PARADIGM pathway analysis of mRNASeq expression data - Colorectal Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	234
Syndecan-1-mediated signaling events	205
Reelin signaling pathway	171
Osteopontin-mediated events	107
Lissencephaly gene (LIS1) in neuronal migration and development	101
FOXA2 and FOXA3 transcription factor networks	85
IL4-mediated signaling events	82
Glypican 1 network	81
Syndecan-4-mediated signaling events	71
Ephrin A reverse signaling	66

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
TCGA08_retinoblastoma	0.3756	234	1875	8	-0.14	0.097	1000	-1000	-0.015	-1000
Syndecan-1-mediated signaling events	0.3291	205	6992	34	-0.72	0.013	1000	-1000	-0.062	-1000
Reelin signaling pathway	0.2745	171	9592	56	-0.58	0.036	1000	-1000	-0.075	-1000
Osteopontin-mediated events	0.1717	107	4091	38	-0.31	0.02	1000	-1000	-0.089	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1621	101	5457	54	-0.52	0.024	1000	-1000	-0.094	-1000
FOXA2 and FOXA3 transcription factor networks	0.1364	85	3945	46	-0.7	0.022	1000	-1000	-0.14	-1000
IL4-mediated signaling events	0.1316	82	7473	91	-0.81	0.59	1000	-1000	-0.19	-1000
Glypican 1 network	0.1300	81	3912	48	-0.34	0.025	1000	-1000	-0.052	-1000
Syndecan-4-mediated signaling events	0.1140	71	4786	67	-0.4	0.047	1000	-1000	-0.068	-1000
Ephrin A reverse signaling	0.1059	66	467	7	-0.084	0	1000	-1000	-0.022	-1000
BCR signaling pathway	0.1011	63	6317	99	-0.2	0.013	1000	-1000	-0.087	-1000
IL23-mediated signaling events	0.1011	63	3795	60	-0.47	0.013	1000	-1000	-0.22	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0995	62	4862	78	-0.16	0.069	1000	-1000	-0.075	-1000
HIF-1-alpha transcription factor network	0.0867	54	4179	76	-0.77	0.019	1000	-1000	-0.18	-1000
Caspase cascade in apoptosis	0.0851	53	3975	74	-0.13	0.066	1000	-1000	-0.046	-1000
Endothelins	0.0835	52	5068	96	-0.38	0.088	1000	-1000	-0.093	-1000
Glucocorticoid receptor regulatory network	0.0770	48	5525	114	-0.64	0.29	1000	-1000	-0.081	-1000
Presenilin action in Notch and Wnt signaling	0.0754	47	2910	61	-0.5	0.21	1000	-1000	-0.061	-1000
Fc-epsilon receptor I signaling in mast cells	0.0738	46	4525	97	-0.14	0.032	1000	-1000	-0.084	-1000
Visual signal transduction: Rods	0.0738	46	2404	52	-0.22	0.013	1000	-1000	-0.09	-1000
Signaling events mediated by the Hedgehog family	0.0722	45	2386	52	-0.12	0.11	1000	-1000	-0.055	-1000
Calcium signaling in the CD4+ TCR pathway	0.0722	45	1402	31	-0.47	0.013	1000	-1000	-0.065	-1000
BMP receptor signaling	0.0706	44	3587	81	-0.27	0.044	1000	-1000	-0.093	-1000
Ephrin B reverse signaling	0.0690	43	2091	48	-0.15	0.067	1000	-1000	-0.058	-1000
Syndecan-2-mediated signaling events	0.0642	40	2824	69	-0.41	0.036	1000	-1000	-0.044	-1000
IL1-mediated signaling events	0.0626	39	2446	62	-0.21	0.018	1000	-1000	-0.1	-1000
Canonical Wnt signaling pathway	0.0626	39	2021	51	-0.5	0.22	1000	-1000	-0.069	-1000
Effects of Botulinum toxin	0.0626	39	1023	26	-0.094	0.019	1000	-1000	-0.061	-1000
Ras signaling in the CD4+ TCR pathway	0.0610	38	654	17	-0.083	0.024	1000	-1000	-0.037	-1000
JNK signaling in the CD4+ TCR pathway	0.0594	37	634	17	-0.11	0.017	1000	-1000	-0.045	-1000
p75(NTR)-mediated signaling	0.0578	36	4567	125	-0.88	0.037	1000	-1000	-0.1	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0578	36	2456	68	-0.5	0.046	1000	-1000	-0.12	-1000
TCGA08_p53	0.0546	34	243	7	-0.1	0.052	1000	-1000	-0.014	-1000
Syndecan-3-mediated signaling events	0.0546	34	1204	35	-0.41	0.037	1000	-1000	-0.05	-1000
Wnt signaling	0.0546	34	238	7	-0.14	0.013	1000	-1000	-0.039	-1000
amb2 Integrin signaling	0.0530	33	2765	82	-0.16	0.017	1000	-1000	-0.075	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0498	31	2731	88	-0.26	0.072	1000	-1000	-0.1	-1000
Signaling events mediated by PRL	0.0433	27	943	34	-0.11	0.052	1000	-1000	-0.042	-1000
EPHB forward signaling	0.0417	26	2238	85	-0.15	0.075	1000	-1000	-0.092	-1000
Plasma membrane estrogen receptor signaling	0.0417	26	2247	86	-0.22	0.066	1000	-1000	-0.091	-1000
TCR signaling in naïve CD8+ T cells	0.0401	25	2370	93	-0.065	0.037	1000	-1000	-0.089	-1000
LPA receptor mediated events	0.0385	24	2480	102	-0.2	0.024	1000	-1000	-0.09	-1000
IL12-mediated signaling events	0.0369	23	2032	87	-0.18	0.034	1000	-1000	-0.15	-1000
Visual signal transduction: Cones	0.0369	23	907	38	-0.12	0.013	1000	-1000	-0.034	-1000
Nectin adhesion pathway	0.0369	23	1503	63	-0.68	0.041	1000	-1000	-0.065	-1000
S1P5 pathway	0.0369	23	398	17	-0.14	0.054	1000	-1000	-0.036	-1000
HIF-2-alpha transcription factor network	0.0369	23	995	43	-0.34	0.16	1000	-1000	-0.07	-1000
Signaling events regulated by Ret tyrosine kinase	0.0353	22	1812	82	-0.15	0.013	1000	-1000	-0.088	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0353	22	1195	52	-0.19	0.028	1000	-1000	-0.04	-1000
ErbB4 signaling events	0.0321	20	1426	69	-0.29	0.066	1000	-1000	-0.11	-1000
Retinoic acid receptors-mediated signaling	0.0321	20	1176	58	-0.25	0.026	1000	-1000	-0.069	-1000
S1P4 pathway	0.0321	20	503	25	-0.14	0.023	1000	-1000	-0.041	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0305	19	532	28	-0.14	0.023	1000	-1000	-0.043	-1000
Noncanonical Wnt signaling pathway	0.0305	19	502	26	-0.14	0.013	1000	-1000	-0.065	-1000
EGFR-dependent Endothelin signaling events	0.0305	19	409	21	-0.086	0.019	1000	-1000	-0.068	-1000
Thromboxane A2 receptor signaling	0.0289	18	1902	105	-0.22	0.074	1000	-1000	-0.07	-1000
Signaling events mediated by HDAC Class III	0.0289	18	726	40	-0.14	0.023	1000	-1000	-0.03	-1000
S1P1 pathway	0.0289	18	678	36	-0.14	0.015	1000	-1000	-0.059	-1000
Signaling mediated by p38-alpha and p38-beta	0.0289	18	803	44	-0.038	0.013	1000	-1000	-0.047	-1000
Glypican 2 network	0.0289	18	75	4	-0.011	-0.005	1000	-1000	-0.02	-1000
IL27-mediated signaling events	0.0289	18	929	51	-0.18	0.023	1000	-1000	-0.075	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0273	17	2043	120	-0.13	0.11	1000	-1000	-0.071	-1000
Arf6 signaling events	0.0241	15	961	62	-0.13	0.031	1000	-1000	-0.05	-1000
Signaling events mediated by PTP1B	0.0241	15	1203	76	-0.34	0.052	1000	-1000	-0.087	-1000
IL6-mediated signaling events	0.0241	15	1164	75	-0.11	0.05	1000	-1000	-0.075	-1000
S1P3 pathway	0.0241	15	666	42	-0.14	0.025	1000	-1000	-0.041	-1000
Regulation of nuclear SMAD2/3 signaling	0.0225	14	1976	136	-0.42	0.092	1000	-1000	-0.062	-1000
Aurora A signaling	0.0225	14	864	60	-0.24	0.035	1000	-1000	-0.037	-1000
Integrins in angiogenesis	0.0225	14	1243	84	-0.31	0.031	1000	-1000	-0.085	-1000
Nongenotropic Androgen signaling	0.0225	14	773	52	-0.14	0.025	1000	-1000	-0.058	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0209	13	463	34	-0.01	0.017	1000	-1000	-0.041	-1000
Regulation of Telomerase	0.0209	13	1332	102	-0.37	0.042	1000	-1000	-0.11	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0193	12	457	37	-0.18	0.033	1000	-1000	-0.056	-1000
Signaling mediated by p38-gamma and p38-delta	0.0193	12	188	15	-0.042	0.023	1000	-1000	-0.037	-1000
Regulation of Androgen receptor activity	0.0193	12	843	70	-0.2	0.025	1000	-1000	-0.075	-1000
FAS signaling pathway (CD95)	0.0177	11	562	47	-0.055	0.027	1000	-1000	-0.056	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0177	11	375	33	-0.14	0.036	1000	-1000	-0.041	-1000
Coregulation of Androgen receptor activity	0.0161	10	796	76	-0.19	0.047	1000	-1000	-0.034	-1000
a4b1 and a4b7 Integrin signaling	0.0161	10	50	5	-0.003	0.009	1000	-1000	-0.024	-1000
Cellular roles of Anthrax toxin	0.0161	10	410	39	-0.053	0.013	1000	-1000	-0.022	-1000
IFN-gamma pathway	0.0161	10	744	68	-0.065	0.031	1000	-1000	-0.097	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0144	9	763	83	-0.25	0.061	1000	-1000	-0.076	-1000
Class I PI3K signaling events	0.0144	9	679	73	-0.14	0.031	1000	-1000	-0.072	-1000
Aurora B signaling	0.0144	9	668	67	-0.36	0.075	1000	-1000	-0.058	-1000
ErbB2/ErbB3 signaling events	0.0128	8	568	65	-0.049	0.032	1000	-1000	-0.072	-1000
PDGFR-beta signaling pathway	0.0128	8	861	97	-0.18	0.043	1000	-1000	-0.083	-1000
Rapid glucocorticoid signaling	0.0112	7	143	20	-0.01	0.013	1000	-1000	-0.029	-1000
Hedgehog signaling events mediated by Gli proteins	0.0096	6	430	65	-0.14	0.051	1000	-1000	-0.069	-1000
Ceramide signaling pathway	0.0096	6	524	76	-0.086	0.044	1000	-1000	-0.053	-1000
FoxO family signaling	0.0096	6	432	64	-0.099	0.091	1000	-1000	-0.085	-1000
Regulation of p38-alpha and p38-beta	0.0096	6	373	54	-0.14	0.032	1000	-1000	-0.066	-1000
TCGA08_rtk_signaling	0.0096	6	178	26	-0.053	0.039	1000	-1000	-0.024	-1000
EPO signaling pathway	0.0080	5	320	55	-0.019	0.045	1000	-1000	-0.091	-1000
IGF1 pathway	0.0080	5	297	57	-0.082	0.026	1000	-1000	-0.1	-1000
VEGFR1 specific signals	0.0080	5	295	56	-0.026	0.042	1000	-1000	-0.066	-1000
Class IB PI3K non-lipid kinase events	0.0080	5	15	3	-0.009	0.009	1000	-1000	-0.018	-1000
FOXM1 transcription factor network	0.0080	5	298	51	-0.14	0.13	1000	-1000	-0.23	-1000
Signaling events mediated by HDAC Class II	0.0064	4	332	75	-0.046	0.03	1000	-1000	-0.041	-1000
IL2 signaling events mediated by PI3K	0.0064	4	239	58	-0.056	0.055	1000	-1000	-0.084	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0064	4	368	74	-0.086	0.063	1000	-1000	-0.092	-1000
E-cadherin signaling in keratinocytes	0.0064	4	210	43	-0.1	0.045	1000	-1000	-0.05	-1000
PLK2 and PLK4 events	0.0048	3	10	3	0.006	0.014	1000	-1000	-0.028	-1000
PLK1 signaling events	0.0048	3	333	85	-0.04	0.03	1000	-1000	-0.043	-1000
PDGFR-alpha signaling pathway	0.0048	3	151	44	-0.005	0.028	1000	-1000	-0.048	-1000
TRAIL signaling pathway	0.0048	3	167	48	-0.038	0.04	1000	-1000	-0.06	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0048	3	151	45	-0.013	0.056	1000	-1000	-0.094	-1000
IL2 signaling events mediated by STAT5	0.0048	3	81	22	0.002	0.058	1000	-1000	-0.064	-1000
Insulin Pathway	0.0048	3	242	74	-0.032	0.033	1000	-1000	-0.1	-1000
LPA4-mediated signaling events	0.0032	2	26	12	-0.094	0.016	1000	-1000	-0.032	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0032	2	226	85	-0.015	0.049	1000	-1000	-0.067	-1000
Arf6 downstream pathway	0.0032	2	94	43	-0.027	0.03	1000	-1000	-0.035	-1000
ceramide signaling pathway	0.0032	2	118	49	-0.008	0.045	1000	-1000	-0.056	-1000
Paxillin-dependent events mediated by a4b1	0.0032	2	81	36	-0.028	0.029	1000	-1000	-0.063	-1000
E-cadherin signaling in the nascent adherens junction	0.0032	2	153	76	-0.028	0.051	1000	-1000	-0.085	-1000
Arf6 trafficking events	0.0032	2	211	71	-0.037	0.035	1000	-1000	-0.073	-1000
p38 MAPK signaling pathway	0.0032	2	98	44	-0.028	0.034	1000	-1000	-0.066	-1000
Canonical NF-kappaB pathway	0.0016	1	52	39	-0.008	0.067	1000	-1000	-0.086	-1000
Circadian rhythm pathway	0.0016	1	28	22	-0.012	0.043	1000	-1000	-0.057	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0016	1	220	125	-0.002	0.073	1000	-1000	-0.091	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	8	23	0.011	0.039	1000	-1000	-0.049	-1000
BARD1 signaling events	0.0000	0	31	57	-0.031	0.059	1000	-1000	-0.058	-1000
Aurora C signaling	0.0000	0	4	7	0	0.023	1000	-1000	-0.028	-1000
Insulin-mediated glucose transport	0.0000	0	25	32	-0.002	0.038	1000	-1000	-0.047	-1000
mTOR signaling pathway	0.0000	0	29	53	-0.001	0.033	1000	-1000	-0.064	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	18	68	-0.037	0.049	1000	-1000	-0.055	-1000
Signaling events mediated by HDAC Class I	0.0000	0	84	104	-0.025	0.047	1000	-1000	-0.061	-1000
Atypical NF-kappaB pathway	0.0000	0	11	31	0	0.041	1000	-1000	-0.047	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	17	27	0	0.031	1000	-1000	-0.048	-1000
E-cadherin signaling events	0.0000	0	1	5	0.012	0.025	1000	-1000	-0.024	-1000
Arf1 pathway	0.0000	0	37	54	-0.002	0.025	1000	-1000	-0.037	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.037	1000	-1000	-0.046	-1000
Total	NA	3314	182016	7203	-23	6.3	131000	-131000	-8.9	-131000

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.12	0.18	-10000	0	-0.36	219	219
CDKN2C	0.022	0.031	-10000	0	-10000	0	0
CDKN2A	-0.14	0.31	-10000	0	-0.77	120	120
CCND2	0.093	0.1	0.19	306	-10000	0	306
RB1	-0.091	0.11	-10000	0	-0.2	308	308
CDK4	0.095	0.12	0.2	308	-10000	0	308
CDK6	0.097	0.12	0.21	308	-10000	0	308
G1/S progression	0.091	0.11	0.2	306	-10000	0	306

×

Syndecan-1-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.011	0.031	-9999	-0.75	1	1
CCL5	-0.004	0.08	-9999	-0.4	25	25
SDCBP	0.011	0.023	-9999	-0.4	2	2
FGFR/FGF2/Syndecan-1	-0.34	0.14	-9999	-0.44	408	408
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.32	0.14	-9999	-0.41	411	411
Syndecan-1/Syntenin	-0.32	0.14	-9999	-0.41	408	408
MAPK3	-0.28	0.13	-9999	-0.51	46	46
HGF/MET	0.006	0.077	-9999	-0.38	20	20
TGFB1/TGF beta receptor Type II	0.011	0.031	-9999	-0.75	1	1
BSG	0.012	0.016	-9999	-0.4	1	1
keratinocyte migration	-0.32	0.14	-9999	-0.41	411	411
Syndecan-1/RANTES	-0.33	0.14	-9999	-0.41	420	420
Syndecan-1/CD147	-0.3	0.13	-9999	-0.39	406	406
Syndecan-1/Syntenin/PIP2	-0.31	0.13	-9999	-0.4	408	408
LAMA5	0.007	0.063	-9999	-0.68	5	5
positive regulation of cell-cell adhesion	-0.3	0.13	-9999	-0.39	408	408
MMP7	-0.72	0.16	-9999	-0.75	595	595
HGF	0.002	0.067	-9999	-0.42	15	15
Syndecan-1/CASK	-0.32	0.14	-9999	-0.42	408	408
Syndecan-1/HGF/MET	-0.31	0.14	-9999	-0.4	412	412
regulation of cell adhesion	-0.27	0.12	-9999	-0.51	41	41
HPSE	0.008	0.043	-9999	-0.4	7	7
positive regulation of cell migration	-0.34	0.14	-9999	-0.44	408	408
SDC1	-0.34	0.14	-9999	-0.44	408	408
Syndecan-1/Collagen	-0.34	0.14	-9999	-0.44	408	408
PPIB	0.013	0	-9999	-10000	0	0
MET	0.005	0.075	-9999	-0.75	6	6
PRKACA	0.013	0	-9999	-10000	0	0
MMP9	-0.045	0.2	-9999	-0.72	49	49
MAPK1	-0.28	0.13	-9999	-0.53	41	41
homophilic cell adhesion	-0.34	0.14	-9999	-0.43	408	408
MMP1	-0.48	0.36	-9999	-0.75	405	405

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.018	0.024	-9999	-0.57	1	1
VLDLR	-0.021	0.11	-9999	-0.4	52	52
CRKL	0.013	0	-9999	-10000	0	0
LRPAP1	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
ITGA3	0.012	0.016	-9999	-0.4	1	1
RELN/VLDLR/Fyn	-0.11	0.14	-9999	-0.43	38	38
MAPK8IP1/MKK7/MAP3K11/JNK1	0.036	0.03	-9999	-0.48	2	2
AKT1	-0.12	0.15	-9999	-0.41	72	72
MAP2K7	0.012	0.016	-9999	-0.4	1	1
RAPGEF1	0.012	0.016	-9999	-0.4	1	1
DAB1	-0.079	0.24	-9999	-0.75	73	73
RELN/LRP8/DAB1	-0.45	0.27	-9999	-0.59	459	459
LRPAP1/LRP8	-0.39	0.27	-9999	-0.57	431	431
RELN/LRP8/DAB1/Fyn	-0.43	0.26	-9999	-0.55	459	459
DAB1/alpha3/beta1 Integrin	-0.4	0.24	-9999	-0.52	459	459
long-term memory	-0.58	0.33	-9999	-0.7	500	500
DAB1/LIS1	-0.41	0.26	-9999	-0.54	459	459
DAB1/CRLK/C3G	-0.4	0.24	-9999	-0.52	459	459
PIK3CA	0.012	0.016	-9999	-0.4	1	1
DAB1/NCK2	-0.42	0.26	-9999	-0.54	459	459
ARHGEF2	0.013	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.099	0.18	-9999	-0.4	164	164
CDK5R1	0.011	0.031	-9999	-0.75	1	1
RELN	-0.18	0.2	-9999	-0.4	300	300
PIK3R1	0.013	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.43	0.26	-9999	-0.59	431	431
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.47	0.28	-9999	-0.59	481	481
MAPK8	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.15	0.2	-9999	-0.5	108	108
ITGB1	0.013	0	-9999	-10000	0	0
MAP1B	-0.42	0.26	-9999	-0.53	471	471
RELN/LRP8	-0.43	0.26	-9999	-0.59	431	431
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.56	0.33	-9999	-0.68	500	500
PI3K	0.018	0.011	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.018	0.011	-9999	-0.27	1	1
RAP1A	-0.37	0.23	-9999	-0.58	260	260
PAFAH1B1	0.013	0	-9999	-10000	0	0
MAPK8IP1	0.011	0.035	-9999	-0.57	2	2
CRLK/C3G	0.018	0.011	-9999	-0.27	1	1
GRIN2B	-0.24	0.36	-9999	-0.75	207	207
NCK2	0.013	0	-9999	-10000	0	0
neuron differentiation	-0.21	0.14	-9999	-0.35	252	252
neuron adhesion	-0.35	0.22	-9999	-0.55	260	260
LRP8	-0.52	0.35	-9999	-0.75	431	431
GSK3B	-0.1	0.14	-9999	-0.38	72	72
RELN/VLDLR/DAB1/Fyn	-0.14	0.19	-9999	-0.47	108	108
MAP3K11	0.012	0.016	-9999	-0.4	1	1
RELN/VLDLR/DAB1/P13K	-0.13	0.16	-9999	-0.44	72	72
CDK5	0.013	0	-9999	-10000	0	0
MAPT	-0.063	0.16	-9999	-0.34	146	146
neuron migration	-0.32	0.2	-9999	-0.51	271	271
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.21	0.14	-9999	-0.36	252	252
RELN/VLDLR	-0.41	0.25	-9999	-0.55	442	442

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.15	0.22	-9999	-0.41	263	263
NF kappa B1 p50/RelA/I kappa B alpha	-0.12	0.2	-9999	-0.5	33	33
alphaV/beta3 Integrin/Osteopontin/Src	-0.23	0.29	-9999	-0.56	263	263
AP1	-0.12	0.22	-9999	-0.68	9	9
ILK	-0.16	0.23	-9999	-0.43	263	263
bone resorption	-0.12	0.2	-9999	-0.47	6	6
PTK2B	0.011	0.023	-9999	-0.4	2	2
PYK2/p130Cas	-0.14	0.22	-9999	-0.39	263	263
ITGAV	0.015	0.004	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.018	0.016	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.19	0.26	-9999	-0.48	263	263
MAP3K1	-0.17	0.23	-9999	-0.44	263	263
JUN	0.013	0.001	-9999	-10000	0	0
MAPK3	-0.15	0.23	-9999	-0.41	263	263
MAPK1	-0.15	0.23	-9999	-0.41	263	263
Rac1/GDP	0.009	0	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	-0.15	0.22	-9999	-0.4	263	263
ITGB3	0.01	0.043	-9999	-0.39	7	7
NFKBIA	-0.14	0.22	-9999	-0.38	263	263
FOS	0.006	0.051	-9999	-0.39	10	10
CD44	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
PLAU	-0.14	0.25	-9999	-0.83	32	32
NF kappa B1 p50/RelA	-0.15	0.18	-9999	-0.55	33	33
BCAR1	0.012	0.016	-9999	-0.4	1	1
RELA	0.013	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.02	0.031	-9999	-0.28	1	1
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.17	0.23	-9999	-0.44	263	263
VAV3	-0.17	0.23	-9999	-0.43	263	263
MAP3K14	-0.17	0.24	-9999	-0.44	263	263
ROCK2	0.011	0.023	-9999	-0.4	2	2
SPP1	-0.31	0.38	-9999	-0.74	267	267
RAC1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.15	0.22	-9999	-0.39	263	263
MMP2	-0.096	0.19	-9999	-0.82	6	6

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.013	0	-9999	-10000	0	0
VLDLR	-0.021	0.11	-9999	-0.4	52	52
LRPAP1	0.013	0	-9999	-10000	0	0
NUDC	0.013	0	-9999	-10000	0	0
RELN/LRP8	-0.43	0.26	-9999	-0.59	431	431
CaM/Ca2+	0.009	0	-9999	-10000	0	0
KATNA1	0.013	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.39	0.24	-9999	-0.54	431	431
IQGAP1/CaM	0.019	0	-9999	-10000	0	0
DAB1	-0.079	0.24	-9999	-0.75	73	73
IQGAP1	0.013	0	-9999	-10000	0	0
PLA2G7	0.009	0.04	-9999	-0.4	6	6
CALM1	0.013	0	-9999	-10000	0	0
DYNLT1	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.39	0.27	-9999	-0.57	431	431
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.012	0.016	-9999	-0.4	1	1
CDK5R1	0.011	0.031	-9999	-0.75	1	1
LIS1/Poliovirus Protein 3A	0.014	0	-9999	-10000	0	0
CDK5R2	-0.034	0.14	-9999	-0.43	63	63
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.17	0.21	-9999	-0.55	108	108
YWHAE	0.013	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.31	0.2	-9999	-0.5	236	236
MAP1B	-0.006	0.039	-9999	-0.25	16	16
RAC1	0.019	0	-9999	-10000	0	0
p35/CDK5	-0.34	0.22	-9999	-0.47	431	431
RELN	-0.18	0.2	-9999	-0.4	300	300
PAFAH/LIS1	0.021	0.023	-9999	-10000	0	0
LIS1/CLIP170	0.023	0.01	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.25	0.15	-9999	-0.4	236	236
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.13	0.17	-9999	-0.48	76	76
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.34	0.21	-9999	-0.54	236	236
LIS1/IQGAP1	0.024	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
PAFAH1B1	0.019	0	-9999	-10000	0	0
PAFAH1B3	-0.001	0.1	-9999	-0.75	11	11
PAFAH1B2	0.013	0.001	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.018	0.026	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.3	0.19	-9999	-0.48	236	236
LRP8	-0.52	0.35	-9999	-0.75	431	431
NDEL1/Katanin 60	-0.31	0.2	-9999	-0.5	236	236
P39/CDK5	-0.36	0.22	-9999	-0.49	432	432
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.024	0	-9999	-10000	0	0
CDK5	-0.36	0.22	-9999	-0.5	431	431
PPP2R5D	0.013	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.02	0.008	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.13	0.19	-9999	-0.47	108	108
RELN/VLDLR	-0.41	0.25	-9999	-0.55	442	442
CDC42	0.017	0.021	-9999	-0.35	2	2

