Glioblastoma Multiforme: PARADIGM pathway analysis of mRNA expression data

Pathway.Name	Avg.Num.Perturbations
HIF-1-alpha transcription factor network	142
Syndecan-4-mediated signaling events	100
FOXM1 transcription factor network	92
Angiopoietin receptor Tie2-mediated signaling	81
Noncanonical Wnt signaling pathway	76
LPA receptor mediated events	71
Endothelins	70
HIF-2-alpha transcription factor network	68
Syndecan-1-mediated signaling events	67
Wnt signaling	67

Pathway.Name	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
HIF-1-alpha transcription factor network	142	10848	76	-0.37	0.022	1000	-1000	-0.036	-1000
Syndecan-4-mediated signaling events	100	6736	67	-0.18	0.022	1000	-1000	-0.006	-1000
FOXM1 transcription factor network	92	4720	51	-0.42	0.019	1000	-1000	-0.12	-1000
Angiopoietin receptor Tie2-mediated signaling	81	7161	88	-0.31	0.066	1000	-1000	-0.044	-1000
Noncanonical Wnt signaling pathway	76	1976	26	-0.033	0.019	1000	-1000	-0.026	-1000
LPA receptor mediated events	71	7287	102	-0.2	0.019	1000	-1000	-0.022	-1000
Endothelins	70	6787	96	-0.17	0.042	1000	-1000	-0.013	-1000
HIF-2-alpha transcription factor network	68	2951	43	-0.17	0.13	1000	-1000	-0.073	-1000
Syndecan-1-mediated signaling events	67	2301	34	-0.097	0.019	1000	-1000	-0.003	-1000
Wnt signaling	67	475	7	-0.033	0.019	1000	-1000	0.009	-1000
Glypican 2 network	66	267	4	-0.025	0	1000	-1000	0	-1000
EGFR-dependent Endothelin signaling events	65	1382	21	-0.08	0.014	1000	-1000	0	-1000
PDGFR-alpha signaling pathway	64	2843	44	-0.12	0.019	1000	-1000	-0.003	-1000
S1P4 pathway	61	1548	25	-0.046	0.017	1000	-1000	0	-1000
Effects of Botulinum toxin	60	1570	26	-0.087	0.023	1000	-1000	0	-1000
ErbB2/ErbB3 signaling events	59	3856	65	-0.082	0.025	1000	-1000	-0.027	-1000
Fc-epsilon receptor I signaling in mast cells	59	5807	97	-0.078	0.021	1000	-1000	-0.027	-1000
Syndecan-2-mediated signaling events	58	4020	69	-0.091	0.019	1000	-1000	-0.001	-1000
S1P5 pathway	58	994	17	-0.046	0.034	1000	-1000	-0.006	-1000
Thromboxane A2 receptor signaling	54	5751	105	-0.11	0.039	1000	-1000	-0.032	-1000
amb2 Integrin signaling	54	4484	82	-0.097	0.025	1000	-1000	-0.022	-1000
Syndecan-3-mediated signaling events	53	1856	35	-0.091	0.041	1000	-1000	-0.007	-1000
Osteopontin-mediated events	51	1951	38	-0.066	0.018	1000	-1000	-0.015	-1000
Nongenotropic Androgen signaling	51	2699	52	-0.1	0.052	1000	-1000	-0.014	-1000
EPHB forward signaling	50	4285	85	-0.04	0.027	1000	-1000	-0.024	-1000
S1P1 pathway	49	1798	36	-0.07	0.015	1000	-1000	-0.02	-1000
Signaling events mediated by VEGFR1 and VEGFR2	48	6123	125	-0.081	0.023	1000	-1000	-0.024	-1000
BCR signaling pathway	46	4571	99	-0.078	0.029	1000	-1000	-0.031	-1000
S1P3 pathway	46	1938	42	-0.065	0.016	1000	-1000	-0.013	-1000
TCGA08_retinoblastoma	45	360	8	-0.016	0.006	1000	-1000	-0.004	-1000
Glypican 1 network	44	2135	48	-0.078	0.019	1000	-1000	-0.008	-1000
PLK2 and PLK4 events	43	131	3	-0.013	0.017	1000	-1000	0.007	-1000
E-cadherin signaling in keratinocytes	43	1882	43	-0.08	0.027	1000	-1000	-0.006	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	42	2892	68	-0.12	0.036	1000	-1000	-0.029	-1000
IL6-mediated signaling events	41	3081	75	-0.084	0.035	1000	-1000	-0.009	-1000
Reelin signaling pathway	40	2246	56	-0.031	0.051	1000	-1000	-0.002	-1000
Class I PI3K signaling events	40	2946	73	-0.058	0.038	1000	-1000	-0.008	-1000
IL1-mediated signaling events	39	2447	62	-0.034	0.035	1000	-1000	-0.019	-1000
IL2 signaling events mediated by STAT5	39	863	22	-0.12	0.019	1000	-1000	-0.005	-1000
Signaling events mediated by HDAC Class III	38	1536	40	-0.052	0.038	1000	-1000	-0.017	-1000
TCGA08_p53	38	272	7	-0.021	0.013	1000	-1000	-0.001	-1000
TCGA08_rtk_signaling	37	969	26	-0.08	0.028	1000	-1000	-0.008	-1000
IGF1 pathway	37	2146	57	-0.022	0.021	1000	-1000	-0.017	-1000
Signaling events mediated by PTP1B	36	2802	76	-0.081	0.045	1000	-1000	-0.02	-1000
Ceramide signaling pathway	36	2763	76	-0.045	0.037	1000	-1000	-0.012	-1000
Aurora B signaling	36	2426	67	-0.052	0.028	1000	-1000	-0.01	-1000
PLK1 signaling events	35	2978	85	-0.064	0.024	1000	-1000	-0.016	-1000
IL2 signaling events mediated by PI3K	35	2061	58	-0.07	0.034	1000	-1000	-0.016	-1000
Integrins in angiogenesis	35	2965	84	-0.068	0.03	1000	-1000	-0.019	-1000
mTOR signaling pathway	34	1811	53	-0.042	0.026	1000	-1000	-0.02	-1000
IFN-gamma pathway	34	2322	68	-0.048	0.039	1000	-1000	-0.028	-1000
FoxO family signaling	34	2182	64	-0.16	0.022	1000	-1000	-0.015	-1000
Stabilization and expansion of the E-cadherin adherens junction	34	2566	74	-0.08	0.033	1000	-1000	-0.024	-1000
Neurotrophic factor-mediated Trk receptor signaling	34	4108	120	-0.066	0.048	1000	-1000	-0.023	-1000
Ephrin B reverse signaling	33	1629	48	-0.077	0.032	1000	-1000	-0.018	-1000
Regulation of nuclear SMAD2/3 signaling	32	4449	136	-0.28	0.27	1000	-1000	-0.026	-1000
Ras signaling in the CD4+ TCR pathway	32	545	17	-0.015	0.016	1000	-1000	-0.004	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	31	1717	54	-0.022	0.022	1000	-1000	-0.001	-1000
Aurora A signaling	30	1853	60	-0.03	0.027	1000	-1000	-0.002	-1000
IL4-mediated signaling events	30	2819	91	-0.39	0.09	1000	-1000	-0.12	-1000
Paxillin-independent events mediated by a4b1 and a4b7	30	1144	37	-0.079	0.047	1000	-1000	-0.005	-1000
Signaling events mediated by PRL	30	1053	34	-0.037	0.022	1000	-1000	-0.003	-1000
Sphingosine 1-phosphate (S1P) pathway	29	838	28	-0.046	0.024	1000	-1000	0	-1000
Plasma membrane estrogen receptor signaling	29	2544	86	-0.082	0.036	1000	-1000	-0.03	-1000
p38 MAPK signaling pathway	29	1309	44	-0.048	0.022	1000	-1000	-0.023	-1000
p75(NTR)-mediated signaling	28	3502	125	-0.1	0.041	1000	-1000	-0.021	-1000
Arf6 downstream pathway	28	1204	43	-0.031	0.021	1000	-1000	-0.009	-1000
Presenilin action in Notch and Wnt signaling	27	1693	61	-0.12	0.04	1000	-1000	-0.027	-1000
Regulation of p38-alpha and p38-beta	27	1462	54	-0.04	0.034	1000	-1000	-0.002	-1000
PDGFR-beta signaling pathway	27	2711	97	-0.073	0.035	1000	-1000	-0.021	-1000
EPO signaling pathway	26	1476	55	-0.017	0.044	1000	-1000	-0.001	-1000
Paxillin-dependent events mediated by a4b1	26	949	36	-0.079	0.048	1000	-1000	-0.018	-1000
E-cadherin signaling in the nascent adherens junction	26	1980	76	-0.031	0.04	1000	-1000	-0.03	-1000
BMP receptor signaling	25	2080	81	-0.05	0.048	1000	-1000	-0.031	-1000
FAS signaling pathway (CD95)	25	1204	47	-0.027	0.024	1000	-1000	-0.016	-1000
IL23-mediated signaling events	25	1531	60	-0.21	0.03	1000	-1000	-0.012	-1000
Canonical Wnt signaling pathway	24	1252	51	-0.14	0.08	1000	-1000	-0.015	-1000
Regulation of Telomerase	24	2480	102	-0.08	0.036	1000	-1000	-0.041	-1000
Class I PI3K signaling events mediated by Akt	23	1566	68	-0.014	0.038	1000	-1000	-0.007	-1000
Signaling mediated by p38-gamma and p38-delta	23	347	15	-0.019	0.022	1000	-1000	0	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	23	1043	45	-0.028	0.027	1000	-1000	-0.021	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	23	1824	78	-0.022	0.034	1000	-1000	-0.022	-1000
BARD1 signaling events	22	1299	57	-0.02	0.036	1000	-1000	-0.023	-1000
Hedgehog signaling events mediated by Gli proteins	22	1479	65	-0.045	0.04	1000	-1000	-0.018	-1000
Insulin Pathway	22	1687	74	-0.031	0.04	1000	-1000	-0.02	-1000
E-cadherin signaling events	22	110	5	0.008	0.027	1000	-1000	0.008	-1000
Arf6 signaling events	21	1326	62	-0.08	0.048	1000	-1000	0	-1000
Glucocorticoid receptor regulatory network	21	2478	114	-0.21	0.062	1000	-1000	-0.032	-1000
Calcium signaling in the CD4+ TCR pathway	21	661	31	-0.042	0.083	1000	-1000	-0.029	-1000
VEGFR1 specific signals	21	1222	56	-0.071	0.031	1000	-1000	-0.007	-1000
Coregulation of Androgen receptor activity	20	1593	76	-0.045	0.038	1000	-1000	-0.014	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	20	464	23	-0.01	0.024	1000	-1000	-0.007	-1000
ErbB4 signaling events	20	1392	69	-0.084	0.034	1000	-1000	-0.011	-1000
Circadian rhythm pathway	20	450	22	-0.014	0.019	1000	-1000	-0.029	-1000
TRAIL signaling pathway	20	980	48	-0.014	0.033	1000	-1000	-0.008	-1000
Visual signal transduction: Cones	19	729	38	-0.065	0.042	1000	-1000	0	-1000
Retinoic acid receptors-mediated signaling	19	1123	58	-0.051	0.045	1000	-1000	-0.013	-1000
IL12-mediated signaling events	18	1594	87	-0.17	0.04	1000	-1000	-0.067	-1000
JNK signaling in the CD4+ TCR pathway	18	312	17	-0.012	0.028	1000	-1000	-0.003	-1000
Insulin-mediated glucose transport	18	595	32	-0.006	0.019	1000	-1000	0	-1000
Signaling events mediated by HDAC Class I	18	1907	104	-0.025	0.031	1000	-1000	-0.014	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	17	1482	85	-0.12	0.031	1000	-1000	-0.025	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	17	583	33	-0.019	0.037	1000	-1000	-0.005	-1000
Signaling events regulated by Ret tyrosine kinase	16	1374	82	-0.032	0.047	1000	-1000	-0.028	-1000
Signaling events mediated by HDAC Class II	15	1197	75	-0.017	0.044	1000	-1000	-0.016	-1000
Nectin adhesion pathway	15	960	63	-0.015	0.046	1000	-1000	-0.033	-1000
Atypical NF-kappaB pathway	15	485	31	-0.016	0.028	1000	-1000	-0.002	-1000
FOXA2 and FOXA3 transcription factor networks	14	682	46	-0.022	0.15	1000	-1000	-0.013	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	14	1214	83	-0.035	0.05	1000	-1000	-0.01	-1000
TCR signaling in naïve CD8+ T cells	14	1380	93	-0.031	0.039	1000	-1000	-0.027	-1000
Caspase cascade in apoptosis	13	989	74	-0.055	0.032	1000	-1000	-0.016	-1000
Cellular roles of Anthrax toxin	13	526	39	-0.087	0.018	1000	-1000	-0.005	-1000
ceramide signaling pathway	13	676	49	-0.01	0.025	1000	-1000	-0.006	-1000
Regulation of Androgen receptor activity	13	919	70	-0.032	0.064	1000	-1000	-0.015	-1000
Signaling mediated by p38-alpha and p38-beta	12	546	44	-0.001	0.03	1000	-1000	-0.001	-1000
Arf6 trafficking events	12	888	71	-0.028	0.03	1000	-1000	-0.011	-1000
Canonical NF-kappaB pathway	11	460	39	-0.01	0.061	1000	-1000	0	-1000
IL27-mediated signaling events	11	562	51	-0.009	0.026	1000	-1000	-0.022	-1000
Sumoylation by RanBP2 regulates transcriptional repression	11	307	27	-0.01	0.036	1000	-1000	-0.018	-1000
Aurora C signaling	9	65	7	0	0.03	1000	-1000	-0.004	-1000
RXR and RAR heterodimerization with other nuclear receptor	9	480	52	-0.029	0.057	1000	-1000	-0.013	-1000
Nephrin/Neph1 signaling in the kidney podocyte	8	300	34	-0.028	0.047	1000	-1000	-0.013	-1000
Signaling events mediated by the Hedgehog family	8	428	52	-0.016	0.053	1000	-1000	-0.006	-1000
Arf1 pathway	8	457	54	-0.003	0.028	1000	-1000	-0.005	-1000
LPA4-mediated signaling events	7	89	12	0	0.015	1000	-1000	0	-1000
Alternative NF-kappaB pathway	6	87	13	0	0.048	1000	-1000	0	-1000
Rapid glucocorticoid signaling	4	85	20	0	0.018	1000	-1000	0	-1000
a4b1 and a4b7 Integrin signaling	3	17	5	0.016	0.026	1000	-1000	0.008	-1000
Visual signal transduction: Rods	2	136	52	0	0.043	1000	-1000	0	-1000
Ephrin A reverse signaling	0	1	7	0	0.026	1000	-1000	0	-1000
Class IB PI3K non-lipid kinase events	0	0	3	-0.019	0.019	1000	-1000	-0.009	-1000
Total	4292	248855	7203	-8.9	4.8	131000	-131000	-2	-131000

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.32	0.52	-9999	-0.9	194	194
HDAC7	-0.003	0.006	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.22	0.45	-9999	-0.78	167	167
SMAD4	-0.003	0.079	-9999	-0.26	44	44
ID2	-0.32	0.53	-9999	-0.91	194	194
AP1	-0.029	0.11	-9999	-0.24	93	93
ABCG2	-0.34	0.54	-9999	-0.9	207	207
HIF1A	-0.04	0.095	-9999	-0.14	166	166
TFF3	-0.32	0.52	-9999	-0.9	193	193
GATA2	0.019	0.012	-9999	-0.11	4	4
AKT1	-0.043	0.11	-9999	-0.2	90	90
response to hypoxia	-0.043	0.072	-9999	-0.12	178	178
MCL1	-0.32	0.52	-9999	-0.89	196	196
NDRG1	-0.34	0.54	-9999	-0.9	207	207
SERPINE1	-0.35	0.54	-9999	-0.92	207	207
FECH	-0.32	0.52	-9999	-0.9	193	193
FURIN	-0.32	0.52	-9999	-0.89	193	193
NCOA2	0.02	0.01	-9999	-0.11	3	3
EP300	-0.038	0.12	-9999	-0.38	31	31
HMOX1	-0.35	0.54	-9999	-0.91	206	206
BHLHE40	-0.33	0.51	-9999	-0.88	199	199
BHLHE41	-0.33	0.51	-9999	-0.88	199	199
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.015	0.13	-9999	-0.21	73	73
ENG	-0.028	0.1	-9999	-0.22	50	50
JUN	-0.001	0.077	-9999	-0.28	37	37
RORA	-0.33	0.52	-9999	-0.91	195	195
ABCB1	-0.16	0.34	-9999	-1.2	42	42
TFRC	-0.33	0.53	-9999	-0.91	196	196
CXCR4	-0.34	0.53	-9999	-0.91	202	202
TF	-0.37	0.53	-9999	-0.89	221	221
CITED2	-0.33	0.52	-9999	-0.9	195	195
HIF1A/ARNT	-0.35	0.7	-9999	-1.1	176	176
LDHA	-0.11	0.32	-9999	-1.2	38	38
ETS1	-0.32	0.52	-9999	-0.88	196	196
PGK1	-0.32	0.53	-9999	-0.9	198	198
NOS2	-0.33	0.51	-9999	-0.88	199	199
ITGB2	-0.34	0.54	-9999	-0.92	200	200
ALDOA	-0.32	0.52	-9999	-0.9	193	193
Cbp/p300/CITED2	-0.32	0.55	-9999	-0.96	184	184
FOS	-0.046	0.12	-9999	-0.22	146	146
HK2	-0.32	0.52	-9999	-0.89	195	195
SP1	0.019	0.021	-9999	-10000	0	0
GCK	-0.047	0.16	-9999	-0.52	18	18
HK1	-0.32	0.52	-9999	-0.88	199	199
NPM1	-0.32	0.52	-9999	-0.88	199	199
EGLN1	-0.32	0.52	-9999	-0.9	194	194
CREB1	0.019	0.038	-9999	-0.27	7	7
PGM1	-0.32	0.52	-9999	-0.89	195	195
SMAD3	0.019	0.006	-9999	-0.11	1	1
EDN1	-0.048	0.17	-9999	-0.64	21	21
IGFBP1	-0.32	0.52	-9999	-0.89	197	197
VEGFA	-0.26	0.4	-9999	-0.7	200	200
HIF1A/JAB1	-0.013	0.074	-9999	-0.28	17	17
CP	-0.35	0.54	-9999	-0.91	206	206
CXCL12	-0.32	0.52	-9999	-0.89	196	196
COPS5	0.017	0.03	-9999	-0.29	5	5
SMAD3/SMAD4	0.013	0.056	-9999	-0.19	36	36
BNIP3	-0.32	0.53	-9999	-0.9	196	196
EGLN3	-0.33	0.52	-9999	-0.88	205	205
CA9	-0.32	0.52	-9999	-0.88	202	202
TERT	-0.32	0.52	-9999	-0.89	193	193
ENO1	-0.32	0.52	-9999	-0.9	194	194
PFKL	-0.32	0.52	-9999	-0.88	199	199
NCOA1	-0.005	0.084	-9999	-0.28	43	43
ADM	-0.35	0.54	-9999	-0.9	213	213
ARNT	-0.033	0.075	-9999	-0.13	118	118
HNF4A	0.022	0.004	-9999	-10000	0	0
ADFP	-0.35	0.54	-9999	-0.92	203	203
SLC2A1	-0.23	0.39	-9999	-0.67	189	189
LEP	-0.32	0.52	-9999	-0.88	196	196
HIF1A/ARNT/Cbp/p300	-0.23	0.46	-9999	-0.78	174	174
EPO	-0.14	0.3	-9999	-0.55	122	122
CREBBP	-0.032	0.11	-9999	-0.32	27	27
HIF1A/ARNT/Cbp/p300/HDAC7	-0.25	0.48	-9999	-0.82	173	173
PFKFB3	-0.33	0.53	-9999	-0.9	202	202
NT5E	-0.34	0.53	-9999	-0.9	208	208

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.038	0.15	-10000	0	-0.48	45	45
Syndecan-4/Syndesmos	-0.17	0.28	-10000	0	-0.47	205	205
positive regulation of JNK cascade	-0.16	0.26	-10000	0	-0.45	206	206
Syndecan-4/ADAM12	-0.16	0.28	-10000	0	-0.46	205	205
CCL5	0.006	0.039	-10000	0	-10000	0	0
Rac1/GDP	0.011	0.024	-10000	0	-0.2	7	7
DNM2	0.019	0	-10000	0	-10000	0	0
ITGA5	-0.002	0.07	-10000	0	-0.19	53	53
SDCBP	0.011	0.05	-10000	0	-0.29	14	14
PLG	0.022	0.006	-10000	0	-10000	0	0
ADAM12	0.016	0.019	-10000	0	-0.11	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.002	0.01	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.17	0.28	-10000	0	-0.47	205	205
Syndecan-4/CXCL12/CXCR4	-0.18	0.29	-10000	0	-0.48	206	206
Syndecan-4/Laminin alpha3	-0.17	0.28	-10000	0	-0.46	206	206
MDK	-0.025	0.1	-10000	0	-0.24	89	89
Syndecan-4/FZD7	-0.18	0.3	-10000	0	-0.5	206	206
Syndecan-4/Midkine	-0.18	0.3	-10000	0	-0.49	205	205
FZD7	-0.047	0.12	-10000	0	-0.22	148	148
Syndecan-4/FGFR1/FGF	-0.14	0.27	-10000	0	-0.42	206	206
THBS1	0	0.046	-10000	0	-0.11	79	79
integrin-mediated signaling pathway	-0.17	0.28	-10000	0	-0.47	208	208
positive regulation of MAPKKK cascade	-0.16	0.26	-10000	0	-0.45	206	206
Syndecan-4/TACI	-0.16	0.28	-10000	0	-0.46	205	205
CXCR4	-0.032	0.11	-10000	0	-0.22	111	111
cell adhesion	0.002	0.074	-10000	0	-0.26	33	33
Syndecan-4/Dynamin	-0.16	0.28	-10000	0	-0.46	205	205
Syndecan-4/TSP1	-0.17	0.28	-10000	0	-0.46	206	206
Syndecan-4/GIPC	-0.16	0.28	-10000	0	-0.46	205	205
Syndecan-4/RANTES	-0.17	0.28	-10000	0	-0.46	205	205
ITGB1	0.019	0	-10000	0	-10000	0	0
LAMA1	0	0	-10000	0	-10000	0	0
LAMA3	0.01	0.034	-10000	0	-0.11	38	38
RAC1	0.015	0.036	-10000	0	-0.29	7	7
PRKCA	0.022	0.028	0.12	2	-10000	0	2
Syndecan-4/alpha-Actinin	-0.18	0.3	-10000	0	-0.5	206	206
TFPI	-0.02	0.086	-10000	0	-0.17	106	106
F2	0.007	0.016	-10000	0	-0.13	2	2
alpha5/beta1 Integrin	0.013	0.049	-10000	0	-0.19	24	24
positive regulation of cell adhesion	-0.16	0.27	-10000	0	-0.45	206	206
ACTN1	-0.034	0.11	-10000	0	-0.24	109	109
TNC	-0.041	0.12	-10000	0	-0.25	118	118
Syndecan-4/CXCL12	-0.17	0.28	-10000	0	-0.47	205	205
FGF6	0.019	0	-10000	0	-10000	0	0
RHOA	0.015	0.036	-10000	0	-0.29	7	7
CXCL12	-0.001	0.048	-10000	0	-0.29	1	1
TNFRSF13B	0.019	0.006	-10000	0	-0.11	1	1
FGF2	0.013	0.036	-10000	0	-0.16	19	19
FGFR1	0.019	0.008	-10000	0	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.17	0.28	-10000	0	-0.47	205	205
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.004	0.066	-10000	0	-0.24	34	34
cell migration	-0.003	0.003	-10000	0	-10000	0	0
PRKCD	0.015	0.029	-10000	0	-0.11	27	27
vasculogenesis	-0.16	0.27	-10000	0	-0.44	206	206
SDC4	-0.18	0.3	-10000	0	-0.5	205	205
Syndecan-4/Tenascin C	-0.18	0.3	-10000	0	-0.5	207	207
Syndecan-4/PI-4-5-P2/PKC alpha	-0.003	0.007	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.16	0.29	-10000	0	-0.46	206	206
MMP9	-0.1	0.13	-10000	0	-0.21	271	271
Rac1/GTP	0.002	0.076	-10000	0	-0.27	33	33
cytoskeleton organization	-0.16	0.26	-10000	0	-0.44	206	206
GIPC1	0.019	0	-10000	0	-10000	0	0
Syndecan-4/TFPI	-0.18	0.29	-10000	0	-0.48	205	205

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.22	0.6	-9999	-1.2	113	113
PLK1	0.013	0.063	-9999	-10000	0	0
BIRC5	-0.15	0.45	-9999	-1.3	64	64
HSPA1B	-0.23	0.6	-9999	-1.2	122	122
MAP2K1	0.012	0.058	-9999	-0.3	8	8
BRCA2	-0.22	0.6	-9999	-1.2	113	113
FOXM1	-0.42	1	-9999	-2.1	119	119
XRCC1	-0.22	0.6	-9999	-1.2	117	117
FOXM1B/p19	-0.4	0.6	-9999	-1.4	125	125
Cyclin D1/CDK4	-0.22	0.56	-9999	-1.1	125	125
CDC2	-0.26	0.67	-9999	-1.4	123	123
TGFA	-0.18	0.52	-9999	-1	120	120
SKP2	-0.22	0.6	-9999	-1.2	110	110
CCNE1	0.01	0.035	-9999	-0.12	37	37
CKS1B	-0.24	0.62	-9999	-1.3	118	118
RB1	-0.17	0.34	-9999	-0.75	97	97
FOXM1C/SP1	-0.31	0.74	-9999	-1.5	122	122
AURKB	0.012	0.087	-9999	-1.4	1	1
CENPF	-0.26	0.64	-9999	-1.3	129	129
CDK4	-0.008	0.07	-9999	-0.15	80	80
MYC	-0.2	0.54	-9999	-1	125	125
CHEK2	0.009	0.057	-9999	-0.15	29	29
ONECUT1	-0.22	0.58	-9999	-1.2	122	122
CDKN2A	-0.021	0.059	-9999	-0.11	155	155
LAMA4	-0.22	0.6	-9999	-1.2	114	114
FOXM1B/HNF6	-0.3	0.74	-9999	-1.5	122	122
FOS	-0.3	0.66	-9999	-1.2	153	153
SP1	0.018	0.01	-9999	-10000	0	0
CDC25B	-0.23	0.61	-9999	-1.3	117	117
response to radiation	0.001	0.034	-9999	-10000	0	0
CENPB	-0.23	0.6	-9999	-1.2	113	113
CENPA	-0.23	0.61	-9999	-1.3	115	115
NEK2	-0.22	0.6	-9999	-1.2	113	113
HIST1H2BA	-0.23	0.6	-9999	-1.2	122	122
CCNA2	-0.027	0.1	-9999	-0.2	117	117
EP300	0.012	0.046	-9999	-0.24	15	15
CCNB1/CDK1	-0.34	0.8	-9999	-1.6	129	129
CCNB2	-0.26	0.64	-9999	-1.3	122	122
CCNB1	-0.28	0.68	-9999	-1.4	127	127
ETV5	-0.26	0.64	-9999	-1.2	136	136
ESR1	-0.22	0.6	-9999	-1.2	113	113
CCND1	-0.22	0.57	-9999	-1.1	125	125
GSK3A	0.018	0.037	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.003	0.087	-9999	-0.18	71	71
CDK2	0.011	0.037	-9999	-0.13	29	29
G2/M transition of mitotic cell cycle	0.001	0.041	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.27	0.67	-9999	-1.4	121	121
GAS1	-0.24	0.61	-9999	-1.3	116	116
MMP2	-0.26	0.64	-9999	-1.3	129	129
RB1/FOXM1C	-0.23	0.6	-9999	-1.2	127	127
CREBBP	0.019	0	-9999	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.24	0.42	-10000	0	-0.84	156	156
NCK1/PAK1/Dok-R	-0.13	0.18	-10000	0	-0.4	149	149
NCK1/Dok-R	-0.14	0.37	-10000	0	-0.91	99	99
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
mol:beta2-estradiol	0.043	0.091	0.23	99	-10000	0	99
RELA	0.018	0.02	-10000	0	-0.23	3	3
SHC1	0.003	0.052	-10000	0	-0.15	48	48
Rac/GDP	0.011	0.024	-10000	0	-0.2	7	7
F2	0.066	0.094	0.26	99	-10000	0	99
TNIP2	0.016	0.031	-10000	0	-0.24	7	7
NF kappa B/RelA	-0.12	0.36	-10000	0	-0.86	99	99
FN1	0.001	0.071	-10000	0	-0.26	34	34
PLD2	-0.15	0.38	-10000	0	-0.94	99	99
PTPN11	0.015	0.033	-10000	0	-0.27	7	7
GRB14	0.001	0.047	-10000	0	-0.12	70	70
ELK1	-0.13	0.35	-10000	0	-0.86	99	99
GRB7	0.016	0.019	-10000	0	-0.11	11	11
PAK1	0.017	0.017	-10000	0	-0.11	9	9
Tie2/Ang1/alpha5/beta1 Integrin	-0.14	0.38	-10000	0	-0.91	99	99
CDKN1A	-0.2	0.36	-10000	0	-0.72	153	153
ITGA5	-0.002	0.07	-10000	0	-0.19	53	53
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.15	0.37	-10000	0	-0.91	99	99
CRK	0.009	0.054	-10000	0	-0.28	17	17
mol:NO	-0.17	0.31	-10000	0	-0.61	160	160
PLG	-0.15	0.38	-10000	0	-0.94	99	99
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.2	0.38	-10000	0	-0.8	136	136
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PIK3R1	-0.016	0.096	-10000	0	-0.27	62	62
ANGPT2	-0.27	0.47	-10000	0	-1.1	110	110
BMX	-0.15	0.38	-10000	0	-0.94	99	99
ANGPT1	-0.21	0.45	-10000	0	-1.1	99	99
tube development	-0.22	0.37	-10000	0	-0.71	178	178
ANGPT4	0.016	0.007	-10000	0	-10000	0	0
response to hypoxia	-0.012	0.026	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.16	0.39	-10000	0	-0.97	99	99
alpha5/beta1 Integrin	0.013	0.049	-10000	0	-0.19	24	24
FGF2	0.015	0.036	-10000	0	-0.15	19	19
STAT5A (dimer)	-0.25	0.44	-10000	0	-0.82	186	186
mol:L-citrulline	-0.17	0.31	-10000	0	-0.61	160	160
AGTR1	0.01	0.025	-10000	0	-0.12	13	13
MAPK14	-0.17	0.39	-10000	0	-0.95	99	99
Tie2/SHP2	-0.019	0.13	-10000	0	-0.79	6	6
TEK	-0.028	0.14	-10000	0	-0.92	5	5
RPS6KB1	-0.21	0.38	-10000	0	-0.79	146	146
Angiotensin II/AT1	0.004	0.026	-10000	0	-0.11	6	6
Tie2/Ang1/GRB2	-0.15	0.39	-10000	0	-0.96	99	99
MAPK3	-0.14	0.36	-10000	0	-0.88	99	99
MAPK1	-0.14	0.36	-10000	0	-0.88	99	99
Tie2/Ang1/GRB7	-0.15	0.39	-10000	0	-0.96	99	99
NFKB1	0.014	0.037	-10000	0	-0.23	11	11
MAPK8	-0.15	0.38	-10000	0	-0.94	99	99
PI3K	-0.26	0.46	-10000	0	-0.94	146	146
FES	-0.17	0.38	-10000	0	-0.94	99	99
Crk/Dok-R	-0.15	0.37	-10000	0	-0.91	99	99
Tie2/Ang1/ABIN2	-0.15	0.39	-10000	0	-0.96	99	99
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.21	0.37	-10000	0	-0.75	158	158
STAT5A	0.018	0.008	-10000	0	-0.11	2	2
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.22	0.38	-10000	0	-0.79	147	147
Tie2/Ang2	-0.31	0.52	-10000	0	-0.99	177	177
Tie2/Ang1	-0.16	0.4	-10000	0	-1	99	99
FOXO1	-0.24	0.41	-10000	0	-0.79	178	178
ELF1	0.017	0.046	-10000	0	-0.25	14	14
ELF2	-0.15	0.37	-10000	0	-0.92	99	99
mol:Choline	-0.14	0.37	-10000	0	-0.91	99	99
cell migration	-0.073	0.098	-10000	0	-0.22	153	153
FYN	-0.25	0.42	-10000	0	-0.82	178	178
DOK2	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.18	0.32	-10000	0	-0.59	192	192
ETS1	-0.024	0.093	-10000	0	-0.21	99	99
PXN	-0.17	0.32	-10000	0	-0.65	148	148
ITGB1	0.019	0	-10000	0	-10000	0	0
NOS3	-0.2	0.35	-10000	0	-0.7	158	158
RAC1	0.015	0.036	-10000	0	-0.29	7	7
TNF	-0.027	0.096	-10000	0	-0.22	99	99
MAPKKK cascade	-0.14	0.37	-10000	0	-0.91	99	99
RASA1	0.003	0.069	-10000	0	-0.28	29	29
Tie2/Ang1/Shc	-0.16	0.39	-10000	0	-0.97	99	99
NCK1	0.014	0.036	-10000	0	-0.19	14	14
vasculogenesis	-0.15	0.28	-10000	0	-0.55	161	161
mol:Phosphatidic acid	-0.14	0.37	-10000	0	-0.91	99	99
mol:Angiotensin II	-0.005	0.012	-10000	0	-10000	0	0
mol:NADP	-0.17	0.31	-10000	0	-0.61	160	160
Rac1/GTP	-0.2	0.36	-10000	0	-0.74	147	147
MMP2	-0.16	0.39	-10000	0	-0.97	99	99

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0	0	-9999	-10000	0	0
GNB1/GNG2	-0.025	0.11	-9999	-0.19	136	136
mol:DAG	-0.022	0.1	-9999	-0.18	136	136
PLCG1	-0.023	0.11	-9999	-0.18	136	136
YES1	-0.031	0.11	-9999	-0.19	135	135
FZD3	-0.028	0.1	-9999	-0.22	103	103
FZD6	-0.02	0.076	-9999	-0.14	129	129
G protein	-0.023	0.11	-9999	-0.19	136	136
MAP3K7	-0.017	0.096	-9999	-0.22	62	62
mol:Ca2+	-0.022	0.1	-9999	-0.17	136	136
mol:IP3	-0.022	0.1	-9999	-0.18	136	136
NLK	-0.006	0.16	-9999	-0.9	16	16
GNB1	0.007	0.061	-9999	-0.29	21	21
CAMK2A	-0.018	0.096	-9999	-0.23	56	56
MAP3K7IP1	0.019	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.033	0.11	-9999	-0.2	134	134
CSNK1A1	0.014	0.038	-9999	-0.29	8	8
GNAS	-0.029	0.1	-9999	-0.19	134	134
GO:0007205	-0.025	0.1	-9999	-0.26	56	56
WNT6	0.019	0	-9999	-10000	0	0
WNT4	0.018	0.013	-9999	-0.11	5	5
NFAT1/CK1 alpha	-0.019	0.11	-9999	-0.25	61	61
GNG2	0	0	-9999	-10000	0	0
WNT5A	-0.027	0.1	-9999	-0.24	96	96
WNT11	0.017	0.016	-9999	-0.11	8	8
CDC42	-0.027	0.1	-9999	-0.18	136	136

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.011	0.072	-10000	0	-0.18	68	68
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.077	-10000	0	-0.21	41	41
AP1	-0.045	0.095	-10000	0	-0.19	125	125
mol:PIP3	-0.061	0.081	-10000	0	-0.16	169	169
AKT1	-0.011	0.095	-10000	0	-0.26	50	50
PTK2B	-0.006	0.056	-10000	0	-0.16	60	60
RHOA	-0.005	0.059	-10000	0	-0.42	7	7
PIK3CB	0.018	0.013	-10000	0	-0.11	5	5
mol:Ca2+	0.007	0.035	-10000	0	-0.14	20	20
MAGI3	0	0	0.001	9	-10000	0	9
RELA	0.018	0.02	-10000	0	-0.23	3	3
apoptosis	-0.014	0.073	-10000	0	-0.2	61	61
HRAS/GDP	0.007	0.037	-10000	0	-0.19	18	18
positive regulation of microtubule depolymerization	-0.024	0.087	-10000	0	-0.16	122	122
NF kappa B1 p50/RelA	-0.022	0.053	-10000	0	-0.15	63	63
endothelial cell migration	-0.038	0.13	-10000	0	-0.4	60	60
ADCY4	-0.054	0.12	-10000	0	-0.26	109	109
ADCY5	-0.054	0.12	-10000	0	-0.26	109	109
ADCY6	-0.05	0.12	-10000	0	-0.26	101	101
ADCY7	-0.054	0.13	-10000	0	-0.27	106	106
ADCY1	-0.05	0.12	-10000	0	-0.26	101	101
ADCY2	-0.05	0.12	-10000	0	-0.26	101	101
ADCY3	-0.054	0.12	-10000	0	-0.26	109	109
ADCY8	-0.053	0.12	-10000	0	-0.26	102	102
ADCY9	-0.05	0.12	-10000	0	-0.26	101	101
GSK3B	-0.008	0.066	-10000	0	-0.16	72	72
arachidonic acid secretion	-0.054	0.14	-10000	0	-0.27	113	113
GNG2	0	0.001	0.001	70	-10000	0	70
TRIP6	-0.031	0.11	-10000	0	-0.29	81	81
GNAO1	-0.021	0.079	-10000	0	-0.2	76	76
HRAS	0.009	0.055	-10000	0	-0.28	18	18
NFKBIA	-0.006	0.075	-10000	0	-0.22	41	41
GAB1	0.003	0.056	-10000	0	-0.15	50	50
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.008	0.2	-10000	0	-0.93	23	23
JUN	-0.002	0.077	-10000	0	-0.28	37	37
LPA/LPA2/NHERF2	0.004	0.026	-10000	0	-0.064	60	60
TIAM1	-0.021	0.23	-10000	0	-1.1	23	23
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:IP3	0.007	0.036	-10000	0	-0.14	20	20
PLCB3	0.009	0.023	-10000	0	-10000	0	0
FOS	-0.046	0.12	-10000	0	-0.22	146	146
positive regulation of mitosis	-0.054	0.14	-10000	0	-0.27	113	113
LPA/LPA1-2-3	-0.017	0.056	-10000	0	-0.12	102	102
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-0.001	78	78
BCAR1	0	0	-10000	0	-10000	0	0
stress fiber formation	-0.004	0.067	-10000	0	-0.17	68	68
GNAZ	-0.019	0.081	-10000	0	-0.2	75	75
EGFR/PI3K-beta/Gab1	-0.063	0.083	-10000	0	-0.16	169	169
positive regulation of dendritic cell cytokine production	-0.017	0.056	-10000	0	-0.12	102	102
LPA/LPA2/MAGI-3	-0.007	0.023	-10000	0	-0.049	102	102
ARHGEF1	-0.008	0.074	-10000	0	-0.17	81	81
GNAI2	-0.015	0.079	-10000	0	-0.22	60	60
GNAI3	-0.011	0.069	-10000	0	-0.18	64	64
GNAI1	-0.027	0.08	-10000	0	-0.21	73	73
LPA/LPA3	-0.01	0.029	-10000	0	-0.063	102	102
LPA/LPA2	-0.01	0.029	-10000	0	-0.062	102	102
LPA/LPA1	-0.023	0.075	-10000	0	-0.16	102	102
HB-EGF/EGFR	-0.093	0.093	-10000	0	-0.18	261	261
HBEGF	-0.06	0.089	-10000	0	-0.19	153	153
mol:DAG	0.007	0.036	-10000	0	-0.14	20	20
cAMP biosynthetic process	-0.053	0.13	-10000	0	-0.26	113	113
NFKB1	0.014	0.037	-10000	0	-0.23	11	11
SRC	0.019	0	-10000	0	-10000	0	0
GNB1	0.007	0.06	-10000	0	-0.29	21	21
LYN	-0.022	0.097	-10000	0	-0.23	75	75
GNAQ	-0.001	0.026	-10000	0	-0.06	77	77
LPAR2	0	0.001	0.001	8	-0.002	81	89
LPAR3	0	0.001	-10000	0	-0.001	92	92
LPAR1	-0.015	0.045	-10000	0	-0.098	102	102
IL8	-0.2	0.2	-10000	0	-0.42	226	226
PTK2	-0.009	0.062	-10000	0	-0.15	72	72
Rac1/GDP	0.011	0.024	-10000	0	-0.2	7	7
CASP3	-0.014	0.073	-10000	0	-0.2	61	61
EGFR	-0.08	0.12	-10000	0	-0.25	128	128
PLCG1	0.001	0.04	-10000	0	-0.093	62	62
PLD2	-0.007	0.054	-10000	0	-0.11	97	97
G12/G13	-0.007	0.083	-10000	0	-0.19	82	82
PI3K-beta	-0.035	0.081	-10000	0	-0.25	48	48
cell migration	-0.002	0.073	-10000	0	-0.26	29	29
SLC9A3R2	0.019	0	-10000	0	-10000	0	0
PXN	-0.004	0.068	-10000	0	-0.17	68	68
HRAS/GTP	-0.056	0.14	-10000	0	-0.28	113	113
RAC1	0.015	0.036	-10000	0	-0.29	7	7
MMP9	-0.097	0.13	-10000	0	-0.21	271	271
PRKCE	0.019	0	-10000	0	-10000	0	0
PRKCD	0.008	0.036	-10000	0	-0.13	20	20
Gi(beta/gamma)	-0.055	0.14	-10000	0	-0.29	105	105
mol:LPA	-0.015	0.045	-10000	0	-0.098	102	102
TRIP6/p130 Cas/FAK1/Paxillin	-0.021	0.1	-10000	0	-0.24	70	70
MAPKKK cascade	-0.054	0.14	-10000	0	-0.27	113	113
contractile ring contraction involved in cytokinesis	-0.005	0.058	-10000	0	-0.41	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.001	0.025	-10000	0	-0.06	75	75
GNA15	-0.002	0.029	-10000	0	-0.063	84	84
GNA12	-0.005	0.082	-10000	0	-0.29	39	39
GNA13	0.016	0.021	-10000	0	-0.11	14	14
MAPT	-0.024	0.089	-10000	0	-0.17	122	122
GNA11	-0.007	0.051	-10000	0	-0.12	63	63
Rac1/GTP	-0.01	0.21	-10000	0	-1	23	23
MMP2	-0.038	0.13	-10000	0	-0.4	60	60

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.079	0.14	-9999	-0.29	134	134
PTK2B	0.018	0.013	-9999	-0.11	5	5
mol:Ca2+	-0.023	0.16	-9999	-0.56	31	31
EDN1	-0.039	0.086	-9999	-0.18	108	108
EDN3	0.015	0.022	-9999	-0.11	15	15
EDN2	0.018	0.01	-9999	-0.11	3	3
HRAS/GDP	-0.047	0.15	-9999	-0.36	70	70
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.034	0.11	-9999	-0.28	65	65
ADCY4	-0.063	0.11	-9999	-0.25	108	108
ADCY5	-0.063	0.11	-9999	-0.25	108	108
ADCY6	-0.055	0.11	-9999	-0.24	107	107
ADCY7	-0.058	0.12	-9999	-0.25	112	112
ADCY1	-0.055	0.11	-9999	-0.24	107	107
ADCY2	-0.055	0.11	-9999	-0.25	107	107
ADCY3	-0.063	0.11	-9999	-0.25	108	108
ADCY8	-0.061	0.11	-9999	-0.25	112	112
ADCY9	-0.055	0.11	-9999	-0.26	98	98
arachidonic acid secretion	-0.095	0.24	-9999	-0.5	109	109
ETB receptor/Endothelin-1/Gq/GTP	-0.043	0.11	-9999	-0.26	83	83
GNAO1	-0.014	0.085	-9999	-0.2	81	81
HRAS	0.008	0.055	-9999	-0.28	18	18
ETA receptor/Endothelin-1/G12/GTP	-0.067	0.15	-9999	-0.3	116	116
ETA receptor/Endothelin-1/Gs/GTP	-0.053	0.13	-9999	-0.27	98	98
mol:GTP	0	0.005	-9999	-10000	0	0
COL3A1	-0.12	0.2	-9999	-0.44	129	129
EDNRB	-0.062	0.12	-9999	-0.28	113	113
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.071	0.14	-9999	-0.33	89	89
CYSLTR1	-0.08	0.13	-9999	-0.28	132	132
SLC9A1	-0.043	0.09	-9999	-0.21	86	86
mol:GDP	-0.055	0.15	-9999	-0.37	68	68
SLC9A3	-0.11	0.24	-9999	-0.51	104	104
RAF1	-0.071	0.19	-9999	-0.42	95	95
JUN	-0.056	0.28	-9999	-1.1	34	34
JAK2	-0.075	0.14	-9999	-0.28	130	130
mol:IP3	-0.039	0.11	-9999	-0.3	55	55
ETA receptor/Endothelin-1	-0.088	0.17	-9999	-0.34	130	130
PLCB1	0.014	0.024	-9999	-0.12	17	17
PLCB2	0.018	0.004	-9999	-10000	0	0
ETA receptor/Endothelin-3	-0.039	0.1	-9999	-0.19	122	122
FOS	-0.14	0.34	-9999	-0.9	86	86
Gai/GDP	-0.095	0.29	-9999	-0.82	67	67
CRK	0.009	0.054	-9999	-0.28	17	17
mol:Ca ++	-0.092	0.18	-9999	-0.38	115	115
BCAR1	0	0	-9999	-10000	0	0
PRKCB1	-0.044	0.12	-9999	-0.3	63	63
GNAQ	0.014	0.024	-9999	-0.11	17	17
GNAZ	-0.008	0.083	-9999	-0.23	56	56
GNAL	0.018	0.01	-9999	-0.11	3	3
Gs family/GDP	-0.044	0.14	-9999	-0.34	66	66
ETA receptor/Endothelin-1/Gq/GTP	-0.044	0.13	-9999	-0.29	80	80
MAPK14	-0.028	0.099	-9999	-0.26	53	53
TRPC6	-0.025	0.17	-9999	-0.59	31	31
GNAI2	0	0.074	-9999	-0.28	34	34
GNAI3	0.014	0.038	-9999	-0.29	8	8
GNAI1	-0.046	0.11	-9999	-0.2	157	157
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.033	0.1	-9999	-0.27	58	58
ETB receptor/Endothelin-2	-0.028	0.089	-9999	-0.2	105	105
ETB receptor/Endothelin-3	-0.03	0.089	-9999	-0.2	107	107
ETB receptor/Endothelin-1	-0.069	0.12	-9999	-0.22	170	170
MAPK3	-0.12	0.31	-9999	-0.8	87	87
MAPK1	-0.13	0.33	-9999	-0.82	88	88
Rac1/GDP	-0.045	0.15	-9999	-0.36	67	67
cAMP biosynthetic process	-0.036	0.1	-9999	-0.24	82	82
MAPK8	-0.038	0.19	-9999	-0.65	36	36
SRC	0.019	0	-9999	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.097	0.18	-9999	-0.35	121	121
p130Cas/CRK/Src/PYK2	-0.035	0.16	-9999	-0.48	47	47
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.053	0.16	-9999	-0.37	77	77
COL1A2	-0.16	0.26	-9999	-0.56	133	133
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.037	0.099	-9999	-0.2	100	100
mol:DAG	-0.04	0.11	-9999	-0.3	55	55
MAP2K2	-0.093	0.24	-9999	-0.59	90	90
MAP2K1	-0.095	0.25	-9999	-0.6	90	90
EDNRA	-0.072	0.14	-9999	-0.24	163	163
positive regulation of muscle contraction	-0.064	0.13	-9999	-0.29	102	102
Gq family/GDP	-0.025	0.15	-9999	-0.35	64	64
HRAS/GTP	-0.05	0.14	-9999	-0.35	69	69
PRKCH	-0.037	0.11	-9999	-0.29	58	58
RAC1	0.015	0.036	-9999	-0.29	7	7
PRKCA	-0.036	0.11	-9999	-0.29	56	56
PRKCB	-0.041	0.11	-9999	-0.29	60	60
PRKCE	-0.036	0.11	-9999	-0.29	57	57
PRKCD	-0.039	0.12	-9999	-0.29	61	61
PRKCG	-0.037	0.11	-9999	-0.3	57	57
regulation of vascular smooth muscle contraction	-0.17	0.41	-9999	-1.1	86	86
PRKCQ	-0.038	0.11	-9999	-0.29	59	59
PLA2G4A	-0.11	0.26	-9999	-0.55	109	109
GNA14	0.015	0.023	-9999	-0.11	15	15
GNA15	0.011	0.034	-9999	-0.13	26	26
GNA12	-0.005	0.082	-9999	-0.29	39	39
GNA11	0.003	0.07	-9999	-0.3	27	27
Rac1/GTP	-0.058	0.14	-9999	-0.3	99	99
MMP1	0.042	0.084	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.005	0.039	-10000	0	-10000	0	0
oxygen homeostasis	-0.008	0.014	-10000	0	-10000	0	0
TCEB2	0.019	0	-10000	0	-10000	0	0
TCEB1	0.013	0.041	-10000	0	-0.27	10	10
VHL/Elongin B/Elongin C/HIF2A	-0.029	0.11	-10000	0	-0.25	60	60
EPO	-0.11	0.25	-10000	0	-0.48	124	124
FIH (dimer)	0.009	0.016	-10000	0	-10000	0	0
APEX1	0.003	0.039	-10000	0	-0.33	5	5
SERPINE1	-0.17	0.3	-10000	0	-0.57	153	153
FLT1	-0.003	0.043	-10000	0	-10000	0	0
ADORA2A	-0.13	0.26	-10000	0	-0.5	132	132
germ cell development	-0.13	0.26	-10000	0	-0.46	159	159
SLC11A2	-0.13	0.27	-10000	0	-0.52	132	132
BHLHE40	-0.14	0.27	-10000	0	-0.48	159	159
HIF1AN	0.009	0.016	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.057	0.17	-10000	0	-0.3	115	115
ETS1	0.029	0.014	-10000	0	-10000	0	0
CITED2	-0.062	0.24	-10000	0	-1.1	27	27
KDR	-0.03	0.17	-10000	0	-1.1	11	11
PGK1	-0.14	0.28	-10000	0	-0.54	136	136
SIRT1	0.008	0.048	-10000	0	-0.16	32	32
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	-0.14	0.33	-10000	0	-0.55	157	157
EPAS1	-0.044	0.12	-10000	0	-0.24	87	87
SP1	0.026	0.004	-10000	0	-10000	0	0
ABCG2	-0.16	0.3	-10000	0	-0.55	157	157
EFNA1	-0.14	0.28	-10000	0	-0.54	135	135
FXN	-0.13	0.26	-10000	0	-0.5	132	132
POU5F1	-0.14	0.27	-10000	0	-0.48	159	159
neuron apoptosis	0.13	0.32	0.54	157	-10000	0	157
EP300	0.012	0.046	-10000	0	-0.24	15	15
EGLN3	-0.014	0.069	-10000	0	-0.17	72	72
EGLN2	0.009	0.016	-10000	0	-10000	0	0
EGLN1	0	0.055	-10000	0	-0.25	20	20
VHL/Elongin B/Elongin C	0.023	0.024	-10000	0	-0.16	9	9
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.006	0.022	-10000	0	-0.093	1	1
SLC2A1	-0.14	0.27	-10000	0	-0.52	137	137
TWIST1	-0.17	0.29	-10000	0	-0.51	181	181
ELK1	0.022	0.017	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.054	0.16	-10000	0	-0.3	114	114
VEGFA	-0.17	0.3	-10000	0	-0.56	163	163
CREBBP	0.019	0	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.049	-9999	-0.16	37	37
CCL5	0.006	0.039	-9999	-10000	0	0
SDCBP	0.011	0.05	-9999	-0.29	14	14
FGFR/FGF2/Syndecan-1	-0.053	0.089	-9999	-0.17	148	148
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.046	0.091	-9999	-0.22	57	57
Syndecan-1/Syntenin	-0.044	0.091	-9999	-0.22	56	56
MAPK3	-0.043	0.093	-9999	-0.23	58	58
HGF/MET	0.018	0.03	-9999	-0.14	4	4
TGFB1/TGF beta receptor Type II	0.007	0.049	-9999	-0.16	37	37
BSG	0.001	0.068	-9999	-0.22	39	39
keratinocyte migration	-0.045	0.09	-9999	-0.22	57	57
Syndecan-1/RANTES	-0.047	0.09	-9999	-0.21	65	65
Syndecan-1/CD147	-0.046	0.1	-9999	-0.24	60	60
Syndecan-1/Syntenin/PIP2	-0.044	0.088	-9999	-0.21	56	56
LAMA5	0.006	0.053	-9999	-0.18	33	33
positive regulation of cell-cell adhesion	-0.043	0.086	-9999	-0.21	56	56
MMP7	-0.014	0.057	-9999	-0.11	135	135
HGF	0.016	0.02	-9999	-0.11	13	13
Syndecan-1/CASK	-0.051	0.084	-9999	-0.16	146	146
Syndecan-1/HGF/MET	-0.038	0.091	-9999	-0.22	46	46
regulation of cell adhesion	-0.042	0.095	-9999	-0.23	63	63
HPSE	0.003	0.055	-9999	-0.15	52	52
positive regulation of cell migration	-0.053	0.089	-9999	-0.17	148	148
SDC1	-0.053	0.09	-9999	-0.18	148	148
Syndecan-1/Collagen	-0.053	0.089	-9999	-0.17	148	148
PPIB	0.004	0.066	-9999	-0.29	25	25
MET	0.008	0.037	-9999	-0.11	47	47
PRKACA	0.019	0	-9999	-10000	0	0
MMP9	-0.097	0.13	-9999	-0.21	271	271
MAPK1	-0.046	0.098	-9999	-0.24	64	64
homophilic cell adhesion	-0.053	0.089	-9999	-0.17	148	148
MMP1	0.002	0.044	-9999	-0.11	70	70

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.033	0.11	-9999	-0.2	134	134
FZD6	-0.02	0.076	-9999	-0.14	129	129
WNT6	0.019	0	-9999	-10000	0	0
WNT4	0.018	0.013	-9999	-0.11	5	5
FZD3	-0.028	0.1	-9999	-0.22	103	103
WNT5A	-0.027	0.1	-9999	-0.24	96	96
WNT11	0.017	0.016	-9999	-0.11	8	8

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.025	0.1	-9999	-0.24	89	89
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	-0.016	0.071	-9999	-0.16	89	89
neuron projection morphogenesis	-0.016	0.07	-9999	-0.16	89	89

×

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	0.009	0.055	-9999	-0.28	18	18
EGFR	-0.08	0.12	-9999	-0.29	97	97
EGF/EGFR	-0.042	0.073	-9999	-0.14	145	145
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.022	0.069	-9999	-0.13	110	110
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.029	0.099	-9999	-0.2	119	119
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	0.014	0.025	-9999	-0.11	21	21
EGF/EGFR dimer/SHC	-0.034	0.075	-9999	-0.15	120	120
mol:GDP	-0.024	0.067	-9999	-0.13	110	110
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.007	0.041	-9999	-0.12	48	48
GRB2/SOS1	0.011	0.026	-9999	-0.17	10	10
HRAS/GTP	-0.027	0.064	-9999	-0.12	120	120
SHC1	0.004	0.052	-9999	-0.14	48	48
HRAS/GDP	-0.023	0.069	-9999	-0.13	120	120
FRAP1	-0.024	0.059	-9999	-0.12	110	110
EGF/EGFR dimer	-0.044	0.082	-9999	-0.19	107	107
SOS1	0	0	-9999	-10000	0	0
GRB2	0.014	0.039	-9999	-0.26	10	10
ETA receptor/Endothelin-1	-0.014	0.075	-9999	-0.18	69	69

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.022	0.079	-10000	0	-0.16	100	100
PDGF/PDGFRA/CRKL	-0.017	0.076	-10000	0	-0.19	72	72
positive regulation of JUN kinase activity	-0.01	0.067	-10000	0	-0.14	86	86
CRKL	0.018	0.01	-10000	0	-0.11	3	3
PDGF/PDGFRA/Caveolin-3	-0.016	0.076	-10000	0	-0.19	72	72
AP1	-0.12	0.27	-10000	0	-0.72	85	85
mol:IP3	-0.013	0.061	-10000	0	-0.21	31	31
PLCG1	-0.012	0.061	-10000	0	-0.11	100	100
PDGF/PDGFRA/alphaV Integrin	-0.027	0.092	-10000	0	-0.21	89	89
RAPGEF1	0.019	0	-10000	0	-10000	0	0
CRK	0.009	0.054	-10000	0	-0.28	17	17
mol:Ca2+	-0.029	0.079	-10000	0	-0.2	77	77
CAV3	0.019	0.008	-10000	0	-0.11	2	2
CAV1	-0.071	0.13	-10000	0	-0.22	197	197
SHC/Grb2/SOS1	-0.009	0.068	-10000	0	-0.15	86	86
PDGF/PDGFRA/Shf	-0.03	0.072	-10000	0	-0.18	88	88
FOS	-0.12	0.27	-10000	0	-0.71	85	85
JUN	-0.018	0.069	0.25	10	-0.25	28	38
oligodendrocyte development	-0.027	0.091	-10000	0	-0.21	89	89
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:DAG	-0.013	0.061	-10000	0	-0.21	31	31
PDGF/PDGFRA	-0.022	0.079	-10000	0	-0.16	100	100
actin cytoskeleton reorganization	-0.018	0.077	-10000	0	-0.19	73	73
SRF	0.019	0.033	-10000	0	-0.17	14	14
SHC1	0.004	0.052	-10000	0	-0.14	48	48
PI3K	-0.037	0.1	-10000	0	-0.19	145	145
PDGF/PDGFRA/Crk/C3G	-0.006	0.073	-10000	0	-0.16	84	84
JAK1	-0.015	0.071	-10000	0	-0.2	49	49
ELK1/SRF	-0.009	0.072	-10000	0	-0.16	79	79
SHB	0.016	0.02	-10000	0	-0.11	13	13
SHF	0	0	-10000	0	-10000	0	0
CSNK2A1	0.018	0.049	-10000	0	-0.26	14	14
GO:0007205	-0.037	0.093	-10000	0	-0.25	71	71
SOS1	0	0	-10000	0	-10000	0	0
Ras protein signal transduction	-0.01	0.067	-10000	0	-0.14	86	86
PDGF/PDGFRA/SHB	-0.018	0.077	-10000	0	-0.19	73	73
PDGF/PDGFRA/Caveolin-1	-0.078	0.12	-10000	0	-0.23	176	176
ITGAV	0.003	0.067	-10000	0	-0.25	32	32
ELK1	-0.033	0.083	-10000	0	-0.21	79	79
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
PDGF/PDGFRA/Crk	-0.023	0.085	-10000	0	-0.2	84	84
JAK-STAT cascade	-0.015	0.071	-10000	0	-0.2	49	49
cell proliferation	-0.03	0.072	-10000	0	-0.17	88	88

×

S1P4 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.014	0.085	-9999	-0.2	81	81
CDC42/GTP	-0.034	0.11	-9999	-0.19	141	141
PLCG1	-0.04	0.12	-9999	-0.2	141	141
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0	0.074	-9999	-0.28	34	34
GNAI3	0.014	0.038	-9999	-0.29	8	8
G12/G13	0.009	0.059	-9999	-0.19	39	39
cell migration	-0.033	0.11	-9999	-0.19	141	141
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
MAPK3	-0.039	0.11	-9999	-0.2	141	141
MAPK1	-0.043	0.12	-9999	-0.21	141	141
S1P/S1P5/Gi	-0.046	0.12	-9999	-0.22	141	141
GNAI1	-0.046	0.11	-9999	-0.2	157	157
CDC42/GDP	0.013	0.01	-9999	-0.07	8	8
S1P/S1P5/G12	-0.001	0.046	-9999	-0.16	39	39
RHOA	0.008	0.044	-9999	-0.14	39	39
S1P/S1P4/Gi	-0.046	0.12	-9999	-0.22	141	141
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.008	0.083	-9999	-0.23	56	56
S1P/S1P4/G12/G13	0.01	0.045	-9999	-0.14	39	39
GNA12	-0.005	0.082	-9999	-0.29	39	39
GNA13	0.016	0.021	-9999	-0.11	14	14
CDC42	0.017	0.016	-9999	-0.11	8	8

