0.19	4	4
MAP3K11	0.017	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	0.002	0.043	-10000	0	-0.16	30	30
CDK5	0.016	0.004	-10000	0	-10000	0	0
MAPT	0.023	0.08	0.34	32	-10000	0	32
neuron migration	0.01	0.035	-10000	0	-0.16	11	11
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.016	0.021	-10000	0	-0.12	2	2
RELN/VLDLR	0.019	0.03	-10000	0	-0.21	4	4

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.002	0.005	-9999	-10000	0	0
CDC42/GTP	-0.015	0.039	-9999	-0.16	12	12
PLCG1	0.002	0.01	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.017	0.001	-9999	-10000	0	0
GNAI3	-0.036	0.14	-9999	-0.41	65	65
G12/G13	0.022	0.033	-9999	-0.28	6	6
cell migration	-0.015	0.038	-9999	-0.16	12	12
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
MAPK3	0.002	0.01	-9999	-10000	0	0
MAPK1	0.002	0.01	-9999	-10000	0	0
S1P/S1P5/Gi	0.001	0.01	-9999	-0.1	3	3
GNAI1	0.014	0.02	-9999	-0.41	1	1
CDC42/GDP	0.013	0	-9999	-10000	0	0
S1P/S1P5/G12	0.01	0.022	-9999	-0.24	4	4
RHOA	0.016	0.023	-9999	-0.2	6	6
S1P/S1P4/Gi	0.001	0.01	-9999	-0.1	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.015	0.006	-9999	-10000	0	0
S1P/S1P4/G12/G13	0.019	0.025	-9999	-0.22	6	6
GNA12	0.014	0.037	-9999	-0.41	4	4
GNA13	0.015	0.026	-9999	-0.41	2	2
CDC42	0.017	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.033	0.004	-9999	-10000	0	0
HDAC3	0.017	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.007	-9999	-0.17	1	1
GATA1/HDAC4	0.025	0	-9999	-10000	0	0
GATA1/HDAC5	0.025	0	-9999	-10000	0	0
GATA2/HDAC5	0.025	0.014	-9999	-0.28	1	1
HDAC5/BCL6/BCoR	0.024	0.053	-9999	-0.24	21	21
HDAC9	0.015	0.026	-9999	-0.41	2	2
Glucocorticoid receptor/Hsp90/HDAC6	0.035	0	-9999	-10000	0	0
HDAC4/ANKRA2	0.025	0.014	-9999	-0.28	1	1
HDAC5/YWHAB	0.025	0.002	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.018	0.005	-9999	-0.11	1	1
GATA2	0.016	0.019	-9999	-0.41	1	1
HDAC4/RFXANK	-0.006	0.093	-9999	-0.28	53	53
BCOR	0.013	0.042	-9999	-0.41	5	5
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0	0	-9999	-10000	0	0
HDAC5	0.017	0	-9999	-10000	0	0
GNB1/GNG2	0.013	0.001	-9999	-10000	0	0
Histones	0.024	0.008	-9999	-0.1	2	2
ADRBK1	0.017	0	-9999	-10000	0	0
HDAC4	0.017	0	-9999	-10000	0	0
XPO1	0.017	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.025	0.014	-9999	-0.28	1	1
HDAC4/Ubc9	0.025	0	-9999	-10000	0	0
HDAC7	0	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.025	0.002	-9999	-10000	0	0
TUBA1B	0.017	0	-9999	-10000	0	0
HDAC6	0.017	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.006	0.093	-9999	-0.28	53	53
CAMK4	0.017	0	-9999	-10000	0	0
Tubulin/HDAC6	0.033	0.009	-9999	-10000	0	0
SUMO1	0.017	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.017	0.001	-9999	-10000	0	0
GATA1	0.017	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.017	0.001	-9999	-10000	0	0
NR3C1	0.017	0	-9999	-10000	0	0
SUMO1/HDAC4	0.033	0.005	-9999	-10000	0	0
SRF	0.017	0	-9999	-10000	0	0
HDAC4/YWHAB	0.025	0.002	-9999	-10000	0	0
Tubulin	0.024	0.006	-9999	-10000	0	0
HDAC4/14-3-3 E	0.025	0.002	-9999	-10000	0	0
GNB1	0.017	0.002	-9999	-10000	0	0
RANGAP1	0.017	0	-9999	-10000	0	0
BCL6/BCoR	0.013	0.061	-9999	-0.28	21	21
HDAC4/HDAC3/SMRT (N-CoR2)	0.035	0	-9999	-10000	0	0
HDAC4/SRF	0.035	0	-9999	-10000	0	0
HDAC4/ER alpha	0.025	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.024	0.008	-9999	-0.1	2	2
cell motility	0.032	0.008	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.017	0	-9999	-10000	0	0
HDAC7/HDAC3	0.013	0	-9999	-10000	0	0
BCL6	0.004	0.074	-9999	-0.41	16	16
HDAC4/CaMK II delta B	0.017	0	-9999	-10000	0	0
Hsp90/HDAC6	0.025	0	-9999	-10000	0	0
ESR1	0.017	0	-9999	-10000	0	0
HDAC6/HDAC11	0.025	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.034	0.006	-9999	-10000	0	0
NPC	0.01	0.009	-9999	-0.2	1	1
MEF2C	0.014	0.006	-9999	-10000	0	0
RAN	0.017	0.001	-9999	-10000	0	0
HDAC4/MEF2C	0.043	0.019	-9999	-10000	0	0
GNG2	0	0	-9999	-10000	0	0
NCOR2	0.017	0	-9999	-10000	0	0
TUBB2A	0.016	0.004	-9999	-10000	0	0
HDAC11	0.017	0	-9999	-10000	0	0
HSP90AA1	0.017	0	-9999	-10000	0	0
RANBP2	0.016	0.019	-9999	-0.41	1	1
ANKRA2	0.016	0.019	-9999	-0.41	1	1
RFXANK	-0.026	0.13	-9999	-0.41	53	53
nuclear import	-0.029	0.002	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.017	0	-9999	-10000	0	0
ITGB7	0.015	0.026	-9999	-0.41	2	2
ITGA4	0.013	0.042	-9999	-0.41	5	5
alpha4/beta7 Integrin	0.022	0.041	-9999	-0.38	5	5
alpha4/beta1 Integrin	0.023	0.03	-9999	-0.28	5	5