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.42	0.33	-9999	-0.99	100	100
PCK1	-0.7	0.6	-9999	-1.4	276	276
HNF4A	-0.49	0.39	-9999	-1.1	122	122
KCNJ11	-0.42	0.34	-9999	-1	100	100
AKT1	-0.22	0.13	-9999	-10000	0	0
response to starvation	-0.016	0.026	-9999	-10000	0	0
DLK1	-0.44	0.35	-9999	-1	105	105
NKX2-1	-0.25	0.24	-9999	-0.77	75	75
ACADM	-0.43	0.34	-9999	-1	100	100
TAT	-0.66	0.58	-9999	-1.3	272	272
CEBPB	-0.005	0.083	-9999	-0.75	7	7
CEBPA	0.004	0.035	-9999	-0.4	3	3
TTR	-0.45	0.46	-9999	-1.1	190	190
PKLR	-0.49	0.4	-9999	-1.1	155	155
APOA1	-0.52	0.41	-9999	-1.2	114	114
CPT1C	-0.42	0.33	-9999	-0.97	111	111
ALAS1	-0.2	0.13	-9999	-10000	0	0
TFRC	-0.36	0.23	-9999	-0.73	79	79
FOXF1	0.022	0.067	-9999	-0.39	10	10
NF1	0.018	0	-9999	-10000	0	0
HNF1A (dimer)	-0.088	0.054	-9999	-0.46	2	2
CPT1A	-0.42	0.33	-9999	-0.96	113	113
HMGCS1	-0.42	0.33	-9999	-0.99	102	102
NR3C1	-0.079	0.12	-9999	-0.43	46	46
CPT1B	-0.42	0.33	-9999	-1	98	98
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	-0.081	0.042	-9999	-10000	0	0
GCK	-0.43	0.34	-9999	-1	104	104
CREB1	-0.046	0.073	-9999	-10000	0	0
IGFBP1	-0.33	0.28	-9999	-0.8	130	130
PDX1	-0.63	0.24	-9999	-0.78	364	364
UCP2	-0.42	0.33	-9999	-0.98	103	103
ALDOB	-0.48	0.39	-9999	-1.1	140	140
AFP	-0.12	0.2	-9999	-0.69	55	55
BDH1	-0.42	0.33	-9999	-1	91	91
HADH	-0.42	0.33	-9999	-1	93	93
F2	-0.58	0.44	-9999	-1.2	156	156
HNF1A	-0.088	0.054	-9999	-0.46	2	2
G6PC	-0.2	0.31	-9999	-1.3	45	45
SLC2A2	-0.33	0.2	-9999	-0.98	20	20
INS	0.009	0.041	-9999	-10000	0	0
FOXA1	-0.044	0.15	-9999	-0.39	63	63
FOXA3	-0.13	0.13	-9999	-0.38	67	67
FOXA2	-0.49	0.37	-9999	-1.1	107	107
ABCC8	-0.47	0.39	-9999	-1.1	146	146
ALB	-0.13	0.22	-9999	-0.64	79	79

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.53	0.5	-10000	0	-1.2	150	150
STAT6 (cleaved dimer)	-0.6	0.5	-10000	0	-1.2	217	217
IGHG1	-0.18	0.17	-10000	0	-0.5	6	6
IGHG3	-0.52	0.48	-10000	0	-1.1	181	181
AKT1	-0.27	0.27	-10000	0	-0.68	74	74
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.2	0.21	-10000	0	-1.1	3	3
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.26	0.25	-10000	0	-0.76	15	15
THY1	-0.54	0.52	-10000	0	-1.2	157	157
MYB	0.011	0.023	-10000	0	-0.4	2	2
HMGA1	0.01	0.043	-10000	0	-0.75	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.37	0.34	-10000	0	-0.82	151	151
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.26	0.25	-10000	0	-0.72	22	22
SP1	0.018	0.008	-10000	0	-10000	0	0
INPP5D	0.012	0.016	-10000	0	-0.4	1	1
SOCS5	0.033	0.018	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.56	0.53	-10000	0	-1.2	197	197
SOCS1	-0.37	0.33	-10000	0	-0.78	134	134
SOCS3	-0.3	0.29	-10000	0	-0.76	85	85
FCER2	-0.81	0.66	-10000	0	-1.4	320	320
PARP14	0.004	0.016	-10000	0	-10000	0	0
CCL17	-0.54	0.51	-10000	0	-1.2	154	154
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.2	0.2	-10000	0	-0.81	4	4
T cell proliferation	-0.54	0.52	-10000	0	-1.3	154	154
IL4R/JAK1	-0.54	0.51	-10000	0	-1.2	154	154
EGR2	-0.61	0.54	-10000	0	-1.3	176	176
JAK2	-0.019	0.041	-10000	0	-0.43	3	3
JAK3	0.009	0.032	-10000	0	-0.75	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
JAK1	0.004	0.019	-10000	0	-0.39	1	1
COL1A2	-0.18	0.22	-10000	0	-0.8	39	39
CCL26	-0.57	0.53	-10000	0	-1.3	170	170
IL4R	-0.57	0.54	-10000	0	-1.3	153	153
PTPN6	0.025	0.011	-10000	0	-10000	0	0
IL13RA2	-0.56	0.52	-10000	0	-1.2	170	170
IL13RA1	-0.017	0.03	-10000	0	-10000	0	0
IRF4	-0.45	0.63	-10000	0	-1.4	170	170
ARG1	-0.13	0.15	-10000	0	-0.67	9	9
CBL	-0.34	0.32	-10000	0	-0.8	136	136
GTF3A	-0.019	0.15	-10000	0	-0.77	24	24
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
IL13RA1/JAK2	-0.022	0.048	-10000	0	-10000	0	0
IRF4/BCL6	-0.39	0.58	-10000	0	-1.3	170	170
CD40LG	-0.027	0.11	-10000	0	-0.41	44	44
MAPK14	-0.34	0.32	-10000	0	-0.8	132	132
mitosis	-0.26	0.26	-10000	0	-0.65	73	73
STAT6	-0.61	0.6	-10000	0	-1.4	179	179
SPI1	0.009	0.049	-10000	0	-0.39	9	9
RPS6KB1	-0.24	0.25	-10000	0	-0.66	37	37
STAT6 (dimer)	-0.6	0.6	-10000	0	-1.4	179	179
STAT6 (dimer)/PARP14	-0.62	0.56	-10000	0	-1.3	195	195
mast cell activation	0.013	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.26	0.26	-10000	0	-0.67	63	63
FRAP1	-0.27	0.27	-10000	0	-0.69	74	74
LTA	-0.53	0.52	-10000	0	-1.3	138	138
FES	0.011	0.028	-10000	0	-0.4	3	3
T-helper 1 cell differentiation	0.59	0.58	1.3	179	-10000	0	179
CCL11	-0.57	0.56	-10000	0	-1.3	179	179
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.26	0.25	-10000	0	-0.66	53	53
IL2RG	0.008	0.03	-10000	0	-0.39	3	3
IL10	-0.56	0.55	-10000	0	-1.3	160	160
IRS1	0.013	0	-10000	0	-10000	0	0
IRS2	0.013	0	-10000	0	-10000	0	0
IL4	-0.12	0.12	-10000	0	-10000	0	0
IL5	-0.54	0.51	-10000	0	-1.2	156	156
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.42	0.38	-10000	0	-0.92	143	143
COL1A1	-0.28	0.31	-10000	0	-0.8	120	120
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.54	0.52	-10000	0	-1.3	136	136
IL2R gamma/JAK3	0.01	0.034	-10000	0	-0.57	1	1
TFF3	-0.55	0.53	-10000	0	-1.3	163	163
ALOX15	-0.56	0.53	-10000	0	-1.3	166	166
MYBL1	0.01	0.043	-10000	0	-0.75	2	2
T-helper 2 cell differentiation	-0.45	0.4	-10000	0	-0.97	156	156
SHC1	0.013	0	-10000	0	-10000	0	0
CEBPB	0.007	0.081	-10000	0	-0.75	7	7
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.24	0.24	-10000	0	-0.86	9	9
mol:PI-3-4-5-P3	-0.27	0.27	-10000	0	-0.69	74	74
PI3K	-0.28	0.28	-10000	0	-0.73	74	74
DOK2	0.003	0.06	-10000	0	-0.4	14	14
ETS1	0.025	0.021	-10000	0	-0.36	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.18	0.19	-10000	0	-0.76	4	4
ITGB3	-0.53	0.51	-10000	0	-1.2	154	154
PIGR	-0.71	0.67	-10000	0	-1.5	239	239
IGHE	0.042	0.046	0.26	1	-0.25	3	4
MAPKKK cascade	-0.18	0.18	-10000	0	-0.74	4	4
BCL6	0.018	0.01	-10000	0	-10000	0	0
OPRM1	-0.53	0.5	-10000	0	-1.2	154	154
RETNLB	-0.76	0.68	-10000	0	-1.5	272	272
SELP	-0.59	0.59	-10000	0	-1.4	167	167
AICDA	-0.51	0.49	-10000	0	-1.2	147	147

×

Glypican 1 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
GPC1/FGF2 dimer/FGFR1 dimer	0.005	0.07	-10000	0	-0.46	2	2
fibroblast growth factor receptor signaling pathway	0.005	0.07	-10000	0	-0.46	2	2
LAMA1	-0.11	0.18	-10000	0	-0.4	181	181
PRNP	0.011	0.023	-10000	0	-0.4	2	2
GPC1/SLIT2	-0.069	0.13	-10000	0	-0.57	1	1
SMAD2	0.025	0.026	-10000	0	-0.44	1	1
GPC1/PrPc/Cu2+	0.015	0.026	-10000	0	-0.5	1	1
GPC1/Laminin alpha1	-0.066	0.13	-10000	0	-0.57	1	1
TDGF1	-0.34	0.38	-10000	0	-0.74	295	295
CRIPTO/GPC1	-0.26	0.29	-10000	0	-0.57	288	288
APP/GPC1	0.017	0.029	-10000	0	-0.37	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.22	0.26	-10000	0	-0.49	288	288
FLT1	0.013	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.024	0.025	-10000	0	-0.49	1	1
SERPINC1	-0.004	0.096	-10000	0	-0.75	10	10
FYN	-0.22	0.25	-10000	0	-0.49	288	288
FGR	-0.22	0.26	-10000	0	-0.49	289	289
positive regulation of MAPKKK cascade	-0.19	0.2	-10000	0	-0.39	291	291
SLIT2	-0.11	0.19	-10000	0	-0.4	187	187
GPC1/NRG	-0.017	0.095	-10000	0	-0.57	1	1
NRG1	-0.035	0.13	-10000	0	-0.4	73	73
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.023	0.037	-10000	0	-0.49	3	3
LYN	-0.22	0.25	-10000	0	-0.49	288	288
mol:Spermine	0.008	0.026	-10000	0	-0.43	2	2
cell growth	0.005	0.07	-10000	0	-0.46	2	2
BMP signaling pathway	-0.011	0.035	0.57	2	-10000	0	2
SRC	-0.22	0.25	-10000	0	-0.49	288	288
TGFBR1	0.012	0.016	-10000	0	-0.4	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.1	0.19	-10000	0	-0.41	167	167
GPC1	0.011	0.035	-10000	0	-0.57	2	2
TGFBR1 (dimer)	0.012	0.016	-10000	0	-0.39	1	1
VEGFA	0.01	0.043	-10000	0	-0.75	2	2
BLK	-0.3	0.28	-10000	0	-0.57	290	290
HCK	-0.22	0.26	-10000	0	-0.5	288	288
FGF2	-0.017	0.1	-10000	0	-0.4	45	45
FGFR1	0.009	0.036	-10000	0	-0.4	5	5
VEGFR1 homodimer	0.013	0	-10000	0	-10000	0	0
TGFBR2	0.013	0	-10000	0	-10000	0	0
cell death	0.017	0.029	-10000	0	-0.37	3	3
ATIII/GPC1	0.004	0.078	-10000	0	-0.57	11	11
PLA2G2A/GPC1	-0.062	0.14	-10000	0	-0.57	7	7
LCK	-0.22	0.26	-10000	0	-0.49	296	296
neuron differentiation	-0.017	0.095	-10000	0	-0.57	1	1
PrPc/Cu2+	0.008	0.016	-10000	0	-0.28	2	2
APP	0.012	0.016	-10000	0	-0.4	1	1
TGFBR2 (dimer)	0.013	0	-10000	0	-10000	0	0

×

Syndecan-4-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
PTK2	-0.025	0.098	-9999	-0.39	37	37
Syndecan-4/Syndesmos	-0.16	0.22	-9999	-0.53	103	103
positive regulation of JNK cascade	-0.17	0.2	-9999	-0.48	132	132
Syndecan-4/ADAM12	-0.37	0.28	-9999	-0.61	278	278
CCL5	-0.004	0.08	-9999	-0.4	25	25
Rac1/GDP	0.009	0	-9999	-10000	0	0
DNM2	0.013	0	-9999	-10000	0	0
ITGA5	0.01	0.043	-9999	-0.75	2	2
SDCBP	0.011	0.023	-9999	-0.4	2	2
PLG	-0.16	0.31	-9999	-0.76	133	133
ADAM12	-0.4	0.38	-9999	-0.75	334	334
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.069	0.07	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.21	0.22	-9999	-0.53	158	158
Syndecan-4/CXCL12/CXCR4	-0.18	0.22	-9999	-0.51	132	132
Syndecan-4/Laminin alpha3	-0.16	0.22	-9999	-0.53	107	107
MDK	0.005	0.075	-9999	-0.75	6	6
Syndecan-4/FZD7	-0.16	0.22	-9999	-0.53	105	105
Syndecan-4/Midkine	-0.16	0.22	-9999	-0.53	111	111
FZD7	0.013	0	-9999	-10000	0	0
Syndecan-4/FGFR1/FGF	-0.16	0.21	-9999	-0.51	105	105
THBS1	0.011	0.035	-9999	-0.57	2	2
integrin-mediated signaling pathway	-0.16	0.21	-9999	-0.52	107	107
positive regulation of MAPKKK cascade	-0.17	0.2	-9999	-0.48	132	132
Syndecan-4/TACI	-0.24	0.23	-9999	-0.52	201	201
CXCR4	0.013	0	-9999	-10000	0	0
cell adhesion	0.013	0.071	-9999	-0.28	29	29
Syndecan-4/Dynamin	-0.16	0.22	-9999	-0.53	105	105
Syndecan-4/TSP1	-0.16	0.22	-9999	-0.54	104	104
Syndecan-4/GIPC	-0.16	0.22	-9999	-0.53	105	105
Syndecan-4/RANTES	-0.17	0.22	-9999	-0.53	115	115
ITGB1	0.013	0	-9999	-10000	0	0
LAMA1	-0.11	0.18	-9999	-0.4	181	181
LAMA3	0.008	0.047	-9999	-0.45	6	6
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.047	0.049	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.16	0.22	-9999	-0.53	105	105
TFPI	0.009	0.036	-9999	-0.4	5	5
F2	-0.25	0.36	-9999	-0.75	214	214
alpha5/beta1 Integrin	0.017	0.033	-9999	-0.57	2	2
positive regulation of cell adhesion	-0.2	0.22	-9999	-0.52	149	149
ACTN1	0.013	0	-9999	-10000	0	0
TNC	-0.001	0.092	-9999	-0.56	15	15
Syndecan-4/CXCL12	-0.19	0.22	-9999	-0.52	145	145
FGF6	-0.002	0.043	-9999	-0.75	2	2
RHOA	0.013	0	-9999	-10000	0	0
CXCL12	-0.065	0.16	-9999	-0.4	119	119
TNFRSF13B	-0.17	0.2	-9999	-0.4	270	270
FGF2	-0.017	0.1	-9999	-0.4	45	45
FGFR1	0.009	0.036	-9999	-0.4	5	5
Syndecan-4/PI-4-5-P2	-0.16	0.21	-9999	-0.53	105	105
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.025	0.17	-9999	-0.67	37	37
cell migration	-0.025	0.025	-9999	-10000	0	0
PRKCD	0.016	0.011	-9999	-10000	0	0
vasculogenesis	-0.15	0.21	-9999	-0.52	104	104
SDC4	-0.17	0.23	-9999	-0.56	105	105
Syndecan-4/Tenascin C	-0.16	0.22	-9999	-0.54	107	107
Syndecan-4/PI-4-5-P2/PKC alpha	-0.054	0.055	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.16	0.22	-9999	-0.53	106	106
MMP9	-0.048	0.2	-9999	-0.73	49	49
Rac1/GTP	0.013	0.072	-9999	-0.28	29	29
cytoskeleton organization	-0.15	0.21	-9999	-0.51	103	103
GIPC1	0.012	0.016	-9999	-0.4	1	1
Syndecan-4/TFPI	-0.16	0.22	-9999	-0.53	107	107

×

Ephrin A reverse 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
MAPKKK cascade	-0.055	0.12	-9999	-0.26	92	92
EFNA5	-0.084	0.17	-9999	-0.4	147	147
FYN	-0.043	0.11	-9999	-0.39	13	13
neuron projection morphogenesis	-0.055	0.12	-9999	-0.26	92	92
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.055	0.12	-9999	-0.26	92	92
EPHA5	-0.014	0.087	-9999	-0.4	31	31

×

BCR signaling pathway

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
JUN	-0.087	0.18	-9999	-0.45	100	100
IKBKB	-0.037	0.093	-9999	-0.25	47	47
AKT1	-0.064	0.12	-9999	-0.27	91	91
IKBKG	-0.039	0.1	-9999	-0.27	49	49
CALM1	-0.11	0.21	-9999	-0.52	105	105
PIK3CA	0.012	0.016	-9999	-0.4	1	1
MAP3K1	-0.14	0.27	-9999	-0.64	113	113
MAP3K7	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.12	0.22	-9999	-0.55	107	107
DOK1	0.013	0	-9999	-10000	0	0
AP-1	-0.043	0.11	-9999	-0.26	87	87
LYN	0.013	0	-9999	-10000	0	0
BLNK	0.007	0.049	-9999	-0.39	9	9
SHC1	0.013	0	-9999	-10000	0	0
BCR complex	-0.12	0.19	-9999	-0.51	78	78
CD22	-0.19	0.32	-9999	-0.67	161	161
CAMK2G	-0.094	0.19	-9999	-0.5	93	93
CSNK2A1	0.013	0	-9999	-10000	0	0
INPP5D	0.012	0.016	-9999	-0.4	1	1
SHC/GRB2/SOS1	-0.075	0.11	-9999	-0.48	4	4
GO:0007205	-0.12	0.23	-9999	-0.56	107	107
SYK	0.013	0	-9999	-10000	0	0
ELK1	-0.11	0.21	-9999	-0.53	105	105
NFATC1	-0.13	0.23	-9999	-0.47	163	163
B-cell antigen/BCR complex	-0.12	0.19	-9999	-0.51	78	78
PAG1/CSK	0.013	0.039	-9999	-10000	0	0
NFKBIB	-0.003	0.032	-9999	-10000	0	0
HRAS	-0.091	0.18	-9999	-0.48	92	92
NFKBIA	-0.003	0.032	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.003	0.026	-9999	-10000	0	0
RasGAP/Csk	-0.087	0.18	-9999	-0.44	97	97
mol:GDP	-0.12	0.21	-9999	-0.54	105	105
PTEN	0.011	0.023	-9999	-0.4	2	2
CD79B	-0.041	0.14	-9999	-0.39	82	82
NF-kappa-B/RelA/I kappa B alpha	0.004	0.026	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.16	0.26	-9999	-0.54	173	173
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	-0.12	0.23	-9999	-0.57	107	107
CSK	0.013	0	-9999	-10000	0	0
FOS	-0.098	0.2	-9999	-0.51	98	98
CHUK	-0.039	0.099	-9999	-0.26	54	54
IBTK	0.012	0.016	-9999	-0.4	1	1
CARD11/BCL10/MALT1/TAK1	-0.11	0.19	-9999	-0.52	86	86
PTPN6	-0.18	0.3	-9999	-0.63	160	160
RELA	0.013	0	-9999	-10000	0	0
BCL2A1	0.004	0.026	-9999	-0.12	10	10
VAV2	-0.19	0.32	-9999	-0.64	168	168
ubiquitin-dependent protein catabolic process	0	0.031	-9999	-10000	0	0
BTK	-0.13	0.35	-9999	-1.1	73	73
CD19	-0.19	0.32	-9999	-0.65	165	165
MAP4K1	-0.023	0.12	-9999	-0.4	54	54
CD72	0.012	0.016	-9999	-0.4	1	1
PAG1	0.005	0.056	-9999	-0.4	12	12
MAPK14	-0.11	0.22	-9999	-0.54	107	107
SH3BP5	0.009	0.036	-9999	-0.4	5	5
PIK3AP1	-0.11	0.22	-9999	-0.59	94	94
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.14	0.26	-9999	-0.65	102	102
RAF1	-0.081	0.17	-9999	-0.46	86	86
RasGAP/p62DOK/SHIP	-0.081	0.17	-9999	-0.52	42	42
CD79A	-0.14	0.2	-9999	-0.39	228	228
re-entry into mitotic cell cycle	-0.044	0.11	-9999	-0.27	87	87
RASA1	0.013	0.001	-9999	-10000	0	0
MAPK3	-0.058	0.14	-9999	-0.42	58	58
MAPK1	-0.058	0.14	-9999	-0.42	58	58
CD72/SHP1	-0.16	0.28	-9999	-0.58	160	160
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	-0.11	0.22	-9999	-0.54	105	105
actin cytoskeleton organization	-0.15	0.26	-9999	-0.53	165	165
NF-kappa-B/RelA	0.011	0.052	-9999	-0.26	1	1
Calcineurin	-0.076	0.18	-9999	-0.47	86	86
PI3K	-0.17	0.22	-9999	-0.53	136	136
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.12	0.24	-9999	-0.58	107	107
SOS1	0.013	0	-9999	-10000	0	0
Bam32/HPK1	-0.17	0.33	-9999	-0.82	112	112
DAPP1	-0.2	0.36	-9999	-0.95	102	102
cytokine secretion	-0.12	0.22	-9999	-0.44	163	163
mol:DAG	-0.12	0.23	-9999	-0.57	107	107
PLCG2	-0.019	0.11	-9999	-0.39	49	49
MAP2K1	-0.069	0.16	-9999	-0.42	83	83
B-cell antigen/BCR complex/FcgammaRIIB	-0.12	0.2	-9999	-0.52	97	97
mol:PI-3-4-5-P3	-0.12	0.15	-9999	-0.36	136	136
ETS1	-0.08	0.18	-9999	-0.47	85	85
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.067	0.15	-9999	-0.55	4	4
B-cell antigen/BCR complex/LYN	-0.17	0.28	-9999	-0.72	109	109
MALT1	0.012	0.016	-9999	-0.39	1	1
TRAF6	0.013	0	-9999	-10000	0	0
RAC1	-0.16	0.28	-9999	-0.58	165	165
B-cell antigen/BCR complex/LYN/SYK	-0.18	0.27	-9999	-0.72	104	104
CARD11	-0.13	0.23	-9999	-0.55	123	123
FCGR2B	-0.037	0.13	-9999	-0.4	75	75
PPP3CA	0.013	0	-9999	-10000	0	0
BCL10	0.012	0.016	-9999	-0.4	1	1
IKK complex	-0.008	0.041	-9999	-10000	0	0
PTPRC	-0.02	0.11	-9999	-0.4	50	50
PDPK1	-0.062	0.11	-9999	-0.26	84	84
PPP3CB	0.013	0	-9999	-10000	0	0
PPP3CC	0.012	0.016	-9999	-0.4	1	1
POU2F2	0.005	0.024	-9999	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.38	0.44	-10000	0	-1.1	103	103
IL23A	-0.46	0.5	-10000	0	-1.2	114	114
NF kappa B1 p50/RelA/I kappa B alpha	-0.44	0.42	-10000	0	-1.1	113	113
positive regulation of T cell mediated cytotoxicity	-0.41	0.49	-10000	0	-1.2	106	106
ITGA3	-0.38	0.44	-10000	0	-1.1	98	98
IL17F	-0.3	0.34	-10000	0	-0.79	123	123
IL12B	-0.012	0.069	-10000	0	-0.79	4	4
STAT1 (dimer)	-0.39	0.47	-10000	0	-1.2	105	105
CD4	-0.37	0.44	-10000	0	-1.2	91	91
IL23	-0.44	0.47	-10000	0	-1.2	108	108
IL23R	-0.077	0.22	-10000	0	-1.4	15	15
IL1B	-0.43	0.49	-10000	0	-1.3	100	100
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.47	0.49	-10000	0	-1.1	164	164
TYK2	-0.003	0.02	-10000	0	-10000	0	0
STAT4	-0.006	0.084	-10000	0	-0.4	28	28
STAT3	0.012	0.002	-10000	0	-10000	0	0
IL18RAP	-0.008	0.089	-10000	0	-0.4	29	29
IL12RB1	-0.018	0.084	-10000	0	-0.44	22	22
PIK3CA	0.011	0.017	-10000	0	-0.4	1	1
IL12Rbeta1/TYK2	-0.013	0.064	-10000	0	-0.33	16	16
IL23R/JAK2	-0.083	0.22	-10000	0	-1.3	15	15
positive regulation of chronic inflammatory response	-0.41	0.49	-10000	0	-1.2	106	106
natural killer cell activation	0.006	0.013	0.077	15	-10000	0	15
JAK2	-0.003	0.04	-10000	0	-0.42	3	3
PIK3R1	0.012	0.002	-10000	0	-10000	0	0
NFKB1	0.009	0.003	-10000	0	-10000	0	0
RELA	0.009	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.42	0.45	-10000	0	-1.1	108	108
ALOX12B	-0.36	0.43	-10000	0	-1.1	82	82
CXCL1	-0.47	0.49	-10000	0	-1.1	151	151
T cell proliferation	-0.41	0.49	-10000	0	-1.2	106	106
NFKBIA	0.009	0.003	-10000	0	-10000	0	0
IL17A	-0.29	0.3	-10000	0	-0.67	153	153
PI3K	-0.42	0.42	-10000	0	-1.1	113	113
IFNG	-0.016	0.038	0.15	10	-0.099	59	69
STAT3 (dimer)	-0.43	0.42	-10000	0	-1.1	122	122
IL18R1	0.006	0.051	-10000	0	-0.39	10	10
IL23/IL23R/JAK2/TYK2/SOCS3	-0.21	0.26	-10000	0	-0.75	33	33
IL18/IL18R	0.011	0.067	-10000	0	-0.45	2	2
macrophage activation	-0.026	0.017	-10000	0	-0.046	9	9
TNF	-0.42	0.47	-10000	0	-1.2	99	99
STAT3/STAT4	-0.42	0.42	-10000	0	-1.2	107	107
STAT4 (dimer)	-0.4	0.47	-10000	0	-1.2	107	107
IL18	0.01	0.033	-10000	0	-0.39	4	4
IL19	-0.37	0.43	-10000	0	-1.1	94	94
STAT5A (dimer)	-0.39	0.47	-10000	0	-1.2	105	105
STAT1	0.011	0.031	-10000	0	-0.75	1	1
SOCS3	0.01	0.043	-10000	0	-0.75	2	2
CXCL9	-0.4	0.46	-10000	0	-1.2	103	103
MPO	-0.37	0.43	-10000	0	-1.1	85	85
positive regulation of humoral immune response	-0.41	0.49	-10000	0	-1.2	106	106
IL23/IL23R/JAK2/TYK2	-0.43	0.52	-10000	0	-1.3	106	106
IL6	-0.42	0.48	-10000	0	-1.2	115	115
STAT5A	0.013	0	-10000	0	-10000	0	0
IL2	0.007	0.01	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.006	0.013	0.077	15	-10000	0	15
CD3E	-0.38	0.45	-10000	0	-1.2	97	97
keratinocyte proliferation	-0.41	0.49	-10000	0	-1.2	106	106
NOS2	-0.39	0.46	-10000	0	-1.2	106	106