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.007	0.016	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.016	0.048	-9999	-0.19	25	25
STXBP1	-0.021	0.094	-9999	-0.21	93	93
ACh/CHRNA1	-0.009	0.038	-9999	-0.066	150	150
RAB3GAP2/RIMS1/UNC13B	0.023	0.052	-9999	-0.17	33	33
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	0.018	0.011	-9999	-0.11	4	4
mol:ACh	-0.026	0.045	-9999	-0.095	141	141
RAB3GAP2	0.012	0.045	-9999	-0.25	14	14
STX1A/SNAP25/VAMP2	-0.028	0.092	-9999	-0.21	69	69
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.009	0.038	-9999	-0.066	150	150
UNC13B	0.002	0.068	-9999	-0.24	35	35
CHRNA1	0.015	0.022	-9999	-0.11	16	16
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.054	0.083	-9999	-0.11	287	287
SNAP25	-0.061	0.092	-9999	-0.22	135	135
VAMP2	0.001	0.026	-9999	-0.2	8	8
SYT1	-0.087	0.12	-9999	-0.19	274	274
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.003	0.057	-9999	-0.14	67	67
STX1A/SNAP25 fragment 1/VAMP2	-0.028	0.092	-9999	-0.21	69	69

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.011	0.014	-10000	0	-0.081	8	8
RAS family/GTP	-0.022	0.098	-10000	0	-0.16	140	140
NFATC4	-0.01	0.064	0.15	13	-0.12	63	76
ERBB2IP	0	0.074	-10000	0	-0.28	34	34
HSP90 (dimer)	0.018	0.019	-10000	0	-0.29	2	2
mammary gland morphogenesis	-0.021	0.073	0.17	4	-0.14	114	118
JUN	0.001	0.081	-10000	0	-0.37	8	8
HRAS	0.009	0.055	-10000	0	-0.28	18	18
DOCK7	-0.023	0.069	0.16	9	-0.14	114	123
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.022	0.072	0.17	7	-0.14	112	119
AKT1	0.001	0.04	-10000	0	-0.18	23	23
BAD	0.011	0.018	-10000	0	-0.096	11	11
MAPK10	-0.011	0.056	0.12	5	-0.15	40	45
mol:GTP	0	0.001	-10000	0	-0.004	41	41
ErbB2/ErbB3/neuregulin 1 beta	-0.021	0.079	0.18	6	-0.15	114	120
RAF1	-0.027	0.1	-10000	0	-0.2	93	93
ErbB2/ErbB3/neuregulin 2	-0.028	0.065	-10000	0	-0.14	105	105
STAT3	-0.043	0.25	-10000	0	-0.95	37	37
cell migration	-0.011	0.061	0.13	5	-0.16	37	42
mol:PI-3-4-5-P3	-0.001	0.001	0.003	6	-0.003	116	122
cell proliferation	-0.062	0.23	-10000	0	-0.58	66	66
FOS	-0.058	0.2	-10000	0	-0.45	96	96
NRAS	-0.01	0.086	-10000	0	-0.24	59	59
mol:Ca2+	-0.021	0.073	0.17	4	-0.14	114	118
MAPK3	-0.043	0.18	-10000	0	-0.5	49	49
MAPK1	-0.053	0.21	-10000	0	-0.56	55	55
JAK2	-0.019	0.073	0.16	10	-0.14	113	123
NF2	0.013	0.007	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.031	0.084	0.12	1	-0.18	114	115
NRG1	0.018	0.002	-10000	0	-10000	0	0
GRB2/SOS1	0.011	0.026	-10000	0	-0.17	10	10
MAPK8	-0.022	0.093	0.18	4	-0.19	107	111
MAPK9	-0.003	0.047	0.11	11	-0.1	29	40
ERBB2	0.013	0.072	0.29	33	-10000	0	33
ERBB3	-0.082	0.12	-10000	0	-0.18	262	262
SHC1	0.004	0.052	-10000	0	-0.14	48	48
RAC1	0.015	0.036	-10000	0	-0.29	7	7
apoptosis	0.001	0.047	0.24	16	-10000	0	16
STAT3 (dimer)	-0.041	0.24	-10000	0	-0.93	37	37
RNF41	0.012	0.014	-10000	0	-0.059	13	13
FRAP1	0.011	0.015	-10000	0	-0.084	10	10
RAC1-CDC42/GTP	-0.026	0.045	-10000	0	-0.1	114	114
ErbB2/ErbB2/HSP90 (dimer)	0.025	0.048	0.21	32	-0.17	1	33
CHRNA1	-0.025	0.14	-10000	0	-0.38	48	48
myelination	-0.008	0.063	0.15	13	-0.18	11	24
PPP3CB	-0.016	0.069	0.16	10	-0.13	112	122
KRAS	0.011	0.049	-10000	0	-0.28	14	14
RAC1-CDC42/GDP	-0.01	0.081	-10000	0	-0.15	116	116
NRG2	0.019	0.006	-10000	0	-0.11	1	1
mol:GDP	-0.031	0.084	0.12	2	-0.18	114	116
SOS1	0	0.001	-10000	0	-0.003	17	17
MAP2K2	-0.025	0.1	-10000	0	-0.22	79	79
SRC	0.019	0	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-0.003	7	7
PTPN11	-0.017	0.073	0.16	12	-0.14	113	125
MAP2K1	-0.058	0.19	-10000	0	-0.46	64	64
heart morphogenesis	-0.021	0.073	0.17	4	-0.14	114	118
RAS family/GDP	-0.02	0.099	-10000	0	-0.17	136	136
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PRKACA	0.009	0.008	-10000	0	-10000	0	0
CHRNE	0.008	0.026	-10000	0	-0.15	8	8
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
activation of caspase activity	-0.001	0.04	0.18	23	-10000	0	23
nervous system development	-0.021	0.073	0.17	4	-0.14	114	118
CDC42	0.017	0.016	-10000	0	-0.11	8	8

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	-0.014	0.093	-9999	-0.27	60	60
LAT2	-0.027	0.13	-9999	-0.3	82	82
AP1	-0.036	0.16	-9999	-0.38	74	74
mol:PIP3	-0.019	0.14	-9999	-0.3	84	84
IKBKB	-0.006	0.084	-9999	-0.2	66	66
AKT1	-0.034	0.13	-9999	-0.29	83	83
IKBKG	-0.006	0.084	-9999	-0.2	67	67
MS4A2	0.021	0.006	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	-0.012	0.086	-9999	-0.22	66	66
MAP3K1	-0.022	0.13	-9999	-0.32	66	66
mol:Ca2+	-0.011	0.11	-9999	-0.23	84	84
LYN	-0.019	0.1	-9999	-0.26	72	72
CBLB	-0.027	0.13	-9999	-0.3	82	82
SHC1	0.004	0.052	-9999	-0.14	48	48
RasGAP/p62DOK	0.015	0.054	-9999	-0.15	39	39
positive regulation of cell migration	-0.001	0.045	-9999	-0.15	39	39
INPP5D	0	0	-9999	-10000	0	0
PLD2	-0.012	0.07	-9999	-0.13	125	125
PTPN13	-0.052	0.2	-9999	-0.52	63	63
PTPN11	0.013	0.036	-9999	-0.28	7	7
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.026	0.13	-9999	-0.28	81	81
SYK	-0.005	0.075	-9999	-0.31	25	25
GRB2	0.014	0.039	-9999	-0.26	10	10
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.051	0.12	-9999	-0.3	84	84
LAT	-0.028	0.13	-9999	-0.3	82	82
PAK2	-0.029	0.14	-9999	-0.35	67	67
NFATC2	-0.01	0.019	-9999	-0.062	20	20
HRAS	-0.034	0.15	-9999	-0.37	69	69
GAB2	-0.005	0.082	-9999	-0.27	44	44
PLA2G1B	-0.003	0.18	-9999	-0.95	18	18
Fc epsilon R1	0.001	0.067	-9999	-0.14	84	84
Antigen/IgE/Fc epsilon R1	0.003	0.059	-9999	-0.12	84	84
mol:GDP	-0.034	0.15	-9999	-0.38	68	68
JUN	-0.002	0.077	-9999	-0.28	37	37
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
FOS	-0.046	0.12	-9999	-0.22	146	146
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.032	0.14	-9999	-0.31	83	83
CHUK	-0.007	0.084	-9999	-0.2	68	68
KLRG1	-0.019	0.12	-9999	-0.29	70	70
VAV1	-0.03	0.13	-9999	-0.3	82	82
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.027	0.13	-9999	-0.3	82	82
negative regulation of mast cell degranulation	-0.024	0.11	-9999	-0.29	61	61
BTK	-0.034	0.15	-9999	-0.4	58	58
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.052	0.11	-9999	-0.2	153	153
GAB2/PI3K/SHP2	-0.059	0.11	-9999	-0.27	90	90
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.032	0.14	-9999	-0.34	69	69
RAF1	-0.011	0.19	-9999	-1	18	18
Fc epsilon R1/FcgammaRIIB/SHIP	-0.037	0.095	-9999	-0.15	173	173
FCER1G	-0.025	0.1	-9999	-0.23	90	90
FCER1A	0.013	0.027	-9999	-0.11	23	23
Antigen/IgE/Fc epsilon R1/Fyn	-0.006	0.082	-9999	-0.14	126	126
MAPK3	-0.003	0.18	-9999	-0.94	18	18
MAPK1	-0.007	0.19	-9999	-0.99	18	18
NFKB1	0.014	0.037	-9999	-0.23	11	11
MAPK8	0.015	0.076	-9999	-0.61	5	5
DUSP1	-0.005	0.065	-9999	-0.15	74	74
NF-kappa-B/RelA	0.002	0.056	-9999	-0.12	66	66
actin cytoskeleton reorganization	-0.047	0.19	-9999	-0.52	60	60
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.04	0.16	-9999	-0.38	72	72
FER	-0.028	0.13	-9999	-0.29	83	83
RELA	0.018	0.02	-9999	-0.23	3	3
ITK	0.002	0.033	-9999	-0.11	20	20
SOS1	0	0	-9999	-10000	0	0
PLCG1	-0.029	0.15	-9999	-0.38	62	62
cytokine secretion	-0.013	0.033	-9999	-0.092	65	65
SPHK1	-0.031	0.13	-9999	-0.3	83	83
PTK2	-0.05	0.2	-9999	-0.55	60	60
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.052	0.13	-9999	-0.31	84	84
EDG1	-0.001	0.045	-9999	-0.15	39	39
mol:DAG	-0.032	0.15	-9999	-0.37	72	72
MAP2K2	-0.007	0.18	-9999	-0.95	18	18
MAP2K1	-0.008	0.18	-9999	-0.96	18	18
MAP2K7	0.019	0	-9999	-10000	0	0
KLRG1/SHP2	-0.016	0.11	-9999	-0.3	56	56
MAP2K4	0.016	0.098	-9999	-0.98	5	5
Fc epsilon R1/FcgammaRIIB	-0.04	0.1	-9999	-0.17	173	173
mol:Choline	-0.012	0.07	-9999	-0.13	125	125
SHC/Grb2/SOS1	-0.02	0.13	-9999	-0.29	84	84
FYN	-0.019	0.1	-9999	-0.28	68	68
DOK1	0.019	0	-9999	-10000	0	0
PXN	-0.041	0.19	-9999	-0.5	60	60
HCLS1	-0.047	0.16	-9999	-0.35	93	93
PRKCB	-0.017	0.11	-9999	-0.24	84	84
FCGR2B	-0.078	0.12	-9999	-0.2	234	234
IGHE	-0.001	0.004	-9999	-10000	0	0
KLRG1/SHIP	-0.024	0.11	-9999	-0.3	61	61
LCP2	-0.012	0.086	-9999	-0.22	70	70
PLA2G4A	-0.044	0.15	-9999	-0.33	93	93
RASA1	0.003	0.069	-9999	-0.28	29	29
mol:Phosphatidic acid	-0.012	0.07	-9999	-0.13	125	125
IKK complex	0.004	0.067	-9999	-0.15	65	65
WIPF1	0.013	0.038	-9999	-0.18	17	17

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	-0.013	0.08	-9999	-0.17	94	94
EPHB2	0.013	0.027	-9999	-0.11	24	24
Syndecan-2/TACI	-0.003	0.065	-9999	-0.16	75	75
LAMA1	0	0	-9999	-10000	0	0
Syndecan-2/alpha2 ITGB1	-0.007	0.081	-9999	-0.14	114	114
HRAS	0.009	0.055	-9999	-0.28	18	18
Syndecan-2/CASK	-0.015	0.061	-9999	-0.16	78	78
ITGA5	-0.002	0.07	-9999	-0.19	53	53
BAX	0.013	0.097	-9999	-0.94	5	5
EPB41	0.019	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.006	0.067	-9999	-0.15	81	81
LAMA3	0.01	0.034	-9999	-0.11	38	38
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.036	0.11	-9999	-0.21	128	128
Syndecan-2/MMP2	-0.028	0.091	-9999	-0.18	123	123
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.003	0.067	-9999	-0.19	49	49
dendrite morphogenesis	-0.006	0.067	-9999	-0.16	77	77
Syndecan-2/GM-CSF	-0.003	0.065	-9999	-0.15	75	75
determination of left/right symmetry	0.007	0.036	-9999	-0.21	9	9
Syndecan-2/PKC delta	-0.007	0.066	-9999	-0.16	77	77
GNB2L1	0.018	0.019	-9999	-0.29	2	2
MAPK3	0.001	0.057	-9999	-0.13	75	75
MAPK1	-0.003	0.065	-9999	-0.15	76	76
Syndecan-2/RACK1	0.003	0.067	-9999	-0.14	86	86
NF1	0.019	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.007	0.036	-9999	-0.21	9	9
ITGA2	-0.026	0.095	-9999	-0.19	114	114
MAPK8	0.014	0.048	-9999	-0.38	6	6
Syndecan-2/alpha2/beta1 Integrin	-0.013	0.075	-9999	-0.14	110	110
Syndecan-2/Kininogen	-0.003	0.065	-9999	-0.15	75	75
ITGB1	0.019	0	-9999	-10000	0	0
SRC	0.002	0.061	-9999	-0.12	86	86
Syndecan-2/CASK/Protein 4.1	-0.002	0.058	-9999	-0.14	75	75
extracellular matrix organization	-0.01	0.07	-9999	-0.16	89	89
actin cytoskeleton reorganization	-0.013	0.08	-9999	-0.17	94	94
Syndecan-2/Caveolin-2/Ras	-0.024	0.094	-9999	-0.17	129	129
Syndecan-2/Laminin alpha3	-0.008	0.068	-9999	-0.15	82	82
Syndecan-2/RasGAP	0.005	0.078	-9999	-0.14	101	101
alpha5/beta1 Integrin	0.013	0.049	-9999	-0.19	24	24
PRKCD	0.012	0.029	-9999	-0.11	27	27
Syndecan-2 dimer	-0.006	0.067	-9999	-0.16	77	77
GO:0007205	0.002	0.013	-9999	-0.13	5	5
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.006	0.074	-9999	-0.22	24	24
RHOA	0.015	0.036	-9999	-0.29	7	7
SDCBP	0.011	0.05	-9999	-0.29	14	14
TNFRSF13B	0.019	0.006	-9999	-0.11	1	1
RASA1	0.003	0.069	-9999	-0.28	29	29
alpha2/beta1 Integrin	-0.003	0.067	-9999	-0.19	49	49
Syndecan-2/Synbindin	-0.006	0.072	-9999	-0.17	77	77
TGFB1	0.007	0.049	-9999	-0.16	37	37
CASP3	-0.005	0.065	-9999	-0.15	78	78
FN1	0.001	0.071	-9999	-0.26	34	34
Syndecan-2/IL8	-0.063	0.11	-9999	-0.19	181	181
SDC2	0.007	0.036	-9999	-0.21	9	9
KNG1	0.019	0.006	-9999	-0.11	1	1
Syndecan-2/Neurofibromin	-0.003	0.065	-9999	-0.15	75	75
TRAPPC4	0.014	0.038	-9999	-0.27	9	9
CSF2	0.019	0	-9999	-10000	0	0
Syndecan-2/TGFB1	-0.01	0.071	-9999	-0.16	89	89
Syndecan-2/Syntenin/PI-4-5-P2	-0.006	0.067	-9999	-0.15	81	81
Syndecan-2/Ezrin	-0.004	0.064	-9999	-0.15	77	77
PRKACA	0.001	0.057	-9999	-0.13	75	75
angiogenesis	-0.063	0.11	-9999	-0.19	181	181
MMP2	-0.027	0.1	-9999	-0.22	102	102
IL8	-0.091	0.13	-9999	-0.21	255	255
calcineurin-NFAT signaling pathway	-0.003	0.065	-9999	-0.15	75	75

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.034	0.11	0.19	142	-10000	0	142
GNAI2	0	0.074	-10000	0	-0.28	34	34
S1P/S1P5/G12	-0.001	0.046	-10000	0	-0.16	39	39
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.014	0.085	-10000	0	-0.2	81	81
RhoA/GTP	-0.035	0.12	-10000	0	-0.2	142	142
negative regulation of cAMP metabolic process	-0.046	0.12	-10000	0	-0.22	141	141
GNAZ	-0.008	0.083	-10000	0	-0.23	56	56
GNAI3	0.014	0.038	-10000	0	-0.29	8	8
GNA12	-0.005	0.082	-10000	0	-0.29	39	39
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.046	0.12	-10000	0	-0.22	141	141
RhoA/GDP	0.011	0.024	-10000	0	-0.2	7	7
RHOA	0.015	0.036	-10000	0	-0.29	7	7
GNAI1	-0.046	0.11	-10000	0	-0.2	157	157

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.016	0.019	-10000	0	-0.11	11	11
GNB1/GNG2	-0.047	0.074	-10000	0	-0.17	140	140
AKT1	-0.027	0.12	-10000	0	-0.2	157	157
EGF	0.014	0.025	-10000	0	-0.11	21	21
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.024	0.035	-10000	0	-0.19	4	4
mol:Ca2+	-0.036	0.15	-10000	0	-0.28	140	140
LYN	0.022	0.04	-10000	0	-0.19	9	9
RhoA/GTP	-0.031	0.057	-10000	0	-0.12	140	140
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.051	0.17	-10000	0	-0.32	140	140
GNG2	0	0	-10000	0	-10000	0	0
ARRB2	0.013	0.039	-10000	0	-0.29	7	7
TP alpha/Gq family/GDP/G beta5/gamma2	0.015	0.067	-10000	0	-0.25	30	30
G beta5/gamma2	-0.06	0.095	-10000	0	-0.22	140	140
PRKCH	-0.048	0.17	-10000	0	-0.32	140	140
DNM1	0.017	0.017	-10000	0	-0.11	9	9
TXA2/TP beta/beta Arrestin3	0.017	0.015	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.002	140	140
PTGDR	0.019	0	-10000	0	-10000	0	0
G12 family/GTP	-0.08	0.13	-10000	0	-0.29	140	140
ADRBK1	0.018	0.014	-10000	0	-0.11	6	6
ADRBK2	0.019	0.006	-10000	0	-0.11	1	1
RhoA/GTP/ROCK1	0.021	0.029	-10000	0	-0.17	11	11
mol:GDP	0.003	0.086	0.18	1	-10000	0	1
mol:NADP	0.019	0.006	-10000	0	-0.11	1	1
RAB11A	0.016	0.033	-10000	0	-0.29	6	6
PRKG1	0.019	0	-10000	0	-10000	0	0
mol:IP3	-0.051	0.18	-10000	0	-0.34	140	140
cell morphogenesis	0.021	0.029	-10000	0	-0.17	11	11
PLCB2	-0.077	0.23	-10000	0	-0.45	140	140
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.028	0.03	-10000	0	-0.12	1	1
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.017	0.044	-10000	0	-0.19	14	14
RHOA	0.015	0.036	-10000	0	-0.29	7	7
PTGIR	0.019	0	-10000	0	-10000	0	0
PRKCB1	-0.056	0.18	-10000	0	-0.35	140	140
GNAQ	0.015	0.023	-10000	0	-0.11	17	17
mol:L-citrulline	0.019	0.006	-10000	0	-0.11	1	1
TXA2/TXA2-R family	-0.085	0.24	-10000	0	-0.48	140	140
LCK	0.028	0.03	-10000	0	-0.12	2	2
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.037	0.015	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	-0.017	0.16	-10000	0	-0.51	47	47
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.034	0.022	-10000	0	-10000	0	0
MAPK14	-0.026	0.12	-10000	0	-0.22	140	140
TGM2/GTP	-0.056	0.2	-10000	0	-0.37	140	140
MAPK11	-0.026	0.12	-10000	0	-0.22	140	140
ARHGEF1	-0.018	0.094	-10000	0	-0.17	140	140
GNAI2	0	0.074	-10000	0	-0.28	34	34
JNK cascade	-0.056	0.19	-10000	0	-0.36	140	140
RAB11/GDP	0.015	0.032	-10000	0	-0.29	6	6
ICAM1	-0.039	0.14	-10000	0	-0.27	140	140
cAMP biosynthetic process	-0.046	0.17	-10000	0	-0.31	140	140
Gq family/GTP/EBP50	0.009	0.051	-10000	0	-0.17	34	34
actin cytoskeleton reorganization	0.021	0.029	-10000	0	-0.17	11	11
SRC	0.028	0.029	-10000	0	-10000	0	0
GNB5	0.017	0.019	-10000	0	-0.14	7	7
GNB1	0.007	0.061	-10000	0	-0.29	21	21
EGF/EGFR	-0.019	0.095	-10000	0	-0.2	83	83
VCAM1	-0.065	0.18	-10000	0	-0.36	140	140
TP beta/Gq family/GDP/G beta5/gamma2	0.015	0.067	-10000	0	-0.25	30	30
platelet activation	-0.034	0.16	-10000	0	-0.28	140	140
PGI2/IP	0.014	0.001	-10000	0	-10000	0	0
PRKACA	0.022	0.002	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.016	0.061	-10000	0	-0.23	30	30
TXA2/TP beta/beta Arrestin2	0.015	0.029	-10000	0	-0.2	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.024	0.003	-10000	0	-10000	0	0
mol:DAG	-0.062	0.2	-10000	0	-0.38	140	140
EGFR	-0.08	0.12	-10000	0	-0.29	97	97
TXA2/TP alpha	-0.067	0.22	-10000	0	-0.42	140	140
Gq family/GTP	0.009	0.037	-10000	0	-0.14	29	29
YES1	0.025	0.038	-10000	0	-0.18	9	9
GNAI2/GTP	0	0.026	-10000	0	-10000	0	0
PGD2/DP	0.014	0.001	-10000	0	-10000	0	0
SLC9A3R1	0.01	0.042	-10000	0	-0.15	30	30
FYN	0.02	0.052	-10000	0	-0.19	26	26
mol:NO	0.019	0.006	-10000	0	-0.11	1	1
GNA15	0.012	0.033	-10000	0	-0.12	26	26
PGK/cGMP	0.025	0.003	-10000	0	-10000	0	0
RhoA/GDP	0.015	0.035	-10000	0	-0.29	7	7
TP alpha/TGM2/GDP/G beta/gamma	0.034	0.028	-10000	0	-10000	0	0
NOS3	0.019	0.006	-10000	0	-0.11	1	1
RAC1	0.015	0.036	-10000	0	-0.29	7	7
PRKCA	-0.048	0.17	-10000	0	-0.32	140	140
PRKCB	-0.052	0.17	-10000	0	-0.33	140	140
PRKCE	-0.049	0.17	-10000	0	-0.33	140	140
PRKCD	-0.057	0.18	-10000	0	-0.36	140	140
PRKCG	-0.056	0.18	-10000	0	-0.35	140	140
muscle contraction	-0.075	0.23	-10000	0	-0.44	140	140
PRKCZ	-0.048	0.17	-10000	0	-0.32	140	140
ARR3	0.019	0	-10000	0	-10000	0	0
TXA2/TP beta	0.039	0.009	-10000	0	-10000	0	0
PRKCQ	-0.05	0.17	-10000	0	-0.33	140	140
MAPKKK cascade	-0.066	0.21	-10000	0	-0.4	140	140
SELE	-0.04	0.15	-10000	0	-0.28	140	140
TP beta/GNAI2/GDP/G beta/gamma	0.027	0.051	-10000	0	-0.22	15	15
ROCK1	0.016	0.031	-10000	0	-0.26	6	6
GNA14	0.015	0.022	-10000	0	-0.11	15	15
chemotaxis	-0.11	0.29	-10000	0	-0.58	140	140
GNA12	-0.005	0.082	-10000	0	-0.29	39	39
GNA13	0.016	0.021	-10000	0	-0.11	14	14
GNA11	0.003	0.069	-10000	0	-0.29	27	27
Rac1/GTP	0.011	0.024	-10000	0	-0.2	7	7

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.018	0.094	-9999	-0.18	117	117
alphaM/beta2 Integrin/GPIbA	0.008	0.067	-9999	-0.15	74	74
alphaM/beta2 Integrin/proMMP-9	-0.06	0.1	-9999	-0.17	202	202
PLAUR	-0.009	0.078	-9999	-0.18	73	73
HMGB1	0.019	0.014	-9999	-0.29	1	1
alphaM/beta2 Integrin/Talin	-0.004	0.08	-9999	-0.17	87	87
AGER	0.019	0.012	-9999	-0.12	4	4
RAP1A	0.018	0.019	-9999	-0.29	2	2
SELPLG	0.018	0.014	-9999	-0.11	6	6
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.024	0.068	-9999	-0.19	8	8
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.097	0.13	-9999	-0.21	271	271
CYR61	-0.058	0.12	-9999	-0.22	168	168
TLN1	-0.003	0.065	-9999	-0.16	64	64
Rap1/GTP	-0.014	0.055	-9999	-0.23	17	17
RHOA	0.015	0.036	-9999	-0.29	7	7
P-selectin oligomer	0.018	0.011	-9999	-0.11	4	4
MYH2	0.015	0.061	-9999	-0.22	16	16
MST1R	0.017	0.015	-9999	-0.11	7	7
leukocyte activation during inflammatory response	0.015	0.057	-9999	-0.12	74	74
APOB	0.018	0.011	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.027	0.1	-9999	-0.22	102	102
JAM3	-0.007	0.085	-9999	-0.28	46	46
GP1BA	0.019	0	-9999	-10000	0	0
alphaM/beta2 Integrin/CTGF	-0.024	0.097	-9999	-0.17	137	137
alphaM/beta2 Integrin	0.001	0.072	-9999	-0.27	16	16
JAM3 homodimer	-0.007	0.085	-9999	-0.28	46	46
ICAM2	0.011	0.041	-9999	-0.15	26	26
ICAM1	0.005	0.041	-9999	-0.11	58	58
phagocytosis triggered by activation of immune response cell surface activating receptor	0.001	0.072	-9999	-0.27	16	16
cell adhesion	0.008	0.067	-9999	-0.15	74	74
NFKB1	0.013	0.067	-9999	-0.2	12	12
THY1	-0.019	0.097	-9999	-0.29	56	56
RhoA/GDP	0.011	0.024	-9999	-0.2	7	7
Lipoprotein(a)	0.025	0.007	-9999	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	-0.027	0.11	-9999	-0.18	142	142
IL6	0.006	0.072	-9999	-0.28	1	1
ITGB2	-0.032	0.11	-9999	-0.23	109	109
elevation of cytosolic calcium ion concentration	-0.017	0.1	-9999	-0.19	104	104
alphaM/beta2 Integrin/JAM2/JAM3	-0.008	0.11	-9999	-0.19	115	115
JAM2	-0.008	0.087	-9999	-0.28	49	49
alphaM/beta2 Integrin/ICAM1	0.017	0.067	-9999	-0.12	74	74
alphaM/beta2 Integrin/uPA/Plg	-0.003	0.084	-9999	-0.16	89	89
RhoA/GTP	0.011	0.065	-9999	-0.23	18	18
positive regulation of phagocytosis	-0.014	0.11	-9999	-0.26	78	78
Ron/MSP	0.025	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/uPAR/uPA	-0.016	0.1	-9999	-0.19	104	104
alphaM/beta2 Integrin/uPAR	-0.008	0.087	-9999	-0.17	97	97
PLAU	-0.022	0.086	-9999	-0.29	35	35
PLAT	-0.042	0.11	-9999	-0.22	134	134
actin filament polymerization	0.015	0.06	-9999	-0.22	16	16
MST1	0.016	0.02	-9999	-0.11	13	13
alphaM/beta2 Integrin/lipoprotein(a)	0.018	0.059	-9999	-0.12	74	74
TNF	0.015	0.061	-9999	-0.28	1	1
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.016	0.089	-9999	-0.18	96	96
fibrinolysis	-0.004	0.083	-9999	-0.16	89	89
HCK	-0.033	0.11	-9999	-0.21	120	120
dendritic cell antigen processing and presentation	0.001	0.072	-9999	-0.27	16	16
VTN	0.018	0.01	-9999	-0.11	3	3
alphaM/beta2 Integrin/CYR61	-0.037	0.1	-9999	-0.17	165	165
LPA	0.019	0	-9999	-10000	0	0
LRP1	-0.007	0.079	-9999	-0.21	61	61
cell migration	-0.07	0.11	-9999	-0.18	215	215
FN1	0.001	0.071	-9999	-0.26	34	34
alphaM/beta2 Integrin/Thy1	-0.014	0.092	-9999	-0.18	113	113
MPO	0.019	0	-9999	-10000	0	0
KNG1	0.019	0.006	-9999	-0.11	1	1
RAP1/GDP	0.012	0.011	-9999	-0.16	2	2
ROCK1	0.014	0.064	-9999	-0.24	17	17
ELA2	0.019	0	-9999	-10000	0	0
PLG	0.019	0	-9999	-10000	0	0
CTGF	-0.037	0.11	-9999	-0.23	118	118
alphaM/beta2 Integrin/Hck	-0.02	0.11	-9999	-0.21	115	115
ITGAM	0.02	0.003	-9999	-10000	0	0
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.019	0.064	-9999	-0.13	74	74
HP	-0.013	0.056	-9999	-0.11	132	132
leukocyte adhesion	-0.016	0.13	-9999	-0.31	58	58
SELP	0.018	0.011	-9999	-0.11	4	4

×

Syndecan-3-mediated signaling events

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
CTTN	0.018	0.017	-9999	-0.16	4	4
Syndecan-3/Src/Cortactin	-0.045	0.21	-9999	-0.54	76	76
Syndecan-3/Neurocan	-0.076	0.22	-9999	-0.6	76	76
POMC	0.018	0.013	-9999	-0.11	5	5
EGFR	-0.08	0.12	-9999	-0.29	97	97
Syndecan-3/EGFR	-0.084	0.2	-9999	-0.56	77	77
AGRP	0.019	0	-9999	-10000	0	0
NCSTN	0.008	0.056	-9999	-0.26	20	20
PSENEN	0.013	0.041	-9999	-0.27	10	10
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.018	0.02	-9999	-0.23	3	3
APH1A	0.015	0.036	-9999	-0.27	8	8
NCAN	-0.074	0.14	-9999	-0.29	138	138
long-term memory	-0.055	0.21	-9999	-0.55	77	77
Syndecan-3/IL8	-0.08	0.2	-9999	-0.55	77	77
PSEN1	0.011	0.047	-9999	-0.26	15	15
Src/Cortactin	0.027	0.012	-9999	-0.19	1	1
FYN	-0.019	0.1	-9999	-0.28	68	68
limb bud formation	-0.065	0.19	-9999	-0.52	76	76
MC4R	0.019	0.006	-9999	-0.11	1	1
SRC	0.019	0	-9999	-10000	0	0
PTN	-0.015	0.097	-9999	-0.29	58	58
FGFR/FGF/Syndecan-3	-0.065	0.19	-9999	-0.53	76	76
neuron projection morphogenesis	-0.072	0.23	-9999	-0.57	84	84
Syndecan-3/AgRP	-0.053	0.19	-9999	-0.5	76	76
Syndecan-3/AgRP/MC4R	-0.04	0.18	-9999	-0.48	76	76
Fyn/Cortactin	0.001	0.073	-9999	-0.2	63	63
SDC3	-0.066	0.2	-9999	-0.54	76	76
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.078	0.2	-9999	-0.54	77	77
IL8	-0.091	0.13	-9999	-0.21	255	255
Syndecan-3/Fyn/Cortactin	-0.056	0.21	-9999	-0.56	77	77
Syndecan-3/CASK	-0.064	0.18	-9999	-0.51	76	76
alpha-MSH/MC4R	0.027	0.01	-9999	-10000	0	0
Gamma Secretase	0.041	0.063	-9999	-0.17	33	33

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.006	0.087	-9999	-0.21	50	50
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.12	-9999	-0.29	56	56
alphaV/beta3 Integrin/Osteopontin/Src	-0.006	0.096	-9999	-0.23	73	73
AP1	-0.033	0.17	-9999	-0.35	93	93
ILK	-0.004	0.098	-9999	-0.26	50	50
bone resorption	-0.016	0.11	-9999	-0.25	73	73
PTK2B	0.018	0.013	-9999	-0.11	5	5
PYK2/p130Cas	0.009	0.096	-9999	-0.22	58	58
ITGAV	0	0.072	-9999	-0.26	32	32
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.015	0.083	-9999	-0.19	89	89
alphaV/beta3 Integrin/Osteopontin	0.009	0.096	-9999	-0.21	73	73
MAP3K1	-0.002	0.084	-9999	-0.18	77	77
JUN	-0.002	0.078	-9999	-0.28	37	37
MAPK3	-0.005	0.095	-9999	-0.22	64	64
MAPK1	-0.008	0.1	-9999	-0.23	69	69
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
NFKB1	0.014	0.037	-9999	-0.23	11	11
MAPK8	-0.001	0.08	-9999	-0.17	80	80
ITGB3	0.016	0.018	-9999	-0.12	2	2
NFKBIA	-0.011	0.12	-9999	-0.3	59	59
FOS	-0.047	0.12	-9999	-0.22	146	146
CD44	-0.039	0.12	-9999	-0.25	115	115
CHUK	0.016	0.025	-9999	-0.15	10	10
PLAU	-0.066	0.28	-9999	-1	37	37
NF kappa B1 p50/RelA	0.005	0.12	-9999	-0.3	52	52
BCAR1	0	0	-9999	-10000	0	0
RELA	0.018	0.02	-9999	-0.23	3	3
alphaV beta3 Integrin	0.013	0.058	-9999	-0.18	35	35
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.008	0.098	-9999	-0.22	76	76
VAV3	-0.019	0.1	-9999	-0.23	82	82
MAP3K14	-0.003	0.089	-9999	-0.19	82	82
ROCK2	0.015	0.022	-9999	-0.11	16	16
SPP1	-0.013	0.095	-9999	-0.3	52	52
RAC1	0.015	0.036	-9999	-0.29	7	7
Rac1/GTP	-0.016	0.1	-9999	-0.25	68	68
MMP2	-0.05	0.17	-9999	-0.33	112	112

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.004	0.036	-10000	0	-0.2	16	16
GNB1/GNG2	0.015	0.035	-10000	0	-0.14	21	21
regulation of S phase of mitotic cell cycle	-0.011	0.091	-10000	0	-0.2	84	84
GNAO1	-0.014	0.085	-10000	0	-0.2	81	81
HRAS	0.008	0.055	-10000	0	-0.28	18	18
SHBG/T-DHT	0.013	0	-10000	0	-10000	0	0
PELP1	0.014	0.036	-10000	0	-0.29	7	7
AKT1	0.001	0.042	-10000	0	-0.2	22	22
MAP2K1	0	0.07	-10000	0	-0.13	85	85
T-DHT/AR	0.01	0.017	-10000	0	-0.07	22	22
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.007	82	82
GNAI2	0	0.074	-10000	0	-0.28	34	34
GNAI3	0.014	0.038	-10000	0	-0.29	8	8
GNAI1	-0.046	0.11	-10000	0	-0.2	157	157
mol:GDP	-0.019	0.044	-10000	0	-0.16	26	26
cell proliferation	-0.05	0.18	-10000	0	-0.41	92	92
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
FOS	-0.1	0.29	-10000	0	-0.74	89	89
mol:Ca2+	-0.012	0.03	-10000	0	-0.058	130	130
MAPK3	-0.027	0.12	-10000	0	-0.27	94	94
MAPK1	-0.031	0.14	-10000	0	-0.27	92	92
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:IP3	-0.001	0.002	-10000	0	-0.004	82	82
cAMP biosynthetic process	0.012	0.02	0.065	35	-10000	0	35
GNG2	0	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	82	82
HRAS/GTP	0.017	0.046	-10000	0	-0.15	22	22
actin cytoskeleton reorganization	-0.002	0.068	-10000	0	-0.14	85	85
SRC	0.019	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	82	82
PI3K	-0.011	0.078	-10000	0	-0.18	88	88
apoptosis	0.052	0.18	0.43	91	-10000	0	91
T-DHT/AR/PELP1	0.019	0.026	-10000	0	-0.14	9	9
HRAS/GDP	-0.002	0.061	-10000	0	-0.16	43	43
CREB1	-0.057	0.2	-10000	0	-0.46	91	91
RAC1-CDC42/GTP	0.003	0.072	-10000	0	-0.14	85	85
AR	0.013	0.026	-10000	0	-0.11	22	22
GNB1	0.007	0.061	-10000	0	-0.29	21	21
RAF1	0.005	0.06	-10000	0	-0.19	26	26
RAC1-CDC42/GDP	0.012	0.058	-10000	0	-0.19	20	20
T-DHT/AR/PELP1/Src	0.029	0.026	-10000	0	-0.14	7	7
MAP2K2	0.001	0.067	-10000	0	-0.13	74	74
T-DHT/AR/PELP1/Src/PI3K	-0.011	0.091	-10000	0	-0.2	84	84
GNAZ	-0.008	0.083	-10000	0	-0.23	56	56
SHBG	0.019	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.063	0.2	-10000	0	-0.48	73	73
mol:T-DHT	0	0.001	0.002	2	-0.002	75	77
RAC1	0.015	0.036	-10000	0	-0.29	7	7
GNRH1	0.01	0	-10000	0	-10000	0	0
Gi family/GTP	-0.04	0.1	-10000	0	-0.19	141	141
CDC42	0.017	0.016	-10000	0	-0.11	8	8

×

EPHB forward signaling

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
Ephrin A5/EPHB2	0.022	0.016	-10000	0	-10000	0	0
cell-cell adhesion	0.027	0.054	0.17	50	-10000	0	50
Ephrin B/EPHB2/RasGAP	0.013	0.08	-10000	0	-0.14	94	94
ITSN1	0.016	0.031	-10000	0	-0.29	5	5
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
SHC1	0.004	0.052	-10000	0	-0.14	48	48
Ephrin B1/EPHB3	0.021	0.019	-10000	0	-10000	0	0
Ephrin B1/EPHB1	0.012	0.033	-10000	0	-0.16	6	6
HRAS/GDP	-0.037	0.087	-10000	0	-0.21	84	84
Ephrin B/EPHB1/GRB7	0.01	0.074	-10000	0	-0.14	88	88
Endophilin/SYNJ1	0.001	0.054	-10000	0	-0.12	83	83
KRAS	0.011	0.048	-10000	0	-0.28	14	14
Ephrin B/EPHB1/Src	0.011	0.073	-10000	0	-0.13	88	88
endothelial cell migration	-0.018	0.098	-10000	0	-0.17	134	134
GRB2	0.014	0.039	-10000	0	-0.26	10	10
GRB7	0.016	0.019	-10000	0	-0.11	11	11
PAK1	0.005	0.054	-10000	0	-0.11	83	83
HRAS	0.009	0.055	-10000	0	-0.28	18	18
RRAS	-0.006	0.067	-10000	0	-0.14	89	89
DNM1	0.017	0.017	-10000	0	-0.11	9	9
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.008	0.067	-10000	0	-0.14	88	88
lamellipodium assembly	-0.027	0.054	-10000	0	-0.17	50	50
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.011	0.092	-10000	0	-0.2	90	90
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
EPHB2	0.013	0.027	-10000	0	-0.11	24	24
EPHB3	0.01	0.032	-10000	0	-0.11	35	35
EPHB1	-0.005	0.057	-10000	0	-0.12	91	91
EPHB4	0.019	0.006	-10000	0	-0.11	1	1
mol:GDP	-0.017	0.1	-10000	0	-0.24	83	83
Ephrin B/EPHB2	0.011	0.063	-10000	0	-0.12	83	83
Ephrin B/EPHB3	0.01	0.063	-10000	0	-0.12	83	83
JNK cascade	0.011	0.043	-10000	0	-0.17	18	18
Ephrin B/EPHB1	0.002	0.07	-10000	0	-0.14	88	88
RAP1/GDP	-0.008	0.095	-10000	0	-0.22	83	83
EFNB2	-0.035	0.11	-10000	0	-0.25	105	105
EFNB3	0.016	0.022	-10000	0	-0.13	11	11
EFNB1	0.019	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.009	0.072	-10000	0	-0.15	97	97
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.018	0.019	-10000	0	-0.29	2	2
CDC42/GTP	0.002	0.087	-10000	0	-0.18	84	84
Rap1/GTP	-0.03	0.061	-10000	0	-0.19	51	51
axon guidance	0.022	0.016	-10000	0	-10000	0	0
MAPK3	-0.004	0.085	-10000	0	-0.22	47	47
MAPK1	-0.007	0.092	-10000	0	-0.23	53	53
Rac1/GDP	-0.008	0.1	-10000	0	-0.23	83	83
actin cytoskeleton reorganization	-0.037	0.077	-10000	0	-0.2	69	69
CDC42/GDP	-0.007	0.098	-10000	0	-0.22	83	83
PI3K	-0.015	0.1	-10000	0	-0.17	134	134
EFNA5	0.019	0.006	-10000	0	-0.11	1	1
Ephrin B2/EPHB4	-0.006	0.067	-10000	0	-0.16	83	83
Ephrin B/EPHB2/Intersectin/N-WASP	-0.001	0.081	-10000	0	-0.17	85	85
CDC42	0.017	0.016	-10000	0	-0.11	8	8
RAS family/GTP	-0.036	0.077	-10000	0	-0.2	70	70
PTK2	0.002	0.052	-10000	0	-0.29	16	16
MAP4K4	0.011	0.043	-10000	0	-0.17	18	18
SRC	0.019	0	-10000	0	-10000	0	0
KALRN	0.017	0.018	-10000	0	-0.11	10	10
Intersectin/N-WASP	0.024	0.03	-10000	0	-0.19	10	10
neuron projection morphogenesis	0.009	0.079	-10000	0	-0.18	54	54
MAP2K1	-0.008	0.089	-10000	0	-0.18	92	92
WASL	0.016	0.03	-10000	0	-0.29	5	5
Ephrin B1/EPHB1-2/NCK1	0.027	0.044	-10000	0	-0.14	12	12
cell migration	-0.009	0.097	-10000	0	-0.21	86	86
NRAS	-0.01	0.086	-10000	0	-0.24	59	59
SYNJ1	0.001	0.055	-10000	0	-0.12	83	83
PXN	0.018	0.011	-10000	0	-0.11	4	4
TF	-0.026	0.073	-10000	0	-0.16	104	104
HRAS/GTP	0.001	0.079	-10000	0	-0.18	53	53
Ephrin B1/EPHB1-2	0.02	0.036	-10000	0	-0.11	14	14
cell adhesion mediated by integrin	0.01	0.052	0.12	81	-10000	0	81
RAC1	0.015	0.036	-10000	0	-0.29	7	7
mol:GTP	0.002	0.078	-10000	0	-0.18	46	46
RAC1-CDC42/GTP	-0.026	0.055	-10000	0	-0.16	54	54
RASA1	0.003	0.069	-10000	0	-0.28	29	29
RAC1-CDC42/GDP	0	0.1	-10000	0	-0.22	83	83
ruffle organization	-0.001	0.078	-10000	0	-0.19	54	54
NCK1	0.014	0.036	-10000	0	-0.19	14	14
receptor internalization	0.003	0.052	-10000	0	-0.11	83	83
Ephrin B/EPHB2/KALRN	0.019	0.066	-10000	0	-0.12	83	83
ROCK1	0.019	0.016	-10000	0	-10000	0	0
RAS family/GDP	-0.04	0.083	-10000	0	-0.22	68	68
Rac1/GTP	-0.028	0.057	-10000	0	-0.18	50	50
Ephrin B/EPHB1/Src/Paxillin	-0.005	0.077	-10000	0	-0.17	88	88

×

S1P1 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
VEGFR2 homodimer/VEGFA homodimer	-0.047	0.11	-9999	-0.2	149	149
PDGFRB	0.01	0.044	-9999	-0.18	21	21
SPHK1	-0.005	0.025	-9999	-10000	0	0
mol:S1P	0.001	0.037	-9999	-10000	0	0
S1P1/S1P/Gi	-0.064	0.19	-9999	-0.43	84	84
GNAO1	-0.014	0.086	-9999	-0.2	81	81
PDGFB-D/PDGFRB/PLCgamma1	-0.055	0.17	-9999	-0.42	66	66
PLCG1	-0.058	0.18	-9999	-0.41	78	78
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.044	-9999	-0.18	21	21
GNAI2	0	0.074	-9999	-0.28	34	34
GNAI3	0.014	0.038	-9999	-0.3	8	8
GNAI1	-0.046	0.11	-9999	-0.2	157	157
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.044	0.12	-9999	-0.2	141	141
S1P1/S1P	-0.034	0.11	-9999	-0.3	49	49
negative regulation of cAMP metabolic process	-0.063	0.19	-9999	-0.41	86	86
MAPK3	-0.058	0.18	-9999	-0.48	62	62
calcium-dependent phospholipase C activity	-0.001	0.002	-9999	-10000	0	0
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
RhoA/GDP	0.011	0.024	-9999	-0.2	7	7
KDR	-0.002	0.067	-9999	-0.15	72	72
PLCB2	-0.027	0.098	-9999	-0.27	48	48
RAC1	0.015	0.036	-9999	-0.29	7	7
RhoA/GTP	-0.042	0.085	-9999	-0.27	46	46
receptor internalization	-0.032	0.1	-9999	-0.28	49	49
PTGS2	-0.063	0.17	-9999	-0.55	41	41
Rac1/GTP	-0.042	0.087	-9999	-0.28	43	43
RHOA	0.015	0.036	-9999	-0.29	7	7
VEGFA	-0.07	0.13	-9999	-0.25	156	156
negative regulation of T cell proliferation	-0.063	0.19	-9999	-0.41	86	86
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.008	0.084	-9999	-0.24	56	56
MAPK1	-0.061	0.19	-9999	-0.49	64	64
S1P1/S1P/PDGFB-D/PDGFRB	-0.034	0.12	-9999	-0.32	55	55
ABCC1	0.014	0.024	-9999	-0.12	17	17

×

Signaling events mediated by VEGFR1 and VEGFR2

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.016	0.048	-9999	-0.19	25	25
AKT1	-0.081	0.21	-9999	-0.44	94	94
PTK2B	-0.033	0.11	-9999	-0.29	56	56
VEGFR2 homodimer/Frs2	0.006	0.089	-9999	-0.34	22	22
CAV1	-0.071	0.13	-9999	-0.22	197	197
CALM1	0.007	0.056	-9999	-0.21	28	28
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.034	0.12	-9999	-0.29	56	56
endothelial cell proliferation	-0.049	0.17	-9999	-0.36	80	80
mol:Ca2+	-0.041	0.13	-9999	-0.27	87	87
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.035	0.13	-9999	-0.31	63	63
RP11-342D11.1	-0.048	0.13	-9999	-0.28	86	86
CDH5	-0.016	0.088	-9999	-0.2	84	84
VEGFA homodimer	-0.017	0.079	-9999	-0.15	122	122
SHC1	0.004	0.052	-9999	-0.14	48	48
SHC2	0.001	0.071	-9999	-0.26	35	35
HRAS/GDP	-0.06	0.11	-9999	-0.31	64	64
SH2D2A	0.019	0.006	-9999	-0.11	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.027	0.14	-9999	-0.41	41	41
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.033	0.12	-9999	-0.3	54	54
VEGFR1 homodimer	0.019	0.008	-9999	-0.11	2	2
SHC/GRB2/SOS1	-0.033	0.14	-9999	-0.32	65	65
GRB10	-0.057	0.16	-9999	-0.41	67	67
PTPN11	0.015	0.033	-9999	-0.27	7	7
GRB2	0.014	0.039	-9999	-0.26	10	10
PAK1	0.017	0.017	-9999	-0.11	9	9
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.04	0.14	-9999	-0.32	71	71
HRAS	0.009	0.055	-9999	-0.28	18	18
VEGF/Rho/ROCK1/Integrin Complex	-0.032	0.14	-9999	-0.35	50	50
HIF1A	0.011	0.047	-9999	-0.27	14	14
FRS2	0.018	0.013	-9999	-0.11	5	5
oxygen and reactive oxygen species metabolic process	-0.035	0.13	-9999	-0.31	63	63
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.019	0.006	-9999	-0.11	1	1
Nck/Pak	0.023	0.029	-9999	-0.18	8	8
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.051	0.14	-9999	-0.32	75	75
mol:GDP	-0.038	0.13	-9999	-0.31	65	65
mol:NADP	-0.027	0.12	-9999	-0.39	33	33
eNOS/Hsp90	-0.018	0.12	-9999	-0.37	33	33
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
mol:IP3	-0.042	0.13	-9999	-0.28	87	87
HIF1A/ARNT	0.023	0.033	-9999	-0.19	12	12
SHB	0.016	0.02	-9999	-0.11	13	13
VEGFA	-0.072	0.13	-9999	-0.23	188	188
VEGFC	0.01	0.033	-9999	-10000	0	0
FAK1/Vinculin	-0.045	0.17	-9999	-0.4	63	63
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.015	0.036	-9999	-0.29	7	7
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.027	0.13	-9999	-0.3	57	57
PTPN6	0.005	0.057	-9999	-0.2	33	33
EPAS1	0.003	0.076	-9999	-0.28	28	28
mol:L-citrulline	-0.027	0.12	-9999	-0.39	33	33
ITGAV	0.003	0.067	-9999	-0.25	32	32
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.023	0.12	-9999	-0.3	49	49
VEGFR2 homodimer/VEGFA homodimer	-0.04	0.15	-9999	-0.3	86	86
VEGFR2/3 heterodimer	0.006	0.089	-9999	-0.34	22	22
VEGFB	0.017	0.023	-9999	-0.29	3	3
MAPK11	-0.046	0.14	-9999	-0.34	62	62
VEGFR2 homodimer	-0.003	0.1	-9999	-0.38	25	25
FLT1	0.019	0.008	-9999	-0.11	2	2
NEDD4	0.009	0.033	-9999	-0.12	25	25
MAPK3	-0.037	0.12	-9999	-0.3	56	56
MAPK1	-0.039	0.12	-9999	-0.31	58	58
VEGFA145/NRP2	-0.037	0.093	-9999	-0.19	125	125
VEGFR1/2 heterodimer	0.006	0.089	-9999	-0.34	22	22
KDR	-0.003	0.1	-9999	-0.38	25	25
VEGFA165/NRP1/VEGFR2 homodimer	-0.031	0.13	-9999	-0.3	68	68
SRC	0.019	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.038	0.12	-9999	-0.32	56	56
PI3K	-0.06	0.18	-9999	-0.4	85	85
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.036	0.12	-9999	-0.28	63	63
FES	-0.042	0.13	-9999	-0.28	86	86
GAB1	-0.063	0.17	-9999	-0.39	76	76
VEGFR2 homodimer/VEGFA homodimer/Src	-0.033	0.12	-9999	-0.29	54	54
CTNNB1	0.017	0.023	-9999	-0.29	3	3
SOS1	0	0	-9999	-10000	0	0
ARNT	0.019	0.006	-9999	-0.11	1	1
eNOS/Caveolin-1	-0.043	0.14	-9999	-0.35	57	57
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.04	0.13	-9999	-0.29	69	69
PI3K/GAB1	-0.076	0.2	-9999	-0.37	141	141
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.015	0.12	-9999	-0.28	50	50
PRKACA	0.019	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.014	0.088	-9999	-0.32	23	23
HSP90AA1	0.018	0.019	-9999	-0.29	2	2
CDC42	-0.042	0.13	-9999	-0.28	86	86
actin cytoskeleton reorganization	-0.033	0.12	-9999	-0.29	54	54
PTK2	-0.056	0.18	-9999	-0.43	61	61
EDG1	-0.048	0.15	-9999	-0.35	72	72
mol:DAG	-0.042	0.13	-9999	-0.28	87	87
CaM/Ca2+	-0.036	0.13	-9999	-0.33	58	58
MAP2K3	-0.037	0.12	-9999	-0.3	64	64
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.047	0.17	-9999	-0.41	69	69
PLCG1	-0.042	0.13	-9999	-0.28	87	87
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.021	0.12	-9999	-0.3	46	46
IQGAP1	-0.009	0.087	-9999	-0.27	50	50
YES1	0.005	0.061	-9999	-0.24	28	28
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.035	0.12	-9999	-0.3	58	58
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.04	0.12	-9999	-0.27	70	70
cell migration	-0.047	0.18	-9999	-0.41	68	68
mol:PI-3-4-5-P3	-0.056	0.17	-9999	-0.37	85	85
FYN	-0.019	0.1	-9999	-0.28	68	68
VEGFB/NRP1	-0.038	0.12	-9999	-0.3	64	64
mol:NO	-0.027	0.12	-9999	-0.39	33	33
PXN	0.018	0.011	-9999	-0.11	4	4
HRAS/GTP	-0.062	0.11	-9999	-0.31	64	64
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.05	0.16	-9999	-0.41	67	67
VHL	0	0	-9999	-10000	0	0
ITGB3	0.019	0.008	-9999	-0.11	2	2
NOS3	-0.032	0.14	-9999	-0.43	33	33
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.041	0.14	-9999	-0.32	63	63
RAC1	0.015	0.036	-9999	-0.29	7	7
PRKCA	-0.036	0.12	-9999	-0.29	66	66
PRKCB	-0.042	0.12	-9999	-0.26	87	87
VCL	0.017	0.023	-9999	-0.29	3	3
VEGFA165/NRP1	-0.044	0.13	-9999	-0.28	86	86
VEGFR1/2 heterodimer/VEGFA homodimer	-0.033	0.12	-9999	-0.29	57	57
VEGFA165/NRP2	-0.037	0.093	-9999	-0.19	125	125
MAPKKK cascade	-0.041	0.15	-9999	-0.35	77	77
NRP2	0.017	0.016	-9999	-0.11	8	8
VEGFC homodimer	0.01	0.033	-9999	-10000	0	0
NCK1	0.014	0.036	-9999	-0.19	14	14
ROCK1	0.016	0.031	-9999	-0.26	6	6
FAK1/Paxillin	-0.045	0.17	-9999	-0.4	61	61
MAP3K13	-0.041	0.13	-9999	-0.28	86	86
PDPK1	-0.052	0.15	-9999	-0.33	85	85

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.017	0.12	0.19	1	-0.29	70	71
IKBKB	0.008	0.072	0.2	8	-0.21	23	31
AKT1	-0.018	0.072	0.16	3	-0.18	61	64
IKBKG	0.005	0.073	0.18	2	-0.21	35	37
CALM1	-0.03	0.14	0.18	18	-0.36	64	82
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
MAP3K1	-0.017	0.13	-10000	0	-0.39	44	44
MAP3K7	0.007	0.059	-10000	0	-0.25	24	24
mol:Ca2+	-0.031	0.15	0.18	20	-0.38	61	81
DOK1	0.019	0	-10000	0	-10000	0	0
AP-1	-0.016	0.091	0.14	10	-0.21	71	81
LYN	-0.018	0.098	-10000	0	-0.25	72	72
BLNK	-0.036	0.11	-10000	0	-0.29	66	66
SHC1	0.004	0.052	-10000	0	-0.14	48	48
BCR complex	0.027	0.013	-10000	0	-0.14	2	2
CD22	-0.029	0.11	-10000	0	-0.36	42	42
CAMK2G	-0.028	0.14	0.18	18	-0.33	65	83
CSNK2A1	0.01	0.053	-10000	0	-0.29	16	16
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.041	0.081	-10000	0	-0.27	46	46
GO:0007205	-0.032	0.15	0.18	20	-0.38	61	81
SYK	-0.005	0.072	-10000	0	-0.29	25	25
ELK1	-0.026	0.14	0.18	20	-0.36	60	80
NFATC1	-0.019	0.1	-10000	0	-0.32	44	44
B-cell antigen/BCR complex	0.027	0.013	-10000	0	-0.14	2	2
PAG1/CSK	0.01	0.03	-10000	0	-0.2	11	11
NFKBIB	0.011	0.033	0.09	1	-0.13	11	12
HRAS	-0.026	0.13	0.17	8	-0.34	55	63
NFKBIA	0.013	0.029	0.09	1	-0.13	6	7
NF-kappa-B/RelA/I kappa B beta	0.016	0.03	0.092	1	-0.13	9	10
RasGAP/Csk	-0.012	0.082	-10000	0	-0.13	145	145
mol:GDP	-0.028	0.15	0.18	20	-0.37	60	80
PTEN	0.013	0.038	-10000	0	-0.18	17	17
CD79B	0.018	0.011	-10000	0	-0.11	4	4
NF-kappa-B/RelA/I kappa B alpha	0.017	0.028	0.092	2	-0.11	9	11
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PI3K/BCAP/CD19	-0.053	0.17	-10000	0	-0.43	70	70
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:IP3	-0.032	0.15	0.18	20	-0.39	61	81
CSK	0.013	0.044	-10000	0	-0.29	11	11
FOS	-0.044	0.14	0.17	13	-0.35	68	81
CHUK	0.003	0.075	0.18	2	-0.22	32	34
IBTK	0.014	0.039	-10000	0	-0.26	10	10
CARD11/BCL10/MALT1/TAK1	-0.019	0.13	0.22	2	-0.33	63	65
PTPN6	-0.029	0.12	-10000	0	-0.36	46	46
RELA	0.018	0.02	-10000	0	-0.23	3	3
BCL2A1	0.007	0.03	-10000	0	-0.077	42	42
VAV2	-0.028	0.12	-10000	0	-0.4	40	40
ubiquitin-dependent protein catabolic process	0.015	0.032	0.092	1	-0.12	11	12
BTK	0.012	0.009	-10000	0	-10000	0	0
CD19	-0.03	0.11	-10000	0	-0.36	42	42
MAP4K1	0.019	0.006	-10000	0	-0.11	1	1
CD72	0.016	0.019	-10000	0	-0.11	12	12
PAG1	0	0	-10000	0	-10000	0	0
MAPK14	-0.01	0.11	-10000	0	-0.33	45	45
SH3BP5	-0.003	0.075	-10000	0	-0.22	48	48
PIK3AP1	-0.034	0.16	0.19	20	-0.41	61	81
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.035	0.19	-10000	0	-0.48	66	66
RAF1	-0.024	0.13	0.17	8	-0.35	50	58
RasGAP/p62DOK/SHIP	-0.013	0.069	-10000	0	-0.12	142	142
CD79A	0.018	0.013	-10000	0	-10000	0	0
re-entry into mitotic cell cycle	-0.016	0.09	0.14	10	-0.21	71	81
RASA1	0.003	0.069	-10000	0	-0.28	29	29
MAPK3	-0.013	0.11	0.15	7	-0.3	48	55
MAPK1	-0.016	0.11	0.15	7	-0.3	54	61
CD72/SHP1	-0.02	0.11	-10000	0	-0.35	45	45
NFKB1	0.014	0.037	-10000	0	-0.23	11	11
MAPK8	-0.009	0.11	-10000	0	-0.33	44	44
actin cytoskeleton organization	-0.021	0.11	-10000	0	-0.35	42	42
NF-kappa-B/RelA	0.029	0.072	0.18	1	-0.25	18	19
Calcineurin	-0.016	0.13	-10000	0	-0.35	51	51
PI3K	-0.053	0.11	-10000	0	-0.31	60	60
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.036	0.17	0.2	20	-0.44	61	81
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.019	0.14	-10000	0	-0.46	40	40
DAPP1	-0.032	0.15	-10000	0	-0.5	40	40
cytokine secretion	-0.017	0.097	-10000	0	-0.3	44	44
mol:DAG	-0.032	0.15	0.18	20	-0.39	61	81
PLCG2	-0.002	0.069	-10000	0	-0.19	52	52
MAP2K1	-0.02	0.12	0.16	7	-0.34	48	55
B-cell antigen/BCR complex/FcgammaRIIB	-0.023	0.077	-10000	0	-0.15	118	118
mol:PI-3-4-5-P3	-0.04	0.078	0.16	4	-0.23	57	61
ETS1	-0.02	0.12	0.18	18	-0.3	64	82
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.005	0.11	-10000	0	-0.27	50	50
B-cell antigen/BCR complex/LYN	-0.034	0.12	-10000	0	-0.31	69	69
MALT1	0.013	0.036	-10000	0	-0.16	18	18
TRAF6	0.018	0.019	-10000	0	-0.29	2	2
RAC1	-0.023	0.12	-10000	0	-0.37	42	42
B-cell antigen/BCR complex/LYN/SYK	-0.01	0.12	-10000	0	-0.32	57	57
CARD11	-0.03	0.14	0.18	20	-0.36	61	81
FCGR2B	-0.078	0.12	-10000	0	-0.2	234	234
PPP3CA	0.002	0.069	-10000	0	-0.27	31	31
BCL10	0.016	0.028	-10000	0	-0.23	6	6
IKK complex	0.011	0.034	0.1	9	-0.085	18	27
PTPRC	-0.031	0.11	-10000	0	-0.23	107	107
PDPK1	-0.015	0.062	0.15	3	-0.16	56	59
PPP3CB	0.016	0.024	-10000	0	-0.15	9	9
PPP3CC	0.019	0	-10000	0	-10000	0	0
POU2F2	0.014	0.025	-10000	0	-0.082	17	17

