PARADIGM pathway analysis of mRNASeq expression data - Stomach and Esophageal carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXA2 and FOXA3 transcription factor networks	95
Signaling events mediated by the Hedgehog family	88
TCGA08_retinoblastoma	76
IL4-mediated signaling events	69
Nephrin/Neph1 signaling in the kidney podocyte	67
Ephrin A reverse signaling	67
TCGA08_p53	66
Wnt signaling	59
p75(NTR)-mediated signaling	50
Glypican 1 network	49

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
FOXA2 and FOXA3 transcription factor networks	0.2074	95	4399	46	-0.64	0.012	1000	-1000	-0.11	-1000
Signaling events mediated by the Hedgehog family	0.1921	88	4617	52	-0.24	0.17	1000	-1000	-0.068	-1000
TCGA08_retinoblastoma	0.1659	76	614	8	-0.16	0.066	1000	-1000	-0.017	-1000
IL4-mediated signaling events	0.1507	69	6337	91	-0.79	0.61	1000	-1000	-0.17	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.1463	67	2291	34	-0.13	0.01	1000	-1000	-0.05	-1000
Ephrin A reverse signaling	0.1463	67	470	7	-0.087	0	1000	-1000	-0.022	-1000
TCGA08_p53	0.1441	66	462	7	-0.11	0.063	1000	-1000	-0.012	-1000
Wnt signaling	0.1288	59	414	7	-0.12	-0.019	1000	-1000	-0.031	-1000
p75(NTR)-mediated signaling	0.1092	50	6254	125	-0.21	0.014	1000	-1000	-0.087	-1000
Glypican 1 network	0.1070	49	2380	48	-0.24	0.038	1000	-1000	-0.044	-1000
IL23-mediated signaling events	0.1070	49	2979	60	-0.41	0.01	1000	-1000	-0.18	-1000
EGFR-dependent Endothelin signaling events	0.1004	46	970	21	-0.14	0.015	1000	-1000	-0.051	-1000
Signaling events regulated by Ret tyrosine kinase	0.0983	45	3741	82	-0.14	0.01	1000	-1000	-0.078	-1000
HIF-1-alpha transcription factor network	0.0852	39	2993	76	-0.34	0.016	1000	-1000	-0.17	-1000
Glucocorticoid receptor regulatory network	0.0830	38	4367	114	-0.53	0.27	1000	-1000	-0.06	-1000
Visual signal transduction: Cones	0.0808	37	1421	38	-0.15	0.009	1000	-1000	-0.054	-1000
BMP receptor signaling	0.0808	37	3038	81	-0.25	0.027	1000	-1000	-0.081	-1000
Effects of Botulinum toxin	0.0808	37	983	26	-0.14	0.01	1000	-1000	-0.048	-1000
Syndecan-1-mediated signaling events	0.0786	36	1249	34	-0.16	0.01	1000	-1000	-0.054	-1000
Visual signal transduction: Rods	0.0764	35	1843	52	-0.16	0.01	1000	-1000	-0.063	-1000
Fc-epsilon receptor I signaling in mast cells	0.0742	34	3363	97	-0.16	0.023	1000	-1000	-0.085	-1000
Reelin signaling pathway	0.0742	34	1925	56	-0.15	0.014	1000	-1000	-0.067	-1000
BCR signaling pathway	0.0742	34	3450	99	-0.15	0.014	1000	-1000	-0.078	-1000
TCR signaling in naïve CD8+ T cells	0.0721	33	3160	93	-0.15	0.085	1000	-1000	-0.076	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0721	33	2298	68	-0.21	0.057	1000	-1000	-0.11	-1000
Noncanonical Wnt signaling pathway	0.0699	32	854	26	-0.12	0.01	1000	-1000	-0.054	-1000
Endothelins	0.0677	31	3032	96	-0.19	0.026	1000	-1000	-0.078	-1000
amb2 Integrin signaling	0.0655	30	2515	82	-0.18	0.01	1000	-1000	-0.069	-1000
Signaling mediated by p38-alpha and p38-beta	0.0655	30	1321	44	-0.099	0.01	1000	-1000	-0.052	-1000
IL12-mediated signaling events	0.0633	29	2527	87	-0.19	0.03	1000	-1000	-0.13	-1000
ErbB4 signaling events	0.0611	28	1936	69	-0.19	0.051	1000	-1000	-0.076	-1000
Syndecan-4-mediated signaling events	0.0590	27	1856	67	-0.11	0.011	1000	-1000	-0.075	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0568	26	1449	54	-0.11	0.015	1000	-1000	-0.078	-1000
Arf6 signaling events	0.0568	26	1621	62	-0.14	0.01	1000	-1000	-0.056	-1000
EPHB forward signaling	0.0568	26	2224	85	-0.085	0.068	1000	-1000	-0.084	-1000
Calcium signaling in the CD4+ TCR pathway	0.0568	26	819	31	-0.13	0.011	1000	-1000	-0.078	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0568	26	3140	120	-0.26	0.12	1000	-1000	-0.065	-1000
Osteopontin-mediated events	0.0546	25	976	38	-0.11	0.01	1000	-1000	-0.087	-1000
Thromboxane A2 receptor signaling	0.0546	25	2669	105	-0.14	0.019	1000	-1000	-0.056	-1000
Ephrin B reverse signaling	0.0546	25	1237	48	-0.083	0.06	1000	-1000	-0.066	-1000
Retinoic acid receptors-mediated signaling	0.0546	25	1489	58	-0.17	0.01	1000	-1000	-0.064	-1000
Nectin adhesion pathway	0.0524	24	1516	63	-0.073	0.013	1000	-1000	-0.071	-1000
Canonical Wnt signaling pathway	0.0480	22	1151	51	-0.22	0.031	1000	-1000	-0.054	-1000
LPA receptor mediated events	0.0480	22	2248	102	-0.13	0.027	1000	-1000	-0.077	-1000
IGF1 pathway	0.0480	22	1260	57	-0.09	0.023	1000	-1000	-0.097	-1000
ErbB2/ErbB3 signaling events	0.0459	21	1378	65	-0.13	0.019	1000	-1000	-0.058	-1000
S1P5 pathway	0.0459	21	360	17	-0.072	0.048	1000	-1000	-0.034	-1000
LPA4-mediated signaling events	0.0437	20	250	12	-0.049	0.014	1000	-1000	-0.022	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0437	20	1049	52	-0.12	0.015	1000	-1000	-0.055	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0437	20	1540	74	-0.17	0.039	1000	-1000	-0.074	-1000
Presenilin action in Notch and Wnt signaling	0.0415	19	1218	61	-0.22	0.021	1000	-1000	-0.065	-1000
Glypican 2 network	0.0415	19	79	4	-0.032	-0.019	1000	-1000	-0.031	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0415	19	1532	78	-0.06	0.022	1000	-1000	-0.076	-1000
Syndecan-2-mediated signaling events	0.0393	18	1256	69	-0.11	0.029	1000	-1000	-0.046	-1000
Signaling events mediated by PTP1B	0.0393	18	1370	76	-0.14	0.015	1000	-1000	-0.073	-1000
IL27-mediated signaling events	0.0393	18	968	51	-0.18	0.02	1000	-1000	-0.078	-1000
IL1-mediated signaling events	0.0371	17	1073	62	-0.12	0.049	1000	-1000	-0.08	-1000
Syndecan-3-mediated signaling events	0.0371	17	601	35	-0.094	0.01	1000	-1000	-0.055	-1000
Class IB PI3K non-lipid kinase events	0.0371	17	51	3	-0.014	-1000	1000	-1000	-0.007	-1000
FOXM1 transcription factor network	0.0371	17	897	51	-0.16	0.1	1000	-1000	-0.19	-1000
Caspase cascade in apoptosis	0.0328	15	1130	74	-0.062	0.016	1000	-1000	-0.037	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0328	15	445	28	-0.072	0.022	1000	-1000	-0.032	-1000
Hedgehog signaling events mediated by Gli proteins	0.0328	15	995	65	-0.3	0.04	1000	-1000	-0.053	-1000
S1P1 pathway	0.0328	15	565	36	-0.07	0.01	1000	-1000	-0.052	-1000
Nongenotropic Androgen signaling	0.0328	15	782	52	-0.05	0.017	1000	-1000	-0.049	-1000
S1P4 pathway	0.0328	15	376	25	-0.072	0.016	1000	-1000	-0.043	-1000
E-cadherin signaling events	0.0328	15	78	5	-0.029	0.01	1000	-1000	-0.044	-1000
FAS signaling pathway (CD95)	0.0306	14	670	47	-0.1	0.012	1000	-1000	-0.04	-1000
Plasma membrane estrogen receptor signaling	0.0306	14	1270	86	-0.088	0.017	1000	-1000	-0.075	-1000
Ras signaling in the CD4+ TCR pathway	0.0306	14	252	17	-0.036	0.01	1000	-1000	-0.034	-1000
Coregulation of Androgen receptor activity	0.0284	13	990	76	-0.22	0.021	1000	-1000	-0.043	-1000
JNK signaling in the CD4+ TCR pathway	0.0284	13	226	17	-0.036	0.018	1000	-1000	-0.052	-1000
Integrins in angiogenesis	0.0284	13	1107	84	-0.11	0.017	1000	-1000	-0.08	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0284	13	1222	88	-0.12	0.047	1000	-1000	-0.1	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0284	13	451	33	-0.16	0.029	1000	-1000	-0.046	-1000
Cellular roles of Anthrax toxin	0.0262	12	473	39	-0.036	0.012	1000	-1000	-0.026	-1000
Regulation of Androgen receptor activity	0.0262	12	877	70	-0.23	0.02	1000	-1000	-0.06	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0240	11	431	37	-0.11	0.023	1000	-1000	-0.051	-1000
IL2 signaling events mediated by PI3K	0.0240	11	687	58	-0.1	0.024	1000	-1000	-0.081	-1000
Regulation of p38-alpha and p38-beta	0.0240	11	611	54	-0.13	0.01	1000	-1000	-0.057	-1000
Class I PI3K signaling events	0.0240	11	869	73	-0.13	0.017	1000	-1000	-0.055	-1000
Regulation of Telomerase	0.0240	11	1221	102	-0.14	0.034	1000	-1000	-0.088	-1000
S1P3 pathway	0.0240	11	492	42	-0.049	0.015	1000	-1000	-0.033	-1000
Regulation of nuclear SMAD2/3 signaling	0.0218	10	1466	136	-0.14	0.049	1000	-1000	-0.063	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0218	10	864	85	-0.04	0.028	1000	-1000	-0.073	-1000
IL6-mediated signaling events	0.0218	10	781	75	-0.07	0.044	1000	-1000	-0.092	-1000
Signaling events mediated by PRL	0.0218	10	353	34	-0.15	0.023	1000	-1000	-0.041	-1000
IFN-gamma pathway	0.0197	9	622	68	-0.078	0.029	1000	-1000	-0.092	-1000
IL2 signaling events mediated by STAT5	0.0197	9	208	22	-0.048	0.021	1000	-1000	-0.059	-1000
E-cadherin signaling in keratinocytes	0.0197	9	428	43	-0.036	0.02	1000	-1000	-0.062	-1000
Aurora B signaling	0.0197	9	654	67	-0.15	0.01	1000	-1000	-0.068	-1000
PLK2 and PLK4 events	0.0175	8	24	3	-0.003	0.006	1000	-1000	-0.014	-1000
Ceramide signaling pathway	0.0175	8	681	76	-0.14	0.035	1000	-1000	-0.053	-1000
Signaling events mediated by HDAC Class III	0.0175	8	349	40	-0.1	0.017	1000	-1000	-0.033	-1000
Signaling mediated by p38-gamma and p38-delta	0.0175	8	129	15	-0.015	0.02	1000	-1000	-0.023	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0175	8	400	45	-0.047	0.033	1000	-1000	-0.078	-1000
E-cadherin signaling in the nascent adherens junction	0.0175	8	663	76	-0.037	0.032	1000	-1000	-0.08	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0153	7	658	83	-0.17	0.045	1000	-1000	-0.061	-1000
TCGA08_rtk_signaling	0.0153	7	190	26	-0.036	0.031	1000	-1000	-0.021	-1000
Insulin Pathway	0.0153	7	580	74	-0.087	0.027	1000	-1000	-0.077	-1000
PDGFR-beta signaling pathway	0.0153	7	728	97	-0.1	0.041	1000	-1000	-0.071	-1000
a4b1 and a4b7 Integrin signaling	0.0131	6	33	5	-0.002	0.006	1000	-1000	-0.021	-1000
Aurora A signaling	0.0131	6	375	60	-0.061	0.025	1000	-1000	-0.048	-1000
Arf6 downstream pathway	0.0131	6	273	43	-0.036	0.017	1000	-1000	-0.032	-1000
Class I PI3K signaling events mediated by Akt	0.0131	6	427	68	-0.073	0.025	1000	-1000	-0.05	-1000
TRAIL signaling pathway	0.0131	6	312	48	-0.028	0.031	1000	-1000	-0.059	-1000
Rapid glucocorticoid signaling	0.0131	6	136	20	-0.021	0.01	1000	-1000	-0.031	-1000
EPO signaling pathway	0.0109	5	314	55	-0.041	0.029	1000	-1000	-0.089	-1000
PLK1 signaling events	0.0109	5	502	85	-0.022	0.02	1000	-1000	-0.038	-1000
PDGFR-alpha signaling pathway	0.0109	5	258	44	-0.042	0.026	1000	-1000	-0.041	-1000
p38 MAPK signaling pathway	0.0109	5	260	44	-0.078	0.016	1000	-1000	-0.067	-1000
BARD1 signaling events	0.0087	4	247	57	-0.022	0.041	1000	-1000	-0.051	-1000
Circadian rhythm pathway	0.0087	4	108	22	-0.012	0.026	1000	-1000	-0.05	-1000
Aurora C signaling	0.0087	4	33	7	-0.014	0	1000	-1000	-0.036	-1000
FoxO family signaling	0.0087	4	260	64	-0.073	0.099	1000	-1000	-0.071	-1000
Paxillin-dependent events mediated by a4b1	0.0087	4	179	36	-0.011	0.02	1000	-1000	-0.072	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0087	4	580	125	-0.016	0.054	1000	-1000	-0.075	-1000
Arf6 trafficking events	0.0087	4	301	71	-0.051	0.032	1000	-1000	-0.056	-1000
Canonical NF-kappaB pathway	0.0066	3	121	39	-0.028	0.052	1000	-1000	-0.073	-1000
Signaling events mediated by HDAC Class II	0.0066	3	256	75	-0.022	0.023	1000	-1000	-0.05	-1000
Insulin-mediated glucose transport	0.0066	3	120	32	-0.073	0.024	1000	-1000	-0.056	-1000
HIF-2-alpha transcription factor network	0.0066	3	162	43	-0.072	0.073	1000	-1000	-0.088	-1000
Signaling events mediated by HDAC Class I	0.0066	3	330	104	-0.052	0.042	1000	-1000	-0.06	-1000
Atypical NF-kappaB pathway	0.0066	3	95	31	-0.021	0.028	1000	-1000	-0.043	-1000
VEGFR1 specific signals	0.0066	3	209	56	-0.012	0.033	1000	-1000	-0.063	-1000
ceramide signaling pathway	0.0044	2	133	49	-0.032	0.027	1000	-1000	-0.046	-1000
mTOR signaling pathway	0.0022	1	90	53	-0.025	0.016	1000	-1000	-0.059	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	14	23	-0.002	0.033	1000	-1000	-0.05	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	19	27	-0.005	0.025	1000	-1000	-0.047	-1000
Arf1 pathway	0.0000	0	36	54	-0.009	0.021	1000	-1000	-0.043	-1000
Alternative NF-kappaB pathway	0.0000	0	8	13	-0.001	0.014	1000	-1000	-0.062	-1000
Total	NA	2623	147669	7203	-15	-1000	131000	-131000	-8.2	-131000

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.46	0.52	-10000	0	-1.2	133	133
PCK1	-0.61	0.69	-10000	0	-1.4	172	172
HNF4A	-0.61	0.68	-10000	0	-1.5	153	153
KCNJ11	-0.49	0.6	-10000	0	-1.3	138	138
AKT1	-0.12	0.14	-10000	0	-0.42	32	32
response to starvation	-0.014	0.03	-10000	0	-10000	0	0
DLK1	-0.47	0.55	-10000	0	-1.2	136	136
NKX2-1	-0.18	0.32	-10000	0	-1.1	29	29
ACADM	-0.46	0.52	-10000	0	-1.2	136	136
TAT	-0.39	0.45	-10000	0	-1	128	128
CEBPB	0.003	0.039	-10000	0	-0.54	2	2
CEBPA	-0.017	0.11	-10000	0	-0.52	21	21
TTR	-0.52	0.54	-10000	0	-1.3	133	133
PKLR	-0.46	0.52	-10000	0	-1.2	138	138
APOA1	-0.63	0.69	-10000	0	-1.5	153	153
CPT1C	-0.46	0.52	-10000	0	-1.2	139	139
ALAS1	-0.17	0.19	-10000	0	-1	2	2
TFRC	-0.5	0.6	-10000	0	-1.4	129	129
FOXF1	-0.01	0.13	0.24	5	-0.53	24	29
NF1	0.012	0.044	-10000	0	-0.65	2	2
HNF1A (dimer)	-0.15	0.29	-10000	0	-0.68	100	100
CPT1A	-0.46	0.52	-10000	0	-1.2	134	134
HMGCS1	-0.46	0.52	-10000	0	-1.2	135	135
NR3C1	-0.012	0.085	-10000	0	-0.66	6	6
CPT1B	-0.46	0.52	-10000	0	-1.2	133	133
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.007	0.03	-10000	0	-10000	0	0
GCK	-0.48	0.54	-10000	0	-1.2	144	144
CREB1	-0.017	0.054	-10000	0	-0.22	1	1
IGFBP1	-0.22	0.24	-10000	0	-0.81	24	24
PDX1	-0.5	0.78	-10000	0	-1.8	114	114
UCP2	-0.46	0.53	-10000	0	-1.2	137	137
ALDOB	-0.64	0.69	-10000	0	-1.5	169	169
AFP	-0.24	0.33	-10000	0	-0.59	160	160
BDH1	-0.47	0.53	-10000	0	-1.2	138	138
HADH	-0.46	0.55	-10000	0	-1.2	130	130
F2	-0.59	0.66	-10000	0	-1.4	147	147
HNF1A	-0.15	0.29	-10000	0	-0.68	100	100
G6PC	-0.24	0.34	-10000	0	-0.85	97	97
SLC2A2	-0.47	0.62	-10000	0	-1.4	122	122
INS	0.007	0.035	0.22	2	-10000	0	2
FOXA1	-0.1	0.22	0.24	1	-0.57	72	73
FOXA3	-0.23	0.29	-10000	0	-0.64	137	137
FOXA2	-0.53	0.62	-10000	0	-1.3	141	141
ABCC8	-0.52	0.6	-10000	0	-1.3	153	153
ALB	-0.23	0.31	-10000	0	-0.7	97	97

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.15	0.28	-10000	0	-0.61	97	97
IHH	-0.2	0.32	-10000	0	-0.65	143	143
SHH Np/Cholesterol/GAS1	-0.12	0.21	-10000	0	-0.43	128	128
LRPAP1	0.01	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.13	0.2	0.43	128	-10000	0	128
SMO/beta Arrestin2	-0.17	0.3	-10000	0	-0.64	105	105
SMO	-0.19	0.32	-10000	0	-0.62	133	133
AKT1	-0.06	0.12	-10000	0	-0.35	11	11
ARRB2	0.01	0	-10000	0	-10000	0	0
BOC	-0.033	0.14	-10000	0	-0.46	42	42
ADRBK1	0.007	0.04	-10000	0	-0.47	3	3
heart looping	-0.18	0.31	-10000	0	-0.6	137	137
STIL	-0.18	0.29	-10000	0	-0.63	107	107
DHH N/PTCH2	-0.031	0.14	-10000	0	-0.4	51	51
DHH N/PTCH1	-0.14	0.26	-10000	0	-0.56	93	93
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
DHH	-0.032	0.16	-10000	0	-0.61	31	31
PTHLH	-0.21	0.38	-10000	0	-0.86	95	95
determination of left/right symmetry	-0.18	0.31	-10000	0	-0.6	137	137
PIK3R1	0.01	0	-10000	0	-10000	0	0
skeletal system development	-0.2	0.37	-10000	0	-0.84	95	95
IHH N/Hhip	-0.23	0.3	-10000	0	-0.52	201	201
DHH N/Hhip	-0.13	0.22	-10000	0	-0.43	147	147
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.18	0.31	-10000	0	-0.6	137	137
pancreas development	-0.14	0.26	-10000	0	-0.56	123	123
HHAT	-0.015	0.13	-10000	0	-0.64	18	18
PI3K	0.014	0.012	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.063	0.19	-10000	0	-0.52	63	63
somite specification	-0.18	0.31	-10000	0	-0.6	137	137
SHH Np/Cholesterol/PTCH1	-0.19	0.3	-10000	0	-0.65	110	110
SHH Np/Cholesterol/PTCH2	-0.091	0.18	-10000	0	-0.41	100	100
SHH Np/Cholesterol/Megalin	-0.13	0.2	-10000	0	-0.42	135	135
SHH	-0.11	0.22	-10000	0	-0.51	100	100
catabolic process	-0.14	0.25	-10000	0	-0.5	124	124
SMO/Vitamin D3	-0.21	0.33	-10000	0	-0.69	118	118
SHH Np/Cholesterol/Hhip	-0.16	0.25	-10000	0	-0.49	147	147
LRP2	-0.084	0.2	-10000	0	-0.49	86	86
receptor-mediated endocytosis	-0.24	0.3	-10000	0	-0.68	122	122
SHH Np/Cholesterol/BOC	-0.1	0.19	-10000	0	-0.42	108	108
SHH Np/Cholesterol/CDO	-0.093	0.19	-10000	0	-0.41	105	105
mesenchymal cell differentiation	0.17	0.24	0.48	147	-10000	0	147
mol:Vitamin D3	-0.19	0.31	-10000	0	-0.66	110	110
IHH N/PTCH2	-0.13	0.21	-10000	0	-0.44	140	140
CDON	-0.014	0.11	-10000	0	-0.47	23	23
IHH N/PTCH1	-0.14	0.26	-10000	0	-0.51	124	124
Megalin/LRPAP1	-0.053	0.15	-10000	0	-0.34	86	86
PTCH2	-0.011	0.094	-10000	0	-0.41	23	23
SHH Np/Cholesterol	-0.095	0.17	-10000	0	-0.41	99	99
PTCH1	-0.14	0.26	-10000	0	-0.51	124	124
HHIP	-0.14	0.26	-10000	0	-0.56	123	123

×

TCGA08_retinoblastoma

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.038	0.16	-10000	0	-0.54	40	40
CDKN2C	0.022	0.038	-10000	0	-0.63	1	1
CDKN2A	-0.16	0.25	-10000	0	-0.5	149	149
CCND2	0.056	0.11	0.26	84	-0.14	1	85
RB1	-0.062	0.12	-10000	0	-0.28	85	85
CDK4	0.066	0.12	0.29	84	-10000	0	84
CDK6	0.063	0.13	0.29	84	-0.16	1	85
G1/S progression	0.054	0.12	0.28	85	-10000	0	85

×

IL4-mediated signaling events

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
BCL2L1	-0.54	0.56	-10000	0	-1.3	132	132
STAT6 (cleaved dimer)	-0.59	0.55	-10000	0	-1.3	151	151
IGHG1	-0.41	0.6	-10000	0	-1.6	83	83
IGHG3	-0.52	0.53	-10000	0	-1.2	145	145
AKT1	-0.26	0.33	-10000	0	-0.96	52	52
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.23	0.35	-10000	0	-1.1	46	46
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.29	0.37	-10000	0	-1.1	49	49
THY1	-0.54	0.56	-10000	0	-1.3	138	138
MYB	-0.077	0.2	-10000	0	-0.57	63	63
HMGA1	-0.002	0.04	-10000	0	-0.69	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.34	0.4	-10000	0	-0.94	90	90
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.29	0.38	-10000	0	-1.1	50	50
SP1	0.016	0.003	-10000	0	-10000	0	0
INPP5D	-0.008	0.11	-10000	0	-0.59	14	14
SOCS5	0.023	0.014	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.56	0.56	-10000	0	-1.2	149	149
SOCS1	-0.33	0.35	-10000	0	-0.79	104	104
SOCS3	-0.28	0.33	-10000	0	-0.97	49	49
FCER2	-0.49	0.54	-10000	0	-1.3	99	99
PARP14	0.007	0.031	-10000	0	-0.65	1	1
CCL17	-0.56	0.59	-10000	0	-1.3	134	134
GRB2	0.01	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.22	0.29	-10000	0	-0.93	41	41
T cell proliferation	-0.55	0.58	-10000	0	-1.3	134	134
IL4R/JAK1	-0.54	0.56	-10000	0	-1.3	128	128
EGR2	-0.57	0.6	-10000	0	-1.3	136	136
JAK2	-0.022	0.065	-10000	0	-0.5	6	6
JAK3	0.009	0.048	-10000	0	-0.43	5	5
PIK3R1	0.01	0	-10000	0	-10000	0	0
JAK1	0.005	0.011	-10000	0	-10000	0	0
COL1A2	-0.18	0.27	-10000	0	-1.3	15	15
CCL26	-0.57	0.6	-10000	0	-1.3	141	141
IL4R	-0.57	0.6	-10000	0	-1.4	128	128
PTPN6	0.021	0.021	-10000	0	-0.35	1	1
IL13RA2	-0.57	0.59	-10000	0	-1.3	133	133
IL13RA1	-0.018	0.047	-10000	0	-0.52	2	2
IRF4	-0.23	0.44	-10000	0	-1.3	58	58
ARG1	-0.22	0.35	-10000	0	-1.2	34	34
CBL	-0.32	0.37	-10000	0	-0.93	76	76
GTF3A	0.014	0.021	-10000	0	-0.37	1	1
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
IL13RA1/JAK2	-0.025	0.066	-10000	0	-0.39	7	7
IRF4/BCL6	-0.21	0.41	-10000	0	-1.2	58	58
CD40LG	-0.051	0.19	-10000	0	-0.6	48	48
MAPK14	-0.31	0.38	-10000	0	-1	65	65
mitosis	-0.25	0.31	-10000	0	-0.88	52	52
STAT6	-0.65	0.74	-10000	0	-1.5	144	144
SPI1	-0.008	0.1	-10000	0	-0.63	12	12
RPS6KB1	-0.24	0.3	-10000	0	-0.85	50	50
STAT6 (dimer)	-0.65	0.75	-10000	0	-1.5	144	144
STAT6 (dimer)/PARP14	-0.6	0.63	-10000	0	-1.4	146	146
mast cell activation	0.012	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.28	0.38	-10000	0	-1.1	53	53
FRAP1	-0.27	0.33	-10000	0	-0.96	52	52
LTA	-0.55	0.58	-10000	0	-1.3	124	124
FES	0.008	0.036	-10000	0	-0.51	2	2
T-helper 1 cell differentiation	0.61	0.66	1.4	144	-10000	0	144
CCL11	-0.56	0.58	-10000	0	-1.3	139	139
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.28	0.38	-10000	0	-1.1	50	50
IL2RG	-0.045	0.18	-10000	0	-0.61	43	43
IL10	-0.54	0.56	-10000	0	-1.3	129	129
IRS1	0.006	0.047	-10000	0	-0.56	3	3
IRS2	-0.034	0.16	-10000	0	-0.58	34	34
IL4	-0.11	0.12	-10000	0	-10000	0	0
IL5	-0.54	0.56	-10000	0	-1.3	133	133
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.42	0.41	-10000	0	-0.92	134	134
COL1A1	-0.2	0.32	-10000	0	-1.3	23	23
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.55	0.58	-10000	0	-1.3	123	123
IL2R gamma/JAK3	-0.031	0.14	-10000	0	-0.43	48	48
TFF3	-0.76	0.74	-10000	0	-1.6	190	190
ALOX15	-0.63	0.63	-10000	0	-1.4	157	157
MYBL1	0.034	0.099	0.22	44	-0.41	8	52
T-helper 2 cell differentiation	-0.46	0.48	-10000	0	-1.1	138	138
SHC1	0.01	0	-10000	0	-10000	0	0
CEBPB	-0.039	0.11	-10000	0	-0.3	49	49
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.29	0.37	-10000	0	-1	57	57
mol:PI-3-4-5-P3	-0.26	0.33	-10000	0	-0.96	52	52
PI3K	-0.28	0.37	-10000	0	-1.1	52	52
DOK2	-0.006	0.1	-10000	0	-0.65	11	11
ETS1	0.022	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.21	0.28	-10000	0	-0.89	41	41
ITGB3	-0.54	0.57	-10000	0	-1.3	127	127
PIGR	-0.79	0.75	-10000	0	-1.6	201	201
IGHE	-0.2	0.5	-10000	0	-1.4	69	69
MAPKKK cascade	-0.2	0.27	-10000	0	-0.87	41	41
BCL6	-0.001	0.044	-10000	0	-0.53	2	2
OPRM1	-0.54	0.56	-10000	0	-1.3	130	130
RETNLB	-0.59	0.6	-10000	0	-1.4	140	140
SELP	-0.6	0.63	-10000	0	-1.4	137	137
AICDA	-0.55	0.56	-10000	0	-1.3	141	141

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.11	0.18	0.4	115	-10000	0	115
KIRREL	-0.015	0.084	-10000	0	-0.65	7	7
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.11	0.18	-10000	0	-0.4	115	115
PLCG1	0.01	0	-10000	0	-10000	0	0
ARRB2	0.01	0	-10000	0	-10000	0	0
WASL	0.009	0.018	-10000	0	-0.37	1	1
Nephrin/NEPH1/podocin/CD2AP	-0.11	0.17	-10000	0	-0.39	108	108
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.069	0.15	-10000	0	-0.33	105	105
FYN	-0.093	0.17	-10000	0	-0.37	108	108
mol:Ca2+	-0.11	0.17	-10000	0	-0.38	108	108
mol:DAG	-0.11	0.17	-10000	0	-0.39	108	108
NPHS2	-0.084	0.2	-10000	0	-0.56	66	66
mol:IP3	-0.11	0.17	-10000	0	-0.39	108	108
regulation of endocytosis	-0.082	0.16	-10000	0	-0.34	108	108
Nephrin/NEPH1/podocin/Cholesterol	-0.11	0.17	-10000	0	-0.39	108	108
establishment of cell polarity	-0.11	0.18	-10000	0	-0.4	115	115
Nephrin/NEPH1/podocin/NCK1-2	-0.1	0.15	-10000	0	-0.35	108	108
Nephrin/NEPH1/beta Arrestin2	-0.082	0.16	-10000	0	-0.35	108	108
NPHS1	-0.13	0.24	-10000	0	-0.54	110	110
Nephrin/NEPH1/podocin	-0.093	0.17	-10000	0	-0.37	108	108
TJP1	0.007	0.044	-10000	0	-0.65	2	2
NCK1	0.01	0	-10000	0	-10000	0	0
NCK2	0.01	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.11	0.17	-10000	0	-0.39	108	108
CD2AP	0.01	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.11	0.17	-10000	0	-0.39	108	108
GRB2	0.01	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.093	0.17	-10000	0	-0.37	110	110
cytoskeleton organization	-0.084	0.18	-10000	0	-0.4	105	105
Nephrin/NEPH1	-0.075	0.13	-10000	0	-0.35	74	74
Nephrin/NEPH1/ZO-1	-0.084	0.15	-10000	0	-0.4	70	70

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.086	0.18	-9999	-0.42	95	95
EFNA5	-0.065	0.21	-9999	-0.64	53	53
FYN	-0.064	0.17	-9999	-0.41	81	81
neuron projection morphogenesis	-0.086	0.18	-9999	-0.42	95	95
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.087	0.18	-9999	-0.42	95	95
EPHA5	-0.057	0.19	-9999	-0.58	51	51

×

TCGA08_p53

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
CDKN2A	-0.11	0.19	-10000	0	-0.37	149	149
TP53	-0.042	0.084	-10000	0	-0.19	78	78
Senescence	-0.042	0.083	-10000	0	-0.19	78	78
Apoptosis	-0.042	0.083	-10000	0	-0.19	78	78
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.063	0.11	0.28	71	-0.26	8	79
MDM4	0.01	0	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.1	0.19	-9999	-0.37	115	115
FZD6	-0.014	0.11	-9999	-0.45	24	24
WNT6	-0.047	0.16	-9999	-0.48	53	53
WNT4	-0.066	0.2	-9999	-0.55	63	63
FZD3	-0.001	0.083	-9999	-0.62	8	8
WNT5A	-0.019	0.12	-9999	-0.44	30	30
WNT11	-0.12	0.24	-9999	-0.5	121	121

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.011	0.046	-10000	0	-0.48	4	4
Necdin/E2F1	0.001	0.077	-10000	0	-0.4	15	15
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.13	0.2	-10000	0	-0.42	116	116
NGF (dimer)/p75(NTR)/BEX1	-0.21	0.24	-10000	0	-0.5	149	149
NT-4/5 (dimer)/p75(NTR)	-0.19	0.23	-10000	0	-0.51	130	130
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	-0.098	0.18	-10000	0	-0.38	107	107
IKBKG	0.004	0.005	-10000	0	-10000	0	0
BDNF	-0.016	0.11	-10000	0	-0.42	27	27
MGDIs/NGR/p75(NTR)/LINGO1	-0.12	0.17	-10000	0	-0.42	83	83
FURIN	0.009	0.018	-10000	0	-0.37	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.12	0.17	-10000	0	-0.42	83	83
LINGO1	-0.009	0.087	-10000	0	-0.4	21	21
Sortilin/TRAF6/NRIF	-0.006	0.041	-10000	0	-10000	0	0
proBDNF (dimer)	-0.016	0.1	-10000	0	-0.42	27	27
NTRK1	-0.003	0.088	-10000	0	-0.62	9	9
RTN4R	-0.004	0.092	-10000	0	-0.58	11	11
neuron apoptosis	-0.091	0.19	-10000	0	-0.64	24	24
IRAK1	0.01	0	-10000	0	-10000	0	0
SHC1	-0.13	0.21	-10000	0	-0.45	107	107
ARHGDIA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	0.007	0	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.023	-10000	0	-0.34	2	2
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.13	0.2	-10000	0	-0.43	112	112
MAGEH1	0	0.077	-10000	0	-0.61	7	7
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.14	0.2	-10000	0	-0.44	112	112
Mammalian IAPs/DIABLO	-0.023	0.086	-10000	0	-0.37	25	25
proNGF (dimer)	-0.06	0.19	-10000	0	-0.53	59	59
MAGED1	0.003	0.069	-10000	0	-0.65	5	5
APP	0.009	0.031	-10000	0	-0.65	1	1
NT-4/5 (dimer)	-0.12	0.21	-10000	0	-0.43	131	131
ZNF274	0.006	0.053	-10000	0	-0.65	3	3
RhoA/GDP/RHOGDI	-0.1	0.18	-10000	0	-0.39	107	107
NGF	-0.06	0.19	-10000	0	-0.53	59	59
cell cycle arrest	-0.1	0.19	-10000	0	-0.38	110	110
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.067	0.14	-10000	0	-0.57	13	13
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.17	0.2	-10000	0	-0.44	130	130
NCSTN	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.14	0.2	-10000	0	-0.46	110	110
PSENEN	0.01	0	-10000	0	-10000	0	0
mol:ceramide	-0.11	0.19	-10000	0	-0.41	110	110
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.047	0.12	-10000	0	-0.47	13	13
p75(NTR)/beta APP	-0.11	0.19	-10000	0	-0.49	71	71
BEX1	-0.12	0.22	-10000	0	-0.47	120	120
mol:GDP	-0.13	0.2	-10000	0	-0.46	107	107
NGF (dimer)	-0.13	0.18	-10000	0	-0.42	109	109
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.1	0.15	-10000	0	-0.38	83	83
PIK3R1	0.01	0	-10000	0	-10000	0	0
RAC1/GTP	-0.12	0.17	-10000	0	-0.39	107	107
MYD88	0.01	0	-10000	0	-10000	0	0
CHUK	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.14	0.2	-10000	0	-0.46	110	110
RHOB	0.009	0.018	-10000	0	-0.37	1	1
RHOA	0.01	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.011	0.042	-10000	0	-0.42	4	4
NT3 (dimer)	-0.048	0.17	-10000	0	-0.51	51	51
TP53	-0.077	0.16	-10000	0	-0.52	17	17
PRDM4	-0.11	0.19	-10000	0	-0.41	110	110
BDNF (dimer)	-0.21	0.22	-10000	0	-0.45	171	171
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
SORT1	0.004	0.062	-10000	0	-0.65	4	4
activation of caspase activity	-0.13	0.19	-10000	0	-0.42	116	116
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.13	0.18	-10000	0	-0.42	110	110
RHOC	0.01	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
MAPK10	-0.088	0.19	-10000	0	-0.58	33	33
DIABLO	0.01	0	-10000	0	-10000	0	0
SMPD2	-0.11	0.19	-10000	0	-0.41	110	110
APH1B	0.007	0.044	-10000	0	-0.65	2	2
APH1A	0.01	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.14	0.2	-10000	0	-0.46	110	110
PSEN1	0.01	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.014	0.023	-10000	0	-0.48	1	1
NT3 (dimer)/p75(NTR)	-0.15	0.22	-10000	0	-0.51	98	98
MAPK8	-0.076	0.18	-10000	0	-0.54	26	26
MAPK9	-0.076	0.18	-10000	0	-0.54	26	26
APAF1	0.009	0.031	-10000	0	-0.65	1	1
NTF3	-0.048	0.17	-10000	0	-0.51	51	51
NTF4	-0.12	0.21	-10000	0	-0.43	131	131
NDN	-0.003	0.088	-10000	0	-0.55	11	11
RAC1/GDP	0.007	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.11	0.16	-10000	0	-0.36	110	110
p75 CTF/Sortilin/TRAF6/NRIF	-0.006	0.046	-10000	0	-0.37	7	7
RhoA-B-C/GTP	-0.14	0.2	-10000	0	-0.46	110	110
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.098	0.15	-10000	0	-0.37	83	83
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.1	0.15	-10000	0	-0.38	83	83
PRKACB	0.002	0.071	-10000	0	-0.6	6	6
proBDNF (dimer)/p75 ECD	-0.004	0.077	-10000	0	-0.29	28	28
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.032	0.16	-10000	0	-0.59	32	32
BIRC2	0.01	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.097	0.21	0.2	20	-0.43	95	115
BAD	-0.075	0.18	-10000	0	-0.52	33	33
RIPK2	0.01	0	-10000	0	-10000	0	0
NGFR	-0.16	0.26	-10000	0	-0.5	153	153
CYCS	-0.1	0.19	-10000	0	-0.4	111	111
ADAM17	0.009	0.018	-10000	0	-0.37	1	1
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.13	0.18	-10000	0	-0.41	107	107
BCL2L11	-0.075	0.18	-10000	0	-0.52	33	33
BDNF (dimer)/p75(NTR)	-0.13	0.2	-10000	0	-0.36	173	173
PI3K	-0.13	0.18	-10000	0	-0.41	107	107
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.13	0.18	-10000	0	-0.42	110	110
NDNL2	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.16	0.24	-10000	0	-0.53	107	107
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.13	0.19	-10000	0	-0.43	111	111
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.018	-10000	0	-0.37	1	1
PLG	-0.004	0.061	-10000	0	-0.37	12	12
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.12	0.2	-10000	0	-0.43	101	101
SQSTM1	0.009	0.018	-10000	0	-0.37	1	1
NGFRAP1	-0.015	0.13	-10000	0	-0.64	18	18
CASP3	-0.067	0.17	-10000	0	-0.47	33	33
E2F1	0.005	0.056	-10000	0	-0.58	4	4
CASP9	0.01	0	-10000	0	-10000	0	0
IKK complex	-0.072	0.14	-10000	0	-0.46	36	36
NGF (dimer)/TRKA	-0.045	0.16	-10000	0	-0.41	65	65
MMP7	-0.16	0.26	-10000	0	-0.51	152	152
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.12	0.18	-10000	0	-0.4	110	110
MMP3	-0.18	0.28	-10000	0	-0.55	157	157
APAF-1/Caspase 9	-0.1	0.14	-10000	0	-0.48	29	29

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.048	0.12	-10000	0	-0.43	28	28
fibroblast growth factor receptor signaling pathway	-0.048	0.12	-10000	0	-0.43	28	28
LAMA1	-0.08	0.2	-10000	0	-0.47	86	86
PRNP	-0.003	0.077	-10000	0	-0.44	13	13
GPC1/SLIT2	-0.084	0.18	-10000	0	-0.52	51	51
SMAD2	-0.006	0.092	-10000	0	-0.39	16	16
GPC1/PrPc/Cu2+	-0.034	0.1	-10000	0	-0.44	17	17
GPC1/Laminin alpha1	-0.082	0.18	-10000	0	-0.5	60	60
TDGF1	-0.15	0.25	-10000	0	-0.51	139	139
CRIPTO/GPC1	-0.13	0.22	-10000	0	-0.55	78	78
APP/GPC1	-0.02	0.1	-10000	0	-0.48	12	12
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.11	0.19	-10000	0	-0.47	80	80
FLT1	0.007	0.044	-10000	0	-0.65	2	2
GPC1/TGFB/TGFBR1/TGFBR2	-0.032	0.095	-10000	0	-0.43	16	16
SERPINC1	-0.014	0.11	-10000	0	-0.53	20	20
FYN	-0.1	0.19	-10000	0	-0.47	79	79
FGR	-0.11	0.2	-10000	0	-0.48	86	86
positive regulation of MAPKKK cascade	-0.14	0.25	-10000	0	-0.57	90	90
SLIT2	-0.08	0.21	-10000	0	-0.53	76	76
GPC1/NRG	-0.12	0.21	-10000	0	-0.5	96	96
NRG1	-0.13	0.25	-10000	0	-0.53	121	121
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.031	0.089	-10000	0	-0.41	14	14
LYN	-0.11	0.2	-10000	0	-0.48	80	80
mol:Spermine	-0.025	0.1	-10000	0	-0.31	49	49
cell growth	-0.048	0.12	-10000	0	-0.43	28	28
BMP signaling pathway	0.038	0.14	0.44	49	-10000	0	49
SRC	-0.1	0.19	-10000	0	-0.48	78	78
TGFBR1	0.008	0.025	-10000	0	-0.37	2	2
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.24	0.28	-10000	0	-0.52	213	213
GPC1	-0.038	0.14	-10000	0	-0.44	49	49
TGFBR1 (dimer)	0.008	0.025	-10000	0	-0.37	2	2
VEGFA	0.005	0.047	-10000	0	-0.43	5	5
BLK	-0.19	0.26	-10000	0	-0.55	130	130
HCK	-0.11	0.2	-10000	0	-0.48	84	84
FGF2	-0.003	0.081	-10000	0	-0.46	13	13
FGFR1	-0.014	0.11	-10000	0	-0.49	22	22
VEGFR1 homodimer	0.007	0.044	-10000	0	-0.65	2	2
TGFBR2	0.003	0.069	-10000	0	-0.65	5	5
cell death	-0.033	0.1	-10000	0	-0.48	12	12
ATIII/GPC1	-0.036	0.13	-10000	0	-0.51	22	22
PLA2G2A/GPC1	-0.2	0.24	-10000	0	-0.53	122	122
LCK	-0.12	0.21	-10000	0	-0.5	90	90
neuron differentiation	-0.13	0.21	-10000	0	-0.5	96	96
PrPc/Cu2+	-0.002	0.055	-10000	0	-0.31	13	13
APP	0.009	0.031	-10000	0	-0.65	1	1
TGFBR2 (dimer)	0.003	0.069	-10000	0	-0.65	5	5

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.32	0.49	-10000	0	-1.2	77	77
IL23A	-0.33	0.49	-10000	0	-1.3	68	68
NF kappa B1 p50/RelA/I kappa B alpha	-0.35	0.45	-10000	0	-1.1	86	86
positive regulation of T cell mediated cytotoxicity	-0.36	0.55	-10000	0	-1.3	87	87
ITGA3	-0.31	0.47	-10000	0	-1.2	69	69
IL17F	-0.21	0.31	-10000	0	-0.75	65	65
IL12B	-0.027	0.13	-10000	0	-0.6	22	22
STAT1 (dimer)	-0.34	0.52	-10000	0	-1.2	87	87
CD4	-0.3	0.46	-10000	0	-1.2	64	64
IL23	-0.33	0.47	-10000	0	-1.2	70	70
IL23R	-0.081	0.28	-10000	0	-1.5	16	16
IL1B	-0.35	0.53	-10000	0	-1.3	73	73
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.32	0.48	-10000	0	-1.2	78	78
TYK2	0.001	0.019	-10000	0	-10000	0	0
STAT4	-0.002	0.088	-10000	0	-0.62	9	9
STAT3	0.01	0.001	-10000	0	-10000	0	0
IL18RAP	-0.027	0.15	-10000	0	-0.62	26	26
IL12RB1	-0.024	0.13	-10000	0	-0.68	17	17
PIK3CA	0.009	0.019	-10000	0	-0.39	1	1
IL12Rbeta1/TYK2	-0.018	0.1	-10000	0	-0.52	17	17
IL23R/JAK2	-0.087	0.28	-10000	0	-1.4	16	16
positive regulation of chronic inflammatory response	-0.36	0.55	-10000	0	-1.3	87	87
natural killer cell activation	0.006	0.015	0.078	16	-10000	0	16
JAK2	-0.003	0.064	-10000	0	-0.5	6	6
PIK3R1	0.01	0.001	-10000	0	-10000	0	0
NFKB1	0.008	0.004	-10000	0	-10000	0	0
RELA	0.008	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.31	0.45	-10000	0	-1.1	70	70
ALOX12B	-0.41	0.56	-10000	0	-1.3	111	111
CXCL1	-0.37	0.54	-10000	0	-1.2	100	100
T cell proliferation	-0.36	0.55	-10000	0	-1.3	87	87
NFKBIA	0.007	0.019	-10000	0	-0.38	1	1
IL17A	-0.19	0.29	-10000	0	-0.62	83	83
PI3K	-0.36	0.46	-10000	0	-1.2	87	87
IFNG	-0.017	0.05	0.15	11	-0.13	41	52
STAT3 (dimer)	-0.35	0.43	-10000	0	-1.1	82	82
IL18R1	-0.006	0.095	-10000	0	-0.6	11	11
IL23/IL23R/JAK2/TYK2/SOCS3	-0.19	0.31	-10000	0	-0.86	39	39
IL18/IL18R	-0.03	0.16	-10000	0	-0.51	40	40
macrophage activation	-0.018	0.018	-10000	0	-0.046	42	42
TNF	-0.33	0.5	-10000	0	-1.3	71	71
STAT3/STAT4	-0.36	0.46	-10000	0	-1.2	89	89
STAT4 (dimer)	-0.34	0.52	-10000	0	-1.2	88	88
IL18	-0.02	0.13	-10000	0	-0.59	22	22
IL19	-0.33	0.48	-10000	0	-1.2	64	64
STAT5A (dimer)	-0.34	0.52	-10000	0	-1.2	90	90
STAT1	0.01	0	-10000	0	-10000	0	0
SOCS3	0.003	0.064	-10000	0	-0.6	5	5
CXCL9	-0.36	0.53	-10000	0	-1.3	81	81
MPO	-0.31	0.46	-10000	0	-1.1	76	76
positive regulation of humoral immune response	-0.36	0.55	-10000	0	-1.3	87	87
IL23/IL23R/JAK2/TYK2	-0.39	0.64	-10000	0	-1.4	87	87
IL6	-0.36	0.52	-10000	0	-1.2	90	90
STAT5A	0.004	0.062	-10000	0	-0.65	4	4
IL2	0.002	0.052	-10000	0	-0.38	8	8
positive regulation of tyrosine phosphorylation of STAT protein	0.006	0.015	0.078	16	-10000	0	16
CD3E	-0.31	0.47	-10000	0	-1.2	70	70
keratinocyte proliferation	-0.36	0.55	-10000	0	-1.3	87	87
NOS2	-0.34	0.48	-10000	0	-1.2	82	82

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.01	0	-9999	-10000	0	0
EGFR	-0.036	0.14	-9999	-0.44	46	46
EGF/EGFR	-0.1	0.14	-9999	-0.35	91	91
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.092	0.13	-9999	-0.35	79	79
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.002	0.083	-9999	-0.54	10	10
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.14	0.24	-9999	-0.47	144	144
EGF/EGFR dimer/SHC	-0.11	0.16	-9999	-0.42	79	79
mol:GDP	-0.091	0.13	-9999	-0.34	79	79
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.003	0.083	-9999	-0.49	12	12
GRB2/SOS1	0.015	0	-9999	-10000	0	0
HRAS/GTP	-0.082	0.12	-9999	-0.32	79	79
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	-0.084	0.12	-9999	-0.32	79	79
FRAP1	-0.07	0.14	-9999	-0.33	79	79
EGF/EGFR dimer	-0.13	0.2	-9999	-0.36	171	171
SOS1	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.003	0.085	-9999	-0.37	22	22

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.033	0.062	-9999	-0.89	1	1
Crk/p130 Cas/Paxillin	-0.082	0.14	-9999	-0.47	30	30
JUN	-0.051	0.16	-9999	-0.57	21	21
HRAS	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.12	0.2	-9999	-0.44	101	101
RAP1A	0.01	0	-9999	-10000	0	0
FRS2	0.005	0.043	-9999	-0.37	6	6
RAP1A/GDP	0.007	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.12	0.2	-9999	-0.44	104	104
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.088	0.16	-9999	-0.42	74	74
RHOA	0.01	0	-9999	-10000	0	0
RAP1A/GTP	-0.11	0.17	-9999	-0.39	101	101
GRB7	-0.023	0.12	-9999	-0.43	34	34
RET51/GFRalpha1/GDNF	-0.12	0.19	-9999	-0.44	101	101
MAPKKK cascade	-0.096	0.16	-9999	-0.38	85	85
BCAR1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.089	0.16	-9999	-0.42	74	74
lamellipodium assembly	-0.076	0.13	-9999	-0.34	71	71
RET51/GFRalpha1/GDNF/SHC	-0.12	0.19	-9999	-0.44	101	101
PIK3CA	0.009	0.018	-9999	-0.37	1	1
RET9/GFRalpha1/GDNF/SHC	-0.087	0.16	-9999	-0.41	72	72
RET9/GFRalpha1/GDNF/Shank3	-0.088	0.16	-9999	-0.41	73	73
MAPK3	-0.08	0.18	-9999	-0.37	101	101
DOK1	0.002	0.071	-9999	-0.6	6	6
DOK6	-0.003	0.087	-9999	-0.57	10	10
PXN	0.003	0.064	-9999	-0.6	5	5
neurite development	-0.068	0.17	-9999	-0.57	21	21
DOK5	-0.029	0.16	-9999	-0.63	28	28
GFRA1	-0.11	0.24	-9999	-0.54	102	102
MAPK8	-0.06	0.16	-9999	-0.58	23	23
HRAS/GTP	-0.11	0.19	-9999	-0.44	85	85
tube development	-0.081	0.15	-9999	-0.39	73	73
MAPK1	-0.08	0.18	-9999	-0.37	101	101
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.043	0.13	-9999	-0.32	67	67
Rac1/GDP	0.007	0	-9999	-10000	0	0
SRC	0.009	0.031	-9999	-0.65	1	1
PDLIM7	0.007	0.031	-9999	-0.37	3	3
RET51/GFRalpha1/GDNF/Dok6	-0.12	0.18	-9999	-0.41	108	108
SHC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.12	0.19	-9999	-0.44	101	101
RET51/GFRalpha1/GDNF/Dok5	-0.14	0.22	-9999	-0.46	117	117
PRKCA	-0.002	0.087	-9999	-0.65	8	8
HRAS/GDP	0.007	0	-9999	-10000	0	0
CREB1	-0.054	0.15	-9999	-0.38	67	67
PIK3R1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.045	0.14	-9999	-0.34	67	67
RET51/GFRalpha1/GDNF/Grb7	-0.14	0.21	-9999	-0.46	104	104
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.059	0.18	-9999	-0.49	64	64
DOK4	0.008	0.036	-9999	-0.51	2	2
JNK cascade	-0.05	0.15	-9999	-0.56	21	21
RET9/GFRalpha1/GDNF/FRS2	-0.089	0.16	-9999	-0.42	72	72
SHANK3	0.009	0.031	-9999	-0.65	1	1
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.042	0.13	-9999	-0.32	67	67
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.066	0.16	-9999	-0.35	83	83
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.069	0.17	-9999	-0.37	85	85
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.066	0.17	-9999	-0.36	83	83
PI3K	-0.087	0.22	-9999	-0.53	72	72
SOS1	0.01	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.081	0.15	-9999	-0.39	73	73
GRB10	0.006	0.053	-9999	-0.65	3	3
activation of MAPKK activity	-0.061	0.16	-9999	-0.36	67	67
RET51/GFRalpha1/GDNF/FRS2	-0.12	0.19	-9999	-0.44	102	102
GAB1	0.006	0.053	-9999	-0.65	3	3
IRS1	0.006	0.047	-9999	-0.56	3	3
IRS2	-0.034	0.16	-9999	-0.58	34	34
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.07	0.18	-9999	-0.38	83	83
RET51/GFRalpha1/GDNF/PKC alpha	-0.13	0.2	-9999	-0.43	109	109
GRB2	0.01	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GDNF	-0.031	0.14	-9999	-0.47	39	39
RAC1	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.12	0.2	-9999	-0.44	102	102
Rac1/GTP	-0.09	0.16	-9999	-0.41	71	71
RET9/GFRalpha1/GDNF	-0.097	0.18	-9999	-0.35	127	127
GFRalpha1/GDNF	-0.1	0.21	-9999	-0.41	127	127

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.22	0.44	-9999	-1.1	53	53
HDAC7	0.01	0.004	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.18	0.34	-9999	-0.85	51	51
SMAD4	0.01	0.031	-9999	-0.65	1	1
ID2	-0.22	0.45	-9999	-1.1	55	55
AP1	-0.002	0.092	-9999	-0.43	19	19
ABCG2	-0.24	0.46	-9999	-1.1	59	59
HIF1A	-0.024	0.074	-9999	-0.51	1	1
TFF3	-0.34	0.53	-9999	-1.2	92	92
GATA2	0.004	0.064	-9999	-0.6	5	5
AKT1	-0.025	0.078	-9999	-10000	0	0
response to hypoxia	-0.04	0.082	-9999	-0.23	9	9
MCL1	-0.22	0.44	-9999	-1.1	53	53
NDRG1	-0.23	0.46	-9999	-1.1	57	57
SERPINE1	-0.24	0.47	-9999	-1.2	58	58
FECH	-0.22	0.45	-9999	-1.1	53	53
FURIN	-0.22	0.44	-9999	-1.1	53	53
NCOA2	0.007	0.044	-9999	-0.65	2	2
EP300	-0.019	0.11	-9999	-0.31	18	18
HMOX1	-0.22	0.45	-9999	-1.1	55	55
BHLHE40	-0.22	0.44	-9999	-1.1	53	53
BHLHE41	-0.23	0.46	-9999	-1.1	57	57
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.029	0.069	-9999	-0.47	2	2
ENG	0.009	0.098	-9999	-0.59	2	2
JUN	0.01	0.018	-9999	-0.37	1	1
RORA	-0.22	0.45	-9999	-1.1	58	58
ABCB1	-0.1	0.26	-9999	-1.3	18	18
TFRC	-0.23	0.45	-9999	-1.1	54	54
CXCR4	-0.22	0.45	-9999	-1.1	55	55
TF	-0.26	0.48	-9999	-1.1	66	66
CITED2	-0.22	0.44	-9999	-1.1	54	54
HIF1A/ARNT	-0.27	0.52	-9999	-1.3	62	62
LDHA	-0.037	0.081	-9999	-1.4	1	1
ETS1	-0.22	0.44	-9999	-1.1	54	54
PGK1	-0.22	0.44	-9999	-1.1	53	53
NOS2	-0.26	0.46	-9999	-1.1	59	59
ITGB2	-0.23	0.46	-9999	-1.1	58	58
ALDOA	-0.22	0.44	-9999	-1.1	53	53
Cbp/p300/CITED2	-0.22	0.46	-9999	-1.2	52	52
FOS	-0.014	0.12	-9999	-0.58	19	19
HK2	-0.23	0.45	-9999	-1.1	56	56
SP1	0.015	0.015	-9999	-10000	0	0
GCK	-0.13	0.36	-9999	-1.3	24	24
HK1	-0.22	0.44	-9999	-1.1	54	54
NPM1	-0.22	0.44	-9999	-1.1	53	53
EGLN1	-0.22	0.44	-9999	-1.1	53	53
CREB1	0.016	0.001	-9999	-10000	0	0
PGM1	-0.22	0.45	-9999	-1.1	55	55
SMAD3	0.007	0.047	-9999	-0.56	3	3
EDN1	-0.023	0.2	-9999	-0.96	10	10
IGFBP1	-0.26	0.45	-9999	-1.1	57	57
VEGFA	-0.14	0.33	-9999	-0.8	36	36
HIF1A/JAB1	-0.02	0.035	-9999	-0.36	1	1
CP	-0.23	0.45	-9999	-1.1	57	57
CXCL12	-0.23	0.46	-9999	-1.1	57	57
COPS5	0.009	0.004	-9999	-10000	0	0
SMAD3/SMAD4	-0.004	0.04	-9999	-0.42	4	4
BNIP3	-0.23	0.46	-9999	-1.1	57	57
EGLN3	-0.22	0.45	-9999	-1.1	56	56
CA9	-0.3	0.51	-9999	-1.2	77	77
TERT	-0.25	0.47	-9999	-1.1	65	65
ENO1	-0.22	0.44	-9999	-1.1	53	53
PFKL	-0.22	0.44	-9999	-1.1	53	53
NCOA1	0.01	0.001	-9999	-10000	0	0
ADM	-0.23	0.47	-9999	-1.2	59	59
ARNT	-0.024	0.069	-9999	-10000	0	0
HNF4A	-0.14	0.28	-9999	-0.64	105	105
ADFP	-0.22	0.44	-9999	-1.1	56	56
SLC2A1	-0.15	0.36	-9999	-0.84	51	51
LEP	-0.26	0.48	-9999	-1.1	67	67
HIF1A/ARNT/Cbp/p300	-0.19	0.35	-9999	-0.88	51	51
EPO	-0.12	0.29	-9999	-0.74	18	18
CREBBP	-0.019	0.11	-9999	-0.34	12	12
HIF1A/ARNT/Cbp/p300/HDAC7	-0.18	0.35	-9999	-0.86	56	56
PFKFB3	-0.22	0.44	-9999	-1.1	53	53
NT5E	-0.24	0.47	-9999	-1.1	59	59