×

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

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
MAP4K1	-0.047	0.18	-10000	0	-0.42	103	103
CRKL	-0.04	0.17	-10000	0	-0.42	99	99
HRAS	-0.029	0.17	-10000	0	-0.48	33	33
mol:PIP3	-0.047	0.16	-10000	0	-0.4	99	99
SPRED1	0.013	0	-10000	0	-10000	0	0
SPRED2	0.013	0	-10000	0	-10000	0	0
GAB1	-0.047	0.18	-10000	0	-0.44	99	99
FOXO3	-0.03	0.16	-10000	0	-0.38	99	99
AKT1	-0.039	0.17	-10000	0	-0.41	99	99
BAD	-0.03	0.16	-10000	0	-0.38	99	99
megakaryocyte differentiation	-0.08	0.21	-10000	0	-0.45	136	136
GSK3B	-0.03	0.16	-10000	0	-0.38	99	99
RAF1	-0.015	0.14	-10000	0	-0.38	33	33
SHC1	0.013	0	-10000	0	-10000	0	0
STAT3	-0.047	0.18	-10000	0	-0.44	99	99
STAT1	-0.13	0.4	-10000	0	-1	99	99
HRAS/SPRED1	-0.016	0.14	-10000	0	-0.38	33	33
cell proliferation	-0.046	0.17	-10000	0	-0.43	99	99
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
TEC	0.011	0.031	-10000	0	-0.75	1	1
RPS6KB1	-0.047	0.18	-10000	0	-0.44	99	99
HRAS/SPRED2	-0.016	0.14	-10000	0	-0.38	33	33
LYN/TEC/p62DOK	-0.033	0.17	-10000	0	-0.41	100	100
MAPK3	0	0.1	-10000	0	-0.28	22	22
STAP1	-0.093	0.2	-10000	0	-0.5	103	103
GRAP2	-0.003	0.077	-10000	0	-0.4	23	23
JAK2	-0.1	0.34	-10000	0	-0.86	99	99
STAT1 (dimer)	-0.12	0.4	-10000	0	-1	99	99
mol:Gleevec	0.001	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.053	0.2	-10000	0	-0.45	113	113
actin filament polymerization	-0.053	0.18	-10000	0	-0.44	106	106
LYN	0.013	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.11	0.26	-10000	0	-0.66	103	103
PIK3R1	0.012	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.023	0.16	-10000	0	-0.37	99	99
PI3K	-0.033	0.17	-10000	0	-0.42	99	99
PTEN	0.011	0.023	-10000	0	-0.4	2	2
SCF/KIT/EPO/EPOR	-0.15	0.47	-10000	0	-1.2	99	99
MAPK8	-0.047	0.18	-10000	0	-0.44	99	99
STAT3 (dimer)	-0.046	0.17	-10000	0	-0.43	99	99
positive regulation of transcription	0.004	0.088	-10000	0	-0.23	18	18
mol:GDP	-0.036	0.18	-10000	0	-0.49	42	42
PIK3C2B	-0.047	0.18	-10000	0	-0.44	99	99
CBL/CRKL	-0.03	0.16	-10000	0	-0.39	99	99
FER	-0.049	0.18	-10000	0	-0.44	100	100
SH2B3	-0.047	0.18	-10000	0	-0.44	99	99
PDPK1	-0.038	0.15	-10000	0	-0.36	99	99
SNAI2	-0.048	0.18	-10000	0	-0.44	99	99
positive regulation of cell proliferation	-0.086	0.3	-10000	0	-0.75	99	99
KITLG	0.002	0.067	-10000	0	-0.42	15	15
cell motility	-0.086	0.3	-10000	0	-0.75	99	99
PTPN6	0.014	0.009	-10000	0	-10000	0	0
EPOR	-0.011	0.13	-10000	0	-0.81	1	1
STAT5A (dimer)	-0.067	0.25	-10000	0	-0.62	99	99
SOCS1	-0.014	0.14	-10000	0	-0.75	22	22
cell migration	0.069	0.19	0.47	100	-10000	0	100
SOS1	0.013	0	-10000	0	-10000	0	0
EPO	-0.002	0.081	-10000	0	-0.76	7	7
VAV1	-0.004	0.081	-10000	0	-0.4	26	26
GRB10	-0.048	0.18	-10000	0	-0.44	99	99
PTPN11	0.014	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.056	0.19	-10000	0	-0.47	99	99
GO:0007205	0.002	0.009	-10000	0	-10000	0	0
MAP2K1	-0.003	0.11	-10000	0	-0.31	20	20
CBL	0.013	0	-10000	0	-10000	0	0
KIT	-0.16	0.47	-10000	0	-1.2	98	98
MAP2K2	-0.004	0.11	-10000	0	-0.3	25	25
SHC/Grb2/SOS1	-0.032	0.17	-10000	0	-0.41	99	99
STAT5A	-0.07	0.26	-10000	0	-0.64	99	99
GRB2	0.013	0	-10000	0	-10000	0	0
response to radiation	-0.047	0.18	-10000	0	-0.43	99	99
SHC/GRAP2	0.008	0.054	-10000	0	-10000	0	0
PTPRO	-0.082	0.21	-10000	0	-0.46	136	136
SH2B2	-0.054	0.19	-10000	0	-0.45	106	106
DOK1	0.013	0	-10000	0	-10000	0	0
MATK	-0.07	0.19	-10000	0	-0.48	100	100
CREBBP	0.012	0.048	-10000	0	-10000	0	0
BCL2	-0.061	0.31	-10000	0	-1.3	32	32

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.46	0.33	-9999	-1	81	81
HDAC7	0.013	0.003	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.34	0.25	-9999	-0.9	31	31
SMAD4	0.012	0.023	-9999	-0.39	2	2
ID2	-0.46	0.33	-9999	-1	68	68
AP1	0.016	0.036	-9999	-10000	0	0
ABCG2	-0.62	0.35	-9999	-1.1	157	157
HIF1A	-0.072	0.047	-9999	-10000	0	0
TFF3	-0.46	0.33	-9999	-1	80	80
GATA2	0.007	0.054	-9999	-0.39	11	11
AKT1	-0.071	0.052	-9999	-10000	0	0
response to hypoxia	-0.088	0.053	-9999	-10000	0	0
MCL1	-0.46	0.33	-9999	-1	69	69
NDRG1	-0.46	0.33	-9999	-1	69	69
SERPINE1	-0.54	0.4	-9999	-1.1	135	135
FECH	-0.46	0.33	-9999	-1	75	75
FURIN	-0.46	0.33	-9999	-1	78	78
NCOA2	0.011	0.028	-9999	-0.4	3	3
EP300	-0.069	0.069	-9999	-0.36	12	12
HMOX1	-0.46	0.33	-9999	-1	79	79
BHLHE40	-0.46	0.33	-9999	-1	81	81
BHLHE41	-0.47	0.34	-9999	-1.1	75	75
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.065	0.06	-9999	-10000	0	0
ENG	-0.051	0.062	-9999	-10000	0	0
JUN	0.013	0.001	-9999	-10000	0	0
RORA	-0.46	0.33	-9999	-1	83	83
ABCB1	-0.29	0.42	-9999	-1.1	119	119
TFRC	-0.46	0.33	-9999	-1	78	78
CXCR4	-0.46	0.33	-9999	-1	75	75
TF	-0.49	0.35	-9999	-1.1	100	100
CITED2	-0.46	0.33	-9999	-1	86	86
HIF1A/ARNT	-0.51	0.38	-9999	-1.1	87	87
LDHA	-0.056	0.041	-9999	-10000	0	0
ETS1	-0.46	0.33	-9999	-1	75	75
PGK1	-0.46	0.33	-9999	-1	80	80
NOS2	-0.48	0.34	-9999	-1	100	100
ITGB2	-0.46	0.33	-9999	-1.1	69	69
ALDOA	-0.46	0.33	-9999	-1	68	68
Cbp/p300/CITED2	-0.44	0.34	-9999	-1.1	65	65
FOS	0.007	0.051	-9999	-0.39	10	10
HK2	-0.46	0.33	-9999	-1	78	78
SP1	0.01	0.027	-9999	-10000	0	0
GCK	-0.12	0.2	-9999	-1.3	14	14
HK1	-0.46	0.33	-9999	-1	75	75
NPM1	-0.46	0.33	-9999	-1	75	75
EGLN1	-0.46	0.33	-9999	-1	78	78
CREB1	0.019	0	-9999	-10000	0	0
PGM1	-0.46	0.33	-9999	-1	77	77
SMAD3	0.012	0.023	-9999	-0.39	2	2
EDN1	-0.048	0.1	-9999	-0.94	2	2
IGFBP1	-0.53	0.4	-9999	-1.1	127	127
VEGFA	-0.3	0.24	-9999	-0.87	23	23
HIF1A/JAB1	-0.036	0.028	-9999	-10000	0	0
CP	-0.55	0.36	-9999	-1.1	124	124
CXCL12	-0.49	0.35	-9999	-1.1	92	92
COPS5	0.013	0.002	-9999	-10000	0	0
SMAD3/SMAD4	0.019	0.023	-9999	-10000	0	0
BNIP3	-0.46	0.33	-9999	-1	77	77
EGLN3	-0.46	0.33	-9999	-1	82	82
CA9	-0.77	0.39	-9999	-1.1	275	275
TERT	-0.49	0.37	-9999	-1.1	98	98
ENO1	-0.46	0.33	-9999	-1	80	80
PFKL	-0.46	0.33	-9999	-1	78	78
NCOA1	0.013	0.001	-9999	-10000	0	0
ADM	-0.46	0.33	-9999	-1	75	75
ARNT	-0.073	0.05	-9999	-0.46	1	1
HNF4A	0.013	0.02	-9999	-0.39	1	1
ADFP	-0.47	0.33	-9999	-1	90	90
SLC2A1	-0.31	0.27	-9999	-0.94	40	40
LEP	-0.48	0.34	-9999	-1.1	84	84
HIF1A/ARNT/Cbp/p300	-0.36	0.26	-9999	-0.91	35	35
EPO	-0.25	0.19	-9999	-0.89	8	8
CREBBP	-0.069	0.069	-9999	-0.36	12	12
HIF1A/ARNT/Cbp/p300/HDAC7	-0.34	0.26	-9999	-0.98	28	28
PFKFB3	-0.46	0.33	-9999	-1	69	69
NT5E	-0.46	0.33	-9999	-1	78	78

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.049	0.14	-10000	0	-0.29	146	146
ACTA1	-0.075	0.17	-10000	0	-0.36	148	148
NUMA1	-0.049	0.14	-10000	0	-0.29	146	146
SPTAN1	-0.071	0.17	-10000	0	-0.36	146	146
LIMK1	-0.071	0.17	-10000	0	-0.36	146	146
BIRC3	0.005	0.057	-10000	0	-0.43	10	10
BIRC2	0.012	0.016	-10000	0	-0.4	1	1
BAX	0.013	0	-10000	0	-10000	0	0
CASP10	-0.1	0.23	-10000	0	-0.5	149	149
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.012	0	-10000	0	-10000	0	0
PTK2	-0.049	0.14	-10000	0	-0.29	146	146
DIABLO	0.013	0.001	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.07	0.16	-10000	0	-0.36	146	146
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
GSN	-0.075	0.17	-10000	0	-0.37	147	147
MADD	0.013	0	-10000	0	-10000	0	0
TFAP2A	-0.057	0.12	-10000	0	-0.63	7	7
BID	-0.04	0.1	-10000	0	-0.22	149	149
MAP3K1	-0.021	0.064	-10000	0	-0.2	7	7
TRADD	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.019	0.001	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.071	0.17	-10000	0	-0.36	146	146
CASP9	0.013	0.001	-10000	0	-10000	0	0
DNA repair	0.016	0.049	-10000	0	-0.16	7	7
neuron apoptosis	0.011	0.036	-10000	0	-0.72	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.061	0.16	-10000	0	-0.34	146	146
APAF1	0.013	0.001	-10000	0	-10000	0	0
CASP6	-0.012	0.082	-10000	0	-10000	0	0
TRAF2	0.012	0.016	-10000	0	-0.4	1	1
ICAD/CAD	-0.063	0.16	-10000	0	-0.35	145	145
CASP7	0.002	0.039	0.24	10	-0.41	1	11
KRT18	0.005	0.025	-10000	0	-10000	0	0
apoptosis	-0.055	0.15	-10000	0	-0.53	8	8
DFFA	-0.071	0.17	-10000	0	-0.36	146	146
DFFB	-0.071	0.17	-10000	0	-0.36	146	146
PARP1	-0.016	0.05	0.16	7	-10000	0	7
actin filament polymerization	0.066	0.16	0.34	145	-10000	0	145
TNF	0.009	0.036	-10000	0	-0.4	5	5
CYCS	-0.029	0.084	-10000	0	-0.18	148	148
SATB1	-0.009	0.081	-10000	0	-10000	0	0
SLK	-0.072	0.17	-10000	0	-0.36	146	146
p15 BID/BAX	-0.029	0.094	-10000	0	-0.31	7	7
CASP2	0.037	0.03	-10000	0	-0.33	1	1
JNK cascade	0.021	0.064	0.2	7	-10000	0	7
CASP3	-0.081	0.18	-10000	0	-0.38	153	153
LMNB2	0.024	0.036	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
CASP4	0.013	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.028	0.034	-10000	0	-0.45	1	1
negative regulation of DNA binding	-0.056	0.12	-10000	0	-0.62	7	7
stress fiber formation	-0.071	0.17	-10000	0	-0.36	146	146
GZMB	-0.13	0.26	-10000	0	-0.58	149	149
CASP1	0.013	0.02	-10000	0	-0.27	3	3
LMNB1	0.024	0.036	-10000	0	-10000	0	0
APP	0.011	0.036	-10000	0	-0.73	1	1
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.009	0	-10000	0	-10000	0	0
VIM	-0.056	0.15	-10000	0	-0.32	145	145
LMNA	0.024	0.036	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.034	0.031	-10000	0	-0.36	1	1
LRDD	0.012	0.016	-10000	0	-0.4	1	1
SREBF1	-0.071	0.17	-10000	0	-0.36	146	146
APAF-1/Caspase 9	-0.013	0.032	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.048	0.14	-10000	0	-0.28	146	146
CFL2	-0.068	0.16	-10000	0	-0.34	145	145
GAS2	-0.13	0.24	-10000	0	-0.44	201	201
positive regulation of apoptosis	0.028	0.035	-10000	0	-10000	0	0
PRF1	0.002	0.078	-10000	0	-0.5	13	13

×

Endothelins

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
AKT1	0.005	0.22	-10000	0	-0.5	58	58
PTK2B	0.012	0.023	-10000	0	-0.4	2	2
mol:Ca2+	0.016	0.23	-10000	0	-0.96	27	27
EDN1	0.048	0.13	-10000	0	-0.4	1	1
EDN3	-0.18	0.2	-10000	0	-0.4	295	295
EDN2	-0.11	0.19	-10000	0	-0.4	187	187
HRAS/GDP	0.011	0.14	-10000	0	-0.5	10	10
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.039	0.11	-10000	0	-0.35	12	12
ADCY4	-0.025	0.17	-10000	0	-0.49	38	38
ADCY5	-0.09	0.2	-10000	0	-0.53	62	62
ADCY6	-0.025	0.17	-10000	0	-0.52	31	31
ADCY7	-0.025	0.17	-10000	0	-0.51	33	33
ADCY1	-0.035	0.18	-10000	0	-0.51	40	40
ADCY2	-0.05	0.2	-10000	0	-0.51	56	56
ADCY3	-0.025	0.17	-10000	0	-0.52	31	31
ADCY8	-0.037	0.18	-10000	0	-0.48	44	44
ADCY9	-0.025	0.17	-10000	0	-0.53	30	30
arachidonic acid secretion	-0.007	0.16	-10000	0	-0.48	26	26
ETB receptor/Endothelin-1/Gq/GTP	0.028	0.081	-10000	0	-0.47	5	5
GNAO1	-0.14	0.2	-10000	0	-0.4	234	234
HRAS	0.012	0.016	-10000	0	-0.4	1	1
ETA receptor/Endothelin-1/G12/GTP	0.087	0.26	0.31	291	-0.47	54	345
ETA receptor/Endothelin-1/Gs/GTP	0.065	0.26	0.29	279	-0.46	60	339
mol:GTP	0.001	0.004	-10000	0	-10000	0	0
COL3A1	-0.003	0.25	-10000	0	-0.58	62	62
EDNRB	-0.001	0.072	-10000	0	-0.39	18	18
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.021	0.26	-10000	0	-0.6	80	80
CYSLTR1	-0.043	0.29	-10000	0	-0.56	122	122
SLC9A1	0.023	0.12	-10000	0	-0.31	17	17
mol:GDP	0.004	0.15	-10000	0	-0.48	16	16
SLC9A3	-0.18	0.32	-10000	0	-0.58	174	174
RAF1	-0.002	0.13	-10000	0	-0.49	11	11
JUN	0.04	0.14	-10000	0	-0.72	4	4
JAK2	0.004	0.22	-10000	0	-0.49	63	63
mol:IP3	0.033	0.1	-10000	0	-0.54	5	5
ETA receptor/Endothelin-1	0.088	0.32	0.37	296	-0.55	76	372
PLCB1	0.009	0.053	-10000	0	-0.75	3	3
PLCB2	0.013	0.002	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.14	0.23	-10000	0	-0.46	123	123
FOS	0.008	0.15	-10000	0	-0.84	12	12
Gai/GDP	-0.22	0.34	-10000	0	-0.64	234	234
CRK	0.013	0.001	-10000	0	-10000	0	0
mol:Ca ++	0.011	0.2	-10000	0	-0.57	30	30
BCAR1	0.012	0.016	-10000	0	-0.39	1	1
PRKCB1	0.031	0.1	-10000	0	-0.52	5	5
GNAQ	0.012	0.029	-10000	0	-0.4	3	3
GNAZ	0.007	0.046	-10000	0	-0.4	8	8
GNAL	-0.01	0.094	-10000	0	-0.4	35	35
Gs family/GDP	-0.047	0.11	-10000	0	-0.5	15	15
ETA receptor/Endothelin-1/Gq/GTP	0.036	0.14	-10000	0	-0.4	17	17
MAPK14	0.036	0.07	-10000	0	-0.53	3	3
TRPC6	0.013	0.24	-10000	0	-1	27	27
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.075	-10000	0	-0.4	22	22
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.033	0.075	-10000	0	-0.57	3	3
ETB receptor/Endothelin-2	-0.076	0.14	-10000	0	-0.27	201	201
ETB receptor/Endothelin-3	-0.12	0.15	-10000	0	-0.44	18	18
ETB receptor/Endothelin-1	0.037	0.12	-10000	0	-0.38	12	12
MAPK3	0.007	0.14	-10000	0	-0.71	13	13
MAPK1	0.007	0.14	-10000	0	-0.71	13	13
Rac1/GDP	0.011	0.14	-10000	0	-0.49	11	11
cAMP biosynthetic process	-0.073	0.18	-10000	0	-0.48	55	55
MAPK8	0.032	0.16	-10000	0	-0.6	20	20
SRC	0.013	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.048	0.14	-10000	0	-0.4	39	39
p130Cas/CRK/Src/PYK2	-0.022	0.17	-10000	0	-0.58	24	24
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.011	0.14	-10000	0	-0.5	10	10
COL1A2	0.004	0.25	-10000	0	-0.65	50	50
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.084	0.22	-10000	0	-0.42	124	124
mol:DAG	0.033	0.1	-10000	0	-0.54	5	5
MAP2K2	0.004	0.13	-10000	0	-0.55	13	13
MAP2K1	0.005	0.13	-10000	0	-0.55	13	13
EDNRA	-0.001	0.24	-10000	0	-0.74	41	41
positive regulation of muscle contraction	0.011	0.19	-10000	0	-0.53	29	29
Gq family/GDP	-0.047	0.1	-10000	0	-0.59	8	8
HRAS/GTP	-0.01	0.13	-10000	0	-0.47	11	11
PRKCH	0.036	0.1	-10000	0	-0.51	5	5
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	0.036	0.1	-10000	0	-0.51	5	5
PRKCB	-0.008	0.15	-10000	0	-0.44	16	16
PRKCE	0.037	0.099	-10000	0	-0.51	5	5
PRKCD	0.036	0.1	-10000	0	-0.51	5	5
PRKCG	-0.11	0.23	-10000	0	-0.45	112	112
regulation of vascular smooth muscle contraction	0.006	0.17	-10000	0	-0.98	12	12
PRKCQ	0.034	0.1	-10000	0	-0.55	5	5
PLA2G4A	-0.01	0.17	-10000	0	-0.52	26	26
GNA14	0.011	0.037	-10000	0	-0.4	5	5
GNA15	0.006	0.075	-10000	0	-0.75	6	6
GNA12	0.013	0	-10000	0	-10000	0	0
GNA11	0.011	0.033	-10000	0	-0.4	4	4
Rac1/GTP	0.087	0.26	0.31	293	-0.46	62	355
MMP1	-0.38	0.33	-10000	0	-0.61	405	405

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.02	0.076	0.31	2	-10000	0	2
SMARCC2	0.012	0.012	-10000	0	-10000	0	0
SMARCC1	0.012	0.013	-10000	0	-10000	0	0
TBX21	-0.12	0.2	-10000	0	-0.56	70	70
SUMO2	0.013	0.006	-10000	0	-10000	0	0
STAT1 (dimer)	0.019	0.03	-10000	0	-0.74	1	1
FKBP4	0.011	0.031	-10000	0	-0.75	1	1
FKBP5	0.012	0.016	-10000	0	-0.4	1	1
GR alpha/HSP90/FKBP51/HSP90	0.1	0.11	0.33	15	-0.37	2	17
PRL	-0.079	0.13	-10000	0	-0.69	13	13
cortisol/GR alpha (dimer)/TIF2	0.25	0.23	0.54	137	-0.5	4	141
RELA	-0.055	0.083	-10000	0	-10000	0	0
FGG	0.13	0.27	0.49	58	-0.57	46	104
GR beta/TIF2	0.11	0.13	0.34	30	-0.41	8	38
IFNG	-0.35	0.28	-10000	0	-0.77	136	136
apoptosis	0.014	0.16	0.48	16	-0.58	8	24
CREB1	0.013	0.025	-10000	0	-10000	0	0
histone acetylation	-0.066	0.12	0.44	2	-0.39	19	21
BGLAP	-0.08	0.12	-10000	0	-0.54	5	5
GR/PKAc	0.071	0.14	0.32	11	-0.39	11	22
NF kappa B1 p50/RelA	-0.1	0.15	-10000	0	-0.39	51	51
SMARCD1	0.012	0.013	-10000	0	-10000	0	0
MDM2	0.096	0.078	0.27	36	-10000	0	36
GATA3	0.009	0.05	-10000	0	-0.46	5	5
AKT1	0.006	0.001	-10000	0	-10000	0	0
CSF2	-0.23	0.24	-10000	0	-0.52	224	224
GSK3B	0.013	0.006	-10000	0	-10000	0	0
NR1I3	0.023	0.16	0.47	14	-0.78	6	20
CSN2	0.14	0.15	0.42	31	-0.46	5	36
BRG1/BAF155/BAF170/BAF60A	0.031	0.041	-10000	0	-10000	0	0
NFATC1	0.01	0.037	-10000	0	-0.4	5	5
POU2F1	0.011	0.036	-10000	0	-0.74	1	1
CDKN1A	0.028	0.055	-10000	0	-1.3	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.007	-10000	0	-10000	0	0
SFN	0.011	0.023	-10000	0	-0.4	2	2
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.11	0.1	0.34	9	-10000	0	9
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.024	0.14	0.45	14	-0.64	5	19
JUN	-0.28	0.17	-10000	0	-0.55	104	104
IL4	-0.095	0.12	-10000	0	-0.5	4	4
CDK5R1	0.012	0.03	-10000	0	-0.74	1	1
PRKACA	0.013	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.31	0.24	-10000	0	-0.6	171	171
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.1	0.33	12	-10000	0	12
cortisol/GR alpha (monomer)	0.29	0.27	0.63	149	-0.58	4	153
NCOA2	0.011	0.028	-10000	0	-0.4	3	3
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.097	0.064	-10000	0	-0.47	10	10
AP-1/NFAT1-c-4	-0.49	0.28	-10000	0	-0.79	200	200
AFP	-0.22	0.19	-10000	0	-0.74	47	47
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.15	0.13	0.42	33	-10000	0	33
TP53	0.03	0.019	-10000	0	-0.45	1	1
PPP5C	0.013	0	-10000	0	-10000	0	0
KRT17	-0.64	0.31	-10000	0	-0.81	424	424
KRT14	-0.14	0.22	-10000	0	-0.94	28	28
TBP	0.02	0.014	-10000	0	-10000	0	0
CREBBP	0.033	0.07	0.31	7	-10000	0	7
HDAC1	0.012	0.008	-10000	0	-10000	0	0
HDAC2	0.032	0.025	-10000	0	-10000	0	0
AP-1	-0.49	0.28	-10000	0	-0.8	201	201
MAPK14	0.013	0.006	-10000	0	-10000	0	0
MAPK10	-0.038	0.13	-10000	0	-0.39	78	78
MAPK11	0.01	0.044	-10000	0	-0.77	2	2
KRT5	-0.39	0.32	-10000	0	-0.86	150	150
interleukin-1 receptor activity	0.019	0.025	-10000	0	-10000	0	0
NCOA1	0.015	0.001	-10000	0	-10000	0	0
STAT1	0.019	0.03	-10000	0	-0.74	1	1
CGA	-0.095	0.14	-10000	0	-0.62	14	14
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.18	0.2	0.4	212	-0.4	10	222
MAPK3	0.012	0.018	-10000	0	-0.4	1	1
MAPK1	0.012	0.017	-10000	0	-0.4	1	1
ICAM1	-0.18	0.22	-10000	0	-0.6	71	71
NFKB1	-0.055	0.083	-10000	0	-10000	0	0
MAPK8	-0.21	0.15	-10000	0	-0.44	95	95
MAPK9	0.013	0.006	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.01	0.16	0.48	16	-0.61	8	24
BAX	0.029	0.02	-10000	0	-10000	0	0
POMC	-0.15	0.27	-10000	0	-1.3	25	25
EP300	0.036	0.072	0.31	9	-10000	0	9
cortisol/GR alpha (dimer)/p53	0.27	0.22	0.54	150	-0.49	4	154
proteasomal ubiquitin-dependent protein catabolic process	0.068	0.06	0.24	5	-10000	0	5
SGK1	0.043	0.27	-10000	0	-1.2	25	25
IL13	-0.25	0.22	-10000	0	-0.79	52	52
IL6	-0.24	0.32	-10000	0	-0.87	101	101
PRKACG	0.001	0.043	-10000	0	-0.75	2	2
IL5	-0.21	0.16	-10000	0	-0.72	20	20
IL2	-0.31	0.21	-10000	0	-0.67	91	91
CDK5	0.013	0.003	-10000	0	-10000	0	0
PRKACB	-0.037	0.13	-10000	0	-0.4	76	76
HSP90AA1	0.013	0	-10000	0	-10000	0	0
IL8	-0.41	0.38	-10000	0	-0.72	343	343
CDK5R1/CDK5	0.018	0.025	-10000	0	-0.56	1	1
NF kappa B1 p50/RelA/PKAc	-0.079	0.13	-10000	0	-0.48	6	6
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.25	0.21	0.54	110	-0.48	3	113
SMARCA4	0.012	0.012	-10000	0	-10000	0	0
chromatin remodeling	0.14	0.17	0.39	61	-0.5	15	76
NF kappa B1 p50/RelA/Cbp	-0.038	0.13	0.38	3	-0.45	2	5
JUN (dimer)	-0.28	0.17	-10000	0	-0.54	104	104
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.11	0.19	-10000	0	-0.61	53	53
NR3C1	0.15	0.19	0.45	67	-0.41	23	90
NR4A1	-0.011	0.14	-10000	0	-0.57	31	31
TIF2/SUV420H1	0.017	0.02	-10000	0	-10000	0	0
MAPKKK cascade	0.014	0.16	0.48	16	-0.58	8	24
cortisol/GR alpha (dimer)/Src-1	0.26	0.22	0.54	141	-0.5	4	145
PBX1	0.004	0.061	-10000	0	-0.39	13	13
POU1F1	0.001	0.042	-10000	0	-0.9	1	1
SELE	-0.26	0.34	-10000	0	-0.82	133	133
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.17	0.39	60	-0.51	15	75
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.25	0.21	0.54	110	-0.48	3	113
mol:cortisol	0.16	0.15	0.35	169	-0.21	2	171
MMP1	-0.46	0.29	-10000	0	-0.67	405	405