×

S1P3 pathway

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
PDGFRB	0.011	0.043	-9999	-0.18	21	21
mol:S1P	0.001	0.001	-9999	-10000	0	0
S1P1/S1P/Gi	-0.048	0.14	-9999	-0.24	147	147
GNAO1	-0.012	0.085	-9999	-0.2	81	81
S1P/S1P3/G12/G13	0.012	0.045	-9999	-0.14	39	39
AKT1	-0.026	0.16	-9999	-0.62	30	30
AKT3	-0.055	0.14	-9999	-0.55	18	18
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.011	0.043	-9999	-0.18	21	21
GNAI2	0.002	0.074	-9999	-0.28	34	34
GNAI3	0.016	0.038	-9999	-0.29	8	8
GNAI1	-0.044	0.11	-9999	-0.2	157	157
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.001	0.001	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0.001	0.068	-9999	-0.22	39	39
mol:Ca2+	-0.036	0.12	-9999	-0.28	73	73
MAPK3	-0.031	0.12	-9999	-0.31	53	53
MAPK1	-0.034	0.12	-9999	-0.32	58	58
JAK2	-0.04	0.13	-9999	-0.3	75	75
CXCR4	-0.048	0.13	-9999	-0.28	97	97
FLT1	0.021	0.008	-9999	-0.11	2	2
RhoA/GDP	0.011	0.024	-9999	-0.2	7	7
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
SRC	-0.031	0.12	-9999	-0.28	65	65
S1P/S1P3/Gi	-0.037	0.12	-9999	-0.28	73	73
RAC1	0.015	0.036	-9999	-0.29	7	7
RhoA/GTP	-0.026	0.12	-9999	-0.3	55	55
VEGFA	-0.065	0.13	-9999	-0.22	188	188
S1P/S1P2/Gi	-0.04	0.12	-9999	-0.21	141	141
VEGFR1 homodimer/VEGFA homodimer	-0.028	0.093	-9999	-0.19	119	119
RHOA	0.015	0.036	-9999	-0.29	7	7
S1P/S1P3/Gq	0.012	0.045	-9999	-0.16	29	29
GNAQ	0.015	0.023	-9999	-0.11	17	17
GNAZ	-0.006	0.083	-9999	-0.23	56	56
G12/G13	0.009	0.059	-9999	-0.19	39	39
GNA14	0.015	0.022	-9999	-0.11	15	15
GNA15	0.012	0.033	-9999	-0.12	26	26
GNA12	-0.005	0.082	-9999	-0.29	39	39
GNA13	0.016	0.021	-9999	-0.11	14	14
GNA11	0.003	0.069	-9999	-0.29	27	27
Rac1/GTP	-0.026	0.12	-9999	-0.31	54	54

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.011	0.019	-10000	0	-10000	0	0
CDKN2C	-0.011	0.091	-10000	0	-0.24	69	69
CDKN2A	-0.016	0.058	-10000	0	-0.11	138	138
CCND2	0.002	0.034	0.13	28	-0.099	2	30
RB1	-0.003	0.037	-10000	0	-0.14	28	28
CDK4	0.003	0.039	0.15	28	-0.13	3	31
CDK6	0.006	0.037	0.15	28	-10000	0	28
G1/S progression	0.001	0.042	0.14	36	-10000	0	36

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.018	0.057	-10000	0	-0.16	41	41
fibroblast growth factor receptor signaling pathway	0.017	0.057	-10000	0	-0.16	41	41
LAMA1	0	0	-10000	0	-10000	0	0
PRNP	-0.002	0.076	-10000	0	-0.26	41	41
GPC1/SLIT2	-0.007	0.068	-10000	0	-0.2	40	40
SMAD2	0.01	0.05	-10000	0	-0.14	43	43
GPC1/PrPc/Cu2+	-0.002	0.072	-10000	0	-0.19	57	57
GPC1/Laminin alpha1	-0.005	0.056	-10000	0	-0.15	62	62
TDGF1	0.018	0.014	-10000	0	-0.11	6	6
CRIPTO/GPC1	0.008	0.061	-10000	0	-0.2	37	37
APP/GPC1	0.005	0.069	-10000	0	-0.22	41	41
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.006	0.059	-10000	0	-0.18	40	40
FLT1	0.019	0.008	-10000	0	-0.11	2	2
GPC1/TGFB/TGFBR1/TGFBR2	0.018	0.056	-10000	0	-0.16	42	42
SERPINC1	0.019	0.006	-10000	0	-0.11	1	1
FYN	-0.001	0.079	-10000	0	-0.27	38	38
FGR	0.003	0.058	-10000	0	-0.18	39	39
positive regulation of MAPKKK cascade	-0.036	0.15	-10000	0	-0.34	78	78
SLIT2	-0.005	0.05	-10000	0	-0.11	97	97
GPC1/NRG	0.009	0.058	-10000	0	-0.19	37	37
NRG1	0.019	0	-10000	0	-10000	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.031	0.094	-10000	0	-0.17	144	144
LYN	0.002	0.06	-10000	0	-0.19	39	39
mol:Spermine	-0.008	0.055	-10000	0	-0.2	37	37
cell growth	0.017	0.057	-10000	0	-0.16	41	41
BMP signaling pathway	0.009	0.082	0.22	62	-10000	0	62
SRC	0.009	0.049	-10000	0	-0.16	37	37
TGFBR1	0.019	0.006	-10000	0	-0.11	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.078	0.11	-10000	0	-0.17	272	272
GPC1	-0.009	0.082	-10000	0	-0.22	62	62
TGFBR1 (dimer)	0.019	0.006	-10000	0	-0.11	1	1
VEGFA	-0.068	0.13	-10000	0	-0.22	188	188
BLK	0.009	0.049	-10000	0	-0.16	37	37
HCK	-0.004	0.067	-10000	0	-0.21	41	41
FGF2	0.013	0.036	-10000	0	-0.16	19	19
FGFR1	0.019	0.008	-10000	0	-10000	0	0
VEGFR1 homodimer	0.019	0.008	-10000	0	-0.11	2	2
TGFBR2	0.013	0.035	-10000	0	-0.14	21	21
cell death	0.005	0.069	-10000	0	-0.22	41	41
ATIII/GPC1	0.009	0.059	-10000	0	-0.19	37	37
PLA2G2A/GPC1	-0.058	0.094	-10000	0	-0.21	124	124
LCK	0.008	0.051	-10000	0	-0.17	37	37
neuron differentiation	0.009	0.058	-10000	0	-0.19	37	37
PrPc/Cu2+	0	0.052	-10000	0	-0.17	41	41
APP	0.013	0.042	-10000	0	-0.29	10	10
TGFBR2 (dimer)	0.012	0.035	-10000	0	-0.14	21	21

×

PLK2 and PLK4 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
PLK2	-0.013	0.083	-9999	-0.19	82	82
PLK4	0.017	0.017	-9999	-0.11	9	9
regulation of centriole replication	-0.002	0.058	-9999	-0.19	40	40

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.017	0.14	-10000	0	-0.28	85	85
adherens junction organization	0	0.098	-10000	0	-0.3	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.033	0.13	-10000	0	-0.29	70	70
FMN1	0.001	0.086	-10000	0	-0.26	37	37
mol:IP3	-0.009	0.11	-10000	0	-0.26	57	57
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.002	0.091	-10000	0	-0.28	37	37
CTNNB1	0.017	0.024	-10000	0	-0.3	3	3
AKT1	-0.008	0.12	-10000	0	-0.3	57	57
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.016	0.085	-10000	0	-0.37	18	18
CTNND1	0	0.075	-10000	0	-0.3	31	31
mol:PI-4-5-P2	0.005	0.085	-10000	0	-0.24	40	40
VASP	0.005	0.088	-10000	0	-0.3	30	30
ZYX	-0.006	0.11	-10000	0	-0.33	41	41
JUB	0.001	0.086	-10000	0	-0.26	37	37
EGFR(dimer)	-0.02	0.11	-10000	0	-0.29	51	51
E-cadherin/beta catenin-gamma catenin	0.027	0.037	-10000	0	-0.11	28	28
mol:PI-3-4-5-P3	-0.004	0.12	-10000	0	-0.28	57	57
PIK3CA	-0.012	0.088	-10000	0	-0.23	66	66
PI3K	-0.004	0.12	-10000	0	-0.28	57	57
FYN	-0.028	0.16	-10000	0	-0.4	70	70
mol:Ca2+	-0.009	0.11	-10000	0	-0.26	57	57
JUP	0.007	0.037	-10000	0	-0.11	47	47
PIK3R1	-0.015	0.097	-10000	0	-0.27	62	62
mol:DAG	-0.009	0.11	-10000	0	-0.26	57	57
CDH1	0.011	0.03	-10000	0	-0.11	29	29
RhoA/GDP	-0.033	0.12	-10000	0	-0.29	71	71
establishment of polarity of embryonic epithelium	0.005	0.087	-10000	0	-0.29	31	31
SRC	0.019	0	-10000	0	-10000	0	0
RAC1	0.015	0.036	-10000	0	-0.29	7	7
RHOA	0.015	0.036	-10000	0	-0.29	7	7
EGFR	-0.08	0.12	-10000	0	-0.29	97	97
CASR	-0.005	0.1	-10000	0	-0.24	57	57
RhoA/GTP	-0.001	0.1	-10000	0	-0.28	45	45
AKT2	-0.003	0.11	-10000	0	-0.28	48	48
actin cable formation	0.004	0.086	-10000	0	-0.29	31	31
apoptosis	0.013	0.13	0.25	85	-10000	0	85
CTNNA1	0.011	0.05	-10000	0	-0.3	13	13
mol:GDP	-0.036	0.13	-10000	0	-0.28	81	81
PIP5K1A	0.005	0.087	-10000	0	-0.25	40	40
PLCG1	-0.01	0.11	-10000	0	-0.27	57	57
Rac1/GTP	-0.025	0.11	-10000	0	-0.28	50	50
homophilic cell adhesion	-0.001	0.003	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.025	0.006	-10000	0	-10000	0	0
NFATC2	0.015	0.16	-10000	0	-0.44	34	34
NFATC3	-0.005	0.1	0.29	12	-0.22	72	84
CD40LG	-0.08	0.3	-10000	0	-0.71	79	79
ITCH	0.019	0.047	-10000	0	-0.19	9	9
CBLB	0.019	0.046	-10000	0	-0.2	7	7
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.014	0.2	-10000	0	-0.51	43	43
JUNB	-0.003	0.067	-10000	0	-0.17	63	63
CaM/Ca2+/Calcineurin A alpha-beta B1	0.018	0.057	-10000	0	-0.21	16	16
T cell anergy	0.006	0.06	-10000	0	-0.27	10	10
TLE4	0.022	0.11	-10000	0	-0.3	30	30
Jun/NFAT1-c-4/p21SNFT	-0.051	0.31	-10000	0	-0.73	78	78
AP-1/NFAT1-c-4	-0.063	0.36	-10000	0	-0.8	79	79
IKZF1	0.023	0.1	-10000	0	-0.29	32	32
T-helper 2 cell differentiation	0.006	0.14	-10000	0	-0.46	24	24
AP-1/NFAT1	-0.006	0.16	-10000	0	-0.33	74	74
CALM1	0.014	0.051	-10000	0	-0.2	19	19
EGR2	-0.087	0.42	0.5	3	-0.99	78	81
EGR3	-0.095	0.42	0.49	3	-1	75	78
NFAT1/FOXP3	0.036	0.11	-10000	0	-0.29	32	32
EGR1	-0.032	0.11	-10000	0	-0.24	107	107
JUN	-0.002	0.074	-10000	0	-0.28	33	33
EGR4	0.019	0.013	-10000	0	-0.11	5	5
mol:Ca2+	0.004	0.02	-10000	0	-10000	0	0
GBP3	0.011	0.1	-10000	0	-0.3	32	32
FOSL1	0.007	0.038	-10000	0	-0.11	51	51
NFAT1-c-4/MAF/IRF4	-0.029	0.31	-10000	0	-0.71	79	79
DGKA	0.023	0.1	-10000	0	-0.29	30	30
CREM	0.017	0.014	-10000	0	-0.11	6	6
NFAT1-c-4/PPARG	-0.042	0.31	-10000	0	-0.73	79	79
CTLA4	0.027	0.084	-10000	0	-0.23	32	32
NFAT1-c-4 (dimer)/EGR1	-0.058	0.33	-10000	0	-0.79	79	79
NFAT1-c-4 (dimer)/EGR4	-0.034	0.31	-10000	0	-0.73	79	79
FOS	-0.041	0.11	-10000	0	-0.21	133	133
IFNG	0.01	0.13	-10000	0	-0.43	12	12
T cell activation	-0.034	0.2	-10000	0	-0.6	37	37
MAF	0.008	0.059	-10000	0	-0.27	22	22
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.033	0.25	0.59	77	-0.48	6	83
TNF	-0.055	0.3	-10000	0	-0.71	79	79
FASLG	-0.1	0.43	-10000	0	-1.1	79	79
TBX21	0.025	0.007	-10000	0	-0.1	1	1
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.018	0.024	-10000	0	-0.11	19	19
PTPN1	0.018	0.13	-10000	0	-0.38	33	33
NFAT1-c-4/ICER1	-0.043	0.31	-10000	0	-0.73	79	79
GATA3	0.02	0.018	-10000	0	-0.11	10	10
T-helper 1 cell differentiation	0.01	0.13	-10000	0	-0.42	13	13
IL2RA	-0.017	0.2	-10000	0	-0.49	52	52
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.013	0.13	-10000	0	-0.38	40	40
E2F1	0.012	0.045	-10000	0	-0.22	15	15
PPARG	0.015	0.023	-10000	0	-0.11	18	18
SLC3A2	0.01	0.14	-10000	0	-0.46	32	32
IRF4	0.019	0.006	-10000	0	-0.11	1	1
PTGS2	-0.088	0.3	-10000	0	-0.71	79	79
CSF2	-0.08	0.3	-10000	0	-0.71	79	79
JunB/Fra1/NFAT1-c-4	-0.042	0.31	-10000	0	-0.72	79	79
IL4	0.005	0.15	-10000	0	-0.48	23	23
IL5	-0.08	0.3	-10000	0	-0.71	79	79
IL2	-0.035	0.2	-10000	0	-0.61	37	37
IL3	-0.006	0.061	-10000	0	-0.64	2	2
RNF128	0.006	0.065	-10000	0	-0.26	7	7
NFATC1	-0.033	0.25	0.48	6	-0.59	77	83
CDK4	-0.012	0.26	0.49	28	-1.1	15	43
PTPRK	-0.003	0.17	-10000	0	-0.48	51	51
IL8	-0.12	0.32	-10000	0	-0.74	86	86
POU2F1	0.022	0.028	-10000	0	-0.29	2	2

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.01	0.26	-10000	0	-0.68	44	44
CRP	-0.008	0.26	-10000	0	-0.68	44	44
cell cycle arrest	-0.025	0.3	-10000	0	-0.74	55	55
TIMP1	-0.084	0.36	-10000	0	-0.8	93	93
IL6ST	0.003	0.075	-10000	0	-0.28	32	32
Rac1/GDP	0.031	0.11	0.23	8	-0.33	25	33
AP1	-0.032	0.22	-10000	0	-0.57	58	58
GAB2	-0.004	0.082	-10000	0	-0.27	44	44
TNFSF11	-0.008	0.26	-10000	0	-0.7	40	40
HSP90B1	-0.035	0.29	-10000	0	-1	38	38
GAB1	0.004	0.056	-10000	0	-0.15	49	49
MAPK14	0.033	0.075	-10000	0	-0.31	11	11
AKT1	-0.019	0.2	-10000	0	-0.57	43	43
FOXO1	-0.026	0.2	-10000	0	-0.57	46	46
MAP2K6	0.029	0.085	0.22	8	-0.27	23	31
mol:GTP	0	0.003	-10000	0	-10000	0	0
MAP2K4	0.029	0.14	-10000	0	-0.36	34	34
MITF	0.023	0.098	0.23	8	-0.29	27	35
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.007	0.06	-10000	0	-0.28	21	21
A2M	-0.072	0.32	-10000	0	-1.3	36	36
CEBPB	0.002	0.078	-10000	0	-0.22	51	51
GRB2/SOS1/GAB family/SHP2	-0.016	0.16	-10000	0	-0.47	47	47
STAT3	-0.031	0.32	-10000	0	-0.8	55	55
STAT1	0.011	0.066	-10000	0	-0.79	3	3
CEBPD	-0.042	0.34	-10000	0	-0.93	55	55
PIK3CA	-0.01	0.086	-10000	0	-0.22	66	66
PI3K	-0.014	0.094	-10000	0	-0.21	88	88
JUN	-0.002	0.077	-10000	0	-0.28	37	37
PIAS3/MITF	0.028	0.1	0.22	7	-0.27	31	38
MAPK11	0.034	0.075	-10000	0	-0.31	10	10
STAT3 (dimer)/FOXO1	-0.036	0.31	-10000	0	-0.67	80	80
GRB2/SOS1/GAB family	-0.006	0.13	-10000	0	-0.31	60	60
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.015	0.13	-10000	0	-0.28	70	70
GRB2	0.015	0.039	-10000	0	-0.26	10	10
JAK2	0.013	0.026	-10000	0	-10000	0	0
LBP	-0.007	0.25	-10000	0	-0.63	48	48
PIK3R1	-0.014	0.095	-10000	0	-0.27	62	62
JAK1	0.003	0.073	-10000	0	-0.26	34	34
MYC	-0.069	0.37	-10000	0	-0.87	80	80
FGG	-0.009	0.26	-10000	0	-0.72	38	38
macrophage differentiation	-0.025	0.3	-10000	0	-0.74	55	55
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.034	0.07	-10000	0	-0.19	31	31
JUNB	-0.027	0.29	-10000	0	-0.77	49	49
FOS	-0.046	0.12	-10000	0	-0.22	146	146
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.024	0.1	0.24	8	-0.3	27	35
STAT1/PIAS1	0.024	0.12	0.26	8	-0.31	31	39
GRB2/SOS1/GAB family/SHP2/PI3K	-0.02	0.19	-10000	0	-0.48	53	53
STAT3 (dimer)	-0.029	0.31	-10000	0	-0.79	55	55
PRKCD	0.025	0.18	-10000	0	-0.42	45	45
IL6R	0.021	0.007	-10000	0	-10000	0	0
SOCS3	0.035	0.069	-10000	0	-10000	0	0
gp130 (dimer)/JAK1/JAK1/LMO4	0.019	0.088	-10000	0	-0.21	54	54
Rac1/GTP	0.029	0.12	0.24	1	-0.33	29	30
HCK	-0.033	0.11	-10000	0	-0.21	120	120
MAPKKK cascade	-0.026	0.21	-10000	0	-0.64	46	46
bone resorption	-0.005	0.24	-10000	0	-0.65	42	42
IRF1	-0.024	0.29	-10000	0	-0.78	48	48
mol:GDP	0.025	0.1	0.24	8	-0.3	25	33
SOS1	0.001	0.004	-10000	0	-10000	0	0
VAV1	0.025	0.1	0.24	8	-0.3	25	33
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.026	0.089	-10000	0	-0.35	21	21
PTPN11	0.011	0.094	-10000	0	-0.84	6	6
IL6/IL6RA	0.014	0.038	-10000	0	-10000	0	0
gp130 (dimer)/TYK2/TYK2/LMO4	0.021	0.081	-10000	0	-0.22	46	46
gp130 (dimer)/JAK2/JAK2/LMO4	0.024	0.065	-10000	0	-0.19	38	38
IL6	-0.004	0.052	-10000	0	-0.11	101	101
PIAS3	0.014	0.033	-10000	0	-0.19	12	12
PTPRE	-0.016	0.085	-10000	0	-0.24	61	61
PIAS1	0.008	0.056	-10000	0	-0.29	18	18
RAC1	0.015	0.036	-10000	0	-0.3	7	7
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.021	0.081	0.2	13	-0.24	30	43
LMO4	0.014	0.053	-10000	0	-0.3	14	14
STAT3 (dimer)/PIAS3	-0.021	0.29	-10000	0	-0.73	55	55
MCL1	-0.012	0.18	-10000	0	-0.66	26	26

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.014	0.049	-9999	-0.19	25	25
VLDLR	-0.021	0.093	-9999	-0.2	97	97
CRKL	0.018	0.01	-9999	-0.11	3	3
LRPAP1	0.013	0.043	-9999	-0.28	11	11
FYN	-0.019	0.1	-9999	-0.28	68	68
ITGA3	0.005	0.042	-9999	-0.11	57	57
RELN/VLDLR/Fyn	-0.016	0.085	-9999	-0.17	108	108
MAPK8IP1/MKK7/MAP3K11/JNK1	0.051	0.028	-9999	-0.14	7	7
AKT1	-0.03	0.11	-9999	-0.2	123	123
MAP2K7	0.019	0	-9999	-10000	0	0
RAPGEF1	0.019	0	-9999	-10000	0	0
DAB1	0.019	0.006	-9999	-0.11	1	1
RELN/LRP8/DAB1	0.024	0.033	-9999	-0.13	10	10
LRPAP1/LRP8	0.018	0.043	-9999	-0.2	16	16
RELN/LRP8/DAB1/Fyn	0.013	0.066	-9999	-0.15	63	63
DAB1/alpha3/beta1 Integrin	0.015	0.054	-9999	-0.11	64	64
long-term memory	0.024	0.066	-9999	-0.19	18	18
DAB1/LIS1	0.015	0.071	-9999	-0.14	69	69
DAB1/CRLK/C3G	0.019	0.052	-9999	-0.11	61	61
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
DAB1/NCK2	0.016	0.071	-9999	-0.14	70	70
ARHGEF2	0.014	0.034	-9999	-0.18	13	13
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	0.017	0.016	-9999	-0.11	8	8
CDK5R1	0.014	0.025	-9999	-0.11	21	21
RELN	0.007	0.038	-9999	-0.11	50	50
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
RELN/LRP8/Fyn	0.003	0.075	-9999	-0.18	66	66
GRIN2A/RELN/LRP8/DAB1/Fyn	0.022	0.069	-9999	-0.14	63	63
MAPK8	0.019	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	0.008	0.056	-9999	-0.14	54	54
ITGB1	0.019	0	-9999	-10000	0	0
MAP1B	-0.006	0.067	-9999	-0.16	68	68
RELN/LRP8	0.022	0.045	-9999	-0.15	20	20
GRIN2B/RELN/LRP8/DAB1/Fyn	0.023	0.069	-9999	-0.14	63	63
PI3K	-0.016	0.093	-9999	-0.21	88	88
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.018	0.029	-9999	-0.19	1	1
RAP1A	0.013	0.05	-9999	-0.16	12	12
PAFAH1B1	0.009	0.055	-9999	-0.29	17	17
MAPK8IP1	0.016	0.019	-9999	-0.11	11	11
CRLK/C3G	0.028	0.007	-9999	-10000	0	0
GRIN2B	0.019	0	-9999	-10000	0	0
NCK2	0.009	0.054	-9999	-0.28	17	17
neuron differentiation	0.015	0.068	-9999	-0.28	13	13
neuron adhesion	0.017	0.049	-9999	-0.15	14	14
LRP8	0.01	0.043	-9999	-0.16	28	28
GSK3B	-0.031	0.12	-9999	-0.21	123	123
RELN/VLDLR/DAB1/Fyn	-0.003	0.075	-9999	-0.14	109	109
MAP3K11	0.017	0.021	-9999	-0.18	5	5
RELN/VLDLR/DAB1/P13K	-0.03	0.1	-9999	-0.2	123	123
CDK5	0.004	0.064	-9999	-0.24	31	31
MAPT	-0.029	0.089	-9999	-0.24	71	71
neuron migration	-0.022	0.12	-9999	-0.28	72	72
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.015	0.068	-9999	-0.29	13	13
RELN/VLDLR	0.01	0.067	-9999	-0.14	73	73

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.002	0.065	0.18	6	-0.15	62	68
DAPP1	-0.031	0.13	-10000	0	-0.33	69	69
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.058	0.21	-10000	0	-0.49	80	80
mol:DAG	-0.014	0.096	0.17	3	-0.21	79	82
HRAS	0.013	0.04	-10000	0	-0.28	9	9
RAP1A	0.017	0.015	-10000	0	-0.31	1	1
ARF5/GDP	-0.008	0.11	-10000	0	-0.26	65	65
PLCG2	-0.002	0.069	-10000	0	-0.19	52	52
PLCG1	0.017	0.025	-10000	0	-0.29	3	3
ARF5	0.014	0.04	-10000	0	-0.29	9	9
mol:GTP	-0.015	0.056	0.18	6	-0.15	60	66
ARF1/GTP	-0.006	0.061	0.17	6	-0.16	59	65
RHOA	0.015	0.036	-10000	0	-0.29	7	7
YES1	0.005	0.061	-10000	0	-0.24	28	28
RAP1A/GTP	0	0.06	0.18	6	-0.15	60	66
ADAP1	-0.006	0.056	0.17	6	-0.14	60	66
ARAP3	-0.015	0.055	0.18	6	-0.15	60	66
INPPL1	0.016	0.033	-10000	0	-0.29	6	6
PREX1	0	0	-10000	0	-10000	0	0
ARHGEF6	-0.009	0.088	-10000	0	-0.28	48	48
ARHGEF7	0	0.071	-10000	0	-0.25	37	37
ARF1	0.014	0.036	-10000	0	-0.29	7	7
NRAS	0.008	0.049	-10000	0	-0.18	27	27
FYN	-0.019	0.1	-10000	0	-0.28	68	68
ARF6	0.018	0.015	-10000	0	-0.2	2	2
FGR	0.005	0.048	-10000	0	-0.14	46	46
mol:Ca2+	-0.002	0.05	-10000	0	-0.1	79	79
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.003	0.066	-10000	0	-0.23	35	35
ZAP70	0.019	0.006	-10000	0	-0.11	1	1
mol:IP3	-0.006	0.069	-10000	0	-0.14	80	80
LYN	-0.018	0.098	-10000	0	-0.25	72	72
ARF1/GDP	-0.008	0.11	-10000	0	-0.26	63	63
RhoA/GDP	0	0.084	0.18	4	-0.18	73	77
PDK1/Src/Hsp90	0.038	0.012	-10000	0	-0.15	2	2
BLNK	-0.036	0.11	-10000	0	-0.29	66	66
actin cytoskeleton reorganization	-0.005	0.1	0.18	4	-0.3	38	42
SRC	0.019	0	-10000	0	-10000	0	0
PLEKHA2	0.011	0.015	-10000	0	-0.05	30	30
RAC1	0.015	0.036	-10000	0	-0.29	7	7
PTEN	0.013	0.036	-10000	0	-0.17	17	17
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
ARF6/GTP	0.004	0.059	0.18	6	-0.14	59	65
RhoA/GTP	0.003	0.063	0.18	6	-0.15	62	68
Src family/SYK family/BLNK-LAT	-0.057	0.2	-10000	0	-0.46	80	80
BLK	0.018	0.011	-10000	0	-0.11	4	4
PDPK1	0.019	0	-10000	0	-10000	0	0
CYTH1	-0.006	0.056	0.17	6	-0.14	60	66
HCK	-0.033	0.11	-10000	0	-0.21	120	120
CYTH3	-0.006	0.056	0.17	6	-0.14	60	66
CYTH2	-0.006	0.056	0.17	6	-0.14	60	66
KRAS	0.013	0.04	-10000	0	-0.28	9	9
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.01	0.052	0.14	5	-0.22	13	18
SGK1	0.01	0.04	-10000	0	-0.16	14	14
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.018	0.11	-10000	0	-0.27	62	62
SOS1	0	0	-10000	0	-10000	0	0
SYK	-0.005	0.072	-10000	0	-0.29	25	25
ARF6/GDP	-0.003	0.079	0.16	6	-0.17	74	80
mol:PI-3-4-5-P3	-0.006	0.059	0.18	6	-0.15	60	66
ARAP3/RAP1A/GTP	0	0.06	0.18	6	-0.15	60	66
VAV1	0.016	0.019	-10000	0	-0.11	12	12
mol:PI-3-4-P2	0.008	0.022	-10000	0	-0.2	6	6
RAS family/GTP/PI3K Class I	0.012	0.065	0.18	6	-0.15	60	66
PLEKHA1	0.01	0.022	-10000	0	-0.068	28	28
Rac1/GDP	-0.008	0.12	-10000	0	-0.27	62	62
LAT	0.018	0.014	-10000	0	-10000	0	0
Rac1/GTP	-0.02	0.16	-10000	0	-0.42	54	54
ITK	-0.001	0.057	0.18	6	-0.14	60	66
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.025	0.13	0.19	3	-0.28	84	87
LCK	0.017	0.016	-10000	0	-0.11	8	8
BTK	-0.001	0.057	0.18	6	-0.14	60	66

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.011	0.024	-9999	-0.2	7	7
PRKCZ	0	0	-9999	-10000	0	0
MAP3K7IP2	0.008	0.057	-9999	-0.27	20	20
ERC1	-0.002	0.075	-9999	-0.24	43	43
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.032	0.12	-9999	-0.31	69	69
IRAK/TOLLIP	0.019	0.038	-9999	-0.15	23	23
IKBKB	0.019	0	-9999	-10000	0	0
IKBKG	0.019	0	-9999	-10000	0	0
IL1 alpha/IL1R2	0.009	0.039	-9999	-0.14	6	6
IL1A	0.013	0.026	-9999	-0.11	23	23
IL1B	-0.027	0.075	-9999	-0.18	83	83
IRAK/TRAF6/p62/Atypical PKCs	0.027	0.053	-9999	-0.15	38	38
IL1R2	-0.003	0.049	-9999	-0.11	91	91
IL1R1	0.016	0.02	-9999	-0.11	13	13
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.023	0.1	-9999	-0.31	46	46
TOLLIP	0.016	0.021	-9999	-0.11	14	14
TICAM2	0	0	-9999	-10000	0	0
MAP3K3	0.019	0.006	-9999	-0.11	1	1
TAK1/TAB1/TAB2	0.025	0.055	-9999	-0.18	31	31
IKK complex/ELKS	0.026	0.09	-9999	-0.29	33	33
JUN	0.021	0.05	-9999	-0.23	15	15
MAP3K7	0.007	0.059	-9999	-0.25	24	24
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.034	0.1	-9999	-0.16	171	171
IL1 alpha/IL1R1/IL1RAP/MYD88	0.015	0.07	-9999	-0.15	61	61
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.023	0.067	-9999	-0.14	61	61
IL1 beta fragment/IL1R1/IL1RAP	-0.023	0.085	-9999	-0.17	107	107
NFKB1	0.014	0.037	-9999	-0.23	11	11
MAPK8	0.023	0.046	-9999	-0.14	34	34
IRAK1	0.015	0.027	-9999	-0.2	7	7
IL1RN/IL1R1	0.025	0.016	-9999	-10000	0	0
IRAK4	0.019	0.008	-9999	-0.11	2	2
PRKCI	0.015	0.028	-9999	-0.14	15	15
TRAF6	0.018	0.019	-9999	-0.29	2	2
PI3K	-0.016	0.093	-9999	-0.21	88	88
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.027	0.12	-9999	-0.3	69	69
CHUK	0.016	0.025	-9999	-0.15	10	10
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.023	0.085	-9999	-0.17	107	107
IL1 beta/IL1R2	-0.029	0.078	-9999	-0.15	118	118
IRAK/TRAF6/TAK1/TAB1/TAB2	0.035	0.063	-9999	-0.14	48	48
NF kappa B1 p50/RelA	-0.028	0.095	-9999	-0.2	87	87
IRAK3	0.018	0.014	-9999	-0.11	6	6
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.013	0.079	-9999	-0.15	107	107
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.004	0.076	-9999	-0.19	61	61
IL1 alpha/IL1R1/IL1RAP	0.014	0.055	-9999	-0.14	44	44
RELA	0.018	0.02	-9999	-0.23	3	3
MAP3K7IP1	0.019	0	-9999	-10000	0	0
SQSTM1	0.004	0.062	-9999	-0.22	32	32
MYD88	0	0.075	-9999	-0.29	33	33
IRAK/TRAF6/MEKK3	0.032	0.038	-9999	-0.13	25	25
IL1RAP	-0.013	0.084	-9999	-0.2	77	77
UBE2N	0.015	0.036	-9999	-0.29	7	7
IRAK/TRAF6	-0.03	0.06	-9999	-0.19	43	43
CASP1	-0.033	0.11	-9999	-0.29	75	75
IL1RN/IL1R2	0.012	0.036	-9999	-0.14	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.022	0.098	-9999	-0.17	118	118
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.002	0.099	-9999	-0.32	35	35
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
IL1RN	0.018	0.011	-9999	-0.11	4	4
TRAF6/TAK1/TAB1/TAB2	0.033	0.054	-9999	-0.16	34	34
MAP2K6	0.021	0.048	-9999	-0.15	34	34

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	-0.005	0.082	-9999	-0.27	44	44
ELF1	0.016	0.051	-9999	-0.28	12	12
CCNA2	-0.026	0.095	-9999	-0.19	117	117
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
JAK3	0.019	0.002	-9999	-10000	0	0
PIK3R1	-0.014	0.095	-9999	-0.27	62	62
JAK1	0.001	0.071	-9999	-0.26	34	34
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.006	0.2	-9999	-0.53	47	47
SHC1	0.005	0.052	-9999	-0.14	48	48
SP1	-0.034	0.12	-9999	-0.28	99	99
IL2RA	0.019	0.043	-9999	-10000	0	0
IL2RB	0.015	0.024	-9999	-0.11	19	19
SOS1	0	0.002	-9999	-10000	0	0
IL2RG	0.014	0.027	-9999	-0.11	24	24
G1/S transition of mitotic cell cycle	-0.12	0.28	-9999	-0.56	135	135
PTPN11	0.016	0.034	-9999	-0.27	7	7
CCND2	-0.088	0.22	-9999	-0.55	99	99
LCK	0.017	0.016	-9999	-0.11	8	8
GRB2	0.014	0.039	-9999	-0.26	10	10
IL2	0.019	0.006	-9999	-0.11	1	1
CDK6	0.019	0	-9999	-10000	0	0
CCND3	-0.006	0.21	-9999	-0.74	31	31

×

Signaling events mediated by HDAC Class III

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
EP300	0.012	0.046	-10000	0	-0.24	15	15
HDAC4	0.007	0.056	-10000	0	-0.29	16	16
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.015	0.045	0.2	6	-0.12	51	57
CDKN1A	-0.052	0.17	-10000	0	-0.52	62	62
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.014	0.035	-10000	0	-0.17	15	15
FOXO3	-0.007	0.042	0.29	5	-0.16	18	23
FOXO1	-0.012	0.088	-10000	0	-0.23	67	67
FOXO4	0.017	0.032	-10000	0	-0.2	11	11
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.018	0.019	-10000	0	-0.29	2	2
TAT	0.019	0	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.01	0	-10000	0	-10000	0	0
PPARGC1A	-0.006	0.067	-10000	0	-0.15	76	76
FHL2	-0.027	0.088	-10000	0	-0.16	134	134
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.031	0.048	0.14	41	-0.22	7	48
HIST2H4A	0.015	0.045	0.12	51	-0.2	6	57
SIRT1/FOXO3a	0.013	0.051	0.14	45	-0.12	18	63
SIRT1	0.024	0.063	0.18	41	-0.17	20	61
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.035	0.054	0.14	35	-0.17	21	56
SIRT1/Histone H1b	0.03	0.049	0.15	38	-0.19	10	48
apoptosis	-0.037	0.047	0.17	11	-0.14	41	52
SIRT1/PGC1A	0.015	0.053	0.13	32	-0.15	22	54
p53/SIRT1	0.031	0.11	0.34	48	-0.19	28	76
SIRT1/FOXO4	0.032	0.048	0.15	40	-0.18	10	50
FOXO1/FHL2/SIRT1	-0.003	0.073	0.14	18	-0.15	70	88
HIST1H1E	0.015	0.033	-10000	0	-0.2	11	11
SIRT1/p300	0.027	0.056	0.14	40	-0.2	17	57
muscle cell differentiation	-0.022	0.039	0.16	6	-0.13	41	47
TP53	0.012	0.083	0.18	45	-0.2	42	87
KU70/SIRT1/BAX	0.038	0.048	0.14	41	-0.17	11	52
CREBBP	0.019	0	-10000	0	-10000	0	0
MEF2D	0.019	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.032	0.044	0.14	41	-0.19	6	47
ACSS2	0.015	0.045	0.12	51	-0.2	6	57
SIRT1/PCAF/MYOD	0.022	0.039	0.13	41	-0.16	6	47

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.013	0.037	-9999	-0.07	156	156
TP53	-0.021	0.065	-9999	-0.27	31	31
Senescence	-0.021	0.065	-9999	-0.27	31	31
Apoptosis	-0.021	0.065	-9999	-0.27	31	31
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.011	0.025	-9999	-10000	0	0
MDM4	0.013	0.026	-9999	-0.11	23	23

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.042	0.11	-10000	0	-0.2	148	148
HRAS	0.009	0.055	-10000	0	-0.28	18	18
EGFR	-0.08	0.12	-10000	0	-0.29	97	97
AKT	0.019	0.026	0.13	3	-0.12	4	7
FOXO3	0.002	0.07	-10000	0	-0.27	32	32
AKT1	0.005	0.063	-10000	0	-0.25	28	28
FOXO1	-0.012	0.088	-10000	0	-0.23	67	67
AKT3	0.018	0.011	-10000	0	-0.11	4	4
FOXO4	0.019	0	-10000	0	-10000	0	0
MET	0.008	0.037	-10000	0	-0.11	47	47
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
PIK3CB	0.018	0.013	-10000	0	-0.11	5	5
NRAS	-0.01	0.086	-10000	0	-0.24	59	59
PIK3CG	0.019	0	-10000	0	-10000	0	0
PIK3R3	0.017	0.016	-10000	0	-0.11	8	8
PIK3R2	0.018	0.01	-10000	0	-0.11	3	3
NF1	0.019	0	-10000	0	-10000	0	0
RAS	-0.049	0.086	-10000	0	-0.17	130	130
ERBB2	0.019	0.008	-10000	0	-0.11	2	2
proliferation/survival/translation	-0.015	0.085	0.33	23	-0.18	2	25
PI3K	-0.021	0.069	0.13	3	-0.13	120	123
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
KRAS	0.011	0.048	-10000	0	-0.28	14	14
FOXO	0.028	0.028	0.14	3	-0.049	4	7
AKT2	0.019	0	-10000	0	-10000	0	0
PTEN	0.013	0.038	-10000	0	-0.18	17	17

×

IGF1 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
NCK2	0.009	0.054	-10000	0	-0.28	17	17
PTK2	0.009	0.054	-10000	0	-0.27	18	18
CRKL	0.006	0.047	-10000	0	-0.16	27	27
GRB2/SOS1/SHC	0.014	0.039	-10000	0	-0.17	16	16
HRAS	0.009	0.055	-10000	0	-0.28	18	18
IRS1/Crk	0.007	0.055	-10000	0	-0.16	41	41
IGF-1R heterotetramer/IGF1/PTP1B	0.018	0.055	-10000	0	-0.17	33	33
AKT1	-0.014	0.089	-10000	0	-0.17	98	98
BAD	-0.012	0.087	-10000	0	-0.21	59	59
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.005	0.05	-10000	0	-0.18	29	29
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.01	0.052	-10000	0	-0.16	32	32
RAF1	-0.022	0.16	-10000	0	-0.57	32	32
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.014	0.052	-10000	0	-0.16	34	34
YWHAZ	0.014	0.037	-10000	0	-0.23	11	11
IGF-1R heterotetramer/IGF1/IRS1	0.007	0.053	-10000	0	-0.15	38	38
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
RPS6KB1	-0.009	0.074	-10000	0	-0.15	98	98
GNB2L1	0.018	0.019	-10000	0	-0.29	2	2
positive regulation of MAPKKK cascade	-0.018	0.12	0.2	2	-0.42	34	36
PXN	0.018	0.011	-10000	0	-0.11	4	4
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.011	0.026	-10000	0	-0.17	10	10
HRAS/GTP	-0.019	0.049	-10000	0	-0.15	51	51
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.021	0.054	-10000	0	-0.13	42	42
IGF-1R heterotetramer	0.009	0.048	-10000	0	-0.17	28	28
IGF-1R heterotetramer/IGF1/IRS/Nck	0.013	0.06	-10000	0	-0.17	41	41
Crk/p130 Cas/Paxillin	0.015	0.053	-10000	0	-0.14	40	40
IGF1R	0.009	0.048	-10000	0	-0.17	28	28
IGF1	0.011	0.029	-10000	0	-0.1	28	28
IRS2/Crk	-0.007	0.079	-10000	0	-0.17	82	82
PI3K	-0.004	0.089	-10000	0	-0.17	100	100
apoptosis	0.003	0.084	0.22	51	-10000	0	51
HRAS/GDP	0.007	0.037	-10000	0	-0.19	18	18
PRKCD	0.006	0.063	-10000	0	-0.22	31	31
RAF1/14-3-3 E	-0.009	0.14	-10000	0	-0.46	34	34
BAD/14-3-3	-0.003	0.089	-10000	0	-0.23	51	51
PRKCZ	-0.014	0.073	-10000	0	-0.15	99	99
Crk/p130 Cas/Paxillin/FAK1	-0.003	0.08	-10000	0	-0.22	44	44
PTPN1	0.013	0.042	-10000	0	-0.29	10	10
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.005	0.065	-10000	0	-0.23	30	30
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.003	0.078	-10000	0	-0.16	76	76
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	0.007	0.058	-10000	0	-0.17	41	41
GRB10	-0.018	0.091	-10000	0	-0.2	89	89
PTPN11	0.006	0.048	-10000	0	-0.17	27	27
IRS1	0.003	0.049	-10000	0	-0.16	37	37
IRS2	-0.004	0.067	-10000	0	-0.2	43	43
IGF-1R heterotetramer/IGF1	0.008	0.058	-10000	0	-0.22	27	27
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PDPK1	-0.012	0.078	-10000	0	-0.16	99	99
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
PRKD1	-0.001	0.078	-10000	0	-0.24	41	41
SHC1	0.004	0.052	-10000	0	-0.14	48	48

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.043	-10000	0	-0.18	21	21
Jak2/Leptin Receptor	-0.002	0.063	-10000	0	-0.27	3	3
PTP1B/AKT1	-0.036	0.11	-10000	0	-0.27	64	64
FYN	-0.019	0.1	-10000	0	-0.28	68	68
p210 bcr-abl/PTP1B	-0.045	0.1	-10000	0	-0.28	57	57
EGFR	-0.081	0.12	-10000	0	-0.28	109	109
EGF/EGFR	-0.066	0.11	-10000	0	-0.29	70	70
CSF1	0.019	0	-10000	0	-10000	0	0
AKT1	0.005	0.064	-10000	0	-0.26	28	28
INSR	0.019	0.002	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.043	0.12	-10000	0	-0.28	75	75
Insulin Receptor/Insulin	-0.011	0.096	-10000	0	-0.28	36	36
HCK	-0.033	0.11	-10000	0	-0.21	120	120
CRK	0.009	0.054	-10000	0	-0.28	17	17
TYK2	-0.043	0.11	-10000	0	-0.3	60	60
EGF	0.01	0.026	-10000	0	-0.11	21	21
YES1	0.005	0.061	-10000	0	-0.24	28	28
CAV1	-0.076	0.13	-10000	0	-0.3	89	89
TXN	0.006	0.051	-10000	0	-0.23	19	19
PTP1B/IRS1/GRB2	-0.035	0.11	-10000	0	-0.27	68	68
cell migration	0.045	0.1	0.28	57	-10000	0	57
STAT3	-0.003	0.08	-10000	0	-0.29	37	37
PRLR	0.023	0	-10000	0	-10000	0	0
ITGA2B	0.018	0.001	-10000	0	-10000	0	0
CSF1R	-0.042	0.11	-10000	0	-0.29	83	83
Prolactin Receptor/Prolactin	0.035	0.014	-10000	0	-10000	0	0
FGR	0.005	0.048	-10000	0	-0.14	46	46
PTP1B/p130 Cas	-0.043	0.098	-10000	0	-0.26	58	58
Crk/p130 Cas	-0.037	0.1	-10000	0	-0.26	65	65
DOK1	-0.029	0.099	-10000	0	-0.3	41	41
JAK2	-0.007	0.061	-10000	0	-0.3	2	2
Jak2/Leptin Receptor/Leptin	-0.01	0.11	-10000	0	-0.28	47	47
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
PTPN1	-0.045	0.1	-10000	0	-0.28	57	57
LYN	-0.018	0.098	-10000	0	-0.25	72	72
CDH2	-0.006	0.082	-10000	0	-0.26	46	46
SRC	-0.008	0.09	-10000	0	-0.56	11	11
ITGB3	0.018	0.008	-10000	0	-0.11	2	2
CAT1/PTP1B	-0.069	0.17	-10000	0	-0.38	92	92
CAPN1	0.017	0.006	-10000	0	-0.11	1	1
CSK	0.013	0.044	-10000	0	-0.29	11	11
PI3K	-0.026	0.12	-10000	0	-0.31	59	59
mol:H2O2	-0.001	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.007	0.099	-10000	0	-0.26	46	46
negative regulation of transcription	-0.007	0.06	-10000	0	-0.29	2	2
FCGR2A	-0.032	0.1	-10000	0	-0.22	114	114
FER	0.014	0.018	-10000	0	-0.11	10	10
alphaIIb/beta3 Integrin	0.025	0.006	-10000	0	-10000	0	0
BLK	0.018	0.011	-10000	0	-0.11	4	4
Insulin Receptor/Insulin/Shc	0.029	0.033	-10000	0	-0.16	9	9
RHOA	0.013	0.036	-10000	0	-0.3	7	7
LEPR	0.016	0.019	-10000	0	-0.11	11	11
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.014	0.039	-10000	0	-0.26	10	10
mol:NADPH	-0.002	0.002	-10000	0	-10000	0	0
TRPV6	-0.046	0.16	-10000	0	-0.39	77	77
PRL	0.02	0.019	-10000	0	-10000	0	0
SOCS3	0.012	0.012	-10000	0	-10000	0	0
SPRY2	-0.051	0.13	-10000	0	-0.27	127	127
Insulin Receptor/Insulin/IRS1	0.025	0.044	-10000	0	-0.16	24	24
CSF1/CSF1R	-0.05	0.12	-10000	0	-0.3	68	68
Ras protein signal transduction	0.018	0.039	0.11	9	-0.19	8	17
IRS1	-0.002	0.07	-10000	0	-0.19	53	53
INS	0.019	0.002	-10000	0	-10000	0	0
LEP	0.019	0.001	-10000	0	-10000	0	0
STAT5B	-0.025	0.085	-10000	0	-0.26	35	35
STAT5A	-0.025	0.085	-10000	0	-0.26	33	33
GRB2	0.014	0.039	-10000	0	-0.26	10	10
PDGFB-D/PDGFRB	-0.037	0.1	-10000	0	-0.27	61	61
CSN2	0.034	0.02	-10000	0	-10000	0	0
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
LAT	-0.063	0.18	-10000	0	-0.52	66	66
YBX1	0.016	0.062	-10000	0	-0.31	18	18
LCK	0.017	0.016	-10000	0	-0.11	8	8
SHC1	0.004	0.052	-10000	0	-0.14	48	48
NOX4	-0.015	0.086	-10000	0	-0.21	76	76

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.022	0.079	-10000	0	-0.19	87	87
MAP4K4	0.015	0.061	-10000	0	-0.27	10	10
BAG4	0.018	0.011	-10000	0	-0.11	4	4
PKC zeta/ceramide	0.011	0.03	0.075	87	-10000	0	87
NFKBIA	0.002	0.067	-10000	0	-0.24	34	34
BIRC3	0	0.046	-10000	0	-0.11	78	78
BAX	0.011	0.042	-10000	0	-0.38	5	5
RIPK1	0.016	0.019	-10000	0	-0.11	11	11
AKT1	-0.004	0.058	-10000	0	-0.26	24	24
BAD	0.014	0.036	0.085	85	-0.14	5	90
SMPD1	0.008	0.043	-10000	0	-0.12	50	50
RB1	0.015	0.034	0.085	85	-0.14	2	87
FADD/Caspase 8	0.028	0.05	-10000	0	-0.19	2	2
MAP2K4	0.017	0.035	0.086	81	-0.12	4	85
NSMAF	0.006	0.063	-10000	0	-0.28	24	24
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.016	0.037	0.086	78	-0.13	11	89
EGF	0.014	0.025	-10000	0	-0.11	21	21
mol:ceramide	0.013	0.035	0.087	87	-10000	0	87
MADD	0.018	0.015	-10000	0	-0.2	2	2
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.021	0.078	-10000	0	-0.19	84	84
ASAH1	0.017	0.023	-10000	0	-0.29	3	3
negative regulation of cell cycle	0.015	0.034	0.085	85	-0.14	2	87
cell proliferation	0.034	0.038	-10000	0	-0.096	14	14
BID	-0.006	0.15	-10000	0	-0.61	27	27
MAP3K1	0.015	0.034	0.085	86	-0.069	1	87
EIF2A	0.014	0.037	0.082	80	-0.12	14	94
TRADD	0.019	0	-10000	0	-10000	0	0
CRADD	0.017	0.015	-10000	0	-0.11	7	7
MAPK3	0.022	0.037	0.093	2	-0.11	14	16
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.019	0.048	0.091	12	-0.17	18	30
Cathepsin D/ceramide	0.019	0.034	0.088	78	-0.051	29	107
FADD	0.021	0.049	-10000	0	-0.18	3	3
KSR1	0.016	0.032	0.085	87	-10000	0	87
MAPK8	0.02	0.032	0.09	3	-10000	0	3
PRKRA	0.012	0.041	0.085	82	-0.14	14	96
PDGFA	-0.045	0.12	-10000	0	-0.22	141	141
TRAF2	0.019	0	-10000	0	-10000	0	0
IGF1	0.014	0.025	-10000	0	-0.11	21	21
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.013	0.035	0.087	87	-10000	0	87
CTSD	0.005	0.053	-10000	0	-0.16	43	43
regulation of nitric oxide biosynthetic process	0.024	0.03	-10000	0	-0.19	9	9
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.037	0.04	-10000	0	-0.1	14	14
PRKCD	0.012	0.029	-10000	0	-0.11	27	27
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.021	0.078	-10000	0	-0.19	84	84
RelA/NF kappa B1	0.024	0.03	-10000	0	-0.19	9	9
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.019	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.019	0.051	-10000	0	-0.17	4	4
TNFR1A/BAG4/TNF-alpha	0.02	0.057	-10000	0	-0.16	50	50
mol:Sphingosine-1-phosphate	-0.022	0.079	-10000	0	-0.19	87	87
MAP2K1	0.017	0.039	0.087	77	-0.13	16	93
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.018	0.02	-10000	0	-0.23	3	3
CYCS	0.011	0.033	-10000	0	-0.16	9	9
TNFRSF1A	-0.01	0.091	-10000	0	-0.29	50	50
NFKB1	0.014	0.037	-10000	0	-0.23	11	11
TNFR1A/BAG4	0.007	0.065	-10000	0	-0.19	50	50
EIF2AK2	0.015	0.039	0.086	80	-0.13	14	94
TNF-alpha/TNFR1A/FAN	0.013	0.071	-10000	0	-0.17	65	65
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.027	0.045	-10000	0	-0.33	2	2
MAP2K2	0.019	0.037	0.087	73	-0.12	12	85
SMPD3	0.011	0.047	-10000	0	-0.16	11	11
TNF	0.018	0.01	-10000	0	-0.11	3	3
PKC zeta/PAR4	0.014	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.01	0.033	0.088	52	-10000	0	52
NF kappa B1/RelA/I kappa B alpha	0.033	0.044	-10000	0	-0.14	30	30
AIFM1	0.01	0.034	-10000	0	-0.18	7	7
BCL2	0.019	0	-10000	0	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.025	0.13	-9999	-0.26	89	89
STMN1	0.007	0.043	-9999	-0.14	33	33
Aurora B/RasGAP/Survivin	-0.007	0.082	-9999	-0.16	107	107
Chromosomal passenger complex/Cul3 protein complex	-0.036	0.092	-9999	-0.21	79	79
BIRC5	-0.032	0.11	-9999	-0.22	111	111
DES	0.015	0.054	-9999	-1.1	1	1
Aurora C/Aurora B/INCENP	0.028	0.024	-9999	-0.11	5	5
Aurora B/TACC1	0.016	0.036	-9999	-0.17	15	15
Aurora B/PP2A	0.021	0.025	-9999	-0.17	2	2
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.002	0.06	-9999	-0.21	35	35
mitotic metaphase/anaphase transition	0	0.002	-9999	-10000	0	0
NDC80	-0.01	0.068	-9999	-0.14	99	99
Cul3 protein complex	-0.016	0.077	-9999	-0.16	116	116
KIF2C	-0.027	0.14	-9999	-0.37	56	56
PEBP1	0.011	0.048	-9999	-0.28	14	14
KIF20A	-0.029	0.1	-9999	-0.21	109	109
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.01	0.054	-9999	-0.2	29	29
SEPT1	0	0	-9999	-10000	0	0
SMC2	0	0.064	-9999	-0.17	53	53
SMC4	-0.009	0.083	-9999	-0.22	62	62
NSUN2/NPM1/Nucleolin	0.001	0.063	-9999	-0.39	4	4
PSMA3	0.012	0.043	-9999	-0.25	13	13
G2/M transition of mitotic cell cycle	0	0.003	-9999	-10000	0	0
H3F3B	0.008	0.039	-9999	-0.23	12	12
AURKB	0.01	0.034	-9999	-0.12	32	32
AURKC	0.015	0.022	-9999	-0.11	16	16
CDCA8	0.003	0.059	-9999	-0.17	44	44
cytokinesis	-0.036	0.18	-9999	-0.48	59	59
Aurora B/Septin1	-0.031	0.16	-9999	-0.44	59	59
AURKA	0.006	0.056	-9999	-0.2	32	32
INCENP	0.018	0.007	-9999	-0.12	1	1
KLHL13	0	0	-9999	-10000	0	0
BUB1	0.017	0.018	-9999	-0.11	10	10
hSgo1/Aurora B/Survivin	-0.007	0.061	-9999	-0.14	84	84
EVI5	0.018	0.008	-9999	-0.11	2	2
RhoA/GTP	-0.02	0.15	-9999	-0.34	75	75
SGOL1	0	0	-9999	-10000	0	0
CENPA	-0.015	0.12	-9999	-0.39	38	38
NCAPG	-0.018	0.089	-9999	-0.2	89	89
Aurora B/HC8 Proteasome	0.017	0.039	-9999	-0.18	14	14
NCAPD2	-0.008	0.079	-9999	-0.2	64	64
Aurora B/PP1-gamma	0.019	0.033	-9999	-0.2	7	7
RHOA	0.015	0.036	-9999	-0.29	7	7
NCAPH	0.011	0.034	-9999	-0.12	28	28
NPM1	0.005	0.053	-9999	-0.37	8	8
RASA1	0.003	0.069	-9999	-0.28	29	29
KLHL9	-0.052	0.13	-9999	-0.28	126	126
mitotic prometaphase	-0.001	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.017	0.039	-9999	-0.18	14	14
PPP1CC	0.016	0.033	-9999	-0.29	6	6
Centraspindlin	-0.027	0.16	-9999	-0.36	78	78
RhoA/GDP	0.011	0.024	-9999	-0.2	7	7
NSUN2	0.003	0.03	-9999	-0.47	1	1
MYLK	-0.033	0.091	-9999	-0.24	83	83
KIF23	-0.01	0.078	-9999	-0.18	78	78
VIM	-0.002	0.065	-9999	-0.21	44	44
RACGAP1	-0.013	0.091	-9999	-0.24	68	68
mitosis	0	0	-9999	-10000	0	0
NCL	0.002	0.065	-9999	-0.35	15	15
Chromosomal passenger complex	-0.021	0.12	-9999	-0.3	67	67
Chromosomal passenger complex/EVI5	0.011	0.081	-9999	-0.16	77	77
TACC1	0.01	0.049	-9999	-0.29	13	13
PPP2R5D	0.018	0.013	-9999	-0.11	5	5
CUL3	0.018	0.019	-9999	-0.29	2	2
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.001	0.005	0.02	3	-10000	0	3
BUB1B	-0.027	0.099	-10000	0	-0.28	60	60
PLK1	0.005	0.021	-10000	0	-0.07	21	21
PLK1S1	0.003	0.01	-10000	0	-0.035	8	8
KIF2A	-0.004	0.05	-10000	0	-0.15	48	48
regulation of mitotic centrosome separation	0.005	0.021	-10000	0	-0.07	21	21
GOLGA2	0.013	0.041	-10000	0	-0.27	10	10
Hec1/SPC24	-0.002	0.054	-10000	0	-0.14	58	58
WEE1	-0.03	0.15	-10000	0	-0.66	27	27
cytokinesis	-0.039	0.14	-10000	0	-0.36	69	69
PP2A-alpha B56	0.024	0.056	-10000	0	-0.29	4	4
AURKA	0.002	0.042	-10000	0	-0.23	15	15
PICH/PLK1	-0.028	0.12	-10000	0	-0.21	123	123
CENPE	-0.002	0.044	-10000	0	-0.14	36	36
RhoA/GTP	0.011	0.024	-10000	0	-0.2	7	7
positive regulation of microtubule depolymerization	-0.004	0.05	-10000	0	-0.15	48	48
PPP2CA	0.011	0.05	-10000	0	-0.28	15	15
FZR1	0.019	0	-10000	0	-10000	0	0
TPX2	-0.033	0.093	-10000	0	-0.24	90	90
PAK1	0.016	0.017	-10000	0	-0.11	9	9
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.011	0.047	-10000	0	-0.27	14	14
CLSPN	0.01	0.012	-10000	0	-10000	0	0
GORASP1	0.006	0.061	-10000	0	-0.28	22	22
metaphase	-0.001	0.001	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.003	0.01	-10000	0	-0.035	8	8
G2 phase of mitotic cell cycle	-0.001	0.002	-10000	0	-0.01	15	15
STAG2	0.005	0.065	-10000	0	-0.29	24	24
GRASP65/GM130/RAB1/GTP	-0.018	0.15	-10000	0	-0.66	23	23
spindle elongation	0.005	0.021	-10000	0	-0.07	21	21
ODF2	0.016	0.018	-10000	0	-10000	0	0
BUB1	0.014	0.027	-10000	0	-10000	0	0
TPT1	0.009	0.01	-10000	0	-10000	0	0
CDC25C	0.011	0.012	-10000	0	-10000	0	0
CDC25B	0.001	0.066	-10000	0	-0.27	28	28
SGOL1	0.001	0.005	-10000	0	-0.02	3	3
RHOA	0.015	0.036	-10000	0	-0.29	7	7
CCNB1/CDK1	-0.038	0.14	-10000	0	-0.29	109	109
CDC14B	0.003	0.036	-10000	0	-0.19	17	17
CDC20	-0.042	0.12	-10000	0	-0.24	127	127
PLK1/PBIP1	-0.018	0.058	-10000	0	-0.13	94	94
mitosis	0	0.006	0.032	15	-10000	0	15
FBXO5	-0.014	0.07	-10000	0	-0.23	43	43
CDC2	-0.032	0.1	-10000	0	-0.2	123	123
NDC80	-0.019	0.093	-10000	0	-0.21	89	89
metaphase plate congression	0.001	0.054	-10000	0	-0.3	16	16
ERCC6L	-0.038	0.14	-10000	0	-0.27	110	110
NLP/gamma Tubulin	0.001	0.027	-10000	0	-0.11	23	23
microtubule cytoskeleton organization	0.009	0.01	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-10000	0	0
PPP1R12A	0.011	0.046	-10000	0	-0.25	15	15
interphase	0	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.022	0.1	-10000	0	-0.19	120	120
GRASP65/GM130/RAB1/GTP/PLK1	0.023	0.052	-10000	0	-0.15	36	36
RAB1A	0.012	0.046	-10000	0	-0.29	12	12
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.004	0.025	-10000	0	-0.081	27	27
mitotic prometaphase	0	0.004	0.023	16	-10000	0	16
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.073	-10000	0	-0.37	14	14
microtubule-based process	0.004	0.047	-10000	0	-0.12	51	51
Golgi organization	0.005	0.021	-10000	0	-0.07	21	21
Cohesin/SA2	0.008	0.037	-10000	0	-0.13	27	27
PPP1CB/MYPT1	0.02	0.041	-10000	0	-0.2	16	16
KIF20A	-0.028	0.1	-10000	0	-0.21	109	109
APC/C/CDC20	0.004	0.047	-10000	0	-0.13	41	41
PPP2R1A	0.003	0.069	-10000	0	-0.29	27	27
chromosome segregation	-0.018	0.057	-10000	0	-0.13	94	94
PRC1	-0.041	0.12	-10000	0	-0.24	121	121
ECT2	-0.011	0.058	-10000	0	-0.14	72	72
C13orf34	0.005	0.023	-10000	0	-0.069	27	27
NUDC	0.001	0.054	-10000	0	-0.3	16	16
regulation of attachment of spindle microtubules to kinetochore	-0.027	0.098	-10000	0	-0.28	60	60
spindle assembly	0.003	0.024	-10000	0	-0.077	28	28
spindle stabilization	0.003	0.01	-10000	0	-0.035	8	8
APC/C/HCDH1	0.016	0.031	-10000	0	-0.16	16	16
MKLP2/PLK1	0.004	0.047	-10000	0	-0.12	51	51
CCNB1	-0.041	0.12	-10000	0	-0.24	122	122
PPP1CB	0.015	0.034	-10000	0	-0.27	7	7
BTRC	0.019	0	-10000	0	-10000	0	0
ROCK2	0.013	0.027	-10000	0	-0.17	6	6
TUBG1	-0.001	0.052	-10000	0	-0.25	22	22
G2/M transition of mitotic cell cycle	-0.064	0.13	-10000	0	-0.29	108	108
MLF1IP	-0.033	0.078	-10000	0	-0.2	84	84
INCENP	0.019	0.006	-10000	0	-0.11	1	1