×

Glucocorticoid receptor regulatory network

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
PCK2	0.019	0.072	0.36	1	-10000	0	1
SMARCC2	0.01	0.01	-10000	0	-10000	0	0
SMARCC1	0.01	0.011	-10000	0	-10000	0	0
TBX21	-0.11	0.25	-10000	0	-0.82	38	38
SUMO2	0.01	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.016	0.02	-10000	0	-0.41	1	1
FKBP4	0.01	0	-10000	0	-10000	0	0
FKBP5	0.001	0.071	-10000	0	-0.51	8	8
GR alpha/HSP90/FKBP51/HSP90	0.093	0.11	0.3	34	-0.34	4	38
PRL	-0.085	0.14	-10000	0	-0.6	5	5
cortisol/GR alpha (dimer)/TIF2	0.23	0.23	0.53	118	-0.38	1	119
RELA	-0.025	0.078	-10000	0	-0.24	10	10
FGG	0.15	0.24	0.47	75	-0.57	20	95
GR beta/TIF2	0.1	0.11	0.32	42	-0.38	3	45
IFNG	-0.36	0.41	-10000	0	-0.97	100	100
apoptosis	0.006	0.16	0.56	10	-0.52	12	22
CREB1	0.004	0.036	-10000	0	-10000	0	0
histone acetylation	0.004	0.14	0.33	27	-0.35	25	52
BGLAP	-0.068	0.13	-10000	0	-0.5	8	8
GR/PKAc	0.092	0.1	0.28	41	-0.3	5	46
NF kappa B1 p50/RelA	-0.043	0.14	-10000	0	-0.4	23	23
SMARCD1	0.01	0.011	-10000	0	-10000	0	0
MDM2	0.089	0.088	0.24	72	-10000	0	72
GATA3	-0.005	0.1	-10000	0	-0.48	19	19
AKT1	0	0.001	-10000	0	-10000	0	0
CSF2	-0.12	0.32	-10000	0	-1.2	31	31
GSK3B	0.01	0.008	-10000	0	-10000	0	0
NR1I3	0.032	0.15	0.55	9	-0.57	2	11
CSN2	0.15	0.15	0.38	69	-0.39	4	73
BRG1/BAF155/BAF170/BAF60A	0.025	0.039	-10000	0	-0.37	3	3
NFATC1	0.002	0.084	-10000	0	-0.61	8	8
POU2F1	0.008	0.021	-10000	0	-10000	0	0
CDKN1A	0.014	0.058	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.009	-10000	0	-10000	0	0
SFN	-0.073	0.19	-10000	0	-0.45	82	82
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.053	0.14	0.3	23	-0.34	14	37
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.023	0.17	0.53	9	-0.83	6	15
JUN	-0.23	0.2	-10000	0	-0.48	121	121
IL4	-0.085	0.14	-10000	0	-0.5	20	20
CDK5R1	-0.015	0.1	-10000	0	-0.4	28	28
PRKACA	0.01	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.19	0.21	0.23	17	-0.48	113	130
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.094	0.1	0.29	32	-0.34	2	34
cortisol/GR alpha (monomer)	0.27	0.28	0.62	125	-0.43	2	127
NCOA2	0.007	0.044	-10000	0	-0.65	2	2
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.082	0.14	-10000	0	-0.65	19	19
AP-1/NFAT1-c-4	-0.37	0.32	-10000	0	-0.72	155	155
AFP	-0.23	0.34	-10000	0	-1	46	46
SUV420H1	0.009	0.018	-10000	0	-0.37	1	1
IRF1	0.14	0.14	0.51	13	-0.74	1	14
TP53	0.013	0.094	-10000	0	-0.61	10	10
PPP5C	0.01	0	-10000	0	-10000	0	0
KRT17	-0.53	0.53	-10000	0	-1.1	176	176
KRT14	-0.4	0.51	-10000	0	-1.3	100	100
TBP	0.017	0.006	-10000	0	-10000	0	0
CREBBP	0.093	0.11	0.3	73	-10000	0	73
HDAC1	0.004	0.033	-10000	0	-0.65	1	1
HDAC2	0.016	0.023	-10000	0	-10000	0	0
AP-1	-0.37	0.32	-10000	0	-0.73	156	156
MAPK14	0.01	0.007	-10000	0	-10000	0	0
MAPK10	-0.033	0.14	-10000	0	-0.48	40	40
MAPK11	0.01	0.008	-10000	0	-10000	0	0
KRT5	-0.47	0.47	-10000	0	-0.99	156	156
interleukin-1 receptor activity	0.007	0.023	-10000	0	-10000	0	0
NCOA1	0.012	0.001	-10000	0	-10000	0	0
STAT1	0.016	0.02	-10000	0	-0.41	1	1
CGA	-0.096	0.15	-10000	0	-0.46	24	24
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.17	0.18	0.42	108	-0.38	1	109
MAPK3	0.01	0.009	-10000	0	-10000	0	0
MAPK1	0.01	0.007	-10000	0	-10000	0	0
ICAM1	-0.14	0.27	-10000	0	-0.74	42	42
NFKB1	-0.025	0.078	-10000	0	-0.3	1	1
MAPK8	-0.18	0.17	-10000	0	-0.44	83	83
MAPK9	0.007	0.036	-10000	0	-0.5	2	2
cortisol/GR alpha (dimer)	0	0.16	0.56	10	-0.54	12	22
BAX	0.014	0.058	-10000	0	-10000	0	0
POMC	-0.18	0.31	-10000	0	-1	32	32
EP300	0.094	0.11	0.3	74	-0.26	1	75
cortisol/GR alpha (dimer)/p53	0.24	0.24	0.53	121	-0.5	2	123
proteasomal ubiquitin-dependent protein catabolic process	0.064	0.069	0.22	24	-10000	0	24
SGK1	0.13	0.19	-10000	0	-1.3	5	5
IL13	-0.22	0.21	-10000	0	-0.7	31	31
IL6	-0.2	0.37	-10000	0	-0.89	76	76
PRKACG	0.004	0.031	-10000	0	-0.37	3	3
IL5	-0.19	0.18	-10000	0	-0.64	21	21
IL2	-0.27	0.24	-10000	0	-0.65	78	78
CDK5	0.01	0.005	-10000	0	-10000	0	0
PRKACB	0.002	0.071	-10000	0	-0.6	6	6
HSP90AA1	0.009	0.031	-10000	0	-0.65	1	1
IL8	-0.23	0.41	-10000	0	-0.96	89	89
CDK5R1/CDK5	-0.013	0.07	-10000	0	-0.37	6	6
NF kappa B1 p50/RelA/PKAc	-0.017	0.11	-10000	0	-0.42	11	11
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.23	0.21	0.5	120	-10000	0	120
SMARCA4	0.009	0.021	-10000	0	-0.37	1	1
chromatin remodeling	0.15	0.14	0.36	73	-10000	0	73
NF kappa B1 p50/RelA/Cbp	0.054	0.16	0.34	39	-0.5	4	43
JUN (dimer)	-0.23	0.2	-10000	0	-0.48	121	121
YWHAH	0.01	0	-10000	0	-10000	0	0
VIPR1	-0.1	0.23	-10000	0	-0.76	37	37
NR3C1	0.15	0.17	0.42	83	-0.44	2	85
NR4A1	-0.029	0.14	-10000	0	-0.5	31	31
TIF2/SUV420H1	0.012	0.035	-10000	0	-0.4	3	3
MAPKKK cascade	0.006	0.16	0.56	10	-0.52	12	22
cortisol/GR alpha (dimer)/Src-1	0.24	0.23	0.53	119	-10000	0	119
PBX1	-0.019	0.13	-10000	0	-0.64	19	19
POU1F1	0.002	0.037	-10000	0	-0.37	3	3
SELE	-0.2	0.36	-10000	0	-0.91	68	68
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.15	0.14	0.37	73	-10000	0	73
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.23	0.21	0.5	120	-10000	0	120
mol:cortisol	0.15	0.17	0.36	130	-0.23	3	133
MMP1	-0.26	0.46	-10000	0	-1.4	60	60

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.015	0.068	-9999	-0.35	17	17
RGS9BP	-0.041	0.16	-9999	-0.52	44	44
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.003	0.052	-9999	-0.37	9	9
mol:Na +	-0.1	0.17	-9999	-0.33	143	143
mol:ADP	-0.018	0.098	-9999	-0.32	40	40
GNAT2	-0.003	0.087	-9999	-0.57	10	10
RGS9-1/Gbeta5/R9AP	-0.046	0.13	-9999	-0.45	33	33
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.01	0.058	-9999	-0.31	15	15
GRK7	-0.024	0.13	-9999	-0.47	31	31
CNGB3	-0.085	0.22	-9999	-0.55	77	77
Cone Metarhodopsin II/X-Arrestin	-0.004	0.073	-9999	-0.49	10	10
mol:Ca2+	-0.14	0.21	-9999	-0.44	126	126
Cone PDE6	-0.052	0.13	-9999	-0.38	48	48
Cone Metarhodopsin II	-0.021	0.073	-9999	-0.39	11	11
Na + (4 Units)	-0.15	0.2	-9999	-0.44	126	126
GNAT2/GDP	-0.045	0.12	-9999	-0.41	38	38
GNB5	0.009	0.031	-9999	-0.65	1	1
mol:GMP (4 units)	-0.008	0.092	-9999	-0.4	22	22
Cone Transducin	-0.015	0.072	-9999	-0.37	17	17
SLC24A2	-0.095	0.23	-9999	-0.57	83	83
GNB3/GNGT2	0.003	0.074	-9999	-0.46	11	11
GNB3	0.001	0.073	-9999	-0.57	7	7
GNAT2/GTP	-0.002	0.064	-9999	-0.42	10	10
CNGA3	-0.07	0.19	-9999	-0.5	70	70
ARR3	-0.005	0.097	-9999	-0.65	10	10
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.1	0.17	-9999	-0.33	143	143
mol:Pi	-0.046	0.13	-9999	-0.45	33	33
Cone CNG Channel	-0.1	0.15	-9999	-0.36	101	101
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.095	0.23	-9999	-0.57	83	83
RGS9	-0.018	0.12	-9999	-0.48	26	26
PDE6C	-0.013	0.12	-9999	-0.64	16	16
GNGT2	0.003	0.064	-9999	-0.6	5	5
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.001	0.039	-9999	-0.37	5	5

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.18	0.21	-9999	-0.42	162	162
SMAD6-7/SMURF1	-0.013	0.071	-9999	-0.41	14	14
NOG	-0.071	0.2	-9999	-0.56	65	65
SMAD9	-0.031	0.12	-9999	-0.72	10	10
SMAD4	0.009	0.031	-9999	-0.65	1	1
SMAD5	-0.045	0.14	-9999	-0.47	24	24
BMP7/USAG1	-0.25	0.29	-9999	-0.49	240	240
SMAD5/SKI	-0.038	0.13	-9999	-0.45	23	23
SMAD1	0.023	0.036	-9999	-0.39	1	1
BMP2	-0.019	0.13	-9999	-0.59	22	22
SMAD1/SMAD1/SMAD4	-0.011	0.052	-9999	-0.47	1	1
BMPR1A	0.007	0.044	-9999	-0.65	2	2
BMPR1B	-0.093	0.23	-9999	-0.56	82	82
BMPR1A-1B/BAMBI	-0.1	0.18	-9999	-0.46	81	81
AHSG	-0.029	0.13	-9999	-0.46	36	36
CER1	-0.013	0.077	-9999	-0.37	20	20
BMP2-4/CER1	-0.05	0.13	-9999	-0.45	35	35
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.056	0.15	-9999	-0.5	27	27
BMP2-4 (homodimer)	-0.035	0.15	-9999	-0.43	51	51
RGMB	0.007	0.036	-9999	-0.37	4	4
BMP6/BMPR2/BMPR1A-1B	-0.057	0.13	-9999	-0.38	56	56
RGMA	-0.094	0.22	-9999	-0.51	92	92
SMURF1	0.009	0.018	-9999	-0.37	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.06	0.15	-9999	-0.46	32	32
BMP2-4/USAG1	-0.16	0.21	-9999	-0.46	129	129
SMAD6/SMURF1/SMAD5	-0.038	0.13	-9999	-0.46	21	21
SOSTDC1	-0.19	0.28	-9999	-0.53	171	171
BMP7/BMPR2/BMPR1A-1B	-0.15	0.19	-9999	-0.42	127	127
SKI	0.009	0.018	-9999	-0.37	1	1
BMP6 (homodimer)	0.01	0	-9999	-10000	0	0
HFE2	-0.001	0.05	-9999	-0.37	8	8
ZFYVE16	0.01	0	-9999	-10000	0	0
MAP3K7	0.01	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.051	0.14	-9999	-0.47	43	43
SMAD5/SMAD5/SMAD4	-0.038	0.13	-9999	-0.44	25	25
MAPK1	0.01	0	-9999	-10000	0	0
TAK1/TAB family	-0.064	0.12	-9999	-0.44	24	24
BMP7 (homodimer)	-0.16	0.26	-9999	-0.52	149	149
NUP214	0.01	0	-9999	-10000	0	0
BMP6/FETUA	-0.013	0.095	-9999	-0.32	36	36
SMAD1/SKI	0.027	0.035	-9999	-0.37	1	1
SMAD6	-0.01	0.11	-9999	-0.65	14	14
CTDSP2	0.01	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.062	0.14	-9999	-0.45	46	46
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.081	0.22	-9999	-0.57	72	72
BMPR2 (homodimer)	0.01	0	-9999	-10000	0	0
GADD34/PP1CA	0	0.009	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.063	0.18	-9999	-0.5	56	56
CHRDL1	-0.17	0.27	-9999	-0.53	155	155
ENDOFIN/SMAD1	0.027	0.034	-9999	-0.37	1	1
SMAD6-7/SMURF1/SMAD1	-0.013	0.057	-9999	-0.52	1	1
SMAD6/SMURF1	0.009	0.018	-9999	-0.37	1	1
BAMBI	-0.059	0.18	-9999	-0.5	61	61
SMURF2	0.009	0.018	-9999	-0.37	1	1
BMP2-4/CHRDL1	-0.15	0.21	-9999	-0.46	114	114
BMP2-4/GREM1	-0.095	0.17	-9999	-0.44	83	83
SMAD7	0.01	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.024	0.11	-9999	-0.65	11	11
SMAD1/SMAD6	0.027	0.035	-9999	-0.37	1	1
TAK1/SMAD6	0.014	0.012	-9999	-10000	0	0
BMP7	-0.16	0.26	-9999	-0.52	149	149
BMP6	0.01	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.05	0.14	-9999	-0.41	32	32
PPM1A	0.01	0	-9999	-10000	0	0
SMAD1/SMURF2	0.027	0.035	-9999	-0.37	1	1
SMAD7/SMURF1	0.014	0.012	-9999	-0.25	1	1
CTDSPL	0.009	0.031	-9999	-0.65	1	1
PPP1CA	0.01	0	-9999	-10000	0	0
XIAP	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
PPP1R15A	0.009	0.018	-9999	-0.37	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.099	0.21	-9999	-0.58	49	49
CHRD	-0.007	0.1	-9999	-0.63	12	12
BMPR2	0.01	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.069	0.16	-9999	-0.5	32	32
BMP4	-0.03	0.15	-9999	-0.54	33	33
FST	-0.079	0.18	-9999	-0.42	94	94
BMP2-4/NOG	-0.088	0.18	-9999	-0.46	72	72
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.14	0.18	-9999	-0.4	127	127

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.004	0.041	-9999	-0.34	6	6
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.095	0.19	-9999	-0.38	127	127
STXBP1	-0.004	0.09	-9999	-0.54	12	12
ACh/CHRNA1	-0.035	0.12	-9999	-0.4	42	42
RAB3GAP2/RIMS1/UNC13B	-0.088	0.15	-9999	-0.42	70	70
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.14	0.25	-9999	-0.52	124	124
mol:ACh	-0.009	0.04	-9999	-0.14	34	34
RAB3GAP2	0.01	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.085	0.13	-9999	-0.33	79	79
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.035	0.12	-9999	-0.4	42	42
UNC13B	0.004	0.062	-9999	-0.65	4	4
CHRNA1	-0.043	0.17	-9999	-0.58	41	41
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.1	0.18	-9999	-0.41	113	113
SNAP25	-0.029	0.088	-9999	-0.2	79	79
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.14	0.27	-9999	-0.6	113	113
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.001	0.067	-9999	-0.31	18	18
STX1A/SNAP25 fragment 1/VAMP2	-0.085	0.13	-9999	-0.33	79	79

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.004	0.062	-9999	-0.65	4	4
CCL5	-0.044	0.17	-9999	-0.56	43	43
SDCBP	0.01	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.1	0.18	-9999	-0.49	47	47
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.1	0.18	-9999	-0.46	54	54
Syndecan-1/Syntenin	-0.093	0.17	-9999	-0.48	45	45
MAPK3	-0.074	0.16	-9999	-0.5	29	29
HGF/MET	-0.022	0.12	-9999	-0.37	43	43
TGFB1/TGF beta receptor Type II	0.004	0.061	-9999	-0.65	4	4
BSG	0.01	0	-9999	-10000	0	0
keratinocyte migration	-0.099	0.18	-9999	-0.45	54	54
Syndecan-1/RANTES	-0.12	0.2	-9999	-0.5	70	70
Syndecan-1/CD147	-0.084	0.17	-9999	-0.48	38	38
Syndecan-1/Syntenin/PIP2	-0.11	0.16	-9999	-0.46	45	45
LAMA5	-0.004	0.097	-9999	-0.65	10	10
positive regulation of cell-cell adhesion	-0.1	0.15	-9999	-0.45	45	45
MMP7	-0.16	0.26	-9999	-0.51	152	152
HGF	-0.028	0.15	-9999	-0.55	31	31
Syndecan-1/CASK	-0.099	0.17	-9999	-0.48	45	45
Syndecan-1/HGF/MET	-0.11	0.19	-9999	-0.48	56	56
regulation of cell adhesion	-0.067	0.16	-9999	-0.48	29	29
HPSE	-0.002	0.085	-9999	-0.59	9	9
positive regulation of cell migration	-0.1	0.18	-9999	-0.49	47	47
SDC1	-0.1	0.18	-9999	-0.51	45	45
Syndecan-1/Collagen	-0.1	0.18	-9999	-0.49	47	47
PPIB	0.01	0	-9999	-10000	0	0
MET	-0.002	0.073	-9999	-0.42	13	13
PRKACA	0.01	0	-9999	-10000	0	0
MMP9	-0.034	0.15	-9999	-0.53	37	37
MAPK1	-0.074	0.16	-9999	-0.5	29	29
homophilic cell adhesion	-0.1	0.18	-9999	-0.38	91	91
MMP1	-0.099	0.23	-9999	-0.56	87	87

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.01	0	-9999	-10000	0	0
GNAT1/GTP	-0.004	0.047	-9999	-0.26	15	15
Metarhodopsin II/Arrestin	-0.004	0.031	-9999	-0.41	1	1
PDE6G/GNAT1/GTP	-0.02	0.08	-9999	-0.3	31	31
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.006	0.068	-9999	-0.37	15	15
GRK1	-0.003	0.052	-9999	-0.37	9	9
CNG Channel	-0.11	0.17	-9999	-0.4	96	96
mol:Na +	-0.13	0.16	-9999	-0.35	132	132
mol:ADP	-0.003	0.052	-9999	-0.37	9	9
RGS9-1/Gbeta5/R9AP	-0.046	0.13	-9999	-0.45	33	33
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.13	0.17	-9999	-0.36	132	132
CNGB1	-0.097	0.2	-9999	-0.46	104	104
RDH5	0.01	0	-9999	-10000	0	0
SAG	0.004	0.025	-9999	-0.37	2	2
mol:Ca2+	-0.1	0.17	-9999	-0.54	24	24
Na + (4 Units)	-0.12	0.15	-9999	-0.53	24	24
RGS9	-0.018	0.12	-9999	-0.48	26	26
GNB1/GNGT1	-0.11	0.2	-9999	-0.41	138	138
GNAT1/GDP	-0.045	0.12	-9999	-0.39	35	35
GUCY2D	-0.065	0.18	-9999	-0.48	70	70
GNGT1	-0.16	0.27	-9999	-0.56	138	138
GUCY2F	0.002	0.031	-9999	-0.37	3	3
GNB5	0.009	0.031	-9999	-0.65	1	1
mol:GMP (4 units)	-0.033	0.14	-9999	-0.42	43	43
mol:11-cis-retinal	0.01	0	-9999	-10000	0	0
mol:cGMP	-0.057	0.15	-9999	-0.39	59	59
GNB1	0.01	0	-9999	-10000	0	0
Rhodopsin	0.007	0.03	-9999	-10000	0	0
SLC24A1	0.01	0	-9999	-10000	0	0
CNGA1	-0.03	0.14	-9999	-0.5	36	36
Metarhodopsin II	-0.006	0.034	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.077	0.15	-9999	-0.41	59	59
RGS9BP	-0.041	0.16	-9999	-0.52	44	44
Metarhodopsin II/Transducin	-0.064	0.12	-9999	-0.3	94	94
GCAP Family/Ca ++	-0.039	0.11	-9999	-0.4	31	31
PDE6A/B	-0.036	0.14	-9999	-0.39	57	57
mol:Pi	-0.046	0.13	-9999	-0.45	33	33
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.1	0.16	-9999	-0.38	96	96
PDE6B	-0.016	0.11	-9999	-0.48	24	24
PDE6A	-0.035	0.16	-9999	-0.53	38	38
PDE6G	-0.012	0.11	-9999	-0.54	18	18
RHO	-0.001	0.043	-9999	-0.37	6	6
PDE6	-0.079	0.16	-9999	-0.4	72	72
GUCA1A	-0.036	0.16	-9999	-0.55	37	37
GC2/GCAP Family	-0.04	0.11	-9999	-0.4	32	32
GUCA1C	-0.007	0.06	-9999	-0.37	12	12
GUCA1B	-0.007	0.096	-9999	-0.53	14	14

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.01	0	-9999	-10000	0	0
LAT2	-0.084	0.21	-9999	-0.52	58	58
AP1	-0.096	0.19	-9999	-0.63	40	40
mol:PIP3	-0.089	0.22	-9999	-0.59	48	48
IKBKB	-0.041	0.12	-9999	-0.31	43	43
AKT1	-0.087	0.2	-9999	-0.57	40	40
IKBKG	-0.043	0.12	-9999	-0.32	43	43
MS4A2	-0.058	0.19	-9999	-0.56	54	54
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.009	0.018	-9999	-0.37	1	1
MAP3K1	-0.05	0.18	-9999	-0.55	37	37
mol:Ca2+	-0.062	0.16	-9999	-0.42	48	48
LYN	0.002	0.063	-9999	-0.67	4	4
CBLB	-0.081	0.2	-9999	-0.51	57	57
SHC1	0.01	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.013	0.066	-9999	-0.39	12	12
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.008	0.11	-9999	-0.59	14	14
PLD2	-0.12	0.23	-9999	-0.48	97	97
PTPN13	-0.11	0.22	-9999	-0.65	45	45
PTPN11	0.005	0.01	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.046	0.15	-9999	-0.39	38	38
SYK	0.004	0.054	-9999	-0.66	3	3
GRB2	0.01	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.2	-9999	-0.56	59	59
LAT	-0.081	0.2	-9999	-0.51	57	57
PAK2	-0.064	0.2	-9999	-0.6	42	42
NFATC2	-0.093	0.2	-9999	-0.71	34	34
HRAS	-0.078	0.23	-9999	-0.67	43	43
GAB2	0.006	0.053	-9999	-0.65	3	3
PLA2G1B	0.023	0.017	-9999	-10000	0	0
Fc epsilon R1	-0.098	0.2	-9999	-0.49	76	76
Antigen/IgE/Fc epsilon R1	-0.16	0.24	-9999	-0.5	125	125
mol:GDP	-0.086	0.24	-9999	-0.72	43	43
JUN	0.009	0.018	-9999	-0.37	1	1
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.009	0.001	-9999	-10000	0	0
FOS	-0.014	0.12	-9999	-0.58	19	19
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.092	0.21	-9999	-0.55	57	57
CHUK	-0.041	0.12	-9999	-0.31	43	43
KLRG1	-0.086	0.2	-9999	-0.56	49	49
VAV1	-0.087	0.22	-9999	-0.54	59	59
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.081	0.2	-9999	-0.51	57	57
negative regulation of mast cell degranulation	-0.083	0.2	-9999	-0.54	54	54
BTK	-0.093	0.26	-9999	-0.78	41	41
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.068	0.22	-9999	-0.47	72	72
GAB2/PI3K/SHP2	-0.13	0.2	-9999	-0.62	43	43
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.1	0.24	-9999	-0.43	104	104
RAF1	0.014	0.02	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.1	0.22	-9999	-0.47	89	89
FCER1G	-0.01	0.11	-9999	-0.64	13	13
FCER1A	-0.084	0.2	-9999	-0.48	86	86
Antigen/IgE/Fc epsilon R1/Fyn	-0.15	0.23	-9999	-0.47	125	125
MAPK3	0.022	0.017	-9999	-10000	0	0
MAPK1	0.022	0.017	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.009	0.074	-9999	-0.48	5	5
DUSP1	-0.005	0.092	-9999	-0.52	13	13
NF-kappa-B/RelA	-0.038	0.06	-9999	-0.23	10	10
actin cytoskeleton reorganization	-0.078	0.2	-9999	-0.62	38	38
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.093	0.2	-9999	-0.64	38	38
FER	-0.085	0.2	-9999	-0.5	63	63
RELA	0.01	0	-9999	-10000	0	0
ITK	-0.053	0.14	-9999	-0.6	26	26
SOS1	0.01	0	-9999	-10000	0	0
PLCG1	-0.085	0.24	-9999	-0.71	43	43
cytokine secretion	-0.028	0.043	-9999	-10000	0	0
SPHK1	-0.087	0.21	-9999	-0.52	61	61
PTK2	-0.082	0.21	-9999	-0.66	38	38
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.13	0.22	-9999	-0.59	60	60
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.084	0.21	-9999	-0.57	48	48
MAP2K2	0.019	0.018	-9999	-10000	0	0
MAP2K1	0.019	0.018	-9999	-10000	0	0
MAP2K7	0.009	0.031	-9999	-0.65	1	1
KLRG1/SHP2	-0.1	0.18	-9999	-0.55	45	45
MAP2K4	0.004	0.088	-9999	-0.92	4	4
Fc epsilon R1/FcgammaRIIB	-0.1	0.22	-9999	-0.48	84	84
mol:Choline	-0.12	0.22	-9999	-0.47	97	97
SHC/Grb2/SOS1	-0.091	0.18	-9999	-0.57	39	39
FYN	0.009	0.031	-9999	-0.65	1	1
DOK1	0.002	0.071	-9999	-0.6	6	6
PXN	-0.073	0.19	-9999	-0.61	37	37
HCLS1	-0.089	0.23	-9999	-0.55	59	59
PRKCB	-0.067	0.17	-9999	-0.43	53	53
FCGR2B	-0.019	0.13	-9999	-0.61	21	21
IGHE	-0.14	0.25	-9999	-0.54	121	121
KLRG1/SHIP	-0.085	0.21	-9999	-0.56	54	54
LCP2	0.004	0.062	-9999	-0.66	4	4
PLA2G4A	-0.11	0.23	-9999	-0.52	78	78
RASA1	0.01	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.12	0.22	-9999	-0.47	97	97
IKK complex	-0.022	0.092	-9999	-0.24	35	35
WIPF1	-0.001	0.083	-9999	-0.62	8	8

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.003	0.072	-9999	-0.48	3	3
VLDLR	-0.044	0.18	-9999	-0.61	40	40
CRKL	0.009	0.018	-9999	-0.37	1	1
LRPAP1	0.01	0	-9999	-10000	0	0
FYN	0.009	0.031	-9999	-0.65	1	1
ITGA3	0	0.073	-9999	-0.5	9	9
RELN/VLDLR/Fyn	-0.094	0.18	-9999	-0.46	76	76
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.011	0.058	-9999	-0.39	7	7
AKT1	-0.034	0.12	-9999	-0.29	76	76
MAP2K7	0.009	0.031	-9999	-0.65	1	1
RAPGEF1	0.01	0	-9999	-10000	0	0
DAB1	0.009	0.018	-9999	-0.37	1	1
RELN/LRP8/DAB1	-0.066	0.14	-9999	-0.39	60	60
LRPAP1/LRP8	0.001	0.079	-9999	-0.43	14	14
RELN/LRP8/DAB1/Fyn	-0.061	0.13	-9999	-0.36	61	61
DAB1/alpha3/beta1 Integrin	-0.083	0.15	-9999	-0.58	14	14
long-term memory	-0.15	0.2	-9999	-0.4	146	146
DAB1/LIS1	-0.082	0.15	-9999	-0.37	86	86
DAB1/CRLK/C3G	-0.079	0.14	-9999	-0.58	14	14
PIK3CA	0.009	0.018	-9999	-0.37	1	1
DAB1/NCK2	-0.082	0.15	-9999	-0.37	86	86
ARHGEF2	0.01	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.13	0.24	-9999	-0.52	121	121
CDK5R1	-0.015	0.1	-9999	-0.4	28	28
RELN	-0.092	0.22	-9999	-0.54	86	86
PIK3R1	0.01	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.072	0.15	-9999	-0.42	61	61
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.13	0.18	-9999	-0.39	127	127
MAPK8	0.009	0.031	-9999	-0.65	1	1
RELN/VLDLR/DAB1	-0.085	0.16	-9999	-0.42	76	76
ITGB1	0.01	0	-9999	-10000	0	0
MAP1B	-0.074	0.18	-9999	-0.38	97	97
RELN/LRP8	-0.072	0.15	-9999	-0.42	60	60
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.093	0.15	-9999	-0.39	80	80
PI3K	0.014	0.012	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.008	0.054	-9999	-0.48	4	4
RAP1A	-0.042	0.15	-9999	-0.54	14	14
PAFAH1B1	0.01	0	-9999	-10000	0	0
MAPK8IP1	-0.012	0.1	-9999	-0.45	22	22
CRLK/C3G	0.014	0.012	-9999	-0.25	1	1
GRIN2B	-0.064	0.17	-9999	-0.43	75	75
NCK2	0.01	0	-9999	-10000	0	0
neuron differentiation	-0.01	0.091	-9999	-0.37	8	8
neuron adhesion	-0.035	0.15	-9999	-0.51	14	14
LRP8	-0.008	0.11	-9999	-0.59	14	14
GSK3B	-0.027	0.12	-9999	-0.47	10	10
RELN/VLDLR/DAB1/Fyn	-0.08	0.16	-9999	-0.39	76	76
MAP3K11	0.01	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.043	0.13	-9999	-0.32	76	76
CDK5	0.01	0	-9999	-10000	0	0
MAPT	-0.054	0.17	-9999	-0.45	64	64
neuron migration	-0.039	0.16	-9999	-0.51	19	19
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.01	0.092	-9999	-0.37	8	8
RELN/VLDLR	-0.094	0.17	-9999	-0.42	86	86

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.031	0.17	0.24	26	-0.44	46	72
IKBKB	-0.023	0.081	-10000	0	-0.27	14	14
AKT1	-0.045	0.11	0.21	1	-0.27	57	58
IKBKG	-0.026	0.085	-10000	0	-0.29	16	16
CALM1	-0.057	0.16	-10000	0	-0.5	38	38
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
MAP3K1	-0.079	0.23	-10000	0	-0.64	52	52
MAP3K7	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	-0.067	0.17	-10000	0	-0.54	38	38
DOK1	0.002	0.071	-10000	0	-0.6	6	6
AP-1	-0.008	0.11	0.22	26	-0.25	40	66
LYN	0.004	0.062	-10000	0	-0.65	4	4
BLNK	-0.023	0.14	-10000	0	-0.65	23	23
SHC1	0.01	0	-10000	0	-10000	0	0
BCR complex	-0.12	0.24	-10000	0	-0.52	108	108
CD22	-0.14	0.3	-10000	0	-0.62	96	96
CAMK2G	-0.048	0.15	-10000	0	-0.46	38	38
CSNK2A1	-0.036	0.17	-10000	0	-0.65	32	32
INPP5D	-0.008	0.11	-10000	0	-0.59	14	14
SHC/GRB2/SOS1	-0.095	0.18	-10000	0	-0.65	30	30
GO:0007205	-0.068	0.18	-10000	0	-0.56	38	38
SYK	0.006	0.053	-10000	0	-0.65	3	3
ELK1	-0.058	0.16	-10000	0	-0.52	38	38
NFATC1	-0.076	0.21	-10000	0	-0.53	61	61
B-cell antigen/BCR complex	-0.12	0.24	-10000	0	-0.52	108	108
PAG1/CSK	0.005	0.049	-10000	0	-0.48	4	4
NFKBIB	0	0.028	-10000	0	-0.088	1	1
HRAS	-0.057	0.16	-10000	0	-0.5	39	39
NFKBIA	0	0.027	-10000	0	-0.086	1	1
NF-kappa-B/RelA/I kappa B beta	0.005	0.022	-10000	0	-10000	0	0
RasGAP/Csk	-0.1	0.21	-10000	0	-0.46	95	95
mol:GDP	-0.064	0.16	-10000	0	-0.52	38	38
PTEN	0.006	0.053	-10000	0	-0.65	3	3
CD79B	-0.043	0.16	-10000	0	-0.5	48	48
NF-kappa-B/RelA/I kappa B alpha	0.006	0.022	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.096	0.23	-10000	0	-0.54	80	80
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.069	0.18	-10000	0	-0.57	38	38
CSK	0.01	0	-10000	0	-10000	0	0
FOS	-0.06	0.16	-10000	0	-0.45	51	51
CHUK	-0.023	0.086	-10000	0	-0.29	15	15
IBTK	0.01	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.079	0.16	-10000	0	-0.5	41	41
PTPN6	-0.13	0.28	-10000	0	-0.72	62	62
RELA	0.01	0	-10000	0	-10000	0	0
BCL2A1	0.004	0.027	-10000	0	-0.11	14	14
VAV2	-0.14	0.29	-10000	0	-0.78	60	60
ubiquitin-dependent protein catabolic process	0.003	0.027	-10000	0	-10000	0	0
BTK	-0.034	0.21	0.38	7	-1.1	16	23
CD19	-0.15	0.31	-10000	0	-0.69	83	83
MAP4K1	-0.01	0.1	-10000	0	-0.52	17	17
CD72	0.004	0.05	-10000	0	-0.42	6	6
PAG1	0.003	0.066	-10000	0	-0.56	6	6
MAPK14	-0.059	0.19	-10000	0	-0.52	51	51
SH3BP5	0.01	0	-10000	0	-10000	0	0
PIK3AP1	-0.079	0.21	-10000	0	-0.54	56	56
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.082	0.23	-10000	0	-0.56	69	69
RAF1	-0.048	0.15	-10000	0	-0.48	36	36
RasGAP/p62DOK/SHIP	-0.11	0.23	-10000	0	-0.49	97	97
CD79A	-0.12	0.24	-10000	0	-0.56	102	102
re-entry into mitotic cell cycle	-0.009	0.11	0.21	26	-0.25	40	66
RASA1	0.01	0	-10000	0	-10000	0	0
MAPK3	-0.029	0.13	-10000	0	-0.42	30	30
MAPK1	-0.029	0.13	-10000	0	-0.42	30	30
CD72/SHP1	-0.097	0.26	-10000	0	-0.76	48	48
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	-0.059	0.19	-10000	0	-0.53	51	51
actin cytoskeleton organization	-0.091	0.24	-10000	0	-0.62	60	60
NF-kappa-B/RelA	0.014	0.044	-10000	0	-10000	0	0
Calcineurin	-0.055	0.13	-10000	0	-0.46	30	30
PI3K	-0.12	0.21	-10000	0	-0.53	77	77
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.082	0.19	-10000	0	-0.6	41	41
SOS1	0.01	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.11	0.3	-10000	0	-0.9	50	50
DAPP1	-0.15	0.33	-10000	0	-1	48	48
cytokine secretion	-0.069	0.19	-10000	0	-0.49	61	61
mol:DAG	-0.069	0.18	-10000	0	-0.57	38	38
PLCG2	-0.003	0.085	-10000	0	-0.52	11	11
MAP2K1	-0.039	0.14	-10000	0	-0.46	32	32
B-cell antigen/BCR complex/FcgammaRIIB	-0.12	0.24	-10000	0	-0.54	95	95
mol:PI-3-4-5-P3	-0.084	0.14	0.29	1	-0.36	75	76
ETS1	-0.038	0.13	-10000	0	-0.43	35	35
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.11	0.21	-10000	0	-0.46	106	106
B-cell antigen/BCR complex/LYN	-0.12	0.28	-10000	0	-0.65	72	72
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
RAC1	-0.1	0.26	-10000	0	-0.68	60	60
B-cell antigen/BCR complex/LYN/SYK	-0.14	0.28	-10000	0	-0.72	61	61
CARD11	-0.088	0.2	-10000	0	-0.52	61	61
FCGR2B	-0.019	0.13	-10000	0	-0.61	21	21
PPP3CA	0.01	0	-10000	0	-10000	0	0
BCL10	0.01	0	-10000	0	-10000	0	0
IKK complex	-0.004	0.036	-10000	0	-0.1	7	7
PTPRC	-0.03	0.16	-10000	0	-0.6	30	30
PDPK1	-0.053	0.12	0.2	1	-0.27	59	60
PPP3CB	0.01	0	-10000	0	-10000	0	0
PPP3CC	0.009	0.031	-10000	0	-0.65	1	1
POU2F2	0.006	0.021	-10000	0	-0.13	2	2

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.068	0.18	-10000	0	-0.59	40	40
FYN	-0.047	0.27	-10000	0	-0.73	49	49
LAT/GRAP2/SLP76	-0.064	0.21	-10000	0	-0.61	48	48
IKBKB	0.01	0	-10000	0	-10000	0	0
AKT1	-0.023	0.17	-10000	0	-0.46	49	49
B2M	0.01	0.004	-10000	0	-10000	0	0
IKBKG	-0.027	0.047	-10000	0	-0.15	31	31
MAP3K8	0.009	0.018	-10000	0	-0.37	1	1
mol:Ca2+	-0.029	0.041	-10000	0	-0.09	133	133
integrin-mediated signaling pathway	-0.003	0.033	-10000	0	-0.41	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.037	0.25	-10000	0	-0.66	52	52
TRPV6	-0.15	0.25	-10000	0	-0.53	133	133
CD28	-0.016	0.12	-10000	0	-0.59	20	20
SHC1	-0.045	0.26	-10000	0	-0.73	46	46
receptor internalization	-0.058	0.29	-10000	0	-0.8	48	48
PRF1	-0.057	0.3	-10000	0	-1.1	32	32
KRAS	-0.007	0.078	-10000	0	-0.37	20	20
GRB2	0.01	0	-10000	0	-10000	0	0
COT/AKT1	-0.011	0.13	-10000	0	-0.38	41	41
LAT	-0.045	0.26	-10000	0	-0.74	45	45
EntrezGene:6955	0	0.003	-10000	0	-10000	0	0
CD3D	-0.027	0.15	-10000	0	-0.61	28	28
CD3E	-0.01	0.11	-10000	0	-0.61	15	15
CD3G	-0.034	0.16	-10000	0	-0.62	33	33
RASGRP2	-0.001	0.029	-10000	0	-0.17	7	7
RASGRP1	-0.01	0.17	-10000	0	-0.47	48	48
HLA-A	0.006	0.054	-10000	0	-0.66	3	3
RASSF5	0.006	0.053	-10000	0	-0.65	3	3
RAP1A/GTP/RAPL	-0.003	0.034	-10000	0	-0.42	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.051	-10000	0	-0.12	40	40
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.047	0.083	-10000	0	-0.25	46	46
PRKCA	-0.026	0.098	-10000	0	-0.28	44	44
GRAP2	-0.021	0.14	-10000	0	-0.6	23	23
mol:IP3	-0.004	0.18	0.21	111	-0.45	43	154
EntrezGene:6957	0	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.065	0.32	-10000	0	-0.89	42	42
ORAI1	0.085	0.13	0.29	133	-10000	0	133
CSK	-0.048	0.26	-10000	0	-0.76	45	45
B7 family/CD28	-0.1	0.26	-10000	0	-0.78	49	49
CHUK	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.066	0.31	-10000	0	-0.88	48	48
PTPN6	-0.05	0.26	-10000	0	-0.74	47	47
VAV1	-0.049	0.27	-10000	0	-0.73	50	50
Monovalent TCR/CD3	-0.049	0.26	-10000	0	-0.73	42	42
CBL	0.01	0	-10000	0	-10000	0	0
LCK	-0.056	0.29	-10000	0	-0.8	48	48
PAG1	-0.05	0.26	-10000	0	-0.77	45	45
RAP1A	0.01	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.065	0.31	-10000	0	-0.83	51	51
CD80	-0.008	0.1	-10000	0	-0.58	14	14
CD86	-0.01	0.11	-10000	0	-0.64	14	14
PDK1/CARD11/BCL10/MALT1	-0.057	0.1	-10000	0	-0.31	46	46
HRAS	0.01	0	-10000	0	-10000	0	0
GO:0035030	-0.038	0.22	-10000	0	-0.62	49	49
CD8A	-0.045	0.18	-10000	0	-0.57	44	44
CD8B	-0.051	0.18	-10000	0	-0.57	49	49
PTPRC	-0.031	0.16	-10000	0	-0.61	30	30
PDK1/PKC theta	-0.037	0.21	-10000	0	-0.58	48	48
CSK/PAG1	-0.044	0.26	-10000	0	-0.79	40	40
SOS1	0.01	0	-10000	0	-10000	0	0
peptide-MHC class I	0.012	0.041	-10000	0	-0.49	3	3
GRAP2/SLP76	-0.079	0.25	-10000	0	-0.71	50	50
STIM1	0.043	0.066	-10000	0	-10000	0	0
RAS family/GTP	0.016	0.069	-10000	0	-0.18	34	34
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.068	0.33	-10000	0	-0.9	48	48
mol:DAG	-0.029	0.14	-10000	0	-0.4	44	44
RAP1A/GDP	0.008	0.022	-10000	0	-0.064	3	3
PLCG1	0.01	0	-10000	0	-10000	0	0
CD247	-0.023	0.14	-10000	0	-0.64	24	24
cytotoxic T cell degranulation	-0.052	0.28	-10000	0	-0.96	33	33
RAP1A/GTP	-0.003	0.009	-10000	0	-0.069	6	6
mol:PI-3-4-5-P3	-0.022	0.2	-10000	0	-0.53	52	52
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.019	0.23	0.22	107	-0.6	43	150
NRAS	0.008	0.036	-10000	0	-0.51	2	2
ZAP70	-0.024	0.14	-10000	0	-0.55	28	28
GRB2/SOS1	0.015	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.06	0.2	-10000	0	-0.6	45	45
MALT1	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.065	0.22	-10000	0	-0.59	59	59
CARD11	-0.053	0.18	-10000	0	-0.54	53	53
PRKCB	-0.035	0.12	-10000	0	-0.33	49	49
PRKCE	-0.022	0.093	-10000	0	-0.28	40	40
PRKCQ	-0.032	0.24	-10000	0	-0.64	52	52
LCP2	0.004	0.062	-10000	0	-0.65	4	4
BCL10	0.01	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.016	0.14	-10000	0	-0.39	48	48
IKK complex	0.014	0.052	-10000	0	-0.11	32	32
RAS family/GDP	-0.005	0.012	-10000	0	-0.074	2	2
MAP3K14	-0.001	0.1	-10000	0	-0.29	36	36
PDPK1	-0.029	0.17	-10000	0	-0.47	44	44
TCR/CD3/MHC I/CD8/Fyn	-0.069	0.32	-10000	0	-0.9	47	47

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.007	0.061	-10000	0	-0.8	2	2
NFATC2	-0.048	0.24	-10000	0	-0.71	43	43
NFATC3	-0.009	0.066	-10000	0	-0.29	2	2
CD40LG	-0.19	0.42	-10000	0	-1	70	70
ITCH	-0.002	0.099	-10000	0	-10000	0	0
CBLB	-0.002	0.099	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.17	0.35	-10000	0	-1.1	46	46
JUNB	0.009	0.031	-10000	0	-0.65	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.041	0.11	-10000	0	-0.32	60	60
T cell anergy	-0.044	0.17	-10000	0	-0.46	60	60
TLE4	-0.028	0.2	-10000	0	-0.63	34	34
Jun/NFAT1-c-4/p21SNFT	-0.14	0.32	-10000	0	-0.94	47	47
AP-1/NFAT1-c-4	-0.19	0.45	-10000	0	-1.1	63	63
IKZF1	-0.042	0.25	-10000	0	-0.85	31	31
T-helper 2 cell differentiation	-0.056	0.24	-10000	0	-0.77	35	35
AP-1/NFAT1	-0.081	0.18	-10000	0	-0.56	45	45
CALM1	-0.004	0.065	-10000	0	-10000	0	0
EGR2	-0.083	0.36	-10000	0	-1.1	34	34
EGR3	-0.082	0.35	-10000	0	-1.1	34	34
NFAT1/FOXP3	-0.029	0.2	-10000	0	-0.63	35	35
EGR1	-0.002	0.08	-10000	0	-0.52	10	10
JUN	-0.003	0.032	-10000	0	-0.4	1	1
EGR4	-0.1	0.23	-10000	0	-0.55	92	92
mol:Ca2+	-0.015	0.068	-10000	0	-10000	0	0
GBP3	-0.052	0.27	-10000	0	-0.81	41	41
FOSL1	-0.053	0.18	-10000	0	-0.53	53	53
NFAT1-c-4/MAF/IRF4	-0.14	0.34	-10000	0	-1	50	50
DGKA	-0.02	0.18	-10000	0	-0.6	29	29
CREM	0.01	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.17	0.33	-10000	0	-0.94	54	54
CTLA4	-0.031	0.22	-10000	0	-0.72	33	33
NFAT1-c-4 (dimer)/EGR1	-0.095	0.33	-10000	0	-0.98	42	42
NFAT1-c-4 (dimer)/EGR4	-0.15	0.35	-10000	0	-0.96	52	52
FOS	-0.027	0.13	-10000	0	-0.61	19	19
IFNG	-0.21	0.44	-10000	0	-1.2	67	67
T cell activation	-0.064	0.21	-10000	0	-0.68	21	21
MAF	-0.012	0.11	-10000	0	-0.54	18	18
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.057	0.26	0.8	34	-10000	0	34
TNF	-0.15	0.34	-10000	0	-0.93	53	53
FASLG	-0.15	0.49	-10000	0	-1.5	49	49
TBX21	-0.036	0.16	-10000	0	-0.62	29	29
BATF3	0.006	0.053	-10000	0	-0.65	3	3
PRKCQ	-0.026	0.15	-10000	0	-0.62	26	26
PTPN1	-0.019	0.18	-10000	0	-0.59	28	28
NFAT1-c-4/ICER1	-0.13	0.3	-10000	0	-0.93	44	44
GATA3	-0.009	0.1	-10000	0	-0.49	19	19
T-helper 1 cell differentiation	-0.17	0.44	-10000	0	-1.1	68	68
IL2RA	-0.16	0.32	-10000	0	-0.98	48	48
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.019	0.18	-10000	0	-0.58	29	29
E2F1	0.009	0.056	-10000	0	-0.58	4	4
PPARG	-0.064	0.21	-10000	0	-0.64	52	52
SLC3A2	-0.019	0.18	-10000	0	-0.64	22	22
IRF4	-0.041	0.17	-10000	0	-0.56	41	41
PTGS2	-0.19	0.41	-10000	0	-0.98	68	68
CSF2	-0.2	0.41	-10000	0	-0.93	78	78
JunB/Fra1/NFAT1-c-4	-0.14	0.31	-10000	0	-0.94	43	43
IL4	-0.06	0.26	-10000	0	-0.81	35	35
IL5	-0.17	0.37	-10000	0	-0.93	61	61
IL2	-0.065	0.22	-10000	0	-0.71	18	18
IL3	-0.041	0.053	-10000	0	-10000	0	0
RNF128	-0.065	0.26	-10000	0	-0.73	60	60
NFATC1	-0.057	0.26	-10000	0	-0.81	34	34
CDK4	0.038	0.16	0.58	14	-10000	0	14
PTPRK	-0.021	0.19	-10000	0	-0.63	26	26
IL8	-0.21	0.42	-10000	0	-0.93	88	88
POU2F1	0.011	0.004	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.031	0.16	-9999	-0.64	29	29
GNB1/GNG2	-0.084	0.18	-9999	-0.54	35	35
mol:DAG	-0.071	0.16	-9999	-0.55	25	25
PLCG1	-0.073	0.17	-9999	-0.58	25	25
YES1	-0.092	0.19	-9999	-0.57	34	34
FZD3	-0.001	0.083	-9999	-0.62	8	8
FZD6	-0.014	0.11	-9999	-0.45	24	24
G protein	-0.075	0.17	-9999	-0.58	25	25
MAP3K7	-0.076	0.16	-9999	-0.48	40	40
mol:Ca2+	-0.069	0.16	-9999	-0.53	25	25
mol:IP3	-0.071	0.16	-9999	-0.55	25	25
NLK	-0.005	0.009	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
CAMK2A	-0.088	0.18	-9999	-0.53	41	41
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.1	0.19	-9999	-0.37	115	115
CSNK1A1	0.01	0	-9999	-10000	0	0
GNAS	-0.091	0.18	-9999	-0.56	33	33
GO:0007205	-0.069	0.16	-9999	-0.54	25	25
WNT6	-0.047	0.16	-9999	-0.48	53	53
WNT4	-0.066	0.2	-9999	-0.55	63	63
NFAT1/CK1 alpha	-0.089	0.19	-9999	-0.55	41	41
GNG2	0.006	0.047	-9999	-0.56	3	3
WNT5A	-0.019	0.12	-9999	-0.44	30	30
WNT11	-0.12	0.24	-9999	-0.5	121	121
CDC42	-0.082	0.18	-9999	-0.54	34	34

×

Endothelins

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
AKT1	0.017	0.18	-10000	0	-0.63	20	20
PTK2B	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0.021	0.16	-10000	0	-0.76	9	9
EDN1	0.013	0.13	-10000	0	-0.43	18	18
EDN3	-0.19	0.28	-10000	0	-0.55	167	167
EDN2	-0.1	0.22	-10000	0	-0.52	98	98
HRAS/GDP	-0.016	0.18	-10000	0	-0.55	30	30
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.007	0.14	-10000	0	-0.46	24	24
ADCY4	-0.003	0.17	-10000	0	-0.51	32	32
ADCY5	-0.049	0.22	-10000	0	-0.54	52	52
ADCY6	-0.005	0.18	-10000	0	-0.55	28	28
ADCY7	-0.003	0.17	-10000	0	-0.51	32	32
ADCY1	-0.013	0.18	-10000	0	-0.53	32	32
ADCY2	-0.052	0.23	-10000	0	-0.51	61	61
ADCY3	-0.003	0.17	-10000	0	-0.52	30	30
ADCY8	-0.014	0.17	-10000	0	-0.5	34	34
ADCY9	-0.003	0.17	-10000	0	-0.54	28	28
arachidonic acid secretion	-0.015	0.18	-10000	0	-0.55	35	35
ETB receptor/Endothelin-1/Gq/GTP	-0.003	0.14	-10000	0	-0.44	30	30
GNAO1	-0.05	0.16	-10000	0	-0.45	60	60
HRAS	0.01	0.002	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.008	0.2	0.36	52	-0.6	19	71
ETA receptor/Endothelin-1/Gs/GTP	-0.008	0.2	0.33	52	-0.53	32	84
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
COL3A1	0.004	0.23	-10000	0	-0.86	20	20
EDNRB	-0.01	0.12	-10000	0	-0.6	16	16
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.004	0.24	-10000	0	-0.85	26	26
CYSLTR1	0	0.23	-10000	0	-0.79	24	24
SLC9A1	-0.002	0.11	0.19	48	-0.38	14	62
mol:GDP	-0.023	0.19	-10000	0	-0.57	33	33
SLC9A3	-0.086	0.25	-10000	0	-0.55	89	89
RAF1	-0.021	0.17	-10000	0	-0.52	34	34
JUN	0.026	0.14	-10000	0	-0.64	9	9
JAK2	0.014	0.19	-10000	0	-0.63	21	21
mol:IP3	0.001	0.15	-10000	0	-0.52	25	25
ETA receptor/Endothelin-1	0.004	0.24	0.43	52	-0.72	20	72
PLCB1	-0.018	0.13	-10000	0	-0.62	20	20
PLCB2	0.006	0.047	-10000	0	-0.56	3	3
ETA receptor/Endothelin-3	-0.15	0.23	-10000	0	-0.49	113	113
FOS	-0.017	0.21	-10000	0	-0.76	26	26
Gai/GDP	-0.029	0.18	-10000	0	-0.82	17	17
CRK	0.01	0	-10000	0	-10000	0	0
mol:Ca ++	-0.001	0.22	-10000	0	-0.71	27	27
BCAR1	0.01	0	-10000	0	-10000	0	0
PRKCB1	0.001	0.15	-10000	0	-0.5	25	25
GNAQ	0.011	0.003	-10000	0	-10000	0	0
GNAZ	-0.032	0.15	-10000	0	-0.55	34	34
GNAL	-0.021	0.13	-10000	0	-0.52	27	27
Gs family/GDP	-0.073	0.16	-10000	0	-0.55	37	37
ETA receptor/Endothelin-1/Gq/GTP	0.011	0.15	-10000	0	-0.47	25	25
MAPK14	0.002	0.12	-10000	0	-0.49	18	18
TRPC6	0.02	0.17	-10000	0	-0.94	7	7
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.093	-10000	0	-0.56	12	12
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.004	0.13	-10000	0	-0.42	30	30
ETB receptor/Endothelin-2	-0.082	0.19	-10000	0	-0.5	63	63
ETB receptor/Endothelin-3	-0.15	0.22	-10000	0	-0.5	117	117
ETB receptor/Endothelin-1	-0.014	0.13	-10000	0	-0.5	21	21
MAPK3	-0.018	0.2	-10000	0	-0.68	29	29
MAPK1	-0.018	0.2	-10000	0	-0.69	28	28
Rac1/GDP	-0.016	0.18	-10000	0	-0.55	30	30
cAMP biosynthetic process	-0.029	0.19	-10000	0	-0.6	34	34
MAPK8	0.017	0.17	-10000	0	-0.66	15	15
SRC	0.009	0.031	-10000	0	-0.65	1	1
ETB receptor/Endothelin-1/Gi/GTP	-0.014	0.13	-10000	0	-0.43	22	22
p130Cas/CRK/Src/PYK2	-0.021	0.18	-10000	0	-0.6	27	27
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.016	0.18	-10000	0	-0.55	30	30
COL1A2	0.002	0.25	-10000	0	-0.85	24	24
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.08	0.19	-10000	0	-0.49	62	62
mol:DAG	0.001	0.15	-10000	0	-0.52	25	25
MAP2K2	-0.016	0.18	-10000	0	-0.56	33	33
MAP2K1	-0.016	0.18	-10000	0	-0.56	33	33
EDNRA	0.011	0.15	0.22	24	-0.55	16	40
positive regulation of muscle contraction	0.022	0.16	-10000	0	-0.64	15	15
Gq family/GDP	-0.075	0.17	-10000	0	-0.59	34	34
HRAS/GTP	-0.026	0.17	-10000	0	-0.54	31	31
PRKCH	0.005	0.15	-10000	0	-0.56	20	20
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	0	0.16	-10000	0	-0.53	27	27
PRKCB	-0.016	0.19	-10000	0	-0.59	33	33
PRKCE	0.007	0.15	-10000	0	-0.51	23	23
PRKCD	0.006	0.15	-10000	0	-0.51	23	23
PRKCG	-0.085	0.21	-10000	0	-0.5	58	58
regulation of vascular smooth muscle contraction	-0.025	0.24	-10000	0	-0.88	26	26
PRKCQ	-0.012	0.17	-10000	0	-0.5	35	35
PLA2G4A	-0.019	0.2	-10000	0	-0.6	35	35
GNA14	-0.024	0.14	-10000	0	-0.56	29	29
GNA15	-0.034	0.13	-10000	0	-0.39	51	51
GNA12	0.01	0	-10000	0	-10000	0	0
GNA11	0.011	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.008	0.2	0.36	52	-0.6	19	71
MMP1	-0.13	0.35	-10000	0	-0.99	60	60

