PARADIGM pathway analysis of mRNASeq expression data - Liver Hepatocellular Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Plasma membrane estrogen receptor signaling	76
Signaling events regulated by Ret tyrosine kinase	68
PDGFR-alpha signaling pathway	67
FOXM1 transcription factor network	65
Nongenotropic Androgen signaling	59
Glypican 2 network	58
IL4-mediated signaling events	56
FOXA2 and FOXA3 transcription factor networks	55
IGF1 pathway	55
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	52

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
Plasma membrane estrogen receptor signaling	0.2836	76	6605	86	-0.53	0.48	1000	-1000	-0.065	-1000
Signaling events regulated by Ret tyrosine kinase	0.2537	68	5622	82	-0.48	0.013	1000	-1000	-0.073	-1000
PDGFR-alpha signaling pathway	0.2500	67	2964	44	-0.7	0.031	1000	-1000	-0.041	-1000
FOXM1 transcription factor network	0.2425	65	3323	51	-0.22	0.48	1000	-1000	-0.12	-1000
Nongenotropic Androgen signaling	0.2201	59	3119	52	-0.4	0.23	1000	-1000	-0.044	-1000
Glypican 2 network	0.2164	58	233	4	0.048	0.15	1000	-1000	-0.014	-1000
IL4-mediated signaling events	0.2090	56	5106	91	-0.99	0.49	1000	-1000	-0.095	-1000
FOXA2 and FOXA3 transcription factor networks	0.2052	55	2560	46	-0.77	0.037	1000	-1000	-0.016	-1000
IGF1 pathway	0.2052	55	3171	57	-0.38	0.14	1000	-1000	-0.069	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1940	52	3537	68	-0.71	0.21	1000	-1000	-0.08	-1000
HIF-1-alpha transcription factor network	0.1903	51	3898	76	-0.58	0.013	1000	-1000	-0.046	-1000
EPO signaling pathway	0.1903	51	2825	55	-0.3	0	1000	-1000	-0.076	-1000
TCGA08_retinoblastoma	0.1903	51	410	8	-0.082	0.21	1000	-1000	-0.013	-1000
p75(NTR)-mediated signaling	0.1866	50	6335	125	-0.58	0.19	1000	-1000	-0.084	-1000
Reelin signaling pathway	0.1866	50	2817	56	-0.3	0.061	1000	-1000	-0.075	-1000
IL6-mediated signaling events	0.1791	48	3647	75	-0.51	0.039	1000	-1000	-0.062	-1000
Signaling mediated by p38-alpha and p38-beta	0.1679	45	2002	44	-0.36	0	1000	-1000	-0.039	-1000
Aurora B signaling	0.1679	45	3026	67	-0.018	0.28	1000	-1000	-0.061	-1000
Ephrin B reverse signaling	0.1567	42	2035	48	-0.27	0.09	1000	-1000	-0.046	-1000
Ephrin A reverse signaling	0.1530	41	288	7	-0.14	0.011	1000	-1000	-0.025	-1000
Wnt signaling	0.1530	41	289	7	-0.23	0.014	1000	-1000	-0.038	-1000
EPHB forward signaling	0.1381	37	3200	85	-0.24	0.19	1000	-1000	-0.087	-1000
Endothelins	0.1343	36	3461	96	-0.51	0.15	1000	-1000	-0.058	-1000
IL23-mediated signaling events	0.1306	35	2144	60	-0.3	0.034	1000	-1000	-0.11	-1000
PLK1 signaling events	0.1269	34	2908	85	-0.051	0.26	1000	-1000	-0.047	-1000
Calcium signaling in the CD4+ TCR pathway	0.1269	34	1057	31	-0.42	0.002	1000	-1000	-0.05	-1000
Glypican 1 network	0.1231	33	1611	48	-0.36	0.041	1000	-1000	-0.036	-1000
ErbB2/ErbB3 signaling events	0.1194	32	2114	65	-0.36	0.068	1000	-1000	-0.054	-1000
LPA receptor mediated events	0.1194	32	3316	102	-0.39	0.032	1000	-1000	-0.073	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.1157	31	2673	85	-0.44	0.016	1000	-1000	-0.062	-1000
Thromboxane A2 receptor signaling	0.1119	30	3200	105	-0.15	0.081	1000	-1000	-0.055	-1000
Signaling events mediated by the Hedgehog family	0.1082	29	1535	52	-0.42	0.29	1000	-1000	-0.056	-1000
ErbB4 signaling events	0.1045	28	1966	69	-0.28	0.068	1000	-1000	-0.06	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1045	28	2519	88	-0.25	0.011	1000	-1000	-0.097	-1000
IL12-mediated signaling events	0.1007	27	2352	87	-0.62	0.016	1000	-1000	-0.095	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1007	27	1464	54	-0.32	0.037	1000	-1000	-0.071	-1000
Noncanonical Wnt signaling pathway	0.1007	27	714	26	-0.23	0.014	1000	-1000	-0.065	-1000
BCR signaling pathway	0.1007	27	2679	99	-0.44	0.012	1000	-1000	-0.081	-1000
amb2 Integrin signaling	0.0970	26	2203	82	-0.42	0.078	1000	-1000	-0.059	-1000
Syndecan-4-mediated signaling events	0.0970	26	1791	67	-0.36	0.17	1000	-1000	-0.068	-1000
Syndecan-1-mediated signaling events	0.0933	25	869	34	-0.44	0.078	1000	-1000	-0.058	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0933	25	3007	120	-0.61	0.17	1000	-1000	-0.056	-1000
S1P1 pathway	0.0896	24	878	36	-0.4	0.15	1000	-1000	-0.053	-1000
Signaling events mediated by PRL	0.0896	24	827	34	-0.34	0.05	1000	-1000	-0.05	-1000
Glucocorticoid receptor regulatory network	0.0858	23	2661	114	-0.78	0.2	1000	-1000	-0.062	-1000
Ras signaling in the CD4+ TCR pathway	0.0858	23	396	17	-0.2	0.002	1000	-1000	-0.046	-1000
Osteopontin-mediated events	0.0821	22	836	38	-0.39	0.057	1000	-1000	-0.07	-1000
Arf6 signaling events	0.0784	21	1333	62	-0.44	0.081	1000	-1000	-0.044	-1000
S1P5 pathway	0.0784	21	370	17	-0.39	0.15	1000	-1000	-0.042	-1000
Aurora C signaling	0.0746	20	140	7	0	0.16	1000	-1000	-0.024	-1000
BMP receptor signaling	0.0672	18	1531	81	-0.19	0.063	1000	-1000	-0.072	-1000
Fc-epsilon receptor I signaling in mast cells	0.0672	18	1759	97	-0.44	0.05	1000	-1000	-0.076	-1000
Integrins in angiogenesis	0.0672	18	1540	84	-0.38	0.084	1000	-1000	-0.084	-1000
TCR signaling in naïve CD8+ T cells	0.0672	18	1736	93	-0.28	0.12	1000	-1000	-0.065	-1000
Coregulation of Androgen receptor activity	0.0634	17	1308	76	-0.25	0.21	1000	-1000	-0.035	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0634	17	478	28	-0.39	0.15	1000	-1000	-0.039	-1000
p38 MAPK signaling pathway	0.0634	17	748	44	-0.43	0.009	1000	-1000	-0.048	-1000
Presenilin action in Notch and Wnt signaling	0.0597	16	979	61	-0.39	0.1	1000	-1000	-0.057	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0597	16	1230	74	-0.44	0.081	1000	-1000	-0.075	-1000
S1P4 pathway	0.0597	16	423	25	-0.39	0.15	1000	-1000	-0.043	-1000
PLK2 and PLK4 events	0.0560	15	47	3	0	0.055	1000	-1000	-0.018	-1000
S1P3 pathway	0.0560	15	630	42	-0.39	0.15	1000	-1000	-0.042	-1000
LPA4-mediated signaling events	0.0522	14	171	12	-0.21	0.018	1000	-1000	-0.01	-1000
Nectin adhesion pathway	0.0522	14	940	63	-0.1	0.007	1000	-1000	-0.055	-1000
IL27-mediated signaling events	0.0522	14	749	51	-0.22	0.14	1000	-1000	-0.058	-1000
Visual signal transduction: Rods	0.0522	14	753	52	-0.22	0.041	1000	-1000	-0.063	-1000
IL1-mediated signaling events	0.0485	13	806	62	-0.14	0.004	1000	-1000	-0.082	-1000
FAS signaling pathway (CD95)	0.0485	13	615	47	-0.44	0.027	1000	-1000	-0.042	-1000
Regulation of nuclear SMAD2/3 signaling	0.0448	12	1663	136	-0.47	0.4	1000	-1000	-0.056	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0448	12	451	37	-0.3	0.004	1000	-1000	-0.056	-1000
IL2 signaling events mediated by STAT5	0.0410	11	249	22	-0.066	0.17	1000	-1000	-0.047	-1000
Regulation of Telomerase	0.0410	11	1179	102	-0.47	0.2	1000	-1000	-0.074	-1000
Regulation of Androgen receptor activity	0.0410	11	835	70	-0.28	0.069	1000	-1000	-0.049	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0373	10	364	34	-0.05	0.019	1000	-1000	-0.048	-1000
FoxO family signaling	0.0373	10	684	64	-0.22	0.25	1000	-1000	-0.064	-1000
IL2 signaling events mediated by PI3K	0.0373	10	613	58	-0.072	0.13	1000	-1000	-0.066	-1000
Canonical Wnt signaling pathway	0.0373	10	546	51	-0.18	0.13	1000	-1000	-0.054	-1000
JNK signaling in the CD4+ TCR pathway	0.0336	9	169	17	-0.075	0.02	1000	-1000	-0.046	-1000
Signaling events mediated by PTP1B	0.0336	9	709	76	-0.17	0.13	1000	-1000	-0.067	-1000
Signaling events mediated by HDAC Class III	0.0336	9	368	40	-0.36	0.01	1000	-1000	-0.025	-1000
Syndecan-3-mediated signaling events	0.0336	9	315	35	-0.18	0.012	1000	-1000	-0.055	-1000
Class IB PI3K non-lipid kinase events	0.0336	9	27	3	-0.03	-1000	1000	-1000	-0.008	-1000
Syndecan-2-mediated signaling events	0.0299	8	566	69	-0.18	0.061	1000	-1000	-0.035	-1000
Aurora A signaling	0.0299	8	522	60	-0.019	0.2	1000	-1000	-0.038	-1000
Ceramide signaling pathway	0.0299	8	626	76	-0.38	0.081	1000	-1000	-0.044	-1000
HIF-2-alpha transcription factor network	0.0299	8	382	43	-0.24	0.076	1000	-1000	-0.067	-1000
Effects of Botulinum toxin	0.0299	8	229	26	-0.12	0.014	1000	-1000	-0.041	-1000
E-cadherin signaling events	0.0299	8	42	5	-0.046	0	1000	-1000	-0.021	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0261	7	407	52	-0.12	0.032	1000	-1000	-0.048	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0261	7	333	45	-0.085	0.029	1000	-1000	-0.073	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0261	7	246	33	-0.026	0.21	1000	-1000	-0.049	-1000
Hedgehog signaling events mediated by Gli proteins	0.0224	6	403	65	-0.39	0.15	1000	-1000	-0.064	-1000
Insulin-mediated glucose transport	0.0224	6	203	32	-0.036	0.18	1000	-1000	-0.047	-1000
Retinoic acid receptors-mediated signaling	0.0224	6	376	58	-0.16	0.042	1000	-1000	-0.052	-1000
E-cadherin signaling in the nascent adherens junction	0.0224	6	511	76	-0.049	0.023	1000	-1000	-0.071	-1000
E-cadherin signaling in keratinocytes	0.0224	6	282	43	-0.096	0.022	1000	-1000	-0.054	-1000
Caspase cascade in apoptosis	0.0187	5	421	74	-0.04	0.027	1000	-1000	-0.037	-1000
Cellular roles of Anthrax toxin	0.0187	5	211	39	-0.075	0.016	1000	-1000	-0.019	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0187	5	484	83	-0.13	0.18	1000	-1000	-0.066	-1000
Regulation of p38-alpha and p38-beta	0.0187	5	286	54	-0.17	0.034	1000	-1000	-0.055	-1000
TCGA08_rtk_signaling	0.0187	5	154	26	-0.33	0.022	1000	-1000	-0.024	-1000
EGFR-dependent Endothelin signaling events	0.0187	5	125	21	-0.015	0.081	1000	-1000	-0.039	-1000
Rapid glucocorticoid signaling	0.0187	5	108	20	-0.02	0.054	1000	-1000	-0.021	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0187	5	444	78	-0.31	0.025	1000	-1000	-0.1	-1000
Signaling events mediated by HDAC Class II	0.0149	4	373	75	-0.47	0.008	1000	-1000	-0.039	-1000
BARD1 signaling events	0.0149	4	235	57	-0.012	0.11	1000	-1000	-0.04	-1000
a4b1 and a4b7 Integrin signaling	0.0149	4	21	5	-0.02	-0.009	1000	-1000	-0.026	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0149	4	584	125	-0.061	0.049	1000	-1000	-0.091	-1000
Visual signal transduction: Cones	0.0112	3	140	38	-0.011	0.034	1000	-1000	-0.046	-1000
Arf6 downstream pathway	0.0112	3	135	43	-0.033	0.02	1000	-1000	-0.033	-1000
IFN-gamma pathway	0.0112	3	217	68	-0.43	0.063	1000	-1000	-0.07	-1000
Class I PI3K signaling events mediated by Akt	0.0112	3	263	68	-0.085	0.18	1000	-1000	-0.06	-1000
TRAIL signaling pathway	0.0112	3	191	48	-0.023	0.011	1000	-1000	-0.051	-1000
Signaling mediated by p38-gamma and p38-delta	0.0112	3	57	15	-0.017	0.056	1000	-1000	-0.037	-1000
Paxillin-dependent events mediated by a4b1	0.0112	3	116	36	-0.044	0.017	1000	-1000	-0.052	-1000
Class I PI3K signaling events	0.0112	3	248	73	-0.17	0.022	1000	-1000	-0.059	-1000
PDGFR-beta signaling pathway	0.0112	3	324	97	-0.13	0.05	1000	-1000	-0.081	-1000
mTOR signaling pathway	0.0075	2	123	53	-0.059	0.027	1000	-1000	-0.051	-1000
Atypical NF-kappaB pathway	0.0075	2	67	31	-0.026	0.017	1000	-1000	-0.059	-1000
Insulin Pathway	0.0075	2	154	74	-0.077	0.03	1000	-1000	-0.072	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0037	1	33	23	-0.043	0.033	1000	-1000	-0.037	-1000
Canonical NF-kappaB pathway	0.0037	1	51	39	-0.04	0.062	1000	-1000	-0.069	-1000
ceramide signaling pathway	0.0037	1	77	49	-0.045	0.035	1000	-1000	-0.034	-1000
Signaling events mediated by HDAC Class I	0.0037	1	173	104	-0.04	0.008	1000	-1000	-0.052	-1000
Arf6 trafficking events	0.0037	1	81	71	-0.051	0.028	1000	-1000	-0.07	-1000
VEGFR1 specific signals	0.0037	1	83	56	-0.043	0.049	1000	-1000	-0.068	-1000
Arf1 pathway	0.0037	1	60	54	-0.066	0.015	1000	-1000	-0.03	-1000
Circadian rhythm pathway	0.0000	0	14	22	-0.01	0.033	1000	-1000	-0.046	-1000
TCGA08_p53	0.0000	0	0	7	-0.054	0.026	1000	-1000	-0.008	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	1	27	0	0.001	1000	-1000	-0.044	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	0	0.001	1000	-1000	-0.029	-1000
Total	NA	2553	153835	7203	-32	-990	131000	-131000	-7.1	-131000

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.28	0.26	-10000	0	-0.52	144	144
ER alpha/Gai/GDP/Gbeta gamma	-0.48	0.46	-10000	0	-0.77	164	164
AKT1	-0.52	0.49	-10000	0	-0.97	144	144
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.53	0.5	-10000	0	-0.99	144	144
mol:Ca2+	-0.19	0.3	-10000	0	-0.76	52	52
IGF1R	-0.006	0.099	0.32	3	-0.88	3	6
E2/ER alpha (dimer)/Striatin	-0.34	0.31	-10000	0	-0.62	148	148
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	0.48	0.46	0.91	144	-10000	0	144
RhoA/GTP	-0.24	0.23	-10000	0	-0.46	143	143
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.43	0.37	-10000	0	-0.75	143	143
regulation of stress fiber formation	0.18	0.2	0.36	147	-10000	0	147
E2/ERA-ERB (dimer)	-0.32	0.3	-10000	0	-0.6	143	143
KRAS	0	0	-10000	0	-10000	0	0
G13/GTP	-0.3	0.28	-10000	0	-0.56	143	143
pseudopodium formation	-0.18	0.2	-10000	0	-0.36	147	147
E2/ER alpha (dimer)/PELP1	-0.32	0.3	-10000	0	-0.6	143	143
GRB2	0	0	-10000	0	-10000	0	0
GNG2	-0.003	0.054	-10000	0	-0.88	1	1
GNAO1	-0.39	0.44	-10000	0	-0.88	120	120
HRAS	0.002	0.027	0.32	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.41	0.4	-10000	0	-0.75	145	145
E2/ER beta (dimer)	0.002	0.018	-10000	0	-10000	0	0
mol:GDP	-0.32	0.3	-10000	0	-0.6	143	143
mol:NADP	-0.41	0.4	-10000	0	-0.75	145	145
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
mol:IP3	-0.22	0.32	-10000	0	-0.82	52	52
IGF-1R heterotetramer	-0.006	0.098	0.32	3	-0.88	3	6
PLCB1	-0.22	0.32	-10000	0	-0.86	49	49
PLCB2	-0.23	0.33	-10000	0	-0.86	52	52
IGF1	-0.38	0.44	-10000	0	-0.88	115	115
mol:L-citrulline	-0.41	0.4	-10000	0	-0.75	145	145
RHOA	0	0	-10000	0	-10000	0	0
Gai/GDP	-0.41	0.49	-10000	0	-0.94	120	120
JNK cascade	0.002	0.018	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0.002	0.027	0.32	2	-10000	0	2
GNAQ	-0.003	0.054	-10000	0	-0.88	1	1
ESR1	-0.47	0.44	-10000	0	-0.88	143	143
Gq family/GDP/Gbeta gamma	-0.087	0.17	-10000	0	-0.43	44	44
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.19	0.19	-10000	0	-0.37	143	143
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.43	0.37	-10000	0	-0.75	143	143
GNAZ	0.15	0.16	0.32	125	-10000	0	125
E2/ER alpha (dimer)	-0.37	0.34	-10000	0	-0.69	143	143
STRN	-0.026	0.15	-10000	0	-0.88	8	8
GNAL	0.054	0.12	0.32	46	-10000	0	46
PELP1	0	0	-10000	0	-10000	0	0
MAPK11	0.006	0.031	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.007	0.076	-10000	0	-0.88	2	2
HBEGF	-0.38	0.38	-10000	0	-0.7	137	137
cAMP biosynthetic process	-0.25	0.26	-10000	0	-0.49	143	143
SRC	-0.43	0.44	-10000	0	-0.77	143	143
PI3K	-0.005	0.075	-10000	0	-1.2	1	1
GNB1	0	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.28	0.26	-10000	0	-0.53	144	144
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.43	0.33	-10000	0	-0.66	163	163
Gs family/GTP	-0.25	0.27	-10000	0	-0.5	143	143
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.001	0.016	-10000	0	-10000	0	0
vasodilation	-0.38	0.37	-10000	0	-0.7	145	145
mol:DAG	-0.22	0.32	-10000	0	-0.82	52	52
Gs family/GDP/Gbeta gamma	-0.25	0.25	-10000	0	-0.48	144	144
MSN	-0.21	0.2	-10000	0	-0.56	8	8
Gq family/GTP	-0.24	0.35	-10000	0	-0.91	51	51
mol:PI-3-4-5-P3	-0.5	0.47	-10000	0	-0.93	144	144
NRAS	0	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.38	0.37	0.7	145	-10000	0	145
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.3	0.28	-10000	0	-0.56	143	143
NOS3	-0.44	0.44	-10000	0	-0.81	145	145
GNA11	-0.02	0.13	-10000	0	-0.88	6	6
MAPKKK cascade	-0.42	0.4	-10000	0	-0.77	148	148
E2/ER alpha (dimer)/PELP1/Src	-0.46	0.4	-10000	0	-0.8	143	143
ruffle organization	-0.18	0.2	-10000	0	-0.36	147	147
ROCK2	-0.24	0.22	-10000	0	-0.43	147	147
GNA14	-0.15	0.33	-10000	0	-0.88	47	47
GNA15	0.002	0.027	0.32	2	-10000	0	2
GNA13	0	0	-10000	0	-10000	0	0
MMP9	-0.4	0.4	-10000	0	-0.79	117	117
MMP2	-0.4	0.4	-10000	0	-0.71	145	145

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.1	0.079	-10000	0	-10000	0	0
Crk/p130 Cas/Paxillin	-0.26	0.21	-10000	0	-0.48	81	81
JUN	-0.28	0.28	-10000	0	-0.7	59	59
HRAS	0.002	0.027	0.32	2	-10000	0	2
RET51/GFRalpha1/GDNF/GRB10	-0.44	0.39	-10000	0	-0.69	171	171
RAP1A	0	0	-10000	0	-10000	0	0
FRS2	0	0	-10000	0	-10000	0	0
RAP1A/GDP	0	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.44	0.39	-10000	0	-0.69	171	171
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.17	0.26	-10000	0	-0.56	84	84
RHOA	0	0	-10000	0	-10000	0	0
RAP1A/GTP	-0.39	0.35	-10000	0	-0.62	171	171
GRB7	-0.004	0.1	0.32	5	-0.88	3	8
RET51/GFRalpha1/GDNF	-0.44	0.39	-10000	0	-0.69	171	171
MAPKKK cascade	-0.35	0.31	-10000	0	-0.56	166	166
BCAR1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.17	0.26	-10000	0	-0.56	84	84
lamellipodium assembly	-0.22	0.18	-10000	0	-0.43	84	84
RET51/GFRalpha1/GDNF/SHC	-0.44	0.39	-10000	0	-0.69	171	171
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
RET9/GFRalpha1/GDNF/SHC	-0.17	0.26	-10000	0	-0.56	84	84
RET9/GFRalpha1/GDNF/Shank3	-0.17	0.26	-10000	0	-0.56	84	84
MAPK3	-0.37	0.32	-10000	0	-0.58	171	171
DOK1	0	0	-10000	0	-10000	0	0
DOK6	-0.12	0.31	0.32	4	-0.88	37	41
PXN	0	0	-10000	0	-10000	0	0
neurite development	-0.36	0.31	-10000	0	-0.57	167	167
DOK5	0	0.11	0.32	8	-0.88	3	11
GFRA1	-0.28	0.41	-10000	0	-0.88	84	84
MAPK8	-0.3	0.28	-10000	0	-0.54	106	106
HRAS/GTP	-0.41	0.36	-10000	0	-0.65	171	171
tube development	-0.16	0.25	-10000	0	-0.52	84	84
MAPK1	-0.37	0.32	-10000	0	-0.58	171	171
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.11	0.17	-10000	0	-0.36	84	84
Rac1/GDP	0	0	-10000	0	-10000	0	0
SRC	0.001	0.019	0.32	1	-10000	0	1
PDLIM7	0.002	0.027	0.32	2	-10000	0	2
RET51/GFRalpha1/GDNF/Dok6	-0.48	0.43	-10000	0	-0.73	178	178
SHC1	0	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.44	0.39	-10000	0	-0.69	171	171
RET51/GFRalpha1/GDNF/Dok5	-0.44	0.39	-10000	0	-0.69	173	173
PRKCA	0	0	-10000	0	-10000	0	0
HRAS/GDP	0.002	0.018	0.21	2	-10000	0	2
CREB1	-0.22	0.24	-10000	0	-0.55	84	84
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.11	0.17	-10000	0	-0.36	84	84
RET51/GFRalpha1/GDNF/Grb7	-0.44	0.39	-10000	0	-0.69	173	173
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.44	0.44	0.32	2	-0.88	134	136
DOK4	0	0	-10000	0	-10000	0	0
JNK cascade	-0.26	0.28	-10000	0	-0.67	59	59
RET9/GFRalpha1/GDNF/FRS2	-0.17	0.26	-10000	0	-0.56	84	84
SHANK3	0.001	0.019	0.32	1	-10000	0	1
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.11	0.17	-10000	0	-0.36	84	84
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.29	0.26	-10000	0	-0.46	166	166
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.29	0.27	-10000	0	-0.47	166	166
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.34	0.36	-10000	0	-0.54	171	171
PI3K	-0.36	0.33	-10000	0	-0.74	84	84
SOS1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.16	0.25	-10000	0	-0.52	84	84
GRB10	0	0	-10000	0	-10000	0	0
activation of MAPKK activity	-0.23	0.22	-10000	0	-0.5	81	81
RET51/GFRalpha1/GDNF/FRS2	-0.44	0.39	-10000	0	-0.69	171	171
GAB1	0	0	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
IRS2	-0.016	0.12	-10000	0	-0.88	5	5
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.34	0.36	-10000	0	-0.54	171	171
RET51/GFRalpha1/GDNF/PKC alpha	-0.44	0.39	-10000	0	-0.69	171	171
GRB2	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
GDNF	0.013	0.063	0.32	11	-10000	0	11
RAC1	0	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.44	0.39	-10000	0	-0.69	171	171
Rac1/GTP	-0.27	0.23	-10000	0	-0.54	84	84
RET9/GFRalpha1/GDNF	-0.18	0.29	-10000	0	-0.61	84	84
GFRalpha1/GDNF	-0.21	0.32	-10000	0	-0.69	84	84

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.34	0.44	-9999	-0.91	100	100
PDGF/PDGFRA/CRKL	-0.26	0.34	-9999	-0.7	100	100
positive regulation of JUN kinase activity	-0.2	0.26	-9999	-0.54	100	100
CRKL	0	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.26	0.34	-9999	-0.7	100	100
AP1	-0.7	0.68	-9999	-1.2	157	157
mol:IP3	-0.27	0.35	-9999	-0.72	100	100
PLCG1	-0.27	0.35	-9999	-0.73	100	100
PDGF/PDGFRA/alphaV Integrin	-0.26	0.34	-9999	-0.7	100	100
RAPGEF1	0	0	-9999	-10000	0	0
CRK	0	0	-9999	-10000	0	0
mol:Ca2+	-0.27	0.35	-9999	-0.72	100	100
CAV3	0	0	-9999	-10000	0	0
CAV1	0	0	-9999	-10000	0	0
SHC/Grb2/SOS1	-0.2	0.26	-9999	-0.55	100	100
PDGF/PDGFRA/Shf	-0.3	0.37	-9999	-0.73	111	111
FOS	-0.67	0.68	-9999	-1.2	157	157
JUN	-0.047	0.1	-9999	-0.77	5	5
oligodendrocyte development	-0.26	0.33	-9999	-0.69	100	100
GRB2	0	0	-9999	-10000	0	0
PIK3R1	-0.003	0.054	-9999	-0.88	1	1
mol:DAG	-0.27	0.35	-9999	-0.72	100	100
PDGF/PDGFRA	-0.34	0.43	-9999	-0.91	100	100
actin cytoskeleton reorganization	-0.26	0.34	-9999	-0.69	101	101
SRF	0.023	0.02	-9999	-10000	0	0
SHC1	0	0	-9999	-10000	0	0
PI3K	-0.23	0.3	-9999	-0.61	100	100
PDGF/PDGFRA/Crk/C3G	-0.22	0.29	-9999	-0.6	100	100
JAK1	-0.25	0.34	-9999	-0.69	100	100
ELK1/SRF	-0.21	0.27	-9999	-0.56	100	100
SHB	-0.003	0.054	-9999	-0.88	1	1
SHF	-0.059	0.22	-9999	-0.88	18	18
CSNK2A1	0.031	0.026	-9999	-10000	0	0
GO:0007205	-0.28	0.36	-9999	-0.74	100	100
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.2	0.26	-9999	-0.54	100	100
PDGF/PDGFRA/SHB	-0.26	0.34	-9999	-0.7	101	101
PDGF/PDGFRA/Caveolin-1	-0.26	0.34	-9999	-0.7	100	100
ITGAV	0	0	-9999	-10000	0	0
ELK1	-0.26	0.33	-9999	-0.68	100	100
PIK3CA	-0.003	0.054	-9999	-0.88	1	1
PDGF/PDGFRA/Crk	-0.26	0.34	-9999	-0.7	100	100
JAK-STAT cascade	-0.25	0.34	-9999	-0.69	100	100
cell proliferation	-0.3	0.37	-9999	-0.73	111	111

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.4	0.5	1	65	-0.83	6	71
PLK1	0.28	0.23	0.59	61	-10000	0	61
BIRC5	0.29	0.22	0.59	62	-10000	0	62
HSPA1B	0.41	0.51	1	64	-0.9	3	67
MAP2K1	0.12	0.12	0.36	18	-10000	0	18
BRCA2	0.4	0.53	1	65	-1.1	8	73
FOXM1	0.46	0.6	1.2	75	-0.93	8	83
XRCC1	0.4	0.5	1	66	-0.81	7	73
FOXM1B/p19	0.23	0.46	0.7	106	-0.89	10	116
Cyclin D1/CDK4	0.25	0.5	0.89	54	-0.95	12	66
CDC2	0.43	0.55	1.1	74	-0.84	8	82
TGFA	0.2	0.64	0.94	56	-1	34	90
SKP2	0.4	0.5	1	65	-0.8	8	73
CCNE1	0.14	0.16	0.35	94	-10000	0	94
CKS1B	0.4	0.5	1	65	-0.8	8	73
RB1	0.15	0.31	0.65	66	-10000	0	66
FOXM1C/SP1	0.24	0.5	0.8	98	-0.91	9	107
AURKB	0.26	0.23	0.59	57	-10000	0	57
CENPF	0.46	0.55	1.1	75	-0.83	6	81
CDK4	0.044	0.045	-10000	0	-10000	0	0
MYC	0.27	0.53	0.9	62	-0.87	21	83
CHEK2	0.13	0.13	0.4	22	-10000	0	22
ONECUT1	0.3	0.52	0.95	60	-0.95	12	72
CDKN2A	0.087	0.18	0.31	54	-10000	0	54
LAMA4	0.41	0.51	1	66	-0.83	6	72
FOXM1B/HNF6	0.29	0.55	0.97	56	-1.1	12	68
FOS	-0.08	0.85	1	59	-1.1	84	143
SP1	-0.009	0.035	-10000	0	-0.28	1	1
CDC25B	0.4	0.5	1	65	-0.83	6	71
response to radiation	0.076	0.087	-10000	0	-10000	0	0
CENPB	0.4	0.5	1	65	-0.83	6	71
CENPA	0.46	0.55	1.1	75	-0.84	5	80
NEK2	0.48	0.54	1.1	77	-0.8	6	83
HIST1H2BA	0.4	0.5	1	65	-0.82	7	72
CCNA2	0.19	0.17	0.35	141	-10000	0	141
EP300	0	0	-10000	0	-10000	0	0
CCNB1/CDK1	0.42	0.55	1.1	65	-0.91	7	72
CCNB2	0.47	0.54	1.1	76	-0.84	5	81
CCNB1	0.45	0.56	1.2	70	-0.85	7	77
ETV5	0.4	0.5	1	65	-0.81	7	72
ESR1	-0.22	0.72	1.1	31	-1	78	109
CCND1	0.3	0.54	0.96	60	-0.98	12	72
GSK3A	0.085	0.084	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.25	0.21	0.48	103	-10000	0	103
CDK2	0.031	0.03	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.11	0.12	0.34	29	-10000	0	29
FOXM1B/Cbp/p300	-0.071	0.18	-10000	0	-0.81	9	9
GAS1	0.25	0.72	1	64	-1.1	39	103
MMP2	0.38	0.56	1	65	-1.1	12	77
RB1/FOXM1C	0.34	0.49	0.93	62	-0.87	11	73
CREBBP	0	0	-10000	0	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	-0.16	0.25	-10000	0	-0.56	75	75
regulation of S phase of mitotic cell cycle	-0.1	0.17	-10000	0	-0.37	75	75
GNAO1	-0.39	0.44	-10000	0	-0.88	120	120
HRAS	0.002	0.027	0.31	2	-10000	0	2
SHBG/T-DHT	-0.25	0.3	-10000	0	-0.61	109	109
PELP1	0	0	-10000	0	-10000	0	0
AKT1	0.008	0.003	-10000	0	-10000	0	0
MAP2K1	-0.14	0.23	-10000	0	-0.5	74	74
T-DHT/AR	-0.19	0.31	-10000	0	-0.7	74	74
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.003	0.003	-10000	0	-0.006	120	120
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.007	0.076	-10000	0	-0.88	2	2
mol:GDP	-0.19	0.3	-10000	0	-0.66	75	75
cell proliferation	-0.25	0.29	-10000	0	-0.52	110	110
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
FOS	-0.4	0.44	-10000	0	-0.89	120	120
mol:Ca2+	-0.049	0.057	-10000	0	-0.1	126	126
MAPK3	-0.21	0.26	-10000	0	-0.56	74	74
MAPK1	-0.11	0.13	-10000	0	-0.32	40	40
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
mol:IP3	-0.002	0.002	-10000	0	-0.004	120	120
cAMP biosynthetic process	-0.2	0.29	-10000	0	-0.56	109	109
GNG2	-0.003	0.054	-10000	0	-0.88	1	1
potassium channel inhibitor activity	-0.002	0.002	-10000	0	-0.004	120	120
HRAS/GTP	-0.15	0.23	-10000	0	-0.53	74	74
actin cytoskeleton reorganization	-0.004	0.058	-10000	0	-0.94	1	1
SRC	0.001	0.019	0.31	1	-10000	0	1
voltage-gated calcium channel activity	-0.002	0.002	-10000	0	-0.004	120	120
PI3K	-0.004	0.069	-10000	0	-1.1	1	1
apoptosis	0.23	0.26	0.49	121	-10000	0	121
T-DHT/AR/PELP1	-0.17	0.27	-10000	0	-0.61	74	74
HRAS/GDP	-0.18	0.28	-10000	0	-0.63	75	75
CREB1	-0.25	0.28	-10000	0	-0.53	120	120
RAC1-CDC42/GTP	-0.004	0.06	-10000	0	-0.98	1	1
AR	-0.24	0.39	-10000	0	-0.88	74	74
GNB1	0	0	-10000	0	-10000	0	0
RAF1	-0.16	0.22	-10000	0	-0.51	74	74
RAC1-CDC42/GDP	-0.17	0.27	-10000	0	-0.6	75	75
T-DHT/AR/PELP1/Src	-0.16	0.25	-10000	0	-0.56	74	74
MAP2K2	-0.14	0.23	-10000	0	-0.5	74	74
T-DHT/AR/PELP1/Src/PI3K	-0.1	0.17	-10000	0	-0.37	75	75
GNAZ	0.15	0.16	0.32	125	-10000	0	125
SHBG	-0.36	0.43	-10000	0	-0.88	109	109
Gi family/GNB1/GNG2/GDP	-0.23	0.29	-10000	0	-0.53	120	120
mol:T-DHT	-0.001	0.002	-10000	0	-0.003	79	79
RAC1	0	0	-10000	0	-10000	0	0
GNRH1	0.009	0.008	-10000	0	-10000	0	0
Gi family/GTP	-0.2	0.27	-10000	0	-0.48	104	104
CDC42	0	0	-10000	0	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.17	0.16	0.32	142	-9999	142
GPC2	0.048	0.11	0.32	41	-9999	41
GPC2/Midkine	0.15	0.14	0.44	25	-9999	25
neuron projection morphogenesis	0.15	0.14	0.44	25	-9999	25

×

IL4-mediated signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.44	0.58	-10000	0	-1.1	94	94
STAT6 (cleaved dimer)	-0.54	0.55	-10000	0	-1.1	121	121
IGHG1	-0.15	0.23	0.48	1	-0.41	60	61
IGHG3	-0.43	0.55	-10000	0	-0.98	117	117
AKT1	-0.21	0.35	0.58	1	-0.66	69	70
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.17	0.31	0.56	1	-0.59	57	58
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.2	0.32	0.55	1	-0.57	84	85
THY1	-0.41	0.6	-10000	0	-1.1	93	93
MYB	0.034	0.098	0.32	29	-10000	0	29
HMGA1	0.015	0.068	0.32	13	-10000	0	13
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.3	0.46	0.65	1	-0.81	95	96
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.2	0.33	0.55	1	-0.57	82	83
SP1	0.019	0.023	-10000	0	-10000	0	0
INPP5D	-0.003	0.054	-10000	0	-0.88	1	1
SOCS5	0.02	0.024	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.52	0.54	-10000	0	-1.1	116	116
SOCS1	-0.29	0.38	-10000	0	-0.73	89	89
SOCS3	-0.32	0.52	-10000	0	-1.2	56	56
FCER2	-0.42	0.58	-10000	0	-1.1	98	98
PARP14	-0.002	0.054	-10000	0	-0.88	1	1
CCL17	-0.43	0.59	-10000	0	-1.1	94	94
GRB2	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.16	0.27	-10000	0	-0.53	39	39
T cell proliferation	-0.45	0.6	-10000	0	-1.1	98	98
IL4R/JAK1	-0.44	0.58	-10000	0	-1.1	95	95
EGR2	-0.63	0.8	-10000	0	-1.5	109	109
JAK2	-0.007	0.069	-10000	0	-0.91	1	1
JAK3	0.006	0.061	0.34	2	-0.86	1	3
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
JAK1	0.009	0.019	-10000	0	-10000	0	0
COL1A2	-0.1	0.22	-10000	0	-1.7	1	1
CCL26	-0.43	0.59	-10000	0	-1.1	93	93
IL4R	-0.47	0.63	-10000	0	-1.2	95	95
PTPN6	0.016	0.013	-10000	0	-10000	0	0
IL13RA2	-0.99	0.76	-10000	0	-1.4	190	190
IL13RA1	-0.003	0.042	-10000	0	-10000	0	0
IRF4	-0.36	0.67	0.7	1	-1.6	59	60
ARG1	-0.38	0.65	-10000	0	-1.6	58	58
CBL	-0.28	0.43	0.57	1	-0.76	93	94
GTF3A	0.024	0.032	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
IL13RA1/JAK2	-0.004	0.076	-10000	0	-0.72	1	1
IRF4/BCL6	-0.36	0.59	-10000	0	-1.4	59	59
CD40LG	-0.023	0.18	0.39	2	-0.89	11	13
MAPK14	-0.3	0.47	0.58	1	-0.86	86	87
mitosis	-0.2	0.33	0.57	1	-0.63	68	69
STAT6	-0.51	0.71	-10000	0	-1.2	117	117
SPI1	-0.023	0.097	-10000	0	-0.6	4	4
RPS6KB1	-0.19	0.32	0.56	1	-0.63	58	59
STAT6 (dimer)	-0.51	0.71	-10000	0	-1.2	117	117
STAT6 (dimer)/PARP14	-0.48	0.62	-10000	0	-1.1	114	114
mast cell activation	0.008	0.018	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.21	0.35	0.58	1	-0.64	70	71
FRAP1	-0.22	0.35	0.58	1	-0.66	69	70
LTA	-0.43	0.58	-10000	0	-1.1	94	94
FES	-0.007	0.076	-10000	0	-0.88	2	2
T-helper 1 cell differentiation	0.49	0.67	1.1	117	-10000	0	117
CCL11	-0.42	0.56	-10000	0	-1.1	95	95
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.21	0.35	0.58	1	-0.63	70	71
IL2RG	0.001	0.12	0.32	6	-0.87	4	10
IL10	-0.51	0.67	-10000	0	-1.2	101	101
IRS1	0	0	-10000	0	-10000	0	0
IRS2	-0.016	0.12	-10000	0	-0.88	5	5
IL4	-0.083	0.17	-10000	0	-10000	0	0
IL5	-0.44	0.58	-10000	0	-1.1	95	95
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.33	0.46	-10000	0	-0.82	100	100
COL1A1	-0.11	0.29	-10000	0	-1.8	3	3
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.45	0.6	-10000	0	-1.2	91	91
IL2R gamma/JAK3	-0.005	0.11	0.52	1	-0.82	4	5
TFF3	-0.45	0.61	-10000	0	-1.1	96	96
ALOX15	-0.43	0.58	-10000	0	-1.1	93	93
MYBL1	0.005	0.038	0.32	4	-10000	0	4
T-helper 2 cell differentiation	-0.36	0.48	-10000	0	-0.85	113	113
SHC1	0	0	-10000	0	-10000	0	0
CEBPB	-0.016	0.059	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.2	0.32	0.53	1	-0.55	84	85
mol:PI-3-4-5-P3	-0.21	0.35	0.58	1	-0.66	69	70
PI3K	-0.23	0.37	0.58	1	-0.71	69	70
DOK2	-0.01	0.092	-10000	0	-0.88	3	3
ETS1	0.013	0.02	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.14	0.26	-10000	0	-0.52	31	31
ITGB3	-0.48	0.64	-10000	0	-1.2	96	96
PIGR	-0.61	0.72	-10000	0	-1.3	128	128
IGHE	0.021	0.056	-10000	0	-10000	0	0
MAPKKK cascade	-0.14	0.26	-10000	0	-0.51	31	31
BCL6	0	0.002	-10000	0	-10000	0	0
OPRM1	-0.44	0.58	-10000	0	-1.1	94	94
RETNLB	-0.44	0.58	-10000	0	-1.1	95	95
SELP	-0.67	0.8	-10000	0	-1.5	119	119
AICDA	-0.43	0.56	-10000	0	-1.1	95	95

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.4	0.61	-10000	0	-1.2	81	81
PCK1	-0.77	0.86	-10000	0	-1.6	126	126
HNF4A	-0.48	0.73	-10000	0	-1.4	91	91
KCNJ11	-0.4	0.64	-10000	0	-1.2	80	80
AKT1	-0.15	0.22	-10000	0	-0.43	62	62
response to starvation	-0.006	0.025	-10000	0	-10000	0	0
DLK1	-0.4	0.65	0.67	1	-1.2	80	81
NKX2-1	-0.11	0.23	-10000	0	-10000	0	0
ACADM	-0.42	0.64	-10000	0	-1.2	87	87
TAT	-0.75	0.87	-10000	0	-1.7	117	117
CEBPB	-0.006	0.023	-10000	0	-10000	0	0
CEBPA	-0.01	0.1	0.32	1	-0.91	3	4
TTR	-0.49	0.69	-10000	0	-1.5	83	83
PKLR	-0.46	0.68	-10000	0	-1.3	90	90
APOA1	-0.56	0.82	-10000	0	-1.5	93	93
CPT1C	-0.4	0.61	-10000	0	-1.2	85	85
ALAS1	-0.18	0.35	-10000	0	-1.7	7	7
TFRC	-0.33	0.5	-10000	0	-0.9	84	84
FOXF1	-0.076	0.25	-10000	0	-0.88	23	23
NF1	0.007	0.056	-10000	0	-0.88	1	1
HNF1A (dimer)	-0.013	0.13	-10000	0	-0.71	6	6
CPT1A	-0.41	0.62	-10000	0	-1.2	85	85
HMGCS1	-0.4	0.61	-10000	0	-1.2	86	86
NR3C1	-0.064	0.092	-10000	0	-0.29	3	3
CPT1B	-0.4	0.62	-10000	0	-1.2	81	81
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.01	0.055	-10000	0	-10000	0	0
GCK	-0.67	0.79	-10000	0	-1.4	135	135
CREB1	-0.048	0.084	-10000	0	-0.28	2	2
IGFBP1	-0.49	0.71	-10000	0	-1.6	75	75
PDX1	-0.21	0.48	-10000	0	-1.6	22	22
UCP2	-0.4	0.61	-10000	0	-1.2	81	81
ALDOB	-0.57	0.82	-10000	0	-1.6	97	97
AFP	-0.12	0.36	-10000	0	-0.78	43	43
BDH1	-0.43	0.67	-10000	0	-1.2	88	88
HADH	-0.4	0.63	-10000	0	-1.2	82	82
F2	-0.48	0.73	-10000	0	-1.4	85	85
HNF1A	-0.013	0.13	-10000	0	-0.72	6	6
G6PC	-0.33	0.62	-10000	0	-1.6	51	51
SLC2A2	-0.35	0.66	-10000	0	-1.7	41	41
INS	0.037	0.085	0.32	7	-10000	0	7
FOXA1	-0.02	0.18	-10000	0	-0.75	10	10
FOXA3	-0.18	0.3	-10000	0	-0.63	55	55
FOXA2	-0.48	0.78	0.72	1	-1.3	96	97
ABCC8	-0.39	0.63	-10000	0	-1.2	79	79
ALB	-0.26	0.55	-10000	0	-1.4	48	48

×

IGF1 pathway

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
NCK2	0.001	0.019	0.32	1	-10000	0	1
PTK2	0	0	-10000	0	-10000	0	0
CRKL	-0.21	0.25	-10000	0	-0.49	116	116
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0.002	0.027	0.32	2	-10000	0	2
IRS1/Crk	-0.21	0.25	-10000	0	-0.5	116	116
IGF-1R heterotetramer/IGF1/PTP1B	-0.25	0.29	-10000	0	-0.57	116	116
AKT1	-0.18	0.22	-10000	0	-0.42	114	114
BAD	-0.14	0.22	-10000	0	-0.82	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.21	0.25	-10000	0	-0.49	116	116
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.22	0.25	-10000	0	-0.5	116	116
RAF1	-0.13	0.21	-10000	0	-0.75	3	3
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.2	0.24	-10000	0	-0.47	116	116
YWHAZ	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.23	0.27	-10000	0	-0.54	116	116
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
RPS6KB1	-0.18	0.22	-10000	0	-0.42	114	114
GNB2L1	0	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.12	0.18	-10000	0	-0.6	3	3
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.18	0.21	-10000	0	-0.42	116	116
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.2	0.24	-10000	0	-0.46	116	116
IGF-1R heterotetramer	-0.048	0.11	0.33	1	-0.96	3	4
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.21	0.25	-10000	0	-0.5	116	116
Crk/p130 Cas/Paxillin	-0.19	0.22	-10000	0	-0.44	116	116
IGF1R	-0.048	0.11	0.33	1	-0.96	3	4
IGF1	-0.38	0.44	-10000	0	-0.89	115	115
IRS2/Crk	-0.21	0.24	-10000	0	-0.48	119	119
PI3K	-0.2	0.25	-10000	0	-0.48	116	116
apoptosis	0.14	0.17	0.66	3	-10000	0	3
HRAS/GDP	0.002	0.018	0.21	2	-10000	0	2
PRKCD	-0.24	0.28	-10000	0	-0.55	116	116
RAF1/14-3-3 E	-0.14	0.16	-10000	0	-0.6	3	3
BAD/14-3-3	-0.15	0.18	-10000	0	-0.72	3	3
PRKCZ	-0.2	0.24	-10000	0	-0.45	118	118
Crk/p130 Cas/Paxillin/FAK1	-0.15	0.18	-10000	0	-0.75	3	3
PTPN1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.25	0.3	-10000	0	-0.59	116	116
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.22	0.26	-10000	0	-0.51	116	116
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.21	0.25	-10000	0	-0.49	116	116
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	-0.21	0.25	-10000	0	-0.49	116	116
IRS1	-0.23	0.27	-10000	0	-0.54	116	116
IRS2	-0.22	0.26	-10000	0	-0.5	119	119
IGF-1R heterotetramer/IGF1	-0.31	0.36	-10000	0	-0.71	116	116
GRB2	0	0	-10000	0	-10000	0	0
PDPK1	-0.19	0.23	-10000	0	-0.45	116	116
YWHAE	0	0	-10000	0	-10000	0	0
PRKD1	-0.24	0.28	-10000	0	-0.56	116	116
SHC1	0	0	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.008	0.15	0.32	14	-0.88	5	19
NFATC2	-0.16	0.37	0.56	1	-0.82	58	59
NFATC3	-0.05	0.11	-10000	0	-10000	0	0
CD40LG	-0.54	0.58	0.64	1	-1.2	109	110
ITCH	-0.005	0.04	-10000	0	-10000	0	0
CBLB	-0.005	0.04	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.32	0.5	0.6	6	-1.1	54	60
JUNB	-0.033	0.17	-10000	0	-0.88	10	10
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.007	0.048	-10000	0	-0.36	5	5
T cell anergy	-0.001	0.092	-10000	0	-0.5	5	5
TLE4	-0.099	0.3	-10000	0	-0.68	47	47
Jun/NFAT1-c-4/p21SNFT	-0.37	0.55	0.55	1	-1.1	81	82
AP-1/NFAT1-c-4	-0.71	0.84	0.67	4	-1.6	107	111
IKZF1	-0.11	0.34	0.54	1	-0.74	49	50
T-helper 2 cell differentiation	-0.24	0.4	0.48	1	-0.84	68	69
AP-1/NFAT1	-0.39	0.44	0.48	1	-0.76	141	142
CALM1	-0.004	0.026	-10000	0	-10000	0	0
EGR2	-0.49	0.84	-10000	0	-1.7	78	78
EGR3	-0.37	0.73	-10000	0	-1.6	56	56
NFAT1/FOXP3	-0.12	0.32	0.42	7	-0.67	55	62
EGR1	-0.28	0.41	-10000	0	-0.88	86	86
JUN	-0.017	0.12	-10000	0	-0.88	5	5
EGR4	0.002	0.028	0.31	2	-10000	0	2
mol:Ca2+	-0.004	0.029	-10000	0	-10000	0	0
GBP3	-0.14	0.37	-10000	0	-0.77	59	59
FOSL1	-0.029	0.17	0.32	3	-0.88	10	13
NFAT1-c-4/MAF/IRF4	-0.43	0.6	0.57	2	-1.2	92	94
DGKA	-0.092	0.29	0.54	1	-0.62	54	55
CREM	0	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.36	0.54	-10000	0	-1.1	84	84
CTLA4	-0.071	0.32	0.47	4	-0.66	47	51
NFAT1-c-4 (dimer)/EGR1	-0.52	0.66	-10000	0	-1.3	92	92
NFAT1-c-4 (dimer)/EGR4	-0.36	0.54	-10000	0	-1.1	85	85
FOS	-0.4	0.44	-10000	0	-0.89	120	120
IFNG	-0.2	0.34	0.49	1	-0.85	42	43
T cell activation	-0.31	0.44	-10000	0	-0.93	77	77
MAF	-0.003	0.054	-10000	0	-0.88	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.21	0.41	0.8	72	-10000	0	72
TNF	-0.43	0.55	-10000	0	-1.2	88	88
FASLG	-0.46	0.78	-10000	0	-1.5	85	85
TBX21	-0.015	0.15	-10000	0	-0.88	8	8
BATF3	-0.005	0.078	0.32	1	-0.88	2	3
PRKCQ	-0.022	0.15	0.32	2	-0.88	8	10
PTPN1	-0.094	0.29	-10000	0	-0.66	46	46
NFAT1-c-4/ICER1	-0.36	0.54	-10000	0	-1.1	84	84
GATA3	-0.064	0.23	0.32	1	-0.88	20	21
T-helper 1 cell differentiation	-0.19	0.33	0.45	3	-0.83	42	45
IL2RA	-0.31	0.45	0.58	6	-1	56	62
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.097	0.29	-10000	0	-0.67	47	47
E2F1	0.2	0.15	0.32	161	-10000	0	161
PPARG	0.001	0.019	0.32	1	-10000	0	1
SLC3A2	-0.094	0.29	-10000	0	-0.62	54	54
IRF4	-0.17	0.36	0.32	7	-0.88	54	61
PTGS2	-0.62	0.67	-10000	0	-1.3	110	110
CSF2	-0.51	0.59	-10000	0	-1.2	106	106
JunB/Fra1/NFAT1-c-4	-0.37	0.55	0.55	1	-1.1	84	85
IL4	-0.26	0.42	0.48	1	-0.9	67	68
IL5	-0.5	0.6	-10000	0	-1.2	106	106
IL2	-0.32	0.45	-10000	0	-0.97	75	75
IL3	-0.079	0.066	-10000	0	-10000	0	0
RNF128	-0.017	0.13	-10000	0	-0.94	5	5
NFATC1	-0.22	0.41	-10000	0	-0.8	72	72
CDK4	0.2	0.28	0.63	53	-10000	0	53
PTPRK	-0.094	0.29	-10000	0	-0.63	53	53
IL8	-0.6	0.63	0.58	1	-1.2	123	124
POU2F1	0.002	0.005	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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
PKM2	-0.26	0.49	-10000	0	-1	57	57
HDAC7	0.001	0.019	0.32	1	-10000	0	1
HIF1A/ARNT/Cbp/p300/Src-1	-0.37	0.42	0.65	3	-0.88	84	87
SMAD4	-0.003	0.053	-10000	0	-0.88	1	1
ID2	-0.28	0.49	-10000	0	-1	60	60
AP1	-0.32	0.36	-10000	0	-0.71	120	120
ABCG2	-0.34	0.54	-10000	0	-1.1	70	70
HIF1A	-0.03	0.061	-10000	0	-10000	0	0
TFF3	-0.27	0.5	-10000	0	-1	60	60
GATA2	-0.004	0.081	0.32	2	-0.88	2	4
AKT1	-0.047	0.11	-10000	0	-10000	0	0
response to hypoxia	-0.062	0.12	-10000	0	-0.22	58	58
MCL1	-0.27	0.48	-10000	0	-1	58	58
NDRG1	-0.27	0.49	-10000	0	-1	57	57
SERPINE1	-0.4	0.58	-10000	0	-1.1	91	91
FECH	-0.27	0.48	-10000	0	-1	57	57
FURIN	-0.28	0.5	-10000	0	-1	59	59
NCOA2	-0.097	0.27	-10000	0	-0.88	29	29
EP300	-0.092	0.2	-10000	0	-0.34	82	82
HMOX1	-0.29	0.5	-10000	0	-1.1	60	60
BHLHE40	-0.28	0.49	-10000	0	-1	59	59
BHLHE41	-0.27	0.5	0.78	1	-1	60	61
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.03	0.062	-10000	0	-0.45	1	1
ENG	-0.025	0.055	-10000	0	-10000	0	0
JUN	-0.016	0.12	-10000	0	-0.88	5	5
RORA	-0.28	0.49	-10000	0	-1	59	59
ABCB1	-0.24	0.48	-10000	0	-1.4	37	37
TFRC	-0.27	0.48	-10000	0	-1	58	58
CXCR4	-0.28	0.49	-10000	0	-1	59	59
TF	-0.31	0.53	-10000	0	-1.1	67	67
CITED2	-0.28	0.49	-10000	0	-1	59	59
HIF1A/ARNT	-0.35	0.54	0.85	2	-1.2	59	61
LDHA	-0.06	0.055	-10000	0	-10000	0	0
ETS1	-0.27	0.48	-10000	0	-1	58	58
PGK1	-0.27	0.48	-10000	0	-1	59	59
NOS2	-0.26	0.5	0.78	1	-1	59	60
ITGB2	-0.27	0.49	-10000	0	-1	58	58
ALDOA	-0.27	0.48	-10000	0	-1	59	59
Cbp/p300/CITED2	-0.43	0.53	-10000	0	-1.1	80	80
FOS	-0.39	0.44	-10000	0	-0.88	120	120
HK2	-0.27	0.5	-10000	0	-1.1	56	56
SP1	0.006	0.03	-10000	0	-10000	0	0
GCK	-0.58	0.81	-10000	0	-1.5	113	113
HK1	-0.27	0.48	-10000	0	-1	58	58
NPM1	-0.27	0.48	-10000	0	-1	57	57
EGLN1	-0.27	0.48	-10000	0	-1	59	59
CREB1	0.013	0	-10000	0	-10000	0	0
PGM1	-0.28	0.49	-10000	0	-1	59	59
SMAD3	0	0	-10000	0	-10000	0	0
EDN1	-0.25	0.33	-10000	0	-0.74	52	52
IGFBP1	-0.39	0.57	-10000	0	-1.1	81	81
VEGFA	-0.29	0.36	-10000	0	-0.79	58	58
HIF1A/JAB1	-0.018	0.038	-10000	0	-10000	0	0
CP	-0.33	0.57	-10000	0	-1.2	66	66
CXCL12	-0.47	0.58	-10000	0	-1.1	105	105
COPS5	-0.001	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.003	0.041	-10000	0	-0.68	1	1
BNIP3	-0.27	0.48	-10000	0	-1	58	58
EGLN3	-0.27	0.51	0.8	1	-1.1	57	58
CA9	-0.38	0.58	0.8	1	-1	94	95
TERT	-0.23	0.52	0.8	1	-1	58	59
ENO1	-0.27	0.48	-10000	0	-1	59	59
PFKL	-0.27	0.48	-10000	0	-1	59	59
NCOA1	-0.001	0.006	-10000	0	-10000	0	0
ADM	-0.27	0.48	-10000	0	-1	59	59
ARNT	-0.028	0.059	-10000	0	-10000	0	0
HNF4A	-0.045	0.14	-10000	0	-0.91	6	6
ADFP	-0.27	0.49	-10000	0	-1	60	60
SLC2A1	-0.29	0.37	0.68	1	-0.77	66	67
LEP	-0.27	0.5	0.78	1	-1	59	60
HIF1A/ARNT/Cbp/p300	-0.37	0.43	0.68	2	-0.91	81	83
EPO	-0.54	0.61	-10000	0	-1.2	114	114
CREBBP	-0.092	0.2	-10000	0	-0.34	74	74
HIF1A/ARNT/Cbp/p300/HDAC7	-0.35	0.41	0.7	2	-0.9	72	74
PFKFB3	-0.28	0.49	-10000	0	-1	58	58
NT5E	-0.28	0.51	-10000	0	-1.1	59	59