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.01	0.097	-9999	-0.42	8	8
UGCG	-0.029	0.19	-9999	-0.81	28	28
AKT1/mTOR/p70S6K/Hsp90/TERT	0.009	0.14	-9999	-0.3	73	73
mol:GTP	0	0	-9999	-10000	0	0
mol:glucosylceramide	-0.029	0.19	-9999	-0.79	28	28
mol:DAG	-0.014	0.13	-9999	-0.91	10	10
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.011	0.19	-9999	-0.4	83	83
FRAP1	-0.017	0.21	-9999	-0.44	84	84
FOXO3	-0.029	0.22	-9999	-0.47	89	89
AKT1	-0.032	0.23	-9999	-0.48	88	88
GAB2	-0.005	0.082	-9999	-0.27	44	44
SMPD1	0.012	0.034	-9999	-10000	0	0
SGMS1	-0.003	0.1	-9999	-0.66	10	10
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
mol:GDP	-0.019	0.075	-9999	-0.18	88	88
CALM1	0.007	0.056	-9999	-0.21	28	28
cell proliferation	-0.036	0.2	-9999	-0.37	93	93
EIF3A	0.011	0.048	-9999	-0.29	12	12
PI3K	-0.013	0.094	-9999	-0.21	88	88
RPS6KB1	0.02	0.024	-9999	-10000	0	0
mol:sphingomyelin	-0.014	0.13	-9999	-0.91	10	10
natural killer cell activation	0	0.003	-9999	-0.01	50	50
JAK3	0.02	0.004	-9999	-10000	0	0
PIK3R1	-0.013	0.095	-9999	-0.27	62	62
JAK1	0.002	0.071	-9999	-0.26	34	34
NFKB1	0.014	0.037	-9999	-0.23	11	11
MYC	-0.07	0.32	-9999	-0.8	74	74
MYB	0.028	0.029	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.012	0.17	-9999	-0.33	92	92
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.034	0.04	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.011	0.17	-9999	-0.37	67	67
Rac1/GDP	-0.008	0.076	-9999	-0.16	89	89
T cell proliferation	-0.01	0.16	-9999	-0.35	67	67
SHC1	0.004	0.052	-9999	-0.14	48	48
RAC1	0.015	0.036	-9999	-0.29	7	7
positive regulation of cyclin-dependent protein kinase activity	0.004	0.004	-9999	-10000	0	0
PRKCZ	-0.012	0.16	-9999	-0.36	67	67
NF kappa B1 p50/RelA	0.001	0.19	-9999	-0.39	81	81
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.005	0.1	-9999	-0.34	27	27
HSP90AA1	0.018	0.019	-9999	-0.29	2	2
RELA	0.018	0.02	-9999	-0.23	3	3
IL2RA	0.012	0.029	-9999	-0.11	28	28
IL2RB	0.016	0.024	-9999	-0.11	19	19
TERT	0.019	0.008	-9999	-0.11	2	2
E2F1	0.026	0.021	-9999	-10000	0	0
SOS1	0	0.003	-9999	-0.009	49	49
RPS6	0.015	0.036	-9999	-0.29	7	7
mol:cAMP	-0.002	0.002	-9999	-10000	0	0
PTPN11	0.015	0.034	-9999	-0.27	7	7
IL2RG	0.014	0.027	-9999	-0.11	24	24
actin cytoskeleton organization	-0.01	0.16	-9999	-0.35	67	67
GRB2	0.014	0.039	-9999	-0.26	10	10
IL2	0.02	0.007	-9999	-0.12	1	1
PIK3CA	-0.01	0.087	-9999	-0.22	66	66
Rac1/GTP	0.005	0.078	-9999	-0.15	89	89
LCK	0.018	0.016	-9999	-0.11	8	8
BCL2	0.002	0.16	-9999	-0.44	39	39

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.045	0.096	-9999	-0.2	132	132
alphaV beta3 Integrin	0.025	0.049	-9999	-0.16	31	31
PTK2	-0.031	0.14	-9999	-0.32	60	60
IGF1R	-0.001	0.07	-9999	-0.21	46	46
PI4KB	0.018	0.017	-9999	-0.16	4	4
MFGE8	0.016	0.025	-9999	-0.29	2	2
SRC	0.019	0	-9999	-10000	0	0
CDKN1B	0.003	0.092	-9999	-0.36	29	29
VEGFA	-0.068	0.13	-9999	-0.22	188	188
ILK	0.013	0.07	-9999	-0.37	15	15
ROCK1	0.016	0.031	-9999	-0.26	6	6
AKT1	0.012	0.076	-9999	-0.38	17	17
PTK2B	-0.025	0.075	-9999	-0.14	136	136
alphaV/beta3 Integrin/JAM-A	0.03	0.054	-9999	-0.15	35	35
CBL	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.028	0.042	-9999	-0.15	25	25
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.021	0.065	-9999	-0.14	59	59
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.021	0.1	-9999	-0.32	29	29
alphaV/beta3 Integrin/Syndecan-1	0.017	0.052	-9999	-0.16	28	28
PI4KA	-0.007	0.083	-9999	-0.26	49	49
IGF-1R heterotetramer/IGF1/IRS1	0.009	0.076	-9999	-0.24	29	29
PI4 Kinase	0.009	0.061	-9999	-0.2	40	40
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
alphaV/beta3 Integrin/Osteopontin	0.011	0.076	-9999	-0.18	63	63
RPS6KB1	0.005	0.071	-9999	-0.23	28	28
TLN1	-0.003	0.065	-9999	-0.16	64	64
MAPK3	0.008	0.1	-9999	-0.39	28	28
GPR124	0.014	0.024	-9999	-0.11	19	19
MAPK1	0.004	0.11	-9999	-0.4	29	29
PXN	0.018	0.011	-9999	-0.11	4	4
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
alphaV/beta3 Integrin/Tumstatin	0.028	0.042	-9999	-0.15	25	25
cell adhesion	0.027	0.053	-9999	-0.17	33	33
ANGPTL3	0.019	0.006	-9999	-0.11	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	-0.025	0.083	-9999	-0.16	132	132
IGF-1R heterotetramer	-0.001	0.07	-9999	-0.21	46	46
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
TGFBR2	0.013	0.035	-9999	-0.14	21	21
ITGB3	0.019	0.008	-9999	-0.11	2	2
IGF1	0.014	0.025	-9999	-0.11	21	21
RAC1	0.015	0.036	-9999	-0.29	7	7
regulation of cell-matrix adhesion	0.025	0.043	-9999	-0.15	25	25
apoptosis	0.003	0.067	-9999	-0.25	32	32
CD47	0.012	0.043	-9999	-0.21	16	16
alphaV/beta3 Integrin/CD47	0.024	0.051	-9999	-0.16	32	32
VCL	0.017	0.023	-9999	-0.29	3	3
alphaV/beta3 Integrin/Del1	0.028	0.042	-9999	-0.15	25	25
CSF1	0.019	0	-9999	-10000	0	0
PIK3C2A	0.013	0.023	-9999	-10000	0	0
PI4 Kinase/Pyk2	-0.035	0.069	-9999	-0.2	49	49
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.021	0.089	-9999	-0.15	136	136
FAK1/Vinculin	-0.016	0.12	-9999	-0.27	52	52
alphaV beta3/Integrin/ppsTEM5	0.025	0.044	-9999	-0.15	25	25
RHOA	0.015	0.036	-9999	-0.29	7	7
VTN	0.018	0.01	-9999	-0.11	3	3
BCAR1	0	0	-9999	-10000	0	0
FGF2	0.013	0.036	-9999	-0.16	19	19
F11R	0.007	0.044	-9999	-0.21	14	14
alphaV/beta3 Integrin/Lactadherin	0.027	0.045	-9999	-0.16	27	27
alphaV/beta3 Integrin/TGFBR2	0.024	0.047	-9999	-0.15	32	32
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.028	0.037	-9999	-0.14	25	25
HSP90AA1	0.018	0.019	-9999	-0.29	2	2
alphaV/beta3 Integrin/Talin	0.015	0.053	-9999	-0.14	44	44
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.001	0.071	-9999	-0.26	34	34
alphaV/beta3 Integrin/Pyk2	-0.018	0.081	-9999	-0.14	136	136
SDC1	0	0.046	-9999	-0.11	77	77
VAV3	0.009	0.044	-9999	-0.16	25	25
PTPN11	0.015	0.033	-9999	-0.27	7	7
IRS1	-0.002	0.07	-9999	-0.19	53	53
FAK1/Paxillin	-0.016	0.12	-9999	-0.27	51	51
cell migration	-0.011	0.11	-9999	-0.25	51	51
ITGAV	0.003	0.067	-9999	-0.25	32	32
PI3K	0.011	0.091	-9999	-0.22	46	46
SPP1	-0.011	0.092	-9999	-0.29	51	51
KDR	0.001	0.057	-9999	-0.14	59	59
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.003	0.067	-9999	-0.25	32	32
COL4A3	0.019	0	-9999	-10000	0	0
angiogenesis	0.008	0.11	-9999	-0.42	28	28
Rac1/GTP	0.008	0.058	-9999	-0.13	65	65
EDIL3	0.019	0	-9999	-10000	0	0
cell proliferation	0.024	0.047	-9999	-0.15	32	32

×

mTOR signaling pathway

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
GBL	0.016	0.029	-10000	0	-0.2	8	8
MKNK1	0.003	0.068	-10000	0	-0.27	30	30
mol:PIP3	-0.025	0.083	0.19	4	-0.18	97	101
FRAP1	-0.002	0.09	-10000	0	-0.55	12	12
AKT1	-0.021	0.093	0.19	4	-0.19	95	99
INSR	0.019	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.026	0	-10000	0	-10000	0	0
mol:GTP	-0.007	0.098	0.17	4	-0.24	55	59
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.022	0.055	-10000	0	-0.18	41	41
TSC2	0.009	0.052	-10000	0	-0.23	22	22
RHEB/GDP	-0.011	0.085	-10000	0	-0.22	54	54
TSC1	0.008	0.055	-10000	0	-0.25	21	21
Insulin Receptor/IRS1	0.004	0.062	-10000	0	-0.28	24	24
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.002	0.068	-10000	0	-0.2	39	39
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.011	0.048	-10000	0	-0.29	12	12
RPS6KB1	-0.001	0.066	0.16	3	-0.22	24	27
MAP3K5	-0.02	0.087	-10000	0	-0.29	49	49
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
apoptosis	-0.019	0.087	-10000	0	-0.29	49	49
mol:LY294002	0	0	0.001	28	-0.001	19	47
EIF4B	0.002	0.066	0.16	3	-0.23	22	25
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.011	0.069	-10000	0	-0.23	21	21
eIF4E/eIF4G1/eIF4A1	-0.022	0.065	-10000	0	-0.27	26	26
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.013	0.091	-10000	0	-0.18	99	99
mTOR/RHEB/GTP/Raptor/GBL	0.008	0.058	0.15	4	-0.18	25	29
FKBP1A	0.007	0.052	-10000	0	-0.18	31	31
RHEB/GTP	-0.001	0.088	-10000	0	-0.21	54	54
mol:Amino Acids	0	0	0.001	28	-0.001	19	47
FKBP12/Rapamycin	0.006	0.035	-10000	0	-0.12	31	31
PDPK1	-0.019	0.079	0.19	4	-0.16	93	97
EIF4E	0.002	0.07	-10000	0	-0.28	31	31
ASK1/PP5C	-0.038	0.19	-10000	0	-0.57	58	58
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.002	0.097	-10000	0	-0.37	31	31
TSC1/TSC2	-0.007	0.11	0.19	4	-0.26	55	59
tumor necrosis factor receptor activity	0	0	0.001	19	-0.001	28	47
RPS6	0.015	0.036	-10000	0	-0.29	7	7
PPP5C	0.017	0.015	-10000	0	-0.11	7	7
EIF4G1	0	0.073	-10000	0	-0.27	34	34
IRS1	-0.008	0.064	-10000	0	-0.3	24	24
INS	0.019	0	-10000	0	-10000	0	0
PTEN	0.013	0.037	-10000	0	-0.17	17	17
PDK2	-0.019	0.079	0.19	4	-0.16	94	98
EIF4EBP1	-0.042	0.26	-10000	0	-1.1	27	27
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
PPP2R5D	0.002	0.081	-10000	0	-0.48	12	12
peptide biosynthetic process	0.023	0.003	-10000	0	-10000	0	0
RHEB	0.019	0	-10000	0	-10000	0	0
EIF4A1	0.015	0.033	-10000	0	-0.27	7	7
mol:Rapamycin	0	0.001	0.003	6	-0.002	37	43
EEF2	0.023	0.003	-10000	0	-10000	0	0
eIF4E/4E-BP1	-0.032	0.25	-10000	0	-1.1	27	27

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.024	0.062	-10000	0	-0.14	53	53
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.018	0.01	-10000	0	-0.11	3	3
STAT1 (dimer)/Cbp/p300	0.026	0.083	-10000	0	-0.21	37	37
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.014	0.066	-10000	0	-0.17	52	52
antigen processing and presentation of peptide antigen via MHC class I	-0.047	0.092	-10000	0	-0.2	114	114
CaM/Ca2+	0.022	0.071	-10000	0	-0.15	58	58
RAP1A	0.018	0.019	-10000	0	-0.29	2	2
STAT1 (dimer)/SHP2	0.012	0.062	-10000	0	-0.18	24	24
AKT1	-0.012	0.1	-10000	0	-0.26	53	53
MAP2K1	0.013	0.058	-10000	0	-0.21	18	18
MAP3K11	0.012	0.055	-10000	0	-0.13	53	53
IFNGR1	0.013	0.038	-10000	0	-0.21	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.028	0.14	-10000	0	-0.29	81	81
Rap1/GTP	-0.01	0.032	-10000	0	-0.15	16	16
CRKL/C3G	0.028	0.007	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.033	0.061	-10000	0	-0.13	52	52
CEBPB	0.02	0.12	-10000	0	-0.43	23	23
STAT3	-0.003	0.079	-10000	0	-0.29	37	37
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.039	0.052	-10000	0	-10000	0	0
STAT1	0.006	0.059	-10000	0	-0.13	60	60
CALM1	0.007	0.056	-10000	0	-0.22	28	28
IFN-gamma (dimer)	0.017	0.012	-10000	0	-0.12	3	3
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
STAT1 (dimer)/PIAS1	0.012	0.072	-10000	0	-0.24	26	26
CEBPB/PTGES2/Cbp/p300	-0.022	0.088	-10000	0	-0.33	30	30
mol:Ca2+	0.022	0.06	-10000	0	-0.14	53	53
MAPK3	0.024	0.066	-10000	0	-0.41	4	4
STAT1 (dimer)	-0.035	0.14	-10000	0	-0.3	86	86
MAPK1	0.005	0.15	-10000	0	-0.76	17	17
JAK2	0.013	0.028	-10000	0	-0.11	23	23
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
JAK1	0.012	0.042	-10000	0	-0.22	14	14
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	0.026	0.091	-10000	0	-0.4	13	13
SMAD7	-0.007	0.064	-10000	0	-0.14	62	62
CBL/CRKL/C3G	0.031	0.053	-10000	0	-0.17	14	14
PI3K	-0.001	0.095	-10000	0	-0.24	48	48
IFNG	0.017	0.012	-10000	0	-0.12	3	3
apoptosis	0.021	0.075	0.21	2	-0.34	11	13
CAMK2G	0.007	0.047	-10000	0	-0.14	40	40
STAT3 (dimer)	-0.003	0.079	-10000	0	-0.29	37	37
CAMK2A	0.018	0.01	-10000	0	-0.11	3	3
CAMK2B	-0.048	0.11	-10000	0	-0.19	166	166
FRAP1	-0.008	0.094	-10000	0	-0.25	50	50
PRKCD	-0.009	0.087	-10000	0	-0.23	50	50
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.047	0.092	-10000	0	-0.2	114	114
PTPN2	0.018	0.013	-10000	0	-0.11	5	5
EP300	0.012	0.046	-10000	0	-0.24	15	15
IRF1	0.014	0.083	-10000	0	-0.27	27	27
STAT1 (dimer)/PIASy	0.013	0.059	-10000	0	-0.2	17	17
SOCS1	0.021	0.002	-10000	0	-10000	0	0
mol:GDP	0.028	0.05	-10000	0	-0.17	14	14
CASP1	-0.023	0.091	-10000	0	-0.19	99	99
PTGES2	0.019	0	-10000	0	-10000	0	0
IRF9	0.02	0.064	-10000	0	-0.2	31	31
mol:PI-3-4-5-P3	-0.01	0.089	-10000	0	-0.24	48	48
RAP1/GDP	0.018	0.043	-10000	0	-0.15	16	16
CBL	0.012	0.052	-10000	0	-0.13	53	53
MAP3K1	0.012	0.054	-10000	0	-0.14	40	40
PIAS1	0.008	0.056	-10000	0	-0.29	18	18
PIAS4	0.018	0.006	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.047	0.092	-10000	0	-0.2	114	114
PTPN11	0.008	0.054	-10000	0	-0.14	52	52
CREBBP	0.019	0.001	-10000	0	-10000	0	0
RAPGEF1	0.019	0	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.013	0.082	-9999	-0.42	8	8
PLK1	-0.041	0.22	-9999	-0.67	24	24
CDKN1B	-0.037	0.19	-9999	-0.38	84	84
FOXO3	-0.05	0.24	-9999	-0.46	105	105
KAT2B	-0.003	0.02	-9999	-0.043	91	91
FOXO1/SIRT1	0.005	0.09	-9999	-0.28	37	37
CAT	-0.054	0.27	-9999	-1	22	22
CTNNB1	0.017	0.023	-9999	-0.29	3	3
AKT1	0.002	0.069	-9999	-0.3	22	22
FOXO1	0.006	0.09	-9999	-0.29	33	33
MAPK10	-0.002	0.069	-9999	-0.18	60	60
mol:GTP	-0.001	0.004	-9999	-10000	0	0
FOXO4	-0.029	0.21	-9999	-0.49	62	62
response to oxidative stress	-0.001	0.022	-9999	-0.041	92	92
FOXO3A/SIRT1	-0.065	0.23	-9999	-0.46	109	109
XPO1	0.017	0.024	-9999	-0.29	3	3
EP300	0.013	0.046	-9999	-0.24	15	15
BCL2L11	0.018	0.031	-9999	-10000	0	0
FOXO1/SKP2	0.014	0.086	-9999	-0.29	29	29
mol:GDP	-0.001	0.022	-9999	-0.041	92	92
RAN	0.015	0.031	-9999	-0.24	7	7
GADD45A	-0.1	0.34	-9999	-0.9	74	74
YWHAQ	0.018	0.019	-9999	-0.29	2	2
FOXO1/14-3-3 family	0.018	0.16	-9999	-0.55	24	24
MST1	0.011	0.03	-9999	-0.13	7	7
CSNK1D	0.01	0.052	-9999	-0.27	17	17
CSNK1E	0.003	0.064	-9999	-0.23	34	34
FOXO4/14-3-3 family	0	0.16	-9999	-0.41	44	44
YWHAB	0.015	0.036	-9999	-0.29	7	7
MAPK8	0.01	0.047	-9999	-0.15	28	28
MAPK9	0.009	0.05	-9999	-0.16	31	31
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0.011	0.045	-9999	-0.21	19	19
YWHAZ	0.014	0.037	-9999	-0.23	11	11
SIRT1	0.004	0.048	-9999	-0.17	32	32
SOD2	-0.13	0.36	-9999	-0.81	104	104
RBL2	-0.061	0.3	-9999	-1	34	34
RAL/GDP	0.012	0.051	-9999	-0.18	28	28
CHUK	0.011	0.034	-9999	-0.19	6	6
Ran/GTP	0.011	0.023	-9999	-0.17	7	7
CSNK1G2	0.018	0.014	-9999	-0.29	1	1
RAL/GTP	0.013	0.051	-9999	-0.16	28	28
CSNK1G1	0.019	0	-9999	-10000	0	0
FASLG	0.018	0.031	-9999	-10000	0	0
SKP2	0.017	0.018	-9999	-10000	0	0
USP7	0.014	0.039	-9999	-0.28	9	9
IKBKB	0.014	0.023	-9999	-10000	0	0
CCNB1	-0.16	0.45	-9999	-1.1	97	97
FOXO1-3a-4/beta catenin	-0.033	0.21	-9999	-0.39	97	97
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.085	-9999	-0.28	29	29
CSNK1A1	0.014	0.038	-9999	-0.29	8	8
SGK1	-0.003	0.02	-9999	-0.043	91	91
CSNK1G3	0.017	0.025	-9999	-0.22	5	5
Ran/GTP/Exportin 1	0.022	0.029	-9999	-0.21	6	6
ZFAND5	-0.013	0.18	-9999	-0.55	31	31
SFN	0.002	0.044	-9999	-0.11	70	70
CDK2	0.014	0.034	-9999	-0.12	29	29
FOXO3A/14-3-3	-0.004	0.17	-9999	-0.48	36	36
CREBBP	0.022	0.002	-9999	-10000	0	0
FBXO32	-0.045	0.22	-9999	-0.42	105	105
BCL6	-0.084	0.34	-9999	-1.1	43	43
RALB	0.013	0.037	-9999	-0.19	15	15
RALA	0.005	0.063	-9999	-0.27	26	26
YWHAH	-0.006	0.083	-9999	-0.26	49	49

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.006	0.11	-10000	0	-0.25	65	65
epithelial cell differentiation	0.024	0.059	-10000	0	-0.18	34	34
CYFIP2	-0.02	0.099	-10000	0	-0.25	75	75
ENAH	0.014	0.069	-10000	0	-0.2	35	35
EGFR	-0.08	0.12	-10000	0	-0.29	97	97
EPHA2	0.008	0.036	-10000	0	-0.11	45	45
MYO6	0.011	0.065	-10000	0	-0.2	36	36
CTNNB1	0.017	0.023	-10000	0	-0.29	3	3
ABI1/Sra1/Nap1	0.009	0.072	-10000	0	-0.17	70	70
AQP5	0.017	0.089	-10000	0	-0.38	20	20
CTNND1	0.001	0.073	-10000	0	-0.29	31	31
mol:PI-4-5-P2	0.01	0.068	-10000	0	-0.21	39	39
regulation of calcium-dependent cell-cell adhesion	0.015	0.052	-10000	0	-0.17	34	34
EGF	0.014	0.025	-10000	0	-0.11	21	21
NCKAP1	0.019	0	-10000	0	-10000	0	0
AQP3	0.016	0.09	-10000	0	-0.38	20	20
cortical microtubule organization	0.024	0.059	-10000	0	-0.18	34	34
GO:0000145	0.005	0.064	-10000	0	-0.2	39	39
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.027	0.06	-10000	0	-0.18	34	34
MLLT4	0.019	0	-10000	0	-10000	0	0
ARF6/GDP	-0.018	0.054	-10000	0	-0.21	27	27
ARF6	0.018	0.015	-10000	0	-0.2	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.028	0.053	-10000	0	-0.14	36	36
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.017	0.13	-10000	0	-0.32	63	63
PVRL2	0.016	0.026	-10000	0	-0.19	7	7
ZYX	0.002	0.078	-10000	0	-0.23	45	45
ARF6/GTP	0.033	0.052	-10000	0	-0.14	31	31
CDH1	0.012	0.03	-10000	0	-0.11	29	29
EGFR/EGFR/EGF/EGF	-0.024	0.078	-10000	0	-0.14	113	113
RhoA/GDP	0.024	0.06	-10000	0	-0.17	38	38
actin cytoskeleton organization	0.012	0.065	-10000	0	-0.2	36	36
IGF-1R heterotetramer	-0.001	0.07	-10000	0	-0.21	46	46
GIT1	0.019	0.006	-10000	0	-0.11	1	1
IGF1R	-0.001	0.07	-10000	0	-0.21	46	46
IGF1	0.014	0.025	-10000	0	-0.11	21	21
DIAPH1	-0.035	0.21	-10000	0	-0.57	69	69
Wnt receptor signaling pathway	-0.024	0.059	0.18	34	-10000	0	34
RHOA	0.015	0.036	-10000	0	-0.29	7	7
RhoA/GTP	-0.019	0.057	-10000	0	-0.22	28	28
CTNNA1	0.011	0.048	-10000	0	-0.29	13	13
VCL	0.012	0.066	-10000	0	-0.2	36	36
EFNA1	-0.001	0.07	-10000	0	-0.21	46	46
LPP	0.004	0.076	-10000	0	-0.24	36	36
Ephrin A1/EPHA2	0.009	0.066	-10000	0	-0.15	59	59
SEC6/SEC8	-0.011	0.043	-10000	0	-0.2	19	19
MGAT3	0.015	0.053	-10000	0	-0.17	34	34
HGF/MET	0.016	0.055	-10000	0	-0.16	34	34
HGF	0.016	0.02	-10000	0	-0.11	13	13
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.006	0.11	-10000	0	-0.25	65	65
actin cable formation	-0.006	0.11	-10000	0	-0.26	65	65
KIAA1543	0.003	0.048	-10000	0	-0.16	34	34
KIFC3	0.015	0.053	-10000	0	-0.17	34	34
NCK1	0.014	0.036	-10000	0	-0.19	14	14
EXOC3	0.017	0.021	-10000	0	-0.2	4	4
ACTN1	0.003	0.073	-10000	0	-0.24	36	36
NCK1/GIT1	0.024	0.026	-10000	0	-0.19	6	6
mol:GDP	0.024	0.059	-10000	0	-0.18	34	34
EXOC4	0	0	-10000	0	-10000	0	0
STX4	0.013	0.064	-10000	0	-0.2	36	36
PIP5K1C	0.01	0.069	-10000	0	-0.21	39	39
LIMA1	-0.013	0.09	-10000	0	-0.24	66	66
ABI1	0.008	0.055	-10000	0	-0.24	22	22
ROCK1	0.017	0.066	-10000	0	-0.2	29	29
adherens junction assembly	0.007	0.089	-10000	0	-0.34	27	27
IGF-1R heterotetramer/IGF1	0.011	0.066	-10000	0	-0.16	50	50
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.026	0.018	-10000	0	-0.19	3	3
MET	0.008	0.037	-10000	0	-0.11	47	47
PLEKHA7	0.004	0.051	-10000	0	-0.17	34	34
mol:GTP	0.026	0.052	-10000	0	-0.14	36	36
establishment of epithelial cell apical/basal polarity	0.022	0.06	-10000	0	-0.25	18	18
cortical actin cytoskeleton stabilization	-0.006	0.11	-10000	0	-0.25	65	65
regulation of cell-cell adhesion	0.012	0.065	-10000	0	-0.2	36	36
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.006	0.11	-10000	0	-0.25	65	65

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.018	0.01	-10000	0	-0.11	3	3
RAS family/GTP/Tiam1	-0.006	0.096	-10000	0	-0.22	76	76
NT3 (dimer)/TRKC	0.021	0.032	-10000	0	-0.2	7	7
NT3 (dimer)/TRKB	-0.01	0.074	-10000	0	-0.15	95	95
SHC/Grb2/SOS1/GAB1/PI3K	-0.022	0.11	-10000	0	-0.23	93	93
RAPGEF1	0.019	0	-10000	0	-10000	0	0
BDNF	0.004	0.042	-10000	0	-0.11	62	62
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
DYNLT1	0.012	0.045	-10000	0	-0.28	12	12
NTRK1	0.018	0.011	-10000	0	-0.11	4	4
NTRK2	-0.043	0.12	-10000	0	-0.23	132	132
NTRK3	0.01	0.043	-10000	0	-0.29	7	7
NT-4/5 (dimer)/TRKB	-0.02	0.07	-10000	0	-0.16	95	95
neuron apoptosis	0.033	0.13	0.33	61	-10000	0	61
SHC 2-3/Grb2	-0.036	0.14	-10000	0	-0.36	61	61
SHC1	0.004	0.052	-10000	0	-0.14	48	48
SHC2	-0.039	0.13	-10000	0	-0.4	48	48
SHC3	-0.041	0.13	-10000	0	-0.4	46	46
STAT3 (dimer)	-0.025	0.12	-10000	0	-0.32	64	64
NT3 (dimer)/TRKA	0.027	0.03	-10000	0	-0.1	2	2
RIN/GDP	0.001	0.075	-10000	0	-0.21	38	38
GIPC1	0.019	0	-10000	0	-10000	0	0
KRAS	0.011	0.048	-10000	0	-0.28	14	14
DNAJA3	-0.004	0.044	0.18	3	-0.17	8	11
RIN/GTP	-0.019	0.056	-10000	0	-0.092	164	164
CCND1	-0.04	0.16	-10000	0	-0.41	64	64
MAGED1	0.004	0.066	-10000	0	-0.28	26	26
PTPN11	0.015	0.033	-10000	0	-0.27	7	7
RICS	0.001	0.066	-10000	0	-0.21	41	41
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.014	0.039	-10000	0	-0.17	16	16
GRB2	0.014	0.039	-10000	0	-0.26	10	10
NGF (dimer)/TRKA/MATK	0.025	0.009	-10000	0	-10000	0	0
TRKA/NEDD4-2	0.022	0.024	-10000	0	-0.19	1	1
ELMO1	-0.047	0.11	-10000	0	-0.21	154	154
RhoG/GTP/ELMO1/DOCK1	-0.017	0.073	-10000	0	-0.16	90	90
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.009	0.055	-10000	0	-0.28	18	18
DOCK1	0.011	0.047	-10000	0	-0.22	19	19
GAB2	-0.005	0.082	-10000	0	-0.27	44	44
RIT2	-0.031	0.084	-10000	0	-0.14	164	164
RIT1	-0.008	0.083	-10000	0	-0.23	57	57
FRS2	0.018	0.013	-10000	0	-0.11	5	5
DNM1	0.017	0.017	-10000	0	-0.11	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.009	0.054	-10000	0	-0.28	17	17
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.022	0.069	0.17	3	-0.2	37	40
mol:GDP	0.005	0.1	-10000	0	-0.31	34	34
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	-0.03	0.077	-10000	0	-0.14	154	154
RIT1/GDP	0.007	0.081	-10000	0	-0.2	46	46
TIAM1	0.003	0.066	-10000	0	-0.23	35	35
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
BDNF (dimer)/TRKB	-0.015	0.083	-10000	0	-0.17	106	106
KIDINS220/CRKL/C3G	0.028	0.007	-10000	0	-10000	0	0
SHC/RasGAP	0.007	0.062	-10000	0	-0.2	35	35
FRS2 family/SHP2	0.036	0.022	-10000	0	-0.15	6	6
SHC/GRB2/SOS1/GAB1	0.016	0.047	-10000	0	-0.14	29	29
RIT1/GTP	-0.004	0.056	-10000	0	-0.2	38	38
NT3 (dimer)	0.018	0.01	-10000	0	-0.11	3	3
RAP1/GDP	-0.017	0.049	-10000	0	-0.17	36	36
KIDINS220/CRKL	0.018	0.01	-10000	0	-0.11	3	3
BDNF (dimer)	0.004	0.042	-10000	0	-0.11	62	62
ubiquitin-dependent protein catabolic process	0.02	0.02	-10000	0	-0.16	1	1
Schwann cell development	-0.014	0.021	-10000	0	-0.088	10	10
EHD4	0.007	0.057	-10000	0	-0.23	25	25
FRS2 family/GRB2/SOS1	0.033	0.023	-10000	0	-0.14	8	8
FRS2 family/SHP2/CRK family/C3G/GAB2	0.018	0.071	-10000	0	-0.35	12	12
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.018	0.019	-10000	0	-0.29	2	2
CDC42/GTP	-0.016	0.089	-10000	0	-0.21	68	68
ABL1	-0.012	0.093	-10000	0	-0.28	55	55
SH2B family/GRB2/SOS1	0.011	0.026	-10000	0	-0.17	10	10
Rap1/GTP	0.01	0.055	-10000	0	-0.2	11	11
STAT3	-0.025	0.12	-10000	0	-0.32	64	64
axon guidance	-0.022	0.082	-10000	0	-0.2	68	68
MAPK3	0.022	0.008	-10000	0	-10000	0	0
MAPK1	0.021	0.014	-10000	0	-0.19	1	1
CDC42/GDP	0.013	0.072	-10000	0	-0.2	35	35
NTF3	0.018	0.01	-10000	0	-0.11	3	3
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.021	0.027	-10000	0	-0.16	10	10
PI3K	-0.016	0.093	-10000	0	-0.21	88	88
FRS3	0.019	0.006	-10000	0	-10000	0	0
FAIM	0.011	0.045	-10000	0	-0.21	18	18
GAB1	0.003	0.056	-10000	0	-0.15	50	50
RASGRF1	-0.003	0.043	0.16	4	-0.15	9	13
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	0.013	0.04	-10000	0	-0.18	14	14
RGS19	0.013	0.041	-10000	0	-0.29	9	9
CDC42	0.017	0.016	-10000	0	-0.11	8	8
RAS family/GTP	0.008	0.099	-10000	0	-0.37	26	26
Rac1/GDP	0.013	0.075	-10000	0	-0.21	35	35
NGF (dimer)/TRKA/GRIT	0.015	0.039	-10000	0	-0.16	22	22
neuron projection morphogenesis	-0.066	0.26	-10000	0	-0.94	38	38
NGF (dimer)/TRKA/NEDD4-2	0.02	0.02	-10000	0	-0.16	1	1
MAP2K1	0.009	0.046	-10000	0	-0.15	29	29
NGFR	0.002	0.044	-10000	0	-0.11	70	70
NGF (dimer)/TRKA/GIPC/GAIP	0.023	0.047	-10000	0	-0.22	16	16
RAS family/GTP/PI3K	-0.033	0.12	-10000	0	-0.22	127	127
FRS2 family/SHP2/GRB2/SOS1	0.04	0.033	-10000	0	-0.18	10	10
NRAS	-0.01	0.086	-10000	0	-0.24	59	59
GRB2/SOS1	0.011	0.026	-10000	0	-0.17	10	10
PRKCI	0.015	0.028	-10000	0	-0.14	15	15
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.015	0.036	-10000	0	-0.29	7	7
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.008	0.079	-10000	0	-0.52	10	10
RASA1	0.003	0.069	-10000	0	-0.28	29	29
TRKA/c-Abl	0.006	0.066	-10000	0	-0.19	52	52
SQSTM1	0.004	0.062	-10000	0	-0.22	32	32
BDNF (dimer)/TRKB/GIPC	0	0.077	-10000	0	-0.15	94	94
NGF (dimer)/TRKA/p62/Atypical PKCs	0.024	0.035	-10000	0	-0.13	22	22
MATK	0.018	0.01	-10000	0	-0.11	3	3
NEDD4L	0.011	0.033	-10000	0	-0.12	32	32
RAS family/GDP	-0.025	0.055	-10000	0	-0.17	54	54
NGF (dimer)/TRKA	-0.007	0.046	0.19	4	-0.16	9	13
Rac1/GTP	-0.035	0.068	-10000	0	-0.2	59	59
FRS2 family/SHP2/CRK family	0.048	0.038	-10000	0	-0.13	20	20

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.035	0.11	-10000	0	-0.25	105	105
EPHB2	0.014	0.027	-10000	0	-0.11	24	24
EFNB1	0.02	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.028	0.052	-10000	0	-0.21	7	7
Ephrin B2/EPHB1-2	-0.008	0.072	-10000	0	-0.14	96	96
neuron projection morphogenesis	0.016	0.044	-10000	0	-0.2	7	7
Ephrin B1/EPHB1-2/Tiam1	0.024	0.048	-10000	0	-0.12	13	13
DNM1	0.017	0.017	-10000	0	-0.11	8	8
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.041	0.17	-10000	0	-0.56	49	49
YES1	-0.06	0.24	-10000	0	-0.81	48	48
Ephrin B1/EPHB1-2/NCK2	0.028	0.044	-10000	0	-0.12	8	8
PI3K	-0.049	0.2	-10000	0	-0.63	52	52
mol:GDP	0.023	0.047	-10000	0	-0.12	13	13
ITGA2B	0.019	0	-10000	0	-10000	0	0
endothelial cell proliferation	-0.006	0.066	-10000	0	-0.16	83	83
FYN	-0.071	0.25	-10000	0	-0.84	48	48
MAP3K7	-0.046	0.18	-10000	0	-0.59	48	48
FGR	-0.059	0.23	-10000	0	-0.78	48	48
TIAM1	0.003	0.066	-10000	0	-0.23	35	35
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
RGS3	0.017	0.016	-10000	0	-0.11	8	8
cell adhesion	-0.038	0.19	-10000	0	-0.58	51	51
LYN	-0.073	0.23	-10000	0	-0.79	48	48
Ephrin B1/EPHB1-2/Src Family Kinases	-0.058	0.22	-10000	0	-0.74	48	48
Ephrin B1/EPHB1-2	-0.049	0.18	-10000	0	-0.63	48	48
SRC	-0.055	0.23	-10000	0	-0.78	48	48
ITGB3	0.019	0.008	-10000	0	-0.11	2	2
EPHB1	-0.005	0.057	-10000	0	-0.12	91	91
EPHB4	0.019	0.006	-10000	0	-0.11	1	1
RAC1	0.015	0.036	-10000	0	-0.29	7	7
Ephrin B2/EPHB4	-0.006	0.067	-10000	0	-0.16	83	83
alphaIIb/beta3 Integrin	0.028	0.006	-10000	0	-10000	0	0
BLK	-0.056	0.23	-10000	0	-0.78	48	48
HCK	-0.077	0.24	-10000	0	-0.8	48	48
regulation of stress fiber formation	-0.026	0.043	0.12	8	-10000	0	8
MAPK8	-0.035	0.16	-10000	0	-0.53	49	49
Ephrin B1/EPHB1-2/RGS3	0.032	0.038	-10000	0	-0.12	6	6
endothelial cell migration	-0.051	0.17	-10000	0	-0.55	48	48
NCK2	0.009	0.054	-10000	0	-0.28	17	17
PTPN13	-0.006	0.098	-10000	0	-0.36	33	33
regulation of focal adhesion formation	-0.026	0.043	0.12	8	-10000	0	8
chemotaxis	-0.031	0.037	0.12	6	-10000	0	6
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
Rac1/GTP	0.023	0.048	-10000	0	-0.21	7	7
angiogenesis	-0.048	0.18	-10000	0	-0.62	48	48
LCK	-0.056	0.23	-10000	0	-0.78	48	48

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.002	0.048	-10000	0	-0.25	15	15
HSPA8	0.01	0.057	-10000	0	-0.29	18	18
SMAD3/SMAD4/ER alpha	0.045	0.078	0.2	33	-0.17	20	53
AKT1	0.006	0.064	-10000	0	-0.28	23	23
GSC	0.013	0.024	-10000	0	-10000	0	0
NKX2-5	0.014	0.025	-10000	0	-0.11	18	18
muscle cell differentiation	-0.01	0.11	0.31	44	-10000	0	44
SMAD2-3/SMAD4/SP1	0.018	0.12	-10000	0	-0.25	57	57
SMAD4	0.007	0.068	-10000	0	-0.19	37	37
CBFB	0.017	0.018	-10000	0	-0.15	5	5
SAP18	0.011	0.052	-10000	0	-0.29	15	15
Cbp/p300/MSG1	-0.023	0.081	-10000	0	-0.17	107	107
SMAD3/SMAD4/VDR	0.021	0.09	-10000	0	-0.21	43	43
MYC	-0.026	0.098	-10000	0	-0.22	96	96
CDKN2B	0.029	0.048	-10000	0	-10000	0	0
AP1	-0.007	0.13	-10000	0	-0.32	63	63
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.007	0.15	-10000	0	-0.46	33	33
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.025	0.18	-10000	0	-0.45	56	56
SP3	0.012	0.047	-10000	0	-0.29	12	12
CREB1	0.015	0.033	-10000	0	-0.27	7	7
FOXH1	0.019	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	0.035	0.083	0.17	19	-0.2	31	50
GATA3	0.023	0.017	-10000	0	-0.1	1	1
SKI/SIN3/HDAC complex/NCoR1	0.012	0.1	-10000	0	-0.36	23	23
MEF2C/TIF2	0.028	0.077	-10000	0	-0.27	24	24
endothelial cell migration	0.27	0.51	1.3	111	-10000	0	111
MAX	0.028	0.018	-10000	0	-10000	0	0
RBBP7	0.016	0.034	-10000	0	-0.25	8	8
RBBP4	-0.005	0.079	-10000	0	-0.24	50	50
RUNX2	0.019	0	-10000	0	-10000	0	0
RUNX3	0.014	0.024	-10000	0	-0.11	19	19
RUNX1	0.019	0	-10000	0	-10000	0	0
CTBP1	0.007	0.059	-10000	0	-0.29	20	20
NR3C1	0.024	0.041	-10000	0	-0.3	7	7
VDR	0.019	0.008	-10000	0	-0.11	2	2
CDKN1A	-0.12	0.39	-10000	0	-1.2	62	62
KAT2B	-0.004	0.007	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.025	0.072	-10000	0	-0.18	46	46
DCP1A	0.012	0.046	-10000	0	-0.29	12	12
SKI	0.02	0.001	-10000	0	-10000	0	0
SERPINE1	-0.28	0.52	-10000	0	-1.3	111	111
SMAD3/SMAD4/ATF2	0.022	0.071	-10000	0	-0.16	38	38
SMAD3/SMAD4/ATF3	-0.008	0.11	-10000	0	-0.2	99	99
SAP30	0.017	0.027	-10000	0	-0.29	4	4
Cbp/p300/PIAS3	0.014	0.046	-10000	0	-0.17	18	18
JUN	-0.014	0.13	-10000	0	-0.32	62	62
SMAD3/SMAD4/IRF7	0.024	0.077	-10000	0	-0.18	34	34
TFE3	-0.006	0.065	-10000	0	-0.2	37	37
COL1A2	-0.13	0.26	-10000	0	-0.72	81	81
mesenchymal cell differentiation	-0.023	0.07	0.16	38	-10000	0	38
DLX1	0	0	-10000	0	-10000	0	0
TCF3	0.019	0	-10000	0	-10000	0	0
FOS	-0.02	0.096	-10000	0	-0.19	97	97
SMAD3/SMAD4/Max	0.04	0.072	0.17	19	-0.17	24	43
Cbp/p300/SNIP1	0.025	0.033	-10000	0	-0.16	11	11
ZBTB17	0.017	0.006	-10000	0	-0.11	1	1
LAMC1	-0.009	0.12	-10000	0	-0.34	51	51
TGIF2/HDAC complex/SMAD3/SMAD4	0.021	0.072	-10000	0	-0.18	30	30
IRF7	0.014	0.043	-10000	0	-0.17	24	24
ESR1	0.029	0.025	-10000	0	-10000	0	0
HNF4A	0.019	0	-10000	0	-10000	0	0
MEF2C	0.018	0.079	-10000	0	-0.27	27	27
SMAD2-3/SMAD4	0.022	0.087	-10000	0	-0.22	34	34
Cbp/p300/Src-1	0.008	0.064	-10000	0	-0.18	48	48
IGHV3OR16-13	-0.005	0.064	-10000	0	-0.59	6	6
TGIF2/HDAC complex	0.014	0.024	-10000	0	-0.11	19	19
CREBBP	0.012	0.012	-10000	0	-10000	0	0
SKIL	0.019	0.006	-10000	0	-0.11	1	1
HDAC1	0.014	0.04	-10000	0	-0.22	13	13
HDAC2	0.005	0.061	-10000	0	-0.22	33	33
SNIP1	0.02	0.01	-10000	0	-0.11	3	3
GCN5L2	0.009	0.03	-10000	0	-0.18	9	9
SMAD3/SMAD4/TFE3	0.009	0.11	-10000	0	-0.23	63	63
MSG1/HSC70	-0.027	0.093	-10000	0	-0.2	111	111
SMAD2	0.013	0.05	-10000	0	-0.28	14	14
SMAD3	0.015	0.041	-10000	0	-0.11	25	25
SMAD3/E2F4-5/DP1/p107/SMAD4	0.013	0.073	-10000	0	-0.2	38	38
SMAD2/SMAD2/SMAD4	-0.011	0.065	0.11	2	-0.22	37	39
NCOR1	0.01	0.054	-10000	0	-0.27	18	18
NCOA2	0.018	0.01	-10000	0	-0.11	3	3
NCOA1	-0.006	0.083	-10000	0	-0.28	43	43
MYOD/E2A	0.028	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.03	0.12	-10000	0	-0.24	48	48
IFNB1	0.023	0.062	-10000	0	-0.19	16	16
SMAD3/SMAD4/MEF2C	0.035	0.094	-10000	0	-0.28	28	28
CITED1	-0.054	0.12	-10000	0	-0.22	162	162
SMAD2-3/SMAD4/ARC105	0.035	0.082	-10000	0	-0.22	26	26
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.01	0.16	-10000	0	-0.45	47	47
RUNX1-3/PEBPB2	0.035	0.019	-10000	0	-0.15	1	1
SMAD7	-0.041	0.2	-10000	0	-0.5	66	66
MYC/MIZ-1	-0.007	0.069	-10000	0	-0.2	54	54
SMAD3/SMAD4	-0.099	0.21	-10000	0	-0.46	120	120
IL10	0.03	0.059	-10000	0	-0.22	9	9
PIASy/HDAC complex	0.025	0.012	-10000	0	-10000	0	0
PIAS3	0.012	0.034	-10000	0	-0.19	12	12
CDK2	0.005	0.037	-10000	0	-0.13	29	29
IL5	0.03	0.059	-10000	0	-0.22	9	9
CDK4	-0.013	0.067	-10000	0	-0.15	80	80
PIAS4	0.025	0.012	-10000	0	-10000	0	0
ATF3	-0.036	0.11	-10000	0	-0.22	121	121
SMAD3/SMAD4/SP1	0.001	0.12	-10000	0	-0.23	72	72
FOXG1	-0.03	0.11	-10000	0	-0.27	91	91
FOXO3	0.013	0.046	-10000	0	-0.21	18	18
FOXO1	0.003	0.06	-10000	0	-0.2	35	35
FOXO4	0.013	0.044	-10000	0	-0.19	22	22
heart looping	0.018	0.078	-10000	0	-0.27	27	27
CEBPB	-0.003	0.076	-10000	0	-0.22	51	51
SMAD3/SMAD4/DLX1	0.013	0.067	-10000	0	-0.15	48	48
MYOD1	0.019	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.023	0.07	-10000	0	-0.18	26	26
SMAD3/SMAD4/GATA3	0.036	0.075	-10000	0	-0.23	13	13
SnoN/SIN3/HDAC complex/NCoR1	0.019	0.006	-10000	0	-0.11	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.042	0.066	-10000	0	-0.18	14	14
SMAD3/SMAD4/SP1-3	0.014	0.12	-10000	0	-0.24	57	57
MED15	0.018	0.013	-10000	0	-0.11	5	5
SP1	-0.011	0.057	-10000	0	-0.12	92	92
SIN3B	0.017	0.025	-10000	0	-0.2	6	6
SIN3A	0.001	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.038	0.076	-10000	0	-0.21	31	31
ITGB5	-0.004	0.11	-10000	0	-0.27	47	47
TGIF/SIN3/HDAC complex/CtBP	-0.004	0.13	-10000	0	-0.44	29	29
SMAD3/SMAD4/AR	0.02	0.071	-10000	0	-0.15	44	44
AR	0.014	0.026	-10000	0	-0.11	22	22
negative regulation of cell growth	-0.018	0.14	-10000	0	-0.32	73	73
SMAD3/SMAD4/MYOD	0.023	0.07	-10000	0	-0.16	38	38
E2F5	0.019	0	-10000	0	-10000	0	0
E2F4	0.019	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.031	0.08	-10000	0	-0.2	40	40
SMAD2-3/SMAD4/FOXO1-3a-4	-0.01	0.16	-10000	0	-0.47	40	40
TFDP1	0.005	0.059	-10000	0	-0.2	33	33
SMAD3/SMAD4/AP1	0.002	0.14	-10000	0	-0.32	62	62
SMAD3/SMAD4/RUNX2	0.023	0.07	-10000	0	-0.16	38	38
TGIF2	0.014	0.024	-10000	0	-0.11	19	19
TGIF1	-0.005	0.077	-10000	0	-0.22	55	55
ATF2	0.017	0.017	-10000	0	-0.11	9	9

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.015	0.14	-9999	-0.29	89	89
MAP3K8	0.003	0.042	-9999	-0.11	62	62
FOS	-0.006	0.095	-9999	-0.34	21	21
PRKCA	0.016	0.008	-9999	-10000	0	0
PTPN7	0.014	0.017	-9999	-0.12	5	5
HRAS	0.008	0.055	-9999	-0.28	18	18
PRKCB	-0.002	0.006	-9999	-0.015	85	85
NRAS	-0.01	0.086	-9999	-0.24	59	59
RAS family/GTP	0.008	0.069	-9999	-0.17	59	59
MAPK3	0.012	0.041	-9999	-10000	0	0
MAP2K1	0.001	0.057	-9999	-0.25	17	17
ELK1	0.014	0.013	-9999	-10000	0	0
BRAF	0.008	0.025	-9999	-10000	0	0
mol:GTP	-0.001	0.002	-9999	-0.004	85	85
MAPK1	-0.002	0.1	-9999	-0.57	13	13
RAF1	-0.003	0.077	-9999	-0.39	18	18
KRAS	0.011	0.049	-9999	-0.28	14	14

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.008	0.056	-9999	-0.29	18	18
VLDLR	-0.021	0.093	-9999	-0.2	97	97
LRPAP1	0.013	0.043	-9999	-0.28	11	11
NUDC	0.01	0.053	-9999	-0.29	16	16
RELN/LRP8	0.022	0.045	-9999	-0.15	20	20
CaM/Ca2+	0.006	0.038	-9999	-0.2	16	16
KATNA1	0.012	0.045	-9999	-0.28	12	12
GO:0030286	0	0	-9999	-10000	0	0
ABL1	0.009	0.054	-9999	-0.2	24	24
IQGAP1/CaM	0.001	0.074	-9999	-0.2	58	58
DAB1	0.019	0.006	-9999	-0.11	1	1
IQGAP1	-0.009	0.087	-9999	-0.27	50	50
PLA2G7	0.007	0.038	-9999	-0.11	49	49
CALM1	0.007	0.056	-9999	-0.21	28	28
DYNLT1	0.012	0.045	-9999	-0.28	12	12
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.018	0.043	-9999	-0.2	16	16
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.012	0.036	-9999	-0.14	23	23
CDK5R1	0.014	0.025	-9999	-0.11	21	21
LIS1/Poliovirus Protein 3A	0.005	0.049	-9999	-0.2	26	26
CDK5R2	0.015	0.023	-9999	-0.11	17	17
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	0.007	0.061	-9999	-0.15	54	54
YWHAE	0.011	0.045	-9999	-0.21	19	19
NDEL1/14-3-3 E	0.01	0.09	-9999	-0.29	29	29
MAP1B	-0.022	0.082	-9999	-0.24	62	62
RAC1	-0.001	0.071	-9999	-0.29	18	18
p35/CDK5	0.004	0.072	-9999	-0.15	74	74
RELN	0.007	0.038	-9999	-0.11	50	50
PAFAH/LIS1	0.012	0.055	-9999	-0.2	26	26
LIS1/CLIP170	0.015	0.056	-9999	-0.2	28	28
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	0.006	0.1	-9999	-0.28	45	45
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.013	0.1	-9999	-0.23	83	83
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.002	0.086	-9999	-0.28	28	28
LIS1/IQGAP1	0.003	0.077	-9999	-0.19	62	62
RHOA	-0.001	0.076	-9999	-0.32	16	16
PAFAH1B1	0.013	0.039	-9999	-0.19	19	19
PAFAH1B3	-0.007	0.08	-9999	-0.22	57	57
PAFAH1B2	0.019	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.004	0.094	-9999	-0.21	71	71
NDEL1/Katanin 60/Dynein heavy chain	0.014	0.098	-9999	-0.28	36	36
LRP8	0.01	0.043	-9999	-0.16	28	28
NDEL1/Katanin 60	0.01	0.091	-9999	-0.28	31	31
P39/CDK5	0.004	0.072	-9999	-0.15	72	72
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.014	0.07	-9999	-0.27	28	28
CDK5	0.008	0.059	-9999	-0.21	27	27
PPP2R5D	0.018	0.013	-9999	-0.11	5	5
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.013	0.048	-9999	-0.17	28	28
CSNK2A1	0.01	0.053	-9999	-0.29	16	16
RELN/VLDLR/DAB1/LIS1	0.012	0.071	-9999	-0.14	69	69
RELN/VLDLR	0.01	0.067	-9999	-0.14	73	73
CDC42	0.004	0.046	-9999	-0.13	48	48

×

Aurora A signaling

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
Aurora A/GADD45A	0.005	0.08	-10000	0	-0.25	38	38
BIRC5	-0.03	0.1	-10000	0	-0.22	111	111
NFKBIA	0.007	0.06	-10000	0	-0.18	43	43
CPEB1	-0.004	0.076	-10000	0	-0.22	51	51
AKT1	0.009	0.066	-10000	0	-0.24	29	29
NDEL1	0.013	0.043	-10000	0	-0.28	11	11
Aurora A/BRCA1	0.015	0.05	-10000	0	-0.18	25	25
NDEL1/TACC3	0.013	0.071	-10000	0	-0.19	47	47
GADD45A	-0.022	0.1	-10000	0	-0.26	78	78
GSK3B	0.007	0.064	-10000	0	-0.26	26	26
PAK1/Aurora A	0.016	0.056	-10000	0	-0.2	25	25
MDM2	0.011	0.032	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.019	0.079	-10000	0	-0.19	89	89
TP53	0.004	0.081	-10000	0	-0.28	33	33
DLG7	-0.011	0.069	-10000	0	-0.18	66	66
AURKAIP1	0.018	0.015	-10000	0	-0.2	2	2
ARHGEF7	0	0.071	-10000	0	-0.25	37	37
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.014	0.075	-10000	0	-0.2	47	47
G2/M transition of mitotic cell cycle	0.015	0.049	-10000	0	-0.18	25	25
AURKA	0.012	0.063	0.14	16	-0.24	25	41
AURKB	0.006	0.037	-10000	0	-0.16	17	17
CDC25B	0.001	0.095	-10000	0	-0.32	36	36
G2/M transition checkpoint	0.003	0.047	-10000	0	-0.18	25	25
mRNA polyadenylation	0.004	0.064	-10000	0	-0.16	57	57
Aurora A/CPEB	0.004	0.064	-10000	0	-0.16	57	57
Aurora A/TACC1/TRAP/chTOG	0.021	0.087	-10000	0	-0.25	35	35
BRCA1	0.017	0.015	-10000	0	-0.11	7	7
centrosome duplication	0.016	0.056	-10000	0	-0.2	25	25
regulation of centrosome cycle	0.012	0.07	-10000	0	-0.18	47	47
spindle assembly	0.019	0.086	-10000	0	-0.24	35	35
TDRD7	0.004	0.065	-10000	0	-0.27	27	27
Aurora A/RasGAP/Survivin	0.004	0.086	-10000	0	-0.24	42	42
CENPA	-0.006	0.092	-10000	0	-0.35	31	31
Aurora A/PP2A	0.017	0.055	-10000	0	-0.2	25	25
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0	0.078	-10000	0	-0.25	35	35
negative regulation of DNA binding	0	0.084	-10000	0	-0.28	33	33
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.015	0.05	-10000	0	-0.19	28	28
RASA1	0.003	0.069	-10000	0	-0.28	29	29
Ajuba/Aurora A	0.004	0.047	-10000	0	-0.18	25	25
mitotic prometaphase	-0.001	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.063	0.14	16	-0.24	25	41
TACC1	0.01	0.049	-10000	0	-0.29	13	13
TACC3	-0.004	0.075	-10000	0	-0.21	54	54
Aurora A/Antizyme1	0.027	0.053	-10000	0	-0.18	27	27
Aurora A/RasGAP	0.012	0.073	-10000	0	-0.29	25	25
OAZ1	0.017	0.023	-10000	0	-0.29	3	3
RAN	0.016	0.031	-10000	0	-0.24	7	7
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.021	0.011	-10000	0	-10000	0	0
GIT1	0.019	0.006	-10000	0	-0.11	1	1
GIT1/beta-PIX/PAK1	0.026	0.045	-10000	0	-0.15	29	29
Importin alpha/Importin beta/TPX2	-0.019	0.079	-10000	0	-0.19	89	89
PPP2R5D	0.018	0.013	-10000	0	-0.11	5	5
Aurora A/TPX2	-0.009	0.087	-10000	0	-0.18	85	85
PAK1	0.017	0.017	-10000	0	-0.11	9	9
CKAP5	0.004	0.066	-10000	0	-0.29	25	25