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.001	0.018	-10000	0	-10000	0	0
HDAC1	0.01	0.004	-10000	0	-10000	0	0
AES	0.012	0.001	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
DTX1	0.009	0.036	-10000	0	-0.4	5	5
LRP6/FZD1	0.018	0.016	-10000	0	-10000	0	0
TLE1	0.011	0.016	-10000	0	-0.4	1	1
AP1	-0.17	0.14	-10000	0	-0.26	413	413
NCSTN	0.013	0	-10000	0	-10000	0	0
ADAM10	0.012	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.058	0.04	-10000	0	-0.45	1	1
NICD/RBPSUH	0.03	0.012	-10000	0	-10000	0	0
WIF1	-0.15	0.31	-10000	0	-0.75	127	127
NOTCH1	0	0.012	-10000	0	-10000	0	0
PSENEN	0.012	0.016	-10000	0	-0.4	1	1
KREMEN2	-0.08	0.25	-10000	0	-0.75	76	76
DKK1	-0.15	0.31	-10000	0	-0.75	131	131
beta catenin/beta TrCP1	0.13	0.08	0.23	1	-10000	0	1
APH1B	0.013	0.001	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
AXIN1	-0.043	0.038	-10000	0	-0.41	1	1
CtBP/CBP/TCF1/TLE1/AES	0.02	0.02	-10000	0	-10000	0	0
PSEN1	0.013	0	-10000	0	-10000	0	0
FOS	0.006	0.051	-10000	0	-0.4	10	10
JUN	0.013	0	-10000	0	-10000	0	0
MAP3K7	0.011	0.002	-10000	0	-10000	0	0
CTNNB1	0.13	0.086	0.2	294	-10000	0	294
MAPK3	0.012	0.016	-10000	0	-0.4	1	1
DKK2/LRP6/Kremen 2	-0.11	0.23	-10000	0	-0.51	154	154
HNF1A	0.011	0.023	-10000	0	-0.39	2	2
CTBP1	0.012	0.001	-10000	0	-10000	0	0
MYC	0.016	0.076	-10000	0	-0.55	11	11
NKD1	-0.5	0.36	-10000	0	-0.75	415	415
FZD1	0.011	0.023	-10000	0	-0.4	2	2
NOTCH1 precursor/Deltex homolog 1	0.028	0.021	-10000	0	-10000	0	0
apoptosis	-0.17	0.14	-10000	0	-0.26	413	413
Delta 1/NOTCHprecursor	0.029	0.02	-10000	0	-10000	0	0
DLL1	0.01	0.033	-10000	0	-0.4	4	4
PPARD	0.023	0.053	-10000	0	-1.3	1	1
Gamma Secretase	0.038	0.009	-10000	0	-10000	0	0
APC	-0.049	0.061	-10000	0	-0.44	10	10
DVL1	0.008	0.041	-10000	0	-0.35	1	1
CSNK2A1	0.013	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.14	0.26	-10000	0	-0.53	191	191
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.013	0.001	-10000	0	-10000	0	0
NLK	0.011	0.005	-10000	0	-10000	0	0
CCND1	0.021	0.052	-10000	0	-0.55	5	5
WNT1	0.005	0.053	-10000	0	-0.75	3	3
Axin1/APC/beta catenin	0.071	0.049	-10000	0	-0.41	1	1
DKK2	-0.095	0.26	-10000	0	-0.73	90	90
NOTCH1 precursor/DVL1	-0.007	0.02	-10000	0	-10000	0	0
GSK3B	0.012	0.001	-10000	0	-10000	0	0
FRAT1	0.012	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.001	0.019	-10000	0	-10000	0	0
PPP2R5D	0.21	0.15	0.32	415	-10000	0	415
MAPK1	0.012	0.016	-10000	0	-0.4	1	1
WNT1/LRP6/FZD1	-0.072	0.2	-10000	0	-0.45	129	129
RBPJ	0.013	0	-10000	0	-10000	0	0
CREBBP	0.015	0.003	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.009	0.036	-9999	-0.4	5	5
LAT2	-0.085	0.16	-9999	-0.38	95	95
AP1	-0.1	0.22	-9999	-0.61	70	70
mol:PIP3	-0.1	0.2	-9999	-0.47	104	104
IKBKB	-0.067	0.13	-9999	-0.31	84	84
AKT1	-0.045	0.12	-9999	-0.42	2	2
IKBKG	-0.068	0.13	-9999	-0.31	84	84
MS4A2	-0.11	0.18	-9999	-0.4	184	184
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.011	0.016	-9999	-0.4	1	1
MAP3K1	-0.079	0.18	-9999	-0.49	53	53
mol:Ca2+	-0.076	0.15	-9999	-0.35	104	104
LYN	0.012	0.003	-9999	-10000	0	0
CBLB	-0.084	0.15	-9999	-0.38	95	95
SHC1	0.013	0	-9999	-10000	0	0
RasGAP/p62DOK	0.023	0.015	-9999	-10000	0	0
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.012	0.016	-9999	-0.4	1	1
PLD2	-0.075	0.14	-9999	-0.41	13	13
PTPN13	-0.1	0.19	-9999	-0.42	114	114
PTPN11	0.009	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.043	0.13	-9999	-0.35	13	13
SYK	0.012	0.003	-9999	-10000	0	0
GRB2	0.012	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.18	-9999	-0.48	105	105
LAT	-0.085	0.16	-9999	-0.38	96	96
PAK2	-0.094	0.2	-9999	-0.53	63	63
NFATC2	-0.055	0.11	-9999	-0.57	21	21
HRAS	-0.11	0.21	-9999	-0.48	117	117
GAB2	0.013	0	-9999	-10000	0	0
PLA2G1B	0.032	0.021	-9999	-10000	0	0
Fc epsilon R1	-0.11	0.17	-9999	-0.44	93	93
Antigen/IgE/Fc epsilon R1	-0.098	0.16	-9999	-0.39	93	93
mol:GDP	-0.12	0.24	-9999	-0.54	121	121
JUN	0.013	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.012	0.001	-9999	-10000	0	0
FOS	0.006	0.051	-9999	-0.4	10	10
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.094	0.16	-9999	-0.4	95	95
CHUK	-0.067	0.13	-9999	-0.31	84	84
KLRG1	-0.077	0.14	-9999	-0.34	95	95
VAV1	-0.091	0.17	-9999	-0.4	104	104
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.083	0.15	-9999	-0.38	95	95
negative regulation of mast cell degranulation	-0.066	0.13	-9999	-0.49	13	13
BTK	-0.14	0.27	-9999	-0.59	128	128
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.13	0.22	-9999	-0.53	123	123
GAB2/PI3K/SHP2	-0.079	0.11	-9999	-0.45	5	5
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.09	0.16	-9999	-0.42	93	93
RAF1	0.025	0.024	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.1	0.18	-9999	-0.56	38	38
FCER1G	0.013	0.042	-9999	-0.41	6	6
FCER1A	-0.11	0.19	-9999	-0.41	179	179
Antigen/IgE/Fc epsilon R1/Fyn	-0.085	0.14	-9999	-0.36	93	93
MAPK3	0.032	0.021	-9999	-10000	0	0
MAPK1	0.032	0.021	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	-0.017	0.072	-9999	-0.47	4	4
DUSP1	0.011	0.028	-9999	-0.4	3	3
NF-kappa-B/RelA	-0.054	0.066	-9999	-0.23	2	2
actin cytoskeleton reorganization	-0.095	0.17	-9999	-0.42	95	95
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.11	0.16	-9999	-0.5	53	53
FER	-0.085	0.16	-9999	-0.38	98	98
RELA	0.013	0	-9999	-10000	0	0
ITK	-0.035	0.098	-9999	-0.44	29	29
SOS1	0.013	0	-9999	-10000	0	0
PLCG1	-0.12	0.23	-9999	-0.52	121	121
cytokine secretion	-0.039	0.048	-9999	-10000	0	0
SPHK1	-0.11	0.18	-9999	-0.41	128	128
PTK2	-0.099	0.18	-9999	-0.44	95	95
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.19	-9999	-0.5	104	104
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.1	0.2	-9999	-0.46	107	107
MAP2K2	0.028	0.023	-9999	-10000	0	0
MAP2K1	0.029	0.021	-9999	-10000	0	0
MAP2K7	0.012	0.016	-9999	-0.4	1	1
KLRG1/SHP2	-0.064	0.13	-9999	-0.47	13	13
MAP2K4	0.007	0.075	-9999	-0.92	4	4
Fc epsilon R1/FcgammaRIIB	-0.12	0.19	-9999	-0.44	123	123
mol:Choline	-0.074	0.14	-9999	-0.4	13	13
SHC/Grb2/SOS1	-0.068	0.15	-9999	-0.5	13	13
FYN	0.013	0	-9999	-10000	0	0
DOK1	0.013	0	-9999	-10000	0	0
PXN	-0.087	0.17	-9999	-0.4	95	95
HCLS1	-0.085	0.16	-9999	-0.38	95	95
PRKCB	-0.1	0.18	-9999	-0.39	143	143
FCGR2B	-0.037	0.13	-9999	-0.4	75	75
IGHE	-0.002	0.005	-9999	-10000	0	0
KLRG1/SHIP	-0.067	0.14	-9999	-0.5	13	13
LCP2	0.008	0.04	-9999	-0.4	6	6
PLA2G4A	-0.11	0.18	-9999	-0.4	137	137
RASA1	0.013	0.001	-9999	-10000	0	0
mol:Phosphatidic acid	-0.074	0.14	-9999	-0.4	13	13
IKK complex	-0.04	0.1	-9999	-0.24	47	47
WIPF1	0.011	0.028	-9999	-0.4	3	3

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.013	0	-9999	-10000	0	0
GNAT1/GTP	0.001	0.023	-9999	-0.58	1	1
Metarhodopsin II/Arrestin	0	0.035	-9999	-0.5	3	3
PDE6G/GNAT1/GTP	-0.004	0.059	-9999	-0.5	1	1
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.001	0.031	-9999	-0.75	1	1
GRK1	-0.002	0.052	-9999	-0.75	3	3
CNG Channel	-0.15	0.14	-9999	-0.53	28	28
mol:Na +	-0.076	0.15	-9999	-0.59	26	26
mol:ADP	-0.002	0.052	-9999	-0.75	3	3
RGS9-1/Gbeta5/R9AP	-0.019	0.098	-9999	-0.49	4	4
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.062	0.17	-9999	-0.64	23	23
CNGB1	-0.048	0.14	-9999	-0.4	83	83
RDH5	-0.017	0.1	-9999	-0.4	45	45
SAG	0.003	0.005	-9999	-10000	0	0
mol:Ca2+	-0.052	0.16	-9999	-0.61	22	22
Na + (4 Units)	-0.07	0.14	-9999	-0.58	22	22
RGS9	-0.055	0.15	-9999	-0.4	103	103
GNB1/GNGT1	-0.16	0.27	-9999	-0.57	186	186
GNAT1/GDP	-0.015	0.084	-9999	-0.42	5	5
GUCY2D	-0.021	0.15	-9999	-0.75	24	24
GNGT1	-0.22	0.35	-9999	-0.75	186	186
GUCY2F	-0.001	0.03	-9999	-0.75	1	1
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.12	0.12	-9999	-0.39	43	43
mol:11-cis-retinal	-0.017	0.1	-9999	-0.39	45	45
mol:cGMP	-0.029	0.15	-9999	-0.47	60	60
GNB1	0.013	0	-9999	-10000	0	0
Rhodopsin	-0.013	0.083	-9999	-0.3	43	43
SLC24A1	0.013	0	-9999	-10000	0	0
CNGA1	-0.024	0.12	-9999	-0.4	56	56
Metarhodopsin II	-0.002	0.051	-9999	-0.55	5	5
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.029	0.16	-9999	-0.49	60	60
RGS9BP	0.006	0.061	-9999	-0.75	4	4
Metarhodopsin II/Transducin	-0.068	0.12	-9999	-0.25	187	187
GCAP Family/Ca ++	-0.017	0.12	-9999	-0.46	41	41
PDE6A/B	-0.16	0.15	-9999	-0.28	369	369
mol:Pi	-0.019	0.097	-9999	-0.49	4	4
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.13	0.22	-9999	-0.46	186	186
PDE6B	-0.008	0.091	-9999	-0.41	30	30
PDE6A	-0.22	0.2	-9999	-0.4	359	359
PDE6G	-0.011	0.094	-9999	-0.4	35	35
RHO	-0.003	0.052	-9999	-0.75	3	3
PDE6	-0.13	0.15	-9999	-0.54	22	22
GUCA1A	-0.036	0.18	-9999	-0.75	37	37
GC2/GCAP Family	-0.017	0.12	-9999	-0.47	41	41
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.008	0.061	-9999	-0.75	4	4

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.019	0.14	-10000	0	-0.6	26	26
IHH	0.007	0.078	-10000	0	-0.45	16	16
SHH Np/Cholesterol/GAS1	-0.11	0.21	-10000	0	-0.49	125	125
LRPAP1	0.013	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.11	0.2	0.48	125	-10000	0	125
SMO/beta Arrestin2	0.013	0.094	-10000	0	-0.51	7	7
SMO	0.007	0.099	-10000	0	-0.49	10	10
AKT1	0.023	0.05	-10000	0	-0.31	1	1
ARRB2	0.013	0	-10000	0	-10000	0	0
BOC	-0.004	0.081	-10000	0	-0.4	26	26
ADRBK1	0.013	0	-10000	0	-10000	0	0
heart looping	0.007	0.097	-10000	0	-0.49	10	10
STIL	-0.05	0.18	-10000	0	-0.5	13	13
DHH N/PTCH2	0.004	0.07	-10000	0	-0.32	26	26
DHH N/PTCH1	0.018	0.09	-10000	0	-0.48	8	8
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
DHH	-0.003	0.075	-10000	0	-0.4	22	22
PTHLH	0.015	0.16	-10000	0	-0.87	14	14
determination of left/right symmetry	0.007	0.097	-10000	0	-0.49	10	10
PIK3R1	0.013	0	-10000	0	-10000	0	0
skeletal system development	0.016	0.16	-10000	0	-0.86	14	14
IHH N/Hhip	-0.044	0.14	-10000	0	-0.32	117	117
DHH N/Hhip	-0.045	0.13	-10000	0	-0.51	11	11
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.007	0.097	-10000	0	-0.49	10	10
pancreas development	-0.063	0.16	-10000	0	-0.39	116	116
HHAT	0.009	0.036	-10000	0	-0.4	5	5
PI3K	0.018	0.011	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.054	0.16	-10000	0	-0.41	99	99
somite specification	0.007	0.097	-10000	0	-0.49	10	10
SHH Np/Cholesterol/PTCH1	-0.057	0.18	-10000	0	-0.41	123	123
SHH Np/Cholesterol/PTCH2	-0.074	0.19	-10000	0	-0.45	124	124
SHH Np/Cholesterol/Megalin	-0.12	0.23	-10000	0	-0.49	163	163
SHH	-0.097	0.23	-10000	0	-0.56	125	125
catabolic process	0.022	0.088	-10000	0	-0.51	7	7
SMO/Vitamin D3	-0.046	0.18	-10000	0	-0.55	11	11
SHH Np/Cholesterol/Hhip	-0.11	0.2	-10000	0	-0.47	123	123
LRP2	-0.062	0.22	-10000	0	-0.75	56	56
receptor-mediated endocytosis	-0.062	0.19	-10000	0	-0.57	25	25
SHH Np/Cholesterol/BOC	-0.08	0.19	-10000	0	-0.46	120	120
SHH Np/Cholesterol/CDO	-0.072	0.19	-10000	0	-0.45	120	120
mesenchymal cell differentiation	0.11	0.19	0.46	123	-10000	0	123
mol:Vitamin D3	-0.054	0.19	-10000	0	-0.41	123	123
IHH N/PTCH2	0.012	0.069	-10000	0	-0.43	10	10
CDON	0.012	0.016	-10000	0	-0.4	1	1
IHH N/PTCH1	0.024	0.089	-10000	0	-0.52	7	7
Megalin/LRPAP1	-0.038	0.17	-10000	0	-0.57	56	56
PTCH2	0.008	0.061	-10000	0	-0.75	4	4
SHH Np/Cholesterol	-0.079	0.19	-10000	0	-0.46	120	120
PTCH1	0.022	0.088	-10000	0	-0.51	7	7
HHIP	-0.064	0.16	-10000	0	-0.4	116	116

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.009	0.04	-9999	-0.26	3	3
NFATC2	-0.015	0.055	-9999	-0.27	14	14
NFATC3	-0.007	0.033	-9999	-10000	0	0
CD40LG	-0.13	0.24	-9999	-0.58	68	68
PTGS2	-0.14	0.25	-9999	-0.68	56	56
JUNB	0.011	0.023	-9999	-0.4	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.006	0.021	-9999	-10000	0	0
CaM/Ca2+	-0.006	0.021	-9999	-10000	0	0
CALM1	0.004	0.012	-9999	-10000	0	0
JUN	0.005	0.011	-9999	-10000	0	0
mol:Ca2+	-0.011	0.013	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.003	0.007	-9999	-10000	0	0
FOSL1	-0.47	0.37	-9999	-0.75	390	390
CREM	0.012	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.063	0.14	-9999	-0.59	9	9
FOS	-0.002	0.051	-9999	-0.39	10	10
IFNG	-0.15	0.28	-9999	-0.71	83	83
AP-1/NFAT1-c-4	-0.14	0.25	-9999	-0.65	63	63
FASLG	-0.13	0.23	-9999	-0.59	53	53
NFAT1-c-4/ICER1	-0.03	0.088	-9999	-0.39	3	3
IL2RA	-0.12	0.22	-9999	-0.56	68	68
FKBP12/FK506	0.009	0	-9999	-10000	0	0
CSF2	-0.26	0.36	-9999	-0.65	263	263
JunB/Fra1/NFAT1-c-4	-0.28	0.22	-9999	-0.49	259	259
IL4	-0.12	0.22	-9999	-0.56	50	50
IL2	-0.007	0.011	-9999	-10000	0	0
IL3	-0.018	0.021	-9999	-10000	0	0
FKBP1A	0.013	0	-9999	-10000	0	0
BATF3	0.004	0.076	-9999	-0.7	7	7
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.011	0.031	-9999	-0.75	1	1

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.17	0.24	-9999	-0.44	258	258
SMAD6-7/SMURF1	0.024	0.031	-9999	-0.49	2	2
NOG	0.007	0.043	-9999	-0.75	2	2
SMAD9	-0.047	0.16	-9999	-0.55	51	51
SMAD4	0.011	0.023	-9999	-0.4	2	2
SMAD5	-0.025	0.11	-9999	-0.34	30	30
BMP7/USAG1	-0.25	0.29	-9999	-0.6	231	231
SMAD5/SKI	-0.017	0.1	-9999	-0.35	19	19
SMAD1	0.031	0.025	-9999	-10000	0	0
BMP2	-0.014	0.1	-9999	-0.4	41	41
SMAD1/SMAD1/SMAD4	-0.003	0.021	-9999	-10000	0	0
BMPR1A	0.013	0	-9999	-10000	0	0
BMPR1B	-0.04	0.18	-9999	-0.66	47	47
BMPR1A-1B/BAMBI	-0.039	0.17	-9999	-0.5	70	70
AHSG	-0.087	0.25	-9999	-0.75	78	78
CER1	-0.015	0.12	-9999	-0.75	16	16
BMP2-4/CER1	-0.042	0.16	-9999	-0.53	55	55
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.039	0.12	-9999	-0.35	50	50
BMP2-4 (homodimer)	-0.038	0.16	-9999	-0.6	39	39
RGMB	0.013	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.008	0.12	-9999	-0.44	36	36
RGMA	-0.075	0.17	-9999	-0.4	134	134
SMURF1	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.044	0.12	-9999	-0.36	48	48
BMP2-4/USAG1	-0.067	0.17	-9999	-0.52	53	53
SMAD6/SMURF1/SMAD5	-0.017	0.1	-9999	-0.35	19	19
SOSTDC1	-0.062	0.16	-9999	-0.4	114	114
BMP7/BMPR2/BMPR1A-1B	-0.18	0.25	-9999	-0.46	254	254
SKI	0.013	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.002	0.077	-9999	-0.39	23	23
HFE2	0.001	0.043	-9999	-0.75	2	2
ZFYVE16	0.011	0.023	-9999	-0.4	2	2
MAP3K7	0.013	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.024	0.14	-9999	-0.52	39	39
SMAD5/SMAD5/SMAD4	-0.018	0.1	-9999	-0.35	19	19
MAPK1	0.012	0.016	-9999	-0.4	1	1
TAK1/TAB family	-0.054	0.089	-9999	-0.34	18	18
BMP7 (homodimer)	-0.27	0.36	-9999	-0.73	237	237
NUP214	0.013	0	-9999	-10000	0	0
BMP6/FETUA	-0.068	0.2	-9999	-0.58	78	78
SMAD1/SKI	0.037	0.025	-9999	-10000	0	0
SMAD6	0.01	0.043	-9999	-0.75	2	2
CTDSP2	0.013	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.089	0.22	-9999	-0.54	109	109
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.015	0.12	-9999	-0.5	34	34
BMPR2 (homodimer)	0.012	0.016	-9999	-0.39	1	1
GADD34/PP1CA	0.025	0.014	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.021	0.14	-9999	-0.49	47	47
CHRDL1	-0.21	0.2	-9999	-0.4	339	339
ENDOFIN/SMAD1	0.036	0.027	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.044	0.032	-9999	-10000	0	0
SMAD6/SMURF1	0.013	0	-9999	-10000	0	0
BAMBI	-0.032	0.18	-9999	-0.74	37	37
SMURF2	0.011	0.035	-9999	-0.57	2	2
BMP2-4/CHRDL1	-0.15	0.18	-9999	-0.54	65	65
BMP2-4/GREM1	-0.041	0.16	-9999	-0.52	51	51
SMAD7	0.012	0.016	-9999	-0.4	1	1
SMAD8A/SMAD8A/SMAD4	-0.038	0.16	-9999	-0.52	50	50
SMAD1/SMAD6	0.037	0.025	-9999	-10000	0	0
TAK1/SMAD6	0.019	0	-9999	-10000	0	0
BMP7	-0.27	0.36	-9999	-0.73	237	237
BMP6	-0.003	0.077	-9999	-0.4	23	23
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.037	0.11	-9999	-0.33	49	49
PPM1A	0.013	0	-9999	-10000	0	0
SMAD1/SMURF2	0.036	0.031	-9999	-0.38	1	1
SMAD7/SMURF1	0.018	0.011	-9999	-0.27	1	1
CTDSPL	0.013	0	-9999	-10000	0	0
PPP1CA	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
PPP1R15A	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.06	0.15	-9999	-0.44	58	58
CHRD	0.012	0.016	-9999	-0.4	1	1
BMPR2	0.012	0.016	-9999	-0.4	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.052	0.13	-9999	-0.39	48	48
BMP4	-0.037	0.19	-9999	-0.73	42	42
FST	-0.005	0.088	-9999	-0.42	25	25
BMP2-4/NOG	-0.027	0.14	-9999	-0.52	41	41
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.16	0.23	-9999	-0.44	254	254

×

Ephrin B reverse 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
EFNB2	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.053	-10000	0	-0.75	3	3
EFNB1	0.011	0.062	-10000	0	-0.57	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.077	0.19	-10000	0	-0.41	138	138
Ephrin B2/EPHB1-2	-0.078	0.2	-10000	0	-0.46	132	132
neuron projection morphogenesis	-0.099	0.17	-10000	0	-0.4	138	138
Ephrin B1/EPHB1-2/Tiam1	-0.087	0.2	-10000	0	-0.44	139	139
DNM1	0.003	0.081	-10000	0	-0.75	7	7
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.001	0.077	-10000	0	-0.64	6	6
YES1	-0.015	0.096	-10000	0	-0.71	8	8
Ephrin B1/EPHB1-2/NCK2	-0.067	0.19	-10000	0	-0.42	138	138
PI3K	0.003	0.078	-10000	0	-0.64	6	6
mol:GDP	-0.087	0.2	-10000	0	-0.44	139	139
ITGA2B	-0.019	0.15	-10000	0	-0.75	25	25
endothelial cell proliferation	0.017	0.001	-10000	0	-10000	0	0
FYN	-0.014	0.096	-10000	0	-0.62	10	10
MAP3K7	-0.007	0.08	-10000	0	-0.68	6	6
FGR	-0.017	0.099	-10000	0	-0.8	7	7
TIAM1	-0.028	0.12	-10000	0	-0.4	62	62
PIK3R1	0.013	0	-10000	0	-10000	0	0
RGS3	0.013	0	-10000	0	-10000	0	0
cell adhesion	-0.005	0.11	-10000	0	-0.45	30	30
LYN	-0.014	0.096	-10000	0	-0.62	10	10
Ephrin B1/EPHB1-2/Src Family Kinases	-0.015	0.088	-10000	0	-0.36	28	28
Ephrin B1/EPHB1-2	-0.02	0.085	-10000	0	-0.36	28	28
SRC	-0.015	0.096	-10000	0	-0.39	28	28
ITGB3	0.008	0.043	-10000	0	-0.4	7	7
EPHB1	-0.15	0.31	-10000	0	-0.75	132	132
EPHB4	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.017	0.001	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.009	0.12	-10000	0	-0.5	32	32
BLK	-0.077	0.13	-10000	0	-0.57	19	19
HCK	-0.021	0.1	-10000	0	-0.4	28	28
regulation of stress fiber formation	0.067	0.19	0.42	138	-10000	0	138
MAPK8	0.005	0.073	-10000	0	-0.6	6	6
Ephrin B1/EPHB1-2/RGS3	-0.067	0.19	-10000	0	-0.42	138	138
endothelial cell migration	-0.003	0.071	-10000	0	-0.57	6	6
NCK2	0.013	0	-10000	0	-10000	0	0
PTPN13	-0.015	0.14	-10000	0	-0.66	28	28
regulation of focal adhesion formation	0.067	0.19	0.42	138	-10000	0	138
chemotaxis	0.067	0.19	0.42	138	-10000	0	138
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
Rac1/GTP	-0.079	0.18	-10000	0	-0.41	138	138
angiogenesis	-0.02	0.085	-10000	0	-0.36	28	28
LCK	-0.017	0.098	-10000	0	-0.45	19	19