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.017	0	-10000	0	-10000	0	0
NFATC1	0.038	0.016	-10000	0	-10000	0	0
NFATC2	0.009	0.032	-10000	0	-0.11	7	7
NFATC3	0.012	0.003	-10000	0	-10000	0	0
YWHAE	0.017	0.001	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.001	0.011	-10000	0	-0.14	2	2
Exportin 1/Ran/NUP214	0.035	0.003	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.029	0.012	-10000	0	-10000	0	0
BCL2/BAX	0.021	0.036	-10000	0	-0.28	7	7
CaM/Ca2+/Calcineurin A alpha-beta B1	0.013	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.013	0.003	-10000	0	-10000	0	0
BAX	0.011	0.049	-10000	0	-0.41	7	7
MAPK14	0.016	0.026	-10000	0	-0.41	2	2
BAD	0.017	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.016	0.011	-10000	0	-0.13	2	2
Calcineurin A alpha-beta B1/BCL2	0.017	0	-10000	0	-10000	0	0
FKBP8	0.017	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.015	0.011	0.13	2	-10000	0	2
KPNB1	0.017	0	-10000	0	-10000	0	0
KPNA2	0.007	0.064	-10000	0	-0.41	12	12
XPO1	0.017	0	-10000	0	-10000	0	0
SFN	-0.01	0.1	-10000	0	-0.41	33	33
MAP3K8	-0.017	0.12	-10000	0	-0.41	42	42
NFAT4/CK1 alpha	0.027	0.011	-10000	0	-0.19	1	1
MEF2D/NFAT1/Cbp/p300	0.047	0.031	-10000	0	-10000	0	0
CABIN1	0.001	0.011	-10000	0	-0.14	2	2
CALM1	0.016	0.004	-10000	0	-10000	0	0
RAN	0.017	0.001	-10000	0	-10000	0	0
MAP3K1	0.016	0.019	-10000	0	-0.41	1	1
CAMK4	0.017	0	-10000	0	-10000	0	0
mol:Ca2+	0.001	0	-10000	0	-10000	0	0
MAPK3	0.017	0	-10000	0	-10000	0	0
YWHAH	0.008	0.009	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.026	0	-10000	0	-10000	0	0
YWHAB	0.017	0.001	-10000	0	-10000	0	0
MAPK8	0.017	0	-10000	0	-10000	0	0
MAPK9	0.017	0.001	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0.016	0.019	-10000	0	-0.41	1	1
NFAT1-c-4/YWHAQ	0.043	0.024	-10000	0	-10000	0	0
PRKCH	0.015	0.026	-10000	0	-0.41	2	2
CABIN1/Cbp/p300	0.026	0	-10000	0	-10000	0	0
CASP3	-0.062	0.17	-10000	0	-0.41	97	97
PIM1	0.015	0.026	-10000	0	-0.41	2	2
Calcineurin A alpha-beta B1/FKBP12/FK506	0.012	0.011	-10000	0	-0.24	1	1
apoptosis	0.015	0.019	-10000	0	-0.15	7	7
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.006	0.038	-10000	0	-0.14	25	25
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.017	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.022	0.005	-10000	0	-10000	0	0
BAD/BCL-XL	0.025	0	-10000	0	-10000	0	0
PRKCD	0.017	0	-10000	0	-10000	0	0
NUP214	0.017	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
PRKCA	0.017	0	-10000	0	-10000	0	0
PRKCG	0.017	0	-10000	0	-10000	0	0