×

EPO signaling pathway

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
BCL2L1	-0.11	0.24	-10000	0	-10000	0	0
CRKL	-0.16	0.22	-10000	0	-0.45	97	97
mol:DAG	-0.17	0.24	-10000	0	-0.49	96	96
HRAS	-0.13	0.18	-10000	0	-10000	0	0
MAPK8	-0.2	0.27	-10000	0	-0.53	104	104
RAP1A	-0.16	0.22	-10000	0	-0.45	97	97
GAB1	-0.16	0.22	-10000	0	-0.45	97	97
MAPK14	-0.18	0.25	-10000	0	-0.51	96	96
EPO	-0.3	0.43	0.32	8	-0.88	96	104
PLCG1	-0.18	0.25	-10000	0	-0.5	96	96
EPOR/TRPC2/IP3 Receptors	-0.012	0.017	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.27	0.34	-10000	0	-0.64	114	114
GAB1/SHC/GRB2/SOS1	-0.14	0.18	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.24	0.33	-10000	0	-0.68	96	96
IRS2	-0.17	0.23	-10000	0	-0.46	99	99
STAT1	-0.18	0.25	-10000	0	-0.5	96	96
STAT5B	-0.18	0.24	-10000	0	-0.5	96	96
cell proliferation	-0.17	0.26	-10000	0	-0.5	104	104
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.14	0.18	-10000	0	-0.76	1	1
TEC	-0.17	0.23	-10000	0	-0.46	101	101
SOCS3	-0.1	0.28	-10000	0	-0.88	31	31
STAT1 (dimer)	-0.16	0.24	-10000	0	-0.49	96	96
JAK2	-0.015	0.055	-10000	0	-0.88	1	1
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
EPO/EPOR (dimer)/JAK2	-0.14	0.25	-10000	0	-0.48	97	97
EPO/EPOR	-0.24	0.33	-10000	0	-0.68	96	96
LYN	0	0	-10000	0	-10000	0	0
TEC/VAV2	-0.16	0.22	-10000	0	-0.44	101	101
elevation of cytosolic calcium ion concentration	-0.012	0.017	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.2	0.28	-10000	0	-0.57	96	96
mol:IP3	-0.17	0.24	-10000	0	-0.49	96	96
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.16	0.21	-10000	0	-0.96	3	3
SH2B3	-0.012	0.017	-10000	0	-10000	0	0
NFKB1	-0.18	0.25	-10000	0	-0.51	96	96
EPO/EPOR (dimer)/JAK2/SOCS3	-0.17	0.22	-10000	0	-0.41	114	114
PTPN6	-0.17	0.23	-10000	0	-0.47	97	97
TEC/VAV2/GRB2	-0.16	0.21	-10000	0	-0.59	6	6
EPOR	-0.012	0.017	-10000	0	-10000	0	0
INPP5D	-0.003	0.054	-10000	0	-0.88	1	1
mol:GDP	-0.14	0.19	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	-0.016	0.12	-10000	0	-0.88	5	5
CRKL/CBL/C3G	-0.15	0.2	-10000	0	-10000	0	0
VAV2	-0.16	0.22	-10000	0	-0.45	97	97
CBL	-0.16	0.22	-10000	0	-0.45	97	97
SHC/Grb2/SOS1	-0.15	0.2	-10000	0	-10000	0	0
STAT5A	-0.18	0.24	-10000	0	-0.5	96	96
GRB2	0	0	-10000	0	-10000	0	0
STAT5 (dimer)	-0.16	0.22	-10000	0	-10000	0	0
LYN/PLCgamma2	-0.013	0.093	-10000	0	-0.68	5	5
PTPN11	0	0	-10000	0	-10000	0	0
BTK	-0.17	0.23	-10000	0	-0.46	99	99
BCL2	-0.11	0.24	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.025	0.07	0.32	14	-10000	0	14
CDKN2C	0.03	0.085	0.31	22	-10000	0	22
CDKN2A	0.21	0.15	0.31	176	-10000	0	176
CCND2	-0.067	0.059	-10000	0	-0.17	40	40
RB1	0.075	0.065	0.19	42	-10000	0	42
CDK4	-0.072	0.059	-10000	0	-0.18	31	31
CDK6	-0.082	0.079	-10000	0	-0.22	43	43
G1/S progression	-0.075	0.065	-10000	0	-0.19	42	42

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.007	0.062	-10000	0	-0.68	1	1
Necdin/E2F1	0.12	0.15	0.44	6	-0.66	4	10
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.23	0.32	-10000	0	-0.59	107	107
NGF (dimer)/p75(NTR)/BEX1	-0.42	0.44	-10000	0	-0.76	153	153
NT-4/5 (dimer)/p75(NTR)	-0.26	0.34	-10000	0	-0.69	102	102
IKBKB	0	0	-10000	0	-10000	0	0
AKT1	-0.22	0.29	-10000	0	-0.55	105	105
IKBKG	0	0	-10000	0	-10000	0	0
BDNF	0.012	0.06	0.32	10	-10000	0	10
MGDIs/NGR/p75(NTR)/LINGO1	-0.2	0.32	-10000	0	-0.6	102	102
FURIN	-0.013	0.11	-10000	0	-0.88	4	4
proBDNF (dimer)/p75(NTR)/Sortilin	-0.22	0.3	0.39	2	-0.6	102	104
LINGO1	0.05	0.12	0.32	42	-10000	0	42
Sortilin/TRAF6/NRIF	-0.002	0.028	-10000	0	-10000	0	0
proBDNF (dimer)	0.012	0.06	0.32	10	-10000	0	10
NTRK1	0.002	0.027	0.32	2	-10000	0	2
RTN4R	-0.007	0.076	-10000	0	-0.88	2	2
neuron apoptosis	-0.12	0.28	-10000	0	-0.54	35	35
IRAK1	0.001	0.019	0.32	1	-10000	0	1
SHC1	-0.25	0.32	-10000	0	-0.64	105	105
ARHGDIA	0	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.23	0.31	-10000	0	-0.6	105	105
MAGEH1	-0.007	0.076	-10000	0	-0.88	2	2
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.23	0.32	0.38	1	-0.6	105	106
Mammalian IAPs/DIABLO	0.005	0.049	-10000	0	-0.55	1	1
proNGF (dimer)	-0.035	0.18	0.32	1	-0.88	11	12
MAGED1	-0.003	0.054	-10000	0	-0.88	1	1
APP	-0.01	0.092	-10000	0	-0.88	3	3
NT-4/5 (dimer)	0.004	0.033	0.32	3	-10000	0	3
ZNF274	0	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.22	0.28	-10000	0	-0.55	105	105
NGF	-0.035	0.18	0.32	1	-0.88	11	12
cell cycle arrest	-0.17	0.31	-10000	0	-0.53	105	105
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.15	0.2	-10000	0	-0.39	104	104
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.23	0.3	-10000	0	-0.6	103	103
NCSTN	0	0	-10000	0	-10000	0	0
mol:GTP	-0.25	0.32	-10000	0	-0.63	106	106
PSENEN	0	0	-10000	0	-10000	0	0
mol:ceramide	-0.22	0.3	-10000	0	-0.58	105	105
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.14	0.19	-10000	0	-0.68	15	15
p75(NTR)/beta APP	-0.27	0.34	-10000	0	-0.7	103	103
BEX1	-0.26	0.44	0.32	20	-0.88	88	108
mol:GDP	-0.25	0.32	-10000	0	-0.64	105	105
NGF (dimer)	-0.24	0.33	-10000	0	-0.6	110	110
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.19	0.3	-10000	0	-0.55	102	102
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
RAC1/GTP	-0.22	0.29	-10000	0	-0.56	105	105
MYD88	0	0	-10000	0	-10000	0	0
CHUK	0	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.25	0.32	-10000	0	-0.64	106	106
RHOB	-0.049	0.2	-10000	0	-0.88	15	15
RHOA	0	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.13	0.11	-10000	0	-10000	0	0
NT3 (dimer)	-0.46	0.44	-10000	0	-0.88	141	141
TP53	-0.18	0.24	-10000	0	-0.48	103	103
PRDM4	-0.22	0.3	-10000	0	-0.58	105	105
BDNF (dimer)	-0.2	0.31	0.42	4	-0.56	104	108
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
SORT1	0.014	0.065	0.32	12	-10000	0	12
activation of caspase activity	-0.22	0.31	-10000	0	-0.58	107	107
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.22	0.31	-10000	0	-0.59	105	105
RHOC	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.16	0.28	-10000	0	-0.5	103	103
DIABLO	0	0	-10000	0	-10000	0	0
SMPD2	-0.22	0.3	-10000	0	-0.58	105	105
APH1B	0	0	-10000	0	-10000	0	0
APH1A	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.24	0.33	-10000	0	-0.64	105	105
PSEN1	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.58	0.52	-10000	0	-0.96	162	162
MAPK8	-0.16	0.27	-10000	0	-0.48	105	105
MAPK9	-0.15	0.26	-10000	0	-0.47	105	105
APAF1	0	0	-10000	0	-10000	0	0
NTF3	-0.46	0.44	-10000	0	-0.88	141	141
NTF4	0.004	0.033	0.32	3	-10000	0	3
NDN	-0.005	0.12	0.32	7	-0.88	4	11
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.23	0.3	-10000	0	-0.56	110	110
p75 CTF/Sortilin/TRAF6/NRIF	0.007	0.053	-10000	0	-0.55	1	1
RhoA-B-C/GTP	-0.25	0.32	-10000	0	-0.63	106	106
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.19	0.26	0.36	2	-0.51	103	105
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.2	0.28	0.38	2	-0.55	103	105
PRKACB	-0.003	0.054	-10000	0	-0.88	1	1
proBDNF (dimer)/p75 ECD	0.008	0.041	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.007	0.079	0.32	9	-0.88	1	10
BIRC2	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.16	0.32	0.28	1	-0.53	105	106
BAD	-0.15	0.27	-10000	0	-0.48	104	104
RIPK2	0	0	-10000	0	-10000	0	0
NGFR	-0.33	0.43	-10000	0	-0.88	102	102
CYCS	-0.21	0.28	-10000	0	-0.55	106	106
ADAM17	0	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.23	0.3	-10000	0	-0.59	105	105
BCL2L11	-0.15	0.27	-10000	0	-0.48	104	104
BDNF (dimer)/p75(NTR)	-0.25	0.34	-10000	0	-0.68	102	102
PI3K	-0.23	0.31	-10000	0	-0.59	105	105
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.22	0.3	-10000	0	-0.58	105	105
NDNL2	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.28	0.37	-10000	0	-0.73	105	105
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.22	0.31	-10000	0	-0.58	106	106
TRAF6	-0.003	0.054	-10000	0	-0.88	1	1
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.036	0.17	-10000	0	-0.88	11	11
PLG	-0.16	0.34	-10000	0	-0.88	48	48
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.22	0.3	-10000	0	-0.58	105	105
SQSTM1	0.004	0.033	0.32	3	-10000	0	3
NGFRAP1	-0.033	0.17	-10000	0	-0.88	10	10
CASP3	-0.14	0.25	-10000	0	-0.44	104	104
E2F1	0.19	0.16	0.32	161	-10000	0	161
CASP9	0	0	-10000	0	-10000	0	0
IKK complex	-0.12	0.18	-10000	0	-0.69	17	17
NGF (dimer)/TRKA	-0.026	0.14	-10000	0	-0.69	11	11
MMP7	-0.17	0.39	0.32	26	-0.88	60	86
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.21	0.29	-10000	0	-0.56	105	105
MMP3	0.02	0.077	0.32	17	-10000	0	17
APAF-1/Caspase 9	-0.16	0.2	-10000	0	-0.72	8	8

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.001	0.013	-10000	0	-10000	0	0
VLDLR	-0.025	0.26	0.32	32	-0.88	19	51
CRKL	0	0	-10000	0	-10000	0	0
LRPAP1	0	0	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
ITGA3	0.028	0.09	0.32	24	-10000	0	24
RELN/VLDLR/Fyn	-0.22	0.35	-10000	0	-0.65	100	100
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.024	0.11	-10000	0	-0.51	13	13
AKT1	-0.19	0.24	-10000	0	-0.44	89	89
MAP2K7	0	0	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
DAB1	-0.14	0.33	-10000	0	-0.88	44	44
RELN/LRP8/DAB1	-0.27	0.33	-10000	0	-0.6	124	124
LRPAP1/LRP8	0.025	0.07	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.25	0.31	-10000	0	-0.56	124	124
DAB1/alpha3/beta1 Integrin	-0.25	0.32	0.36	3	-0.56	118	121
long-term memory	-0.23	0.3	-10000	0	-0.53	124	124
DAB1/LIS1	-0.26	0.34	-10000	0	-0.57	131	131
DAB1/CRLK/C3G	-0.26	0.32	-10000	0	-0.55	131	131
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
DAB1/NCK2	-0.26	0.34	-10000	0	-0.57	130	130
ARHGEF2	0.001	0.019	0.32	1	-10000	0	1
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.051	0.12	0.32	43	-10000	0	43
CDK5R1	0.001	0.019	0.32	1	-10000	0	1
RELN	-0.3	0.42	0.32	2	-0.88	92	94
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
RELN/LRP8/Fyn	-0.19	0.3	-10000	0	-0.59	92	92
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.24	0.32	0.36	4	-0.55	124	128
MAPK8	-0.036	0.17	-10000	0	-0.88	11	11
RELN/VLDLR/DAB1	-0.3	0.37	-10000	0	-0.64	131	131
ITGB1	0	0	-10000	0	-10000	0	0
MAP1B	-0.28	0.33	-10000	0	-0.59	131	131
RELN/LRP8	-0.19	0.3	-10000	0	-0.59	92	92
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.25	0.31	-10000	0	-0.56	124	124
PI3K	-0.005	0.075	-10000	0	-1.2	1	1
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.02	0.062	-10000	0	-10000	0	0
RAP1A	-0.25	0.28	-10000	0	-0.53	107	107
PAFAH1B1	0	0	-10000	0	-10000	0	0
MAPK8IP1	-0.007	0.076	-10000	0	-0.88	2	2
CRLK/C3G	0	0	-10000	0	-10000	0	0
GRIN2B	0	0	-10000	0	-10000	0	0
NCK2	0.001	0.019	0.32	1	-10000	0	1
neuron differentiation	-0.13	0.17	-10000	0	-0.4	42	42
neuron adhesion	-0.22	0.27	-10000	0	-0.81	23	23
LRP8	0.037	0.1	0.32	31	-10000	0	31
GSK3B	-0.18	0.22	-10000	0	-0.67	24	24
RELN/VLDLR/DAB1/Fyn	-0.28	0.35	-10000	0	-0.61	131	131
MAP3K11	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.2	0.25	-10000	0	-0.44	122	122
CDK5	0	0	-10000	0	-10000	0	0
MAPT	0.061	0.058	-10000	0	-10000	0	0
neuron migration	-0.19	0.28	-10000	0	-0.47	128	128
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.13	0.17	-10000	0	-0.4	42	42
RELN/VLDLR	-0.19	0.34	0.37	7	-0.6	100	107

×

IL6-mediated signaling events

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
BCL2L1	-0.31	0.38	-10000	0	-0.75	91	91
CRP	-0.51	0.56	-10000	0	-1.1	124	124
cell cycle arrest	-0.38	0.46	-10000	0	-0.91	96	96
TIMP1	-0.27	0.34	-10000	0	-0.66	92	92
IL6ST	-0.19	0.37	-10000	0	-0.89	58	58
Rac1/GDP	-0.22	0.27	-10000	0	-0.58	76	76
AP1	-0.21	0.27	-10000	0	-0.51	110	110
GAB2	0.004	0.01	-10000	0	-10000	0	0
TNFSF11	-0.45	0.52	-10000	0	-1	111	111
HSP90B1	-0.023	0.06	-10000	0	-10000	0	0
GAB1	0.003	0.007	-10000	0	-10000	0	0
MAPK14	-0.2	0.33	-10000	0	-0.87	39	39
AKT1	0.021	0.044	-10000	0	-0.53	1	1
FOXO1	0.033	0.066	-10000	0	-0.48	4	4
MAP2K6	-0.21	0.3	-10000	0	-0.58	82	82
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
MAP2K4	-0.22	0.31	-10000	0	-0.62	78	78
MITF	-0.18	0.27	-10000	0	-0.48	95	95
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0	0	-10000	0	-10000	0	0
A2M	-0.2	0.54	-10000	0	-1.5	37	37
CEBPB	0.013	0.003	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.044	0.087	-10000	0	-0.29	1	1
STAT3	-0.41	0.52	-10000	0	-0.99	96	96
STAT1	-0.017	0.036	0.25	2	-10000	0	2
CEBPD	-0.31	0.38	-10000	0	-0.77	91	91
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
PI3K	-0.005	0.075	-10000	0	-1.2	1	1
JUN	-0.016	0.12	-10000	0	-0.88	5	5
PIAS3/MITF	-0.18	0.24	-10000	0	-0.52	70	70
MAPK11	-0.2	0.33	-10000	0	-0.87	39	39
STAT3 (dimer)/FOXO1	-0.28	0.38	-10000	0	-0.68	101	101
GRB2/SOS1/GAB family	-0.13	0.22	-10000	0	-0.64	22	22
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.18	0.26	-10000	0	-0.48	96	96
GRB2	0.003	0.007	-10000	0	-10000	0	0
JAK2	-0.003	0.054	-10000	0	-0.88	1	1
LBP	-0.28	0.37	-10000	0	-0.75	79	79
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
JAK1	-0.001	0.006	-10000	0	-10000	0	0
MYC	-0.36	0.46	-10000	0	-0.88	95	95
FGG	-0.36	0.45	-10000	0	-0.86	98	98
macrophage differentiation	-0.38	0.46	-10000	0	-0.91	96	96
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.21	0.3	-10000	0	-0.6	95	95
JUNB	-0.31	0.38	-10000	0	-0.76	91	91
FOS	-0.39	0.44	-10000	0	-0.88	120	120
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.2	0.28	-10000	0	-0.5	102	102
STAT1/PIAS1	-0.21	0.24	-10000	0	-0.54	73	73
GRB2/SOS1/GAB family/SHP2/PI3K	0.006	0.041	-10000	0	-0.57	1	1
STAT3 (dimer)	-0.4	0.51	-10000	0	-0.98	96	96
PRKCD	-0.25	0.34	-10000	0	-0.67	83	83
IL6R	-0.017	0.12	-10000	0	-0.89	5	5
SOCS3	-0.22	0.45	-10000	0	-1.3	35	35
gp130 (dimer)/JAK1/JAK1/LMO4	-0.14	0.25	-10000	0	-0.61	58	58
Rac1/GTP	-0.24	0.29	-10000	0	-0.6	81	81
HCK	-0.029	0.16	-10000	0	-0.88	9	9
MAPKKK cascade	-0.002	0.079	-10000	0	-10000	0	0
bone resorption	-0.41	0.47	-10000	0	-0.92	111	111
IRF1	-0.31	0.38	-10000	0	-0.75	91	91
mol:GDP	-0.2	0.3	-10000	0	-0.58	81	81
SOS1	0.004	0.01	-10000	0	-10000	0	0
VAV1	-0.21	0.31	-10000	0	-0.6	81	81
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.18	0.28	-10000	0	-0.63	51	51
PTPN11	-0.017	0.026	-10000	0	-10000	0	0
IL6/IL6RA	-0.11	0.27	-10000	0	-0.7	44	44
gp130 (dimer)/TYK2/TYK2/LMO4	-0.13	0.25	-10000	0	-0.61	58	58
gp130 (dimer)/JAK2/JAK2/LMO4	-0.13	0.26	-10000	0	-0.62	58	58
IL6	-0.12	0.32	0.32	7	-0.89	39	46
PIAS3	0	0	-10000	0	-10000	0	0
PTPRE	0.011	0.081	0.3	1	-0.88	2	3
PIAS1	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.17	0.24	-10000	0	-0.46	92	92
LMO4	0.005	0.01	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.4	0.41	-10000	0	-0.89	93	93
MCL1	0.039	0.035	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.36	0.64	-10000	0	-1.3	81	81
MKNK1	0	0	-10000	0	-10000	0	0
MAPK14	-0.067	0.16	-10000	0	-0.38	6	6
ATF2/c-Jun	-0.082	0.21	-10000	0	-1.2	6	6
MAPK11	-0.059	0.17	0.36	6	-0.38	5	11
MITF	-0.069	0.19	-10000	0	-0.37	72	72
MAPKAPK5	-0.07	0.19	-10000	0	-0.37	71	71
KRT8	-0.074	0.19	-10000	0	-0.37	74	74
MAPKAPK3	0	0	-10000	0	-10000	0	0
MAPKAPK2	0	0	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.12	0.23	0.37	1	-0.46	72	73
CEBPB	-0.07	0.19	-10000	0	-0.37	71	71
SLC9A1	-0.07	0.19	-10000	0	-0.37	71	71
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.073	0.22	-10000	0	-0.38	73	73
p38alpha-beta/MNK1	-0.09	0.18	-10000	0	-0.49	5	5
JUN	-0.061	0.21	-10000	0	-1.2	6	6
PPARGC1A	-0.15	0.3	-10000	0	-0.5	92	92
USF1	-0.07	0.19	-10000	0	-0.37	71	71
RAB5/GDP/GDI1	-0.074	0.12	-10000	0	-0.35	5	5
NOS2	-0.053	0.2	0.42	1	-0.47	5	6
DDIT3	-0.069	0.19	-10000	0	-0.37	70	70
RAB5A	0	0	-10000	0	-10000	0	0
HSPB1	-0.049	0.16	-10000	0	-0.39	4	4
p38alpha-beta/HBP1	-0.09	0.18	-10000	0	-0.49	5	5
CREB1	-0.08	0.21	-10000	0	-0.4	72	72
RAB5/GDP	0	0	-10000	0	-10000	0	0
EIF4E	-0.059	0.16	-10000	0	-0.43	5	5
RPS6KA4	-0.07	0.19	-10000	0	-0.37	71	71
PLA2G4A	-0.097	0.26	-10000	0	-0.76	24	24
GDI1	-0.07	0.19	-10000	0	-0.37	71	71
TP53	-0.093	0.23	-10000	0	-0.45	72	72
RPS6KA5	-0.085	0.24	-10000	0	-0.42	72	72
ESR1	-0.36	0.37	-10000	0	-0.56	177	177
HBP1	0	0	-10000	0	-10000	0	0
MEF2C	-0.07	0.19	-10000	0	-0.37	71	71
MEF2A	-0.07	0.19	-10000	0	-0.37	71	71
EIF4EBP1	-0.079	0.21	-10000	0	-0.4	72	72
KRT19	-0.25	0.39	-10000	0	-0.59	126	126
ELK4	-0.07	0.19	-10000	0	-0.37	71	71
ATF6	-0.07	0.19	-10000	0	-0.37	71	71
ATF1	-0.08	0.21	-10000	0	-0.4	71	71
p38alpha-beta/MAPKAPK2	-0.09	0.18	-10000	0	-0.49	5	5
p38alpha-beta/MAPKAPK3	-0.09	0.18	0.31	1	-0.47	6	7

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.14	0.11	0.25	103	-10000	0	103
STMN1	0.086	0.085	-10000	0	-10000	0	0
Aurora B/RasGAP/Survivin	0.22	0.18	0.38	130	-0.54	2	132
Chromosomal passenger complex/Cul3 protein complex	0.11	0.11	0.23	14	-0.29	4	18
BIRC5	0.21	0.16	0.32	174	-10000	0	174
DES	0.036	0.24	0.42	2	-0.54	25	27
Aurora C/Aurora B/INCENP	0.1	0.095	0.36	2	-10000	0	2
Aurora B/TACC1	0.098	0.094	-10000	0	-10000	0	0
Aurora B/PP2A	0.11	0.1	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.033	0.031	-10000	0	-10000	0	0
mitotic metaphase/anaphase transition	-0.007	0.005	-10000	0	-10000	0	0
NDC80	0.16	0.11	-10000	0	-10000	0	0
Cul3 protein complex	-0.017	0.1	-10000	0	-0.6	8	8
KIF2C	0.18	0.12	0.26	173	-10000	0	173
PEBP1	-0.015	0.12	-10000	0	-0.88	5	5
KIF20A	0.22	0.14	0.31	185	-10000	0	185
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.1	0.12	-10000	0	-0.66	2	2
SEPT1	0.001	0.019	0.32	1	-10000	0	1
SMC2	0.001	0.019	0.32	1	-10000	0	1
SMC4	0.004	0.033	0.32	3	-10000	0	3
NSUN2/NPM1/Nucleolin	0.15	0.12	0.31	29	-10000	0	29
PSMA3	0	0	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.005	0.005	-10000	0	-10000	0	0
H3F3B	0.069	0.066	-10000	0	-10000	0	0
AURKB	0.16	0.16	0.31	135	-10000	0	135
AURKC	0.001	0.019	0.32	1	-10000	0	1
CDCA8	0.16	0.16	0.33	128	-10000	0	128
cytokinesis	0.2	0.18	0.38	119	-10000	0	119
Aurora B/Septin1	0.21	0.21	0.41	131	-10000	0	131
AURKA	0.081	0.14	0.31	70	-10000	0	70
INCENP	0.012	0.029	0.33	2	-10000	0	2
KLHL13	-0.018	0.13	0.32	1	-0.88	6	7
BUB1	0.21	0.14	0.31	184	-10000	0	184
hSgo1/Aurora B/Survivin	0.28	0.23	0.48	145	-10000	0	145
EVI5	0.005	0.007	-10000	0	-10000	0	0
RhoA/GTP	0.2	0.22	0.42	124	-10000	0	124
SGOL1	0.13	0.16	0.32	110	-10000	0	110
CENPA	0.19	0.13	0.31	128	-10000	0	128
NCAPG	0.2	0.15	0.32	174	-10000	0	174
Aurora B/HC8 Proteasome	0.11	0.1	-10000	0	-10000	0	0
NCAPD2	0.005	0.038	0.32	4	-10000	0	4
Aurora B/PP1-gamma	0.11	0.1	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
NCAPH	0.15	0.16	0.32	129	-10000	0	129
NPM1	0.097	0.094	-10000	0	-10000	0	0
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
KLHL9	-0.007	0.076	-10000	0	-0.88	2	2
mitotic prometaphase	0.002	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.11	0.1	-10000	0	-10000	0	0
PPP1CC	0	0	-10000	0	-10000	0	0
Centraspindlin	0.23	0.25	0.47	127	-10000	0	127
RhoA/GDP	0	0	-10000	0	-10000	0	0
NSUN2	0.097	0.094	-10000	0	-10000	0	0
MYLK	0.06	0.085	-10000	0	-0.34	5	5
KIF23	0.16	0.16	0.33	129	-10000	0	129
VIM	0.08	0.075	-10000	0	-10000	0	0
RACGAP1	0.057	0.11	0.34	38	-10000	0	38
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.097	0.094	-10000	0	-10000	0	0
Chromosomal passenger complex	0.2	0.14	0.31	151	-10000	0	151
Chromosomal passenger complex/EVI5	0.27	0.21	0.48	118	-10000	0	118
TACC1	0	0	-10000	0	-10000	0	0
PPP2R5D	0	0	-10000	0	-10000	0	0
CUL3	0	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

Figure S19. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S19. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0	0	-10000	0	-10000	0	0
EPHB2	0.061	0.12	0.32	52	-10000	0	52
EFNB1	0.005	0.11	-10000	0	-0.69	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.1	0.26	-10000	0	-0.5	70	70
Ephrin B2/EPHB1-2	-0.094	0.25	-10000	0	-0.54	59	59
neuron projection morphogenesis	-0.1	0.24	-10000	0	-0.48	70	70
Ephrin B1/EPHB1-2/Tiam1	-0.11	0.28	-10000	0	-0.54	70	70
DNM1	0.004	0.14	0.32	17	-0.88	5	22
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.18	0.36	-10000	0	-0.83	61	61
YES1	-0.24	0.44	-10000	0	-1.1	61	61
Ephrin B1/EPHB1-2/NCK2	-0.09	0.26	0.47	1	-0.52	63	64
PI3K	-0.2	0.36	-10000	0	-0.85	61	61
mol:GDP	-0.11	0.27	-10000	0	-0.53	70	70
ITGA2B	0.008	0.05	0.32	7	-10000	0	7
endothelial cell proliferation	0.001	0.012	-10000	0	-10000	0	0
FYN	-0.24	0.44	-10000	0	-1.1	61	61
MAP3K7	-0.2	0.37	-10000	0	-0.88	61	61
FGR	-0.24	0.44	-10000	0	-1.1	61	61
TIAM1	-0.033	0.17	-10000	0	-0.88	10	10
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
RGS3	0	0	-10000	0	-10000	0	0
cell adhesion	-0.2	0.36	-10000	0	-0.8	68	68
LYN	-0.24	0.44	-10000	0	-1.1	61	61
Ephrin B1/EPHB1-2/Src Family Kinases	-0.23	0.42	-10000	0	-1	61	61
Ephrin B1/EPHB1-2	-0.22	0.4	-10000	0	-0.94	61	61
SRC	-0.24	0.44	-10000	0	-1.1	61	61
ITGB3	-0.052	0.21	-10000	0	-0.88	16	16
EPHB1	-0.19	0.36	-10000	0	-0.88	59	59
EPHB4	0.001	0.019	0.32	1	-10000	0	1
RAC1	0	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.001	0.012	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.035	0.17	-10000	0	-0.69	16	16
BLK	-0.27	0.46	-10000	0	-1.1	61	61
HCK	-0.24	0.45	-10000	0	-1.1	61	61
regulation of stress fiber formation	0.089	0.25	0.51	63	-0.46	1	64
MAPK8	-0.18	0.35	-10000	0	-0.76	70	70
Ephrin B1/EPHB1-2/RGS3	-0.09	0.25	-10000	0	-0.52	63	63
endothelial cell migration	-0.17	0.33	-10000	0	-0.77	61	61
NCK2	0.001	0.019	0.32	1	-10000	0	1
PTPN13	-0.22	0.42	0.32	2	-0.99	61	63
regulation of focal adhesion formation	0.089	0.25	0.51	63	-0.46	1	64
chemotaxis	0.09	0.25	0.51	63	-10000	0	63
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
Rac1/GTP	-0.1	0.25	-10000	0	-0.49	70	70
angiogenesis	-0.22	0.39	-10000	0	-0.94	61	61
LCK	-0.24	0.45	-10000	0	-1.1	61	61

×

Ephrin A reverse 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
MAPKKK cascade	-0.092	0.26	0.38	3	-0.61	50	53
EFNA5	-0.14	0.36	0.32	20	-0.88	50	70
FYN	-0.096	0.22	-10000	0	-0.56	50	50
neuron projection morphogenesis	-0.092	0.26	0.38	3	-0.61	50	53
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	-0.093	0.26	0.39	3	-0.61	50	53
EPHA5	0.011	0.057	0.32	9	-10000	0	9

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.18	0.3	-10000	0	-0.49	102	102
FZD6	0.001	0.019	0.32	1	-10000	0	1
WNT6	0.014	0.065	0.32	12	-10000	0	12
WNT4	-0.087	0.33	0.32	29	-0.88	37	66
FZD3	-0.02	0.13	-10000	0	-0.88	6	6
WNT5A	-0.079	0.27	0.32	5	-0.88	26	31
WNT11	-0.23	0.39	-10000	0	-0.88	71	71

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.066	0.27	0.39	2	-0.6	50	52
cell-cell adhesion	0.19	0.26	0.77	26	-10000	0	26
Ephrin B/EPHB2/RasGAP	-0.11	0.25	0.36	1	-0.52	69	70
ITSN1	0	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
SHC1	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.05	0.18	-10000	0	-0.6	25	25
Ephrin B1/EPHB1	-0.14	0.26	-10000	0	-0.61	59	59
HRAS/GDP	-0.19	0.27	-10000	0	-0.6	60	60
Ephrin B/EPHB1/GRB7	-0.24	0.34	-10000	0	-0.63	105	105
Endophilin/SYNJ1	-0.11	0.21	-10000	0	-0.48	68	68
KRAS	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.24	0.34	-10000	0	-0.64	102	102
endothelial cell migration	-0.003	0.062	-10000	0	-1	1	1
GRB2	0	0	-10000	0	-10000	0	0
GRB7	-0.004	0.1	0.32	5	-0.88	3	8
PAK1	-0.11	0.22	-10000	0	-0.48	68	68
HRAS	0.002	0.027	0.32	2	-10000	0	2
RRAS	-0.11	0.22	-10000	0	-0.48	68	68
DNM1	0.004	0.14	0.32	17	-0.88	5	22
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.23	0.32	-10000	0	-0.6	102	102
lamellipodium assembly	-0.19	0.26	-10000	0	-0.77	26	26
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.15	0.21	-10000	0	-0.48	59	59
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
EPHB2	0.061	0.12	0.32	52	-10000	0	52
EPHB3	-0.069	0.26	0.32	8	-0.88	24	32
EPHB1	-0.19	0.36	-10000	0	-0.88	59	59
EPHB4	0.001	0.019	0.32	1	-10000	0	1
mol:GDP	-0.17	0.26	-10000	0	-0.58	60	60
Ephrin B/EPHB2	-0.1	0.25	0.35	1	-0.51	68	69
Ephrin B/EPHB3	-0.17	0.3	0.35	1	-0.62	77	78
JNK cascade	-0.1	0.22	-10000	0	-0.5	60	60
Ephrin B/EPHB1	-0.24	0.34	-10000	0	-0.64	102	102
RAP1/GDP	-0.15	0.22	-10000	0	-0.61	26	26
EFNB2	0	0	-10000	0	-10000	0	0
EFNB3	-0.22	0.38	0.32	1	-0.88	67	68
EFNB1	-0.003	0.054	-10000	0	-0.88	1	1
Ephrin B2/EPHB1-2	-0.094	0.25	-10000	0	-0.55	59	59
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.2	0.3	-10000	0	-0.63	60	60
Rap1/GTP	-0.2	0.27	-10000	0	-0.8	26	26
axon guidance	-0.066	0.27	0.38	2	-0.59	50	52
MAPK3	-0.11	0.2	-10000	0	-0.57	25	25
MAPK1	-0.11	0.2	-10000	0	-0.57	25	25
Rac1/GDP	-0.15	0.24	-10000	0	-0.53	60	60
actin cytoskeleton reorganization	-0.14	0.2	-10000	0	-0.57	26	26
CDC42/GDP	-0.15	0.24	-10000	0	-0.53	60	60
PI3K	-0.003	0.063	-10000	0	-1	1	1
EFNA5	-0.14	0.36	0.32	20	-0.88	50	70
Ephrin B2/EPHB4	0.001	0.012	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.072	0.16	-10000	0	-0.36	54	54
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.19	0.26	-10000	0	-0.77	26	26
PTK2	0.023	0.044	-10000	0	-10000	0	0
MAP4K4	-0.1	0.22	-10000	0	-0.51	60	60
SRC	0.001	0.019	0.32	1	-10000	0	1
KALRN	-0.003	0.054	-10000	0	-0.88	1	1
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.14	0.22	-10000	0	-0.58	26	26
MAP2K1	-0.14	0.2	-10000	0	-0.6	25	25
WASL	0	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.096	0.25	-10000	0	-0.55	60	60
cell migration	-0.13	0.24	-10000	0	-0.5	57	57
NRAS	0	0	-10000	0	-10000	0	0
SYNJ1	-0.11	0.22	-10000	0	-0.48	68	68
PXN	0	0	-10000	0	-10000	0	0
TF	-0.15	0.24	-10000	0	-0.47	89	89
HRAS/GTP	-0.2	0.3	-10000	0	-0.57	84	84
Ephrin B1/EPHB1-2	-0.096	0.25	-10000	0	-0.55	59	59
cell adhesion mediated by integrin	0.13	0.24	0.53	68	-10000	0	68
RAC1	0	0	-10000	0	-10000	0	0
mol:GTP	-0.21	0.32	-10000	0	-0.59	103	103
RAC1-CDC42/GTP	-0.22	0.3	-10000	0	-0.84	37	37
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
RAC1-CDC42/GDP	-0.15	0.22	-10000	0	-0.51	55	55
ruffle organization	-0.2	0.27	-10000	0	-0.8	26	26
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
receptor internalization	-0.11	0.22	-10000	0	-0.48	53	53
Ephrin B/EPHB2/KALRN	-0.1	0.25	0.36	1	-0.52	68	69
ROCK1	-0.049	0.16	-10000	0	-0.55	25	25
RAS family/GDP	-0.14	0.19	-10000	0	-0.55	26	26
Rac1/GTP	-0.21	0.29	-10000	0	-0.86	26	26
Ephrin B/EPHB1/Src/Paxillin	-0.17	0.24	-10000	0	-0.44	102	102

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.034	0.14	-10000	0	-0.61	8	8
PTK2B	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.042	0.24	0.49	1	-0.68	17	18
EDN1	-0.031	0.14	-10000	0	-0.73	7	7
EDN3	0.008	0.05	0.32	7	-10000	0	7
EDN2	-0.076	0.26	0.32	5	-0.88	25	30
HRAS/GDP	-0.14	0.25	0.32	1	-0.62	43	44
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.078	0.2	0.3	1	-0.46	43	44
ADCY4	-0.019	0.11	-10000	0	-0.5	8	8
ADCY5	-0.1	0.23	-10000	0	-0.55	50	50
ADCY6	-0.019	0.11	-10000	0	-0.5	8	8
ADCY7	-0.019	0.11	-10000	0	-0.5	8	8
ADCY1	-0.2	0.28	-10000	0	-0.54	101	101
ADCY2	-0.015	0.12	0.39	1	-0.51	8	9
ADCY3	-0.017	0.12	-10000	0	-0.5	8	8
ADCY8	0.001	0.14	0.33	1	-0.51	8	9
ADCY9	-0.019	0.11	-10000	0	-0.5	8	8
arachidonic acid secretion	-0.2	0.33	0.43	1	-0.52	116	117
ETB receptor/Endothelin-1/Gq/GTP	-0.11	0.27	-10000	0	-0.56	57	57
GNAO1	-0.39	0.44	-10000	0	-0.88	120	120
HRAS	0.002	0.027	0.32	2	-10000	0	2
ETA receptor/Endothelin-1/G12/GTP	-0.031	0.13	0.48	1	-0.57	8	9
ETA receptor/Endothelin-1/Gs/GTP	-0.002	0.14	0.45	1	-0.54	8	9
mol:GTP	-0.001	0.007	-10000	0	-10000	0	0
COL3A1	-0.047	0.22	0.43	4	-0.87	13	17
EDNRB	-0.055	0.22	-10000	0	-0.88	18	18
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.049	0.2	-10000	0	-0.82	13	13
CYSLTR1	-0.049	0.2	-10000	0	-0.77	15	15
SLC9A1	-0.02	0.074	0.24	1	-0.31	8	9
mol:GDP	-0.13	0.3	0.34	1	-0.62	54	55
SLC9A3	-0.029	0.26	0.39	2	-0.8	21	23
RAF1	-0.2	0.33	-10000	0	-0.72	55	55
JUN	-0.061	0.28	-10000	0	-0.89	16	16
JAK2	-0.036	0.14	-10000	0	-0.61	9	9
mol:IP3	-0.12	0.26	0.28	1	-0.58	54	55
ETA receptor/Endothelin-1	-0.044	0.16	0.57	1	-0.62	12	13
PLCB1	0.014	0.065	0.31	12	-10000	0	12
PLCB2	-0.016	0.12	-10000	0	-0.88	5	5
ETA receptor/Endothelin-3	-0.005	0.058	0.31	1	-10000	0	1
FOS	-0.44	0.54	-10000	0	-1	124	124
Gai/GDP	-0.32	0.41	-10000	0	-0.76	120	120
CRK	0	0	-10000	0	-10000	0	0
mol:Ca ++	-0.098	0.3	-10000	0	-0.78	31	31
BCAR1	0	0.001	-10000	0	-10000	0	0
PRKCB1	-0.1	0.26	-10000	0	-0.56	54	54
GNAQ	-0.001	0.054	-10000	0	-0.88	1	1
GNAZ	0.15	0.16	0.32	125	-10000	0	125
GNAL	0.054	0.12	0.32	46	-10000	0	46
Gs family/GDP	-0.13	0.24	0.26	16	-0.56	49	65
ETA receptor/Endothelin-1/Gq/GTP	-0.084	0.22	0.35	1	-0.48	51	52
MAPK14	-0.074	0.23	-10000	0	-0.56	35	35
TRPC6	-0.045	0.25	0.49	1	-0.73	16	17
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GNAI1	-0.007	0.076	-10000	0	-0.88	2	2
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.1	0.24	-10000	0	-0.48	58	58
ETB receptor/Endothelin-2	-0.1	0.26	-10000	0	-0.7	42	42
ETB receptor/Endothelin-3	-0.038	0.18	-10000	0	-0.69	18	18
ETB receptor/Endothelin-1	-0.059	0.22	-10000	0	-0.75	21	21
MAPK3	-0.36	0.47	-10000	0	-0.84	124	124
MAPK1	-0.36	0.47	-10000	0	-0.84	124	124
Rac1/GDP	-0.15	0.24	0.29	2	-0.62	44	46
cAMP biosynthetic process	-0.077	0.2	-10000	0	-0.49	35	35
MAPK8	-0.076	0.3	0.44	1	-0.72	31	32
SRC	0.001	0.019	0.32	1	-10000	0	1
ETB receptor/Endothelin-1/Gi/GTP	-0.13	0.22	-10000	0	-0.45	50	50
p130Cas/CRK/Src/PYK2	-0.092	0.28	0.38	2	-0.63	43	45
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.15	0.24	0.29	2	-0.62	44	46
COL1A2	-0.053	0.21	0.43	4	-0.71	15	19
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.068	0.2	-10000	0	-0.68	25	25
mol:DAG	-0.12	0.27	0.28	1	-0.58	54	55
MAP2K2	-0.27	0.38	-10000	0	-0.63	123	123
MAP2K1	-0.27	0.38	-10000	0	-0.63	123	123
EDNRA	-0.016	0.073	0.49	1	-10000	0	1
positive regulation of muscle contraction	-0.027	0.12	-10000	0	-0.53	8	8
Gq family/GDP	-0.19	0.3	-10000	0	-0.7	59	59
HRAS/GTP	-0.15	0.3	-10000	0	-0.6	61	61
PRKCH	-0.099	0.26	-10000	0	-0.59	46	46
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.099	0.26	-10000	0	-0.56	53	53
PRKCB	-0.15	0.32	-10000	0	-0.66	61	61
PRKCE	-0.1	0.27	-10000	0	-0.57	52	52
PRKCD	-0.1	0.26	-10000	0	-0.6	46	46
PRKCG	-0.1	0.26	-10000	0	-0.58	50	50
regulation of vascular smooth muscle contraction	-0.51	0.62	-10000	0	-1.2	124	124
PRKCQ	-0.12	0.29	-10000	0	-0.58	57	57
PLA2G4A	-0.23	0.37	0.44	1	-0.58	116	117
GNA14	-0.15	0.34	-10000	0	-0.88	47	47
GNA15	0.004	0.028	0.32	2	-10000	0	2
GNA12	0	0	-10000	0	-10000	0	0
GNA11	-0.018	0.13	-10000	0	-0.88	6	6
Rac1/GTP	-0.031	0.13	0.48	1	-0.57	8	9
MMP1	0.076	0.12	0.45	6	-10000	0	6

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.17	0.62	0.77	3	-1.2	59	62
IL23A	-0.15	0.6	0.79	3	-1.3	47	50
NF kappa B1 p50/RelA/I kappa B alpha	-0.27	0.46	-10000	0	-1.1	55	55
positive regulation of T cell mediated cytotoxicity	-0.16	0.65	0.78	9	-1.3	55	64
ITGA3	-0.12	0.56	0.79	5	-1.2	42	47
IL17F	-0.05	0.38	0.61	2	-0.73	42	44
IL12B	0.026	0.066	0.48	2	-10000	0	2
STAT1 (dimer)	-0.27	0.54	0.59	14	-1.2	55	69
CD4	-0.15	0.6	0.81	1	-1.2	48	49
IL23	-0.19	0.55	0.73	4	-1.2	47	51
IL23R	0.029	0.13	-10000	0	-10000	0	0
IL1B	-0.2	0.69	0.77	2	-1.4	53	55
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.12	0.54	0.92	1	-1.1	43	44
TYK2	0.019	0.034	-10000	0	-10000	0	0
STAT4	-0.032	0.17	0.32	1	-0.88	10	11
STAT3	0	0	-10000	0	-10000	0	0
IL18RAP	-0.051	0.21	-10000	0	-0.88	16	16
IL12RB1	-0.011	0.17	-10000	0	-0.91	9	9
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
IL12Rbeta1/TYK2	-0.012	0.14	-10000	0	-0.73	9	9
IL23R/JAK2	0.034	0.16	-10000	0	-0.71	1	1
positive regulation of chronic inflammatory response	-0.16	0.65	0.78	9	-1.3	55	64
natural killer cell activation	-0.002	0.012	-10000	0	-0.049	2	2
JAK2	0.031	0.073	-10000	0	-0.91	1	1
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
NFKB1	0.001	0.005	-10000	0	-10000	0	0
RELA	0.001	0.005	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.16	0.53	0.73	4	-1.1	47	51
ALOX12B	-0.12	0.54	0.78	2	-1.1	53	55
CXCL1	-0.3	0.74	0.78	6	-1.3	86	92
T cell proliferation	-0.16	0.65	0.78	9	-1.3	55	64
NFKBIA	0.001	0.005	-10000	0	-10000	0	0
IL17A	-0.011	0.31	0.56	5	-0.56	39	44
PI3K	-0.29	0.48	-10000	0	-1.1	55	55
IFNG	-0.002	0.05	0.17	6	-0.1	24	30
STAT3 (dimer)	-0.27	0.44	-10000	0	-1.1	55	55
IL18R1	-0.12	0.3	-10000	0	-0.88	37	37
IL23/IL23R/JAK2/TYK2/SOCS3	-0.072	0.43	0.61	9	-0.89	37	46
IL18/IL18R	-0.12	0.29	-10000	0	-0.7	48	48
macrophage activation	-0.01	0.024	0.06	13	-0.044	47	60
TNF	-0.16	0.62	0.79	2	-1.4	43	45
STAT3/STAT4	-0.29	0.48	-10000	0	-1.1	55	55
STAT4 (dimer)	-0.28	0.55	0.59	13	-1.2	55	68
IL18	-0.013	0.12	0.31	2	-0.88	5	7
IL19	-0.13	0.54	0.8	1	-1	54	55
STAT5A (dimer)	-0.27	0.54	0.59	13	-1.2	55	68
STAT1	0.002	0.027	0.32	2	-10000	0	2
SOCS3	-0.1	0.28	-10000	0	-0.88	31	31
CXCL9	-0.12	0.55	0.82	4	-1.1	49	53
MPO	-0.14	0.57	0.81	1	-1.2	48	49
positive regulation of humoral immune response	-0.16	0.65	0.78	9	-1.3	55	64
IL23/IL23R/JAK2/TYK2	-0.19	0.72	0.78	9	-1.4	55	64
IL6	-0.22	0.67	0.75	2	-1.3	67	69
STAT5A	0	0	-10000	0	-10000	0	0
IL2	0.004	0.012	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	-0.002	0.012	-10000	0	-0.049	2	2
CD3E	-0.13	0.57	0.92	1	-1.2	45	46
keratinocyte proliferation	-0.16	0.65	0.78	9	-1.3	55	64
NOS2	-0.11	0.54	0.77	3	-1	55	58

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.051	0.048	-10000	0	-10000	0	0
BUB1B	0.098	0.062	0.16	110	-10000	0	110
PLK1	0.053	0.028	0.11	2	-10000	0	2
PLK1S1	0.031	0.016	0.14	2	-10000	0	2
KIF2A	0.055	0.024	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.053	0.028	0.11	2	-10000	0	2
GOLGA2	0	0	-10000	0	-10000	0	0
Hec1/SPC24	0.25	0.18	0.36	179	-10000	0	179
WEE1	0.055	0.051	-10000	0	-0.61	1	1
cytokinesis	0.14	0.093	0.22	127	-0.23	2	129
PP2A-alpha B56	0	0.002	-10000	0	-10000	0	0
AURKA	0.057	0.048	0.14	64	-10000	0	64
PICH/PLK1	0.1	0.11	0.26	74	-0.3	1	75
CENPE	0.072	0.04	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.055	0.024	-10000	0	-10000	0	0
PPP2CA	0	0	-10000	0	-10000	0	0
FZR1	0	0	-10000	0	-10000	0	0
TPX2	0.043	0.039	0.14	35	-10000	0	35
PAK1	0	0	-10000	0	-10000	0	0
SPC24	0.14	0.16	0.32	120	-10000	0	120
FBXW11	0	0	-10000	0	-10000	0	0
CLSPN	0.071	0.062	0.15	93	-10000	0	93
GORASP1	0	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.027	0.013	0.052	1	-10000	0	1
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-10000	0	0
STAG2	0	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0	0.002	-10000	0	-10000	0	0
spindle elongation	0.053	0.028	0.11	2	-10000	0	2
ODF2	0.003	0.005	-10000	0	-10000	0	0
BUB1	0.14	0.097	0.41	1	-10000	0	1
TPT1	0.031	0.013	-10000	0	-10000	0	0
CDC25C	0.13	0.067	0.17	186	-10000	0	186
CDC25B	0.009	0.021	0.33	1	-10000	0	1
SGOL1	0.051	0.048	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
CCNB1/CDK1	0.089	0.1	0.38	1	-0.38	1	2
CDC14B	-0.016	0.12	-10000	0	-0.7	8	8
CDC20	0.22	0.14	0.32	188	-10000	0	188
PLK1/PBIP1	0.018	0.049	0.15	20	-10000	0	20
mitosis	-0.004	0.006	-10000	0	-10000	0	0
FBXO5	0.047	0.021	-10000	0	-10000	0	0
CDC2	0.005	0.005	0.011	121	-0.011	1	122
NDC80	0.21	0.15	0.32	180	-10000	0	180
metaphase plate congression	0.037	0.018	-10000	0	-10000	0	0
ERCC6L	0.098	0.11	0.26	44	-0.35	1	45
NLP/gamma Tubulin	0.032	0.014	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.031	0.013	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.001	-10000	0	-10000	0	0
PPP1R12A	0	0	-10000	0	-10000	0	0
interphase	-0.001	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	0.26	0.19	0.38	187	-10000	0	187
GRASP65/GM130/RAB1/GTP/PLK1	0	0	-10000	0	-10000	0	0
RAB1A	0	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.046	0.024	-10000	0	-10000	0	0
mitotic prometaphase	0.001	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.065	0.061	-10000	0	-10000	0	0
microtubule-based process	0.18	0.12	0.26	185	-10000	0	185
Golgi organization	0.053	0.028	0.11	2	-10000	0	2
Cohesin/SA2	0	0	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	0.22	0.15	0.32	185	-10000	0	185
APC/C/CDC20	0.18	0.12	0.26	188	-10000	0	188
PPP2R1A	0	0	-10000	0	-10000	0	0
chromosome segregation	0.018	0.048	0.15	21	-10000	0	21
PRC1	0.16	0.16	0.32	134	-10000	0	134
ECT2	0.065	0.036	-10000	0	-10000	0	0
C13orf34	0.047	0.022	-10000	0	-10000	0	0
NUDC	0.037	0.018	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.098	0.061	0.16	110	-10000	0	110
spindle assembly	0.044	0.02	0.086	1	-10000	0	1
spindle stabilization	0.031	0.016	0.14	2	-10000	0	2
APC/C/HCDH1	-0.018	0.1	-10000	0	-0.61	8	8
MKLP2/PLK1	0.18	0.12	0.26	185	-10000	0	185
CCNB1	0.14	0.16	0.32	121	-10000	0	121
PPP1CB	0	0	-10000	0	-10000	0	0
BTRC	0	0	-10000	0	-10000	0	0
ROCK2	0.028	0.094	-10000	0	-0.5	8	8
TUBG1	0.031	0.013	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.052	0.064	-10000	0	-0.37	1	1
MLF1IP	0.021	0.048	-10000	0	-10000	0	0
INCENP	0.004	0.027	0.32	2	-10000	0	2