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.007	0.11	-9999	-0.49	31	31
EPHB2	0.009	0.053	-9999	-0.75	3	3
Syndecan-2/TACI	-0.085	0.12	-9999	-0.43	4	4
LAMA1	-0.11	0.18	-9999	-0.4	181	181
Syndecan-2/alpha2 ITGB1	0.032	0.03	-9999	-0.42	1	1
HRAS	0.012	0.016	-9999	-0.4	1	1
Syndecan-2/CASK	0.011	0.019	-9999	-0.22	4	4
ITGA5	0.01	0.043	-9999	-0.75	2	2
BAX	0.031	0.017	-9999	-10000	0	0
EPB41	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.018	0.021	-9999	-10000	0	0
LAMA3	0.008	0.047	-9999	-0.45	6	6
EZR	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.008	0.058	-9999	-0.61	5	5
Syndecan-2/MMP2	0.015	0.053	-9999	-0.48	6	6
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.019	0	-9999	-10000	0	0
dendrite morphogenesis	0.018	0.04	-9999	-0.49	3	3
Syndecan-2/GM-CSF	-0.19	0.25	-9999	-0.49	256	256
determination of left/right symmetry	0.015	0.023	-9999	-0.27	4	4
Syndecan-2/PKC delta	0.02	0.019	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
MAPK3	-0.17	0.23	-9999	-0.44	256	256
MAPK1	-0.17	0.23	-9999	-0.44	256	256
Syndecan-2/RACK1	0.025	0.018	-9999	-10000	0	0
NF1	0.013	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.015	0.023	-9999	-0.27	4	4
ITGA2	0.013	0	-9999	-10000	0	0
MAPK8	0.026	0.019	-9999	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	-0.026	0.095	-9999	-0.36	1	1
Syndecan-2/Kininogen	-0.032	0.1	-9999	-0.43	2	2
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.029	0.017	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	0.019	0.017	-9999	-10000	0	0
extracellular matrix organization	0.019	0.028	-9999	-0.49	1	1
actin cytoskeleton reorganization	-0.007	0.11	-9999	-0.48	31	31
Syndecan-2/Caveolin-2/Ras	0.024	0.042	-9999	-0.43	4	4
Syndecan-2/Laminin alpha3	0.018	0.035	-9999	-0.49	1	1
Syndecan-2/RasGAP	0.031	0.017	-9999	-10000	0	0
alpha5/beta1 Integrin	0.017	0.033	-9999	-0.57	2	2
PRKCD	0.013	0	-9999	-10000	0	0
Syndecan-2 dimer	0.018	0.04	-9999	-0.49	3	3
GO:0007205	0.003	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.036	0.017	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
SDCBP	0.011	0.023	-9999	-0.4	2	2
TNFRSF13B	-0.17	0.2	-9999	-0.4	270	270
RASA1	0.013	0.001	-9999	-10000	0	0
alpha2/beta1 Integrin	0.019	0	-9999	-10000	0	0
Syndecan-2/Synbindin	0.02	0.019	-9999	-10000	0	0
TGFB1	0.011	0.031	-9999	-0.75	1	1
CASP3	0.025	0.017	-9999	-10000	0	0
FN1	-0.028	0.17	-9999	-0.67	37	37
Syndecan-2/IL8	-0.27	0.25	-9999	-0.49	347	347
SDC2	0.015	0.023	-9999	-0.27	4	4
KNG1	-0.076	0.16	-9999	-0.4	132	132
Syndecan-2/Neurofibromin	0.02	0.019	-9999	-10000	0	0
TRAPPC4	0.013	0	-9999	-10000	0	0
CSF2	-0.3	0.38	-9999	-0.75	256	256
Syndecan-2/TGFB1	0.02	0.028	-9999	-0.49	1	1
Syndecan-2/Syntenin/PI-4-5-P2	0.018	0.021	-9999	-10000	0	0
Syndecan-2/Ezrin	0.027	0.017	-9999	-10000	0	0
PRKACA	0.025	0.017	-9999	-10000	0	0
angiogenesis	-0.26	0.25	-9999	-0.49	347	347
MMP2	0.004	0.074	-9999	-0.62	8	8
IL8	-0.41	0.38	-9999	-0.75	347	347
calcineurin-NFAT signaling pathway	-0.084	0.12	-9999	-0.43	4	4

×

IL1-mediated signaling events

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
UBC13/UEV1A	-0.059	0.19	-9999	-0.57	76	76
PRKCZ	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.006	0.064	-9999	-10000	0	0
IRAK/TOLLIP	-0.033	0.16	-9999	-0.45	76	76
IKBKB	0.013	0	-9999	-10000	0	0
IKBKG	0.012	0.016	-9999	-0.4	1	1
IL1 alpha/IL1R2	-0.21	0.26	-9999	-0.6	173	173
IL1A	-0.2	0.34	-9999	-0.75	173	173
IL1B	-0.035	0.17	-9999	-0.57	54	54
IRAK/TRAF6/p62/Atypical PKCs	-0.012	0.14	-9999	-0.39	76	76
IL1R2	-0.087	0.18	-9999	-0.4	152	152
IL1R1	0.008	0.043	-9999	-0.4	7	7
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.002	0.081	-9999	-0.31	12	12
TOLLIP	0.013	0	-9999	-10000	0	0
TICAM2	0.003	0.056	-9999	-0.4	12	12
MAP3K3	0.013	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.009	0	-9999	-10000	0	0
IKK complex/ELKS	0.012	0.11	-9999	-0.49	1	1
JUN	-0.012	0.12	-9999	-0.48	1	1
MAP3K7	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.001	0.13	-9999	-0.4	54	54
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.1	0.22	-9999	-0.45	173	173
PIK3R1	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.091	0.2	-9999	-0.42	173	173
IL1 beta fragment/IL1R1/IL1RAP	-0.016	0.14	-9999	-0.44	55	55
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	-0.018	0.13	-9999	-0.36	76	76
IRAK1	-0.045	0.17	-9999	-0.5	76	76
IL1RN/IL1R1	-0.043	0.18	-9999	-0.57	62	62
IRAK4	0.013	0	-9999	-10000	0	0
PRKCI	0.011	0.023	-9999	-0.4	2	2
TRAF6	0.013	0	-9999	-10000	0	0
PI3K	0.018	0.011	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.009	0.073	-9999	-0.32	1	1
CHUK	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.016	0.14	-9999	-0.44	55	55
IL1 beta/IL1R2	-0.082	0.17	-9999	-0.5	59	59
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.025	0.14	-9999	-0.39	76	76
NF kappa B1 p50/RelA	-0.034	0.1	-9999	-10000	0	0
IRAK3	0.005	0.056	-9999	-0.4	12	12
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.006	0.13	-9999	-0.4	54	54
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.043	0.12	-9999	-0.43	2	2
IL1 alpha/IL1R1/IL1RAP	-0.12	0.23	-9999	-0.49	173	173
RELA	0.013	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.013	0	-9999	-10000	0	0
MYD88	0.013	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	-0.024	0.15	-9999	-0.42	76	76
IL1RAP	0.013	0	-9999	-10000	0	0
UBE2N	0.013	0	-9999	-10000	0	0
IRAK/TRAF6	-0.076	0.15	-9999	-0.6	19	19
CASP1	0.011	0.028	-9999	-0.4	3	3
IL1RN/IL1R2	-0.11	0.2	-9999	-0.57	62	62
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.007	0.13	-9999	-0.42	55	55
TMEM189-UBE2V1	-0.089	0.25	-9999	-0.74	78	78
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.045	0.11	-9999	-0.38	21	21
PIK3CA	0.012	0.016	-9999	-0.4	1	1
IL1RN	-0.063	0.23	-9999	-0.75	62	62
TRAF6/TAK1/TAB1/TAB2	-0.032	0.14	-9999	-0.41	76	76
MAP2K6	-0.025	0.14	-9999	-0.38	76	76

×

Canonical Wnt signaling pathway

Figure S27. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S27. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.014	0.017	-10000	0	-10000	0	0
AES	0.014	0.014	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.019	0.016	-10000	0	-10000	0	0
SMAD4	0.011	0.023	-10000	0	-0.4	2	2
DKK2	-0.095	0.26	-10000	0	-0.73	90	90
TLE1	0.013	0.02	-10000	0	-0.38	1	1
MACF1	0.013	0	-10000	0	-10000	0	0
CTNNB1	0.071	0.091	0.25	16	-10000	0	16
WIF1	-0.15	0.31	-10000	0	-0.75	127	127
beta catenin/RanBP3	0.031	0.11	0.31	73	-10000	0	73
KREMEN2	-0.08	0.25	-10000	0	-0.75	76	76
DKK1	-0.15	0.31	-10000	0	-0.75	131	131
beta catenin/beta TrCP1	0.074	0.086	0.25	13	-10000	0	13
FZD1	0.012	0.023	-10000	0	-0.39	2	2
AXIN2	-0.051	0.19	-10000	0	-0.55	74	74
AXIN1	0.013	0.016	-10000	0	-0.4	1	1
RAN	0.013	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.024	0.041	-10000	0	-0.52	1	1
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.045	0.084	-10000	0	-0.42	2	2
Axin1/APC/GSK3	0.11	0.061	-10000	0	-0.33	1	1
Axin1/APC/GSK3/beta catenin/Macf1	0.058	0.054	-10000	0	-10000	0	0
HNF1A	0.013	0.027	-10000	0	-0.4	2	2
CTBP1	0.014	0.014	-10000	0	-10000	0	0
MYC	-0.004	0.087	-10000	0	-0.57	11	11
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.11	0.23	-10000	0	-0.51	154	154
NKD1	-0.5	0.36	-10000	0	-0.75	415	415
TCF4	0.012	0.032	-10000	0	-0.39	3	3
TCF3	0.014	0.014	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.029	0.037	-10000	0	-0.44	3	3
Ran/GTP	0.01	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.02	0.11	0.57	1	-10000	0	1
LEF1	-0.079	0.25	-10000	0	-0.74	76	76
DVL1	0.044	0.035	-10000	0	-0.25	1	1
CSNK2A1	0.013	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.039	0.093	-10000	0	-0.49	2	2
DKK1/LRP6/Kremen 2	-0.14	0.26	-10000	0	-0.53	191	191
LRP6	0.013	0.001	-10000	0	-10000	0	0
CSNK1A1	0.015	0.016	-10000	0	-10000	0	0
NLK	0.012	0.003	-10000	0	-10000	0	0
CCND1	0	0.068	-10000	0	-0.56	5	5
WNT1	0.005	0.053	-10000	0	-0.75	3	3
GSK3A	0.013	0.001	-10000	0	-10000	0	0
GSK3B	0.013	0.001	-10000	0	-10000	0	0
FRAT1	0.012	0	-10000	0	-10000	0	0
PPP2R5D	0.22	0.15	0.33	415	-10000	0	415
APC	0.026	0.042	-10000	0	-0.41	3	3
WNT1/LRP6/FZD1	0.065	0.081	0.22	126	-10000	0	126
CREBBP	0.014	0.014	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.023	0.13	-9999	-0.58	34	34
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.012	0.047	-9999	-0.57	4	4
STXBP1	0.004	0.081	-9999	-0.75	7	7
ACh/CHRNA1	-0.046	0.083	-9999	-0.27	57	57
RAB3GAP2/RIMS1/UNC13B	0.019	0.042	-9999	-0.49	4	4
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	0.003	0.061	-9999	-0.75	4	4
mol:ACh	-0.042	0.056	-9999	-0.1	274	274
RAB3GAP2	0.012	0.016	-9999	-0.4	1	1
STX1A/SNAP25/VAMP2	-0.068	0.1	-9999	-0.38	44	44
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.046	0.083	-9999	-0.27	57	57
UNC13B	0.013	0	-9999	-10000	0	0
CHRNA1	-0.025	0.12	-9999	-0.4	57	57
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.053	0.095	-9999	-0.28	76	76
SNAP25	-0.094	0.12	-9999	-0.25	244	244
VAMP2	0.006	0	-9999	-10000	0	0
SYT1	-0.037	0.13	-9999	-0.4	76	76
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.017	0.13	-9999	-0.51	40	40
STX1A/SNAP25 fragment 1/VAMP2	-0.068	0.1	-9999	-0.38	44	44

×

Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1	-0.007	0.12	-9999	-0.51	12	12
MAP3K8	0.013	0.001	-9999	-10000	0	0
FOS	-0.016	0.11	-9999	-0.48	12	12
PRKCA	0.013	0.002	-9999	-10000	0	0
PTPN7	0	0.098	-9999	-0.62	14	14
HRAS	0.012	0.016	-9999	-0.39	1	1
PRKCB	-0.083	0.17	-9999	-0.4	147	147
NRAS	0.011	0.023	-9999	-0.39	2	2
RAS family/GTP	0.024	0.018	-9999	-10000	0	0
MAPK3	-0.009	0.089	-9999	-0.55	7	7
MAP2K1	-0.051	0.16	-9999	-0.34	147	147
ELK1	0.013	0.003	-9999	-10000	0	0
BRAF	-0.057	0.15	-9999	-0.33	147	147
mol:GTP	0	0.001	-9999	-0.005	10	10
MAPK1	-0.01	0.091	-9999	-0.59	7	7
RAF1	-0.057	0.15	-9999	-0.33	147	147
KRAS	0.012	0.016	-9999	-0.39	1	1

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.001	0.094	-9999	-0.41	19	19
MAP4K1	-0.023	0.12	-9999	-0.4	54	54
MAP3K8	0.013	0	-9999	-10000	0	0
PRKCB	-0.084	0.17	-9999	-0.4	147	147
DBNL	0.013	0	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
MAP3K1	0.012	0.082	-9999	-0.36	17	17
JUN	-0.1	0.25	-9999	-0.54	147	147
MAP3K7	0.012	0.081	-9999	-0.36	17	17
GRAP2	-0.003	0.077	-9999	-0.4	23	23
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.017	0.082	-9999	-0.36	17	17
LAT	0.009	0.049	-9999	-0.57	4	4
LCP2	0.009	0.04	-9999	-0.4	6	6
MAPK8	-0.11	0.26	-9999	-0.57	147	147
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.006	0.086	-9999	-0.39	17	17
LAT/GRAP2/SLP76/HPK1/HIP-55	0.008	0.089	-9999	-0.38	19	19

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.019	0	-9999	-10000	0	0
Necdin/E2F1	-0.007	0.1	-9999	-0.59	13	13
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.023	0.1	-9999	-0.37	13	13
NGF (dimer)/p75(NTR)/BEX1	-0.11	0.16	-9999	-0.45	69	69
NT-4/5 (dimer)/p75(NTR)	-0.08	0.16	-9999	-0.34	119	119
IKBKB	0.013	0	-9999	-10000	0	0
AKT1	-0.027	0.099	-9999	-0.37	11	11
IKBKG	0.012	0.016	-9999	-0.4	1	1
BDNF	0	0.096	-9999	-0.75	10	10
MGDIs/NGR/p75(NTR)/LINGO1	-0.071	0.17	-9999	-0.55	40	40
FURIN	0.012	0.016	-9999	-0.4	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.043	0.12	-9999	-0.51	10	10
LINGO1	-0.017	0.15	-9999	-0.75	24	24
Sortilin/TRAF6/NRIF	-0.002	0.018	-9999	-10000	0	0
proBDNF (dimer)	0	0.096	-9999	-0.75	10	10
NTRK1	0.001	0.087	-9999	-0.71	9	9
RTN4R	-0.012	0.13	-9999	-0.72	21	21
neuron apoptosis	-0.032	0.13	-9999	-0.51	9	9
IRAK1	0.011	0.031	-9999	-0.75	1	1
SHC1	-0.046	0.12	-9999	-0.44	11	11
ARHGDIA	0.012	0.016	-9999	-0.4	1	1
RhoA/GTP	0.009	0	-9999	-10000	0	0
Gamma Secretase	0.037	0.009	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.034	0.11	-9999	-0.42	12	12
MAGEH1	0.009	0.04	-9999	-0.4	6	6
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.041	0.12	-9999	-0.4	28	28
Mammalian IAPs/DIABLO	0.028	0.034	-9999	-0.45	1	1
proNGF (dimer)	-0.003	0.082	-9999	-0.43	21	21
MAGED1	0.013	0	-9999	-10000	0	0
APP	0.012	0.016	-9999	-0.4	1	1
NT-4/5 (dimer)	-0.023	0.14	-9999	-0.75	23	23
ZNF274	0.009	0.04	-9999	-0.4	6	6
RhoA/GDP/RHOGDI	-0.031	0.1	-9999	-0.38	11	11
NGF	-0.003	0.082	-9999	-0.43	21	21
cell cycle arrest	-0.018	0.1	-9999	-0.43	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.03	0.1	-9999	-0.39	9	9
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.059	0.14	-9999	-0.53	23	23
NCSTN	0.013	0	-9999	-10000	0	0
mol:GTP	-0.073	0.14	-9999	-0.44	34	34
PSENEN	0.012	0.016	-9999	-0.4	1	1
mol:ceramide	-0.035	0.1	-9999	-0.4	11	11
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.019	0.092	-9999	-0.34	9	9
p75(NTR)/beta APP	-0.054	0.12	-9999	-0.27	157	157
BEX1	-0.099	0.18	-9999	-0.4	167	167
mol:GDP	-0.054	0.12	-9999	-0.31	30	30
NGF (dimer)	-0.53	0.2	-9999	-0.55	599	599
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.057	0.16	-9999	-0.5	41	41
PIK3R1	0.013	0	-9999	-10000	0	0
RAC1/GTP	-0.037	0.1	-9999	-0.38	11	11
MYD88	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.073	0.14	-9999	-0.45	34	34
RHOB	0.013	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
MAGE-G1/E2F1	0.006	0.084	-9999	-0.57	13	13
NT3 (dimer)	0.007	0.05	-9999	-0.44	7	7
TP53	-0.021	0.1	-9999	-0.41	10	10
PRDM4	-0.035	0.1	-9999	-0.4	11	11
BDNF (dimer)	-0.88	0.26	-9999	-0.89	615	615
PIK3CA	0.012	0.016	-9999	-0.4	1	1
SORT1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.026	0.1	-9999	-0.37	13	13
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.032	0.11	-9999	-0.4	11	11
RHOC	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
MAPK10	-0.049	0.15	-9999	-0.43	41	41
DIABLO	0.013	0.001	-9999	-10000	0	0
SMPD2	-0.035	0.1	-9999	-0.4	11	11
APH1B	0.013	0.001	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.044	0.12	-9999	-0.44	11	11
PSEN1	0.013	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0.019	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.057	0.13	-9999	-0.27	161	161
MAPK8	-0.025	0.12	-9999	-0.5	1	1
MAPK9	-0.025	0.12	-9999	-0.5	1	1
APAF1	0.013	0.001	-9999	-10000	0	0
NTF3	0.007	0.05	-9999	-0.45	7	7
NTF4	-0.023	0.14	-9999	-0.75	23	23
NDN	-0.006	0.086	-9999	-0.4	29	29
RAC1/GDP	0.009	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.064	0.097	-9999	-0.35	34	34
p75 CTF/Sortilin/TRAF6/NRIF	0.03	0.022	-9999	-10000	0	0
RhoA-B-C/GTP	-0.073	0.14	-9999	-0.44	34	34
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.024	0.11	-9999	-0.42	13	13
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.031	0.11	-9999	-0.46	10	10
PRKACB	-0.037	0.13	-9999	-0.4	76	76
proBDNF (dimer)/p75 ECD	0.009	0.074	-9999	-0.57	10	10
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	0.005	0.057	-9999	-0.43	10	10
BIRC2	0.012	0.016	-9999	-0.4	1	1
neuron projection morphogenesis	-0.048	0.13	-9999	-0.37	32	32
BAD	-0.033	0.14	-9999	-0.45	7	7
RIPK2	0.013	0	-9999	-10000	0	0
NGFR	-0.089	0.18	-9999	-0.4	156	156
CYCS	-0.027	0.099	-9999	-0.37	11	11
ADAM17	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.032	0.11	-9999	-0.4	11	11
BCL2L11	-0.033	0.14	-9999	-0.45	7	7
BDNF (dimer)/p75(NTR)	-0.063	0.14	-9999	-0.59	10	10
PI3K	-0.032	0.11	-9999	-0.4	11	11
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.032	0.11	-9999	-0.4	11	11
NDNL2	0.013	0.001	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
PRKCI	0.011	0.023	-9999	-0.4	2	2
NGF (dimer)/p75(NTR)	-0.064	0.14	-9999	-0.28	168	168
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.032	0.11	-9999	-0.4	11	11
TRAF6	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
PLG	-0.16	0.31	-9999	-0.75	133	133
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.043	0.12	-9999	-0.38	21	21
SQSTM1	0.013	0	-9999	-10000	0	0
NGFRAP1	0.011	0.023	-9999	-0.4	2	2
CASP3	-0.03	0.13	-9999	-0.42	7	7
E2F1	-0.003	0.11	-9999	-0.75	13	13
CASP9	0.013	0	-9999	-10000	0	0
IKK complex	-0.041	0.08	-9999	-0.4	11	11
NGF (dimer)/TRKA	-0.001	0.092	-9999	-0.38	29	29
MMP7	-0.72	0.16	-9999	-0.75	595	595
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.025	0.1	-9999	-0.37	14	14
MMP3	-0.62	0.28	-9999	-0.75	519	519
APAF-1/Caspase 9	-0.035	0.062	-9999	-0.46	1	1

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.021	0.17	-10000	0	-0.79	28	28
NFATC2	-0.012	0.16	-10000	0	-0.6	17	17
NFATC3	-0.019	0.056	-10000	0	-10000	0	0
CD40LG	-0.3	0.35	-10000	0	-0.95	64	64
ITCH	0.038	0.024	-10000	0	-0.48	1	1
CBLB	0.038	0.024	-10000	0	-0.48	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.15	0.26	-10000	0	-0.88	41	41
JUNB	0.011	0.023	-10000	0	-0.4	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.034	0.019	-10000	0	-10000	0	0
T cell anergy	0.036	0.044	-10000	0	-10000	0	0
TLE4	0.005	0.12	-10000	0	-0.59	6	6
Jun/NFAT1-c-4/p21SNFT	-0.14	0.24	-10000	0	-0.89	26	26
AP-1/NFAT1-c-4	-0.33	0.39	-10000	0	-0.97	86	86
IKZF1	-0.024	0.2	-10000	0	-0.64	49	49
T-helper 2 cell differentiation	-0.081	0.17	-10000	0	-0.71	21	21
AP-1/NFAT1	-0.07	0.12	-10000	0	-0.53	5	5
CALM1	0.024	0.011	-10000	0	-10000	0	0
EGR2	-0.045	0.22	-10000	0	-1.1	15	15
EGR3	-0.051	0.24	-10000	0	-1	22	22
NFAT1/FOXP3	-0.023	0.19	-10000	0	-0.63	36	36
EGR1	0.012	0.023	-10000	0	-0.39	2	2
JUN	-0.027	0.037	-10000	0	-10000	0	0
EGR4	-0.11	0.28	-10000	0	-0.75	102	102
mol:Ca2+	0.012	0.011	-10000	0	-10000	0	0
GBP3	-0.033	0.2	-10000	0	-0.62	58	58
FOSL1	-0.47	0.37	-10000	0	-0.75	390	390
NFAT1-c-4/MAF/IRF4	-0.11	0.24	-10000	0	-0.95	25	25
DGKA	0.005	0.12	-10000	0	-0.58	7	7
CREM	0.012	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.065	0.21	-10000	0	-0.97	16	16
CTLA4	-0.026	0.2	-10000	0	-0.63	43	43
NFAT1-c-4 (dimer)/EGR1	-0.062	0.21	-10000	0	-0.97	16	16
NFAT1-c-4 (dimer)/EGR4	-0.14	0.27	-10000	0	-0.89	30	30
FOS	-0.034	0.059	-10000	0	-0.4	10	10
IFNG	-0.12	0.24	-10000	0	-0.63	82	82
T cell activation	-0.095	0.15	-10000	0	-0.7	5	5
MAF	0.003	0.06	-10000	0	-0.4	14	14
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.046	0.18	0.92	14	-10000	0	14
TNF	-0.11	0.23	-10000	0	-0.88	21	21
FASLG	-0.12	0.36	-10000	0	-1.3	45	45
TBX21	-0.017	0.1	-10000	0	-0.41	36	36
BATF3	0.005	0.076	-10000	0	-0.7	7	7
PRKCQ	0.005	0.055	-10000	0	-0.4	10	10
PTPN1	0.006	0.11	-10000	0	-0.52	6	6
NFAT1-c-4/ICER1	-0.065	0.21	-10000	0	-0.97	16	16
GATA3	0.009	0.045	-10000	0	-0.47	5	5
T-helper 1 cell differentiation	-0.11	0.24	-10000	0	-0.62	82	82
IL2RA	-0.18	0.22	-10000	0	-0.8	44	44
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.006	0.11	-10000	0	-0.52	6	6
E2F1	0.002	0.11	-10000	0	-0.74	13	13
PPARG	0.011	0.023	-10000	0	-0.39	2	2
SLC3A2	0.006	0.11	-10000	0	-0.52	6	6
IRF4	-0.095	0.18	-10000	0	-0.4	164	164
PTGS2	-0.31	0.36	-10000	0	-1	64	64
CSF2	-0.44	0.47	-10000	0	-0.96	246	246
JunB/Fra1/NFAT1-c-4	-0.33	0.29	-10000	0	-0.81	73	73
IL4	-0.084	0.18	-10000	0	-0.78	18	18
IL5	-0.3	0.34	-10000	0	-0.95	59	59
IL2	-0.096	0.15	-10000	0	-0.71	5	5
IL3	-0.063	0.05	-10000	0	-10000	0	0
RNF128	0.038	0.024	-10000	0	-0.48	1	1
NFATC1	-0.046	0.18	-10000	0	-0.93	14	14
CDK4	0.03	0.12	0.64	5	-10000	0	5
PTPRK	0.006	0.11	-10000	0	-0.52	6	6
IL8	-0.5	0.47	-10000	0	-0.95	267	267
POU2F1	0.011	0.031	-10000	0	-0.75	1	1

×

TCGA08_p53

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
CDKN2A	-0.1	0.23	-10000	0	-0.58	120	120
TP53	-0.027	0.059	0.28	1	-10000	0	1
Senescence	-0.027	0.059	0.28	1	-10000	0	1
Apoptosis	-0.027	0.059	0.28	1	-10000	0	1
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.052	0.11	0.27	119	-10000	0	119
MDM4	0.011	0.031	-10000	0	-0.75	1	1

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.013	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.005	0.069	-9999	-10000	0	0
Syndecan-3/Neurocan	0.009	0.027	-9999	-0.41	2	2
POMC	-0.004	0.081	-9999	-0.41	23	23
EGFR	0.011	0.023	-9999	-0.4	2	2
Syndecan-3/EGFR	0.022	0.011	-9999	-10000	0	0
AGRP	-0.003	0.074	-9999	-0.75	6	6
NCSTN	0.013	0	-9999	-10000	0	0
PSENEN	0.012	0.016	-9999	-0.4	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.013	0.001	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
NCAN	0.003	0.043	-9999	-0.75	2	2
long-term memory	0.029	0.002	-9999	-10000	0	0
Syndecan-3/IL8	-0.22	0.22	-9999	-0.41	347	347
PSEN1	0.013	0	-9999	-10000	0	0
Src/Cortactin	0.019	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
limb bud formation	0	0.002	-9999	-10000	0	0
MC4R	-0.002	0.06	-9999	-0.75	4	4
SRC	0.013	0	-9999	-10000	0	0
PTN	-0.054	0.15	-9999	-0.4	101	101
FGFR/FGF/Syndecan-3	0	0.002	-9999	-10000	0	0
neuron projection morphogenesis	-0.01	0.065	-9999	-0.37	2	2
Syndecan-3/AgRP	0.004	0.043	-9999	-0.41	6	6
Syndecan-3/AgRP/MC4R	0.005	0.058	-9999	-0.45	9	9
Fyn/Cortactin	0.019	0	-9999	-10000	0	0
SDC3	0	0.002	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.22	0.21	-9999	-0.41	347	347
IL8	-0.41	0.38	-9999	-0.75	347	347
Syndecan-3/Fyn/Cortactin	0.03	0.002	-9999	-10000	0	0
Syndecan-3/CASK	0	0.001	-9999	-10000	0	0
alpha-MSH/MC4R	-0.004	0.074	-9999	-0.57	5	5
Gamma Secretase	0.037	0.009	-9999	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.054	0.14	-9999	-0.47	22	22
FZD6	0.013	0	-9999	-10000	0	0
WNT6	-0.032	0.15	-9999	-0.5	53	53
WNT4	-0.003	0.088	-9999	-0.47	20	20
FZD3	0.006	0.065	-9999	-0.63	6	6
WNT5A	0.003	0.082	-9999	-0.71	8	8
WNT11	-0.14	0.3	-9999	-0.72	129	129