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.08	0.36	-10000	0	-1	28	28
STAT6 (cleaved dimer)	-0.17	0.27	-10000	0	-0.85	50	50
IGHG1	-0.037	0.23	-10000	0	-0.62	38	38
IGHG3	-0.087	0.34	-10000	0	-0.9	38	38
AKT1	-0.035	0.26	-10000	0	-0.72	34	34
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.004	0.18	-10000	0	-0.48	18	18
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.03	0.25	-10000	0	-0.69	30	30
THY1	-0.16	0.5	-10000	0	-1.3	65	65
MYB	0.013	0.028	-10000	0	-0.11	26	26
HMGA1	0.016	0.019	-10000	0	-0.11	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.021	0.23	-10000	0	-0.54	31	31
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.026	0.24	-10000	0	-0.69	26	26
SP1	-0.001	0.05	-10000	0	-0.14	36	36
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.011	0.032	-10000	0	-0.2	7	7
STAT6 (dimer)/ETS1	-0.07	0.34	-10000	0	-0.91	38	38
SOCS1	-0.031	0.27	-10000	0	-0.66	35	35
SOCS3	-0.003	0.2	-10000	0	-0.65	3	3
FCER2	-0.05	0.29	-10000	0	-0.74	26	26
PARP14	0.002	0.001	-10000	0	-10000	0	0
CCL17	-0.079	0.35	-10000	0	-1	26	26
GRB2	0.014	0.039	-10000	0	-0.26	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.015	0.2	-10000	0	-0.58	25	25
T cell proliferation	-0.085	0.36	-10000	0	-0.98	39	39
IL4R/JAK1	-0.092	0.36	-10000	0	-0.99	36	36
EGR2	-0.14	0.48	-10000	0	-1.3	59	59
JAK2	0.014	0.048	-10000	0	-0.15	12	12
JAK3	0.023	0.004	-10000	0	-10000	0	0
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
JAK1	0.005	0.073	-10000	0	-0.26	34	34
COL1A2	-0.18	0.47	-10000	0	-1.2	81	81
CCL26	-0.087	0.35	-10000	0	-0.94	38	38
IL4R	-0.086	0.38	-10000	0	-1.1	28	28
PTPN6	0.005	0.057	-10000	0	-0.19	33	33
IL13RA2	-0.39	0.65	-10000	0	-1.2	201	201
IL13RA1	-0.007	0.091	-10000	0	-0.29	40	40
IRF4	0.029	0.098	-10000	0	-10000	0	0
ARG1	-0.002	0.16	-10000	0	-0.58	12	12
CBL	-0.017	0.22	-10000	0	-0.51	31	31
GTF3A	0.02	0.024	-10000	0	-0.2	3	3
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
IL13RA1/JAK2	0.009	0.084	-10000	0	-0.19	39	39
IRF4/BCL6	0.019	0.1	-10000	0	-10000	0	0
CD40LG	0.028	0.001	-10000	0	-10000	0	0
MAPK14	-0.012	0.22	-10000	0	-0.53	23	23
mitosis	-0.031	0.25	-10000	0	-0.67	34	34
STAT6	-0.092	0.4	-10000	0	-1	38	38
SPI1	0.019	0.028	-10000	0	-10000	0	0
RPS6KB1	-0.026	0.24	-10000	0	-0.64	34	34
STAT6 (dimer)	-0.092	0.4	-10000	0	-1	38	38
STAT6 (dimer)/PARP14	-0.098	0.36	-10000	0	-0.98	38	38
mast cell activation	-0.001	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.008	0.2	-10000	0	-0.5	23	23
FRAP1	-0.035	0.26	-10000	0	-0.72	34	34
LTA	-0.079	0.36	-10000	0	-1.1	26	26
FES	0.017	0.016	-10000	0	-0.11	8	8
T-helper 1 cell differentiation	0.09	0.39	1	38	-10000	0	38
CCL11	-0.08	0.34	-10000	0	-1	26	26
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.003	0.2	-10000	0	-0.51	18	18
IL2RG	0.017	0.027	-10000	0	-0.1	24	24
IL10	-0.079	0.35	-10000	0	-1	26	26
IRS1	-0.002	0.07	-10000	0	-0.19	53	53
IRS2	-0.021	0.1	-10000	0	-0.25	79	79
IL4	0.013	0.12	-10000	0	-10000	0	0
IL5	-0.079	0.35	-10000	0	-1	26	26
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.075	0.34	-10000	0	-0.84	40	40
COL1A1	-0.018	0.21	-10000	0	-1.2	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.091	0.36	-10000	0	-1.1	30	30
IL2R gamma/JAK3	0.031	0.02	-10000	0	-10000	0	0
TFF3	-0.082	0.36	-10000	0	-1.1	27	27
ALOX15	-0.079	0.35	-10000	0	-1	26	26
MYBL1	-0.016	0.085	-10000	0	-0.18	93	93
T-helper 2 cell differentiation	-0.064	0.31	-10000	0	-0.77	42	42
SHC1	0.004	0.052	-10000	0	-0.14	48	48
CEBPB	0.002	0.077	-10000	0	-0.22	51	51
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.034	0.25	-10000	0	-0.66	36	36
mol:PI-3-4-5-P3	-0.034	0.26	-10000	0	-0.72	34	34
PI3K	-0.039	0.27	-10000	0	-0.77	34	34
DOK2	0	0	-10000	0	-10000	0	0
ETS1	0.016	0.018	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.014	0.2	-10000	0	-0.57	29	29
ITGB3	-0.079	0.36	-10000	0	-1.1	26	26
PIGR	-0.079	0.36	-10000	0	-1.1	26	26
IGHE	0.005	0.077	0.2	35	-0.18	28	63
MAPKKK cascade	-0.013	0.2	-10000	0	-0.56	29	29
BCL6	-0.009	0.082	-10000	0	-0.23	56	56
OPRM1	-0.079	0.35	-10000	0	-1	30	30
RETNLB	-0.087	0.35	-10000	0	-0.94	38	38
SELP	-0.079	0.36	-10000	0	-1.1	26	26
AICDA	-0.079	0.34	-10000	0	-1	27	27

×

Paxillin-independent events mediated by a4b1 and a4b7

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.027	0.017	-9999	-0.26	1	1
CRKL	0.018	0.01	-9999	-0.11	3	3
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
DOCK1	0.011	0.047	-9999	-0.22	19	19
ITGA4	0.016	0.019	-9999	-0.11	12	12
alpha4/beta7 Integrin/MAdCAM1	0.044	0.025	-9999	-0.13	7	7
EPO	0.019	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.026	0.016	-9999	-0.14	2	2
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.009	0.054	-9999	-0.28	17	17
alpha4/beta1 Integrin	0.026	0.014	-9999	-10000	0	0
EPO/EPOR (dimer)	0.028	0	-9999	-10000	0	0
lamellipodium assembly	-0.011	0.1	-9999	-0.33	22	22
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
PI3K	-0.016	0.093	-9999	-0.21	88	88
ARF6	0.018	0.015	-9999	-0.2	2	2
JAK2	0.031	0.015	-9999	-10000	0	0
PXN	0.018	0.011	-9999	-0.11	4	4
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
MADCAM1	0.019	0.006	-9999	-0.11	1	1
cell adhesion	0.043	0.025	-9999	-0.13	7	7
CRKL/CBL	0.028	0.007	-9999	-10000	0	0
ITGB1	0.019	0	-9999	-10000	0	0
SRC	-0.022	0.069	-9999	-0.13	144	144
ITGB7	0.018	0.01	-9999	-0.11	3	3
RAC1	0.015	0.036	-9999	-0.29	7	7
alpha4/beta1 Integrin/VCAM1	-0.023	0.083	-9999	-0.15	144	144
p130Cas/Crk/Dock1	-0.011	0.075	-9999	-0.12	152	152
VCAM1	-0.079	0.14	-9999	-0.24	202	202
RHOA	0.015	0.036	-9999	-0.29	7	7
alpha4/beta1 Integrin/Paxillin/GIT1	0.047	0.015	-9999	-10000	0	0
BCAR1	-0.023	0.062	-9999	-0.12	144	144
EPOR	0.019	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.019	0	-9999	-10000	0	0
GIT1	0.019	0.006	-9999	-0.11	1	1
Rac1/GTP	-0.012	0.1	-9999	-0.36	20	20

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.01	0.033	-10000	0	-0.11	37	37
mol:Halofuginone	-0.001	0.033	-10000	0	-0.19	15	15
ITGA1	0	0	-10000	0	-10000	0	0
CDKN1A	-0.037	0.16	-10000	0	-0.4	76	76
PRL-3/alpha Tubulin	0.012	0.05	-10000	0	-0.19	24	24
mol:Ca2+	-0.023	0.088	0.29	12	-0.2	73	85
AGT	-0.035	0.11	-10000	0	-0.26	104	104
CCNA2	-0.011	0.12	-10000	0	-0.64	17	17
TUBA1B	0.018	0.014	-10000	0	-0.29	1	1
EGR1	0.002	0.072	-10000	0	-0.36	18	18
CDK2/Cyclin E1	-0.025	0.15	-10000	0	-0.36	76	76
MAPK3	0.005	0.047	-10000	0	-0.19	23	23
PRL-2 /Rab GGTase beta	0.022	0.039	-10000	0	-0.22	12	12
MAPK1	0	0.056	-10000	0	-0.19	36	36
PTP4A1	-0.002	0.12	-10000	0	-0.64	18	18
PTP4A3	-0.004	0.07	-10000	0	-0.18	63	63
PTP4A2	0.017	0.025	-10000	0	-0.2	6	6
ITGB1	0.005	0.047	-10000	0	-0.19	23	23
SRC	0.019	0	-10000	0	-10000	0	0
RAC1	-0.01	0.12	-10000	0	-0.37	44	44
Rab GGTase beta/Rab GGTase alpha	0.022	0.034	-10000	0	-0.19	11	11
PRL-1/ATF-5	-0.007	0.13	-10000	0	-0.67	15	15
RABGGTA	0.017	0.016	-10000	0	-0.11	8	8
BCAR1	0.006	0.062	0.28	23	-10000	0	23
RHOC	-0.013	0.12	-10000	0	-0.38	47	47
RHOA	-0.012	0.14	-10000	0	-0.43	41	41
cell motility	-0.014	0.13	-10000	0	-0.39	44	44
PRL-1/alpha Tubulin	-0.007	0.13	-10000	0	-0.67	15	15
PRL-3/alpha1 Integrin	-0.001	0.047	-10000	0	-0.12	63	63
ROCK1	-0.014	0.13	-10000	0	-0.39	44	44
RABGGTB	0.012	0.045	-10000	0	-0.25	14	14
CDK2	0.011	0.034	-10000	0	-0.12	29	29
mitosis	-0.002	0.12	-10000	0	-0.63	18	18
ATF5	0.018	0.01	-10000	0	-0.11	3	3

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.019	0	-9999	-10000	0	0
SPHK1	0.008	0.037	-9999	-0.11	46	46
GNAI2	0	0.074	-9999	-0.28	34	34
mol:S1P	0.016	0.016	-9999	-10000	0	0
GNAO1	-0.014	0.085	-9999	-0.2	81	81
mol:Sphinganine-1-P	0.014	0.024	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.021	0.045	-9999	-0.13	39	39
GNAI3	0.014	0.038	-9999	-0.29	8	8
G12/G13	0.009	0.059	-9999	-0.19	39	39
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0.001	0.068	-9999	-0.22	39	39
S1P1/S1P	0.019	0.033	-9999	-0.18	10	10
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
GNAI1	-0.046	0.11	-9999	-0.2	157	157
S1P/S1P5/G12	0.01	0.044	-9999	-0.14	39	39
S1P/S1P3/Gq	0.024	0.03	-9999	-0.18	8	8
S1P/S1P4/Gi	-0.037	0.12	-9999	-0.23	127	127
GNAQ	0.015	0.023	-9999	-0.11	17	17
GNAZ	-0.008	0.083	-9999	-0.23	56	56
GNA14	0.015	0.022	-9999	-0.11	15	15
GNA15	0.012	0.033	-9999	-0.12	26	26
GNA12	-0.005	0.082	-9999	-0.29	39	39
GNA13	0.016	0.021	-9999	-0.11	14	14
GNA11	0.003	0.069	-9999	-0.29	27	27
ABCC1	0.015	0.023	-9999	-0.11	17	17

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.028	0.031	-10000	0	-0.13	21	21
ER alpha/Gai/GDP/Gbeta gamma	-0.037	0.18	-10000	0	-0.41	72	72
AKT1	-0.038	0.19	-10000	0	-0.59	44	44
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.036	0.19	-10000	0	-0.59	44	44
mol:Ca2+	0.024	0.039	-10000	0	-0.16	2	2
IGF1R	-0.001	0.07	-10000	0	-0.21	46	46
E2/ER alpha (dimer)/Striatin	0.026	0	-10000	0	-10000	0	0
SHC1	0.004	0.052	-10000	0	-0.14	48	48
apoptosis	0.036	0.18	0.56	44	-10000	0	44
RhoA/GTP	-0.017	0.049	-10000	0	-0.13	62	62
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.05	0.13	-10000	0	-0.38	51	51
regulation of stress fiber formation	-0.008	0.06	0.2	29	-10000	0	29
E2/ERA-ERB (dimer)	0.026	0	-10000	0	-10000	0	0
KRAS	0.011	0.048	-10000	0	-0.28	14	14
G13/GTP	0.023	0.011	-10000	0	-10000	0	0
pseudopodium formation	0.008	0.06	-10000	0	-0.2	29	29
E2/ER alpha (dimer)/PELP1	0.023	0.021	-10000	0	-0.16	7	7
GRB2	0.014	0.039	-10000	0	-0.26	10	10
GNG2	0	0	-10000	0	-10000	0	0
GNAO1	-0.014	0.085	-10000	0	-0.2	81	81
HRAS	0.009	0.055	-10000	0	-0.28	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.024	0.13	-10000	0	-0.36	52	52
E2/ER beta (dimer)	0.014	0	-10000	0	-10000	0	0
mol:GDP	0.016	0.033	-10000	0	-0.18	1	1
mol:NADP	-0.024	0.13	-10000	0	-0.36	52	52
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:IP3	0.024	0.039	-10000	0	-0.16	2	2
IGF-1R heterotetramer	-0.001	0.07	-10000	0	-0.21	46	46
PLCB1	0.021	0.041	-10000	0	-0.17	2	2
PLCB2	0.023	0.04	-10000	0	-0.17	2	2
IGF1	0.014	0.025	-10000	0	-0.11	21	21
mol:L-citrulline	-0.024	0.13	-10000	0	-0.36	52	52
RHOA	0.015	0.036	-10000	0	-0.29	7	7
Gai/GDP	-0.082	0.24	-10000	0	-0.7	64	64
JNK cascade	0.014	0	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0.019	0	-10000	0	-10000	0	0
GNAQ	0.015	0.023	-10000	0	-0.11	17	17
ESR1	0.019	0	-10000	0	-10000	0	0
Gq family/GDP/Gbeta gamma	-0.004	0.15	-10000	0	-0.52	36	36
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.003	0.14	-10000	0	-0.73	16	16
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.026	0.14	-10000	0	-0.37	56	56
GNAZ	-0.008	0.083	-10000	0	-0.23	56	56
E2/ER alpha (dimer)	0.014	0	-10000	0	-10000	0	0
STRN	0.019	0	-10000	0	-10000	0	0
GNAL	0.018	0.01	-10000	0	-0.11	3	3
PELP1	0.015	0.036	-10000	0	-0.29	7	7
MAPK11	0.018	0	-10000	0	-10000	0	0
GNAI2	0	0.074	-10000	0	-0.28	34	34
GNAI3	0.014	0.038	-10000	0	-0.29	8	8
GNAI1	-0.046	0.11	-10000	0	-0.2	157	157
HBEGF	-0.068	0.16	-10000	0	-0.4	74	74
cAMP biosynthetic process	0.022	0.004	-10000	0	-10000	0	0
SRC	-0.042	0.17	-10000	0	-0.39	72	72
PI3K	-0.016	0.093	-10000	0	-0.21	88	88
GNB1	0.007	0.061	-10000	0	-0.29	21	21
G13/GDP/Gbeta gamma	0.019	0.045	-10000	0	-0.2	10	10
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.05	0.11	-10000	0	-0.3	60	60
Gs family/GTP	0.028	0.005	-10000	0	-10000	0	0
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.011	0.068	-10000	0	-0.17	59	59
vasodilation	-0.022	0.13	-10000	0	-0.35	52	52
mol:DAG	0.024	0.039	-10000	0	-0.16	2	2
Gs family/GDP/Gbeta gamma	-0.01	0.033	-10000	0	-0.19	10	10
MSN	0.008	0.064	-10000	0	-0.22	28	28
Gq family/GTP	0.021	0.042	-10000	0	-0.19	2	2
mol:PI-3-4-5-P3	-0.034	0.18	-10000	0	-0.57	44	44
NRAS	-0.01	0.086	-10000	0	-0.24	59	59
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.022	0.13	0.35	52	-10000	0	52
GRB2/SOS1	0.011	0.026	-10000	0	-0.17	10	10
RhoA/GDP	0.024	0.04	-10000	0	-0.22	4	4
NOS3	-0.026	0.14	-10000	0	-0.38	52	52
GNA11	0.003	0.069	-10000	0	-0.29	27	27
MAPKKK cascade	0	0.11	-10000	0	-0.41	20	20
E2/ER alpha (dimer)/PELP1/Src	-0.026	0.14	-10000	0	-0.4	51	51
ruffle organization	0.008	0.06	-10000	0	-0.2	29	29
ROCK2	0.012	0.056	-10000	0	-0.12	63	63
GNA14	0.015	0.022	-10000	0	-0.11	15	15
GNA15	0.012	0.033	-10000	0	-0.12	26	26
GNA13	0.016	0.021	-10000	0	-0.11	14	14
MMP9	-0.069	0.16	-10000	0	-0.38	87	87
MMP2	-0.05	0.17	-10000	0	-0.41	72	72

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.001	0.061	-9999	-0.16	60	60
TRAF2/ASK1	0.007	0.054	-9999	-0.16	49	49
ATM	0.01	0.042	-9999	-0.15	30	30
MAP2K3	0.001	0.085	-9999	-0.3	28	28
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.002	0.088	-9999	-0.24	54	54
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.005	0.041	-9999	-0.11	58	58
TXN	0.002	0.037	-9999	-0.24	12	12
CALM1	0.007	0.056	-9999	-0.21	28	28
GADD45A	-0.022	0.1	-9999	-0.26	78	78
GADD45B	-0.005	0.072	-9999	-0.18	66	66
MAP3K1	0.015	0.022	-9999	-0.11	16	16
MAP3K6	0.016	0.019	-9999	-0.11	11	11
MAP3K7	0.007	0.059	-9999	-0.25	24	24
MAP3K4	-0.002	0.076	-9999	-0.26	39	39
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.003	0.066	-9999	-0.19	51	51
TAK1/TAB family	-0.004	0.075	-9999	-0.28	30	30
RAC1/OSM/MEKK3	0.022	0.019	-9999	-0.14	7	7
TRAF2	0.019	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.015	0.064	-9999	-0.25	28	28
TRAF6	0.008	0.047	-9999	-0.23	20	20
RAC1	0.015	0.036	-9999	-0.29	7	7
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.048	0.11	-9999	-0.19	166	166
CCM2	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.019	0.08	-9999	-0.18	88	88
MAPK11	0.019	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.023	0.092	-9999	-0.16	128	128
OSM/MEKK3	0.014	0.004	-9999	-0.07	1	1
TAOK1	0.003	0.028	-9999	-0.24	6	6
TAOK2	0.012	0.028	-9999	-0.23	6	6
TAOK3	0.005	0.052	-9999	-0.24	20	20
MAP3K7IP1	0.019	0	-9999	-10000	0	0
MAPK14	0.018	0.013	-9999	-0.11	5	5
MAP3K7IP2	0.008	0.057	-9999	-0.27	20	20
MAP3K5	-0.014	0.092	-9999	-0.25	65	65
MAP3K10	0.019	0	-9999	-10000	0	0
MAP3K3	0.019	0.006	-9999	-0.11	1	1
TRX/ASK1	0.009	0.043	-9999	-0.24	12	12
GADD45/MTK1/MTK1	-0.007	0.086	-9999	-0.16	95	95

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.025	0.026	-10000	0	-0.19	7	7
Necdin/E2F1	-0.059	0.096	-10000	0	-0.19	168	168
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.025	0.048	-10000	0	-0.15	24	24
NGF (dimer)/p75(NTR)/BEX1	-0.023	0.073	-10000	0	-0.16	111	111
NT-4/5 (dimer)/p75(NTR)	0.003	0.028	-10000	0	-0.07	70	70
IKBKB	0.019	0	-10000	0	-10000	0	0
AKT1	-0.016	0.08	-10000	0	-0.17	84	84
IKBKG	0.019	0	-10000	0	-10000	0	0
BDNF	0.004	0.042	-10000	0	-0.11	62	62
MGDIs/NGR/p75(NTR)/LINGO1	0.004	0.023	-10000	0	-10000	0	0
FURIN	0.018	0.01	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.017	0.044	-10000	0	-0.12	20	20
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	-0.016	0.059	-10000	0	-0.3	15	15
proBDNF (dimer)	0.004	0.042	-10000	0	-0.11	62	62
NTRK1	0.018	0.011	-10000	0	-0.11	4	4
RTN4R	0	0	-10000	0	-10000	0	0
neuron apoptosis	-0.006	0.12	-10000	0	-0.4	32	32
IRAK1	0.008	0.057	-10000	0	-0.27	20	20
SHC1	0.004	0.029	-10000	0	-0.11	6	6
ARHGDIA	0.015	0.022	-10000	0	-0.11	15	15
RhoA/GTP	0.011	0.024	-10000	0	-0.2	7	7
Gamma Secretase	0.041	0.063	-10000	0	-0.17	33	33
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.005	0.06	-10000	0	-0.14	69	69
MAGEH1	-0.018	0.098	-10000	0	-0.25	72	72
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.043	0.078	-10000	0	-0.14	188	188
Mammalian IAPs/DIABLO	0.023	0.037	-10000	0	-0.21	6	6
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.004	0.066	-10000	0	-0.28	26	26
APP	0.013	0.042	-10000	0	-0.29	10	10
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0	0.072	-10000	0	-0.26	36	36
RhoA/GDP/RHOGDI	0.018	0.031	-10000	0	-0.11	14	14
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.023	0.047	0.11	95	-0.1	12	107
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.006	0.067	-10000	0	-0.19	46	46
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.015	0.028	-10000	0	-0.16	2	2
NCSTN	0.008	0.056	-10000	0	-0.26	20	20
mol:GTP	0.003	0.05	-10000	0	-0.16	35	35
PSENEN	0.013	0.041	-10000	0	-0.27	10	10
mol:ceramide	0.013	0.027	-10000	0	-0.13	7	7
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.01	0.061	-10000	0	-0.19	35	35
p75(NTR)/beta APP	0.012	0.042	-10000	0	-0.19	10	10
BEX1	-0.047	0.12	-10000	0	-0.26	125	125
mol:GDP	-0.001	0.021	-10000	0	-10000	0	0
NGF (dimer)	0.017	0.034	-10000	0	-0.093	1	1
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.014	0.027	-10000	0	-0.098	7	7
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
RAC1/GTP	0.012	0.027	-10000	0	-0.13	7	7
MYD88	0	0.075	-10000	0	-0.29	33	33
CHUK	0.016	0.025	-10000	0	-0.15	10	10
NGF (dimer)/p75(NTR)/PKA	0.004	0.05	-10000	0	-0.16	35	35
RHOB	-0.012	0.087	-10000	0	-0.29	43	43
RHOA	0.015	0.036	-10000	0	-0.29	7	7
MAGE-G1/E2F1	0.014	0.004	-10000	0	-0.07	1	1
NT3 (dimer)	0.018	0.01	-10000	0	-0.11	3	3
TP53	0.004	0.054	-10000	0	-0.14	41	41
PRDM4	0.013	0.027	-10000	0	-0.13	7	7
BDNF (dimer)	0.017	0.045	-10000	0	-0.14	4	4
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
SORT1	0.016	0.031	-10000	0	-0.24	7	7
activation of caspase activity	0.022	0.046	-10000	0	-0.14	24	24
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.024	0.033	-10000	0	-0.13	9	9
RHOC	0.012	0.045	-10000	0	-0.28	12	12
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.004	0.099	-10000	0	-0.28	44	44
DIABLO	0.016	0.028	-10000	0	-0.26	5	5
SMPD2	0.013	0.027	-10000	0	-0.13	7	7
APH1B	0.018	0.02	-10000	0	-0.23	3	3
APH1A	0.015	0.036	-10000	0	-0.27	8	8
proNGF (dimer)/p75(NTR)/Sortilin	0.014	0.032	-10000	0	-0.15	7	7
PSEN1	0.011	0.047	-10000	0	-0.26	15	15
APAF-1/Pro-Caspase 9	0.025	0.02	-10000	0	-0.19	2	2
NT3 (dimer)/p75(NTR)	0.016	0.032	-10000	0	-0.14	1	1
MAPK8	0.016	0.06	-10000	0	-0.23	17	17
MAPK9	0.015	0.065	-10000	0	-0.25	20	20
APAF1	0.019	0	-10000	0	-10000	0	0
NTF3	0.018	0.01	-10000	0	-0.11	3	3
NTF4	0	0	-10000	0	-10000	0	0
NDN	-0.1	0.14	-10000	0	-0.22	269	269
RAC1/GDP	0.011	0.024	-10000	0	-0.2	7	7
RhoA-B-C/GDP	0.005	0.075	-10000	0	-0.17	65	65
p75 CTF/Sortilin/TRAF6/NRIF	0.035	0.048	-10000	0	-0.14	35	35
RhoA-B-C/GTP	0.003	0.049	-10000	0	-0.16	35	35
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.024	0.057	-10000	0	-0.13	35	35
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.027	0.044	-10000	0	-0.16	7	7
PRKACB	-0.002	0.076	-10000	0	-0.26	39	39
proBDNF (dimer)/p75 ECD	0.017	0.032	-10000	0	-0.14	3	3
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0	0.046	-10000	0	-0.11	78	78
BIRC2	0.016	0.03	-10000	0	-0.29	5	5
neuron projection morphogenesis	-0.033	0.075	0.11	46	-0.17	65	111
BAD	0.01	0.08	-10000	0	-0.26	28	28
RIPK2	0.017	0.021	-10000	0	-0.18	5	5
NGFR	0.002	0.044	-10000	0	-0.11	70	70
CYCS	0.01	0.042	-10000	0	-0.14	28	28
ADAM17	0.017	0.015	-10000	0	-0.11	7	7
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.025	0.03	-10000	0	-0.14	4	4
BCL2L11	0.011	0.078	-10000	0	-0.26	27	27
BDNF (dimer)/p75(NTR)	0.006	0.043	-10000	0	-0.14	13	13
PI3K	-0.008	0.074	-10000	0	-0.15	94	94
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.014	0.029	-10000	0	-0.14	7	7
NDNL2	0	0	-10000	0	-10000	0	0
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
PRKCI	0.015	0.028	-10000	0	-0.14	15	15
NGF (dimer)/p75(NTR)	0.003	0.028	-10000	0	-0.07	70	70
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.017	0.048	-10000	0	-0.14	30	30
TRAF6	0.018	0.019	-10000	0	-0.29	2	2
RAC1	0.015	0.036	-10000	0	-0.29	7	7
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	0.019	0	-10000	0	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.012	0.035	-10000	0	-0.19	6	6
SQSTM1	0.004	0.062	-10000	0	-0.22	32	32
NGFRAP1	0.011	0.048	-10000	0	-0.29	13	13
CASP3	0.01	0.078	-10000	0	-0.25	29	29
E2F1	0.019	0.006	-10000	0	-0.11	1	1
CASP9	0.014	0.029	-10000	0	-0.13	18	18
IKK complex	0.031	0.054	-10000	0	-0.27	10	10
NGF (dimer)/TRKA	0.014	0.007	-10000	0	-0.07	4	4
MMP7	-0.014	0.057	-10000	0	-0.11	135	135
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.023	0.049	-10000	0	-0.13	35	35
MMP3	0.015	0.022	-10000	0	-0.11	15	15
APAF-1/Caspase 9	-0.009	0.036	-10000	0	-0.16	20	20

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.031	0.22	-10000	0	-0.88	31	31
regulation of axonogenesis	-0.012	0.041	0.15	30	-10000	0	30
myoblast fusion	0.005	0.098	0.38	31	-10000	0	31
mol:GTP	-0.001	0.056	-10000	0	-0.22	31	31
regulation of calcium-dependent cell-cell adhesion	-0.004	0.068	0.19	53	-10000	0	53
ARF1/GTP	0.01	0.05	-10000	0	-0.16	36	36
mol:GM1	-0.001	0.041	-10000	0	-0.16	30	30
mol:Choline	0.012	0.037	-10000	0	-0.13	30	30
lamellipodium assembly	-0.006	0.11	-10000	0	-0.42	31	31
MAPK3	0.003	0.08	-10000	0	-0.3	31	31
ARF6/GTP/NME1/Tiam1	0.004	0.068	-10000	0	-0.19	53	53
ARF1	0.014	0.036	-10000	0	-0.29	7	7
ARF6/GDP	-0.005	0.098	-10000	0	-0.39	31	31
ARF1/GDP	0.003	0.094	-10000	0	-0.35	33	33
ARF6	0.01	0.033	-10000	0	-0.12	30	30
RAB11A	0.016	0.033	-10000	0	-0.29	6	6
TIAM1	0.001	0.067	-10000	0	-0.23	35	35
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.001	0.082	-10000	0	-0.31	31	31
actin filament bundle formation	-0.001	0.095	0.35	33	-10000	0	33
KALRN	-0.001	0.075	-10000	0	-0.29	31	31
RAB11FIP3/RAB11A	0.021	0.04	-10000	0	-0.22	12	12
RhoA/GDP	0.001	0.096	-10000	0	-0.36	33	33
NME1	-0.001	0.008	-10000	0	-10000	0	0
Rac1/GDP	0.001	0.094	-10000	0	-0.35	32	32
substrate adhesion-dependent cell spreading	-0.001	0.056	-10000	0	-0.22	31	31
cortical actin cytoskeleton organization	-0.006	0.11	-10000	0	-0.42	31	31
RAC1	0.015	0.036	-10000	0	-0.29	7	7
liver development	-0.001	0.056	-10000	0	-0.22	31	31
ARF6/GTP	-0.001	0.056	-10000	0	-0.22	31	31
RhoA/GTP	0.011	0.051	-10000	0	-0.17	35	35
mol:GDP	-0.006	0.098	-10000	0	-0.39	31	31
ARF6/GTP/RAB11FIP3/RAB11A	0.019	0.052	-10000	0	-0.14	41	41
RHOA	0.015	0.036	-10000	0	-0.29	7	7
PLD1	0.009	0.043	-10000	0	-0.16	30	30
RAB11FIP3	0.013	0.041	-10000	0	-0.21	15	15
tube morphogenesis	-0.006	0.11	-10000	0	-0.42	31	31
ruffle organization	0.012	0.041	-10000	0	-0.15	30	30
regulation of epithelial cell migration	-0.001	0.056	-10000	0	-0.22	31	31
PLD2	0.009	0.043	-10000	0	-0.16	30	30
PIP5K1A	0.012	0.041	-10000	0	-0.15	30	30
mol:Phosphatidic acid	0.012	0.037	-10000	0	-0.13	30	30
Rac1/GTP	-0.006	0.11	-10000	0	-0.42	31	31

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	-0.034	0.16	-10000	0	-0.51	53	53
HDAC1	0.019	0.033	-10000	0	-0.2	8	8
AES	0.013	0.045	-10000	0	-0.22	16	16
FBXW11	0.011	0.047	-10000	0	-0.27	14	14
DTX1	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.021	0.026	-10000	0	-0.16	2	2
TLE1	0.017	0.026	-10000	0	-0.2	6	6
AP1	-0.025	0.099	-10000	0	-0.23	84	84
NCSTN	0.008	0.056	-10000	0	-0.26	20	20
ADAM10	0.008	0.036	-10000	0	-0.11	45	45
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.01	0.12	-10000	0	-0.41	23	23
NICD/RBPSUH	-0.025	0.17	-10000	0	-0.51	53	53
WIF1	-0.006	0.051	-10000	0	-0.11	100	100
NOTCH1	-0.034	0.17	-10000	0	-0.53	53	53
PSENEN	0.013	0.041	-10000	0	-0.28	10	10
KREMEN2	0.019	0.006	-10000	0	-0.11	1	1
DKK1	-0.018	0.058	-10000	0	-0.11	150	150
beta catenin/beta TrCP1	0.016	0.068	-10000	0	-0.29	16	16
APH1B	0.018	0.02	-10000	0	-0.23	3	3
APH1A	0.015	0.036	-10000	0	-0.27	8	8
AXIN1	-0.005	0.056	0.19	7	-0.19	3	10
CtBP/CBP/TCF1/TLE1/AES	0.035	0.071	0.26	9	-0.32	5	14
PSEN1	0.011	0.047	-10000	0	-0.26	15	15
FOS	-0.046	0.12	-10000	0	-0.22	146	146
JUN	-0.002	0.077	-10000	0	-0.28	37	37
MAP3K7	0.012	0.048	-10000	0	-0.24	17	17
CTNNB1	0.008	0.06	-10000	0	-0.26	14	14
MAPK3	0.019	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.031	0.025	-10000	0	-0.13	2	2
HNF1A	0.02	0.005	-10000	0	-10000	0	0
CTBP1	0.01	0.055	-10000	0	-0.29	17	17
MYC	-0.12	0.39	-10000	0	-1.3	54	54
NKD1	0	0.002	-10000	0	-10000	0	0
FZD1	0.015	0.023	-10000	0	-0.11	17	17
NOTCH1 precursor/Deltex homolog 1	-0.034	0.16	-10000	0	-0.5	53	53
apoptosis	-0.025	0.099	-10000	0	-0.23	84	84
Delta 1/NOTCHprecursor	-0.034	0.16	-10000	0	-0.5	53	53
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.008	0.033	-10000	0	-10000	0	0
Gamma Secretase	0.04	0.063	-10000	0	-0.18	33	33
APC	-0.04	0.17	0.19	7	-0.65	33	40
DVL1	0.007	0.1	-10000	0	-0.45	22	22
CSNK2A1	0.009	0.053	-10000	0	-0.29	16	16
MAP3K7IP1	0.021	0.007	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.012	0.041	-10000	0	-0.12	6	6
LRP6	0.013	0.029	-10000	0	-0.12	22	22
CSNK1A1	0.014	0.038	-10000	0	-0.29	8	8
NLK	0.013	0.064	-10000	0	-0.25	25	25
CCND1	-0.097	0.34	-10000	0	-1.3	39	39
WNT1	0.019	0.006	-10000	0	-10000	0	0
Axin1/APC/beta catenin	-0.01	0.13	0.2	3	-0.4	42	45
DKK2	0.013	0.028	-10000	0	-0.11	25	25
NOTCH1 precursor/DVL1	-0.024	0.19	-10000	0	-0.51	61	61
GSK3B	0.004	0.066	-10000	0	-0.26	29	29
FRAT1	0.016	0.023	-10000	0	-0.12	12	12
NOTCH/Deltex homolog 1	-0.034	0.16	-10000	0	-0.51	53	53
PPP2R5D	0.014	0.041	-10000	0	-0.18	18	18
MAPK1	0.009	0.051	-10000	0	-0.22	22	22
WNT1/LRP6/FZD1	0.027	0.039	-10000	0	-0.14	2	2
RBPJ	0.012	0.041	-10000	0	-0.2	17	17
CREBBP	0.018	0.008	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.024	0.011	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.016	0.019	-9999	-0.11	11	11
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.019	0.006	-9999	-0.11	1	1
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.014	0.034	-9999	-0.18	13	13
RAC1-CDC42/GTP/PAK family	-0.006	0.063	-9999	-0.16	71	71
response to UV	0	0	-9999	-10000	0	0
YES1	0.005	0.061	-9999	-0.24	28	28
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.019	0.006	-9999	-0.11	1	1
FYN	-0.019	0.1	-9999	-0.28	68	68
MAP3K12	0.019	0	-9999	-10000	0	0
FGR	0.005	0.048	-9999	-0.14	46	46
p38 alpha/TAB1	0	0.1	-9999	-0.23	64	64
PRKG1	0.019	0	-9999	-10000	0	0
DUSP8	0.013	0.027	-9999	-0.11	24	24
PGK/cGMP/p38 alpha	-0.003	0.1	-9999	-0.23	63	63
apoptosis	0	0.1	-9999	-0.22	64	64
RAL/GTP	0.014	0.043	-9999	-0.16	27	27
LYN	-0.018	0.098	-9999	-0.25	72	72
DUSP1	-0.005	0.065	-9999	-0.15	74	74
PAK1	0.017	0.017	-9999	-0.11	9	9
SRC	0.019	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.034	0.021	-9999	-0.14	7	7
TRAF6	0.018	0.019	-9999	-0.29	2	2
RAC1	0.015	0.036	-9999	-0.29	7	7
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.022	0.023	-9999	-0.16	7	7
MAPK11	-0.019	0.13	-9999	-0.29	76	76
BLK	0.018	0.011	-9999	-0.11	4	4
HCK	-0.033	0.11	-9999	-0.21	120	120
MAP2K3	0.018	0.01	-9999	-0.11	3	3
DUSP16	0	0	-9999	-10000	0	0
DUSP10	0.01	0.035	-9999	-0.12	36	36
TRAF6/MEKK3	0.024	0.011	-9999	-0.14	2	2
MAP3K7IP1	0.019	0	-9999	-10000	0	0
MAPK14	-0.009	0.11	-9999	-0.25	65	65
positive regulation of innate immune response	-0.018	0.15	-9999	-0.33	73	73
LCK	0.017	0.016	-9999	-0.11	8	8
p38alpha-beta/MKP7	-0.02	0.14	-9999	-0.32	73	73
p38alpha-beta/MKP5	-0.012	0.14	-9999	-0.32	72	72
PGK/cGMP	0.014	0	-9999	-10000	0	0
PAK2	0.014	0.028	-9999	-0.29	1	1
p38alpha-beta/MKP1	-0.017	0.15	-9999	-0.32	75	75
CDC42	0.017	0.016	-9999	-0.11	8	8
RALB	0.013	0.037	-9999	-0.18	15	15
RALA	0.005	0.063	-9999	-0.26	26	26
PAK3	-0.04	0.11	-9999	-0.19	146	146

×

PDGFR-beta signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.003	0.1	-10000	0	-0.32	31	31
PDGFB-D/PDGFRB/SLAP	-0.019	0.09	-10000	0	-0.21	82	82
PDGFB-D/PDGFRB/APS/CBL	0.021	0.025	-10000	0	-0.16	8	8
AKT1	0	0.082	-10000	0	-0.22	46	46
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.001	0.098	-10000	0	-0.36	24	24
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
FGR	-0.014	0.097	-10000	0	-0.5	13	13
mol:Ca2+	-0.003	0.099	-10000	0	-0.4	22	22
MYC	-0.066	0.25	-10000	0	-0.71	64	64
SHC1	0.004	0.052	-10000	0	-0.14	48	48
HRAS/GDP	0.016	0.059	-10000	0	-0.15	50	50
LRP1/PDGFRB/PDGFB	0.017	0.059	-10000	0	-0.17	37	37
GRB10	-0.018	0.091	-10000	0	-0.2	89	89
PTPN11	0.015	0.033	-10000	0	-0.27	7	7
GO:0007205	-0.004	0.1	-10000	0	-0.4	22	22
PTEN	0.013	0.038	-10000	0	-0.18	17	17
GRB2	0.014	0.039	-10000	0	-0.26	10	10
GRB7	0.016	0.019	-10000	0	-0.11	11	11
PDGFB-D/PDGFRB/SHP2	0.02	0.038	-10000	0	-0.2	14	14
PDGFB-D/PDGFRB/GRB10	-0.004	0.071	-10000	0	-0.2	52	52
cell cycle arrest	-0.019	0.09	-10000	0	-0.21	82	82
HRAS	0.009	0.055	-10000	0	-0.28	18	18
HIF1A	0.001	0.082	-10000	0	-0.22	47	47
GAB1	-0.016	0.12	-10000	0	-0.37	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	-0.012	0.11	-10000	0	-0.32	40	40
PDGFB-D/PDGFRB	0.027	0.041	-10000	0	-0.17	18	18
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.016	0.047	-10000	0	-0.2	22	22
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.001	0.11	-10000	0	-0.27	55	55
positive regulation of MAPKKK cascade	0.019	0.038	-10000	0	-0.2	14	14
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
mol:IP3	-0.004	0.1	-10000	0	-0.41	22	22
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.013	0.044	-10000	0	-0.29	11	11
PDGFB-D/PDGFRB/GRB7	0.021	0.035	-10000	0	-0.21	9	9
SHB	0.016	0.02	-10000	0	-0.11	13	13
BLK	-0.001	0.044	-10000	0	-0.23	8	8
PTPN2	0.017	0.013	-10000	0	-0.11	5	5
PDGFB-D/PDGFRB/SNX15	0.022	0.031	-10000	0	-0.2	8	8
BCAR1	0	0	-10000	0	-10000	0	0
VAV2	-0.03	0.15	-10000	0	-0.34	70	70
CBL	0.019	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.022	0.031	-10000	0	-0.2	8	8
LCK	-0.003	0.045	-10000	0	-0.26	7	7
PDGFRB	0.01	0.044	-10000	0	-0.18	21	21
ACP1	0.01	0.051	-10000	0	-0.25	18	18
HCK	-0.073	0.19	-10000	0	-0.51	73	73
ABL1	-0.017	0.11	-10000	0	-0.32	42	42
PDGFB-D/PDGFRB/CBL	-0.018	0.13	-10000	0	-0.42	35	35
PTPN1	0.013	0.043	-10000	0	-0.3	10	10
SNX15	0.019	0	-10000	0	-10000	0	0
STAT3	-0.003	0.079	-10000	0	-0.29	37	37
STAT1	0.008	0.04	-10000	0	-0.12	41	41
cell proliferation	-0.056	0.22	-10000	0	-0.61	66	66
SLA	-0.04	0.11	-10000	0	-0.22	127	127
actin cytoskeleton reorganization	0.024	0.049	-10000	0	-0.15	32	32
SRC	-0.002	0.043	-10000	0	-0.23	9	9
PI3K	-0.028	0.061	-10000	0	-0.2	41	41
PDGFB-D/PDGFRB/GRB7/SHC	0.023	0.045	-10000	0	-0.16	21	21
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.001	0.1	-10000	0	-0.37	24	24
LYN	-0.058	0.16	-10000	0	-0.47	65	65
LRP1	-0.007	0.079	-10000	0	-0.21	61	61
SOS1	0	0	-10000	0	-10000	0	0
STAT5B	0.018	0.015	-10000	0	-0.2	2	2
STAT5A	0.019	0.008	-10000	0	-0.11	2	2
NCK1-2/p130 Cas	0.03	0.053	-10000	0	-0.15	32	32
SPHK1	0.008	0.037	-10000	0	-0.11	46	46
EDG1	0.001	0.068	-10000	0	-0.22	39	39
mol:DAG	-0.004	0.1	-10000	0	-0.41	22	22
PLCG1	-0.004	0.1	-10000	0	-0.42	22	22
NHERF/PDGFRB	0.028	0.038	-10000	0	-0.16	15	15
YES1	-0.024	0.12	-10000	0	-0.48	29	29
cell migration	0.027	0.038	-10000	0	-0.16	15	15
SHC/Grb2/SOS1	0.027	0.052	-10000	0	-0.15	30	30
SLC9A3R2	0.019	0	-10000	0	-10000	0	0
SLC9A3R1	0.01	0.042	-10000	0	-0.15	30	30
NHERF1-2/PDGFRB/PTEN	0.035	0.043	-10000	0	-0.14	22	22
FYN	-0.067	0.2	-10000	0	-0.56	66	66
DOK1	0.02	0.032	-10000	0	-0.14	18	18
HRAS/GTP	0.007	0.037	-10000	0	-0.2	17	17
PDGFB	0.019	0	-10000	0	-10000	0	0
RAC1	-0.043	0.19	-10000	0	-0.47	73	73
PRKCD	0.017	0.037	-10000	0	-0.14	22	22
FER	0.019	0.034	-10000	0	-0.14	18	18
MAPKKK cascade	-0.008	0.038	0.091	3	-0.14	28	31
RASA1	0.017	0.041	-10000	0	-0.18	18	18
NCK1	0.014	0.036	-10000	0	-0.19	14	14
NCK2	0.009	0.054	-10000	0	-0.28	17	17
p62DOK/Csk	0.029	0.04	-10000	0	-0.13	26	26
PDGFB-D/PDGFRB/SHB	0.02	0.035	-10000	0	-0.2	9	9
chemotaxis	-0.016	0.11	-10000	0	-0.32	42	42
STAT1-3-5/STAT1-3-5	0.024	0.054	-10000	0	-0.14	32	32
Bovine Papilomavirus E5/PDGFRB	0.008	0.03	-10000	0	-0.19	9	9
PTPRJ	0.019	0	-10000	0	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0.093	-10000	0	-0.31	14	14
CRKL	0.021	0.049	-10000	0	-0.17	8	8
mol:DAG	0.011	0.09	-10000	0	-0.21	59	59
HRAS	0.015	0.067	-10000	0	-0.21	27	27
MAPK8	0.012	0.054	-10000	0	-0.14	57	57
RAP1A	0.021	0.05	-10000	0	-0.17	11	11
GAB1	0.016	0.053	-10000	0	-0.19	12	12
MAPK14	0.011	0.054	-10000	0	-0.14	57	57
EPO	0.02	0.006	-10000	0	-10000	0	0
PLCG1	0.011	0.091	-10000	0	-0.22	59	59
EPOR/TRPC2/IP3 Receptors	0.02	0.006	-10000	0	-10000	0	0
RAPGEF1	0.019	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.04	0.009	-10000	0	-10000	0	0
GAB1/SHC/GRB2/SOS1	0.019	0.064	-10000	0	-0.2	24	24
EPO/EPOR (dimer)	0.029	0.013	-10000	0	-10000	0	0
IRS2	0.01	0.068	-10000	0	-0.22	32	32
STAT1	0.015	0.094	-10000	0	-0.3	25	25
STAT5B	0.016	0.09	-10000	0	-0.21	57	57
cell proliferation	0.013	0.049	-10000	0	-0.12	57	57
GAB1/SHIP/PIK3R1/SHP2/SHC	0.002	0.075	-10000	0	-0.2	44	44
TEC	0.021	0.048	-10000	0	-0.17	8	8
SOCS3	0.019	0	-10000	0	-10000	0	0
STAT1 (dimer)	0.015	0.092	-10000	0	-0.29	25	25
JAK2	0.014	0.028	-10000	0	-0.11	23	23
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
EPO/EPOR (dimer)/JAK2	0.044	0.061	-10000	0	-0.12	45	45
EPO/EPOR	0.029	0.013	-10000	0	-10000	0	0
LYN	-0.017	0.098	-10000	0	-0.25	72	72
TEC/VAV2	0.033	0.05	-10000	0	-0.18	6	6
elevation of cytosolic calcium ion concentration	0.02	0.006	-10000	0	-10000	0	0
SHC1	0.004	0.052	-10000	0	-0.14	48	48
EPO/EPOR (dimer)/LYN	0.022	0.068	-10000	0	-0.16	57	57
mol:IP3	0.011	0.09	-10000	0	-0.21	59	59
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.002	0.09	-10000	0	-0.23	51	51
SH2B3	0.013	0.037	-10000	0	-0.15	20	20
NFKB1	0.01	0.057	-10000	0	-0.14	59	59
EPO/EPOR (dimer)/JAK2/SOCS3	0.031	0.052	0.2	43	-10000	0	43
PTPN6	0.018	0.048	-10000	0	-0.12	44	44
TEC/VAV2/GRB2	0.039	0.057	-10000	0	-0.22	10	10
EPOR	0.02	0.006	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.064	-10000	0	-0.2	24	24
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	-0.002	0.069	-10000	0	-0.19	52	52
CRKL/CBL/C3G	0.041	0.05	-10000	0	-0.2	4	4
VAV2	0.021	0.048	-10000	0	-0.17	8	8
CBL	0.021	0.048	-10000	0	-0.17	8	8
SHC/Grb2/SOS1	0.013	0.058	-10000	0	-0.2	22	22
STAT5A	0.016	0.09	-10000	0	-0.21	57	57
GRB2	0.014	0.039	-10000	0	-0.26	10	10
STAT5 (dimer)	0.036	0.089	-10000	0	-0.25	23	23
LYN/PLCgamma2	-0.009	0.095	-10000	0	-0.23	72	72
PTPN11	0.015	0.033	-10000	0	-0.27	7	7
BTK	0.02	0.05	-10000	0	-0.17	9	9
BCL2	0.027	0.092	-10000	0	-0.37	5	5

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.018	0.01	-9999	-0.11	3	3
Rac1/GDP	0.01	0.034	-9999	-0.29	7	7
DOCK1	0.011	0.047	-9999	-0.22	19	19
ITGA4	0.016	0.019	-9999	-0.11	12	12
RAC1	0.015	0.036	-9999	-0.29	7	7
alpha4/beta7 Integrin	0.026	0.016	-9999	-0.14	2	2
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.009	0.054	-9999	-0.28	17	17
alpha4/beta1 Integrin	0.037	0.012	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.038	0.015	-9999	-10000	0	0
lamellipodium assembly	-0.028	0.15	-9999	-0.34	87	87
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
PI3K	-0.016	0.093	-9999	-0.21	88	88
ARF6	0.018	0.015	-9999	-0.2	2	2
TLN1	-0.003	0.065	-9999	-0.16	64	64
PXN	0.02	0.007	-9999	-10000	0	0
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
ARF6/GTP	0.044	0.014	-9999	-10000	0	0
cell adhesion	0.034	0.038	-9999	-0.12	18	18
CRKL/CBL	0.028	0.007	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.038	0.013	-9999	-10000	0	0
ITGB1	0.019	0	-9999	-10000	0	0
ITGB7	0.018	0.01	-9999	-0.11	3	3
ARF6/GDP	0.013	0.014	-9999	-0.2	2	2
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.005	0.074	-9999	-0.12	140	140
p130Cas/Crk/Dock1	0.015	0.044	-9999	-0.18	24	24
VCAM1	-0.079	0.14	-9999	-0.24	202	202
alpha4/beta1 Integrin/Paxillin/Talin	0.036	0.039	-9999	-0.12	18	18
alpha4/beta1 Integrin/Paxillin/GIT1	0.048	0.014	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	-0.046	0.013	-9999	-10000	0	0
CBL	0.019	0	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
GIT1	0.019	0.006	-9999	-0.11	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.036	0.039	-9999	-0.12	18	18
Rac1/GTP	-0.033	0.16	-9999	-0.37	87	87

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.017	0.074	-9999	-0.34	16	16
KLHL20	0.011	0.065	-9999	-0.2	29	29
CYFIP2	-0.02	0.099	-9999	-0.25	75	75
Rac1/GDP	0.028	0.072	-9999	-0.28	23	23
ENAH	0.012	0.087	-9999	-0.38	20	20
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	0	22	22
RAP1A	0.018	0.019	-9999	-0.29	2	2
CTNNB1	0.017	0.023	-9999	-0.29	3	3
CDC42/GTP	-0.012	0.052	-9999	-0.23	23	23
ABI1/Sra1/Nap1	-0.019	0.043	-9999	-0.14	44	44
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.04	0.033	-9999	-0.14	11	11
RAPGEF1	0.02	0.074	-9999	-0.31	21	21
CTNND1	0.001	0.073	-9999	-0.29	31	31
regulation of calcium-dependent cell-cell adhesion	0.015	0.076	-9999	-0.36	16	16
CRK	0.017	0.08	-9999	-0.34	21	21
E-cadherin/gamma catenin/alpha catenin	0.023	0.046	-9999	-0.13	36	36
alphaE/beta7 Integrin	0.024	0.027	-9999	-0.19	7	7
IQGAP1	-0.009	0.087	-9999	-0.27	50	50
NCKAP1	0.019	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.024	0.01	-9999	-0.14	2	2
DLG1	0.015	0.078	-9999	-0.35	17	17
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.02	0.054	-9999	-0.2	36	36
MLLT4	0.019	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.015	0.036	-9999	-0.14	24	24
PI3K	-0.026	0.071	-9999	-0.26	36	36
ARF6	0.018	0.015	-9999	-0.2	2	2
mol:Ca2+	0	0	-9999	0	37	37
E-cadherin/gamma catenin	0.016	0.039	-9999	-0.14	25	25
TIAM1	0.003	0.066	-9999	-0.23	35	35
E-cadherin(dimer)/Ca2+	0.027	0.06	-9999	-0.18	34	34
AKT1	0.006	0.061	-9999	-0.19	38	38
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
CDH1	0.012	0.03	-9999	-0.11	29	29
RhoA/GDP	0.029	0.069	-9999	-0.26	23	23
actin cytoskeleton organization	0.01	0.049	-9999	-0.15	29	29
CDC42/GDP	0.029	0.068	-9999	-0.26	22	22
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.004	0.068	-9999	-0.24	33	33
ITGB7	0.018	0.01	-9999	-0.11	3	3
RAC1	0.015	0.036	-9999	-0.29	7	7
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.03	0.065	-9999	-0.19	34	34
E-cadherin/Ca2+/beta catenin/alpha catenin	0.025	0.033	-9999	-0.14	15	15
mol:GDP	0.021	0.075	-9999	-0.31	21	21
CDC42/GTP/IQGAP1	0.009	0.053	-9999	-0.16	45	45
JUP	0.008	0.037	-9999	-0.11	47	47
p120 catenin/RhoA/GDP	0.029	0.077	-9999	-0.25	33	33
RAC1/GTP/IQGAP1	0.007	0.056	-9999	-0.16	51	51
PIP5K1C/AP1M1	0.005	0.041	-9999	-0.16	27	27
RHOA	0.015	0.036	-9999	-0.29	7	7
CDC42	0.017	0.016	-9999	-0.11	8	8
CTNNA1	0.011	0.048	-9999	-0.29	13	13
positive regulation of S phase of mitotic cell cycle	0	0.054	-9999	-0.14	50	50
NME1	0	0	-9999	0	105	105
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.014	0.081	-9999	-0.37	17	17
regulation of cell-cell adhesion	-0.011	0.045	-9999	-0.2	23	23
WASF2	-0.011	0.023	-9999	-0.078	44	44
Rap1/GTP	0.019	0.067	-9999	-0.23	29	29
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.039	0.049	-9999	-0.14	20	20
CCND1	-0.001	0.066	-9999	-0.18	50	50
VAV2	0.024	0.079	-9999	-0.4	13	13
RAP1/GDP	0.022	0.068	-9999	-0.27	22	22
adherens junction assembly	0.015	0.078	-9999	-0.36	17	17
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.008	0.055	-9999	-0.24	22	22
PIP5K1C	0.006	0.061	-9999	-0.24	27	27
regulation of heterotypic cell-cell adhesion	0.037	0.048	-9999	-0.14	22	22
E-cadherin/beta catenin	0.008	0.034	-9999	-0.15	16	16
mol:GTP	0	0	-9999	0	106	106
SRC	0.017	0.074	-9999	-0.34	16	16
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
Rac1/GTP	-0.031	0.082	-9999	-0.32	29	29
E-cadherin/beta catenin/alpha catenin	0.029	0.04	-9999	-0.17	15	15
ITGAE	0.014	0.037	-9999	-0.24	10	10
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.015	0.078	-9999	-0.36	16	16

×

BMP receptor 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.041	0.041	-9999	-0.12	18	18
SMAD6-7/SMURF1	0.034	0.022	-9999	-0.15	3	3
NOG	0	0	-9999	-10000	0	0
SMAD9	0.017	0.046	-9999	-0.49	3	3
SMAD4	-0.004	0.079	-9999	-0.26	44	44
SMAD5	0.007	0.082	-9999	-0.31	25	25
BMP7/USAG1	0.022	0.024	-9999	-10000	0	0
SMAD5/SKI	0.017	0.08	-9999	-0.29	25	25
SMAD1	-0.013	0.16	-9999	-0.41	56	56
BMP2	-0.02	0.089	-9999	-0.18	101	101
SMAD1/SMAD1/SMAD4	-0.038	0.12	-9999	-0.34	56	56
BMPR1A	0.011	0.045	-9999	-0.29	10	10
BMPR1B	0.018	0.011	-9999	-0.11	4	4
BMPR1A-1B/BAMBI	-0.009	0.075	-9999	-0.16	94	94
AHSG	0.019	0.008	-9999	-0.11	2	2
CER1	0.019	0	-9999	-10000	0	0
BMP2-4/CER1	0.011	0.057	-9999	-0.15	45	45
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	0.002	0.077	-9999	-0.26	22	22
BMP2-4 (homodimer)	-0.003	0.066	-9999	-0.19	45	45
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.038	0.039	-9999	-0.14	18	18
RGMA	0	0	-9999	-10000	0	0
SMURF1	0.019	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	0.001	0.054	-9999	-0.15	55	55
BMP2-4/USAG1	0.007	0.062	-9999	-0.15	54	54
SMAD6/SMURF1/SMAD5	0.017	0.08	-9999	-0.29	25	25
SOSTDC1	0.011	0.031	-9999	-0.11	32	32
BMP7/BMPR2/BMPR1A-1B	0.04	0.036	-9999	-0.13	18	18
SKI	0.019	0	-9999	-10000	0	0
BMP6 (homodimer)	0.014	0.025	-9999	-0.11	20	20
HFE2	0	0	-9999	-10000	0	0
ZFYVE16	0.004	0.064	-9999	-0.25	29	29
MAP3K7	0.007	0.059	-9999	-0.25	24	24
BMP2-4/CHRD	0.011	0.057	-9999	-0.15	45	45
SMAD5/SMAD5/SMAD4	0.012	0.091	-9999	-0.31	29	29
MAPK1	0.009	0.051	-9999	-0.22	22	22
TAK1/TAB family	0.026	0.072	-9999	-0.25	18	18
BMP7 (homodimer)	0.017	0.015	-9999	-0.11	7	7
NUP214	0.019	0	-9999	-10000	0	0
BMP6/FETUA	0.025	0.019	-9999	-0.14	1	1
SMAD1/SKI	-0.001	0.15	-9999	-0.38	56	56
SMAD6	0.019	0	-9999	-10000	0	0
CTDSP2	0.004	0.052	-9999	-0.14	50	50
BMP2-4/FETUA	0.011	0.058	-9999	-0.15	47	47
MAP3K7IP1	0.019	0	-9999	-10000	0	0
GREM1	0.006	0.039	-9999	-0.11	52	52
BMPR2 (homodimer)	0.014	0.039	-9999	-0.26	10	10
GADD34/PP1CA	0.02	0.055	-9999	-0.17	36	36
BMPR1A-1B (homodimer)	0.022	0.032	-9999	-0.19	10	10
CHRDL1	0	0	-9999	-10000	0	0
ENDOFIN/SMAD1	-0.006	0.16	-9999	-0.41	56	56
SMAD6-7/SMURF1/SMAD1	0.013	0.15	-9999	-0.36	56	56
SMAD6/SMURF1	0.019	0	-9999	-10000	0	0
BAMBI	-0.05	0.11	-9999	-0.2	167	167
SMURF2	0.011	0.047	-9999	-0.26	15	15
BMP2-4/CHRDL1	0	0.055	-9999	-0.16	45	45
BMP2-4/GREM1	0.003	0.062	-9999	-0.15	52	52
SMAD7	0.011	0.035	-9999	-0.13	27	27
SMAD8A/SMAD8A/SMAD4	0.021	0.057	-9999	-0.39	6	6
SMAD1/SMAD6	-0.001	0.15	-9999	-0.38	56	56
TAK1/SMAD6	0.02	0.042	-9999	-0.19	19	19
BMP7	0.017	0.015	-9999	-0.11	7	7
BMP6	0.014	0.025	-9999	-0.11	20	20
MAP3K7IP2	0.008	0.057	-9999	-0.27	20	20
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0.007	0.057	-9999	-0.21	14	14
PPM1A	0.017	0.023	-9999	-0.29	3	3
SMAD1/SMURF2	-0.004	0.16	-9999	-0.41	56	56
SMAD7/SMURF1	0.023	0.025	-9999	-0.19	3	3
CTDSPL	0.019	0.006	-9999	-0.11	1	1
PPP1CA	0.009	0.055	-9999	-0.29	17	17
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.011	0.049	-9999	-0.27	15	15
PPP1R15A	0.013	0.028	-9999	-0.11	25	25
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	0.003	0.055	-9999	-0.2	14	14
CHRD	0.019	0	-9999	-10000	0	0
BMPR2	0.014	0.039	-9999	-0.26	10	10
BMP2-4/BMPR2/BMPR1A-1B/RGM	0	0.06	-9999	-0.16	55	55
BMP4	0.013	0.028	-9999	-10000	0	0
FST	0.008	0.037	-9999	-0.11	47	47
BMP2-4/NOG	0	0.055	-9999	-0.16	45	45
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.048	0.035	-9999	-0.12	18	18