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.005	0.055	-10000	0	-0.61	2	2
NFATC2	-0.098	0.23	-10000	0	-0.62	43	43
NFATC3	0	0.018	-10000	0	-10000	0	0
CD40LG	-0.33	0.37	0.49	2	-0.79	87	89
PTGS2	-0.42	0.47	-10000	0	-1	94	94
JUNB	-0.033	0.17	-10000	0	-0.88	10	10
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.011	-10000	0	-10000	0	0
CaM/Ca2+	-0.001	0.01	-10000	0	-10000	0	0
CALM1	0	0.005	-10000	0	-10000	0	0
JUN	-0.016	0.12	-10000	0	-0.88	5	5
mol:Ca2+	-0.003	0.008	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.001	-10000	0	-10000	0	0
FOSL1	-0.029	0.17	0.32	3	-0.88	10	13
CREM	0	0	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.1	0.23	0.36	3	-0.59	38	41
FOS	-0.4	0.44	-10000	0	-0.89	120	120
IFNG	-0.32	0.35	0.51	4	-0.76	86	90
AP-1/NFAT1-c-4	-0.4	0.47	0.56	5	-0.98	86	91
FASLG	-0.33	0.37	0.53	2	-0.79	87	89
NFAT1-c-4/ICER1	-0.09	0.21	-10000	0	-0.54	43	43
IL2RA	-0.32	0.36	0.5	5	-0.76	88	93
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSF2	-0.32	0.35	-10000	0	-0.76	86	86
JunB/Fra1/NFAT1-c-4	-0.12	0.25	0.39	1	-0.55	58	59
IL4	-0.32	0.35	-10000	0	-0.76	86	86
IL2	-0.016	0.023	-10000	0	-10000	0	0
IL3	-0.031	0.029	-10000	0	-10000	0	0
FKBP1A	0	0	-10000	0	-10000	0	0
BATF3	-0.005	0.078	0.32	1	-0.88	2	3
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.002	0.005	-10000	0	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.068	0.21	0.39	1	-0.63	31	32
fibroblast growth factor receptor signaling pathway	-0.067	0.21	0.39	1	-0.63	31	32
LAMA1	-0.078	0.29	0.32	17	-0.88	30	47
PRNP	-0.059	0.22	-10000	0	-0.88	18	18
GPC1/SLIT2	-0.079	0.24	0.44	1	-0.68	35	36
SMAD2	-0.026	0.12	-10000	0	-0.54	13	13
GPC1/PrPc/Cu2+	-0.068	0.22	-10000	0	-0.71	26	26
GPC1/Laminin alpha1	-0.095	0.27	0.44	1	-0.71	41	42
TDGF1	-0.004	0.28	0.32	52	-0.88	20	72
CRIPTO/GPC1	-0.044	0.26	-10000	0	-0.7	32	32
APP/GPC1	-0.04	0.16	-10000	0	-0.68	16	16
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.054	0.21	-10000	0	-0.61	32	32
FLT1	0	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.028	0.13	-10000	0	-0.6	13	13
SERPINC1	-0.16	0.34	-10000	0	-0.88	48	48
FYN	-0.054	0.21	-10000	0	-0.61	32	32
FGR	-0.056	0.21	-10000	0	-0.61	33	33
positive regulation of MAPKKK cascade	-0.085	0.26	-10000	0	-0.65	38	38
SLIT2	-0.058	0.25	0.32	12	-0.88	22	34
GPC1/NRG	-0.31	0.37	-10000	0	-0.72	117	117
NRG1	-0.36	0.43	-10000	0	-0.88	111	111
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.028	0.13	-10000	0	-0.6	13	13
LYN	-0.054	0.21	-10000	0	-0.61	32	32
mol:Spermine	-0.025	0.15	-10000	0	-0.69	13	13
cell growth	-0.067	0.21	0.39	1	-0.63	31	32
BMP signaling pathway	0.041	0.19	0.88	13	-0.32	1	14
SRC	-0.054	0.21	-10000	0	-0.61	32	32
TGFBR1	0	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.32	0.46	0.32	23	-0.88	106	129
GPC1	-0.041	0.19	0.32	1	-0.88	13	14
TGFBR1 (dimer)	0	0	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.17	0.33	-10000	0	-0.67	75	75
HCK	-0.074	0.23	-10000	0	-0.62	40	40
FGF2	-0.051	0.22	0.32	4	-0.88	17	21
FGFR1	-0.007	0.097	0.32	2	-0.88	3	5
VEGFR1 homodimer	0	0	-10000	0	-10000	0	0
TGFBR2	0	0	-10000	0	-10000	0	0
cell death	-0.04	0.16	-10000	0	-0.68	16	16
ATIII/GPC1	-0.16	0.29	-10000	0	-0.69	60	60
PLA2G2A/GPC1	-0.28	0.38	-10000	0	-0.71	114	114
LCK	-0.071	0.23	-10000	0	-0.62	39	39
neuron differentiation	-0.31	0.36	-10000	0	-0.72	117	117
PrPc/Cu2+	-0.046	0.17	-10000	0	-0.69	18	18
APP	-0.01	0.092	-10000	0	-0.88	3	3
TGFBR2 (dimer)	0	0	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.01	0.008	-10000	0	-10000	0	0
RAS family/GTP	-0.13	0.17	-10000	0	-0.5	6	6
NFATC4	-0.12	0.18	-10000	0	-0.51	4	4
ERBB2IP	0.006	0.007	-10000	0	-10000	0	0
HSP90 (dimer)	0	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.19	0.22	-10000	0	-0.45	113	113
JUN	-0.051	0.089	-10000	0	-0.49	4	4
HRAS	0.002	0.027	0.32	2	-10000	0	2
DOCK7	-0.18	0.21	-10000	0	-0.42	113	113
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.23	0.28	-10000	0	-0.54	113	113
AKT1	0.005	0.005	-10000	0	-10000	0	0
BAD	0.01	0.008	-10000	0	-10000	0	0
MAPK10	-0.099	0.13	0.16	2	-0.39	17	19
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.2	0.25	-10000	0	-0.49	113	113
RAF1	-0.11	0.17	-10000	0	-0.46	7	7
ErbB2/ErbB3/neuregulin 2	0.026	0.12	-10000	0	-0.55	6	6
STAT3	-0.002	0.014	-10000	0	-10000	0	0
cell migration	-0.076	0.13	-10000	0	-0.31	16	16
mol:PI-3-4-5-P3	-0.003	0.004	-10000	0	-10000	0	0
cell proliferation	-0.19	0.23	-10000	0	-0.53	48	48
FOS	-0.25	0.28	-10000	0	-0.54	120	120
NRAS	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.19	0.22	-10000	0	-0.45	113	113
MAPK3	-0.15	0.19	-10000	0	-0.44	48	48
MAPK1	-0.15	0.19	-10000	0	-0.44	48	48
JAK2	-0.18	0.22	-10000	0	-0.43	113	113
NF2	-0.011	0.013	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.17	0.2	-10000	0	-0.4	113	113
NRG1	-0.36	0.43	-10000	0	-0.88	111	111
GRB2/SOS1	0	0	-10000	0	-10000	0	0
MAPK8	-0.16	0.18	-10000	0	-0.36	121	121
MAPK9	-0.088	0.1	-10000	0	-0.3	4	4
ERBB2	-0.008	0.074	-10000	0	-0.71	3	3
ERBB3	-0.01	0.093	-10000	0	-0.88	3	3
SHC1	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.003	0.011	-10000	0	-10000	0	0
STAT3 (dimer)	-0.002	0.014	-10000	0	-10000	0	0
RNF41	0.008	0.011	-10000	0	-10000	0	0
FRAP1	0.005	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.12	0.15	-10000	0	-0.45	4	4
ErbB2/ErbB2/HSP90 (dimer)	-0.007	0.065	-10000	0	-0.61	3	3
CHRNA1	-0.11	0.15	-10000	0	-0.41	6	6
myelination	-0.12	0.18	-10000	0	-0.5	4	4
PPP3CB	-0.16	0.2	-10000	0	-0.39	113	113
KRAS	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.14	0.17	-10000	0	-0.35	53	53
NRG2	0.068	0.13	0.32	58	-10000	0	58
mol:GDP	-0.17	0.2	-10000	0	-0.39	113	113
SOS1	0	0	-10000	0	-10000	0	0
MAP2K2	-0.098	0.17	-10000	0	-0.48	5	5
SRC	0.001	0.019	0.32	1	-10000	0	1
mol:cAMP	-0.002	0.003	-10000	0	-10000	0	0
PTPN11	-0.18	0.21	-10000	0	-0.42	113	113
MAP2K1	-0.18	0.21	-10000	0	-0.51	46	46
heart morphogenesis	-0.19	0.22	-10000	0	-0.45	113	113
RAS family/GDP	-0.14	0.17	-10000	0	-0.57	4	4
GRB2	0	0	-10000	0	-10000	0	0
PRKACA	-0.014	0.017	-10000	0	-10000	0	0
CHRNE	-0.006	0.034	-10000	0	-0.25	4	4
HSP90AA1	0	0	-10000	0	-10000	0	0
activation of caspase activity	-0.005	0.005	-10000	0	-10000	0	0
nervous system development	-0.19	0.22	-10000	0	-0.45	113	113
CDC42	0	0	-10000	0	-10000	0	0

×

LPA receptor mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.12	0.24	0.32	2	-0.57	55	57
NF kappa B1 p50/RelA/I kappa B alpha	-0.043	0.083	-10000	0	-0.53	2	2
AP1	-0.32	0.37	-10000	0	-0.63	139	139
mol:PIP3	-0.1	0.19	-10000	0	-0.46	58	58
AKT1	-0.079	0.15	-10000	0	-0.58	5	5
PTK2B	-0.043	0.15	-10000	0	-0.3	57	57
RHOA	-0.02	0.064	-10000	0	-0.55	1	1
PIK3CB	0	0	-10000	0	-10000	0	0
mol:Ca2+	0.008	0.087	-10000	0	-0.5	3	3
MAGI3	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
apoptosis	-0.089	0.2	0.26	1	-0.46	56	57
HRAS/GDP	0.002	0.018	0.21	2	-10000	0	2
positive regulation of microtubule depolymerization	-0.016	0.13	-10000	0	-0.42	6	6
NF kappa B1 p50/RelA	-0.089	0.21	-10000	0	-0.53	29	29
endothelial cell migration	-0.14	0.29	0.36	2	-0.65	59	61
ADCY4	-0.23	0.32	-10000	0	-0.74	59	59
ADCY5	-0.3	0.41	-10000	0	-0.88	74	74
ADCY6	-0.23	0.32	-10000	0	-0.74	59	59
ADCY7	-0.23	0.32	-10000	0	-0.74	59	59
ADCY1	-0.37	0.43	-10000	0	-0.86	99	99
ADCY2	-0.23	0.32	-10000	0	-0.75	59	59
ADCY3	-0.23	0.32	-10000	0	-0.74	59	59
ADCY8	-0.22	0.32	-10000	0	-0.74	59	59
ADCY9	-0.23	0.32	-10000	0	-0.74	59	59
GSK3B	-0.034	0.14	-10000	0	-0.37	18	18
arachidonic acid secretion	-0.25	0.3	-10000	0	-0.72	59	59
GNG2	-0.003	0.053	-10000	0	-0.88	1	1
TRIP6	-0.006	0.07	-10000	0	-0.49	5	5
GNAO1	-0.39	0.38	-10000	0	-0.7	150	150
HRAS	0.002	0.027	0.32	2	-10000	0	2
NFKBIA	-0.014	0.12	-10000	0	-0.47	5	5
GAB1	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.039	0.2	-10000	0	-0.99	11	11
JUN	-0.016	0.12	-10000	0	-0.88	5	5
LPA/LPA2/NHERF2	0.003	0.079	-10000	0	-0.6	3	3
TIAM1	-0.047	0.24	-10000	0	-1.2	11	11
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
mol:IP3	0.007	0.088	-10000	0	-0.51	3	3
PLCB3	-0.002	0.062	-10000	0	-0.55	3	3
FOS	-0.39	0.44	-10000	0	-0.88	120	120
positive regulation of mitosis	-0.25	0.3	-10000	0	-0.72	59	59
LPA/LPA1-2-3	-0.092	0.26	0.37	6	-0.57	55	61
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
stress fiber formation	-0.054	0.18	-10000	0	-0.39	57	57
GNAZ	-0.058	0.29	0.28	4	-0.58	59	63
EGFR/PI3K-beta/Gab1	-0.11	0.2	-10000	0	-0.48	58	58
positive regulation of dendritic cell cytokine production	-0.092	0.26	0.36	6	-0.57	55	61
LPA/LPA2/MAGI-3	0.008	0.06	-10000	0	-0.6	1	1
ARHGEF1	-0.11	0.22	-10000	0	-0.52	55	55
GNAI2	-0.13	0.25	-10000	0	-0.6	57	57
GNAI3	-0.13	0.25	-10000	0	-0.59	59	59
GNAI1	-0.13	0.26	-10000	0	-0.6	60	60
LPA/LPA3	0.02	0.069	0.22	26	-10000	0	26
LPA/LPA2	0.008	0.067	0.22	14	-0.69	1	15
LPA/LPA1	-0.14	0.29	0.37	2	-0.68	59	61
HB-EGF/EGFR	-0.011	0.14	-10000	0	-0.59	14	14
HBEGF	0.012	0.15	-10000	0	-0.68	10	10
mol:DAG	0.007	0.088	-10000	0	-0.51	3	3
cAMP biosynthetic process	-0.32	0.38	-10000	0	-0.61	148	148
NFKB1	0	0	-10000	0	-10000	0	0
SRC	0.001	0.019	0.32	1	-10000	0	1
GNB1	0	0	-10000	0	-10000	0	0
LYN	-0.014	0.12	-10000	0	-0.56	3	3
GNAQ	0.01	0.056	-10000	0	-0.46	2	2
LPAR2	0.013	0.089	0.32	14	-0.88	1	15
LPAR3	0.032	0.095	0.32	27	-10000	0	27
LPAR1	-0.18	0.36	0.35	4	-0.88	55	59
IL8	-0.19	0.28	0.34	4	-0.53	92	96
PTK2	-0.1	0.23	-10000	0	-0.54	55	55
Rac1/GDP	0	0	-10000	0	-10000	0	0
CASP3	-0.089	0.2	0.26	1	-0.46	56	57
EGFR	-0.013	0.11	-10000	0	-0.88	4	4
PLCG1	-0.018	0.08	-10000	0	-0.34	5	5
PLD2	-0.1	0.23	-10000	0	-0.54	55	55
G12/G13	-0.11	0.24	0.32	2	-0.56	55	57
PI3K-beta	-0.092	0.18	-10000	0	-0.45	46	46
cell migration	-0.037	0.097	-10000	0	-0.28	15	15
SLC9A3R2	-0.007	0.076	-10000	0	-0.88	2	2
PXN	-0.056	0.18	-10000	0	-0.39	57	57
HRAS/GTP	-0.26	0.32	-10000	0	-0.75	59	59
RAC1	0	0	-10000	0	-10000	0	0
MMP9	0.026	0.21	0.32	47	-0.88	9	56
PRKCE	-0.002	0.057	0.32	1	-0.88	1	2
PRKCD	0.013	0.084	-10000	0	-0.48	3	3
Gi(beta/gamma)	-0.23	0.3	-10000	0	-0.72	59	59
mol:LPA	-0.002	0.03	-10000	0	-0.22	4	4
TRIP6/p130 Cas/FAK1/Paxillin	-0.09	0.22	-10000	0	-0.5	55	55
MAPKKK cascade	-0.25	0.3	-10000	0	-0.72	59	59
contractile ring contraction involved in cytokinesis	-0.002	0.07	-10000	0	-0.54	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.07	0.18	-10000	0	-0.45	48	48
GNA15	0.012	0.05	-10000	0	-0.46	1	1
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
MAPT	-0.017	0.13	-10000	0	-0.43	6	6
GNA11	0.001	0.085	-10000	0	-0.46	7	7
Rac1/GTP	-0.042	0.21	-10000	0	-1.1	11	11
MMP2	-0.14	0.3	0.36	2	-0.65	59	61

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.002	0.044	-10000	0	-0.68	1	1
CRKL	-0.12	0.16	-10000	0	-0.5	2	2
mol:PIP3	-0.004	0.068	0.77	2	-10000	0	2
AKT1	0.01	0.041	0.48	2	-10000	0	2
PTK2B	0	0	-10000	0	-10000	0	0
RAPGEF1	-0.11	0.15	-10000	0	-0.46	2	2
RANBP10	0	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
HGF/MET/SHIP2	-0.3	0.3	-10000	0	-0.6	133	133
MAP3K5	-0.15	0.23	-10000	0	-0.66	32	32
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.27	0.28	-10000	0	-0.55	133	133
AP1	-0.29	0.33	-10000	0	-0.64	120	120
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
apoptosis	-0.39	0.44	-10000	0	-0.87	120	120
STAT3 (dimer)	-0.17	0.17	-10000	0	-0.34	134	134
GAB1/CRKL/SHP2/PI3K	-0.12	0.13	-10000	0	-0.74	2	2
INPP5D	-0.003	0.054	-10000	0	-0.88	1	1
CBL/CRK	-0.13	0.13	-10000	0	-0.46	2	2
PTPN11	0	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0	0	-10000	0	-10000	0	0
PTEN	-0.007	0.076	-10000	0	-0.88	2	2
ELK1	-0.013	0.024	-10000	0	-0.29	1	1
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.1	0.1	-10000	0	-0.34	2	2
PAK1	0.016	0.038	0.44	2	-10000	0	2
HGF/MET/RANBP10	-0.3	0.3	-10000	0	-0.6	133	133
HRAS	-0.21	0.22	-10000	0	-0.43	132	132
DOCK1	-0.12	0.17	-10000	0	-0.64	7	7
GAB1	-0.14	0.16	-10000	0	-0.3	133	133
CRK	-0.12	0.16	-10000	0	-0.5	2	2
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.3	0.31	-10000	0	-0.61	133	133
JUN	-0.016	0.12	-10000	0	-0.88	5	5
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.14	0.14	-10000	0	-0.28	133	133
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
cell morphogenesis	-0.14	0.2	-10000	0	-0.69	3	3
GRB2/SHC	-0.12	0.12	-10000	0	-0.57	1	1
FOS	-0.39	0.44	-10000	0	-0.88	120	120
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.013	0.024	-10000	0	-0.29	1	1
HGF/MET/MUC20	-0.3	0.31	-10000	0	-0.61	133	133
cell migration	-0.11	0.12	-10000	0	-0.56	1	1
GRB2	0	0	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
MET/RANBP10	-0.002	0.044	-10000	0	-0.68	1	1
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.18	0.18	-10000	0	-0.36	134	134
MET/MUC20	-0.002	0.044	0.21	1	-0.69	1	2
RAP1B	-0.099	0.14	-10000	0	-0.54	1	1
RAP1A	-0.099	0.14	-10000	0	-0.54	1	1
HGF/MET/RANBP9	-0.3	0.3	-10000	0	-0.6	133	133
RAF1	-0.18	0.22	-10000	0	-0.71	2	2
STAT3	-0.17	0.18	-10000	0	-0.34	134	134
cell proliferation	-0.21	0.26	-10000	0	-0.46	133	133
RPS6KB1	-0.047	0.049	-10000	0	-0.2	1	1
MAPK3	-0.013	0.02	-10000	0	-0.26	1	1
MAPK1	-0.013	0.02	-10000	0	-0.26	1	1
RANBP9	0	0	-10000	0	-10000	0	0
MAPK8	-0.12	0.21	-10000	0	-0.52	39	39
SRC	-0.17	0.17	-10000	0	-0.34	133	133
PI3K	-0.12	0.13	-10000	0	-0.78	2	2
MET/Glomulin	-0.001	0.041	0.23	1	-0.63	1	2
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	-0.16	0.21	-10000	0	-0.88	1	1
MET	-0.002	0.057	0.32	1	-0.88	1	2
MAP4K1	-0.12	0.16	-10000	0	-0.51	8	8
PTK2	0	0	-10000	0	-10000	0	0
MAP2K2	-0.16	0.21	-10000	0	-0.88	1	1
BAD	0.016	0.038	0.44	2	-10000	0	2
MAP2K4	-0.13	0.21	-10000	0	-0.58	32	32
SHP2/GRB2/SOS1/GAB1	-0.12	0.13	-10000	0	-0.77	1	1
INPPL1	0	0	-10000	0	-10000	0	0
PXN	0	0	-10000	0	-10000	0	0
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	-0.12	0.13	-10000	0	-0.6	1	1
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.44	0.44	-10000	0	-0.88	133	133
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
PTPRJ	0	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.13	0.14	-10000	0	-0.55	2	2
PDPK1	0.003	0.049	0.56	2	-10000	0	2
HGF/MET/SHIP	-0.3	0.31	-10000	0	-0.6	133	133

×

Thromboxane A2 receptor signaling

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
TGM2	-0.013	0.11	-10000	0	-0.88	4	4
GNB1/GNG2	-0.064	0.088	-10000	0	-0.19	75	75
AKT1	-0.026	0.12	0.22	1	-0.22	36	37
EGF	0.081	0.14	0.32	69	-10000	0	69
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.052	0.13	-10000	0	-0.45	16	16
mol:Ca2+	-0.05	0.17	-10000	0	-0.31	79	79
LYN	-0.051	0.13	-10000	0	-0.48	12	12
RhoA/GTP	-0.038	0.057	-10000	0	-0.14	5	5
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.058	0.19	-10000	0	-0.35	79	79
GNG2	-0.003	0.054	-10000	0	-0.88	1	1
ARRB2	0	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.033	0.13	-10000	0	-0.54	8	8
G beta5/gamma2	-0.085	0.12	-10000	0	-0.29	41	41
PRKCH	-0.061	0.2	-10000	0	-0.36	78	78
DNM1	0.004	0.14	0.32	17	-0.88	5	22
TXA2/TP beta/beta Arrestin3	-0.007	0.058	-10000	0	-0.33	5	5
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.052	0.21	-10000	0	-0.88	16	16
G12 family/GTP	-0.094	0.14	-10000	0	-0.31	78	78
ADRBK1	0	0	-10000	0	-10000	0	0
ADRBK2	0.009	0.081	0.32	10	-0.88	1	11
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.045	0.16	0.39	29	-10000	0	29
mol:NADP	-0.007	0.076	-10000	0	-0.88	2	2
RAB11A	0	0	-10000	0	-10000	0	0
PRKG1	-0.028	0.16	0.32	1	-0.88	9	10
mol:IP3	-0.071	0.21	-10000	0	-0.39	79	79
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.11	0.28	-10000	0	-0.53	79	79
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.13	0.22	-10000	0	-0.49	63	63
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.063	0.16	-10000	0	-0.49	22	22
RHOA	0	0	-10000	0	-10000	0	0
PTGIR	-0.062	0.23	-10000	0	-0.88	19	19
PRKCB1	-0.071	0.21	-10000	0	-0.38	79	79
GNAQ	-0.003	0.054	-10000	0	-0.88	1	1
mol:L-citrulline	-0.007	0.076	-10000	0	-0.88	2	2
TXA2/TXA2-R family	-0.11	0.29	-10000	0	-0.55	78	78
LCK	-0.062	0.16	-10000	0	-0.48	21	21
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.068	0.18	-10000	0	-0.59	16	16
TXA2-R family/G12 family/GDP/G beta/gamma	-0.017	0.044	-10000	0	-0.38	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.068	0.17	-10000	0	-0.59	16	16
MAPK14	-0.027	0.14	-10000	0	-0.24	34	34
TGM2/GTP	-0.084	0.24	-10000	0	-0.44	79	79
MAPK11	-0.026	0.14	0.26	1	-0.24	39	40
ARHGEF1	-0.052	0.085	0.17	4	-0.19	17	21
GNAI2	0	0	-10000	0	-10000	0	0
JNK cascade	-0.071	0.22	-10000	0	-0.4	78	78
RAB11/GDP	0	0	-10000	0	-10000	0	0
ICAM1	-0.043	0.16	-10000	0	-0.28	78	78
cAMP biosynthetic process	-0.066	0.2	-10000	0	-0.36	79	79
Gq family/GTP/EBP50	-0.055	0.13	-10000	0	-0.29	52	52
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.05	0.13	-10000	0	-0.45	15	15
GNB5	0.001	0.019	0.32	1	-10000	0	1
GNB1	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.019	0.14	-10000	0	-0.35	22	22
VCAM1	-0.054	0.18	0.27	3	-0.32	77	80
TP beta/Gq family/GDP/G beta5/gamma2	-0.033	0.13	-10000	0	-0.54	8	8
platelet activation	-0.038	0.18	0.29	2	-0.31	78	80
PGI2/IP	-0.049	0.18	-10000	0	-0.69	19	19
PRKACA	-0.056	0.17	-10000	0	-0.47	32	32
Gq family/GDP/G beta5/gamma2	-0.033	0.13	-10000	0	-0.51	9	9
TXA2/TP beta/beta Arrestin2	-0.005	0.11	-10000	0	-0.7	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.08	0.2	-10000	0	-0.5	43	43
mol:DAG	-0.082	0.23	-10000	0	-0.43	79	79
EGFR	-0.013	0.11	-10000	0	-0.88	4	4
TXA2/TP alpha	-0.098	0.27	-10000	0	-0.49	79	79
Gq family/GTP	-0.059	0.14	-10000	0	-0.32	52	52
YES1	-0.051	0.13	-10000	0	-0.45	15	15
GNAI2/GTP	-0.059	0.16	-10000	0	-0.53	16	16
PGD2/DP	-0.041	0.16	-10000	0	-0.69	16	16
SLC9A3R1	-0.003	0.054	-10000	0	-0.88	1	1
FYN	-0.051	0.13	-10000	0	-0.45	15	15
mol:NO	-0.007	0.076	-10000	0	-0.88	2	2
GNA15	0.002	0.027	0.32	2	-10000	0	2
PGK/cGMP	-0.024	0.12	-10000	0	-0.6	11	11
RhoA/GDP	0	0	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.075	0.19	-10000	0	-0.64	18	18
NOS3	-0.007	0.076	-10000	0	-0.88	2	2
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.061	0.2	-10000	0	-0.36	78	78
PRKCB	-0.085	0.23	-10000	0	-0.4	86	86
PRKCE	-0.062	0.2	-10000	0	-0.36	78	78
PRKCD	-0.07	0.21	-10000	0	-0.39	78	78
PRKCG	-0.072	0.21	-10000	0	-0.39	78	78
muscle contraction	-0.097	0.27	-10000	0	-0.5	78	78
PRKCZ	-0.067	0.2	-10000	0	-0.36	82	82
ARR3	0.001	0.019	0.32	1	-10000	0	1
TXA2/TP beta	-0.065	0.19	-10000	0	-0.62	16	16
PRKCQ	-0.069	0.21	-10000	0	-0.38	80	80
MAPKKK cascade	-0.093	0.25	-10000	0	-0.47	79	79
SELE	-0.082	0.22	0.26	1	-0.42	78	79
TP beta/GNAI2/GDP/G beta/gamma	-0.069	0.18	-10000	0	-0.61	16	16
ROCK1	0	0	-10000	0	-10000	0	0
GNA14	-0.15	0.33	-10000	0	-0.88	47	47
chemotaxis	-0.13	0.32	-10000	0	-0.63	78	78
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.02	0.13	-10000	0	-0.88	6	6
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.08	0.22	0.52	13	-0.66	14	27
IHH	0.024	0.18	0.37	14	-0.88	8	22
SHH Np/Cholesterol/GAS1	-0.11	0.24	-10000	0	-0.6	49	49
LRPAP1	0	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.11	0.24	0.59	49	-10000	0	49
SMO/beta Arrestin2	0.006	0.21	0.34	1	-0.74	15	16
SMO	0.007	0.22	0.38	1	-0.79	15	16
AKT1	0.015	0.14	-10000	0	-1.6	1	1
ARRB2	0	0	-10000	0	-10000	0	0
BOC	0.011	0.057	0.32	9	-10000	0	9
ADRBK1	0	0	-10000	0	-10000	0	0
heart looping	0.009	0.22	0.38	1	-0.77	15	16
STIL	0.02	0.2	0.35	7	-0.62	16	23
DHH N/PTCH2	0	0.048	-10000	0	-0.68	1	1
DHH N/PTCH1	0.014	0.19	0.35	2	-0.66	15	17
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
DHH	0.001	0.019	0.32	1	-10000	0	1
PTHLH	0.086	0.24	0.6	1	-0.85	8	9
determination of left/right symmetry	0.009	0.22	0.38	1	-0.77	15	16
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
skeletal system development	0.086	0.23	0.6	1	-0.84	8	9
IHH N/Hhip	-0.36	0.39	-10000	0	-0.74	134	134
DHH N/Hhip	-0.33	0.34	-10000	0	-0.68	130	130
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.009	0.22	0.38	1	-0.77	15	16
pancreas development	-0.42	0.44	0.32	1	-0.88	130	131
HHAT	-0.001	0.06	0.32	2	-0.88	1	3
PI3K	-0.005	0.075	-10000	0	-1.2	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.14	0.32	0.32	1	-0.88	42	43
somite specification	0.009	0.22	0.38	1	-0.77	15	16
SHH Np/Cholesterol/PTCH1	-0.004	0.2	0.32	1	-0.61	21	22
SHH Np/Cholesterol/PTCH2	-0.022	0.12	-10000	0	-0.6	11	11
SHH Np/Cholesterol/Megalin	-0.083	0.23	-10000	0	-0.56	46	46
SHH	-0.01	0.15	-10000	0	-0.74	10	10
catabolic process	0.044	0.21	0.35	13	-0.72	15	28
SMO/Vitamin D3	0.003	0.23	0.42	1	-0.65	22	23
SHH Np/Cholesterol/Hhip	-0.29	0.29	-10000	0	-0.57	137	137
LRP2	-0.097	0.32	0.32	18	-0.88	36	54
receptor-mediated endocytosis	-0.044	0.24	-10000	0	-0.71	19	19
SHH Np/Cholesterol/BOC	-0.016	0.12	-10000	0	-0.6	10	10
SHH Np/Cholesterol/CDO	-0.022	0.12	-10000	0	-0.6	10	10
mesenchymal cell differentiation	0.29	0.29	0.56	137	-10000	0	137
mol:Vitamin D3	0.032	0.21	0.42	1	-0.61	21	22
IHH N/PTCH2	0.008	0.13	0.27	1	-0.6	9	10
CDON	0	0	-10000	0	-10000	0	0
IHH N/PTCH1	0.034	0.23	0.4	16	-0.73	15	31
Megalin/LRPAP1	-0.077	0.24	-10000	0	-0.68	36	36
PTCH2	-0.001	0.06	0.32	2	-0.88	1	3
SHH Np/Cholesterol	-0.021	0.12	-10000	0	-0.61	10	10
PTCH1	0.044	0.21	0.35	13	-0.73	15	28
HHIP	-0.42	0.44	0.32	1	-0.88	130	131

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.001	0.039	-10000	0	-0.57	1	1
epithelial cell differentiation	-0.061	0.1	-10000	0	-0.47	12	12
ITCH	0	0.004	-10000	0	-10000	0	0
WWP1	0.001	0.017	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
EGFR	-0.013	0.11	-10000	0	-0.88	4	4
PRL	0.004	0.033	0.32	3	-10000	0	3
neuron projection morphogenesis	-0.17	0.21	-10000	0	-0.42	106	106
PTPRZ1	0.013	0.063	0.32	11	-10000	0	11
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.19	0.23	-10000	0	-0.47	111	111
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.23	0.27	-10000	0	-0.55	111	111
ADAM17	0	0.004	-10000	0	-10000	0	0
ErbB4/ErbB4	0.001	0.022	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.088	0.22	0.29	1	-0.57	44	45
NCOR1	-0.007	0.076	-10000	0	-0.88	2	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.21	0.25	-10000	0	-0.51	111	111
GRIN2B	-0.2	0.24	-10000	0	-0.49	111	111
ErbB4/ErbB2/betacellulin	-0.006	0.056	-10000	0	-0.51	3	3
STAT1	0.002	0.027	0.32	2	-10000	0	2
HBEGF	-0.003	0.054	-10000	0	-0.88	1	1
PRLR	-0.033	0.17	-10000	0	-0.88	10	10
E4ICDs/ETO2	-0.074	0.19	-10000	0	-0.57	35	35
axon guidance	-0.057	0.096	-10000	0	-10000	0	0
NEDD4	-0.007	0.076	-10000	0	-0.88	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.024	0.13	-10000	0	-0.69	10	10
CBFA2T3	-0.12	0.3	-10000	0	-0.88	35	35
ErbB4/ErbB2/HBEGF	-0.008	0.063	-10000	0	-0.51	4	4
MAPK3	-0.18	0.22	-10000	0	-0.44	111	111
STAT1 (dimer)	0.003	0.027	-10000	0	-10000	0	0
MAPK1	-0.18	0.22	-10000	0	-0.44	111	111
JAK2	-0.003	0.054	-10000	0	-0.88	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.22	0.26	-10000	0	-0.53	111	111
NRG1	-0.28	0.35	-10000	0	-0.69	111	111
NRG3	-0.14	0.33	0.32	5	-0.88	44	49
NRG2	0.068	0.13	0.32	58	-10000	0	58
NRG4	-0.13	0.32	-10000	0	-0.88	41	41
heart development	-0.057	0.096	-10000	0	-10000	0	0
neural crest cell migration	-0.22	0.26	-10000	0	-0.52	111	111
ERBB2	0.01	0.075	-10000	0	-0.69	3	3
WWOX/E4ICDs	0.001	0.018	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.089	0.2	-10000	0	-0.54	44	44
apoptosis	0.056	0.16	0.4	44	-0.23	1	45
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.052	0.1	0.29	2	-10000	0	2
ErbB4/ErbB2/epiregulin	0.015	0.087	-10000	0	-0.52	3	3
ErbB4/ErbB4/betacellulin/betacellulin	0.002	0.023	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.021	0.1	-10000	0	-0.49	12	12
MDM2	0.017	0.024	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.22	0.26	-10000	0	-0.53	111	111
STAT5A	-0.047	0.09	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.22	0.26	-10000	0	-0.52	114	114
DLG4	0	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.005	0.047	-10000	0	-0.54	2	2
STAT5A (dimer)	-0.064	0.11	-10000	0	-0.51	12	12
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.064	0.075	-10000	0	-10000	0	0
LRIG1	0	0	-10000	0	-10000	0	0
EREG	0.031	0.094	0.32	26	-10000	0	26
BTC	0.001	0.019	0.32	1	-10000	0	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.067	0.089	-10000	0	-10000	0	0
ERBB4	0.001	0.022	-10000	0	-10000	0	0
STAT5B	0	0	-10000	0	-10000	0	0
YAP1	0.001	0.007	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.085	0.19	-10000	0	-0.51	44	44
glial cell differentiation	0.005	0.047	0.53	2	-10000	0	2
WWOX	0	0	-10000	0	-10000	0	0
cell proliferation	-0.2	0.27	-10000	0	-0.51	111	111

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.1	0.42	-10000	0	-0.99	48	48
NCK1/PAK1/Dok-R	-0.083	0.17	-10000	0	-0.44	48	48
NCK1/Dok-R	-0.22	0.46	-10000	0	-1.2	48	48
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
mol:beta2-estradiol	-0.002	0.028	0.25	2	-10000	0	2
RELA	0	0	-10000	0	-10000	0	0
SHC1	0	0.002	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.072	0.25	-10000	0	-0.88	24	24
TNIP2	0	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.2	0.41	-10000	0	-1.1	48	48
FN1	-0.003	0.054	-10000	0	-0.88	1	1
PLD2	-0.16	0.5	-10000	0	-1.2	48	48
PTPN11	0	0	-10000	0	-10000	0	0
GRB14	-0.023	0.14	-10000	0	-0.88	7	7
ELK1	-0.14	0.45	-10000	0	-1.1	48	48
GRB7	-0.004	0.1	0.32	5	-0.88	3	8
PAK1	0	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.21	0.44	-10000	0	-1.1	48	48
CDKN1A	-0.055	0.31	-10000	0	-0.69	49	49
ITGA5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.22	0.46	-10000	0	-1.2	48	48
CRK	0	0	-10000	0	-10000	0	0
mol:NO	-0.052	0.32	-10000	0	-0.71	48	48
PLG	-0.25	0.53	-10000	0	-1.3	49	49
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.16	0.36	-10000	0	-0.93	48	48
GRB2	0	0	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
ANGPT2	-0.002	0.16	-10000	0	-0.64	6	6
BMX	-0.21	0.56	-10000	0	-1.4	48	48
ANGPT1	0.003	0.18	-10000	0	-1.6	2	2
tube development	-0.069	0.34	-10000	0	-0.77	48	48
ANGPT4	0.009	0.051	0.32	7	-10000	0	7
response to hypoxia	-0.009	0.028	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.24	0.49	-10000	0	-1.3	48	48
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	-0.051	0.22	0.32	4	-0.88	17	21
STAT5A (dimer)	-0.091	0.39	-10000	0	-0.9	48	48
mol:L-citrulline	-0.052	0.32	-10000	0	-0.71	48	48
AGTR1	-0.1	0.28	-10000	0	-0.88	31	31
MAPK14	-0.17	0.52	-10000	0	-1.3	48	48
Tie2/SHP2	-0.23	0.48	-10000	0	-1.3	48	48
TEK	-0.25	0.54	-10000	0	-1.4	48	48
RPS6KB1	-0.097	0.4	-10000	0	-0.95	48	48
Angiotensin II/AT1	-0.077	0.22	-10000	0	-0.69	31	31
Tie2/Ang1/GRB2	-0.23	0.48	-10000	0	-1.3	48	48
MAPK3	-0.14	0.46	-10000	0	-1.1	48	48
MAPK1	-0.14	0.46	-10000	0	-1.1	48	48
Tie2/Ang1/GRB7	-0.23	0.49	-10000	0	-1.3	48	48
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.18	0.52	-10000	0	-1.3	48	48
PI3K	-0.14	0.49	-10000	0	-1.2	48	48
FES	-0.17	0.52	-10000	0	-1.3	48	48
Crk/Dok-R	-0.22	0.46	-10000	0	-1.2	48	48
Tie2/Ang1/ABIN2	-0.23	0.48	-10000	0	-1.3	48	48
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.082	0.38	-10000	0	-0.87	48	48
STAT5A	0	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.097	0.4	-10000	0	-0.95	48	48
Tie2/Ang2	-0.13	0.47	-10000	0	-1.1	48	48
Tie2/Ang1	-0.19	0.54	-10000	0	-1.3	48	48
FOXO1	-0.081	0.38	-10000	0	-0.88	48	48
ELF1	-0.007	0.069	-10000	0	-0.92	1	1
ELF2	-0.17	0.51	-10000	0	-1.2	48	48
mol:Choline	-0.15	0.48	-10000	0	-1.2	48	48
cell migration	-0.046	0.093	-10000	0	-0.24	48	48
FYN	-0.09	0.39	-10000	0	-0.9	48	48
DOK2	-0.01	0.092	-10000	0	-0.88	3	3
negative regulation of cell cycle	-0.044	0.28	-10000	0	-0.62	49	49
ETS1	0.011	0.023	-10000	0	-10000	0	0
PXN	-0.062	0.33	-10000	0	-0.76	48	48
ITGB1	0	0	-10000	0	-10000	0	0
NOS3	-0.071	0.36	-10000	0	-0.82	48	48
RAC1	0	0	-10000	0	-10000	0	0
TNF	-0.029	0.2	0.33	2	-0.88	13	15
MAPKKK cascade	-0.15	0.48	-10000	0	-1.2	48	48
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
Tie2/Ang1/Shc	-0.21	0.5	-10000	0	-1.3	48	48
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
vasculogenesis	-0.039	0.28	-10000	0	-0.63	48	48
mol:Phosphatidic acid	-0.15	0.48	-10000	0	-1.2	48	48
mol:Angiotensin II	0.002	0.004	-10000	0	-10000	0	0
mol:NADP	-0.052	0.32	-10000	0	-0.71	48	48
Rac1/GTP	-0.16	0.33	-10000	0	-0.87	48	48
MMP2	-0.17	0.52	-10000	0	-1.3	48	48

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.013	0.14	-10000	0	-0.42	20	20
TBX21	-0.18	0.44	0.62	1	-1.1	36	37
B2M	-0.002	0.009	-10000	0	-10000	0	0
TYK2	0.008	0.019	-10000	0	-10000	0	0
IL12RB1	-0.022	0.17	-10000	0	-0.91	9	9
GADD45B	-0.3	0.58	-10000	0	-1.2	71	71
IL12RB2	-0.016	0.18	0.32	5	-0.88	10	15
GADD45G	-0.3	0.57	-10000	0	-1.2	70	70
natural killer cell activation	-0.004	0.023	-10000	0	-10000	0	0
RELB	0.001	0.019	0.32	1	-10000	0	1
RELA	0	0	-10000	0	-10000	0	0
IL18	-0.007	0.12	0.32	2	-0.89	5	7
IL2RA	-0.005	0.14	0.32	10	-0.88	5	15
IFNG	0.011	0.057	0.32	9	-10000	0	9
STAT3 (dimer)	-0.16	0.36	0.54	1	-0.74	55	56
HLA-DRB5	-0.016	0.14	0.31	3	-0.88	6	9
FASLG	-0.18	0.45	0.72	1	-1.1	38	39
NF kappa B2 p52/RelB	-0.22	0.36	-10000	0	-0.85	51	51
CD4	-0.066	0.23	-10000	0	-0.89	20	20
SOCS1	-0.005	0.078	0.32	1	-0.88	2	3
EntrezGene:6955	-0.012	0.018	-10000	0	-10000	0	0
CD3D	-0.025	0.17	0.31	7	-0.89	9	16
CD3E	-0.038	0.18	0.32	1	-0.9	11	12
CD3G	-0.037	0.19	0.31	6	-0.9	12	18
IL12Rbeta2/JAK2	-0.011	0.15	-10000	0	-0.7	11	11
CCL3	-0.23	0.54	0.62	1	-1.3	42	43
CCL4	-0.2	0.5	0.62	1	-1.2	39	40
HLA-A	-0.002	0.008	-10000	0	-10000	0	0
IL18/IL18R	-0.098	0.31	-10000	0	-0.72	48	48
NOS2	-0.14	0.39	0.61	1	-0.84	47	48
IL12/IL12R/TYK2/JAK2/SPHK2	-0.011	0.13	0.3	1	-0.39	19	20
IL1R1	-0.16	0.42	0.62	1	-1.1	34	35
IL4	0.004	0.023	-10000	0	-10000	0	0
JAK2	0.005	0.059	-10000	0	-0.91	1	1
EntrezGene:6957	-0.011	0.018	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.18	0.53	0.39	1	-1.4	38	39
RAB7A	-0.2	0.4	-10000	0	-0.77	69	69
lysosomal transport	-0.19	0.38	-10000	0	-0.72	71	71
FOS	-0.62	0.75	0.46	1	-1.4	121	122
STAT4 (dimer)	-0.2	0.42	0.55	1	-0.79	71	72
STAT5A (dimer)	-0.22	0.36	0.4	4	-0.85	51	55
GZMA	-0.17	0.44	0.69	1	-1.1	34	35
GZMB	-0.18	0.44	0.69	1	-1	41	42
HLX	0	0	-10000	0	-10000	0	0
LCK	-0.18	0.47	0.62	1	-0.98	51	52
TCR/CD3/MHC II/CD4	-0.14	0.31	0.29	1	-0.71	40	41
IL2/IL2R	-0.048	0.2	0.38	2	-0.64	25	27
MAPK14	-0.28	0.51	0.55	1	-0.91	89	90
CCR5	-0.16	0.4	-10000	0	-0.9	42	42
IL1B	-0.13	0.33	-10000	0	-0.9	41	41
STAT6	-0.034	0.14	0.39	1	-0.36	12	13
STAT4	-0.032	0.17	0.32	1	-0.88	10	11
STAT3	0	0	-10000	0	-10000	0	0
STAT1	0.002	0.027	0.32	2	-10000	0	2
NFKB1	0	0	-10000	0	-10000	0	0
NFKB2	0	0	-10000	0	-10000	0	0
IL12B	0.006	0.035	0.32	2	-10000	0	2
CD8A	-0.062	0.23	0.32	3	-0.89	19	22
CD8B	-0.044	0.21	0.32	7	-0.89	15	22
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.013	0.14	0.41	20	-10000	0	20
IL2RB	-0.066	0.23	-10000	0	-0.88	20	20
proteasomal ubiquitin-dependent protein catabolic process	-0.18	0.38	0.55	1	-0.71	71	72
IL2RG	-0.006	0.12	0.32	6	-0.88	4	10
IL12	0.016	0.053	-10000	0	-10000	0	0
STAT5A	0	0	-10000	0	-10000	0	0
CD247	-0.008	0.08	0.32	1	-0.89	2	3
IL2	0	0	-10000	0	-10000	0	0
SPHK2	0	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.016	0.057	0.32	7	-10000	0	7
IL12/IL12R/TYK2/JAK2	-0.2	0.53	0.7	1	-1.1	51	52
MAP2K3	-0.27	0.52	0.55	1	-0.9	89	90
RIPK2	0	0	-10000	0	-10000	0	0
MAP2K6	-0.28	0.52	0.55	1	-0.9	92	93
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.012	0.11	0.32	1	-0.88	4	5
IL18RAP	-0.046	0.21	-10000	0	-0.89	16	16
IL12Rbeta1/TYK2	-0.015	0.14	-10000	0	-0.73	9	9
EOMES	-0.17	0.5	-10000	0	-1.5	34	34
STAT1 (dimer)	-0.14	0.35	0.68	1	-0.72	53	54
T cell proliferation	-0.16	0.33	0.49	1	-0.61	72	73
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.12	0.31	-10000	0	-0.89	37	37
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.26	0.32	-10000	0	-0.72	71	71
ATF2	-0.25	0.46	0.53	1	-0.81	91	92

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0	0	-10000	0	-10000	0	0
VLDLR	-0.025	0.26	0.32	32	-0.88	19	51
LRPAP1	0	0	-10000	0	-10000	0	0
NUDC	0	0	-10000	0	-10000	0	0
RELN/LRP8	-0.19	0.3	-10000	0	-0.59	92	92
CaM/Ca2+	0	0	-10000	0	-10000	0	0
KATNA1	0	0	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.18	0.26	-10000	0	-0.54	92	92
IQGAP1/CaM	0	0	-10000	0	-10000	0	0
DAB1	-0.14	0.33	-10000	0	-0.88	44	44
IQGAP1	0	0	-10000	0	-10000	0	0
PLA2G7	0.009	0.081	0.32	10	-0.88	1	11
CALM1	0	0	-10000	0	-10000	0	0
DYNLT1	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.025	0.07	-10000	0	-10000	0	0
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0	0	-10000	0	-10000	0	0
CDK5R1	0.001	0.019	0.32	1	-10000	0	1
LIS1/Poliovirus Protein 3A	0	0	-10000	0	-10000	0	0
CDK5R2	0.009	0.054	0.32	8	-10000	0	8
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.32	0.39	-10000	0	-0.69	131	131
YWHAE	0	0	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.14	0.2	-10000	0	-0.42	87	87
MAP1B	0.002	0.016	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
p35/CDK5	-0.16	0.23	-10000	0	-0.47	92	92
RELN	-0.3	0.42	0.32	2	-0.88	92	94
PAFAH/LIS1	0.006	0.057	-10000	0	-0.6	1	1
LIS1/CLIP170	0	0	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.11	0.16	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.19	0.27	-10000	0	-0.46	106	106
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.15	0.22	-10000	0	-0.45	89	89
LIS1/IQGAP1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PAFAH1B1	0.017	0	-10000	0	-10000	0	0
PAFAH1B3	0.03	0.092	0.32	25	-10000	0	25
PAFAH1B2	0	0	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0	0	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.13	0.19	-10000	0	-10000	0	0
LRP8	0.037	0.1	0.32	31	-10000	0	31
NDEL1/Katanin 60	-0.14	0.2	-10000	0	-0.42	87	87
P39/CDK5	-0.16	0.23	-10000	0	-0.48	92	92
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-10000	0	-10000	0	0
CDK5	-0.17	0.24	-10000	0	-0.5	92	92
PPP2R5D	0	0	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.28	0.35	-10000	0	-0.6	131	131
RELN/VLDLR	-0.19	0.34	0.37	7	-0.6	100	107
CDC42	0	0	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.14	0.32	-10000	0	-0.88	43	43
GNB1/GNG2	-0.16	0.26	-10000	0	-0.77	27	27
mol:DAG	-0.14	0.23	-10000	0	-0.67	27	27
PLCG1	-0.15	0.24	-10000	0	-0.71	27	27
YES1	-0.17	0.28	-10000	0	-0.81	26	26
FZD3	-0.02	0.13	-10000	0	-0.88	6	6
FZD6	0.001	0.019	0.32	1	-10000	0	1
G protein	-0.15	0.25	-10000	0	-0.72	27	27
MAP3K7	-0.089	0.2	-10000	0	-0.53	27	27
mol:Ca2+	-0.14	0.22	-10000	0	-0.64	27	27
mol:IP3	-0.14	0.23	-10000	0	-0.67	27	27
NLK	-0.008	0.012	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
CAMK2A	-0.12	0.21	-10000	0	-0.59	27	27
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.18	0.3	-10000	0	-0.49	102	102
CSNK1A1	0	0	-10000	0	-10000	0	0
GNAS	-0.17	0.28	-10000	0	-0.81	26	26
GO:0007205	-0.12	0.24	-10000	0	-0.66	27	27
WNT6	0.014	0.065	0.32	12	-10000	0	12
WNT4	-0.087	0.33	0.32	29	-0.88	37	66
NFAT1/CK1 alpha	-0.22	0.3	-10000	0	-0.68	60	60
GNG2	-0.003	0.054	-10000	0	-0.88	1	1
WNT5A	-0.079	0.27	0.32	5	-0.88	26	31
WNT11	-0.23	0.39	-10000	0	-0.88	71	71
CDC42	-0.16	0.26	-10000	0	-0.76	26	26

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.086	0.16	0.36	1	-0.44	20	21
IKBKB	-0.025	0.081	-10000	0	-0.34	2	2
AKT1	-0.061	0.12	0.23	2	-0.27	28	30
IKBKG	-0.024	0.086	-10000	0	-0.31	4	4
CALM1	-0.055	0.12	-10000	0	-0.51	7	7
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
MAP3K1	-0.13	0.22	0.44	1	-0.47	54	55
MAP3K7	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.07	0.13	-10000	0	-0.55	7	7
DOK1	0	0	-10000	0	-10000	0	0
AP-1	-0.11	0.13	0.26	1	-0.27	66	67
LYN	0	0	-10000	0	-10000	0	0
BLNK	-0.02	0.13	-10000	0	-0.88	6	6
SHC1	0	0	-10000	0	-10000	0	0
BCR complex	-0.17	0.3	0.44	1	-0.68	69	70
CD22	-0.23	0.3	0.35	1	-0.61	86	87
CAMK2G	-0.045	0.12	-10000	0	-0.47	7	7
CSNK2A1	0	0	-10000	0	-10000	0	0
INPP5D	-0.003	0.054	-10000	0	-0.88	1	1
SHC/GRB2/SOS1	-0.13	0.22	-10000	0	-0.88	4	4
GO:0007205	-0.065	0.13	-10000	0	-0.56	7	7
SYK	-0.003	0.054	-10000	0	-0.88	1	1
ELK1	-0.056	0.13	-10000	0	-0.52	7	7
NFATC1	-0.11	0.19	-10000	0	-0.42	48	48
B-cell antigen/BCR complex	-0.17	0.3	0.44	1	-0.68	69	70
PAG1/CSK	-0.004	0.06	-10000	0	-0.68	2	2
NFKBIB	-0.001	0.028	-10000	0	-10000	0	0
HRAS	-0.048	0.14	-10000	0	-0.53	7	7
NFKBIA	-0.001	0.028	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.004	0.022	-10000	0	-10000	0	0
RasGAP/Csk	-0.39	0.38	0.35	1	-0.66	159	160
mol:GDP	-0.052	0.12	0.26	1	-0.52	7	8
PTEN	-0.007	0.076	-10000	0	-0.88	2	2
CD79B	0.001	0.019	0.32	1	-10000	0	1
NF-kappa-B/RelA/I kappa B alpha	0.004	0.022	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.14	0.23	0.34	1	-0.5	69	70
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
mol:IP3	-0.071	0.13	-10000	0	-0.56	7	7
CSK	0	0	-10000	0	-10000	0	0
FOS	-0.26	0.28	-10000	0	-0.56	122	122
CHUK	-0.024	0.086	-10000	0	-0.28	8	8
IBTK	0	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.067	0.13	-10000	0	-0.52	13	13
PTPN6	-0.21	0.28	0.32	1	-0.61	70	71
RELA	0	0	-10000	0	-10000	0	0
BCL2A1	0	0.039	-10000	0	-0.14	15	15
VAV2	-0.18	0.24	0.31	1	-0.54	68	69
ubiquitin-dependent protein catabolic process	0.002	0.027	-10000	0	-10000	0	0
BTK	-0.024	0.14	-10000	0	-1.1	4	4
CD19	-0.19	0.25	0.35	1	-0.53	80	81
MAP4K1	-0.017	0.13	0.32	2	-0.88	6	8
CD72	-0.011	0.11	0.32	2	-0.88	4	6
PAG1	-0.005	0.078	0.32	1	-0.88	2	3
MAPK14	-0.1	0.18	0.42	1	-0.47	22	23
SH3BP5	-0.007	0.076	-10000	0	-0.88	2	2
PIK3AP1	-0.061	0.15	-10000	0	-0.57	10	10
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.13	0.23	-10000	0	-0.5	69	69
RAF1	-0.039	0.14	-10000	0	-0.52	6	6
RasGAP/p62DOK/SHIP	-0.37	0.36	-10000	0	-0.63	159	159
CD79A	-0.22	0.39	0.32	6	-0.88	69	75
re-entry into mitotic cell cycle	-0.11	0.13	0.25	1	-0.27	66	67
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
MAPK3	-0.02	0.12	-10000	0	-0.42	6	6
MAPK1	-0.02	0.12	-10000	0	-0.42	6	6
CD72/SHP1	-0.2	0.27	0.48	1	-0.6	63	64
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.12	0.2	0.42	1	-0.43	61	62
actin cytoskeleton organization	-0.14	0.22	-10000	0	-0.46	68	68
NF-kappa-B/RelA	0.012	0.044	-10000	0	-10000	0	0
Calcineurin	-0.054	0.095	-10000	0	-0.44	6	6
PI3K	-0.17	0.22	-10000	0	-0.53	59	59
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.073	0.14	0.28	1	-0.55	8	9
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.17	0.27	0.65	1	-1	15	16
DAPP1	-0.19	0.29	0.5	1	-1.1	14	15
cytokine secretion	-0.1	0.17	-10000	0	-0.39	48	48
mol:DAG	-0.071	0.13	-10000	0	-0.56	7	7
PLCG2	-0.016	0.12	-10000	0	-0.88	5	5
MAP2K1	-0.03	0.13	-10000	0	-0.47	6	6
B-cell antigen/BCR complex/FcgammaRIIB	-0.44	0.42	0.39	1	-0.75	158	159
mol:PI-3-4-5-P3	-0.12	0.15	0.35	1	-0.36	58	59
ETS1	-0.036	0.11	-10000	0	-0.44	6	6
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.14	0.25	0.36	1	-0.54	72	73
B-cell antigen/BCR complex/LYN	-0.21	0.26	0.35	1	-0.56	80	81
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	-0.003	0.054	-10000	0	-0.88	1	1
RAC1	-0.15	0.23	-10000	0	-0.49	67	67
B-cell antigen/BCR complex/LYN/SYK	-0.24	0.32	0.39	1	-0.7	73	74
CARD11	-0.07	0.17	-10000	0	-0.62	14	14
FCGR2B	-0.44	0.44	0.32	2	-0.88	136	138
PPP3CA	0	0	-10000	0	-10000	0	0
BCL10	0	0	-10000	0	-10000	0	0
IKK complex	-0.005	0.038	0.12	1	-0.14	1	2
PTPRC	-0.064	0.23	0.32	1	-0.88	20	21
PDPK1	-0.075	0.1	0.21	2	-0.27	24	26
PPP3CB	0	0	-10000	0	-10000	0	0
PPP3CC	0	0	-10000	0	-10000	0	0
POU2F2	0.004	0.03	0.11	1	-0.15	7	8