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.002	0.093	-9999	-0.48	15	15
alphaM/beta2 Integrin/GPIbA	-0.001	0.083	-9999	-0.45	10	10
alphaM/beta2 Integrin/proMMP-9	-0.035	0.16	-9999	-0.51	54	54
PLAUR	0.013	0	-9999	-10000	0	0
HMGB1	0.009	0.016	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	0.003	0.077	-9999	-0.44	10	10
AGER	0.007	0.036	-9999	-0.8	1	1
RAP1A	0.013	0	-9999	-10000	0	0
SELPLG	0.011	0.023	-9999	-0.4	2	2
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.001	0.1	-9999	-0.45	13	13
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.045	0.2	-9999	-0.72	49	49
CYR61	0.005	0.075	-9999	-0.75	6	6
TLN1	0.013	0	-9999	-10000	0	0
Rap1/GTP	-0.053	0.091	-9999	-0.42	13	13
RHOA	0.013	0	-9999	-10000	0	0
P-selectin oligomer	-0.037	0.13	-9999	-0.39	75	75
MYH2	-0.049	0.13	-9999	-0.42	35	35
MST1R	0.012	0.016	-9999	-0.4	1	1
leukocyte activation during inflammatory response	-0.058	0.15	-9999	-0.44	67	67
APOB	-0.069	0.2	-9999	-0.5	95	95
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.004	0.074	-9999	-0.62	8	8
JAM3	0.013	0	-9999	-10000	0	0
GP1BA	0.005	0.049	-9999	-0.4	9	9
alphaM/beta2 Integrin/CTGF	0.001	0.085	-9999	-0.46	13	13
alphaM/beta2 Integrin	-0.047	0.12	-9999	-0.37	49	49
JAM3 homodimer	0.013	0	-9999	-10000	0	0
ICAM2	0.013	0	-9999	-10000	0	0
ICAM1	0.011	0.031	-9999	-0.75	1	1
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.047	0.12	-9999	-0.36	49	49
cell adhesion	-0.001	0.082	-9999	-0.45	10	10
NFKB1	-0.007	0.14	-9999	-0.64	7	7
THY1	-0.014	0.14	-9999	-0.75	22	22
RhoA/GDP	0.009	0	-9999	-10000	0	0
Lipoprotein(a)	-0.062	0.16	-9999	-0.52	56	56
alphaM/beta2 Integrin/LRP/tPA	0.01	0.076	-9999	-0.42	10	10
IL6	-0.045	0.23	-9999	-0.59	88	88
ITGB2	0.001	0.056	-9999	-0.4	11	11
elevation of cytosolic calcium ion concentration	-0.02	0.14	-9999	-0.45	51	51
alphaM/beta2 Integrin/JAM2/JAM3	-0.039	0.13	-9999	-0.44	33	33
JAM2	-0.084	0.17	-9999	-0.4	147	147
alphaM/beta2 Integrin/ICAM1	-0.054	0.18	-9999	-0.43	103	103
alphaM/beta2 Integrin/uPA/Plg	-0.12	0.22	-9999	-0.46	182	182
RhoA/GTP	-0.051	0.14	-9999	-0.44	36	36
positive regulation of phagocytosis	-0.041	0.12	-9999	-0.53	16	16
Ron/MSP	-0.075	0.22	-9999	-0.57	99	99
alphaM/beta2 Integrin/uPAR/uPA	-0.02	0.14	-9999	-0.45	51	51
alphaM/beta2 Integrin/uPAR	0.003	0.077	-9999	-0.44	10	10
PLAU	-0.039	0.19	-9999	-0.75	42	42
PLAT	0.009	0.042	-9999	-0.48	4	4
actin filament polymerization	-0.047	0.13	-9999	-0.41	35	35
MST1	-0.11	0.28	-9999	-0.75	99	99
alphaM/beta2 Integrin/lipoprotein(a)	-0.058	0.15	-9999	-0.44	67	67
TNF	-0.002	0.14	-9999	-0.77	7	7
RAP1B	0.013	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.031	0.15	-9999	-0.5	51	51
fibrinolysis	-0.12	0.22	-9999	-0.46	182	182
HCK	0.003	0.062	-9999	-0.4	15	15
dendritic cell antigen processing and presentation	-0.047	0.12	-9999	-0.36	49	49
VTN	-0.013	0.13	-9999	-0.75	19	19
alphaM/beta2 Integrin/CYR61	-0.001	0.092	-9999	-0.46	16	16
LPA	-0.029	0.16	-9999	-0.75	29	29
LRP1	0.011	0.023	-9999	-0.4	2	2
cell migration	-0.03	0.16	-9999	-0.49	57	57
FN1	-0.028	0.17	-9999	-0.67	37	37
alphaM/beta2 Integrin/Thy1	-0.015	0.12	-9999	-0.48	31	31
MPO	-0.013	0.14	-9999	-0.75	20	20
KNG1	-0.076	0.16	-9999	-0.4	132	132
RAP1/GDP	0.017	0	-9999	-10000	0	0
ROCK1	-0.043	0.13	-9999	-0.42	32	32
ELA2	0	0	-9999	-10000	0	0
PLG	-0.16	0.31	-9999	-0.75	133	133
CTGF	0.009	0.053	-9999	-0.75	3	3
alphaM/beta2 Integrin/Hck	-0.002	0.097	-9999	-0.54	13	13
ITGAM	-0.014	0.094	-9999	-0.4	34	34
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.014	0.11	-9999	-0.45	21	21
HP	-0.031	0.17	-9999	-0.75	34	34
leukocyte adhesion	-0.045	0.15	-9999	-0.54	19	19
SELP	-0.037	0.13	-9999	-0.4	75	75

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.061	0.25	-10000	0	-0.84	33	33
NCK1/PAK1/Dok-R	-0.029	0.099	-10000	0	-0.41	32	32
NCK1/Dok-R	0.028	0.27	-10000	0	-0.93	43	43
PIK3CA	0.011	0.016	-10000	0	-0.39	1	1
mol:beta2-estradiol	0.002	0.055	0.26	27	-10000	0	27
RELA	0.013	0	-10000	0	-10000	0	0
SHC1	0.013	0.001	-10000	0	-10000	0	0
Rac/GDP	0.009	0	-10000	0	-10000	0	0
F2	-0.26	0.36	0.24	12	-0.75	214	226
TNIP2	0.013	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.016	0.24	-10000	0	-0.86	43	43
FN1	-0.028	0.17	-10000	0	-0.67	37	37
PLD2	0.028	0.28	-10000	0	-0.95	43	43
PTPN11	0.013	0	-10000	0	-10000	0	0
GRB14	-0.024	0.14	-10000	0	-0.5	42	42
ELK1	0.036	0.25	-10000	0	-0.86	43	43
GRB7	-0.006	0.12	-10000	0	-0.75	15	15
PAK1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.038	0.26	-10000	0	-0.9	45	45
CDKN1A	0.071	0.2	-10000	0	-0.62	26	26
ITGA5	0.01	0.043	-10000	0	-0.75	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.028	0.27	-10000	0	-0.93	43	43
CRK	0.013	0	-10000	0	-10000	0	0
mol:NO	0.066	0.2	-10000	0	-0.63	34	34
PLG	-0.069	0.32	-10000	0	-1	43	43
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.054	0.24	-10000	0	-0.77	40	40
GRB2	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.002	-10000	0	-10000	0	0
ANGPT2	0.041	0.19	0.38	7	-0.52	17	24
BMX	-0.05	0.3	-10000	0	-1	43	43
ANGPT1	0.036	0.26	-10000	0	-1.1	27	27
tube development	0.065	0.22	-10000	0	-0.66	30	30
ANGPT4	0.001	0.061	-10000	0	-0.75	4	4
response to hypoxia	-0.001	0.017	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	0.007	0.3	-10000	0	-1	43	43
alpha5/beta1 Integrin	0.017	0.033	-10000	0	-0.57	2	2
FGF2	-0.018	0.1	-10000	0	-0.39	45	45
STAT5A (dimer)	0.066	0.24	-10000	0	-0.77	27	27
mol:L-citrulline	0.066	0.2	-10000	0	-0.63	34	34
AGTR1	-0.13	0.19	-10000	0	-0.39	220	220
MAPK14	0.033	0.29	-10000	0	-1	40	40
Tie2/SHP2	-0.014	0.2	-10000	0	-1	22	22
TEK	-0.017	0.22	-10000	0	-1.1	22	22
RPS6KB1	0.06	0.24	-10000	0	-0.81	33	33
Angiotensin II/AT1	-0.091	0.14	-10000	0	-0.27	220	220
Tie2/Ang1/GRB2	0.024	0.29	-10000	0	-0.98	43	43
MAPK3	0.033	0.26	-10000	0	-0.87	43	43
MAPK1	0.033	0.26	-10000	0	-0.87	43	43
Tie2/Ang1/GRB7	0.015	0.3	-10000	0	-1	43	43
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	0.028	0.28	-10000	0	-0.95	43	43
PI3K	0.05	0.28	-10000	0	-0.91	40	40
FES	0.032	0.29	-10000	0	-1	40	40
Crk/Dok-R	0.028	0.27	-10000	0	-0.93	43	43
Tie2/Ang1/ABIN2	0.024	0.29	-10000	0	-0.98	43	43
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.065	0.23	-10000	0	-0.75	33	33
STAT5A	0.013	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.06	0.24	-10000	0	-0.8	35	35
Tie2/Ang2	0.053	0.27	-10000	0	-0.9	30	30
Tie2/Ang1	0.023	0.3	-10000	0	-1	43	43
FOXO1	0.069	0.23	-10000	0	-0.76	32	32
ELF1	0.018	0.02	-10000	0	-10000	0	0
ELF2	0.027	0.28	-10000	0	-0.95	43	43
mol:Choline	0.03	0.27	-10000	0	-0.91	43	43
cell migration	-0.021	0.059	-10000	0	-0.24	12	12
FYN	0.062	0.23	-10000	0	-0.75	30	30
DOK2	0.003	0.06	-10000	0	-0.4	14	14
negative regulation of cell cycle	0.072	0.19	-10000	0	-0.56	26	26
ETS1	0.008	0.058	-10000	0	-0.37	3	3
PXN	0.068	0.21	-10000	0	-0.67	33	33
ITGB1	0.013	0	-10000	0	-10000	0	0
NOS3	0.063	0.22	-10000	0	-0.72	34	34
RAC1	0.013	0	-10000	0	-10000	0	0
TNF	0.007	0.067	-10000	0	-0.43	5	5
MAPKKK cascade	0.03	0.27	-10000	0	-0.91	43	43
RASA1	0.013	0.001	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.026	0.29	-10000	0	-0.98	43	43
NCK1	0.013	0	-10000	0	-10000	0	0
vasculogenesis	0.068	0.19	-10000	0	-0.56	34	34
mol:Phosphatidic acid	0.03	0.27	-10000	0	-0.91	43	43
mol:Angiotensin II	0.001	0.004	-10000	0	-10000	0	0
mol:NADP	0.066	0.2	-10000	0	-0.63	34	34
Rac1/GTP	-0.043	0.18	-10000	0	-0.72	40	40
MMP2	0.024	0.29	-10000	0	-0.96	43	43

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.006	0.068	-10000	0	-0.75	5	5
mol:Halofuginone	0.005	0	-10000	0	-10000	0	0
ITGA1	0.013	0	-10000	0	-10000	0	0
CDKN1A	0.028	0.016	-10000	0	-0.36	1	1
PRL-3/alpha Tubulin	-0.074	0.21	-10000	0	-0.57	98	98
mol:Ca2+	-0.036	0.23	0.33	73	-0.55	85	158
AGT	-0.092	0.26	-10000	0	-0.75	85	85
CCNA2	0.033	0.011	-10000	0	-10000	0	0
TUBA1B	0.013	0	-10000	0	-10000	0	0
EGR1	0.02	0.016	-10000	0	-0.26	2	2
CDK2/Cyclin E1	0.035	0.042	-10000	0	-0.4	5	5
MAPK3	-0.074	0.22	-10000	0	-0.57	98	98
PRL-2 /Rab GGTase beta	0.019	0	-10000	0	-10000	0	0
MAPK1	-0.074	0.22	-10000	0	-0.57	98	98
PTP4A1	0.029	0.012	-10000	0	-10000	0	0
PTP4A3	-0.11	0.28	-10000	0	-0.75	98	98
PTP4A2	0.013	0	-10000	0	-10000	0	0
ITGB1	-0.074	0.21	-10000	0	-0.57	98	98
SRC	0.013	0	-10000	0	-10000	0	0
RAC1	-0.005	0.078	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.019	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.034	0.011	-10000	0	-10000	0	0
RABGGTA	0.013	0	-10000	0	-10000	0	0
BCAR1	0.052	0.12	0.33	98	-0.28	1	99
RHOC	-0.005	0.078	-10000	0	-10000	0	0
RHOA	-0.005	0.078	-10000	0	-10000	0	0
cell motility	-0.002	0.08	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.034	0.011	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.074	0.21	-10000	0	-0.57	98	98
ROCK1	-0.002	0.08	-10000	0	-10000	0	0
RABGGTB	0.013	0	-10000	0	-10000	0	0
CDK2	0.013	0	-10000	0	-10000	0	0
mitosis	0.029	0.012	-10000	0	-10000	0	0
ATF5	0.013	0	-10000	0	-10000	0	0

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.042	0.11	-10000	0	-0.56	3	3
cell-cell adhesion	0.075	0.14	0.61	4	-10000	0	4
Ephrin B/EPHB2/RasGAP	0.031	0.047	-10000	0	-0.42	5	5
ITSN1	0.012	0.016	-10000	0	-0.4	1	1
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
SHC1	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.014	0.12	-10000	0	-0.5	38	38
Ephrin B1/EPHB1	-0.091	0.21	-10000	0	-0.5	131	131
HRAS/GDP	-0.076	0.14	-10000	0	-0.36	120	120
Ephrin B/EPHB1/GRB7	-0.073	0.21	-10000	0	-0.44	140	140
Endophilin/SYNJ1	0.024	0.044	-10000	0	-0.39	5	5
KRAS	0.012	0.016	-10000	0	-0.4	1	1
Ephrin B/EPHB1/Src	-0.063	0.19	-10000	0	-0.42	132	132
endothelial cell migration	0.027	0.008	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
GRB7	-0.006	0.12	-10000	0	-0.75	15	15
PAK1	0.03	0.045	-10000	0	-0.39	5	5
HRAS	0.012	0.016	-10000	0	-0.4	1	1
RRAS	0.024	0.044	-10000	0	-0.4	5	5
DNM1	0.004	0.081	-10000	0	-0.75	7	7
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.064	0.18	-10000	0	-0.4	132	132
lamellipodium assembly	-0.075	0.14	-10000	0	-0.61	4	4
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.024	0.11	-10000	0	-0.41	2	2
PIK3R1	0.013	0	-10000	0	-10000	0	0
EPHB2	0.009	0.053	-10000	0	-0.75	3	3
EPHB3	-0.034	0.18	-10000	0	-0.75	38	38
EPHB1	-0.15	0.31	-10000	0	-0.75	132	132
EPHB4	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.031	0.14	-10000	0	-0.47	4	4
Ephrin B/EPHB2	0.023	0.047	-10000	0	-0.42	5	5
Ephrin B/EPHB3	-0.002	0.11	-10000	0	-0.43	40	40
JNK cascade	-0.063	0.18	-10000	0	-0.42	132	132
Ephrin B/EPHB1	-0.07	0.19	-10000	0	-0.43	132	132
RAP1/GDP	-0.016	0.13	-10000	0	-0.44	3	3
EFNB2	0.013	0	-10000	0	-10000	0	0
EFNB3	0.004	0.065	-10000	0	-0.46	11	11
EFNB1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.078	0.2	-10000	0	-0.46	132	132
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.078	0.15	-10000	0	-0.61	6	6
Rap1/GTP	-0.076	0.14	-10000	0	-0.63	4	4
axon guidance	-0.042	0.11	-10000	0	-0.56	3	3
MAPK3	-0.011	0.098	-10000	0	-0.36	2	2
MAPK1	-0.011	0.098	-10000	0	-0.36	2	2
Rac1/GDP	-0.022	0.14	-10000	0	-0.47	3	3
actin cytoskeleton reorganization	-0.063	0.12	-10000	0	-0.45	6	6
CDC42/GDP	-0.022	0.14	-10000	0	-0.5	4	4
PI3K	0.029	0.008	-10000	0	-10000	0	0
EFNA5	-0.084	0.17	-10000	0	-0.4	147	147
Ephrin B2/EPHB4	0.017	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.026	0.036	-10000	0	-10000	0	0
CDC42	0.011	0.023	-10000	0	-0.4	2	2
RAS family/GTP	-0.075	0.14	-10000	0	-0.57	6	6
PTK2	0.019	0.037	-10000	0	-10000	0	0
MAP4K4	-0.064	0.19	-10000	0	-0.42	132	132
SRC	0.013	0	-10000	0	-10000	0	0
KALRN	0.012	0.016	-10000	0	-0.4	1	1
Intersectin/N-WASP	0.018	0.011	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.013	0.13	-10000	0	-0.44	6	6
MAP2K1	-0.017	0.1	-10000	0	-0.38	2	2
WASL	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.071	0.2	-10000	0	-0.45	132	132
cell migration	-0.012	0.11	-10000	0	-0.43	2	2
NRAS	0.011	0.023	-10000	0	-0.4	2	2
SYNJ1	0.024	0.044	-10000	0	-0.4	5	5
PXN	0.013	0	-10000	0	-10000	0	0
TF	-0.002	0.097	-10000	0	-0.4	21	21
HRAS/GTP	-0.081	0.15	-10000	0	-0.67	4	4
Ephrin B1/EPHB1-2	-0.078	0.2	-10000	0	-0.46	132	132
cell adhesion mediated by integrin	0	0.061	0.34	6	-10000	0	6
RAC1	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.057	0.18	-10000	0	-0.39	133	133
RAC1-CDC42/GTP	-0.096	0.17	-10000	0	-0.66	17	17
RASA1	0.013	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.016	0.13	-10000	0	-0.48	4	4
ruffle organization	-0.038	0.16	-10000	0	-0.63	4	4
NCK1	0.013	0	-10000	0	-10000	0	0
receptor internalization	0.024	0.063	-10000	0	-0.4	12	12
Ephrin B/EPHB2/KALRN	0.03	0.048	-10000	0	-0.42	5	5
ROCK1	-0.008	0.11	-10000	0	-0.45	38	38
RAS family/GDP	-0.053	0.1	-10000	0	-0.42	5	5
Rac1/GTP	-0.08	0.15	-10000	0	-0.67	4	4
Ephrin B/EPHB1/Src/Paxillin	-0.027	0.11	-10000	0	-0.45	2	2

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0	0.079	-10000	0	-0.37	8	8
ER alpha/Gai/GDP/Gbeta gamma	-0.12	0.23	-10000	0	-0.64	70	70
AKT1	-0.063	0.25	-10000	0	-0.81	60	60
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.068	0.25	-10000	0	-0.84	60	60
mol:Ca2+	0.019	0.061	-10000	0	-0.41	6	6
IGF1R	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.006	0.07	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.059	0.24	0.77	60	-10000	0	60
RhoA/GTP	-0.015	0.044	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.1	0.17	-10000	0	-0.6	49	49
regulation of stress fiber formation	-0.024	0.048	-10000	0	-10000	0	0
E2/ERA-ERB (dimer)	-0.008	0.074	-10000	0	-0.44	1	1
KRAS	0.012	0.016	-10000	0	-0.4	1	1
G13/GTP	-0.005	0.063	-10000	0	-10000	0	0
pseudopodium formation	0.024	0.048	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1	-0.006	0.07	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
GNG2	-0.004	0.081	-10000	0	-0.4	26	26
GNAO1	-0.14	0.2	-10000	0	-0.4	234	234
HRAS	0.012	0.016	-10000	0	-0.4	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.07	0.2	-10000	0	-0.59	65	65
E2/ER beta (dimer)	0.007	0.025	-10000	0	-0.28	5	5
mol:GDP	-0.031	0.09	-10000	0	-0.48	1	1
mol:NADP	-0.07	0.2	-10000	0	-0.59	65	65
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	0.019	0.063	-10000	0	-0.42	6	6
IGF-1R heterotetramer	0.013	0	-10000	0	-10000	0	0
PLCB1	0.014	0.064	-10000	0	-0.38	10	10
PLCB2	0.016	0.058	-10000	0	-0.45	4	4
IGF1	-0.08	0.17	-10000	0	-0.4	142	142
mol:L-citrulline	-0.07	0.2	-10000	0	-0.59	65	65
RHOA	0.013	0	-10000	0	-10000	0	0
Gai/GDP	-0.22	0.34	-10000	0	-0.65	234	234
JNK cascade	0.007	0.025	-10000	0	-0.28	5	5
BCAR1	0.012	0.016	-10000	0	-0.4	1	1
ESR2	0.009	0.036	-10000	0	-0.4	5	5
GNAQ	0.011	0.028	-10000	0	-0.4	3	3
ESR1	-0.027	0.12	-10000	0	-0.4	59	59
Gq family/GDP/Gbeta gamma	0.018	0.067	-10000	0	-0.43	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.008	0.08	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.1	0.17	-10000	0	-0.6	49	49
GNAZ	0.007	0.046	-10000	0	-0.4	8	8
E2/ER alpha (dimer)	-0.018	0.083	-10000	0	-0.28	59	59
STRN	0.013	0.001	-10000	0	-10000	0	0
GNAL	-0.01	0.094	-10000	0	-0.4	35	35
PELP1	0.013	0	-10000	0	-10000	0	0
MAPK11	0.012	0.036	-10000	0	-0.5	2	2
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.075	-10000	0	-0.4	22	22
HBEGF	-0.11	0.2	-10000	0	-0.54	77	77
cAMP biosynthetic process	-0.028	0.073	-10000	0	-0.35	13	13
SRC	-0.11	0.22	-10000	0	-0.6	70	70
PI3K	0.018	0.011	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.032	0.085	-10000	0	-0.42	8	8
SOS1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.11	0.16	-10000	0	-0.49	68	68
Gs family/GTP	-0.012	0.08	-10000	0	-0.36	13	13
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.023	0.018	-10000	0	-10000	0	0
vasodilation	-0.066	0.19	-10000	0	-0.56	65	65
mol:DAG	0.019	0.063	-10000	0	-0.42	6	6
Gs family/GDP/Gbeta gamma	-0.038	0.095	-10000	0	-0.41	18	18
MSN	0.024	0.051	-10000	0	-10000	0	0
Gq family/GTP	0.011	0.061	-10000	0	-0.41	7	7
mol:PI-3-4-5-P3	-0.064	0.24	-10000	0	-0.8	60	60
NRAS	0.011	0.023	-10000	0	-0.4	2	2
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.066	0.19	0.56	65	-10000	0	65
GRB2/SOS1	0.019	0	-10000	0	-10000	0	0
RhoA/GDP	-0.028	0.084	-10000	0	-0.45	1	1
NOS3	-0.075	0.21	-10000	0	-0.63	65	65
GNA11	0.01	0.033	-10000	0	-0.4	4	4
MAPKKK cascade	-0.053	0.2	-10000	0	-0.63	59	59
E2/ER alpha (dimer)/PELP1/Src	-0.11	0.18	-10000	0	-0.63	49	49
ruffle organization	0.024	0.048	-10000	0	-10000	0	0
ROCK2	0.02	0.054	-10000	0	-10000	0	0
GNA14	0.009	0.036	-10000	0	-0.4	5	5
GNA15	0.005	0.075	-10000	0	-0.75	6	6
GNA13	0.013	0	-10000	0	-10000	0	0
MMP9	-0.12	0.22	-10000	0	-0.51	101	101
MMP2	-0.098	0.21	-10000	0	-0.61	58	58

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.009	0.14	-10000	0	-0.52	34	34
FYN	-0.007	0.19	-10000	0	-0.62	43	43
LAT/GRAP2/SLP76	-0.043	0.15	-10000	0	-0.53	41	41
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	0.01	0.14	-10000	0	-0.43	41	41
B2M	0.012	0.023	-10000	0	-0.4	2	2
IKBKG	-0.015	0.038	-10000	0	-0.17	9	9
MAP3K8	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	-0.016	0.042	-10000	0	-0.15	54	54
integrin-mediated signaling pathway	0.015	0.023	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.003	0.19	-10000	0	-0.61	45	45
TRPV6	-0.065	0.21	-10000	0	-0.75	54	54
CD28	-0.004	0.081	-10000	0	-0.4	25	25
SHC1	-0.005	0.18	-10000	0	-0.63	39	39
receptor internalization	-0.016	0.2	-10000	0	-0.65	44	44
PRF1	-0.013	0.21	-10000	0	-0.88	26	26
KRAS	0.012	0.016	-10000	0	-0.4	1	1
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	0.018	0.11	-10000	0	-0.35	34	34
LAT	-0.006	0.18	-10000	0	-0.59	45	45
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	0.001	0.072	-10000	0	-0.4	19	19
CD3E	-0.004	0.084	-10000	0	-0.4	26	26
CD3G	-0.021	0.11	-10000	0	-0.4	52	52
RASGRP2	-0.007	0.051	-10000	0	-0.17	52	52
RASGRP1	0.016	0.14	-10000	0	-0.45	38	38
HLA-A	0.013	0.017	-10000	0	-0.4	1	1
RASSF5	0.009	0.04	-10000	0	-0.4	6	6
RAP1A/GTP/RAPL	0.015	0.023	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.021	0.047	-10000	0	-0.13	29	29
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.027	0.066	-10000	0	-0.26	23	23
PRKCA	-0.02	0.071	-10000	0	-0.27	30	30
GRAP2	-0.003	0.077	-10000	0	-0.4	23	23
mol:IP3	-0.017	0.14	0.26	52	-0.43	34	86
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.016	0.17	-10000	0	-0.57	45	45
ORAI1	0.037	0.1	0.36	53	-10000	0	53
CSK	-0.006	0.18	-10000	0	-0.63	39	39
B7 family/CD28	-0.006	0.19	-10000	0	-0.66	38	38
CHUK	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.015	0.21	-10000	0	-0.69	43	43
PTPN6	-0.007	0.18	-10000	0	-0.62	41	41
VAV1	-0.011	0.19	-10000	0	-0.63	45	45
Monovalent TCR/CD3	-0.017	0.15	-10000	0	-0.6	32	32
CBL	0.013	0	-10000	0	-10000	0	0
LCK	-0.01	0.19	-10000	0	-0.64	41	41
PAG1	-0.008	0.18	-10000	0	-0.62	41	41
RAP1A	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.016	0.21	-10000	0	-0.69	43	43
CD80	0.009	0.049	-10000	0	-0.57	4	4
CD86	0.004	0.059	-10000	0	-0.4	13	13
PDK1/CARD11/BCL10/MALT1	-0.032	0.08	-10000	0	-0.3	31	31
HRAS	0.012	0.016	-10000	0	-0.4	1	1
GO:0035030	-0.002	0.16	-10000	0	-0.54	38	38
CD8A	-0.016	0.11	-10000	0	-0.4	45	45
CD8B	0.003	0.068	-10000	0	-0.42	15	15
PTPRC	-0.02	0.11	-10000	0	-0.4	50	50
PDK1/PKC theta	0.012	0.16	-10000	0	-0.54	38	38
CSK/PAG1	-0.002	0.18	-10000	0	-0.63	36	36
SOS1	0.013	0	-10000	0	-10000	0	0
peptide-MHC class I	0.019	0.021	-10000	0	-10000	0	0
GRAP2/SLP76	-0.05	0.17	-10000	0	-0.62	42	42
STIM1	0.018	0.052	-10000	0	-10000	0	0
RAS family/GTP	0.03	0.059	-10000	0	-0.18	19	19
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.02	0.22	-10000	0	-0.7	44	44
mol:DAG	-0.026	0.11	-10000	0	-0.38	36	36
RAP1A/GDP	0.011	0.021	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
CD247	0.003	0.066	-10000	0	-0.4	16	16
cytotoxic T cell degranulation	-0.011	0.2	-10000	0	-0.79	29	29
RAP1A/GTP	-0.006	0.017	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.005	0.16	-10000	0	-0.5	45	45
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.027	0.17	0.28	49	-0.57	34	83
NRAS	0.011	0.023	-10000	0	-0.4	2	2
ZAP70	0.002	0.071	-10000	0	-0.45	14	14
GRB2/SOS1	0.019	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.045	0.15	-10000	0	-0.55	38	38
MALT1	0.012	0.016	-10000	0	-0.4	1	1
TRAF6	0.013	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.007	0.098	-10000	0	-0.52	9	9
CARD11	-0.023	0.15	-10000	0	-0.62	35	35
PRKCB	-0.036	0.099	-10000	0	-0.31	54	54
PRKCE	-0.02	0.071	-10000	0	-0.27	30	30
PRKCQ	0.003	0.18	-10000	0	-0.58	45	45
LCP2	0.009	0.04	-10000	0	-0.4	6	6
BCL10	0.012	0.016	-10000	0	-0.4	1	1
regulation of survival gene product expression	0.014	0.12	-10000	0	-0.37	39	39
IKK complex	0.019	0.05	-10000	0	-0.12	26	26
RAS family/GDP	-0.003	0.008	-10000	0	-10000	0	0
MAP3K14	0.022	0.085	-10000	0	-0.28	25	25
PDPK1	0.013	0.13	-10000	0	-0.42	36	36
TCR/CD3/MHC I/CD8/Fyn	-0.018	0.21	-10000	0	-0.72	41	41