PRKCQ	0.017	0	-10000	0	-10000	0	0
FKBP38/BCL2	0.025	0	-10000	0	-10000	0	0
EP300	0.018	0	-10000	0	-10000	0	0
PRKCB1	0.001	0.004	-10000	0	-10000	0	0
CSNK2A1	0.017	0	-10000	0	-10000	0	0
NFATc/JNK1	0.047	0.017	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.023	0.005	-10000	0	-10000	0	0
FKBP12/FK506	0.012	0.013	-10000	0	-0.29	1	1
CSNK1A1	0.016	0.004	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.023	0.005	-10000	0	-10000	0	0
NFATc/ERK1	0.046	0.017	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.029	0.012	-10000	0	-10000	0	0
NR4A1	0.032	0.028	-10000	0	-10000	0	0
GSK3B	0.017	0.002	-10000	0	-10000	0	0
positive T cell selection	0.012	0.003	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.013	0.023	-10000	0	-10000	0	0
RCH1/ KPNB1	0.018	0.046	-10000	0	-0.28	12	12
YWHAQ	0.017	0	-10000	0	-10000	0	0
PRKACA	0.017	0	-10000	0	-10000	0	0
AKAP5	0.017	0	-10000	0	-10000	0	0
MEF2D	0.018	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.017	0.002	-10000	0	-10000	0	0
NFATc/p38 alpha	0.046	0.022	-10000	0	-0.21	2	2
CREBBP	0.018	0	-10000	0	-10000	0	0
BCL2	0.017	0	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.006	0	-9999	-10000	0	0
ADCY5	0.006	0	-9999	-10000	0	0
ADCY6	0.012	0	-9999	-10000	0	0
ADCY7	0.009	0.024	-9999	-0.24	5	5
ADCY1	0.012	0	-9999	-10000	0	0
ADCY2	0.012	0	-9999	-10000	0	0
ADCY3	0.006	0	-9999	-10000	0	0
ADCY8	0.008	0.029	-9999	-0.24	7	7
PRKCE	0.009	0	-9999	-10000	0	0
ADCY9	0.012	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	0.014	0.013	-9999	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0	0.002	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.025	0.001	-10000	0	-10000	0	0
STXBP1	0.002	0.005	-10000	0	-10000	0	0
ACh/CHRNA1	0.029	0.021	-10000	0	-0.24	3	3
RAB3GAP2/RIMS1/UNC13B	0.035	0.002	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.017	0	-10000	0	-10000	0	0
mol:ACh	0.03	0.012	0.051	32	-0.037	1	33
RAB3GAP2	0.017	0	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.001	0.006	-10000	0	-10000	0	0
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.029	0.021	-10000	0	-0.24	3	3
UNC13B	0.017	0.001	-10000	0	-10000	0	0
CHRNA1	0.015	0.032	-10000	0	-0.41	3	3
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.002	0.008	-10000	0	-10000	0	0
SNAP25	0.001	0.002	-10000	0	-10000	0	0
VAMP2	0.005	0.002	-10000	0	-10000	0	0
SYT1	0.001	0.004	-10000	0	-10000	0	0
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.001	0.003	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.001	0.006	-10000	0	-10000	0	0