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.029	0.16	-10000	0	-0.8	9	9
alphaM/beta2 Integrin/GPIbA	-0.024	0.12	0.34	1	-0.62	9	10
alphaM/beta2 Integrin/proMMP-9	-0.002	0.18	0.4	1	-0.67	13	14
PLAUR	-0.003	0.083	0.32	3	-0.88	2	5
HMGB1	-0.007	0.016	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.018	0.091	-10000	0	-0.64	5	5
AGER	-0.002	0.043	0.32	4	-10000	0	4
RAP1A	0	0	-10000	0	-10000	0	0
SELPLG	-0.003	0.054	-10000	0	-0.88	1	1
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.038	0.13	0.32	1	-0.68	5	6
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.026	0.21	0.32	47	-0.88	9	56
CYR61	-0.085	0.26	-10000	0	-0.88	26	26
TLN1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.11	0.19	-10000	0	-0.55	31	31
RHOA	0	0	-10000	0	-10000	0	0
P-selectin oligomer	-0.27	0.4	-10000	0	-0.88	82	82
MYH2	-0.16	0.32	-10000	0	-0.69	52	52
MST1R	0.038	0.16	0.32	43	-0.88	4	47
leukocyte activation during inflammatory response	-0.29	0.29	-10000	0	-0.55	140	140
APOB	-0.049	0.2	-10000	0	-0.88	15	15
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	-0.017	0.15	0.32	5	-0.88	7	12
JAM3	0.001	0.019	0.32	1	-10000	0	1
GP1BA	-0.008	0.11	0.32	4	-0.88	4	8
alphaM/beta2 Integrin/CTGF	-0.027	0.12	-10000	0	-0.7	8	8
alphaM/beta2 Integrin	-0.13	0.22	-10000	0	-0.53	45	45
JAM3 homodimer	0.001	0.019	0.32	1	-10000	0	1
ICAM2	0.001	0.019	0.32	1	-10000	0	1
ICAM1	0	0	-10000	0	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.13	0.22	-10000	0	-0.52	45	45
cell adhesion	-0.024	0.12	0.34	1	-0.62	9	10
NFKB1	-0.073	0.2	-10000	0	-0.77	10	10
THY1	0.078	0.14	0.32	66	-10000	0	66
RhoA/GDP	0	0	-10000	0	-10000	0	0
Lipoprotein(a)	-0.32	0.33	-10000	0	-0.64	136	136
alphaM/beta2 Integrin/LRP/tPA	-0.018	0.11	-10000	0	-0.65	7	7
IL6	-0.15	0.39	-10000	0	-1.1	39	39
ITGB2	-0.013	0.082	0.32	1	-0.9	2	3
elevation of cytosolic calcium ion concentration	-0.012	0.1	0.37	2	-0.57	7	9
alphaM/beta2 Integrin/JAM2/JAM3	-0.036	0.14	0.38	1	-0.57	16	17
JAM2	-0.035	0.18	0.32	1	-0.88	11	12
alphaM/beta2 Integrin/ICAM1	-0.044	0.19	-10000	0	-0.51	33	33
alphaM/beta2 Integrin/uPA/Plg	-0.11	0.22	-10000	0	-0.56	52	52
RhoA/GTP	-0.19	0.33	-10000	0	-0.55	91	91
positive regulation of phagocytosis	-0.1	0.19	-10000	0	-0.61	26	26
Ron/MSP	-0.045	0.22	-10000	0	-0.67	28	28
alphaM/beta2 Integrin/uPAR/uPA	-0.012	0.11	0.38	2	-0.58	7	9
alphaM/beta2 Integrin/uPAR	-0.02	0.11	-10000	0	-0.63	7	7
PLAU	0.007	0.047	0.32	6	-10000	0	6
PLAT	-0.002	0.085	0.32	4	-0.88	2	6
actin filament polymerization	-0.15	0.29	-10000	0	-0.56	69	69
MST1	-0.079	0.25	-10000	0	-0.88	24	24
alphaM/beta2 Integrin/lipoprotein(a)	-0.29	0.29	-10000	0	-0.56	140	140
TNF	-0.093	0.27	-10000	0	-1	16	16
RAP1B	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.013	0.097	-10000	0	-0.64	5	5
fibrinolysis	-0.11	0.22	-10000	0	-0.56	52	52
HCK	-0.03	0.16	-10000	0	-0.88	9	9
dendritic cell antigen processing and presentation	-0.13	0.22	-10000	0	-0.52	45	45
VTN	-0.039	0.18	-10000	0	-0.88	12	12
alphaM/beta2 Integrin/CYR61	-0.075	0.21	-10000	0	-0.67	28	28
LPA	-0.42	0.44	-10000	0	-0.88	129	129
LRP1	-0.003	0.054	-10000	0	-0.88	1	1
cell migration	-0.025	0.19	0.3	1	-0.69	17	18
FN1	-0.003	0.054	-10000	0	-0.88	1	1
alphaM/beta2 Integrin/Thy1	0.033	0.14	0.4	2	-0.64	5	7
MPO	-0.025	0.15	0.32	1	-0.88	8	9
KNG1	-0.089	0.26	-10000	0	-0.88	27	27
RAP1/GDP	0	0	-10000	0	-10000	0	0
ROCK1	-0.15	0.3	-10000	0	-0.51	87	87
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.16	0.34	-10000	0	-0.88	48	48
CTGF	-0.013	0.11	-10000	0	-0.88	4	4
alphaM/beta2 Integrin/Hck	-0.037	0.17	-10000	0	-0.8	11	11
ITGAM	-0.015	0.1	0.3	2	-0.92	3	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.18	0.28	-10000	0	-0.59	84	84
HP	-0.28	0.41	-10000	0	-0.88	86	86
leukocyte adhesion	-0.014	0.16	0.34	2	-0.55	11	13
SELP	-0.27	0.4	-10000	0	-0.88	82	82

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.007	0.065	-10000	0	-0.86	1	1
Syndecan-4/Syndesmos	-0.12	0.31	-10000	0	-0.85	34	34
positive regulation of JNK cascade	-0.29	0.3	-10000	0	-0.8	48	48
Syndecan-4/ADAM12	-0.11	0.31	-10000	0	-0.84	35	35
CCL5	-0.025	0.15	0.32	1	-0.88	8	9
Rac1/GDP	0	0	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
ITGA5	0	0	-10000	0	-10000	0	0
SDCBP	0	0	-10000	0	-10000	0	0
PLG	-0.15	0.33	-10000	0	-0.86	48	48
ADAM12	0.033	0.12	0.32	31	-0.88	1	32
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.026	0.046	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.17	0.33	-10000	0	-0.7	63	63
Syndecan-4/CXCL12/CXCR4	-0.32	0.33	-10000	0	-0.88	48	48
Syndecan-4/Laminin alpha3	-0.099	0.33	-10000	0	-0.86	34	34
MDK	0.17	0.16	0.32	142	-10000	0	142
Syndecan-4/FZD7	-0.12	0.31	-10000	0	-0.82	37	37
Syndecan-4/Midkine	-0.031	0.36	-10000	0	-0.84	34	34
FZD7	-0.005	0.1	0.32	4	-0.88	3	7
Syndecan-4/FGFR1/FGF	-0.15	0.29	-10000	0	-0.79	40	40
THBS1	-0.12	0.3	-10000	0	-0.88	37	37
integrin-mediated signaling pathway	-0.14	0.3	-10000	0	-0.74	45	45
positive regulation of MAPKKK cascade	-0.29	0.3	-10000	0	-0.8	48	48
Syndecan-4/TACI	-0.12	0.31	-10000	0	-0.84	35	35
CXCR4	-0.007	0.076	-10000	0	-0.88	2	2
cell adhesion	-0.001	0.025	-10000	0	-0.4	1	1
Syndecan-4/Dynamin	-0.12	0.31	-10000	0	-0.85	34	34
Syndecan-4/TSP1	-0.18	0.34	-10000	0	-0.71	67	67
Syndecan-4/GIPC	-0.12	0.31	-10000	0	-0.85	34	34
Syndecan-4/RANTES	-0.13	0.32	-10000	0	-0.82	40	40
ITGB1	0	0	-10000	0	-10000	0	0
LAMA1	-0.078	0.29	0.32	17	-0.88	30	47
LAMA3	0.039	0.15	0.32	41	-0.88	3	44
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	0.026	0.056	-10000	0	-10000	0	0
Syndecan-4/alpha-Actinin	-0.12	0.31	-10000	0	-0.85	34	34
TFPI	-0.043	0.19	-10000	0	-0.88	13	13
F2	-0.074	0.25	-10000	0	-0.86	24	24
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
positive regulation of cell adhesion	-0.15	0.33	-10000	0	-0.82	37	37
ACTN1	0	0	-10000	0	-10000	0	0
TNC	-0.043	0.21	0.32	5	-0.88	15	20
Syndecan-4/CXCL12	-0.32	0.36	-10000	0	-0.63	129	129
FGF6	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
CXCL12	-0.36	0.43	-10000	0	-0.88	111	111
TNFRSF13B	-0.001	0.06	0.32	2	-0.88	1	3
FGF2	-0.051	0.22	0.32	4	-0.88	17	21
FGFR1	-0.007	0.097	0.32	2	-0.88	3	5
Syndecan-4/PI-4-5-P2	-0.1	0.32	-10000	0	-0.86	34	34
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.001	0.051	-10000	0	-0.83	1	1
cell migration	-0.007	0.014	-10000	0	-10000	0	0
PRKCD	0.003	0.009	-10000	0	-10000	0	0
vasculogenesis	-0.17	0.32	-10000	0	-0.67	67	67
SDC4	-0.11	0.35	-10000	0	-0.94	34	34
Syndecan-4/Tenascin C	-0.14	0.33	-10000	0	-0.79	45	45
Syndecan-4/PI-4-5-P2/PKC alpha	-0.021	0.036	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.12	0.31	-10000	0	-0.85	34	34
MMP9	0.026	0.21	0.32	47	-0.88	9	56
Rac1/GTP	-0.001	0.026	-10000	0	-0.42	1	1
cytoskeleton organization	-0.11	0.29	-10000	0	-0.8	34	34
GIPC1	0.001	0.019	0.32	1	-10000	0	1
Syndecan-4/TFPI	-0.14	0.34	-10000	0	-0.85	41	41

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.004	0.033	0.32	3	-10000	0	3
CCL5	-0.025	0.15	0.32	1	-0.88	8	9
SDCBP	0	0	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.047	0.22	-10000	0	-0.63	17	17
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.082	0.19	0.37	2	-0.74	11	13
Syndecan-1/Syntenin	-0.086	0.18	-10000	0	-0.74	11	11
MAPK3	-0.074	0.16	-10000	0	-0.67	11	11
HGF/MET	-0.34	0.35	-10000	0	-0.69	133	133
TGFB1/TGF beta receptor Type II	0.004	0.033	0.32	3	-10000	0	3
BSG	0.002	0.027	0.32	2	-10000	0	2
keratinocyte migration	-0.08	0.19	0.37	2	-0.73	11	13
Syndecan-1/RANTES	-0.1	0.22	0.4	1	-0.81	16	17
Syndecan-1/CD147	-0.088	0.17	-10000	0	-0.72	11	11
Syndecan-1/Syntenin/PIP2	-0.09	0.17	-10000	0	-0.72	11	11
LAMA5	0.006	0.043	0.32	5	-10000	0	5
positive regulation of cell-cell adhesion	-0.088	0.17	-10000	0	-0.7	11	11
MMP7	-0.17	0.39	0.32	26	-0.88	60	86
HGF	-0.44	0.44	-10000	0	-0.88	133	133
Syndecan-1/CASK	-0.061	0.2	-10000	0	-0.6	17	17
Syndecan-1/HGF/MET	-0.32	0.33	0.27	1	-0.62	131	132
regulation of cell adhesion	-0.038	0.18	-10000	0	-0.64	11	11
HPSE	-0.051	0.21	0.32	1	-0.88	16	17
positive regulation of cell migration	-0.047	0.22	-10000	0	-0.63	17	17
SDC1	-0.048	0.22	-10000	0	-0.64	17	17
Syndecan-1/Collagen	-0.047	0.22	-10000	0	-0.63	17	17
PPIB	0	0	-10000	0	-10000	0	0
MET	-0.002	0.057	0.32	1	-0.88	1	2
PRKACA	0	0	-10000	0	-10000	0	0
MMP9	0.026	0.21	0.32	47	-0.88	9	56
MAPK1	-0.074	0.16	-10000	0	-0.67	11	11
homophilic cell adhesion	-0.046	0.22	-10000	0	-0.62	17	17
MMP1	0.078	0.14	0.32	66	-10000	0	66

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.15	0.16	-10000	0	-0.47	19	19
NT3 (dimer)/TRKC	-0.4	0.37	-10000	0	-0.72	148	148
NT3 (dimer)/TRKB	-0.61	0.57	-10000	0	-1	165	165
SHC/Grb2/SOS1/GAB1/PI3K	-0.003	0.044	-10000	0	-0.72	1	1
RAPGEF1	0	0	-10000	0	-10000	0	0
BDNF	0.012	0.06	0.32	10	-10000	0	10
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
DYNLT1	0	0	-10000	0	-10000	0	0
NTRK1	0.002	0.027	0.32	2	-10000	0	2
NTRK2	-0.16	0.35	0.32	8	-0.88	50	58
NTRK3	-0.048	0.21	0.32	4	-0.88	16	20
NT-4/5 (dimer)/TRKB	-0.32	0.42	-10000	0	-0.77	116	116
neuron apoptosis	0.17	0.23	0.58	47	-0.29	1	48
SHC 2-3/Grb2	-0.18	0.25	0.3	1	-0.65	47	48
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.19	0.27	-10000	0	-0.48	101	101
SHC3	-0.16	0.25	0.29	2	-0.46	90	92
STAT3 (dimer)	-0.015	0.075	-10000	0	-0.4	10	10
NT3 (dimer)/TRKA	-0.52	0.47	-10000	0	-0.86	162	162
RIN/GDP	-0.095	0.13	-10000	0	-0.26	44	44
GIPC1	0.001	0.019	0.32	1	-10000	0	1
KRAS	0	0	-10000	0	-10000	0	0
DNAJA3	-0.19	0.24	0.28	1	-0.48	105	106
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	-0.019	0.21	-10000	0	-1.1	10	10
MAGED1	-0.003	0.054	-10000	0	-0.88	1	1
PTPN11	0	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.004	0.033	0.32	3	-10000	0	3
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.021	0.12	-10000	0	-0.6	11	11
TRKA/NEDD4-2	0.002	0.019	-10000	0	-10000	0	0
ELMO1	-0.003	0.054	-10000	0	-0.88	1	1
RhoG/GTP/ELMO1/DOCK1	-0.013	0.1	-10000	0	-0.71	5	5
NGF	-0.035	0.18	0.32	1	-0.88	11	12
HRAS	0.002	0.027	0.32	2	-10000	0	2
DOCK1	-0.016	0.12	-10000	0	-0.88	5	5
GAB2	0	0	-10000	0	-10000	0	0
RIT2	0	0	-10000	0	-10000	0	0
RIT1	0	0	-10000	0	-10000	0	0
FRS2	0	0	-10000	0	-10000	0	0
DNM1	0.004	0.14	0.32	17	-0.88	5	22
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.18	0.24	0.27	1	-0.47	105	106
mol:GDP	-0.14	0.19	-10000	0	-0.36	84	84
NGF (dimer)	-0.035	0.18	0.32	1	-0.88	11	12
RhoG/GDP	-0.003	0.042	-10000	0	-0.69	1	1
RIT1/GDP	-0.092	0.13	-10000	0	-0.25	40	40
TIAM1	-0.033	0.17	-10000	0	-0.88	10	10
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
BDNF (dimer)/TRKB	-0.098	0.24	0.39	2	-0.6	50	52
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.005	0.059	-10000	0	-0.68	2	2
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.46	0.44	-10000	0	-0.88	141	141
RAP1/GDP	-0.095	0.087	-10000	0	-0.24	6	6
KIDINS220/CRKL	0	0	-10000	0	-10000	0	0
BDNF (dimer)	0.012	0.06	0.32	10	-10000	0	10
ubiquitin-dependent protein catabolic process	-0.022	0.12	-10000	0	-0.6	11	11
Schwann cell development	-0.056	0.045	-10000	0	-10000	0	0
EHD4	0	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0	0	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.34	0.34	-10000	0	-0.59	158	158
ABL1	0	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.035	0.086	-10000	0	-10000	0	0
STAT3	-0.015	0.075	-10000	0	-0.4	10	10
axon guidance	-0.32	0.32	-10000	0	-0.56	158	158
MAPK3	-0.021	0.11	-10000	0	-0.55	11	11
MAPK1	-0.021	0.11	-10000	0	-0.55	11	11
CDC42/GDP	-0.092	0.13	-10000	0	-0.25	42	42
NTF3	-0.46	0.44	-10000	0	-0.88	141	141
NTF4	0.004	0.033	0.32	3	-10000	0	3
NGF (dimer)/TRKA/FAIM	-0.022	0.12	-10000	0	-0.6	11	11
PI3K	-0.005	0.075	-10000	0	-1.2	1	1
FRS3	0	0	-10000	0	-10000	0	0
FAIM	0.001	0.019	0.32	1	-10000	0	1
GAB1	0	0	-10000	0	-10000	0	0
RASGRF1	-0.18	0.25	0.28	1	-0.48	105	106
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.35	0.33	-10000	0	-0.63	148	148
RGS19	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.02	0.092	-10000	0	-10000	0	0
Rac1/GDP	-0.092	0.13	-10000	0	-0.25	44	44
NGF (dimer)/TRKA/GRIT	-0.023	0.12	-10000	0	-0.61	11	11
neuron projection morphogenesis	-0.16	0.25	-10000	0	-0.63	20	20
NGF (dimer)/TRKA/NEDD4-2	-0.022	0.12	-10000	0	-0.6	11	11
MAP2K1	0	0	-10000	0	-10000	0	0
NGFR	-0.33	0.43	-10000	0	-0.88	102	102
NGF (dimer)/TRKA/GIPC/GAIP	-0.013	0.089	-10000	0	-0.36	13	13
RAS family/GTP/PI3K	-0.002	0.038	-10000	0	-0.61	1	1
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.036	0.17	-10000	0	-0.88	11	11
MAPKKK cascade	-0.064	0.15	-10000	0	-0.75	11	11
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
TRKA/c-Abl	0.002	0.019	-10000	0	-10000	0	0
SQSTM1	0.004	0.033	0.32	3	-10000	0	3
BDNF (dimer)/TRKB/GIPC	-0.088	0.23	0.38	2	-0.55	50	52
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.039	0.14	-10000	0	-0.52	22	22
MATK	0.002	0.027	0.32	2	-10000	0	2
NEDD4L	0	0	-10000	0	-10000	0	0
RAS family/GDP	-0.091	0.083	-10000	0	-0.24	1	1
NGF (dimer)/TRKA	-0.2	0.26	0.31	1	-0.51	105	106
Rac1/GTP	-0.17	0.16	-10000	0	-0.37	94	94
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.015	0.1	-10000	0	-0.69	6	6
PDGFRB	0.007	0.047	0.31	6	-10000	0	6
SPHK1	-0.003	0.12	-10000	0	-0.95	2	2
mol:S1P	-0.011	0.11	-10000	0	-0.85	2	2
S1P1/S1P/Gi	-0.23	0.28	-10000	0	-0.6	68	68
GNAO1	-0.4	0.44	-10000	0	-0.88	120	120
PDGFB-D/PDGFRB/PLCgamma1	-0.19	0.24	0.29	2	-0.61	44	46
PLCG1	-0.2	0.27	-10000	0	-0.66	45	45
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.007	0.046	0.31	6	-10000	0	6
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0.001	-10000	0	-10000	0	0
GNAI1	-0.007	0.076	-10000	0	-0.89	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.002	0.093	-10000	0	-0.61	6	6
S1P1/S1P	-0.027	0.13	-10000	0	-0.64	7	7
negative regulation of cAMP metabolic process	-0.22	0.28	-10000	0	-0.58	68	68
MAPK3	-0.27	0.35	-10000	0	-0.7	83	83
calcium-dependent phospholipase C activity	-0.004	0.004	-10000	0	-10000	0	0
Rac1/GDP	0	0	-10000	0	-10000	0	0
RhoA/GDP	0	0	-10000	0	-10000	0	0
KDR	-0.02	0.13	-10000	0	-0.88	6	6
PLCB2	-0.017	0.14	-10000	0	-0.57	11	11
RAC1	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.036	0.094	-10000	0	-0.52	7	7
receptor internalization	-0.026	0.12	-10000	0	-0.58	7	7
PTGS2	-0.39	0.52	-10000	0	-1.1	82	82
Rac1/GTP	-0.036	0.094	-10000	0	-0.52	7	7
RHOA	0	0	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
negative regulation of T cell proliferation	-0.22	0.28	-10000	0	-0.58	68	68
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.15	0.16	0.31	125	-10000	0	125
MAPK1	-0.27	0.35	-10000	0	-0.7	83	83
S1P1/S1P/PDGFB-D/PDGFRB	-0.026	0.14	-10000	0	-0.65	7	7
ABCC1	0.009	0.054	0.32	8	-10000	0	8

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.11	0.15	0.32	94	-10000	0	94
mol:Halofuginone	0	0.004	-10000	0	-10000	0	0
ITGA1	-0.003	0.054	-10000	0	-0.88	1	1
CDKN1A	-0.074	0.13	-10000	0	-0.71	5	5
PRL-3/alpha Tubulin	0.034	0.079	-10000	0	-10000	0	0
mol:Ca2+	-0.043	0.11	-10000	0	-0.69	4	4
AGT	-0.013	0.11	-10000	0	-0.88	4	4
CCNA2	-0.12	0.26	-10000	0	-0.49	86	86
TUBA1B	0	0	-10000	0	-10000	0	0
EGR1	-0.21	0.33	-10000	0	-0.69	86	86
CDK2/Cyclin E1	-0.01	0.16	-10000	0	-0.71	4	4
MAPK3	0.039	0.05	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.039	0.05	-10000	0	-10000	0	0
PTP4A1	-0.16	0.28	-10000	0	-0.55	86	86
PTP4A3	0.05	0.12	0.32	42	-10000	0	42
PTP4A2	0	0	-10000	0	-10000	0	0
ITGB1	0.039	0.05	-10000	0	-10000	0	0
SRC	0.001	0.019	0.32	1	-10000	0	1
RAC1	-0.039	0.11	-10000	0	-0.32	1	1
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.34	0.34	-10000	0	-0.62	146	146
RABGGTA	0	0	-10000	0	-10000	0	0
BCAR1	-0.032	0.075	-10000	0	-10000	0	0
RHOC	-0.039	0.11	-10000	0	-0.32	1	1
RHOA	-0.039	0.11	-10000	0	-0.32	1	1
cell motility	-0.028	0.12	-10000	0	-0.35	1	1
PRL-1/alpha Tubulin	-0.16	0.24	-10000	0	-0.51	86	86
PRL-3/alpha1 Integrin	0.032	0.091	-10000	0	-0.68	1	1
ROCK1	-0.028	0.12	-10000	0	-0.36	1	1
RABGGTB	0	0	-10000	0	-10000	0	0
CDK2	0	0	-10000	0	-10000	0	0
mitosis	-0.15	0.27	-10000	0	-0.54	86	86
ATF5	-0.3	0.42	-10000	0	-0.88	90	90

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.098	0.42	-10000	0	-1.3	30	30
SMARCC2	-0.002	0.009	-10000	0	-10000	0	0
SMARCC1	-0.002	0.009	-10000	0	-10000	0	0
TBX21	-0.093	0.25	-10000	0	-1.1	10	10
SUMO2	0.002	0.007	-10000	0	-10000	0	0
STAT1 (dimer)	0.016	0.027	0.32	2	-10000	0	2
FKBP4	0	0	-10000	0	-10000	0	0
FKBP5	-0.003	0.054	-10000	0	-0.88	1	1
GR alpha/HSP90/FKBP51/HSP90	0.065	0.11	0.33	3	-0.48	1	4
PRL	-0.051	0.14	-10000	0	-0.54	7	7
cortisol/GR alpha (dimer)/TIF2	0.097	0.37	0.52	65	-0.62	30	95
RELA	-0.067	0.11	-10000	0	-0.3	6	6
FGG	0.02	0.38	0.49	20	-0.96	28	48
GR beta/TIF2	-0.008	0.26	0.34	8	-0.68	29	37
IFNG	-0.12	0.26	0.54	2	-0.64	18	20
apoptosis	-0.18	0.31	0.56	3	-0.71	38	41
CREB1	0.016	0.032	-10000	0	-10000	0	0
histone acetylation	-0.066	0.13	-10000	0	-0.38	16	16
BGLAP	-0.037	0.13	-10000	0	-0.49	1	1
GR/PKAc	0.066	0.1	0.36	1	-0.53	1	2
NF kappa B1 p50/RelA	-0.12	0.2	-10000	0	-0.47	34	34
SMARCD1	-0.002	0.009	-10000	0	-10000	0	0
MDM2	0.054	0.093	0.25	17	-10000	0	17
GATA3	-0.053	0.24	0.33	1	-0.87	20	21
AKT1	0.018	0.05	-10000	0	-10000	0	0
CSF2	-0.052	0.11	-10000	0	-10000	0	0
GSK3B	0.002	0.007	-10000	0	-10000	0	0
NR1I3	-0.28	0.45	0.54	3	-1	66	69
CSN2	0.06	0.19	0.4	10	-0.46	5	15
BRG1/BAF155/BAF170/BAF60A	-0.006	0.032	-10000	0	-10000	0	0
NFATC1	-0.007	0.076	-10000	0	-0.88	2	2
POU2F1	0.003	0.011	-10000	0	-10000	0	0
CDKN1A	0.013	0.2	-10000	0	-1.6	4	4
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.005	0.009	-10000	0	-10000	0	0
SFN	0.18	0.16	0.32	155	-10000	0	155
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.17	0.14	0.38	37	-0.4	1	38
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.32	0.46	0.52	3	-0.94	89	92
JUN	-0.018	0.23	0.43	6	-0.63	18	24
IL4	-0.057	0.14	-10000	0	-0.75	3	3
CDK5R1	0.001	0.019	0.31	1	-10000	0	1
PRKACA	0	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.27	0.3	-10000	0	-0.56	117	117
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.068	0.1	0.36	1	-0.44	1	2
cortisol/GR alpha (monomer)	0.2	0.34	0.6	75	-0.54	8	83
NCOA2	-0.095	0.27	-10000	0	-0.88	29	29
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.35	0.45	-10000	0	-0.86	120	120
AP-1/NFAT1-c-4	-0.23	0.42	0.51	4	-0.69	101	105
AFP	-0.024	0.35	0.49	2	-1.1	19	21
SUV420H1	0	0	-10000	0	-10000	0	0
IRF1	0.095	0.15	0.46	4	-10000	0	4
TP53	0.017	0.064	-10000	0	-0.5	4	4
PPP5C	0	0	-10000	0	-10000	0	0
KRT17	-0.13	0.38	0.52	5	-0.98	23	28
KRT14	-0.032	0.15	-10000	0	-10000	0	0
TBP	0.015	0.01	-10000	0	-10000	0	0
CREBBP	-0.008	0.05	-10000	0	-10000	0	0
HDAC1	0	0	-10000	0	-10000	0	0
HDAC2	0	0	-10000	0	-10000	0	0
AP-1	-0.23	0.42	0.51	4	-0.69	100	104
MAPK14	0.002	0.006	-10000	0	-10000	0	0
MAPK10	-0.033	0.2	0.3	7	-0.88	13	20
MAPK11	0.011	0.052	0.31	8	-10000	0	8
KRT5	-0.11	0.29	0.54	3	-0.71	16	19
interleukin-1 receptor activity	-0.001	0.001	-10000	0	-10000	0	0
NCOA1	-0.007	0.023	-10000	0	-10000	0	0
STAT1	0.016	0.027	0.32	2	-10000	0	2
CGA	-0.03	0.14	-10000	0	-0.49	1	1
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.027	0.14	0.36	3	-0.41	3	6
MAPK3	0.002	0.007	-10000	0	-10000	0	0
MAPK1	0.002	0.006	-10000	0	-10000	0	0
ICAM1	-0.14	0.24	-10000	0	-0.62	29	29
NFKB1	-0.067	0.11	-10000	0	-10000	0	0
MAPK8	-0.062	0.23	0.39	6	-0.52	33	39
MAPK9	0.002	0.006	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.2	0.33	0.57	3	-0.76	38	41
BAX	0.031	0.052	-10000	0	-10000	0	0
POMC	-0.11	0.24	-10000	0	-0.77	13	13
EP300	-0.008	0.05	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.18	0.29	0.53	71	-0.52	6	77
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.072	0.23	2	-10000	0	2
SGK1	0.001	0.27	-10000	0	-1.5	8	8
IL13	-0.14	0.3	0.53	1	-0.9	22	23
IL6	-0.29	0.55	-10000	0	-1.4	48	48
PRKACG	0	0	-10000	0	-10000	0	0
IL5	-0.13	0.25	-10000	0	-0.79	19	19
IL2	-0.14	0.25	-10000	0	-0.62	20	20
CDK5	0	0.003	-10000	0	-10000	0	0
PRKACB	-0.003	0.054	-10000	0	-0.88	1	1
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.37	0.61	0.44	1	-1.4	66	67
CDK5R1/CDK5	0.001	0.014	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.093	0.14	-10000	0	-0.58	4	4
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.18	0.26	0.49	69	-0.45	5	74
SMARCA4	-0.002	0.009	-10000	0	-10000	0	0
chromatin remodeling	0.091	0.17	0.39	20	-0.44	3	23
NF kappa B1 p50/RelA/Cbp	-0.11	0.15	-10000	0	-0.56	8	8
JUN (dimer)	-0.018	0.23	0.43	6	-0.63	18	24
YWHAH	0	0	-10000	0	-10000	0	0
VIPR1	-0.78	0.59	-10000	0	-1.2	178	178
NR3C1	0.1	0.19	0.41	36	-10000	0	36
NR4A1	-0.11	0.3	-10000	0	-0.85	38	38
TIF2/SUV420H1	-0.074	0.21	-10000	0	-0.68	29	29
MAPKKK cascade	-0.18	0.31	0.56	3	-0.71	38	41
cortisol/GR alpha (dimer)/Src-1	0.16	0.3	0.52	69	-0.51	11	80
PBX1	-0.045	0.2	0.32	1	-0.88	15	16
POU1F1	0.003	0.021	0.32	1	-10000	0	1
SELE	-0.41	0.64	-10000	0	-1.4	71	71
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.091	0.17	0.39	20	-0.45	3	23
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.18	0.26	0.49	69	-0.45	5	74
mol:cortisol	0.09	0.19	0.33	72	-0.28	12	84
MMP1	0.022	0.16	0.46	2	-10000	0	2

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.2	0.23	-10000	0	-0.43	120	120
MAP3K8	-0.007	0.076	-10000	0	-0.88	2	2
FOS	-0.096	0.18	-10000	0	-0.55	19	19
PRKCA	0	0	-10000	0	-10000	0	0
PTPN7	0	0.064	0.32	3	-0.88	1	4
HRAS	0.002	0.027	0.31	2	-10000	0	2
PRKCB	-0.076	0.25	-10000	0	-0.89	23	23
NRAS	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.001	0.015	-10000	0	-10000	0	0
MAPK3	-0.043	0.11	-10000	0	-0.31	19	19
MAP2K1	-0.063	0.19	-10000	0	-0.64	23	23
ELK1	-0.006	0.007	-10000	0	-10000	0	0
BRAF	-0.065	0.17	-10000	0	-0.6	23	23
mol:GTP	-0.003	0.003	-10000	0	-0.006	119	119
MAPK1	-0.043	0.11	-10000	0	-0.31	19	19
RAF1	-0.065	0.17	-10000	0	-0.6	23	23
KRAS	0	0	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.026	0.18	-10000	0	-0.5	32	32
NF kappa B1 p50/RelA/I kappa B alpha	-0.052	0.14	-10000	0	-0.44	25	25
alphaV/beta3 Integrin/Osteopontin/Src	0.037	0.21	-10000	0	-0.67	17	17
AP1	-0.24	0.35	0.41	1	-0.95	33	34
ILK	-0.03	0.19	-10000	0	-0.53	32	32
bone resorption	-0.031	0.2	-10000	0	-0.87	5	5
PTK2B	0	0	-10000	0	-10000	0	0
PYK2/p130Cas	0.007	0.21	-10000	0	-0.5	32	32
ITGAV	0.001	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.019	0.13	-10000	0	-0.68	9	9
alphaV/beta3 Integrin/Osteopontin	-0.001	0.24	-10000	0	-0.59	32	32
MAP3K1	-0.031	0.19	-10000	0	-0.54	32	32
JUN	-0.016	0.12	-10000	0	-0.88	5	5
MAPK3	0.003	0.19	-10000	0	-0.5	32	32
MAPK1	0.003	0.19	-10000	0	-0.5	32	32
Rac1/GDP	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.025	0.23	-10000	0	-0.55	39	39
ITGB3	-0.051	0.21	-10000	0	-0.87	16	16
NFKBIA	0.012	0.19	-10000	0	-0.48	32	32
FOS	-0.39	0.44	-10000	0	-0.88	120	120
CD44	0.003	0.069	0.32	5	-0.88	1	6
CHUK	0	0	-10000	0	-10000	0	0
PLAU	0.005	0.18	-10000	0	-0.84	1	1
NF kappa B1 p50/RelA	-0.047	0.14	-10000	0	-0.82	1	1
BCAR1	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin	-0.04	0.16	-10000	0	-0.67	16	16
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.034	0.2	-10000	0	-0.55	32	32
VAV3	-0.006	0.19	-10000	0	-0.52	32	32
MAP3K14	-0.006	0.2	-10000	0	-0.54	32	32
ROCK2	-0.026	0.15	-10000	0	-0.88	8	8
SPP1	0.057	0.28	0.32	94	-0.87	17	111
RAC1	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.03	0.17	-10000	0	-0.47	32	32
MMP2	-0.2	0.28	0.38	4	-0.73	35	39

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.006	0.098	-10000	0	-0.6	6	6
ARNO/beta Arrestin1-2	-0.073	0.17	-10000	0	-0.46	43	43
EGFR	-0.013	0.11	-10000	0	-0.88	4	4
EPHA2	-0.036	0.17	-10000	0	-0.88	11	11
USP6	0	0	-10000	0	-10000	0	0
IQSEC1	0	0	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	0.045	0.13	-10000	0	-0.68	4	4
ARRB2	0	0	-10000	0	-10000	0	0
mol:GTP	0.005	0.049	-10000	0	-0.23	7	7
ARRB1	-0.01	0.092	-10000	0	-0.88	3	3
FBXO8	0	0	-10000	0	-10000	0	0
TSHR	0	0	-10000	0	-10000	0	0
EGF	0.081	0.14	0.32	69	-10000	0	69
somatostatin receptor activity	0	0	-10000	0	-0.001	62	62
ARAP2	-0.03	0.16	-10000	0	-0.88	9	9
mol:GDP	-0.078	0.13	-10000	0	-0.34	40	40
mol:PI-3-4-5-P3	0	0	-10000	0	-0.001	40	40
ITGA2B	0.008	0.05	0.32	7	-10000	0	7
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.031	0.13	-10000	0	-0.55	15	15
ADAP1	-0.008	0.14	0.32	10	-0.88	6	16
KIF13B	0	0	-10000	0	-10000	0	0
HGF/MET	-0.34	0.35	-10000	0	-0.69	133	133
PXN	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.08	0.14	-10000	0	-0.3	57	57
EGFR/EGFR/EGF/EGF/ARFGEP100	0.042	0.12	-10000	0	-0.59	4	4
ADRB2	-0.13	0.31	-10000	0	-0.88	40	40
receptor agonist activity	0	0	-10000	0	0	67	67
actin filament binding	0	0	-10000	0	-0.001	63	63
SRC	0.001	0.019	0.32	1	-10000	0	1
ITGB3	-0.052	0.21	-10000	0	-0.88	16	16
GNAQ	-0.003	0.054	-10000	0	-0.88	1	1
EFA6/PI-4-5-P2	0	0	-10000	0	-0.001	45	45
ARF6/GDP	-0.024	0.11	-10000	0	-0.38	15	15
ARF6/GDP/GULP/ACAP1	-0.097	0.2	-10000	0	-0.53	38	38
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.028	0.14	-10000	0	-0.55	16	16
ACAP1	-0.018	0.13	0.32	1	-0.88	6	7
ACAP2	0	0	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0	0	-10000	0	-10000	0	0
EFNA1	-0.01	0.092	-10000	0	-0.88	3	3
HGF	-0.44	0.44	-10000	0	-0.88	133	133
CYTH3	0.007	0.013	-10000	0	-10000	0	0
CYTH2	0.004	0.002	-10000	0	-10000	0	0
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
fibronectin binding	0	0	-10000	0	0	62	62
endosomal lumen acidification	0	0	-10000	0	0	55	55
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.016	0.28	0.32	45	-0.88	21	66
GNAQ/ARNO	-0.002	0.032	-10000	0	-0.52	1	1
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
PIP3-E	0	0	-10000	0	0	13	13
MET	-0.002	0.057	0.32	1	-0.88	1	2
GNA14	-0.15	0.33	-10000	0	-0.88	47	47
GNA15	0.002	0.027	0.32	2	-10000	0	2
GIT1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-0.001	52	52
GNA11	-0.02	0.13	-10000	0	-0.88	6	6
LHCGR	0	0	-10000	0	-10000	0	0
AGTR1	-0.1	0.28	-10000	0	-0.88	31	31
desensitization of G-protein coupled receptor protein signaling pathway	0	0	-10000	0	-10000	0	0
IPCEF1/ARNO	0.037	0.099	-10000	0	-0.48	4	4
alphaIIb/beta3 Integrin	-0.035	0.17	-10000	0	-0.69	16	16

×

S1P5 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	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	0.14	0.15	0.63	3	-10000	0	3
GNAI2	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.008	0.074	-10000	0	-0.6	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.39	0.44	-10000	0	-0.88	120	120
RhoA/GTP	-0.14	0.16	-10000	0	-0.66	3	3
negative regulation of cAMP metabolic process	-0.13	0.19	-10000	0	-0.38	54	54
GNAZ	0.15	0.16	0.32	125	-10000	0	125
GNAI3	0	0	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
S1PR5	-0.012	0.11	0.32	1	-0.88	4	5
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.14	0.2	-10000	0	-0.38	54	54
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
GNAI1	-0.007	0.076	-10000	0	-0.88	2	2

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.002	0.027	0.32	2	-9999	2
Aurora C/Aurora B/INCENP	0.098	0.098	0.37	2	-9999	2
metaphase	0	0	-10000	0	-9999	0
mitosis	0	0	-10000	0	-9999	0
H3F3B	0	0	-10000	0	-9999	0
AURKB	0.16	0.16	0.32	135	-9999	135
AURKC	0.001	0.019	0.32	1	-9999	1

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.14	0.27	0.36	1	-0.53	80	81
SMAD6-7/SMURF1	-0.025	0.12	-10000	0	-0.6	11	11
NOG	0.005	0.038	0.32	4	-10000	0	4
SMAD9	-0.06	0.16	-10000	0	-0.67	14	14
SMAD4	-0.003	0.054	-10000	0	-0.88	1	1
SMAD5	-0.074	0.18	-10000	0	-0.39	56	56
BMP7/USAG1	0.063	0.11	0.44	7	-10000	0	7
SMAD5/SKI	-0.097	0.15	-10000	0	-0.37	55	55
SMAD1	0.012	0.06	-10000	0	-0.7	1	1
BMP2	-0.01	0.092	-10000	0	-0.88	3	3
SMAD1/SMAD1/SMAD4	-0.025	0.092	-10000	0	-0.65	2	2
BMPR1A	0	0	-10000	0	-10000	0	0
BMPR1B	-0.19	0.37	0.32	3	-0.88	60	63
BMPR1A-1B/BAMBI	-0.17	0.3	-10000	0	-0.66	71	71
AHSG	-0.17	0.34	-10000	0	-0.88	51	51
CER1	0.005	0.038	0.32	4	-10000	0	4
BMP2-4/CER1	0.011	0.085	-10000	0	-0.59	3	3
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.087	0.16	-10000	0	-0.6	7	7
BMP2-4 (homodimer)	0.009	0.092	-10000	0	-0.67	3	3
RGMB	-0.005	0.078	0.32	1	-0.88	2	3
BMP6/BMPR2/BMPR1A-1B	-0.12	0.23	-10000	0	-0.55	61	61
RGMA	0.025	0.085	0.32	21	-10000	0	21
SMURF1	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.094	0.17	-10000	0	-0.32	81	81
BMP2-4/USAG1	0.04	0.11	0.39	4	-0.59	3	7
SMAD6/SMURF1/SMAD5	-0.097	0.15	-10000	0	-0.37	55	55
SOSTDC1	0.051	0.12	0.32	43	-10000	0	43
BMP7/BMPR2/BMPR1A-1B	-0.099	0.25	0.38	1	-0.55	60	61
SKI	0	0	-10000	0	-10000	0	0
BMP6 (homodimer)	-0.001	0.06	0.32	2	-0.88	1	3
HFE2	-0.12	0.3	-10000	0	-0.88	36	36
ZFYVE16	0	0	-10000	0	-10000	0	0
MAP3K7	0	0	-10000	0	-10000	0	0
BMP2-4/CHRD	-0.006	0.12	-10000	0	-0.59	9	9
SMAD5/SMAD5/SMAD4	-0.099	0.16	-10000	0	-0.37	56	56
MAPK1	0	0	-10000	0	-10000	0	0
TAK1/TAB family	-0.087	0.13	-10000	0	-0.56	7	7
BMP7 (homodimer)	0.04	0.1	0.32	34	-10000	0	34
NUP214	0	0	-10000	0	-10000	0	0
BMP6/FETUA	-0.13	0.27	-10000	0	-0.68	52	52
SMAD1/SKI	-0.014	0.045	-10000	0	-0.66	1	1
SMAD6	-0.03	0.16	-10000	0	-0.88	9	9
CTDSP2	0	0	-10000	0	-10000	0	0
BMP2-4/FETUA	-0.11	0.25	-10000	0	-0.6	54	54
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.078	0.31	0.32	23	-0.88	32	55
BMPR2 (homodimer)	0	0	-10000	0	-10000	0	0
GADD34/PP1CA	0.001	0.012	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	-0.15	0.29	-10000	0	-0.68	60	60
CHRDL1	-0.16	0.36	0.32	7	-0.88	52	59
ENDOFIN/SMAD1	-0.014	0.045	-10000	0	-0.66	1	1
SMAD6-7/SMURF1/SMAD1	-0.029	0.1	-10000	0	-0.52	8	8
SMAD6/SMURF1	0	0	-10000	0	-10000	0	0
BAMBI	-0.061	0.23	0.32	1	-0.88	19	20
SMURF2	0	0	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.1	0.26	-10000	0	-0.6	54	54
BMP2-4/GREM1	-0.049	0.22	0.39	1	-0.59	35	36
SMAD7	-0.007	0.076	-10000	0	-0.88	2	2
SMAD8A/SMAD8A/SMAD4	-0.061	0.15	-10000	0	-0.62	15	15
SMAD1/SMAD6	-0.014	0.045	-10000	0	-0.66	1	1
TAK1/SMAD6	0	0	-10000	0	-10000	0	0
BMP7	0.04	0.1	0.32	34	-10000	0	34
BMP6	-0.001	0.06	0.32	2	-0.88	1	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.076	0.14	-10000	0	-0.52	8	8
PPM1A	0	0	-10000	0	-10000	0	0
SMAD1/SMURF2	-0.014	0.045	-10000	0	-0.66	1	1
SMAD7/SMURF1	-0.005	0.059	-10000	0	-0.68	2	2
CTDSPL	0	0	-10000	0	-10000	0	0
PPP1CA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
CTDSP1	0	0	-10000	0	-10000	0	0
PPP1R15A	0.001	0.019	0.32	1	-10000	0	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.11	0.19	-10000	0	-0.56	19	19
CHRD	-0.02	0.13	-10000	0	-0.88	6	6
BMPR2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.095	0.17	-10000	0	-0.68	7	7
BMP4	0.025	0.085	0.32	21	-10000	0	21
FST	-0.074	0.25	0.32	1	-0.88	23	24
BMP2-4/NOG	0.011	0.085	-10000	0	-0.59	3	3
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.093	0.24	0.36	1	-0.52	60	61

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0	0	-10000	0	-10000	0	0
LAT2	-0.04	0.11	-10000	0	-0.45	5	5
AP1	-0.23	0.25	-10000	0	-0.48	120	120
mol:PIP3	-0.025	0.19	-10000	0	-0.46	38	38
IKBKB	-0.007	0.12	-10000	0	-0.34	18	18
AKT1	-0.059	0.15	-10000	0	-0.64	2	2
IKBKG	-0.007	0.12	-10000	0	-0.34	18	18
MS4A2	0.006	0.048	0.32	6	-10000	0	6
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
MAP3K1	0	0.13	-10000	0	-0.63	5	5
mol:Ca2+	-0.012	0.14	-10000	0	-0.34	38	38
LYN	0	0.001	-10000	0	-10000	0	0
CBLB	-0.037	0.099	-10000	0	-0.41	4	4
SHC1	0	0	-10000	0	-10000	0	0
RasGAP/p62DOK	-0.049	0.16	-10000	0	-0.58	23	23
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	-0.003	0.054	-10000	0	-0.88	1	1
PLD2	-0.066	0.17	-10000	0	-0.49	37	37
PTPN13	-0.12	0.24	-10000	0	-0.52	62	62
PTPN11	0	0.003	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.011	0.12	-10000	0	-0.36	4	4
SYK	-0.003	0.054	-10000	0	-0.89	1	1
GRB2	0	0	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.077	0.18	-10000	0	-0.47	39	39
LAT	-0.037	0.099	-10000	0	-0.41	4	4
PAK2	-0.009	0.15	-10000	0	-0.74	5	5
NFATC2	-0.15	0.3	-10000	0	-0.8	43	43
HRAS	-0.018	0.16	-10000	0	-0.55	13	13
GAB2	0	0	-10000	0	-10000	0	0
PLA2G1B	0.05	0.033	-10000	0	-10000	0	0
Fc epsilon R1	-0.079	0.21	-10000	0	-0.61	37	37
Antigen/IgE/Fc epsilon R1	-0.073	0.2	-10000	0	-0.56	37	37
mol:GDP	-0.028	0.18	-10000	0	-0.6	14	14
JUN	-0.016	0.12	-10000	0	-0.88	5	5
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
FOS	-0.39	0.44	-10000	0	-0.88	120	120
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.04	0.11	-10000	0	-0.44	4	4
CHUK	-0.007	0.12	-10000	0	-0.34	18	18
KLRG1	-0.043	0.11	-10000	0	-0.49	6	6
VAV1	-0.06	0.16	-10000	0	-0.6	13	13
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.037	0.099	-10000	0	-0.41	4	4
negative regulation of mast cell degranulation	-0.041	0.11	-10000	0	-0.51	5	5
BTK	-0.049	0.15	-10000	0	-0.79	6	6
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.26	0.31	-10000	0	-0.49	141	141
GAB2/PI3K/SHP2	-0.065	0.16	-10000	0	-0.5	11	11
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.042	0.11	-10000	0	-0.36	6	6
RAF1	0.041	0.038	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.33	0.35	-10000	0	-0.62	144	144
FCER1G	-0.008	0.094	0.31	1	-0.87	3	4
FCER1A	-0.11	0.3	-10000	0	-0.89	34	34
Antigen/IgE/Fc epsilon R1/Fyn	-0.068	0.18	-10000	0	-0.52	37	37
MAPK3	0.046	0.032	-10000	0	-10000	0	0
MAPK1	0.046	0.032	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.014	0.12	-10000	0	-0.57	11	11
DUSP1	-0.072	0.24	-10000	0	-0.88	22	22
NF-kappa-B/RelA	-0.028	0.06	-10000	0	-0.24	1	1
actin cytoskeleton reorganization	-0.011	0.11	-10000	0	-0.41	4	4
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.056	0.15	-10000	0	-0.6	13	13
FER	-0.037	0.099	-10000	0	-0.41	4	4
RELA	0	0	-10000	0	-10000	0	0
ITK	-0.036	0.13	-10000	0	-0.6	13	13
SOS1	0	0	-10000	0	-10000	0	0
PLCG1	-0.024	0.18	-10000	0	-0.6	13	13
cytokine secretion	-0.02	0.044	-10000	0	-10000	0	0
SPHK1	-0.028	0.11	-10000	0	-0.47	5	5
PTK2	-0.012	0.11	-10000	0	-0.42	4	4
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.08	0.18	-10000	0	-0.49	38	38
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.022	0.19	-10000	0	-0.44	38	38
MAP2K2	0.044	0.033	-10000	0	-10000	0	0
MAP2K1	0.043	0.033	-10000	0	-10000	0	0
MAP2K7	0	0	-10000	0	-10000	0	0
KLRG1/SHP2	-0.042	0.11	-10000	0	-0.54	4	4
MAP2K4	0.012	0.009	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.35	0.37	-10000	0	-0.66	144	144
mol:Choline	-0.065	0.17	-10000	0	-0.48	37	37
SHC/Grb2/SOS1	-0.034	0.091	-10000	0	-0.49	1	1
FYN	0	0	-10000	0	-10000	0	0
DOK1	0	0	-10000	0	-10000	0	0
PXN	-0.005	0.1	-10000	0	-0.41	3	3
HCLS1	-0.039	0.1	-10000	0	-0.44	5	5
PRKCB	-0.027	0.17	-10000	0	-0.38	45	45
FCGR2B	-0.44	0.44	0.32	2	-0.88	136	138
IGHE	0	0.005	-10000	0	-10000	0	0
KLRG1/SHIP	-0.042	0.11	-10000	0	-0.52	5	5
LCP2	-0.013	0.11	-10000	0	-0.88	4	4
PLA2G4A	-0.074	0.19	-10000	0	-0.62	22	22
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
mol:Phosphatidic acid	-0.065	0.17	-10000	0	-0.48	37	37
IKK complex	0.01	0.096	-10000	0	-0.26	12	12
WIPF1	0	0	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.015	0.1	-10000	0	-0.68	6	6
alphaV beta3 Integrin	-0.07	0.22	-10000	0	-0.67	29	29
PTK2	-0.012	0.2	-10000	0	-0.58	21	21
IGF1R	-0.006	0.099	0.32	3	-0.88	3	6
PI4KB	0	0	-10000	0	-10000	0	0
MFGE8	0.005	0.038	0.32	4	-10000	0	4
SRC	0.001	0.019	0.32	1	-10000	0	1
CDKN1B	-0.052	0.15	-10000	0	-0.64	12	12
VEGFA	0	0	-10000	0	-10000	0	0
ILK	-0.052	0.15	-10000	0	-0.64	12	12
ROCK1	0	0	-10000	0	-10000	0	0
AKT1	-0.047	0.14	-10000	0	-0.6	12	12
PTK2B	-0.042	0.15	-10000	0	-0.56	20	20
alphaV/beta3 Integrin/JAM-A	-0.084	0.21	-10000	0	-0.56	41	41
CBL	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.11	0.25	-10000	0	-0.63	47	47
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.24	0.28	-10000	0	-0.56	116	116
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.036	0.1	-10000	0	-0.58	2	2
alphaV/beta3 Integrin/Syndecan-1	-0.045	0.16	-10000	0	-0.6	20	20
PI4KA	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.26	0.32	-10000	0	-0.56	126	126
PI4 Kinase	0	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
alphaV/beta3 Integrin/Osteopontin	-0.007	0.24	-10000	0	-0.61	32	32
RPS6KB1	-0.24	0.29	-10000	0	-0.52	121	121
TLN1	0	0	-10000	0	-10000	0	0
MAPK3	-0.16	0.28	-10000	0	-0.89	29	29
GPR124	-0.007	0.076	-10000	0	-0.88	2	2
MAPK1	-0.16	0.28	-10000	0	-0.89	29	29
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
alphaV/beta3 Integrin/Tumstatin	-0.052	0.22	-10000	0	-0.7	25	25
cell adhesion	-0.092	0.21	-10000	0	-0.52	48	48
ANGPTL3	-0.11	0.29	-10000	0	-0.88	34	34
VEGFR2 homodimer/VEGFA homodimer/Src	-0.013	0.089	-10000	0	-0.6	6	6
IGF-1R heterotetramer	-0.006	0.098	0.32	3	-0.88	3	6
Rac1/GDP	0	0	-10000	0	-10000	0	0
TGFBR2	0	0	-10000	0	-10000	0	0
ITGB3	-0.052	0.21	-10000	0	-0.88	16	16
IGF1	-0.38	0.44	-10000	0	-0.88	115	115
RAC1	0	0	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	-0.04	0.15	-10000	0	-0.59	18	18
apoptosis	0	0	-10000	0	-10000	0	0
CD47	-0.003	0.054	-10000	0	-0.88	1	1
alphaV/beta3 Integrin/CD47	-0.038	0.15	-10000	0	-0.6	17	17
VCL	0.001	0.019	0.32	1	-10000	0	1
alphaV/beta3 Integrin/Del1	0.017	0.18	-10000	0	-0.6	16	16
CSF1	-0.004	0.081	0.32	2	-0.88	2	4
PIK3C2A	-0.052	0.15	-10000	0	-0.64	12	12
PI4 Kinase/Pyk2	-0.08	0.19	-10000	0	-0.92	5	5
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.045	0.16	-10000	0	-0.6	20	20
FAK1/Vinculin	0	0.15	-10000	0	-0.46	16	16
alphaV beta3/Integrin/ppsTEM5	-0.04	0.15	-10000	0	-0.6	18	18
RHOA	0	0	-10000	0	-10000	0	0
VTN	-0.039	0.18	-10000	0	-0.88	12	12
BCAR1	0	0	-10000	0	-10000	0	0
FGF2	-0.051	0.22	0.32	4	-0.88	17	21
F11R	-0.025	0.17	-10000	0	-0.68	17	17
alphaV/beta3 Integrin/Lactadherin	-0.033	0.14	-10000	0	-0.6	16	16
alphaV/beta3 Integrin/TGFBR2	-0.036	0.14	-10000	0	-0.6	16	16
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.05	-10000	0	-0.55	2	2
HSP90AA1	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.033	0.13	-10000	0	-0.55	16	16
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.003	0.054	-10000	0	-0.88	1	1
alphaV/beta3 Integrin/Pyk2	-0.042	0.15	-10000	0	-0.56	20	20
SDC1	-0.013	0.11	-10000	0	-0.88	4	4
VAV3	0.001	0.053	-10000	0	-0.51	2	2
PTPN11	0	0	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
FAK1/Paxillin	0	0.15	-10000	0	-0.46	16	16
cell migration	0.01	0.14	-10000	0	-0.43	13	13
ITGAV	0	0	-10000	0	-10000	0	0
PI3K	-0.08	0.2	-10000	0	-0.53	41	41
SPP1	0.055	0.28	0.32	94	-0.88	17	111
KDR	-0.02	0.13	-10000	0	-0.88	6	6
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0	-10000	0	-10000	0	0
COL4A3	-0.025	0.22	0.32	18	-0.88	14	32
angiogenesis	-0.13	0.29	-10000	0	-0.78	37	37
Rac1/GTP	0.001	0.048	-10000	0	-0.47	2	2
EDIL3	0.084	0.14	0.32	71	-10000	0	71
cell proliferation	-0.035	0.14	-10000	0	-0.59	16	16