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	-0.014	0.059	-10000	0	-0.18	49	49
RFC1	-0.009	0.053	-10000	0	-0.21	31	31
PRKDC	-0.011	0.056	-10000	0	-0.21	32	32
RIPK1	0.016	0.019	-10000	0	-0.11	10	10
CASP7	-0.01	0.11	-10000	0	-0.61	16	16
FASLG/FAS/FADD/FAF1	-0.005	0.082	0.17	34	-0.18	69	103
MAP2K4	-0.001	0.098	-10000	0	-0.31	22	22
mol:ceramide	0.006	0.079	-10000	0	-0.24	24	24
GSN	-0.013	0.055	-10000	0	-0.21	30	30
FASLG/FAS/FADD/FAF1/Caspase 8	0.005	0.085	0.16	21	-0.24	22	43
FAS	-0.027	0.099	-10000	0	-0.2	111	111
BID	-0.007	0.04	-10000	0	-0.17	26	26
MAP3K1	-0.004	0.083	-10000	0	-0.36	19	19
MAP3K7	0.007	0.059	-10000	0	-0.25	24	24
RB1	-0.004	0.046	-10000	0	-0.24	18	18
CFLAR	0.016	0.024	-10000	0	-0.15	9	9
HGF/MET	0.012	0.062	-10000	0	-0.16	53	53
ARHGDIB	-0.015	0.061	-10000	0	-0.19	48	48
FADD	0.017	0.021	-10000	0	-0.2	4	4
actin filament polymerization	0.013	0.055	0.21	30	-10000	0	30
NFKB1	-0.001	0.095	-10000	0	-0.78	7	7
MAPK8	0.002	0.094	-10000	0	-0.41	8	8
DFFA	-0.005	0.046	-10000	0	-0.23	20	20
DNA fragmentation during apoptosis	-0.004	0.042	-10000	0	-0.24	15	15
FAS/FADD/MET	0.002	0.066	-10000	0	-0.15	68	68
CFLAR/RIP1	0.024	0.021	-10000	0	-0.19	2	2
FAIM3	0.019	0.008	-10000	0	-0.11	2	2
FAF1	0.006	0.061	-10000	0	-0.28	22	22
PARP1	-0.005	0.048	-10000	0	-0.24	20	20
DFFB	-0.004	0.042	-10000	0	-0.25	15	15
CHUK	0.002	0.089	-10000	0	-0.73	7	7
FASLG	0.019	0.003	-10000	0	-10000	0	0
FAS/FADD	-0.005	0.072	-10000	0	-0.19	56	56
HGF	0.016	0.02	-10000	0	-0.11	13	13
LMNA	-0.002	0.046	-10000	0	-0.22	20	20
CASP6	-0.006	0.048	-10000	0	-0.24	19	19
CASP10	0.019	0.002	-10000	0	-10000	0	0
CASP3	-0.01	0.048	-10000	0	-0.28	15	15
PTPN13	-0.011	0.09	-10000	0	-0.27	54	54
CASP8	-0.006	0.013	-10000	0	-10000	0	0
IL6	-0.004	0.093	-10000	0	-0.64	6	6
MET	0.008	0.037	-10000	0	-0.11	47	47
ICAD/CAD	0	0.043	-10000	0	-0.21	20	20
FASLG/FAS/FADD/FAF1/Caspase 10	0.005	0.08	-10000	0	-0.24	24	24
activation of caspase activity by cytochrome c	-0.007	0.04	-10000	0	-0.17	26	26
PAK2	-0.006	0.044	-10000	0	-0.24	16	16
BCL2	0.019	0	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.21	0.53	-9999	-1.1	135	135
IL23A	-0.025	0.28	-9999	-1	18	18
NF kappa B1 p50/RelA/I kappa B alpha	-0.01	0.27	-9999	-0.74	33	33
positive regulation of T cell mediated cytotoxicity	-0.024	0.28	-9999	-0.82	32	32
ITGA3	-0.022	0.27	-9999	-0.88	20	20
IL17F	-0.027	0.22	-9999	-0.55	41	41
IL12B	0.022	0.03	-9999	-10000	0	0
STAT1 (dimer)	-0.025	0.27	-9999	-0.79	32	32
CD4	-0.045	0.34	-9999	-1.1	35	35
IL23	-0.024	0.28	-9999	-0.97	19	19
IL23R	0.005	0.069	-9999	-0.14	29	29
IL1B	-0.039	0.32	-9999	-1.2	23	23
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.014	0.26	-9999	-0.79	24	24
TYK2	0.01	0.055	-9999	-0.29	14	14
STAT4	0.012	0.03	-9999	-0.11	30	30
STAT3	-0.003	0.079	-9999	-0.29	37	37
IL18RAP	0.018	0.015	-9999	-0.11	7	7
IL12RB1	0.019	0.024	-9999	-0.15	1	1
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
IL12Rbeta1/TYK2	0.018	0.049	-9999	-0.18	21	21
IL23R/JAK2	0.018	0.093	-9999	-0.18	21	21
positive regulation of chronic inflammatory response	-0.024	0.28	-9999	-0.82	32	32
natural killer cell activation	0	0.006	-9999	-10000	0	0
JAK2	0.016	0.042	-9999	-0.12	18	18
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
NFKB1	0.015	0.038	-9999	-0.23	11	11
RELA	0.018	0.02	-9999	-0.23	3	3
positive regulation of dendritic cell antigen processing and presentation	-0.021	0.27	-9999	-0.92	19	19
ALOX12B	-0.014	0.26	-9999	-0.79	23	23
CXCL1	-0.02	0.26	-9999	-0.83	20	20
T cell proliferation	-0.024	0.28	-9999	-0.82	32	32
NFKBIA	0.003	0.068	-9999	-0.24	34	34
IL17A	-0.001	0.19	-9999	-0.44	39	39
PI3K	-0.039	0.28	-9999	-0.78	38	38
IFNG	0.012	0.016	-9999	-10000	0	0
STAT3 (dimer)	-0.037	0.28	-9999	-0.75	41	41
IL18R1	0.019	0.011	-9999	-0.11	4	4
IL23/IL23R/JAK2/TYK2/SOCS3	0.005	0.18	-9999	-0.47	24	24
IL18/IL18R	0.03	0.039	-9999	-0.14	13	13
macrophage activation	-0.002	0.016	-9999	-0.042	18	18
TNF	-0.021	0.27	-9999	-0.91	19	19
STAT3/STAT4	-0.024	0.27	-9999	-0.77	34	34
STAT4 (dimer)	-0.024	0.27	-9999	-0.79	32	32
IL18	0	0.056	-9999	-0.13	70	70
IL19	-0.014	0.26	-9999	-0.79	23	23
STAT5A (dimer)	-0.021	0.27	-9999	-0.79	32	32
STAT1	0.008	0.04	-9999	-0.12	41	41
SOCS3	0.019	0	-9999	-10000	0	0
CXCL9	-0.023	0.26	-9999	-0.82	20	20
MPO	-0.014	0.26	-9999	-0.83	19	19
positive regulation of humoral immune response	-0.024	0.28	-9999	-0.82	32	32
IL23/IL23R/JAK2/TYK2	-0.026	0.29	-9999	-0.84	32	32
IL6	-0.025	0.26	-9999	-0.86	20	20
STAT5A	0.019	0.008	-9999	-0.11	2	2
IL2	0.021	0.007	-9999	-0.1	1	1
positive regulation of tyrosine phosphorylation of STAT protein	0	0.006	-9999	-10000	0	0
CD3E	-0.014	0.26	-9999	-0.81	21	21
keratinocyte proliferation	-0.024	0.28	-9999	-0.82	32	32
NOS2	-0.021	0.26	-9999	-0.74	32	32

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.045	0.19	10	-0.23	6	16
AES	0.025	0.046	0.17	12	-0.19	11	23
FBXW11	0.011	0.047	-10000	0	-0.27	14	14
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.021	0.026	-10000	0	-0.16	2	2
SMAD4	-0.004	0.079	-10000	0	-0.26	44	44
DKK2	0.013	0.028	-10000	0	-0.11	25	25
TLE1	0.026	0.036	0.16	10	-0.18	5	15
MACF1	-0.005	0.082	-10000	0	-0.28	42	42
CTNNB1	0.029	0.085	0.2	2	-0.35	17	19
WIF1	-0.005	0.051	-10000	0	-0.11	100	100
beta catenin/RanBP3	0.063	0.15	0.38	75	-0.32	6	81
KREMEN2	0.019	0.006	-10000	0	-0.11	1	1
DKK1	-0.018	0.058	-10000	0	-0.11	150	150
beta catenin/beta TrCP1	0.037	0.089	0.21	1	-0.36	18	19
FZD1	0.015	0.023	-10000	0	-0.11	17	17
AXIN2	-0.04	0.093	0.12	2	-0.25	74	76
AXIN1	0.019	0.001	-10000	0	-10000	0	0
RAN	0.016	0.031	-10000	0	-0.24	7	7
Axin1/APC/GSK3/beta catenin	0.009	0.16	-10000	0	-0.64	26	26
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.028	0.13	0.25	5	-0.45	24	29
Axin1/APC/GSK3	0.02	0.096	0.19	1	-0.37	23	24
Axin1/APC/GSK3/beta catenin/Macf1	0.013	0.12	-10000	0	-0.4	34	34
HNF1A	0.03	0.03	0.16	12	-10000	0	12
CTBP1	0.023	0.048	0.16	9	-0.29	8	17
MYC	-0.14	0.41	-10000	0	-1.3	54	54
RANBP3	0.019	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.031	0.025	-10000	0	-0.13	2	2
NKD1	0	0	-10000	0	-10000	0	0
TCF4	0.009	0.078	0.18	7	-0.27	32	39
TCF3	0.03	0.03	0.16	12	-10000	0	12
WNT1/LRP6/FZD1/Axin1	0.043	0.023	-10000	0	-0.13	1	1
Ran/GTP	0.013	0.021	-10000	0	-0.2	5	5
CtBP/CBP/TCF/TLE1/AES	0.08	0.18	0.48	71	-0.39	6	77
LEF1	0.029	0.036	0.18	12	-0.11	5	17
DVL1	0.018	0.11	-10000	0	-0.48	17	17
CSNK2A1	0.01	0.053	-10000	0	-0.29	16	16
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.005	0.18	-10000	0	-0.55	34	34
DKK1/LRP6/Kremen 2	0.012	0.041	-10000	0	-0.12	6	6
LRP6	0.013	0.029	-10000	0	-0.12	22	22
CSNK1A1	0.029	0.044	0.19	11	-0.29	4	15
NLK	0.001	0.06	-10000	0	-0.25	21	21
CCND1	-0.12	0.35	-10000	0	-1.3	39	39
WNT1	0.019	0.006	-10000	0	-10000	0	0
GSK3A	0.019	0.001	-10000	0	-10000	0	0
GSK3B	0.004	0.066	-10000	0	-0.26	29	29
FRAT1	0.016	0.023	-10000	0	-0.13	12	12
PPP2R5D	0.021	0.044	-10000	0	-0.21	15	15
APC	0.024	0.027	-10000	0	-0.18	5	5
WNT1/LRP6/FZD1	0.024	0.05	-10000	0	-0.25	9	9
CREBBP	0.03	0.03	0.16	12	-10000	0	12

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0	0.15	-10000	0	-0.57	15	15
RAD9A	0.018	0.013	-10000	0	-0.11	5	5
AP1	-0.03	0.11	-10000	0	-0.24	93	93
IFNAR2	0.018	0.02	-10000	0	-0.29	2	2
AKT1	0.012	0.061	-10000	0	-0.27	22	22
ER alpha/Oestrogen	0.014	0.004	-10000	0	-10000	0	0
NFX1/SIN3/HDAC complex	0.004	0.092	-10000	0	-0.27	37	37
EGF	0.014	0.025	-10000	0	-0.11	21	21
SMG5	0.019	0.008	-10000	0	-0.11	2	2
SMG6	0.016	0.019	-10000	0	-0.11	11	11
SP3/HDAC2	0.014	0.059	-10000	0	-0.21	29	29
TERT/c-Abl	-0.005	0.16	-10000	0	-0.56	22	22
SAP18	0.01	0.052	-10000	0	-0.29	15	15
MRN complex	0.036	0.019	-10000	0	-0.15	4	4
WT1	0.017	0.017	-10000	0	-10000	0	0
WRN	0.014	0.024	-10000	0	-10000	0	0
SP1	0.019	0.009	-10000	0	-10000	0	0
SP3	0.012	0.047	-10000	0	-0.29	12	12
TERF2IP	0.006	0.061	-10000	0	-0.28	23	23
Telomerase/Nucleolin	-0.003	0.14	-10000	0	-0.53	20	20
Mad/Max	0.028	0.009	-10000	0	-10000	0	0
TERT	-0.001	0.16	-10000	0	-0.6	13	13
CCND1	-0.046	0.3	-10000	0	-1	40	40
MAX	0.019	0.006	-10000	0	-0.11	1	1
RBBP7	0.015	0.034	-10000	0	-0.25	8	8
RBBP4	-0.005	0.079	-10000	0	-0.24	50	50
TERF2	-0.002	0.068	-10000	0	-0.23	43	43
PTGES3	0.016	0.03	-10000	0	-0.29	5	5
SIN3A	0	0.001	-10000	0	-10000	0	0
Telomerase/911	0.029	0.1	-10000	0	-0.52	11	11
CDKN1B	0	0.1	-10000	0	-0.38	32	32
RAD1	0.014	0.034	-10000	0	-0.18	13	13
XRCC5	0.014	0.038	-10000	0	-0.27	9	9
XRCC6	0.018	0.019	-10000	0	-0.29	2	2
SAP30	0.017	0.027	-10000	0	-0.29	4	4
TRF2/PARP2	0.005	0.072	-10000	0	-0.21	50	50
UBE3A	0.017	0.027	-10000	0	-0.29	4	4
JUN	-0.002	0.077	-10000	0	-0.28	37	37
E6	0	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.013	0.019	-10000	0	-0.2	4	4
FOS	-0.046	0.12	-10000	0	-0.22	146	146
IFN-gamma/IRF1	0.011	0.072	-10000	0	-0.21	45	45
PARP2	0.006	0.059	-10000	0	-0.25	25	25
BLM	-0.036	0.11	-10000	0	-0.25	110	110
Telomerase	0.013	0.075	-10000	0	-0.44	9	9
IRF1	-0.004	0.07	-10000	0	-0.15	84	84
ESR1	0.019	0.001	-10000	0	-10000	0	0
KU/TER	0.024	0.03	-10000	0	-0.19	10	10
ATM/TRF2	0.015	0.041	-10000	0	-0.098	45	45
ubiquitin-dependent protein catabolic process	0.01	0.092	-10000	0	-0.31	26	26
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.009	0.095	-10000	0	-0.32	26	26
HDAC1	0.013	0.04	-10000	0	-0.22	13	13
HDAC2	0.004	0.062	-10000	0	-0.22	33	33
ATM	0.011	0.05	0.16	39	-0.23	6	45
SMAD3	0.013	0.033	-10000	0	-0.19	9	9
ABL1	-0.012	0.093	-10000	0	-0.28	55	55
MXD1	0.019	0.006	-10000	0	-0.11	1	1
MRE11A	0.019	0.006	-10000	0	-0.11	1	1
HUS1	0.019	0.006	-10000	0	-0.11	1	1
RPS6KB1	0.019	0.008	-10000	0	-0.11	2	2
TERT/NF kappa B1/14-3-3	0.016	0.16	-10000	0	-0.55	17	17
NR2F2	-0.03	0.1	-10000	0	-0.22	106	106
MAPK3	0.021	0.007	-10000	0	-10000	0	0
MAPK1	0.014	0.035	-10000	0	-0.19	13	13
TGFB1/TGF beta receptor Type II	0.007	0.049	-10000	0	-0.16	37	37
NFKB1	0.014	0.037	-10000	0	-0.23	11	11
HNRNPC	0.018	0.019	-10000	0	-0.29	2	2
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.011	0.05	0.16	39	-0.23	6	45
NBN	0.017	0.027	-10000	0	-0.29	4	4
EGFR	-0.08	0.12	-10000	0	-0.25	126	126
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.044	0.082	-10000	0	-0.19	107	107
MYC	-0.023	0.098	-10000	0	-0.21	96	96
IL2	0.019	0.01	-10000	0	-0.11	1	1
KU	0.024	0.03	-10000	0	-0.19	10	10
RAD50	0.018	0.013	-10000	0	-0.11	5	5
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
TGFB1	0.007	0.049	-10000	0	-0.16	37	37
TRF2/BLM	-0.022	0.097	-10000	0	-0.2	104	104
FRAP1	0.019	0.006	-10000	0	-0.11	1	1
KU/TERT	0.014	0.15	-10000	0	-0.56	15	15
SP1/HDAC2	0.019	0.046	-10000	0	-0.18	21	21
PINX1	0	0	-10000	0	-10000	0	0
Telomerase/EST1A	0	0.14	-10000	0	-0.5	18	18
Smad3/Myc	-0.002	0.063	-10000	0	-0.15	67	67
911 complex	0.035	0.023	-10000	0	-0.15	5	5
IFNG	0.015	0.035	-10000	0	-0.12	30	30
Telomerase/PinX1	-0.032	0.12	-10000	0	-0.51	18	18
Telomerase/AKT1/mTOR/p70S6K	0.028	0.1	-10000	0	-0.6	8	8
SIN3B	0.017	0.025	-10000	0	-0.2	6	6
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
Telomerase/EST1B	0	0.14	-10000	0	-0.5	18	18
response to DNA damage stimulus	0.006	0.017	0.055	39	-0.077	6	45
MRN complex/TRF2/Rap1	0.034	0.068	-10000	0	-0.17	45	45
TRF2/WRN	0.01	0.054	-10000	0	-0.16	43	43
Telomerase/hnRNP C1/C2	0	0.14	-10000	0	-0.51	18	18
E2F1	0.019	0.009	-10000	0	-0.12	1	1
ZNFX1	0	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	0.01	0.051	-10000	0	-0.27	16	16
DKC1	0.012	0.042	-10000	0	-0.19	18	18
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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	0.018	0.015	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.032	0.032	-10000	0	-0.14	13	13
CDKN1B	-0.003	0.12	-10000	0	-0.39	40	40
CDKN1A	-0.008	0.12	-10000	0	-0.39	40	40
FRAP1	0.019	0.006	-10000	0	-0.11	1	1
PRKDC	0.002	0.065	-10000	0	-0.2	41	41
FOXO3	-0.005	0.13	-10000	0	-0.42	40	40
AKT1	-0.004	0.12	-10000	0	-0.39	40	40
BAD	0.014	0.036	-10000	0	-0.25	9	9
AKT3	0.017	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.001	0.11	-10000	0	-0.37	40	40
AKT1/ASK1	-0.008	0.13	-10000	0	-0.41	40	40
BAD/YWHAZ	0.033	0.033	-10000	0	-0.16	13	13
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0.008	0.057	-10000	0	-0.28	19	19
JNK cascade	0.008	0.12	0.39	40	-10000	0	40
TSC1	-0.003	0.12	-10000	0	-0.4	40	40
YWHAZ	0.014	0.037	-10000	0	-0.23	11	11
AKT1/RAF1	0.003	0.13	-10000	0	-0.41	40	40
EP300	0.012	0.046	-10000	0	-0.24	15	15
mol:GDP	-0.004	0.12	-10000	0	-0.38	40	40
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	-0.003	0.12	-10000	0	-0.4	40	40
YWHAQ	0.018	0.019	-10000	0	-0.29	2	2
TBC1D4	0.018	0.01	-10000	0	-10000	0	0
MAP3K5	-0.014	0.092	-10000	0	-0.25	65	65
MAPKAP1	0.013	0.038	-10000	0	-0.21	13	13
negative regulation of cell cycle	0.001	0.12	0.38	28	-10000	0	28
YWHAH	-0.006	0.083	-10000	0	-0.26	49	49
AKT1S1	-0.004	0.11	-10000	0	-0.37	40	40
CASP9	-0.001	0.11	-10000	0	-0.37	40	40
YWHAB	0.015	0.036	-10000	0	-0.29	7	7
p27Kip1/KPNA1	0.002	0.12	-10000	0	-0.38	42	42
GBL	0.016	0.029	-10000	0	-0.2	8	8
PDK1/Src/Hsp90	0.038	0.012	-10000	0	-0.15	2	2
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
SRC	0.019	0	-10000	0	-10000	0	0
AKT2/p21CIP1	-0.009	0.11	-10000	0	-0.34	40	40
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.02	0.055	-10000	0	-0.48	4	4
CHUK	0	0.11	-10000	0	-0.37	40	40
BAD/BCL-XL	0.017	0.11	-10000	0	-0.34	40	40
mTORC2	0.032	0.028	-10000	0	-0.15	10	10
AKT2	0.017	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	-0.002	0.15	-10000	0	-0.4	46	46
PDPK1	0.019	0	-10000	0	-10000	0	0
MDM2	-0.003	0.11	-10000	0	-0.37	40	40
MAPKKK cascade	-0.003	0.12	0.4	40	-10000	0	40
MDM2/Cbp/p300	0.016	0.11	-10000	0	-0.36	40	40
TSC1/TSC2	-0.003	0.13	-10000	0	-0.42	40	40
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.11	-10000	0	-0.34	40	40
glucose import	0.02	0.011	-10000	0	-0.13	1	1
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.015	0.073	-10000	0	-0.22	43	43
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.021	0.008	-10000	0	-10000	0	0
GSK3A	0.001	0.11	-10000	0	-0.37	40	40
FOXO1	-0.008	0.13	-10000	0	-0.42	40	40
GSK3B	-0.005	0.13	-10000	0	-0.43	40	40
SFN	0.002	0.044	-10000	0	-0.11	70	70
G1/S transition of mitotic cell cycle	-0.001	0.12	-10000	0	-0.41	40	40
p27Kip1/14-3-3 family	0.007	0.13	-10000	0	-0.44	23	23
PRKACA	0.019	0	-10000	0	-10000	0	0
KPNA1	0.013	0.042	-10000	0	-0.29	10	10
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0.019	0	-10000	0	-10000	0	0
CREBBP	0.019	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.01	0.016	-9999	-0.05	37	37
SNTA1	0.007	0.043	-9999	-0.13	45	45
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.014	0.021	-9999	-0.045	59	59
MAPK12	0.016	0.028	-9999	-0.16	11	11
CCND1	-0.017	0.1	-9999	-0.37	41	41
p38 gamma/SNTA1	0.022	0.031	-9999	-0.15	11	11
MAP2K3	0.018	0.01	-9999	-0.11	3	3
PKN1	0.008	0.049	-9999	-0.18	28	28
G2/M transition checkpoint	0.016	0.028	-9999	-0.16	11	11
MAP2K6	0.014	0.031	-9999	-0.19	11	11
MAPT	-0.019	0.097	-9999	-0.24	79	79
MAPK13	0.015	0.021	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.01	0.036	-9999	-0.23	11	11

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.018	0.011	-9999	-0.11	4	4
Caspase 8 (4 units)	0.006	0.09	-9999	-0.29	22	22
NEF	0.005	0	-9999	-10000	0	0
NFKBIA	-0.001	0.068	-9999	-0.24	34	34
BIRC3	0.006	0.062	-9999	-0.2	13	13
CYCS	-0.004	0.089	-9999	-0.28	32	32
RIPK1	0.016	0.019	-9999	-0.11	11	11
CD247	0.022	0.015	-9999	-10000	0	0
MAP2K7	0.006	0.098	-9999	-0.4	15	15
protein ubiquitination	0.026	0.063	-9999	-0.21	17	17
CRADD	0.017	0.015	-9999	-0.11	7	7
DAXX	0.017	0.018	-9999	-0.15	5	5
FAS	-0.027	0.099	-9999	-0.2	111	111
BID	-0.007	0.091	-9999	-0.28	31	31
NF-kappa-B/RelA/I kappa B alpha	0.021	0.062	-9999	-0.16	37	37
TRADD	0.019	0	-9999	-10000	0	0
MAP3K5	-0.014	0.092	-9999	-0.25	65	65
CFLAR	0.016	0.024	-9999	-0.15	9	9
FADD	0.017	0.021	-9999	-0.2	4	4
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.021	0.062	-9999	-0.16	37	37
MAPK8	0.011	0.093	-9999	-0.38	15	15
APAF1	0.019	0	-9999	-10000	0	0
TRAF1	0.017	0.015	-9999	-0.11	7	7
TRAF2	0.019	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.005	0.088	-9999	-0.18	91	91
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.022	0.075	-9999	-0.26	17	17
CHUK	0.026	0.067	-9999	-0.22	17	17
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.009	0.08	-9999	-0.14	92	92
TCRz/NEF	0.024	0.01	-9999	-10000	0	0
TNF	0.018	0.01	-9999	-0.11	3	3
FASLG	0.027	0.008	-9999	-10000	0	0
NFKB1	0.011	0.039	-9999	-0.23	11	11
TNFR1A/BAG4/TNF-alpha	0.02	0.057	-9999	-0.16	50	50
CASP6	0.008	0.11	-9999	-0.45	19	19
CASP7	0.002	0.1	-9999	-0.32	28	28
RELA	0.014	0.025	-9999	-0.24	3	3
CASP2	0.017	0.017	-9999	-0.11	9	9
CASP3	0.005	0.1	-9999	-0.31	25	25
TNFRSF1A	-0.01	0.091	-9999	-0.29	50	50
TNFR1A/BAG4	0.007	0.065	-9999	-0.19	50	50
CASP8	0.016	0.021	-9999	-0.11	14	14
CASP9	0.014	0.029	-9999	-0.13	18	18
MAP3K14	0.024	0.071	-9999	-0.24	17	17
APAF-1/Caspase 9	-0.028	0.066	-9999	-0.22	38	38
BCL2	0.015	0.087	-9999	-0.35	15	15

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.011	0.095	-10000	0	-0.37	25	25
CRKL	0.009	0.099	-10000	0	-0.4	25	25
HRAS	0.023	0.096	-10000	0	-0.32	29	29
mol:PIP3	-0.006	0.098	0.28	3	-0.38	25	28
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0.019	0.006	-10000	0	-0.11	1	1
GAB1	0.005	0.1	-10000	0	-0.42	25	25
FOXO3	-0.016	0.14	-10000	0	-0.41	48	48
AKT1	-0.015	0.13	-10000	0	-0.41	47	47
BAD	-0.011	0.13	-10000	0	-0.38	47	47
megakaryocyte differentiation	-0.001	0.1	-10000	0	-0.43	25	25
GSK3B	-0.015	0.14	-10000	0	-0.41	48	48
RAF1	0.023	0.085	-10000	0	-0.27	32	32
SHC1	0.004	0.052	-10000	0	-0.14	48	48
STAT3	0.005	0.1	-10000	0	-0.42	25	25
STAT1	0.003	0.21	-10000	0	-0.92	25	25
HRAS/SPRED1	0.018	0.083	-10000	0	-0.27	29	29
cell proliferation	0.01	0.099	-10000	0	-0.4	25	25
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
TEC	0.019	0	-10000	0	-10000	0	0
RPS6KB1	0.005	0.1	-10000	0	-0.41	25	25
HRAS/SPRED2	0.028	0.085	-10000	0	-0.27	29	29
LYN/TEC/p62DOK	0.015	0.11	-10000	0	-0.4	25	25
MAPK3	0.023	0.071	-10000	0	-0.21	33	33
STAP1	0.009	0.1	-10000	0	-0.41	25	25
GRAP2	0.019	0	-10000	0	-10000	0	0
JAK2	0.007	0.18	-10000	0	-0.78	25	25
STAT1 (dimer)	0.004	0.21	-10000	0	-0.9	25	25
mol:Gleevec	-0.001	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.029	0.099	-10000	0	-0.38	25	25
actin filament polymerization	0.005	0.099	-10000	0	-0.41	25	25
LYN	-0.018	0.098	-10000	0	-0.25	72	72
STAP1/STAT5A (dimer)	0.016	0.13	-10000	0	-0.56	25	25
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
CBL/CRKL/GRB2	0.023	0.095	-10000	0	-0.36	25	25
PI3K	-0.004	0.12	-10000	0	-0.37	35	35
PTEN	0.013	0.038	-10000	0	-0.18	17	17
SCF/KIT/EPO/EPOR	0.005	0.25	-10000	0	-1.1	25	25
MAPK8	0.01	0.1	-10000	0	-0.41	25	25
STAT3 (dimer)	0.005	0.1	-10000	0	-0.41	25	25
positive regulation of transcription	0.023	0.061	0.13	2	-0.17	33	35
mol:GDP	0.026	0.093	-10000	0	-0.34	25	25
PIK3C2B	0.004	0.1	-10000	0	-0.42	25	25
CBL/CRKL	0.017	0.097	-10000	0	-0.37	25	25
FER	0.009	0.1	-10000	0	-0.41	25	25
SH2B3	0.003	0.1	-10000	0	-0.42	25	25
PDPK1	-0.002	0.092	0.27	3	-0.35	25	28
SNAI2	-0.005	0.11	-10000	0	-0.45	25	25
positive regulation of cell proliferation	0.008	0.16	-10000	0	-0.69	25	25
KITLG	0.021	0.01	-10000	0	-10000	0	0
cell motility	0.008	0.16	-10000	0	-0.69	25	25
PTPN6	0.005	0.056	-10000	0	-0.2	33	33
EPOR	0.034	0.067	-10000	0	-10000	0	0
STAT5A (dimer)	0.014	0.14	-10000	0	-0.57	25	25
SOCS1	0.019	0	-10000	0	-10000	0	0
cell migration	-0.01	0.1	0.4	25	-10000	0	25
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.02	0.006	-10000	0	-10000	0	0
VAV1	0.016	0.019	-10000	0	-0.11	12	12
GRB10	0	0.11	-10000	0	-0.43	25	25
PTPN11	0.014	0.033	-10000	0	-0.26	7	7
SCF/KIT	0.006	0.11	-10000	0	-0.43	25	25
GO:0007205	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	0.022	0.074	-10000	0	-0.22	35	35
CBL	0.019	0	-10000	0	-10000	0	0
KIT	-0.022	0.26	-10000	0	-1.2	25	25
MAP2K2	0.023	0.073	-10000	0	-0.22	34	34
SHC/Grb2/SOS1	0.01	0.098	-10000	0	-0.39	25	25
STAT5A	0.014	0.14	-10000	0	-0.58	25	25
GRB2	0.014	0.039	-10000	0	-0.26	10	10
response to radiation	-0.005	0.11	-10000	0	-0.44	25	25
SHC/GRAP2	0.018	0.036	-10000	0	-0.19	9	9
PTPRO	-0.001	0.11	-10000	0	-0.44	25	25
SH2B2	0.005	0.1	-10000	0	-0.41	25	25
DOK1	0.019	0	-10000	0	-10000	0	0
MATK	0.01	0.1	-10000	0	-0.41	25	25
CREBBP	0.031	0.029	-10000	0	-10000	0	0
BCL2	0.034	0.065	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.019	0.044	-10000	0	-0.19	22	22
ATM	0.01	0.042	-10000	0	-0.15	30	30
UBE2D3	0.017	0.023	-10000	0	-0.29	3	3
PRKDC	0.002	0.065	-10000	0	-0.2	41	41
ATR	0.011	0.049	-10000	0	-0.26	16	16
UBE2L3	0.014	0.038	-10000	0	-0.29	8	8
FANCD2	0.006	0.053	-10000	0	-0.26	17	17
protein ubiquitination	0.029	0.052	-10000	0	-0.13	34	34
XRCC5	0.014	0.038	-10000	0	-0.27	9	9
XRCC6	0.018	0.019	-10000	0	-0.29	2	2
M/R/N Complex	0.036	0.019	-10000	0	-0.15	4	4
MRE11A	0.019	0.006	-10000	0	-0.11	1	1
DNA-PK	0.025	0.052	-10000	0	-0.19	26	26
FA complex/FANCD2/Ubiquitin	0.017	0.072	-10000	0	-0.3	20	20
FANCF	0.011	0.048	-10000	0	-0.25	16	16
BRCA1	0.017	0.015	-10000	0	-0.11	7	7
CCNE1	0.01	0.033	-10000	0	-0.11	37	37
CDK2/Cyclin E1	0.017	0.036	-10000	0	-0.14	14	14
FANCG	0	0.064	-10000	0	-0.18	50	50
BRCA1/BACH1/BARD1	0.018	0.045	-10000	0	-0.19	23	23
FANCE	0.018	0.011	-10000	0	-0.11	4	4
FANCC	0.019	0.008	-10000	0	-10000	0	0
NBN	0.017	0.027	-10000	0	-0.29	4	4
FANCA	0.019	0.006	-10000	0	-0.11	1	1
DNA repair	0.021	0.077	-10000	0	-0.3	15	15
BRCA1/BARD1/ubiquitin	0.018	0.045	-10000	0	-0.19	23	23
BARD1/DNA-PK	0.029	0.065	-10000	0	-0.17	41	41
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.019	0.044	0.19	22	-10000	0	22
BRCA1/BARD1/CTIP/M/R/N Complex	0.015	0.067	-10000	0	-0.23	28	28
BRCA1/BACH1/BARD1/TopBP1	0.017	0.064	-10000	0	-0.16	54	54
BRCA1/BARD1/P53	0.021	0.067	-10000	0	-0.15	58	58
BARD1/CSTF1/BRCA1	0.029	0.04	-10000	0	-0.15	23	23
BRCA1/BACH1	0.017	0.015	-10000	0	-0.11	7	7
BARD1	0.006	0.063	-10000	0	-0.28	24	24
PCNA	0.004	0.065	-10000	0	-0.25	30	30
BRCA1/BARD1/UbcH5C	0.029	0.044	-10000	0	-0.16	24	24
BRCA1/BARD1/UbcH7	0.027	0.047	-10000	0	-0.16	29	29
BRCA1/BARD1/RAD51/PCNA	0.032	0.057	-10000	0	-0.16	38	38
BARD1/DNA-PK/P53	0.023	0.076	-10000	0	-0.15	68	68
BRCA1/BARD1/Ubiquitin	0.018	0.045	-10000	0	-0.19	23	23
BRCA1/BARD1/CTIP	0.015	0.064	-10000	0	-0.16	49	49
FA complex	0.016	0.059	-10000	0	-0.21	21	21
BARD1/EWS	0.019	0.044	-10000	0	-0.19	22	22
RBBP8	0.001	0.055	-10000	0	-0.19	34	34
TP53	-0.007	0.077	-10000	0	-0.2	62	62
TOPBP1	-0.003	0.078	-10000	0	-0.27	40	40
G1/S transition of mitotic cell cycle	-0.02	0.067	0.15	58	-10000	0	58
BRCA1/BARD1	0.034	0.054	-10000	0	-0.13	34	34
CSTF1	0.019	0.006	-10000	0	-0.11	1	1
BARD1/EWS-Fli1	0.005	0.042	-10000	0	-0.2	22	22
CDK2	0.011	0.034	-10000	0	-0.12	29	29
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.018	0.01	-10000	0	-0.11	3	3
RAD50	0.018	0.013	-10000	0	-0.11	5	5
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.018	0.045	-10000	0	-0.19	23	23
EWSR1	0.019	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.013	0.04	-9999	-0.22	13	13
HDAC2	0.004	0.061	-9999	-0.22	33	33
GNB1/GNG2	0.019	0.036	-9999	-0.16	21	21
forebrain development	0.021	0.067	-9999	-0.4	5	5
GNAO1	-0.013	0.085	-9999	-0.2	81	81
SMO/beta Arrestin2	0.026	0.029	-9999	-0.19	7	7
SMO	0.019	0.011	-9999	-0.11	4	4
ARRB2	0.014	0.039	-9999	-0.29	7	7
GLI3/SPOP	-0.003	0.11	-9999	-0.29	57	57
mol:GTP	0.001	0.001	-9999	-10000	0	0
GSK3B	0.004	0.066	-9999	-0.26	29	29
GNAI2	0.001	0.074	-9999	-0.28	34	34
SIN3/HDAC complex	0.029	0.038	-9999	-0.16	19	19
GNAI1	-0.045	0.11	-9999	-0.2	157	157
XPO1	0.02	0.024	-9999	-0.29	3	3
GLI1/Su(fu)	0.022	0.063	-9999	-0.4	5	5
SAP30	0.016	0.027	-9999	-0.29	4	4
mol:GDP	0.019	0.011	-9999	-0.11	4	4
MIM/GLI2A	0.026	0.005	-9999	-10000	0	0
IFT88	0.017	0.022	-9999	-0.17	6	6
GNAI3	0.015	0.038	-9999	-0.29	8	8
GLI2	0.018	0.093	-9999	-0.39	20	20
GLI3	-0.01	0.11	-9999	-0.28	56	56
CSNK1D	0.01	0.052	-9999	-0.27	17	17
CSNK1E	0.003	0.064	-9999	-0.23	34	34
SAP18	0.01	0.052	-9999	-0.29	15	15
embryonic digit morphogenesis	0.017	0.022	-9999	-0.17	6	6
GNG2	0	0	-9999	-10000	0	0
Gi family/GTP	-0.035	0.12	-9999	-0.28	72	72
SIN3B	0.016	0.025	-9999	-0.2	6	6
SIN3A	0	0	-9999	-10000	0	0
GLI3/Su(fu)	0	0.091	-9999	-0.27	41	41
GLI2/Su(fu)	0.021	0.084	-9999	-0.33	22	22
FOXA2	0.033	0.027	-9999	-10000	0	0
neural tube patterning	0.021	0.067	-9999	-0.4	5	5
SPOP	0.008	0.058	-9999	-0.29	19	19
Su(fu)/PIAS1	0.015	0.034	-9999	-0.13	24	24
GNB1	0.007	0.061	-9999	-0.29	21	21
CSNK1G2	0.018	0.014	-9999	-0.29	1	1
CSNK1G3	0.017	0.025	-9999	-0.22	5	5
MTSS1	0.026	0.005	-9999	-10000	0	0
embryonic limb morphogenesis	0.021	0.067	-9999	-0.4	5	5
SUFU	0.009	0.017	-9999	-0.13	7	7
LGALS3	-0.039	0.12	-9999	-0.27	106	106
catabolic process	0.011	0.14	-9999	-0.46	36	36
GLI3A/CBP	0.027	0.016	-9999	-10000	0	0
KIF3A	-0.007	0.083	-9999	-0.26	49	49
GLI1	0.021	0.068	-9999	-0.41	5	5
RAB23	0.01	0.041	-9999	-0.14	31	31
CSNK1A1	0.014	0.038	-9999	-0.29	8	8
IFT172	0	0	-9999	-10000	0	0
RBBP7	0.015	0.034	-9999	-0.25	8	8
Su(fu)/Galectin3	-0.009	0.062	-9999	-0.14	100	100
GNAZ	-0.007	0.083	-9999	-0.23	56	56
RBBP4	-0.005	0.079	-9999	-0.24	50	50
CSNK1G1	0.019	0	-9999	-10000	0	0
PIAS1	0.008	0.056	-9999	-0.29	18	18
PRKACA	0.019	0	-9999	-10000	0	0
GLI2/SPOP	0.023	0.098	-9999	-0.37	25	25
STK36	0.003	0.002	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.041	0.14	-9999	-0.37	58	58
PTCH1	0.026	0.065	-9999	-0.53	2	2
MIM/GLI1	0.04	0.07	-9999	-0.48	3	3
CREBBP	0.027	0.016	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.006	0.098	-9999	-0.25	51	51

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.024	0.033	-9999	-0.11	24	24
TC10/GTP	0.023	0.035	-9999	-0.13	25	25
Insulin Receptor/Insulin/IRS1/Shp2	0.034	0.049	-9999	-0.14	30	30
HRAS	0.009	0.055	-9999	-0.28	18	18
APS homodimer	0	0	-9999	-10000	0	0
GRB14	0.001	0.047	-9999	-0.12	70	70
FOXO3	-0.031	0.18	-9999	-0.79	28	28
AKT1	-0.006	0.083	-9999	-0.23	43	43
INSR	0.019	0.007	-9999	-0.036	2	2
Insulin Receptor/Insulin	0.039	0.065	-9999	-0.34	10	10
mol:GTP	0	0	-9999	-10000	0	0
GRB10	-0.018	0.091	-9999	-0.2	89	89
SORBS1	0.019	0	-9999	-10000	0	0
CRK	0.009	0.054	-9999	-0.28	17	17
PTPN1	0.014	0.058	-9999	-0.34	10	10
CAV1	-0.002	0.058	-9999	-0.17	43	43
CBL/APS/CAP/Crk-II/C3G	0.04	0.029	-9999	-0.12	16	16
Insulin Receptor/Insulin/IRS1/NCK2	0.031	0.058	-9999	-0.16	36	36
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.078	-9999	-0.15	99	99
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.021	0.07	-9999	-0.35	14	14
RPS6KB1	-0.003	0.077	-9999	-0.21	43	43
PARD6A	0.015	0.026	-9999	-0.14	12	12
CBL	0.019	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.02	0.013	-9999	-10000	0	0
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.005	0.084	-9999	-0.25	36	36
HRAS/GTP	-0.014	0.04	-9999	-0.12	50	50
Insulin Receptor	0.019	0.007	-9999	-0.036	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.033	0.058	-9999	-0.14	39	39
PRKCI	0.01	0.095	-9999	-0.48	17	17
Insulin Receptor/Insulin/GRB14/PDK1	-0.03	0.06	-9999	-0.18	49	49
SHC1	0.004	0.052	-9999	-0.14	48	48
negative regulation of MAPKKK cascade	0.028	0.045	-9999	-0.26	5	5
PI3K	0.006	0.083	-9999	-0.15	99	99
NCK2	0.009	0.054	-9999	-0.28	17	17
RHOQ	0.011	0.048	-9999	-0.28	14	14
mol:H2O2	-0.002	0.007	-9999	-10000	0	0
HRAS/GDP	0.007	0.037	-9999	-0.19	18	18
AKT2	-0.001	0.07	-9999	-0.19	36	36
PRKCZ	-0.017	0.082	-9999	-0.47	16	16
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	0.01	0.042	-9999	-0.13	34	34
F2RL2	0.019	0.008	-9999	-0.11	2	2
TRIP10	0.015	0.029	-9999	-0.15	13	13
Insulin Receptor/Insulin/Shc	0.028	0.033	-9999	-0.15	9	9
TC10/GTP/CIP4/Exocyst	0.019	0.033	-9999	-0.16	16	16
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.034	0.04	-9999	-0.15	16	16
RAPGEF1	0.019	0	-9999	-10000	0	0
RASA1	0.003	0.069	-9999	-0.28	29	29
NCK1	0.014	0.036	-9999	-0.19	14	14
CBL/APS/CAP/Crk-II	0.032	0.03	-9999	-0.14	16	16
TC10/GDP	0.009	0.033	-9999	-0.19	14	14
Insulin Receptor/Insulin/SHC/GRB10	0.018	0.065	-9999	-0.15	51	51
INPP5D	0.005	0.033	-9999	-0.13	24	24
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.003	0.007	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.015	0.033	-9999	-0.27	7	7
IRS1	-0.002	0.07	-9999	-0.19	53	53
p62DOK/RasGAP	0.028	0.046	-9999	-0.26	5	5
INS	0.019	0.007	-9999	-10000	0	0
mol:PI-3-4-P2	0.005	0.033	-9999	-0.13	24	24
GRB2	0.014	0.039	-9999	-0.26	10	10
EIF4EBP1	-0.006	0.082	-9999	-0.22	46	46
PTPRA	0.017	0.024	-9999	-0.22	4	4
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
TC10/GTP/CIP4	0.019	0.033	-9999	-0.16	16	16
PDPK1	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.011	0.056	-9999	-0.17	39	39
Insulin Receptor/Insulin/IRS1	0.025	0.042	-9999	-0.15	24	24
Insulin Receptor/Insulin/IRS3	0.028	0.014	-9999	-10000	0	0
Par3/Par6	0.036	0.033	-9999	-0.12	18	18

×

E-cadherin 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
E-cadherin/beta catenin-gamma catenin	0.027	0.037	-9999	-0.11	28	28
E-cadherin/beta catenin	0.022	0.026	-9999	-0.19	3	3
CTNNB1	0.017	0.023	-9999	-0.29	3	3
JUP	0.008	0.037	-9999	-0.11	47	47
CDH1	0.012	0.03	-9999	-0.11	29	29

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.003	0.048	-9999	-0.13	57	57
ARNO/beta Arrestin1-2	0.022	0.022	-9999	-0.099	8	8
EGFR	-0.08	0.12	-9999	-0.29	97	97
EPHA2	0.008	0.036	-9999	-0.11	45	45
USP6	0.017	0.017	-9999	-0.11	9	9
IQSEC1	0.016	0.022	-9999	-0.13	10	10
EGFR/EGFR/EGF/EGF	-0.044	0.082	-9999	-0.19	107	107
ARRB2	0.013	0.029	-9999	-0.23	7	7
mol:GTP	0.006	0.01	-9999	-10000	0	0
ARRB1	0.018	0.011	-9999	-0.11	4	4
FBXO8	0	0	-9999	-10000	0	0
TSHR	0.015	0.022	-9999	-0.11	16	16
EGF	0.014	0.025	-9999	-0.11	21	21
somatostatin receptor activity	0	0	-9999	0	7	7
ARAP2	0	0	-9999	0	1	1
mol:GDP	0.016	0.034	-9999	-0.13	16	16
mol:PI-3-4-5-P3	0	0	-9999	0	3	3
ITGA2B	0.019	0	-9999	-10000	0	0
ARF6	0.018	0.015	-9999	-0.2	2	2
Ephrin A1/EPHA2/NCK1/GIT1	0.028	0.053	-9999	-0.14	36	36
ADAP1	0	0	-9999	-10000	0	0
KIF13B	-0.009	0.085	-9999	-0.24	57	57
HGF/MET	0.018	0.03	-9999	-0.14	4	4
PXN	0.018	0.011	-9999	-0.11	4	4
ARF6/GTP	0.022	0.039	-9999	-0.17	3	3
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.027	0.072	-9999	-0.15	108	108
ADRB2	0.01	0.032	-9999	-0.11	35	35
receptor agonist activity	0	0	-9999	0	2	2
actin filament binding	0	0	-9999	0	7	7
SRC	0.019	0	-9999	-10000	0	0
ITGB3	0.019	0.008	-9999	-0.11	2	2
GNAQ	0.015	0.023	-9999	-0.11	17	17
EFA6/PI-4-5-P2	0	0	-9999	-0.001	4	4
ARF6/GDP	0.026	0.03	-9999	-0.37	1	1
ARF6/GDP/GULP/ACAP1	0.005	0.055	-9999	-0.16	11	11
alphaIIb/beta3 Integrin/paxillin/GIT1	0.048	0.01	-9999	-10000	0	0
ACAP1	0	0	-9999	-10000	0	0
ACAP2	0	0	-9999	0	1	1
LHCGR/beta Arrestin2	0.017	0.022	-9999	-0.17	7	7
EFNA1	-0.001	0.07	-9999	-0.21	46	46
HGF	0.016	0.02	-9999	-0.11	13	13
CYTH3	0	0	-9999	0	2	2
CYTH2	0	0.001	-9999	-0.003	6	6
NCK1	0.014	0.036	-9999	-0.19	14	14
fibronectin binding	0	0	-9999	0	3	3
endosomal lumen acidification	0	0	-9999	0	16	16
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.046	0.11	-9999	-0.18	173	173
GNAQ/ARNO	0.012	0.01	-9999	-0.042	17	17
mol:Phosphatidic acid	0	0	-9999	0	1	1
PIP3-E	0.002	0.048	-9999	-0.12	64	64
MET	0.008	0.037	-9999	-0.11	47	47
GNA14	0.015	0.022	-9999	-0.11	15	15
GNA15	0.012	0.033	-9999	-0.12	26	26
GIT1	0.019	0.006	-9999	-0.11	1	1
mol:PI-4-5-P2	0	0	-9999	0	3	3
GNA11	0.003	0.069	-9999	-0.29	27	27
LHCGR	0.019	0	-9999	-10000	0	0
AGTR1	0.016	0.02	-9999	-0.11	13	13
desensitization of G-protein coupled receptor protein signaling pathway	0.017	0.022	-9999	-0.17	7	7
IPCEF1/ARNO	-0.022	0.059	-9999	-0.11	123	123
alphaIIb/beta3 Integrin	0.028	0.006	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory network

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.029	0.12	0.29	3	-0.72	13	16
SMARCC2	-0.001	0.075	-10000	0	-0.28	35	35
SMARCC1	0.012	0.038	-10000	0	-0.15	23	23
TBX21	0.039	0.036	-10000	0	-10000	0	0
SUMO2	0.02	0.007	-10000	0	-10000	0	0
STAT1 (dimer)	0.007	0.055	-10000	0	-0.17	35	35
FKBP4	0.014	0.029	-10000	0	-0.13	17	17
FKBP5	-0.023	0.087	-10000	0	-0.16	121	121
GR alpha/HSP90/FKBP51/HSP90	-0.01	0.067	-10000	0	-0.2	26	26
PRL	0.042	0.041	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	-0.029	0.073	-10000	0	-0.32	1	1
RELA	-0.031	0.077	-10000	0	-0.15	139	139
FGG	-0.019	0.083	-10000	0	-0.32	1	1
GR beta/TIF2	-0.001	0.052	-10000	0	-0.24	9	9
IFNG	0.042	0.068	-10000	0	-10000	0	0
apoptosis	-0.002	0.21	0.46	30	-0.58	30	60
CREB1	0.024	0.036	-10000	0	-0.29	6	6
histone acetylation	0.024	0.043	-10000	0	-0.22	8	8
BGLAP	0.037	0.049	-10000	0	-10000	0	0
GR/PKAc	0.02	0.062	-10000	0	-0.2	21	21
NF kappa B1 p50/RelA	-0.055	0.13	-10000	0	-0.25	144	144
SMARCD1	0.018	0.013	-10000	0	-0.11	5	5
MDM2	-0.005	0.033	-10000	0	-10000	0	0
GATA3	0.032	0.018	-10000	0	-10000	0	0
AKT1	0.005	0.066	0.16	13	-0.26	26	39
CSF2	0.028	0.032	-10000	0	-10000	0	0
GSK3B	0.005	0.067	-10000	0	-0.27	28	28
NR1I3	0.01	0.19	0.46	21	-0.52	23	44
CSN2	-0.015	0.073	-10000	0	-0.29	1	1
BRG1/BAF155/BAF170/BAF60A	0.021	0.08	-10000	0	-0.21	48	48
NFATC1	0.029	0	-10000	0	-10000	0	0
POU2F1	0.021	0.028	-10000	0	-0.24	3	3
CDKN1A	-0.15	0.44	-10000	0	-1.3	62	62
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.008	-10000	0	-10000	0	0
SFN	0.002	0.044	-10000	0	-0.11	70	70
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.002	0.07	-10000	0	-0.19	32	32
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.057	0.3	0.44	21	-0.72	78	99
JUN	0.05	0.064	-10000	0	-0.25	5	5
IL4	0.045	0.035	-10000	0	-10000	0	0
CDK5R1	0.014	0.025	-10000	0	-0.11	21	21
PRKACA	0.019	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.028	0.073	-10000	0	-0.26	32	32
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.007	0.064	-10000	0	-0.19	21	21
cortisol/GR alpha (monomer)	-0.046	0.082	-10000	0	-0.38	1	1
NCOA2	0.018	0.01	-10000	0	-0.11	3	3
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.007	0.076	-10000	0	-0.27	26	26
AP-1/NFAT1-c-4	0.062	0.1	-10000	0	-0.37	7	7
AFP	0.05	0.067	-10000	0	-10000	0	0
SUV420H1	-0.009	0.088	-10000	0	-0.28	49	49
IRF1	-0.027	0.14	-10000	0	-0.73	17	17
TP53	-0.04	0.18	-10000	0	-0.5	66	66
PPP5C	0.017	0.015	-10000	0	-0.11	7	7
KRT17	0.038	0.077	-10000	0	-10000	0	0
KRT14	0.026	0.048	0.39	1	-10000	0	1
TBP	0.023	0.032	-10000	0	-0.28	4	4
CREBBP	0.01	0.007	-10000	0	-10000	0	0
HDAC1	0.007	0.037	-10000	0	-0.22	12	12
HDAC2	0.003	0.061	-10000	0	-0.22	33	33
AP-1	0.062	0.1	-10000	0	-0.37	7	7
MAPK14	0.019	0.015	-10000	0	-0.11	5	5
MAPK10	-0.016	0.098	-10000	0	-0.29	58	58
MAPK11	0.02	0.007	-10000	0	-10000	0	0
KRT5	0.04	0.074	-10000	0	-10000	0	0
interleukin-1 receptor activity	-0.002	0	-10000	0	-10000	0	0
NCOA1	-0.006	0.084	-10000	0	-0.29	42	42
STAT1	0.007	0.055	-10000	0	-0.17	35	35
CGA	0.039	0.047	-10000	0	-0.35	1	1
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.047	0.07	-10000	0	-0.45	7	7
MAPK3	0.02	0.01	-10000	0	-10000	0	0
MAPK1	0.011	0.05	-10000	0	-0.22	21	21
ICAM1	-0.02	0.11	-10000	0	-10000	0	0
NFKB1	-0.033	0.081	-10000	0	-0.15	143	143
MAPK8	0.053	0.045	-10000	0	-10000	0	0
MAPK9	0.017	0.029	-10000	0	-0.23	6	6
cortisol/GR alpha (dimer)	-0.004	0.22	0.47	27	-0.61	30	57
BAX	-0.038	0.18	-10000	0	-1.4	5	5
POMC	0.035	0.06	-10000	0	-10000	0	0
EP300	0.002	0.046	-10000	0	-0.3	11	11
cortisol/GR alpha (dimer)/p53	-0.056	0.12	-10000	0	-0.42	19	19
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.073	0.24	39	-10000	0	39
SGK1	-0.006	0.051	-10000	0	-0.31	11	11
IL13	0.048	0.058	-10000	0	-10000	0	0
IL6	-0.028	0.11	-10000	0	-10000	0	0
PRKACG	0.019	0	-10000	0	-10000	0	0
IL5	0.043	0.051	-10000	0	-10000	0	0
IL2	0.042	0.067	-10000	0	-10000	0	0
CDK5	0.005	0.061	-10000	0	-0.24	29	29
PRKACB	-0.002	0.076	-10000	0	-0.26	39	39
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
IL8	-0.21	0.39	-10000	0	-0.85	139	139
CDK5R1/CDK5	0.015	0.049	-10000	0	-0.18	25	25
NF kappa B1 p50/RelA/PKAc	-0.018	0.11	-10000	0	-0.2	47	47
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.011	0.082	-10000	0	-0.56	1	1
SMARCA4	-0.004	0.08	-10000	0	-0.27	42	42
chromatin remodeling	-0.024	0.12	-10000	0	-0.4	32	32
NF kappa B1 p50/RelA/Cbp	-0.032	0.11	-10000	0	-0.23	35	35
JUN (dimer)	0.05	0.064	-10000	0	-0.25	5	5
YWHAH	-0.006	0.083	-10000	0	-0.26	49	49
VIPR1	0.037	0.042	-10000	0	-10000	0	0
NR3C1	-0.018	0.069	-10000	0	-0.35	9	9
NR4A1	0.024	0.01	-10000	0	-10000	0	0
TIF2/SUV420H1	0.008	0.062	-10000	0	-0.19	46	46
MAPKKK cascade	-0.002	0.21	0.46	30	-0.58	30	60
cortisol/GR alpha (dimer)/Src-1	-0.033	0.098	-10000	0	-0.37	12	12
PBX1	0.021	0.033	-10000	0	-0.23	7	7
POU1F1	0.025	0.008	-10000	0	-10000	0	0
SELE	-0.012	0.11	-10000	0	-10000	0	0
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.024	0.12	-10000	0	-0.41	32	32
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.011	0.082	-10000	0	-0.56	1	1
mol:cortisol	-0.028	0.051	-10000	0	-0.2	1	1
MMP1	0.013	0.064	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	0.02	0.033	-9999	-0.15	16	16
NFATC2	0.009	0.032	-9999	-0.16	16	16
NFATC3	0.02	0.033	-9999	-0.15	16	16
CD40LG	0.046	0.084	-9999	-0.27	12	12
PTGS2	0.037	0.093	-9999	-0.28	14	14
JUNB	-0.003	0.067	-9999	-0.17	63	63
CaM/Ca2+/Calcineurin A alpha-beta B1	0.011	0.039	-9999	-0.18	19	19
CaM/Ca2+	0.011	0.039	-9999	-0.18	19	19
CALM1	0.009	0.056	-9999	-0.21	28	28
JUN	0.002	0.077	-9999	-0.27	37	37
mol:Ca2+	0.002	0.003	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.008	0.029	-9999	-0.096	31	31
FOSL1	0.007	0.038	-9999	-0.11	51	51
CREM	0.017	0.014	-9999	-0.11	6	6
Jun/NFAT1-c-4/p21SNFT	0.055	0.061	-9999	-0.22	14	14
FOS	-0.042	0.12	-9999	-0.21	146	146
IFNG	0.045	0.085	-9999	-0.27	13	13
AP-1/NFAT1-c-4	0.083	0.11	-9999	-0.29	14	14
FASLG	0.046	0.084	-9999	-0.27	12	12
NFAT1-c-4/ICER1	0.043	0.034	-9999	-0.13	7	7
IL2RA	0.043	0.087	-9999	-0.27	13	13
FKBP12/FK506	0.006	0.035	-9999	-0.12	31	31
CSF2	0.046	0.084	-9999	-0.27	12	12
JunB/Fra1/NFAT1-c-4	0.041	0.053	-9999	-0.14	12	12
IL4	0.046	0.084	-9999	-0.27	12	12
IL2	0.005	0.009	-9999	-10000	0	0
IL3	0.009	0.05	-9999	-0.75	2	2
FKBP1A	0.007	0.052	-9999	-0.18	31	31
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.022	0.028	-9999	-0.13	14	14

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.031	0.031	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.018	0.027	-9999	-10000	0	0
mol:DAG	0.025	0.029	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	-0.016	0.073	-9999	-0.27	8	8
CaM/Ca2+	0.027	0.044	-9999	-0.25	4	4
HIF1A	0.021	0.047	-9999	-0.28	12	12
GAB1	0.003	0.056	-9999	-0.15	50	50
AKT1	-0.005	0.1	-9999	-0.35	30	30
PLCG1	0.025	0.03	-9999	-10000	0	0
NOS3	0.02	0.072	-9999	-0.33	12	12
CBL	0.019	0	-9999	-10000	0	0
mol:NO	0.02	0.07	-9999	-0.32	12	12
FLT1	0.025	0.033	-9999	-10000	0	0
PGF	0.009	0.036	-9999	-0.12	39	39
VEGFR1 homodimer/NRP2/VEGFR121	-0.007	0.077	-9999	-0.26	9	9
CALM1	0.007	0.056	-9999	-0.21	28	28
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
eNOS/Hsp90	0.029	0.073	-9999	-0.32	13	13
endothelial cell proliferation	0.021	0.04	-9999	-0.28	3	3
mol:Ca2+	0.025	0.029	-9999	-10000	0	0
MAPK3	0.027	0.025	-9999	-10000	0	0
MAPK1	0.025	0.029	-9999	-0.23	2	2
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
PLGF homodimer	0.009	0.036	-9999	-0.12	39	39
PRKACA	0.019	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.071	0.13	-9999	-0.22	197	197
VEGFA homodimer	-0.067	0.13	-9999	-0.22	188	188
VEGFR1 homodimer/VEGFA homodimer	-0.018	0.082	-9999	-0.3	8	8
platelet activating factor biosynthetic process	0.027	0.028	-9999	-0.22	2	2
PI3K	0.013	0.081	-9999	-0.27	17	17
PRKCA	0.025	0.027	-9999	-10000	0	0
PRKCB	0.019	0.026	-9999	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	0.026	0.034	-9999	-10000	0	0
VEGFA	-0.068	0.13	-9999	-0.22	188	188
VEGFB	0.017	0.023	-9999	-0.29	3	3
mol:IP3	0.025	0.029	-9999	-10000	0	0
RASA1	0.026	0.04	-9999	-0.27	7	7
NRP2	0.017	0.016	-9999	-0.11	8	8
VEGFR1 homodimer	0.025	0.033	-9999	-10000	0	0
VEGFB homodimer	0.017	0.023	-9999	-0.29	3	3
NCK1	0.014	0.036	-9999	-0.19	14	14
eNOS/Caveolin-1	0.009	0.087	-9999	-0.34	21	21
PTPN11	0.015	0.033	-9999	-0.27	7	7
mol:PI-3-4-5-P3	0.012	0.079	-9999	-0.27	17	17
mol:L-citrulline	0.02	0.07	-9999	-0.32	12	12
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.003	0.081	-9999	-0.27	10	10
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.008	0.081	-9999	-0.26	14	14
CD2AP	0.003	0.062	-9999	-0.2	40	40
PI3K/GAB1	0.017	0.083	-9999	-0.25	25	25
PDPK1	0.004	0.069	-9999	-0.25	17	17
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.007	0.081	-9999	-0.29	11	11
mol:NADP	0.02	0.07	-9999	-0.32	12	12
HSP90AA1	0.018	0.019	-9999	-0.29	2	2
ubiquitin-dependent protein catabolic process	-0.004	0.08	-9999	-0.27	10	10
VEGFR1 homodimer/NRP2	0.031	0.029	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