×

Arf1 pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.015	0.006	0.11	2	-10000	0	2
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.015	0.007	-10000	0	-0.075	3	3
AP2	0.012	0.002	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.024	0.001	-10000	0	-10000	0	0
CLTB	0.017	0.001	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.021	0.002	-10000	0	-10000	0	0
CD4	0.001	0.082	-10000	0	-0.41	20	20
CLTA	0.017	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
ARFGAP1	0.009	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.008	0.007	-10000	0	-0.15	1	1
ARF1/GTP	0.01	0.006	-10000	0	-0.12	1	1
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.019	0.002	-10000	0	-10000	0	0
mol:Choline	0.007	0.007	-10000	0	-0.14	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.017	0.001	-10000	0	-10000	0	0
DDEF1	0.007	0.007	-10000	0	-0.14	1	1
ARF1/GDP	0.007	0.002	-10000	0	-10000	0	0
AP2M1	0.017	0.002	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.013	0.001	-10000	0	-10000	0	0
Rac/GTP	0.013	0.001	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.027	0.002	-10000	0	-10000	0	0
ARFIP2	0.016	0.001	-10000	0	-10000	0	0
COPA	0.017	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.019	0.003	-10000	0	-10000	0	0
ARF1/GTP/ARHGAP10	0.011	0.001	-10000	0	-10000	0	0
GGA3	0.017	0	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.016	0.004	-10000	0	-10000	0	0
AP2A1	0	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.021	0.002	-10000	0	-10000	0	0
ARF1/GDP/Membrin	0.018	0.003	-10000	0	-10000	0	0
Arfaptin 2/Rac/GDP	0.023	0.001	-10000	0	-10000	0	0
CYTH2	0	0.001	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.022	0.001	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.013	0	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.019	0.024	-10000	0	-0.1	20	20
PLD2	0.007	0.007	-10000	0	-0.15	1	1
ARF-GAP1/v-SNARE	0.009	0	-10000	0	-10000	0	0
PIP5K1A	0.008	0.007	-10000	0	-0.15	1	1
ARF1/GTP/Membrin/GBF1/p115	0.016	0.005	-10000	0	-0.099	1	1
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.007	0.007	-10000	0	-0.14	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-10000	0	-10000	0	0
GOSR2	0.012	0.003	-10000	0	-0.06	1	1
USO1	0.012	0.003	-10000	0	-10000	0	0
GBF1	0.012	0.003	-10000	0	-0.06	1	1
ARF1/GTP/Arfaptin 2	0.023	0.002	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.013	0.05	-10000	0	-0.24	20	20

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.024	0.023	-9999	-0.28	3	3
FBXW11	0.017	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
CHUK	0.016	0.019	-9999	-0.41	1	1
NF kappa B2 p100/RelB	0.049	0.021	-9999	-0.19	4	4
NFKB1	0.014	0.037	-9999	-0.41	4	4
MAP3K14	0.015	0.026	-9999	-0.41	2	2
NF kappa B1 p50/RelB	0.023	0.03	-9999	-0.28	5	5
RELB	0.016	0.019	-9999	-0.41	1	1
NFKB2	0.017	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.023	0.011	-9999	-0.24	1	1
regulation of B cell activation	0.022	0.011	-9999	-0.24	1	1

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
PLK2	0.012	0.008	-9999	-9999
PLK4	0.017	0	-9999	-9999
regulation of centriole replication	0.013	0.008	-9999	-9999