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.06	0.17	-10000	0	-0.6	21	21
FYN	-0.034	0.27	0.47	1	-0.75	27	28
LAT/GRAP2/SLP76	-0.049	0.2	0.43	2	-0.63	24	26
IKBKB	0	0	-10000	0	-10000	0	0
AKT1	0.002	0.17	0.36	3	-0.47	24	27
B2M	0	0.001	-10000	0	-10000	0	0
IKBKG	-0.015	0.042	-10000	0	-0.18	7	7
MAP3K8	-0.007	0.076	-10000	0	-0.88	2	2
mol:Ca2+	-0.043	0.062	-10000	0	-0.13	83	83
integrin-mediated signaling pathway	-0.007	0.063	-10000	0	-0.6	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.02	0.25	0.4	3	-0.73	24	27
TRPV6	-0.28	0.41	-10000	0	-0.89	84	84
CD28	-0.002	0.057	0.32	1	-0.88	1	2
SHC1	-0.026	0.25	0.37	3	-0.75	24	27
receptor internalization	-0.033	0.26	0.37	3	-0.7	27	30
PRF1	-0.029	0.26	-10000	0	-0.94	16	16
KRAS	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
COT/AKT1	0.007	0.14	0.32	3	-0.4	21	24
LAT	-0.026	0.25	0.38	3	-0.75	24	27
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	-0.021	0.17	0.32	7	-0.88	9	16
CD3E	-0.035	0.18	0.33	1	-0.89	11	12
CD3G	-0.032	0.19	0.32	6	-0.88	12	18
RASGRP2	-0.004	0.028	0.13	5	-0.2	1	6
RASGRP1	0.011	0.17	0.43	3	-0.48	23	26
HLA-A	0	0.002	-10000	0	-10000	0	0
RASSF5	-0.01	0.092	-10000	0	-0.88	3	3
RAP1A/GTP/RAPL	-0.007	0.064	-10000	0	-0.6	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.027	0.058	0.25	4	-0.12	16	20
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.029	0.076	-10000	0	-0.27	19	19
PRKCA	-0.016	0.095	0.38	1	-0.29	21	22
GRAP2	-0.018	0.15	0.32	4	-0.88	7	11
mol:IP3	0.025	0.2	0.28	69	-0.46	22	91
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.039	0.25	0.32	3	-0.73	24	27
ORAI1	0.12	0.18	0.4	84	-10000	0	84
CSK	-0.029	0.26	0.36	3	-0.78	24	27
B7 family/CD28	-0.093	0.25	0.49	1	-0.71	31	32
CHUK	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.076	0.29	0.38	3	-0.92	24	27
PTPN6	-0.034	0.26	0.45	1	-0.79	24	25
VAV1	-0.039	0.28	0.4	2	-0.8	27	29
Monovalent TCR/CD3	-0.046	0.19	0.36	1	-0.57	24	25
CBL	0	0	-10000	0	-10000	0	0
LCK	-0.043	0.29	0.48	1	-0.86	25	26
PAG1	-0.03	0.26	0.4	2	-0.79	24	26
RAP1A	0	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.088	0.29	0.37	3	-0.92	24	27
CD80	-0.028	0.16	0.32	1	-0.88	9	10
CD86	-0.026	0.15	-10000	0	-0.88	8	8
PDK1/CARD11/BCL10/MALT1	-0.033	0.093	-10000	0	-0.34	18	18
HRAS	0.002	0.027	0.32	2	-10000	0	2
GO:0035030	-0.074	0.2	0.41	1	-0.57	31	32
CD8A	-0.059	0.23	0.32	3	-0.89	19	22
CD8B	-0.041	0.21	0.32	7	-0.89	15	22
PTPRC	-0.065	0.23	0.32	1	-0.88	20	21
PDK1/PKC theta	0	0.21	0.4	3	-0.6	24	27
CSK/PAG1	-0.024	0.25	0.39	2	-0.82	21	23
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	0	0	-10000	0	-10000	0	0
GRAP2/SLP76	-0.063	0.24	0.63	1	-0.76	24	25
STIM1	0.066	0.096	-10000	0	-10000	0	0
RAS family/GTP	0.028	0.074	0.3	3	-0.18	16	19
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.04	0.28	0.38	3	-0.77	27	30
mol:DAG	-0.018	0.14	0.17	2	-0.42	22	24
RAP1A/GDP	0.012	0.026	0.14	3	-10000	0	3
PLCG1	0	0	-10000	0	-10000	0	0
CD247	-0.005	0.079	0.32	1	-0.88	2	3
cytotoxic T cell degranulation	-0.026	0.24	-10000	0	-0.88	16	16
RAP1A/GTP	-0.002	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.007	0.2	0.38	3	-0.57	24	27
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.012	0.25	0.3	65	-0.63	22	87
NRAS	0	0	-10000	0	-10000	0	0
ZAP70	-0.002	0.085	0.32	4	-0.88	2	6
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.049	0.2	0.62	1	-0.64	23	24
MALT1	0	0	-10000	0	-10000	0	0
TRAF6	-0.003	0.054	-10000	0	-0.88	1	1
CD8 heterodimer	-0.075	0.28	0.45	3	-0.86	26	29
CARD11	-0.02	0.16	0.32	5	-0.88	8	13
PRKCB	-0.036	0.15	0.38	1	-0.44	27	28
PRKCE	-0.016	0.098	0.29	2	-0.29	23	25
PRKCQ	-0.014	0.24	0.4	3	-0.69	25	28
LCP2	-0.013	0.11	-10000	0	-0.88	4	4
BCL10	0	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.007	0.14	0.34	3	-0.39	24	27
IKK complex	0.029	0.059	0.23	3	-0.13	17	20
RAS family/GDP	-0.003	0.007	-10000	0	-10000	0	0
MAP3K14	0.017	0.11	0.29	3	-0.3	19	22
PDPK1	0.006	0.16	0.36	3	-0.44	24	27
TCR/CD3/MHC I/CD8/Fyn	-0.06	0.33	0.4	3	-1	24	27

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.003	0.055	-10000	0	-0.88	1	1
SVIL	-0.003	0.054	-10000	0	-0.86	1	1
ZNF318	0.003	0.028	-10000	0	-10000	0	0
JMJD2C	0.012	0.032	0.12	23	-10000	0	23
T-DHT/AR/Ubc9	-0.18	0.28	-10000	0	-0.63	74	74
CARM1	0	0	-10000	0	-10000	0	0
PRDX1	0	0.002	-10000	0	-10000	0	0
PELP1	0.001	0.005	-10000	0	-10000	0	0
CTNNB1	0	0.008	-10000	0	-10000	0	0
AKT1	0.001	0.008	-10000	0	-10000	0	0
PTK2B	0	0.006	-10000	0	-10000	0	0
MED1	0.001	0.007	-10000	0	-10000	0	0
MAK	0.003	0.028	-10000	0	-10000	0	0
response to oxidative stress	0	0.002	-10000	0	-10000	0	0
HIP1	-0.013	0.11	-10000	0	-0.88	4	4
GSN	0	0.011	-10000	0	-10000	0	0
NCOA2	-0.095	0.27	-10000	0	-0.88	29	29
NCOA6	0	0.01	-10000	0	-10000	0	0
DNA-PK	0.004	0.026	-10000	0	-10000	0	0
NCOA4	0	0	-10000	0	-10000	0	0
PIAS3	0	0.008	-10000	0	-10000	0	0
cell proliferation	-0.03	0.051	-10000	0	-10000	0	0
XRCC5	0.001	0.007	-10000	0	-10000	0	0
UBE3A	0	0.015	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.19	0.29	-10000	0	-0.64	77	77
FHL2	-0.14	0.33	-10000	0	-1.3	18	18
RANBP9	0	0.01	-10000	0	-10000	0	0
JMJD1A	-0.012	0.053	-10000	0	-0.13	46	46
CDK6	-0.059	0.22	-10000	0	-0.88	18	18
TGFB1I1	0	0.01	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.2	0.31	-10000	0	-0.66	80	80
XRCC6	0.001	0.007	-10000	0	-10000	0	0
T-DHT/AR	-0.19	0.3	-10000	0	-0.64	78	78
CTDSP1	0	0.003	-10000	0	-10000	0	0
CTDSP2	0.003	0.017	-10000	0	-10000	0	0
BRCA1	0	0.01	-10000	0	-10000	0	0
TCF4	0.002	0.012	-10000	0	-10000	0	0
CDKN2A	0.21	0.15	0.32	176	-10000	0	176
SRF	0.005	0.034	-10000	0	-10000	0	0
NKX3-1	-0.23	0.46	-10000	0	-1.3	40	40
KLK3	-0.027	0.25	-10000	0	-1.6	6	6
TMF1	0	0.002	-10000	0	-10000	0	0
HNRNPA1	0.001	0.009	-10000	0	-10000	0	0
AOF2	0	0.012	-10000	0	-0.072	6	6
APPL1	0.017	0.016	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.18	0.28	-10000	0	-0.63	74	74
AR	-0.25	0.4	-10000	0	-0.9	74	74
UBA3	0	0.003	-10000	0	-10000	0	0
PATZ1	0.001	0.009	-10000	0	-10000	0	0
PAWR	0	0.002	-10000	0	-10000	0	0
PRKDC	0.001	0.007	-10000	0	-10000	0	0
PA2G4	0.002	0.012	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.17	0.26	-10000	0	-0.58	74	74
RPS6KA3	-0.003	0.055	-10000	0	-0.88	1	1
T-DHT/AR/ARA70	-0.18	0.28	-10000	0	-0.63	74	74
LATS2	0.002	0.01	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.17	0.26	-10000	0	-0.58	74	74
Cyclin D3/CDK11 p58	0	0	-10000	0	-10000	0	0
VAV3	0.006	0.044	0.32	5	-10000	0	5
KLK2	-0.047	0.13	-10000	0	-10000	0	0
CASP8	0	0.004	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.22	0.34	-10000	0	-0.68	86	86
TMPRSS2	-0.15	0.31	-10000	0	-0.86	28	28
CCND1	-0.033	0.17	-10000	0	-0.88	10	10
PIAS1	0	0.015	-10000	0	-10000	0	0
mol:T-DHT	-0.007	0.032	-10000	0	-0.084	33	33
CDC2L1	0	0.001	-10000	0	-10000	0	0
PIAS4	-0.001	0.026	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.22	0.32	-10000	0	-0.66	86	86
CMTM2	0.003	0.027	0.32	2	-10000	0	2
SNURF	-0.007	0.12	0.32	5	-0.88	4	9
ZMIZ1	-0.005	0.031	0.3	1	-10000	0	1
CCND3	0	0	-10000	0	-10000	0	0
TGIF1	0.001	0.009	-10000	0	-10000	0	0
FKBP4	0	0.01	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0	0	-10000	0	-10000	0	0
SPHK1	0.05	0.14	0.32	48	-0.88	2	50
GNAI2	0	0	-10000	0	-10000	0	0
mol:S1P	0.021	0.063	0.21	7	-0.39	2	9
GNAO1	-0.39	0.44	-10000	0	-0.88	120	120
mol:Sphinganine-1-P	0.037	0.082	-10000	0	-0.68	2	2
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	-0.004	0.039	-10000	0	-0.51	1	1
GNAI3	0	0	-10000	0	-10000	0	0
G12/G13	0	0	-10000	0	-10000	0	0
S1PR3	-0.012	0.11	0.32	1	-0.88	4	5
S1PR2	-0.003	0.054	-10000	0	-0.88	1	1
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.013	0.046	-10000	0	-0.34	2	2
S1PR5	-0.012	0.11	0.32	1	-0.88	4	5
S1PR4	0.001	0.019	0.32	1	-10000	0	1
GNAI1	-0.007	0.076	-10000	0	-0.88	2	2
S1P/S1P5/G12	-0.009	0.079	-10000	0	-0.61	4	4
S1P/S1P3/Gq	-0.057	0.15	-10000	0	-0.35	42	42
S1P/S1P4/Gi	-0.11	0.18	-10000	0	-0.35	45	45
GNAQ	-0.003	0.054	-10000	0	-0.88	1	1
GNAZ	0.15	0.16	0.32	125	-10000	0	125
GNA14	-0.15	0.33	-10000	0	-0.88	47	47
GNA15	0.002	0.027	0.32	2	-10000	0	2
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.02	0.13	-10000	0	-0.88	6	6
ABCC1	0.009	0.054	0.32	8	-10000	0	8

×

p38 MAPK 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.053	0.16	-10000	0	-0.52	27	27
TRAF2/ASK1	-0.059	0.18	-10000	0	-0.6	26	26
ATM	0	0	-10000	0	-10000	0	0
MAP2K3	-0.052	0.094	-10000	0	-0.3	13	13
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.079	0.18	-10000	0	-0.56	28	28
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.13	0.32	-10000	0	-0.88	41	41
TXN	0	0	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
GADD45A	-0.016	0.12	-10000	0	-0.88	5	5
GADD45B	-0.14	0.32	-10000	0	-0.88	42	42
MAP3K1	0	0	-10000	0	-10000	0	0
MAP3K6	0.001	0.019	0.32	1	-10000	0	1
MAP3K7	0	0	-10000	0	-10000	0	0
MAP3K4	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.066	0.2	-10000	0	-0.68	26	26
TAK1/TAB family	-0.003	0.018	-10000	0	-0.22	1	1
RAC1/OSM/MEKK3	0	0	-10000	0	-10000	0	0
TRAF2	0	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.046	0.062	-10000	0	-10000	0	0
TRAF6	-0.002	0.029	-10000	0	-0.48	1	1
RAC1	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.43	0.44	-10000	0	-0.88	130	130
CCM2	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.29	0.3	-10000	0	-0.6	130	130
MAPK11	0.009	0.054	0.32	8	-10000	0	8
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.32	0.32	-10000	0	-0.6	144	144
OSM/MEKK3	0	0	-10000	0	-10000	0	0
TAOK1	-0.004	0.041	-10000	0	-0.47	2	2
TAOK2	0	0	-10000	0	-10000	0	0
TAOK3	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	-0.085	0.26	-10000	0	-0.88	26	26
MAP3K10	0	0	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
TRX/ASK1	-0.058	0.18	-10000	0	-0.59	26	26
GADD45/MTK1/MTK1	-0.17	0.3	-10000	0	-0.64	71	71

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.011	0.1	-10000	0	-0.66	5	5
HDAC1	0.006	0.017	-10000	0	-10000	0	0
AES	0.003	0.008	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
DTX1	-0.26	0.4	-10000	0	-0.88	78	78
LRP6/FZD1	-0.007	0.073	-10000	0	-0.68	3	3
TLE1	-0.002	0.054	-10000	0	-0.88	1	1
AP1	-0.18	0.24	-10000	0	-0.4	127	127
NCSTN	0	0	-10000	0	-10000	0	0
ADAM10	-0.003	0.054	-10000	0	-0.88	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.037	0.1	-10000	0	-0.69	2	2
NICD/RBPSUH	-0.003	0.047	-10000	0	-0.76	1	1
WIF1	0.028	0.09	0.32	24	-10000	0	24
NOTCH1	-0.003	0.049	-10000	0	-0.81	1	1
PSENEN	0	0	-10000	0	-10000	0	0
KREMEN2	0.035	0.1	0.32	30	-10000	0	30
DKK1	0.1	0.15	0.32	85	-10000	0	85
beta catenin/beta TrCP1	-0.012	0.021	-10000	0	-10000	0	0
APH1B	0	0	-10000	0	-10000	0	0
APH1A	0	0	-10000	0	-10000	0	0
AXIN1	0.004	0.032	0.35	1	-10000	0	1
CtBP/CBP/TCF1/TLE1/AES	0.015	0.083	0.28	5	-0.49	3	8
PSEN1	0	0	-10000	0	-10000	0	0
FOS	-0.39	0.44	-10000	0	-0.88	120	120
JUN	-0.016	0.12	-10000	0	-0.88	5	5
MAP3K7	0.003	0.009	-10000	0	-10000	0	0
CTNNB1	0.007	0.056	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.049	0.091	0.39	3	-10000	0	3
HNF1A	-0.01	0.11	-10000	0	-0.88	4	4
CTBP1	0.003	0.008	-10000	0	-10000	0	0
MYC	-0.18	0.49	-10000	0	-1.6	30	30
NKD1	0.027	0.23	0.32	56	-0.88	12	68
FZD1	-0.009	0.095	0.32	1	-0.88	3	4
NOTCH1 precursor/Deltex homolog 1	-0.15	0.23	-10000	0	-0.51	79	79
apoptosis	-0.18	0.24	-10000	0	-0.4	127	127
Delta 1/NOTCHprecursor	-0.011	0.099	-10000	0	-0.65	5	5
DLL1	-0.014	0.12	0.32	2	-0.88	5	7
PPARD	-0.01	0.029	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	0.004	0.032	0.35	1	-10000	0	1
DVL1	-0.001	0.009	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0.001	0.007	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.085	0.12	0.39	13	-10000	0	13
LRP6	0	0	-10000	0	-10000	0	0
CSNK1A1	0	0	-10000	0	-10000	0	0
NLK	0.007	0.019	-10000	0	-10000	0	0
CCND1	-0.066	0.3	-10000	0	-1.6	10	10
WNT1	0.003	0.033	0.32	3	-10000	0	3
Axin1/APC/beta catenin	0.024	0.04	0.33	1	-10000	0	1
DKK2	0.042	0.11	0.32	36	-10000	0	36
NOTCH1 precursor/DVL1	-0.003	0.042	-10000	0	-0.69	1	1
GSK3B	0.001	0.004	-10000	0	-10000	0	0
FRAT1	-0.001	0.054	-10000	0	-0.88	1	1
NOTCH/Deltex homolog 1	-0.15	0.23	-10000	0	-0.51	79	79
PPP2R5D	0.003	0.083	0.37	12	-10000	0	12
MAPK1	0	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.014	0.085	-10000	0	-0.56	3	3
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.009	0.004	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.019	0.08	-10000	0	-0.36	14	14
epithelial cell differentiation	-0.027	0.11	-10000	0	-0.51	14	14
CYFIP2	-0.049	0.2	-10000	0	-0.88	15	15
ENAH	0.022	0.12	-10000	0	-0.52	5	5
EGFR	-0.013	0.11	-10000	0	-0.88	4	4
EPHA2	-0.036	0.17	-10000	0	-0.88	11	11
MYO6	-0.026	0.11	-10000	0	-0.49	14	14
CTNNB1	0	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.033	0.14	-10000	0	-0.6	15	15
AQP5	-0.018	0.097	-10000	0	-10000	0	0
CTNND1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.025	0.11	-10000	0	-0.48	14	14
regulation of calcium-dependent cell-cell adhesion	-0.013	0.12	-10000	0	-0.48	15	15
EGF	0.081	0.14	0.32	69	-10000	0	69
NCKAP1	0	0	-10000	0	-10000	0	0
AQP3	-0.074	0.2	-10000	0	-0.6	33	33
cortical microtubule organization	-0.027	0.11	-10000	0	-0.51	14	14
GO:0000145	-0.024	0.1	-10000	0	-0.46	14	14
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.027	0.12	-10000	0	-0.52	14	14
MLLT4	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.044	0.15	-10000	0	-0.8	5	5
ARF6	0	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.031	0.13	-10000	0	-0.55	15	15
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.024	0.1	-10000	0	-0.45	14	14
PVRL2	0	0	-10000	0	-10000	0	0
ZYX	-0.026	0.11	-10000	0	-0.49	14	14
ARF6/GTP	-0.028	0.12	-10000	0	-0.5	15	15
CDH1	-0.046	0.2	-10000	0	-0.88	14	14
EGFR/EGFR/EGF/EGF	-0.003	0.14	-10000	0	-0.52	16	16
RhoA/GDP	-0.025	0.11	-10000	0	-0.48	14	14
actin cytoskeleton organization	-0.024	0.1	-10000	0	-0.46	14	14
IGF-1R heterotetramer	-0.006	0.098	0.32	3	-0.88	3	6
GIT1	0	0	-10000	0	-10000	0	0
IGF1R	-0.006	0.099	0.32	3	-0.88	3	6
IGF1	-0.38	0.44	-10000	0	-0.88	115	115
DIAPH1	-0.047	0.17	-10000	0	-0.73	16	16
Wnt receptor signaling pathway	0.027	0.11	0.51	14	-10000	0	14
RHOA	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.044	0.15	-10000	0	-0.55	14	14
CTNNA1	0	0	-10000	0	-10000	0	0
VCL	-0.025	0.1	-10000	0	-0.47	14	14
EFNA1	-0.01	0.092	-10000	0	-0.88	3	3
LPP	-0.024	0.1	-10000	0	-0.46	14	14
Ephrin A1/EPHA2	-0.049	0.17	-10000	0	-0.57	23	23
SEC6/SEC8	-0.023	0.096	-10000	0	-0.43	14	14
MGAT3	-0.013	0.13	-10000	0	-0.49	15	15
HGF/MET	-0.26	0.28	-10000	0	-0.52	136	136
HGF	-0.44	0.44	-10000	0	-0.88	133	133
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.019	0.081	-10000	0	-0.36	14	14
actin cable formation	0.03	0.11	-10000	0	-0.43	6	6
KIAA1543	-0.035	0.14	-10000	0	-0.55	17	17
KIFC3	-0.026	0.11	-10000	0	-0.49	14	14
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
EXOC3	0	0	-10000	0	-10000	0	0
ACTN1	-0.026	0.11	-10000	0	-0.49	14	14
NCK1/GIT1	-0.003	0.042	-10000	0	-0.68	1	1
mol:GDP	-0.027	0.11	-10000	0	-0.51	14	14
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.026	0.11	-10000	0	-0.49	14	14
PIP5K1C	-0.026	0.11	-10000	0	-0.49	14	14
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0	0	-10000	0	-10000	0	0
ROCK1	-0.037	0.12	-10000	0	-0.65	5	5
adherens junction assembly	0.012	0.14	-10000	0	-0.71	5	5
IGF-1R heterotetramer/IGF1	-0.23	0.25	-10000	0	-0.49	127	127
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-10000	0	-10000	0	0
MET	-0.002	0.057	0.32	1	-0.88	1	2
PLEKHA7	-0.029	0.12	-10000	0	-0.49	16	16
mol:GTP	-0.03	0.12	-10000	0	-0.54	15	15
establishment of epithelial cell apical/basal polarity	-0.022	0.092	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	-0.019	0.08	-10000	0	-0.36	14	14
regulation of cell-cell adhesion	-0.024	0.1	-10000	0	-0.46	14	14
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.019	0.081	-10000	0	-0.36	14	14

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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
GNAO1	-0.39	0.44	-10000	0	-0.88	120	120
CDC42/GTP	-0.13	0.15	-10000	0	-0.51	2	2
PLCG1	-0.12	0.18	-10000	0	-0.53	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
G12/G13	0	0	-10000	0	-10000	0	0
cell migration	-0.13	0.15	-10000	0	-0.5	2	2
S1PR5	-0.012	0.11	0.32	1	-0.88	4	5
S1PR4	0.001	0.019	0.32	1	-10000	0	1
MAPK3	-0.12	0.18	-10000	0	-0.53	2	2
MAPK1	-0.12	0.18	-10000	0	-0.34	52	52
S1P/S1P5/Gi	-0.14	0.2	-10000	0	-0.38	54	54
GNAI1	-0.007	0.076	-10000	0	-0.88	2	2
CDC42/GDP	0	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.008	0.074	-10000	0	-0.6	4	4
RHOA	0	0.004	-10000	0	-10000	0	0
S1P/S1P4/Gi	-0.13	0.19	-10000	0	-0.37	52	52
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.15	0.16	0.32	125	-10000	0	125
S1P/S1P4/G12/G13	0.001	0.012	-10000	0	-10000	0	0
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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.Total.Perturbations
PLK2	0	0	-10000	0	-9999	0
PLK4	0.055	0.12	0.32	47	-9999	47
regulation of centriole replication	0.042	0.052	-10000	0	-9999	0

×

S1P3 pathway

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
PDGFRB	0.007	0.047	0.32	6	-10000	0	6
mol:S1P	0.001	0.001	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.096	0.16	-10000	0	-0.3	53	53
GNAO1	-0.39	0.44	-10000	0	-0.88	120	120
S1P/S1P3/G12/G13	-0.007	0.068	-10000	0	-0.55	4	4
AKT1	-0.037	0.077	-10000	0	-10000	0	0
AKT3	-0.056	0.11	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.007	0.047	0.32	6	-10000	0	6
GNAI2	0	0.002	-10000	0	-10000	0	0
GNAI3	0	0.001	-10000	0	-10000	0	0
GNAI1	-0.006	0.076	-10000	0	-0.88	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	-0.012	0.11	0.32	1	-0.88	4	5
S1PR2	-0.003	0.054	-10000	0	-0.88	1	1
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.13	0.2	-10000	0	-0.39	53	53
MAPK3	-0.12	0.19	-10000	0	-0.79	5	5
MAPK1	-0.12	0.19	-10000	0	-0.79	5	5
JAK2	-0.1	0.2	-10000	0	-0.72	6	6
CXCR4	-0.12	0.2	-10000	0	-0.7	7	7
FLT1	0	0.003	-10000	0	-10000	0	0
RhoA/GDP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0	0	-10000	0	-10000	0	0
SRC	-0.12	0.19	-10000	0	-0.79	5	5
S1P/S1P3/Gi	-0.13	0.21	-10000	0	-0.4	53	53
RAC1	0	0	-10000	0	-10000	0	0
RhoA/GTP	-0.14	0.17	-10000	0	-0.76	5	5
VEGFA	0	0.003	-10000	0	-10000	0	0
S1P/S1P2/Gi	-0.13	0.19	-10000	0	-0.38	53	53
VEGFR1 homodimer/VEGFA homodimer	0	0.007	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.079	0.17	-10000	0	-0.39	55	55
GNAQ	-0.003	0.054	-10000	0	-0.88	1	1
GNAZ	0.15	0.16	0.32	125	-10000	0	125
G12/G13	0	0	-10000	0	-10000	0	0
GNA14	-0.15	0.33	-10000	0	-0.88	47	47
GNA15	0.002	0.027	0.32	2	-10000	0	2
GNA12	0	0	-10000	0	-10000	0	0
GNA13	0	0	-10000	0	-10000	0	0
GNA11	-0.02	0.13	-10000	0	-0.88	6	6
Rac1/GTP	-0.14	0.17	-10000	0	-0.76	5	5

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.014	0.038	-9999	-0.6	1	1
ADCY5	-0.09	0.24	-9999	-0.61	46	46
ADCY6	0.014	0.038	-9999	-0.6	1	1
ADCY7	0.014	0.038	-9999	-0.6	1	1
ADCY1	-0.21	0.3	-9999	-0.61	96	96
ADCY2	0.012	0.04	-9999	-0.61	1	1
ADCY3	0.015	0.039	-9999	-0.6	1	1
ADCY8	0.018	0.047	-9999	-0.61	1	1
PRKCE	0.007	0.044	-9999	-0.69	1	1
ADCY9	0.014	0.038	-9999	-0.6	1	1
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.034	0.093	-9999	-0.28	21	21

×

Nectin adhesion 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
PDGFRB	0.007	0.047	0.32	6	-10000	0	6
alphaV beta3 Integrin	-0.041	0.16	-10000	0	-0.68	16	16
PTK2	-0.082	0.22	-10000	0	-0.64	32	32
positive regulation of JNK cascade	-0.045	0.12	-10000	0	-0.36	33	33
CDC42/GDP	-0.06	0.16	-10000	0	-0.49	32	32
Rac1/GDP	-0.022	0.17	-10000	0	-0.48	32	32
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CTNNB1	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.056	0.15	-10000	0	-0.44	33	33
nectin-3/I-afadin	-0.082	0.22	-10000	0	-0.68	32	32
RAPGEF1	-0.031	0.2	-10000	0	-0.56	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.047	0.23	-10000	0	-0.66	32	32
PDGFB-D/PDGFRB	0.007	0.047	0.32	6	-10000	0	6
TLN1	-0.031	0.086	-10000	0	-0.48	1	1
Rap1/GTP	-0.047	0.12	-10000	0	-0.38	32	32
IQGAP1	0	0	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0	0	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.082	0.22	-10000	0	-0.68	32	32
PVR	0	0	-10000	0	-10000	0	0
Necl-5(dimer)	0	0	-10000	0	-10000	0	0
mol:GDP	-0.038	0.22	-10000	0	-0.62	32	32
MLLT4	0	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
PI3K	-0.061	0.18	-10000	0	-0.53	33	33
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.001	0.013	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	-0.046	0.12	-10000	0	-0.37	32	32
PVRL1	0.001	0.019	0.32	1	-10000	0	1
PVRL3	-0.1	0.28	-10000	0	-0.88	32	32
PVRL2	0	0	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
CDH1	-0.046	0.2	-10000	0	-0.88	14	14
CLDN1	-0.016	0.12	-10000	0	-0.88	5	5
JAM-A/CLDN1	-0.075	0.19	-10000	0	-0.56	36	36
SRC	-0.092	0.25	-10000	0	-0.75	32	32
ITGB3	-0.052	0.21	-10000	0	-0.88	16	16
nectin-1(dimer)/I-afadin/I-afadin	0.001	0.013	-10000	0	-10000	0	0
FARP2	-0.043	0.21	-10000	0	-0.6	33	33
RAC1	0	0	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.071	0.19	-10000	0	-0.6	32	32
nectin-1/I-afadin	0.001	0.013	-10000	0	-10000	0	0
nectin-2/I-afadin	0	0	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.071	0.19	-10000	0	-0.6	32	32
CDC42/GTP/IQGAP1/filamentous actin	0	0	-10000	0	-10000	0	0
F11R	0	0	-10000	0	-10000	0	0
positive regulation of filopodium formation	-0.045	0.12	-10000	0	-0.36	33	33
alphaV/beta3 Integrin/Talin	-0.057	0.16	-10000	0	-0.64	16	16
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-10000	0	-10000	0	0
PIP5K1C	-0.034	0.095	-10000	0	-0.52	1	1
VAV2	-0.042	0.21	-10000	0	-0.62	32	32
RAP1/GDP	-0.056	0.15	-10000	0	-0.45	32	32
ITGAV	0	0	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.071	0.19	-10000	0	-0.6	32	32
nectin-3(dimer)/I-afadin/I-afadin	-0.082	0.22	-10000	0	-0.68	32	32
Rac1/GTP	-0.057	0.15	-10000	0	-0.46	32	32
PTPRM	-0.039	0.11	-10000	0	-0.32	33	33
E-cadherin/beta catenin/alpha catenin	-0.025	0.11	-10000	0	-0.49	14	14
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.034	0.32	3	-10000	0	3
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.14	0.24	0.82	16	-10000	0	16
IL27/IL27R/JAK1	-0.22	0.3	-10000	0	-0.9	19	19
TBX21	-0.14	0.26	-10000	0	-0.67	24	24
IL12B	0.003	0.029	0.33	2	-10000	0	2
IL12A	0.012	0.024	-10000	0	-10000	0	0
IL6ST	-0.19	0.36	-10000	0	-0.88	58	58
IL27RA/JAK1	-0.007	0.017	-10000	0	-10000	0	0
IL27	-0.17	0.35	-10000	0	-0.88	53	53
TYK2	0.003	0.008	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.038	0.14	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.14	0.24	0.82	16	-10000	0	16
T cell proliferation during immune response	0.14	0.24	0.82	16	-10000	0	16
MAPKKK cascade	-0.14	0.24	-10000	0	-0.82	16	16
STAT3	0	0	-10000	0	-10000	0	0
STAT2	0	0	-10000	0	-10000	0	0
STAT1	0.003	0.027	0.32	2	-10000	0	2
IL12RB1	-0.029	0.16	-10000	0	-0.88	9	9
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.14	0.27	-10000	0	-0.69	24	24
IL27/IL27R/JAK2/TYK2	-0.15	0.25	-10000	0	-0.86	15	15
positive regulation of T cell mediated cytotoxicity	-0.14	0.24	-10000	0	-0.82	16	16
STAT1 (dimer)	-0.21	0.32	0.5	9	-0.94	20	29
JAK2	-0.001	0.055	-10000	0	-0.89	1	1
JAK1	0	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.15	0.22	-10000	0	-0.84	14	14
T cell proliferation	-0.21	0.29	-10000	0	-0.68	50	50
IL12/IL12R/TYK2/JAK2	0.005	0.076	-10000	0	-10000	0	0
IL17A	-0.038	0.14	-10000	0	-10000	0	0
mast cell activation	0.14	0.24	0.82	16	-10000	0	16
IFNG	-0.012	0.035	0.11	3	-0.092	10	13
T cell differentiation	-0.006	0.007	-10000	0	-0.022	14	14
STAT3 (dimer)	-0.15	0.22	-10000	0	-0.84	14	14
STAT5A (dimer)	-0.15	0.22	-10000	0	-0.84	14	14
STAT4 (dimer)	-0.17	0.25	-10000	0	-0.81	23	23
STAT4	-0.032	0.17	0.32	1	-0.88	10	11
T cell activation	-0.013	0.011	-10000	0	-0.12	1	1
IL27R/JAK2/TYK2	-0.11	0.23	-10000	0	-0.55	40	40
GATA3	-0.072	0.41	-10000	0	-1.5	20	20
IL18	-0.003	0.096	-10000	0	-0.69	5	5
positive regulation of mast cell cytokine production	-0.15	0.22	-10000	0	-0.82	14	14
IL27/EBI3	-0.17	0.3	-10000	0	-0.68	67	67
IL27RA	-0.011	0.023	-10000	0	-10000	0	0
IL6	-0.12	0.32	0.32	7	-0.88	39	46
STAT5A	0	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.01	0.019	-10000	0	-10000	0	0
IL1B	-0.099	0.25	-10000	0	-0.69	41	41
EBI3	-0.044	0.2	-10000	0	-0.88	14	14
TNF	-0.025	0.15	-10000	0	-0.69	13	13

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0	0	-10000	0	-10000	0	0
GNAT1/GTP	0.002	0.022	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.006	0.033	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	-0.014	0.099	-10000	0	-0.6	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.004	0.033	0.32	3	-10000	0	3
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	-0.12	0.23	-10000	0	-0.49	72	72
mol:Na +	-0.12	0.22	-10000	0	-0.48	68	68
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0	0.12	0.39	2	-0.6	8	10
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.12	0.23	-10000	0	-0.5	65	65
CNGB1	0.012	0.06	0.32	10	-10000	0	10
RDH5	-0.13	0.31	-10000	0	-0.88	40	40
SAG	0.001	0.019	0.32	1	-10000	0	1
mol:Ca2+	-0.12	0.21	-10000	0	-0.47	59	59
Na + (4 Units)	-0.12	0.2	-10000	0	-0.46	59	59
RGS9	-0.011	0.17	0.32	13	-0.88	8	21
GNB1/GNGT1	0.029	0.074	-10000	0	-10000	0	0
GNAT1/GDP	0.002	0.11	0.35	2	-0.52	8	10
GUCY2D	0.032	0.095	0.32	27	-10000	0	27
GNGT1	0.041	0.11	0.32	35	-10000	0	35
GUCY2F	0	0	-10000	0	-10000	0	0
GNB5	0.001	0.019	0.32	1	-10000	0	1
mol:GMP (4 units)	-0.002	0.12	-10000	0	-0.58	8	8
mol:11-cis-retinal	-0.13	0.31	-10000	0	-0.88	40	40
mol:cGMP	-0.001	0.087	-10000	0	-0.53	6	6
GNB1	0	0	-10000	0	-10000	0	0
Rhodopsin	-0.098	0.25	-10000	0	-0.68	40	40
SLC24A1	0	0	-10000	0	-10000	0	0
CNGA1	-0.22	0.38	-10000	0	-0.88	66	66
Metarhodopsin II	0.005	0.029	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.008	0.1	0.37	1	-0.56	6	7
RGS9BP	0.012	0.06	0.32	10	-10000	0	10
Metarhodopsin II/Transducin	0.017	0.039	-10000	0	-10000	0	0
GCAP Family/Ca ++	-0.011	0.085	-10000	0	-0.56	6	6
PDE6A/B	0.015	0.088	-10000	0	-0.69	2	2
mol:Pi	0	0.12	0.39	2	-0.59	8	10
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.027	0.066	-10000	0	-10000	0	0
PDE6B	0.009	0.1	0.32	13	-0.88	2	15
PDE6A	0.014	0.065	0.32	12	-10000	0	12
PDE6G	-0.023	0.14	-10000	0	-0.88	7	7
RHO	0.008	0.05	0.32	7	-10000	0	7
PDE6	-0.003	0.15	-10000	0	-0.52	15	15
GUCA1A	0.002	0.027	0.32	2	-10000	0	2
GC2/GCAP Family	-0.011	0.085	-10000	0	-0.56	6	6
GUCA1C	0	0	-10000	0	-10000	0	0
GUCA1B	-0.02	0.13	-10000	0	-0.88	6	6

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-10000	0	-10000	0	0
PRKCZ	-0.036	0.17	-10000	0	-0.88	11	11
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.076	0.16	-10000	0	-0.4	27	27
IRAK/TOLLIP	0.001	0.01	-10000	0	-10000	0	0
IKBKB	0	0	-10000	0	-10000	0	0
IKBKG	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0	0.048	-10000	0	-0.68	1	1
IL1A	0.002	0.027	0.32	2	-10000	0	2
IL1B	-0.09	0.25	-10000	0	-0.69	41	41
IRAK/TRAF6/p62/Atypical PKCs	-0.019	0.1	-10000	0	-0.47	12	12
IL1R2	-0.002	0.057	0.32	1	-0.88	1	2
IL1R1	-0.01	0.092	-10000	0	-0.88	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.062	0.14	-10000	0	-0.77	5	5
TOLLIP	0	0	-10000	0	-10000	0	0
TICAM2	-0.003	0.054	-10000	0	-0.88	1	1
MAP3K3	0	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	-0.005	0.032	-10000	0	-10000	0	0
JUN	-0.001	0.15	-10000	0	-0.49	20	20
MAP3K7	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.13	0.26	-10000	0	-0.55	64	64
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.06	0.19	-10000	0	-0.61	27	27
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.056	0.18	-10000	0	-0.57	27	27
IL1 beta fragment/IL1R1/IL1RAP	-0.14	0.28	-10000	0	-0.6	64	64
NFKB1	0	0	-10000	0	-10000	0	0
MAPK8	-0.029	0.12	-10000	0	-0.49	17	17
IRAK1	0.001	0.011	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.094	0.24	-10000	0	-0.68	37	37
IRAK4	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
TRAF6	-0.003	0.054	-10000	0	-0.88	1	1
PI3K	-0.005	0.075	-10000	0	-1.2	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.084	0.18	-10000	0	-0.45	27	27
CHUK	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.14	0.28	-10000	0	-0.6	64	64
IL1 beta/IL1R2	-0.093	0.22	-10000	0	-0.61	41	41
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.031	-10000	0	-0.49	1	1
NF kappa B1 p50/RelA	-0.12	0.22	-10000	0	-1	5	5
IRAK3	-0.02	0.13	-10000	0	-0.88	6	6
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.13	0.25	-10000	0	-0.54	65	65
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.039	0.13	-10000	0	-0.4	27	27
IL1 alpha/IL1R1/IL1RAP	-0.065	0.21	-10000	0	-0.66	27	27
RELA	0	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.004	0.033	0.32	3	-10000	0	3
MYD88	0	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	-0.001	0.033	-10000	0	-0.52	1	1
IL1RAP	-0.089	0.26	-10000	0	-0.88	27	27
UBE2N	0	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.11	0.2	-10000	0	-0.91	5	5
CASP1	0	0	-10000	0	-10000	0	0
IL1RN/IL1R2	-0.088	0.24	-10000	0	-0.7	34	34
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.14	0.26	-10000	0	-0.57	64	64
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.031	0.1	-10000	0	-0.69	3	3
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
IL1RN	-0.11	0.29	-10000	0	-0.88	34	34
TRAF6/TAK1/TAB1/TAB2	-0.002	0.031	-10000	0	-0.51	1	1
MAP2K6	-0.01	0.091	-10000	0	-0.56	6	6

×

FAS signaling pathway (CD95)

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
SPTAN1	0	0.03	-10000	0	-0.39	1	1
RFC1	0	0.03	-10000	0	-0.39	1	1
PRKDC	0	0.03	-10000	0	-0.39	1	1
RIPK1	0	0	-10000	0	-10000	0	0
CASP7	-0.012	0.044	0.27	1	-10000	0	1
FASLG/FAS/FADD/FAF1	0.027	0.15	0.27	43	-0.4	13	56
MAP2K4	-0.016	0.15	-10000	0	-0.45	12	12
mol:ceramide	-0.045	0.13	-10000	0	-0.54	12	12
GSN	0	0.03	-10000	0	-0.39	1	1
FASLG/FAS/FADD/FAF1/Caspase 8	0.009	0.14	0.31	2	-0.45	9	11
FAS	-0.032	0.17	-10000	0	-0.88	10	10
BID	0.002	0.03	0.32	2	-10000	0	2
MAP3K1	-0.001	0.087	-10000	0	-0.3	6	6
MAP3K7	0	0.002	-10000	0	-10000	0	0
RB1	0	0.03	-10000	0	-0.39	1	1
CFLAR	0	0	-10000	0	-10000	0	0
HGF/MET	-0.42	0.43	-10000	0	-0.78	145	145
ARHGDIB	0	0.03	-10000	0	-0.39	1	1
FADD	0.002	0.02	0.32	1	-10000	0	1
actin filament polymerization	0	0.03	0.39	1	-10000	0	1
NFKB1	-0.033	0.084	-10000	0	-10000	0	0
MAPK8	-0.052	0.22	-10000	0	-0.47	49	49
DFFA	0	0.03	-10000	0	-0.39	1	1
DNA fragmentation during apoptosis	-0.002	0.046	-10000	0	-0.48	2	2
FAS/FADD/MET	-0.024	0.12	-10000	0	-0.6	11	11
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.004	0.078	0.32	1	-0.88	2	3
FAF1	0.001	0.005	-10000	0	-10000	0	0
PARP1	0	0.03	-10000	0	-0.39	1	1
DFFB	-0.002	0.046	-10000	0	-0.48	2	2
CHUK	-0.028	0.075	-10000	0	-10000	0	0
FASLG	-0.03	0.17	0.32	2	-0.88	10	12
FAS/FADD	-0.025	0.13	-10000	0	-0.69	10	10
HGF	-0.44	0.44	-10000	0	-0.88	133	133
LMNA	0	0.028	-10000	0	-0.36	1	1
CASP6	0	0.03	-10000	0	-0.39	1	1
CASP10	0.001	0.004	-10000	0	-10000	0	0
CASP3	0	0.035	0.24	2	-0.44	1	3
PTPN13	-0.2	0.37	0.32	2	-0.88	61	63
CASP8	0.003	0.042	0.47	2	-10000	0	2
IL6	-0.18	0.51	-10000	0	-1.4	39	39
MET	-0.002	0.057	0.32	1	-0.88	1	2
ICAD/CAD	-0.002	0.043	-10000	0	-0.45	2	2
FASLG/FAS/FADD/FAF1/Caspase 10	-0.046	0.14	-10000	0	-0.55	12	12
activation of caspase activity by cytochrome c	0.002	0.03	0.32	2	-10000	0	2
PAK2	0	0.03	-10000	0	-0.39	1	1
BCL2	0	0	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	-0.005	0.009	-10000	0	-10000	0	0
HSPA8	0.001	0.054	-10000	0	-0.88	1	1
SMAD3/SMAD4/ER alpha	-0.35	0.32	-10000	0	-0.65	143	143
AKT1	0.002	0.01	-10000	0	-10000	0	0
GSC	0.038	0.063	-10000	0	-10000	0	0
NKX2-5	0.018	0.073	0.32	15	-10000	0	15
muscle cell differentiation	0.012	0.054	0.66	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.001	0.072	-10000	0	-0.57	1	1
SMAD4	-0.009	0.075	-10000	0	-0.94	1	1
CBFB	0	0	-10000	0	-10000	0	0
SAP18	0	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.003	0.037	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	-0.018	0.098	-10000	0	-0.55	7	7
MYC	-0.1	0.28	-10000	0	-0.89	30	30
CDKN2B	0.071	0.087	0.49	2	-10000	0	2
AP1	-0.23	0.28	-10000	0	-0.51	120	120
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.001	0.026	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.006	0.053	-10000	0	-0.37	1	1
SP3	0	0	-10000	0	-10000	0	0
CREB1	0	0	-10000	0	-10000	0	0
FOXH1	0.032	0.095	0.33	25	-10000	0	25
SMAD3/SMAD4/GR	-0.016	0.06	-10000	0	-0.64	1	1
GATA3	-0.08	0.24	0.32	1	-0.92	20	21
SKI/SIN3/HDAC complex/NCoR1	0.015	0.033	-10000	0	-10000	0	0
MEF2C/TIF2	-0.045	0.15	-10000	0	-0.49	18	18
endothelial cell migration	0.4	0.67	1.5	72	-10000	0	72
MAX	0.015	0.025	-10000	0	-10000	0	0
RBBP7	0	0.001	-10000	0	-10000	0	0
RBBP4	0	0.001	-10000	0	-10000	0	0
RUNX2	-0.01	0.11	0.32	3	-0.88	4	7
RUNX3	-0.023	0.14	-10000	0	-0.88	7	7
RUNX1	-0.003	0.054	-10000	0	-0.88	1	1
CTBP1	0	0	-10000	0	-10000	0	0
NR3C1	0.015	0.025	-10000	0	-10000	0	0
VDR	-0.01	0.14	0.32	8	-0.88	6	14
CDKN1A	0.009	0.19	-10000	0	-1.2	5	5
KAT2B	-0.01	0.093	-10000	0	-0.88	3	3
SMAD2/SMAD2/SMAD4/FOXH1	0.021	0.082	0.34	4	-0.59	1	5
DCP1A	0	0	-10000	0	-10000	0	0
SKI	0	0.001	-10000	0	-10000	0	0
SERPINE1	-0.41	0.69	-10000	0	-1.5	72	72
SMAD3/SMAD4/ATF2	-0.027	0.096	-10000	0	-0.63	5	5
SMAD3/SMAD4/ATF3	-0.048	0.16	-10000	0	-0.68	14	14
SAP30	0	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	-0.008	0.014	-10000	0	-10000	0	0
JUN	-0.22	0.28	-10000	0	-0.5	120	120
SMAD3/SMAD4/IRF7	-0.025	0.092	-10000	0	-0.66	4	4
TFE3	-0.009	0.017	-10000	0	-10000	0	0
COL1A2	0.11	0.14	0.46	9	-1.2	1	10
mesenchymal cell differentiation	0.025	0.11	0.69	5	-0.33	1	6
DLX1	0.025	0.085	0.32	21	-10000	0	21
TCF3	0	0	-10000	0	-10000	0	0
FOS	-0.39	0.44	-10000	0	-0.88	120	120
SMAD3/SMAD4/Max	-0.016	0.06	-10000	0	-0.64	1	1
Cbp/p300/SNIP1	-0.001	0.002	-10000	0	-10000	0	0
ZBTB17	-0.001	0.005	-10000	0	-10000	0	0
LAMC1	0.01	0.069	-10000	0	-0.56	1	1
TGIF2/HDAC complex/SMAD3/SMAD4	-0.018	0.062	-10000	0	-0.64	1	1
IRF7	-0.01	0.092	-10000	0	-0.88	3	3
ESR1	-0.47	0.44	-10000	0	-0.88	143	143
HNF4A	-0.02	0.13	-10000	0	-0.88	6	6
MEF2C	0.013	0.051	-10000	0	-0.49	1	1
SMAD2-3/SMAD4	-0.014	0.064	-10000	0	-0.64	1	1
Cbp/p300/Src-1	-0.003	0.005	-10000	0	-10000	0	0
IGHV3OR16-13	-0.005	0.024	-10000	0	-10000	0	0
TGIF2/HDAC complex	0	0	-10000	0	-10000	0	0
CREBBP	-0.002	0.004	-10000	0	-10000	0	0
SKIL	0	0	-10000	0	-10000	0	0
HDAC1	0	0.001	-10000	0	-10000	0	0
HDAC2	0	0.001	-10000	0	-10000	0	0
SNIP1	0.004	0.006	-10000	0	-10000	0	0
GCN5L2	-0.008	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.02	0.065	-10000	0	-0.64	1	1
MSG1/HSC70	0.013	0.059	-10000	0	-0.64	1	1
SMAD2	0.004	0.013	-10000	0	-10000	0	0
SMAD3	-0.01	0.05	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0	0.057	-10000	0	-0.39	3	3
SMAD2/SMAD2/SMAD4	-0.009	0.066	-10000	0	-0.49	4	4
NCOR1	-0.006	0.076	-10000	0	-0.88	2	2
NCOA2	-0.095	0.27	-10000	0	-0.88	29	29
NCOA1	0	0	-10000	0	-10000	0	0
MYOD/E2A	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.004	0.07	-10000	0	-0.53	1	1
IFNB1	-0.007	0.088	-10000	0	-0.6	4	4
SMAD3/SMAD4/MEF2C	0.008	0.062	-10000	0	-0.51	1	1
CITED1	0.013	0.063	0.32	11	-10000	0	11
SMAD2-3/SMAD4/ARC105	-0.008	0.057	-10000	0	-0.57	1	1
RBL1	0.013	0.063	0.32	11	-10000	0	11
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.007	0.058	-10000	0	-0.36	1	1
RUNX1-3/PEBPB2	-0.018	0.11	-10000	0	-0.67	7	7
SMAD7	-0.16	0.22	-10000	0	-0.74	11	11
MYC/MIZ-1	-0.08	0.22	-10000	0	-0.69	30	30
SMAD3/SMAD4	-0.14	0.21	-10000	0	-0.47	72	72
IL10	-0.13	0.33	-10000	0	-0.85	43	43
PIASy/HDAC complex	0.011	0.015	-10000	0	-10000	0	0
PIAS3	0	0	-10000	0	-10000	0	0
CDK2	0	0.001	-10000	0	-10000	0	0
IL5	-0.064	0.21	-10000	0	-0.67	21	21
CDK4	0	0.002	-10000	0	-10000	0	0
PIAS4	0.011	0.015	-10000	0	-10000	0	0
ATF3	-0.043	0.19	-10000	0	-0.88	13	13
SMAD3/SMAD4/SP1	-0.01	0.074	-10000	0	-0.63	1	1
FOXG1	0.01	0.058	0.32	9	-10000	0	9
FOXO3	0.023	0.011	-10000	0	-10000	0	0
FOXO1	0.015	0.075	-10000	0	-0.68	3	3
FOXO4	0.023	0.011	-10000	0	-10000	0	0
heart looping	0.013	0.05	-10000	0	-0.48	1	1
CEBPB	0.001	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.004	0.085	0.33	1	-0.65	1	2
MYOD1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.032	0.11	-10000	0	-0.64	7	7
SMAD3/SMAD4/GATA3	-0.088	0.22	-10000	0	-0.62	33	33
SnoN/SIN3/HDAC complex/NCoR1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.026	0.12	-10000	0	-0.64	8	8
SMAD3/SMAD4/SP1-3	-0.005	0.065	-10000	0	-0.56	1	1
MED15	0	0	-10000	0	-10000	0	0
SP1	0.002	0.017	-10000	0	-10000	0	0
SIN3B	0	0.001	-10000	0	-10000	0	0
SIN3A	0	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.032	0.097	0.4	6	-0.54	1	7
ITGB5	-0.003	0.055	-10000	0	-0.51	1	1
TGIF/SIN3/HDAC complex/CtBP	0.001	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.19	0.28	-10000	0	-0.64	75	75
AR	-0.24	0.39	-10000	0	-0.88	74	74
negative regulation of cell growth	-0.011	0.077	-10000	0	-0.42	2	2
SMAD3/SMAD4/MYOD	-0.021	0.064	-10000	0	-0.65	1	1
E2F5	0.005	0.074	0.32	7	-0.88	1	8
E2F4	0	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.018	0.07	-10000	0	-0.5	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	0.003	0.055	-10000	0	-0.38	1	1
TFDP1	-0.003	0.054	-10000	0	-0.88	1	1
SMAD3/SMAD4/AP1	-0.22	0.29	-10000	0	-0.51	120	120
SMAD3/SMAD4/RUNX2	-0.025	0.11	0.33	1	-0.69	5	6
TGIF2	0	0	-10000	0	-10000	0	0
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	-0.013	0.11	-10000	0	-0.88	4	4