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.041	0.15	-9999	-0.6	24	24
alphaM/beta2 Integrin/GPIbA	-0.055	0.16	-9999	-0.5	41	41
alphaM/beta2 Integrin/proMMP-9	-0.057	0.17	-9999	-0.63	30	30
PLAUR	0.001	0.075	-9999	-0.65	6	6
HMGB1	0.005	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.032	0.12	-9999	-0.57	18	18
AGER	0	0.058	-9999	-0.68	3	3
RAP1A	0.01	0	-9999	-10000	0	0
SELPLG	-0.005	0.098	-9999	-0.63	11	11
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.055	0.14	-9999	-0.53	25	25
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.034	0.15	-9999	-0.53	37	37
CYR61	-0.005	0.093	-9999	-0.56	12	12
TLN1	0.01	0	-9999	-10000	0	0
Rap1/GTP	-0.065	0.14	-9999	-0.57	23	23
RHOA	0.01	0	-9999	-10000	0	0
P-selectin oligomer	-0.076	0.21	-9999	-0.59	66	66
MYH2	-0.069	0.17	-9999	-0.54	31	31
MST1R	-0.023	0.14	-9999	-0.64	23	23
leukocyte activation during inflammatory response	-0.16	0.19	-9999	-0.43	122	122
APOB	-0.18	0.26	-9999	-0.49	177	177
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.007	0.1	-9999	-0.59	13	13
JAM3	-0.001	0.071	-9999	-0.42	12	12
GP1BA	-0.029	0.15	-9999	-0.56	31	31
alphaM/beta2 Integrin/CTGF	-0.043	0.14	-9999	-0.55	28	28
alphaM/beta2 Integrin	-0.065	0.18	-9999	-0.56	32	32
JAM3 homodimer	-0.001	0.07	-9999	-0.42	12	12
ICAM2	-0.005	0.095	-9999	-0.6	11	11
ICAM1	-0.006	0.093	-9999	-0.51	14	14
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.064	0.18	-9999	-0.55	32	32
cell adhesion	-0.054	0.15	-9999	-0.5	41	41
NFKB1	-0.039	0.19	-9999	-0.74	19	19
THY1	-0.002	0.088	-9999	-0.62	9	9
RhoA/GDP	0.007	0	-9999	-10000	0	0
Lipoprotein(a)	-0.16	0.19	-9999	-0.33	223	223
alphaM/beta2 Integrin/LRP/tPA	-0.035	0.12	-9999	-0.51	22	22
IL6	-0.077	0.28	-9999	-0.81	50	50
ITGB2	-0.019	0.12	-9999	-0.62	17	17
elevation of cytosolic calcium ion concentration	-0.042	0.13	-9999	-0.5	28	28
alphaM/beta2 Integrin/JAM2/JAM3	-0.046	0.14	-9999	-0.52	30	30
JAM2	-0.016	0.11	-9999	-0.46	25	25
alphaM/beta2 Integrin/ICAM1	-0.054	0.16	-9999	-0.47	43	43
alphaM/beta2 Integrin/uPA/Plg	-0.043	0.13	-9999	-0.52	23	23
RhoA/GTP	-0.071	0.18	-9999	-0.42	65	65
positive regulation of phagocytosis	-0.064	0.16	-9999	-0.67	23	23
Ron/MSP	-0.018	0.12	-9999	-0.4	36	36
alphaM/beta2 Integrin/uPAR/uPA	-0.042	0.14	-9999	-0.5	28	28
alphaM/beta2 Integrin/uPAR	-0.037	0.13	-9999	-0.55	24	24
PLAU	-0.01	0.098	-9999	-0.46	19	19
PLAT	-0.001	0.073	-9999	-0.45	11	11
actin filament polymerization	-0.066	0.16	-9999	-0.51	31	31
MST1	-0.002	0.073	-9999	-0.42	13	13
alphaM/beta2 Integrin/lipoprotein(a)	-0.16	0.2	-9999	-0.44	122	122
TNF	-0.049	0.23	-9999	-0.76	32	32
RAP1B	0.008	0.025	-9999	-0.37	2	2
alphaM/beta2 Integrin/uPA	-0.043	0.13	-9999	-0.55	23	23
fibrinolysis	-0.042	0.13	-9999	-0.51	23	23
HCK	-0.002	0.087	-9999	-0.65	8	8
dendritic cell antigen processing and presentation	-0.064	0.18	-9999	-0.55	32	32
VTN	-0.051	0.15	-9999	-0.42	66	66
alphaM/beta2 Integrin/CYR61	-0.04	0.14	-9999	-0.57	24	24
LPA	-0.071	0.19	-9999	-0.49	72	72
LRP1	0.006	0.047	-9999	-0.56	3	3
cell migration	-0.038	0.19	-9999	-0.62	34	34
FN1	-0.034	0.15	-9999	-0.54	36	36
alphaM/beta2 Integrin/Thy1	-0.039	0.15	-9999	-0.62	22	22
MPO	-0.001	0.077	-9999	-0.53	9	9
KNG1	-0.044	0.16	-9999	-0.47	51	51
RAP1/GDP	-0.001	0.014	-9999	-10000	0	0
ROCK1	-0.062	0.17	-9999	-0.55	30	30
ELA2	0	0	-9999	-10000	0	0
PLG	-0.004	0.061	-9999	-0.37	12	12
CTGF	-0.01	0.11	-9999	-0.6	15	15
alphaM/beta2 Integrin/Hck	-0.038	0.15	-9999	-0.7	19	19
ITGAM	-0.014	0.11	-9999	-0.57	15	15
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.083	0.19	-9999	-0.46	70	70
HP	-0.082	0.2	-9999	-0.48	86	86
leukocyte adhesion	-0.064	0.17	-9999	-0.61	29	29
SELP	-0.076	0.22	-9999	-0.59	66	66

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.088	0.3	-9999	-1.2	30	30
MKNK1	0.01	0	-9999	-10000	0	0
MAPK14	-0.033	0.1	-9999	-0.39	6	6
ATF2/c-Jun	-0.008	0.081	-9999	-0.33	7	7
MAPK11	-0.033	0.1	-9999	-0.39	6	6
MITF	-0.033	0.13	-9999	-0.37	45	45
MAPKAPK5	-0.028	0.12	-9999	-0.36	40	40
KRT8	-0.072	0.19	-9999	-0.45	74	74
MAPKAPK3	0.01	0	-9999	-10000	0	0
MAPKAPK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.047	0.15	-9999	-0.46	40	40
CEBPB	-0.03	0.12	-9999	-0.38	40	40
SLC9A1	-0.029	0.12	-9999	-0.38	40	40
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.024	0.12	-9999	-0.35	40	40
p38alpha-beta/MNK1	-0.027	0.12	-9999	-0.36	40	40
JUN	-0.008	0.08	-9999	-0.33	7	7
PPARGC1A	-0.099	0.23	-9999	-0.5	89	89
USF1	-0.028	0.12	-9999	-0.36	40	40
RAB5/GDP/GDI1	-0.036	0.075	-9999	-0.36	6	6
NOS2	-0.08	0.23	-9999	-1.1	16	16
DDIT3	-0.029	0.12	-9999	-0.36	40	40
RAB5A	0.01	0	-9999	-10000	0	0
HSPB1	-0.028	0.12	-9999	-0.46	15	15
p38alpha-beta/HBP1	-0.027	0.12	-9999	-0.36	40	40
CREB1	-0.026	0.13	-9999	-0.39	40	40
RAB5/GDP	0.007	0	-9999	-10000	0	0
EIF4E	-0.018	0.1	-9999	-0.45	6	6
RPS6KA4	-0.029	0.12	-9999	-0.38	40	40
PLA2G4A	-0.047	0.16	-9999	-0.5	35	35
GDI1	-0.028	0.12	-9999	-0.36	40	40
TP53	-0.044	0.15	-9999	-0.47	41	41
RPS6KA5	-0.029	0.12	-9999	-0.36	41	41
ESR1	-0.045	0.14	-9999	-0.37	55	55
HBP1	0.01	0	-9999	-10000	0	0
MEF2C	-0.031	0.12	-9999	-0.37	42	42
MEF2A	-0.028	0.12	-9999	-0.36	40	40
EIF4EBP1	-0.026	0.13	-9999	-0.39	40	40
KRT19	-0.035	0.12	-9999	-0.37	40	40
ELK4	-0.035	0.12	-9999	-0.37	40	40
ATF6	-0.028	0.12	-9999	-0.36	40	40
ATF1	-0.026	0.13	-9999	-0.39	40	40
p38alpha-beta/MAPKAPK2	-0.027	0.12	-9999	-0.36	40	40
p38alpha-beta/MAPKAPK3	-0.027	0.12	-9999	-0.36	40	40

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.03	0.16	-10000	0	-0.45	38	38
TBX21	-0.12	0.44	-10000	0	-1.2	51	51
B2M	0.008	0.01	-10000	0	-10000	0	0
TYK2	0.011	0.018	-10000	0	-10000	0	0
IL12RB1	-0.014	0.13	-10000	0	-0.69	17	17
GADD45B	-0.065	0.31	-10000	0	-0.89	39	39
IL12RB2	-0.034	0.14	-10000	0	-0.42	51	51
GADD45G	-0.071	0.32	-10000	0	-0.9	43	43
natural killer cell activation	0.003	0.019	-10000	0	-10000	0	0
RELB	0.009	0.031	-10000	0	-0.65	1	1
RELA	0.01	0	-10000	0	-10000	0	0
IL18	-0.018	0.13	-10000	0	-0.59	22	22
IL2RA	-0.011	0.11	-10000	0	-0.6	16	16
IFNG	-0.071	0.2	-10000	0	-0.53	69	69
STAT3 (dimer)	-0.067	0.31	-10000	0	-0.8	53	53
HLA-DRB5	-0.033	0.16	-10000	0	-0.61	32	32
FASLG	-0.12	0.44	-10000	0	-1.1	57	57
NF kappa B2 p52/RelB	-0.16	0.34	-10000	0	-0.97	55	55
CD4	-0.005	0.098	-10000	0	-0.63	11	11
SOCS1	0.004	0.056	-10000	0	-0.47	6	6
EntrezGene:6955	-0.002	0.013	-10000	0	-10000	0	0
CD3D	-0.029	0.15	-10000	0	-0.61	28	28
CD3E	-0.011	0.11	-10000	0	-0.6	15	15
CD3G	-0.036	0.16	-10000	0	-0.62	33	33
IL12Rbeta2/JAK2	-0.019	0.11	-10000	0	-0.43	18	18
CCL3	-0.12	0.42	-10000	0	-1.1	54	54
CCL4	-0.11	0.41	-10000	0	-1.2	49	49
HLA-A	0.004	0.055	-10000	0	-0.67	3	3
IL18/IL18R	-0.014	0.17	-10000	0	-0.51	40	40
NOS2	-0.12	0.39	-10000	0	-1.1	49	49
IL12/IL12R/TYK2/JAK2/SPHK2	-0.028	0.15	-10000	0	-0.43	39	39
IL1R1	-0.099	0.38	-10000	0	-1	50	50
IL4	0.002	0.041	-10000	0	-0.39	4	4
JAK2	0.005	0.059	-10000	0	-0.47	6	6
EntrezGene:6957	-0.002	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.14	0.46	-10000	0	-1.2	59	59
RAB7A	-0.042	0.27	-10000	0	-0.75	36	36
lysosomal transport	-0.037	0.25	-10000	0	-0.71	36	36
FOS	-0.091	0.37	-10000	0	-1	51	51
STAT4 (dimer)	-0.071	0.35	-10000	0	-0.9	53	53
STAT5A (dimer)	-0.19	0.36	-10000	0	-0.98	63	63
GZMA	-0.13	0.46	-10000	0	-1.3	54	54
GZMB	-0.11	0.41	-10000	0	-1.2	47	47
HLX	0.004	0.059	-10000	0	-0.54	5	5
LCK	-0.12	0.43	-10000	0	-1.1	56	56
TCR/CD3/MHC II/CD4	-0.076	0.33	-10000	0	-0.92	44	44
IL2/IL2R	-0.056	0.17	-10000	0	-0.5	46	46
MAPK14	-0.067	0.33	-10000	0	-0.9	44	44
CCR5	-0.094	0.39	-10000	0	-1.1	45	45
IL1B	-0.066	0.19	-10000	0	-0.5	69	69
STAT6	-0.008	0.1	-10000	0	-0.26	8	8
STAT4	-0.002	0.088	-10000	0	-0.62	9	9
STAT3	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
NFKB2	0.01	0	-10000	0	-10000	0	0
IL12B	-0.015	0.13	-10000	0	-0.58	22	22
CD8A	-0.047	0.18	-10000	0	-0.57	44	44
CD8B	-0.053	0.18	-10000	0	-0.57	49	49
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.03	0.16	0.44	38	-10000	0	38
IL2RB	-0.007	0.1	-10000	0	-0.63	12	12
proteasomal ubiquitin-dependent protein catabolic process	-0.059	0.31	-10000	0	-0.8	53	53
IL2RG	-0.049	0.18	-10000	0	-0.61	43	43
IL12	-0.036	0.16	-10000	0	-0.46	53	53
STAT5A	0.004	0.062	-10000	0	-0.65	4	4
CD247	-0.025	0.14	-10000	0	-0.63	24	24
IL2	0	0.05	-10000	0	-0.37	8	8
SPHK2	0.009	0.018	-10000	0	-0.37	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.036	0.17	-10000	0	-0.61	35	35
IL12/IL12R/TYK2/JAK2	-0.13	0.48	-10000	0	-1.2	61	61
MAP2K3	-0.068	0.32	-10000	0	-0.88	46	46
RIPK2	0.01	0	-10000	0	-10000	0	0
MAP2K6	-0.076	0.34	-10000	0	-0.92	46	46
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.028	0.15	-10000	0	-0.61	28	28
IL18RAP	-0.025	0.15	-10000	0	-0.63	26	26
IL12Rbeta1/TYK2	-0.002	0.11	-10000	0	-0.53	17	17
EOMES	-0.11	0.38	-10000	0	-1.4	36	36
STAT1 (dimer)	-0.099	0.34	-10000	0	-0.84	61	61
T cell proliferation	-0.041	0.25	-10000	0	-0.65	45	45
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.004	0.097	-10000	0	-0.61	11	11
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.12	0.24	-10000	0	-0.73	49	49
ATF2	-0.054	0.3	-10000	0	-0.83	41	41

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.002	0.066	-10000	0	-0.39	4	4
epithelial cell differentiation	-0.075	0.12	-10000	0	-0.42	19	19
ITCH	0.015	0.013	-10000	0	-10000	0	0
WWP1	0.008	0.053	-10000	0	-10000	0	0
FYN	0.009	0.031	-10000	0	-0.65	1	1
EGFR	-0.036	0.14	-10000	0	-0.44	46	46
PRL	-0.021	0.098	-10000	0	-0.37	33	33
neuron projection morphogenesis	-0.029	0.13	-10000	0	-0.38	13	13
PTPRZ1	-0.19	0.27	-10000	0	-0.51	179	179
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.07	0.12	-10000	0	-0.42	13	13
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.069	0.16	-10000	0	-0.39	69	69
ADAM17	0.015	0.022	-10000	0	-0.37	1	1
ErbB4/ErbB4	0.003	0.067	-10000	0	-0.45	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.026	0.1	-10000	0	-0.4	15	15
NCOR1	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.06	0.15	-10000	0	-0.37	68	68
GRIN2B	-0.087	0.16	-10000	0	-0.48	30	30
ErbB4/ErbB2/betacellulin	-0.019	0.12	-10000	0	-0.39	29	29
STAT1	0.01	0	-10000	0	-10000	0	0
HBEGF	0.003	0.062	-10000	0	-0.51	6	6
PRLR	-0.13	0.25	-10000	0	-0.56	111	111
E4ICDs/ETO2	-0.011	0.097	-10000	0	-0.45	12	12
axon guidance	0.026	0.087	-10000	0	-10000	0	0
NEDD4	0.009	0.063	-10000	0	-0.64	4	4
Prolactin receptor/Prolactin receptor/Prolactin	-0.11	0.2	-10000	0	-0.39	136	136
CBFA2T3	-0.02	0.12	-10000	0	-0.48	28	28
ErbB4/ErbB2/HBEGF	-0.003	0.081	-10000	0	-0.38	9	9
MAPK3	-0.035	0.13	-10000	0	-0.39	13	13
STAT1 (dimer)	0.006	0.056	-10000	0	-0.4	1	1
MAPK1	-0.035	0.13	-10000	0	-0.39	13	13
JAK2	0.004	0.056	-10000	0	-0.47	6	6
ErbB4/ErbB2/neuregulin 1 beta	-0.076	0.16	-10000	0	-0.39	70	70
NRG1	-0.087	0.19	-10000	0	-0.38	121	121
NRG3	-0.044	0.15	-10000	0	-0.43	55	55
NRG2	-0.05	0.17	-10000	0	-0.5	54	54
NRG4	-0.035	0.15	-10000	0	-0.52	39	39
heart development	0.026	0.087	-10000	0	-10000	0	0
neural crest cell migration	-0.075	0.16	-10000	0	-0.39	70	70
ERBB2	-0.004	0.089	-10000	0	-0.29	36	36
WWOX/E4ICDs	0.005	0.06	-10000	0	-0.39	2	2
SHC1	0.01	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.037	0.13	-10000	0	-0.38	41	41
apoptosis	0.051	0.089	0.43	13	-10000	0	13
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.029	0.12	-10000	0	-0.41	26	26
ErbB4/ErbB2/epiregulin	-0.093	0.15	-10000	0	-0.36	82	82
ErbB4/ErbB4/betacellulin/betacellulin	-0.015	0.11	-10000	0	-0.42	24	24
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.091	0.14	-10000	0	-0.47	15	15
MDM2	0.005	0.065	-10000	0	-0.36	3	3
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.078	0.14	-10000	0	-0.37	68	68
STAT5A	0.027	0.086	-10000	0	-0.38	2	2
ErbB4/EGFR/neuregulin 1 beta	-0.082	0.18	-10000	0	-0.4	87	87
DLG4	0.01	0	-10000	0	-10000	0	0
GRB2/SHC	0.015	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.016	0.044	-10000	0	-0.37	1	1
STAT5A (dimer)	-0.079	0.13	-10000	0	-0.46	17	17
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.028	0.077	-10000	0	-10000	0	0
LRIG1	0	0.081	-10000	0	-0.65	7	7
EREG	-0.17	0.26	-10000	0	-0.5	158	158
BTC	-0.025	0.15	-10000	0	-0.63	25	25
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.026	0.087	-10000	0	-10000	0	0
ERBB4	0.003	0.067	-10000	0	-0.45	1	1
STAT5B	0.01	0	-10000	0	-10000	0	0
YAP1	-0.008	0.046	-10000	0	-0.66	2	2
GRB2	0.01	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.024	0.11	-10000	0	-0.37	27	27
glial cell differentiation	0.016	0.043	0.37	1	-10000	0	1
WWOX	0.008	0.036	-10000	0	-0.51	2	2
cell proliferation	-0.061	0.17	-10000	0	-0.5	27	27

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.019	0.13	-9999	-0.58	23	23
Syndecan-4/Syndesmos	-0.044	0.17	-9999	-0.56	36	36
positive regulation of JNK cascade	-0.08	0.17	-9999	-0.53	44	44
Syndecan-4/ADAM12	-0.068	0.2	-9999	-0.6	45	45
CCL5	-0.044	0.17	-9999	-0.56	43	43
Rac1/GDP	0.007	0	-9999	-10000	0	0
DNM2	0.01	0	-9999	-10000	0	0
ITGA5	0.001	0.069	-9999	-0.47	9	9
SDCBP	0.01	0	-9999	-10000	0	0
PLG	-0.004	0.061	-9999	-0.37	12	12
ADAM12	-0.04	0.16	-9999	-0.52	43	43
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.019	0.032	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.086	0.21	-9999	-0.62	41	41
Syndecan-4/CXCL12/CXCR4	-0.061	0.19	-9999	-0.57	44	44
Syndecan-4/Laminin alpha3	-0.067	0.19	-9999	-0.55	47	47
MDK	-0.005	0.098	-9999	-0.63	11	11
Syndecan-4/FZD7	-0.053	0.18	-9999	-0.59	37	37
Syndecan-4/Midkine	-0.052	0.18	-9999	-0.57	38	38
FZD7	-0.01	0.1	-9999	-0.5	18	18
Syndecan-4/FGFR1/FGF	-0.08	0.17	-9999	-0.56	39	39
THBS1	-0.007	0.098	-9999	-0.52	15	15
integrin-mediated signaling pathway	-0.076	0.19	-9999	-0.57	43	43
positive regulation of MAPKKK cascade	-0.08	0.17	-9999	-0.53	44	44
Syndecan-4/TACI	-0.1	0.22	-9999	-0.61	53	53
CXCR4	-0.007	0.096	-9999	-0.53	14	14
cell adhesion	-0.007	0.1	-9999	-0.38	28	28
Syndecan-4/Dynamin	-0.044	0.17	-9999	-0.56	36	36
Syndecan-4/TSP1	-0.052	0.18	-9999	-0.57	41	41
Syndecan-4/GIPC	-0.044	0.17	-9999	-0.56	36	36
Syndecan-4/RANTES	-0.07	0.2	-9999	-0.6	42	42
ITGB1	0.01	0	-9999	-10000	0	0
LAMA1	-0.08	0.2	-9999	-0.47	86	86
LAMA3	-0.037	0.16	-9999	-0.52	41	41
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.008	0.087	-9999	-0.6	8	8
Syndecan-4/alpha-Actinin	-0.044	0.17	-9999	-0.56	36	36
TFPI	-0.01	0.1	-9999	-0.52	17	17
F2	-0.055	0.16	-9999	-0.43	67	67
alpha5/beta1 Integrin	0.008	0.05	-9999	-0.33	9	9
positive regulation of cell adhesion	-0.1	0.22	-9999	-0.58	57	57
ACTN1	0.009	0.018	-9999	-0.37	1	1
TNC	-0.064	0.18	-9999	-0.45	73	73
Syndecan-4/CXCL12	-0.061	0.19	-9999	-0.59	38	38
FGF6	-0.001	0.035	-9999	-0.37	4	4
RHOA	0.01	0	-9999	-10000	0	0
CXCL12	-0.024	0.13	-9999	-0.5	31	31
TNFRSF13B	-0.11	0.24	-9999	-0.54	101	101
FGF2	-0.003	0.081	-9999	-0.46	13	13
FGFR1	-0.014	0.11	-9999	-0.49	22	22
Syndecan-4/PI-4-5-P2	-0.05	0.17	-9999	-0.57	36	36
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.032	0.15	-9999	-0.53	36	36
cell migration	-0.004	0.013	-9999	-10000	0	0
PRKCD	0.011	0.007	-9999	-10000	0	0
vasculogenesis	-0.05	0.18	-9999	-0.55	41	41
SDC4	-0.053	0.18	-9999	-0.6	36	36
Syndecan-4/Tenascin C	-0.079	0.2	-9999	-0.59	43	43
Syndecan-4/PI-4-5-P2/PKC alpha	-0.015	0.025	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.044	0.17	-9999	-0.56	36	36
MMP9	-0.034	0.15	-9999	-0.53	37	37
Rac1/GTP	-0.008	0.11	-9999	-0.39	28	28
cytoskeleton organization	-0.042	0.16	-9999	-0.54	36	36
GIPC1	0.01	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.054	0.18	-9999	-0.55	41	41

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.01	0	-9999	-10000	0	0
VLDLR	-0.044	0.18	-9999	-0.61	40	40
LRPAP1	0.01	0	-9999	-10000	0	0
NUDC	0.01	0	-9999	-10000	0	0
RELN/LRP8	-0.072	0.15	-9999	-0.42	60	60
CaM/Ca2+	0.007	0	-9999	-10000	0	0
KATNA1	0.01	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.044	0.14	-9999	-0.38	60	60
IQGAP1/CaM	0.015	0	-9999	-10000	0	0
DAB1	0.009	0.018	-9999	-0.37	1	1
IQGAP1	0.01	0	-9999	-10000	0	0
PLA2G7	-0.007	0.1	-9999	-0.59	13	13
CALM1	0.01	0	-9999	-10000	0	0
DYNLT1	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.001	0.079	-9999	-0.43	14	14
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.01	0	-9999	-10000	0	0
CDK5R1	-0.015	0.1	-9999	-0.4	28	28
LIS1/Poliovirus Protein 3A	-0.017	0.11	-9999	-0.42	32	32
CDK5R2	-0.11	0.24	-9999	-0.53	103	103
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.093	0.18	-9999	-0.45	76	76
YWHAE	0.01	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.064	0.15	-9999	-0.44	23	23
MAP1B	-0.031	0.09	-9999	-0.33	35	35
RAC1	-0.012	0.045	-9999	-10000	0	0
p35/CDK5	-0.039	0.14	-9999	-0.35	61	61
RELN	-0.092	0.22	-9999	-0.54	86	86
PAFAH/LIS1	-0.02	0.13	-9999	-0.42	41	41
LIS1/CLIP170	-0.01	0.11	-9999	-0.41	32	32
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.084	0.12	-9999	-0.43	18	18
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.052	0.14	-9999	-0.32	79	79
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.073	0.16	-9999	-0.48	23	23
LIS1/IQGAP1	-0.01	0.11	-9999	-0.41	32	32
RHOA	-0.012	0.045	-9999	-10000	0	0
PAFAH1B1	-0.018	0.13	-9999	-0.48	32	32
PAFAH1B3	0.009	0.031	-9999	-0.65	1	1
PAFAH1B2	0.01	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.019	0.12	-9999	-0.45	32	32
NDEL1/Katanin 60/Dynein heavy chain	-0.081	0.13	-9999	-0.42	23	23
LRP8	-0.008	0.11	-9999	-0.59	14	14
NDEL1/Katanin 60	-0.064	0.15	-9999	-0.44	23	23
P39/CDK5	-0.091	0.17	-9999	-0.35	119	119
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	-0.01	0.11	-9999	-0.41	32	32
CDK5	-0.034	0.13	-9999	-0.35	60	60
PPP2R5D	0.009	0.018	-9999	-0.37	1	1
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.025	0.09	-9999	-0.35	32	32
CSNK2A1	-0.036	0.17	-9999	-0.65	32	32
RELN/VLDLR/DAB1/LIS1	-0.081	0.18	-9999	-0.39	105	105
RELN/VLDLR	-0.094	0.17	-9999	-0.42	86	86
CDC42	-0.012	0.045	-9999	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.024	0.1	-9999	0	-0.43	25	25
ARNO/beta Arrestin1-2	-0.042	0.099	-9999	0	-0.46	7	7
EGFR	-0.036	0.14	-9999	0	-0.45	46	46
EPHA2	-0.006	0.1	-9999	0	-0.65	11	11
USP6	-0.002	0.088	-9999	0	-0.62	9	9
IQSEC1	0.01	0	-9999	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.13	0.2	-9999	0	-0.36	171	171
ARRB2	0.003	0.034	-9999	0	-10000	0	0
mol:GTP	0.005	0.041	-9999	0	-0.16	22	22
ARRB1	-0.009	0.11	-9999	0	-0.65	13	13
FBXO8	0.009	0.018	-9999	0	-0.37	1	1
TSHR	-0.035	0.16	-9999	0	-0.59	34	34
EGF	-0.14	0.24	-9999	0	-0.47	144	144
somatostatin receptor activity	0	0	-9999	0	-0.001	44	44
ARAP2	0.003	0.064	-9999	0	-0.6	5	5
mol:GDP	-0.049	0.1	-9999	0	-0.28	44	44
mol:PI-3-4-5-P3	0	0	-9999	0	-0.001	29	29
ITGA2B	-0.026	0.14	-9999	0	-0.52	31	31
ARF6	0.01	0	-9999	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.011	0.068	-9999	0	-0.4	13	13
ADAP1	-0.02	0.14	-9999	0	-0.65	21	21
KIF13B	0.002	0.071	-9999	0	-0.6	6	6
HGF/MET	-0.029	0.12	-9999	0	-0.37	43	43
PXN	0.003	0.064	-9999	0	-0.6	5	5
ARF6/GTP	-0.053	0.1	-9999	0	-0.28	41	41
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.11	0.16	-9999	0	-0.42	79	79
ADRB2	-0.061	0.18	-9999	0	-0.48	66	66
receptor agonist activity	0	0	-9999	0	0	45	45
actin filament binding	0	0	-9999	0	-0.001	46	46
SRC	0.008	0.031	-9999	0	-0.65	1	1
ITGB3	-0.003	0.087	-9999	0	-0.57	10	10
GNAQ	0.01	0	-9999	0	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	0	-0.001	41	41
ARF6/GDP	-0.002	0.076	-9999	0	-0.37	8	8
ARF6/GDP/GULP/ACAP1	-0.065	0.13	-9999	0	-0.44	39	39
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.024	0.1	-9999	0	-0.4	27	27
ACAP1	-0.001	0.077	-9999	0	-0.53	9	9
ACAP2	0.01	0	-9999	0	-10000	0	0
LHCGR/beta Arrestin2	-0.003	0.046	-9999	0	-10000	0	0
EFNA1	0.007	0.044	-9999	0	-0.65	2	2
HGF	-0.028	0.15	-9999	0	-0.55	31	31
CYTH3	0.009	0	-9999	0	-10000	0	0
CYTH2	0.006	0.002	-9999	0	-10000	0	0
NCK1	0.01	0	-9999	0	-10000	0	0
fibronectin binding	0	0	-9999	0	0	37	37
endosomal lumen acidification	0	0	0	1	0	44	45
microtubule-based process	0	0	-9999	0	-10000	0	0
GULP1	-0.027	0.15	-9999	0	-0.64	26	26
GNAQ/ARNO	0.01	0.005	-9999	0	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	0	-10000	0	0
PIP3-E	0	0	-9999	0	0	28	28
MET	-0.002	0.073	-9999	0	-0.42	13	13
GNA14	-0.026	0.14	-9999	0	-0.56	29	29
GNA15	-0.035	0.13	-9999	0	-0.4	51	51
GIT1	0.008	0.031	-9999	0	-0.65	1	1
mol:PI-4-5-P2	0	0	-9999	0	-0.001	42	42
GNA11	0.01	0	-9999	0	-10000	0	0
LHCGR	-0.014	0.086	-9999	0	-0.37	25	25
AGTR1	-0.12	0.24	-9999	0	-0.53	114	114
desensitization of G-protein coupled receptor protein signaling pathway	-0.003	0.046	-9999	0	-10000	0	0
IPCEF1/ARNO	-0.077	0.13	-9999	0	-0.55	2	2
alphaIIb/beta3 Integrin	-0.024	0.12	-9999	0	-0.4	39	39

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.076	0.17	-10000	0	-0.44	73	73
cell-cell adhesion	0.068	0.13	0.53	19	-10000	0	19
Ephrin B/EPHB2/RasGAP	-0.061	0.14	-10000	0	-0.4	53	53
ITSN1	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
SHC1	0.01	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.033	0.12	-10000	0	-0.38	40	40
Ephrin B1/EPHB1	-0.038	0.1	-10000	0	-0.45	18	18
HRAS/GDP	-0.054	0.12	-10000	0	-0.43	31	31
Ephrin B/EPHB1/GRB7	-0.077	0.15	-10000	0	-0.43	52	52
Endophilin/SYNJ1	-0.034	0.14	-10000	0	-0.38	53	53
KRAS	-0.007	0.078	-10000	0	-0.37	20	20
Ephrin B/EPHB1/Src	-0.063	0.13	-10000	0	-0.42	44	44
endothelial cell migration	-0.006	0.043	-10000	0	-0.34	7	7
GRB2	0.01	0	-10000	0	-10000	0	0
GRB7	-0.023	0.12	-10000	0	-0.43	34	34
PAK1	-0.043	0.17	-10000	0	-0.42	62	62
HRAS	0.01	0	-10000	0	-10000	0	0
RRAS	-0.035	0.15	-10000	0	-0.39	53	53
DNM1	-0.017	0.12	-10000	0	-0.52	23	23
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.037	0.14	-10000	0	-0.4	43	43
lamellipodium assembly	-0.068	0.13	-10000	0	-0.53	19	19
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.015	0.1	-10000	0	-0.37	22	22
PIK3R1	0.01	0	-10000	0	-10000	0	0
EPHB2	-0.039	0.16	-10000	0	-0.55	40	40
EPHB3	-0.036	0.16	-10000	0	-0.57	36	36
EPHB1	-0.047	0.15	-10000	0	-0.43	59	59
EPHB4	0.009	0.031	-10000	0	-0.65	1	1
mol:GDP	-0.046	0.13	-10000	0	-0.44	31	31
Ephrin B/EPHB2	-0.062	0.14	-10000	0	-0.41	53	53
Ephrin B/EPHB3	-0.061	0.14	-10000	0	-0.39	56	56
JNK cascade	-0.03	0.13	-10000	0	-0.4	40	40
Ephrin B/EPHB1	-0.064	0.14	-10000	0	-0.42	43	43
RAP1/GDP	-0.039	0.12	-10000	0	-0.45	17	17
EFNB2	0	0.077	-10000	0	-0.61	7	7
EFNB3	-0.048	0.16	-10000	0	-0.48	54	54
EFNB1	0.001	0.075	-10000	0	-0.65	6	6
Ephrin B2/EPHB1-2	-0.06	0.13	-10000	0	-0.41	43	43
RAP1B	0.008	0.025	-10000	0	-0.37	2	2
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.073	0.15	-10000	0	-0.6	19	19
Rap1/GTP	-0.068	0.13	-10000	0	-0.54	19	19
axon guidance	-0.075	0.17	-10000	0	-0.44	73	73
MAPK3	-0.002	0.093	-10000	0	-0.39	12	12
MAPK1	-0.002	0.093	-10000	0	-0.39	12	12
Rac1/GDP	-0.017	0.13	-10000	0	-0.46	18	18
actin cytoskeleton reorganization	-0.058	0.11	-10000	0	-0.41	23	23
CDC42/GDP	-0.017	0.13	-10000	0	-0.4	31	31
PI3K	-0.006	0.044	-10000	0	-0.35	7	7
EFNA5	-0.065	0.21	-10000	0	-0.64	53	53
Ephrin B2/EPHB4	-0.007	0.052	-10000	0	-0.39	8	8
Ephrin B/EPHB2/Intersectin/N-WASP	-0.022	0.12	-10000	0	-0.33	52	52
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.072	0.13	-10000	0	-0.5	23	23
PTK2	0.012	0.042	-10000	0	-0.64	1	1
MAP4K4	-0.03	0.14	-10000	0	-0.4	40	40
SRC	0.009	0.031	-10000	0	-0.65	1	1
KALRN	-0.015	0.12	-10000	0	-0.65	17	17
Intersectin/N-WASP	0.014	0.012	-10000	0	-0.25	1	1
neuron projection morphogenesis	-0.024	0.14	-10000	0	-0.45	27	27
MAP2K1	-0.008	0.098	-10000	0	-0.41	12	12
WASL	0.009	0.018	-10000	0	-0.37	1	1
Ephrin B1/EPHB1-2/NCK1	-0.059	0.13	-10000	0	-0.43	40	40
cell migration	-0.006	0.11	-10000	0	-0.45	13	13
NRAS	0.008	0.036	-10000	0	-0.51	2	2
SYNJ1	-0.034	0.14	-10000	0	-0.38	53	53
PXN	0.003	0.064	-10000	0	-0.6	5	5
TF	-0.076	0.17	-10000	0	-0.38	89	89
HRAS/GTP	-0.073	0.14	-10000	0	-0.57	19	19
Ephrin B1/EPHB1-2	-0.06	0.14	-10000	0	-0.44	40	40
cell adhesion mediated by integrin	0.042	0.12	0.38	37	-10000	0	37
RAC1	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.079	0.15	-10000	0	-0.62	19	19
RAC1-CDC42/GTP	-0.085	0.15	-10000	0	-0.55	26	26
RASA1	0.01	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.038	0.12	-10000	0	-0.44	18	18
ruffle organization	-0.035	0.15	-10000	0	-0.54	19	19
NCK1	0.01	0	-10000	0	-10000	0	0
receptor internalization	-0.04	0.16	-10000	0	-0.39	65	65
Ephrin B/EPHB2/KALRN	-0.073	0.17	-10000	0	-0.46	60	60
ROCK1	-0.013	0.11	-10000	0	-0.4	31	31
RAS family/GDP	-0.057	0.11	-10000	0	-0.42	22	22
Rac1/GTP	-0.072	0.14	-10000	0	-0.57	19	19
Ephrin B/EPHB1/Src/Paxillin	-0.026	0.13	-10000	0	-0.37	42	42

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.004	0.063	-9999	-0.41	8	8
NFATC2	-0.025	0.11	-9999	-0.45	28	28
NFATC3	0.003	0.03	-9999	-10000	0	0
CD40LG	-0.12	0.31	-9999	-0.72	72	72
PTGS2	-0.12	0.3	-9999	-0.66	79	79
JUNB	0.009	0.031	-9999	-0.65	1	1
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.008	0.013	-9999	-10000	0	0
CaM/Ca2+	-0.008	0.012	-9999	-10000	0	0
CALM1	0.006	0.009	-9999	-10000	0	0
JUN	0.006	0.021	-9999	-0.39	1	1
mol:Ca2+	-0.008	0.011	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.003	-9999	-10000	0	0
FOSL1	-0.053	0.18	-9999	-0.53	53	53
CREM	0.01	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.089	0.15	-9999	-0.53	31	31
FOS	-0.018	0.12	-9999	-0.59	19	19
IFNG	-0.13	0.31	-9999	-0.67	89	89
AP-1/NFAT1-c-4	-0.12	0.32	-9999	-0.72	71	71
FASLG	-0.11	0.3	-9999	-0.68	74	74
NFAT1-c-4/ICER1	-0.06	0.12	-9999	-0.47	25	25
IL2RA	-0.1	0.28	-9999	-0.67	63	63
FKBP12/FK506	0.007	0	-9999	-10000	0	0
CSF2	-0.13	0.3	-9999	-0.62	96	96
JunB/Fra1/NFAT1-c-4	-0.085	0.14	-9999	-0.46	43	43
IL4	-0.097	0.26	-9999	-0.61	63	63
IL2	-0.006	0.037	-9999	-10000	0	0
IL3	-0.016	0.027	-9999	-10000	0	0
FKBP1A	0.01	0	-9999	-10000	0	0
BATF3	0.006	0.053	-9999	-0.65	3	3
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.011	0.002	-9999	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.009	0.018	-10000	0	-0.37	1	1
RAS family/GTP/Tiam1	-0.039	0.11	-10000	0	-0.33	29	29
NT3 (dimer)/TRKC	-0.092	0.2	-10000	0	-0.51	66	66
NT3 (dimer)/TRKB	-0.22	0.26	-10000	0	-0.54	154	154
SHC/Grb2/SOS1/GAB1/PI3K	0.026	0.025	-10000	0	-0.28	3	3
RAPGEF1	0.01	0	-10000	0	-10000	0	0
BDNF	-0.016	0.11	-10000	0	-0.42	27	27
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
DYNLT1	0.01	0	-10000	0	-10000	0	0
NTRK1	-0.003	0.088	-10000	0	-0.62	9	9
NTRK2	-0.15	0.25	-10000	0	-0.51	140	140
NTRK3	-0.081	0.21	-10000	0	-0.52	78	78
NT-4/5 (dimer)/TRKB	-0.26	0.27	-10000	0	-0.54	186	186
neuron apoptosis	0.12	0.18	0.52	59	-10000	0	59
SHC 2-3/Grb2	-0.11	0.21	-10000	0	-0.58	59	59
SHC1	0.01	0	-10000	0	-10000	0	0
SHC2	-0.12	0.2	-10000	0	-0.59	55	55
SHC3	-0.12	0.21	-10000	0	-0.61	54	54
STAT3 (dimer)	0.008	0.045	-10000	0	-0.36	4	4
NT3 (dimer)/TRKA	-0.14	0.2	-10000	0	-0.46	102	102
RIN/GDP	-0.018	0.077	-10000	0	-0.24	14	14
GIPC1	0.01	0	-10000	0	-10000	0	0
KRAS	-0.007	0.078	-10000	0	-0.37	20	20
DNAJA3	-0.1	0.16	0.25	1	-0.42	69	70
RIN/GTP	0.001	0.017	-10000	0	-0.26	2	2
CCND1	0.008	0.097	-10000	0	-0.88	4	4
MAGED1	0.003	0.069	-10000	0	-0.65	5	5
PTPN11	0.01	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.12	0.21	-10000	0	-0.43	131	131
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.01	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.063	0.15	-10000	0	-0.45	49	49
TRKA/NEDD4-2	0.004	0.07	-10000	0	-0.46	10	10
ELMO1	0.002	0.071	-10000	0	-0.6	6	6
RhoG/GTP/ELMO1/DOCK1	-0.005	0.044	-10000	0	-0.42	5	5
NGF	-0.06	0.19	-10000	0	-0.53	59	59
HRAS	0.01	0	-10000	0	-10000	0	0
DOCK1	0.01	0	-10000	0	-10000	0	0
GAB2	0.006	0.053	-10000	0	-0.65	3	3
RIT2	0.001	0.025	-10000	0	-0.37	2	2
RIT1	0.009	0.018	-10000	0	-0.37	1	1
FRS2	0.005	0.043	-10000	0	-0.37	6	6
DNM1	-0.017	0.12	-10000	0	-0.52	23	23
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.1	0.16	0.24	1	-0.42	72	73
mol:GDP	-0.028	0.11	-10000	0	-0.34	24	24
NGF (dimer)	-0.06	0.19	-10000	0	-0.53	59	59
RhoG/GDP	0.001	0.053	-10000	0	-0.45	6	6
RIT1/GDP	-0.014	0.077	-10000	0	-0.24	11	11
TIAM1	-0.037	0.15	-10000	0	-0.46	46	46
PIK3R1	0.01	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.11	0.17	-10000	0	-0.43	82	82
KIDINS220/CRKL/C3G	0.014	0.012	-10000	0	-0.25	1	1
SHC/RasGAP	0.015	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.003	0.025	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	-0.002	0.03	-10000	0	-0.37	3	3
RIT1/GTP	0.007	0.012	-10000	0	-0.26	1	1
NT3 (dimer)	-0.048	0.17	-10000	0	-0.51	51	51
RAP1/GDP	-0.03	0.053	-10000	0	-0.24	3	3
KIDINS220/CRKL	0.009	0.018	-10000	0	-0.37	1	1
BDNF (dimer)	-0.016	0.1	-10000	0	-0.42	27	27
ubiquitin-dependent protein catabolic process	-0.05	0.13	-10000	0	-0.43	41	41
Schwann cell development	-0.034	0.034	-10000	0	-10000	0	0
EHD4	0.01	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	-0.003	0.021	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.028	0.024	-10000	0	-10000	0	0
RAP1B	0.008	0.025	-10000	0	-0.37	2	2
RAP1A	0.01	0	-10000	0	-10000	0	0
CDC42/GTP	-0.15	0.2	-10000	0	-0.6	48	48
ABL1	0.01	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.015	0	-10000	0	-10000	0	0
Rap1/GTP	-0.036	0.06	-10000	0	-10000	0	0
STAT3	0.009	0.044	-10000	0	-0.36	4	4
axon guidance	-0.14	0.19	-10000	0	-0.57	48	48
MAPK3	-0.036	0.14	-10000	0	-0.41	49	49
MAPK1	-0.036	0.14	-10000	0	-0.41	49	49
CDC42/GDP	-0.014	0.077	-10000	0	-0.24	14	14
NTF3	-0.048	0.17	-10000	0	-0.51	51	51
NTF4	-0.12	0.21	-10000	0	-0.43	131	131
NGF (dimer)/TRKA/FAIM	-0.051	0.13	-10000	0	-0.43	42	42
PI3K	0.014	0.012	-10000	0	-10000	0	0
FRS3	0.009	0.018	-10000	0	-0.37	1	1
FAIM	0.006	0.047	-10000	0	-0.56	3	3
GAB1	0.006	0.053	-10000	0	-0.65	3	3
RASGRF1	-0.12	0.18	0.25	1	-0.43	81	82
SOS1	0.01	0	-10000	0	-10000	0	0
MCF2L	-0.082	0.2	-10000	0	-0.48	68	68
RGS19	0.008	0.036	-10000	0	-0.51	2	2
CDC42	0.01	0	-10000	0	-10000	0	0
RAS family/GTP	-0.007	0.069	-10000	0	-10000	0	0
Rac1/GDP	-0.014	0.077	-10000	0	-0.24	11	11
NGF (dimer)/TRKA/GRIT	-0.05	0.13	-10000	0	-0.35	65	65
neuron projection morphogenesis	-0.074	0.16	-10000	0	-0.6	16	16
NGF (dimer)/TRKA/NEDD4-2	-0.05	0.13	-10000	0	-0.43	41	41
MAP2K1	0.028	0.03	-10000	0	-0.34	3	3
NGFR	-0.16	0.26	-10000	0	-0.5	153	153
NGF (dimer)/TRKA/GIPC/GAIP	-0.018	0.12	-10000	0	-0.33	48	48
RAS family/GTP/PI3K	0.018	0.028	-10000	0	-0.28	1	1
FRS2 family/SHP2/GRB2/SOS1	-0.002	0.019	-10000	0	-10000	0	0
NRAS	0.008	0.036	-10000	0	-0.51	2	2
GRB2/SOS1	0.015	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.018	-10000	0	-0.37	1	1
MAPKKK cascade	-0.08	0.2	-10000	0	-0.67	42	42
RASA1	0.01	0	-10000	0	-10000	0	0
TRKA/c-Abl	0.005	0.066	-10000	0	-0.46	9	9
SQSTM1	0.009	0.018	-10000	0	-0.37	1	1
BDNF (dimer)/TRKB/GIPC	-0.095	0.15	-10000	0	-0.39	82	82
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.041	0.11	-10000	0	-0.36	40	40
MATK	-0.015	0.12	-10000	0	-0.53	21	21
NEDD4L	0.009	0.031	-10000	0	-0.65	1	1
RAS family/GDP	-0.028	0.052	-10000	0	-0.22	3	3
NGF (dimer)/TRKA	-0.11	0.17	0.27	1	-0.4	93	94
Rac1/GTP	-0.089	0.11	-10000	0	-0.35	43	43
FRS2 family/SHP2/CRK family	-0.003	0.021	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.032	0.14	-9999	-0.35	61	61
NF kappa B1 p50/RelA/I kappa B alpha	-0.011	0.13	-9999	-0.5	8	8
alphaV/beta3 Integrin/Osteopontin/Src	-0.084	0.16	-9999	-0.47	57	57
AP1	-0.024	0.16	-9999	-0.54	16	16
ILK	-0.04	0.15	-9999	-0.37	61	61
bone resorption	-0.027	0.14	-9999	-0.54	9	9
PTK2B	0.01	0	-9999	-10000	0	0
PYK2/p130Cas	-0.061	0.12	-9999	-0.4	13	13
ITGAV	0.01	0.036	-9999	-0.52	2	2
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.002	0.094	-9999	-0.53	13	13
alphaV/beta3 Integrin/Osteopontin	-0.077	0.15	-9999	-0.42	60	60
MAP3K1	-0.041	0.15	-9999	-0.37	60	60
JUN	0.009	0.018	-9999	-0.38	1	1
MAPK3	-0.031	0.14	-9999	-0.35	61	61
MAPK1	-0.031	0.14	-9999	-0.35	61	61
Rac1/GDP	0.007	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
MAPK8	-0.032	0.14	-9999	-0.35	61	61
ITGB3	0	0.087	-9999	-0.57	10	10
NFKBIA	-0.023	0.14	-9999	-0.56	8	8
FOS	-0.014	0.12	-9999	-0.58	19	19
CD44	-0.011	0.11	-9999	-0.58	16	16
CHUK	0.01	0	-9999	-10000	0	0
PLAU	-0.027	0.19	-9999	-1.1	8	8
NF kappa B1 p50/RelA	-0.054	0.11	-9999	-0.5	8	8
BCAR1	0.01	0	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.011	0.067	-9999	-0.46	9	9
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.044	0.15	-9999	-0.37	63	63
VAV3	-0.068	0.17	-9999	-0.37	89	89
MAP3K14	-0.041	0.15	-9999	-0.38	61	61
ROCK2	0.007	0.044	-9999	-0.65	2	2
SPP1	-0.11	0.23	-9999	-0.51	104	104
RAC1	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.086	0.14	-9999	-0.47	22	22
MMP2	-0.02	0.16	-9999	-0.66	13	13

×

Thromboxane A2 receptor 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
TGM2	-0.04	0.17	-10000	0	-0.6	37	37
GNB1/GNG2	-0.041	0.065	-10000	0	-0.19	51	51
AKT1	-0.013	0.089	-10000	0	-0.21	42	42
EGF	-0.14	0.24	-10000	0	-0.47	144	144
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.01	0.089	-10000	0	-0.45	10	10
mol:Ca2+	-0.034	0.13	-10000	0	-0.31	58	58
LYN	0.013	0.071	-10000	0	-0.33	7	7
RhoA/GTP	-0.025	0.043	-10000	0	-0.14	17	17
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.038	0.14	-10000	0	-0.34	58	58
GNG2	0.006	0.047	-10000	0	-0.56	3	3
ARRB2	0.01	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.002	0.077	-10000	0	-0.49	5	5
G beta5/gamma2	-0.05	0.085	-10000	0	-0.25	50	50
PRKCH	-0.037	0.14	-10000	0	-0.35	57	57
DNM1	-0.017	0.12	-10000	0	-0.52	23	23
TXA2/TP beta/beta Arrestin3	-0.023	0.09	-10000	0	-0.39	21	21
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.027	0.14	-10000	0	-0.55	30	30
G12 family/GTP	-0.063	0.1	-10000	0	-0.3	57	57
ADRBK1	0.007	0.04	-10000	0	-0.47	3	3
ADRBK2	0.008	0.036	-10000	0	-0.51	2	2
RhoA/GTP/ROCK1	0.005	0.021	-10000	0	-0.42	1	1
mol:GDP	0.019	0.091	0.32	13	-10000	0	13
mol:NADP	0.003	0.059	-10000	0	-0.45	7	7
RAB11A	0.01	0	-10000	0	-10000	0	0
PRKG1	0.004	0.056	-10000	0	-0.47	6	6
mol:IP3	-0.046	0.15	-10000	0	-0.38	58	58
cell morphogenesis	-0.001	0.019	-10000	0	-0.42	1	1
PLCB2	-0.067	0.2	-10000	0	-0.52	58	58
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.048	0.13	-10000	0	-0.31	73	73
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.011	0.085	-10000	0	-0.44	9	9
RHOA	0.01	0	-10000	0	-10000	0	0
PTGIR	0.004	0.059	-10000	0	-0.54	5	5
PRKCB1	-0.043	0.15	-10000	0	-0.37	57	57
GNAQ	0.01	0	-10000	0	-10000	0	0
mol:L-citrulline	0.003	0.059	-10000	0	-0.45	7	7
TXA2/TXA2-R family	-0.069	0.2	-10000	0	-0.53	57	57
LCK	0.002	0.091	-10000	0	-0.34	18	18
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.023	0.08	-10000	0	-0.34	15	15
TXA2-R family/G12 family/GDP/G beta/gamma	0.018	0.03	-10000	0	-0.3	2	2
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.017	0.068	-10000	0	-0.42	5	5
MAPK14	-0.018	0.098	-10000	0	-0.23	42	42
TGM2/GTP	-0.063	0.19	-10000	0	-0.48	61	61
MAPK11	-0.018	0.098	-10000	0	-0.23	48	48
ARHGEF1	-0.014	0.077	-10000	0	-0.18	45	45
GNAI2	0.01	0	-10000	0	-10000	0	0
JNK cascade	-0.046	0.16	-10000	0	-0.39	58	58
RAB11/GDP	0.01	0.001	-10000	0	-10000	0	0
ICAM1	-0.031	0.12	-10000	0	-0.3	49	49
cAMP biosynthetic process	-0.05	0.15	-10000	0	-0.38	61	61
Gq family/GTP/EBP50	-0.001	0.067	-10000	0	-0.26	22	22
actin cytoskeleton reorganization	-0.001	0.019	-10000	0	-0.42	1	1
SRC	0.015	0.067	-10000	0	-0.36	4	4
GNB5	0.008	0.031	-10000	0	-0.65	1	1
GNB1	0.01	0	-10000	0	-10000	0	0
EGF/EGFR	-0.031	0.1	-10000	0	-0.33	25	25
VCAM1	-0.035	0.13	-10000	0	-0.32	50	50
TP beta/Gq family/GDP/G beta5/gamma2	0.002	0.077	-10000	0	-0.49	5	5
platelet activation	-0.025	0.13	-10000	0	-0.3	57	57
PGI2/IP	0	0.044	-10000	0	-0.4	5	5
PRKACA	-0.004	0.079	-10000	0	-0.34	21	21
Gq family/GDP/G beta5/gamma2	0.001	0.076	-10000	0	-0.44	6	6
TXA2/TP beta/beta Arrestin2	-0.019	0.091	-10000	0	-0.56	12	12
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.001	0.084	-10000	0	-0.33	24	24
mol:DAG	-0.048	0.16	-10000	0	-0.41	57	57
EGFR	-0.036	0.14	-10000	0	-0.44	46	46
TXA2/TP alpha	-0.07	0.2	-10000	0	-0.52	61	61
Gq family/GTP	-0.02	0.067	-10000	0	-0.29	22	22
YES1	0.014	0.068	-10000	0	-0.35	5	5
GNAI2/GTP	-0.018	0.065	-10000	0	-0.35	7	7
PGD2/DP	-0.022	0.1	-10000	0	-0.4	30	30
SLC9A3R1	0.01	0	-10000	0	-10000	0	0
FYN	0.015	0.067	-10000	0	-0.37	4	4
mol:NO	0.003	0.059	-10000	0	-0.45	7	7
GNA15	-0.035	0.13	-10000	0	-0.39	51	51
PGK/cGMP	-0.006	0.049	-10000	0	-0.27	13	13
RhoA/GDP	0.01	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.04	0.12	-10000	0	-0.37	33	33
NOS3	0.003	0.059	-10000	0	-0.45	7	7
RAC1	0.01	0	-10000	0	-10000	0	0
PRKCA	-0.04	0.14	-10000	0	-0.36	57	57
PRKCB	-0.049	0.16	-10000	0	-0.39	54	54
PRKCE	-0.034	0.14	-10000	0	-0.35	49	49
PRKCD	-0.039	0.14	-10000	0	-0.38	48	48
PRKCG	-0.078	0.18	-10000	0	-0.45	65	65
muscle contraction	-0.063	0.19	-10000	0	-0.5	58	58
PRKCZ	-0.037	0.14	-10000	0	-0.34	57	57
ARR3	-0.005	0.097	-10000	0	-0.65	10	10
TXA2/TP beta	-0.019	0.073	-10000	0	-0.33	13	13
PRKCQ	-0.046	0.15	-10000	0	-0.38	57	57
MAPKKK cascade	-0.059	0.18	-10000	0	-0.47	58	58
SELE	-0.045	0.14	-10000	0	-0.37	51	51
TP beta/GNAI2/GDP/G beta/gamma	-0.018	0.078	-10000	0	-0.54	5	5
ROCK1	0.009	0.031	-10000	0	-0.65	1	1
GNA14	-0.026	0.14	-10000	0	-0.56	29	29
chemotaxis	-0.076	0.22	-10000	0	-0.61	50	50
GNA12	0.01	0	-10000	0	-10000	0	0
GNA13	0.01	0	-10000	0	-10000	0	0
GNA11	0.01	0	-10000	0	-10000	0	0
Rac1/GTP	0.004	0.004	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0	0.077	-10000	0	-0.61	7	7
EPHB2	-0.039	0.16	-10000	0	-0.55	40	40
EFNB1	-0.01	0.1	-10000	0	-0.4	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.08	0.16	-10000	0	-0.6	24	24
Ephrin B2/EPHB1-2	-0.056	0.13	-10000	0	-0.41	43	43
neuron projection morphogenesis	-0.079	0.15	-10000	0	-0.58	24	24
Ephrin B1/EPHB1-2/Tiam1	-0.07	0.18	-10000	0	-0.45	67	67
DNM1	-0.017	0.12	-10000	0	-0.52	23	23
cell-cell signaling	-0.001	0.003	-10000	0	-10000	0	0
MAP2K4	-0.03	0.16	-10000	0	-0.7	22	22
YES1	-0.051	0.2	-10000	0	-0.98	19	19
Ephrin B1/EPHB1-2/NCK2	-0.046	0.16	-10000	0	-0.43	51	51
PI3K	-0.028	0.16	-10000	0	-0.77	19	19
mol:GDP	-0.083	0.17	-10000	0	-0.45	67	67
ITGA2B	-0.026	0.14	-10000	0	-0.52	31	31
endothelial cell proliferation	-0.004	0.052	-10000	0	-0.39	8	8
FYN	-0.05	0.2	-10000	0	-0.99	19	19
MAP3K7	-0.043	0.16	-10000	0	-0.8	19	19
FGR	-0.054	0.2	-10000	0	-0.99	19	19
TIAM1	-0.037	0.15	-10000	0	-0.46	46	46
PIK3R1	0.01	0	-10000	0	-10000	0	0
RGS3	0.01	0	-10000	0	-10000	0	0
cell adhesion	-0.038	0.18	-10000	0	-0.68	24	24
LYN	-0.052	0.2	-10000	0	-0.98	19	19
Ephrin B1/EPHB1-2/Src Family Kinases	-0.049	0.18	-10000	0	-0.93	19	19
Ephrin B1/EPHB1-2	-0.051	0.17	-10000	0	-0.86	19	19
SRC	-0.051	0.2	-10000	0	-0.97	19	19
ITGB3	-0.003	0.087	-10000	0	-0.57	10	10
EPHB1	-0.048	0.16	-10000	0	-0.44	59	59
EPHB4	0.009	0.031	-10000	0	-0.65	1	1
RAC1	0.01	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.004	0.053	-10000	0	-0.39	8	8
alphaIIb/beta3 Integrin	-0.02	0.12	-10000	0	-0.4	39	39
BLK	-0.079	0.22	-10000	0	-1	19	19
HCK	-0.053	0.2	-10000	0	-0.99	19	19
regulation of stress fiber formation	0.06	0.15	0.42	51	-10000	0	51
MAPK8	-0.024	0.15	-10000	0	-0.65	23	23
Ephrin B1/EPHB1-2/RGS3	-0.046	0.16	-10000	0	-0.43	51	51
endothelial cell migration	-0.042	0.15	-10000	0	-0.61	26	26
NCK2	0.01	0	-10000	0	-10000	0	0
PTPN13	-0.079	0.19	-10000	0	-0.43	89	89
regulation of focal adhesion formation	0.06	0.15	0.42	51	-10000	0	51
chemotaxis	0.06	0.15	0.42	51	-10000	0	51
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
Rac1/GTP	-0.081	0.16	-10000	0	-0.6	24	24
angiogenesis	-0.05	0.17	-10000	0	-0.86	19	19
LCK	-0.056	0.2	-10000	0	-0.98	19	19