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.011	0.096	-9999	-0.42	11	11
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.07	-9999	-10000	0	0
AP1	-0.04	0.087	-9999	-0.42	9	9
mol:PIP3	-0.034	0.075	-9999	-0.51	1	1
AKT1	0.024	0.071	-9999	-0.39	1	1
PTK2B	-0.005	0.072	-9999	-0.26	13	13
RHOA	0.019	0.032	-9999	-10000	0	0
PIK3CB	0.011	0.031	-9999	-0.75	1	1
mol:Ca2+	0.013	0.062	-9999	-0.35	1	1
MAGI3	0.011	0.023	-9999	-0.39	2	2
RELA	0.012	0	-9999	-10000	0	0
apoptosis	-0.028	0.11	-9999	-0.41	16	16
HRAS/GDP	0.009	0.011	-9999	-0.28	1	1
positive regulation of microtubule depolymerization	-0.036	0.1	-9999	-0.37	5	5
NF kappa B1 p50/RelA	-0.035	0.075	-9999	-0.45	2	2
endothelial cell migration	-0.016	0.11	-9999	-0.64	8	8
ADCY4	-0.079	0.17	-9999	-0.46	84	84
ADCY5	-0.18	0.24	-9999	-0.46	217	217
ADCY6	-0.079	0.17	-9999	-0.46	84	84
ADCY7	-0.079	0.17	-9999	-0.46	84	84
ADCY1	-0.083	0.18	-9999	-0.45	88	88
ADCY2	-0.11	0.22	-9999	-0.48	137	137
ADCY3	-0.079	0.17	-9999	-0.46	84	84
ADCY8	-0.085	0.18	-9999	-0.46	86	86
ADCY9	-0.08	0.17	-9999	-0.45	86	86
GSK3B	0.001	0.068	-9999	-0.3	3	3
arachidonic acid secretion	-0.088	0.18	-9999	-0.53	65	65
GNG2	-0.005	0.081	-9999	-0.39	26	26
TRIP6	0.019	0.023	-9999	-0.32	2	2
GNAO1	-0.1	0.16	-9999	-0.44	61	61
HRAS	0.012	0.016	-9999	-0.4	1	1
NFKBIA	0.004	0.08	-9999	-0.37	1	1
GAB1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.065	0.27	-9999	-0.87	62	62
JUN	0.012	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	0.016	0.025	-9999	-0.49	1	1
TIAM1	-0.099	0.31	-9999	-1	62	62
PIK3R1	0.012	0	-9999	-10000	0	0
mol:IP3	0.013	0.063	-9999	-0.35	1	1
PLCB3	0.02	0.023	-9999	-0.45	1	1
FOS	0.006	0.051	-9999	-0.4	10	10
positive regulation of mitosis	-0.088	0.18	-9999	-0.53	65	65
LPA/LPA1-2-3	-0.026	0.11	-9999	-0.43	17	17
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	-0.001	0.001	-9999	-10000	0	0
BCAR1	0.012	0.016	-9999	-0.4	1	1
stress fiber formation	-0.006	0.082	-9999	-0.3	11	11
GNAZ	-0.015	0.092	-9999	-0.35	10	10
EGFR/PI3K-beta/Gab1	-0.035	0.077	-9999	-0.53	1	1
positive regulation of dendritic cell cytokine production	-0.027	0.11	-9999	-0.42	17	17
LPA/LPA2/MAGI-3	0.016	0.027	-9999	-0.49	1	1
ARHGEF1	0.002	0.073	-9999	-0.35	2	2
GNAI2	-0.012	0.087	-9999	-0.42	2	2
GNAI3	-0.012	0.087	-9999	-0.42	2	2
GNAI1	-0.02	0.1	-9999	-0.44	13	13
LPA/LPA3	-0.015	0.09	-9999	-0.32	44	44
LPA/LPA2	0.009	0.026	-9999	-0.57	1	1
LPA/LPA1	-0.025	0.1	-9999	-0.27	89	89
HB-EGF/EGFR	-0.028	0.14	-9999	-0.49	47	47
HBEGF	-0.029	0.16	-9999	-0.57	47	47
mol:DAG	0.013	0.063	-9999	-0.35	1	1
cAMP biosynthetic process	-0.11	0.19	-9999	-0.53	74	74
NFKB1	0.012	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
GNB1	0.012	0	-9999	-10000	0	0
LYN	0.004	0.08	-9999	-0.37	1	1
GNAQ	-0.001	0.068	-9999	-0.33	9	9
LPAR2	0.011	0.031	-9999	-0.75	1	1
LPAR3	-0.023	0.12	-9999	-0.45	44	44
LPAR1	-0.04	0.14	-9999	-0.39	83	83
IL8	-0.2	0.19	-9999	-0.44	84	84
PTK2	-0.018	0.1	-9999	-0.4	17	17
Rac1/GDP	0.009	0	-9999	-10000	0	0
CASP3	-0.028	0.11	-9999	-0.41	16	16
EGFR	0.01	0.023	-9999	-0.4	2	2
PLCG1	0.003	0.072	-9999	-0.31	9	9
PLD2	-0.018	0.1	-9999	-0.4	17	17
G12/G13	-0.002	0.079	-9999	-0.38	2	2
PI3K-beta	-0.022	0.057	-9999	-0.45	1	1
cell migration	-0.01	0.094	-9999	-0.26	62	62
SLC9A3R2	0.012	0.016	-9999	-0.4	1	1
PXN	-0.006	0.083	-9999	-0.31	11	11
HRAS/GTP	-0.091	0.19	-9999	-0.55	65	65
RAC1	0.013	0	-9999	-10000	0	0
MMP9	-0.046	0.2	-9999	-0.72	49	49
PRKCE	0.012	0.001	-9999	-10000	0	0
PRKCD	0.016	0.06	-9999	-10000	0	0
Gi(beta/gamma)	-0.079	0.18	-9999	-0.5	65	65
mol:LPA	0.001	0.019	-9999	-0.19	5	5
TRIP6/p130 Cas/FAK1/Paxillin	-0.001	0.1	-9999	-0.43	3	3
MAPKKK cascade	-0.088	0.18	-9999	-0.53	65	65
contractile ring contraction involved in cytokinesis	0.019	0.031	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.002	0.069	-9999	-0.33	9	9
GNA15	-0.004	0.075	-9999	-0.34	14	14
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
MAPT	-0.037	0.1	-9999	-0.38	5	5
GNA11	-0.002	0.068	-9999	-0.34	8	8
Rac1/GTP	-0.07	0.28	-9999	-0.92	62	62
MMP2	-0.016	0.11	-9999	-0.64	8	8

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	0.003	0.12	-10000	0	-0.36	26	26
TBX21	-0.094	0.4	-10000	0	-1.1	62	62
B2M	0.011	0.024	-10000	0	-0.39	2	2
TYK2	0.014	0.021	-10000	0	-10000	0	0
IL12RB1	-0.001	0.087	-10000	0	-0.44	22	22
GADD45B	-0.03	0.28	-10000	0	-0.96	22	22
IL12RB2	0.003	0.082	-10000	0	-0.51	13	13
GADD45G	-0.035	0.28	-10000	0	-0.91	27	27
natural killer cell activation	0.001	0.022	-10000	0	-10000	0	0
RELB	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL18	0.013	0.034	-10000	0	-0.4	4	4
IL2RA	0.004	0.058	-10000	0	-0.4	13	13
IFNG	-0.067	0.23	-10000	0	-0.75	63	63
STAT3 (dimer)	-0.032	0.28	-10000	0	-0.76	42	42
HLA-DRB5	-0.02	0.14	-10000	0	-0.53	38	38
FASLG	-0.094	0.4	-10000	0	-1.1	58	58
NF kappa B2 p52/RelB	-0.15	0.27	-10000	0	-0.88	55	55
CD4	0.002	0.066	-10000	0	-0.39	17	17
SOCS1	-0.014	0.14	-10000	0	-0.75	22	22
EntrezGene:6955	0	0.01	-10000	0	-10000	0	0
CD3D	0.001	0.071	-10000	0	-0.4	19	19
CD3E	-0.004	0.082	-10000	0	-0.4	26	26
CD3G	-0.021	0.12	-10000	0	-0.4	52	52
IL12Rbeta2/JAK2	0.014	0.073	-10000	0	-0.4	12	12
CCL3	-0.077	0.35	-10000	0	-0.99	50	50
CCL4	-0.067	0.34	-10000	0	-0.97	48	48
HLA-A	0.012	0.018	-10000	0	-0.39	1	1
IL18/IL18R	0.034	0.08	-10000	0	-0.46	2	2
NOS2	-0.084	0.39	-10000	0	-1.1	53	53
IL12/IL12R/TYK2/JAK2/SPHK2	0.012	0.1	-10000	0	-0.37	13	13
IL1R1	-0.069	0.34	-10000	0	-0.96	53	53
IL4	0.001	0.022	-10000	0	-10000	0	0
JAK2	0.012	0.037	-10000	0	-0.42	3	3
EntrezGene:6957	0	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.044	0.26	-10000	0	-0.86	49	49
RAB7A	-0.007	0.25	-10000	0	-0.79	19	19
lysosomal transport	-0.004	0.24	-10000	0	-0.74	19	19
FOS	-0.035	0.27	-10000	0	-0.92	39	39
STAT4 (dimer)	-0.032	0.31	-10000	0	-0.86	43	43
STAT5A (dimer)	-0.18	0.3	-10000	0	-0.88	70	70
GZMA	-0.11	0.43	-10000	0	-1.2	71	71
GZMB	-0.13	0.39	-10000	0	-0.91	77	77
HLX	0.012	0.016	-10000	0	-0.4	1	1
LCK	-0.078	0.36	-10000	0	-0.97	55	55
TCR/CD3/MHC II/CD4	-0.027	0.2	-10000	0	-0.58	51	51
IL2/IL2R	0.015	0.06	-10000	0	-0.42	7	7
MAPK14	-0.025	0.29	-10000	0	-0.91	27	27
CCR5	-0.042	0.31	-10000	0	-1.1	26	26
IL1B	-0.055	0.22	-10000	0	-0.73	58	58
STAT6	0.001	0.11	0.2	5	-0.25	5	10
STAT4	-0.006	0.084	-10000	0	-0.4	28	28
STAT3	0.013	0	-10000	0	-10000	0	0
STAT1	0.011	0.031	-10000	0	-0.75	1	1
NFKB1	0.013	0	-10000	0	-10000	0	0
NFKB2	0.013	0	-10000	0	-10000	0	0
IL12B	0.005	0.065	-10000	0	-0.75	4	4
CD8A	-0.017	0.11	-10000	0	-0.4	45	45
CD8B	0.002	0.068	-10000	0	-0.42	15	15
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.003	0.12	0.36	26	-10000	0	26
IL2RB	0.001	0.066	-10000	0	-0.4	17	17
proteasomal ubiquitin-dependent protein catabolic process	-0.024	0.28	-10000	0	-0.78	42	42
IL2RG	0.011	0.028	-10000	0	-0.4	3	3
IL12	0.012	0.071	-10000	0	-0.44	10	10
STAT5A	0.013	0	-10000	0	-10000	0	0
CD247	0.002	0.066	-10000	0	-0.4	16	16
IL2	0.003	0.006	-10000	0	-10000	0	0
SPHK2	0.012	0.016	-10000	0	-0.4	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.007	0.058	-10000	0	-0.45	8	8
IL12/IL12R/TYK2/JAK2	-0.082	0.38	-10000	0	-0.98	62	62
MAP2K3	-0.029	0.29	-10000	0	-0.86	33	33
RIPK2	0.013	0	-10000	0	-10000	0	0
MAP2K6	-0.03	0.29	-10000	0	-0.86	34	34
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.002	0.067	-10000	0	-0.4	17	17
IL18RAP	-0.004	0.092	-10000	0	-0.41	29	29
IL12Rbeta1/TYK2	0.01	0.07	-10000	0	-0.33	19	19
EOMES	-0.043	0.26	-10000	0	-1.2	29	29
STAT1 (dimer)	-0.052	0.29	-10000	0	-0.74	51	51
T cell proliferation	-0.013	0.24	-10000	0	-0.64	39	39
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.009	0.053	-10000	0	-0.4	10	10
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.1	0.2	-10000	0	-0.71	31	31
ATF2	-0.016	0.27	-10000	0	-0.88	22	22

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.007	0.075	-9999	-0.43	16	16
RGS9BP	0.006	0.061	-9999	-0.75	4	4
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.002	0.052	-9999	-0.75	3	3
mol:Na +	-0.094	0.16	-9999	-0.56	34	34
mol:ADP	0.001	0.067	-9999	-0.65	6	6
GNAT2	-0.005	0.11	-9999	-0.75	13	13
RGS9-1/Gbeta5/R9AP	-0.019	0.098	-9999	-0.49	4	4
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.003	0.076	-9999	-0.5	14	14
GRK7	0.003	0.061	-9999	-0.75	4	4
CNGB3	-0.036	0.17	-9999	-0.75	33	33
Cone Metarhodopsin II/X-Arrestin	0	0.04	-9999	-0.58	3	3
mol:Ca2+	-0.12	0.2	-9999	-0.55	83	83
Cone PDE6	-0.014	0.084	-9999	-0.42	5	5
Cone Metarhodopsin II	0.001	0.055	-9999	-0.53	6	6
Na + (4 Units)	-0.12	0.2	-9999	-0.55	83	83
GNAT2/GDP	-0.018	0.1	-9999	-0.44	17	17
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.002	0.069	-9999	-0.46	14	14
Cone Transducin	0.008	0.079	-9999	-0.45	16	16
SLC24A2	-0.065	0.22	-9999	-0.75	59	59
GNB3/GNGT2	0.012	0.053	-9999	-0.34	12	12
GNB3	0.008	0.055	-9999	-0.66	4	4
GNAT2/GTP	-0.004	0.084	-9999	-0.58	13	13
CNGA3	-0.12	0.19	-9999	-0.4	201	201
ARR3	0	0.053	-9999	-0.75	3	3
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.095	0.16	-9999	-0.56	34	34
mol:Pi	-0.019	0.097	-9999	-0.49	4	4
Cone CNG Channel	-0.08	0.14	-9999	-0.47	48	48
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.064	0.22	-9999	-0.75	59	59
RGS9	-0.055	0.15	-9999	-0.4	103	103
PDE6C	0.003	0.006	-9999	-10000	0	0
GNGT2	0.007	0.046	-9999	-0.4	8	8
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0	0.03	-9999	-0.75	1	1

×

Nectin adhesion 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.004	0.081	-9999	-0.75	7	7
alphaV beta3 Integrin	0.015	0.03	-9999	-0.27	7	7
PTK2	0.03	0.059	-9999	-0.5	1	1
positive regulation of JNK cascade	-0.008	0.043	-9999	-0.26	17	17
CDC42/GDP	0.04	0.068	-9999	-0.35	17	17
Rac1/GDP	0.041	0.067	-9999	-0.34	17	17
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	-0.009	0.052	-9999	-0.32	17	17
nectin-3/I-afadin	0.011	0.047	-9999	-0.27	17	17
RAPGEF1	0.036	0.07	-9999	-0.38	17	17
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.032	0.078	-9999	-0.43	17	17
PDGFB-D/PDGFRB	0.004	0.08	-9999	-0.75	7	7
TLN1	0.022	0.027	-9999	-10000	0	0
Rap1/GTP	-0.008	0.045	-9999	-0.34	1	1
IQGAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.024	0.009	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.011	0.047	-9999	-0.27	17	17
PVR	0.013	0	-9999	-10000	0	0
Necl-5(dimer)	0.013	0	-9999	-10000	0	0
mol:GDP	0.037	0.08	-9999	-0.42	17	17
MLLT4	0.012	0.016	-9999	-0.4	1	1
PIK3CA	0.012	0.016	-9999	-0.4	1	1
PI3K	0.026	0.059	-9999	-0.42	7	7
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.018	0.011	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.011	0.052	-9999	-0.27	19	19
PVRL1	0.013	0	-9999	-10000	0	0
PVRL3	0.002	0.064	-9999	-0.4	16	16
PVRL2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
CLDN1	-0.68	0.22	-9999	-0.75	569	569
JAM-A/CLDN1	-0.41	0.14	-9999	-0.45	569	569
SRC	0.027	0.084	-9999	-0.47	17	17
ITGB3	0.008	0.043	-9999	-0.4	7	7
nectin-1(dimer)/I-afadin/I-afadin	0.018	0.011	-9999	-10000	0	0
FARP2	0.035	0.075	-9999	-0.41	17	17
RAC1	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.019	0.04	-9999	-10000	0	0
nectin-1/I-afadin	0.018	0.011	-9999	-10000	0	0
nectin-2/I-afadin	0.018	0.011	-9999	-0.27	1	1
RAC1/GTP/IQGAP1/filamentous actin	0.017	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.019	0.04	-9999	-10000	0	0
CDC42/GTP/IQGAP1/filamentous actin	0.016	0.014	-9999	-10000	0	0
F11R	0.013	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.008	0.043	-9999	-0.26	17	17
alphaV/beta3 Integrin/Talin	0.032	0.035	-9999	-0.4	1	1
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.018	0.011	-9999	-0.27	1	1
nectin-2(dimer)/I-afadin/I-afadin	0.018	0.011	-9999	-0.27	1	1
PIP5K1C	0.017	0.029	-9999	-0.28	1	1
VAV2	0.028	0.093	-9999	-0.42	26	26
RAP1/GDP	-0.01	0.053	-9999	-0.32	17	17
ITGAV	0.013	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.019	0.04	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin	0.011	0.047	-9999	-0.27	17	17
Rac1/GTP	-0.013	0.062	-9999	-0.33	19	19
PTPRM	0.012	0.031	-9999	-0.31	1	1
E-cadherin/beta catenin/alpha catenin	0.037	0.008	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.011	0.023	-9999	-0.4	2	2

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.054	0.11	0.33	26	-10000	0	26
GNAI2	0.013	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.005	0.079	-10000	0	-0.5	15	15
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.14	0.2	-10000	0	-0.4	234	234
RhoA/GTP	-0.054	0.11	-10000	0	-0.34	26	26
negative regulation of cAMP metabolic process	-0.066	0.12	-10000	0	-0.37	26	26
GNAZ	0.007	0.046	-10000	0	-0.4	8	8
GNAI3	0.013	0	-10000	0	-10000	0	0
GNA12	0.013	0	-10000	0	-10000	0	0
S1PR5	-0.006	0.12	-10000	0	-0.75	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.066	0.12	-10000	0	-0.38	26	26
RhoA/GDP	0.009	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.075	-10000	0	-0.4	22	22

×

HIF-2-alpha transcription factor network

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
MMP14	-0.015	0.078	-10000	0	-0.63	9	9
oxygen homeostasis	-0.011	0.013	-10000	0	-10000	0	0
TCEB2	0.01	0.043	-10000	0	-0.75	2	2
TCEB1	0.013	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.028	0.06	-10000	0	-0.41	2	2
EPO	-0.13	0.2	-10000	0	-0.6	50	50
FIH (dimer)	0.003	0.011	-10000	0	-10000	0	0
APEX1	-0.002	0.015	-10000	0	-10000	0	0
SERPINE1	-0.21	0.34	-10000	0	-0.83	124	124
FLT1	-0.005	0.037	-10000	0	-0.68	1	1
ADORA2A	-0.14	0.22	-10000	0	-0.68	46	46
germ cell development	-0.14	0.22	-10000	0	-0.68	49	49
SLC11A2	-0.14	0.23	-10000	0	-0.7	46	46
BHLHE40	-0.14	0.23	-10000	0	-0.71	46	46
HIF1AN	0.003	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.065	0.12	-10000	0	-0.4	1	1
ETS1	0.025	0.017	-10000	0	-0.39	1	1
CITED2	-0.009	0.049	-10000	0	-1.1	1	1
KDR	-0.006	0.057	-10000	0	-0.89	2	2
PGK1	-0.14	0.23	-10000	0	-0.7	46	46
SIRT1	0.013	0.001	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.16	0.27	-10000	0	-0.84	47	47
EPAS1	-0.039	0.081	-10000	0	-0.32	2	2
SP1	0.019	0.002	-10000	0	-10000	0	0
ABCG2	-0.34	0.28	-10000	0	-0.71	153	153
EFNA1	-0.14	0.23	-10000	0	-0.7	46	46
FXN	-0.14	0.22	-10000	0	-0.68	46	46
POU5F1	-0.14	0.23	-10000	0	-0.71	49	49
neuron apoptosis	0.16	0.26	0.8	47	-10000	0	47
EP300	0.013	0	-10000	0	-10000	0	0
EGLN3	0	0.041	-10000	0	-0.4	6	6
EGLN2	0.003	0.02	-10000	0	-0.4	1	1
EGLN1	0.003	0.011	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.024	0.029	-10000	0	-0.49	2	2
VHL	0.013	0	-10000	0	-10000	0	0
ARNT	-0.003	0.022	-10000	0	-0.42	1	1
SLC2A1	-0.15	0.25	-10000	0	-0.74	64	64
TWIST1	-0.16	0.27	-10000	0	-0.86	58	58
ELK1	0.019	0.001	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.06	0.12	-10000	0	-10000	0	0
VEGFA	-0.14	0.23	-10000	0	-0.71	47	47
CREBBP	0.013	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.016	0.048	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.093	0.11	-9999	-0.38	2	2
JUN	-0.067	0.13	-9999	-0.4	2	2
HRAS	0.012	0.016	-9999	-0.4	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.089	0.15	-9999	-0.4	63	63
RAP1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0.001	-9999	-10000	0	0
RAP1A/GDP	0.009	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.089	0.15	-9999	-0.4	63	63
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.064	0.11	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.077	0.13	-9999	-0.49	2	2
GRB7	-0.006	0.12	-9999	-0.75	15	15
RET51/GFRalpha1/GDNF	-0.089	0.15	-9999	-0.4	63	63
MAPKKK cascade	-0.096	0.12	-9999	-0.49	2	2
BCAR1	0.012	0.016	-9999	-0.4	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.064	0.11	-9999	-10000	0	0
lamellipodium assembly	-0.092	0.11	-9999	-0.3	62	62
RET51/GFRalpha1/GDNF/SHC	-0.089	0.15	-9999	-0.4	63	63
PIK3CA	0.012	0.016	-9999	-0.4	1	1
RET9/GFRalpha1/GDNF/SHC	-0.064	0.11	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3	-0.064	0.11	-9999	-0.4	1	1
MAPK3	-0.068	0.12	-9999	-0.46	2	2
DOK1	0.013	0	-9999	-10000	0	0
DOK6	0.003	0.06	-9999	-0.4	14	14
PXN	0.013	0	-9999	-10000	0	0
neurite development	-0.059	0.12	-9999	-0.46	2	2
DOK5	0.002	0.067	-9999	-0.42	15	15
GFRA1	-0.15	0.2	-9999	-0.4	245	245
MAPK8	-0.076	0.14	-9999	-0.37	62	62
HRAS/GTP	-0.11	0.14	-9999	-0.42	63	63
tube development	-0.054	0.1	-9999	-0.37	1	1
MAPK1	-0.068	0.12	-9999	-0.55	1	1
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.06	0.11	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
PDLIM7	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.082	0.15	-9999	-0.39	70	70
SHC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.09	0.15	-9999	-0.4	64	64
RET51/GFRalpha1/GDNF/Dok5	-0.095	0.15	-9999	-0.4	69	69
PRKCA	0.013	0	-9999	-10000	0	0
HRAS/GDP	0.009	0.011	-9999	-0.28	1	1
CREB1	-0.093	0.15	-9999	-0.4	62	62
PIK3R1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.06	0.11	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Grb7	-0.1	0.17	-9999	-0.44	75	75
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.051	0.15	-9999	-0.4	96	96
DOK4	0.012	0.016	-9999	-0.4	1	1
JNK cascade	-0.066	0.13	-9999	-0.4	2	2
RET9/GFRalpha1/GDNF/FRS2	-0.064	0.11	-9999	-10000	0	0
SHANK3	0.012	0.016	-9999	-0.4	1	1
RASA1	0.013	0.001	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.061	0.11	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.087	0.14	-9999	-0.39	62	62
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.087	0.14	-9999	-0.39	62	62
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.096	0.16	-9999	-0.48	62	62
PI3K	-0.1	0.18	-9999	-0.45	62	62
SOS1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.054	0.1	-9999	-0.37	1	1
GRB10	0.013	0	-9999	-10000	0	0
activation of MAPKK activity	-0.073	0.12	-9999	-0.32	62	62
RET51/GFRalpha1/GDNF/FRS2	-0.09	0.15	-9999	-0.4	63	63
GAB1	0.013	0	-9999	-10000	0	0
IRS1	0.013	0	-9999	-10000	0	0
IRS2	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.096	0.16	-9999	-0.48	62	62
RET51/GFRalpha1/GDNF/PKC alpha	-0.089	0.15	-9999	-0.4	63	63
GRB2	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GDNF	0.009	0.017	-9999	-0.4	1	1
RAC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.089	0.15	-9999	-0.4	63	63
Rac1/GTP	-0.11	0.13	-9999	-0.36	62	62
RET9/GFRalpha1/GDNF	-0.08	0.12	-9999	-10000	0	0
GFRalpha1/GDNF	-0.097	0.14	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.019	0.034	-9999	-0.56	1	1
VDR	0.013	0	-9999	-10000	0	0
FAM120B	0.013	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.045	0.11	-9999	-0.43	3	3
RXRs/LXRs/DNA/Oxysterols	-0.029	0.11	-9999	-0.39	12	12
MED1	0.01	0.043	-9999	-0.75	2	2
mol:9cRA	0.004	0.007	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.034	0.1	-9999	-0.39	2	2
RXRs/NUR77	-0.06	0.12	-9999	-0.53	10	10
RXRs/PPAR	-0.056	0.11	-9999	-0.41	3	3
NCOR2	0.012	0.016	-9999	-0.4	1	1
VDR/VDR/Vit D3	0.009	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	0.028	0.026	-9999	-0.42	1	1
RARA	0.011	0.035	-9999	-0.57	2	2
NCOA1	0.013	0	-9999	-10000	0	0
VDR/VDR/DNA	0.013	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	0.023	0.026	-9999	-0.43	1	1
RARG	0.013	0	-9999	-10000	0	0
RPS6KB1	0.028	0.039	-9999	-0.37	1	1
RARs/THRs/DNA/SMRT	-0.034	0.1	-9999	-0.39	3	3
THRA	0.011	0.031	-9999	-0.75	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0.009	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.057	0.11	-9999	-0.3	2	2
NR1H4	-0.19	0.2	-9999	-0.4	312	312
RXRs/LXRs/DNA	-0.033	0.11	-9999	-0.35	1	1
NR1H2	0.017	0.017	-9999	-0.39	1	1
NR1H3	0.017	0.006	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.05	0.1	-9999	-10000	0	0
NR4A1	0.001	0.093	-9999	-0.72	10	10
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.16	0.15	-9999	-0.36	150	150
RXRG	-0.16	0.2	-9999	-0.39	262	262
RXR alpha/CCPG	0.022	0.012	-9999	-0.26	1	1
RXRA	0.016	0.017	-9999	-0.39	1	1
RXRB	0.017	0.006	-9999	-10000	0	0
THRB	-0.11	0.18	-9999	-0.4	181	181
PPARG	0.011	0.023	-9999	-0.4	2	2
PPARD	0.012	0.016	-9999	-0.4	1	1
TNF	-0.024	0.13	-9999	-0.88	6	6
mol:Oxysterols	0.005	0.006	-9999	-10000	0	0
cholesterol transport	-0.029	0.11	-9999	-0.39	12	12
PPARA	0.013	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.01	0.033	-9999	-0.4	4	4
RXRs/NUR77/BCL2	-0.079	0.12	-9999	-0.47	17	17
SREBF1	-0.02	0.099	-9999	-0.49	2	2
RXRs/RXRs/DNA/9cRA	-0.057	0.11	-9999	-0.3	2	2
ABCA1	-0.025	0.13	-9999	-0.89	7	7
RARs/THRs	-0.026	0.099	-9999	-0.42	2	2
RXRs/FXR	-0.16	0.15	-9999	-0.38	144	144
BCL2	-0.008	0.09	-9999	-0.4	32	32