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.016	0.094	-10000	0	-0.54	8	8
CRKL	0	0	-10000	0	-10000	0	0
Rac1/GDP	0	0	-10000	0	-10000	0	0
DOCK1	-0.016	0.12	-10000	0	-0.88	5	5
ITGA4	-0.012	0.11	0.32	1	-0.88	4	5
alpha4/beta7 Integrin/MAdCAM1	-0.014	0.098	0.38	1	-0.55	8	9
EPO	-0.3	0.43	0.32	8	-0.88	96	104
alpha4/beta7 Integrin	-0.02	0.12	-10000	0	-0.68	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.009	0.084	-10000	0	-0.68	4	4
EPO/EPOR (dimer)	-0.24	0.34	-10000	0	-0.68	96	96
lamellipodium assembly	-0.003	0.054	-10000	0	-0.88	1	1
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
PI3K	-0.005	0.075	-10000	0	-1.2	1	1
ARF6	0	0	-10000	0	-10000	0	0
JAK2	-0.15	0.2	-10000	0	-0.41	98	98
PXN	0	0	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
MADCAM1	0.004	0.033	0.32	3	-10000	0	3
cell adhesion	-0.013	0.097	0.36	1	-0.54	8	9
CRKL/CBL	0	0	-10000	0	-10000	0	0
ITGB1	0	0	-10000	0	-10000	0	0
SRC	-0.036	0.15	-10000	0	-0.6	17	17
ITGB7	-0.013	0.11	-10000	0	-0.88	4	4
RAC1	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.038	0.17	-10000	0	-0.66	17	17
p130Cas/Crk/Dock1	-0.041	0.16	-10000	0	-0.58	19	19
VCAM1	-0.044	0.21	0.32	4	-0.88	15	19
RHOA	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.007	0.067	-10000	0	-0.55	4	4
BCAR1	-0.034	0.14	-10000	0	-0.56	17	17
EPOR	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
GIT1	0	0	-10000	0	-10000	0	0
Rac1/GTP	-0.004	0.058	-10000	0	-0.94	1	1

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0	0	-10000	0	-10000	0	0
ELF1	-0.005	0.081	-10000	0	-0.47	6	6
CCNA2	0.17	0.16	0.32	141	-10000	0	141
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
JAK3	-0.001	0.06	0.32	2	-0.88	1	3
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
JAK1	0	0	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.028	0.15	0.3	1	-0.67	10	11
SHC1	0	0	-10000	0	-10000	0	0
SP1	0.003	0.021	-10000	0	-10000	0	0
IL2RA	0.01	0.16	-10000	0	-1	6	6
IL2RB	-0.066	0.23	-10000	0	-0.88	20	20
SOS1	0	0	-10000	0	-10000	0	0
IL2RG	-0.006	0.12	0.32	6	-0.88	4	10
G1/S transition of mitotic cell cycle	0.052	0.15	-10000	0	-0.47	18	18
PTPN11	0	0	-10000	0	-10000	0	0
CCND2	0.028	0.036	-10000	0	-10000	0	0
LCK	-0.025	0.15	0.32	1	-0.88	8	9
GRB2	0	0	-10000	0	-10000	0	0
IL2	0	0	-10000	0	-10000	0	0
CDK6	-0.059	0.22	-10000	0	-0.88	18	18
CCND3	0.031	0.13	-10000	0	-0.7	5	5

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0.083	0.16	-10000	0	-0.58	3	3
RAD9A	0	0	-10000	0	-10000	0	0
AP1	-0.31	0.36	-10000	0	-0.7	120	120
IFNAR2	0.01	0.014	-10000	0	-10000	0	0
AKT1	-0.15	0.16	-10000	0	-0.31	97	97
ER alpha/Oestrogen	-0.36	0.35	-10000	0	-0.69	143	143
NFX1/SIN3/HDAC complex	0.024	0.033	-10000	0	-10000	0	0
EGF	0.085	0.14	0.32	69	-10000	0	69
SMG5	0	0	-10000	0	-10000	0	0
SMG6	0	0	-10000	0	-10000	0	0
SP3/HDAC2	0.017	0.023	-10000	0	-10000	0	0
TERT/c-Abl	-0.025	0.071	-10000	0	-0.54	3	3
SAP18	0.002	0.005	-10000	0	-10000	0	0
MRN complex	0	0	-10000	0	-10000	0	0
WT1	0.029	0.076	0.33	16	-10000	0	16
WRN	0	0	-10000	0	-10000	0	0
SP1	0.014	0.019	-10000	0	-10000	0	0
SP3	0.006	0.008	-10000	0	-10000	0	0
TERF2IP	0	0	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.019	0.062	-10000	0	-0.51	2	2
Mad/Max	0.015	0.024	-10000	0	-10000	0	0
TERT	0.083	0.16	-10000	0	-0.59	3	3
CCND1	0.051	0.28	-10000	0	-1.2	10	10
MAX	0.007	0.009	-10000	0	-10000	0	0
RBBP7	0.002	0.005	-10000	0	-10000	0	0
RBBP4	0.002	0.005	-10000	0	-10000	0	0
TERF2	0	0	-10000	0	-10000	0	0
PTGES3	0	0	-10000	0	-10000	0	0
SIN3A	0.002	0.005	-10000	0	-10000	0	0
Telomerase/911	0.029	0.047	-10000	0	-10000	0	0
CDKN1B	0.019	0.028	-10000	0	-10000	0	0
RAD1	0	0	-10000	0	-10000	0	0
XRCC5	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
SAP30	0.002	0.005	-10000	0	-10000	0	0
TRF2/PARP2	0	0	-10000	0	-10000	0	0
UBE3A	0.006	0.008	-10000	0	-10000	0	0
JUN	-0.013	0.12	-10000	0	-0.88	5	5
E6	0.004	0.005	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.01	0.014	-10000	0	-10000	0	0
FOS	-0.39	0.44	-10000	0	-0.87	120	120
IFN-gamma/IRF1	0.023	0.046	-10000	0	-10000	0	0
PARP2	0	0	-10000	0	-10000	0	0
BLM	0.11	0.15	0.32	91	-10000	0	91
Telomerase	0.041	0.064	-10000	0	-10000	0	0
IRF1	0.008	0.011	-10000	0	-10000	0	0
ESR1	-0.47	0.44	-10000	0	-0.88	143	143
KU/TER	0	0	-10000	0	-10000	0	0
ATM/TRF2	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.025	0.034	-10000	0	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.025	0.034	-10000	0	-10000	0	0
HDAC1	0.002	0.005	-10000	0	-10000	0	0
HDAC2	0.012	0.016	-10000	0	-10000	0	0
ATM	0	0	-10000	0	-10000	0	0
SMAD3	0.005	0.017	-10000	0	-10000	0	0
ABL1	0	0	-10000	0	-10000	0	0
MXD1	0.008	0.022	0.33	1	-10000	0	1
MRE11A	0	0	-10000	0	-10000	0	0
HUS1	0	0	-10000	0	-10000	0	0
RPS6KB1	0	0	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.044	0.11	-10000	0	-0.62	2	2
NR2F2	0.001	0.003	-10000	0	-10000	0	0
MAPK3	0.018	0.01	-10000	0	-10000	0	0
MAPK1	0.018	0.01	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.004	0.033	0.32	3	-10000	0	3
NFKB1	0	0	-10000	0	-10000	0	0
HNRNPC	0	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-10000	0	-10000	0	0
NBN	0	0	-10000	0	-10000	0	0
EGFR	-0.008	0.11	-10000	0	-0.88	4	4
mol:Oestrogen	0.001	0.002	-10000	0	-10000	0	0
EGF/EGFR	0.052	0.13	0.24	21	-0.67	4	25
MYC	-0.092	0.28	-10000	0	-0.88	30	30
IL2	0.013	0.017	-10000	0	-10000	0	0
KU	0	0	-10000	0	-10000	0	0
RAD50	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
TGFB1	0.004	0.033	0.32	3	-10000	0	3
TRF2/BLM	0.071	0.099	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	-0.023	0.07	-10000	0	-0.54	3	3
SP1/HDAC2	0.026	0.035	-10000	0	-10000	0	0
PINX1	0	0	-10000	0	-10000	0	0
Telomerase/EST1A	-0.019	0.062	-10000	0	-0.51	2	2
Smad3/Myc	-0.066	0.19	-10000	0	-0.6	30	30
911 complex	0	0	-10000	0	-10000	0	0
IFNG	0.019	0.059	0.33	9	-10000	0	9
Telomerase/PinX1	-0.019	0.062	-10000	0	-0.51	2	2
Telomerase/AKT1/mTOR/p70S6K	0.007	0.081	-10000	0	-10000	0	0
SIN3B	0.002	0.005	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
Telomerase/EST1B	-0.019	0.062	-10000	0	-0.51	2	2
response to DNA damage stimulus	0.002	0	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-10000	0	-10000	0	0
TRF2/WRN	0	0	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	-0.019	0.062	-10000	0	-0.51	2	2
E2F1	0.2	0.16	0.33	161	-10000	0	161
ZNFX1	0.002	0.005	-10000	0	-10000	0	0
PIF1	0.089	0.14	0.32	75	-10000	0	75
NCL	0	0	-10000	0	-10000	0	0
DKC1	0	0	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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
HDAC1	0.017	0.003	-10000	0	-10000	0	0
SMARCC1	0.004	0.009	-10000	0	-10000	0	0
REL	-0.026	0.15	-10000	0	-0.88	8	8
HDAC7	-0.035	0.17	-10000	0	-0.56	17	17
JUN	-0.016	0.12	-10000	0	-0.88	5	5
EP300	0	0	-10000	0	-10000	0	0
KAT2B	-0.01	0.092	-10000	0	-0.88	3	3
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	0.003	0.11	-10000	0	-0.69	6	6
FOXO1	-0.01	0.092	-10000	0	-0.88	3	3
T-DHT/AR	-0.075	0.16	-10000	0	-0.59	18	18
MAP2K6	-0.015	0.14	0.32	4	-0.88	6	10
BRM/BAF57	-0.019	0.12	-10000	0	-0.69	8	8
MAP2K4	0	0.003	-10000	0	-10000	0	0
SMARCA2	-0.025	0.15	-10000	0	-0.88	8	8
PDE9A	-0.13	0.37	-10000	0	-1.2	27	27
NCOA2	-0.094	0.27	-10000	0	-0.88	29	29
CEBPA	-0.009	0.095	0.32	1	-0.88	3	4
EHMT2	0.001	0.004	-10000	0	-10000	0	0
cell proliferation	-0.015	0.17	-10000	0	-0.53	16	16
NR0B1	0.059	0.12	0.32	50	-10000	0	50
EGR1	-0.28	0.41	-10000	0	-0.88	86	86
RXRs/9cRA	0.013	0.1	-10000	0	-0.55	5	5
AR/RACK1/Src	-0.045	0.15	-10000	0	-0.56	17	17
AR/GR	-0.11	0.18	-10000	0	-0.36	68	68
GNB2L1	0.001	0.004	-10000	0	-10000	0	0
PKN1	0.001	0.019	0.32	1	-10000	0	1
RCHY1	0	0	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0.001	0.002	-10000	0	-10000	0	0
MAPK8	-0.012	0.14	-10000	0	-0.69	11	11
T-DHT/AR/TIF2/CARM1	-0.1	0.26	-10000	0	-0.72	35	35
SRC	0.001	0.14	-10000	0	-0.52	17	17
NR3C1	0	0	-10000	0	-10000	0	0
KLK3	-0.022	0.22	-10000	0	-1.1	8	8
APPBP2	0	0.001	-10000	0	-10000	0	0
TRIM24	0.001	0.006	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.066	0.15	-10000	0	-0.6	17	17
TMPRSS2	-0.079	0.3	-10000	0	-1.3	14	14
RXRG	0.025	0.15	0.32	32	-0.88	4	36
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	-0.003	0.054	-10000	0	-0.88	1	1
RXRB	0	0	-10000	0	-10000	0	0
CARM1	0.001	0.004	-10000	0	-10000	0	0
NR2C2	-0.01	0.092	-10000	0	-0.88	3	3
KLK2	-0.024	0.19	-10000	0	-0.58	16	16
AR	-0.12	0.2	-10000	0	-0.39	83	83
SENP1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
MDM2	0.001	0.006	-10000	0	-10000	0	0
SRY	0.003	0.034	0.32	3	-10000	0	3
GATA2	-0.004	0.081	0.32	2	-0.88	2	4
MYST2	0	0	-10000	0	-10000	0	0
HOXB13	0.069	0.13	0.32	57	-10000	0	57
T-DHT/AR/RACK1/Src	-0.054	0.15	-10000	0	-0.57	17	17
positive regulation of transcription	-0.004	0.08	0.32	2	-0.88	2	4
DNAJA1	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.001	0.005	-10000	0	-10000	0	0
NCOA1	0.007	0.01	-10000	0	-10000	0	0
SPDEF	0.053	0.12	0.32	44	-10000	0	44
T-DHT/AR/TIF2	-0.045	0.2	-10000	0	-0.57	24	24
T-DHT/AR/Hsp90	-0.067	0.15	-10000	0	-0.6	17	17
GSK3B	0.001	0.003	-10000	0	-10000	0	0
NR2C1	0	0	-10000	0	-10000	0	0
mol:T-DHT	-0.007	0.15	-10000	0	-0.56	17	17
SIRT1	-0.003	0.054	-10000	0	-0.88	1	1
ZMIZ2	0.001	0.006	-10000	0	-10000	0	0
POU2F1	0.008	0.03	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.03	0.18	-10000	0	-0.6	17	17
CREBBP	0	0	-10000	0	-10000	0	0
SMARCE1	0.001	0.005	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.027	0.17	0.69	16	-10000	0	16
KIRREL	-0.05	0.21	0.32	1	-0.88	16	17
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.027	0.18	-10000	0	-0.69	16	16
PLCG1	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
WASL	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.017	0.14	-10000	0	-0.53	16	16
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.015	0.1	-10000	0	-0.38	17	17
FYN	-0.025	0.12	-10000	0	-0.5	16	16
mol:Ca2+	-0.017	0.14	-10000	0	-0.52	16	16
mol:DAG	-0.017	0.14	-10000	0	-0.53	16	16
NPHS2	0.004	0.047	0.32	5	-10000	0	5
mol:IP3	-0.017	0.14	-10000	0	-0.53	16	16
regulation of endocytosis	-0.015	0.12	-10000	0	-0.47	16	16
Nephrin/NEPH1/podocin/Cholesterol	-0.018	0.14	-10000	0	-0.54	16	16
establishment of cell polarity	-0.027	0.17	-10000	0	-0.69	16	16
Nephrin/NEPH1/podocin/NCK1-2	-0.016	0.13	-10000	0	-0.49	17	17
Nephrin/NEPH1/beta Arrestin2	-0.015	0.12	-10000	0	-0.48	16	16
NPHS1	0.019	0.082	0.32	18	-10000	0	18
Nephrin/NEPH1/podocin	-0.015	0.13	-10000	0	-0.5	16	16
TJP1	0	0	-10000	0	-10000	0	0
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
NCK2	0.001	0.019	0.32	1	-10000	0	1
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.017	0.14	-10000	0	-0.53	16	16
CD2AP	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.017	0.14	-10000	0	-0.53	16	16
GRB2	0	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.006	0.14	-10000	0	-0.49	16	16
cytoskeleton organization	-0.021	0.12	-10000	0	-0.5	16	16
Nephrin/NEPH1	-0.019	0.13	-10000	0	-0.52	16	16
Nephrin/NEPH1/ZO-1	-0.022	0.15	-10000	0	-0.57	16	16

×

FoxO family signaling

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
G6PC	-0.22	0.58	-10000	0	-1.4	49	49
PLK1	0.26	0.25	0.68	4	-0.78	3	7
CDKN1B	0.16	0.16	0.46	6	-0.37	1	7
FOXO3	0.22	0.25	0.48	88	-0.76	5	93
KAT2B	0.039	0.1	-10000	0	-0.88	3	3
FOXO1/SIRT1	-0.071	0.17	-10000	0	-0.4	49	49
CAT	0.16	0.38	0.58	4	-1.3	13	17
CTNNB1	0	0	-10000	0	-10000	0	0
AKT1	0.043	0.038	-10000	0	-10000	0	0
FOXO1	-0.037	0.19	-10000	0	-0.42	50	50
MAPK10	0.017	0.12	-10000	0	-0.52	13	13
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
FOXO4	0.072	0.12	-10000	0	-0.55	5	5
response to oxidative stress	0.037	0.04	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.021	0.18	0.41	22	-0.81	5	27
XPO1	0	0	-10000	0	-10000	0	0
EP300	-0.002	0.019	-10000	0	-10000	0	0
BCL2L11	0.07	0.057	-10000	0	-10000	0	0
FOXO1/SKP2	-0.072	0.16	-10000	0	-0.39	49	49
mol:GDP	0.037	0.04	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
GADD45A	0.15	0.21	0.47	1	-0.89	7	8
YWHAQ	0	0	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.072	0.05	-10000	0	-10000	0	0
MST1	-0.029	0.26	-10000	0	-0.84	24	24
CSNK1D	0	0	-10000	0	-10000	0	0
CSNK1E	0.001	0.019	0.32	1	-10000	0	1
FOXO4/14-3-3 family	0.075	0.065	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	0.017	0.12	-10000	0	-0.54	11	11
MAPK9	0.039	0.019	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
YWHAZ	0	0	-10000	0	-10000	0	0
SIRT1	0.001	0.056	-10000	0	-0.87	1	1
SOD2	0.16	0.21	0.48	4	-0.72	6	10
RBL2	0.17	0.28	-10000	0	-1.3	6	6
RAL/GDP	0.03	0.032	-10000	0	-10000	0	0
CHUK	0.05	0.034	-10000	0	-10000	0	0
Ran/GTP	0	0	-10000	0	-10000	0	0
CSNK1G2	0	0	-10000	0	-10000	0	0
RAL/GTP	0.042	0.027	-10000	0	-10000	0	0
CSNK1G1	0	0	-10000	0	-10000	0	0
FASLG	0.017	0.31	-10000	0	-1.5	10	10
SKP2	0	0	-10000	0	-10000	0	0
USP7	0	0	-10000	0	-10000	0	0
IKBKB	0.05	0.034	-10000	0	-10000	0	0
CCNB1	0.25	0.25	0.65	5	-0.78	3	8
FOXO1-3a-4/beta catenin	-0.025	0.087	-10000	0	-0.42	7	7
proteasomal ubiquitin-dependent protein catabolic process	-0.072	0.15	-10000	0	-0.38	49	49
CSNK1A1	0	0	-10000	0	-10000	0	0
SGK1	0.022	0.16	-10000	0	-0.86	8	8
CSNK1G3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
ZFAND5	0.074	0.12	-10000	0	-0.74	2	2
SFN	0.18	0.16	0.32	155	-10000	0	155
CDK2	-0.014	0.031	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.12	0.088	-10000	0	-10000	0	0
CREBBP	-0.014	0.031	-10000	0	-10000	0	0
FBXO32	0.21	0.25	0.68	4	-0.93	4	8
BCL6	0.19	0.19	0.5	4	-0.74	3	7
RALB	0	0	-10000	0	-10000	0	0
RALA	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.004	0.17	-10000	0	-0.78	9	9
UGCG	-0.059	0.2	-10000	0	-0.77	18	18
AKT1/mTOR/p70S6K/Hsp90/TERT	0.05	0.13	0.31	1	-0.36	8	9
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.04	0.2	-10000	0	-0.76	18	18
mol:DAG	-0.001	0.005	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.057	0.14	-10000	0	-0.55	9	9
FRAP1	0.002	0.19	0.34	1	-0.46	29	30
FOXO3	0.001	0.19	-10000	0	-0.46	29	29
AKT1	-0.008	0.21	0.32	1	-0.47	38	39
GAB2	0	0	-10000	0	-10000	0	0
SMPD1	-0.008	0.028	-10000	0	-10000	0	0
SGMS1	-0.008	0.028	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.012	0.07	-10000	0	-1.1	1	1
CALM1	0	0	-10000	0	-10000	0	0
cell proliferation	-0.032	0.19	-10000	0	-0.37	46	46
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	-0.005	0.075	-10000	0	-1.2	1	1
RPS6KB1	0.026	0.037	-10000	0	-10000	0	0
mol:sphingomyelin	-0.001	0.005	-10000	0	-10000	0	0
natural killer cell activation	0	0.004	-10000	0	-0.013	1	1
JAK3	0	0.06	0.32	2	-0.88	1	3
PIK3R1	-0.002	0.054	-10000	0	-0.88	1	1
JAK1	0.001	0.003	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
MYC	-0.072	0.37	-10000	0	-1	33	33
MYB	0.13	0.1	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.002	0.18	0.32	1	-0.63	13	14
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.002	0.005	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.003	0.18	0.32	1	-0.61	13	14
Rac1/GDP	-0.004	0.064	-10000	0	-1	1	1
T cell proliferation	-0.009	0.18	-10000	0	-0.5	24	24
SHC1	0	0	-10000	0	-10000	0	0
RAC1	0	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.015	0.03	0.1	29	-10000	0	29
PRKCZ	-0.011	0.19	-10000	0	-0.53	24	24
NF kappa B1 p50/RelA	-0.056	0.13	-10000	0	-0.58	8	8
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.038	0.18	0.26	1	-0.89	9	10
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
IL2RA	-0.005	0.14	0.32	10	-0.88	5	15
IL2RB	-0.065	0.23	-10000	0	-0.88	20	20
TERT	0.12	0.15	0.32	100	-10000	0	100
E2F1	0.13	0.1	0.36	26	-10000	0	26
SOS1	0	0	-10000	0	-10000	0	0
RPS6	0	0	-10000	0	-10000	0	0
mol:cAMP	-0.007	0.012	-10000	0	-0.042	29	29
PTPN11	0	0	-10000	0	-10000	0	0
IL2RG	-0.005	0.12	0.32	6	-0.88	4	10
actin cytoskeleton organization	-0.009	0.18	-10000	0	-0.5	24	24
GRB2	0	0	-10000	0	-10000	0	0
IL2	0.001	0.004	-10000	0	-10000	0	0
PIK3CA	-0.002	0.054	-10000	0	-0.88	1	1
Rac1/GTP	-0.001	0.063	-10000	0	-1	1	1
LCK	-0.024	0.15	0.32	1	-0.88	8	9
BCL2	0.017	0.15	-10000	0	-0.52	7	7

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0.04	-10000	0	-10000	0	0
AES	0.013	0.034	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
LRP6/FZD1	-0.007	0.073	-10000	0	-0.68	3	3
SMAD4	-0.003	0.054	-10000	0	-0.88	1	1
DKK2	0.042	0.11	0.32	36	-10000	0	36
TLE1	0.01	0.065	-10000	0	-0.88	1	1
MACF1	0	0	-10000	0	-10000	0	0
CTNNB1	0.041	0.06	-10000	0	-0.38	2	2
WIF1	0.028	0.09	0.32	24	-10000	0	24
beta catenin/RanBP3	0.049	0.16	0.41	40	-10000	0	40
KREMEN2	0.035	0.1	0.32	30	-10000	0	30
DKK1	0.1	0.15	0.32	85	-10000	0	85
beta catenin/beta TrCP1	0.002	0.048	-10000	0	-10000	0	0
FZD1	-0.009	0.095	0.32	1	-0.88	3	4
AXIN2	-0.051	0.33	-10000	0	-1.3	14	14
AXIN1	0	0	-10000	0	-10000	0	0
RAN	0	0.002	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.011	0.029	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.057	0.077	0.31	1	-0.52	2	3
Axin1/APC/GSK3	0.002	0.043	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.034	0.06	-10000	0	-0.49	2	2
HNF1A	0.001	0.11	-10000	0	-0.87	4	4
CTBP1	0.015	0.037	-10000	0	-10000	0	0
MYC	-0.18	0.53	-10000	0	-1.7	30	30
RANBP3	0	0.002	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.049	0.091	0.39	3	-10000	0	3
NKD1	0.027	0.23	0.32	56	-0.88	12	68
TCF4	0.014	0.036	-10000	0	-10000	0	0
TCF3	0.014	0.036	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.003	0.063	-10000	0	-0.55	3	3
Ran/GTP	0.001	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.08	0.22	0.54	40	-0.66	1	41
LEF1	0.13	0.15	0.31	102	-10000	0	102
DVL1	0.009	0.031	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.049	0.11	-10000	0	-0.55	2	2
DKK1/LRP6/Kremen 2	0.086	0.12	0.39	13	-10000	0	13
LRP6	0	0	-10000	0	-10000	0	0
CSNK1A1	0.016	0.04	-10000	0	-10000	0	0
NLK	0.002	0.004	-10000	0	-10000	0	0
CCND1	-0.079	0.34	-10000	0	-1.4	13	13
WNT1	0.004	0.033	0.32	3	-10000	0	3
GSK3A	0	0	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
FRAT1	-0.003	0.054	-10000	0	-0.88	1	1
PPP2R5D	0.006	0.088	0.38	12	-10000	0	12
APC	-0.005	0.055	-10000	0	-0.51	3	3
WNT1/LRP6/FZD1	-0.007	0.047	-10000	0	-0.37	3	3
CREBBP	0.014	0.036	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.029	0.17	0.56	1	-0.7	13	14
MAP4K1	-0.017	0.13	0.32	2	-0.88	6	8
MAP3K8	-0.007	0.076	-10000	0	-0.88	2	2
PRKCB	-0.075	0.25	-10000	0	-0.88	23	23
DBNL	0	0	-10000	0	-10000	0	0
CRKL	0	0	-10000	0	-10000	0	0
MAP3K1	-0.019	0.12	-10000	0	-0.93	3	3
JUN	-0.069	0.25	-10000	0	-0.66	38	38
MAP3K7	-0.019	0.12	-10000	0	-0.93	3	3
GRAP2	-0.018	0.15	0.32	4	-0.88	7	11
CRK	0	0	-10000	0	-10000	0	0
MAP2K4	0.02	0.12	-10000	0	-0.79	4	4
LAT	0.001	0.019	0.32	1	-10000	0	1
LCP2	-0.013	0.11	-10000	0	-0.88	4	4
MAPK8	-0.069	0.25	-10000	0	-0.7	34	34
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.021	0.13	0.25	1	-0.57	9	10
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.027	0.16	0.53	1	-0.66	13	14

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.007	0.047	0.32	6	-10000	0	6
Jak2/Leptin Receptor	-0.072	0.2	-10000	0	-0.48	48	48
PTP1B/AKT1	-0.003	0.025	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.055	0.05	-10000	0	-0.29	1	1
EGFR	-0.009	0.11	-10000	0	-0.88	4	4
EGF/EGFR	0.046	0.12	0.24	33	-0.49	4	37
CSF1	-0.004	0.081	0.32	2	-0.88	2	4
AKT1	0	0.002	-10000	0	-10000	0	0
INSR	0	0.002	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.02	0.091	-10000	0	-0.49	9	9
Insulin Receptor/Insulin	0	0.036	-10000	0	-10000	0	0
HCK	-0.03	0.16	-10000	0	-0.88	9	9
CRK	0	0	-10000	0	-10000	0	0
TYK2	0.059	0.047	-10000	0	-0.27	1	1
EGF	0.082	0.14	0.32	69	-10000	0	69
YES1	0	0	-10000	0	-10000	0	0
CAV1	0.064	0.053	-10000	0	-10000	0	0
TXN	0.001	0.004	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.004	0.022	-10000	0	-10000	0	0
cell migration	-0.055	0.05	0.29	1	-10000	0	1
STAT3	0	0	-10000	0	-10000	0	0
PRLR	-0.03	0.17	-10000	0	-0.88	10	10
ITGA2B	0.008	0.051	0.32	7	-10000	0	7
CSF1R	-0.023	0.14	-10000	0	-0.88	7	7
Prolactin Receptor/Prolactin	-0.019	0.13	-10000	0	-0.69	10	10
FGR	-0.003	0.054	-10000	0	-0.88	1	1
PTP1B/p130 Cas	-0.004	0.024	-10000	0	-0.27	1	1
Crk/p130 Cas	-0.004	0.022	-10000	0	-10000	0	0
DOK1	0.061	0.045	-10000	0	-10000	0	0
JAK2	0.037	0.075	-10000	0	-0.44	2	2
Jak2/Leptin Receptor/Leptin	-0.1	0.22	-10000	0	-0.66	31	31
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
PTPN1	0.055	0.05	-10000	0	-0.3	1	1
LYN	0	0	-10000	0	-10000	0	0
CDH2	-0.03	0.16	-10000	0	-0.88	9	9
SRC	0.036	0.024	-10000	0	-10000	0	0
ITGB3	-0.053	0.21	-10000	0	-0.88	16	16
CAT1/PTP1B	-0.066	0.19	-10000	0	-0.49	24	24
CAPN1	0.002	0.004	-10000	0	-10000	0	0
CSK	0	0	-10000	0	-10000	0	0
PI3K	-0.003	0.063	-10000	0	-0.92	1	1
mol:H2O2	-0.001	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.1	0.23	-10000	0	-0.7	31	31
negative regulation of transcription	0.037	0.074	-10000	0	-0.44	2	2
FCGR2A	0.002	0.027	0.32	2	-10000	0	2
FER	0.001	0.004	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.035	0.17	-10000	0	-0.69	16	16
BLK	-0.17	0.35	0.32	2	-0.88	53	55
Insulin Receptor/Insulin/Shc	0.004	0.027	-10000	0	-10000	0	0
RHOA	0.002	0.004	-10000	0	-10000	0	0
LEPR	-0.15	0.34	-10000	0	-0.87	48	48
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0	0	-10000	0	-10000	0	0
mol:NADPH	0.002	0.002	-10000	0	-10000	0	0
TRPV6	-0.14	0.23	-10000	0	-0.44	57	57
PRL	0.005	0.033	0.32	3	-10000	0	3
SOCS3	-0.17	0.49	-10000	0	-1.5	31	31
SPRY2	-0.005	0.076	-10000	0	-0.88	2	2
Insulin Receptor/Insulin/IRS1	0.004	0.027	-10000	0	-10000	0	0
CSF1/CSF1R	-0.018	0.095	0.26	2	-0.5	9	11
Ras protein signal transduction	-0.006	0.017	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
INS	0.007	0.043	0.32	5	-10000	0	5
LEP	0.009	0.054	0.32	8	-10000	0	8
STAT5B	0.051	0.052	-10000	0	-0.24	2	2
STAT5A	0.051	0.052	-10000	0	-0.24	1	1
GRB2	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.002	0.048	0.28	6	-10000	0	6
CSN2	-0.017	0.045	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
LAT	0.037	0.026	-10000	0	-10000	0	0
YBX1	0	0	-10000	0	-10000	0	0
LCK	-0.025	0.15	0.32	1	-0.88	8	9
SHC1	0	0	-10000	0	-10000	0	0
NOX4	0.13	0.16	0.32	109	-10000	0	109

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0	0	-10000	0	-10000	0	0
HDAC4	0.001	0.019	0.32	1	-10000	0	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.01	0.057	0.65	1	-10000	0	1
CDKN1A	-0.015	0.12	-10000	0	-1	4	4
KAT2B	-0.01	0.092	-10000	0	-0.88	3	3
BAX	0	0	-10000	0	-10000	0	0
FOXO3	0.001	0.01	-10000	0	-10000	0	0
FOXO1	-0.01	0.092	-10000	0	-0.88	3	3
FOXO4	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
TAT	-0.36	0.43	-10000	0	-0.88	110	110
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.001	0.074	-10000	0	-0.69	3	3
PPARGC1A	-0.12	0.3	-10000	0	-0.88	35	35
FHL2	-0.059	0.22	-10000	0	-0.88	18	18
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.046	-10000	0	-0.68	1	1
HIST2H4A	0.01	0.058	-10000	0	-0.65	1	1
SIRT1/FOXO3a	0	0.041	-10000	0	-0.6	1	1
SIRT1	0	0.059	-10000	0	-0.88	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.042	-10000	0	-0.6	1	1
SIRT1/Histone H1b	0.004	0.041	-10000	0	-0.53	1	1
apoptosis	0	0.04	0.59	1	-10000	0	1
SIRT1/PGC1A	-0.08	0.2	-10000	0	-0.6	36	36
p53/SIRT1	0.004	0.067	0.43	4	-0.68	1	5
SIRT1/FOXO4	0	0.041	-10000	0	-0.58	1	1
FOXO1/FHL2/SIRT1	-0.044	0.15	-10000	0	-0.55	22	22
HIST1H1E	0.005	0.024	-10000	0	-10000	0	0
SIRT1/p300	0	0.046	-10000	0	-0.68	1	1
muscle cell differentiation	0.007	0.087	0.77	3	-10000	0	3
TP53	0.003	0.025	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.04	-10000	0	-0.6	1	1
CREBBP	0	0	-10000	0	-10000	0	0
MEF2D	0	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.28	0.34	-10000	0	-0.69	110	110
ACSS2	-0.001	0.045	-10000	0	-0.68	1	1
SIRT1/PCAF/MYOD	-0.007	0.088	-10000	0	-0.78	3	3

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0	0	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	-0.053	0.16	-10000	0	-0.49	30	30
Syndecan-3/Neurocan	0	0.054	-10000	0	-0.78	1	1
POMC	-0.003	0.083	0.32	3	-0.88	2	5
EGFR	-0.013	0.11	-10000	0	-0.88	4	4
Syndecan-3/EGFR	-0.011	0.078	-10000	0	-0.56	5	5
AGRP	0.012	0.06	0.32	10	-10000	0	10
NCSTN	0	0	-10000	0	-10000	0	0
PSENEN	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0	0	-10000	0	-10000	0	0
APH1A	0	0	-10000	0	-10000	0	0
NCAN	0.005	0.038	0.32	4	-10000	0	4
long-term memory	-0.003	0.044	-10000	0	-0.72	1	1
Syndecan-3/IL8	-0.11	0.23	-10000	0	-0.53	58	58
PSEN1	0	0	-10000	0	-10000	0	0
Src/Cortactin	0.001	0.013	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
limb bud formation	-0.003	0.048	-10000	0	-0.79	1	1
MC4R	0	0	-10000	0	-10000	0	0
SRC	0.001	0.019	0.32	1	-10000	0	1
PTN	-0.095	0.28	0.32	3	-0.88	30	33
FGFR/FGF/Syndecan-3	-0.003	0.049	-10000	0	-0.81	1	1
neuron projection morphogenesis	-0.049	0.16	-10000	0	-0.48	29	29
Syndecan-3/AgRP	0.005	0.062	-10000	0	-0.78	1	1
Syndecan-3/AgRP/MC4R	0.004	0.059	-10000	0	-0.76	1	1
Fyn/Cortactin	0	0	-10000	0	-10000	0	0
SDC3	-0.003	0.05	-10000	0	-0.82	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	-0.1	0.22	-10000	0	-0.52	58	58
IL8	-0.18	0.37	0.32	9	-0.88	58	67
Syndecan-3/Fyn/Cortactin	-0.003	0.045	-10000	0	-0.74	1	1
Syndecan-3/CASK	-0.003	0.047	-10000	0	-0.78	1	1
alpha-MSH/MC4R	-0.003	0.064	-10000	0	-0.69	2	2
Gamma Secretase	0	0	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.029	0.16	0.88	9	-10000	0	9
PI3K Class IB/PDE3B	-0.029	0.16	-10000	0	-0.88	9	9
PDE3B	-0.03	0.16	-10000	0	-0.88	9	9

×

Syndecan-2-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
Syndecan-2/Fibronectin	-0.002	0.037	-10000	0	-0.6	1	1
EPHB2	0.061	0.12	0.32	52	-10000	0	52
Syndecan-2/TACI	-0.001	0.041	-10000	0	-0.6	1	1
LAMA1	-0.078	0.29	0.32	17	-0.88	30	47
Syndecan-2/alpha2 ITGB1	0.06	0.13	0.38	20	-0.52	3	23
HRAS	0.002	0.027	0.32	2	-10000	0	2
Syndecan-2/CASK	0	0	-10000	0	-10000	0	0
ITGA5	0	0	-10000	0	-10000	0	0
BAX	0.009	0.11	-10000	0	-0.53	11	11
EPB41	0	0	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0	0	-10000	0	-10000	0	0
LAMA3	0.039	0.15	0.32	41	-0.88	3	44
EZR	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	-0.02	0.13	-10000	0	-0.88	6	6
Syndecan-2/MMP2	-0.011	0.1	-10000	0	-0.6	7	7
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.04	0.084	-10000	0	-10000	0	0
dendrite morphogenesis	0.043	0.088	-10000	0	-10000	0	0
Syndecan-2/GM-CSF	0	0	-10000	0	-10000	0	0
determination of left/right symmetry	0.015	0.001	-10000	0	-10000	0	0
Syndecan-2/PKC delta	0	0	-10000	0	-10000	0	0
GNB2L1	0	0	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
Syndecan-2/RACK1	0.001	0.017	-10000	0	-10000	0	0
NF1	-0.003	0.054	-10000	0	-0.88	1	1
FGFR/FGF/Syndecan-2	0.015	0.001	-10000	0	-10000	0	0
ITGA2	0.058	0.12	0.32	49	-10000	0	49
MAPK8	0.002	0.12	-10000	0	-0.59	11	11
Syndecan-2/alpha2/beta1 Integrin	-0.013	0.2	0.38	5	-0.51	30	35
Syndecan-2/Kininogen	-0.06	0.18	-10000	0	-0.6	27	27
ITGB1	0	0	-10000	0	-10000	0	0
SRC	0.001	0.013	-10000	0	-10000	0	0
Syndecan-2/CASK/Protein 4.1	0	0	-10000	0	-10000	0	0
extracellular matrix organization	0.003	0.024	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.002	0.036	-10000	0	-0.6	1	1
Syndecan-2/Caveolin-2/Ras	-0.011	0.083	-10000	0	-0.55	6	6
Syndecan-2/Laminin alpha3	0.028	0.1	-10000	0	-0.6	3	3
Syndecan-2/RasGAP	-0.003	0.043	-10000	0	-0.48	2	2
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
PRKCD	0	0	-10000	0	-10000	0	0
Syndecan-2 dimer	0.044	0.089	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	-0.003	0.042	-10000	0	-0.46	2	2
RHOA	0	0	-10000	0	-10000	0	0
SDCBP	0	0	-10000	0	-10000	0	0
TNFRSF13B	-0.001	0.06	0.32	2	-0.88	1	3
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
alpha2/beta1 Integrin	0.04	0.084	-10000	0	-10000	0	0
Syndecan-2/Synbindin	0	0	-10000	0	-10000	0	0
TGFB1	0.004	0.033	0.32	3	-10000	0	3
CASP3	-0.002	0.034	-10000	0	-0.55	1	1
FN1	-0.003	0.054	-10000	0	-0.88	1	1
Syndecan-2/IL8	-0.12	0.25	-10000	0	-0.6	58	58
SDC2	0.015	0.001	-10000	0	-10000	0	0
KNG1	-0.089	0.26	-10000	0	-0.88	27	27
Syndecan-2/Neurofibromin	-0.002	0.037	-10000	0	-0.6	1	1
TRAPPC4	0	0	-10000	0	-10000	0	0
CSF2	0	0	-10000	0	-10000	0	0
Syndecan-2/TGFB1	0.003	0.024	-10000	0	-10000	0	0
Syndecan-2/Syntenin/PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-2/Ezrin	0	0	-10000	0	-10000	0	0
PRKACA	-0.002	0.033	-10000	0	-0.55	1	1
angiogenesis	-0.12	0.25	-10000	0	-0.6	58	58
MMP2	-0.017	0.15	0.32	5	-0.88	7	12
IL8	-0.18	0.37	0.32	9	-0.88	58	67
calcineurin-NFAT signaling pathway	-0.001	0.041	-10000	0	-0.6	1	1

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.003	0.092	-10000	0	-0.62	5	5
BIRC5	0.2	0.15	0.32	174	-10000	0	174
NFKBIA	0.018	0.031	-10000	0	-10000	0	0
CPEB1	0.013	0.063	0.32	11	-10000	0	11
AKT1	0.018	0.031	-10000	0	-10000	0	0
NDEL1	0	0	-10000	0	-10000	0	0
Aurora A/BRCA1	0.007	0.031	-10000	0	-10000	0	0
NDEL1/TACC3	0.031	0.07	-10000	0	-10000	0	0
GADD45A	-0.016	0.12	-10000	0	-0.88	5	5
GSK3B	-0.002	0.004	-10000	0	-10000	0	0
PAK1/Aurora A	0.008	0.035	-10000	0	-10000	0	0
MDM2	0	0	-10000	0	-10000	0	0
JUB	-0.003	0.054	-10000	0	-0.88	1	1
TPX2	0.035	0.047	-10000	0	-10000	0	0
TP53	0.015	0.026	-10000	0	-10000	0	0
DLG7	0.004	0.036	-10000	0	-10000	0	0
AURKAIP1	0	0	-10000	0	-10000	0	0
ARHGEF7	0	0	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.033	0.074	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.007	0.031	-10000	0	-10000	0	0
AURKA	0.008	0.051	-10000	0	-10000	0	0
AURKB	0.1	0.084	0.18	124	-10000	0	124
CDC25B	0.017	0.033	-10000	0	-10000	0	0
G2/M transition checkpoint	0.005	0.046	-10000	0	-0.55	1	1
mRNA polyadenylation	0.013	0.05	0.24	4	-10000	0	4
Aurora A/CPEB	0.013	0.05	0.24	4	-10000	0	4
Aurora A/TACC1/TRAP/chTOG	0.015	0.03	-10000	0	-10000	0	0
BRCA1	0	0	-10000	0	-10000	0	0
centrosome duplication	0.008	0.035	-10000	0	-10000	0	0
regulation of centrosome cycle	0.03	0.068	-10000	0	-10000	0	0
spindle assembly	0.014	0.029	-10000	0	-10000	0	0
TDRD7	0	0	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.12	0.1	-10000	0	-0.48	2	2
CENPA	0.11	0.091	0.19	155	-10000	0	155
Aurora A/PP2A	0.008	0.035	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.019	0.031	-10000	0	-10000	0	0
negative regulation of DNA binding	0.015	0.025	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0	0	-10000	0	-10000	0	0
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
Ajuba/Aurora A	0.005	0.046	-10000	0	-0.55	1	1
mitotic prometaphase	-0.019	0.019	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.008	0.051	-10000	0	-10000	0	0
TACC1	0	0	-10000	0	-10000	0	0
TACC3	0.037	0.1	0.32	31	-10000	0	31
Aurora A/Antizyme1	0.011	0.031	-10000	0	-10000	0	0
Aurora A/RasGAP	0.003	0.064	-10000	0	-0.61	2	2
OAZ1	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.002	0.004	-10000	0	-10000	0	0
GIT1	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.035	0.046	-10000	0	-10000	0	0
PPP2R5D	0	0	-10000	0	-10000	0	0
Aurora A/TPX2	0.027	0.056	-10000	0	-10000	0	0
PAK1	0	0	-10000	0	-10000	0	0
CKAP5	0	0	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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
SPHK2	0.025	0.031	-10000	0	-10000	0	0
MAP4K4	-0.012	0.066	-10000	0	-10000	0	0
BAG4	-0.026	0.15	-10000	0	-0.88	8	8
PKC zeta/ceramide	-0.024	0.11	-10000	0	-0.53	11	11
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	0.007	0.079	0.32	9	-0.88	1	10
BAX	0.003	0.007	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AKT1	0.015	0.019	-10000	0	-10000	0	0
BAD	0.004	0.014	-10000	0	-10000	0	0
SMPD1	0.01	0.063	-10000	0	-0.27	13	13
RB1	0.004	0.014	-10000	0	-10000	0	0
FADD/Caspase 8	-0.01	0.062	-10000	0	-10000	0	0
MAP2K4	0.01	0.013	-10000	0	-10000	0	0
NSMAF	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.01	0.013	-10000	0	-10000	0	0
EGF	0.081	0.14	0.32	69	-10000	0	69
mol:ceramide	-0.003	0.015	-10000	0	-10000	0	0
MADD	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.025	0.033	-10000	0	-10000	0	0
ASAH1	0.001	0.019	0.32	1	-10000	0	1
negative regulation of cell cycle	0.004	0.014	-10000	0	-10000	0	0
cell proliferation	-0.18	0.2	-10000	0	-0.41	115	115
BID	0.019	0.051	-10000	0	-10000	0	0
MAP3K1	0.004	0.014	-10000	0	-10000	0	0
EIF2A	0.016	0.013	-10000	0	-10000	0	0
TRADD	-0.003	0.054	-10000	0	-0.88	1	1
CRADD	-0.003	0.054	-10000	0	-0.88	1	1
MAPK3	0.019	0.012	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.019	0.012	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.002	0.006	-10000	0	-10000	0	0
FADD	-0.011	0.066	-10000	0	-10000	0	0
KSR1	0.004	0.014	-10000	0	-10000	0	0
MAPK8	-0.014	0.11	-10000	0	-0.35	20	20
PRKRA	0.004	0.014	-10000	0	-10000	0	0
PDGFA	0.017	0.07	0.32	14	-10000	0	14
TRAF2	0	0	-10000	0	-10000	0	0
IGF1	-0.38	0.44	-10000	0	-0.88	115	115
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.003	0.015	-10000	0	-10000	0	0
CTSD	0	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.19	0.22	-10000	0	-0.45	115	115
PRKCD	0	0	-10000	0	-10000	0	0
PRKCZ	-0.036	0.17	-10000	0	-0.88	11	11
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.025	0.033	-10000	0	-10000	0	0
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.013	0.071	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.045	0.16	-10000	0	-0.6	21	21
mol:Sphingosine-1-phosphate	0.025	0.031	-10000	0	-10000	0	0
MAP2K1	0.016	0.013	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
CYCS	0.004	0.01	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.02	0.12	-10000	0	-0.68	8	8
EIF2AK2	0.01	0.013	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.027	0.13	-10000	0	-0.6	13	13
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.006	0.039	-10000	0	-10000	0	0
MAP2K2	0.017	0.013	-10000	0	-10000	0	0
SMPD3	-0.03	0.15	-10000	0	-0.39	36	36
TNF	-0.04	0.19	0.32	2	-0.88	13	15
PKC zeta/PAR4	-0.028	0.14	-10000	0	-0.68	11	11
mol:PHOSPHOCHOLINE	-0.039	0.045	-10000	0	-0.17	7	7
NF kappa B1/RelA/I kappa B alpha	-0.021	0.1	-10000	0	-0.51	11	11
AIFM1	0.004	0.01	-10000	0	-10000	0	0
BCL2	0	0	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.003	0.045	-10000	0	-10000	0	0
oxygen homeostasis	0	0.018	-10000	0	-10000	0	0
TCEB2	0.001	0.019	0.32	1	-10000	0	1
TCEB1	0	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.029	0.065	-10000	0	-0.43	1	1
EPO	-0.24	0.47	0.61	2	-0.81	97	99
FIH (dimer)	0.01	0.014	-10000	0	-10000	0	0
APEX1	0.001	0.015	-10000	0	-10000	0	0
SERPINE1	-0.14	0.44	0.6	1	-0.81	72	73
FLT1	-0.011	0.025	-10000	0	-10000	0	0
ADORA2A	-0.023	0.26	0.56	1	-0.72	5	6
germ cell development	0.01	0.25	0.64	3	-0.66	5	8
SLC11A2	-0.007	0.24	0.6	1	-0.69	5	6
BHLHE40	-0.012	0.26	0.6	1	-0.82	6	7
HIF1AN	0.01	0.014	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.075	0.16	0.41	5	-0.48	7	12
ETS1	0.017	0.015	-10000	0	-10000	0	0
CITED2	-0.021	0.12	-10000	0	-1.4	2	2
KDR	-0.036	0.18	-10000	0	-1.2	6	6
PGK1	-0.007	0.24	0.6	1	-0.69	5	6
SIRT1	-0.003	0.054	-10000	0	-0.88	1	1
response to hypoxia	-0.005	0.008	-10000	0	-10000	0	0
HIF2A/ARNT	-0.078	0.24	0.66	3	-0.72	9	12
EPAS1	0.016	0.13	0.4	1	-0.43	6	7
SP1	0.016	0.017	-10000	0	-10000	0	0
ABCG2	-0.083	0.35	0.6	1	-0.76	40	41
EFNA1	-0.013	0.26	0.6	1	-0.78	8	9
FXN	-0.023	0.26	-10000	0	-0.72	5	5
POU5F1	0.009	0.26	0.65	3	-0.69	5	8
neuron apoptosis	0.076	0.24	0.7	9	-0.65	3	12
EP300	0	0	-10000	0	-10000	0	0
EGLN3	0.02	0.18	0.33	28	-0.88	7	35
EGLN2	0.01	0.014	-10000	0	-10000	0	0
EGLN1	0.01	0.014	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.001	0.012	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.001	0.016	-10000	0	-10000	0	0
SLC2A1	-0.021	0.26	0.65	1	-0.74	6	7
TWIST1	-0.02	0.26	0.65	1	-0.72	5	6
ELK1	0.013	0.001	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.037	0.12	0.4	3	-0.46	3	6
VEGFA	-0.007	0.24	0.6	1	-0.69	5	6
CREBBP	0	0	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.013	0.025	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.003	0.026	-10000	0	-10000	0	0
STXBP1	0	0	-10000	0	-10000	0	0
ACh/CHRNA1	0.004	0.063	0.26	12	-10000	0	12
RAB3GAP2/RIMS1/UNC13B	0.003	0.024	-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	0.004	0.033	0.32	3	-10000	0	3
mol:ACh	0	0.047	-10000	0	-0.16	20	20
RAB3GAP2	0	0	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.012	0.057	-10000	0	-10000	0	0
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.004	0.063	0.26	12	-10000	0	12
UNC13B	0.001	0.019	0.32	1	-10000	0	1
CHRNA1	0.014	0.065	0.32	12	-10000	0	12
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.096	0.25	0.24	15	-0.65	44	59
SNAP25	-0.018	0.11	0.1	29	-0.4	20	49
VAMP2	0	0	-10000	0	-10000	0	0
SYT1	-0.12	0.34	0.32	17	-0.88	44	61
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.004	0.02	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.012	0.057	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.031	0.13	-9999	-0.6	14	14
E-cadherin/beta catenin	-0.036	0.15	-9999	-0.68	14	14
CTNNB1	0	0	-9999	-10000	0	0
JUP	0	0	-9999	-10000	0	0
CDH1	-0.046	0.2	-9999	-0.88	14	14

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.007	0.032	-10000	0	-10000	0	0
VDR	-0.01	0.14	0.32	8	-0.88	6	14
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.006	0.09	-10000	0	-0.34	5	5
RXRs/LXRs/DNA/Oxysterols	-0.014	0.11	-10000	0	-0.4	15	15
MED1	0	0	-10000	0	-10000	0	0
mol:9cRA	0.002	0.015	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.016	0.074	-10000	0	-0.36	12	12
RXRs/NUR77	-0.065	0.22	-10000	0	-0.55	40	40
RXRs/PPAR	0.006	0.064	-10000	0	-0.35	5	5
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.009	0.11	0.21	8	-0.69	6	14
RARs/VDR/DNA/Vit D3	-0.024	0.12	-10000	0	-0.52	15	15
RARA	0	0	-10000	0	-10000	0	0
NCOA1	0	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.01	0.14	0.32	8	-0.88	6	14
RARs/RARs/DNA/9cRA	-0.018	0.095	-10000	0	-0.52	9	9
RARG	0	0	-10000	0	-10000	0	0
RPS6KB1	0.008	0.029	-10000	0	-10000	0	0
RARs/THRs/DNA/SMRT	-0.016	0.074	-10000	0	-0.36	12	12
THRA	0	0	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	-0.009	0.11	0.21	8	-0.69	6	14
RXRs/PPAR/9cRA/PGJ2/DNA	0.007	0.11	-10000	0	-0.54	5	5
NR1H4	-0.033	0.17	-10000	0	-0.88	10	10
RXRs/LXRs/DNA	0.006	0.1	-10000	0	-0.5	5	5
NR1H2	0.01	0.01	-10000	0	-10000	0	0
NR1H3	0.009	0.012	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.003	0.13	0.36	4	-0.52	11	15
NR4A1	-0.12	0.3	-10000	0	-0.88	36	36
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.012	0.093	-10000	0	-0.36	14	14
RXRG	0.032	0.15	0.32	31	-0.87	4	35
RXR alpha/CCPG	-0.003	0.042	-10000	0	-0.68	1	1
RXRA	0.006	0.055	-10000	0	-0.87	1	1
RXRB	0.009	0.012	-10000	0	-10000	0	0
THRB	-0.01	0.092	-10000	0	-0.88	3	3
PPARG	0.001	0.019	0.32	1	-10000	0	1
PPARD	0	0	-10000	0	-10000	0	0
TNF	-0.009	0.29	-10000	0	-1.2	13	13
mol:Oxysterols	0.002	0.013	-10000	0	-10000	0	0
cholesterol transport	-0.014	0.11	-10000	0	-0.4	15	15
PPARA	0	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	-0.03	0.16	-10000	0	-0.88	9	9
RXRs/NUR77/BCL2	-0.044	0.14	-10000	0	-0.36	40	40
SREBF1	0.03	0.13	-10000	0	-1.2	1	1
RXRs/RXRs/DNA/9cRA	0.007	0.11	-10000	0	-0.54	5	5
ABCA1	0.024	0.17	-10000	0	-1.2	3	3
RARs/THRs	-0.023	0.11	-10000	0	-0.51	12	12
RXRs/FXR	-0.01	0.15	-10000	0	-0.58	14	14
BCL2	0	0	-10000	0	-10000	0	0