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
NRIP1	-0.001	0.078	-9999	-0.27	40	40
SVIL	0.008	0.038	-9999	-0.11	50	50
ZNF318	0.015	0.013	-9999	-0.11	5	5
JMJD2C	0.026	0	-9999	-10000	0	0
T-DHT/AR/Ubc9	0.027	0.029	-9999	-10000	0	0
CARM1	0.018	0.015	-9999	-0.2	2	2
PRDX1	0.012	0.044	-9999	-0.24	14	14
PELP1	0.014	0.036	-9999	-0.29	7	7
CTNNB1	0.018	0.023	-9999	-0.29	3	3
AKT1	0.004	0.063	-9999	-0.26	28	28
PTK2B	0.019	0.013	-9999	-0.11	5	5
MED1	-0.003	0.078	-9999	-0.29	36	36
MAK	0.01	0.026	-9999	-0.11	22	22
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	-0.01	0.08	-9999	-0.29	31	31
GSN	0	0.065	-9999	-0.29	18	18
NCOA2	0.018	0.01	-9999	-0.11	3	3
NCOA6	0.004	0.07	-9999	-0.28	29	29
DNA-PK	0.022	0.052	-9999	-0.19	26	26
NCOA4	0.014	0.038	-9999	-0.29	8	8
PIAS3	0.015	0.033	-9999	-0.19	12	12
cell proliferation	0.006	0.028	-9999	-10000	0	0
XRCC5	0.013	0.038	-9999	-0.27	9	9
UBE3A	0.019	0.027	-9999	-0.29	4	4
T-DHT/AR/SNURF	0.013	0.027	-9999	-0.067	2	2
FHL2	-0.045	0.2	-9999	-0.74	37	37
RANBP9	0.012	0.05	-9999	-0.29	14	14
JMJD1A	0.022	0.062	-9999	-0.29	20	20
CDK6	0.019	0	-9999	-10000	0	0
TGFB1I1	-0.01	0.089	-9999	-0.25	58	58
T-DHT/AR/CyclinD1	0.004	0.059	-9999	-0.14	53	53
XRCC6	0.017	0.019	-9999	-0.29	2	2
T-DHT/AR	0.019	0.074	-9999	-0.15	46	46
CTDSP1	0.011	0.049	-9999	-0.29	13	13
CTDSP2	0.002	0.052	-9999	-0.14	50	50
BRCA1	0.019	0.015	-9999	-0.11	7	7
TCF4	-0.009	0.085	-9999	-0.28	47	47
CDKN2A	-0.02	0.059	-9999	-0.11	156	156
SRF	0.007	0.039	-9999	-0.12	37	37
NKX3-1	0.017	0.096	-9999	-0.46	18	18
KLK3	0.02	0.035	-9999	-10000	0	0
TMF1	0.015	0.034	-9999	-0.23	9	9
HNRNPA1	0.016	0.027	-9999	-0.29	4	4
AOF2	0.004	0.066	-9999	-0.22	37	37
APPL1	0.006	0.046	-9999	-0.19	25	25
T-DHT/AR/Caspase 8	0.023	0.032	-9999	-0.11	2	2
AR	0.014	0.03	-9999	-0.1	22	22
UBA3	0	0	-9999	-10000	0	0
PATZ1	0.018	0	-9999	-10000	0	0
PAWR	0.019	0	-9999	-10000	0	0
PRKDC	0.001	0.065	-9999	-0.2	41	41
PA2G4	0.014	0.031	-9999	-0.29	5	5
UBE2I	0.019	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.019	0.039	-9999	-0.13	18	18
RPS6KA3	0.015	0.032	-9999	-0.14	18	18
T-DHT/AR/ARA70	0.024	0.036	-9999	-0.15	8	8
LATS2	-0.001	0	-9999	-10000	0	0
T-DHT/AR/PRX1	0.02	0.035	-9999	-0.15	10	10
Cyclin D3/CDK11 p58	0.006	0.037	-9999	-0.16	24	24
VAV3	-0.022	0.091	-9999	-0.18	110	110
KLK2	0.027	0.031	-9999	-10000	0	0
CASP8	0.015	0.021	-9999	-0.11	14	14
T-DHT/AR/TIF2/CARM1	0.038	0.03	-9999	-0.13	1	1
TMPRSS2	0.016	0.096	-9999	-0.46	18	18
CCND1	-0.021	0.088	-9999	-0.17	112	112
PIAS1	0.011	0.057	-9999	-0.29	18	18
mol:T-DHT	0	0.016	-9999	-0.054	37	37
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.022	0.006	-9999	-10000	0	0
T-DHT/AR/CDK6	0.026	0.029	-9999	-10000	0	0
CMTM2	0	0	-9999	-10000	0	0
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	-0.008	0.087	-9999	-0.26	52	52
CCND3	0.008	0.055	-9999	-0.23	24	24
TGIF1	-0.007	0.077	-9999	-0.22	55	55
FKBP4	0.016	0.029	-9999	-0.13	17	17

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.004	0.079	-10000	0	-0.26	44	44
SMAD2	0.003	0.051	0.2	2	-0.22	16	18
SMAD3	0.019	0.065	-10000	0	-0.39	8	8
SMAD3/SMAD4	-0.01	0.18	-10000	0	-0.51	49	49
SMAD4/Ubc9/PIASy	0.024	0.049	-10000	0	-0.15	36	36
SMAD2/SMAD2/SMAD4	0.016	0.091	-10000	0	-0.31	22	22
PPM1A	0.017	0.023	-10000	0	-0.29	3	3
CALM1	0.007	0.056	-10000	0	-0.21	28	28
SMAD2/SMAD4	0.009	0.056	-10000	0	-0.23	18	18
MAP3K1	0.015	0.022	-10000	0	-0.11	16	16
TRAP-1/SMAD4	0.009	0.061	-10000	0	-0.19	43	43
MAPK3	0.019	0.006	-10000	0	-10000	0	0
MAPK1	0.009	0.051	-10000	0	-0.22	22	22
NUP214	0.019	0	-10000	0	-10000	0	0
CTDSP1	0.011	0.049	-10000	0	-0.27	15	15
CTDSP2	0.004	0.052	-10000	0	-0.14	50	50
CTDSPL	0.019	0.006	-10000	0	-0.11	1	1
KPNB1	0.007	0.06	-10000	0	-0.28	21	21
TGFBRAP1	0.015	0.033	-10000	0	-0.29	6	6
UBE2I	0.019	0	-10000	0	-10000	0	0
NUP153	0.004	0.066	-10000	0	-0.27	28	28
KPNA2	0	0.074	-10000	0	-0.27	36	36
PIAS4	0.019	0.006	-10000	0	-10000	0	0

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.008	0.13	-10000	0	-0.63	19	19
epithelial cell differentiation	0.013	0.12	-10000	0	-0.64	18	18
ITCH	0.015	0.024	-10000	0	-0.093	23	23
WWP1	-0.014	0.23	-10000	0	-1.2	18	18
FYN	-0.019	0.1	-10000	0	-0.28	68	68
EGFR	-0.08	0.12	-10000	0	-0.29	97	97
PRL	0.016	0.019	-10000	0	-0.11	12	12
neuron projection morphogenesis	0.02	0.11	-10000	0	-0.45	22	22
PTPRZ1	-0.01	0.09	-10000	0	-0.29	49	49
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.031	0.11	-10000	0	-0.5	20	20
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.01	0.11	-10000	0	-0.56	19	19
ADAM17	0.014	0.025	-10000	0	-0.11	7	7
ErbB4/ErbB4	0.004	0.14	-10000	0	-0.69	19	19
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.003	0.12	-10000	0	-0.63	19	19
NCOR1	0.009	0.054	-10000	0	-0.27	18	18
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.01	0.12	-10000	0	-0.54	22	22
GRIN2B	0.01	0.12	-10000	0	-0.55	20	20
ErbB4/ErbB2/betacellulin	0.02	0.11	-10000	0	-0.53	19	19
STAT1	0.008	0.04	-10000	0	-0.12	41	41
HBEGF	0.015	0.022	-10000	0	-0.11	15	15
PRLR	0.019	0	-10000	0	-10000	0	0
E4ICDs/ETO2	0.009	0.13	-10000	0	-0.63	19	19
axon guidance	-0.001	0.16	-10000	0	-0.8	18	18
NEDD4	0.01	0.034	-10000	0	-0.11	25	25
Prolactin receptor/Prolactin receptor/Prolactin	0.026	0.014	-10000	0	-10000	0	0
CBFA2T3	0.016	0.019	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	0.018	0.11	-10000	0	-0.53	19	19
MAPK3	0.021	0.1	-10000	0	-0.47	20	20
STAT1 (dimer)	0.006	0.13	-10000	0	-0.62	19	19
MAPK1	0.019	0.11	-10000	0	-0.47	22	22
JAK2	0.013	0.026	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	0.015	0.11	-10000	0	-0.53	19	19
NRG1	0.018	0.016	-10000	0	-10000	0	0
NRG3	0	0	-10000	0	-10000	0	0
NRG2	0.019	0.006	-10000	0	-0.11	1	1
NRG4	0	0	-10000	0	-10000	0	0
heart development	-0.001	0.16	-10000	0	-0.8	18	18
neural crest cell migration	0.015	0.11	-10000	0	-0.52	19	19
ERBB2	0.018	0.016	-10000	0	-10000	0	0
WWOX/E4ICDs	0.01	0.13	-10000	0	-0.63	19	19
SHC1	0.004	0.052	-10000	0	-0.14	48	48
ErbB4/EGFR/neuregulin 4	-0.037	0.13	-10000	0	-0.59	21	21
apoptosis	-0.004	0.12	0.58	19	-10000	0	19
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.01	0.13	-10000	0	-0.63	19	19
ErbB4/ErbB2/epiregulin	0.018	0.11	-10000	0	-0.53	19	19
ErbB4/ErbB4/betacellulin/betacellulin	0.01	0.13	-10000	0	-0.63	19	19
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.034	0.12	-10000	0	-0.54	19	19
MDM2	0.003	0.12	-10000	0	-0.63	19	19
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.016	0.1	-10000	0	-0.51	18	18
STAT5A	0.003	0.15	-10000	0	-0.76	18	18
ErbB4/EGFR/neuregulin 1 beta	-0.009	0.12	-10000	0	-0.59	18	18
DLG4	0.019	0	-10000	0	-10000	0	0
GRB2/SHC	0.014	0.046	-10000	0	-0.21	16	16
E4ICDs/TAB2/NCoR1	0.011	0.13	-10000	0	-0.63	19	19
STAT5A (dimer)	0.023	0.14	-10000	0	-0.7	18	18
MAP3K7IP2	0.008	0.057	-10000	0	-0.27	20	20
STAT5B (dimer)	0.008	0.15	-10000	0	-0.76	18	18
LRIG1	-0.02	0.098	-10000	0	-0.24	80	80
EREG	0.015	0.023	-10000	0	-0.11	17	17
BTC	0.019	0.006	-10000	0	-0.11	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.001	0.16	-10000	0	-0.81	18	18
ERBB4	0.004	0.14	-10000	0	-0.7	19	19
STAT5B	0.018	0.015	-10000	0	-0.2	2	2
YAP1	-0.084	0.21	-10000	0	-0.51	96	96
GRB2	0.014	0.039	-10000	0	-0.26	10	10
ErbB4/ErbB2/neuregulin 4	0.007	0.11	-10000	0	-0.54	19	19
glial cell differentiation	-0.011	0.13	0.62	19	-10000	0	19
WWOX	0.019	0.008	-10000	0	-0.11	2	2
cell proliferation	0.019	0.11	-10000	0	-0.57	18	18

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.004	0.17	-10000	0	-1.1	12	12
CLOCK	0.009	0.055	-10000	0	-0.25	19	19
TIMELESS/CRY2	0.001	0.18	-10000	0	-1.1	12	12
DEC1/BMAL1	0.005	0.065	-10000	0	-0.19	49	49
ATR	0.011	0.049	-10000	0	-0.26	16	16
NR1D1	0.013	0.07	-10000	0	-10000	0	0
ARNTL	-0.014	0.093	-10000	0	-0.24	70	70
TIMELESS	-0.007	0.18	-10000	0	-1.2	12	12
NPAS2	0.018	0.019	-10000	0	-0.11	9	9
CRY2	0.017	0.016	-10000	0	-0.11	8	8
mol:CO	-0.006	0.024	0.14	12	-10000	0	12
CHEK1	0.006	0.046	-10000	0	-0.13	48	48
mol:HEME	0.006	0.024	-10000	0	-0.14	12	12
PER1	-0.003	0.077	-10000	0	-0.25	44	44
BMAL/CLOCK/NPAS2	0.017	0.076	-10000	0	-0.17	59	59
BMAL1/CLOCK	-0.009	0.14	-10000	0	-0.56	20	20
S phase of mitotic cell cycle	0.004	0.17	-10000	0	-1.1	12	12
TIMELESS/CHEK1/ATR	0.003	0.18	-10000	0	-1.1	12	12
mol:NADPH	0.006	0.024	-10000	0	-0.14	12	12
PER1/TIMELESS	-0.005	0.18	-10000	0	-1.1	12	12
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.019	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.014	0.079	-9999	-0.16	96	96
positive regulation of NF-kappaB transcription factor activity	0.005	0.056	-9999	-0.19	28	28
MAP2K4	0.021	0.049	-9999	-0.21	8	8
IKBKB	0.019	0	-9999	-10000	0	0
TNFRSF10B	0.015	0.022	-9999	-0.11	15	15
TNFRSF10A	0	0	-9999	-10000	0	0
SMPD1	0.005	0.035	-9999	-0.12	29	29
IKBKG	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.019	0.006	-9999	-0.11	1	1
TRAIL/TRAILR2	0.003	0.058	-9999	-0.19	33	33
TRAIL/TRAILR3	0.005	0.056	-9999	-0.19	30	30
TRAIL/TRAILR1	-0.008	0.053	-9999	-0.11	96	96
TRAIL/TRAILR4	0.005	0.056	-9999	-0.19	28	28
TRAIL/TRAILR1/DAP3/GTP	0.003	0.049	-9999	-0.15	40	40
IKK complex	0.029	0.029	-9999	-0.27	2	2
RIPK1	0.016	0.019	-9999	-0.11	11	11
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.009	0.033	-9999	-0.2	13	13
MAPK3	-0.001	0.053	-9999	-0.19	28	28
MAP3K1	0.019	0.049	-9999	-0.19	8	8
TRAILR4 (trimer)	0.019	0.006	-9999	-0.11	1	1
TRADD	0.019	0	-9999	-10000	0	0
TRAILR1 (trimer)	0	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.014	0.045	-9999	-0.16	30	30
CFLAR	0.016	0.024	-9999	-0.15	9	9
MAPK1	-0.007	0.063	-9999	-0.2	42	42
TRAIL/TRAILR1/FADD/TRADD/RIP	0.024	0.046	-9999	-0.12	30	30
mol:ceramide	0.005	0.035	-9999	-0.12	29	29
FADD	0.017	0.021	-9999	-0.2	4	4
MAPK8	0.023	0.048	-9999	-0.3	2	2
TRAF2	0.019	0	-9999	-10000	0	0
TRAILR3 (trimer)	0.019	0.008	-9999	-0.11	2	2
CHUK	0.016	0.025	-9999	-0.15	10	10
TRAIL/TRAILR1/FADD	0.005	0.048	-9999	-0.16	31	31
DAP3	0.011	0.048	-9999	-0.28	14	14
CASP10	-0.002	0.05	-9999	-0.19	30	30
JNK cascade	0.005	0.056	-9999	-0.19	28	28
TRAIL (trimer)	-0.014	0.079	-9999	-0.16	96	96
TNFRSF10C	0.019	0.008	-9999	-0.11	2	2
TRAIL/TRAILR1/DAP3/GTP/FADD	0.012	0.051	-9999	-0.14	41	41
TRAIL/TRAILR2/FADD	0.015	0.053	-9999	-0.15	36	36
cell death	0.005	0.035	-9999	-0.12	29	29
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.019	0.046	-9999	-0.19	3	3
TRAILR2 (trimer)	0.015	0.022	-9999	-0.11	15	15
CASP8	0.014	0.022	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.033	0.05	-9999	-0.12	30	30

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.023	0	-9999	-10000	0	0
RGS9BP	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	-0.024	0.07	-9999	-0.16	99	99
mol:ADP	0	0	-9999	-10000	0	0
GNAT2	0.019	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.023	0.016	-9999	-0.16	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.026	0	-9999	-10000	0	0
GRK7	0	0	-9999	-10000	0	0
CNGB3	0.019	0	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.014	0	-9999	-10000	0	0
mol:Ca2+	-0.019	0.061	-9999	-0.14	99	99
Cone PDE6	0.042	0.016	-9999	-0.12	1	1
Cone Metarhodopsin II	0	0	-9999	-10000	0	0
Na + (4 Units)	-0.011	0.066	-9999	-0.13	99	99
GNAT2/GDP	0.031	0.015	-9999	-0.13	1	1
GNB5	0.017	0.019	-9999	-0.14	7	7
mol:GMP (4 units)	0.023	0	-9999	-10000	0	0
Cone Transducin	0.025	0	-9999	-10000	0	0
SLC24A2	0.019	0.008	-9999	-0.11	2	2
GNB3/GNGT2	0.014	0	-9999	-10000	0	0
GNB3	0.019	0	-9999	-10000	0	0
GNAT2/GTP	0.014	0	-9999	-10000	0	0
CNGA3	-0.065	0.12	-9999	-0.2	206	206
ARR3	0.019	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.024	0.07	-9999	-0.16	99	99
mol:Pi	0.022	0.016	-9999	-0.16	1	1
Cone CNG Channel	0.003	0.062	-9999	-0.11	99	99
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.019	0.008	-9999	-0.11	2	2
RGS9	0.016	0.02	-9999	-0.11	13	13
PDE6C	0.019	0	-9999	-10000	0	0
GNGT2	0	0	-9999	-10000	0	0
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.019	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.013	0.04	-10000	0	-0.22	13	13
HDAC3	0.018	0.014	-10000	0	-0.29	1	1
VDR	0.019	0.008	-10000	0	-0.11	2	2
Cbp/p300/PCAF	0.021	0.027	-10000	0	-0.16	11	11
EP300	0.012	0.046	-10000	0	-0.24	15	15
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.032	0.034	-10000	0	-0.21	5	5
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.018	0.013	-10000	0	-0.11	5	5
AKT1	0.045	0.073	0.18	87	-0.18	16	103
RAR alpha/9cRA/Cyclin H	0.021	0.085	-10000	0	-0.27	25	25
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.024	0.055	-10000	0	-0.26	16	16
CDC2	-0.03	0.1	-10000	0	-0.19	123	123
response to UV	-0.001	0.007	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.023	0.022	-10000	0	-10000	0	0
NCOR2	0.019	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.014	0.005	-10000	0	-0.07	2	2
RXRs/RARs/NRIP1/9cRA	0.019	0.15	-10000	0	-0.52	35	35
NCOA2	0.018	0.01	-10000	0	-0.11	3	3
NCOA3	0.018	0.013	-10000	0	-0.11	5	5
NCOA1	-0.006	0.083	-10000	0	-0.28	43	43
VDR/VDR/DNA	0.019	0.008	-10000	0	-0.11	2	2
RARG	0.019	0.005	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.025	0.004	-10000	0	-10000	0	0
MAPK3	0.018	0.008	-10000	0	-10000	0	0
MAPK1	0.009	0.051	-10000	0	-0.22	22	22
MAPK8	0.018	0.009	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.018	0.097	-10000	0	-0.32	35	35
RARA	0.023	0.024	-10000	0	-10000	0	0
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.031	0.028	-10000	0	-0.2	5	5
PRKCA	0.018	0.016	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.006	0.16	-10000	0	-0.59	35	35
RXRG	0.023	0.026	-10000	0	-10000	0	0
RXRA	0.003	0.074	-10000	0	-0.26	14	14
RXRB	0.024	0.024	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.014	0.005	-10000	0	-0.07	2	2
RBP1	-0.051	0.12	-10000	0	-0.24	145	145
CRBP1/9-cic-RA	-0.033	0.083	-10000	0	-0.16	145	145
RARB	0.019	0.01	-10000	0	-0.12	1	1
PRKCG	0.018	0.016	-10000	0	-10000	0	0
MNAT1	0.015	0.033	-10000	0	-0.19	11	11
RAR alpha/RXRs	0.039	0.12	-10000	0	-0.37	26	26
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.038	0.081	-10000	0	-0.26	26	26
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.033	-10000	0	-0.16	5	5
RXRs/RARs/NRIP1/9cRA/HDAC3	0.007	0.16	-10000	0	-0.59	35	35
positive regulation of DNA binding	0.014	0.078	-10000	0	-0.25	25	25
NRIP1	-0.027	0.29	-10000	0	-1.1	35	35
RXRs/RARs	0.017	0.12	-10000	0	-0.41	35	35
RXRs/RXRs/DNA/9cRA	0.008	0.097	-10000	0	-0.33	35	35
PRKACA	0.019	0	-10000	0	-10000	0	0
CDK7	0.011	0.048	-10000	0	-0.24	17	17
TFIIH	0.027	0.056	-10000	0	-0.2	24	24
RAR alpha/9cRA	0.039	0.05	-10000	0	-0.24	10	10
CCNH	0.011	0.048	-10000	0	-0.28	14	14
CREBBP	0.019	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.028	0.044	-10000	0	-0.2	12	12

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	0.036	0.064	-10000	0	-0.22	12	12
TBX21	0.016	0.17	-10000	0	-0.54	14	14
B2M	0.017	0.027	-10000	0	-0.29	4	4
TYK2	0.008	0.066	-10000	0	-0.3	21	21
IL12RB1	0.02	0.018	-10000	0	-0.13	1	1
GADD45B	-0.016	0.28	-10000	0	-1.1	28	28
IL12RB2	0.021	0.017	-10000	0	-10000	0	0
GADD45G	0.02	0.16	-10000	0	-0.54	8	8
natural killer cell activation	0.002	0.015	-10000	0	-10000	0	0
RELB	0.018	0.011	-10000	0	-0.11	4	4
RELA	0.018	0.02	-10000	0	-0.23	3	3
IL18	0	0.058	-10000	0	-0.14	56	56
IL2RA	0.012	0.029	-10000	0	-0.11	28	28
IFNG	0.018	0.01	-10000	0	-0.11	3	3
STAT3 (dimer)	0.011	0.21	-10000	0	-0.56	37	37
HLA-DRB5	-0.003	0.008	-10000	0	-10000	0	0
FASLG	0.016	0.17	-10000	0	-0.6	8	8
NF kappa B2 p52/RelB	0.017	0.16	-10000	0	-0.48	22	22
CD4	-0.007	0.071	-10000	0	-0.19	56	56
SOCS1	0.019	0	-10000	0	-10000	0	0
EntrezGene:6955	-0.003	0.009	-10000	0	-10000	0	0
CD3D	0.005	0.036	-10000	0	-0.12	39	39
CD3E	0.015	0.013	-10000	0	-0.12	2	2
CD3G	0.012	0.022	-10000	0	-0.13	3	3
IL12Rbeta2/JAK2	0.028	0.034	-10000	0	-10000	0	0
CCL3	0.008	0.17	-10000	0	-0.49	22	22
CCL4	-0.042	0.31	-10000	0	-1	38	38
HLA-A	0.012	0.046	-10000	0	-0.29	12	12
IL18/IL18R	0.04	0.053	-10000	0	-0.15	14	14
NOS2	0.012	0.16	-10000	0	-0.41	32	32
IL12/IL12R/TYK2/JAK2/SPHK2	0.036	0.064	-10000	0	-0.22	12	12
IL1R1	0.015	0.17	-10000	0	-0.6	8	8
IL4	0.017	0.015	-10000	0	-10000	0	0
JAK2	0.015	0.032	-10000	0	-0.12	14	14
EntrezGene:6957	-0.003	0.008	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.016	0.039	-10000	0	-0.17	11	11
RAB7A	0.009	0.24	-10000	0	-0.83	28	28
lysosomal transport	0.012	0.23	-10000	0	-0.76	29	29
FOS	-0.17	0.46	-10000	0	-1.2	85	85
STAT4 (dimer)	0.029	0.19	-10000	0	-0.55	26	26
STAT5A (dimer)	0.018	0.16	-10000	0	-0.48	21	21
GZMA	0.01	0.17	-10000	0	-0.64	6	6
GZMB	0.012	0.17	-10000	0	-0.6	9	9
HLX	0.015	0.023	-10000	0	-0.11	17	17
LCK	0.011	0.17	-10000	0	-0.5	23	23
TCR/CD3/MHC II/CD4	-0.045	0.12	-10000	0	-0.24	104	104
IL2/IL2R	0.039	0.032	-10000	0	-0.14	2	2
MAPK14	0.01	0.23	-10000	0	-0.73	30	30
CCR5	0.02	0.17	-10000	0	-0.61	10	10
IL1B	-0.008	0.068	-10000	0	-0.13	96	96
STAT6	0.019	0.071	-10000	0	-0.21	5	5
STAT4	0.012	0.03	-10000	0	-0.11	30	30
STAT3	-0.003	0.079	-10000	0	-0.29	37	37
STAT1	0.008	0.04	-10000	0	-0.12	41	41
NFKB1	0.014	0.037	-10000	0	-0.23	11	11
NFKB2	0.019	0.008	-10000	0	-0.11	2	2
IL12B	0.021	0.017	-10000	0	-10000	0	0
CD8A	0	0	-10000	0	-10000	0	0
CD8B	0.018	0.011	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.036	0.064	0.22	12	-10000	0	12
IL2RB	0.014	0.024	-10000	0	-0.11	19	19
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.18	-10000	0	-0.51	26	26
IL2RG	0.013	0.027	-10000	0	-0.11	24	24
IL12	0.032	0.027	-10000	0	-10000	0	0
STAT5A	0.019	0.008	-10000	0	-0.11	2	2
CD247	0.014	0.018	-10000	0	-0.11	7	7
IL2	0.019	0.006	-10000	0	-0.11	1	1
SPHK2	0.019	0	-10000	0	-10000	0	0
FRAP1	0.019	0.006	-10000	0	-0.11	1	1
IL12A	0.02	0.017	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	0.01	0.18	-10000	0	-0.53	22	22
MAP2K3	0.011	0.21	-10000	0	-0.66	30	30
RIPK2	0.017	0.021	-10000	0	-0.18	5	5
MAP2K6	0.011	0.21	-10000	0	-0.66	30	30
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.05	0.12	-10000	0	-0.24	138	138
IL18RAP	0.019	0.017	-10000	0	-0.11	7	7
IL12Rbeta1/TYK2	0.021	0.053	-10000	0	-0.22	20	20
EOMES	-0.001	0.021	0.059	5	-10000	0	5
STAT1 (dimer)	0.028	0.16	-10000	0	-0.46	21	21
T cell proliferation	0.019	0.16	-10000	0	-0.45	32	32
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.02	0.014	-10000	0	-0.11	4	4
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.051	0.14	-10000	0	-0.5	34	34
ATF2	0.015	0.21	-10000	0	-0.67	30	30

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.03	0.051	-9999	-0.13	40	40
MAP4K1	0.019	0.006	-9999	-0.11	1	1
MAP3K8	0.004	0.042	-9999	-0.11	62	62
PRKCB	0	0	-9999	-10000	0	0
DBNL	0	0	-9999	-10000	0	0
CRKL	0.018	0.01	-9999	-0.11	3	3
MAP3K1	0.013	0.055	-9999	-0.22	6	6
JUN	0.01	0.041	-9999	-0.22	1	1
MAP3K7	0.012	0.063	-9999	-0.24	15	15
GRAP2	0.019	0	-9999	-10000	0	0
CRK	0.009	0.054	-9999	-0.28	17	17
MAP2K4	0.013	0.063	-9999	-0.21	17	17
LAT	0.018	0.014	-9999	-10000	0	0
LCP2	-0.012	0.086	-9999	-0.21	70	70
MAPK8	0.016	0.018	-9999	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.012	0.058	-9999	-0.16	40	40
LAT/GRAP2/SLP76/HPK1/HIP-55	0.028	0.048	-9999	-0.12	40	40

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.017	0.069	-9999	-0.25	23	23
CaM/Ca2+	0.006	0.038	-9999	-0.14	28	28
AKT1	0.005	0.063	-9999	-0.25	28	28
AKT2	0.019	0	-9999	-10000	0	0
STXBP4	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.007	0.069	-9999	-0.28	21	21
YWHAZ	0.014	0.037	-9999	-0.23	11	11
CALM1	0.007	0.056	-9999	-0.21	28	28
YWHAQ	0.018	0.019	-9999	-0.29	2	2
TBC1D4	0.009	0.045	-9999	-0.19	23	23
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	-0.006	0.083	-9999	-0.26	49	49
YWHAB	0.015	0.036	-9999	-0.29	7	7
SNARE/Synip	0.014	0.042	-9999	-0.17	19	19
YWHAG	0	0	-9999	-10000	0	0
ASIP	0.019	0	-9999	-10000	0	0
PRKCI	0.015	0.028	-9999	-0.14	15	15
AS160/CaM/Ca2+	0.006	0.038	-9999	-0.14	28	28
RHOQ	0.011	0.048	-9999	-0.28	14	14
GYS1	-0.003	0.11	-9999	-0.41	31	31
PRKCZ	0	0	-9999	-10000	0	0
TRIP10	0.015	0.029	-9999	-0.15	13	13
TC10/GTP/CIP4/Exocyst	0.019	0.033	-9999	-0.16	16	16
AS160/14-3-3	0.002	0.12	-9999	-0.3	44	44
VAMP2	0.006	0.048	-9999	-0.15	40	40
SLC2A4	0.006	0.076	-9999	-0.3	21	21
STX4	0.011	0.048	-9999	-0.28	14	14
GSK3B	0.003	0.095	-9999	-0.35	31	31
SFN	0.002	0.044	-9999	-0.11	70	70
LNPEP	0.018	0.011	-9999	-10000	0	0
YWHAE	0.011	0.045	-9999	-0.21	19	19

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.02	0.086	-9999	-0.2	58	58
Ran/GTP/Exportin 1/HDAC1	-0.008	0.034	-9999	-0.13	28	28
NF kappa B1 p50/RelA/I kappa B alpha	0.008	0.11	-9999	-0.27	60	60
SUMO1	0.017	0.027	-9999	-0.29	4	4
ZFPM1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.013	0.036	-9999	-0.16	21	21
FKBP3	0.016	0.033	-9999	-0.29	6	6
Histones	0.017	0.074	-9999	-0.24	26	26
YY1/LSF	0.023	0.043	-9999	-0.23	12	12
SMG5	0.019	0.008	-9999	-0.11	2	2
RAN	0.016	0.031	-9999	-0.24	7	7
I kappa B alpha/HDAC3	0	0.094	-9999	-0.22	68	68
I kappa B alpha/HDAC1	0.002	0.1	-9999	-0.32	39	39
SAP18	0.01	0.052	-9999	-0.29	15	15
RELA	0.011	0.079	-9999	-0.18	60	60
HDAC1/Smad7	0.03	0.033	-9999	-0.16	11	11
RANGAP1	0.017	0.015	-9999	-0.11	7	7
HDAC3/TR2	0.017	0.064	-9999	-0.29	14	14
NuRD/MBD3 Complex	-0.003	0.13	-9999	-0.4	36	36
NF kappa B1 p50/RelA	0.017	0.078	-9999	-0.17	60	60
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.018	0.011	-9999	-0.11	4	4
GATA1	0.019	0	-9999	-10000	0	0
Mad/Max	0.028	0.006	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.002	0.13	-9999	-0.39	36	36
RBBP7	0.015	0.034	-9999	-0.25	8	8
NPC	0.006	0.027	-9999	-0.14	18	18
RBBP4	-0.005	0.079	-9999	-0.24	50	50
MAX	0.019	0.006	-9999	-0.11	1	1
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.011	0.047	-9999	-0.27	14	14
NFKBIA	-0.007	0.1	-9999	-0.36	34	34
KAT2B	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.004	0.097	-9999	-0.38	22	22
SIN3 complex	0.029	0.038	-9999	-0.16	19	19
SMURF1	0.019	0	-9999	-10000	0	0
CHD3	0.019	0.006	-9999	-0.11	1	1
SAP30	0.017	0.027	-9999	-0.29	4	4
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.009	0.054	-9999	-0.27	18	18
YY1/HDAC3	0.016	0.073	-9999	-0.35	13	13
YY1/HDAC2	0.021	0.041	-9999	-0.22	11	11
YY1/HDAC1	0.023	0.041	-9999	-0.22	11	11
NuRD/MBD2 Complex (MeCP1)	0.003	0.11	-9999	-0.34	31	31
PPARG	0.003	0.088	-9999	-0.22	64	64
HDAC8/hEST1B	0.026	0.005	-9999	-10000	0	0
UBE2I	0.019	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0.047	-9999	-0.27	14	14
TNFRSF1A	-0.01	0.091	-9999	-0.29	50	50
HDAC3/SMRT (N-CoR2)	0.017	0.064	-9999	-0.29	14	14
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.03	0.033	-9999	-0.16	11	11
CREBBP	0.019	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.001	0.12	-9999	-0.37	37	37
HDAC1	0.013	0.04	-9999	-0.22	13	13
HDAC3	0.007	0.069	-9999	-0.31	15	15
HDAC2	0.004	0.061	-9999	-0.22	33	33
YY1	0.016	0.041	-9999	-0.25	11	11
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0.011	0.035	-9999	-0.13	27	27
NCOR2	0.019	0	-9999	-10000	0	0
MXD1	0.019	0.006	-9999	-0.11	1	1
STAT3	0.003	0.08	-9999	-0.25	43	43
NFKB1	0.014	0.037	-9999	-0.23	11	11
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.007	0.057	-9999	-0.26	22	22
YY1/LSF/HDAC1	0.029	0.05	-9999	-0.17	26	26
YY1/SAP30/HDAC1	0.031	0.044	-9999	-0.16	22	22
EP300	0.012	0.046	-9999	-0.24	15	15
STAT3 (dimer non-phopshorylated)	0.003	0.08	-9999	-0.25	43	43
proteasomal ubiquitin-dependent protein catabolic process	-0.006	0.1	-9999	-0.36	34	34
histone deacetylation	0.004	0.1	-9999	-0.34	31	31
STAT3 (dimer non-phopshorylated)/HDAC3	0.007	0.1	-9999	-0.37	25	25
nuclear export	-0.025	0.005	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	0	0.075	-9999	-0.29	33	33
GATA2/HDAC3	0.017	0.065	-9999	-0.29	14	14
GATA1/HDAC1	0.024	0.028	-9999	-0.19	8	8
GATA1/HDAC3	0.017	0.064	-9999	-0.29	14	14
CHD4	0.007	0.059	-9999	-0.29	20	20
TNF-alpha/TNFR1A	0.007	0.065	-9999	-0.19	50	50
SIN3/HDAC complex/Mad/Max	0.012	0.088	-9999	-0.33	22	22
NuRD Complex	0.004	0.12	-9999	-0.38	37	37
positive regulation of chromatin silencing	0.015	0.072	-9999	-0.24	26	26
SIN3B	0.017	0.025	-9999	-0.2	6	6
MTA2	0.019	0.006	-9999	-0.11	1	1
SIN3A	0	0	-9999	-10000	0	0
XPO1	0.017	0.023	-9999	-0.29	3	3
SUMO1/HDAC1	0.027	0.043	-9999	-0.18	11	11
HDAC complex	0.022	0.075	-9999	-0.18	49	49
GATA1/Fog1	0.014	0	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0.024	0.052	-9999	-0.17	29	29
TNF	0.018	0.01	-9999	-0.11	3	3
negative regulation of cell growth	0.012	0.087	-9999	-0.33	22	22
NuRD/MBD2/PRMT5 Complex	0.003	0.11	-9999	-0.34	31	31
Ran/GTP/Exportin 1	0.03	0.046	-9999	-0.16	21	21
NF kappa B/RelA/I kappa B alpha	0.002	0.11	-9999	-0.28	59	59
SIN3/HDAC complex/NCoR1	0.002	0.11	-9999	-0.37	26	26
TFCP2	0.012	0.043	-9999	-0.25	13	13
NR2C1	0.019	0	-9999	-10000	0	0
MBD3	0.008	0.056	-9999	-0.29	18	18
MBD2	0.019	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.014	0.043	-10000	0	-0.2	14	14
CRKL	0.015	0.078	-10000	0	-0.47	12	12
mol:PIP3	-0.01	0.037	0.23	9	-10000	0	9
AKT1	-0.005	0.039	0.22	5	-0.15	20	25
PTK2B	0.018	0.013	-10000	0	-0.11	5	5
RAPGEF1	0.018	0.074	-10000	0	-0.44	12	12
RANBP10	0.019	0	-10000	0	-10000	0	0
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
HGF/MET/SHIP2	0.027	0.034	-10000	0	-0.14	10	10
MAP3K5	0.014	0.084	-10000	0	-0.38	15	15
HGF/MET/CIN85/CBL/ENDOPHILINS	0.028	0.025	-10000	0	-0.093	4	4
AP1	-0.027	0.092	-10000	0	-0.2	93	93
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.004	0.052	-10000	0	-0.14	48	48
apoptosis	-0.12	0.31	-10000	0	-0.78	93	93
STAT3 (dimer)	0.015	0.073	-10000	0	-0.28	22	22
GAB1/CRKL/SHP2/PI3K	0.013	0.11	-10000	0	-0.4	24	24
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.021	0.082	-10000	0	-0.41	14	14
PTPN11	0.015	0.033	-10000	0	-0.27	7	7
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.017	0.025	-10000	0	-0.29	3	3
PTEN	0.013	0.038	-10000	0	-0.18	17	17
ELK1	-0.001	0.04	0.23	13	-10000	0	13
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.016	0.043	-10000	0	-0.18	19	19
PAK1	-0.001	0.037	0.21	5	-0.14	18	23
HGF/MET/RANBP10	0.03	0.027	-10000	0	-0.1	4	4
HRAS	0.011	0.098	-10000	0	-0.52	14	14
DOCK1	0.015	0.078	-10000	0	-0.45	12	12
GAB1	0.011	0.082	-10000	0	-0.49	12	12
CRK	0.011	0.084	-10000	0	-0.44	14	14
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.016	0.08	-10000	0	-0.44	14	14
JUN	-0.002	0.077	-10000	0	-0.28	37	37
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.012	0.014	-10000	0	-10000	0	0
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
cell morphogenesis	0.007	0.099	-10000	0	-0.3	38	38
GRB2/SHC	0.024	0.037	-10000	0	-0.13	15	15
FOS	-0.046	0.12	-10000	0	-0.22	146	146
GLMN	0.002	0.016	0.086	2	-0.19	3	5
cell motility	-0.001	0.04	0.23	13	-10000	0	13
HGF/MET/MUC20	0.017	0.025	-10000	0	-0.11	4	4
cell migration	0.023	0.036	-10000	0	-0.13	15	15
GRB2	0.014	0.039	-10000	0	-0.26	10	10
CBL	0.019	0	-10000	0	-10000	0	0
MET/RANBP10	0.02	0.026	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.016	0.062	-10000	0	-0.27	13	13
MET/MUC20	0.007	0.024	-10000	0	-10000	0	0
RAP1B	0.018	0.07	-10000	0	-0.41	12	12
RAP1A	0.022	0.071	-10000	0	-0.41	12	12
HGF/MET/RANBP9	0.025	0.04	-10000	0	-0.14	18	18
RAF1	0.01	0.1	-10000	0	-0.47	19	19
STAT3	0.015	0.073	-10000	0	-0.29	22	22
cell proliferation	0.019	0.068	-10000	0	-0.3	15	15
RPS6KB1	0.013	0.011	-10000	0	-10000	0	0
MAPK3	-0.013	0.016	-10000	0	-10000	0	0
MAPK1	0.005	0.11	0.71	13	-10000	0	13
RANBP9	0.011	0.05	-10000	0	-0.29	14	14
MAPK8	0.019	0.082	-10000	0	-0.33	17	17
SRC	0.019	0.058	-10000	0	-0.25	13	13
PI3K	0.003	0.067	-10000	0	-0.14	82	82
MET/Glomulin	0.01	0.025	-10000	0	-0.15	4	4
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	0.013	0.1	-10000	0	-0.46	19	19
MET	0.008	0.037	-10000	0	-0.11	47	47
MAP4K1	0.023	0.076	-10000	0	-0.44	12	12
PTK2	0.009	0.054	-10000	0	-0.27	18	18
MAP2K2	0.014	0.099	-10000	0	-0.44	19	19
BAD	-0.002	0.041	0.21	5	-0.16	21	26
MAP2K4	0.016	0.08	-10000	0	-0.35	16	16
SHP2/GRB2/SOS1/GAB1	-0.013	0.067	-10000	0	-0.35	18	18
INPPL1	0.016	0.033	-10000	0	-0.29	6	6
PXN	0.018	0.011	-10000	0	-0.11	4	4
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	0.013	0.017	-10000	0	-0.16	2	2
PLCgamma1/PKC	0.013	0.017	-10000	0	-0.2	3	3
HGF	0.016	0.02	-10000	0	-0.11	13	13
RASA1	0.003	0.069	-10000	0	-0.28	29	29
NCK1	0.014	0.036	-10000	0	-0.19	14	14
PTPRJ	0.019	0	-10000	0	-10000	0	0
NCK/PLCgamma1	0.031	0.027	-10000	0	-0.13	7	7
PDPK1	-0.004	0.031	0.2	8	-10000	0	8
HGF/MET/SHIP	0.017	0.025	-10000	0	-0.11	4	4

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.017	0.018	-9999	-10000	0	0
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.019	0	-9999	-10000	0	0
TCEB1	0.013	0.041	-9999	-0.27	10	10
HIF1A/p53	0.018	0.044	-9999	-0.21	9	9
HIF1A	0.013	0.035	-9999	-0.21	6	6
COPS5	0.016	0.03	-9999	-0.29	5	5
VHL/Elongin B/Elongin C/RBX1/CUL2	0.032	0.053	-9999	-0.15	33	33
FIH (dimer)	0.019	0	-9999	-10000	0	0
CDKN2A	-0.019	0.059	-9999	-0.11	156	156
ARNT/IPAS	0.026	0.013	-9999	-10000	0	0
HIF1AN	0.019	0	-9999	-10000	0	0
GNB2L1	0.018	0.019	-9999	-0.29	2	2
HIF1A/ARNT	0.024	0.035	-9999	-0.2	6	6
CUL2	0.005	0.064	-9999	-0.26	27	27
OS9	-0.005	0.069	-9999	-0.17	67	67
RACK1/Elongin B/Elongin C	0.035	0.029	-9999	-0.17	10	10
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.023	0.038	-9999	-0.22	6	6
PHD1-3/OS9	0.016	0.067	-9999	-0.17	43	43
HIF1A/RACK1/Elongin B/Elongin C	0.037	0.043	-9999	-0.2	7	7
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0.018	0.019	-9999	-0.29	2	2
HIF1A/JAB1	0.023	0.039	-9999	-0.21	8	8
EGLN3	-0.005	0.067	-9999	-0.16	72	72
EGLN2	0.019	0	-9999	-10000	0	0
EGLN1	0.009	0.052	-9999	-0.24	20	20
TP53	-0.007	0.077	-9999	-0.2	62	62
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.015	0.095	-9999	-0.66	9	9
ARNT	0.019	0.006	-9999	-0.11	1	1
ARD1A	0.018	0.017	-9999	-0.16	4	4
RBX1	0.013	0.041	-9999	-0.27	10	10
HIF1A/p19ARF	0.008	0.045	-9999	-0.21	8	8

×

Signaling events regulated by Ret tyrosine kinase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0.089	-9999	-0.43	20	20
Crk/p130 Cas/Paxillin	-0.032	0.071	-9999	-0.24	43	43
JUN	0.022	0.059	-9999	-0.27	14	14
HRAS	0.009	0.055	-9999	-0.28	18	18
RET51/GFRalpha1/GDNF/GRB10	0.024	0.055	-9999	-0.13	45	45
RAP1A	0.018	0.019	-9999	-0.29	2	2
FRS2	0.018	0.013	-9999	-0.11	5	5
RAP1A/GDP	0.013	0.013	-9999	-0.2	2	2
RET51/GFRalpha1/GDNF/DOK1	0.047	0.015	-9999	-10000	0	0
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.015	0.033	-9999	-0.27	7	7
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.009	0.054	-9999	-0.28	17	17
RET9/GFRalpha1/GDNF/Enigma	0.037	0.005	-9999	-10000	0	0
RHOA	0.015	0.036	-9999	-0.29	7	7
RAP1A/GTP	0.043	0.016	-9999	-0.11	2	2
GRB7	0.016	0.019	-9999	-0.11	11	11
RET51/GFRalpha1/GDNF	0.047	0.015	-9999	-10000	0	0
MAPKKK cascade	0.026	0.044	-9999	-0.21	12	12
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.025	0.039	-9999	-0.13	25	25
lamellipodium assembly	-0.03	0.072	-9999	-0.22	47	47
RET51/GFRalpha1/GDNF/SHC	0.037	0.034	-9999	-0.13	9	9
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
RET9/GFRalpha1/GDNF/SHC	0.028	0.03	-9999	-0.13	11	11
RET9/GFRalpha1/GDNF/Shank3	0.024	0.004	-9999	-10000	0	0
MAPK3	0.031	0.013	-9999	-0.1	2	2
DOK1	0.019	0	-9999	-10000	0	0
DOK6	0	0	-9999	-10000	0	0
PXN	0.018	0.011	-9999	-0.11	4	4
neurite development	0.031	0.037	-9999	-0.18	13	13
DOK5	-0.026	0.11	-9999	-0.27	82	82
GFRA1	0.019	0.008	-9999	-0.11	2	2
MAPK8	0.025	0.048	-9999	-0.16	29	29
HRAS/GTP	0.035	0.042	-9999	-0.17	12	12
tube development	0.025	0.019	-9999	-0.13	8	8
MAPK1	0.03	0.015	-9999	-0.1	2	2
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.026	0.037	-9999	-0.23	10	10
Rac1/GDP	0.011	0.024	-9999	-0.2	7	7
SRC	0.019	0	-9999	-10000	0	0
PDLIM7	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	0.043	0.014	-9999	-10000	0	0
SHC1	0.004	0.052	-9999	-0.14	48	48
RET51/GFRalpha1/GDNF/Dok4	0.047	0.015	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok5	0.02	0.063	-9999	-0.13	73	73
PRKCA	0.019	0	-9999	-10000	0	0
HRAS/GDP	0.007	0.037	-9999	-0.2	17	17
CREB1	0.02	0.049	-9999	-0.21	20	20
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.014	0.046	-9999	-0.17	28	28
RET51/GFRalpha1/GDNF/Grb7	0.045	0.019	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
RET	0.015	0.022	-9999	-0.11	15	15
DOK4	0.019	0	-9999	-10000	0	0
JNK cascade	0.022	0.058	-9999	-0.27	14	14
RET9/GFRalpha1/GDNF/FRS2	0.036	0.009	-9999	-10000	0	0
SHANK3	0	0	-9999	-10000	0	0
RASA1	0.003	0.069	-9999	-0.28	29	29
NCK1	0.014	0.036	-9999	-0.19	14	14
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.016	0.037	-9999	-0.18	16	16
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.031	0.038	-9999	-0.22	10	10
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.024	0.052	-9999	-0.18	29	29
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.021	0.038	-9999	-0.17	16	16
PI3K	-0.002	0.11	-9999	-0.31	44	44
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.031	0.02	-9999	-0.13	8	8
GRB10	-0.018	0.091	-9999	-0.2	89	89
activation of MAPKK activity	0.029	0.043	-9999	-0.26	10	10
RET51/GFRalpha1/GDNF/FRS2	0.046	0.017	-9999	-10000	0	0
GAB1	0.003	0.056	-9999	-0.15	50	50
IRS1	-0.002	0.07	-9999	-0.19	53	53
IRS2	-0.021	0.1	-9999	-0.25	79	79
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.019	0.048	-9999	-0.16	28	28
RET51/GFRalpha1/GDNF/PKC alpha	0.047	0.015	-9999	-10000	0	0
GRB2	0.014	0.039	-9999	-0.26	10	10
PRKACA	0.019	0	-9999	-10000	0	0
GDNF	0.019	0	-9999	-10000	0	0
RAC1	0.015	0.036	-9999	-0.29	7	7
RET51/GFRalpha1/GDNF/IRS1	0.034	0.043	-9999	-0.13	24	24
Rac1/GTP	-0.007	0.098	-9999	-0.26	47	47
RET9/GFRalpha1/GDNF	0.026	0.005	-9999	-10000	0	0
GFRalpha1/GDNF	0.028	0.006	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.027	0.037	-10000	0	-0.14	21	21
HDAC3	0.018	0.014	-10000	0	-0.29	1	1
Ran/GTP/Exportin 1/HDAC4	-0.009	0.034	-10000	0	-0.12	37	37
GATA1/HDAC4	0.02	0.039	-10000	0	-0.19	16	16
GATA1/HDAC5	0.026	0.016	-10000	0	-0.19	1	1
GATA2/HDAC5	0.026	0.017	-10000	0	-0.19	1	1
HDAC5/BCL6/BCoR	0.016	0.058	-10000	0	-0.16	43	43
HDAC9	-0.017	0.094	-10000	0	-0.24	74	74
Glucocorticoid receptor/Hsp90/HDAC6	0.033	0.035	-10000	0	-0.16	16	16
HDAC4/ANKRA2	0.017	0.047	-10000	0	-0.2	21	21
HDAC5/YWHAB	0.023	0.031	-10000	0	-0.22	7	7
NPC/RanGAP1/SUMO1/Ubc9	0.013	0.036	-10000	0	-0.16	21	21
GATA2	0.018	0.011	-10000	0	-0.11	4	4
HDAC4/RFXANK	0.011	0.058	-10000	0	-0.2	34	34
BCOR	0.01	0.032	-10000	0	-0.11	35	35
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0	-10000	0	-10000	0	0
HDAC5	0.016	0.022	-10000	0	-0.13	11	11
GNB1/GNG2	0.006	0.041	-10000	0	-0.2	21	21
Histones	0.003	0.069	-10000	0	-0.17	60	60
ADRBK1	0.018	0.014	-10000	0	-0.11	6	6
HDAC4	0.007	0.056	-10000	0	-0.29	16	16
XPO1	0.017	0.023	-10000	0	-0.29	3	3
HDAC5/ANKRA2	0.023	0.029	-10000	0	-0.19	7	7
HDAC4/Ubc9	0.02	0.039	-10000	0	-0.19	16	16
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.021	0.035	-10000	0	-0.19	11	11
TUBA1B	0.018	0.014	-10000	0	-0.29	1	1
HDAC6	0.019	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.018	0.045	-10000	0	-0.19	21	21
CAMK4	0.018	0.011	-10000	0	-0.11	4	4
Tubulin/HDAC6	0.024	0.051	-10000	0	-0.16	39	39
SUMO1	0.017	0.027	-10000	0	-0.29	4	4
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.015	0.036	-10000	0	-0.29	7	7
GATA1	0.019	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
NR3C1	0.01	0.052	-10000	0	-0.28	16	16
SUMO1/HDAC4	0.024	0.045	-10000	0	-0.27	5	5
SRF	0.019	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.017	0.049	-10000	0	-0.21	21	21
Tubulin	0.012	0.059	-10000	0	-0.2	39	39
HDAC4/14-3-3 E	0.014	0.051	-10000	0	-0.2	26	26
GNB1	0.007	0.061	-10000	0	-0.29	21	21
RANGAP1	0.017	0.015	-10000	0	-0.11	7	7
BCL6/BCoR	0.004	0.063	-10000	0	-0.2	40	40
HDAC4/HDAC3/SMRT (N-CoR2)	0.031	0.035	-10000	0	-0.15	17	17
HDAC4/SRF	0.031	0.036	-10000	0	-0.16	16	16
HDAC4/ER alpha	0.02	0.039	-10000	0	-0.19	16	16
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.003	0.069	-10000	0	-0.17	60	60
cell motility	0.024	0.051	-10000	0	-0.16	39	39
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.019	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.014	0.009	-10000	0	-0.2	1	1
BCL6	-0.007	0.082	-10000	0	-0.23	56	56
HDAC4/CaMK II delta B	0.007	0.056	-10000	0	-0.29	16	16
Hsp90/HDAC6	0.028	0.013	-10000	0	-0.19	2	2
ESR1	0.019	0	-10000	0	-10000	0	0
HDAC6/HDAC11	0.028	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.03	0.046	-10000	0	-0.16	21	21
NPC	0.006	0.027	-10000	0	-0.14	18	18
MEF2C	0.009	0.051	-10000	0	-0.21	24	24
RAN	0.016	0.031	-10000	0	-0.24	7	7
HDAC4/MEF2C	0.044	0.044	-10000	0	-0.12	29	29
GNG2	0	0	-10000	0	-10000	0	0
NCOR2	0.019	0	-10000	0	-10000	0	0
TUBB2A	-0.004	0.081	-10000	0	-0.29	40	40
HDAC11	0.019	0	-10000	0	-10000	0	0
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
RANBP2	0.007	0.057	-10000	0	-0.26	22	22
ANKRA2	0.015	0.034	-10000	0	-0.23	9	9
RFXANK	0.007	0.06	-10000	0	-0.28	22	22
nuclear import	-0.017	0.064	0.23	27	-10000	0	27

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.043	-9999	-0.18	21	21
alphaV beta3 Integrin	0.016	0.048	-9999	-0.19	25	25
PTK2	0.014	0.087	-9999	-0.36	20	20
positive regulation of JNK cascade	-0.003	0.034	-9999	-0.28	5	5
CDC42/GDP	0.044	0.057	-9999	-0.38	5	5
Rac1/GDP	0.045	0.062	-9999	-0.34	8	8
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0.018	0.019	-9999	-0.29	2	2
CTNNB1	0.017	0.023	-9999	-0.29	3	3
CDC42/GTP	0.035	0.05	-9999	-0.35	5	5
nectin-3/I-afadin	0.018	0.033	-9999	-0.19	5	5
RAPGEF1	0.03	0.063	-9999	-0.37	7	7
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.028	0.068	-9999	-0.39	9	9
PDGFB-D/PDGFRB	0.011	0.043	-9999	-0.18	21	21
TLN1	0	0.065	-9999	-0.24	30	30
Rap1/GTP	-0.007	0.038	-9999	-0.27	7	7
IQGAP1	-0.009	0.087	-9999	-0.27	50	50
Rap1/GTP/I-afadin	0.024	0.01	-9999	-0.14	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.018	0.033	-9999	-0.19	5	5
PVR	0.019	0.008	-9999	-0.11	2	2
Necl-5(dimer)	0.019	0.008	-9999	-0.11	2	2
mol:GDP	0.039	0.066	-9999	-0.47	5	5
MLLT4	0.019	0	-9999	-10000	0	0
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
PI3K	0.01	0.085	-9999	-0.16	89	89
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.028	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.004	0.039	-9999	-0.28	7	7
PVRL1	0.019	0	-9999	-10000	0	0
PVRL3	0.005	0.047	-9999	-0.13	51	51
PVRL2	0.016	0.026	-9999	-0.19	7	7
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
CDH1	0.012	0.03	-9999	-0.11	29	29
CLDN1	0.016	0.019	-9999	-0.11	11	11
JAM-A/CLDN1	0.03	0.045	-9999	-0.12	26	26
SRC	0.029	0.067	-9999	-0.53	5	5
ITGB3	0.019	0.008	-9999	-0.11	2	2
nectin-1(dimer)/I-afadin/I-afadin	0.028	0	-9999	-10000	0	0
FARP2	0.037	0.062	-9999	-0.46	5	5
RAC1	0.015	0.036	-9999	-0.29	7	7
CTNNA1	0.011	0.048	-9999	-0.29	13	13
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.03	0.03	-9999	-0.14	7	7
nectin-1/I-afadin	0.028	0	-9999	-10000	0	0
nectin-2/I-afadin	0.026	0.018	-9999	-0.19	3	3
RAC1/GTP/IQGAP1/filamentous actin	0.007	0.056	-9999	-0.16	51	51
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.03	0.029	-9999	-0.15	5	5
CDC42/GTP/IQGAP1/filamentous actin	0.009	0.053	-9999	-0.16	45	45
F11R	0.004	0.051	-9999	-0.14	49	49
positive regulation of filopodium formation	-0.003	0.034	-9999	-0.28	5	5
alphaV/beta3 Integrin/Talin	0.008	0.078	-9999	-0.24	32	32
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.026	0.018	-9999	-0.19	3	3
nectin-2(dimer)/I-afadin/I-afadin	0.026	0.018	-9999	-0.19	3	3
PIP5K1C	0.003	0.061	-9999	-0.25	25	25
VAV2	0.038	0.063	-9999	-0.47	5	5
RAP1/GDP	0.036	0.053	-9999	-0.35	5	5
ITGAV	0.003	0.067	-9999	-0.25	32	32
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.028	0.035	-9999	-0.16	8	8
nectin-3(dimer)/I-afadin/I-afadin	0.018	0.033	-9999	-0.19	5	5
Rac1/GTP	0.037	0.056	-9999	-0.34	7	7
PTPRM	0.001	0.061	-9999	-0.26	25	25
E-cadherin/beta catenin/alpha catenin	0.046	0.037	-9999	-0.12	18	18
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.017	0.016	-9999	-0.11	8	8

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.027	0.015	-9999	-0.19	2	2
FBXW11	0.011	0.047	-9999	-0.27	14	14
NF kappa B1 p50/c-Rel	0.027	0.022	-9999	-0.15	7	7
NF kappa B1 p50/RelA/I kappa B alpha	0.026	0.063	-9999	-0.27	13	13
NFKBIA	0.005	0.062	-9999	-0.19	41	41
MAPK14	0.018	0.013	-9999	-0.11	5	5
NF kappa B1 p105/p50	0.022	0.036	-9999	-0.16	18	18
ARRB2	0.013	0.029	-9999	-0.23	7	7
REL	0.019	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.026	0.022	-9999	-0.15	7	7
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.026	0.024	-9999	-0.15	9	9
PIK3CA	-0.011	0.086	-9999	-0.22	66	66
NF kappa B1 p50 dimer	0.018	0.025	-9999	-0.19	7	7
PIK3R1	-0.015	0.095	-9999	-0.27	62	62
NFKB1	0.017	0.025	-9999	-0.19	7	7
RELA	0.018	0.02	-9999	-0.23	3	3
positive regulation of anti-apoptosis	0.019	0.039	-9999	-0.2	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.028	0.064	-9999	-0.27	13	13
SRC	0.019	0	-9999	-10000	0	0
PI3K	-0.016	0.093	-9999	-0.21	88	88
NF kappa B1 p50/RelA	0.019	0.04	-9999	-0.2	2	2
IKBKB	0.019	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0.047	-9999	-0.27	14	14
SYK	-0.005	0.072	-9999	-0.29	25	25
I kappa B alpha/PIK3R1	0.009	0.076	-9999	-0.22	43	43
cell death	0.027	0.062	-9999	-0.26	13	13
NF kappa B1 p105/c-Rel	0.027	0.022	-9999	-0.15	7	7
LCK	0.017	0.016	-9999	-0.11	8	8
BCL3	0.019	0.008	-9999	-0.11	2	2