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.009	0.031	-10000	0	-0.65	1	1
HDAC3	0.01	0	-10000	0	-10000	0	0
VDR	0.001	0.075	-10000	0	-0.65	6	6
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.01	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.003	0.056	-10000	0	-0.28	2	2
KAT2B	0.01	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
AKT1	-0.006	0.069	0.21	6	-0.27	10	16
RAR alpha/9cRA/Cyclin H	-0.055	0.11	-10000	0	-0.47	10	10
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0	0.057	-10000	0	-0.28	2	2
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.055	0.098	-10000	0	-0.49	7	7
NCOR2	0.01	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.001	0.056	-10000	0	-0.49	6	6
RXRs/RARs/NRIP1/9cRA	-0.079	0.22	-10000	0	-0.5	86	86
NCOA2	0.007	0.044	-10000	0	-0.65	2	2
NCOA3	0.01	0	-10000	0	-10000	0	0
NCOA1	0.01	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.001	0.075	-10000	0	-0.65	6	6
RARG	0.005	0.056	-10000	0	-0.58	4	4
RAR gamma1/9cRA	0.005	0.036	-10000	0	-0.42	3	3
MAPK3	0.01	0.001	-10000	0	-10000	0	0
MAPK1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.009	0.031	-10000	0	-0.65	1	1
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.12	0.22	-10000	0	-0.54	86	86
RARA	-0.053	0.13	-10000	0	-0.29	85	85
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.001	0.061	-10000	0	-0.34	3	3
PRKCA	0.001	0.087	-10000	0	-0.65	8	8
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.087	0.22	-10000	0	-0.51	86	86
RXRG	-0.12	0.22	-10000	0	-0.45	110	110
RXRA	-0.04	0.12	-10000	0	-0.26	86	86
RXRB	-0.081	0.17	-10000	0	-0.4	85	85
VDR/Vit D3/DNA	0.001	0.056	-10000	0	-0.49	6	6
RBP1	-0.055	0.16	-10000	0	-0.4	72	72
CRBP1/9-cic-RA	-0.038	0.11	-10000	0	-0.28	72	72
RARB	0.001	0.071	-10000	0	-0.46	10	10
PRKCG	-0.17	0.26	-10000	0	-0.51	159	159
MNAT1	0.01	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.081	0.22	-10000	0	-0.52	85	85
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.066	0.19	-10000	0	-0.43	86	86
proteasomal ubiquitin-dependent protein catabolic process	-0.019	0.097	-10000	0	-0.49	5	5
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.087	0.22	-10000	0	-0.51	86	86
positive regulation of DNA binding	-0.052	0.1	-10000	0	-0.44	10	10
NRIP1	-0.078	0.21	-10000	0	-0.69	21	21
RXRs/RARs	-0.091	0.22	-10000	0	-0.51	85	85
RXRs/RXRs/DNA/9cRA	-0.12	0.22	-10000	0	-0.55	86	86
PRKACA	0.01	0	-10000	0	-10000	0	0
CDK7	0.01	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.039	0.075	-10000	0	-0.46	5	5
CCNH	0.01	0	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	-0.002	0.026	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.087	-9999	-0.65	8	8
alphaV beta3 Integrin	0.004	0.069	-9999	-0.48	8	8
PTK2	-0.057	0.16	-9999	-0.5	44	44
positive regulation of JNK cascade	-0.033	0.097	-9999	-0.32	44	44
CDC42/GDP	-0.007	0.14	-9999	-0.44	44	44
Rac1/GDP	-0.005	0.14	-9999	-0.43	44	44
RAP1B	0.008	0.025	-9999	-0.37	2	2
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	-0.041	0.12	-9999	-0.4	44	44
nectin-3/I-afadin	-0.034	0.15	-9999	-0.47	46	46
RAPGEF1	-0.015	0.16	-9999	-0.49	44	44
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.026	0.18	-9999	-0.57	44	44
PDGFB-D/PDGFRB	-0.002	0.087	-9999	-0.65	8	8
TLN1	0.002	0.075	-9999	-0.56	2	2
Rap1/GTP	-0.036	0.1	-9999	-0.35	44	44
IQGAP1	0.01	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.002	0.021	-9999	-0.38	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.034	0.15	-9999	-0.47	46	46
PVR	0.005	0.05	-9999	-0.51	4	4
Necl-5(dimer)	0.005	0.05	-9999	-0.51	4	4
mol:GDP	-0.017	0.18	-9999	-0.54	44	44
MLLT4	0.009	0.031	-9999	-0.65	1	1
PIK3CA	0.009	0.018	-9999	-0.37	1	1
PI3K	-0.04	0.12	-9999	-0.36	49	49
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.013	0.089	-9999	-0.28	44	44
positive regulation of lamellipodium assembly	-0.036	0.1	-9999	-0.34	46	46
PVRL1	-0.028	0.12	-9999	-0.4	43	43
PVRL3	-0.054	0.19	-9999	-0.64	45	45
PVRL2	0.008	0.025	-9999	-0.37	2	2
PIK3R1	0.01	0	-9999	-10000	0	0
CDH1	-0.016	0.13	-9999	-0.65	18	18
CLDN1	-0.057	0.19	-9999	-0.55	55	55
JAM-A/CLDN1	-0.073	0.16	-9999	-0.42	74	74
SRC	-0.067	0.19	-9999	-0.64	44	44
ITGB3	-0.003	0.087	-9999	-0.57	10	10
nectin-1(dimer)/I-afadin/I-afadin	-0.013	0.089	-9999	-0.28	44	44
FARP2	-0.02	0.17	-9999	-0.53	44	44
RAC1	0.01	0	-9999	-10000	0	0
CTNNA1	0.007	0.044	-9999	-0.65	2	2
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.043	0.13	-9999	-0.42	45	45
nectin-1/I-afadin	-0.013	0.089	-9999	-0.28	44	44
nectin-2/I-afadin	0.013	0.029	-9999	-0.48	1	1
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.061	0.15	-9999	-0.46	48	48
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.007	0.044	-9999	-0.65	2	2
positive regulation of filopodium formation	-0.033	0.097	-9999	-0.32	44	44
alphaV/beta3 Integrin/Talin	0.006	0.094	-9999	-0.56	6	6
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.013	0.029	-9999	-0.48	1	1
nectin-2(dimer)/I-afadin/I-afadin	0.013	0.029	-9999	-0.48	1	1
PIP5K1C	-0.004	0.08	-9999	-0.6	2	2
VAV2	-0.023	0.18	-9999	-0.54	46	46
RAP1/GDP	-0.042	0.12	-9999	-0.41	44	44
ITGAV	0.008	0.036	-9999	-0.51	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.041	0.12	-9999	-0.41	44	44
nectin-3(dimer)/I-afadin/I-afadin	-0.034	0.15	-9999	-0.47	46	46
Rac1/GTP	-0.044	0.13	-9999	-0.41	46	46
PTPRM	-0.012	0.087	-9999	-0.26	45	45
E-cadherin/beta catenin/alpha catenin	-0.031	0.086	-9999	-0.58	2	2
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.006	0.035	-10000	0	-0.64	1	1
AES	0.011	0.014	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.006	0.032	-10000	0	-0.31	4	4
SMAD4	0.009	0.031	-10000	0	-0.65	1	1
DKK2	-0.03	0.15	-10000	0	-0.58	31	31
TLE1	0.001	0.063	-10000	0	-0.64	4	4
MACF1	0.008	0.025	-10000	0	-0.37	2	2
CTNNB1	-0.004	0.092	0.24	1	-0.39	5	6
WIF1	-0.072	0.17	-10000	0	-0.43	83	83
beta catenin/RanBP3	0	0.11	0.36	20	-0.54	1	21
KREMEN2	-0.055	0.16	-10000	0	-0.43	67	67
DKK1	-0.22	0.29	-10000	0	-0.55	190	190
beta catenin/beta TrCP1	0.003	0.086	0.23	1	-0.41	3	4
FZD1	0.007	0.031	-10000	0	-0.37	3	3
AXIN2	-0.046	0.27	-10000	0	-1.5	15	15
AXIN1	0.009	0.031	-10000	0	-0.65	1	1
RAN	0.01	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.003	0.039	-10000	0	-0.48	2	2
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.025	0.14	-10000	0	-0.41	19	19
Axin1/APC/GSK3	-0.003	0.074	0.21	2	-0.42	3	5
Axin1/APC/GSK3/beta catenin/Macf1	0.002	0.1	-10000	0	-0.34	24	24
HNF1A	-0.13	0.27	-10000	0	-0.65	97	97
CTBP1	0.006	0.018	-10000	0	-10000	0	0
MYC	0.007	0.11	-10000	0	-1.5	2	2
RANBP3	0.01	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.059	0.13	-10000	0	-0.42	38	38
NKD1	-0.059	0.18	-10000	0	-0.48	64	64
TCF4	0.003	0.052	-10000	0	-0.51	4	4
TCF3	0.006	0.018	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.032	0.11	-10000	0	-0.37	37	37
Ran/GTP	0.002	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.017	0.14	0.44	13	-0.53	2	15
LEF1	-0.002	0.074	-10000	0	-0.56	7	7
DVL1	-0.003	0.1	-10000	0	-0.34	30	30
CSNK2A1	-0.036	0.17	-10000	0	-0.65	32	32
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.029	0.15	-10000	0	-0.45	21	21
DKK1/LRP6/Kremen 2	-0.17	0.2	-10000	0	-0.44	138	138
LRP6	0.008	0.031	-10000	0	-0.65	1	1
CSNK1A1	0.007	0.018	-10000	0	-10000	0	0
NLK	0.009	0.003	-10000	0	-10000	0	0
CCND1	-0.004	0.15	-10000	0	-1.5	4	4
WNT1	-0.05	0.18	-10000	0	-0.58	46	46
GSK3A	0.009	0.031	-10000	0	-0.65	1	1
GSK3B	0.01	0.001	-10000	0	-10000	0	0
FRAT1	0.008	0.031	-10000	0	-0.65	1	1
PPP2R5D	0.031	0.091	0.24	45	-0.27	2	47
APC	-0.007	0.11	-10000	0	-0.34	39	39
WNT1/LRP6/FZD1	0.01	0.091	0.24	15	-0.24	29	44
CREBBP	0.006	0.018	-10000	0	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.02	0.085	-9999	-0.41	16	16
NF kappa B1 p50/RelA/I kappa B alpha	-0.048	0.083	-9999	-0.35	3	3
AP1	-0.084	0.13	-9999	-0.35	64	64
mol:PIP3	-0.084	0.13	-9999	-0.51	13	13
AKT1	0.027	0.064	-9999	-0.39	3	3
PTK2B	-0.005	0.06	-9999	-0.27	7	7
RHOA	0.02	0.031	-9999	-10000	0	0
PIK3CB	0.01	0	-9999	-10000	0	0
mol:Ca2+	-0.035	0.11	-9999	-0.3	33	33
MAGI3	0.008	0.031	-9999	-0.65	1	1
RELA	0.01	0	-9999	-10000	0	0
apoptosis	-0.058	0.12	-9999	-0.34	56	56
HRAS/GDP	0.007	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.026	0.1	-9999	-0.34	30	30
NF kappa B1 p50/RelA	-0.066	0.11	-9999	-0.44	6	6
endothelial cell migration	-0.011	0.14	-9999	-0.53	26	26
ADCY4	-0.023	0.15	-9999	-0.6	20	20
ADCY5	-0.048	0.18	-9999	-0.58	33	33
ADCY6	-0.024	0.15	-9999	-0.59	21	21
ADCY7	-0.024	0.15	-9999	-0.62	19	19
ADCY1	-0.028	0.15	-9999	-0.62	21	21
ADCY2	-0.052	0.19	-9999	-0.61	32	32
ADCY3	-0.023	0.14	-9999	-0.62	19	19
ADCY8	-0.027	0.15	-9999	-0.6	20	20
ADCY9	-0.023	0.15	-9999	-0.6	20	20
GSK3B	0.001	0.057	-9999	-0.3	3	3
arachidonic acid secretion	-0.019	0.14	-9999	-0.58	20	20
GNG2	0.006	0.047	-9999	-0.56	3	3
TRIP6	-0.002	0.095	-9999	-0.44	20	20
GNAO1	-0.036	0.14	-9999	-0.48	31	31
HRAS	0.01	0	-9999	-10000	0	0
NFKBIA	-0.031	0.11	-9999	-0.34	32	32
GAB1	0.006	0.053	-9999	-0.65	3	3
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.03	0.16	-9999	-0.93	14	14
JUN	0.009	0.018	-9999	-0.37	1	1
LPA/LPA2/NHERF2	-0.002	0.013	-9999	-10000	0	0
TIAM1	-0.037	0.19	-9999	-1.1	14	14
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	-0.035	0.11	-9999	-0.3	33	33
PLCB3	0.018	0.03	-9999	-0.37	2	2
FOS	-0.015	0.12	-9999	-0.58	19	19
positive regulation of mitosis	-0.019	0.14	-9999	-0.58	20	20
LPA/LPA1-2-3	-0.087	0.13	-9999	-0.38	51	51
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0.001	-9999	-10000	0	0
BCAR1	0.01	0	-9999	-10000	0	0
stress fiber formation	-0.026	0.1	-9999	-0.33	22	22
GNAZ	-0.027	0.13	-9999	-0.4	44	44
EGFR/PI3K-beta/Gab1	-0.087	0.13	-9999	-0.54	13	13
positive regulation of dendritic cell cytokine production	-0.086	0.13	-9999	-0.38	51	51
LPA/LPA2/MAGI-3	-0.003	0.023	-9999	-0.41	1	1
ARHGEF1	0.012	0.077	-9999	-0.36	14	14
GNAI2	0	0.09	-9999	-0.37	23	23
GNAI3	0	0.09	-9999	-0.37	23	23
GNAI1	-0.009	0.12	-9999	-0.47	25	25
LPA/LPA3	-0.099	0.15	-9999	-0.31	145	145
LPA/LPA2	-0.003	0.018	-9999	-10000	0	0
LPA/LPA1	-0.024	0.1	-9999	-0.42	25	25
HB-EGF/EGFR	-0.042	0.13	-9999	-0.42	40	40
HBEGF	-0.02	0.12	-9999	-0.38	43	43
mol:DAG	-0.035	0.11	-9999	-0.3	33	33
cAMP biosynthetic process	-0.036	0.16	-9999	-0.56	28	28
NFKB1	0.01	0	-9999	-10000	0	0
SRC	0.009	0.031	-9999	-0.65	1	1
GNB1	0.01	0	-9999	-10000	0	0
LYN	-0.034	0.12	-9999	-0.35	36	36
GNAQ	-0.046	0.1	-9999	-0.33	35	35
LPAR2	0.01	0	-9999	-10000	0	0
LPAR3	-0.13	0.22	-9999	-0.43	145	145
LPAR1	-0.013	0.12	-9999	-0.62	16	16
IL8	-0.11	0.2	-9999	-0.48	79	79
PTK2	-0.061	0.14	-9999	-0.36	51	51
Rac1/GDP	0.007	0	-9999	-10000	0	0
CASP3	-0.058	0.12	-9999	-0.34	56	56
EGFR	-0.036	0.14	-9999	-0.45	46	46
PLCG1	-0.05	0.12	-9999	-0.32	54	54
PLD2	-0.061	0.13	-9999	-0.36	51	51
G12/G13	-0.018	0.076	-9999	-0.39	14	14
PI3K-beta	-0.014	0.061	-9999	-0.46	3	3
cell migration	-0.037	0.063	-9999	-0.26	19	19
SLC9A3R2	0.01	0	-9999	-10000	0	0
PXN	-0.027	0.1	-9999	-0.34	22	22
HRAS/GTP	-0.02	0.15	-9999	-0.6	20	20
RAC1	0.01	0	-9999	-10000	0	0
MMP9	-0.034	0.15	-9999	-0.53	37	37
PRKCE	0.01	0.002	-9999	-10000	0	0
PRKCD	-0.029	0.1	-9999	-0.38	3	3
Gi(beta/gamma)	-0.019	0.14	-9999	-0.58	20	20
mol:LPA	-0.002	0.03	-9999	-0.2	9	9
TRIP6/p130 Cas/FAK1/Paxillin	-0.073	0.12	-9999	-0.52	11	11
MAPKKK cascade	-0.019	0.14	-9999	-0.58	20	20
contractile ring contraction involved in cytokinesis	0.02	0.031	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.065	0.13	-9999	-0.38	54	54
GNA15	-0.063	0.12	-9999	-0.3	82	82
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
MAPT	-0.027	0.11	-9999	-0.35	30	30
GNA11	-0.046	0.1	-9999	-0.33	35	35
Rac1/GTP	-0.032	0.17	-9999	-1	14	14
MMP2	-0.011	0.14	-9999	-0.54	26	26

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.01	0	-10000	0	-10000	0	0
PTK2	0.009	0.031	-10000	0	-0.65	1	1
CRKL	-0.036	0.13	-10000	0	-0.37	48	48
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0.01	0	-10000	0	-10000	0	0
IRS1/Crk	-0.036	0.13	-10000	0	-0.38	47	47
IGF-1R heterotetramer/IGF1/PTP1B	-0.063	0.14	-10000	0	-0.42	47	47
AKT1	-0.04	0.14	-10000	0	-0.55	11	11
BAD	-0.033	0.13	-10000	0	-0.51	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.036	0.13	-10000	0	-0.38	47	47
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.036	0.13	-10000	0	-0.38	47	47
RAF1	-0.031	0.14	-10000	0	-0.52	10	10
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.028	0.12	-10000	0	-0.36	47	47
YWHAZ	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.046	0.14	-10000	0	-0.41	48	48
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
RPS6KB1	-0.04	0.14	-10000	0	-0.55	11	11
GNB2L1	0.01	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.027	0.12	-10000	0	-0.43	10	10
PXN	0.003	0.064	-10000	0	-0.6	5	5
PIK3R1	0.01	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.015	0	-10000	0	-10000	0	0
HRAS/GTP	-0.042	0.1	-10000	0	-0.59	6	6
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.048	0.11	-10000	0	-0.34	46	46
IGF-1R heterotetramer	-0.021	0.11	-10000	0	-0.59	16	16
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.036	0.13	-10000	0	-0.38	48	48
Crk/p130 Cas/Paxillin	-0.049	0.12	-10000	0	-0.57	10	10
IGF1R	-0.021	0.11	-10000	0	-0.59	16	16
IGF1	-0.09	0.21	-10000	0	-0.51	88	88
IRS2/Crk	-0.051	0.16	-10000	0	-0.39	64	64
PI3K	-0.028	0.12	-10000	0	-0.36	46	46
apoptosis	0.023	0.12	0.43	11	-10000	0	11
HRAS/GDP	0.007	0	-10000	0	-10000	0	0
PRKCD	-0.026	0.15	-10000	0	-0.46	40	40
RAF1/14-3-3 E	-0.021	0.12	-10000	0	-0.44	10	10
BAD/14-3-3	-0.024	0.12	-10000	0	-0.46	11	11
PRKCZ	-0.041	0.14	-10000	0	-0.55	11	11
Crk/p130 Cas/Paxillin/FAK1	-0.056	0.11	-10000	0	-0.5	11	11
PTPN1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.033	0.15	-10000	0	-0.47	46	46
BCAR1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.056	0.13	-10000	0	-0.39	47	47
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.036	0.13	-10000	0	-0.37	48	48
GRB10	0.006	0.053	-10000	0	-0.65	3	3
PTPN11	-0.036	0.13	-10000	0	-0.38	47	47
IRS1	-0.046	0.14	-10000	0	-0.41	48	48
IRS2	-0.06	0.16	-10000	0	-0.41	67	67
IGF-1R heterotetramer/IGF1	-0.072	0.18	-10000	0	-0.54	48	48
GRB2	0.01	0	-10000	0	-10000	0	0
PDPK1	-0.049	0.15	-10000	0	-0.4	39	39
YWHAE	0.01	0	-10000	0	-10000	0	0
PRKD1	-0.034	0.16	-10000	0	-0.5	42	42
SHC1	0.01	0	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.013	0.005	-10000	0	-10000	0	0
RAS family/GTP	-0.034	0.12	-10000	0	-0.4	15	15
NFATC4	-0.031	0.11	-10000	0	-0.39	8	8
ERBB2IP	0.006	0.053	-10000	0	-0.65	3	3
HSP90 (dimer)	0.009	0.031	-10000	0	-0.65	1	1
mammary gland morphogenesis	-0.052	0.14	0.23	3	-0.33	72	75
JUN	0.019	0.058	0.16	3	-10000	0	3
HRAS	0.01	0.001	-10000	0	-10000	0	0
DOCK7	-0.044	0.13	-10000	0	-0.51	8	8
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.077	0.16	0.24	3	-0.39	75	78
AKT1	0.008	0.003	-10000	0	-10000	0	0
BAD	0.014	0.003	-10000	0	-10000	0	0
MAPK10	-0.046	0.075	-10000	0	-0.26	22	22
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.055	0.15	0.25	3	-0.36	72	75
RAF1	-0.022	0.12	-10000	0	-0.43	11	11
ErbB2/ErbB3/neuregulin 2	-0.054	0.13	0.25	2	-0.44	34	36
STAT3	-0.001	0.051	-10000	0	-1.1	1	1
cell migration	-0.013	0.081	0.17	2	-0.26	10	12
mol:PI-3-4-5-P3	-0.001	0.002	-10000	0	-10000	0	0
cell proliferation	-0.029	0.2	-10000	0	-0.61	36	36
FOS	-0.01	0.15	-10000	0	-0.39	46	46
NRAS	0.008	0.036	-10000	0	-0.51	2	2
mol:Ca2+	-0.052	0.14	0.23	3	-0.33	72	75
MAPK3	-0.024	0.17	-10000	0	-0.49	36	36
MAPK1	-0.024	0.17	-10000	0	-0.49	36	36
JAK2	-0.047	0.14	-10000	0	-0.5	9	9
NF2	-0.003	0.007	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.049	0.13	-10000	0	-0.33	72	72
NRG1	-0.13	0.25	-10000	0	-0.53	121	121
GRB2/SOS1	0.013	0.005	-10000	0	-10000	0	0
MAPK8	-0.031	0.12	0.21	3	-0.3	73	76
MAPK9	-0.034	0.062	-10000	0	-0.27	6	6
ERBB2	-0.021	0.091	0.41	3	-0.3	35	38
ERBB3	-0.002	0.083	-10000	0	-0.62	8	8
SHC1	0.01	0.001	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
apoptosis	0.002	0.01	-10000	0	-10000	0	0
STAT3 (dimer)	0.001	0.049	-10000	0	-1	1	1
RNF41	0.016	0.008	-10000	0	-10000	0	0
FRAP1	0.006	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.049	0.084	-10000	0	-0.34	8	8
ErbB2/ErbB2/HSP90 (dimer)	-0.018	0.076	0.27	3	-0.25	36	39
CHRNA1	-0.029	0.2	-10000	0	-0.64	35	35
myelination	-0.029	0.11	-10000	0	-0.38	8	8
PPP3CB	-0.041	0.12	-10000	0	-0.37	17	17
KRAS	-0.007	0.078	-10000	0	-0.37	20	20
RAC1-CDC42/GDP	-0.033	0.12	-10000	0	-0.46	8	8
NRG2	-0.05	0.17	-10000	0	-0.5	54	54
mol:GDP	-0.049	0.13	-10000	0	-0.32	72	72
SOS1	0.01	0.001	-10000	0	-10000	0	0
MAP2K2	-0.016	0.12	-10000	0	-0.43	10	10
SRC	0.009	0.031	-10000	0	-0.65	1	1
mol:cAMP	-0.001	0.002	-10000	0	-10000	0	0
PTPN11	-0.045	0.13	-10000	0	-0.5	8	8
MAP2K1	-0.03	0.16	-10000	0	-0.48	22	22
heart morphogenesis	-0.052	0.14	0.23	3	-0.33	72	75
RAS family/GDP	-0.035	0.12	-10000	0	-0.4	15	15
GRB2	0.01	0.001	-10000	0	-10000	0	0
PRKACA	-0.005	0.009	-10000	0	-10000	0	0
CHRNE	0.012	0.014	-10000	0	-10000	0	0
HSP90AA1	0.009	0.031	-10000	0	-0.65	1	1
activation of caspase activity	-0.007	0.003	-10000	0	-10000	0	0
nervous system development	-0.052	0.14	0.23	3	-0.33	72	75
CDC42	0.01	0	-10000	0	-10000	0	0

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.048	0.091	0.31	29	-10000	0	29
GNAI2	0.01	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.045	0.092	-10000	0	-0.42	6	6
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.05	0.16	-10000	0	-0.45	60	60
RhoA/GTP	-0.049	0.093	-10000	0	-0.32	29	29
negative regulation of cAMP metabolic process	-0.039	0.11	-10000	0	-0.3	48	48
GNAZ	-0.032	0.15	-10000	0	-0.55	34	34
GNAI3	0.01	0	-10000	0	-10000	0	0
GNA12	0.01	0	-10000	0	-10000	0	0
S1PR5	-0.072	0.16	-10000	0	-0.39	94	94
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.04	0.11	-10000	0	-0.31	48	48
RhoA/GDP	0.007	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.093	-10000	0	-0.56	12	12

×

LPA4-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.014	0.02	-9999	-0.42	1	1
ADCY5	-0.045	0.13	-9999	-0.3	88	88
ADCY6	0.011	0.04	-9999	-0.42	4	4
ADCY7	0.013	0.028	-9999	-0.42	2	2
ADCY1	0	0.063	-9999	-0.25	25	25
ADCY2	-0.049	0.14	-9999	-0.32	86	86
ADCY3	0.014	0.02	-9999	-0.42	1	1
ADCY8	0	0.048	-9999	-0.21	23	23
PRKCE	0.009	0	-9999	-10000	0	0
ADCY9	0.014	0.02	-9999	-0.42	1	1
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.02	0.076	-9999	-0.25	19	19

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	-0.003	0.12	-10000	0	-1.3	4	4
VDR	0.001	0.075	-10000	0	-0.65	6	6
FAM120B	0.01	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0	0.1	-10000	0	-0.44	5	5
RXRs/LXRs/DNA/Oxysterols	0.004	0.11	-10000	0	-0.42	16	16
MED1	0.009	0.018	-10000	0	-0.37	1	1
mol:9cRA	0.002	0.011	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.007	0.092	-10000	0	-0.28	43	43
RXRs/NUR77	-0.02	0.13	-10000	0	-0.38	43	43
RXRs/PPAR	-0.032	0.13	-10000	0	-0.3	81	81
NCOR2	0.01	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.001	0.056	-10000	0	-0.49	6	6
RARs/VDR/DNA/Vit D3	-0.014	0.065	-10000	0	-0.38	11	11
RARA	0.006	0.04	-10000	0	-0.37	5	5
NCOA1	0.01	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.001	0.075	-10000	0	-0.65	6	6
RARs/RARs/DNA/9cRA	0.008	0.053	-10000	0	-0.36	6	6
RARG	0.005	0.056	-10000	0	-0.58	4	4
RPS6KB1	0.009	0.049	-10000	0	-0.42	4	4
RARs/THRs/DNA/SMRT	-0.007	0.092	-10000	0	-0.28	43	43
THRA	0.004	0.053	-10000	0	-0.41	7	7
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.001	0.056	-10000	0	-0.49	6	6
RXRs/PPAR/9cRA/PGJ2/DNA	-0.021	0.11	0.25	2	-0.38	34	36
NR1H4	-0.12	0.23	-10000	0	-0.49	120	120
RXRs/LXRs/DNA	0	0.12	-10000	0	-0.35	36	36
NR1H2	0.013	0.008	-10000	0	-10000	0	0
NR1H3	0.009	0.046	-10000	0	-0.67	2	2
RXRs/VDR/DNA/Vit D3	-0.014	0.12	-10000	0	-0.36	40	40
NR4A1	-0.009	0.1	-10000	0	-0.53	16	16
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.05	0.12	-10000	0	-0.29	79	79
RXRG	-0.056	0.19	-10000	0	-0.53	57	57
RXR alpha/CCPG	0.015	0.024	-10000	0	-0.48	1	1
RXRA	0.011	0.032	-10000	0	-0.65	1	1
RXRB	0.012	0.009	-10000	0	-10000	0	0
THRB	-0.049	0.18	-10000	0	-0.6	44	44
PPARG	-0.064	0.21	-10000	0	-0.64	52	52
PPARD	0.009	0.018	-10000	0	-0.37	1	1
TNF	-0.018	0.22	-10000	0	-1.1	16	16
mol:Oxysterols	0.002	0.01	-10000	0	-10000	0	0
cholesterol transport	0.004	0.11	-10000	0	-0.42	16	16
PPARA	0.01	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0	0.071	-10000	0	-0.46	10	10
RXRs/NUR77/BCL2	-0.015	0.099	-10000	0	-0.3	46	46
SREBF1	0.01	0.1	-10000	0	-0.6	2	2
RXRs/RXRs/DNA/9cRA	-0.013	0.12	0.24	2	-0.37	36	38
ABCA1	0.008	0.11	-10000	0	-0.6	2	2
RARs/THRs	-0.042	0.11	-10000	0	-0.34	46	46
RXRs/FXR	-0.083	0.17	-10000	0	-0.4	84	84
BCL2	0.002	0.069	-10000	0	-0.53	7	7

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.009	0.072	-10000	0	-0.31	21	21
epithelial cell differentiation	-0.016	0.076	-10000	0	-0.36	20	20
CYFIP2	-0.013	0.12	-10000	0	-0.6	17	17
ENAH	0.029	0.082	-10000	0	-0.46	6	6
EGFR	-0.036	0.14	-10000	0	-0.44	46	46
EPHA2	-0.006	0.1	-10000	0	-0.65	11	11
MYO6	0.01	0.085	-10000	0	-0.36	22	22
CTNNB1	0.01	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.015	0.077	-10000	0	-0.42	15	15
AQP5	-0.17	0.23	-10000	0	-0.52	131	131
CTNND1	0.009	0.031	-10000	0	-0.65	1	1
mol:PI-4-5-P2	0.013	0.076	-10000	0	-0.34	20	20
regulation of calcium-dependent cell-cell adhesion	-0.029	0.14	-10000	0	-0.34	71	71
EGF	-0.14	0.24	-10000	0	-0.47	144	144
NCKAP1	0.009	0.031	-10000	0	-0.65	1	1
AQP3	-0.039	0.11	-10000	0	-0.54	17	17
cortical microtubule organization	-0.016	0.076	-10000	0	-0.36	20	20
GO:0000145	0.012	0.073	-10000	0	-0.32	20	20
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.016	0.076	-10000	0	-0.37	20	20
MLLT4	0.009	0.031	-10000	0	-0.65	1	1
ARF6/GDP	-0.021	0.092	-10000	0	-0.63	6	6
ARF6	0.01	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.011	0.068	-10000	0	-0.4	13	13
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.019	0.079	-10000	0	-0.47	4	4
PVRL2	0.008	0.025	-10000	0	-0.37	2	2
ZYX	0.012	0.079	-10000	0	-0.34	21	21
ARF6/GTP	-0.01	0.062	-10000	0	-0.36	13	13
CDH1	-0.016	0.13	-10000	0	-0.65	18	18
EGFR/EGFR/EGF/EGF	-0.098	0.14	-10000	0	-0.34	95	95
RhoA/GDP	-0.015	0.071	-10000	0	-0.34	20	20
actin cytoskeleton organization	0.015	0.082	-10000	0	-0.34	20	20
IGF-1R heterotetramer	-0.009	0.1	-10000	0	-0.55	16	16
GIT1	0.009	0.031	-10000	0	-0.65	1	1
IGF1R	-0.01	0.1	-10000	0	-0.55	16	16
IGF1	-0.088	0.21	-10000	0	-0.5	88	88
DIAPH1	-0.024	0.12	-10000	0	-0.65	16	16
Wnt receptor signaling pathway	0.016	0.076	0.36	20	-10000	0	20
RHOA	0.01	0	-10000	0	-10000	0	0
RhoA/GTP	-0.021	0.092	-10000	0	-0.63	6	6
CTNNA1	0.007	0.044	-10000	0	-0.65	2	2
VCL	0.015	0.084	-10000	0	-0.35	20	20
EFNA1	0.007	0.044	-10000	0	-0.65	2	2
LPP	0.015	0.085	-10000	0	-0.35	21	21
Ephrin A1/EPHA2	-0.023	0.11	-10000	0	-0.41	26	26
SEC6/SEC8	-0.014	0.064	-10000	0	-0.59	1	1
MGAT3	-0.03	0.14	-10000	0	-0.34	71	71
HGF/MET	-0.036	0.1	-10000	0	-0.34	41	41
HGF	-0.028	0.15	-10000	0	-0.55	31	31
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.008	0.072	-10000	0	-0.31	21	21
actin cable formation	0.039	0.075	-10000	0	-0.38	6	6
KIAA1543	0.003	0.098	-10000	0	-0.36	29	29
KIFC3	0.01	0.082	-10000	0	-0.34	23	23
NCK1	0.01	0	-10000	0	-10000	0	0
EXOC3	0.01	0	-10000	0	-10000	0	0
ACTN1	0.012	0.079	-10000	0	-0.35	20	20
NCK1/GIT1	0.014	0.023	-10000	0	-0.48	1	1
mol:GDP	-0.016	0.076	-10000	0	-0.36	20	20
EXOC4	0.01	0	-10000	0	-10000	0	0
STX4	0.013	0.077	-10000	0	-0.34	20	20
PIP5K1C	0.013	0.077	-10000	0	-0.34	20	20
LIMA1	0.007	0.044	-10000	0	-0.65	2	2
ABI1	0.01	0	-10000	0	-10000	0	0
ROCK1	0.026	0.089	-10000	0	-0.53	6	6
adherens junction assembly	0.013	0.1	-10000	0	-0.51	7	7
IGF-1R heterotetramer/IGF1	-0.066	0.14	-10000	0	-0.38	52	52
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.013	0.029	-10000	0	-0.48	1	1
MET	-0.002	0.073	-10000	0	-0.42	13	13
PLEKHA7	0.003	0.1	-10000	0	-0.37	29	29
mol:GTP	-0.011	0.067	-10000	0	-0.39	13	13
establishment of epithelial cell apical/basal polarity	0.031	0.071	-10000	0	-0.56	1	1
cortical actin cytoskeleton stabilization	0.009	0.072	-10000	0	-0.31	21	21
regulation of cell-cell adhesion	0.015	0.082	-10000	0	-0.34	20	20
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.008	0.072	-10000	0	-0.31	21	21

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	-0.004	0.038	-10000	0	-0.49	2	2
HDAC1	0.006	0.031	-10000	0	-0.66	1	1
AES	0.009	0.001	-10000	0	-10000	0	0
FBXW11	0.01	0	-10000	0	-10000	0	0
DTX1	-0.004	0.086	-10000	0	-0.51	12	12
LRP6/FZD1	0.012	0.032	-10000	0	-0.31	4	4
TLE1	0.004	0.062	-10000	0	-0.65	4	4
AP1	-0.02	0.1	-10000	0	-0.34	38	38
NCSTN	0.01	0	-10000	0	-10000	0	0
ADAM10	0.01	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.025	0.12	-10000	0	-0.44	6	6
NICD/RBPSUH	-0.002	0.031	-10000	0	-0.64	1	1
WIF1	-0.072	0.17	-10000	0	-0.43	83	83
NOTCH1	-0.002	0.032	-10000	0	-0.68	1	1
PSENEN	0.01	0	-10000	0	-10000	0	0
KREMEN2	-0.055	0.16	-10000	0	-0.43	67	67
DKK1	-0.22	0.29	-10000	0	-0.55	190	190
beta catenin/beta TrCP1	0.018	0.072	0.24	1	-0.34	1	2
APH1B	0.007	0.044	-10000	0	-0.65	2	2
APH1A	0.01	0	-10000	0	-10000	0	0
AXIN1	-0.004	0.035	0.28	1	-0.51	1	2
CtBP/CBP/TCF1/TLE1/AES	-0.049	0.13	-10000	0	-0.3	90	90
PSEN1	0.01	0	-10000	0	-10000	0	0
FOS	-0.014	0.12	-10000	0	-0.58	19	19
JUN	0.009	0.018	-10000	0	-0.37	1	1
MAP3K7	0.009	0.002	-10000	0	-10000	0	0
CTNNB1	0.013	0.076	0.21	17	-0.37	1	18
MAPK3	0.01	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.061	0.13	-10000	0	-0.42	38	38
HNF1A	-0.13	0.27	-10000	0	-0.65	97	97
CTBP1	0.009	0.001	-10000	0	-10000	0	0
MYC	0.015	0.098	-10000	0	-1.4	2	2
NKD1	-0.059	0.18	-10000	0	-0.48	64	64
FZD1	0.007	0.031	-10000	0	-0.37	3	3
NOTCH1 precursor/Deltex homolog 1	-0.008	0.052	-10000	0	-0.38	7	7
apoptosis	-0.02	0.1	-10000	0	-0.34	38	38
Delta 1/NOTCHprecursor	-0.004	0.038	-10000	0	-0.49	2	2
DLL1	0.004	0.05	-10000	0	-0.42	6	6
PPARD	0.021	0.018	-10000	0	-10000	0	0
Gamma Secretase	-0.001	0.023	-10000	0	-0.34	2	2
APC	-0.005	0.041	0.28	1	-0.48	2	3
DVL1	-0.045	0.14	-10000	0	-0.51	32	32
CSNK2A1	-0.036	0.17	-10000	0	-0.65	32	32
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.17	0.2	-10000	0	-0.44	138	138
LRP6	0.009	0.031	-10000	0	-0.65	1	1
CSNK1A1	0.01	0.001	-10000	0	-10000	0	0
NLK	0.011	0.005	-10000	0	-10000	0	0
CCND1	0.003	0.14	-10000	0	-1.4	4	4
WNT1	-0.05	0.18	-10000	0	-0.58	46	46
Axin1/APC/beta catenin	0.008	0.089	0.31	1	-0.35	9	10
DKK2	-0.03	0.15	-10000	0	-0.58	31	31
NOTCH1 precursor/DVL1	-0.033	0.11	-10000	0	-0.52	11	11
GSK3B	0.01	0	-10000	0	-10000	0	0
FRAT1	0.008	0.031	-10000	0	-0.65	1	1
NOTCH/Deltex homolog 1	-0.008	0.052	-10000	0	-0.38	7	7
PPP2R5D	0.013	0.097	0.25	41	-0.25	5	46
MAPK1	0.01	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.056	0.15	-10000	0	-0.4	54	54
RBPJ	0.01	0	-10000	0	-10000	0	0
CREBBP	0.012	0.003	-10000	0	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.005	0.098	-9999	-0.63	11	11
GPC2	-0.021	0.12	-9999	-0.47	30	30
GPC2/Midkine	-0.019	0.12	-9999	-0.5	19	19
neuron projection morphogenesis	-0.032	0.11	-9999	-0.5	19	19

×

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

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
MAP4K1	-0.006	0.13	-10000	0	-0.46	30	30
CRKL	-0.003	0.12	-10000	0	-0.48	24	24
HRAS	0.003	0.13	-10000	0	-0.43	28	28
mol:PIP3	-0.013	0.1	-10000	0	-0.39	25	25
SPRED1	0.007	0.044	-10000	0	-0.65	2	2
SPRED2	0.01	0	-10000	0	-10000	0	0
GAB1	-0.009	0.13	-10000	0	-0.49	26	26
FOXO3	-0.002	0.11	-10000	0	-0.42	22	22
AKT1	-0.009	0.12	-10000	0	-0.45	23	23
BAD	-0.002	0.11	-10000	0	-0.42	22	22
megakaryocyte differentiation	-0.022	0.14	-10000	0	-0.45	35	35
GSK3B	-0.002	0.11	-10000	0	-0.41	23	23
RAF1	0.012	0.11	-10000	0	-0.42	13	13
SHC1	0.01	0	-10000	0	-10000	0	0
STAT3	-0.006	0.12	-10000	0	-0.45	26	26
STAT1	-0.028	0.26	-10000	0	-1	27	27
HRAS/SPRED1	0.008	0.11	-10000	0	-0.42	14	14
cell proliferation	-0.007	0.12	-10000	0	-0.44	27	27
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
TEC	0.007	0.044	-10000	0	-0.65	2	2
RPS6KB1	-0.008	0.12	-10000	0	-0.45	26	26
HRAS/SPRED2	0.009	0.11	-10000	0	-0.42	13	13
LYN/TEC/p62DOK	-0.034	0.12	-10000	0	-0.44	31	31
MAPK3	0.02	0.08	-10000	0	-0.3	11	11
STAP1	-0.036	0.16	-10000	0	-0.44	49	49
GRAP2	-0.021	0.14	-10000	0	-0.6	23	23
JAK2	-0.06	0.22	-10000	0	-0.88	27	27
STAT1 (dimer)	-0.026	0.25	-10000	0	-0.99	27	27
mol:Gleevec	-0.001	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.035	0.12	-10000	0	-0.48	26	26
actin filament polymerization	-0.006	0.12	-10000	0	-0.45	26	26
LYN	0.004	0.062	-10000	0	-0.65	4	4
STAP1/STAT5A (dimer)	-0.038	0.2	-10000	0	-0.72	27	27
PIK3R1	0.01	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.009	0.11	-10000	0	-0.42	24	24
PI3K	0	0.12	-10000	0	-0.45	23	23
PTEN	0.006	0.053	-10000	0	-0.65	3	3
SCF/KIT/EPO/EPOR	-0.045	0.31	-10000	0	-1.3	23	23
MAPK8	-0.007	0.12	-10000	0	-0.45	27	27
STAT3 (dimer)	-0.006	0.12	-10000	0	-0.44	26	26
positive regulation of transcription	0.021	0.067	-10000	0	-0.24	11	11
mol:GDP	-0.04	0.13	-10000	0	-0.46	28	28
PIK3C2B	-0.01	0.12	-10000	0	-0.44	30	30
CBL/CRKL	0.004	0.12	-10000	0	-0.44	24	24
FER	-0.011	0.12	-10000	0	-0.45	30	30
SH2B3	-0.008	0.12	-10000	0	-0.46	27	27
PDPK1	-0.029	0.12	-10000	0	-0.34	52	52
SNAI2	-0.026	0.14	-10000	0	-0.49	28	28
positive regulation of cell proliferation	-0.017	0.2	-10000	0	-0.76	27	27
KITLG	0	0.09	-10000	0	-0.68	8	8
cell motility	-0.017	0.2	-10000	0	-0.76	27	27
PTPN6	0.009	0.018	-10000	0	-0.35	1	1
EPOR	0.014	0.11	-10000	0	-1.6	1	1
STAT5A (dimer)	-0.013	0.17	-10000	0	-0.63	28	28
SOCS1	0.004	0.056	-10000	0	-0.47	6	6
cell migration	0.018	0.14	0.44	36	-10000	0	36
SOS1	0.01	0	-10000	0	-10000	0	0
EPO	-0.042	0.13	-10000	0	-0.37	61	61
VAV1	-0.003	0.087	-10000	0	-0.57	10	10
GRB10	-0.009	0.13	-10000	0	-0.47	27	27
PTPN11	0.01	0.004	-10000	0	-10000	0	0
SCF/KIT	-0.014	0.12	-10000	0	-0.45	30	30
GO:0007205	0	0.006	-10000	0	-10000	0	0
MAP2K1	0.018	0.087	-10000	0	-0.33	12	12
CBL	0.01	0	-10000	0	-10000	0	0
KIT	-0.041	0.31	-10000	0	-1.4	22	22
MAP2K2	0.018	0.087	-10000	0	-0.33	12	12
SHC/Grb2/SOS1	-0.027	0.1	-10000	0	-0.44	23	23
STAT5A	-0.014	0.18	-10000	0	-0.66	27	27
GRB2	0.01	0	-10000	0	-10000	0	0
response to radiation	-0.025	0.14	-10000	0	-0.48	28	28
SHC/GRAP2	-0.008	0.1	-10000	0	-0.44	23	23
PTPRO	-0.023	0.14	-10000	0	-0.46	35	35
SH2B2	-0.007	0.12	-10000	0	-0.46	26	26
DOK1	0.002	0.071	-10000	0	-0.6	6	6
MATK	-0.019	0.14	-10000	0	-0.45	36	36
CREBBP	0.022	0.025	-10000	0	-10000	0	0
BCL2	0.008	0.15	-10000	0	-1.3	4	4

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.012	0.12	-9999	-0.48	22	22
EPHB2	-0.039	0.16	-9999	-0.55	40	40
Syndecan-2/TACI	-0.061	0.16	-9999	-0.42	61	61
LAMA1	-0.08	0.2	-9999	-0.47	86	86
Syndecan-2/alpha2 ITGB1	-0.008	0.11	-9999	-0.36	33	33
HRAS	0.01	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.004	0.039	-9999	-0.41	4	4
ITGA5	0.001	0.069	-9999	-0.47	9	9
BAX	0.026	0.04	-9999	-10000	0	0
EPB41	0.01	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.003	0.035	-9999	-0.37	4	4
LAMA3	-0.037	0.16	-9999	-0.52	41	41
EZR	0.01	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.005	0.082	-9999	-0.42	16	16
Syndecan-2/MMP2	0.005	0.09	-9999	-0.56	10	10
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.003	0.072	-9999	-0.42	12	12
dendrite morphogenesis	-0.015	0.11	-9999	-0.42	28	28
Syndecan-2/GM-CSF	-0.034	0.12	-9999	-0.42	30	30
determination of left/right symmetry	0.011	0.046	-9999	-0.48	4	4
Syndecan-2/PKC delta	0.015	0.04	-9999	-0.41	4	4
GNB2L1	0.01	0	-9999	-10000	0	0
MAPK3	-0.023	0.11	-9999	-0.38	30	30
MAPK1	-0.023	0.11	-9999	-0.38	30	30
Syndecan-2/RACK1	0.02	0.034	-9999	-0.35	4	4
NF1	0.007	0.044	-9999	-0.65	2	2
FGFR/FGF/Syndecan-2	0.011	0.046	-9999	-0.48	4	4
ITGA2	-0.006	0.097	-9999	-0.58	12	12
MAPK8	0.021	0.045	-9999	-0.4	5	5
Syndecan-2/alpha2/beta1 Integrin	-0.03	0.13	-9999	-0.38	41	41
Syndecan-2/Kininogen	-0.019	0.1	-9999	-0.41	21	21
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.024	0.037	-9999	-0.33	5	5
Syndecan-2/CASK/Protein 4.1	-0.003	0.035	-9999	-0.37	4	4
extracellular matrix organization	0.012	0.07	-9999	-0.63	5	5
actin cytoskeleton reorganization	-0.012	0.12	-9999	-0.48	22	22
Syndecan-2/Caveolin-2/Ras	0.012	0.067	-9999	-0.51	5	5
Syndecan-2/Laminin alpha3	-0.014	0.1	-9999	-0.41	25	25
Syndecan-2/RasGAP	-0.003	0.031	-9999	-0.33	4	4
alpha5/beta1 Integrin	0.008	0.05	-9999	-0.33	9	9
PRKCD	0.01	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.015	0.11	-9999	-0.42	28	28
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.029	0.036	-9999	-0.31	5	5
RHOA	0.01	0	-9999	-10000	0	0
SDCBP	0.01	0	-9999	-10000	0	0
TNFRSF13B	-0.11	0.24	-9999	-0.54	101	101
RASA1	0.01	0	-9999	-10000	0	0
alpha2/beta1 Integrin	0.003	0.072	-9999	-0.42	12	12
Syndecan-2/Synbindin	0.015	0.04	-9999	-0.41	4	4
TGFB1	0.004	0.062	-9999	-0.65	4	4
CASP3	0.021	0.036	-9999	-0.37	4	4
FN1	-0.034	0.15	-9999	-0.54	36	36
Syndecan-2/IL8	-0.051	0.15	-9999	-0.41	58	58
SDC2	0.011	0.046	-9999	-0.48	4	4
KNG1	-0.044	0.16	-9999	-0.47	51	51
Syndecan-2/Neurofibromin	0.013	0.049	-9999	-0.41	6	6
TRAPPC4	0.01	0	-9999	-10000	0	0
CSF2	-0.07	0.19	-9999	-0.47	75	75
Syndecan-2/TGFB1	0.012	0.07	-9999	-0.63	5	5
Syndecan-2/Syntenin/PI-4-5-P2	-0.003	0.035	-9999	-0.37	4	4
Syndecan-2/Ezrin	0.021	0.036	-9999	-0.37	4	4
PRKACA	0.02	0.045	-9999	-0.37	6	6
angiogenesis	-0.05	0.15	-9999	-0.41	58	58
MMP2	-0.007	0.1	-9999	-0.59	13	13
IL8	-0.094	0.22	-9999	-0.55	85	85
calcineurin-NFAT signaling pathway	-0.061	0.16	-9999	-0.42	61	61

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.002	0.087	-10000	0	-0.65	8	8
Jak2/Leptin Receptor	-0.055	0.11	-10000	0	-0.47	11	11
PTP1B/AKT1	-0.003	0.057	-10000	0	-0.27	7	7
FYN	0.009	0.031	-10000	0	-0.65	1	1
p210 bcr-abl/PTP1B	-0.01	0.063	-10000	0	-0.28	10	10
EGFR	-0.038	0.14	-10000	0	-0.45	46	46
EGF/EGFR	-0.094	0.14	-10000	0	-0.35	83	83
CSF1	0.007	0.044	-10000	0	-0.65	2	2
AKT1	0.01	0.001	-10000	0	-10000	0	0
INSR	0.009	0.031	-10000	0	-0.66	1	1
PTP1B/N-cadherin	-0.033	0.11	-10000	0	-0.37	31	31
Insulin Receptor/Insulin	-0.013	0.042	-10000	0	-0.49	1	1
HCK	-0.002	0.087	-10000	0	-0.65	8	8
CRK	0.01	0	-10000	0	-10000	0	0
TYK2	-0.004	0.06	-10000	0	-0.28	8	8
EGF	-0.14	0.24	-10000	0	-0.47	144	144
YES1	0.006	0.047	-10000	0	-0.56	3	3
CAV1	-0.024	0.083	-10000	0	-0.3	10	10
TXN	0.007	0.018	-10000	0	-0.37	1	1
PTP1B/IRS1/GRB2	-0.001	0.062	-10000	0	-0.3	8	8
cell migration	0.01	0.063	0.28	10	-10000	0	10
STAT3	0.01	0.001	-10000	0	-10000	0	0
PRLR	-0.13	0.25	-10000	0	-0.56	111	111
ITGA2B	-0.026	0.14	-10000	0	-0.52	31	31
CSF1R	-0.009	0.11	-10000	0	-0.61	14	14
Prolactin Receptor/Prolactin	-0.11	0.19	-10000	0	-0.47	86	86
FGR	-0.004	0.093	-10000	0	-0.62	10	10
PTP1B/p130 Cas	-0.004	0.059	-10000	0	-0.28	8	8
Crk/p130 Cas	0.001	0.056	-10000	0	-0.28	5	5
DOK1	-0.004	0.079	-10000	0	-0.33	16	16
JAK2	-0.05	0.12	-10000	0	-0.36	36	36
Jak2/Leptin Receptor/Leptin	-0.06	0.11	-10000	0	-0.43	20	20
PIK3R1	0.01	0	-10000	0	-10000	0	0
PTPN1	-0.01	0.063	-10000	0	-0.29	10	10
LYN	0.004	0.062	-10000	0	-0.65	4	4
CDH2	-0.047	0.17	-10000	0	-0.5	51	51
SRC	0.007	0.034	-10000	0	-0.46	1	1
ITGB3	-0.003	0.087	-10000	0	-0.57	10	10
CAT1/PTP1B	-0.076	0.16	-10000	0	-0.45	45	45
CAPN1	0.009	0.002	-10000	0	-10000	0	0
CSK	0.01	0	-10000	0	-10000	0	0
PI3K	-0.009	0.038	-10000	0	-0.45	1	1
mol:H2O2	-0.002	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.053	0.1	-10000	0	-0.43	15	15
negative regulation of transcription	-0.049	0.12	-10000	0	-0.35	36	36
FCGR2A	-0.005	0.098	-10000	0	-0.63	11	11
FER	-0.001	0.072	-10000	0	-0.61	6	6
alphaIIb/beta3 Integrin	-0.033	0.12	-10000	0	-0.42	35	35
BLK	-0.13	0.25	-10000	0	-0.54	118	118
Insulin Receptor/Insulin/Shc	0	0.02	-10000	0	-0.42	1	1
RHOA	0.009	0.002	-10000	0	-10000	0	0
LEPR	0.008	0.025	-10000	0	-0.37	2	2
BCAR1	0.01	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.01	0	-10000	0	-10000	0	0
mol:NADPH	-0.002	0.003	-10000	0	-10000	0	0
TRPV6	-0.094	0.19	-10000	0	-0.44	71	71
PRL	-0.021	0.098	-10000	0	-0.37	33	33
SOCS3	0.001	0.13	-10000	0	-1.4	4	4
SPRY2	0.001	0.065	-10000	0	-0.6	5	5
Insulin Receptor/Insulin/IRS1	-0.002	0.035	-10000	0	-0.42	3	3
CSF1/CSF1R	-0.01	0.091	-10000	0	-0.39	16	16
Ras protein signal transduction	0.015	0.019	-10000	0	-10000	0	0
IRS1	0.006	0.047	-10000	0	-0.56	3	3
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.071	0.2	-10000	0	-0.52	69	69
STAT5B	-0.023	0.073	-10000	0	-0.3	12	12
STAT5A	-0.026	0.085	-10000	0	-0.34	13	13
GRB2	0.01	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.01	0.081	-10000	0	-0.37	14	14
CSN2	-0.035	0.078	-10000	0	-0.43	2	2
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
LAT	-0.004	0.091	-10000	0	-0.58	10	10
YBX1	0.015	0.002	-10000	0	-10000	0	0
LCK	-0.021	0.13	-10000	0	-0.53	26	26
SHC1	0.01	0	-10000	0	-10000	0	0
NOX4	-0.009	0.1	-10000	0	-0.63	12	12

×

IL27-mediated signaling events

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
TGFB1	-0.036	0.14	-10000	0	-0.43	46	46
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.02	0.13	0.54	11	-10000	0	11
IL27/IL27R/JAK1	-0.034	0.16	0.36	1	-0.82	6	7
TBX21	-0.025	0.2	0.37	1	-0.61	32	33
IL12B	-0.02	0.13	-10000	0	-0.58	22	22
IL12A	-0.027	0.12	-10000	0	-0.44	35	35
IL6ST	0.009	0.007	-10000	0	-10000	0	0
IL27RA/JAK1	0.005	0.094	-10000	0	-1.3	2	2
IL27	-0.023	0.14	-10000	0	-0.59	24	24
TYK2	0.01	0.007	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.18	0.46	-10000	0	-1.5	46	46
T-helper 2 cell differentiation	0.02	0.13	0.54	11	-10000	0	11
T cell proliferation during immune response	0.02	0.13	0.54	11	-10000	0	11
MAPKKK cascade	-0.02	0.13	-10000	0	-0.54	11	11
STAT3	0.01	0	-10000	0	-10000	0	0
STAT2	0.01	0	-10000	0	-10000	0	0
STAT1	0.01	0.003	-10000	0	-10000	0	0
IL12RB1	-0.016	0.12	-10000	0	-0.65	17	17
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.032	0.19	0.37	1	-0.56	28	29
IL27/IL27R/JAK2/TYK2	-0.02	0.13	-10000	0	-0.55	11	11
positive regulation of T cell mediated cytotoxicity	-0.02	0.13	-10000	0	-0.54	11	11
STAT1 (dimer)	-0.043	0.22	0.4	23	-0.72	20	43
JAK2	0.004	0.058	-10000	0	-0.48	6	6
JAK1	0.01	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.015	0.12	-10000	0	-0.54	10	10
T cell proliferation	-0.075	0.18	-10000	0	-0.55	35	35
IL12/IL12R/TYK2/JAK2	-0.061	0.21	-10000	0	-0.79	25	25
IL17A	-0.18	0.46	-10000	0	-1.5	46	46
mast cell activation	0.02	0.13	0.54	11	-10000	0	11
IFNG	-0.011	0.043	0.071	1	-0.13	41	42
T cell differentiation	-0.004	0.007	0.02	1	-0.023	37	38
STAT3 (dimer)	-0.015	0.12	-10000	0	-0.54	10	10
STAT5A (dimer)	-0.017	0.14	-10000	0	-0.56	12	12
STAT4 (dimer)	-0.021	0.14	-10000	0	-0.59	14	14
STAT4	-0.002	0.088	-10000	0	-0.62	9	9
T cell activation	-0.006	0.01	0.078	5	-10000	0	5
IL27R/JAK2/TYK2	-0.011	0.1	-10000	0	-1.4	2	2
GATA3	-0.016	0.19	-10000	0	-1.4	8	8
IL18	-0.013	0.098	-10000	0	-0.44	22	22
positive regulation of mast cell cytokine production	-0.014	0.12	-10000	0	-0.53	10	10
IL27/EBI3	-0.042	0.15	-10000	0	-0.45	48	48
IL27RA	-0.008	0.098	-10000	0	-1.4	2	2
IL6	-0.11	0.24	-10000	0	-0.51	106	106
STAT5A	0.004	0.062	-10000	0	-0.65	4	4
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.004	0.046	0.5	2	-10000	0	2
IL1B	-0.048	0.14	-10000	0	-0.36	69	69
EBI3	-0.026	0.14	-10000	0	-0.59	27	27
TNF	-0.019	0.1	-10000	0	-0.35	35	35