×

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

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
BAG4	-0.026	0.15	-10000	0	-0.88	8	8
Caspase 8 (4 units)	-0.057	0.17	-10000	0	-0.83	8	8
NEF	-0.007	0.041	-10000	0	-10000	0	0
NFKBIA	0.001	0.01	-10000	0	-10000	0	0
BIRC3	0.007	0.076	-10000	0	-0.88	1	1
CYCS	-0.017	0.17	-10000	0	-0.79	8	8
RIPK1	0	0	-10000	0	-10000	0	0
CD247	-0.012	0.094	0.32	1	-0.98	2	3
MAP2K7	-0.016	0.16	-10000	0	-0.61	11	11
protein ubiquitination	0.022	0.11	-10000	0	-0.5	5	5
CRADD	-0.003	0.054	-10000	0	-0.88	1	1
DAXX	0	0	-10000	0	-10000	0	0
FAS	-0.033	0.17	-10000	0	-0.88	10	10
BID	-0.059	0.17	-10000	0	-0.46	31	31
NF-kappa-B/RelA/I kappa B alpha	0.005	0.04	-10000	0	-10000	0	0
TRADD	-0.003	0.054	-10000	0	-0.88	1	1
MAP3K5	-0.085	0.26	-10000	0	-0.88	26	26
CFLAR	0	0	-10000	0	-10000	0	0
FADD	0.001	0.019	0.32	1	-10000	0	1
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.005	0.04	-10000	0	-10000	0	0
MAPK8	-0.028	0.18	-10000	0	-0.55	22	22
APAF1	0	0	-10000	0	-10000	0	0
TRAF1	0.001	0.019	0.32	1	-10000	0	1
TRAF2	0	0	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.063	0.19	-10000	0	-0.46	36	36
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.036	0.12	-10000	0	-0.66	6	6
CHUK	0.02	0.12	-10000	0	-0.56	5	5
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.068	0.2	-10000	0	-0.6	31	31
TCRz/NEF	-0.017	0.1	-10000	0	-0.47	11	11
TNF	-0.04	0.19	0.32	2	-0.88	13	15
FASLG	-0.037	0.2	-10000	0	-0.97	11	11
NFKB1	0.001	0.01	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.045	0.16	-10000	0	-0.6	21	21
CASP6	-0.041	0.12	-10000	0	-0.66	5	5
CASP7	0.029	0.14	-10000	0	-0.58	6	6
RELA	0.001	0.01	-10000	0	-10000	0	0
CASP2	0	0	-10000	0	-10000	0	0
CASP3	0.027	0.14	-10000	0	-0.58	7	7
TNFRSF1A	0	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.02	0.12	-10000	0	-0.68	8	8
CASP8	0	0	-10000	0	-10000	0	0
CASP9	0	0	-10000	0	-10000	0	0
MAP3K14	0.013	0.13	-10000	0	-0.64	5	5
APAF-1/Caspase 9	-0.03	0.11	0.26	1	-0.48	9	10
BCL2	-0.018	0.17	-10000	0	-0.52	19	19

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

Figure S91. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S91. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.026	0.17	0.32	6	-0.88	10	16
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.001	0.019	0.32	1	-10000	0	1
TCEB1	0	0	-10000	0	-10000	0	0
HIF1A/p53	-0.003	0.018	-10000	0	-10000	0	0
HIF1A	0.001	0.024	-10000	0	-10000	0	0
COPS5	0	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.001	0.011	-10000	0	-10000	0	0
FIH (dimer)	0	0	-10000	0	-10000	0	0
CDKN2A	0.21	0.15	0.32	176	-10000	0	176
ARNT/IPAS	-0.021	0.14	-10000	0	-0.68	10	10
HIF1AN	0	0	-10000	0	-10000	0	0
GNB2L1	0	0	-10000	0	-10000	0	0
HIF1A/ARNT	-0.003	0.018	-10000	0	-10000	0	0
CUL2	0	0	-10000	0	-10000	0	0
OS9	0	0	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.001	0.012	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.003	0.018	-10000	0	-10000	0	0
PHD1-3/OS9	0.007	0.11	-10000	0	-0.55	7	7
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.019	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
HIF1A/JAB1	-0.003	0.018	-10000	0	-10000	0	0
EGLN3	0.011	0.18	0.32	29	-0.88	7	36
EGLN2	0	0	-10000	0	-10000	0	0
EGLN1	0	0	-10000	0	-10000	0	0
TP53	0	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0	0.006	-10000	0	-10000	0	0
ARNT	0	0	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0	0	-10000	0	-10000	0	0
HIF1A/p19ARF	0.13	0.1	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0	0.001	-10000	0	-10000	0	0
HDAC2	0	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.007	0.063	-10000	0	-0.6	3	3
forebrain development	-0.013	0.12	-10000	0	-0.53	8	8
GNAO1	-0.39	0.44	-10000	0	-0.88	120	120
SMO/beta Arrestin2	-0.005	0.059	-10000	0	-0.69	2	2
SMO	-0.007	0.076	-10000	0	-0.88	2	2
ARRB2	0	0	-10000	0	-10000	0	0
GLI3/SPOP	-0.002	0.021	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
GNAI2	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0	0	-10000	0	-10000	0	0
GNAI1	-0.007	0.076	-10000	0	-0.88	2	2
XPO1	0	0.002	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.035	0.093	-10000	0	-0.54	6	6
SAP30	0	0.001	-10000	0	-10000	0	0
mol:GDP	-0.007	0.076	-10000	0	-0.88	2	2
MIM/GLI2A	0.013	0.009	-10000	0	-10000	0	0
IFT88	0	0	-10000	0	-10000	0	0
GNAI3	0	0	-10000	0	-10000	0	0
GLI2	0.015	0.072	-10000	0	-10000	0	0
GLI3	0.032	0.031	0.3	1	-0.33	1	2
CSNK1D	0	0	-10000	0	-10000	0	0
CSNK1E	0.001	0.019	0.32	1	-10000	0	1
SAP18	0	0.001	-10000	0	-10000	0	0
embryonic digit morphogenesis	0	0	-10000	0	-10000	0	0
GNG2	-0.003	0.054	-10000	0	-0.88	1	1
Gi family/GTP	-0.13	0.2	-10000	0	-0.38	59	59
SIN3B	0	0.001	-10000	0	-10000	0	0
SIN3A	0	0.001	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.001	0.021	-10000	0	-10000	0	0
GLI2/Su(fu)	-0.015	0.058	-10000	0	-0.45	1	1
FOXA2	-0.009	0.11	-10000	0	-1.3	2	2
neural tube patterning	-0.013	0.12	-10000	0	-0.53	8	8
SPOP	0	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	-0.002	0.024	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
CSNK1G2	0	0	-10000	0	-10000	0	0
CSNK1G3	0	0	-10000	0	-10000	0	0
MTSS1	0.013	0.009	-10000	0	-10000	0	0
embryonic limb morphogenesis	-0.013	0.12	-10000	0	-0.53	8	8
SUFU	-0.002	0.027	-10000	0	-10000	0	0
LGALS3	0.024	0.083	0.32	20	-10000	0	20
catabolic process	-0.012	0.043	-10000	0	-10000	0	0
GLI3A/CBP	0.007	0.044	-10000	0	-0.4	1	1
KIF3A	0	0	-10000	0	-10000	0	0
GLI1	-0.013	0.12	-10000	0	-0.54	8	8
RAB23	0	0	-10000	0	-10000	0	0
CSNK1A1	0	0	-10000	0	-10000	0	0
IFT172	0	0	-10000	0	-10000	0	0
RBBP7	0	0.001	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.015	0.064	-10000	0	-10000	0	0
GNAZ	0.15	0.16	0.32	125	-10000	0	125
RBBP4	0	0.001	-10000	0	-10000	0	0
CSNK1G1	0	0	-10000	0	-10000	0	0
PIAS1	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
GLI2/SPOP	-0.016	0.056	-10000	0	-10000	0	0
STK36	0	0.002	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.097	0.16	-10000	0	-0.48	5	5
PTCH1	-0.028	0.23	-10000	0	-1.3	8	8
MIM/GLI1	-0.005	0.12	-10000	0	-0.54	8	8
CREBBP	0.007	0.044	-10000	0	-0.39	1	1
Su(fu)/SIN3/HDAC complex	0.002	0.011	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.018	0.079	-10000	0	-0.37	11	11
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0	0	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
STXBP4	0.002	0.027	0.32	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.029	0.1	-10000	0	-0.41	11	11
YWHAZ	0	0	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	0.012	0.061	-10000	0	-0.69	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
SNARE/Synip	0.001	0.017	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
ASIP	0	0	-10000	0	-10000	0	0
PRKCI	0	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0	0	-10000	0	-10000	0	0
GYS1	0	0	-10000	0	-10000	0	0
PRKCZ	-0.036	0.17	-10000	0	-0.88	11	11
TRIP10	0	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.058	0.055	-10000	0	-10000	0	0
VAMP2	0	0	-10000	0	-10000	0	0
SLC2A4	0.028	0.11	-10000	0	-0.46	11	11
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0	0	-10000	0	-10000	0	0
SFN	0.18	0.16	0.32	155	-10000	0	155
LNPEP	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-10000	0	-10000	0	0
HDAC3	0	0	-10000	0	-10000	0	0
VDR	-0.01	0.14	0.32	8	-0.88	6	14
Cbp/p300/PCAF	-0.007	0.063	-10000	0	-0.6	3	3
EP300	0	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.018	0.061	-10000	0	-0.35	1	1
KAT2B	-0.01	0.092	-10000	0	-0.88	3	3
MAPK14	0	0	-10000	0	-10000	0	0
AKT1	0.042	0.11	0.24	46	-0.36	6	52
RAR alpha/9cRA/Cyclin H	-0.013	0.059	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.016	0.064	-10000	0	-0.29	12	12
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.029	0.14	-10000	0	-0.71	11	11
NCOR2	0	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.009	0.11	0.21	8	-0.69	6	14
RXRs/RARs/NRIP1/9cRA	0.036	0.083	-10000	0	-0.55	1	1
NCOA2	-0.095	0.27	-10000	0	-0.88	29	29
NCOA3	0	0	-10000	0	-10000	0	0
NCOA1	0	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.01	0.14	0.32	8	-0.88	6	14
RARG	0	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
MAPK8	-0.036	0.17	-10000	0	-0.88	11	11
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.014	0.092	-10000	0	-0.46	6	6
RARA	-0.012	0.065	-10000	0	-0.32	11	11
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.049	0.13	-10000	0	-0.36	36	36
PRKCA	0	0.002	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.023	0.076	-10000	0	-0.6	1	1
RXRG	0.025	0.074	-10000	0	-0.47	4	4
RXRA	0.012	0.069	-10000	0	-0.3	12	12
RXRB	0.018	0.015	-10000	0	-10000	0	0
VDR/Vit D3/DNA	-0.009	0.11	0.21	8	-0.69	6	14
RBP1	-0.16	0.35	0.32	4	-0.88	51	55
CRBP1/9-cic-RA	-0.13	0.27	0.21	4	-0.69	51	55
RARB	-0.03	0.16	-10000	0	-0.88	9	9
PRKCG	0.005	0.033	0.32	3	-10000	0	3
MNAT1	0	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.026	0.11	0.35	1	-10000	0	1
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.038	0.077	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.074	-10000	0	-0.45	1	1
RXRs/RARs/NRIP1/9cRA/HDAC3	0.023	0.076	-10000	0	-0.6	1	1
positive regulation of DNA binding	-0.013	0.056	-10000	0	-10000	0	0
NRIP1	0.022	0.1	-10000	0	-1.3	1	1
RXRs/RARs	0.02	0.067	-10000	0	-0.43	1	1
RXRs/RXRs/DNA/9cRA	-0.004	0.056	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
CDK7	0	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.008	0.04	-10000	0	-10000	0	0
CCNH	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.032	0.14	-10000	0	-0.62	14	14
KLHL20	-0.023	0.066	-10000	0	-0.36	3	3
CYFIP2	-0.049	0.2	-10000	0	-0.88	15	15
Rac1/GDP	-0.016	0.086	-10000	0	-0.38	14	14
ENAH	-0.031	0.14	-10000	0	-0.62	14	14
AP1M1	0	0	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0	0	-10000	0	-10000	0	0
CTNNB1	0	0	-10000	0	-10000	0	0
CDC42/GTP	-0.017	0.071	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.025	0.058	-10000	0	-0.19	17	17
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.035	0.14	-10000	0	-0.55	18	18
RAPGEF1	0.014	0.12	-10000	0	-0.52	14	14
CTNND1	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.034	0.14	-10000	0	-0.64	14	14
CRK	0.006	0.14	-10000	0	-0.57	14	14
E-cadherin/gamma catenin/alpha catenin	-0.031	0.13	-10000	0	-0.6	14	14
alphaE/beta7 Integrin	-0.008	0.086	-10000	0	-0.68	4	4
IQGAP1	0	0	-10000	0	-10000	0	0
NCKAP1	0	0	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0	0	-10000	0	-10000	0	0
DLG1	-0.032	0.14	-10000	0	-0.62	14	14
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.013	0.055	-10000	0	-0.37	1	1
MLLT4	0	0	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.019	0.11	-10000	0	-0.56	10	10
PI3K	-0.017	0.073	-10000	0	-0.52	1	1
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	-0.036	0.15	-10000	0	-0.68	14	14
TIAM1	-0.033	0.17	-10000	0	-0.88	10	10
E-cadherin(dimer)/Ca2+	-0.027	0.12	-10000	0	-0.52	14	14
AKT1	-0.01	0.04	-10000	0	-0.26	1	1
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
CDH1	-0.046	0.2	-10000	0	-0.88	14	14
RhoA/GDP	-0.016	0.086	-10000	0	-0.38	14	14
actin cytoskeleton organization	-0.017	0.048	-10000	0	-0.25	3	3
CDC42/GDP	-0.016	0.086	-10000	0	-0.38	14	14
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.019	0.082	-10000	0	-0.37	14	14
ITGB7	-0.013	0.11	-10000	0	-0.88	4	4
RAC1	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.029	0.12	-10000	0	-0.55	14	14
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.028	0.12	-10000	0	-0.53	14	14
mol:GDP	0.023	0.11	-10000	0	-0.45	14	14
CDC42/GTP/IQGAP1	0	0	-10000	0	-10000	0	0
JUP	0	0	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	-0.02	0.085	-10000	0	-0.38	14	14
RAC1/GTP/IQGAP1	0	0	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
CDC42	0	0	-10000	0	-10000	0	0
CTNNA1	0	0	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.017	0.057	-10000	0	-0.28	10	10
NME1	0.002	0.027	0.32	2	-10000	0	2
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.032	0.14	-10000	0	-0.62	14	14
regulation of cell-cell adhesion	-0.014	0.062	-10000	0	-10000	0	0
WASF2	-0.013	0.03	-10000	0	-0.14	1	1
Rap1/GTP	-0.019	0.081	-10000	0	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.032	0.13	-10000	0	-0.51	18	18
CCND1	-0.021	0.072	-10000	0	-0.36	10	10
VAV2	0.008	0.13	-10000	0	-0.55	14	14
RAP1/GDP	-0.019	0.082	-10000	0	-10000	0	0
adherens junction assembly	-0.031	0.13	-10000	0	-0.6	14	14
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0	0	-10000	0	-10000	0	0
PIP5K1C	0	0	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.031	0.12	-10000	0	-0.49	18	18
E-cadherin/beta catenin	-0.028	0.12	-10000	0	-0.54	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.032	0.14	-10000	0	-0.62	14	14
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
Rac1/GTP	-0.038	0.11	-10000	0	-0.44	10	10
E-cadherin/beta catenin/alpha catenin	-0.031	0.13	-10000	0	-0.6	14	14
ITGAE	0.004	0.033	0.32	3	-10000	0	3
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.035	0.15	-10000	0	-0.66	14	14

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.012	0.066	-10000	0	-0.89	1	1
adherens junction organization	0.017	0.082	-10000	0	-0.33	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.018	0.085	-10000	0	-0.57	5	5
FMN1	-0.014	0.075	-10000	0	-10000	0	0
mol:IP3	-0.013	0.066	-10000	0	-0.85	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.019	0.078	-10000	0	-0.35	14	14
CTNNB1	0.001	0.005	-10000	0	-10000	0	0
AKT1	-0.014	0.07	-10000	0	-0.85	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.031	0.13	-10000	0	-0.57	14	14
CTNND1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.015	0.079	-10000	0	-0.32	14	14
VASP	-0.018	0.073	-10000	0	-0.32	14	14
ZYX	-0.018	0.073	-10000	0	-0.32	14	14
JUB	-0.019	0.078	-10000	0	-0.49	1	1
EGFR(dimer)	-0.025	0.1	-10000	0	-0.41	16	16
E-cadherin/beta catenin-gamma catenin	-0.03	0.13	-10000	0	-0.58	14	14
mol:PI-3-4-5-P3	-0.015	0.075	-10000	0	-0.92	1	1
PIK3CA	-0.003	0.055	-10000	0	-0.9	1	1
PI3K	-0.016	0.078	-10000	0	-0.97	1	1
FYN	-0.048	0.17	-10000	0	-0.39	51	51
mol:Ca2+	-0.013	0.064	-10000	0	-0.82	1	1
JUP	0.001	0.005	-10000	0	-10000	0	0
PIK3R1	-0.003	0.055	-10000	0	-0.9	1	1
mol:DAG	-0.013	0.066	-10000	0	-0.85	1	1
CDH1	-0.046	0.2	-10000	0	-0.88	14	14
RhoA/GDP	-0.018	0.085	-10000	0	-0.57	5	5
establishment of polarity of embryonic epithelium	0.015	0.079	-10000	0	-0.32	14	14
SRC	0.001	0.019	0.32	1	-10000	0	1
RAC1	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
EGFR	-0.013	0.11	-10000	0	-0.88	4	4
CASR	-0.096	0.19	-10000	0	-0.48	51	51
RhoA/GTP	-0.011	0.057	-10000	0	-0.73	1	1
AKT2	-0.014	0.07	-10000	0	-0.85	1	1
actin cable formation	0.022	0.079	-10000	0	-10000	0	0
apoptosis	0.014	0.068	0.83	1	-10000	0	1
CTNNA1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.02	0.094	-10000	0	-0.63	5	5
PIP5K1A	-0.018	0.073	-10000	0	-10000	0	0
PLCG1	-0.013	0.068	-10000	0	-0.89	1	1
Rac1/GTP	-0.023	0.095	-10000	0	-0.59	4	4
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.001	0.1	-10000	0	-0.46	11	11
ACTA1	-0.005	0.13	-10000	0	-0.61	11	11
NUMA1	0.001	0.1	-10000	0	-0.46	11	11
SPTAN1	-0.005	0.13	-10000	0	-0.6	11	11
LIMK1	-0.004	0.13	-10000	0	-0.6	11	11
BIRC3	0.007	0.079	0.32	9	-0.88	1	10
BIRC2	0	0	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
CASP10	-0.003	0.14	-10000	0	-0.64	11	11
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.001	0.1	-10000	0	-0.46	11	11
DIABLO	0	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.005	0.13	-10000	0	-0.59	11	11
response to UV	0	0	-10000	0	-10000	0	0
CRADD	-0.003	0.054	-10000	0	-0.88	1	1
GSN	-0.005	0.13	-10000	0	-0.6	11	11
MADD	0	0	-10000	0	-10000	0	0
TFAP2A	0.014	0.16	0.37	2	-0.65	13	15
BID	-0.012	0.06	-10000	0	-0.3	11	11
MAP3K1	0.003	0.041	-10000	0	-0.25	1	1
TRADD	-0.003	0.054	-10000	0	-0.88	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.005	0.13	-10000	0	-0.6	11	11
CASP9	0	0	-10000	0	-10000	0	0
DNA repair	0	0.034	0.18	1	-0.23	1	2
neuron apoptosis	0.007	0.08	-10000	0	-0.73	3	3
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.002	0.13	-10000	0	-0.57	12	12
APAF1	0	0	-10000	0	-10000	0	0
CASP6	0.014	0.062	-10000	0	-0.41	1	1
TRAF2	0	0	-10000	0	-10000	0	0
ICAD/CAD	0	0.13	-10000	0	-0.57	12	12
CASP7	-0.011	0.032	0.34	1	-10000	0	1
KRT18	0.01	0.017	-10000	0	-10000	0	0
apoptosis	0.005	0.11	-10000	0	-0.52	11	11
DFFA	-0.005	0.13	-10000	0	-0.6	11	11
DFFB	-0.007	0.13	-10000	0	-0.6	12	12
PARP1	0	0.034	0.23	1	-0.18	1	2
actin filament polymerization	-0.001	0.12	0.54	12	-10000	0	12
TNF	-0.04	0.19	0.32	2	-0.88	13	15
CYCS	0.01	0.048	-10000	0	-0.22	11	11
SATB1	-0.021	0.15	-10000	0	-0.5	22	22
SLK	-0.005	0.13	-10000	0	-0.6	11	11
p15 BID/BAX	-0.011	0.053	-10000	0	-0.36	1	1
CASP2	-0.011	0.065	-10000	0	-10000	0	0
JNK cascade	-0.003	0.041	0.25	1	-10000	0	1
CASP3	-0.012	0.14	-10000	0	-0.64	11	11
LMNB2	0.026	0.056	-10000	0	-0.31	1	1
RIPK1	0	0	-10000	0	-10000	0	0
CASP4	-0.003	0.054	-10000	0	-0.88	1	1
Mammalian IAPs/DIABLO	0.005	0.049	-10000	0	-0.55	1	1
negative regulation of DNA binding	0.014	0.16	0.37	2	-0.64	13	15
stress fiber formation	-0.005	0.13	-10000	0	-0.59	11	11
GZMB	-0.013	0.15	-10000	0	-0.74	11	11
CASP1	-0.002	0.029	-10000	0	-0.47	1	1
LMNB1	0.024	0.055	-10000	0	-0.31	1	1
APP	0.007	0.081	-10000	0	-0.74	3	3
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.002	-10000	0	-10000	0	0
VIM	0	0.11	-10000	0	-0.5	11	11
LMNA	0.024	0.055	-10000	0	-0.31	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.013	0.07	-10000	0	-10000	0	0
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.007	0.13	-10000	0	-0.6	12	12
APAF-1/Caspase 9	-0.005	0.022	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.001	0.098	-10000	0	-0.46	11	11
CFL2	0.001	0.13	-10000	0	-0.56	12	12
GAS2	-0.031	0.17	-10000	0	-0.56	24	24
positive regulation of apoptosis	0.027	0.056	-10000	0	-0.3	1	1
PRF1	-0.013	0.11	-10000	0	-0.88	4	4

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.002	0.057	0.32	1	-0.88	1	2
ANTXR2	-0.01	0.092	-10000	0	-0.88	3	3
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.013	-10000	0	-0.11	4	4
monocyte activation	-0.051	0.19	-10000	0	-0.6	24	24
MAP2K2	0	0.014	-10000	0	-10000	0	0
MAP2K1	-0.001	0.011	-10000	0	-10000	0	0
MAP2K7	-0.001	0.011	-10000	0	-10000	0	0
MAP2K6	-0.013	0.081	-10000	0	-0.54	6	6
CYAA	-0.008	0.064	-10000	0	-0.53	4	4
MAP2K4	-0.001	0.011	-10000	0	-10000	0	0
IL1B	-0.068	0.2	-10000	0	-0.53	41	41
Channel	-0.008	0.069	-10000	0	-0.56	4	4
NLRP1	-0.001	0.012	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.002	0.016	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.013	0.11	4	-10000	0	4
MAPK3	-0.001	0.011	-10000	0	-10000	0	0
MAPK1	-0.001	0.011	-10000	0	-10000	0	0
PGR	-0.075	0.19	-10000	0	-0.54	37	37
PA/Cellular Receptors	-0.008	0.074	-10000	0	-0.6	4	4
apoptosis	-0.002	0.013	-10000	0	-0.11	4	4
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.007	0.065	-10000	0	-0.52	4	4
macrophage activation	0.016	0.012	-10000	0	-10000	0	0
TNF	-0.04	0.19	0.32	2	-0.88	13	15
VCAM1	-0.051	0.2	-10000	0	-0.61	24	24
platelet activation	-0.002	0.016	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.022	0.11	6	-10000	0	6
IL18	0.004	0.076	-10000	0	-0.54	5	5
negative regulation of macrophage activation	-0.002	0.013	-10000	0	-0.11	4	4
LEF	-0.002	0.013	-10000	0	-0.11	4	4
CASP1	-0.001	0.012	-10000	0	-0.093	4	4
mol:cAMP	-0.002	0.016	-10000	0	-10000	0	0
necrosis	-0.002	0.013	-10000	0	-0.11	4	4
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.007	0.066	-10000	0	-0.53	4	4
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0	0	-10000	0	-10000	0	0
NFATC1	0.022	0.083	-10000	0	-0.38	3	3
NFATC2	-0.028	0.11	-10000	0	-0.34	15	15
NFATC3	-0.023	0.11	-10000	0	-0.56	11	11
YWHAE	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.004	0.11	-10000	0	-0.57	6	6
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.066	0.16	-10000	0	-0.51	28	28
BCL2/BAX	0	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.002	0.004	-10000	0	-10000	0	0
CaM/Ca2+	-0.002	0.004	-10000	0	-10000	0	0
BAX	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.029	0.099	-10000	0	-0.59	5	5
Calcineurin A alpha-beta B1/BCL2	0	0	-10000	0	-10000	0	0
FKBP8	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.029	0.097	0.58	5	-10000	0	5
KPNB1	0	0	-10000	0	-10000	0	0
KPNA2	0.001	0.019	0.32	1	-10000	0	1
XPO1	0	0	-10000	0	-10000	0	0
SFN	0.18	0.16	0.32	155	-10000	0	155
MAP3K8	-0.007	0.076	-10000	0	-0.88	2	2
NFAT4/CK1 alpha	-0.016	0.075	-10000	0	-0.38	11	11
MEF2D/NFAT1/Cbp/p300	-0.078	0.14	-10000	0	-0.52	9	9
CABIN1	-0.004	0.11	-10000	0	-0.57	6	6
CALM1	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
MAP3K1	0	0	-10000	0	-10000	0	0
CAMK4	-0.078	0.25	0.32	1	-0.88	24	25
mol:Ca2+	-0.002	0.007	-10000	0	-10000	0	0
MAPK3	0	0	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.001	0.013	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
MAPK8	-0.036	0.17	-10000	0	-0.88	11	11
MAPK9	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.029	0.1	-10000	0	-0.47	12	12
PRKCH	0	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.005	-10000	0	-10000	0	0
CASP3	-0.003	0.054	-10000	0	-0.88	1	1
PIM1	0	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	0	0	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.053	0.046	-10000	0	-10000	0	0
PRKCB	-0.075	0.25	-10000	0	-0.88	23	23
PRKCE	-0.002	0.057	0.32	1	-0.88	1	2
JNK2/NFAT4	-0.021	0.1	-10000	0	-0.51	11	11
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0	0	-10000	0	-10000	0	0
NUP214	0	0	-10000	0	-10000	0	0
PRKCZ	-0.036	0.17	-10000	0	-0.88	11	11
PRKCA	0	0	-10000	0	-10000	0	0
PRKCG	0.004	0.033	0.32	3	-10000	0	3
PRKCQ	-0.024	0.15	0.32	2	-0.88	8	10
FKBP38/BCL2	0	0	-10000	0	-10000	0	0
EP300	-0.001	0.002	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0	0	-10000	0	-10000	0	0
NFATc/JNK1	-0.034	0.12	-10000	0	-0.5	12	12
CaM/Ca2+/FKBP38	0	0.001	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	-0.001	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.054	0.17	-10000	0	-0.6	24	24
NFATc/ERK1	-0.015	0.069	-10000	0	-0.38	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.066	0.16	-10000	0	-0.5	28	28
NR4A1	-0.13	0.27	-10000	0	-0.79	37	37
GSK3B	0	0	-10000	0	-10000	0	0
positive T cell selection	-0.023	0.11	-10000	0	-0.56	11	11
NFAT1/CK1 alpha	-0.04	0.074	-10000	0	-0.39	3	3
RCH1/ KPNB1	0.001	0.013	-10000	0	-10000	0	0
YWHAQ	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
AKAP5	0.001	0.019	0.32	1	-10000	0	1
MEF2D	-0.001	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0	0	-10000	0	-10000	0	0
NFATc/p38 alpha	-0.015	0.069	-10000	0	-0.39	1	1
CREBBP	-0.001	0.002	-10000	0	-10000	0	0
BCL2	0	0	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0	0	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.015	0.14	0.32	4	-0.88	6	10
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.01	0.028	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
YES1	0	0	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0	0	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
MAP3K12	0.001	0.019	0.32	1	-10000	0	1
FGR	-0.003	0.054	-10000	0	-0.88	1	1
p38 alpha/TAB1	-0.038	0.078	-10000	0	-0.35	9	9
PRKG1	-0.028	0.16	0.32	1	-0.88	9	10
DUSP8	-0.003	0.054	-10000	0	-0.88	1	1
PGK/cGMP/p38 alpha	-0.049	0.11	0.24	1	-0.41	17	18
apoptosis	-0.037	0.075	-10000	0	-0.33	9	9
RAL/GTP	0	0	-10000	0	-10000	0	0
LYN	0	0	-10000	0	-10000	0	0
DUSP1	-0.072	0.24	-10000	0	-0.88	22	22
PAK1	0	0	-10000	0	-10000	0	0
SRC	0.001	0.019	0.32	1	-10000	0	1
RAC1/OSM/MEKK3/MKK3	0	0	-10000	0	-10000	0	0
TRAF6	-0.003	0.054	-10000	0	-0.88	1	1
RAC1	0	0	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
MAPK11	-0.015	0.14	-10000	0	-0.46	10	10
BLK	-0.17	0.35	0.32	2	-0.88	53	55
HCK	-0.03	0.16	-10000	0	-0.88	9	9
MAP2K3	0	0	-10000	0	-10000	0	0
DUSP16	-0.003	0.054	-10000	0	-0.88	1	1
DUSP10	-0.013	0.11	-10000	0	-0.88	4	4
TRAF6/MEKK3	-0.002	0.034	-10000	0	-0.56	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	-0.004	0.1	-10000	0	-0.37	9	9
positive regulation of innate immune response	-0.013	0.14	-10000	0	-0.49	10	10
LCK	-0.025	0.15	0.32	1	-0.88	8	9
p38alpha-beta/MKP7	-0.058	0.12	-10000	0	-0.46	11	11
p38alpha-beta/MKP5	-0.063	0.12	-10000	0	-0.47	14	14
PGK/cGMP	-0.022	0.12	0.21	1	-0.69	9	10
PAK2	0	0	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.09	0.16	-10000	0	-0.48	31	31
CDC42	0	0	-10000	0	-10000	0	0
RALB	0	0	-10000	0	-10000	0	0
RALA	0	0	-10000	0	-10000	0	0
PAK3	0.034	0.098	0.32	29	-10000	0	29

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.33	0.42	-10000	0	-0.88	100	100
HRAS	0.002	0.027	0.32	2	-10000	0	2
EGFR	-0.013	0.11	-10000	0	-0.88	4	4
AKT	0.02	0.02	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0	0	-10000	0	-10000	0	0
FOXO1	-0.01	0.092	-10000	0	-0.88	3	3
AKT3	0.001	0.019	0.32	1	-10000	0	1
FOXO4	0	0	-10000	0	-10000	0	0
MET	-0.002	0.057	0.32	1	-0.88	1	2
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
PIK3CB	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
PIK3CG	-0.033	0.18	0.32	3	-0.88	11	14
PIK3R3	0.001	0.019	0.32	1	-10000	0	1
PIK3R2	0	0	-10000	0	-10000	0	0
NF1	-0.003	0.054	-10000	0	-0.88	1	1
RAS	-0.073	0.096	-10000	0	-0.39	4	4
ERBB2	-0.01	0.092	-10000	0	-0.88	3	3
proliferation/survival/translation	-0.016	0.036	0.23	2	-10000	0	2
PI3K	-0.051	0.11	-10000	0	-0.29	13	13
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
KRAS	0	0	-10000	0	-10000	0	0
FOXO	0.022	0.023	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
PTEN	-0.007	0.076	-10000	0	-0.88	2	2

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.002	0.027	0.32	2	-10000	0	2
EGFR	-0.013	0.11	-10000	0	-0.88	4	4
EGF/EGFR	0.023	0.12	0.3	1	-0.5	9	10
EGF/EGFR dimer/SHC/GRB2/SOS1	0.04	0.1	-10000	0	-0.51	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.001	0.019	0.32	1	-10000	0	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.081	0.14	0.32	69	-10000	0	69
EGF/EGFR dimer/SHC	0.042	0.12	-10000	0	-0.59	4	4
mol:GDP	0.036	0.1	-10000	0	-0.5	4	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	-0.015	0.12	0.32	1	-0.88	5	6
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	0.021	0.076	-10000	0	-0.46	4	4
SHC1	0	0	-10000	0	-10000	0	0
HRAS/GDP	0.03	0.088	-10000	0	-0.47	4	4
FRAP1	0.01	0.068	-10000	0	-0.48	4	4
EGF/EGFR dimer	0.045	0.13	-10000	0	-0.68	4	4
SOS1	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.011	0.095	-10000	0	-0.68	5	5

×

Rapid glucocorticoid 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.028	0.075	-10000	0	-0.53	1	1
MAPK9	0	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.003	0.013	-10000	0	-10000	0	0
GNB1/GNG2	-0.002	0.037	-10000	0	-0.6	1	1
GNB1	0	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0	0	-10000	0	-10000	0	0
Gs family/GTP	0.031	0.068	0.18	46	-10000	0	46
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0	0	-10000	0	-10000	0	0
GNAL	0.054	0.12	0.32	46	-10000	0	46
GNG2	-0.003	0.054	-10000	0	-0.88	1	1
CRH	0.002	0.027	0.32	2	-10000	0	2
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	-0.02	0.095	-10000	0	-0.48	11	11
MAPK11	0.004	0.022	-10000	0	-10000	0	0

×

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

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
MAP4K1	0.008	0.1	-10000	0	-0.48	9	9
CRKL	0.012	0.065	-10000	0	-0.42	4	4
HRAS	-0.022	0.12	-10000	0	-0.65	5	5
mol:PIP3	0	0.065	-10000	0	-0.4	4	4
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0	0	-10000	0	-10000	0	0
GAB1	-0.014	0.061	-10000	0	-0.44	4	4
FOXO3	0.016	0.06	-10000	0	-0.38	4	4
AKT1	0.01	0.064	-10000	0	-0.41	4	4
BAD	0.016	0.06	-10000	0	-0.38	4	4
megakaryocyte differentiation	-0.021	0.13	-10000	0	-0.49	18	18
GSK3B	0.016	0.06	-10000	0	-0.38	4	4
RAF1	0.016	0.1	-10000	0	-0.5	5	5
SHC1	0	0	-10000	0	-10000	0	0
STAT3	-0.014	0.061	-10000	0	-0.44	4	4
STAT1	-0.026	0.16	-10000	0	-1.1	4	4
HRAS/SPRED1	-0.019	0.088	-10000	0	-0.5	5	5
cell proliferation	-0.015	0.12	-10000	0	-0.47	15	15
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
TEC	-0.02	0.13	-10000	0	-0.88	6	6
RPS6KB1	0.006	0.067	-10000	0	-0.44	4	4
HRAS/SPRED2	-0.019	0.088	-10000	0	-0.5	5	5
LYN/TEC/p62DOK	-0.023	0.085	-10000	0	-0.45	10	10
MAPK3	0.025	0.074	-10000	0	-0.33	5	5
STAP1	-0.014	0.062	-10000	0	-0.44	4	4
GRAP2	-0.018	0.15	0.32	4	-0.88	7	11
JAK2	-0.053	0.13	-10000	0	-0.9	4	4
STAT1 (dimer)	-0.024	0.16	-10000	0	-1.1	4	4
mol:Gleevec	-0.001	0.003	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.036	0.12	-10000	0	-0.49	17	17
actin filament polymerization	0.006	0.067	-10000	0	-0.43	4	4
LYN	0	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.023	0.085	-10000	0	-0.62	4	4
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
CBL/CRKL/GRB2	-0.01	0.045	-10000	0	-10000	0	0
PI3K	-0.016	0.076	-10000	0	-0.52	5	5
PTEN	-0.007	0.076	-10000	0	-0.88	2	2
SCF/KIT/EPO/EPOR	-0.19	0.3	-10000	0	-1.5	4	4
MAPK8	-0.035	0.11	-10000	0	-0.48	15	15
STAT3 (dimer)	0.006	0.067	-10000	0	-0.43	4	4
positive regulation of transcription	0.025	0.062	-10000	0	-0.27	5	5
mol:GDP	-0.032	0.13	0.29	1	-0.66	7	8
PIK3C2B	-0.014	0.061	-10000	0	-0.44	4	4
CBL/CRKL	-0.009	0.053	-10000	0	-0.39	4	4
FER	-0.014	0.061	-10000	0	-0.44	4	4
SH2B3	-0.014	0.061	-10000	0	-0.44	4	4
PDPK1	0.007	0.061	-10000	0	-0.36	4	4
SNAI2	-0.014	0.072	-10000	0	-0.48	5	5
positive regulation of cell proliferation	-0.007	0.12	-10000	0	-0.77	4	4
KITLG	0.01	0.027	-10000	0	-10000	0	0
cell motility	-0.007	0.12	-10000	0	-0.77	4	4
PTPN6	0.004	0.006	-10000	0	-10000	0	0
EPOR	0.016	0.053	-10000	0	-10000	0	0
STAT5A (dimer)	-0.004	0.1	-10000	0	-0.63	4	4
SOCS1	-0.005	0.078	0.32	1	-0.88	2	3
cell migration	-0.006	0.067	0.43	4	-10000	0	4
SOS1	0	0	-10000	0	-10000	0	0
EPO	-0.31	0.43	0.32	8	-0.88	96	104
VAV1	-0.039	0.18	-10000	0	-0.88	12	12
GRB10	-0.014	0.061	-10000	0	-0.44	4	4
PTPN11	0	0.003	-10000	0	-10000	0	0
SCF/KIT	-0.019	0.065	-10000	0	-0.47	4	4
GO:0007205	0	0.004	-10000	0	-10000	0	0
MAP2K1	0.024	0.081	-10000	0	-0.37	5	5
CBL	0	0	-10000	0	-10000	0	0
KIT	0.001	0.19	-10000	0	-1.5	4	4
MAP2K2	0.024	0.081	-10000	0	-0.37	5	5
SHC/Grb2/SOS1	-0.013	0.05	-10000	0	-0.41	4	4
STAT5A	-0.005	0.1	-10000	0	-0.65	4	4
GRB2	0	0	-10000	0	-10000	0	0
response to radiation	0.005	0.076	-10000	0	-0.46	5	5
SHC/GRAP2	-0.015	0.11	-10000	0	-0.68	7	7
PTPRO	-0.04	0.13	-10000	0	-0.5	18	18
SH2B2	-0.013	0.061	-10000	0	-0.44	4	4
DOK1	0	0	-10000	0	-10000	0	0
MATK	-0.013	0.062	-10000	0	-0.44	4	4
CREBBP	0.024	0.016	-10000	0	-10000	0	0
BCL2	0.019	0.049	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.002	0.033	-10000	0	-0.55	1	1
HDAC3	0	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-10000	0	-10000	0	0
GATA1/HDAC4	0.003	0.026	-10000	0	-10000	0	0
GATA1/HDAC5	0.002	0.023	-10000	0	-10000	0	0
GATA2/HDAC5	-0.003	0.062	-10000	0	-0.68	2	2
HDAC5/BCL6/BCoR	0	0	-10000	0	-10000	0	0
HDAC9	-0.036	0.17	-10000	0	-0.88	11	11
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
HDAC4/ANKRA2	-0.002	0.044	-10000	0	-0.68	1	1
HDAC5/YWHAB	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
GATA2	-0.004	0.081	0.32	2	-0.88	2	4
HDAC4/RFXANK	0.002	0.023	-10000	0	-10000	0	0
BCOR	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0	-10000	0	-10000	0	0
HDAC5	0	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.003	0.042	-10000	0	-0.68	1	1
Histones	-0.008	0.06	-10000	0	-10000	0	0
ADRBK1	0	0	-10000	0	-10000	0	0
HDAC4	0.001	0.019	0.32	1	-10000	0	1
XPO1	0	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	-0.003	0.042	-10000	0	-0.68	1	1
HDAC4/Ubc9	0.001	0.013	-10000	0	-10000	0	0
HDAC7	0.001	0.019	0.32	1	-10000	0	1
HDAC5/14-3-3 E	0	0	-10000	0	-10000	0	0
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.002	0.019	-10000	0	-10000	0	0
CAMK4	-0.078	0.25	0.32	1	-0.88	24	25
Tubulin/HDAC6	0	0	-10000	0	-10000	0	0
SUMO1	0	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
GATA1	0.004	0.033	0.32	3	-10000	0	3
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
NR3C1	0	0	-10000	0	-10000	0	0
SUMO1/HDAC4	0.001	0.012	-10000	0	-10000	0	0
SRF	0	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.001	0.013	-10000	0	-10000	0	0
Tubulin	0	0	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.001	0.013	-10000	0	-10000	0	0
GNB1	0	0	-10000	0	-10000	0	0
RANGAP1	0	0	-10000	0	-10000	0	0
BCL6/BCoR	0	0	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.001	0.012	-10000	0	-10000	0	0
HDAC4/SRF	-0.052	0.17	-10000	0	-0.6	24	24
HDAC4/ER alpha	-0.36	0.34	-10000	0	-0.68	143	143
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.008	0.059	-10000	0	-10000	0	0
cell motility	0	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.001	0.013	-10000	0	-10000	0	0
BCL6	0	0	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.001	0.019	0.32	1	-10000	0	1
Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
ESR1	-0.47	0.44	-10000	0	-0.88	143	143
HDAC6/HDAC11	0.006	0.035	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.001	0.011	-10000	0	-10000	0	0
GNG2	-0.003	0.054	-10000	0	-0.88	1	1
NCOR2	0	0	-10000	0	-10000	0	0
TUBB2A	0	0	-10000	0	-10000	0	0
HDAC11	0.008	0.05	0.32	7	-10000	0	7
HSP90AA1	0	0	-10000	0	-10000	0	0
RANBP2	0	0	-10000	0	-10000	0	0
ANKRA2	-0.003	0.054	-10000	0	-0.88	1	1
RFXANK	0.002	0.027	0.32	2	-10000	0	2
nuclear import	-0.001	0.009	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.012	0.05	-10000	0	-10000	0	0
ATM	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
PRKDC	0	0	-10000	0	-10000	0	0
ATR	0	0	-10000	0	-10000	0	0
UBE2L3	0	0	-10000	0	-10000	0	0
FANCD2	0.036	0.062	-10000	0	-10000	0	0
protein ubiquitination	0.069	0.094	0.33	9	-10000	0	9
XRCC5	0	0	-10000	0	-10000	0	0
XRCC6	0	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.024	0.057	-10000	0	-0.51	1	1
FANCF	0	0	-10000	0	-10000	0	0
BRCA1	0	0	-10000	0	-10000	0	0
CCNE1	0.11	0.15	0.32	94	-10000	0	94
CDK2/Cyclin E1	0.077	0.1	-10000	0	-10000	0	0
FANCG	0.002	0.027	0.32	2	-10000	0	2
BRCA1/BACH1/BARD1	0.012	0.05	-10000	0	-10000	0	0
FANCE	0.009	0.054	0.32	8	-10000	0	8
FANCC	-0.003	0.054	-10000	0	-0.88	1	1
NBN	0	0	-10000	0	-10000	0	0
FANCA	0	0	-10000	0	-10000	0	0
DNA repair	0.085	0.048	-10000	0	-10000	0	0
BRCA1/BARD1/ubiquitin	0.012	0.05	-10000	0	-10000	0	0
BARD1/DNA-PK	0.011	0.045	-10000	0	-10000	0	0
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.012	0.05	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.006	0.026	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0.011	0.046	-10000	0	-10000	0	0
BRCA1/BARD1/P53	0.011	0.045	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	0.011	0.046	-10000	0	-10000	0	0
BRCA1/BACH1	0	0	-10000	0	-10000	0	0
BARD1	0.018	0.073	0.32	15	-10000	0	15
PCNA	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.011	0.046	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	0.011	0.046	-10000	0	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.062	0.1	0.38	9	-10000	0	9
BARD1/DNA-PK/P53	0.01	0.043	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.012	0.05	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP	0.012	0.048	-10000	0	-10000	0	0
FA complex	0.003	0.028	-10000	0	-0.29	1	1
BARD1/EWS	0.012	0.05	-10000	0	-10000	0	0
RBBP8	0.017	0	-10000	0	-10000	0	0
TP53	0	0	-10000	0	-10000	0	0
TOPBP1	0	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.011	0.044	-10000	0	-10000	0	0
BRCA1/BARD1	0.075	0.1	0.36	9	-10000	0	9
CSTF1	0	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.012	0.049	0.21	15	-10000	0	15
CDK2	0	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.084	0.14	0.32	71	-10000	0	71
RAD50	0	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.012	0.05	-10000	0	-10000	0	0
EWSR1	0	0	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0	0	-10000	0	-10000	0	0
ITGB7	-0.013	0.11	-10000	0	-0.88	4	4
ITGA4	-0.012	0.11	0.32	1	-0.88	4	5
alpha4/beta7 Integrin	-0.02	0.12	-10000	0	-0.68	8	8
alpha4/beta1 Integrin	-0.009	0.084	-10000	0	-0.68	4	4

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.041	0.16	-10000	0	-0.68	16	16
AKT1	0.049	0.12	-10000	0	-0.68	6	6
PTK2B	-0.046	0.18	-10000	0	-0.96	6	6
VEGFR2 homodimer/Frs2	-0.022	0.14	-10000	0	-0.97	6	6
CAV1	0	0	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.02	0.13	-10000	0	-0.91	6	6
endothelial cell proliferation	0.037	0.14	-10000	0	-0.66	6	6
mol:Ca2+	-0.022	0.14	-10000	0	-0.82	7	7
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.019	0.13	-10000	0	-0.87	6	6
RP11-342D11.1	-0.022	0.14	-10000	0	-0.83	7	7
CDH5	-0.003	0.054	-10000	0	-0.88	1	1
VEGFA homodimer	0	0	-10000	0	-10000	0	0
SHC1	0	0	-10000	0	-10000	0	0
SHC2	-0.02	0.13	-10000	0	-0.88	6	6
HRAS/GDP	-0.018	0.11	-10000	0	-0.74	6	6
SH2D2A	-0.023	0.15	0.32	3	-0.88	8	11
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.019	0.11	-10000	0	-0.72	6	6
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.034	0.17	-10000	0	-0.75	13	13
VEGFR1 homodimer	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.021	0.13	-10000	0	-0.85	6	6
GRB10	-0.021	0.14	-10000	0	-0.88	6	6
PTPN11	0	0	-10000	0	-10000	0	0
GRB2	0	0	-10000	0	-10000	0	0
PAK1	0	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.02	0.14	-10000	0	-0.91	6	6
HRAS	0.002	0.027	0.32	2	-10000	0	2
VEGF/Rho/ROCK1/Integrin Complex	-0.025	0.095	-10000	0	-0.49	6	6
HIF1A	0	0	-10000	0	-10000	0	0
FRS2	0	0	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.019	0.13	-10000	0	-0.85	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	-0.003	0.054	-10000	0	-0.88	1	1
Nck/Pak	-0.003	0.042	-10000	0	-0.68	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.02	0.13	-10000	0	-0.91	6	6
mol:GDP	-0.02	0.12	-10000	0	-0.81	6	6
mol:NADP	0.044	0.11	-10000	0	-0.57	7	7
eNOS/Hsp90	0.045	0.099	-10000	0	-0.53	7	7
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
mol:IP3	-0.022	0.14	-10000	0	-0.84	7	7
HIF1A/ARNT	0	0	-10000	0	-10000	0	0
SHB	-0.003	0.054	-10000	0	-0.88	1	1
VEGFA	0	0	-10000	0	-10000	0	0
VEGFC	0.001	0.019	0.32	1	-10000	0	1
FAK1/Vinculin	-0.035	0.15	-10000	0	-0.89	6	6
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.049	0.19	-10000	0	-0.66	20	20
PTPN6	0	0	-10000	0	-10000	0	0
EPAS1	-0.009	0.058	-10000	0	-0.4	6	6
mol:L-citrulline	0.044	0.11	-10000	0	-0.57	7	7
ITGAV	0	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.019	0.13	-10000	0	-0.87	6	6
VEGFR2 homodimer/VEGFA homodimer	-0.024	0.15	-10000	0	-0.92	7	7
VEGFR2/3 heterodimer	-0.024	0.16	-10000	0	-1.1	6	6
VEGFB	-0.024	0.15	0.32	2	-0.88	8	10
MAPK11	0.027	0.15	-10000	0	-0.86	7	7
VEGFR2 homodimer	0.003	0.16	-10000	0	-1.1	6	6
FLT1	0	0	-10000	0	-10000	0	0
NEDD4	-0.007	0.075	-10000	0	-0.88	2	2
MAPK3	0.018	0.14	-10000	0	-0.82	6	6
MAPK1	0.018	0.14	-10000	0	-0.76	7	7
VEGFA145/NRP2	-0.004	0.06	-10000	0	-0.68	2	2
VEGFR1/2 heterodimer	-0.022	0.14	-10000	0	-0.97	6	6
KDR	0.003	0.16	-10000	0	-1.1	6	6
VEGFA165/NRP1/VEGFR2 homodimer	-0.025	0.16	-10000	0	-0.98	6	6
SRC	0.001	0.019	0.32	1	-10000	0	1
platelet activating factor biosynthetic process	0.02	0.14	-10000	0	-0.79	7	7
PI3K	-0.025	0.14	-10000	0	-0.89	6	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.022	0.15	-10000	0	-0.99	6	6
FES	-0.026	0.15	-10000	0	-0.92	6	6
GAB1	-0.02	0.13	-10000	0	-0.86	6	6
VEGFR2 homodimer/VEGFA homodimer/Src	-0.02	0.14	-10000	0	-0.91	6	6
CTNNB1	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
ARNT	0	0	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.045	0.099	-10000	0	-0.53	7	7
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.02	0.13	-10000	0	-0.91	6	6
PI3K/GAB1	-0.019	0.11	-10000	0	-0.7	6	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.02	0.14	-10000	0	-0.91	6	6
PRKACA	0	0	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.021	0.15	-10000	0	-0.99	6	6
HSP90AA1	0	0	-10000	0	-10000	0	0
CDC42	-0.023	0.14	-10000	0	-0.92	6	6
actin cytoskeleton reorganization	-0.033	0.17	-10000	0	-0.74	13	13
PTK2	0.013	0.18	-10000	0	-0.99	6	6
EDG1	-0.022	0.14	-10000	0	-0.83	7	7
mol:DAG	-0.022	0.14	-10000	0	-0.84	7	7
CaM/Ca2+	-0.02	0.13	-10000	0	-0.82	6	6
MAP2K3	-0.026	0.14	-10000	0	-0.87	6	6
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.023	0.14	-10000	0	-0.94	6	6
PLCG1	-0.023	0.14	-10000	0	-0.92	6	6
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.02	0.13	-10000	0	-0.82	7	7
IQGAP1	0	0	-10000	0	-10000	0	0
YES1	0	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.02	0.13	-10000	0	-0.91	6	6
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.02	0.13	-10000	0	-0.91	6	6
cell migration	0.041	0.14	-10000	0	-0.72	6	6
mol:PI-3-4-5-P3	-0.022	0.12	-10000	0	-0.78	6	6
FYN	0	0	-10000	0	-10000	0	0
VEGFB/NRP1	-0.034	0.15	-10000	0	-0.63	14	14
mol:NO	0.044	0.11	-10000	0	-0.57	7	7
PXN	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.018	0.11	-10000	0	-0.75	6	6
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.023	0.14	-10000	0	-0.94	6	6
VHL	0	0	-10000	0	-10000	0	0
ITGB3	-0.052	0.21	-10000	0	-0.88	16	16
NOS3	0.043	0.12	-10000	0	-0.67	7	7
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.032	0.16	-10000	0	-0.72	12	12
RAC1	0	0	-10000	0	-10000	0	0
PRKCA	-0.02	0.13	-10000	0	-0.83	6	6
PRKCB	-0.061	0.19	-10000	0	-0.9	6	6
VCL	0.001	0.019	0.32	1	-10000	0	1
VEGFA165/NRP1	-0.022	0.14	-10000	0	-0.83	7	7
VEGFR1/2 heterodimer/VEGFA homodimer	-0.02	0.13	-10000	0	-0.91	6	6
VEGFA165/NRP2	-0.004	0.06	-10000	0	-0.68	2	2
MAPKKK cascade	-0.018	0.11	-10000	0	-0.75	6	6
NRP2	-0.005	0.078	0.32	1	-0.88	2	3
VEGFC homodimer	0.001	0.019	0.32	1	-10000	0	1
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
ROCK1	0	0	-10000	0	-10000	0	0
FAK1/Paxillin	-0.036	0.15	-10000	0	-0.89	6	6
MAP3K13	-0.027	0.15	-10000	0	-0.92	6	6
PDPK1	-0.019	0.1	-10000	0	-0.66	6	6

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.001	0.064	-10000	0	-0.53	3	3
RGS9BP	0.012	0.06	0.32	10	-10000	0	10
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
mol:Na +	0.021	0.062	0.38	1	-10000	0	1
mol:ADP	0.003	0.004	-10000	0	-10000	0	0
GNAT2	0.001	0.019	0.32	1	-10000	0	1
RGS9-1/Gbeta5/R9AP	0	0.12	0.39	2	-0.6	8	10
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.001	0.012	-10000	0	-10000	0	0
GRK7	0	0	-10000	0	-10000	0	0
CNGB3	0.034	0.098	0.32	29	-10000	0	29
Cone Metarhodopsin II/X-Arrestin	0.001	0.013	0.21	1	-10000	0	1
mol:Ca2+	0.007	0.021	-10000	0	-10000	0	0
Cone PDE6	0.007	0.11	0.35	3	-0.52	8	11
Cone Metarhodopsin II	0	0	-10000	0	-10000	0	0
Na + (4 Units)	0.02	0.058	0.36	1	-10000	0	1
GNAT2/GDP	0.001	0.11	0.35	2	-0.52	8	10
GNB5	0.001	0.019	0.32	1	-10000	0	1
mol:GMP (4 units)	0.007	0.035	-10000	0	-10000	0	0
Cone Transducin	-0.001	0.067	-10000	0	-0.55	3	3
SLC24A2	0	0	-10000	0	-10000	0	0
GNB3/GNGT2	-0.002	0.081	-10000	0	-0.68	3	3
GNB3	0.008	0.05	0.32	7	-10000	0	7
GNAT2/GTP	0.001	0.013	0.21	1	-10000	0	1
CNGA3	0.001	0.019	0.32	1	-10000	0	1
ARR3	0.001	0.019	0.32	1	-10000	0	1
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.021	0.063	0.39	1	-10000	0	1
mol:Pi	0	0.12	0.39	2	-0.59	8	10
Cone CNG Channel	0.023	0.055	0.3	1	-10000	0	1
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0	0	-10000	0	-10000	0	0
RGS9	-0.011	0.17	0.32	13	-0.88	8	21
PDE6C	0.012	0.06	0.32	10	-10000	0	10
GNGT2	-0.01	0.092	-10000	0	-0.88	3	3
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0	0	-10000	0	-10000	0	0