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	0.084	0.22	-10000	0	-0.73	24	24
PCK1	0.084	0.14	-10000	0	-0.66	4	4
HNF4A	0.11	0.18	-10000	0	-0.76	8	8
KCNJ11	0.1	0.2	-10000	0	-0.66	16	16
AKT1	0.069	0.13	-10000	0	-0.4	20	20
response to starvation	0.006	0.003	-10000	0	-10000	0	0
DLK1	0.1	0.21	-10000	0	-0.75	12	12
NKX2-1	0.077	0.12	-10000	0	-10000	0	0
ACADM	0.095	0.2	-10000	0	-0.8	13	13
TAT	0.083	0.14	-10000	0	-0.65	6	6
CEBPB	0.001	0.076	-10000	0	-0.22	51	51
CEBPA	-0.022	0.1	-10000	0	-0.22	104	104
TTR	0.039	0.18	-10000	0	-0.6	18	18
PKLR	0.099	0.18	-10000	0	-0.69	12	12
APOA1	0.12	0.22	-10000	0	-0.85	11	11
CPT1C	0.091	0.18	-10000	0	-0.69	12	12
ALAS1	0.056	0.27	-10000	0	-1.3	16	16
TFRC	0.042	0.33	-10000	0	-1	39	39
FOXF1	-0.002	0.04	-10000	0	-0.12	55	55
NF1	0.021	0.028	-10000	0	-0.15	10	10
HNF1A (dimer)	0.038	0.003	-10000	0	-10000	0	0
CPT1A	0.099	0.18	-10000	0	-0.71	11	11
HMGCS1	0.095	0.18	-10000	0	-0.71	12	12
NR3C1	0.021	0.054	-10000	0	-0.28	15	15
CPT1B	0.099	0.18	-10000	0	-0.71	11	11
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.026	0	-10000	0	-10000	0	0
GCK	0.098	0.18	-10000	0	-0.71	11	11
CREB1	0.024	0.035	-10000	0	-0.29	6	6
IGFBP1	0.069	0.14	-10000	0	-0.68	6	6
PDX1	0.11	0.12	-10000	0	-10000	0	0
UCP2	0.049	0.28	-10000	0	-0.69	57	57
ALDOB	0.11	0.2	-10000	0	-0.74	12	12
AFP	0.023	0.033	-10000	0	-10000	0	0
BDH1	0.085	0.21	-10000	0	-0.71	23	23
HADH	0.11	0.22	-10000	0	-0.82	16	16
F2	0.12	0.22	-10000	0	-0.85	11	11
HNF1A	0.038	0.003	-10000	0	-10000	0	0
G6PC	0.02	0.092	-10000	0	-0.38	1	1
SLC2A2	0.11	0.14	-10000	0	-0.47	3	3
INS	0.013	0.029	0.2	6	-10000	0	6
FOXA1	0.013	0.011	-10000	0	-10000	0	0
FOXA3	0.026	0.058	-10000	0	-0.2	26	26
FOXA2	0.15	0.24	-10000	0	-0.85	12	12
ABCC8	0.11	0.2	-10000	0	-0.74	12	12
ALB	0.024	0.03	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.015	0.023	-10000	0	-0.11	17	17
NFATC1	0.012	0.12	-10000	0	-0.44	25	25
NFATC2	0.013	0.054	-10000	0	-0.16	29	29
NFATC3	0.01	0.025	-10000	0	-0.12	16	16
YWHAE	0.011	0.045	-10000	0	-0.21	19	19
Calcineurin A alpha-beta B1/CABIN1	0.026	0.029	-10000	0	-0.17	1	1
Exportin 1/Ran/NUP214	0.036	0.027	-10000	0	-0.2	6	6
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.043	0.038	-10000	0	-0.17	1	1
BCL2/BAX	0.025	0.024	-10000	0	-0.19	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.007	0.038	-10000	0	-0.14	28	28
CaM/Ca2+	0.007	0.038	-10000	0	-0.14	28	28
BAX	0.014	0.035	-10000	0	-0.17	15	15
MAPK14	0.018	0.013	-10000	0	-0.11	5	5
BAD	0.014	0.036	-10000	0	-0.25	9	9
CABIN1/MEF2D	0.035	0.029	-10000	0	-0.15	1	1
Calcineurin A alpha-beta B1/BCL2	0.019	0	-10000	0	-10000	0	0
FKBP8	0.018	0.014	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.035	0.029	0.15	1	-10000	0	1
KPNB1	0.007	0.06	-10000	0	-0.28	21	21
KPNA2	0	0.074	-10000	0	-0.27	36	36
XPO1	0.017	0.023	-10000	0	-0.29	3	3
SFN	0.002	0.044	-10000	0	-0.11	70	70
MAP3K8	0.004	0.042	-10000	0	-0.11	62	62
NFAT4/CK1 alpha	0.022	0.046	-10000	0	-0.19	19	19
MEF2D/NFAT1/Cbp/p300	0.05	0.063	-10000	0	-0.25	14	14
CABIN1	0.026	0.03	-10000	0	-0.17	1	1
CALM1	0.007	0.056	-10000	0	-0.21	28	28
RAN	0.016	0.031	-10000	0	-0.24	7	7
MAP3K1	0.015	0.022	-10000	0	-0.11	16	16
CAMK4	0.018	0.011	-10000	0	-0.11	4	4
mol:Ca2+	0.001	0	-10000	0	-10000	0	0
MAPK3	0.019	0.006	-10000	0	-10000	0	0
YWHAH	-0.006	0.083	-10000	0	-0.26	49	49
Calcineurin A alpha-beta B1/AKAP79/PKA	0.028	0.004	-10000	0	-10000	0	0
YWHAB	0.015	0.036	-10000	0	-0.29	7	7
MAPK8	0.019	0	-10000	0	-10000	0	0
MAPK9	0.016	0.028	-10000	0	-0.23	6	6
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0.007	0.052	-10000	0	-0.18	31	31
NFAT1-c-4/YWHAQ	0.03	0.1	-10000	0	-0.36	25	25
PRKCH	0.016	0.019	-10000	0	-0.11	12	12
CABIN1/Cbp/p300	0.024	0.032	-10000	0	-0.19	11	11
CASP3	0.009	0.053	-10000	0	-0.25	20	20
PIM1	0.017	0.017	-10000	0	-0.11	9	9
Calcineurin A alpha-beta B1/FKBP12/FK506	0.007	0.029	-10000	0	-0.097	31	31
apoptosis	0.013	0.033	-10000	0	-0.19	12	12
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.004	0.11	-10000	0	-0.38	26	26
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.019	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.02	0.026	-10000	0	-0.12	16	16
BAD/BCL-XL	0.022	0.03	-10000	0	-0.19	7	7
PRKCD	0.012	0.029	-10000	0	-0.11	27	27
NUP214	0.019	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
PRKCA	0.019	0	-10000	0	-10000	0	0
PRKCG	0.019	0	-10000	0	-10000	0	0
PRKCQ	0.014	0.024	-10000	0	-0.11	19	19
FKBP38/BCL2	0.027	0.01	-10000	0	-10000	0	0
EP300	0.012	0.046	-10000	0	-0.24	15	15
PRKCB1	-0.003	0.057	-10000	0	-0.13	77	77
CSNK2A1	0.01	0.053	-10000	0	-0.29	16	16
NFATc/JNK1	0.023	0.11	-10000	0	-0.41	25	25
CaM/Ca2+/FKBP38	0.019	0.035	-10000	0	-0.15	20	20
FKBP12/FK506	0.006	0.035	-10000	0	-0.12	31	31
CSNK1A1	0.011	0.041	-10000	0	-0.14	28	28
CaM/Ca2+/CAMK IV	0.019	0.034	-10000	0	-0.16	17	17
NFATc/ERK1	0.023	0.11	-10000	0	-0.41	25	25
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.041	0.04	-10000	0	-0.19	3	3
NR4A1	0.038	0.054	-10000	0	-0.25	11	11
GSK3B	0.004	0.066	-10000	0	-0.26	29	29
positive T cell selection	0.01	0.025	-10000	0	-0.12	16	16
NFAT1/CK1 alpha	0.013	0.064	-10000	0	-0.27	18	18
RCH1/ KPNB1	0.006	0.068	-10000	0	-0.2	49	49
YWHAQ	0.018	0.019	-10000	0	-0.29	2	2
PRKACA	0.019	0	-10000	0	-10000	0	0
AKAP5	0.019	0.006	-10000	0	-0.11	1	1
MEF2D	0.02	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.014	0.037	-10000	0	-0.23	11	11
NFATc/p38 alpha	0.023	0.11	-10000	0	-0.41	25	25
CREBBP	0.02	0	-10000	0	-10000	0	0
BCL2	0.019	0	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.029	0.06	-9999	-0.25	13	13
FYN	0.003	0.1	-9999	-0.3	36	36
LAT/GRAP2/SLP76	0.031	0.073	-9999	-0.27	14	14
IKBKB	0.019	0	-9999	-10000	0	0
AKT1	0.028	0.07	-9999	-0.22	21	21
B2M	0.018	0.027	-9999	-0.3	4	4
IKBKG	0.021	0.027	-9999	-0.081	15	15
MAP3K8	0.004	0.042	-9999	-0.11	62	62
mol:Ca2+	-0.001	0.004	-9999	-0.026	7	7
integrin-mediated signaling pathway	0.012	0.011	-9999	-0.16	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.029	0.085	-9999	-0.29	20	20
TRPV6	0.003	0.004	-9999	-10000	0	0
CD28	0.019	0.001	-9999	-10000	0	0
SHC1	0.028	0.062	-9999	-0.29	10	10
receptor internalization	0.034	0.042	-9999	-0.19	2	2
PRF1	0.031	0.047	-9999	-10000	0	0
KRAS	0.011	0.048	-9999	-0.28	14	14
GRB2	0.014	0.039	-9999	-0.26	10	10
COT/AKT1	0.029	0.063	-9999	-0.18	20	20
LAT	0.032	0.058	-9999	-0.27	9	9
EntrezGene:6955	0.001	0.002	-9999	-10000	0	0
CD3D	0.01	0.034	-9999	-0.11	39	39
CD3E	0.019	0.009	-9999	-0.12	2	2
CD3G	0.017	0.019	-9999	-10000	0	0
RASGRP2	0.011	0.01	-9999	-10000	0	0
RASGRP1	-0.012	0.12	-9999	-0.23	99	99
HLA-A	0.013	0.047	-9999	-0.3	12	12
RASSF5	0	0	-9999	-10000	0	0
RAP1A/GTP/RAPL	0.012	0.011	-9999	-0.16	2	2
mol:GTP	0	0	-9999	-10000	0	0
mol:GDP	0.008	0.042	-9999	-0.095	35	35
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.009	0.028	-9999	-0.13	18	18
PRKCA	0.026	0.041	-9999	-0.15	11	11
GRAP2	0.019	0	-9999	-10000	0	0
mol:IP3	-0.014	0.041	-9999	-0.22	12	12
EntrezGene:6957	0.001	0.002	-9999	-10000	0	0
TCR/CD3/MHC I/CD8	0.028	0.034	-9999	-10000	0	0
ORAI1	0	0	-9999	-10000	0	0
CSK	0.031	0.059	-9999	-0.28	8	8
B7 family/CD28	0.039	0.072	-9999	-0.24	15	15
CHUK	0.016	0.025	-9999	-0.15	10	10
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.03	0.061	-9999	-0.29	9	9
PTPN6	0.025	0.068	-9999	-0.25	15	15
VAV1	0.032	0.059	-9999	-0.27	8	8
Monovalent TCR/CD3	0.023	0.021	-9999	-0.14	1	1
CBL	0.019	0	-9999	-10000	0	0
LCK	0.016	0.082	-9999	-0.29	19	19
PAG1	0.028	0.057	-9999	-0.27	9	9
RAP1A	0.018	0.019	-9999	-0.29	2	2
TCR/CD3/MHC I/CD8/LCK	0.027	0.062	-9999	-0.29	9	9
CD80	0.019	0.006	-9999	-0.11	1	1
CD86	-0.003	0.074	-9999	-0.21	53	53
PDK1/CARD11/BCL10/MALT1	-0.011	0.034	-9999	-0.15	22	22
HRAS	0.009	0.055	-9999	-0.28	18	18
GO:0035030	0.025	0.062	-9999	-0.21	15	15
CD8A	0.001	0.002	-9999	-10000	0	0
CD8B	0.019	0.012	-9999	-0.12	1	1
PTPRC	-0.031	0.11	-9999	-0.23	107	107
PDK1/PKC theta	0.036	0.075	-9999	-0.27	15	15
CSK/PAG1	0.029	0.058	-9999	-0.27	8	8
SOS1	0	0	-9999	-10000	0	0
peptide-MHC class I	0.023	0.039	-9999	-0.2	16	16
GRAP2/SLP76	0.031	0.079	-9999	-0.28	17	17
STIM1	0.003	0.004	-9999	-10000	0	0
RAS family/GTP	0.007	0.066	-9999	-0.15	49	49
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.035	0.043	-9999	-0.2	2	2
mol:DAG	-0.013	0.038	-9999	-0.19	15	15
RAP1A/GDP	0.006	0.02	-9999	-0.045	33	33
PLCG1	0.017	0.025	-9999	-0.29	3	3
CD247	0.018	0.015	-9999	-0.11	7	7
cytotoxic T cell degranulation	0.031	0.047	-9999	-10000	0	0
RAP1A/GTP	0	0.004	-9999	-0.052	2	2
mol:PI-3-4-5-P3	0.029	0.076	-9999	-0.26	20	20
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.015	0.049	-9999	-0.26	12	12
NRAS	-0.01	0.086	-9999	-0.24	59	59
ZAP70	0.019	0.006	-9999	-0.11	1	1
GRB2/SOS1	0.011	0.026	-9999	-0.17	10	10
LAT/GRAP2/SLP76/VAV1	0.028	0.068	-9999	-0.25	15	15
MALT1	0.013	0.036	-9999	-0.16	18	18
TRAF6	0.018	0.019	-9999	-0.29	2	2
CD8 heterodimer	0.015	0.009	-9999	-0.078	1	1
CARD11	0	0	-9999	-10000	0	0
PRKCB	-0.01	0.028	-9999	-0.14	16	16
PRKCE	0.026	0.041	-9999	-0.14	12	12
PRKCQ	0.032	0.08	-9999	-0.3	15	15
LCP2	-0.012	0.086	-9999	-0.21	70	70
BCL10	0.016	0.028	-9999	-0.23	6	6
regulation of survival gene product expression	0.027	0.063	-9999	-0.19	21	21
IKK complex	0.03	0.025	-9999	-0.064	6	6
RAS family/GDP	-0.007	0.014	-9999	-0.036	80	80
MAP3K14	0.027	0.051	-9999	-0.15	16	16
PDPK1	0.031	0.066	-9999	-0.21	19	19
TCR/CD3/MHC I/CD8/Fyn	0.03	0.05	-9999	-0.28	3	3

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.019	0.064	-10000	0	-0.26	20	20
ACTA1	0.015	0.04	-10000	0	-0.17	11	11
NUMA1	0.025	0.043	-10000	0	-0.23	7	7
SPTAN1	0.01	0.053	-10000	0	-0.16	23	23
LIMK1	0.02	0.037	-10000	0	-0.15	10	10
BIRC3	0	0.046	-10000	0	-0.11	78	78
BIRC2	0.016	0.03	-10000	0	-0.29	5	5
BAX	0.014	0.035	-10000	0	-0.17	15	15
CASP10	0.013	0.025	-10000	0	-0.053	62	62
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.019	0.064	-10000	0	-0.24	22	22
DIABLO	0.016	0.028	-10000	0	-0.26	5	5
apoptotic nuclear changes	0.01	0.052	-10000	0	-0.16	23	23
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.017	0.015	-10000	0	-0.11	7	7
GSN	0.011	0.047	-10000	0	-0.18	13	13
MADD	0.018	0.015	-10000	0	-0.2	2	2
TFAP2A	0.029	0.021	-10000	0	-10000	0	0
BID	0.002	0.049	-10000	0	-0.2	26	26
MAP3K1	0.016	0.018	-10000	0	-10000	0	0
TRADD	0.019	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.025	0.02	-10000	0	-0.19	2	2
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.009	0.049	-10000	0	-0.2	11	11
CASP9	0.014	0.029	-10000	0	-0.13	18	18
DNA repair	-0.009	0.043	0.28	8	-10000	0	8
neuron apoptosis	0.013	0.096	-10000	0	-0.67	10	10
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.026	0.042	-10000	0	-0.26	3	3
APAF1	0.019	0	-10000	0	-10000	0	0
CASP6	0.022	0.1	-10000	0	-0.88	6	6
TRAF2	0.019	0	-10000	0	-10000	0	0
ICAD/CAD	0.021	0.039	-10000	0	-0.18	5	5
CASP7	-0.006	0.067	-10000	0	-0.36	16	16
KRT18	0.015	0.025	-10000	0	-10000	0	0
apoptosis	0.014	0.068	-10000	0	-0.27	16	16
DFFA	0.018	0.041	-10000	0	-0.17	8	8
DFFB	0.019	0.037	-10000	0	-0.16	6	6
PARP1	0.008	0.043	-10000	0	-0.28	8	8
actin filament polymerization	-0.019	0.035	0.14	10	-10000	0	10
TNF	0.018	0.01	-10000	0	-0.11	3	3
CYCS	0.01	0.03	-10000	0	-0.26	4	4
SATB1	0.004	0.11	-10000	0	-0.84	6	6
SLK	0.015	0.043	-10000	0	-0.18	8	8
p15 BID/BAX	0.011	0.047	-10000	0	-0.18	26	26
CASP2	0.025	0.044	-10000	0	-10000	0	0
JNK cascade	-0.016	0.018	-10000	0	-10000	0	0
CASP3	0.016	0.039	-10000	0	-0.16	11	11
LMNB2	0.029	0.069	-10000	0	-0.38	9	9
RIPK1	0.016	0.019	-10000	0	-0.11	11	11
CASP4	-0.025	0.1	-10000	0	-0.23	96	96
Mammalian IAPs/DIABLO	0.023	0.037	-10000	0	-0.21	6	6
negative regulation of DNA binding	0.029	0.021	-10000	0	-10000	0	0
stress fiber formation	0.015	0.042	-10000	0	-0.17	8	8
GZMB	0.01	0.032	-10000	0	-0.14	9	9
CASP1	-0.055	0.15	-10000	0	-0.34	97	97
LMNB1	0.009	0.1	-10000	0	-0.28	45	45
APP	0.013	0.098	-10000	0	-0.68	10	10
TNFRSF1A	-0.01	0.091	-10000	0	-0.29	50	50
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.013	-10000	0	-0.07	14	14
VIM	0.014	0.068	-10000	0	-0.29	14	14
LMNA	0.032	0.053	-10000	0	-0.33	7	7
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.023	0.047	-10000	0	-0.17	1	1
LRDD	0.018	0.01	-10000	0	-0.11	3	3
SREBF1	0.015	0.04	-10000	0	-0.16	9	9
APAF-1/Caspase 9	0.002	0.049	0.21	1	-0.69	2	3
nuclear fragmentation during apoptosis	0.025	0.043	-10000	0	-0.23	7	7
CFL2	0.019	0.035	-10000	0	-0.14	10	10
GAS2	0.013	0.039	-10000	0	-0.15	11	11
positive regulation of apoptosis	0.023	0.078	-10000	0	-0.37	11	11
PRF1	0.008	0.036	-10000	0	-0.11	44	44

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.015	0.022	-10000	0	-0.11	16	16
ANTXR2	0	0	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.002	-10000	0	-10000	0	0
monocyte activation	-0.086	0.16	-10000	0	-0.36	140	140
MAP2K2	0.012	0.03	-10000	0	-0.68	1	1
MAP2K1	0.005	0.005	-10000	0	-0.044	4	4
MAP2K7	0.006	0.002	-10000	0	-10000	0	0
MAP2K6	0.006	0.003	-10000	0	-0.044	1	1
CYAA	0.003	0.009	-10000	0	-0.045	16	16
MAP2K4	0.005	0.007	-10000	0	-0.046	8	8
IL1B	-0.013	0.039	-10000	0	-0.16	18	18
Channel	0.01	0.011	-10000	0	-0.049	16	16
NLRP1	0.006	0.002	-10000	0	-10000	0	0
CALM1	0.007	0.056	-10000	0	-0.21	28	28
negative regulation of phagocytosis	-0.004	0.082	-10000	0	-0.47	16	16
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.002	-10000	0	-10000	0	0
MAPK3	0.006	0.003	-10000	0	-0.044	1	1
MAPK1	0.005	0.007	-10000	0	-0.046	9	9
PGR	0.006	0.002	-10000	0	-10000	0	0
PA/Cellular Receptors	0.011	0.012	-10000	0	-0.056	16	16
apoptosis	0	0.002	-10000	0	-10000	0	0
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.01	0.009	-10000	0	-0.043	16	16
macrophage activation	0.006	0.022	-10000	0	-0.12	13	13
TNF	0.018	0.01	-10000	0	-0.11	3	3
VCAM1	-0.087	0.16	-10000	0	-0.36	140	140
platelet activation	-0.004	0.082	-10000	0	-0.47	16	16
MAPKKK cascade	-0.008	0.009	0.07	3	-10000	0	3
IL18	-0.008	0.034	-10000	0	-0.15	12	12
negative regulation of macrophage activation	0	0.002	-10000	0	-10000	0	0
LEF	0	0.002	-10000	0	-10000	0	0
CASP1	0.004	0.005	-10000	0	-0.08	1	1
mol:cAMP	-0.004	0.083	-10000	0	-0.47	16	16
necrosis	0	0.002	-10000	0	-10000	0	0
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.01	0.01	-10000	0	-0.046	16	16
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.013	0.082	-9999	-0.32	12	12
BAG4	0.018	0.011	-9999	-0.11	4	4
BAD	0.014	0.032	-9999	-0.14	10	10
NFKBIA	0.002	0.067	-9999	-0.24	34	34
BIRC3	0	0.046	-9999	-0.11	78	78
BAX	0.014	0.03	-9999	-0.12	9	9
EnzymeConsortium:3.1.4.12	0.007	0.019	-9999	-0.062	9	9
IKBKB	0.013	0.081	-9999	-0.3	12	12
MAP2K2	0.02	0.035	-9999	-0.15	12	12
MAP2K1	0.019	0.038	-9999	-0.14	16	16
SMPD1	0.012	0.019	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.024	0.072	-9999	-0.24	8	8
MAP2K4	0.017	0.03	-9999	-0.12	8	8
protein ubiquitination	0.013	0.082	-9999	-0.31	12	12
EnzymeConsortium:2.7.1.37	0.022	0.037	-9999	-0.16	12	12
response to UV	0	0	-9999	-0.001	7	7
RAF1	0.017	0.036	-9999	-0.13	18	18
CRADD	0.017	0.015	-9999	-0.11	7	7
mol:ceramide	0.012	0.027	-9999	-0.098	6	6
I-kappa-B-alpha/RELA/p50/ubiquitin	0.015	0.041	-9999	-0.16	26	26
MADD	0.018	0.015	-9999	-0.2	2	2
MAP3K1	0.015	0.027	-9999	-0.098	7	7
TRADD	0.019	0	-9999	-10000	0	0
RELA/p50	0.018	0.02	-9999	-0.23	3	3
MAPK3	0.023	0.036	-9999	-0.15	12	12
MAPK1	0.02	0.046	-9999	-0.21	14	14
p50/RELA/I-kappa-B-alpha	0.016	0.049	-9999	-0.19	26	26
FADD	0.019	0.072	-9999	-0.23	10	10
KSR1	0.016	0.026	-9999	-0.1	4	4
MAPK8	0.021	0.029	-9999	-0.12	5	5
TRAF2	0.019	0	-9999	-10000	0	0
response to radiation	0	0	-9999	-0.001	3	3
CHUK	0.012	0.081	-9999	-0.31	12	12
TNF R/SODD	0.007	0.065	-9999	-0.19	50	50
TNF	0.018	0.01	-9999	-0.11	3	3
CYCS	0.013	0.031	-9999	-0.12	11	11
IKBKG	0.013	0.081	-9999	-0.3	12	12
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.016	0.075	-9999	-0.21	50	50
RELA	0.018	0.02	-9999	-0.23	3	3
RIPK1	0.016	0.019	-9999	-0.11	11	11
AIFM1	0.012	0.033	-9999	-0.13	13	13
TNF/TNF R/SODD	0.02	0.057	-9999	-0.16	50	50
TNFRSF1A	-0.01	0.091	-9999	-0.29	50	50
response to heat	0	0	-9999	-0.001	3	3
CASP8	0.025	0.046	-9999	-0.63	2	2
NSMAF	0.016	0.077	-9999	-0.28	13	13
response to hydrogen peroxide	0	0	-9999	-0.001	7	7
BCL2	0.019	0	-9999	-10000	0	0

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.007	0.026	-10000	0	-0.15	13	13
SMARCC1	0.001	0.14	-10000	0	-1.2	5	5
REL	0.018	0	-10000	0	-10000	0	0
HDAC7	0.03	0.064	-10000	0	-0.22	18	18
JUN	-0.001	0.077	-10000	0	-0.28	37	37
EP300	0.012	0.046	-10000	0	-0.24	15	15
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	0.023	0.012	-10000	0	-0.15	1	1
FOXO1	-0.012	0.088	-10000	0	-0.23	67	67
T-DHT/AR	0.051	0.074	-10000	0	-0.23	18	18
MAP2K6	0.02	0.007	-10000	0	-0.12	1	1
BRM/BAF57	0.028	0.019	-10000	0	-0.19	3	3
MAP2K4	0.016	0.032	-10000	0	-0.17	12	12
SMARCA2	0.018	0.015	-10000	0	-0.11	7	7
PDE9A	-0.003	0.2	-10000	0	-0.92	24	24
NCOA2	0.019	0.01	-10000	0	-0.11	3	3
CEBPA	-0.028	0.1	-10000	0	-0.22	104	104
EHMT2	0.019	0.006	-10000	0	-0.11	1	1
cell proliferation	0.064	0.076	0.23	4	-0.3	8	12
NR0B1	-0.004	0.049	-10000	0	-0.11	92	92
EGR1	-0.032	0.11	-10000	0	-0.24	107	107
RXRs/9cRA	0.037	0.011	-10000	0	-0.13	1	1
AR/RACK1/Src	0.048	0.033	-10000	0	-0.26	2	2
AR/GR	0.026	0.057	-10000	0	-0.2	26	26
GNB2L1	0.018	0.019	-10000	0	-0.29	2	2
PKN1	0.009	0.049	-10000	0	-0.18	28	28
RCHY1	0.013	0.042	-10000	0	-0.29	10	10
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	0.021	0.022	-10000	0	-0.19	4	4
T-DHT/AR/TIF2/CARM1	0.054	0.035	-10000	0	-0.22	3	3
SRC	0.03	0.017	-10000	0	-0.1	3	3
NR3C1	0.01	0.052	-10000	0	-0.28	16	16
KLK3	0.01	0.07	-10000	0	-0.41	1	1
APPBP2	0.008	0.061	-10000	0	-0.28	22	22
TRIM24	0.007	0.061	-10000	0	-0.25	26	26
T-DHT/AR/TIP60	0.025	0.03	-10000	0	-0.16	6	6
TMPRSS2	0.033	0.063	-10000	0	-0.74	2	2
RXRG	0.018	0.013	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	0.019	0.014	-10000	0	-0.29	1	1
RXRB	0.019	0	-10000	0	-10000	0	0
CARM1	0.019	0.015	-10000	0	-0.2	2	2
NR2C2	0.019	0	-10000	0	-10000	0	0
KLK2	0.057	0.031	-10000	0	-0.24	2	2
AR	0.022	0.05	-10000	0	-0.19	24	24
SENP1	0	0	-10000	0	-10000	0	0
HSP90AA1	0.018	0.019	-10000	0	-0.29	2	2
MDM2	0.009	0.032	-10000	0	-10000	0	0
SRY	0.017	0.01	-10000	0	-0.11	3	3
GATA2	0.018	0.011	-10000	0	-0.11	4	4
MYST2	0.001	0.072	-10000	0	-0.27	34	34
HOXB13	0.02	0.006	-10000	0	-0.11	1	1
T-DHT/AR/RACK1/Src	0.044	0.033	-10000	0	-0.2	4	4
positive regulation of transcription	0.018	0.011	-10000	0	-0.11	4	4
DNAJA1	0.006	0.064	-10000	0	-0.28	24	24
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.042	-10000	0	-0.28	10	10
NCOA1	0.017	0.037	-10000	0	-0.24	8	8
SPDEF	0.021	0.006	-10000	0	-0.11	1	1
T-DHT/AR/TIF2	0.03	0.06	-10000	0	-0.22	20	20
T-DHT/AR/Hsp90	0.037	0.034	-10000	0	-0.19	5	5
GSK3B	0.004	0.066	-10000	0	-0.26	29	29
NR2C1	0.019	0	-10000	0	-10000	0	0
mol:T-DHT	0.028	0.019	-10000	0	-0.12	3	3
SIRT1	0.008	0.048	-10000	0	-0.16	32	32
ZMIZ2	0.017	0	-10000	0	-10000	0	0
POU2F1	0.023	0.036	-10000	0	-0.21	4	4
T-DHT/AR/DAX-1	0.028	0.039	-10000	0	-0.16	7	7
CREBBP	0.019	0	-10000	0	-10000	0	0
SMARCE1	0.018	0.023	-10000	0	-0.29	3	3

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.012	0.056	-9999	-10000	0	0
MKNK1	0.003	0.068	-9999	-0.27	30	30
MAPK14	0.013	0.037	-9999	-0.13	12	12
ATF2/c-Jun	0.003	0.11	-9999	-0.43	34	34
MAPK11	0.014	0.033	-9999	-0.12	8	8
MITF	0.017	0.046	-9999	-0.22	7	7
MAPKAPK5	0.022	0.033	-9999	-10000	0	0
KRT8	0.018	0.041	-9999	-0.22	1	1
MAPKAPK3	0.016	0.023	-9999	-0.16	8	8
MAPKAPK2	0.019	0.008	-9999	-0.11	2	2
p38alpha-beta/CK2	0.019	0.046	-9999	-0.23	1	1
CEBPB	0.006	0.07	-9999	-0.23	33	33
SLC9A1	0.021	0.038	-9999	-0.29	2	2
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.019	0.051	-9999	-0.2	8	8
p38alpha-beta/MNK1	0.02	0.06	-9999	-0.18	27	27
JUN	0.002	0.11	-9999	-0.43	34	34
PPARGC1A	0.007	0.059	-9999	-0.23	20	20
USF1	0.013	0.033	-9999	-0.17	1	1
RAB5/GDP/GDI1	0.002	0.082	-9999	-0.25	43	43
NOS2	0.013	0.033	-9999	-0.17	1	1
DDIT3	0.003	0.065	-9999	-0.22	30	30
RAB5A	0.004	0.067	-9999	-0.29	26	26
HSPB1	0.009	0.052	-9999	-0.16	34	34
p38alpha-beta/HBP1	0.03	0.039	-9999	-0.17	1	1
CREB1	0.024	0.036	-9999	-0.19	2	2
RAB5/GDP	0.004	0.046	-9999	-0.2	26	26
EIF4E	0.01	0.055	-9999	-0.17	31	31
RPS6KA4	0.022	0.033	-9999	-10000	0	0
PLA2G4A	-0.001	0.061	-9999	-0.18	36	36
GDI1	0.003	0.086	-9999	-0.28	40	40
TP53	0.011	0.044	-9999	-0.2	6	6
RPS6KA5	0.018	0.037	-9999	-0.2	1	1
ESR1	0.022	0.033	-9999	-10000	0	0
HBP1	0.019	0	-9999	-10000	0	0
MEF2C	0.015	0.057	-9999	-0.27	13	13
MEF2A	0.018	0.048	-9999	-0.25	9	9
EIF4EBP1	0.02	0.041	-9999	-0.19	5	5
KRT19	0.018	0.041	-9999	-0.17	7	7
ELK4	0.022	0.033	-9999	-0.16	1	1
ATF6	0.021	0.036	-9999	-0.27	1	1
ATF1	0.022	0.037	-9999	-0.19	1	1
p38alpha-beta/MAPKAPK2	0.03	0.04	-9999	-0.17	1	1
p38alpha-beta/MAPKAPK3	0.029	0.042	-9999	-0.18	3	3

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.019	0	-10000	0	-10000	0	0
CLTC	0.014	0.052	-10000	0	-0.45	3	3
calcium ion-dependent exocytosis	0.006	0.064	-10000	0	-0.25	23	23
Dynamin 2/GTP	0.02	0.007	-10000	0	-0.14	1	1
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.009	0.056	-10000	0	-0.38	5	5
CPE	0.014	0.016	-10000	0	-0.18	2	2
CTNNB1	0.017	0.023	-10000	0	-0.29	3	3
membrane fusion	0.006	0.062	-10000	0	-0.18	43	43
CTNND1	0.02	0.013	-10000	0	-0.26	1	1
DNM2	0.019	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.009	0.06	-10000	0	-0.24	21	21
TSHR	0.016	0.014	-10000	0	-0.16	1	1
INS	0.015	0.018	-10000	0	-10000	0	0
BIN1	-0.016	0.092	-10000	0	-0.23	74	74
mol:Choline	0.006	0.062	-10000	0	-0.18	43	43
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.007	0.008	-10000	0	-0.16	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.018	0.015	-10000	0	-0.2	2	2
mol:Ca2+	0.019	0.007	-10000	0	-0.14	1	1
JUP	0.011	0.043	-10000	0	-0.76	1	1
ASAP2/amphiphysin II	0.006	0.05	-10000	0	-0.14	49	49
ARF6/GTP	0.014	0.01	-10000	0	-0.13	2	2
CDH1	0.013	0.043	-10000	0	-0.76	1	1
clathrin-independent pinocytosis	0.014	0.01	-10000	0	-0.13	2	2
MAPK8IP3	0.019	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0.014	0.01	-10000	0	-0.13	2	2
EXOC2	0.015	0.022	-10000	0	-0.11	15	15
substrate adhesion-dependent cell spreading	0.011	0.052	-10000	0	-0.36	4	4
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.001	0.071	-10000	0	-0.26	33	33
regulation of calcium-dependent cell-cell adhesion	-0.028	0.042	0.47	2	-10000	0	2
positive regulation of phagocytosis	0.016	0.018	-10000	0	-0.26	2	2
ARF6/GTP/JIP3	0.025	0.009	-10000	0	-0.16	1	1
ACAP1	0.005	0.059	-10000	0	-0.17	43	43
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.014	0.041	-10000	0	-0.76	1	1
clathrin heavy chain/ACAP1	0.012	0.064	-10000	0	-0.26	14	14
JIP4/KLC1	0.016	0.069	-10000	0	-0.2	43	43
EXOC1	0.008	0.051	-10000	0	-0.2	25	25
exocyst	0.011	0.052	-10000	0	-0.37	4	4
RALA/GTP	0.005	0.043	-10000	0	-0.2	22	22
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.015	0.044	-10000	0	-0.16	28	28
receptor recycling	0.014	0.01	-10000	0	-0.13	2	2
CTNNA1	0.02	0.013	-10000	0	-0.26	1	1
NME1	0.007	0.008	-10000	0	-0.16	1	1
clathrin coat assembly	0.014	0.051	-10000	0	-0.44	3	3
IL2RA	0.013	0.042	-10000	0	-0.76	1	1
VAMP3	0.016	0.018	-10000	0	-0.26	2	2
GLUT4/clathrin heavy chain/ACAP1	0.018	0.061	-10000	0	-0.24	14	14
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	0.006	0.056	-10000	0	-0.22	22	22
PLD2	0.006	0.055	-10000	0	-0.22	22	22
EXOC5	-0.006	0.073	-10000	0	-0.18	65	65
PIP5K1C	0.009	0.061	-10000	0	-0.25	21	21
SDC1	0.01	0.043	-10000	0	-0.76	1	1
ARF6/GDP	0.014	0.008	-10000	0	-0.11	2	2
EXOC7	0.018	0.014	-10000	0	-0.29	1	1
E-cadherin/beta catenin	0.03	0.044	-10000	0	-0.49	2	2
mol:Phosphatidic acid	0.006	0.062	-10000	0	-0.18	43	43
endocytosis	-0.005	0.05	0.14	49	-10000	0	49
SCAMP2	0.006	0.062	-10000	0	-0.29	22	22
ADRB2	0.015	0.05	-10000	0	-0.43	3	3
EXOC3	0.017	0.021	-10000	0	-0.2	4	4
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.019	0.007	-10000	0	-0.14	1	1
KLC1	-0.002	0.077	-10000	0	-0.28	37	37
AVPR2	0.018	0.048	-10000	0	-0.42	3	3
RALA	0.005	0.063	-10000	0	-0.26	26	26
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.025	0.07	-10000	0	-0.25	22	22

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.01	0.053	-9999	-0.28	14	14
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.052	0.069	-9999	-0.26	12	12
ERC1	-0.002	0.075	-9999	-0.24	43	43
RIP2/NOD2	0.025	0.02	-9999	-0.19	2	2
NFKBIA	0.01	0.086	-9999	-0.31	31	31
BIRC2	0.016	0.03	-9999	-0.29	5	5
IKBKB	0.019	0	-9999	-10000	0	0
RIPK2	0.017	0.021	-9999	-0.18	5	5
IKBKG	0.037	0.034	-9999	-0.28	4	4
IKK complex/A20	0.049	0.055	-9999	-0.24	5	5
NEMO/A20/RIP2	0.017	0.021	-9999	-0.18	5	5
XPO1	0.017	0.023	-9999	-0.29	3	3
NEMO/ATM	0.043	0.037	-9999	-0.26	5	5
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.016	0.031	-9999	-0.24	7	7
Exportin 1/RanGTP	0.023	0.026	-9999	-0.21	6	6
IKK complex/ELKS	0.041	0.048	-9999	-0.27	5	5
BCL10/MALT1/TRAF6	0.033	0.03	-9999	-0.15	11	11
NOD2	0.016	0.02	-9999	-0.11	13	13
NFKB1	0.012	0.043	-9999	-0.24	11	11
RELA	0.016	0.026	-9999	-0.23	3	3
MALT1	0.013	0.036	-9999	-0.16	18	18
cIAP1/UbcH5C	0.025	0.031	-9999	-0.25	6	6
ATM	0.01	0.042	-9999	-0.15	30	30
TNF/TNFR1A	0.007	0.065	-9999	-0.19	50	50
TRAF6	0.018	0.019	-9999	-0.29	2	2
PRKCA	0.019	0	-9999	-10000	0	0
CHUK	0.016	0.025	-9999	-0.15	10	10
UBE2D3	0.017	0.023	-9999	-0.29	3	3
TNF	0.018	0.01	-9999	-0.11	3	3
NF kappa B1 p50/RelA	0.03	0.068	-9999	-0.2	38	38
BCL10	0.016	0.028	-9999	-0.23	6	6
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.086	-9999	-0.31	31	31
beta TrCP1/SCF ubiquitin ligase complex	0.01	0.053	-9999	-0.28	14	14
TNFRSF1A	-0.01	0.091	-9999	-0.29	50	50
IKK complex	0.055	0.035	-9999	-0.27	3	3
CYLD	0.018	0.016	-9999	-0.17	3	3
IKK complex/PKC alpha	0.061	0.035	-9999	-0.26	3	3

×

IL27-mediated signaling 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
TGFB1	0.015	0.049	-10000	0	-0.28	9	9
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.009	0.076	0.4	12	-10000	0	12
IL27/IL27R/JAK1	0.022	0.065	-10000	0	-10000	0	0
TBX21	0.015	0.066	-10000	0	-0.33	9	9
IL12B	0.02	0	-10000	0	-10000	0	0
IL12A	0.011	0	-10000	0	-10000	0	0
IL6ST	0	0.075	-10000	0	-0.3	30	30
IL27RA/JAK1	0.018	0.029	-10000	0	-10000	0	0
IL27	0	0.002	-10000	0	-10000	0	0
TYK2	0.008	0.061	-10000	0	-0.29	21	21
T-helper cell lineage commitment	0.018	0.038	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.009	0.076	0.4	12	-10000	0	12
T cell proliferation during immune response	-0.009	0.076	0.4	12	-10000	0	12
MAPKKK cascade	0.009	0.076	-10000	0	-0.4	12	12
STAT3	-0.003	0.079	-10000	0	-0.29	37	37
STAT2	0.019	0	-10000	0	-10000	0	0
STAT1	0.008	0.04	-10000	0	-0.12	41	41
IL12RB1	0.019	0.006	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.017	0.066	-10000	0	-0.33	9	9
IL27/IL27R/JAK2/TYK2	0.009	0.076	-10000	0	-0.41	12	12
positive regulation of T cell mediated cytotoxicity	0.009	0.076	-10000	0	-0.4	12	12
STAT1 (dimer)	0.022	0.083	-10000	0	-0.42	9	9
JAK2	0.013	0.027	-10000	0	-10000	0	0
JAK1	0.001	0.071	-10000	0	-0.26	34	34
STAT2 (dimer)	0.019	0.074	-10000	0	-0.38	12	12
T cell proliferation	0.006	0.076	-10000	0	-0.4	12	12
IL12/IL12R/TYK2/JAK2	0.016	0.17	-10000	0	-0.83	20	20
IL17A	0.018	0.038	-10000	0	-10000	0	0
mast cell activation	-0.009	0.076	0.4	12	-10000	0	12
IFNG	0.007	0.019	-10000	0	-0.096	12	12
T cell differentiation	0	0.003	-10000	0	-0.017	13	13
STAT3 (dimer)	0.014	0.091	-10000	0	-0.47	12	12
STAT5A (dimer)	0.019	0.074	-10000	0	-0.38	12	12
STAT4 (dimer)	0.016	0.077	-10000	0	-0.4	12	12
STAT4	0.012	0.03	-10000	0	-0.11	30	30
T cell activation	-0.008	0.004	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.026	0.065	-10000	0	-10000	0	0
GATA3	0.007	0.017	-10000	0	-10000	0	0
IL18	-0.002	0.036	-10000	0	-0.2	9	9
positive regulation of mast cell cytokine production	0.014	0.089	-10000	0	-0.46	12	12
IL27/EBI3	0.012	0.014	-10000	0	-0.076	1	1
IL27RA	0.011	0.012	-10000	0	-10000	0	0
IL6	0.002	0.051	-10000	0	-10000	0	0
STAT5A	0.019	0.008	-10000	0	-0.11	2	2
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.005	0.006	-10000	0	-10000	0	0
IL1B	-0.009	0.046	-10000	0	-0.092	102	102
EBI3	0.015	0.022	-10000	0	-0.11	15	15
TNF	0.01	0.006	-10000	0	-0.07	3	3

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.013	0.04	-9999	-0.22	13	13
Ran/GTP/Exportin 1/HDAC4	-0.01	0.038	-9999	-0.16	21	21
MDM2/SUMO1	0.026	0.038	-9999	-0.25	4	4
HDAC4	0.007	0.056	-9999	-0.29	16	16
Ran/GTP/Exportin 1/HDAC1	-0.008	0.038	-9999	-0.15	28	28
SUMO1	0.017	0.027	-9999	-0.29	4	4
NPC/RanGAP1/SUMO1	0.009	0.037	-9999	-0.16	21	21
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.016	0.04	-9999	-0.16	21	21
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.016	0.031	-9999	-0.24	7	7
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.007	0.057	-9999	-0.26	22	22
SUMO1/HDAC4	0.024	0.045	-9999	-0.27	5	5
SUMO1/HDAC1	0.027	0.043	-9999	-0.18	11	11
RANGAP1	0.017	0.015	-9999	-0.11	7	7
MDM2/SUMO1/SUMO1	0.036	0.042	-9999	-0.14	21	21
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.013	0.036	-9999	-0.16	21	21
Ran/GTP	0.021	0.04	-9999	-0.15	24	24
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.011	0.032	-9999	-10000	0	0
UBE2I	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.045	-9999	-0.16	21	21
NPC	0.006	0.027	-9999	-0.14	18	18
PIAS2	0.018	0.011	-9999	-0.11	4	4
PIAS1	0.008	0.056	-9999	-0.29	18	18
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.019	0.006	-9999	-0.11	1	1
Aurora C/Aurora B/INCENP	0.03	0.024	-9999	-0.1	5	5
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.006	0.062	-9999	-0.42	11	11
AURKB	0.011	0.033	-9999	-0.12	32	32
AURKC	0.015	0.022	-9999	-0.11	16	16

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.001	0.14	-10000	0	-1.1	9	9
VDR	0.019	0.008	-10000	0	-0.11	2	2
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.025	0.097	-10000	0	-0.26	48	48
RXRs/LXRs/DNA/Oxysterols	0.016	0.15	-10000	0	-0.41	52	52
MED1	-0.002	0.078	-10000	0	-0.29	36	36
mol:9cRA	0	0.017	-10000	0	-0.073	5	5
RARs/THRs/DNA/Src-1	0.022	0.053	-10000	0	-0.16	41	41
RXRs/NUR77	0.05	0.04	-10000	0	-0.15	1	1
RXRs/PPAR	0.036	0.027	-10000	0	-0.18	1	1
NCOR2	0.019	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.014	0.005	-10000	0	-0.07	2	2
RARs/VDR/DNA/Vit D3	0.045	0.007	-10000	0	-10000	0	0
RARA	0.019	0	-10000	0	-10000	0	0
NCOA1	-0.006	0.083	-10000	0	-0.28	43	43
VDR/VDR/DNA	0.019	0.008	-10000	0	-0.11	2	2
RARs/RARs/DNA/9cRA	0.033	0.014	-10000	0	-10000	0	0
RARG	0.019	0	-10000	0	-10000	0	0
RPS6KB1	-0.005	0.055	-10000	0	-0.39	9	9
RARs/THRs/DNA/SMRT	0.037	0.01	-10000	0	-0.15	1	1
THRA	0.017	0.02	-10000	0	-0.13	8	8
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.014	0.005	-10000	0	-0.07	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	0.04	0.058	0.29	2	-0.18	6	8
NR1H4	0.019	0.008	-10000	0	-0.11	2	2
RXRs/LXRs/DNA	0.057	0.076	-10000	0	-0.22	14	14
NR1H2	0.018	0.02	-10000	0	-10000	0	0
NR1H3	0.014	0.038	-10000	0	-0.15	16	16
RXRs/VDR/DNA/Vit D3	0.047	0.037	-10000	0	-0.14	1	1
NR4A1	0.019	0.008	-10000	0	-0.11	2	2
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.016	0.061	-10000	0	-0.24	15	15
RXRG	0.018	0.021	-10000	0	-10000	0	0
RXR alpha/CCPG	0.014	0.015	-10000	0	-0.2	1	1
RXRA	0.018	0.022	-10000	0	-0.3	1	1
RXRB	0.019	0.019	-10000	0	-10000	0	0
THRB	0.019	0	-10000	0	-10000	0	0
PPARG	0.015	0.024	-10000	0	-0.11	18	18
PPARD	0.019	0	-10000	0	-10000	0	0
TNF	0.021	0.14	-10000	0	-0.56	12	12
mol:Oxysterols	0.001	0.015	-10000	0	-10000	0	0
cholesterol transport	0.016	0.15	-10000	0	-0.4	52	52
PPARA	0.019	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.019	0.008	-10000	0	-10000	0	0
RXRs/NUR77/BCL2	0.03	0.016	-10000	0	-0.17	1	1
SREBF1	0.008	0.19	-10000	0	-0.81	18	18
RXRs/RXRs/DNA/9cRA	0.04	0.058	0.29	2	-0.18	6	8
ABCA1	-0.029	0.28	-10000	0	-0.92	47	47
RARs/THRs	0.055	0.013	-10000	0	-0.12	1	1
RXRs/FXR	0.05	0.04	-10000	0	-0.15	1	1
BCL2	0.019	0	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.028	0.011	-9999	-10000	0	0
KIRREL	0.019	0.013	-9999	-0.12	5	5
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.028	0.011	-9999	-10000	0	0
PLCG1	0.017	0.025	-9999	-0.29	3	3
ARRB2	0.013	0.039	-9999	-0.29	7	7
WASL	0.016	0.03	-9999	-0.29	5	5
Nephrin/NEPH1/podocin/CD2AP	0.036	0.044	-9999	-0.15	19	19
ChemicalAbstracts:57-88-5	0	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.026	0.047	-9999	-0.23	12	12
FYN	0.021	0.01	-9999	-10000	0	0
mol:Ca2+	0.045	0.02	-9999	-0.17	3	3
mol:DAG	0.046	0.02	-9999	-0.17	3	3
NPHS2	0.02	0.003	-9999	-10000	0	0
mol:IP3	0.046	0.02	-9999	-0.17	3	3
regulation of endocytosis	0.027	0.045	-9999	-0.17	9	9
Nephrin/NEPH1/podocin/Cholesterol	0.036	0.01	-9999	-10000	0	0
establishment of cell polarity	0.028	0.011	-9999	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2	0.047	0.046	-9999	-0.16	21	21
Nephrin/NEPH1/beta Arrestin2	0.028	0.046	-9999	-0.17	9	9
NPHS1	0.02	0.006	-9999	-0.11	1	1
Nephrin/NEPH1/podocin	0.023	0.04	-9999	-0.084	63	63
TJP1	0.01	0.046	-9999	-0.19	22	22
NCK1	0.014	0.036	-9999	-0.19	14	14
NCK2	0.009	0.054	-9999	-0.28	17	17
heterophilic cell adhesion	0	0	-9999	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.047	0.02	-9999	-0.17	3	3
CD2AP	0.003	0.062	-9999	-0.2	40	40
Nephrin/NEPH1/podocin/GRB2	0.045	0.029	-9999	-0.18	8	8
GRB2	0.014	0.039	-9999	-0.26	10	10
homophilic cell adhesion	0	0	-9999	-10000	0	0
TRPC6	0.021	0.016	-9999	-0.079	1	1
cytoskeleton organization	0.028	0.044	-9999	-0.22	12	12
Nephrin/NEPH1	0.024	0.007	-9999	-10000	0	0
Nephrin/NEPH1/ZO-1	0.032	0.033	-9999	-0.18	10	10

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.043	0.041	-10000	0	-10000	0	0
IHH	0.028	0.014	-10000	0	-0.094	1	1
SHH Np/Cholesterol/GAS1	0.012	0.039	-10000	0	-0.14	24	24
LRPAP1	0.013	0.043	-10000	0	-0.28	11	11
dorsoventral neural tube patterning	-0.012	0.039	0.14	24	-10000	0	24
SMO/beta Arrestin2	0.053	0.031	-10000	0	-10000	0	0
SMO	0.047	0.027	-10000	0	-10000	0	0
AKT1	-0.012	0.15	-10000	0	-0.49	33	33
ARRB2	0.013	0.039	-10000	0	-0.29	7	7
BOC	0	0	-10000	0	-10000	0	0
ADRBK1	0.018	0.014	-10000	0	-0.11	6	6
heart looping	0.047	0.027	-10000	0	-10000	0	0
STIL	0.035	0.032	-10000	0	-0.18	2	2
DHH N/PTCH2	0.014	0	-10000	0	-10000	0	0
DHH N/PTCH1	0.031	0.029	-10000	0	-10000	0	0
PIK3CA	-0.011	0.086	-10000	0	-0.22	66	66
DHH	0	0	-10000	0	-10000	0	0
PTHLH	0.044	0.041	-10000	0	-10000	0	0
determination of left/right symmetry	0.047	0.027	-10000	0	-10000	0	0
PIK3R1	-0.015	0.095	-10000	0	-0.27	62	62
skeletal system development	0.044	0.04	-10000	0	-10000	0	0
IHH N/Hhip	0.019	0.008	-10000	0	-10000	0	0
DHH N/Hhip	0	0	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.047	0.027	-10000	0	-10000	0	0
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	0.018	0.014	-10000	0	-0.11	6	6
PI3K	-0.016	0.093	-10000	0	-0.21	88	88
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.008	0.073	-10000	0	-0.17	78	78
somite specification	0.047	0.027	-10000	0	-10000	0	0
SHH Np/Cholesterol/PTCH1	0.043	0.029	-10000	0	-10000	0	0
SHH Np/Cholesterol/PTCH2	0.026	0.007	-10000	0	-10000	0	0
SHH Np/Cholesterol/Megalin	0.025	0.011	-10000	0	-10000	0	0
SHH	0.02	0.009	-10000	0	-10000	0	0
catabolic process	0.038	0.034	-10000	0	-10000	0	0
SMO/Vitamin D3	0.051	0.029	-10000	0	-10000	0	0
SHH Np/Cholesterol/Hhip	0.014	0.006	-10000	0	-10000	0	0
LRP2	0.017	0.018	-10000	0	-0.11	10	10
receptor-mediated endocytosis	0.05	0.031	-10000	0	-10000	0	0
SHH Np/Cholesterol/BOC	0.014	0.006	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	0.026	0.007	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.013	0.006	-10000	0	-10000	0	0
mol:Vitamin D3	0.045	0.03	-10000	0	-10000	0	0
IHH N/PTCH2	0.034	0.008	-10000	0	-10000	0	0
CDON	0.019	0	-10000	0	-10000	0	0
IHH N/PTCH1	0.045	0.037	-10000	0	-10000	0	0
Megalin/LRPAP1	0.022	0.032	-10000	0	-0.19	10	10
PTCH2	0.019	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	0.016	0.006	-10000	0	-10000	0	0
PTCH1	0.038	0.035	-10000	0	-10000	0	0
HHIP	0	0	-10000	0	-10000	0	0

×

Arf1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.017	0.018	-10000	0	-0.25	2	2
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.015	0.028	-10000	0	-0.21	7	7
AP2	0.008	0.036	-10000	0	-0.17	19	19
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.019	0.039	-10000	0	-0.18	19	19
CLTB	0.018	0.014	-10000	0	-0.29	1	1
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0.032	-10000	0	-0.2	10	10
CD4	-0.003	0.07	-10000	0	-0.19	56	56
CLTA	0.017	0.023	-10000	0	-0.29	3	3
mol:GTP	0	0.003	-10000	0	-10000	0	0
ARFGAP1	0.01	0.013	-10000	0	-0.2	2	2
mol:PI-4-5-P2	0.011	0.021	0.12	13	-10000	0	13
ARF1/GTP	0.008	0.019	-10000	0	-0.13	8	8
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.018	0.032	-10000	0	-0.19	11	11
mol:Choline	0.011	0.021	0.12	13	-10000	0	13
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.018	0.008	-10000	0	-0.11	2	2
DDEF1	0.009	0.019	0.12	10	-10000	0	10
ARF1/GDP	0.007	0.013	-10000	0	-0.18	2	2
AP2M1	0.009	0.053	-10000	0	-0.25	19	19
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.011	0.027	-10000	0	-0.15	13	13
Rac/GTP	0.011	0.025	-10000	0	-0.2	7	7
ARF1/GTP/GGA3/ARF-GAP1	0.028	0.02	-10000	0	-0.12	9	9
ARFIP2	0.009	0.047	-10000	0	-0.25	17	17
COPA	0.017	0.018	-10000	0	-0.14	6	6
RAC1	0.015	0.036	-10000	0	-0.29	7	7
ARF1/GTP/coatomer protein complex	0.019	0.031	-10000	0	-0.2	9	9
ARF1/GTP/ARHGAP10	0.009	0.02	-10000	0	-0.16	7	7
GGA3	0.019	0	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.016	0.018	-10000	0	-0.14	5	5
AP2A1	0	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.02	0.032	-10000	0	-0.19	10	10
ARF1/GDP/Membrin	0.018	0.017	-10000	0	-10000	0	0
Arfaptin 2/Rac/GDP	0.018	0.039	-10000	0	-0.17	19	19
CYTH2	0	0.003	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.022	0.021	-10000	0	-0.16	7	7
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.011	0.024	-10000	0	-0.2	7	7
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.01	0.063	-10000	0	-0.19	40	40
PLD2	0.011	0.021	0.12	13	-10000	0	13
ARF-GAP1/v-SNARE	0.01	0.013	-10000	0	-0.2	2	2
PIP5K1A	0.008	0.011	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.015	0.019	-10000	0	-0.14	7	7
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.011	0.021	0.12	13	-10000	0	13
KDEL Receptor/Ligand/ARF-GAP1	0.01	0.013	-10000	0	-0.2	2	2
GOSR2	0.013	0.006	-10000	0	-10000	0	0
USO1	0.01	0.028	-10000	0	-0.3	4	4
GBF1	0.012	0.009	-10000	0	-10000	0	0
ARF1/GTP/Arfaptin 2	0.018	0.038	-10000	0	-0.16	20	20
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.007	0.053	-10000	0	-0.17	36	36

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.007	0	-9999	-10000	0	0
ADCY5	0.007	0	-9999	-10000	0	0
ADCY6	0.014	0.003	-9999	-0.05	1	1
ADCY7	0.012	0.011	-9999	-0.05	15	15
ADCY1	0.014	0	-9999	-10000	0	0
ADCY2	0.014	0.005	-9999	-0.05	3	3
ADCY3	0.007	0	-9999	-10000	0	0
ADCY8	0.007	0.021	-9999	-0.05	64	64
PRKCE	0.01	0	-9999	-10000	0	0
ADCY9	0.014	0.007	-9999	-0.05	6	6
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	0.015	0.012	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.025	0.021	-9999	-0.19	2	2
FBXW11	0.011	0.047	-9999	-0.27	14	14
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0.047	-9999	-0.27	14	14
CHUK	0.016	0.025	-9999	-0.15	10	10
NF kappa B2 p100/RelB	0.048	0.033	-9999	-0.12	14	14
NFKB1	0.014	0.037	-9999	-0.23	11	11
MAP3K14	0.017	0.017	-9999	-0.11	9	9
NF kappa B1 p50/RelB	0.024	0.027	-9999	-0.19	7	7
RELB	0.018	0.011	-9999	-0.11	4	4
NFKB2	0.019	0.008	-9999	-0.11	2	2
NF kappa B2 p52/RelB	0.025	0.008	-9999	-10000	0	0
regulation of B cell activation	0.025	0.008	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.016	0.03	-10000	0	-0.13	21	21
MAPK9	0.007	0.022	-10000	0	-0.24	4	4
adrenocorticotropin secretion	0.009	0.01	-10000	0	-10000	0	0
GNB1/GNG2	0.006	0.034	-10000	0	-0.16	21	21
GNB1	0.007	0.061	-10000	0	-0.29	21	21
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	0.008	0.005	-10000	0	-10000	0	0
Gs family/GTP	0.012	0.005	-10000	0	-0.049	3	3
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0	0.001	0.015	3	-10000	0	3
GNAL	0.018	0.01	-10000	0	-0.11	3	3
GNG2	0	0	-10000	0	-10000	0	0
CRH	0.017	0.017	-10000	0	-0.11	9	9
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.009	0	-10000	0	-10000	0	0
MAPK11	0.009	0	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin 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
ITGB1	0.019	0	-9999	-10000	0	0
ITGB7	0.018	0.01	-9999	-0.11	3	3
ITGA4	0.016	0.019	-9999	-0.11	12	12
alpha4/beta7 Integrin	0.026	0.016	-9999	-0.14	2	2
alpha4/beta1 Integrin	0.026	0.014	-9999	-10000	0	0

×

Visual signal transduction: Rods

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
mol:K +	0.019	0	-9999	-10000	0	0
GNAT1/GTP	0.014	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	0.026	0.005	-9999	-10000	0	0
PDE6G/GNAT1/GTP	0.026	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.019	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
CNG Channel	0.037	0.008	-9999	-10000	0	0
mol:Na +	0.03	0.004	-9999	-10000	0	0
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.023	0.016	-9999	-0.16	1	1
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	0.038	0.005	-9999	-10000	0	0
CNGB1	0.019	0	-9999	-10000	0	0
RDH5	0.017	0.016	-9999	-0.11	8	8
SAG	0.019	0.008	-9999	-0.11	2	2
mol:Ca2+	0.032	0.004	-9999	-10000	0	0
Na + (4 Units)	0.027	0.003	-9999	-10000	0	0
RGS9	0.016	0.02	-9999	-0.11	13	13
GNB1/GNGT1	0.019	0.044	-9999	-0.19	21	21
GNAT1/GDP	0.031	0.015	-9999	-0.13	1	1
GUCY2D	0.019	0	-9999	-10000	0	0
GNGT1	0.019	0.008	-9999	-0.11	2	2
GUCY2F	0.019	0	-9999	-10000	0	0
GNB5	0.017	0.019	-9999	-0.14	7	7
mol:GMP (4 units)	0.032	0.007	-9999	-10000	0	0
mol:11-cis-retinal	0.017	0.016	-9999	-0.11	8	8
mol:cGMP	0.026	0	-9999	-10000	0	0
GNB1	0.007	0.061	-9999	-0.29	21	21
Rhodopsin	0.027	0.011	-9999	-10000	0	0
SLC24A1	0.019	0	-9999	-10000	0	0
CNGA1	0.018	0.01	-9999	-0.11	3	3
Metarhodopsin II	0.012	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.025	0	-9999	-10000	0	0
RGS9BP	0	0	-9999	-10000	0	0
Metarhodopsin II/Transducin	0.018	0.037	-9999	-0.16	21	21
GCAP Family/Ca ++	0.012	0	-9999	-10000	0	0
PDE6A/B	0.027	0.01	-9999	-10000	0	0
mol:Pi	0.022	0.016	-9999	-0.16	1	1
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.03	0.034	-9999	-0.14	21	21
PDE6B	0.018	0.013	-9999	-0.11	5	5
PDE6A	0.019	0.006	-9999	-10000	0	0
PDE6G	0.019	0	-9999	-10000	0	0
RHO	0.019	0	-9999	-10000	0	0
PDE6	0.043	0.017	-9999	-0.11	1	1
GUCA1A	0	0	-9999	-10000	0	0
GC2/GCAP Family	0.025	0	-9999	-10000	0	0
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.019	0	-9999	-10000	0	0

×

Ephrin A reverse signaling

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
MAPKKK cascade	0.025	0.003	-9999	-10000	0	0
EFNA5	0.019	0.006	-9999	-0.11	1	1
FYN	0.02	0.01	-9999	-10000	0	0
neuron projection morphogenesis	0.025	0.003	-9999	-10000	0	0
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	0.026	0.003	-9999	-10000	0	0
EPHA5	0.019	0	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
cAMP biosynthetic process	-0.019	-9999	-9999
PI3K Class IB/PDE3B	0.019	-9999	-9999
PDE3B	0.019	-9999	-9999