×

IL1-mediated signaling events

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
UBC13/UEV1A	0.015	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.018	-10000	0	-0.37	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.009	0.018	-10000	0	-0.37	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.026	0.058	-10000	0	-0.33	2	2
IRAK/TOLLIP	0.025	0	-10000	0	-10000	0	0
IKBKB	0.01	0	-10000	0	-10000	0	0
IKBKG	0.004	0.005	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.12	0.2	-10000	0	-0.51	74	74
IL1A	-0.11	0.22	-10000	0	-0.46	115	115
IL1B	-0.046	0.15	-10000	0	-0.49	36	36
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.009	-10000	0	-10000	0	0
IL1R2	-0.065	0.19	-10000	0	-0.49	68	68
IL1R1	0.002	0.071	-10000	0	-0.6	6	6
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.008	0.066	0.21	8	-0.46	1	9
TOLLIP	0.01	0	-10000	0	-10000	0	0
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0.01	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.049	0.007	-10000	0	-10000	0	0
JUN	0.023	0.062	-10000	0	-10000	0	0
MAP3K7	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.051	0.11	-10000	0	-0.66	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.074	0.13	-10000	0	-0.38	60	60
PIK3R1	0.01	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.068	0.12	-10000	0	-0.35	60	60
IL1 beta fragment/IL1R1/IL1RAP	-0.039	0.13	-10000	0	-0.38	42	42
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.019	0.066	-10000	0	-0.31	1	1
IRAK1	0.021	0	-10000	0	-10000	0	0
IL1RN/IL1R1	-0.057	0.17	-10000	0	-0.41	78	78
IRAK4	0.01	0	-10000	0	-10000	0	0
PRKCI	0.01	0	-10000	0	-10000	0	0
TRAF6	0.01	0	-10000	0	-10000	0	0
PI3K	0.014	0.012	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.005	0.078	-10000	0	-0.43	2	2
CHUK	0.01	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.039	0.13	-10000	0	-0.38	42	42
IL1 beta/IL1R2	-0.079	0.18	-10000	0	-0.46	66	66
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.045	0.095	-10000	0	-0.6	2	2
IRAK3	-0.015	0.12	-10000	0	-0.55	20	20
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.052	0.11	-10000	0	-0.34	42	42
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.024	0.099	-10000	0	-0.29	41	41
IL1 alpha/IL1R1/IL1RAP	-0.083	0.15	-10000	0	-0.42	60	60
RELA	0.01	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.009	0.018	-10000	0	-0.37	1	1
MYD88	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.03	0	-10000	0	-10000	0	0
IL1RAP	-0.01	0.085	-10000	0	-0.37	24	24
UBE2N	0.01	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.041	0.087	-10000	0	-0.55	2	2
CASP1	-0.001	0.077	-10000	0	-0.53	9	9
IL1RN/IL1R2	-0.1	0.22	-10000	0	-0.57	67	67
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.03	0.12	-10000	0	-0.36	42	42
TMEM189-UBE2V1	0.01	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.007	0.085	-10000	0	-0.4	5	5
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
IL1RN	-0.081	0.21	-10000	0	-0.54	75	75
TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
MAP2K6	0.014	0.067	-10000	0	-0.32	17	17

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.001	0.064	-9999	-0.44	9	9
Syndecan-3/Src/Cortactin	-0.024	0.081	-9999	-0.37	17	17
Syndecan-3/Neurocan	-0.021	0.085	-9999	-0.39	20	20
POMC	-0.047	0.16	-9999	-0.45	57	57
EGFR	-0.036	0.14	-9999	-0.44	46	46
Syndecan-3/EGFR	-0.026	0.088	-9999	-0.42	15	15
AGRP	-0.008	0.1	-9999	-0.61	13	13
NCSTN	0.01	0	-9999	-10000	0	0
PSENEN	0.01	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.007	0.044	-9999	-0.65	2	2
APH1A	0.01	0	-9999	-10000	0	0
NCAN	-0.025	0.14	-9999	-0.54	28	28
long-term memory	-0.009	0.058	-9999	-0.46	6	6
Syndecan-3/IL8	-0.056	0.12	-9999	-0.36	57	57
PSEN1	0.01	0	-9999	-10000	0	0
Src/Cortactin	0.008	0.051	-9999	-0.32	10	10
FYN	0.009	0.031	-9999	-0.65	1	1
limb bud formation	-0.005	0.054	-9999	-0.66	3	3
MC4R	-0.004	0.058	-9999	-0.37	11	11
SRC	0.009	0.031	-9999	-0.65	1	1
PTN	-0.028	0.13	-9999	-0.43	40	40
FGFR/FGF/Syndecan-3	-0.005	0.055	-9999	-0.67	3	3
neuron projection morphogenesis	-0.037	0.098	-9999	-0.59	5	5
Syndecan-3/AgRP	-0.014	0.08	-9999	-0.44	13	13
Syndecan-3/AgRP/MC4R	-0.017	0.08	-9999	-0.42	13	13
Fyn/Cortactin	0.008	0.051	-9999	-0.32	10	10
SDC3	-0.005	0.055	-9999	-0.68	3	3
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.055	0.12	-9999	-0.35	57	57
IL8	-0.094	0.22	-9999	-0.55	85	85
Syndecan-3/Fyn/Cortactin	-0.009	0.059	-9999	-0.47	6	6
Syndecan-3/CASK	-0.005	0.053	-9999	-0.65	3	3
alpha-MSH/MC4R	-0.035	0.12	-9999	-0.32	65	65
Gamma Secretase	-0.001	0.023	-9999	-0.34	2	2

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	0.014	0.12	0.63	17	-10000	0	17
PI3K Class IB/PDE3B	-0.014	0.12	-10000	0	-0.64	17	17
PDE3B	-0.014	0.12	-10000	0	-0.64	17	17

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.098	0.33	-9999	-1.2	17	17
PLK1	0.028	0.21	-9999	-1.5	8	8
BIRC5	0.031	0.2	-9999	-1.5	7	7
HSPA1B	0.093	0.34	-9999	-1.2	19	19
MAP2K1	0.033	0.026	-9999	-10000	0	0
BRCA2	0.093	0.35	-9999	-1.3	19	19
FOXM1	0.044	0.61	-9999	-2.4	18	18
XRCC1	0.097	0.33	-9999	-1.2	18	18
FOXM1B/p19	-0.1	0.31	-9999	-1.1	28	28
Cyclin D1/CDK4	0.062	0.33	-9999	-1	19	19
CDC2	0.094	0.35	-9999	-1.2	18	18
TGFA	0.052	0.35	-9999	-0.99	19	19
SKP2	0.097	0.33	-9999	-1.2	17	17
CCNE1	-0.017	0.12	-9999	-0.44	32	32
CKS1B	0.098	0.33	-9999	-1.2	17	17
RB1	-0.053	0.17	-9999	-1.1	8	8
FOXM1C/SP1	0.082	0.38	-9999	-1.4	18	18
AURKB	0.025	0.22	-9999	-1.5	9	9
CENPF	0.086	0.37	-9999	-1.3	21	21
CDK4	0.015	0.027	-9999	-0.35	2	2
MYC	0.1	0.3	-9999	-0.98	19	19
CHEK2	0.032	0.043	-9999	-0.7	1	1
ONECUT1	0.062	0.35	-9999	-1.1	19	19
CDKN2A	-0.16	0.25	-9999	-0.51	149	149
LAMA4	0.095	0.34	-9999	-1.3	17	17
FOXM1B/HNF6	0.048	0.42	-9999	-1.5	19	19
FOS	0.073	0.39	-9999	-1.2	29	29
SP1	0.011	0.001	-9999	-10000	0	0
CDC25B	0.098	0.33	-9999	-1.2	17	17
response to radiation	0.019	0.025	-9999	-10000	0	0
CENPB	0.098	0.33	-9999	-1.2	17	17
CENPA	0.093	0.35	-9999	-1.3	18	18
NEK2	0.094	0.35	-9999	-1.3	17	17
HIST1H2BA	0.092	0.33	-9999	-1.2	17	17
CCNA2	0.007	0.071	-9999	-0.66	5	5
EP300	0.01	0	-9999	-10000	0	0
CCNB1/CDK1	0.084	0.39	-9999	-1.5	17	17
CCNB2	0.092	0.35	-9999	-1.2	19	19
CCNB1	0.094	0.36	-9999	-1.3	17	17
ETV5	0.088	0.36	-9999	-1.2	20	20
ESR1	0.07	0.4	-9999	-1.2	30	30
CCND1	0.065	0.34	-9999	-1.1	19	19
GSK3A	0.028	0.04	-9999	-0.67	1	1
Cyclin A-E1/CDK1-2	0.017	0.11	-9999	-0.5	12	12
CDK2	0.013	0.032	-9999	-0.66	1	1
G2/M transition of mitotic cell cycle	0.023	0.028	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.092	0.28	-9999	-1.3	18	18
GAS1	0.034	0.45	-9999	-1.2	44	44
MMP2	0.084	0.37	-9999	-1.3	22	22
RB1/FOXM1C	0.068	0.34	-9999	-1.1	19	19
CREBBP	0.01	0	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.001	0.11	-10000	0	-0.41	22	22
ACTA1	-0.012	0.14	-10000	0	-0.49	25	25
NUMA1	-0.001	0.11	-10000	0	-0.38	26	26
SPTAN1	-0.007	0.14	-10000	0	-0.49	25	25
LIMK1	-0.007	0.14	-10000	0	-0.49	25	25
BIRC3	-0.032	0.16	-10000	0	-0.59	32	32
BIRC2	0.01	0	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
CASP10	-0.024	0.14	-10000	0	-0.47	37	37
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0	-10000	0	-10000	0	0
PTK2	-0.001	0.11	-10000	0	-0.41	22	22
DIABLO	0.01	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.007	0.14	-10000	0	-0.48	25	25
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.01	0	-10000	0	-10000	0	0
GSN	-0.007	0.14	-10000	0	-0.49	25	25
MADD	0.01	0	-10000	0	-10000	0	0
TFAP2A	-0.062	0.2	-10000	0	-0.57	58	58
BID	0	0.066	-10000	0	-0.26	23	23
MAP3K1	0.004	0.048	-10000	0	-0.23	5	5
TRADD	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.002	0.023	-10000	0	-0.48	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.01	0.14	-10000	0	-0.56	21	21
CASP9	0.01	0	-10000	0	-10000	0	0
DNA repair	-0.009	0.053	0.16	5	-0.2	20	25
neuron apoptosis	0.014	0.036	-10000	0	-0.66	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.003	0.14	-10000	0	-0.5	22	22
APAF1	0.009	0.031	-10000	0	-0.65	1	1
CASP6	0.007	0.08	-10000	0	-0.54	4	4
TRAF2	0.01	0	-10000	0	-10000	0	0
ICAD/CAD	-0.002	0.14	-10000	0	-0.5	21	21
CASP7	0.012	0.072	0.3	25	-10000	0	25
KRT18	-0.021	0.14	-10000	0	-0.6	23	23
apoptosis	0.003	0.13	-10000	0	-0.47	21	21
DFFA	-0.007	0.14	-10000	0	-0.49	25	25
DFFB	-0.008	0.14	-10000	0	-0.49	25	25
PARP1	0.009	0.053	0.2	20	-0.16	5	25
actin filament polymerization	0.007	0.13	0.46	23	-10000	0	23
TNF	-0.028	0.14	-10000	0	-0.48	35	35
CYCS	-0.001	0.052	-10000	0	-0.18	28	28
SATB1	0.008	0.087	-10000	0	-0.56	4	4
SLK	-0.007	0.14	-10000	0	-0.49	25	25
p15 BID/BAX	0.005	0.059	-10000	0	-0.32	5	5
CASP2	0.011	0.069	-10000	0	-0.38	3	3
JNK cascade	-0.005	0.048	0.23	5	-10000	0	5
CASP3	-0.014	0.15	-10000	0	-0.47	31	31
LMNB2	0.014	0.058	-10000	0	-0.32	6	6
RIPK1	0.01	0	-10000	0	-10000	0	0
CASP4	0.01	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.001	0.092	-10000	0	-0.37	25	25
negative regulation of DNA binding	-0.061	0.2	-10000	0	-0.56	58	58
stress fiber formation	-0.007	0.14	-10000	0	-0.48	25	25
GZMB	-0.025	0.15	-10000	0	-0.45	41	41
CASP1	0.008	0.043	-10000	0	-0.38	5	5
LMNB1	0.014	0.06	-10000	0	-0.31	7	7
APP	0.014	0.036	-10000	0	-0.67	1	1
TNFRSF1A	0.009	0.018	-10000	0	-0.37	1	1
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0	-10000	0	-10000	0	0
VIM	-0.001	0.13	0.22	19	-0.47	21	40
LMNA	0.015	0.057	-10000	0	-0.32	6	6
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.006	0.071	-10000	0	-0.44	2	2
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.008	0.14	-10000	0	-0.49	25	25
APAF-1/Caspase 9	0.003	0.038	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.001	0.11	-10000	0	-0.37	26	26
CFL2	-0.007	0.14	-10000	0	-0.48	23	23
GAS2	-0.056	0.17	-10000	0	-0.42	65	65
positive regulation of apoptosis	0.016	0.059	-10000	0	-0.32	6	6
PRF1	-0.013	0.12	-10000	0	-0.55	19	19

×

Sphingosine 1-phosphate (S1P) 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.009	0.018	-9999	-0.37	1	1
SPHK1	-0.002	0.081	-9999	-0.5	11	11
GNAI2	0.01	0	-9999	-10000	0	0
mol:S1P	0.006	0.047	-9999	-0.3	7	7
GNAO1	-0.05	0.16	-9999	-0.45	60	60
mol:Sphinganine-1-P	0.008	0.061	-9999	-0.35	12	12
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.022	0.036	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0.015	0	-9999	-10000	0	0
S1PR3	-0.01	0.11	-9999	-0.56	16	16
S1PR2	0.009	0.018	-9999	-0.37	1	1
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.008	0.037	-9999	-0.28	6	6
S1PR5	-0.072	0.16	-9999	-0.39	94	94
S1PR4	-0.006	0.09	-9999	-0.46	16	16
GNAI1	-0.005	0.093	-9999	-0.56	12	12
S1P/S1P5/G12	-0.026	0.1	-9999	-0.3	27	27
S1P/S1P3/Gq	-0.011	0.11	-9999	-0.39	29	29
S1P/S1P4/Gi	-0.019	0.12	-9999	-0.44	20	20
GNAQ	0.01	0	-9999	-10000	0	0
GNAZ	-0.032	0.15	-9999	-0.55	34	34
GNA14	-0.026	0.14	-9999	-0.56	29	29
GNA15	-0.035	0.13	-9999	-0.39	51	51
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
GNA11	0.01	0	-9999	-10000	0	0
ABCC1	-0.007	0.08	-9999	-0.39	19	19

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.009	0.031	-10000	0	-0.65	1	1
HDAC2	0.01	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.028	0.1	-10000	0	-0.42	24	24
forebrain development	-0.073	0.21	-10000	0	-0.62	40	40
GNAO1	-0.052	0.16	-10000	0	-0.45	60	60
SMO/beta Arrestin2	-0.02	0.12	-10000	0	-0.39	38	38
SMO	-0.037	0.16	-10000	0	-0.54	38	38
ARRB2	0.008	0.005	-10000	0	-10000	0	0
GLI3/SPOP	0.033	0.052	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
GSK3B	0.01	0	-10000	0	-10000	0	0
GNAI2	0.008	0.004	-10000	0	-10000	0	0
SIN3/HDAC complex	0.008	0.017	-10000	0	-10000	0	0
GNAI1	-0.007	0.093	-10000	0	-0.56	12	12
XPO1	0.008	0.031	-10000	0	-0.65	1	1
GLI1/Su(fu)	-0.093	0.18	-10000	0	-0.58	37	37
SAP30	0.009	0.018	-10000	0	-0.37	1	1
mol:GDP	-0.037	0.16	-10000	0	-0.54	38	38
MIM/GLI2A	-0.055	0.16	-10000	0	-0.51	50	50
IFT88	0.009	0.031	-10000	0	-0.65	1	1
GNAI3	0.008	0.004	-10000	0	-10000	0	0
GLI2	0.021	0.047	-10000	0	-10000	0	0
GLI3	0.029	0.056	0.2	2	-0.28	5	7
CSNK1D	0.01	0	-10000	0	-10000	0	0
CSNK1E	0.01	0	-10000	0	-10000	0	0
SAP18	0.01	0.001	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.009	0.031	-10000	0	-0.65	1	1
GNG2	0.006	0.047	-10000	0	-0.56	3	3
Gi family/GTP	-0.043	0.15	-10000	0	-0.37	54	54
SIN3B	0.01	0.001	-10000	0	-10000	0	0
SIN3A	0.01	0.001	-10000	0	-10000	0	0
GLI3/Su(fu)	0.026	0.049	-10000	0	-0.39	1	1
GLI2/Su(fu)	0.013	0.073	-10000	0	-0.34	10	10
FOXA2	-0.3	0.52	-10000	0	-1.2	113	113
neural tube patterning	-0.073	0.21	-10000	0	-0.62	40	40
SPOP	0.01	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.004	0.057	-10000	0	-0.4	1	1
GNB1	0.01	0	-10000	0	-10000	0	0
CSNK1G2	0.01	0	-10000	0	-10000	0	0
CSNK1G3	0.01	0	-10000	0	-10000	0	0
MTSS1	-0.055	0.17	-10000	0	-0.51	50	50
embryonic limb morphogenesis	-0.073	0.21	-10000	0	-0.62	40	40
SUFU	0	0.063	-10000	0	-0.24	24	24
LGALS3	0	0.077	-10000	0	-0.61	7	7
catabolic process	0.04	0.059	-10000	0	-0.36	3	3
GLI3A/CBP	-0.012	0.087	-10000	0	-0.36	22	22
KIF3A	0.01	0	-10000	0	-10000	0	0
GLI1	-0.076	0.22	-10000	0	-0.64	40	40
RAB23	0.003	0.05	-10000	0	-0.37	8	8
CSNK1A1	0.01	0	-10000	0	-10000	0	0
IFT172	0.01	0	-10000	0	-10000	0	0
RBBP7	0.01	0.001	-10000	0	-10000	0	0
Su(fu)/Galectin3	-0.001	0.071	-10000	0	-0.38	7	7
GNAZ	-0.033	0.15	-10000	0	-0.56	34	34
RBBP4	0.01	0.001	-10000	0	-10000	0	0
CSNK1G1	0.01	0	-10000	0	-10000	0	0
PIAS1	0.01	0	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
GLI2/SPOP	0.025	0.044	-10000	0	-10000	0	0
STK36	0.008	0.032	-10000	0	-0.66	1	1
Gi family/GNB1/GNG2/GDP	-0.029	0.13	-10000	0	-0.48	21	21
PTCH1	-0.073	0.24	-10000	0	-0.9	25	25
MIM/GLI1	-0.16	0.33	-10000	0	-0.67	120	120
CREBBP	-0.012	0.087	-10000	0	-0.36	22	22
Su(fu)/SIN3/HDAC complex	0.035	0.022	-10000	0	-10000	0	0

×

S1P1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.006	0.058	-9999	-0.38	9	9
PDGFRB	-0.003	0.087	-9999	-0.66	8	8
SPHK1	-0.02	0.1	-9999	-0.97	5	5
mol:S1P	-0.027	0.1	-9999	-0.81	6	6
S1P1/S1P/Gi	-0.037	0.16	-9999	-0.43	48	48
GNAO1	-0.05	0.16	-9999	-0.45	60	60
PDGFB-D/PDGFRB/PLCgamma1	-0.031	0.16	-9999	-0.51	26	26
PLCG1	-0.031	0.15	-9999	-0.44	38	38
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.003	0.087	-9999	-0.66	8	8
GNAI2	0.009	0.004	-9999	-10000	0	0
GNAI3	0.009	0.004	-9999	-10000	0	0
GNAI1	-0.006	0.094	-9999	-0.56	12	12
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.006	0.05	-9999	-0.33	9	9
S1P1/S1P	-0.029	0.094	-9999	-0.5	12	12
negative regulation of cAMP metabolic process	-0.035	0.16	-9999	-0.41	48	48
MAPK3	-0.042	0.19	-9999	-0.6	37	37
calcium-dependent phospholipase C activity	-0.001	0.002	-9999	-10000	0	0
Rac1/GDP	0.007	0	-9999	-10000	0	0
RhoA/GDP	0.007	0	-9999	-10000	0	0
KDR	0.004	0.062	-9999	-0.65	4	4
PLCB2	-0.002	0.096	-9999	-0.49	11	11
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.026	0.076	-9999	-0.44	10	10
receptor internalization	-0.028	0.086	-9999	-0.46	12	12
PTGS2	-0.07	0.29	-9999	-1	33	33
Rac1/GTP	-0.026	0.076	-9999	-0.44	10	10
RHOA	0.01	0	-9999	-10000	0	0
VEGFA	0.005	0.048	-9999	-0.43	5	5
negative regulation of T cell proliferation	-0.035	0.16	-9999	-0.41	48	48
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.033	0.15	-9999	-0.56	34	34
MAPK1	-0.042	0.19	-9999	-0.6	37	37
S1P1/S1P/PDGFB-D/PDGFRB	-0.008	0.12	-9999	-0.49	16	16
ABCC1	-0.007	0.08	-9999	-0.39	19	19

×

Nongenotropic Androgen signaling

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
PTK2	0.008	0.023	-10000	0	-0.49	1	1
GNB1/GNG2	-0.022	0.081	-10000	0	-0.4	14	14
regulation of S phase of mitotic cell cycle	0.008	0.058	-10000	0	-0.28	14	14
GNAO1	-0.05	0.16	-10000	0	-0.45	60	60
HRAS	0.01	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.023	0.088	-10000	0	-0.32	33	33
PELP1	0.01	0.001	-10000	0	-10000	0	0
AKT1	0.009	0	-10000	0	-10000	0	0
MAP2K1	0.014	0.071	-10000	0	-0.3	14	14
T-DHT/AR	-0.028	0.099	-10000	0	-0.34	39	39
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.006	19	19
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.093	-10000	0	-0.56	12	12
mol:GDP	-0.022	0.087	-10000	0	-0.5	13	13
cell proliferation	0.017	0.1	-10000	0	-0.38	18	18
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
FOS	0.006	0.16	-10000	0	-0.8	15	15
mol:Ca2+	-0.011	0.024	-10000	0	-0.072	49	49
MAPK3	0.016	0.085	-10000	0	-0.33	10	10
MAPK1	0.013	0.05	-10000	0	-0.22	6	6
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.004	19	19
cAMP biosynthetic process	-0.012	0.087	-10000	0	-0.3	33	33
GNG2	0.006	0.047	-10000	0	-0.56	3	3
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	19	19
HRAS/GTP	-0.02	0.067	-10000	0	-0.34	14	14
actin cytoskeleton reorganization	0	0.007	-10000	0	-10000	0	0
SRC	0.009	0.031	-10000	0	-0.65	1	1
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	19	19
PI3K	0	0.01	-10000	0	-10000	0	0
apoptosis	-0.016	0.091	0.42	14	-10000	0	14
T-DHT/AR/PELP1	-0.023	0.083	-10000	0	-0.28	39	39
HRAS/GDP	-0.02	0.081	-10000	0	-0.47	13	13
CREB1	0.015	0.096	-10000	0	-0.44	14	14
RAC1-CDC42/GTP	0	0.007	-10000	0	-10000	0	0
AR	-0.031	0.14	-10000	0	-0.47	39	39
GNB1	0.01	0	-10000	0	-10000	0	0
RAF1	0.009	0.072	-10000	0	-0.32	14	14
RAC1-CDC42/GDP	-0.018	0.078	-10000	0	-0.45	13	13
T-DHT/AR/PELP1/Src	-0.022	0.076	-10000	0	-0.38	14	14
MAP2K2	0.014	0.071	-10000	0	-0.3	14	14
T-DHT/AR/PELP1/Src/PI3K	0.008	0.058	-10000	0	-0.28	14	14
GNAZ	-0.032	0.15	-10000	0	-0.55	34	34
SHBG	-0.028	0.14	-10000	0	-0.52	33	33
Gi family/GNB1/GNG2/GDP	-0.012	0.12	-10000	0	-0.42	21	21
mol:T-DHT	0	0	0.001	1	-0.002	15	16
RAC1	0.01	0	-10000	0	-10000	0	0
GNRH1	-0.009	0.092	-10000	0	-0.49	16	16
Gi family/GTP	-0.025	0.11	-10000	0	-0.29	48	48
CDC42	0.01	0	-10000	0	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.05	0.16	-9999	-0.45	60	60
CDC42/GTP	-0.038	0.099	-9999	-0.4	19	19
PLCG1	-0.015	0.11	-9999	-0.56	10	10
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.01	0	-9999	-10000	0	0
GNAI3	0.01	0	-9999	-10000	0	0
G12/G13	0.015	0	-9999	-10000	0	0
cell migration	-0.037	0.097	-9999	-0.39	19	19
S1PR5	-0.072	0.16	-9999	-0.39	94	94
S1PR4	-0.006	0.09	-9999	-0.46	16	16
MAPK3	-0.015	0.11	-9999	-0.56	10	10
MAPK1	-0.015	0.11	-9999	-0.42	19	19
S1P/S1P5/Gi	-0.04	0.11	-9999	-0.31	48	48
GNAI1	-0.005	0.093	-9999	-0.56	12	12
CDC42/GDP	0.007	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.045	0.092	-9999	-0.42	6	6
RHOA	0.016	0.048	-9999	-0.35	5	5
S1P/S1P4/Gi	-0.022	0.12	-9999	-0.44	19	19
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.032	0.15	-9999	-0.55	34	34
S1P/S1P4/G12/G13	-0.008	0.047	-9999	-0.38	5	5
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.029	0.12	-9999	-0.51	22	22
E-cadherin/beta catenin	-0.005	0.097	-9999	-0.48	18	18
CTNNB1	0.01	0	-9999	-10000	0	0
JUP	-0.013	0.11	-9999	-0.51	20	20
CDH1	-0.016	0.13	-9999	-0.65	18	18

×

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	0.007	0.034	0.21	10	-10000	0	10
RFC1	0.007	0.034	0.21	10	-10000	0	10
PRKDC	0.005	0.04	0.21	10	-0.4	1	11
RIPK1	0.011	0.003	-10000	0	-10000	0	0
CASP7	-0.008	0.037	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	0.002	0.09	0.24	14	-0.27	23	37
MAP2K4	-0.012	0.12	-10000	0	-0.34	29	29
mol:ceramide	-0.018	0.12	-10000	0	-0.43	28	28
GSN	0.007	0.034	0.22	9	-10000	0	9
FASLG/FAS/FADD/FAF1/Caspase 8	0.006	0.094	-10000	0	-0.33	22	22
FAS	0.003	0.059	-10000	0	-0.54	5	5
BID	0.006	0.034	0.3	5	-10000	0	5
MAP3K1	0.004	0.07	-10000	0	-0.26	5	5
MAP3K7	0.009	0.003	-10000	0	-10000	0	0
RB1	0.005	0.043	0.21	10	-0.4	2	12
CFLAR	0.011	0.003	-10000	0	-10000	0	0
HGF/MET	-0.077	0.15	-10000	0	-0.47	42	42
ARHGDIB	0.004	0.036	0.23	7	-0.25	2	9
FADD	-0.001	0.061	-10000	0	-0.38	12	12
actin filament polymerization	-0.007	0.034	-10000	0	-0.22	9	9
NFKB1	-0.029	0.061	-10000	0	-10000	0	0
MAPK8	-0.022	0.15	-10000	0	-0.43	44	44
DFFA	0.007	0.034	0.22	9	-10000	0	9
DNA fragmentation during apoptosis	0.006	0.038	0.22	9	-0.39	1	10
FAS/FADD/MET	-0.016	0.063	-10000	0	-0.41	6	6
CFLAR/RIP1	0.012	0.005	-10000	0	-10000	0	0
FAIM3	-0.008	0.093	-10000	0	-0.45	18	18
FAF1	0.009	0.006	-10000	0	-10000	0	0
PARP1	0.007	0.034	0.21	10	-10000	0	10
DFFB	0.006	0.038	0.22	9	-0.4	1	10
CHUK	-0.025	0.053	-10000	0	-10000	0	0
FASLG	-0.037	0.16	-10000	0	-0.54	38	38
FAS/FADD	0.002	0.063	-10000	0	-0.41	6	6
HGF	-0.028	0.15	-10000	0	-0.55	31	31
LMNA	0.005	0.035	0.23	4	-0.36	1	5
CASP6	0.006	0.038	0.21	10	-0.4	1	11
CASP10	-0.007	0.1	-10000	0	-0.65	11	11
CASP3	0.008	0.04	0.26	10	-10000	0	10
PTPN13	-0.076	0.18	-10000	0	-0.43	89	89
CASP8	0.009	0.049	0.4	5	-10000	0	5
IL6	-0.1	0.36	-10000	0	-1.3	35	35
MET	-0.002	0.073	-10000	0	-0.42	13	13
ICAD/CAD	0.006	0.036	0.23	4	-0.36	1	5
FASLG/FAS/FADD/FAF1/Caspase 10	-0.018	0.13	-10000	0	-0.44	28	28
activation of caspase activity by cytochrome c	0.006	0.034	0.3	5	-10000	0	5
PAK2	0.007	0.033	0.22	9	-10000	0	9
BCL2	0.002	0.069	-10000	0	-0.53	7	7

×

Plasma membrane estrogen receptor 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
GNB1/GNG2	-0.021	0.089	-10000	0	-0.4	20	20
ER alpha/Gai/GDP/Gbeta gamma	-0.022	0.15	-10000	0	-0.53	27	27
AKT1	-0.008	0.17	-10000	0	-0.88	16	16
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.012	0.17	-10000	0	-0.9	16	16
mol:Ca2+	-0.019	0.13	-10000	0	-0.48	22	22
IGF1R	-0.01	0.1	-10000	0	-0.55	16	16
E2/ER alpha (dimer)/Striatin	-0.019	0.081	-10000	0	-0.42	16	16
SHC1	0.01	0	-10000	0	-10000	0	0
apoptosis	0.006	0.16	0.83	16	-10000	0	16
RhoA/GTP	-0.02	0.07	-10000	0	-0.33	16	16
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.042	0.12	-10000	0	-0.58	19	19
regulation of stress fiber formation	-0.017	0.074	0.46	4	-10000	0	4
E2/ERA-ERB (dimer)	-0.023	0.098	-10000	0	-0.46	19	19
KRAS	-0.007	0.078	-10000	0	-0.37	20	20
G13/GTP	-0.017	0.074	-10000	0	-0.38	16	16
pseudopodium formation	0.017	0.074	-10000	0	-0.46	4	4
E2/ER alpha (dimer)/PELP1	-0.019	0.081	-10000	0	-0.42	16	16
GRB2	0.01	0	-10000	0	-10000	0	0
GNG2	0.006	0.047	-10000	0	-0.56	3	3
GNAO1	-0.05	0.16	-10000	0	-0.45	60	60
HRAS	0.01	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.007	0.14	-10000	0	-0.65	17	17
E2/ER beta (dimer)	0.001	0.053	-10000	0	-0.45	6	6
mol:GDP	-0.026	0.1	-10000	0	-0.49	19	19
mol:NADP	-0.007	0.14	-10000	0	-0.65	17	17
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:IP3	-0.021	0.13	-10000	0	-0.5	22	22
IGF-1R heterotetramer	-0.009	0.1	-10000	0	-0.55	16	16
PLCB1	-0.025	0.14	-10000	0	-0.44	37	37
PLCB2	-0.013	0.12	-10000	0	-0.47	23	23
IGF1	-0.088	0.21	-10000	0	-0.5	88	88
mol:L-citrulline	-0.007	0.14	-10000	0	-0.65	17	17
RHOA	0.01	0	-10000	0	-10000	0	0
Gai/GDP	-0.05	0.16	-10000	0	-0.81	16	16
JNK cascade	0.001	0.053	-10000	0	-0.45	6	6
BCAR1	0.01	0	-10000	0	-10000	0	0
ESR2	0.002	0.071	-10000	0	-0.6	6	6
GNAQ	0.01	0	-10000	0	-10000	0	0
ESR1	-0.021	0.13	-10000	0	-0.55	25	25
Gq family/GDP/Gbeta gamma	0.001	0.091	-10000	0	-0.42	13	13
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.012	0.064	-10000	0	-0.32	10	10
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.042	0.12	-10000	0	-0.58	19	19
GNAZ	-0.032	0.15	-10000	0	-0.55	34	34
E2/ER alpha (dimer)	-0.015	0.097	-10000	0	-0.41	25	25
STRN	0.01	0	-10000	0	-10000	0	0
GNAL	-0.021	0.13	-10000	0	-0.52	27	27
PELP1	0.01	0	-10000	0	-10000	0	0
MAPK11	0.009	0.046	-10000	0	-0.41	5	5
GNAI2	0.01	0	-10000	0	-10000	0	0
GNAI3	0.01	0	-10000	0	-10000	0	0
GNAI1	-0.005	0.093	-10000	0	-0.56	12	12
HBEGF	-0.022	0.15	-10000	0	-0.55	24	24
cAMP biosynthetic process	-0.033	0.11	-10000	0	-0.39	31	31
SRC	-0.016	0.14	-10000	0	-0.57	20	20
PI3K	0.014	0.012	-10000	0	-10000	0	0
GNB1	0.01	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.024	0.094	-10000	0	-0.44	20	20
SOS1	0.01	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.071	0.15	-10000	0	-0.52	33	33
Gs family/GTP	-0.034	0.11	-10000	0	-0.39	31	31
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.009	0.042	-10000	0	-0.38	1	1
vasodilation	-0.005	0.13	-10000	0	-0.61	17	17
mol:DAG	-0.021	0.13	-10000	0	-0.5	22	22
Gs family/GDP/Gbeta gamma	-0.033	0.1	-10000	0	-0.45	19	19
MSN	0.017	0.08	-10000	0	-0.5	4	4
Gq family/GTP	-0.018	0.12	-10000	0	-0.52	21	21
mol:PI-3-4-5-P3	-0.01	0.16	-10000	0	-0.85	16	16
NRAS	0.008	0.036	-10000	0	-0.51	2	2
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.005	0.13	0.61	17	-10000	0	17
GRB2/SOS1	0.015	0	-10000	0	-10000	0	0
RhoA/GDP	-0.024	0.096	-10000	0	-0.46	19	19
NOS3	-0.009	0.15	-10000	0	-0.7	17	17
GNA11	0.01	0	-10000	0	-10000	0	0
MAPKKK cascade	0.003	0.14	-10000	0	-0.69	16	16
E2/ER alpha (dimer)/PELP1/Src	-0.045	0.13	-10000	0	-0.61	19	19
ruffle organization	0.017	0.074	-10000	0	-0.46	4	4
ROCK2	0.013	0.077	-10000	0	-0.4	4	4
GNA14	-0.026	0.14	-10000	0	-0.56	29	29
GNA15	-0.035	0.13	-10000	0	-0.39	51	51
GNA13	0.01	0	-10000	0	-10000	0	0
MMP9	-0.03	0.16	-10000	0	-0.57	25	25
MMP2	-0.017	0.15	-10000	0	-0.58	21	21

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.003	0.13	-9999	-0.45	25	25
MAP3K8	0.009	0.018	-9999	-0.37	1	1
FOS	0	0.12	-9999	-0.5	15	15
PRKCA	-0.001	0.087	-9999	-0.65	8	8
PTPN7	-0.007	0.1	-9999	-0.54	15	15
HRAS	0.01	0.001	-9999	-10000	0	0
PRKCB	-0.036	0.16	-9999	-0.52	40	40
NRAS	0.008	0.036	-9999	-0.51	2	2
RAS family/GTP	0.01	0.046	-9999	-0.37	1	1
MAPK3	0.001	0.099	-9999	-0.52	11	11
MAP2K1	-0.006	0.13	-9999	-0.48	28	28
ELK1	0.01	0.004	-9999	-10000	0	0
BRAF	-0.035	0.12	-9999	-0.48	28	28
mol:GTP	0	0.001	-9999	-0.005	19	19
MAPK1	0.001	0.099	-9999	-0.52	11	11
RAF1	-0.035	0.12	-9999	-0.48	28	28
KRAS	-0.007	0.078	-9999	-0.37	20	20

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.005	0.038	-9999	-0.51	2	2
SVIL	-0.004	0.069	-9999	-0.4	13	13
ZNF318	0.014	0.044	-9999	-0.38	3	3
JMJD2C	0.002	0.016	-9999	-0.068	19	19
T-DHT/AR/Ubc9	-0.028	0.097	-9999	-0.4	17	17
CARM1	0.01	0.002	-9999	-10000	0	0
PRDX1	0.009	0.031	-9999	-0.65	1	1
PELP1	0.011	0.005	-9999	-10000	0	0
CTNNB1	0.008	0.01	-9999	-10000	0	0
AKT1	0.012	0.009	-9999	-10000	0	0
PTK2B	0.008	0.009	-9999	-10000	0	0
MED1	0.011	0.021	-9999	-0.37	1	1
MAK	0.013	0.048	-9999	-0.37	4	4
response to oxidative stress	0	0.002	-9999	-10000	0	0
HIP1	0.003	0.055	-9999	-0.65	3	3
GSN	0.008	0.014	-9999	-10000	0	0
NCOA2	0.007	0.044	-9999	-0.65	2	2
NCOA6	0.008	0.012	-9999	-10000	0	0
DNA-PK	0.008	0.04	-9999	-0.41	1	1
NCOA4	0.01	0.002	-9999	-10000	0	0
PIAS3	0.008	0.01	-9999	-10000	0	0
cell proliferation	-0.009	0.041	-9999	-10000	0	0
XRCC5	0.011	0.007	-9999	-10000	0	0
UBE3A	0.006	0.019	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.035	0.097	-9999	-0.28	42	42
FHL2	-0.03	0.18	-9999	-1.1	12	12
RANBP9	0.008	0.012	-9999	-10000	0	0
JMJD1A	-0.027	0.067	-9999	-0.14	116	116
CDK6	-0.006	0.084	-9999	-0.42	17	17
TGFB1I1	-0.005	0.075	-9999	-0.41	14	14
T-DHT/AR/CyclinD1	-0.039	0.11	-9999	-0.4	26	26
XRCC6	0.011	0.007	-9999	-10000	0	0
T-DHT/AR	-0.041	0.13	-9999	-0.38	28	28
CTDSP1	0.009	0.004	-9999	-10000	0	0
CTDSP2	0.014	0.021	-9999	-10000	0	0
BRCA1	0.003	0.055	-9999	-0.65	3	3
TCF4	0.009	0.053	-9999	-0.51	4	4
CDKN2A	-0.16	0.26	-9999	-0.5	149	149
SRF	0.014	0.025	-9999	-10000	0	0
NKX3-1	-0.1	0.24	-9999	-0.99	25	25
KLK3	-0.048	0.28	-9999	-1.5	16	16
TMF1	0.009	0.003	-9999	-10000	0	0
HNRNPA1	0.012	0.011	-9999	-10000	0	0
AOF2	-0.003	0.014	-9999	-0.071	16	16
APPL1	0.021	0.019	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.025	0.099	-9999	-0.4	17	17
AR	-0.044	0.14	-9999	-0.47	39	39
UBA3	0.009	0.004	-9999	-10000	0	0
PATZ1	0.011	0.033	-9999	-0.65	1	1
PAWR	0.008	0.031	-9999	-0.65	1	1
PRKDC	0.009	0.036	-9999	-0.51	2	2
PA2G4	0.013	0.014	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.023	0.09	-9999	-0.37	17	17
RPS6KA3	0.008	0.014	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.029	0.097	-9999	-0.3	33	33
LATS2	0.012	0.011	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.022	0.096	-9999	-0.39	17	17
Cyclin D3/CDK11 p58	0.007	0.013	-9999	-0.26	1	1
VAV3	-0.057	0.18	-9999	-0.51	57	57
KLK2	-0.036	0.073	-9999	-10000	0	0
CASP8	0.011	0.004	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.021	0.092	-9999	-0.38	18	18
TMPRSS2	-0.22	0.42	-9999	-1.1	88	88
CCND1	-0.006	0.085	-9999	-0.45	15	15
PIAS1	0.006	0.019	-9999	-10000	0	0
mol:T-DHT	-0.016	0.035	-9999	-0.075	110	110
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.004	0.03	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.036	0.11	-9999	-0.4	24	24
CMTM2	-0.007	0.1	-9999	-0.57	14	14
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	-0.004	0.032	-9999	-10000	0	0
CCND3	0.009	0.018	-9999	-0.37	1	1
TGIF1	0.011	0.033	-9999	-0.65	1	1
FKBP4	0.008	0.012	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.031	0.12	-9999	-0.49	25	25
MAP4K1	-0.01	0.1	-9999	-0.52	17	17
MAP3K8	0.009	0.018	-9999	-0.37	1	1
PRKCB	-0.036	0.16	-9999	-0.52	40	40
DBNL	0.01	0	-9999	-10000	0	0
CRKL	0.009	0.018	-9999	-0.37	1	1
MAP3K1	0.013	0.096	-9999	-0.55	8	8
JUN	-0.008	0.15	-9999	-0.63	22	22
MAP3K7	0.013	0.096	-9999	-0.55	8	8
GRAP2	-0.021	0.14	-9999	-0.6	23	23
CRK	0.01	0	-9999	-10000	0	0
MAP2K4	0.018	0.096	-9999	-0.54	8	8
LAT	0.009	0.018	-9999	-0.37	1	1
LCP2	0.004	0.062	-9999	-0.65	4	4
MAPK8	-0.014	0.15	-9999	-0.67	22	22
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.007	0.1	-9999	-0.4	21	21
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.029	0.12	-9999	-0.46	25	25

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.007	0.057	-9999	-0.38	9	9
alphaV beta3 Integrin	-0.016	0.082	-9999	-0.48	11	11
PTK2	0.002	0.12	-9999	-0.8	6	6
IGF1R	-0.01	0.1	-9999	-0.55	16	16
PI4KB	0.01	0	-9999	-10000	0	0
MFGE8	0.009	0.031	-9999	-0.65	1	1
SRC	0.009	0.031	-9999	-0.65	1	1
CDKN1B	-0.033	0.098	-9999	-0.57	11	11
VEGFA	0.005	0.047	-9999	-0.43	5	5
ILK	-0.032	0.096	-9999	-0.58	10	10
ROCK1	0.009	0.031	-9999	-0.65	1	1
AKT1	-0.006	0.096	-9999	-0.54	10	10
PTK2B	0.016	0.077	-9999	-0.44	10	10
alphaV/beta3 Integrin/JAM-A	-0.017	0.11	-9999	-0.4	22	22
CBL	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.023	0.079	-9999	-0.41	12	12
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.063	0.14	-9999	-0.42	48	48
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.007	0.078	-9999	-0.56	4	4
alphaV/beta3 Integrin/Syndecan-1	-0.018	0.082	-9999	-0.45	13	13
PI4KA	0.009	0.018	-9999	-0.37	1	1
IGF-1R heterotetramer/IGF1/IRS1	-0.084	0.17	-9999	-0.66	23	23
PI4 Kinase	0.014	0.012	-9999	-10000	0	0
PIK3CA	0.009	0.018	-9999	-0.37	1	1
alphaV/beta3 Integrin/Osteopontin	-0.079	0.15	-9999	-0.42	60	60
RPS6KB1	-0.047	0.17	-9999	-0.61	23	23
TLN1	0.01	0	-9999	-10000	0	0
MAPK3	-0.024	0.13	-9999	-0.71	11	11
GPR124	0	0.079	-9999	-0.58	8	8
MAPK1	-0.024	0.13	-9999	-0.71	11	11
PXN	0.003	0.064	-9999	-0.6	5	5
PIK3R1	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.049	0.12	-9999	-0.43	31	31
cell adhesion	-0.018	0.067	-9999	-0.36	13	13
ANGPTL3	-0.016	0.1	-9999	-0.41	27	27
VEGFR2 homodimer/VEGFA homodimer/Src	-0.007	0.05	-9999	-0.41	6	6
IGF-1R heterotetramer	-0.009	0.1	-9999	-0.55	16	16
Rac1/GDP	0.007	0	-9999	-10000	0	0
TGFBR2	0.003	0.069	-9999	-0.65	5	5
ITGB3	-0.003	0.087	-9999	-0.57	10	10
IGF1	-0.088	0.21	-9999	-0.5	88	88
RAC1	0.01	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.015	0.085	-9999	-0.51	11	11
apoptosis	0.008	0.036	-9999	-0.51	2	2
CD47	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.009	0.057	-9999	-0.41	8	8
VCL	0.01	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.025	0.11	-9999	-0.51	19	19
CSF1	0.007	0.044	-9999	-0.65	2	2
PIK3C2A	-0.032	0.095	-9999	-0.58	10	10
PI4 Kinase/Pyk2	-0.036	0.098	-9999	-0.8	4	4
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.013	0.077	-9999	-0.48	10	10
FAK1/Vinculin	0.009	0.098	-9999	-0.57	6	6
alphaV beta3/Integrin/ppsTEM5	-0.015	0.085	-9999	-0.51	11	11
RHOA	0.01	0	-9999	-10000	0	0
VTN	-0.051	0.15	-9999	-0.42	66	66
BCAR1	0.01	0	-9999	-10000	0	0
FGF2	-0.003	0.081	-9999	-0.46	13	13
F11R	0.006	0.067	-9999	-0.34	15	15
alphaV/beta3 Integrin/Lactadherin	-0.01	0.06	-9999	-0.41	9	9
alphaV/beta3 Integrin/TGFBR2	-0.013	0.074	-9999	-0.44	12	12
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.003	0.031	-9999	-0.37	3	3
HSP90AA1	0.009	0.031	-9999	-0.65	1	1
alphaV/beta3 Integrin/Talin	-0.008	0.052	-9999	-0.38	8	8
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.034	0.15	-9999	-0.54	36	36
alphaV/beta3 Integrin/Pyk2	0.017	0.077	-9999	-0.45	10	10
SDC1	-0.006	0.088	-9999	-0.47	15	15
VAV3	-0.008	0.1	-9999	-0.36	31	31
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.006	0.047	-9999	-0.56	3	3
FAK1/Paxillin	0.007	0.1	-9999	-0.53	8	8
cell migration	0.014	0.095	-9999	-0.46	8	8
ITGAV	0.008	0.036	-9999	-0.51	2	2
PI3K	-0.037	0.091	-9999	-0.63	4	4
SPP1	-0.11	0.23	-9999	-0.52	104	104
KDR	0.004	0.062	-9999	-0.65	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.008	0.036	-9999	-0.51	2	2
COL4A3	-0.06	0.18	-9999	-0.48	66	66
angiogenesis	-0.021	0.14	-9999	-0.71	11	11
Rac1/GTP	-0.03	0.087	-9999	-0.32	30	30
EDIL3	-0.018	0.13	-9999	-0.58	22	22
cell proliferation	-0.013	0.074	-9999	-0.44	12	12

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.04	0.18	-10000	0	-0.95	13	13
NCK1/PAK1/Dok-R	-0.02	0.082	-10000	0	-0.45	13	13
NCK1/Dok-R	0.001	0.22	-10000	0	-1.2	13	13
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
mol:beta2-estradiol	-0.003	0.034	0.22	9	-10000	0	9
RELA	0.01	0	-10000	0	-10000	0	0
SHC1	0.01	0.001	-10000	0	-10000	0	0
Rac/GDP	0.007	0	-10000	0	-10000	0	0
F2	-0.059	0.16	0.24	7	-0.44	67	74
TNIP2	0.01	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.034	0.18	-10000	0	-1.1	13	13
FN1	-0.034	0.15	-10000	0	-0.54	36	36
PLD2	0.021	0.22	-10000	0	-1.2	13	13
PTPN11	0.01	0	-10000	0	-10000	0	0
GRB14	-0.087	0.23	-10000	0	-0.61	71	71
ELK1	0.031	0.19	-10000	0	-1.1	13	13
GRB7	-0.023	0.12	-10000	0	-0.43	34	34
PAK1	0.008	0.036	-10000	0	-0.51	2	2
Tie2/Ang1/alpha5/beta1 Integrin	-0.055	0.21	-10000	0	-1.2	14	14
CDKN1A	0.039	0.14	-10000	0	-0.62	14	14
ITGA5	0.001	0.069	-10000	0	-0.47	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.001	0.22	-10000	0	-1.2	13	13
CRK	0.01	0	-10000	0	-10000	0	0
mol:NO	0.046	0.14	-10000	0	-0.7	13	13
PLG	0.014	0.22	-10000	0	-1.2	13	13
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.037	0.17	-10000	0	-0.91	13	13
GRB2	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.001	-10000	0	-10000	0	0
ANGPT2	-0.005	0.16	0.39	1	-0.62	11	12
BMX	0.005	0.23	-10000	0	-1.2	13	13
ANGPT1	0.005	0.21	-10000	0	-1.4	9	9
tube development	0.035	0.16	-10000	0	-0.71	14	14
ANGPT4	-0.024	0.14	-10000	0	-0.57	27	27
response to hypoxia	0.001	0.013	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.032	0.26	-10000	0	-1.3	13	13
alpha5/beta1 Integrin	0.008	0.05	-10000	0	-0.33	9	9
FGF2	-0.004	0.081	-10000	0	-0.46	13	13
STAT5A (dimer)	0.034	0.18	-10000	0	-0.81	14	14
mol:L-citrulline	0.046	0.14	-10000	0	-0.7	13	13
AGTR1	-0.12	0.24	-10000	0	-0.53	114	114
MAPK14	0.022	0.22	-10000	0	-1.2	13	13
Tie2/SHP2	-0.02	0.14	-10000	0	-1.2	6	6
TEK	0.009	0.16	-10000	0	-1.4	6	6
RPS6KB1	0.041	0.18	-10000	0	-0.91	13	13
Angiotensin II/AT1	-0.088	0.18	-10000	0	-0.38	114	114
Tie2/Ang1/GRB2	0.019	0.23	-10000	0	-1.3	13	13
MAPK3	0.028	0.2	-10000	0	-1.1	13	13
MAPK1	0.028	0.2	-10000	0	-1.1	13	13
Tie2/Ang1/GRB7	0.003	0.23	-10000	0	-1.3	13	13
NFKB1	0.01	0	-10000	0	-10000	0	0
MAPK8	0.021	0.22	-10000	0	-1.2	13	13
PI3K	0.032	0.21	-10000	0	-1.1	13	13
FES	0.021	0.22	-10000	0	-1.2	13	13
Crk/Dok-R	0.001	0.22	-10000	0	-1.2	13	13
Tie2/Ang1/ABIN2	0.019	0.23	-10000	0	-1.3	13	13
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.042	0.16	-10000	0	-0.84	13	13
STAT5A	0.004	0.062	-10000	0	-0.65	4	4
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.04	0.18	-10000	0	-0.91	13	13
Tie2/Ang2	0.024	0.2	-10000	0	-0.98	14	14
Tie2/Ang1	0.015	0.24	-10000	0	-1.3	13	13
FOXO1	0.044	0.17	-10000	0	-0.84	14	14
ELF1	0.016	0.013	-10000	0	-10000	0	0
ELF2	0.019	0.22	-10000	0	-1.2	13	13
mol:Choline	0.023	0.21	-10000	0	-1.1	13	13
cell migration	-0.016	0.049	-10000	0	-0.24	14	14
FYN	0.032	0.18	-10000	0	-0.82	14	14
DOK2	-0.006	0.1	-10000	0	-0.65	11	11
negative regulation of cell cycle	0.04	0.14	-10000	0	-0.56	14	14
ETS1	0.012	0.033	-10000	0	-10000	0	0
PXN	0.044	0.15	-10000	0	-0.74	13	13
ITGB1	0.01	0	-10000	0	-10000	0	0
NOS3	0.045	0.16	-10000	0	-0.81	13	13
RAC1	0.01	0	-10000	0	-10000	0	0
TNF	-0.025	0.15	-10000	0	-0.46	41	41
MAPKKK cascade	0.023	0.21	-10000	0	-1.1	13	13
RASA1	0.01	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.019	0.23	-10000	0	-1.3	13	13
NCK1	0.01	0	-10000	0	-10000	0	0
vasculogenesis	0.047	0.13	-10000	0	-0.62	13	13
mol:Phosphatidic acid	0.023	0.21	-10000	0	-1.1	13	13
mol:Angiotensin II	0.001	0.002	-10000	0	-10000	0	0
mol:NADP	0.046	0.14	-10000	0	-0.7	13	13
Rac1/GTP	-0.029	0.14	-10000	0	-0.84	13	13
MMP2	0.014	0.24	-10000	0	-1.3	13	13

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.098	0.22	-9999	-0.5	96	96
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0	-9999	-10000	0	0
TCEB1	0.01	0	-9999	-10000	0	0
HIF1A/p53	0.015	0.05	-9999	-0.32	9	9
HIF1A	0.017	0.014	-9999	-10000	0	0
COPS5	0.01	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0	0	-9999	-10000	0	0
FIH (dimer)	0.01	0	-9999	-10000	0	0
CDKN2A	-0.16	0.25	-9999	-0.51	149	149
ARNT/IPAS	-0.064	0.16	-9999	-0.36	96	96
HIF1AN	0.01	0	-9999	-10000	0	0
GNB2L1	0.01	0	-9999	-10000	0	0
HIF1A/ARNT	0.023	0.014	-9999	-10000	0	0
CUL2	0.01	0	-9999	-10000	0	0
OS9	0.01	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.022	0.021	-9999	-0.32	1	1
PHD1-3/OS9	-0.006	0.043	-9999	-0.37	5	5
HIF1A/RACK1/Elongin B/Elongin C	-0.001	0.008	-9999	-10000	0	0
VHL	0.01	0	-9999	-10000	0	0
HSP90AA1	0.009	0.031	-9999	-0.65	1	1
HIF1A/JAB1	0.023	0.014	-9999	-10000	0	0
EGLN3	-0.002	0.081	-9999	-0.5	11	11
EGLN2	0.01	0	-9999	-10000	0	0
EGLN1	0.01	0	-9999	-10000	0	0
TP53	-0.004	0.093	-9999	-0.62	10	10
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.029	0.003	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.01	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.06	0.13	-9999	-0.32	73	73

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.004	0.093	-10000	0	-0.62	10	10
ANTXR2	-0.004	0.092	-10000	0	-0.58	11	11
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.017	-10000	0	-0.082	18	18
monocyte activation	-0.018	0.12	-10000	0	-0.49	24	24
MAP2K2	-0.001	0.007	-10000	0	-10000	0	0
MAP2K1	-0.003	0.014	-10000	0	-10000	0	0
MAP2K7	-0.004	0.026	-10000	0	-0.47	1	1
MAP2K6	-0.017	0.072	-10000	0	-0.35	19	19
CYAA	-0.004	0.082	-10000	0	-0.43	14	14
MAP2K4	-0.005	0.033	-10000	0	-0.36	3	3
IL1B	-0.036	0.11	-10000	0	-0.37	34	34
Channel	-0.016	0.084	-10000	0	-0.46	14	14
NLRP1	-0.014	0.061	-10000	0	-0.29	18	18
CALM1	0.01	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.004	0.02	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.017	0.082	18	-10000	0	18
MAPK3	-0.003	0.014	-10000	0	-10000	0	0
MAPK1	-0.003	0.014	-10000	0	-10000	0	0
PGR	-0.029	0.092	-10000	0	-0.29	43	43
PA/Cellular Receptors	-0.017	0.091	-10000	0	-0.5	14	14
apoptosis	-0.003	0.017	-10000	0	-0.082	18	18
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.002	0.081	-10000	0	-0.43	14	14
macrophage activation	0.012	0.015	-10000	0	-10000	0	0
TNF	-0.028	0.14	-10000	0	-0.48	35	35
VCAM1	-0.019	0.12	-10000	0	-0.5	24	24
platelet activation	-0.004	0.02	-10000	0	-10000	0	0
MAPKKK cascade	-0.005	0.028	0.096	23	-10000	0	23
IL18	-0.012	0.088	-10000	0	-0.32	29	29
negative regulation of macrophage activation	-0.003	0.017	-10000	0	-0.082	18	18
LEF	-0.003	0.017	-10000	0	-0.082	18	18
CASP1	-0.01	0.042	-10000	0	-0.17	21	21
mol:cAMP	-0.004	0.02	-10000	0	-10000	0	0
necrosis	-0.003	0.017	-10000	0	-0.082	18	18
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.003	0.082	-10000	0	-0.43	14	14
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0.023	-9999	-0.48	1	1
SMARCC1	0.003	0.007	-9999	-10000	0	0
REL	0.01	0.018	-9999	-0.37	1	1
HDAC7	-0.016	0.13	-9999	-0.51	13	13
JUN	0.008	0.018	-9999	-0.37	1	1
EP300	0.01	0	-9999	-10000	0	0
KAT2B	0.01	0.001	-9999	-10000	0	0
KAT5	0.01	0.001	-9999	-10000	0	0
MAPK14	-0.007	0.1	-9999	-0.5	17	17
FOXO1	0.004	0.062	-9999	-0.65	4	4
T-DHT/AR	-0.021	0.14	-9999	-0.53	14	14
MAP2K6	-0.019	0.13	-9999	-0.63	19	19
BRM/BAF57	0.008	0.047	-9999	-0.41	3	3
MAP2K4	0.003	0.054	-9999	-0.66	3	3
SMARCA2	0.006	0.044	-9999	-0.66	2	2
PDE9A	-0.089	0.26	-9999	-1.2	23	23
NCOA2	0.007	0.044	-9999	-0.65	2	2
CEBPA	-0.014	0.11	-9999	-0.5	21	21
EHMT2	0.009	0.003	-9999	-10000	0	0
cell proliferation	-0.002	0.14	-9999	-0.46	15	15
NR0B1	-0.017	0.087	-9999	-0.37	26	26
EGR1	-0.002	0.079	-9999	-0.52	10	10
RXRs/9cRA	-0.028	0.11	-9999	-0.38	34	34
AR/RACK1/Src	-0.011	0.095	-9999	-0.41	14	14
AR/GR	-0.006	0.091	-9999	-0.34	19	19
GNB2L1	0.01	0.001	-9999	-10000	0	0
PKN1	0.007	0.044	-9999	-0.65	2	2
RCHY1	0.009	0.018	-9999	-0.37	1	1
epidermal growth factor receptor activity	0	0.001	-9999	-10000	0	0
MAPK8	0.008	0.049	-9999	-0.49	4	4
T-DHT/AR/TIF2/CARM1	0	0.1	-9999	-0.46	15	15
SRC	0.001	0.091	-9999	-0.38	22	22
NR3C1	0.001	0.075	-9999	-0.65	6	6
KLK3	-0.11	0.26	-9999	-1.1	20	20
APPBP2	0.008	0.007	-9999	-10000	0	0
TRIM24	0.009	0.003	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.006	0.1	-9999	-0.4	21	21
TMPRSS2	-0.23	0.46	-9999	-1.2	88	88
RXRG	-0.059	0.19	-9999	-0.53	57	57
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.008	0.031	-9999	-0.65	1	1
RXRB	0.01	0.001	-9999	-10000	0	0
CARM1	0.01	0.001	-9999	-10000	0	0
NR2C2	0.01	0.001	-9999	-10000	0	0
KLK2	0.003	0.1	-9999	-0.51	4	4
AR	-0.007	0.083	-9999	-0.29	26	26
SENP1	0.01	0.001	-9999	-10000	0	0
HSP90AA1	0.009	0.031	-9999	-0.65	1	1
MDM2	0.004	0.05	-9999	-0.36	8	8
SRY	-0.012	0.091	-9999	-0.48	15	15
GATA2	0.003	0.064	-9999	-0.6	5	5
MYST2	0	0.001	-9999	-10000	0	0
HOXB13	-0.11	0.24	-9999	-0.61	85	85
T-DHT/AR/RACK1/Src	0	0.099	-9999	-0.42	14	14
positive regulation of transcription	0.003	0.064	-9999	-0.6	5	5
DNAJA1	0.008	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.02	-9999	-0.27	1	1
NCOA1	0.013	0.005	-9999	-10000	0	0
SPDEF	-0.2	0.29	-9999	-0.58	160	160
T-DHT/AR/TIF2	0.015	0.068	-9999	-0.42	3	3
T-DHT/AR/Hsp90	-0.007	0.1	-9999	-0.4	22	22
GSK3B	0.009	0.003	-9999	-10000	0	0
NR2C1	0.01	0.001	-9999	-10000	0	0
mol:T-DHT	-0.004	0.095	-9999	-0.41	21	21
SIRT1	0.01	0	-9999	-10000	0	0
ZMIZ2	0.011	0.006	-9999	-10000	0	0
POU2F1	0.001	0.042	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.033	0.11	-9999	-0.42	21	21
CREBBP	0.01	0.001	-9999	-10000	0	0
SMARCE1	0.004	0.047	-9999	-0.37	7	7