×

Arf6 downstream 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
PLAUR	-0.007	0.12	-10000	0	-1.3	2	2
regulation of axonogenesis	0.015	0.073	0.34	12	-10000	0	12
myoblast fusion	0.002	0.042	0.43	2	-10000	0	2
mol:GTP	-0.001	0.024	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.02	0.11	0.57	10	-10000	0	10
ARF1/GTP	0	0.018	-10000	0	-10000	0	0
mol:GM1	0.007	0.019	-10000	0	-10000	0	0
mol:Choline	-0.005	0.12	-10000	0	-0.58	12	12
lamellipodium assembly	0.002	0.051	-10000	0	-0.47	2	2
MAPK3	0.02	0.037	-10000	0	-0.36	2	2
ARF6/GTP/NME1/Tiam1	-0.02	0.11	-10000	0	-0.58	10	10
ARF1	0	0	-10000	0	-10000	0	0
ARF6/GDP	-0.002	0.042	-10000	0	-0.43	2	2
ARF1/GDP	0	0.04	-10000	0	-0.39	2	2
ARF6	0	0.013	-10000	0	-10000	0	0
RAB11A	0	0	-10000	0	-10000	0	0
TIAM1	-0.033	0.17	-10000	0	-0.88	10	10
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.02	0.037	-10000	0	-0.36	2	2
actin filament bundle formation	0.003	0.035	0.39	2	-10000	0	2
KALRN	-0.001	0.048	-10000	0	-0.4	3	3
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.003	0.035	-10000	0	-0.4	2	2
NME1	0.003	0.027	0.32	2	-10000	0	2
Rac1/GDP	-0.003	0.035	-10000	0	-0.4	2	2
substrate adhesion-dependent cell spreading	-0.001	0.024	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.002	0.051	-10000	0	-0.47	2	2
RAC1	0	0	-10000	0	-10000	0	0
liver development	-0.001	0.024	-10000	0	-10000	0	0
ARF6/GTP	-0.001	0.024	-10000	0	-10000	0	0
RhoA/GTP	0	0.018	-10000	0	-10000	0	0
mol:GDP	0.002	0.048	-10000	0	-0.43	2	2
ARF6/GTP/RAB11FIP3/RAB11A	0	0.015	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
PLD1	-0.029	0.14	-10000	0	-0.65	12	12
RAB11FIP3	0	0	-10000	0	-10000	0	0
tube morphogenesis	0.002	0.051	-10000	0	-0.47	2	2
ruffle organization	-0.015	0.073	-10000	0	-0.34	12	12
regulation of epithelial cell migration	-0.001	0.024	-10000	0	-10000	0	0
PLD2	0	0.018	-10000	0	-10000	0	0
PIP5K1A	-0.016	0.073	-10000	0	-0.34	12	12
mol:Phosphatidic acid	-0.005	0.12	-10000	0	-0.58	12	12
Rac1/GTP	0.002	0.051	-10000	0	-0.47	2	2

×

IFN-gamma 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.005	0.046	-10000	0	-0.48	1	1
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0	0.03	-10000	0	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.001	0.037	-10000	0	-0.6	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.054	0.064	-10000	0	-0.47	2	2
CaM/Ca2+	0.004	0.04	-10000	0	-0.44	1	1
RAP1A	0	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.003	0.037	-10000	0	-0.45	1	1
AKT1	-0.001	0.068	-10000	0	-1.1	1	1
MAP2K1	0.045	0.03	-10000	0	-0.42	1	1
MAP3K11	0.001	0.031	-10000	0	-0.45	1	1
IFNGR1	0	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.18	0.2	-10000	0	-0.48	4	4
Rap1/GTP	-0.001	0.021	-10000	0	-10000	0	0
CRKL/C3G	0	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.005	0.046	-10000	0	-0.5	1	1
CEBPB	0.062	0.05	-10000	0	-0.41	2	2
STAT3	0	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.005	0.12	-10000	0	-1.3	2	2
STAT1	0.003	0.037	-10000	0	-0.45	1	1
CALM1	0	0	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.011	0.058	0.32	9	-10000	0	9
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
STAT1 (dimer)/PIAS1	0.003	0.035	-10000	0	-0.42	1	1
CEBPB/PTGES2/Cbp/p300	-0.003	0.025	-10000	0	-10000	0	0
mol:Ca2+	0.004	0.044	-10000	0	-0.47	1	1
MAPK3	0.048	0.032	-10000	0	-10000	0	0
STAT1 (dimer)	-0.07	0.094	-10000	0	-0.77	2	2
MAPK1	0.048	0.032	-10000	0	-10000	0	0
JAK2	-0.003	0.053	-10000	0	-0.88	1	1
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
JAK1	0	0.002	-10000	0	-10000	0	0
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	0.055	0.066	-10000	0	-0.67	2	2
SMAD7	0	0.065	-10000	0	-0.41	2	2
CBL/CRKL/C3G	-0.002	0.025	-10000	0	-0.41	1	1
PI3K	0	0.083	-10000	0	-1.3	1	1
IFNG	0.011	0.058	0.32	9	-10000	0	9
apoptosis	0.035	0.048	-10000	0	-0.46	2	2
CAMK2G	0	0	-10000	0	-10000	0	0
STAT3 (dimer)	0	0	-10000	0	-10000	0	0
CAMK2A	0.022	0.081	0.32	19	-10000	0	19
CAMK2B	-0.43	0.44	-10000	0	-0.88	130	130
FRAP1	0.035	0.062	-10000	0	-0.93	1	1
PRKCD	-0.001	0.07	-10000	0	-1.1	1	1
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.054	0.064	-10000	0	-0.47	2	2
PTPN2	0	0	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
IRF1	0.063	0.039	-10000	0	-10000	0	0
STAT1 (dimer)/PIASy	0.004	0.038	-10000	0	-0.42	1	1
SOCS1	-0.01	0.13	-10000	0	-1.5	2	2
mol:GDP	-0.001	0.024	-10000	0	-0.39	1	1
CASP1	0.002	0.057	-10000	0	-0.24	1	1
PTGES2	0.001	0.019	0.32	1	-10000	0	1
IRF9	0.046	0.017	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.075	-10000	0	-1.2	1	1
RAP1/GDP	-0.001	0.021	-10000	0	-10000	0	0
CBL	0.001	0.031	-10000	0	-0.45	1	1
MAP3K1	0.001	0.031	-10000	0	-0.45	1	1
PIAS1	0	0	-10000	0	-10000	0	0
PIAS4	0	0	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.054	0.064	-10000	0	-0.47	2	2
PTPN11	0.001	0.032	-10000	0	-0.48	1	1
CREBBP	0	0	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.017	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-10000	0	-10000	0	0
CDKN1B	0.029	0.002	-10000	0	-10000	0	0
CDKN1A	0.022	0.064	-10000	0	-0.5	4	4
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0	0	-10000	0	-10000	0	0
FOXO3	0.029	0.002	-10000	0	-10000	0	0
AKT1	0	0.003	-10000	0	-10000	0	0
BAD	0	0	-10000	0	-10000	0	0
AKT3	0.001	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.029	0.002	-10000	0	-10000	0	0
AKT1/ASK1	-0.047	0.14	-10000	0	-0.48	26	26
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0	0	-10000	0	-10000	0	0
JNK cascade	0.045	0.14	0.46	26	-10000	0	26
TSC1	0.029	0.002	-10000	0	-10000	0	0
YWHAZ	0	0	-10000	0	-10000	0	0
AKT1/RAF1	0	0	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.003	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.025	0.045	-10000	0	-0.5	2	2
YWHAQ	0	0	-10000	0	-10000	0	0
TBC1D4	-0.004	0.051	-10000	0	-0.59	2	2
MAP3K5	-0.085	0.26	-10000	0	-0.88	26	26
MAPKAP1	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.059	0.024	-10000	0	-10000	0	0
YWHAH	0	0	-10000	0	-10000	0	0
AKT1S1	0.029	0.002	-10000	0	-10000	0	0
CASP9	0.029	0.002	-10000	0	-10000	0	0
YWHAB	0	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0	0	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.001	0.012	-10000	0	-10000	0	0
YWHAE	0	0	-10000	0	-10000	0	0
SRC	0.001	0.019	0.32	1	-10000	0	1
AKT2/p21CIP1	-0.007	0.058	-10000	0	-0.48	4	4
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.013	0.001	-10000	0	-10000	0	0
CHUK	0.029	0.002	-10000	0	-10000	0	0
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
mTORC2	0	0	-10000	0	-10000	0	0
AKT2	0	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.074	0.03	-10000	0	-10000	0	0
PDPK1	0	0	-10000	0	-10000	0	0
MDM2	0.029	0.002	-10000	0	-10000	0	0
MAPKKK cascade	0	0	-10000	0	-10000	0	0
MDM2/Cbp/p300	0	0	-10000	0	-10000	0	0
TSC1/TSC2	0.031	0.044	-10000	0	-0.48	2	2
proteasomal ubiquitin-dependent protein catabolic process	0	0	-10000	0	-10000	0	0
glucose import	0.014	0.084	-10000	0	-0.54	6	6
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.025	0.001	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.01	0.082	-10000	0	-0.55	6	6
GSK3A	0.029	0.002	-10000	0	-10000	0	0
FOXO1	0.023	0.055	-10000	0	-0.5	3	3
GSK3B	0.029	0.002	-10000	0	-10000	0	0
SFN	0.18	0.16	0.32	155	-10000	0	155
G1/S transition of mitotic cell cycle	0.035	0.002	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.057	0.049	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
KPNA1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
CREBBP	0	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.016	0.12	-10000	0	-0.88	5	5
positive regulation of NF-kappaB transcription factor activity	-0.015	0.1	-10000	0	-0.68	6	6
MAP2K4	-0.009	0.053	-10000	0	-0.33	6	6
IKBKB	0	0	-10000	0	-10000	0	0
TNFRSF10B	0	0	-10000	0	-10000	0	0
TNFRSF10A	-0.013	0.11	-10000	0	-0.88	4	4
SMPD1	-0.006	0.042	-10000	0	-0.31	5	5
IKBKG	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.003	0.054	-10000	0	-0.88	1	1
TRAIL/TRAILR2	-0.013	0.093	-10000	0	-0.68	5	5
TRAIL/TRAILR3	-0.011	0.11	-10000	0	-0.68	6	6
TRAIL/TRAILR1	-0.023	0.12	-10000	0	-0.68	9	9
TRAIL/TRAILR4	-0.015	0.1	-10000	0	-0.68	6	6
TRAIL/TRAILR1/DAP3/GTP	-0.019	0.1	-10000	0	-0.55	9	9
IKK complex	-0.007	0.036	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.004	0.095	-10000	0	-0.68	5	5
MAP3K1	-0.01	0.057	-10000	0	-0.36	6	6
TRAILR4 (trimer)	-0.003	0.053	-10000	0	-0.88	1	1
TRADD	-0.003	0.054	-10000	0	-0.88	1	1
TRAILR1 (trimer)	-0.013	0.11	-10000	0	-0.88	4	4
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.013	0.068	-10000	0	-0.36	10	10
CFLAR	0	0	-10000	0	-10000	0	0
MAPK1	0.004	0.095	-10000	0	-0.68	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.018	0.098	-10000	0	-0.51	10	10
mol:ceramide	-0.006	0.042	-10000	0	-0.31	5	5
FADD	0.001	0.019	0.32	1	-10000	0	1
MAPK8	0.011	0.12	-10000	0	-0.52	12	12
TRAF2	0	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.003	0.069	0.32	5	-0.88	1	6
CHUK	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.019	0.11	-10000	0	-0.6	9	9
DAP3	0	0	-10000	0	-10000	0	0
CASP10	-0.013	0.086	0.31	1	-0.57	5	6
JNK cascade	-0.015	0.1	-10000	0	-0.68	6	6
TRAIL (trimer)	-0.016	0.12	-10000	0	-0.88	5	5
TNFRSF10C	0.003	0.069	0.32	5	-0.88	1	6
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.017	0.095	-10000	0	-0.52	9	9
TRAIL/TRAILR2/FADD	-0.01	0.082	-10000	0	-0.6	5	5
cell death	-0.006	0.042	-10000	0	-0.31	5	5
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.008	0.053	-10000	0	-0.36	6	6
TRAILR2 (trimer)	0	0	-10000	0	-10000	0	0
CASP8	0.002	0.022	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.011	0.077	-10000	0	-0.51	6	6

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.028	0.082	-10000	0	-0.6	4	4
SNTA1	0.002	0.027	0.32	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	0.033	0.085	-10000	0	-0.6	4	4
MAPK12	-0.001	0.084	-10000	0	-0.53	6	6
CCND1	-0.017	0.1	-10000	0	-0.42	14	14
p38 gamma/SNTA1	0	0.081	-10000	0	-0.5	6	6
MAP2K3	0	0	-10000	0	-10000	0	0
PKN1	0.001	0.019	0.32	1	-10000	0	1
G2/M transition checkpoint	0.019	0.084	-10000	0	-0.53	6	6
MAP2K6	-0.012	0.088	-10000	0	-0.59	6	6
MAPT	0.056	0.069	-10000	0	-0.32	4	4
MAPK13	0.031	0.1	-10000	0	-0.69	4	4
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.001	0.008	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.001	0.008	-10000	0	-10000	0	0
DOCK1	-0.016	0.12	-10000	0	-0.88	5	5
ITGA4	-0.012	0.11	0.32	1	-0.88	4	5
RAC1	0	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.02	0.12	-10000	0	-0.68	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.008	0.074	-10000	0	-0.6	4	4
alpha4/beta7 Integrin/Paxillin	-0.016	0.094	-10000	0	-0.55	8	8
lamellipodium assembly	-0.009	0.071	-10000	0	-0.5	5	5
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
PI3K	-0.005	0.075	-10000	0	-1.2	1	1
ARF6	0	0	-10000	0	-10000	0	0
TLN1	0	0	-10000	0	-10000	0	0
PXN	0.017	0	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
ARF6/GTP	-0.006	0.058	-10000	0	-0.47	4	4
cell adhesion	-0.007	0.063	-10000	0	-0.51	4	4
CRKL/CBL	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.007	0.068	-10000	0	-0.55	4	4
ITGB1	0	0	-10000	0	-10000	0	0
ITGB7	-0.013	0.11	-10000	0	-0.88	4	4
ARF6/GDP	0.001	0.008	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.033	0.15	-10000	0	-0.57	17	17
p130Cas/Crk/Dock1	-0.011	0.081	-10000	0	-0.6	5	5
VCAM1	-0.044	0.21	0.32	4	-0.88	15	19
alpha4/beta1 Integrin/Paxillin/Talin	-0.007	0.064	-10000	0	-0.51	4	4
alpha4/beta1 Integrin/Paxillin/GIT1	-0.007	0.064	-10000	0	-0.51	4	4
BCAR1	0	0	-10000	0	-10000	0	0
mol:GDP	0.007	0.063	0.51	4	-10000	0	4
CBL	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
GIT1	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.007	0.064	-10000	0	-0.51	4	4
Rac1/GTP	-0.01	0.084	-10000	0	-0.57	5	5

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.003	0.027	-10000	0	-10000	0	0
DAPP1	-0.04	0.16	-10000	0	-0.64	10	10
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.047	0.21	0.32	1	-0.7	14	15
mol:DAG	0.006	0.091	0.25	1	-0.31	6	7
HRAS	0.002	0.028	0.32	2	-10000	0	2
RAP1A	0	0	-10000	0	-10000	0	0
ARF5/GDP	-0.016	0.058	-10000	0	-0.49	1	1
PLCG2	-0.016	0.12	-10000	0	-0.88	5	5
PLCG1	0	0	-10000	0	-10000	0	0
ARF5	0	0	-10000	0	-10000	0	0
mol:GTP	0.002	0.023	-10000	0	-10000	0	0
ARF1/GTP	0.003	0.025	-10000	0	-10000	0	0
RHOA	0	0	-10000	0	-10000	0	0
YES1	0	0	-10000	0	-10000	0	0
RAP1A/GTP	0.002	0.022	-10000	0	-10000	0	0
ADAP1	-0.004	0.079	-10000	0	-0.48	6	6
ARAP3	0.002	0.023	-10000	0	-10000	0	0
INPPL1	0	0	-10000	0	-10000	0	0
PREX1	0	0	-10000	0	-10000	0	0
ARHGEF6	0	0	-10000	0	-10000	0	0
ARHGEF7	0	0	-10000	0	-10000	0	0
ARF1	0	0	-10000	0	-10000	0	0
NRAS	0	0	-10000	0	-10000	0	0
FYN	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
FGR	-0.003	0.054	-10000	0	-0.88	1	1
mol:Ca2+	0.011	0.051	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.033	0.17	-10000	0	-0.88	10	10
ZAP70	-0.002	0.085	0.32	4	-0.88	2	6
mol:IP3	0.01	0.069	0.22	1	-0.23	5	6
LYN	0	0	-10000	0	-10000	0	0
ARF1/GDP	-0.016	0.058	-10000	0	-0.49	1	1
RhoA/GDP	-0.004	0.033	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.001	0.012	-10000	0	-10000	0	0
BLNK	-0.02	0.13	-10000	0	-0.88	6	6
actin cytoskeleton reorganization	0.038	0.063	-10000	0	-10000	0	0
SRC	0.001	0.019	0.32	1	-10000	0	1
PLEKHA2	0.02	0.053	-10000	0	-0.6	2	2
RAC1	0	0	-10000	0	-10000	0	0
PTEN	-0.006	0.074	-10000	0	-0.86	2	2
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	0.002	0.026	-10000	0	-10000	0	0
RhoA/GTP	0.002	0.022	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.073	0.15	0.28	1	-0.62	9	10
BLK	-0.17	0.35	0.32	2	-0.88	53	55
PDPK1	0	0	-10000	0	-10000	0	0
CYTH1	0.002	0.023	-10000	0	-10000	0	0
HCK	-0.03	0.16	-10000	0	-0.88	9	9
CYTH3	0.003	0.025	-10000	0	-10000	0	0
CYTH2	0.002	0.023	-10000	0	-10000	0	0
KRAS	0	0	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.015	0.1	-10000	0	-0.58	8	8
SGK1	-0.017	0.11	-10000	0	-0.64	8	8
INPP5D	-0.003	0.054	-10000	0	-0.88	1	1
mol:GDP	0.012	0.071	-10000	0	-0.24	12	12
SOS1	0	0	-10000	0	-10000	0	0
SYK	-0.003	0.054	-10000	0	-0.88	1	1
ARF6/GDP	-0.004	0.033	0.28	2	-10000	0	2
mol:PI-3-4-5-P3	0.003	0.032	0.37	2	-10000	0	2
ARAP3/RAP1A/GTP	0.002	0.022	-10000	0	-10000	0	0
VAV1	-0.039	0.18	-10000	0	-0.88	12	12
mol:PI-3-4-P2	0.015	0.043	-10000	0	-0.68	1	1
RAS family/GTP/PI3K Class I	0.001	0.016	-10000	0	-10000	0	0
PLEKHA1	0.022	0.038	-10000	0	-0.6	1	1
Rac1/GDP	-0.016	0.058	-10000	0	-0.49	1	1
LAT	0.001	0.019	0.32	1	-10000	0	1
Rac1/GTP	-0.025	0.09	-10000	0	-0.39	10	10
ITK	-0.021	0.11	-10000	0	-0.48	13	13
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0	0.12	0.28	1	-0.47	6	7
LCK	-0.025	0.15	0.32	1	-0.88	8	9
BTK	-0.005	0.063	-10000	0	-0.48	4	4

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.019	0.1	0.31	2	-0.55	2	4
PDGFB-D/PDGFRB/SLAP	-0.016	0.12	-10000	0	-0.69	8	8
PDGFB-D/PDGFRB/APS/CBL	0.006	0.038	0.39	1	-10000	0	1
AKT1	-0.01	0.071	-10000	0	-0.75	1	1
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.021	0.1	0.31	2	-0.56	2	4
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
FGR	-0.006	0.047	-10000	0	-0.66	1	1
mol:Ca2+	0.012	0.05	-10000	0	-10000	0	0
MYC	-0.064	0.29	-10000	0	-0.88	30	30
SHC1	0	0	-10000	0	-10000	0	0
HRAS/GDP	-0.001	0.044	-10000	0	-0.48	2	2
LRP1/PDGFRB/PDGFB	0.003	0.049	-10000	0	-0.6	1	1
GRB10	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
GO:0007205	0.012	0.05	-10000	0	-10000	0	0
PTEN	-0.007	0.076	-10000	0	-0.88	2	2
GRB2	0	0	-10000	0	-10000	0	0
GRB7	-0.004	0.1	0.32	5	-0.88	3	8
PDGFB-D/PDGFRB/SHP2	0.005	0.032	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.005	0.032	-10000	0	-10000	0	0
cell cycle arrest	-0.016	0.12	-10000	0	-0.69	8	8
HRAS	0.002	0.027	0.32	2	-10000	0	2
HIF1A	0.042	0.07	-10000	0	-0.62	1	1
GAB1	0	0.084	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.007	0.083	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.031	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.005	0.032	-10000	0	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.011	0.12	0.36	2	-0.62	2	4
positive regulation of MAPKKK cascade	0.005	0.032	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
mol:IP3	0.012	0.05	-10000	0	-10000	0	0
E5	0	0.001	-10000	0	-10000	0	0
CSK	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.001	0.083	-10000	0	-0.68	3	3
SHB	-0.003	0.054	-10000	0	-0.88	1	1
BLK	-0.13	0.26	-10000	0	-0.65	53	53
PTPN2	0	0.001	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.005	0.032	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
VAV2	-0.005	0.11	-10000	0	-0.4	2	2
CBL	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.005	0.032	-10000	0	-10000	0	0
LCK	-0.023	0.13	-10000	0	-0.72	8	8
PDGFRB	0.009	0.047	0.32	6	-10000	0	6
ACP1	0	0	-10000	0	-10000	0	0
HCK	-0.021	0.12	-10000	0	-0.65	9	9
ABL1	0	0.073	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/CBL	-0.002	0.084	-10000	0	-10000	0	0
PTPN1	0	0.001	-10000	0	-10000	0	0
SNX15	0	0	-10000	0	-10000	0	0
STAT3	0	0	-10000	0	-10000	0	0
STAT1	0.002	0.027	0.32	2	-10000	0	2
cell proliferation	-0.051	0.26	-10000	0	-0.76	30	30
SLA	-0.026	0.15	-10000	0	-0.88	8	8
actin cytoskeleton reorganization	0.001	0.05	-10000	0	-0.45	2	2
SRC	-0.001	0.025	-10000	0	-10000	0	0
PI3K	-0.012	0.08	-10000	0	-0.66	2	2
PDGFB-D/PDGFRB/GRB7/SHC	0.001	0.073	-10000	0	-0.59	3	3
SH2B2	0.002	0.027	0.32	2	-10000	0	2
PLCgamma1/SPHK1	0.021	0.11	0.31	2	-0.58	2	4
LYN	-0.002	0.024	-10000	0	-10000	0	0
LRP1	-0.003	0.054	-10000	0	-0.88	1	1
SOS1	0	0	-10000	0	-10000	0	0
STAT5B	0	0	-10000	0	-10000	0	0
STAT5A	0	0	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.003	0.042	-10000	0	-0.49	1	1
SPHK1	0.05	0.15	0.32	48	-0.88	2	50
EDG1	0.001	0.003	-10000	0	-10000	0	0
mol:DAG	0.012	0.05	-10000	0	-10000	0	0
PLCG1	0.012	0.051	-10000	0	-10000	0	0
NHERF/PDGFRB	-0.002	0.07	-10000	0	-0.6	3	3
YES1	-0.002	0.023	-10000	0	-10000	0	0
cell migration	-0.002	0.07	-10000	0	-0.6	3	3
SHC/Grb2/SOS1	0.004	0.025	-10000	0	-10000	0	0
SLC9A3R2	-0.007	0.076	-10000	0	-0.88	2	2
SLC9A3R1	-0.003	0.054	-10000	0	-0.88	1	1
NHERF1-2/PDGFRB/PTEN	-0.006	0.08	-10000	0	-0.55	5	5
FYN	-0.001	0.023	-10000	0	-10000	0	0
DOK1	0.004	0.014	-10000	0	-10000	0	0
HRAS/GTP	0.002	0.018	0.21	2	-10000	0	2
PDGFB	0.001	0.019	0.32	1	-10000	0	1
RAC1	-0.019	0.16	-10000	0	-0.46	30	30
PRKCD	0.004	0.014	-10000	0	-10000	0	0
FER	0.004	0.014	-10000	0	-10000	0	0
MAPKKK cascade	0.001	0.013	-10000	0	-10000	0	0
RASA1	-0.001	0.05	-10000	0	-0.55	2	2
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
NCK2	0.001	0.019	0.32	1	-10000	0	1
p62DOK/Csk	0.004	0.014	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.002	0.05	-10000	0	-0.65	1	1
chemotaxis	0	0.072	-10000	0	-10000	0	0
STAT1-3-5/STAT1-3-5	0.004	0.021	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.007	0.032	0.21	6	-10000	0	6
PTPRJ	0	0	-10000	0	-10000	0	0

×

mTOR 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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0	0	-10000	0	-10000	0	0
mol:PIP3	-0.001	0.064	0.34	2	-0.94	1	3
FRAP1	0.013	0.027	-10000	0	-10000	0	0
AKT1	-0.002	0.057	0.24	2	-0.84	1	3
INSR	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.004	0.026	-10000	0	-10000	0	0
mol:GTP	-0.006	0.052	-10000	0	-0.47	3	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.014	-10000	0	-10000	0	0
TSC2	-0.007	0.076	-10000	0	-0.88	2	2
RHEB/GDP	-0.005	0.047	-10000	0	-0.42	3	3
TSC1	0	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0	0	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.016	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.022	0.036	-10000	0	-0.44	1	1
MAP3K5	-0.038	0.14	-10000	0	-0.46	26	26
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
apoptosis	-0.038	0.14	-10000	0	-0.46	26	26
mol:LY294002	0	0	0.001	1	-10000	0	1
EIF4B	0.027	0.033	-10000	0	-0.38	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.002	0.023	-10000	0	-0.35	1	1
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.004	0.061	-10000	0	-1	1	1
mTOR/RHEB/GTP/Raptor/GBL	0.024	0.028	-10000	0	-0.31	1	1
FKBP1A	0	0	-10000	0	-10000	0	0
RHEB/GTP	-0.005	0.046	-10000	0	-0.41	3	3
mol:Amino Acids	0	0	0.001	1	-10000	0	1
FKBP12/Rapamycin	0	0.002	-10000	0	-10000	0	0
PDPK1	-0.001	0.057	0.26	2	-0.86	1	3
EIF4E	0	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.059	0.19	-10000	0	-0.63	26	26
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0	0.002	-10000	0	-10000	0	0
TSC1/TSC2	-0.007	0.058	-10000	0	-0.51	3	3
tumor necrosis factor receptor activity	0	0	-10000	0	-0.001	1	1
RPS6	0	0	-10000	0	-10000	0	0
PPP5C	0	0	-10000	0	-10000	0	0
EIF4G1	0	0	-10000	0	-10000	0	0
IRS1	0.006	0.002	-10000	0	-10000	0	0
INS	0.006	0.043	0.32	5	-10000	0	5
PTEN	-0.007	0.076	-10000	0	-0.88	2	2
PDK2	-0.003	0.064	-10000	0	-0.68	2	2
EIF4EBP1	0.008	0.019	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
PPP2R5D	0.018	0.025	-10000	0	-10000	0	0
peptide biosynthetic process	0.001	0.01	-10000	0	-10000	0	0
RHEB	0	0	-10000	0	-10000	0	0
EIF4A1	0	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.004	2	-0.004	1	3
EEF2	0.001	0.01	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0	0	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	-0.018	0.1	-10000	0	-0.6	8	8
NF kappa B1 p50/RelA/I kappa B alpha	-0.009	0.058	-10000	0	-0.71	1	1
NFKBIA	0.012	0.072	-10000	0	-0.36	8	8
MAPK14	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0	0	-10000	0	-10000	0	0
ARRB2	0	0	-10000	0	-10000	0	0
REL	-0.026	0.15	-10000	0	-0.88	8	8
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
NF kappa B1 p50 dimer	0	0	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
NFKB1	0.017	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	-0.009	0.059	-10000	0	-0.33	8	8
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.009	0.056	-10000	0	-0.7	1	1
SRC	0.001	0.019	0.32	1	-10000	0	1
PI3K	-0.005	0.075	-10000	0	-1.2	1	1
NF kappa B1 p50/RelA	-0.009	0.059	-10000	0	-0.33	8	8
IKBKB	0	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-10000	0	-10000	0	0
SYK	-0.003	0.054	-10000	0	-0.88	1	1
I kappa B alpha/PIK3R1	-0.012	0.071	-10000	0	-0.64	2	2
cell death	-0.008	0.053	-10000	0	-0.65	1	1
NF kappa B1 p105/c-Rel	-0.018	0.1	-10000	0	-0.6	8	8
LCK	-0.025	0.15	0.32	1	-0.88	8	9
BCL3	0	0	-10000	0	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.001	0.035	-10000	0	-0.48	1	1
TC10/GTP	-0.001	0.03	-10000	0	-0.47	1	1
Insulin Receptor/Insulin/IRS1/Shp2	0.004	0.026	-10000	0	-10000	0	0
HRAS	0.002	0.027	0.32	2	-10000	0	2
APS homodimer	0.002	0.027	0.32	2	-10000	0	2
GRB14	-0.023	0.14	-10000	0	-0.88	7	7
FOXO3	-0.024	0.13	-10000	0	-0.76	8	8
AKT1	-0.014	0.084	-10000	0	-0.48	8	8
INSR	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.004	0.027	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0	0	-10000	0	-10000	0	0
SORBS1	-0.003	0.054	-10000	0	-0.88	1	1
CRK	0	0	-10000	0	-10000	0	0
PTPN1	0.03	0.006	-10000	0	-10000	0	0
CAV1	0.001	0.009	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II/C3G	-0.001	0.035	-10000	0	-0.51	1	1
Insulin Receptor/Insulin/IRS1/NCK2	0.004	0.029	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.062	-10000	0	-0.96	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.002	0.016	-10000	0	-10000	0	0
RPS6KB1	-0.011	0.076	-10000	0	-0.7	1	1
PARD6A	0.001	0.019	0.32	1	-10000	0	1
CBL	0	0	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0	0	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.01	0.076	-10000	0	-0.69	1	1
HRAS/GTP	-0.001	0.024	-10000	0	-10000	0	0
Insulin Receptor	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.003	0.025	-10000	0	-10000	0	0
PRKCI	-0.004	0.021	-10000	0	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.015	0.092	-10000	0	-0.52	8	8
SHC1	0	0	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	-0.006	0.07	-10000	0	-0.77	2	2
PI3K	-0.001	0.065	-10000	0	-1	1	1
NCK2	0.001	0.019	0.32	1	-10000	0	1
RHOQ	0	0	-10000	0	-10000	0	0
mol:H2O2	0	0	-10000	0	-10000	0	0
HRAS/GDP	0.002	0.018	0.21	2	-10000	0	2
AKT2	-0.014	0.084	-10000	0	-0.48	8	8
PRKCZ	-0.031	0.14	-10000	0	-0.68	11	11
SH2B2	0.002	0.027	0.32	2	-10000	0	2
SHC/SHIP	-0.001	0.03	-10000	0	-0.47	1	1
F2RL2	-0.077	0.27	0.32	7	-0.88	26	33
TRIP10	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.004	0.026	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.003	0.025	-10000	0	-10000	0	0
RAPGEF1	0	0	-10000	0	-10000	0	0
RASA1	-0.007	0.076	-10000	0	-0.88	2	2
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
CBL/APS/CAP/Crk-II	-0.001	0.037	-10000	0	-0.55	1	1
TC10/GDP	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.004	0.026	-10000	0	-10000	0	0
INPP5D	-0.001	0.032	-10000	0	-0.5	1	1
SOS1	0	0	-10000	0	-10000	0	0
SGK1	-0.033	0.18	-10000	0	-1.1	8	8
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
IRS1	0	0	-10000	0	-10000	0	0
p62DOK/RasGAP	-0.006	0.071	-10000	0	-0.79	2	2
INS	0.008	0.043	0.32	5	-10000	0	5
mol:PI-3-4-P2	-0.001	0.031	-10000	0	-0.5	1	1
GRB2	0	0	-10000	0	-10000	0	0
EIF4EBP1	-0.011	0.077	-10000	0	-0.7	1	1
PTPRA	0	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
TC10/GTP/CIP4	0	0	-10000	0	-10000	0	0
PDPK1	0	0	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.002	0.016	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.004	0.026	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.004	0.03	-10000	0	-10000	0	0
Par3/Par6	-0.045	0.16	-10000	0	-0.52	26	26

×

Regulation of cytoplasmic and nuclear SMAD2/3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.003	0.054	-10000	0	-0.88	1	1
SMAD2	0.011	0	-10000	0	-10000	0	0
SMAD3	0.033	0	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.001	0.022	-10000	0	-0.32	1	1
SMAD4/Ubc9/PIASy	-0.002	0.036	-10000	0	-0.6	1	1
SMAD2/SMAD2/SMAD4	-0.001	0.031	-10000	0	-0.47	1	1
PPM1A	0	0	-10000	0	-10000	0	0
CALM1	0	0	-10000	0	-10000	0	0
SMAD2/SMAD4	-0.002	0.033	-10000	0	-0.54	1	1
MAP3K1	0	0	-10000	0	-10000	0	0
TRAP-1/SMAD4	-0.036	0.15	-10000	0	-0.68	14	14
MAPK3	0	0	-10000	0	-10000	0	0
MAPK1	0	0	-10000	0	-10000	0	0
NUP214	0	0	-10000	0	-10000	0	0
CTDSP1	0	0	-10000	0	-10000	0	0
CTDSP2	0	0	-10000	0	-10000	0	0
CTDSPL	0	0	-10000	0	-10000	0	0
KPNB1	0	0	-10000	0	-10000	0	0
TGFBRAP1	-0.043	0.19	-10000	0	-0.88	13	13
UBE2I	0	0	-10000	0	-10000	0	0
NUP153	0	0	-10000	0	-10000	0	0
KPNA2	0.001	0.019	0.32	1	-10000	0	1
PIAS4	0	0	-10000	0	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.062	0.024	-10000	0	-10000	0	0
ERC1	0	0	-10000	0	-10000	0	0
RIP2/NOD2	-0.01	0.083	-10000	0	-0.68	4	4
NFKBIA	0.038	0	-10000	0	-10000	0	0
BIRC2	0	0	-10000	0	-10000	0	0
IKBKB	0	0	-10000	0	-10000	0	0
RIPK2	0	0	-10000	0	-10000	0	0
IKBKG	-0.005	0.036	-10000	0	-10000	0	0
IKK complex/A20	-0.024	0.1	-10000	0	-0.46	13	13
NEMO/A20/RIP2	0	0	-10000	0	-10000	0	0
XPO1	0	0	-10000	0	-10000	0	0
NEMO/ATM	-0.004	0.033	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
Exportin 1/RanGTP	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	-0.004	0.029	-10000	0	-10000	0	0
BCL10/MALT1/TRAF6	-0.002	0.036	-10000	0	-0.6	1	1
NOD2	-0.013	0.11	-10000	0	-0.88	4	4
NFKB1	0	0	-10000	0	-10000	0	0
RELA	0	0	-10000	0	-10000	0	0
MALT1	0	0	-10000	0	-10000	0	0
cIAP1/UbcH5C	0	0	-10000	0	-10000	0	0
ATM	0	0	-10000	0	-10000	0	0
TNF/TNFR1A	-0.032	0.15	-10000	0	-0.68	13	13
TRAF6	-0.003	0.054	-10000	0	-0.88	1	1
PRKCA	0	0	-10000	0	-10000	0	0
CHUK	0	0	-10000	0	-10000	0	0
UBE2D3	0	0	-10000	0	-10000	0	0
TNF	-0.04	0.19	0.32	2	-0.88	13	15
NF kappa B1 p50/RelA	0	0	-10000	0	-10000	0	0
BCL10	0	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.038	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
IKK complex	-0.004	0.031	-10000	0	-10000	0	0
CYLD	0	0	-10000	0	-10000	0	0
IKK complex/PKC alpha	-0.004	0.03	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.027	0.071	-10000	0	-10000	0	0
BAG4	-0.026	0.15	-10000	0	-0.88	8	8
BAD	0.022	0.029	-10000	0	-10000	0	0
NFKBIA	0	0	-10000	0	-10000	0	0
BIRC3	0.007	0.079	0.32	9	-0.88	1	10
BAX	0.022	0.029	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.009	0.021	-10000	0	-0.075	1	1
IKBKB	0.033	0.068	-10000	0	-10000	0	0
MAP2K2	0.032	0.033	-10000	0	-10000	0	0
MAP2K1	0.032	0.033	-10000	0	-10000	0	0
SMPD1	0.014	0.021	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.033	0.069	-10000	0	-10000	0	0
MAP2K4	0.028	0.029	-10000	0	-10000	0	0
protein ubiquitination	0.034	0.069	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.035	0.038	-10000	0	-10000	0	0
response to UV	0	0.001	-10000	0	-10000	0	0
RAF1	0.027	0.032	-10000	0	-10000	0	0
CRADD	-0.003	0.054	-10000	0	-0.88	1	1
mol:ceramide	0.016	0.03	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0	0	-10000	0	-10000	0	0
MAP3K1	0.022	0.03	-10000	0	-10000	0	0
TRADD	-0.003	0.054	-10000	0	-0.88	1	1
RELA/p50	0	0	-10000	0	-10000	0	0
MAPK3	0.033	0.033	-10000	0	-10000	0	0
MAPK1	0.033	0.033	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.028	0.071	-10000	0	-10000	0	0
KSR1	0.022	0.031	-10000	0	-10000	0	0
MAPK8	0.013	0.1	-10000	0	-0.46	11	11
TRAF2	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.033	0.068	-10000	0	-10000	0	0
TNF R/SODD	-0.02	0.12	-10000	0	-0.68	8	8
TNF	-0.04	0.19	0.32	2	-0.88	13	15
CYCS	0.024	0.028	-10000	0	-10000	0	0
IKBKG	0.033	0.068	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.011	0.068	-10000	0	-0.36	1	1
RELA	0	0	-10000	0	-10000	0	0
RIPK1	0	0	-10000	0	-10000	0	0
AIFM1	0.024	0.028	-10000	0	-10000	0	0
TNF/TNF R/SODD	-0.045	0.16	-10000	0	-0.6	21	21
TNFRSF1A	0	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	-0.003	0.015	-10000	0	-10000	0	0
NSMAF	0.027	0.071	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0.001	-10000	0	-10000	0	0
BCL2	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.025	0.12	-10000	0	-0.56	13	13
Ran/GTP/Exportin 1/HDAC1	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.021	0.098	-10000	0	-0.45	13	13
SUMO1	0	0	-10000	0	-10000	0	0
ZFPM1	-0.003	0.054	-10000	0	-0.88	1	1
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
FKBP3	0	0	-10000	0	-10000	0	0
Histones	-0.011	0.05	-10000	0	-10000	0	0
YY1/LSF	-0.004	0.034	-10000	0	-0.32	3	3
SMG5	0	0	-10000	0	-10000	0	0
RAN	0	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	-0.019	0.087	-10000	0	-0.4	13	13
I kappa B alpha/HDAC1	-0.013	0.058	-10000	0	-10000	0	0
SAP18	0	0	-10000	0	-10000	0	0
RELA	-0.016	0.075	-10000	0	-0.34	13	13
HDAC1/Smad7	-0.004	0.051	-10000	0	-0.6	2	2
RANGAP1	0	0	-10000	0	-10000	0	0
HDAC3/TR2	-0.013	0.058	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.003	0.015	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.015	0.067	-10000	0	-10000	0	0
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.004	0.081	0.32	2	-0.88	2	4
GATA1	0.004	0.033	0.32	3	-10000	0	3
Mad/Max	0.001	0.013	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.003	0.025	-10000	0	-10000	0	0
RBBP7	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
RBBP4	0	0	-10000	0	-10000	0	0
MAX	0	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0	0	-10000	0	-10000	0	0
NFKBIA	-0.014	0.066	-10000	0	-0.3	13	13
KAT2B	-0.01	0.092	-10000	0	-0.88	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0	0	-10000	0	-10000	0	0
SIN3 complex	0	0	-10000	0	-10000	0	0
SMURF1	0	0	-10000	0	-10000	0	0
CHD3	0.008	0.05	0.32	7	-10000	0	7
SAP30	0	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	-0.007	0.076	-10000	0	-0.88	2	2
YY1/HDAC3	-0.014	0.064	-10000	0	-0.53	1	1
YY1/HDAC2	-0.004	0.034	-10000	0	-10000	0	0
YY1/HDAC1	-0.004	0.034	-10000	0	-0.32	3	3
NuRD/MBD2 Complex (MeCP1)	0.003	0.015	-10000	0	-10000	0	0
PPARG	-0.026	0.12	-10000	0	-0.52	14	14
HDAC8/hEST1B	0	0	-10000	0	-10000	0	0
UBE2I	0	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-10000	0	-10000	0	0
TNFRSF1A	0	0	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.013	0.058	-10000	0	-10000	0	0
MBD3L2	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.004	0.051	-10000	0	-0.59	2	2
CREBBP	0	0	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.003	0.016	-10000	0	-10000	0	0
HDAC1	0	0	-10000	0	-10000	0	0
HDAC3	-0.014	0.066	-10000	0	-10000	0	0
HDAC2	0	0	-10000	0	-10000	0	0
YY1	-0.004	0.04	-10000	0	-0.38	3	3
HDAC8	0	0	-10000	0	-10000	0	0
SMAD7	-0.007	0.076	-10000	0	-0.88	2	2
NCOR2	0	0	-10000	0	-10000	0	0
MXD1	0.001	0.019	0.32	1	-10000	0	1
STAT3	0	0	-10000	0	-10000	0	0
NFKB1	0	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0	0	-10000	0	-10000	0	0
YY1/LSF/HDAC1	-0.003	0.031	-10000	0	-10000	0	0
YY1/SAP30/HDAC1	-0.003	0.031	-10000	0	-10000	0	0
EP300	0	0	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.014	0.066	-10000	0	-0.3	13	13
histone deacetylation	0.003	0.015	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.011	0.053	-10000	0	-10000	0	0
nuclear export	0	0	-10000	0	-10000	0	0
PRKACA	0	0	-10000	0	-10000	0	0
GATAD2B	0	0	-10000	0	-10000	0	0
GATAD2A	0	0	-10000	0	-10000	0	0
GATA2/HDAC3	-0.015	0.077	-10000	0	-0.55	2	2
GATA1/HDAC1	0.002	0.023	-10000	0	-10000	0	0
GATA1/HDAC3	-0.01	0.064	-10000	0	-10000	0	0
CHD4	0	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	-0.032	0.15	-10000	0	-0.68	13	13
SIN3/HDAC complex/Mad/Max	0	0.006	-10000	0	-10000	0	0
NuRD Complex	0.003	0.016	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.011	0.049	-10000	0	-10000	0	0
SIN3B	0	0	-10000	0	-10000	0	0
MTA2	0	0	-10000	0	-10000	0	0
SIN3A	0	0	-10000	0	-10000	0	0
XPO1	0	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0	0	-10000	0	-10000	0	0
HDAC complex	0	0	-10000	0	-10000	0	0
GATA1/Fog1	0	0.048	-10000	0	-0.69	1	1
FKBP25/HDAC1/HDAC2	0	0	-10000	0	-10000	0	0
TNF	-0.04	0.19	0.32	2	-0.88	13	15
negative regulation of cell growth	0	0.006	-10000	0	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.003	0.015	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.022	0.1	-10000	0	-0.48	13	13
SIN3/HDAC complex/NCoR1	-0.002	0.02	-10000	0	-10000	0	0
TFCP2	0	0	-10000	0	-10000	0	0
NR2C1	0	0	-10000	0	-10000	0	0
MBD3	0	0	-10000	0	-10000	0	0
MBD2	0	0	-10000	0	-10000	0	0

×

Arf6 trafficking events

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
SLC2A4	-0.001	0.12	0.32	10	-0.88	4	14
CLTC	0.021	0.016	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	-0.009	0.042	-10000	0	-10000	0	0
Dynamin 2/GTP	0.001	0.009	-10000	0	-10000	0	0
EXOC4	0	0	-10000	0	-10000	0	0
CD59	-0.003	0.017	-10000	0	-10000	0	0
CPE	0.005	0.03	-10000	0	-10000	0	0
CTNNB1	0	0	-10000	0	-10000	0	0
membrane fusion	-0.01	0.046	-10000	0	-10000	0	0
CTNND1	0.001	0.006	-10000	0	-10000	0	0
DNM2	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.02	0.026	-10000	0	-10000	0	0
TSHR	0	0	-10000	0	-10000	0	0
INS	0.011	0.022	-10000	0	-10000	0	0
BIN1	-0.003	0.054	-10000	0	-0.88	1	1
mol:Choline	-0.01	0.046	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.001	0.015	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0	0	-10000	0	-10000	0	0
mol:Ca2+	0.001	0.009	-10000	0	-10000	0	0
JUP	-0.003	0.017	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.001	0.038	-10000	0	-0.55	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	-0.019	0.075	-10000	0	-0.41	4	4
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.014	0.054	-10000	0	-10000	0	0
positive regulation of phagocytosis	0	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0	-10000	0	-10000	0	0
ACAP1	-0.01	0.042	-10000	0	-0.35	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.007	0.039	-10000	0	-0.41	1	1
clathrin heavy chain/ACAP1	0.022	0.031	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0	0	-10000	0	-10000	0	0
exocyst	0	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.001	0.006	-10000	0	-10000	0	0
NME1	0.001	0.015	-10000	0	-10000	0	0
clathrin coat assembly	0.021	0.016	-10000	0	-10000	0	0
IL2RA	-0.006	0.046	-10000	0	-10000	0	0
VAMP3	0	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.004	0.069	-10000	0	-0.46	4	4
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.016	0.075	-10000	0	-0.36	12	12
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0	0	-10000	0	-10000	0	0
PIP5K1C	0.02	0.026	-10000	0	-10000	0	0
SDC1	-0.008	0.039	-10000	0	-10000	0	0
ARF6/GDP	0.001	0.009	-10000	0	-10000	0	0
EXOC7	0	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.014	0.055	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.01	0.046	-10000	0	-10000	0	0
endocytosis	0.001	0.037	0.55	1	-10000	0	1
SCAMP2	0	0	-10000	0	-10000	0	0
ADRB2	-0.051	0.18	-10000	0	-0.49	40	40
EXOC3	0	0	-10000	0	-10000	0	0
ASAP2	0.002	0.027	0.32	2	-10000	0	2
Dynamin 2/GDP	0.001	0.013	-10000	0	-10000	0	0
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	0.028	0.017	-10000	0	-10000	0	0
RALA	0	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.012	0.049	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.016	0.1	-10000	0	-0.59	8	8
VEGFR1 homodimer/NRP1	0	0	-10000	0	-10000	0	0
mol:DAG	0.001	0.013	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0	0	-10000	0	-10000	0	0
CaM/Ca2+	0.001	0.012	-10000	0	-10000	0	0
HIF1A	0	0	-10000	0	-10000	0	0
GAB1	0	0	-10000	0	-10000	0	0
AKT1	-0.002	0.057	-10000	0	-0.92	1	1
PLCG1	0.001	0.013	-10000	0	-10000	0	0
NOS3	0.048	0.042	-10000	0	-10000	0	0
CBL	0	0	-10000	0	-10000	0	0
mol:NO	0.047	0.041	-10000	0	-10000	0	0
FLT1	0.023	0	-10000	0	-10000	0	0
PGF	0.004	0.033	0.32	3	-10000	0	3
VEGFR1 homodimer/NRP2/VEGFR121	-0.003	0.049	-10000	0	-0.54	2	2
CALM1	0	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.054	-10000	0	-0.88	1	1
eNOS/Hsp90	-0.003	0.033	-10000	0	-10000	0	0
endothelial cell proliferation	0.012	0.11	-10000	0	-10000	0	0
mol:Ca2+	0.001	0.013	-10000	0	-10000	0	0
MAPK3	0.044	0.004	-10000	0	-10000	0	0
MAPK1	0.044	0.004	-10000	0	-10000	0	0
PIK3R1	-0.003	0.054	-10000	0	-0.88	1	1
PLGF homodimer	0.004	0.033	0.32	3	-10000	0	3
PRKACA	0	0	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0	0	-10000	0	-10000	0	0
VEGFA homodimer	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0	0	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.049	0.004	-10000	0	-10000	0	0
PI3K	-0.001	0.066	-10000	0	-1	1	1
PRKCA	0.001	0.01	-10000	0	-10000	0	0
PRKCB	-0.043	0.14	-10000	0	-0.51	23	23
VEGFR1 homodimer/PLGF homodimer	0.003	0.024	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
VEGFB	-0.024	0.15	0.32	2	-0.88	8	10
mol:IP3	0.001	0.013	-10000	0	-10000	0	0
RASA1	-0.019	0.1	-10000	0	-0.54	10	10
NRP2	-0.005	0.078	0.32	1	-0.88	2	3
VEGFR1 homodimer	0.023	0	-10000	0	-10000	0	0
VEGFB homodimer	-0.024	0.15	0.32	2	-0.88	8	10
NCK1	-0.003	0.054	-10000	0	-0.88	1	1
eNOS/Caveolin-1	-0.003	0.033	-10000	0	-10000	0	0
PTPN11	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.064	-10000	0	-0.99	1	1
mol:L-citrulline	0.047	0.041	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.002	0.033	-10000	0	-0.54	1	1
CD2AP	0	0	-10000	0	-10000	0	0
PI3K/GAB1	-0.001	0.063	-10000	0	-0.98	1	1
PDPK1	-0.002	0.057	-10000	0	-0.93	1	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	0	0	-10000	0	-10000	0	0
mol:NADP	0.047	0.041	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	-0.004	0.053	-10000	0	-0.59	2	2

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.015	0	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0	-9999	-10000	0	0
CD4	-0.066	0.23	-9999	-0.88	20	20
CLTA	0	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.009	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0	-9999	-10000	0	0
ARFIP2	0	0	-9999	-10000	0	0
COPA	0	0	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	-0.022	0.077	-9999	-0.29	20	20
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.045	0.16	-9999	-0.6	20	20

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.002	0.034	-10000	0	-10000	0	0
CLOCK	-0.003	0.053	-10000	0	-0.88	1	1
TIMELESS/CRY2	-0.002	0.022	-10000	0	-10000	0	0
DEC1/BMAL1	0	0.001	-10000	0	-10000	0	0
ATR	0	0	-10000	0	-10000	0	0
NR1D1	0.027	0.093	-10000	0	-1.5	1	1
ARNTL	0	0.002	-10000	0	-10000	0	0
TIMELESS	0.031	0.028	-10000	0	-10000	0	0
NPAS2	-0.003	0.053	-10000	0	-0.88	1	1
CRY2	0	0	-10000	0	-10000	0	0
mol:CO	-0.01	0.009	0.14	1	-10000	0	1
CHEK1	0.006	0.043	0.32	5	-10000	0	5
mol:HEME	0.01	0.009	-10000	0	-0.14	1	1
PER1	0	0	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	-0.005	0.051	-10000	0	-0.59	2	2
BMAL1/CLOCK	0.033	0.066	-10000	0	-0.91	1	1
S phase of mitotic cell cycle	0.002	0.034	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.002	0.034	-10000	0	-10000	0	0
mol:NADPH	0.01	0.009	-10000	0	-0.14	1	1
PER1/TIMELESS	-0.002	0.022	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0	0	-10000	0	-10000	0	0

×

TCGA08_p53

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
CDKN2A	0.098	0.065	-9999	-9999
TP53	0.026	0.019	-9999	-9999
Senescence	0.026	0.019	-9999	-9999
Apoptosis	0.026	0.019	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	-0.054	0.039	-9999	-9999
MDM4	0	0	-9999	-9999

×

Sumoylation by RanBP2 regulates transcriptional repression

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0	0	-10000	0	-9999	0
Ran/GTP/Exportin 1/HDAC4	0	0	-10000	0	-9999	0
MDM2/SUMO1	0	0	-10000	0	-9999	0
HDAC4	0.001	0.019	0.32	1	-9999	1
Ran/GTP/Exportin 1/HDAC1	0	0	-10000	0	-9999	0
SUMO1	0	0	-10000	0	-9999	0
NPC/RanGAP1/SUMO1	0	0	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
XPO1	0	0	-10000	0	-9999	0
EntrezGene:23636	0	0	-10000	0	-9999	0
RAN	0	0	-10000	0	-9999	0
EntrezGene:8021	0	0	-10000	0	-9999	0
RANBP2	0	0	-10000	0	-9999	0
SUMO1/HDAC4	0.001	0.012	-10000	0	-9999	0
SUMO1/HDAC1	0	0	-10000	0	-9999	0
RANGAP1	0	0	-10000	0	-9999	0
MDM2/SUMO1/SUMO1	0	0	-10000	0	-9999	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	0	-10000	0	-9999	0
Ran/GTP	0	0	-10000	0	-9999	0
EntrezGene:23225	0	0	-10000	0	-9999	0
MDM2	0	0	-10000	0	-9999	0
UBE2I	0	0	-10000	0	-9999	0
Ran/GTP/Exportin 1	0	0	-10000	0	-9999	0
NPC	0	0	-10000	0	-9999	0
PIAS2	0	0	-10000	0	-9999	0
PIAS1	0	0	-10000	0	-9999	0
EntrezGene:9972	0	0	-10000	0	-9999	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.001	0.013	-10000	0	-9999	0
FBXW11	0	0	-10000	0	-9999	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-10000	0	-9999	0
beta TrCP1/SCF ubiquitin ligase complex	0	0	-10000	0	-9999	0
CHUK	0	0	-10000	0	-9999	0
NF kappa B2 p100/RelB	0.001	0.016	-10000	0	-9999	0
NFKB1	0	0	-10000	0	-9999	0
MAP3K14	0.001	0.019	0.32	1	-9999	1
NF kappa B1 p50/RelB	0.001	0.013	-10000	0	-9999	0
RELB	0.001	0.019	0.32	1	-9999	1
NFKB2	0	0	-10000	0	-9999	0
NF kappa B2 p52/RelB	0.001	0.012	-10000	0	-9999	0
regulation of B cell activation	0.001	0.012	-10000	0	-9999	0

pid_entity	TCGA.ZS.A9CG	TCGA.ZS.A9CF	TCGA.ZS.A9CE	TCGA.ZS.A9CD
109_MAP3K5	-0.24	-0.24	-0.24	0.042
47_PPARGC1A	0	0	0	0
105_BMP4	0	0	0	0
105_BMP6	0	0	0	0
105_BMP7	0	0	0	-5.3e-15
105_BMP2	0	0	0	0
131_RELN/VLDLR	0	-1.1	0	0
30_TGFB1/TGF beta receptor Type II	0	0	0	0
84_STAT5B	0.084	0.1	0.033	0.032
84_STAT5A	0.084	0.1	0.033	0.032