×

Ephrin A reverse signaling

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
MAPKKK cascade	0.023	0	-9999	-10000	0	0
EFNA5	0.017	0	-9999	-10000	0	0
FYN	0.018	0.015	-9999	-0.21	2	2
neuron projection morphogenesis	0.023	0	-9999	-10000	0	0
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	0.023	0	-9999	-10000	0	0
EPHA5	0.017	0	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.02	0.002	-9999	-10000	0	0
MAPK9	0.007	0.001	-9999	-10000	0	0
adrenocorticotropin secretion	0.008	0.013	-9999	-0.29	1	1
GNB1/GNG2	0.011	0.001	-9999	-10000	0	0
GNB1	0.017	0.002	-9999	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0.007	0.012	-9999	-0.19	2	2
Gs family/GTP	0.011	0	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0	0	-9999	-10000	0	0
GNAL	0.017	0	-9999	-10000	0	0
GNG2	0	0	-9999	-10000	0	0
CRH	0.016	0.019	-9999	-0.41	1	1
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.007	0	-9999	-10000	0	0
MAPK11	0.007	0	-9999	-10000	0	0

×

Visual signal transduction: Rods

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
mol:K +	0.017	0	-9999	-10000	0	0
GNAT1/GTP	0.013	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	0.023	0.011	-9999	-0.24	1	1
PDE6G/GNAT1/GTP	0.023	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.017	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
CNG Channel	0.034	0	-9999	-10000	0	0
mol:Na +	0.027	0	-9999	-10000	0	0
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.023	0.003	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	0.034	0	-9999	-10000	0	0
CNGB1	0.017	0	-9999	-10000	0	0
RDH5	0.016	0.019	-9999	-0.41	1	1
SAG	0.016	0.019	-9999	-0.41	1	1
mol:Ca2+	0.027	0	-9999	-10000	0	0
Na + (4 Units)	0.024	0	-9999	-10000	0	0
RGS9	0.017	0	-9999	-10000	0	0
GNB1/GNGT1	0.025	0.003	-9999	-10000	0	0
GNAT1/GDP	0.03	0.003	-9999	-10000	0	0
GUCY2D	0.017	0	-9999	-10000	0	0
GNGT1	0.017	0	-9999	-10000	0	0
GUCY2F	0.017	0	-9999	-10000	0	0
GNB5	0.017	0.002	-9999	-10000	0	0
mol:GMP (4 units)	0.028	0	-9999	-10000	0	0
mol:11-cis-retinal	0.016	0.019	-9999	-0.41	1	1
mol:cGMP	0.022	0	-9999	-10000	0	0
GNB1	0.017	0.002	-9999	-10000	0	0
Rhodopsin	0.025	0.013	-9999	-0.28	1	1
SLC24A1	0.017	0	-9999	-10000	0	0
CNGA1	0.017	0	-9999	-10000	0	0
Metarhodopsin II	0.011	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.022	0	-9999	-10000	0	0
RGS9BP	0	0	-9999	-10000	0	0
Metarhodopsin II/Transducin	0.021	0.002	-9999	-10000	0	0
GCAP Family/Ca ++	0.011	0	-9999	-10000	0	0
PDE6A/B	0.025	0	-9999	-10000	0	0
mol:Pi	0.023	0.003	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.033	0.004	-9999	-10000	0	0
PDE6B	0.017	0	-9999	-10000	0	0
PDE6A	0.017	0	-9999	-10000	0	0
PDE6G	0.017	0	-9999	-10000	0	0
RHO	0.017	0	-9999	-10000	0	0
PDE6	0.042	0.005	-9999	-10000	0	0
GUCA1A	0	0	-9999	-10000	0	0
GC2/GCAP Family	0.022	0	-9999	-10000	0	0
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.017	0	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
cAMP biosynthetic process	-0.017	-9999	-9999
PI3K Class IB/PDE3B	0.017	-9999	-9999
PDE3B	0.017	-9999	-9999

pid_entity	TCGA.87.5896	TCGA.81.5910	TCGA.76.6285	TCGA.76.6282
109_MAP3K5	-0.074	0.041	0.041	0.041
47_PPARGC1A	0.017	0.017	0.017	0.017
105_BMP4	0.017	0.017	0.017	0.017
105_BMP6	0.017	0.017	0.017	0.017
105_BMP7	0.017	0.017	0.017	0.017
105_BMP2	0.017	0.017	-0.41	0.017
131_RELN/VLDLR	0.044	-0.093	0.044	0
30_TGFB1/TGF beta receptor Type II	-0.41	0.017	0.019	-0.41
84_STAT5B	-0.16	-0.098	0.034	-0.098
84_STAT5A	-0.16	-0.098	0.034	-0.098