×

Paxillin-independent events mediated by a4b1 and a4b7

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	0.072	-9999	-0.41	13	13
CRKL	0.009	0.018	-9999	-0.37	1	1
Rac1/GDP	0.007	0	-9999	-10000	0	0
DOCK1	0.01	0	-9999	-10000	0	0
ITGA4	-0.002	0.087	-9999	-0.65	8	8
alpha4/beta7 Integrin/MAdCAM1	-0.072	0.13	-9999	-0.38	56	56
EPO	-0.043	0.13	-9999	-0.37	61	61
alpha4/beta7 Integrin	0.001	0.08	-9999	-0.48	12	12
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.006	0.065	-9999	-0.48	8	8
EPO/EPOR (dimer)	-0.024	0.095	-9999	-0.68	1	1
lamellipodium assembly	0.001	0.011	-9999	-10000	0	0
PIK3CA	0.009	0.018	-9999	-0.37	1	1
PI3K	0.014	0.012	-9999	-10000	0	0
ARF6	0.01	0	-9999	-10000	0	0
JAK2	-0.003	0.083	-9999	-0.52	6	6
PXN	0.003	0.064	-9999	-0.6	5	5
PIK3R1	0.01	0	-9999	-10000	0	0
MADCAM1	-0.11	0.22	-9999	-0.48	112	112
cell adhesion	-0.071	0.13	-9999	-0.38	56	56
CRKL/CBL	0.014	0.012	-9999	-0.25	1	1
ITGB1	0.01	0	-9999	-10000	0	0
SRC	0.006	0.099	-9999	-0.48	16	16
ITGB7	0.003	0.064	-9999	-0.6	5	5
RAC1	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.019	0.1	-9999	-0.53	15	15
p130Cas/Crk/Dock1	0.023	0.087	-9999	-0.62	5	5
VCAM1	-0.011	0.11	-9999	-0.58	16	16
RHOA	0.01	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.011	0.062	-9999	-0.37	13	13
BCAR1	0.012	0.093	-9999	-0.44	16	16
EPOR	0.007	0.04	-9999	-0.47	3	3
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.01	0	-9999	-10000	0	0
GIT1	0.009	0.031	-9999	-0.65	1	1
Rac1/GTP	0.001	0.011	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.008	0.13	-10000	0	-0.73	8	8
UGCG	0.012	0.028	-10000	0	-10000	0	0
AKT1/mTOR/p70S6K/Hsp90/TERT	0	0.14	-10000	0	-0.41	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.013	0.028	-10000	0	-10000	0	0
mol:DAG	-0.001	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.036	0.11	-10000	0	-0.48	21	21
FRAP1	0.016	0.15	-10000	0	-0.54	23	23
FOXO3	0.023	0.14	-10000	0	-0.52	20	20
AKT1	0.017	0.15	-10000	0	-0.54	23	23
GAB2	0.006	0.053	-10000	0	-0.65	3	3
SMPD1	0.012	0.028	-10000	0	-10000	0	0
SGMS1	0.012	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	0.016	0.011	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
cell proliferation	0.021	0.06	-10000	0	-0.25	2	2
EIF3A	0.01	0	-10000	0	-10000	0	0
PI3K	0.017	0.014	-10000	0	-10000	0	0
RPS6KB1	-0.004	0.068	-10000	0	-10000	0	0
mol:sphingomyelin	-0.001	0.004	-10000	0	-10000	0	0
natural killer cell activation	0	0.001	-10000	0	-0.012	2	2
JAK3	0.007	0.047	-10000	0	-0.43	5	5
PIK3R1	0.012	0.002	-10000	0	-10000	0	0
JAK1	0.012	0.002	-10000	0	-10000	0	0
NFKB1	0.01	0	-10000	0	-10000	0	0
MYC	0.022	0.14	-10000	0	-0.6	13	13
MYB	-0.1	0.38	-10000	0	-1.3	41	41
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.009	0.16	-10000	0	-0.61	21	21
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.008	0.062	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.01	0.15	-10000	0	-0.59	21	21
Rac1/GDP	0.02	0.011	-10000	0	-10000	0	0
T cell proliferation	0.015	0.14	-10000	0	-0.56	20	20
SHC1	0.01	0.002	-10000	0	-10000	0	0
RAC1	0.01	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.003	0.02	-10000	0	-0.052	63	63
PRKCZ	0.014	0.15	-10000	0	-0.58	20	20
NF kappa B1 p50/RelA	-0.033	0.11	-10000	0	-0.48	20	20
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.001	0.14	-10000	0	-0.61	18	18
HSP90AA1	0.009	0.031	-10000	0	-0.65	1	1
RELA	0.01	0	-10000	0	-10000	0	0
IL2RA	-0.011	0.11	-10000	0	-0.6	16	16
IL2RB	-0.005	0.1	-10000	0	-0.63	12	12
TERT	-0.064	0.19	-10000	0	-0.49	67	67
E2F1	-0.03	0.15	-10000	0	-0.47	42	42
SOS1	0.01	0.001	-10000	0	-10000	0	0
RPS6	0.01	0	-10000	0	-10000	0	0
mol:cAMP	0.001	0.01	0.025	63	-10000	0	63
PTPN11	0.01	0.002	-10000	0	-10000	0	0
IL2RG	-0.046	0.18	-10000	0	-0.61	43	43
actin cytoskeleton organization	0.015	0.14	-10000	0	-0.56	20	20
GRB2	0.01	0.001	-10000	0	-10000	0	0
IL2	0.002	0.05	-10000	0	-0.37	8	8
PIK3CA	0.011	0.018	-10000	0	-0.37	1	1
Rac1/GTP	0.024	0.014	-10000	0	-10000	0	0
LCK	-0.019	0.13	-10000	0	-0.53	26	26
BCL2	0.021	0.14	-10000	0	-0.59	15	15

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.01	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.016	0.13	-9999	-0.62	19	19
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.006	0.053	-9999	-0.65	3	3
RAC1-CDC42/GTP/PAK family	-0.011	0.08	-9999	-0.24	46	46
response to UV	0	0	-9999	-10000	0	0
YES1	0.006	0.047	-9999	-0.56	3	3
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.01	0	-9999	-10000	0	0
FYN	0.009	0.031	-9999	-0.65	1	1
MAP3K12	0.01	0	-9999	-10000	0	0
FGR	-0.004	0.093	-9999	-0.62	10	10
p38 alpha/TAB1	-0.038	0.086	-9999	-0.32	29	29
PRKG1	0.004	0.056	-9999	-0.47	6	6
DUSP8	-0.002	0.087	-9999	-0.65	8	8
PGK/cGMP/p38 alpha	-0.038	0.087	-9999	-0.33	26	26
apoptosis	-0.037	0.083	-9999	-0.31	28	28
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.004	0.062	-9999	-0.65	4	4
DUSP1	-0.005	0.092	-9999	-0.52	13	13
PAK1	0.008	0.036	-9999	-0.51	2	2
SRC	0.009	0.031	-9999	-0.65	1	1
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.01	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	-0.025	0.14	-9999	-0.43	32	32
BLK	-0.13	0.25	-9999	-0.54	118	118
HCK	-0.002	0.087	-9999	-0.65	8	8
MAP2K3	0.01	0	-9999	-10000	0	0
DUSP16	0.01	0	-9999	-10000	0	0
DUSP10	0.005	0.05	-9999	-0.51	4	4
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.012	0.11	-9999	-0.35	28	28
positive regulation of innate immune response	-0.024	0.15	-9999	-0.48	29	29
LCK	-0.021	0.13	-9999	-0.53	26	26
p38alpha-beta/MKP7	-0.017	0.14	-9999	-0.46	28	28
p38alpha-beta/MKP5	-0.019	0.14	-9999	-0.46	29	29
PGK/cGMP	0.003	0.041	-9999	-0.34	6	6
PAK2	0.01	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.024	0.15	-9999	-0.48	30	30
CDC42	0.01	0	-9999	-10000	0	0
RALB	0.01	0	-9999	-10000	0	0
RALA	0.01	0	-9999	-10000	0	0
PAK3	-0.079	0.21	-9999	-0.54	74	74

×

Class I PI3K 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
ARF5/GTP	-0.005	0.038	0.26	3	-10000	0	3
DAPP1	-0.045	0.18	-10000	0	-0.52	37	37
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.052	0.21	-10000	0	-0.63	39	39
mol:DAG	-0.005	0.095	-10000	0	-0.27	31	31
HRAS	0.01	0.002	-10000	0	-10000	0	0
RAP1A	0.01	0.002	-10000	0	-10000	0	0
ARF5/GDP	0.017	0.063	-10000	0	-0.34	8	8
PLCG2	-0.003	0.085	-10000	0	-0.52	11	11
PLCG1	0.01	0	-10000	0	-10000	0	0
ARF5	0.01	0	-10000	0	-10000	0	0
mol:GTP	-0.006	0.04	0.24	3	-0.31	2	5
ARF1/GTP	-0.005	0.037	0.25	3	-0.29	2	5
RHOA	0.01	0	-10000	0	-10000	0	0
YES1	0.006	0.047	-10000	0	-0.56	3	3
RAP1A/GTP	-0.006	0.039	0.23	3	-0.3	2	5
ADAP1	-0.02	0.077	0.23	3	-0.32	23	26
ARAP3	-0.006	0.039	0.24	3	-0.3	2	5
INPPL1	0.009	0.018	-10000	0	-0.37	1	1
PREX1	0.004	0.062	-10000	0	-0.65	4	4
ARHGEF6	0	0.077	-10000	0	-0.61	7	7
ARHGEF7	0.009	0.018	-10000	0	-0.37	1	1
ARF1	0.01	0	-10000	0	-10000	0	0
NRAS	0.008	0.036	-10000	0	-0.51	2	2
FYN	0.009	0.031	-10000	0	-0.65	1	1
ARF6	0.01	0	-10000	0	-10000	0	0
FGR	-0.004	0.093	-10000	0	-0.62	10	10
mol:Ca2+	0.005	0.051	-10000	0	-0.2	2	2
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.037	0.15	-10000	0	-0.46	46	46
ZAP70	-0.024	0.14	-10000	0	-0.55	28	28
mol:IP3	0.003	0.07	-10000	0	-0.23	13	13
LYN	0.004	0.062	-10000	0	-0.65	4	4
ARF1/GDP	0.017	0.063	-10000	0	-0.34	8	8
RhoA/GDP	-0.009	0.044	0.24	3	-0.3	1	4
PDK1/Src/Hsp90	-0.033	0.11	-10000	0	-0.41	35	35
BLNK	-0.023	0.14	-10000	0	-0.65	23	23
actin cytoskeleton reorganization	0.028	0.071	0.23	3	-0.41	5	8
SRC	0.009	0.031	-10000	0	-0.65	1	1
PLEKHA2	0.01	0.069	-10000	0	-0.41	11	11
RAC1	0.01	0	-10000	0	-10000	0	0
PTEN	-0.003	0.051	-10000	0	-0.63	3	3
HSP90AA1	0.009	0.031	-10000	0	-0.65	1	1
ARF6/GTP	-0.005	0.038	0.26	3	-10000	0	3
RhoA/GTP	-0.005	0.037	0.23	3	-0.29	2	5
Src family/SYK family/BLNK-LAT	-0.05	0.19	-10000	0	-0.59	37	37
BLK	-0.13	0.25	-10000	0	-0.54	118	118
PDPK1	-0.041	0.17	-10000	0	-0.63	36	36
CYTH1	-0.005	0.037	0.23	3	-0.29	2	5
HCK	-0.002	0.087	-10000	0	-0.65	8	8
CYTH3	-0.005	0.037	0.23	3	-0.29	2	5
CYTH2	-0.005	0.037	0.23	3	-0.29	2	5
KRAS	-0.006	0.078	-10000	0	-0.37	20	20
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.003	0.089	-10000	0	-0.43	8	8
SGK1	-0.028	0.086	-10000	0	-0.47	8	8
INPP5D	-0.008	0.11	-10000	0	-0.59	14	14
mol:GDP	0.011	0.066	-10000	0	-0.26	20	20
SOS1	0.01	0	-10000	0	-10000	0	0
SYK	0.006	0.053	-10000	0	-0.65	3	3
ARF6/GDP	-0.009	0.044	0.25	3	-0.3	1	4
mol:PI-3-4-5-P3	-0.006	0.043	0.31	3	-0.31	2	5
ARAP3/RAP1A/GTP	-0.006	0.039	0.23	3	-0.31	2	5
VAV1	-0.003	0.087	-10000	0	-0.57	10	10
mol:PI-3-4-P2	0.003	0.08	-10000	0	-0.42	15	15
RAS family/GTP/PI3K Class I	0.015	0.04	-10000	0	-0.31	2	2
PLEKHA1	0.009	0.074	-10000	0	-0.42	12	12
Rac1/GDP	0.017	0.063	-10000	0	-0.34	8	8
LAT	0.009	0.018	-10000	0	-0.37	1	1
Rac1/GTP	0.003	0.11	-10000	0	-0.46	19	19
ITK	-0.027	0.084	0.23	1	-0.34	25	26
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.014	0.13	-10000	0	-0.39	31	31
LCK	-0.021	0.13	-10000	0	-0.53	26	26
BTK	-0.019	0.075	0.23	3	-0.35	16	19

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.1	0.31	-9999	-1.1	33	33
RAD9A	0.009	0.031	-9999	-0.65	1	1
AP1	-0.005	0.092	-9999	-0.44	19	19
IFNAR2	0.01	0.005	-9999	-10000	0	0
AKT1	0	0.055	-9999	-0.24	16	16
ER alpha/Oestrogen	-0.016	0.098	-9999	-0.41	25	25
NFX1/SIN3/HDAC complex	0.03	0.02	-9999	-10000	0	0
EGF	-0.14	0.24	-9999	-0.47	144	144
SMG5	0.01	0	-9999	-10000	0	0
SMG6	0.01	0	-9999	-10000	0	0
SP3/HDAC2	0.014	0.01	-9999	-10000	0	0
TERT/c-Abl	-0.11	0.28	-9999	-1	33	33
SAP18	0.009	0.003	-9999	-10000	0	0
MRN complex	-0.003	0.033	-9999	-0.41	3	3
WT1	-0.12	0.23	-9999	-0.51	114	114
WRN	0.009	0.031	-9999	-0.65	1	1
SP1	0.009	0.008	-9999	-10000	0	0
SP3	0.009	0.004	-9999	-10000	0	0
TERF2IP	0.01	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.098	0.24	-9999	-0.92	32	32
Mad/Max	0.007	0.052	-9999	-0.32	10	10
TERT	-0.1	0.33	-9999	-1.2	33	33
CCND1	-0.088	0.28	-9999	-1	33	33
MAX	0.009	0.004	-9999	-10000	0	0
RBBP7	0.009	0.003	-9999	-10000	0	0
RBBP4	0.009	0.003	-9999	-10000	0	0
TERF2	0	0.02	-9999	-0.4	1	1
PTGES3	0.01	0	-9999	-10000	0	0
SIN3A	0.009	0.003	-9999	-10000	0	0
Telomerase/911	0.019	0.039	-9999	-0.34	2	2
CDKN1B	-0.025	0.13	-9999	-0.42	39	39
RAD1	0.01	0	-9999	-10000	0	0
XRCC5	0.01	0	-9999	-10000	0	0
XRCC6	0.01	0	-9999	-10000	0	0
SAP30	0.009	0.018	-9999	-0.37	1	1
TRF2/PARP2	0	0.016	-9999	-0.3	1	1
UBE3A	0.009	0.004	-9999	-10000	0	0
JUN	0.008	0.018	-9999	-0.37	1	1
E6	-0.001	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.007	0.005	-9999	-10000	0	0
FOS	-0.015	0.12	-9999	-0.58	19	19
IFN-gamma/IRF1	-0.04	0.15	-9999	-0.48	39	39
PARP2	0.01	0	-9999	-10000	0	0
BLM	0.001	0.073	-9999	-0.57	7	7
Telomerase	0.002	0.086	-9999	-0.8	3	3
IRF1	0.01	0.033	-9999	-0.65	1	1
ESR1	-0.021	0.13	-9999	-0.55	25	25
KU/TER	0.015	0	-9999	-10000	0	0
ATM/TRF2	0.011	0.044	-9999	-0.4	5	5
ubiquitin-dependent protein catabolic process	0.034	0.02	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.034	0.021	-9999	-10000	0	0
HDAC1	0.008	0.031	-9999	-0.65	1	1
HDAC2	0.009	0.008	-9999	-10000	0	0
ATM	-0.004	0.045	-9999	-0.48	4	4
SMAD3	0.011	0.058	-9999	-0.45	7	7
ABL1	0.01	0	-9999	-10000	0	0
MXD1	-0.001	0.071	-9999	-0.46	10	10
MRE11A	0.006	0.053	-9999	-0.65	3	3
HUS1	0.01	0	-9999	-10000	0	0
RPS6KB1	0.01	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.097	0.27	-9999	-0.99	33	33
NR2F2	0.003	0.071	-9999	-0.6	6	6
MAPK3	0.009	0.036	-9999	-0.26	8	8
MAPK1	0.009	0.036	-9999	-0.26	8	8
TGFB1/TGF beta receptor Type II	0.005	0.062	-9999	-0.65	4	4
NFKB1	0.01	0	-9999	-10000	0	0
HNRNPC	0.01	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.004	0.044	-9999	-0.47	4	4
NBN	0.01	0	-9999	-10000	0	0
EGFR	-0.036	0.14	-9999	-0.45	46	46
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.13	0.2	-9999	-0.36	171	171
MYC	0.005	0.047	-9999	-0.56	3	3
IL2	-0.001	0.052	-9999	-0.38	8	8
KU	0.015	0	-9999	-10000	0	0
RAD50	0.01	0	-9999	-10000	0	0
HSP90AA1	0.009	0.031	-9999	-0.65	1	1
TGFB1	0.005	0.062	-9999	-0.65	4	4
TRF2/BLM	-0.006	0.053	-9999	-0.46	6	6
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.084	0.28	-9999	-1	33	33
SP1/HDAC2	0.015	0.013	-9999	-10000	0	0
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.098	0.24	-9999	-0.92	32	32
Smad3/Myc	0.013	0.058	-9999	-0.41	8	8
911 complex	-0.001	0.019	-9999	-0.41	1	1
IFNG	-0.069	0.2	-9999	-0.52	69	69
Telomerase/PinX1	-0.1	0.24	-9999	-0.9	33	33
Telomerase/AKT1/mTOR/p70S6K	0.003	0.071	-9999	-0.72	1	1
SIN3B	0.009	0.003	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
Telomerase/EST1B	-0.098	0.24	-9999	-0.92	32	32
response to DNA damage stimulus	0.001	0.013	-9999	-10000	0	0
MRN complex/TRF2/Rap1	-0.002	0.029	-9999	-0.33	3	3
TRF2/WRN	-0.001	0.026	-9999	-0.38	2	2
Telomerase/hnRNP C1/C2	-0.098	0.24	-9999	-0.92	32	32
E2F1	0.005	0.057	-9999	-0.59	4	4
ZNFX1	0.009	0.003	-9999	-10000	0	0
PIF1	0.006	0.053	-9999	-0.65	3	3
NCL	0.01	0	-9999	-10000	0	0
DKC1	0.01	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.002	0.087	-9999	-0.65	8	8
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	-0.015	0.098	-9999	-0.29	43	43
GNAO1	-0.049	0.16	-9999	-0.45	60	60
S1P/S1P3/G12/G13	0.01	0.064	-9999	-0.38	11	11
AKT1	-0.003	0.11	-9999	-0.65	9	9
AKT3	0.005	0.11	-9999	-0.93	3	3
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.002	0.087	-9999	-0.65	8	8
GNAI2	0.011	0.001	-9999	-10000	0	0
GNAI3	0.011	0.001	-9999	-10000	0	0
GNAI1	-0.004	0.094	-9999	-0.56	12	12
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.009	0.11	-9999	-0.56	16	16
S1PR2	0.009	0.018	-9999	-0.37	1	1
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.018	0.14	-9999	-0.48	22	22
MAPK3	-0.012	0.13	-9999	-0.7	10	10
MAPK1	-0.012	0.13	-9999	-0.7	10	10
JAK2	-0.014	0.14	-9999	-0.73	11	11
CXCR4	-0.02	0.15	-9999	-0.66	15	15
FLT1	0.009	0.044	-9999	-0.65	2	2
RhoA/GDP	0.007	0	-9999	-10000	0	0
Rac1/GDP	0.007	0	-9999	-10000	0	0
SRC	-0.012	0.13	-9999	-0.67	11	11
S1P/S1P3/Gi	-0.019	0.14	-9999	-0.49	22	22
RAC1	0.01	0	-9999	-10000	0	0
RhoA/GTP	-0.013	0.13	-9999	-0.68	10	10
VEGFA	0.007	0.047	-9999	-0.43	5	5
S1P/S1P2/Gi	-0.01	0.095	-9999	-0.27	43	43
VEGFR1 homodimer/VEGFA homodimer	0.015	0.048	-9999	-0.35	7	7
RHOA	0.01	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.013	0.11	-9999	-0.37	29	29
GNAQ	0.01	0	-9999	-10000	0	0
GNAZ	-0.031	0.15	-9999	-0.55	34	34
G12/G13	0.015	0	-9999	-10000	0	0
GNA14	-0.026	0.14	-9999	-0.56	29	29
GNA15	-0.035	0.13	-9999	-0.39	51	51
GNA12	0.01	0	-9999	-10000	0	0
GNA13	0.01	0	-9999	-10000	0	0
GNA11	0.01	0	-9999	-10000	0	0
Rac1/GTP	-0.013	0.13	-9999	-0.68	10	10

×

Regulation of nuclear SMAD2/3 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
EP300	0.014	0.014	-10000	0	-10000	0	0
HSPA8	0.009	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.018	0.1	0.2	3	-0.44	19	22
AKT1	0.007	0.018	-10000	0	-10000	0	0
GSC	-0.13	0.41	-10000	0	-1.5	39	39
NKX2-5	-0.14	0.23	-10000	0	-0.47	136	136
muscle cell differentiation	0.042	0.073	0.38	6	-10000	0	6
SMAD2-3/SMAD4/SP1	0.032	0.079	-10000	0	-0.46	3	3
SMAD4	0.008	0.048	-10000	0	-0.34	4	4
CBFB	0.009	0.031	-10000	0	-0.65	1	1
SAP18	0.01	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.009	0.082	-10000	0	-0.41	7	7
SMAD3/SMAD4/VDR	0.009	0.061	-10000	0	-0.33	6	6
MYC	0.009	0.05	-10000	0	-0.55	3	3
CDKN2B	-0.068	0.35	-10000	0	-1.4	27	27
AP1	0.029	0.079	-10000	0	-0.33	16	16
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.037	0.034	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.004	0.1	-10000	0	-0.36	23	23
SP3	0.012	0.005	-10000	0	-10000	0	0
CREB1	0.01	0	-10000	0	-10000	0	0
FOXH1	-0.013	0.09	-10000	0	-0.54	11	11
SMAD3/SMAD4/GR	-0.005	0.068	-10000	0	-0.43	9	9
GATA3	-0.01	0.11	-10000	0	-0.49	19	19
SKI/SIN3/HDAC complex/NCoR1	0.03	0.019	-10000	0	-10000	0	0
MEF2C/TIF2	-0.059	0.15	-10000	0	-0.54	11	11
endothelial cell migration	0.043	0.25	1.4	14	-10000	0	14
MAX	0.011	0.01	-10000	0	-10000	0	0
RBBP7	0.01	0.002	-10000	0	-10000	0	0
RBBP4	0.01	0.002	-10000	0	-10000	0	0
RUNX2	0.004	0.059	-10000	0	-0.54	5	5
RUNX3	-0.012	0.12	-10000	0	-0.59	17	17
RUNX1	0.009	0.031	-10000	0	-0.65	1	1
CTBP1	0.01	0	-10000	0	-10000	0	0
NR3C1	0.003	0.073	-10000	0	-0.62	6	6
VDR	0.001	0.075	-10000	0	-0.65	6	6
CDKN1A	0.049	0.059	-10000	0	-10000	0	0
KAT2B	0.011	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.008	0.1	-10000	0	-0.4	11	11
DCP1A	0.01	0	-10000	0	-10000	0	0
SKI	0.009	0.018	-10000	0	-0.37	1	1
SERPINE1	-0.044	0.25	-10000	0	-1.4	14	14
SMAD3/SMAD4/ATF2	-0.001	0.043	-10000	0	-0.35	3	3
SMAD3/SMAD4/ATF3	-0.01	0.071	-10000	0	-0.4	10	10
SAP30	0.009	0.018	-10000	0	-0.37	1	1
Cbp/p300/PIAS3	0.019	0.039	-10000	0	-10000	0	0
JUN	0.029	0.078	-10000	0	-0.32	16	16
SMAD3/SMAD4/IRF7	-0.004	0.058	-10000	0	-0.42	6	6
TFE3	0.012	0.016	-10000	0	-10000	0	0
COL1A2	-0.019	0.16	-10000	0	-1.1	10	10
mesenchymal cell differentiation	0.005	0.061	0.42	7	-10000	0	7
DLX1	-0.058	0.15	-10000	0	-0.38	78	78
TCF3	0.01	0	-10000	0	-10000	0	0
FOS	-0.01	0.12	-10000	0	-0.57	19	19
SMAD3/SMAD4/Max	0	0.042	-10000	0	-0.36	3	3
Cbp/p300/SNIP1	0.009	0.018	-10000	0	-10000	0	0
ZBTB17	0.012	0.014	-10000	0	-10000	0	0
LAMC1	0.032	0.07	-10000	0	-0.74	2	2
TGIF2/HDAC complex/SMAD3/SMAD4	-0.001	0.043	-10000	0	-0.35	3	3
IRF7	0.006	0.054	-10000	0	-0.65	3	3
ESR1	-0.021	0.13	-10000	0	-0.55	25	25
HNF4A	-0.14	0.28	-10000	0	-0.64	105	105
MEF2C	-0.066	0.15	-10000	0	-0.5	16	16
SMAD2-3/SMAD4	-0.016	0.05	-10000	0	-0.35	4	4
Cbp/p300/Src-1	0.013	0.026	-10000	0	-10000	0	0
IGHV3OR16-13	-0.004	0.018	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.01	0	-10000	0	-10000	0	0
CREBBP	0.012	0.01	-10000	0	-10000	0	0
SKIL	0.01	0	-10000	0	-10000	0	0
HDAC1	0.008	0.031	-10000	0	-0.65	1	1
HDAC2	0.01	0.002	-10000	0	-10000	0	0
SNIP1	0.009	0.003	-10000	0	-10000	0	0
GCN5L2	0.003	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.025	0.06	-10000	0	-0.37	5	5
MSG1/HSC70	-0.017	0.092	-10000	0	-0.29	44	44
SMAD2	-0.002	0.037	-10000	0	-10000	0	0
SMAD3	0.015	0.054	-10000	0	-0.52	3	3
SMAD3/E2F4-5/DP1/p107/SMAD4	0.028	0.055	-10000	0	-0.28	10	10
SMAD2/SMAD2/SMAD4	0.011	0.026	-10000	0	-0.35	1	1
NCOR1	0.01	0.002	-10000	0	-10000	0	0
NCOA2	0.007	0.044	-10000	0	-0.65	2	2
NCOA1	0.01	0	-10000	0	-10000	0	0
MYOD/E2A	0.005	0.032	-10000	0	-0.25	7	7
SMAD2-3/SMAD4/SP1/MIZ-1	0.037	0.076	-10000	0	-0.44	3	3
IFNB1	0.026	0.059	-10000	0	-0.42	3	3
SMAD3/SMAD4/MEF2C	-0.053	0.15	-10000	0	-0.53	11	11
CITED1	-0.032	0.13	-10000	0	-0.42	44	44
SMAD2-3/SMAD4/ARC105	0.011	0.057	-10000	0	-0.3	4	4
RBL1	0.006	0.047	-10000	0	-0.56	3	3
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.009	0.14	-10000	0	-0.51	27	27
RUNX1-3/PEBPB2	-0.015	0.075	-10000	0	-0.41	15	15
SMAD7	0.043	0.086	-10000	0	-0.47	2	2
MYC/MIZ-1	0.008	0.049	-10000	0	-0.39	3	3
SMAD3/SMAD4	0.025	0.12	0.29	37	-0.44	10	47
IL10	0.016	0.12	-10000	0	-0.57	14	14
PIASy/HDAC complex	0.008	0.01	-10000	0	-10000	0	0
PIAS3	0.011	0.005	-10000	0	-10000	0	0
CDK2	0.011	0.032	-10000	0	-0.64	1	1
IL5	0.016	0.1	-10000	0	-0.44	9	9
CDK4	0.011	0.028	-10000	0	-0.37	2	2
PIAS4	0.008	0.01	-10000	0	-10000	0	0
ATF3	-0.005	0.09	-10000	0	-0.49	14	14
SMAD3/SMAD4/SP1	0.024	0.068	-10000	0	-0.37	6	6
FOXG1	-0.073	0.18	-10000	0	-0.44	80	80
FOXO3	0.014	0.024	-10000	0	-10000	0	0
FOXO1	0.01	0.053	-10000	0	-0.5	4	4
FOXO4	0.014	0.024	-10000	0	-10000	0	0
heart looping	-0.066	0.15	-10000	0	-0.49	16	16
CEBPB	0.006	0.038	-10000	0	-0.53	2	2
SMAD3/SMAD4/DLX1	-0.039	0.092	-10000	0	-0.36	8	8
MYOD1	-0.004	0.046	-10000	0	-0.37	7	7
SMAD3/SMAD4/HNF4	-0.098	0.18	-10000	0	-0.42	104	104
SMAD3/SMAD4/GATA3	-0.017	0.092	-10000	0	-0.43	15	15
SnoN/SIN3/HDAC complex/NCoR1	0.01	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.01	0.081	-10000	0	-0.39	15	15
SMAD3/SMAD4/SP1-3	0.042	0.063	-10000	0	-0.37	2	2
MED15	0.008	0.025	-10000	0	-0.37	2	2
SP1	0.013	0.025	-10000	0	-10000	0	0
SIN3B	0.01	0.002	-10000	0	-10000	0	0
SIN3A	0.01	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.078	0.16	-10000	0	-0.39	64	64
ITGB5	0.043	0.062	-10000	0	-0.62	1	1
TGIF/SIN3/HDAC complex/CtBP	0.032	0.018	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.025	0.1	-10000	0	-0.44	19	19
AR	-0.031	0.14	-10000	0	-0.47	39	39
negative regulation of cell growth	0.03	0.064	-10000	0	-0.36	4	4
SMAD3/SMAD4/MYOD	-0.006	0.051	-10000	0	-0.33	5	5
E2F5	0.001	0.073	-10000	0	-0.57	7	7
E2F4	0.01	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.01	0.076	-10000	0	-0.34	9	9
SMAD2-3/SMAD4/FOXO1-3a-4	0.014	0.099	-10000	0	-0.34	26	26
TFDP1	0.007	0.031	-10000	0	-0.37	3	3
SMAD3/SMAD4/AP1	0.029	0.081	-10000	0	-0.33	16	16
SMAD3/SMAD4/RUNX2	-0.005	0.061	-10000	0	-0.42	7	7
TGIF2	0.01	0	-10000	0	-10000	0	0
TGIF1	0.009	0.031	-10000	0	-0.65	1	1
ATF2	0.01	0	-10000	0	-10000	0	0

×

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

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
MET/RANBP9	0.006	0.052	-10000	0	-0.48	2	2
CRKL	0.006	0.085	-10000	0	-0.42	11	11
mol:PIP3	-0.011	0.048	0.57	3	-10000	0	3
AKT1	-0.025	0.1	0.39	3	-0.37	33	36
PTK2B	0.01	0	-10000	0	-10000	0	0
RAPGEF1	0.011	0.081	-10000	0	-0.39	11	11
RANBP10	0.01	0	-10000	0	-10000	0	0
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
HGF/MET/SHIP2	-0.03	0.098	-10000	0	-0.42	22	22
MAP3K5	0.012	0.096	-10000	0	-0.45	13	13
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.032	0.1	-10000	0	-0.42	26	26
AP1	-0.005	0.082	-10000	0	-0.38	19	19
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.01	0	-10000	0	-10000	0	0
apoptosis	-0.009	0.14	-10000	0	-0.77	14	14
STAT3 (dimer)	0.01	0.076	-10000	0	-0.41	2	2
GAB1/CRKL/SHP2/PI3K	-0.018	0.068	-10000	0	-0.41	8	8
INPP5D	-0.008	0.11	-10000	0	-0.59	14	14
CBL/CRK	0.012	0.081	-10000	0	-0.42	9	9
PTPN11	0.01	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.01	0	-10000	0	-10000	0	0
PTEN	0.006	0.053	-10000	0	-0.65	3	3
ELK1	-0.003	0.028	-10000	0	-0.2	3	3
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.016	0.059	-10000	0	-0.33	10	10
PAK1	-0.02	0.099	0.36	3	-0.35	34	37
HGF/MET/RANBP10	-0.029	0.097	-10000	0	-0.42	22	22
HRAS	0.004	0.093	-10000	0	-0.49	8	8
DOCK1	0.011	0.081	-10000	0	-0.42	9	9
GAB1	0.001	0.089	-10000	0	-0.33	25	25
CRK	0.006	0.085	-10000	0	-0.42	11	11
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.031	0.12	-10000	0	-0.56	22	22
JUN	0.009	0.018	-10000	0	-0.37	1	1
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.01	0.079	-10000	0	-0.3	25	25
PIK3R1	0.01	0	-10000	0	-10000	0	0
cell morphogenesis	0.028	0.083	-10000	0	-0.41	3	3
GRB2/SHC	0.003	0.071	-10000	0	-0.36	11	11
FOS	-0.014	0.12	-10000	0	-0.58	19	19
GLMN	-0.001	0.019	-10000	0	-0.28	2	2
cell motility	-0.003	0.028	-10000	0	-0.23	2	2
HGF/MET/MUC20	-0.03	0.099	-10000	0	-0.42	22	22
cell migration	0.003	0.07	-10000	0	-0.35	11	11
GRB2	0.01	0	-10000	0	-10000	0	0
CBL	0.01	0	-10000	0	-10000	0	0
MET/RANBP10	0.006	0.052	-10000	0	-0.29	13	13
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.005	0.076	-10000	0	-0.28	27	27
MET/MUC20	-0.001	0.052	-10000	0	-0.29	13	13
RAP1B	0.016	0.079	-10000	0	-0.42	8	8
RAP1A	0.017	0.077	-10000	0	-0.41	8	8
HGF/MET/RANBP9	-0.029	0.097	-10000	0	-0.42	22	22
RAF1	0.01	0.089	-10000	0	-0.46	8	8
STAT3	0.01	0.076	-10000	0	-0.41	2	2
cell proliferation	0.011	0.11	-10000	0	-0.42	23	23
RPS6KB1	0.002	0.03	-10000	0	-0.17	5	5
MAPK3	-0.007	0.026	-10000	0	-10000	0	0
MAPK1	-0.007	0.026	-10000	0	-0.21	2	2
RANBP9	0.01	0	-10000	0	-10000	0	0
MAPK8	0.024	0.083	-10000	0	-0.4	8	8
SRC	0.01	0.076	-10000	0	-0.48	2	2
PI3K	0.003	0.071	-10000	0	-0.36	11	11
MET/Glomulin	0.001	0.048	-10000	0	-0.25	15	15
SOS1	0.01	0	-10000	0	-10000	0	0
MAP2K1	0.016	0.083	-10000	0	-0.42	8	8
MET	-0.002	0.073	-10000	0	-0.42	13	13
MAP4K1	0.007	0.1	-10000	0	-0.46	14	14
PTK2	0.009	0.031	-10000	0	-0.65	1	1
MAP2K2	0.016	0.083	-10000	0	-0.42	8	8
BAD	-0.018	0.098	0.36	3	-0.35	33	36
MAP2K4	0.015	0.092	-10000	0	-0.41	12	12
SHP2/GRB2/SOS1/GAB1	-0.019	0.07	-10000	0	-0.39	11	11
INPPL1	0.009	0.018	-10000	0	-0.37	1	1
PXN	0.003	0.064	-10000	0	-0.6	5	5
SH3KBP1	0	0.081	-10000	0	-0.65	7	7
HGS	-0.003	0.074	-10000	0	-0.28	25	25
PLCgamma1/PKC	0.007	0	-10000	0	-10000	0	0
HGF	-0.028	0.15	-10000	0	-0.55	31	31
RASA1	0.01	0	-10000	0	-10000	0	0
NCK1	0.01	0	-10000	0	-10000	0	0
PTPRJ	-0.003	0.09	-10000	0	-0.6	10	10
NCK/PLCgamma1	0.003	0.075	-10000	0	-0.36	11	11
PDPK1	-0.034	0.11	0.44	3	-0.4	33	36
HGF/MET/SHIP	-0.04	0.12	-10000	0	-0.45	31	31

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.004	0.18	-9999	-0.67	9	9
CRP	-0.004	0.18	-9999	-0.7	9	9
cell cycle arrest	-0.008	0.2	-9999	-0.69	16	16
TIMP1	-0.003	0.21	-9999	-0.86	15	15
IL6ST	0.013	0.007	-9999	-10000	0	0
Rac1/GDP	0.001	0.12	-9999	-0.51	11	11
AP1	0.021	0.095	-9999	-0.47	7	7
GAB2	0.006	0.054	-9999	-0.65	3	3
TNFSF11	-0.045	0.32	-9999	-1	35	35
HSP90B1	0.024	0.051	-9999	-0.68	1	1
GAB1	0.006	0.053	-9999	-0.65	3	3
MAPK14	-0.007	0.13	-9999	-0.63	10	10
AKT1	0.04	0.032	-9999	-10000	0	0
FOXO1	0.042	0.045	-9999	-10000	0	0
MAP2K6	-0.013	0.13	-9999	-0.47	20	20
mol:GTP	0	0.002	-9999	-10000	0	0
MAP2K4	0.007	0.14	-9999	-0.53	12	12
MITF	-0.004	0.12	-9999	-0.42	17	17
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.01	0	-9999	-10000	0	0
A2M	-0.013	0.2	-9999	-1.4	9	9
CEBPB	0.013	0.036	-9999	-0.51	2	2
GRB2/SOS1/GAB family/SHP2	0.014	0.064	-9999	-0.39	3	3
STAT3	-0.012	0.2	-9999	-0.72	16	16
STAT1	-0.002	0.013	-9999	-10000	0	0
CEBPD	0.002	0.18	-9999	-0.69	11	11
PIK3CA	0.01	0.018	-9999	-0.37	1	1
PI3K	0.016	0.013	-9999	-10000	0	0
JUN	0.009	0.018	-9999	-0.37	1	1
PIAS3/MITF	0.002	0.11	-9999	-0.44	13	13
MAPK11	-0.007	0.13	-9999	-0.63	10	10
STAT3 (dimer)/FOXO1	0.026	0.18	-9999	-0.64	12	12
GRB2/SOS1/GAB family	-0.029	0.091	-9999	-0.48	8	8
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.007	0.12	-9999	-0.45	16	16
GRB2	0.011	0.002	-9999	-10000	0	0
JAK2	0.004	0.056	-9999	-0.47	6	6
LBP	-0.033	0.24	-9999	-0.9	20	20
PIK3R1	0.011	0	-9999	-10000	0	0
JAK1	0.011	0.004	-9999	-10000	0	0
MYC	0.001	0.19	-9999	-0.79	9	9
FGG	-0.037	0.26	-9999	-0.94	24	24
macrophage differentiation	-0.008	0.2	-9999	-0.69	16	16
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.045	0.12	-9999	-0.38	40	40
JUNB	0.003	0.18	-9999	-0.67	10	10
FOS	-0.015	0.12	-9999	-0.58	19	19
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.006	0.12	-9999	-0.44	14	14
STAT1/PIAS1	0	0.11	-9999	-0.45	9	9
GRB2/SOS1/GAB family/SHP2/PI3K	0.03	0.035	-9999	-10000	0	0
STAT3 (dimer)	-0.012	0.2	-9999	-0.72	16	16
PRKCD	0.013	0.16	-9999	-0.6	9	9
IL6R	0.002	0.071	-9999	-0.51	8	8
SOCS3	-0.008	0.16	-9999	-0.96	7	7
gp130 (dimer)/JAK1/JAK1/LMO4	0.024	0.031	-9999	-0.4	1	1
Rac1/GTP	-0.001	0.13	-9999	-0.53	11	11
HCK	-0.002	0.086	-9999	-0.65	8	8
MAPKKK cascade	0.025	0.066	-9999	-0.55	3	3
bone resorption	-0.038	0.29	-9999	-0.96	35	35
IRF1	0.003	0.18	-9999	-0.76	7	7
mol:GDP	-0.006	0.12	-9999	-0.46	16	16
SOS1	0.01	0.004	-9999	-10000	0	0
VAV1	-0.006	0.13	-9999	-0.47	16	16
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.006	0.12	-9999	-0.54	11	11
PTPN11	-0.002	0.012	-9999	-10000	0	0
IL6/IL6RA	-0.048	0.16	-9999	-0.4	62	62
gp130 (dimer)/TYK2/TYK2/LMO4	0.02	0.029	-9999	-0.4	1	1
gp130 (dimer)/JAK2/JAK2/LMO4	0.016	0.045	-9999	-0.4	3	3
IL6	-0.07	0.2	-9999	-0.51	73	73
PIAS3	0.01	0	-9999	-10000	0	0
PTPRE	0.005	0.028	-9999	-0.38	2	2
PIAS1	0.01	0	-9999	-10000	0	0
RAC1	0.01	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.013	0.1	-9999	-0.31	38	38
LMO4	0.009	0.041	-9999	-0.47	3	3
STAT3 (dimer)/PIAS3	-0.067	0.16	-9999	-0.7	14	14
MCL1	0.044	0.029	-9999	-10000	0	0

×

Signaling events mediated by PRL

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
CCNE1	-0.022	0.12	-10000	0	-0.44	32	32
mol:Halofuginone	0.003	0.009	-10000	0	-10000	0	0
ITGA1	0.002	0.069	-10000	0	-0.53	7	7
CDKN1A	0.022	0.024	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	0.01	0.045	-10000	0	-0.48	3	3
mol:Ca2+	-0.11	0.2	-10000	0	-0.43	121	121
AGT	-0.15	0.27	-10000	0	-0.58	121	121
CCNA2	0.02	0.063	-10000	0	-10000	0	0
TUBA1B	0.01	0	-10000	0	-10000	0	0
EGR1	0.009	0.06	-10000	0	-0.36	10	10
CDK2/Cyclin E1	0.013	0.066	-10000	0	-0.33	9	9
MAPK3	0.012	0.046	-10000	0	-0.37	6	6
PRL-2 /Rab GGTase beta	0.015	0	-10000	0	-10000	0	0
MAPK1	0.012	0.046	-10000	0	-0.37	6	6
PTP4A1	0.019	0.053	-10000	0	-10000	0	0
PTP4A3	0.003	0.062	-10000	0	-0.51	6	6
PTP4A2	0.01	0	-10000	0	-10000	0	0
ITGB1	0.012	0.046	-10000	0	-0.48	3	3
SRC	0.009	0.031	-10000	0	-0.65	1	1
RAC1	0.018	0.043	-10000	0	-0.41	3	3
Rab GGTase beta/Rab GGTase alpha	0.015	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.022	0.052	-10000	0	-10000	0	0
RABGGTA	0.01	0	-10000	0	-10000	0	0
BCAR1	0.004	0.036	0.41	3	-10000	0	3
RHOC	0.018	0.043	-10000	0	-0.41	3	3
RHOA	0.018	0.043	-10000	0	-0.41	3	3
cell motility	0.021	0.045	-10000	0	-0.41	3	3
PRL-1/alpha Tubulin	0.023	0.05	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.004	0.072	-10000	0	-0.55	6	6
ROCK1	0.021	0.045	-10000	0	-0.42	3	3
RABGGTB	0.01	0	-10000	0	-10000	0	0
CDK2	0.009	0.031	-10000	0	-0.65	1	1
mitosis	0.019	0.053	-10000	0	-10000	0	0
ATF5	0.007	0.031	-10000	0	-0.37	3	3

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.014	0.11	-9999	-0.33	40	40
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.009	0.018	-9999	-0.37	1	1
STAT1 (dimer)/Cbp/p300	0.013	0.1	-9999	-0.56	2	2
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.011	0.05	-9999	-0.6	2	2
antigen processing and presentation of peptide antigen via MHC class I	-0.032	0.067	-9999	-0.41	3	3
CaM/Ca2+	-0.036	0.092	-9999	-0.37	6	6
RAP1A	0.01	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.007	0.1	-9999	-0.49	2	2
AKT1	0.003	0.097	-9999	-0.57	1	1
MAP2K1	0	0.1	-9999	-0.41	4	4
MAP3K11	-0.007	0.1	-9999	-0.42	4	4
IFNGR1	0.005	0.039	-9999	-0.53	2	2
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.076	0.16	-9999	-0.52	38	38
Rap1/GTP	-0.028	0.071	-9999	-0.42	2	2
CRKL/C3G	0.014	0.012	-9999	-0.25	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.041	0.1	-9999	-0.34	44	44
CEBPB	0.013	0.13	-9999	-0.48	17	17
STAT3	0.01	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.014	0.14	-9999	-1.1	3	3
STAT1	-0.007	0.1	-9999	-0.49	2	2
CALM1	0.01	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.07	0.2	-9999	-0.52	69	69
PIK3CA	0.009	0.018	-9999	-0.37	1	1
STAT1 (dimer)/PIAS1	0	0.1	-9999	-0.6	1	1
CEBPB/PTGES2/Cbp/p300	-0.025	0.068	-9999	-0.42	4	4
mol:Ca2+	-0.016	0.11	-9999	-0.33	40	40
MAPK3	0.008	0.099	-9999	-0.47	4	4
STAT1 (dimer)	-0.042	0.093	-9999	-0.63	3	3
MAPK1	0.008	0.099	-9999	-0.47	4	4
JAK2	0.001	0.059	-9999	-0.48	6	6
PIK3R1	0.01	0	-9999	-10000	0	0
JAK1	0.007	0.011	-9999	-10000	0	0
CAMK2D	0.007	0.044	-9999	-0.65	2	2
DAPK1	0.011	0.14	-9999	-0.62	17	17
SMAD7	0.014	0.051	-9999	-0.23	1	1
CBL/CRKL/C3G	-0.031	0.086	-9999	-0.5	2	2
PI3K	-0.035	0.089	-9999	-0.62	1	1
IFNG	-0.07	0.2	-9999	-0.52	69	69
apoptosis	0.006	0.1	-9999	-0.44	17	17
CAMK2G	0.01	0	-9999	-10000	0	0
STAT3 (dimer)	0.01	0	-9999	-10000	0	0
CAMK2A	-0.05	0.18	-9999	-0.53	51	51
CAMK2B	-0.078	0.2	-9999	-0.49	80	80
FRAP1	0.004	0.091	-9999	-0.52	1	1
PRKCD	0.004	0.097	-9999	-0.58	1	1
RAP1B	0.008	0.025	-9999	-0.37	2	2
negative regulation of cell growth	-0.032	0.067	-9999	-0.41	3	3
PTPN2	0.01	0	-9999	-10000	0	0
EP300	0.01	0	-9999	-10000	0	0
IRF1	0.022	0.099	-9999	-0.77	2	2
STAT1 (dimer)/PIASy	-0.003	0.1	-9999	-0.61	1	1
SOCS1	-0.004	0.099	-9999	-1.4	2	2
mol:GDP	-0.032	0.082	-9999	-0.48	2	2
CASP1	0.011	0.063	-9999	-0.3	7	7
PTGES2	0.01	0	-9999	-10000	0	0
IRF9	0.029	0.043	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.034	0.087	-9999	-0.6	1	1
RAP1/GDP	-0.028	0.071	-9999	-0.42	2	2
CBL	-0.008	0.1	-9999	-0.4	4	4
MAP3K1	-0.007	0.11	-9999	-0.4	5	5
PIAS1	0.01	0	-9999	-10000	0	0
PIAS4	0.01	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.032	0.067	-9999	-0.41	3	3
PTPN11	-0.014	0.11	-9999	-0.33	40	40
CREBBP	0.01	0	-9999	-10000	0	0
RAPGEF1	0.01	0	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.006	0.053	-9999	-0.65	3	3
ELF1	0.005	0.064	-9999	-0.36	13	13
CCNA2	0.003	0.069	-9999	-0.65	5	5
PIK3CA	0.01	0.018	-9999	-0.37	1	1
JAK3	0.006	0.047	-9999	-0.43	5	5
PIK3R1	0.01	0.001	-9999	-10000	0	0
JAK1	0.011	0.001	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.013	0.15	-9999	-0.62	20	20
SHC1	0.011	0.001	-9999	-10000	0	0
SP1	0.008	0.048	-9999	-0.36	5	5
IL2RA	-0.004	0.15	-9999	-0.77	16	16
IL2RB	-0.006	0.1	-9999	-0.63	12	12
SOS1	0.01	0.001	-9999	-10000	0	0
IL2RG	-0.048	0.18	-9999	-0.61	43	43
G1/S transition of mitotic cell cycle	0.008	0.11	-9999	-0.59	13	13
PTPN11	0.011	0.001	-9999	-10000	0	0
CCND2	0.006	0.11	-9999	-0.88	5	5
LCK	-0.02	0.13	-9999	-0.53	26	26
GRB2	0.01	0.001	-9999	-10000	0	0
IL2	0.001	0.05	-9999	-0.37	8	8
CDK6	-0.006	0.084	-9999	-0.42	17	17
CCND3	0.021	0.13	-9999	-0.56	16	16

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.023	0.067	-10000	0	-0.43	7	7
adherens junction organization	0.005	0.1	-10000	0	-0.4	23	23
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.007	0.094	-10000	0	-0.5	7	7
FMN1	-0.003	0.12	-10000	0	-0.44	24	24
mol:IP3	0.016	0.068	-10000	0	-0.44	7	7
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.005	0.1	-10000	0	-0.4	22	22
CTNNB1	0.01	0.002	-10000	0	-10000	0	0
AKT1	0.02	0.074	-10000	0	-0.47	7	7
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.002	0.12	-10000	0	-0.56	19	19
CTNND1	0.009	0.031	-10000	0	-0.66	1	1
mol:PI-4-5-P2	0.011	0.095	-10000	0	-0.61	7	7
VASP	0.011	0.098	-10000	0	-0.62	7	7
ZYX	0.01	0.099	-10000	0	-0.59	8	8
JUB	0.005	0.098	-10000	0	-0.38	22	22
EGFR(dimer)	-0.012	0.12	-10000	0	-0.48	17	17
E-cadherin/beta catenin-gamma catenin	-0.028	0.11	-10000	0	-0.49	22	22
mol:PI-3-4-5-P3	-0.016	0.071	-10000	0	-0.5	7	7
PIK3CA	0.01	0.018	-10000	0	-0.37	1	1
PI3K	0.014	0.079	-10000	0	-0.51	7	7
FYN	0.008	0.081	-10000	0	-0.36	7	7
mol:Ca2+	0.016	0.067	-10000	0	-0.43	7	7
JUP	-0.013	0.11	-10000	0	-0.51	20	20
PIK3R1	0.01	0.001	-10000	0	-10000	0	0
mol:DAG	0.016	0.068	-10000	0	-0.44	7	7
CDH1	-0.016	0.13	-10000	0	-0.65	18	18
RhoA/GDP	0.007	0.094	-10000	0	-0.5	7	7
establishment of polarity of embryonic epithelium	0.011	0.095	-10000	0	-0.61	7	7
SRC	0.009	0.031	-10000	0	-0.65	1	1
RAC1	0.01	0	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
EGFR	-0.036	0.14	-10000	0	-0.44	46	46
CASR	-0.001	0.09	-10000	0	-0.4	8	8
RhoA/GTP	-0.012	0.054	-10000	0	-0.39	7	7
AKT2	0.02	0.074	-10000	0	-0.47	7	7
actin cable formation	0.002	0.12	-10000	0	-0.42	24	24
apoptosis	0.014	0.064	0.46	7	-10000	0	7
CTNNA1	0.008	0.044	-10000	0	-0.66	2	2
mol:GDP	0.001	0.1	-10000	0	-0.54	7	7
PIP5K1A	0.011	0.098	-10000	0	-0.62	7	7
PLCG1	0.016	0.07	-10000	0	-0.45	7	7
Rac1/GTP	-0.035	0.1	-10000	0	-0.44	17	17
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.005	0.16	-9999	-0.72	14	14
STMN1	0.007	0.082	-9999	-0.54	9	9
Aurora B/RasGAP/Survivin	-0.001	0.11	-9999	-0.73	9	9
Chromosomal passenger complex/Cul3 protein complex	-0.025	0.14	-9999	-0.61	13	13
BIRC5	0	0.086	-9999	-0.69	7	7
DES	-0.15	0.27	-9999	-0.62	102	102
Aurora C/Aurora B/INCENP	-0.002	0.083	-9999	-0.45	13	13
Aurora B/TACC1	-0.002	0.067	-9999	-0.42	11	11
Aurora B/PP2A	-0.001	0.072	-9999	-0.5	9	9
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.008	0.029	-9999	-0.19	10	10
mitotic metaphase/anaphase transition	-0.001	0.002	-9999	-10000	0	0
NDC80	0.004	0.1	-9999	-0.66	10	10
Cul3 protein complex	-0.064	0.15	-9999	-0.43	58	58
KIF2C	-0.009	0.19	-9999	-1.1	11	11
PEBP1	0.01	0.003	-9999	-10000	0	0
KIF20A	-0.002	0.085	-9999	-0.63	8	8
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0	0.071	-9999	-0.5	9	9
SEPT1	0.002	0.061	-9999	-0.44	8	8
SMC2	0.007	0.044	-9999	-0.65	2	2
SMC4	0.006	0.053	-9999	-0.65	3	3
NSUN2/NPM1/Nucleolin	0.006	0.13	-9999	-0.93	9	9
PSMA3	0.01	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.002	-9999	-10000	0	0
H3F3B	0.006	0.06	-9999	-0.39	10	10
AURKB	0	0.097	-9999	-0.68	9	9
AURKC	-0.001	0.077	-9999	-0.53	9	9
CDCA8	-0.001	0.091	-9999	-0.69	8	8
cytokinesis	-0.038	0.19	-9999	-1.3	9	9
Aurora B/Septin1	-0.012	0.17	-9999	-1	11	11
AURKA	-0.001	0.082	-9999	-0.66	7	7
INCENP	0.009	0.033	-9999	-0.69	1	1
KLHL13	-0.083	0.22	-9999	-0.56	75	75
BUB1	-0.005	0.098	-9999	-0.66	10	10
hSgo1/Aurora B/Survivin	-0.006	0.13	-9999	-0.76	11	11
EVI5	0.01	0.001	-9999	-10000	0	0
RhoA/GTP	-0.026	0.18	-9999	-1.2	9	9
SGOL1	0.001	0.075	-9999	-0.65	6	6
CENPA	-0.009	0.22	-9999	-1.2	12	12
NCAPG	0.003	0.069	-9999	-0.65	5	5
Aurora B/HC8 Proteasome	0	0.071	-9999	-0.5	9	9
NCAPD2	0.007	0.044	-9999	-0.65	2	2
Aurora B/PP1-gamma	0	0.071	-9999	-0.5	9	9
RHOA	0.01	0	-9999	-10000	0	0
NCAPH	-0.007	0.11	-9999	-0.65	12	12
NPM1	-0.008	0.095	-9999	-0.68	9	9
RASA1	0.01	0	-9999	-10000	0	0
KLHL9	-0.004	0.097	-9999	-0.65	10	10
mitotic prometaphase	0	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0.071	-9999	-0.5	9	9
PPP1CC	0.01	0	-9999	-10000	0	0
Centraspindlin	-0.032	0.22	-9999	-1.5	9	9
RhoA/GDP	0.007	0	-9999	-10000	0	0
NSUN2	-0.008	0.095	-9999	-0.68	9	9
MYLK	-0.011	0.089	-9999	-0.47	13	13
KIF23	-0.002	0.09	-9999	-0.63	9	9
VIM	0.004	0.084	-9999	-0.5	12	12
RACGAP1	0.007	0.045	-9999	-0.67	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.008	0.095	-9999	-0.68	9	9
Chromosomal passenger complex	-0.003	0.22	-9999	-1.2	11	11
Chromosomal passenger complex/EVI5	0.006	0.15	-9999	-0.91	10	10
TACC1	0.007	0.044	-9999	-0.65	2	2
PPP2R5D	0.009	0.018	-9999	-0.37	1	1
CUL3	0.01	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.007	0.031	-9999	-0.37	3	3
PLK4	-0.003	0.092	-9999	-0.65	9	9
regulation of centriole replication	0.006	0.072	-9999	-0.42	12	12

×

Ceramide signaling pathway

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
SPHK2	0.011	0.05	-10000	0	-0.48	3	3
MAP4K4	0.011	0.078	-10000	0	-0.58	2	2
BAG4	0.008	0.025	-10000	0	-0.37	2	2
PKC zeta/ceramide	-0.015	0.039	0.17	3	-0.18	1	4
NFKBIA	0.009	0.018	-10000	0	-0.37	1	1
BIRC3	-0.032	0.16	-10000	0	-0.59	32	32
BAX	-0.004	0.02	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AKT1	0.017	0.008	-10000	0	-10000	0	0
BAD	-0.014	0.039	0.18	3	-10000	0	3
SMPD1	0.008	0.047	-10000	0	-0.22	14	14
RB1	-0.016	0.046	0.18	3	-0.4	2	5
FADD/Caspase 8	0.015	0.082	-10000	0	-0.44	5	5
MAP2K4	-0.01	0.048	0.18	3	-0.39	3	6
NSMAF	0.01	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.009	0.039	0.18	3	-0.22	1	4
EGF	-0.14	0.24	-10000	0	-0.47	144	144
mol:ceramide	-0.022	0.042	0.19	3	-10000	0	3
MADD	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.011	0.05	-10000	0	-0.48	3	3
ASAH1	0.009	0.018	-10000	0	-0.37	1	1
negative regulation of cell cycle	-0.016	0.046	0.18	3	-0.39	2	5
cell proliferation	-0.038	0.096	-10000	0	-0.3	40	40
BID	0.006	0.054	-10000	0	-0.37	2	2
MAP3K1	-0.014	0.039	0.18	3	-10000	0	3
EIF2A	-0.002	0.035	0.19	1	-10000	0	1
TRADD	0.01	0	-10000	0	-10000	0	0
CRADD	0.01	0	-10000	0	-10000	0	0
MAPK3	0	0.037	0.18	2	-0.2	1	3
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0	0.037	0.18	2	-0.2	1	3
Cathepsin D/ceramide	-0.014	0.038	0.17	3	-10000	0	3
FADD	0.006	0.086	-10000	0	-0.46	5	5
KSR1	-0.015	0.041	0.18	3	-0.21	2	5
MAPK8	-0.006	0.043	0.18	3	-0.24	4	7
PRKRA	-0.014	0.039	0.18	3	-10000	0	3
PDGFA	0.001	0.066	-10000	0	-0.48	8	8
TRAF2	0.01	0	-10000	0	-10000	0	0
IGF1	-0.088	0.21	-10000	0	-0.5	88	88
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.022	0.042	0.19	3	-10000	0	3
CTSD	0.01	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	-0.037	0.1	-10000	0	-0.32	40	40
PRKCD	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.018	-10000	0	-0.37	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.011	0.05	-10000	0	-0.48	3	3
RelA/NF kappa B1	0.015	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.009	0.031	-10000	0	-0.65	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.005	0.082	-10000	0	-0.62	2	2
TNFR1A/BAG4/TNF-alpha	-0.023	0.082	-10000	0	-0.41	14	14
mol:Sphingosine-1-phosphate	0.011	0.05	-10000	0	-0.48	3	3
MAP2K1	-0.003	0.037	0.19	1	-0.2	1	2
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.01	0	-10000	0	-10000	0	0
CYCS	-0.006	0.033	0.16	7	-10000	0	7
TNFRSF1A	0.009	0.018	-10000	0	-0.37	1	1
NFKB1	0.01	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.013	0.021	-10000	0	-10000	0	0
EIF2AK2	-0.008	0.037	0.18	3	-10000	0	3
TNF-alpha/TNFR1A/FAN	-0.022	0.081	-10000	0	-0.41	14	14
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.018	0.047	-10000	0	-0.3	2	2
MAP2K2	-0.003	0.037	0.19	1	-10000	0	1
SMPD3	-0.041	0.14	-10000	0	-0.36	70	70
TNF	-0.028	0.14	-10000	0	-0.48	35	35
PKC zeta/PAR4	0.013	0.026	-10000	0	-0.37	2	2
mol:PHOSPHOCHOLINE	0.035	0.088	0.24	54	-10000	0	54
NF kappa B1/RelA/I kappa B alpha	-0.001	0.019	-10000	0	-0.34	1	1
AIFM1	-0.006	0.032	0.16	7	-10000	0	7
BCL2	0.002	0.069	-10000	0	-0.53	7	7

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.01	0	-9999	-10000	0	0
HDAC4	0.01	0	-9999	-10000	0	0
induction of apoptosis	0	0	-9999	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.007	0.001	-9999	-10000	0	0
CDKN1A	0.002	0.017	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
BAX	0.01	0	-9999	-10000	0	0
FOXO3	0	0	-9999	-10000	0	0
FOXO1	0.004	0.062	-9999	-0.65	4	4
FOXO4	0.017	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
XRCC6	0.01	0	-9999	-10000	0	0
TAT	-0.033	0.15	-9999	-0.52	36	36
mol:Lysophosphatidic acid	0	0	-9999	-10000	0	0
MYOD1	0.006	0.032	-9999	-10000	0	0
PPARGC1A	-0.1	0.24	-9999	-0.58	89	89
FHL2	-0.007	0.11	-9999	-0.65	12	12
response to nutrient levels	0	0	-9999	-10000	0	0
KU70/SIRT1	0	0	-9999	-10000	0	0
HIST2H4A	0.007	0.001	-9999	-10000	0	0
SIRT1/FOXO3a	0	0	-9999	-10000	0	0
SIRT1	0	0.001	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0	-9999	-10000	0	0
SIRT1/Histone H1b	-0.014	0.059	-9999	-0.27	23	23
apoptosis	0	0	-9999	-10000	0	0
SIRT1/PGC1A	-0.071	0.15	-9999	-0.36	89	89
p53/SIRT1	-0.01	0.068	-9999	-0.46	10	10
SIRT1/FOXO4	0	0.003	-9999	-10000	0	0
FOXO1/FHL2/SIRT1	-0.013	0.069	-9999	-0.38	16	16
HIST1H1E	-0.001	0.074	-9999	-0.32	23	23
SIRT1/p300	0	0	-9999	-10000	0	0
muscle cell differentiation	0.003	0.025	-9999	-10000	0	0
TP53	-0.014	0.092	-9999	-0.62	10	10
KU70/SIRT1/BAX	0	0	-9999	-10000	0	0
CREBBP	0.01	0	-9999	-10000	0	0
MEF2D	0.01	0	-9999	-10000	0	0
HIV-1 Tat/SIRT1	-0.029	0.11	-9999	-0.37	36	36
ACSS2	0.014	0.023	-9999	-0.48	1	1
SIRT1/PCAF/MYOD	-0.003	0.025	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.022	0.02	-9999	-0.41	1	1
SNTA1	0.002	0.071	-9999	-0.6	6	6
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.02	0.032	-9999	-0.41	2	2
MAPK12	0.001	0.077	-9999	-0.36	19	19
CCND1	0.002	0.053	-9999	-0.44	4	4
p38 gamma/SNTA1	0.002	0.082	-9999	-0.34	24	24
MAP2K3	0.01	0	-9999	-10000	0	0
PKN1	0.007	0.044	-9999	-0.65	2	2
G2/M transition checkpoint	0.001	0.077	-9999	-0.36	19	19
MAP2K6	-0.005	0.084	-9999	-0.38	21	21
MAPT	-0.015	0.098	-9999	-0.36	28	28
MAPK13	0.016	0.023	-9999	-0.48	1	1
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.005	0.026	-9999	-0.39	2	2

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.008	0.025	-9999	-0.37	2	2
Caspase 8 (4 units)	-0.019	0.058	-9999	-0.39	2	2
NEF	-0.007	0.04	-9999	-0.2	12	12
NFKBIA	0.004	0.033	-9999	-0.37	1	1
BIRC3	-0.01	0.16	-9999	-0.67	25	25
CYCS	0.013	0.077	-9999	-0.42	2	2
RIPK1	0.01	0	-9999	-10000	0	0
CD247	-0.033	0.17	-9999	-0.72	24	24
MAP2K7	0.015	0.073	-9999	-0.44	3	3
protein ubiquitination	0.032	0.056	-9999	-10000	0	0
CRADD	0.01	0	-9999	-10000	0	0
DAXX	0.01	0	-9999	-10000	0	0
FAS	0.004	0.059	-9999	-0.54	5	5
BID	0.008	0.08	-9999	-0.44	2	2
NF-kappa-B/RelA/I kappa B alpha	-0.02	0.073	-9999	-0.31	25	25
TRADD	0.01	0	-9999	-10000	0	0
MAP3K5	0.008	0.036	-9999	-0.51	2	2
CFLAR	0.01	0	-9999	-10000	0	0
FADD	0	0.061	-9999	-0.37	12	12
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.02	0.073	-9999	-0.31	25	25
MAPK8	0.019	0.07	-9999	-0.47	2	2
APAF1	0.009	0.031	-9999	-0.65	1	1
TRAF1	0.007	0.036	-9999	-0.37	4	4
TRAF2	0.01	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.002	0.084	-9999	-0.3	26	26
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.024	0.064	-9999	-0.33	3	3
CHUK	0.033	0.059	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.008	0.044	-9999	-0.34	5	5
TCRz/NEF	-0.047	0.16	-9999	-0.53	36	36
TNF	-0.028	0.14	-9999	-0.48	35	35
FASLG	-0.047	0.22	-9999	-0.63	48	48
NFKB1	0.005	0.028	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.023	0.082	-9999	-0.41	14	14
CASP6	-0.014	0.052	-9999	-0.77	1	1
CASP7	0.013	0.15	-9999	-0.57	25	25
RELA	0.005	0.028	-9999	-10000	0	0
CASP2	0.009	0.031	-9999	-0.65	1	1
CASP3	0.013	0.15	-9999	-0.57	25	25
TNFRSF1A	0.009	0.018	-9999	-0.37	1	1
TNFR1A/BAG4	0.013	0.021	-9999	-10000	0	0
CASP8	0.01	0	-9999	-10000	0	0
CASP9	0.01	0	-9999	-10000	0	0
MAP3K14	0.028	0.063	-9999	-10000	0	0
APAF-1/Caspase 9	-0.037	0.11	-9999	-0.44	26	26
BCL2	0.02	0.076	-9999	-0.39	5	5

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.005	0.12	-9999	-0.53	18	18
KLHL20	-0.019	0.047	-9999	-0.25	5	5
CYFIP2	-0.013	0.12	-9999	-0.6	17	17
Rac1/GDP	0.032	0.074	-9999	-0.39	3	3
ENAH	0.006	0.12	-9999	-0.53	18	18
AP1M1	0.01	0	-9999	-10000	0	0
RAP1B	0.008	0.025	-9999	-0.37	2	2
RAP1A	0.01	0	-9999	-10000	0	0
CTNNB1	0.01	0	-9999	-10000	0	0
CDC42/GTP	-0.011	0.051	-9999	-0.39	2	2
ABI1/Sra1/Nap1	-0.016	0.04	-9999	-0.2	7	7
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.081	-9999	-0.38	22	22
RAPGEF1	0.02	0.097	-9999	-0.44	19	19
CTNND1	0.009	0.031	-9999	-0.65	1	1
regulation of calcium-dependent cell-cell adhesion	-0.022	0.11	-9999	-0.54	18	18
CRK	0.014	0.1	-9999	-0.48	19	19
E-cadherin/gamma catenin/alpha catenin	-0.031	0.12	-9999	-0.5	24	24
alphaE/beta7 Integrin	0.01	0.048	-9999	-0.48	4	4
IQGAP1	0.01	0	-9999	-10000	0	0
NCKAP1	0.009	0.031	-9999	-0.65	1	1
Rap1/GTP/I-afadin	-0.001	0.021	-9999	-0.38	1	1
DLG1	0.009	0.11	-9999	-0.52	18	18
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.037	-9999	-0.27	2	2
MLLT4	0.009	0.031	-9999	-0.65	1	1
ARF6/GTP/NME1/Tiam1	-0.024	0.079	-9999	-0.37	15	15
PI3K	-0.011	0.048	-9999	-0.36	2	2
ARF6	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.02	0.14	-9999	-0.59	22	22
TIAM1	-0.037	0.15	-9999	-0.46	46	46
E-cadherin(dimer)/Ca2+	-0.016	0.076	-9999	-0.37	20	20
AKT1	-0.006	0.027	-9999	-0.2	2	2
PIK3R1	0.01	0	-9999	-10000	0	0
CDH1	-0.016	0.13	-9999	-0.65	18	18
RhoA/GDP	0.032	0.074	-9999	-0.39	3	3
actin cytoskeleton organization	0.013	0.046	-9999	-0.18	5	5
CDC42/GDP	0.032	0.074	-9999	-0.39	3	3
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.004	0.097	-9999	-0.38	24	24
ITGB7	0.003	0.064	-9999	-0.6	5	5
RAC1	0.01	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.007	0.086	-9999	-0.39	20	20
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.015	0.072	-9999	-0.35	20	20
mol:GDP	0.029	0.085	-9999	-0.37	19	19
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	-0.013	0.11	-9999	-0.51	20	20
p120 catenin/RhoA/GDP	-0.014	0.066	-9999	-0.49	2	2
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.015	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
CDC42	0.01	0	-9999	-10000	0	0
CTNNA1	0.007	0.044	-9999	-0.65	2	2
positive regulation of S phase of mitotic cell cycle	0.009	0.044	-9999	-0.18	15	15
NME1	0	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.008	0.12	-9999	-0.53	18	18
regulation of cell-cell adhesion	-0.01	0.045	-9999	-0.34	2	2
WASF2	-0.008	0.021	-9999	-0.12	4	4
Rap1/GTP	-0.013	0.059	-9999	-0.45	2	2
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.029	0.11	-9999	-0.44	27	27
CCND1	0.01	0.054	-9999	-0.22	15	15
VAV2	0.014	0.11	-9999	-0.49	21	21
RAP1/GDP	-0.012	0.06	-9999	-0.44	2	2
adherens junction assembly	0.008	0.11	-9999	-0.51	18	18
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.01	0	-9999	-10000	0	0
PIP5K1C	0.01	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.003	0.12	-9999	-0.68	7	7
E-cadherin/beta catenin	-0.017	0.082	-9999	-0.42	18	18
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.008	0.11	-9999	-0.52	19	19
PIK3CA	0.009	0.018	-9999	-0.37	1	1
Rac1/GTP	-0.029	0.075	-9999	-0.4	6	6
E-cadherin/beta catenin/alpha catenin	-0.018	0.084	-9999	-0.41	20	20
ITGAE	0.01	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.023	0.11	-9999	-0.55	18	18

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.01	0	-10000	0	-10000	0	0
NFATC1	0.009	0.11	-10000	0	-0.33	40	40
NFATC2	0.02	0.043	-10000	0	-0.21	4	4
NFATC3	0.018	0.008	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.054	0.14	-10000	0	-0.52	20	20
Exportin 1/Ran/NUP214	-0.001	0.019	-10000	0	-0.42	1	1
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.068	0.14	-10000	0	-0.49	32	32
BCL2/BAX	0.009	0.051	-10000	0	-0.38	7	7
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.008	0.003	-10000	0	-10000	0	0
BAX	0.01	0	-10000	0	-10000	0	0
MAPK14	0.01	0.002	-10000	0	-10000	0	0
BAD	0.01	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.046	0.13	-10000	0	-0.49	20	20
Calcineurin A alpha-beta B1/BCL2	0.002	0.069	-10000	0	-0.53	7	7
FKBP8	0.01	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.045	0.13	0.48	20	-10000	0	20
KPNB1	0.01	0	-10000	0	-10000	0	0
KPNA2	0.007	0.044	-10000	0	-0.65	2	2
XPO1	0.009	0.031	-10000	0	-0.65	1	1
SFN	-0.073	0.19	-10000	0	-0.45	82	82
MAP3K8	0.009	0.018	-10000	0	-0.37	1	1
NFAT4/CK1 alpha	0	0.005	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.033	0.069	-10000	0	-0.36	9	9
CABIN1	-0.054	0.14	-10000	0	-0.53	20	20
CALM1	0.01	0.002	-10000	0	-10000	0	0
RAN	0.01	0	-10000	0	-10000	0	0
MAP3K1	0.01	0	-10000	0	-10000	0	0
CAMK4	-0.019	0.13	-10000	0	-0.61	21	21
mol:Ca2+	0	0.003	-10000	0	-10000	0	0
MAPK3	0.01	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.009	0.053	-10000	0	-0.44	6	6
YWHAB	0.01	0	-10000	0	-10000	0	0
MAPK8	0.009	0.031	-10000	0	-0.66	1	1
MAPK9	0.008	0.036	-10000	0	-0.51	2	2
YWHAG	0.01	0	-10000	0	-10000	0	0
FKBP1A	0.01	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.025	0.087	-10000	0	-0.37	1	1
PRKCH	0.007	0.044	-10000	0	-0.65	2	2
CABIN1/Cbp/p300	0	0.002	-10000	0	-10000	0	0
CASP3	0.01	0.002	-10000	0	-10000	0	0
PIM1	0.005	0.05	-10000	0	-0.51	4	4
Calcineurin A alpha-beta B1/FKBP12/FK506	0.007	0.001	-10000	0	-10000	0	0
apoptosis	-0.002	0.016	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.012	0.053	-10000	0	-10000	0	0
PRKCB	-0.036	0.16	-10000	0	-0.52	40	40
PRKCE	0.01	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.02	0.021	-10000	0	-0.37	1	1
BAD/BCL-XL	0.015	0	-10000	0	-10000	0	0
PRKCD	0.01	0	-10000	0	-10000	0	0
NUP214	0.01	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.018	-10000	0	-0.37	1	1
PRKCA	-0.002	0.087	-10000	0	-0.65	8	8
PRKCG	-0.17	0.26	-10000	0	-0.52	159	159
PRKCQ	-0.025	0.14	-10000	0	-0.61	26	26
FKBP38/BCL2	0.009	0.051	-10000	0	-0.38	7	7
EP300	0.01	0.002	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	-0.036	0.17	-10000	0	-0.65	32	32
NFATc/JNK1	0.014	0.1	-10000	0	-0.4	3	3
CaM/Ca2+/FKBP38	0.014	0.003	-10000	0	-10000	0	0
FKBP12/FK506	0.007	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.004	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.004	0.085	-10000	0	-0.42	18	18
NFATc/ERK1	0.015	0.1	-10000	0	-0.44	2	2
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.068	0.14	-10000	0	-0.49	32	32
NR4A1	0.028	0.11	-10000	0	-0.65	9	9
GSK3B	0.01	0.002	-10000	0	-10000	0	0
positive T cell selection	0.018	0.008	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.008	0.028	-10000	0	-10000	0	0
RCH1/ KPNB1	0.013	0.033	-10000	0	-0.48	2	2
YWHAQ	0.01	0	-10000	0	-10000	0	0
PRKACA	0.01	0.002	-10000	0	-10000	0	0
AKAP5	0.002	0.071	-10000	0	-0.6	6	6
MEF2D	0.01	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.01	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.015	0.1	-10000	0	-0.44	2	2
CREBBP	0.01	0.002	-10000	0	-10000	0	0
BCL2	0.002	0.069	-10000	0	-0.53	7	7

×

TCGA08_rtk_signaling

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
PDGFRA	0.01	0	-10000	0	-10000	0	0
HRAS	0.01	0	-10000	0	-10000	0	0
EGFR	-0.036	0.14	-10000	0	-0.44	46	46
AKT	0.024	0.032	-10000	0	-0.23	3	3
FOXO3	0.01	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
FOXO1	0.004	0.062	-10000	0	-0.65	4	4
AKT3	0.004	0.05	-10000	0	-0.42	6	6
FOXO4	0.01	0	-10000	0	-10000	0	0
MET	-0.002	0.073	-10000	0	-0.42	13	13
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
PIK3CB	0.01	0	-10000	0	-10000	0	0
NRAS	0.008	0.036	-10000	0	-0.51	2	2
PIK3CG	-0.02	0.13	-10000	0	-0.57	24	24
PIK3R3	0.008	0.036	-10000	0	-0.51	2	2
PIK3R2	0.01	0	-10000	0	-10000	0	0
NF1	0.007	0.044	-10000	0	-0.65	2	2
RAS	-0.001	0.056	0.22	2	-0.21	15	17
ERBB2	-0.023	0.12	-10000	0	-0.42	35	35
proliferation/survival/translation	-0.023	0.033	0.22	2	-10000	0	2
PI3K	0.005	0.058	0.19	2	-0.3	6	8
PIK3R1	0.01	0	-10000	0	-10000	0	0
KRAS	-0.007	0.078	-10000	0	-0.37	20	20
FOXO	0.031	0.022	0.16	2	-10000	0	2
AKT2	0.01	0	-10000	0	-10000	0	0
PTEN	0.006	0.053	-10000	0	-0.65	3	3

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.026	0.074	-9999	-0.32	20	20
TC10/GTP	-0.023	0.067	-9999	-0.31	16	16
Insulin Receptor/Insulin/IRS1/Shp2	-0.003	0.031	-9999	-0.37	3	3
HRAS	0.01	0	-9999	-10000	0	0
APS homodimer	0.009	0.018	-9999	-0.37	1	1
GRB14	-0.087	0.23	-9999	-0.61	71	71
FOXO3	-0.019	0.068	-9999	-0.62	5	5
AKT1	-0.035	0.14	-9999	-0.54	8	8
INSR	0.01	0.031	-9999	-0.65	1	1
Insulin Receptor/Insulin	0.027	0.016	-9999	-0.32	1	1
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.006	0.053	-9999	-0.65	3	3
SORBS1	-0.045	0.16	-9999	-0.46	54	54
CRK	0.01	0	-9999	-10000	0	0
PTPN1	0.026	0.016	-9999	-0.32	1	1
CAV1	0.007	0.053	-9999	-0.35	3	3
CBL/APS/CAP/Crk-II/C3G	-0.025	0.075	-9999	-0.34	16	16
Insulin Receptor/Insulin/IRS1/NCK2	-0.003	0.031	-9999	-0.37	3	3
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.028	-9999	-0.32	3	3
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.027	0.033	-9999	-0.56	1	1
RPS6KB1	-0.026	0.13	-9999	-0.49	8	8
PARD6A	-0.013	0.12	-9999	-0.65	16	16
CBL	0.01	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	-0.009	0.09	-9999	-0.86	5	5
PIK3R1	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.057	0.11	-9999	-0.49	8	8
HRAS/GTP	-0.01	0.05	-9999	-10000	0	0
Insulin Receptor	0.01	0.031	-9999	-0.65	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.003	0.029	-9999	-0.34	3	3
PRKCI	-0.017	0.033	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.07	0.14	-9999	-0.33	92	92
SHC1	0.01	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	-0.008	0.077	-9999	-0.74	5	5
PI3K	-0.003	0.028	-9999	-0.33	3	3
NCK2	0.01	0	-9999	-10000	0	0
RHOQ	0.01	0	-9999	-10000	0	0
mol:H2O2	0	0.002	-9999	-10000	0	0
HRAS/GDP	0.007	0	-9999	-10000	0	0
AKT2	-0.035	0.14	-9999	-0.54	8	8
PRKCZ	-0.017	0.033	-9999	-10000	0	0
SH2B2	0.009	0.018	-9999	-0.37	1	1
SHC/SHIP	0.013	0.064	-9999	-0.33	14	14
F2RL2	-0.045	0.18	-9999	-0.63	39	39
TRIP10	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.001	0.017	-9999	-0.36	1	1
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.001	0.015	-9999	-0.32	1	1
RAPGEF1	0.01	0	-9999	-10000	0	0
RASA1	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.028	0.081	-9999	-0.37	16	16
TC10/GDP	0.007	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.003	0.035	-9999	-0.37	4	4
INPP5D	0.008	0.067	-9999	-0.36	14	14
SOS1	0.01	0	-9999	-10000	0	0
SGK1	-0.017	0.097	-9999	-0.92	5	5
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.01	0	-9999	-10000	0	0
IRS1	0.006	0.047	-9999	-0.56	3	3
p62DOK/RasGAP	-0.008	0.078	-9999	-0.75	5	5
INS	0.002	0.002	-9999	-10000	0	0
mol:PI-3-4-P2	0.008	0.066	-9999	-0.35	14	14
GRB2	0.01	0	-9999	-10000	0	0
EIF4EBP1	-0.027	0.14	-9999	-0.49	10	10
PTPRA	0.011	0.002	-9999	-10000	0	0
PIK3CA	0.009	0.018	-9999	-0.37	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	-0.041	0.17	-9999	-0.63	36	36
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.024	0.025	-9999	-0.28	3	3
Insulin Receptor/Insulin/IRS1	-0.003	0.032	-9999	-0.38	3	3
Insulin Receptor/Insulin/IRS3	-0.001	0.023	-9999	-0.49	1	1
Par3/Par6	-0.041	0.12	-9999	-0.36	50	50

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.018	0.097	-9999	-0.58	11	11
PDGFB-D/PDGFRB/SLAP	-0.002	0.1	-9999	-0.54	14	14
PDGFB-D/PDGFRB/APS/CBL	-0.004	0.055	-9999	-0.41	8	8
AKT1	0.037	0.049	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.006	0.11	-9999	-0.62	11	11
PIK3CA	0.009	0.018	-9999	-0.37	1	1
FGR	-0.017	0.12	-9999	-0.63	14	14
mol:Ca2+	0.005	0.1	-9999	-0.7	8	8
MYC	0.018	0.098	-9999	-0.59	8	8
SHC1	0.01	0	-9999	-10000	0	0
HRAS/GDP	0.022	0.048	-9999	-0.34	8	8
LRP1/PDGFRB/PDGFB	-0.006	0.062	-9999	-0.41	10	10
GRB10	0.006	0.053	-9999	-0.65	3	3
PTPN11	0.01	0	-9999	-10000	0	0
GO:0007205	0.005	0.1	-9999	-0.72	8	8
PTEN	0.006	0.053	-9999	-0.65	3	3
GRB2	0.01	0	-9999	-10000	0	0
GRB7	-0.023	0.12	-9999	-0.43	34	34
PDGFB-D/PDGFRB/SHP2	0.006	0.066	-9999	-0.48	8	8
PDGFB-D/PDGFRB/GRB10	0.003	0.081	-9999	-0.52	10	10
cell cycle arrest	-0.002	0.1	-9999	-0.54	14	14
HRAS	0.01	0	-9999	-10000	0	0
HIF1A	0.041	0.045	-9999	-10000	0	0
GAB1	0	0.11	-9999	-0.68	9	9
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.005	0.1	-9999	-0.62	9	9
PDGFB-D/PDGFRB	0	0.058	-9999	-0.43	8	8
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.006	0.066	-9999	-0.48	8	8
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.017	0.098	-9999	-0.58	11	11
positive regulation of MAPKKK cascade	0.006	0.065	-9999	-0.48	8	8
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	0.005	0.1	-9999	-0.73	8	8
E5	0	0.001	-9999	-10000	0	0
CSK	0.01	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.017	0.11	-9999	-0.34	42	42
SHB	0.01	0	-9999	-10000	0	0
BLK	-0.1	0.23	-9999	-0.6	73	73
PTPN2	0.01	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.006	0.066	-9999	-0.48	8	8
BCAR1	0.01	0	-9999	-10000	0	0
VAV2	0.003	0.12	-9999	-0.71	10	10
CBL	0.01	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.003	0.097	-9999	-0.48	17	17
LCK	-0.025	0.13	-9999	-0.56	21	21
PDGFRB	-0.001	0.088	-9999	-0.66	8	8
ACP1	0.01	0	-9999	-10000	0	0
HCK	-0.013	0.14	-9999	-0.79	11	11
ABL1	-0.002	0.11	-9999	-0.57	11	11
PDGFB-D/PDGFRB/CBL	-0.003	0.12	-9999	-0.71	10	10
PTPN1	0.01	0.002	-9999	-10000	0	0
SNX15	0.01	0	-9999	-10000	0	0
STAT3	0.01	0	-9999	-10000	0	0
STAT1	0.01	0	-9999	-10000	0	0
cell proliferation	0.019	0.089	-9999	-0.51	9	9
SLA	-0.002	0.085	-9999	-0.59	9	9
actin cytoskeleton reorganization	0.033	0.047	-9999	-0.32	7	7
SRC	-0.005	0.065	-9999	-0.46	8	8
PI3K	-0.007	0.046	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.022	0.087	-9999	-0.41	15	15
SH2B2	0.009	0.018	-9999	-0.37	1	1
PLCgamma1/SPHK1	0.005	0.12	-9999	-0.65	11	11
LYN	-0.008	0.075	-9999	-0.47	11	11
LRP1	0.006	0.047	-9999	-0.56	3	3
SOS1	0.01	0	-9999	-10000	0	0
STAT5B	0.01	0	-9999	-10000	0	0
STAT5A	0.004	0.062	-9999	-0.65	4	4
NCK1-2/p130 Cas	0.001	0.047	-9999	-0.33	8	8
SPHK1	-0.002	0.081	-9999	-0.5	11	11
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.005	0.1	-9999	-0.73	8	8
PLCG1	0.004	0.11	-9999	-0.76	8	8
NHERF/PDGFRB	-0.004	0.055	-9999	-0.41	8	8
YES1	-0.006	0.07	-9999	-0.48	9	9
cell migration	-0.004	0.054	-9999	-0.41	8	8
SHC/Grb2/SOS1	0.001	0.047	-9999	-0.33	8	8
SLC9A3R2	0.01	0	-9999	-10000	0	0
SLC9A3R1	0.01	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.016	0.061	-9999	-0.37	11	11
FYN	-0.005	0.078	-9999	-0.55	7	7
DOK1	0.014	0.072	-9999	-0.41	12	12
HRAS/GTP	0.007	0	-9999	-10000	0	0
PDGFB	0.01	0	-9999	-10000	0	0
RAC1	0.012	0.11	-9999	-0.61	11	11
PRKCD	0.019	0.053	-9999	-0.38	8	8
FER	0.014	0.068	-9999	-0.38	13	13
MAPKKK cascade	-0.006	0.043	-9999	-0.32	8	8
RASA1	0.019	0.053	-9999	-0.38	8	8
NCK1	0.01	0	-9999	-10000	0	0
NCK2	0.01	0	-9999	-10000	0	0
p62DOK/Csk	0.019	0.066	-9999	-0.37	12	12
PDGFB-D/PDGFRB/SHB	0.006	0.066	-9999	-0.48	8	8
chemotaxis	-0.001	0.1	-9999	-0.55	11	11
STAT1-3-5/STAT1-3-5	-0.008	0.051	-9999	-0.32	10	10
Bovine Papilomavirus E5/PDGFRB	-0.001	0.066	-9999	-0.5	8	8
PTPRJ	-0.003	0.09	-9999	-0.6	10	10

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.01	0	-9999	-10000	0	0
ITGB7	0.003	0.064	-9999	-0.6	5	5
ITGA4	-0.002	0.087	-9999	-0.65	8	8
alpha4/beta7 Integrin	0.001	0.08	-9999	-0.48	12	12
alpha4/beta1 Integrin	0.006	0.065	-9999	-0.48	8	8

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.016	0.036	-9999	-0.26	7	7
BIRC5	0	0.081	-9999	-0.65	7	7
NFKBIA	0.018	0.037	-9999	-0.26	7	7
CPEB1	-0.061	0.19	-9999	-0.53	60	60
AKT1	0.019	0.035	-9999	-0.26	7	7
NDEL1	0.01	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.005	0.045	-9999	-0.3	9	9
NDEL1/TACC3	-0.005	0.047	-9999	-0.49	3	3
GADD45A	0.009	0.018	-9999	-0.37	1	1
GSK3B	0.01	0.006	-9999	-10000	0	0
PAK1/Aurora A	0.015	0.041	-9999	-0.27	8	8
MDM2	0.003	0.05	-9999	-0.37	8	8
JUB	0	0	-9999	-10000	0	0
TPX2	0.009	0.066	-9999	-0.48	8	8
TP53	0.011	0.056	-9999	-0.32	10	10
DLG7	0.011	0.035	-9999	-0.26	7	7
AURKAIP1	0.01	0	-9999	-10000	0	0
ARHGEF7	0.009	0.018	-9999	-0.37	1	1
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.019	0.052	-9999	-0.52	3	3
G2/M transition of mitotic cell cycle	-0.005	0.045	-9999	-0.3	9	9
AURKA	0.014	0.042	-9999	-0.31	7	7
AURKB	-0.013	0.087	-9999	-0.52	11	11
CDC25B	0.015	0.043	-9999	-0.3	7	7
G2/M transition checkpoint	-0.003	0.03	-9999	-0.24	7	7
mRNA polyadenylation	-0.041	0.11	-9999	-0.37	40	40
Aurora A/CPEB	-0.041	0.11	-9999	-0.37	40	40
Aurora A/TACC1/TRAP/chTOG	0.025	0.043	-9999	-0.48	2	2
BRCA1	0.006	0.053	-9999	-0.65	3	3
centrosome duplication	0.015	0.041	-9999	-0.27	8	8
regulation of centrosome cycle	-0.005	0.046	-9999	-0.49	3	3
spindle assembly	-0.004	0.04	-9999	-0.47	2	2
TDRD7	0.01	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.01	0.073	-9999	-0.49	9	9
CENPA	0.001	0.091	-9999	-0.5	12	12
Aurora A/PP2A	0.016	0.036	-9999	-0.31	1	1
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.019	0.039	-9999	-0.23	7	7
negative regulation of DNA binding	0.011	0.056	-9999	-0.32	10	10
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.013	0.026	-9999	-0.48	1	1
RASA1	0.01	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.003	0.03	-9999	-0.24	7	7
mitotic prometaphase	0.001	0.009	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.042	-9999	-0.31	7	7
TACC1	0.007	0.044	-9999	-0.65	2	2
TACC3	0.006	0.053	-9999	-0.65	3	3
Aurora A/Antizyme1	0.021	0.031	-9999	-0.28	1	1
Aurora A/RasGAP	0.016	0.035	-9999	-0.26	7	7
OAZ1	0.01	0	-9999	-10000	0	0
RAN	0.01	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.01	0.006	-9999	-10000	0	0
GIT1	0.009	0.031	-9999	-0.65	1	1
GIT1/beta-PIX/PAK1	-0.003	0.03	-9999	-0.41	2	2
Importin alpha/Importin beta/TPX2	0.009	0.065	-9999	-0.48	8	8
PPP2R5D	0.009	0.018	-9999	-0.37	1	1
Aurora A/TPX2	0.016	0.074	-9999	-0.49	9	9
PAK1	0.008	0.036	-9999	-0.51	2	2
CKAP5	0.01	0	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.012	0.14	-10000	0	-1.2	6	6
regulation of axonogenesis	-0.015	0.038	0.26	6	-10000	0	6
myoblast fusion	-0.005	0.054	0.4	6	-10000	0	6
mol:GTP	-0.005	0.028	-10000	0	-0.23	6	6
regulation of calcium-dependent cell-cell adhesion	0.011	0.092	0.34	23	-10000	0	23
ARF1/GTP	-0.003	0.019	-10000	0	-10000	0	0
mol:GM1	0.004	0.022	-10000	0	-0.18	5	5
mol:Choline	0.012	0.052	-10000	0	-0.39	6	6
lamellipodium assembly	-0.003	0.061	-10000	0	-0.43	6	6
MAPK3	0.014	0.042	-10000	0	-0.34	6	6
ARF6/GTP/NME1/Tiam1	-0.011	0.093	-10000	0	-0.34	23	23
ARF1	0.01	0	-10000	0	-10000	0	0
ARF6/GDP	0.005	0.054	-10000	0	-0.41	6	6
ARF1/GDP	0.017	0.052	-10000	0	-0.37	6	6
ARF6	0.007	0.016	-10000	0	-10000	0	0
RAB11A	0.01	0	-10000	0	-10000	0	0
TIAM1	-0.036	0.15	-10000	0	-0.46	46	46
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.014	0.042	-10000	0	-0.34	6	6
actin filament bundle formation	0.008	0.046	0.37	6	-10000	0	6
KALRN	-0.012	0.081	-10000	0	-0.35	23	23
RAB11FIP3/RAB11A	0.015	0	-10000	0	-10000	0	0
RhoA/GDP	-0.009	0.046	-10000	0	-0.37	6	6
NME1	0.001	0.004	-10000	0	-10000	0	0
Rac1/GDP	-0.009	0.046	-10000	0	-0.37	6	6
substrate adhesion-dependent cell spreading	-0.005	0.028	-10000	0	-0.23	6	6
cortical actin cytoskeleton organization	-0.003	0.061	-10000	0	-0.44	6	6
RAC1	0.01	0	-10000	0	-10000	0	0
liver development	-0.005	0.028	-10000	0	-0.23	6	6
ARF6/GTP	-0.005	0.028	-10000	0	-0.23	6	6
RhoA/GTP	-0.003	0.019	-10000	0	-10000	0	0
mol:GDP	-0.003	0.057	-10000	0	-0.41	6	6
ARF6/GTP/RAB11FIP3/RAB11A	-0.002	0.016	-10000	0	-10000	0	0
RHOA	0.01	0	-10000	0	-10000	0	0
PLD1	0.006	0.058	-10000	0	-0.39	8	8
RAB11FIP3	0.01	0	-10000	0	-10000	0	0
tube morphogenesis	-0.003	0.061	-10000	0	-0.43	6	6
ruffle organization	0.015	0.038	-10000	0	-0.26	6	6
regulation of epithelial cell migration	-0.005	0.028	-10000	0	-0.23	6	6
PLD2	0.012	0.026	-10000	0	-0.27	1	1
PIP5K1A	0.015	0.039	-10000	0	-0.26	6	6
mol:Phosphatidic acid	0.012	0.052	-10000	0	-0.39	6	6
Rac1/GTP	-0.003	0.061	-10000	0	-0.44	6	6

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.017	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.025	0	-10000	0	-10000	0	0
CDKN1B	0.014	0.053	-10000	0	-0.51	2	2
CDKN1A	0.015	0.051	-10000	0	-0.69	1	1
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.008	0.036	-10000	0	-0.51	2	2
FOXO3	0.015	0.051	-10000	0	-0.69	1	1
AKT1	-0.012	0.048	-10000	0	-0.73	1	1
BAD	0.01	0	-10000	0	-10000	0	0
AKT3	-0.019	0.1	-10000	0	-0.38	34	34
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.015	0.051	-10000	0	-0.69	1	1
AKT1/ASK1	0.013	0.053	-10000	0	-0.42	3	3
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.008	0.036	-10000	0	-0.51	2	2
RAF1	0.01	0	-10000	0	-10000	0	0
JNK cascade	0.011	0.045	0.41	3	-10000	0	3
TSC1	0.015	0.051	-10000	0	-0.69	1	1
YWHAZ	0.01	0	-10000	0	-10000	0	0
AKT1/RAF1	0.015	0.051	-10000	0	-0.69	1	1
EP300	0.01	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.053	-10000	0	-0.72	1	1
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.015	0.051	-10000	0	-0.69	1	1
YWHAQ	0.01	0	-10000	0	-10000	0	0
TBC1D4	-0.015	0.1	-10000	0	-0.34	39	39
MAP3K5	0.008	0.036	-10000	0	-0.51	2	2
MAPKAP1	0.01	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.016	0.04	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
AKT1S1	0.015	0.051	-10000	0	-0.69	1	1
CASP9	0.015	0.051	-10000	0	-0.69	1	1
YWHAB	0.01	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.019	0.051	-10000	0	-0.48	2	2
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	-0.033	0.11	-10000	0	-0.41	35	35
YWHAE	0.01	0	-10000	0	-10000	0	0
SRC	0.009	0.031	-10000	0	-0.65	1	1
AKT2/p21CIP1	-0.022	0.077	-10000	0	-0.66	1	1
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.01	0.015	-10000	0	-10000	0	0
CHUK	0.015	0.051	-10000	0	-0.69	1	1
BAD/BCL-XL	0.025	0.048	-10000	0	-0.64	1	1
mTORC2	-0.001	0.02	-10000	0	-0.38	1	1
AKT2	-0.017	0.1	-10000	0	-0.38	33	33
FOXO1-3a-4/14-3-3 family	0.018	0.056	-10000	0	-0.33	2	2
PDPK1	-0.041	0.17	-10000	0	-0.63	36	36
MDM2	0.012	0.057	-10000	0	-0.42	3	3
MAPKKK cascade	-0.015	0.05	0.67	1	-10000	0	1
MDM2/Cbp/p300	0.022	0.053	-10000	0	-0.62	1	1
TSC1/TSC2	0.02	0.049	-10000	0	-0.66	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.051	-10000	0	-0.59	1	1
glucose import	-0.041	0.13	-10000	0	-0.34	58	58
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.015	0.032	-10000	0	-0.38	1	1
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.041	0.13	-10000	0	-0.34	58	58
GSK3A	0.014	0.053	-10000	0	-0.51	2	2
FOXO1	0.012	0.06	-10000	0	-0.4	5	5
GSK3B	0.015	0.051	-10000	0	-0.69	1	1
SFN	-0.073	0.19	-10000	0	-0.45	82	82
G1/S transition of mitotic cell cycle	0.019	0.052	-10000	0	-0.49	2	2
p27Kip1/14-3-3 family	0.012	0.058	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
KPNA1	0.01	0	-10000	0	-10000	0	0
HSP90AA1	0.009	0.031	-10000	0	-0.65	1	1
YWHAG	0.01	0	-10000	0	-10000	0	0
RHEB	0.01	0	-10000	0	-10000	0	0
CREBBP	0.01	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.002	0.061	-10000	0	-0.44	8	8
positive regulation of NF-kappaB transcription factor activity	-0.021	0.095	-10000	0	-0.49	16	16
MAP2K4	0.027	0.042	-10000	0	-0.32	3	3
IKBKB	0.01	0	-10000	0	-10000	0	0
TNFRSF10B	0.007	0.044	-10000	0	-0.65	2	2
TNFRSF10A	0.006	0.047	-10000	0	-0.56	3	3
SMPD1	0.011	0.027	-10000	0	-10000	0	0
IKBKG	0.004	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.012	0.12	-10000	0	-0.62	16	16
TRAIL/TRAILR2	0.007	0.055	-10000	0	-0.48	4	4
TRAIL/TRAILR3	-0.019	0.11	-10000	0	-0.48	18	18
TRAIL/TRAILR1	0.006	0.056	-10000	0	-0.34	11	11
TRAIL/TRAILR4	-0.007	0.099	-10000	0	-0.5	16	16
TRAIL/TRAILR1/DAP3/GTP	-0.006	0.041	-10000	0	-0.38	4	4
IKK complex	-0.004	0.02	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.007	0	-10000	0	-10000	0	0
MAPK3	0.012	0.045	-10000	0	-0.31	8	8
MAP3K1	0.025	0.033	-10000	0	-0.28	2	2
TRAILR4 (trimer)	-0.012	0.12	-10000	0	-0.62	16	16
TRADD	0.01	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.006	0.047	-10000	0	-0.56	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.021	0.037	-10000	0	-0.28	4	4
CFLAR	0.01	0	-10000	0	-10000	0	0
MAPK1	0.012	0.045	-10000	0	-0.31	8	8
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.01	0.047	-10000	0	-0.34	6	6
mol:ceramide	0.011	0.027	-10000	0	-10000	0	0
FADD	0	0.061	-10000	0	-0.37	12	12
MAPK8	0.031	0.044	-10000	0	-0.31	4	4
TRAF2	0.01	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.028	0.14	-10000	0	-0.5	34	34
CHUK	0.01	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.012	0.058	-10000	0	-0.41	6	6
DAP3	0.01	0	-10000	0	-10000	0	0
CASP10	-0.01	0.096	0.27	12	-0.43	14	26
JNK cascade	-0.021	0.095	-10000	0	-0.49	16	16
TRAIL (trimer)	0.002	0.061	-10000	0	-0.44	8	8
TNFRSF10C	-0.028	0.14	-10000	0	-0.5	34	34
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.01	0.048	-10000	0	-0.35	6	6
TRAIL/TRAILR2/FADD	-0.011	0.057	-10000	0	-0.41	6	6
cell death	0.011	0.027	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.022	0.037	-10000	0	-0.28	4	4
TRAILR2 (trimer)	0.007	0.044	-10000	0	-0.65	2	2
CASP8	0.001	0.012	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.009	0.047	-10000	0	-0.34	6	6

×

Rapid glucocorticoid 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
Gs family/GDP/Gbeta gamma	-0.018	0.074	-10000	0	-0.38	15	15
MAPK9	0.005	0.02	-10000	0	-0.27	2	2
adrenocorticotropin secretion	-0.008	0.048	-10000	0	-0.26	16	16
GNB1/GNG2	-0.002	0.029	-10000	0	-0.42	2	2
GNB1	0.01	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.017	0.073	-10000	0	-0.29	27	27
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	0.004	0.019	0.076	27	-10000	0	27
GNAL	-0.021	0.13	-10000	0	-0.52	27	27
GNG2	0.006	0.047	-10000	0	-0.56	3	3
CRH	-0.011	0.069	-10000	0	-0.37	16	16
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.018	-10000	0	-0.39	1	1
MAPK11	0.007	0	-10000	0	-10000	0	0

×

EPO signaling pathway

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
BCL2L1	0.036	0.077	-10000	0	-0.81	1	1
CRKL	0.01	0.075	-10000	0	-0.56	3	3
mol:DAG	0.016	0.079	-10000	0	-0.55	4	4
HRAS	0.027	0.07	-10000	0	-0.42	5	5
MAPK8	-0.003	0.085	-10000	0	-0.52	5	5
RAP1A	0.01	0.074	-10000	0	-0.56	3	3
GAB1	0.008	0.081	-10000	0	-0.49	6	6
MAPK14	-0.002	0.084	-10000	0	-0.55	4	4
EPO	-0.041	0.13	-10000	0	-0.37	61	61
PLCG1	0.016	0.082	-10000	0	-0.57	4	4
EPOR/TRPC2/IP3 Receptors	0.007	0.043	-10000	0	-0.49	3	3
RAPGEF1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.012	0.088	-10000	0	-0.46	6	6
GAB1/SHC/GRB2/SOS1	-0.019	0.059	-10000	0	-0.45	5	5
EPO/EPOR (dimer)	-0.02	0.096	-10000	0	-0.45	3	3
IRS2	-0.013	0.11	-10000	0	-0.38	27	27
STAT1	0.022	0.085	-10000	0	-0.79	2	2
STAT5B	0.019	0.083	-10000	0	-0.57	4	4
cell proliferation	0.004	0.08	-10000	0	-0.48	5	5
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.025	0.076	-10000	0	-0.48	7	7
TEC	0.009	0.078	-10000	0	-0.49	5	5
SOCS3	0.003	0.064	-10000	0	-0.6	5	5
STAT1 (dimer)	0.022	0.082	-10000	0	-0.75	2	2
JAK2	0.003	0.057	-10000	0	-0.47	6	6
PIK3R1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.013	0.08	-10000	0	-0.52	4	4
EPO/EPOR	-0.02	0.096	-10000	0	-0.45	3	3
LYN	0.006	0.062	-10000	0	-0.65	4	4
TEC/VAV2	0.014	0.079	-10000	0	-0.51	4	4
elevation of cytosolic calcium ion concentration	0.007	0.043	-10000	0	-0.49	3	3
SHC1	0.01	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.006	0.095	-10000	0	-0.61	4	4
mol:IP3	0.016	0.079	-10000	0	-0.55	4	4
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.011	0.12	-10000	0	-0.5	11	11
SH2B3	0.006	0.046	-10000	0	-0.68	2	2
NFKB1	-0.002	0.084	-10000	0	-0.55	4	4
EPO/EPOR (dimer)/JAK2/SOCS3	-0.017	0.05	0.28	1	-0.3	6	7
PTPN6	0.004	0.077	-10000	0	-0.52	4	4
TEC/VAV2/GRB2	0.018	0.077	-10000	0	-0.49	4	4
EPOR	0.007	0.043	-10000	0	-0.5	3	3
INPP5D	-0.008	0.11	-10000	0	-0.59	14	14
mol:GDP	-0.019	0.06	-10000	0	-0.46	5	5
SOS1	0.01	0	-10000	0	-10000	0	0
PLCG2	-0.003	0.085	-10000	0	-0.52	11	11
CRKL/CBL/C3G	0.02	0.071	-10000	0	-0.52	3	3
VAV2	0.009	0.077	-10000	0	-0.46	5	5
CBL	0.01	0.074	-10000	0	-0.56	3	3
SHC/Grb2/SOS1	-0.018	0.056	-10000	0	-0.52	3	3
STAT5A	0.015	0.095	-10000	0	-0.52	8	8
GRB2	0.01	0	-10000	0	-10000	0	0
STAT5 (dimer)	0.028	0.096	-10000	0	-0.75	3	3
LYN/PLCgamma2	0.002	0.077	-10000	0	-0.48	10	10
PTPN11	0.01	0	-10000	0	-10000	0	0
BTK	-0.005	0.11	-10000	0	-0.54	7	7
BCL2	0.029	0.11	-10000	0	-0.89	5	5

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.004	0.038	0.32	6	-10000	0	6
BUB1B	0.003	0.096	-10000	0	-0.58	11	11
PLK1	0.008	0.035	-10000	0	-0.22	10	10
PLK1S1	0.008	0.024	-10000	0	-0.16	6	6
KIF2A	0.014	0.032	-10000	0	-0.23	6	6
regulation of mitotic centrosome separation	0.008	0.035	-10000	0	-0.22	10	10
GOLGA2	0.01	0	-10000	0	-10000	0	0
Hec1/SPC24	0.01	0.083	-10000	0	-0.46	11	11
WEE1	0.013	0.041	-10000	0	-0.3	7	7
cytokinesis	0.008	0.12	-10000	0	-0.84	8	8
PP2A-alpha B56	-0.02	0.14	-10000	0	-0.92	10	10
AURKA	0.005	0.049	-10000	0	-0.38	7	7
PICH/PLK1	0.009	0.11	-10000	0	-0.55	15	15
CENPE	0.004	0.077	-10000	0	-0.38	16	16
RhoA/GTP	0.007	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.014	0.031	-10000	0	-0.23	6	6
PPP2CA	0	0	-10000	0	-10000	0	0
FZR1	0.01	0	-10000	0	-10000	0	0
TPX2	0.004	0.053	-10000	0	-0.39	8	8
PAK1	0.007	0.036	-10000	0	-0.51	2	2
SPC24	0.002	0.071	-10000	0	-0.6	6	6
FBXW11	0.01	0	-10000	0	-10000	0	0
CLSPN	0.004	0.062	-10000	0	-0.44	8	8
GORASP1	0.01	0	-10000	0	-10000	0	0
metaphase	0	0.004	-10000	0	-0.026	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.005	0.016	-10000	0	-0.098	10	10
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.014	7	7
STAG2	0.01	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.001	0.006	-10000	0	-10000	0	0
spindle elongation	0.008	0.035	-10000	0	-0.22	10	10
ODF2	0.009	0.001	-10000	0	-10000	0	0
BUB1	-0.022	0.15	-10000	0	-1	10	10
TPT1	0.009	0.016	-10000	0	-0.12	5	5
CDC25C	0.003	0.073	-10000	0	-0.58	7	7
CDC25B	0.009	0.032	-10000	0	-0.68	1	1
SGOL1	0.004	0.038	-10000	0	-0.32	6	6
RHOA	0.01	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.01	0.078	-10000	0	-0.62	7	7
CDC14B	0.003	0.053	-10000	0	-0.5	5	5
CDC20	-0.004	0.097	-10000	0	-0.65	10	10
PLK1/PBIP1	-0.009	0.057	-10000	0	-0.35	11	11
mitosis	0	0.004	0.032	7	-10000	0	7
FBXO5	0.011	0.045	-10000	0	-0.3	7	7
CDC2	0.001	0.003	-10000	0	-0.022	7	7
NDC80	0.002	0.071	-10000	0	-0.6	6	6
metaphase plate congression	0.009	0.022	-10000	0	-0.16	5	5
ERCC6L	-0.019	0.11	-10000	0	-0.57	15	15
NLP/gamma Tubulin	0.008	0.017	-10000	0	-0.11	9	9
microtubule cytoskeleton organization	0.009	0.016	-10000	0	-0.11	5	5
G2/M transition DNA damage checkpoint	0	0.001	0.011	1	-10000	0	1
PPP1R12A	0.01	0.001	-10000	0	-10000	0	0
interphase	0	0.001	0.011	1	-10000	0	1
PLK1/PRC1-2	0.007	0.11	-10000	0	-0.74	9	9
GRASP65/GM130/RAB1/GTP/PLK1	-0.003	0.024	-10000	0	-10000	0	0
RAB1A	0.01	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.007	0.028	-10000	0	-0.17	10	10
mitotic prometaphase	0	0.002	-10000	0	-0.015	8	8
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.041	-10000	0	-0.28	2	2
microtubule-based process	0.007	0.074	-10000	0	-0.48	9	9
Golgi organization	0.008	0.035	-10000	0	-0.22	10	10
Cohesin/SA2	-0.004	0.03	-10000	0	-0.22	8	8
PPP1CB/MYPT1	0	0.002	-10000	0	-10000	0	0
KIF20A	-0.001	0.083	-10000	0	-0.62	8	8
APC/C/CDC20	0.005	0.082	-10000	0	-0.53	10	10
PPP2R1A	0.01	0	-10000	0	-10000	0	0
chromosome segregation	-0.009	0.056	-10000	0	-0.34	11	11
PRC1	-0.002	0.087	-10000	0	-0.65	8	8
ECT2	0.007	0.07	-10000	0	-0.39	12	12
C13orf34	0.007	0.028	-10000	0	-0.18	10	10
NUDC	0.009	0.022	-10000	0	-0.16	5	5
regulation of attachment of spindle microtubules to kinetochore	0.004	0.094	-10000	0	-0.57	11	11
spindle assembly	0.009	0.026	-10000	0	-0.16	10	10
spindle stabilization	0.008	0.024	-10000	0	-0.16	6	6
APC/C/HCDH1	0.009	0.045	-10000	0	-0.42	5	5
MKLP2/PLK1	0.007	0.075	-10000	0	-0.49	9	9
CCNB1	0	0.083	-10000	0	-0.67	7	7
PPP1CB	0.01	0.001	-10000	0	-10000	0	0
BTRC	0.01	0	-10000	0	-10000	0	0
ROCK2	0.013	0.039	-10000	0	-0.46	2	2
TUBG1	0.009	0.016	-10000	0	-0.12	5	5
G2/M transition of mitotic cell cycle	-0.01	0.075	-10000	0	-0.6	7	7
MLF1IP	0.002	0.058	-10000	0	-0.5	6	6
INCENP	0.008	0.031	-10000	0	-0.66	1	1

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.011	0.008	-10000	0	-10000	0	0
PDGF/PDGFRA/CRKL	-0.001	0.012	-10000	0	-0.26	1	1
positive regulation of JUN kinase activity	0	0	-10000	0	-10000	0	0
CRKL	0.009	0.018	-10000	0	-0.37	1	1
PDGF/PDGFRA/Caveolin-3	0.001	0.025	-10000	0	-0.26	4	4
AP1	-0.016	0.19	-10000	0	-0.98	15	15
mol:IP3	0.02	0.014	-10000	0	-10000	0	0
PLCG1	0.02	0.014	-10000	0	-10000	0	0
PDGF/PDGFRA/alphaV Integrin	-0.002	0.026	-10000	0	-0.37	2	2
RAPGEF1	0.01	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0.02	0.014	-10000	0	-10000	0	0
CAV3	0.001	0.035	-10000	0	-0.37	4	4
CAV1	-0.012	0.089	-10000	0	-0.37	26	26
SHC/Grb2/SOS1	0	0.002	-10000	0	-10000	0	0
PDGF/PDGFRA/Shf	-0.007	0.046	-10000	0	-0.3	10	10
FOS	0.012	0.19	-10000	0	-0.96	15	15
JUN	0.026	0.11	0.41	32	-0.3	1	33
oligodendrocyte development	-0.002	0.026	-10000	0	-0.37	2	2
GRB2	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.01	0	-10000	0	-10000	0	0
mol:DAG	0.02	0.014	-10000	0	-10000	0	0
PDGF/PDGFRA	0.011	0.008	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0	0.001	-10000	0	-10000	0	0
SRF	-0.018	0.12	-10000	0	-0.47	32	32
SHC1	0.01	0	-10000	0	-10000	0	0
PI3K	0	0.01	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk/C3G	0	0.001	-10000	0	-10000	0	0
JAK1	0.019	0.006	-10000	0	-10000	0	0
ELK1/SRF	0.007	0.082	-10000	0	-0.29	32	32
SHB	0.01	0	-10000	0	-10000	0	0
SHF	0	0.066	-10000	0	-0.43	10	10
CSNK2A1	-0.042	0.16	-10000	0	-0.63	32	32
GO:0007205	0.021	0.016	-10000	0	-10000	0	0
SOS1	0.01	0	-10000	0	-10000	0	0
Ras protein signal transduction	0	0	-10000	0	-10000	0	0
PDGF/PDGFRA/SHB	0	0.001	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-1	-0.015	0.06	-10000	0	-0.26	26	26
ITGAV	0.008	0.036	-10000	0	-0.51	2	2
ELK1	0.026	0.023	-10000	0	-10000	0	0
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
PDGF/PDGFRA/Crk	0	0.001	-10000	0	-10000	0	0
JAK-STAT cascade	0.019	0.006	-10000	0	-10000	0	0
cell proliferation	-0.007	0.046	-10000	0	-0.3	10	10

×

p38 MAPK signaling pathway

Figure S111. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S111. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.009	0.019	-9999	-0.27	2	2
TRAF2/ASK1	-0.001	0.022	-9999	-0.42	1	1
ATM	0.004	0.062	-9999	-0.65	4	4
MAP2K3	0.016	0.05	-9999	-0.41	4	4
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.013	0.069	-9999	-0.35	8	8
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.001	0.073	-9999	-0.45	11	11
TXN	0.006	0.007	-9999	-0.14	1	1
CALM1	0.01	0	-9999	-10000	0	0
GADD45A	0.009	0.018	-9999	-0.37	1	1
GADD45B	0.007	0.031	-9999	-0.37	3	3
MAP3K1	0.01	0	-9999	-10000	0	0
MAP3K6	0.007	0.044	-9999	-0.65	2	2
MAP3K7	0.01	0	-9999	-10000	0	0
MAP3K4	0.01	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.011	0.042	-9999	-0.42	4	4
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0	0	-9999	-10000	0	0
TRAF2	0.01	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.006	0.032	-9999	-0.31	4	4
TRAF6	0.007	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.078	0.2	-9999	-0.49	80	80
CCM2	0.01	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.052	0.12	-9999	-0.3	80	80
MAPK11	0.01	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.047	0.11	-9999	-0.38	35	35
OSM/MEKK3	0.015	0	-9999	-10000	0	0
TAOK1	0.01	0.037	-9999	-0.38	4	4
TAOK2	0.01	0.037	-9999	-0.38	4	4
TAOK3	0.01	0.037	-9999	-0.38	4	4
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.01	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.008	0.036	-9999	-0.51	2	2
MAP3K10	0.009	0.031	-9999	-0.65	1	1
MAP3K3	0.01	0	-9999	-10000	0	0
TRX/ASK1	0.011	0.023	-9999	-0.31	2	2
GADD45/MTK1/MTK1	-0.007	0.038	-9999	-0.35	3	3

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.013	0.026	-10000	0	-0.37	2	2
ATM	0.004	0.062	-10000	0	-0.65	4	4
UBE2D3	0.01	0	-10000	0	-10000	0	0
PRKDC	0.008	0.036	-10000	0	-0.51	2	2
ATR	0.009	0.031	-10000	0	-0.65	1	1
UBE2L3	0.01	0	-10000	0	-10000	0	0
FANCD2	0.011	0.077	-10000	0	-0.51	7	7
protein ubiquitination	-0.021	0.091	-10000	0	-0.44	13	13
XRCC5	0.01	0	-10000	0	-10000	0	0
XRCC6	0.01	0	-10000	0	-10000	0	0
M/R/N Complex	-0.003	0.033	-10000	0	-0.41	3	3
MRE11A	0.006	0.053	-10000	0	-0.65	3	3
DNA-PK	-0.001	0.021	-10000	0	-0.41	1	1
FA complex/FANCD2/Ubiquitin	-0.006	0.053	-10000	0	-0.68	2	2
FANCF	0.006	0.053	-10000	0	-0.65	3	3
BRCA1	0.006	0.053	-10000	0	-0.65	3	3
CCNE1	-0.022	0.12	-10000	0	-0.44	32	32
CDK2/Cyclin E1	-0.009	0.089	-10000	0	-0.31	33	33
FANCG	0.009	0.018	-10000	0	-0.37	1	1
BRCA1/BACH1/BARD1	0.01	0.054	-10000	0	-0.52	4	4
FANCE	0.009	0.018	-10000	0	-0.37	1	1
FANCC	0.01	0	-10000	0	-10000	0	0
NBN	0.01	0	-10000	0	-10000	0	0
FANCA	0.007	0.044	-10000	0	-0.65	2	2
DNA repair	0.041	0.09	-10000	0	-0.95	3	3
BRCA1/BARD1/ubiquitin	0.01	0.054	-10000	0	-0.52	4	4
BARD1/DNA-PK	-0.002	0.038	-10000	0	-0.55	2	2
FANCL	0.01	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.002	0.025	0.48	1	-10000	0	1
BRCA1/BARD1/CTIP/M/R/N Complex	0.022	0.078	-10000	0	-0.61	6	6
BRCA1/BACH1/BARD1/TopBP1	-0.005	0.056	-10000	0	-0.66	3	3
BRCA1/BARD1/P53	-0.012	0.077	-10000	0	-0.42	13	13
BARD1/CSTF1/BRCA1	-0.004	0.046	-10000	0	-0.53	3	3
BRCA1/BACH1	0.006	0.053	-10000	0	-0.65	3	3
BARD1	0.008	0.036	-10000	0	-0.51	2	2
PCNA	0.007	0.044	-10000	0	-0.65	2	2
BRCA1/BARD1/UbcH5C	-0.004	0.046	-10000	0	-0.53	3	3
BRCA1/BARD1/UbcH7	-0.004	0.046	-10000	0	-0.53	3	3
BRCA1/BARD1/RAD51/PCNA	-0.008	0.087	-10000	0	-0.71	5	5
BARD1/DNA-PK/P53	-0.009	0.062	-10000	0	-0.39	11	11
BRCA1/BARD1/Ubiquitin	0.01	0.054	-10000	0	-0.52	4	4
BRCA1/BARD1/CTIP	0.017	0.073	-10000	0	-0.54	6	6
FA complex	0.027	0.037	-10000	0	-0.4	2	2
BARD1/EWS	0.013	0.026	-10000	0	-0.48	1	1
RBBP8	0.011	0.053	-10000	0	-0.48	5	5
TP53	-0.004	0.093	-10000	0	-0.62	10	10
TOPBP1	0.009	0.031	-10000	0	-0.65	1	1
G1/S transition of mitotic cell cycle	0.012	0.076	0.42	13	-10000	0	13
BRCA1/BARD1	-0.021	0.093	-10000	0	-0.44	13	13
CSTF1	0.01	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.006	0.026	-10000	0	-0.37	2	2
CDK2	0.009	0.031	-10000	0	-0.65	1	1
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.004	0.062	-10000	0	-0.65	4	4
RAD50	0.01	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.01	0.054	-10000	0	-0.52	4	4
EWSR1	0.01	0	-10000	0	-10000	0	0

×

Circadian rhythm 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
chromatin modification	0.026	0.11	-10000	0	-1.3	3	3
CLOCK	0.012	0.005	-10000	0	-10000	0	0
TIMELESS/CRY2	0.022	0.11	-10000	0	-1.3	3	3
DEC1/BMAL1	0	0.061	-10000	0	-0.26	23	23
ATR	0.009	0.031	-10000	0	-0.65	1	1
NR1D1	0.024	0.076	-10000	0	-1.4	1	1
ARNTL	0.011	0.031	-10000	0	-0.65	1	1
TIMELESS	0.02	0.12	-10000	0	-1.4	3	3
NPAS2	-0.001	0.092	-10000	0	-0.65	9	9
CRY2	0.009	0.018	-10000	0	-0.37	1	1
mol:CO	-0.009	0.015	0.14	4	-10000	0	4
CHEK1	0.009	0.031	-10000	0	-0.65	1	1
mol:HEME	0.009	0.015	-10000	0	-0.14	4	4
PER1	0.005	0.056	-10000	0	-0.58	4	4
BMAL/CLOCK/NPAS2	0.022	0.065	-10000	0	-0.4	10	10
BMAL1/CLOCK	0.026	0.076	-10000	0	-0.6	5	5
S phase of mitotic cell cycle	0.026	0.11	-10000	0	-1.3	3	3
TIMELESS/CHEK1/ATR	0.026	0.12	-10000	0	-1.4	3	3
mol:NADPH	0.009	0.015	-10000	0	-0.14	4	4
PER1/TIMELESS	0.019	0.11	-10000	0	-1.3	3	3
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.012	0.081	-10000	0	-0.37	22	22

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.009	0.031	-9999	-0.65	1	1
Aurora C/Aurora B/INCENP	-0.014	0.076	-9999	-0.43	13	13
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.005	0.035	-9999	-0.6	1	1
AURKB	-0.003	0.092	-9999	-0.65	9	9
AURKC	-0.001	0.077	-9999	-0.53	9	9

×

FoxO family signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.018	0.067	-9999	-0.55	1	1
PLK1	0.045	0.22	-9999	-1.5	8	8
CDKN1B	0.092	0.077	-9999	-0.39	4	4
FOXO3	0.053	0.17	-9999	-0.96	8	8
KAT2B	0.017	0.012	-9999	-10000	0	0
FOXO1/SIRT1	0	0.045	-9999	-0.31	4	4
CAT	0.052	0.17	-9999	-0.92	10	10
CTNNB1	0.01	0	-9999	-10000	0	0
AKT1	0.018	0.014	-9999	-10000	0	0
FOXO1	0.022	0.051	-9999	-0.34	5	5
MAPK10	0.007	0.08	-9999	-0.35	16	16
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.068	0.049	-9999	-0.42	1	1
response to oxidative stress	0.008	0.015	-9999	-10000	0	0
FOXO3A/SIRT1	-0.01	0.13	-9999	-0.86	8	8
XPO1	0.009	0.031	-9999	-0.65	1	1
EP300	0.011	0.004	-9999	-10000	0	0
BCL2L11	0.026	0.025	-9999	-10000	0	0
FOXO1/SKP2	0.022	0.061	-9999	-0.38	6	6
mol:GDP	0.008	0.015	-9999	-10000	0	0
RAN	0.011	0.001	-9999	-10000	0	0
GADD45A	0.081	0.061	-9999	-10000	0	0
YWHAQ	0.01	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.038	0.049	-9999	-10000	0	0
MST1	0.005	0.073	-9999	-0.4	13	13
CSNK1D	0.01	0	-9999	-10000	0	0
CSNK1E	0.01	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.018	0.077	-9999	-0.31	1	1
YWHAB	0.01	0	-9999	-10000	0	0
MAPK8	0.03	0.02	-9999	-0.36	1	1
MAPK9	0.029	0.021	-9999	-0.34	1	1
YWHAG	0.01	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
YWHAZ	0.01	0	-9999	-10000	0	0
SIRT1	0.006	0.016	-9999	-10000	0	0
SOD2	0.096	0.089	-9999	-0.5	3	3
RBL2	0.069	0.1	-9999	-0.56	4	4
RAL/GDP	0.023	0.01	-9999	-10000	0	0
CHUK	0.017	0.012	-9999	-10000	0	0
Ran/GTP	0.011	0.001	-9999	-10000	0	0
CSNK1G2	0.01	0	-9999	-10000	0	0
RAL/GTP	0.029	0.01	-9999	-10000	0	0
CSNK1G1	0.01	0	-9999	-10000	0	0
FASLG	-0.052	0.33	-9999	-1.5	23	23
SKP2	0.005	0.05	-9999	-0.51	4	4
USP7	0.011	0	-9999	-10000	0	0
IKBKB	0.017	0.012	-9999	-10000	0	0
CCNB1	0.046	0.22	-9999	-1.4	8	8
FOXO1-3a-4/beta catenin	0.099	0.093	-9999	-0.41	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.06	-9999	-0.38	6	6
CSNK1A1	0.01	0	-9999	-10000	0	0
SGK1	0.001	0.09	-9999	-0.46	15	15
CSNK1G3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.018	0.02	-9999	-0.41	1	1
ZFAND5	0.07	0.043	-9999	-10000	0	0
SFN	-0.073	0.19	-9999	-0.45	82	82
CDK2	0.008	0.033	-9999	-0.68	1	1
FOXO3A/14-3-3	0.027	0.081	-9999	-0.44	6	6
CREBBP	0.01	0.007	-9999	-10000	0	0
FBXO32	0.044	0.2	-9999	-1	12	12
BCL6	0.066	0.12	-9999	-0.73	4	4
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
YWHAH	0.01	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.009	0.018	-10000	0	-0.37	1	1
Rac1/GDP	0.002	0.009	-10000	0	-10000	0	0
DOCK1	0.01	0	-10000	0	-10000	0	0
ITGA4	-0.002	0.087	-10000	0	-0.65	8	8
RAC1	0.01	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.001	0.08	-10000	0	-0.48	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.01	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.007	0.054	-10000	0	-0.41	8	8
alpha4/beta7 Integrin/Paxillin	0.011	0.077	-10000	0	-0.39	15	15
lamellipodium assembly	0.001	0.009	-10000	0	-10000	0	0
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
PI3K	0.014	0.012	-10000	0	-10000	0	0
ARF6	0.01	0	-10000	0	-10000	0	0
TLN1	0.01	0	-10000	0	-10000	0	0
PXN	0.012	0.048	-10000	0	-0.44	5	5
PIK3R1	0.01	0	-10000	0	-10000	0	0
ARF6/GTP	-0.009	0.052	-10000	0	-0.31	13	13
cell adhesion	-0.009	0.055	-10000	0	-0.34	12	12
CRKL/CBL	0.014	0.012	-10000	0	-0.25	1	1
alpha4/beta1 Integrin/Paxillin	0.015	0.064	-10000	0	-0.37	12	12
ITGB1	0.01	0	-10000	0	-10000	0	0
ITGB7	0.003	0.064	-10000	0	-0.6	5	5
ARF6/GDP	0.002	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.009	0.099	-10000	0	-0.43	19	19
p130Cas/Crk/Dock1	0	0	-10000	0	-10000	0	0
VCAM1	-0.011	0.11	-10000	0	-0.58	16	16
alpha4/beta1 Integrin/Paxillin/Talin	0.02	0.06	-10000	0	-0.34	12	12
alpha4/beta1 Integrin/Paxillin/GIT1	0.02	0.063	-10000	0	-0.34	13	13
BCAR1	0.01	0	-10000	0	-10000	0	0
mol:GDP	0.01	0.057	0.34	13	-10000	0	13
CBL	0.01	0	-10000	0	-10000	0	0
PRKACA	0.01	0	-10000	0	-10000	0	0
GIT1	0.009	0.031	-10000	0	-0.65	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.02	0.06	-10000	0	-0.34	12	12
Rac1/GTP	0.001	0.009	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.004	0.069	-9999	-0.48	8	8
AKT1	0.037	0.1	-9999	-0.59	7	7
PTK2B	0.027	0.1	-9999	-0.82	5	5
VEGFR2 homodimer/Frs2	0.017	0.084	-9999	-0.72	5	5
CAV1	-0.012	0.089	-9999	-0.37	26	26
CALM1	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.012	0.079	-9999	-0.63	6	6
endothelial cell proliferation	0.037	0.11	-9999	-0.57	8	8
mol:Ca2+	0.029	0.09	-9999	-0.7	5	5
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.009	0.073	-9999	-0.73	4	4
RP11-342D11.1	0.022	0.089	-9999	-0.54	9	9
CDH5	0.006	0.053	-9999	-0.65	3	3
VEGFA homodimer	-0.003	0.025	-9999	-0.37	1	1
SHC1	0.01	0	-9999	-10000	0	0
SHC2	-0.003	0.087	-9999	-0.57	10	10
HRAS/GDP	-0.011	0.07	-9999	-0.6	5	5
SH2D2A	0.007	0.044	-9999	-0.65	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.012	0.079	-9999	-0.64	6	6
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.011	0.088	-9999	-0.64	7	7
VEGFR1 homodimer	0.007	0.044	-9999	-0.65	2	2
SHC/GRB2/SOS1	-0.012	0.079	-9999	-0.68	5	5
GRB10	0.027	0.11	-9999	-0.81	6	6
PTPN11	0.01	0	-9999	-10000	0	0
GRB2	0.01	0	-9999	-10000	0	0
PAK1	0.008	0.036	-9999	-0.51	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.011	0.086	-9999	-0.86	4	4
HRAS	0.01	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.028	0.068	-9999	-0.5	5	5
HIF1A	0.009	0.018	-9999	-0.37	1	1
FRS2	0.005	0.043	-9999	-0.37	6	6
oxygen and reactive oxygen species metabolic process	-0.009	0.072	-9999	-0.72	4	4
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.007	0.044	-9999	-0.65	2	2
Nck/Pak	0.013	0.026	-9999	-0.37	2	2
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.011	0.079	-9999	-0.63	6	6
mol:GDP	-0.012	0.076	-9999	-0.65	5	5
mol:NADP	0.042	0.079	-9999	-0.6	5	5
eNOS/Hsp90	0.044	0.075	-9999	-0.55	5	5
PIK3R1	0.01	0	-9999	-10000	0	0
mol:IP3	0.029	0.091	-9999	-0.72	5	5
HIF1A/ARNT	0.014	0.012	-9999	-0.25	1	1
SHB	0.01	0	-9999	-10000	0	0
VEGFA	0.007	0.047	-9999	-0.42	5	5
VEGFC	-0.002	0.079	-9999	-0.47	12	12
FAK1/Vinculin	0.04	0.1	-9999	-0.82	5	5
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.01	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.016	0.1	-9999	-0.88	5	5
PTPN6	0.009	0.018	-9999	-0.37	1	1
EPAS1	0.013	0.047	-9999	-0.42	5	5
mol:L-citrulline	0.042	0.079	-9999	-0.6	5	5
ITGAV	0.008	0.036	-9999	-0.51	2	2
PIK3CA	0.009	0.018	-9999	-0.37	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.011	0.075	-9999	-0.73	4	4
VEGFR2 homodimer/VEGFA homodimer	-0.014	0.092	-9999	-0.59	9	9
VEGFR2/3 heterodimer	0.018	0.092	-9999	-0.73	6	6
VEGFB	0.01	0	-9999	-10000	0	0
MAPK11	0.031	0.095	-9999	-0.69	6	6
VEGFR2 homodimer	0.018	0.09	-9999	-0.82	5	5
FLT1	0.007	0.044	-9999	-0.65	2	2
NEDD4	0.006	0.063	-9999	-0.67	4	4
MAPK3	0.023	0.097	-9999	-0.63	7	7
MAPK1	0.023	0.097	-9999	-0.63	7	7
VEGFA145/NRP2	-0.011	0.057	-9999	-0.48	3	3
VEGFR1/2 heterodimer	0.018	0.092	-9999	-0.73	6	6
KDR	0.018	0.09	-9999	-0.82	5	5
VEGFA165/NRP1/VEGFR2 homodimer	0.023	0.098	-9999	-0.7	6	6
SRC	0.009	0.031	-9999	-0.65	1	1
platelet activating factor biosynthetic process	0.025	0.099	-9999	-0.64	7	7
PI3K	0.044	0.099	-9999	-0.7	6	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.01	0.077	-9999	-0.63	6	6
FES	0.028	0.096	-9999	-0.69	6	6
GAB1	-0.014	0.092	-9999	-0.78	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.011	0.079	-9999	-0.63	6	6
CTNNB1	0.01	0	-9999	-10000	0	0
SOS1	0.01	0	-9999	-10000	0	0
ARNT	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.036	0.082	-9999	-0.57	5	5
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.012	0.084	-9999	-0.64	7	7
PI3K/GAB1	0.053	0.09	-9999	-0.62	6	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.012	0.073	-9999	-0.7	4	4
PRKACA	0.01	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.016	0.1	-9999	-0.63	9	9
HSP90AA1	0.009	0.031	-9999	-0.65	1	1
CDC42	0.029	0.092	-9999	-0.73	5	5
actin cytoskeleton reorganization	-0.011	0.087	-9999	-0.63	7	7
PTK2	0.036	0.11	-9999	-0.91	5	5
EDG1	0.022	0.089	-9999	-0.54	9	9
mol:DAG	0.029	0.091	-9999	-0.72	5	5
CaM/Ca2+	-0.012	0.077	-9999	-0.66	5	5
MAP2K3	0.034	0.092	-9999	-0.68	6	6
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.027	0.11	-9999	-0.84	6	6
PLCG1	0.029	0.092	-9999	-0.73	5	5
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.01	0.075	-9999	-0.73	4	4
IQGAP1	0.01	0	-9999	-10000	0	0
YES1	0.006	0.047	-9999	-0.56	3	3
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.01	0.077	-9999	-0.77	4	4
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.01	0.079	-9999	-0.66	6	6
cell migration	0.054	0.095	-9999	-0.65	6	6
mol:PI-3-4-5-P3	0.043	0.09	-9999	-0.63	6	6
FYN	0.009	0.031	-9999	-0.65	1	1
VEGFB/NRP1	0.027	0.085	-9999	-0.67	5	5
mol:NO	0.042	0.079	-9999	-0.6	5	5
PXN	0.003	0.064	-9999	-0.6	5	5
HRAS/GTP	-0.011	0.07	-9999	-0.6	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.027	0.11	-9999	-0.84	6	6
VHL	0.01	0	-9999	-10000	0	0
ITGB3	-0.003	0.087	-9999	-0.57	10	10
NOS3	0.042	0.091	-9999	-0.7	5	5
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.016	0.09	-9999	-0.51	12	12
RAC1	0.01	0	-9999	-10000	0	0
PRKCA	0.028	0.1	-9999	-0.73	5	5
PRKCB	0.01	0.13	-9999	-0.75	7	7
VCL	0.01	0	-9999	-10000	0	0
VEGFA165/NRP1	0.023	0.09	-9999	-0.54	9	9
VEGFR1/2 heterodimer/VEGFA homodimer	-0.011	0.088	-9999	-0.64	7	7
VEGFA165/NRP2	-0.011	0.057	-9999	-0.48	3	3
MAPKKK cascade	0.044	0.092	-9999	-0.67	6	6
NRP2	-0.001	0.071	-9999	-0.42	12	12
VEGFC homodimer	-0.002	0.079	-9999	-0.46	12	12
NCK1	0.01	0	-9999	-10000	0	0
ROCK1	0.009	0.031	-9999	-0.65	1	1
FAK1/Paxillin	0.037	0.11	-9999	-0.76	6	6
MAP3K13	0.028	0.097	-9999	-0.72	6	6
PDPK1	0.023	0.12	-9999	-0.58	7	7

×

Arf6 trafficking events

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
SLC2A4	-0.051	0.17	-10000	0	-0.47	58	58
CLTC	0.019	0.007	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.018	0.02	-10000	0	-10000	0	0
Dynamin 2/GTP	0.013	0	-10000	0	-10000	0	0
EXOC4	0.01	0	-10000	0	-10000	0	0
CD59	0.017	0.01	-10000	0	-10000	0	0
CPE	-0.014	0.096	-10000	0	-0.42	19	19
CTNNB1	0.01	0	-10000	0	-10000	0	0
membrane fusion	0.017	0.022	-10000	0	-10000	0	0
CTNND1	0.018	0.017	-10000	0	-0.36	1	1
DNM2	0.01	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.021	0.011	-10000	0	-10000	0	0
TSHR	-0.014	0.1	-10000	0	-0.42	26	26
INS	0.008	0.004	-10000	0	-10000	0	0
BIN1	-0.001	0.083	-10000	0	-0.62	8	8
mol:Choline	0.017	0.022	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.007	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.01	0	-10000	0	-10000	0	0
mol:Ca2+	0.013	0	-10000	0	-10000	0	0
JUP	0.01	0.04	-10000	0	-0.24	10	10
ASAP2/amphiphysin II	-0.008	0.058	-10000	0	-0.42	8	8
ARF6/GTP	0.007	0	-10000	0	-10000	0	0
CDH1	0.008	0.051	-10000	0	-0.24	18	18
clathrin-independent pinocytosis	0.007	0	-10000	0	-10000	0	0
MAPK8IP3	0.004	0.062	-10000	0	-0.65	4	4
positive regulation of endocytosis	0.007	0	-10000	0	-10000	0	0
EXOC2	0.01	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.032	0.015	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.01	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.007	0.033	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.014	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	-0.004	0.039	-10000	0	-0.42	4	4
ACAP1	0.016	0.022	-10000	0	-0.16	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.028	0.08	-10000	0	-0.24	47	47
clathrin heavy chain/ACAP1	0.023	0.014	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.01	0	-10000	0	-10000	0	0
exocyst	0.032	0.015	-10000	0	-10000	0	0
RALA/GTP	0.007	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0.007	0	-10000	0	-10000	0	0
CTNNA1	0.017	0.025	-10000	0	-0.36	2	2
NME1	0.007	0	-10000	0	-10000	0	0
clathrin coat assembly	0.019	0.007	-10000	0	-10000	0	0
IL2RA	0.01	0.045	-10000	0	-0.24	13	13
VAMP3	0.014	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.026	0.073	-10000	0	-0.31	21	21
EXOC6	0.009	0.031	-10000	0	-0.65	1	1
PLD1	-0.004	0.032	-10000	0	-0.31	5	5
PLD2	0	0.004	-10000	0	-10000	0	0
EXOC5	0.01	0	-10000	0	-10000	0	0
PIP5K1C	0.021	0.011	-10000	0	-10000	0	0
SDC1	0.013	0.033	-10000	0	-0.25	5	5
ARF6/GDP	0.007	0	-10000	0	-10000	0	0
EXOC7	0.01	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.007	0.033	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.017	0.022	-10000	0	-10000	0	0
endocytosis	0.008	0.057	0.42	8	-10000	0	8
SCAMP2	0.01	0	-10000	0	-10000	0	0
ADRB2	-0.011	0.093	-10000	0	-0.33	26	26
EXOC3	0.01	0	-10000	0	-10000	0	0
ASAP2	0.007	0.044	-10000	0	-0.65	2	2
Dynamin 2/GDP	0.013	0	-10000	0	-10000	0	0
KLC1	0.01	0	-10000	0	-10000	0	0
AVPR2	0.011	0.063	-10000	0	-0.33	13	13
RALA	0.01	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.008	0.042	-10000	0	-0.53	1	1

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.012	0.004	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.052	0.038	-9999	-10000	0	0
ERC1	0.009	0.018	-9999	-0.37	1	1
RIP2/NOD2	-0.012	0.095	-9999	-0.48	10	10
NFKBIA	0.034	0.017	-9999	-10000	0	0
BIRC2	0.01	0	-9999	-10000	0	0
IKBKB	0.01	0	-9999	-10000	0	0
RIPK2	0.01	0	-9999	-10000	0	0
IKBKG	-0.008	0.036	-9999	-10000	0	0
IKK complex/A20	-0.021	0.069	-9999	-0.51	3	3
NEMO/A20/RIP2	0.01	0	-9999	-10000	0	0
XPO1	0.009	0.031	-9999	-0.65	1	1
NEMO/ATM	0.023	0.058	-9999	-0.44	4	4
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.01	0	-9999	-10000	0	0
Exportin 1/RanGTP	-0.001	0.019	-9999	-0.42	1	1
IKK complex/ELKS	-0.006	0.029	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.028	0.13	-9999	-0.45	38	38
NFKB1	0.012	0.004	-9999	-10000	0	0
RELA	0.012	0.004	-9999	-10000	0	0
MALT1	0.01	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.015	0	-9999	-10000	0	0
ATM	0.004	0.062	-9999	-0.65	4	4
TNF/TNFR1A	-0.013	0.1	-9999	-0.48	14	14
TRAF6	0.01	0	-9999	-10000	0	0
PRKCA	-0.002	0.087	-9999	-0.65	8	8
CHUK	0.01	0	-9999	-10000	0	0
UBE2D3	0.01	0	-9999	-10000	0	0
TNF	-0.028	0.14	-9999	-0.48	35	35
NF kappa B1 p50/RelA	0	0.008	-9999	-10000	0	0
BCL10	0.01	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.017	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0.004	-9999	-10000	0	0
TNFRSF1A	0.009	0.018	-9999	-0.37	1	1
IKK complex	0.031	0.04	-9999	-10000	0	0
CYLD	0.01	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.011	0.048	-9999	-0.36	1	1

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.004	0.033	-9999	-0.37	3	3
HDAC3	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.014	-9999	-0.31	1	1
GATA1/HDAC4	-0.006	0.095	-9999	-0.42	22	22
GATA1/HDAC5	-0.006	0.095	-9999	-0.42	22	22
GATA2/HDAC5	0.01	0.048	-9999	-0.44	5	5
HDAC5/BCL6/BCoR	-0.001	0.021	-9999	-0.41	1	1
HDAC9	-0.022	0.13	-9999	-0.55	26	26
Glucocorticoid receptor/Hsp90/HDAC6	-0.006	0.05	-9999	-0.41	7	7
HDAC4/ANKRA2	0.015	0	-9999	-10000	0	0
HDAC5/YWHAB	0.015	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
GATA2	0.003	0.064	-9999	-0.6	5	5
HDAC4/RFXANK	0.015	0	-9999	-10000	0	0
BCOR	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.01	0	-9999	-10000	0	0
HDAC5	0.01	0	-9999	-10000	0	0
GNB1/GNG2	0.012	0.035	-9999	-0.4	3	3
Histones	0.019	0.051	-9999	-0.28	1	1
ADRBK1	0.007	0.04	-9999	-0.47	3	3
HDAC4	0.01	0	-9999	-10000	0	0
XPO1	0.009	0.031	-9999	-0.65	1	1
HDAC5/ANKRA2	0.015	0	-9999	-10000	0	0
HDAC4/Ubc9	0.015	0	-9999	-10000	0	0
HDAC7	0.01	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.015	0	-9999	-10000	0	0
TUBA1B	0.01	0	-9999	-10000	0	0
HDAC6	0.01	0	-9999	-10000	0	0
HDAC5/RFXANK	0.015	0	-9999	-10000	0	0
CAMK4	-0.019	0.13	-9999	-0.61	21	21
Tubulin/HDAC6	-0.005	0.044	-9999	-0.41	5	5
SUMO1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.01	0	-9999	-10000	0	0
GATA1	-0.019	0.13	-9999	-0.58	22	22
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.01	0	-9999	-10000	0	0
NR3C1	0.001	0.075	-9999	-0.65	6	6
SUMO1/HDAC4	0.023	0	-9999	-10000	0	0
SRF	0.01	0	-9999	-10000	0	0
HDAC4/YWHAB	0.015	0	-9999	-10000	0	0
Tubulin	0.009	0.053	-9999	-0.48	5	5
HDAC4/14-3-3 E	0.015	0	-9999	-10000	0	0
GNB1	0.01	0	-9999	-10000	0	0
RANGAP1	0.01	0	-9999	-10000	0	0
BCL6/BCoR	0.013	0.026	-9999	-0.48	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.017	0.081	-9999	-0.41	18	18
HDAC4/ER alpha	-0.008	0.098	-9999	-0.4	25	25
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.019	0.051	-9999	-0.27	1	1
cell motility	-0.005	0.043	-9999	-0.41	5	5
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
HDAC7/HDAC3	0.015	0	-9999	-10000	0	0
BCL6	0.008	0.036	-9999	-0.51	2	2
HDAC4/CaMK II delta B	0.01	0	-9999	-10000	0	0
Hsp90/HDAC6	0.014	0.023	-9999	-0.48	1	1
ESR1	-0.021	0.13	-9999	-0.55	25	25
HDAC6/HDAC11	0.014	0.023	-9999	-0.48	1	1
Ran/GTP/Exportin 1	-0.001	0.015	-9999	-0.32	1	1
NPC	0	0	-9999	-10000	0	0
MEF2C	0.005	0.05	-9999	-0.51	4	4
RAN	0.01	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.002	0.025	-9999	-0.34	2	2
GNG2	0.006	0.047	-9999	-0.56	3	3
NCOR2	0.01	0	-9999	-10000	0	0
TUBB2A	0.002	0.071	-9999	-0.6	6	6
HDAC11	0.009	0.031	-9999	-0.65	1	1
HSP90AA1	0.009	0.031	-9999	-0.65	1	1
RANBP2	0.01	0	-9999	-10000	0	0
ANKRA2	0.01	0	-9999	-10000	0	0
RFXANK	0.01	0	-9999	-10000	0	0
nuclear import	-0.022	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.013	0.045	-10000	0	-10000	0	0
CaM/Ca2+	0.007	0	-10000	0	-10000	0	0
AKT1	0.01	0	-10000	0	-10000	0	0
AKT2	0.01	0	-10000	0	-10000	0	0
STXBP4	0.008	0.036	-10000	0	-0.51	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.013	0.068	0.26	5	-10000	0	5
YWHAZ	0.01	0	-10000	0	-10000	0	0
CALM1	0.01	0	-10000	0	-10000	0	0
YWHAQ	0.01	0	-10000	0	-10000	0	0
TBC1D4	0.009	0.062	-10000	0	-0.39	10	10
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.01	0	-10000	0	-10000	0	0
YWHAB	0.01	0	-10000	0	-10000	0	0
SNARE/Synip	-0.001	0.021	-10000	0	-0.41	1	1
YWHAG	0.01	0	-10000	0	-10000	0	0
ASIP	-0.006	0.095	-10000	0	-0.55	13	13
PRKCI	0.01	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.007	0	-10000	0	-10000	0	0
RHOQ	0.01	0	-10000	0	-10000	0	0
GYS1	0.024	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.018	-10000	0	-0.37	1	1
TRIP10	0.01	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.008	0.066	-10000	0	-0.4	1	1
VAMP2	0.01	0	-10000	0	-10000	0	0
SLC2A4	0.012	0.072	0.27	5	-10000	0	5
STX4	0.01	0	-10000	0	-10000	0	0
GSK3B	0.02	0	-10000	0	-10000	0	0
SFN	-0.073	0.19	-10000	0	-0.45	82	82
LNPEP	0.01	0	-10000	0	-10000	0	0
YWHAE	0.01	0	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.004	0.067	-10000	0	-1.4	1	1
oxygen homeostasis	0.005	0.013	-10000	0	-10000	0	0
TCEB2	0.01	0	-10000	0	-10000	0	0
TCEB1	0.01	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.012	0.044	-10000	0	-0.33	1	1
EPO	0.048	0.21	-10000	0	-0.74	7	7
FIH (dimer)	0.016	0.011	-10000	0	-10000	0	0
APEX1	0.015	0.013	-10000	0	-10000	0	0
SERPINE1	0.049	0.24	-10000	0	-0.88	10	10
FLT1	-0.006	0.09	-10000	0	-1.3	2	2
ADORA2A	0.059	0.21	-10000	0	-0.92	8	8
germ cell development	0.057	0.21	-10000	0	-0.71	11	11
SLC11A2	0.07	0.19	-10000	0	-0.79	7	7
BHLHE40	0.07	0.19	-10000	0	-0.79	7	7
HIF1AN	0.016	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.031	0.08	-10000	0	-0.4	6	6
ETS1	0.021	0.008	-10000	0	-10000	0	0
CITED2	-0.003	0.021	-10000	0	-10000	0	0
KDR	-0.011	0.13	-10000	0	-1.3	4	4
PGK1	0.07	0.19	-10000	0	-0.79	7	7
SIRT1	0.01	0.002	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.073	0.22	-10000	0	-0.93	8	8
EPAS1	0.047	0.091	-10000	0	-0.34	5	5
SP1	0.016	0.001	-10000	0	-10000	0	0
ABCG2	0.051	0.23	-10000	0	-0.92	9	9
EFNA1	0.069	0.2	-10000	0	-0.82	7	7
FXN	0.063	0.19	-10000	0	-0.78	7	7
POU5F1	0.057	0.22	-10000	0	-0.86	7	7
neuron apoptosis	-0.072	0.22	0.89	8	-10000	0	8
EP300	0.01	0	-10000	0	-10000	0	0
EGLN3	0.003	0.083	-10000	0	-0.51	11	11
EGLN2	0.016	0.012	-10000	0	-10000	0	0
EGLN1	0.016	0.011	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0	0	-10000	0	-10000	0	0
VHL	0.01	0	-10000	0	-10000	0	0
ARNT	0.015	0.013	-10000	0	-10000	0	0
SLC2A1	0.044	0.22	-10000	0	-0.79	8	8
TWIST1	0.044	0.24	-10000	0	-0.87	11	11
ELK1	0.016	0.002	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.025	0.07	-10000	0	-0.38	3	3
VEGFA	0.068	0.2	-10000	0	-0.82	7	7
CREBBP	0.01	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.018	0.071	-9999	-0.39	14	14
Ran/GTP/Exportin 1/HDAC1	-0.001	0.02	-9999	-0.31	2	2
NF kappa B1 p50/RelA/I kappa B alpha	0.019	0.07	-9999	-0.35	14	14
SUMO1	0.01	0	-9999	-10000	0	0
ZFPM1	0.004	0.059	-9999	-0.54	5	5
NPC/RanGAP1/SUMO1/Ubc9	0.017	0	-9999	-10000	0	0
FKBP3	0.009	0.031	-9999	-0.65	1	1
Histones	0.023	0.043	-9999	-0.32	1	1
YY1/LSF	0.023	0.019	-9999	-0.39	1	1
SMG5	0.01	0	-9999	-10000	0	0
RAN	0.01	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.01	0.063	-9999	-0.3	14	14
I kappa B alpha/HDAC1	0.012	0.049	-9999	-0.37	1	1
SAP18	0.01	0	-9999	-10000	0	0
RELA	0.015	0.056	-9999	-0.27	14	14
HDAC1/Smad7	-0.001	0.021	-9999	-0.41	1	1
RANGAP1	0.01	0	-9999	-10000	0	0
HDAC3/TR2	0.013	0.044	-9999	-10000	0	0
NuRD/MBD3 Complex	0.036	0.01	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.018	0.051	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.003	0.064	-9999	-0.6	5	5
GATA1	-0.019	0.13	-9999	-0.58	22	22
Mad/Max	0.008	0.051	-9999	-0.32	10	10
NuRD/MBD3 Complex/GATA1/Fog1	0.033	0.049	-9999	-10000	0	0
RBBP7	0.01	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.01	0	-9999	-10000	0	0
MAX	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.01	0	-9999	-10000	0	0
NFKBIA	0.008	0.051	-9999	-10000	0	0
KAT2B	0.01	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.033	0.013	-9999	-10000	0	0
SIN3 complex	0	0.008	-9999	-10000	0	0
SMURF1	0.009	0.018	-9999	-0.37	1	1
CHD3	0.01	0	-9999	-10000	0	0
SAP30	0.009	0.018	-9999	-0.37	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.01	0	-9999	-10000	0	0
YY1/HDAC3	0.023	0.041	-9999	-10000	0	0
YY1/HDAC2	0.024	0	-9999	-10000	0	0
YY1/HDAC1	0.023	0.019	-9999	-0.39	1	1
NuRD/MBD2 Complex (MeCP1)	0.036	0.015	-9999	-10000	0	0
PPARG	-0.052	0.12	-9999	-0.35	64	64
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
TNFRSF1A	0.009	0.018	-9999	-0.37	1	1
HDAC3/SMRT (N-CoR2)	0.013	0.044	-9999	-10000	0	0
MBD3L2	0	0.002	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.001	0.021	-9999	-0.41	1	1
CREBBP	0.01	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.039	0.011	-9999	-10000	0	0
HDAC1	0.009	0.031	-9999	-0.65	1	1
HDAC3	0.009	0.05	-9999	-10000	0	0
HDAC2	0.01	0	-9999	-10000	0	0
YY1	0.023	0	-9999	-10000	0	0
HDAC8	0.01	0	-9999	-10000	0	0
SMAD7	0.01	0	-9999	-10000	0	0
NCOR2	0.01	0	-9999	-10000	0	0
MXD1	0	0.071	-9999	-0.46	10	10
STAT3	0.02	0	-9999	-10000	0	0
NFKB1	0.01	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.027	0.025	-9999	-0.36	2	2
YY1/SAP30/HDAC1	0.027	0.02	-9999	-0.36	1	1
EP300	0.01	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.02	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.008	0.05	-9999	-10000	0	0
histone deacetylation	0.036	0.015	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.021	0.041	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.01	0	-9999	-10000	0	0
GATAD2B	0.01	0	-9999	-10000	0	0
GATAD2A	0.01	0	-9999	-10000	0	0
GATA2/HDAC3	0.009	0.059	-9999	-0.39	4	4
GATA1/HDAC1	-0.008	0.098	-9999	-0.42	23	23
GATA1/HDAC3	-0.004	0.09	-9999	-0.4	16	16
CHD4	0.01	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.013	0.1	-9999	-0.48	14	14
SIN3/HDAC complex/Mad/Max	0.033	0.023	-9999	-10000	0	0
NuRD Complex	0.042	0.016	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.009	0.035	-9999	-0.32	1	1
SIN3B	0.01	0	-9999	-10000	0	0
MTA2	0.01	0	-9999	-10000	0	0
SIN3A	0.01	0	-9999	-10000	0	0
XPO1	0.009	0.031	-9999	-0.65	1	1
SUMO1/HDAC1	0.022	0.017	-9999	-0.34	1	1
HDAC complex	-0.001	0.017	-9999	-0.37	1	1
GATA1/Fog1	-0.011	0.1	-9999	-0.41	27	27
FKBP25/HDAC1/HDAC2	-0.002	0.027	-9999	-0.41	2	2
TNF	-0.028	0.14	-9999	-0.48	35	35
negative regulation of cell growth	0.033	0.023	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.036	0.015	-9999	-10000	0	0
Ran/GTP/Exportin 1	-0.001	0.015	-9999	-0.32	1	1
NF kappa B/RelA/I kappa B alpha	0.014	0.073	-9999	-0.37	14	14
SIN3/HDAC complex/NCoR1	0.034	0.011	-9999	-10000	0	0
TFCP2	0.009	0.031	-9999	-0.65	1	1
NR2C1	0.01	0	-9999	-10000	0	0
MBD3	0.01	0	-9999	-10000	0	0
MBD2	0.009	0.031	-9999	-0.65	1	1

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.012	0.035	-9999	-0.4	3	3
FBXW11	0.01	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.02	0.01	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.025	0.053	-9999	-0.55	1	1
NFKBIA	0.009	0.06	-9999	-0.26	18	18
MAPK14	0.01	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.02	0	-9999	-10000	0	0
ARRB2	0.013	0	-9999	-10000	0	0
REL	0.009	0.018	-9999	-0.37	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.018	0.03	-9999	-0.41	2	2
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.02	0	-9999	-10000	0	0
PIK3CA	0.009	0.018	-9999	-0.37	1	1
NF kappa B1 p50 dimer	0.015	0	-9999	-10000	0	0
PIK3R1	0.01	0	-9999	-10000	0	0
NFKB1	0.017	0	-9999	-10000	0	0
RELA	0.01	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.015	0.056	-9999	-0.25	16	16
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.028	0.051	-9999	-0.54	1	1
SRC	0.009	0.031	-9999	-0.65	1	1
PI3K	0.014	0.012	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.015	0.057	-9999	-0.26	16	16
IKBKB	0.01	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
SYK	0.006	0.053	-9999	-0.65	3	3
I kappa B alpha/PIK3R1	0.014	0.056	-9999	-0.43	2	2
cell death	0.026	0.049	-9999	-0.51	1	1
NF kappa B1 p105/c-Rel	0.02	0.01	-9999	-10000	0	0
LCK	-0.021	0.13	-9999	-0.53	26	26
BCL3	0.006	0.047	-9999	-0.56	3	3

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.021	0.054	-9999	-0.78	2	2
VEGFR1 homodimer/NRP1	0.014	0.054	-9999	-0.79	2	2
mol:DAG	0.022	0.061	-9999	-0.54	4	4
VEGFR1 homodimer/NRP1/VEGFR 121	-0.006	0.054	-9999	-0.61	3	3
CaM/Ca2+	0.026	0.058	-9999	-0.51	4	4
HIF1A	0.014	0.031	-9999	-0.36	3	3
GAB1	0.006	0.053	-9999	-0.65	3	3
AKT1	0.011	0.1	-9999	-0.53	4	4
PLCG1	0.022	0.061	-9999	-0.54	4	4
NOS3	0.029	0.069	-9999	-0.62	2	2
CBL	0.01	0	-9999	-10000	0	0
mol:NO	0.029	0.067	-9999	-0.6	2	2
FLT1	0.019	0.061	-9999	-0.88	2	2
PGF	0.001	0.064	-9999	-0.44	9	9
VEGFR1 homodimer/NRP2/VEGFR121	0.017	0.068	-9999	-0.51	5	5
CALM1	0.01	0	-9999	-10000	0	0
PIK3CA	0.009	0.018	-9999	-0.37	1	1
eNOS/Hsp90	0.033	0.07	-9999	-0.59	3	3
endothelial cell proliferation	0.006	0.11	-9999	-0.58	7	7
mol:Ca2+	0.022	0.06	-9999	-0.53	4	4
MAPK3	0.025	0.077	-9999	-0.78	2	2
MAPK1	0.025	0.077	-9999	-0.78	2	2
PIK3R1	0.01	0	-9999	-10000	0	0
PLGF homodimer	0.001	0.064	-9999	-0.43	9	9
PRKACA	0.01	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.012	0.089	-9999	-0.37	26	26
VEGFA homodimer	0.005	0.047	-9999	-0.43	5	5
VEGFR1 homodimer/VEGFA homodimer	0.018	0.061	-9999	-0.66	3	3
platelet activating factor biosynthetic process	0.03	0.074	-9999	-0.75	2	2
PI3K	0.026	0.059	-9999	-0.68	2	2
PRKCA	0.02	0.081	-9999	-0.43	11	11
PRKCB	0.002	0.11	-9999	-0.4	24	24
VEGFR1 homodimer/PLGF homodimer	0.016	0.067	-9999	-0.59	4	4
VEGFA	0.005	0.047	-9999	-0.43	5	5
VEGFB	0.01	0	-9999	-10000	0	0
mol:IP3	0.022	0.061	-9999	-0.54	4	4
RASA1	0.027	0.05	-9999	-0.72	2	2
NRP2	-0.001	0.071	-9999	-0.42	12	12
VEGFR1 homodimer	0.019	0.061	-9999	-0.88	2	2
VEGFB homodimer	0.01	0	-9999	-10000	0	0
NCK1	0.01	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.024	0.077	-9999	-0.54	3	3
PTPN11	0.01	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.007	0.054	-9999	-0.68	2	2
mol:L-citrulline	0.029	0.067	-9999	-0.6	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.029	0.054	-9999	-0.69	2	2
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.023	0.057	-9999	-0.61	3	3
CD2AP	0.01	0	-9999	-10000	0	0
PI3K/GAB1	-0.009	0.057	-9999	-0.65	2	2
PDPK1	0.003	0.11	-9999	-0.56	4	4
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.023	0.057	-9999	-0.61	3	3
mol:NADP	0.029	0.067	-9999	-0.6	2	2
HSP90AA1	0.009	0.031	-9999	-0.65	1	1
ubiquitin-dependent protein catabolic process	-0.005	0.05	-9999	-0.68	2	2
VEGFR1 homodimer/NRP2	0.014	0.069	-9999	-0.59	4	4

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.012	0.086	-10000	0	-0.5	2	2
BAG4	0.008	0.025	-10000	0	-0.37	2	2
BAD	0.016	0.03	-10000	0	-10000	0	0
NFKBIA	0.009	0.018	-10000	0	-0.37	1	1
BIRC3	-0.032	0.16	-10000	0	-0.59	32	32
BAX	0.016	0.03	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.005	0.022	-10000	0	-0.11	2	2
IKBKB	0.017	0.082	-10000	0	-0.46	2	2
MAP2K2	0.024	0.031	-10000	0	-10000	0	0
MAP2K1	0.024	0.031	-10000	0	-10000	0	0
SMPD1	0.009	0.022	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.013	0.092	-10000	0	-0.45	5	5
MAP2K4	0.019	0.039	-10000	0	-0.3	3	3
protein ubiquitination	0.017	0.083	-10000	0	-0.47	2	2
EnzymeConsortium:2.7.1.37	0.027	0.034	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.02	0.032	-10000	0	-10000	0	0
CRADD	0.01	0	-10000	0	-10000	0	0
mol:ceramide	0.01	0.031	-10000	0	-0.16	2	2
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0.01	-10000	0	-0.21	1	1
MADD	0.01	0	-10000	0	-10000	0	0
MAP3K1	0.016	0.03	-10000	0	-10000	0	0
TRADD	0.01	0	-10000	0	-10000	0	0
RELA/p50	0.01	0	-10000	0	-10000	0	0
MAPK3	0.026	0.031	-10000	0	-10000	0	0
MAPK1	0.026	0.031	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.014	0.012	-10000	0	-0.25	1	1
FADD	0.007	0.094	-10000	0	-0.47	5	5
KSR1	0.015	0.033	-10000	0	-0.18	2	2
MAPK8	0.023	0.04	-10000	0	-0.28	4	4
TRAF2	0.01	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.017	0.082	-10000	0	-0.46	2	2
TNF R/SODD	0	0.021	-10000	0	-10000	0	0
TNF	-0.028	0.14	-10000	0	-0.48	35	35
CYCS	0.018	0.029	0.14	1	-10000	0	1
IKBKG	0.014	0.082	-10000	0	-0.46	2	2
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.006	0.09	-10000	0	-0.53	2	2
RELA	0.01	0	-10000	0	-10000	0	0
RIPK1	0.01	0	-10000	0	-10000	0	0
AIFM1	0.018	0.029	0.14	1	-10000	0	1
TNF/TNF R/SODD	-0.022	0.082	-10000	0	-0.41	14	14
TNFRSF1A	0.009	0.018	-10000	0	-0.37	1	1
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.016	0.023	-10000	0	-10000	0	0
NSMAF	0.012	0.085	-10000	0	-0.49	2	2
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	0.002	0.069	-10000	0	-0.53	7	7

×

mTOR signaling 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	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	0.01	0	-10000	0	-10000	0	0
mol:PIP3	0	0.032	0.29	3	-0.31	2	5
FRAP1	0.005	0.024	-10000	0	-10000	0	0
AKT1	0.006	0.058	0.22	3	-0.25	2	5
INSR	0.009	0.031	-10000	0	-0.65	1	1
Insulin Receptor/Insulin	0	0.02	-10000	0	-0.42	1	1
mol:GTP	-0.012	0.041	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.015	-10000	0	-10000	0	0
TSC2	0.01	0	-10000	0	-10000	0	0
RHEB/GDP	-0.011	0.037	-10000	0	-10000	0	0
TSC1	0.01	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.01	0.031	-10000	0	-0.37	3	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.005	0.018	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.01	0	-10000	0	-10000	0	0
RPS6KB1	0.011	0.041	0.18	3	-10000	0	3
MAP3K5	0.007	0.021	-10000	0	-0.28	2	2
PIK3R1	0.01	0	-10000	0	-10000	0	0
apoptosis	0.007	0.021	-10000	0	-0.28	2	2
mol:LY294002	0	0	-10000	0	-0.001	2	2
EIF4B	0.016	0.037	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.008	0.025	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.002	0.009	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.016	0.025	-10000	0	-0.34	2	2
mTOR/RHEB/GTP/Raptor/GBL	0.016	0.032	0.16	3	-10000	0	3
FKBP1A	0.01	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.011	0.036	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	2	2
FKBP12/Rapamycin	0.007	0.002	-10000	0	-10000	0	0
PDPK1	-0.025	0.089	0.23	3	-0.32	35	38
EIF4E	0.01	0	-10000	0	-10000	0	0
ASK1/PP5C	0.011	0.032	-10000	0	-0.59	1	1
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.013	0.002	-10000	0	-10000	0	0
TSC1/TSC2	-0.011	0.044	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	2	-10000	0	2
RPS6	0.01	0	-10000	0	-10000	0	0
PPP5C	0.01	0	-10000	0	-10000	0	0
EIF4G1	0.01	0	-10000	0	-10000	0	0
IRS1	0.004	0.028	-10000	0	-0.4	2	2
INS	0	0	-10000	0	-10000	0	0
PTEN	0.005	0.053	-10000	0	-0.65	3	3
PDK2	0	0.027	0.23	3	-0.28	2	5
EIF4EBP1	0.007	0.054	-10000	0	-1.1	1	1
PIK3CA	0.009	0.018	-10000	0	-0.37	1	1
PPP2R5D	0.01	0.024	-10000	0	-10000	0	0
peptide biosynthetic process	0.012	0.018	-10000	0	-0.38	1	1
RHEB	0.01	0	-10000	0	-10000	0	0
EIF4A1	0.01	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	3	-10000	0	3
EEF2	0.012	0.018	-10000	0	-0.38	1	1
eIF4E/4E-BP1	0.012	0.05	-10000	0	-1.1	1	1

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.009	0.031	-9999	-0.65	1	1
SMAD2	0.01	0.013	-9999	-0.27	1	1
SMAD3	0.03	0.022	-9999	-10000	0	0
SMAD3/SMAD4	0.033	0.031	-9999	-0.38	2	2
SMAD4/Ubc9/PIASy	-0.001	0.019	-9999	-0.41	1	1
SMAD2/SMAD2/SMAD4	-0.002	0.027	-9999	-0.31	3	3
PPM1A	0.01	0	-9999	-10000	0	0
CALM1	0.01	0	-9999	-10000	0	0
SMAD2/SMAD4	0.015	0.021	-9999	-0.3	2	2
MAP3K1	0.01	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.014	0.023	-9999	-0.48	1	1
MAPK3	0.01	0	-9999	-10000	0	0
MAPK1	0.01	0	-9999	-10000	0	0
NUP214	0.01	0	-9999	-10000	0	0
CTDSP1	0.01	0	-9999	-10000	0	0
CTDSP2	0.01	0	-9999	-10000	0	0
CTDSPL	0.009	0.031	-9999	-0.65	1	1
KPNB1	0.01	0	-9999	-10000	0	0
TGFBRAP1	0.01	0	-9999	-10000	0	0
UBE2I	0.01	0	-9999	-10000	0	0
NUP153	0.01	0	-9999	-10000	0	0
KPNA2	0.007	0.044	-9999	-0.65	2	2
PIAS4	0.01	0	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.009	0.031	-9999	-0.65	1	1
Ran/GTP/Exportin 1/HDAC4	-0.001	0.013	-9999	-0.28	1	1
MDM2/SUMO1	0.02	0.024	-9999	-10000	0	0
HDAC4	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.001	0.019	-9999	-0.29	2	2
SUMO1	0.01	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.021	0.017	-9999	-0.34	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.01	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.01	0	-9999	-10000	0	0
SUMO1/HDAC4	0.023	0	-9999	-10000	0	0
SUMO1/HDAC1	0.022	0.017	-9999	-0.34	1	1
RANGAP1	0.01	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.005	0.031	-9999	-0.37	1	1
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	0	-9999	-10000	0	0
Ran/GTP	0.021	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.003	0.05	-9999	-0.37	8	8
UBE2I	0.01	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.025	0.016	-9999	-0.32	1	1
NPC	0	0	-9999	-10000	0	0
PIAS2	0.007	0.04	-9999	-0.47	3	3
PIAS1	0.01	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	-0.001	0.011	-9999	-0.24	1	1
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.016	0.003	-9999	-10000	0	0
AP2	0.015	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.001	-9999	-10000	0	0
CLTB	0.009	0.031	-9999	-0.65	1	1
coatomer protein complex/ARF1/GTP/ER cargo protein	0.019	0.014	-9999	-0.28	1	1
CD4	-0.005	0.098	-9999	-0.63	11	11
CLTA	0.01	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	0.003	-9999	-10000	0	0
ARF1/GTP	0	0.002	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.021	0.005	-9999	-10000	0	0
mol:Choline	0	0.003	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.01	0	-9999	-10000	0	0
DDEF1	0	0.003	-9999	-10000	0	0
ARF1/GDP	0	0.001	-9999	-10000	0	0
AP2M1	0.01	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.013	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.019	0	-9999	-10000	0	0
ARFIP2	0.009	0.001	-9999	-10000	0	0
COPA	0.01	0	-9999	-10000	0	0
RAC1	0.01	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.019	0.009	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.01	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0.001	-9999	-10000	0	0
AP2A1	0.01	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.02	0.015	-9999	-0.29	1	1
ARF1/GDP/Membrin	0.014	0.002	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.001	-9999	-10000	0	0
CYTH2	0.01	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.001	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.007	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	0.021	0.041	-9999	-0.24	11	11
PLD2	0	0.004	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.009	0	-9999	-10000	0	0
PIP5K1A	0	0.003	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0.002	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0.003	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-9999	-10000	0	0
GOSR2	0	0.001	-9999	-10000	0	0
USO1	0	0.003	-9999	-10000	0	0
GBF1	0	0.001	-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	-0.009	0.061	-9999	-0.41	10	10

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.014	0.023	-9999	-0.48	1	1
FBXW11	0.01	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.01	0	-9999	-10000	0	0
CHUK	0.01	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.001	0.023	-9999	-0.34	2	2
NFKB1	0.01	0	-9999	-10000	0	0
MAP3K14	0.009	0.031	-9999	-0.65	1	1
NF kappa B1 p50/RelB	0.014	0.023	-9999	-0.48	1	1
RELB	0.009	0.031	-9999	-0.65	1	1
NFKB2	0.01	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	-0.001	0.019	-9999	-0.42	1	1
regulation of B cell activation	-0.001	0.019	-9999	-0.41	1	1

pid_entity	TCGA.ZR.A9CJ	TCGA.Z6.AAPN	TCGA.Z6.A9VB	TCGA.Z6.A8JE
109_MAP3K5	0.042	0.042	0.042	0.042
47_PPARGC1A	0.01	0.01	0.01	0.01
105_BMP4	0.01	0.01	0.01	0.01
105_BMP6	0.01	0.01	0.01	0.01
105_BMP7	-0.65	0.01	-0.37	-0.37
105_BMP2	0.01	0.01	0.01	0.01
131_RELN/VLDLR	0	0	0	0
30_TGFB1/TGF beta receptor Type II	0.0094	0.0095	0.0095	0.0094
84_STAT5B	0.015	-0.081	-0.11	0
84_STAT5A	0.015	-0.081	-0.11	0