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.028	0.041	-10000	0	-0.53	3	3
epithelial cell differentiation	-0.014	0.059	-10000	0	-0.54	2	2
ITCH	0.013	0.017	-10000	0	-0.39	1	1
WWP1	0.027	0.051	-10000	0	-1.2	1	1
FYN	0.013	0	-10000	0	-10000	0	0
EGFR	0.011	0.023	-10000	0	-0.4	2	2
PRL	-0.009	0.1	-10000	0	-0.75	12	12
neuron projection morphogenesis	0.031	0.063	-10000	0	-0.47	1	1
PTPRZ1	-0.14	0.2	-10000	0	-0.4	233	233
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.024	0.067	-10000	0	-0.52	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.005	0.074	-10000	0	-0.6	1	1
ADAM17	0.013	0.005	-10000	0	-10000	0	0
ErbB4/ErbB4	0.028	0.033	-10000	0	-0.74	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.024	0.037	-10000	0	-0.57	2	2
NCOR1	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.012	0.069	-10000	0	-0.56	1	1
GRIN2B	-0.13	0.21	-10000	0	-0.41	208	208
ErbB4/ErbB2/betacellulin	0.024	0.069	-10000	0	-0.42	12	12
STAT1	0.011	0.031	-10000	0	-0.75	1	1
HBEGF	0.01	0.043	-10000	0	-0.75	2	2
PRLR	0.002	0.064	-10000	0	-0.4	16	16
E4ICDs/ETO2	0	0.083	-10000	0	-0.56	2	2
axon guidance	0.063	0.081	-10000	0	-0.74	1	1
NEDD4	0.013	0.005	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.005	0.093	-10000	0	-0.59	12	12
CBFA2T3	-0.041	0.14	-10000	0	-0.4	81	81
ErbB4/ErbB2/HBEGF	0.026	0.069	-10000	0	-0.42	14	14
MAPK3	0.026	0.065	-10000	0	-0.49	1	1
STAT1 (dimer)	0.029	0.035	-10000	0	-0.56	2	2
MAPK1	0.027	0.064	-10000	0	-0.49	1	1
JAK2	0.011	0.028	-10000	0	-0.4	3	3
ErbB4/ErbB2/neuregulin 1 beta	0.003	0.092	-10000	0	-0.46	12	12
NRG1	-0.015	0.094	-10000	0	-0.27	73	73
NRG3	0.005	0.035	-10000	0	-0.57	2	2
NRG2	-0.049	0.14	-10000	0	-0.4	89	89
NRG4	-0.026	0.12	-10000	0	-0.4	55	55
heart development	0.063	0.081	-10000	0	-0.74	1	1
neural crest cell migration	0.003	0.091	-10000	0	-0.45	12	12
ERBB2	0.009	0.079	-10000	0	-0.58	11	11
WWOX/E4ICDs	0.029	0.03	-10000	0	-0.67	1	1
SHC1	0.013	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.014	0.066	-10000	0	-0.63	1	1
apoptosis	0.026	0.06	0.61	2	-10000	0	2
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.006	0.086	-10000	0	-0.63	2	2
ErbB4/ErbB2/epiregulin	-0.15	0.23	-10000	0	-0.42	249	249
ErbB4/ErbB4/betacellulin/betacellulin	0.026	0.041	-10000	0	-0.67	1	1
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.026	0.077	-10000	0	-0.54	3	3
MDM2	0.03	0.032	-10000	0	-0.67	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.007	0.071	-10000	0	-0.53	1	1
STAT5A	0.066	0.074	-10000	0	-0.71	1	1
ErbB4/EGFR/neuregulin 1 beta	0.011	0.07	-10000	0	-0.56	1	1
DLG4	0.011	0.031	-10000	0	-0.75	1	1
GRB2/SHC	0.019	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.027	0.028	-10000	0	-0.63	1	1
STAT5A (dimer)	-0.015	0.063	-10000	0	-0.59	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.064	0.071	-10000	0	-0.71	1	1
LRIG1	0.012	0.016	-10000	0	-0.4	1	1
EREG	-0.29	0.37	-10000	0	-0.73	256	256
BTC	0.006	0.051	-10000	0	-0.4	10	10
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.063	0.081	-10000	0	-0.75	1	1
ERBB4	0.028	0.033	-10000	0	-0.74	1	1
STAT5B	0.013	0	-10000	0	-10000	0	0
YAP1	0.016	0.007	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.008	0.085	-10000	0	-0.44	12	12
glial cell differentiation	-0.026	0.027	0.62	1	-10000	0	1
WWOX	0.013	0	-10000	0	-10000	0	0
cell proliferation	0.022	0.1	-10000	0	-0.52	4	4

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	0.013	0	-9999	-10000	0	0
VDR	0.013	0	-9999	-10000	0	0
Cbp/p300/PCAF	0.015	0.049	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.001	0.057	-9999	-0.35	1	1
KAT2B	-0.005	0.083	-9999	-0.4	27	27
MAPK14	0.013	0	-9999	-10000	0	0
AKT1	-0.005	0.066	-9999	-0.29	1	1
RAR alpha/9cRA/Cyclin H	-0.054	0.073	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.003	0.063	-9999	-0.28	12	12
CDC2	0	0.001	-9999	-10000	0	0
response to UV	0.001	0.002	-9999	-10000	0	0
RAR alpha/Jnk1	-0.044	0.091	-9999	-0.37	1	1
NCOR2	0.012	0.016	-9999	-0.4	1	1
VDR/VDR/Vit D3	0.009	0	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.074	0.13	-9999	-0.46	3	3
NCOA2	0.011	0.028	-9999	-0.4	3	3
NCOA3	0.013	0	-9999	-10000	0	0
NCOA1	0.013	0	-9999	-10000	0	0
VDR/VDR/DNA	0.013	0	-9999	-10000	0	0
RARG	0.013	0.001	-9999	-10000	0	0
RAR gamma1/9cRA	0.017	0.001	-9999	-10000	0	0
MAPK3	0.012	0.016	-9999	-0.39	1	1
MAPK1	0.012	0.016	-9999	-0.4	1	1
MAPK8	0.013	0.001	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.092	0.14	-9999	-10000	0	0
RARA	-0.054	0.11	-9999	-0.42	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-9999	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.004	0.066	-9999	-0.29	12	12
PRKCA	0.015	0.003	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.09	0.14	-9999	-0.53	3	3
RXRG	-0.22	0.23	-9999	-0.36	395	395
RXRA	-0.044	0.1	-9999	-10000	0	0
RXRB	-0.092	0.16	-9999	-0.31	217	217
VDR/Vit D3/DNA	0.009	0	-9999	-10000	0	0
RBP1	-0.038	0.19	-9999	-0.75	41	41
CRBP1/9-cic-RA	-0.029	0.14	-9999	-0.58	41	41
RARB	0.012	0.033	-9999	-0.4	4	4
PRKCG	-0.25	0.36	-9999	-0.75	217	217
MNAT1	0.013	0.001	-9999	-10000	0	0
RAR alpha/RXRs	-0.071	0.14	-9999	-0.4	1	1
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.064	0.13	-9999	-0.41	1	1
proteasomal ubiquitin-dependent protein catabolic process	-0.021	0.084	-9999	-0.28	14	14
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.09	0.14	-9999	-0.53	3	3
positive regulation of DNA binding	-0.052	0.07	-9999	-10000	0	0
NRIP1	-0.086	0.14	-9999	-1.1	2	2
RXRs/RARs	-0.098	0.14	-9999	-0.34	87	87
RXRs/RXRs/DNA/9cRA	-0.1	0.14	-9999	-0.34	86	86
PRKACA	0.013	0	-9999	-10000	0	0
CDK7	0.013	0	-9999	-10000	0	0
TFIIH	0.026	0	-9999	-10000	0	0
RAR alpha/9cRA	-0.038	0.057	-9999	-10000	0	0
CCNH	0.013	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
RAR gamma2/9cRA	0	0	-9999	-10000	0	0

×

S1P4 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.14	0.2	-9999	-0.4	234	234
CDC42/GTP	-0.053	0.11	-9999	-0.36	28	28
PLCG1	-0.055	0.12	-9999	-0.37	28	28
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0.019	0	-9999	-10000	0	0
cell migration	-0.052	0.11	-9999	-0.35	28	28
S1PR5	-0.006	0.12	-9999	-0.75	15	15
S1PR4	0.006	0.051	-9999	-0.4	10	10
MAPK3	-0.055	0.12	-9999	-0.37	29	29
MAPK1	-0.055	0.12	-9999	-0.37	28	28
S1P/S1P5/Gi	-0.066	0.12	-9999	-0.38	26	26
GNAI1	-0.002	0.075	-9999	-0.4	22	22
CDC42/GDP	0.008	0.016	-9999	-0.28	2	2
S1P/S1P5/G12	0.005	0.079	-9999	-0.5	15	15
RHOA	0.023	0.025	-9999	-10000	0	0
S1P/S1P4/Gi	-0.064	0.12	-9999	-0.39	28	28
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.007	0.046	-9999	-0.4	8	8
S1P/S1P4/G12/G13	0.021	0.028	-9999	-10000	0	0
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
CDC42	0.011	0.023	-9999	-0.4	2	2

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.012	0.016	-9999	-0.4	1	1
SPHK1	-0.037	0.19	-9999	-0.75	40	40
GNAI2	0.013	0	-9999	-10000	0	0
mol:S1P	0.001	0.067	-9999	-0.25	41	41
GNAO1	-0.14	0.2	-9999	-0.4	234	234
mol:Sphinganine-1-P	-0.019	0.14	-9999	-0.56	41	41
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.023	0.051	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0.019	0	-9999	-10000	0	0
S1PR3	0.011	0.031	-9999	-0.75	1	1
S1PR2	0.013	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.057	-9999	-0.22	41	41
S1PR5	-0.006	0.12	-9999	-0.75	15	15
S1PR4	0.006	0.051	-9999	-0.4	10	10
GNAI1	-0.002	0.075	-9999	-0.4	22	22
S1P/S1P5/G12	0.004	0.096	-9999	-0.51	15	15
S1P/S1P3/Gq	0.018	0.061	-9999	-0.38	8	8
S1P/S1P4/Gi	-0.062	0.12	-9999	-0.37	37	37
GNAQ	0.011	0.028	-9999	-0.4	3	3
GNAZ	0.007	0.046	-9999	-0.4	8	8
GNA14	0.009	0.036	-9999	-0.4	5	5
GNA15	0.005	0.075	-9999	-0.75	6	6
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	0.01	0.033	-9999	-0.4	4	4
ABCC1	0.013	0	-9999	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.001	0.073	-9999	-0.4	21	21
GNB1/GNG2	-0.044	0.13	-9999	-0.41	29	29
mol:DAG	-0.036	0.12	-9999	-0.41	12	12
PLCG1	-0.037	0.12	-9999	-0.42	12	12
YES1	-0.045	0.13	-9999	-0.44	22	22
FZD3	0.006	0.065	-9999	-0.63	6	6
FZD6	0.013	0	-9999	-10000	0	0
G protein	-0.036	0.13	-9999	-0.39	29	29
MAP3K7	-0.035	0.12	-9999	-0.42	6	6
mol:Ca2+	-0.035	0.12	-9999	-0.4	12	12
mol:IP3	-0.036	0.12	-9999	-0.41	12	12
NLK	0.006	0.011	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CAMK2A	-0.043	0.12	-9999	-0.46	6	6
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.054	0.14	-9999	-0.47	22	22
CSNK1A1	0.013	0	-9999	-10000	0	0
GNAS	-0.045	0.13	-9999	-0.44	22	22
GO:0007205	-0.036	0.12	-9999	-0.38	20	20
WNT6	-0.032	0.15	-9999	-0.5	53	53
WNT4	-0.003	0.088	-9999	-0.47	20	20
NFAT1/CK1 alpha	-0.03	0.12	-9999	-0.44	12	12
GNG2	-0.004	0.081	-9999	-0.4	26	26
WNT5A	0.003	0.082	-9999	-0.71	8	8
WNT11	-0.14	0.3	-9999	-0.72	129	129
CDC42	-0.038	0.12	-9999	-0.41	23	23

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.012	0.016	-9999	-0.4	1	1
EGFR	0.011	0.023	-9999	-0.4	2	2
EGF/EGFR	-0.052	0.15	-9999	-0.47	55	55
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.016	0.11	-9999	-0.42	20	20
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.035	0.18	-9999	-0.75	39	39
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.086	0.2	-9999	-0.45	131	131
EGF/EGFR dimer/SHC	-0.036	0.12	-9999	-0.49	20	20
mol:GDP	-0.018	0.11	-9999	-0.41	20	20
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.012	0.016	-9999	-0.4	1	1
GRB2/SOS1	0.019	0	-9999	-10000	0	0
HRAS/GTP	-0.04	0.085	-9999	-0.38	20	20
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	-0.041	0.087	-9999	-0.39	20	20
FRAP1	-0.021	0.1	-9999	-0.4	20	20
EGF/EGFR dimer	-0.053	0.14	-9999	-0.57	20	20
SOS1	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.019	0.14	-9999	-0.56	40	40

×

Thromboxane A2 receptor 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
TGM2	0.007	0.061	-10000	0	-0.75	4	4
GNB1/GNG2	-0.069	0.059	-10000	0	-0.21	17	17
AKT1	-0.036	0.08	-10000	0	-0.22	1	1
EGF	-0.086	0.2	-10000	0	-0.45	131	131
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	-0.056	0.08	-10000	0	-0.34	1	1
mol:Ca2+	-0.065	0.11	-10000	0	-0.3	17	17
LYN	-0.055	0.077	-10000	0	-10000	0	0
RhoA/GTP	-0.031	0.044	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.072	0.12	-10000	0	-0.34	18	18
GNG2	-0.005	0.081	-10000	0	-0.4	26	26
ARRB2	0.013	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.006	0.06	-10000	0	-0.38	8	8
G beta5/gamma2	-0.086	0.075	-10000	0	-0.28	17	17
PRKCH	-0.069	0.12	-10000	0	-0.36	11	11
DNM1	0.004	0.081	-10000	0	-0.75	7	7
TXA2/TP beta/beta Arrestin3	-0.024	0.032	-10000	0	-0.26	5	5
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.22	0.2	-10000	0	-0.4	358	358
G12 family/GTP	-0.083	0.093	-10000	0	-0.31	18	18
ADRBK1	0.012	0	-10000	0	-10000	0	0
ADRBK2	0.012	0.016	-10000	0	-0.4	1	1
RhoA/GTP/ROCK1	0.016	0.01	-10000	0	-10000	0	0
mol:GDP	0.074	0.088	0.26	32	-10000	0	32
mol:NADP	0	0.096	-10000	0	-0.75	10	10
RAB11A	0.013	0	-10000	0	-10000	0	0
PRKG1	-0.003	0.078	-10000	0	-0.4	24	24
mol:IP3	-0.081	0.13	-10000	0	-0.38	19	19
cell morphogenesis	0.016	0.01	-10000	0	-10000	0	0
PLCB2	-0.11	0.17	-10000	0	-0.51	19	19
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.11	0.12	-10000	0	-0.34	2	2
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.058	0.083	-10000	0	-0.41	1	1
RHOA	0.013	0	-10000	0	-10000	0	0
PTGIR	0.01	0.043	-10000	0	-0.75	2	2
PRKCB1	-0.075	0.13	-10000	0	-0.37	17	17
GNAQ	0.011	0.028	-10000	0	-0.4	3	3
mol:L-citrulline	0	0.096	-10000	0	-0.75	10	10
TXA2/TXA2-R family	-0.11	0.18	-10000	0	-0.5	37	37
LCK	-0.06	0.087	-10000	0	-0.4	8	8
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.088	0.084	-10000	0	-0.37	3	3
TXA2-R family/G12 family/GDP/G beta/gamma	-0.015	0.045	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.074	0.09	-10000	0	-10000	0	0
MAPK14	-0.044	0.088	-10000	0	-0.24	8	8
TGM2/GTP	-0.096	0.16	-10000	0	-0.42	36	36
MAPK11	-0.045	0.09	-10000	0	-0.26	10	10
ARHGEF1	-0.035	0.071	-10000	0	-0.2	2	2
GNAI2	0.013	0	-10000	0	-10000	0	0
JNK cascade	-0.084	0.14	-10000	0	-0.37	37	37
RAB11/GDP	0.013	0.001	-10000	0	-10000	0	0
ICAM1	-0.056	0.1	-10000	0	-0.29	14	14
cAMP biosynthetic process	-0.087	0.13	-10000	0	-0.35	36	36
Gq family/GTP/EBP50	0.019	0.041	-10000	0	-0.44	2	2
actin cytoskeleton reorganization	0.016	0.01	-10000	0	-10000	0	0
SRC	-0.055	0.077	-10000	0	-10000	0	0
GNB5	0.012	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
EGF/EGFR	-0.079	0.094	-10000	0	-0.3	10	10
VCAM1	-0.063	0.11	-10000	0	-0.38	15	15
TP beta/Gq family/GDP/G beta5/gamma2	-0.006	0.06	-10000	0	-0.38	8	8
platelet activation	-0.06	0.12	-10000	0	-0.31	14	14
PGI2/IP	0.007	0.033	-10000	0	-0.58	2	2
PRKACA	-0.11	0.11	-10000	0	-0.28	4	4
Gq family/GDP/G beta5/gamma2	-0.017	0.063	-10000	0	-0.38	8	8
TXA2/TP beta/beta Arrestin2	-0.015	0.032	-10000	0	-0.3	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.096	0.1	-10000	0	-10000	0	0
mol:DAG	-0.084	0.14	-10000	0	-0.41	17	17
EGFR	0.011	0.023	-10000	0	-0.4	2	2
TXA2/TP alpha	-0.11	0.17	-10000	0	-0.48	36	36
Gq family/GTP	0.009	0.043	-10000	0	-0.23	13	13
YES1	-0.055	0.077	-10000	0	-10000	0	0
GNAI2/GTP	-0.08	0.069	-10000	0	-10000	0	0
PGD2/DP	-0.16	0.14	-10000	0	-0.28	358	358
SLC9A3R1	0.013	0	-10000	0	-10000	0	0
FYN	-0.055	0.077	-10000	0	-10000	0	0
mol:NO	0	0.096	-10000	0	-0.75	10	10
GNA15	0.005	0.075	-10000	0	-0.75	6	6
PGK/cGMP	-0.001	0.08	-10000	0	-0.52	10	10
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.077	0.1	-10000	0	-0.45	4	4
NOS3	0	0.096	-10000	0	-0.75	10	10
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.069	0.12	-10000	0	-0.34	15	15
PRKCB	-0.094	0.13	-10000	0	-0.42	19	19
PRKCE	-0.065	0.12	-10000	0	-0.35	12	12
PRKCD	-0.071	0.13	-10000	0	-0.37	16	16
PRKCG	-0.13	0.19	-10000	0	-0.47	68	68
muscle contraction	-0.1	0.17	-10000	0	-0.46	37	37
PRKCZ	-0.072	0.12	-10000	0	-0.34	18	18
ARR3	0	0.053	-10000	0	-0.75	3	3
TXA2/TP beta	-0.076	0.092	-10000	0	-0.33	1	1
PRKCQ	-0.068	0.12	-10000	0	-0.35	16	16
MAPKKK cascade	-0.097	0.15	-10000	0	-0.46	19	19
SELE	-0.079	0.14	-10000	0	-0.31	125	125
TP beta/GNAI2/GDP/G beta/gamma	-0.075	0.1	-10000	0	-10000	0	0
ROCK1	0.012	0.016	-10000	0	-0.4	1	1
GNA14	0.009	0.036	-10000	0	-0.4	5	5
chemotaxis	-0.12	0.19	-10000	0	-0.54	37	37
GNA12	0.013	0	-10000	0	-10000	0	0
GNA13	0.013	0	-10000	0	-10000	0	0
GNA11	0.01	0.033	-10000	0	-0.4	4	4
Rac1/GTP	0.009	0.001	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.013	0	-10000	0	-10000	0	0
HDAC4	0.013	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.008	0.07	0.57	9	-10000	0	9
CDKN1A	-0.001	0.024	-10000	0	-0.6	1	1
KAT2B	-0.005	0.083	-10000	0	-0.4	27	27
BAX	0.013	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.012	0.016	-10000	0	-0.4	1	1
FOXO4	0.019	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
TAT	-0.14	0.19	-10000	0	-0.4	231	231
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.003	0.058	-10000	0	-10000	0	0
PPARGC1A	-0.045	0.14	-10000	0	-0.4	88	88
FHL2	0.013	0	-10000	0	-10000	0	0
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.016	0.005	-10000	0	-10000	0	0
HIST2H4A	0.008	0.07	-10000	0	-0.57	9	9
SIRT1/FOXO3a	0	0.005	-10000	0	-10000	0	0
SIRT1	0.008	0.007	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.023	0.004	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.004	0.058	-10000	0	-10000	0	0
apoptosis	-0.023	0.004	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.02	0.083	-10000	0	-0.22	87	87
p53/SIRT1	0.001	0.014	0.36	1	-10000	0	1
SIRT1/FOXO4	0.02	0.005	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	0.021	0.01	-10000	0	-10000	0	0
HIST1H1E	0	0.068	-10000	0	-0.25	42	42
SIRT1/p300	0.016	0.005	-10000	0	-10000	0	0
muscle cell differentiation	-0.005	0.049	-10000	0	-10000	0	0
TP53	0.008	0.007	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.023	0.004	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0
MEF2D	0.013	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.093	0.14	-10000	0	-0.27	230	230
ACSS2	0.016	0.012	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.005	0.049	-10000	0	-10000	0	0

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	0.017	0.035	-9999	-0.47	3	3
PDGFRB	0.003	0.081	-9999	-0.75	7	7
SPHK1	-0.025	0.062	-9999	-0.28	20	20
mol:S1P	-0.025	0.06	-9999	-0.28	20	20
S1P1/S1P/Gi	-0.077	0.16	-9999	-0.44	50	50
GNAO1	-0.14	0.2	-9999	-0.4	234	234
PDGFB-D/PDGFRB/PLCgamma1	-0.059	0.15	-9999	-0.5	23	23
PLCG1	-0.066	0.15	-9999	-0.45	37	37
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.003	0.08	-9999	-0.75	7	7
GNAI2	0.013	0.003	-9999	-10000	0	0
GNAI3	0.012	0.003	-9999	-10000	0	0
GNAI1	-0.003	0.076	-9999	-0.4	22	22
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.015	0.031	-9999	-0.49	2	2
S1P1/S1P	0.007	0.071	-9999	-0.31	12	12
negative regulation of cAMP metabolic process	-0.075	0.16	-9999	-0.43	50	50
MAPK3	-0.073	0.18	-9999	-0.6	29	29
calcium-dependent phospholipase C activity	-0.001	0.002	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
RhoA/GDP	0.009	0	-9999	-10000	0	0
KDR	0.012	0.016	-9999	-0.39	1	1
PLCB2	0.011	0.066	-9999	-0.3	4	4
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.011	0.056	-9999	-0.29	4	4
receptor internalization	-0.012	0.062	-9999	-0.29	12	12
PTGS2	-0.075	0.21	-9999	-0.74	36	36
Rac1/GTP	-0.011	0.056	-9999	-0.29	4	4
RHOA	0.013	0	-9999	-10000	0	0
VEGFA	0.011	0.043	-9999	-0.75	2	2
negative regulation of T cell proliferation	-0.075	0.16	-9999	-0.43	50	50
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.007	0.046	-9999	-0.4	8	8
MAPK1	-0.073	0.18	-9999	-0.6	28	28
S1P1/S1P/PDGFB-D/PDGFRB	0.009	0.089	-9999	-0.4	13	13
ABCC1	0.012	0.002	-9999	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.021	0.2	-9999	-0.72	37	37
MKNK1	0.013	0	-9999	-10000	0	0
MAPK14	-0.003	0.09	-9999	-0.41	4	4
ATF2/c-Jun	0.013	0.072	-9999	-0.38	1	1
MAPK11	-0.005	0.1	-9999	-0.55	6	6
MITF	-0.006	0.12	-9999	-0.37	44	44
MAPKAPK5	0.003	0.11	-9999	-0.33	42	42
KRT8	0.003	0.11	-9999	-0.33	42	42
MAPKAPK3	0.013	0	-9999	-10000	0	0
MAPKAPK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.007	0.14	-9999	-0.42	43	43
CEBPB	-0.001	0.11	-9999	-0.51	6	6
SLC9A1	0.002	0.11	-9999	-0.34	42	42
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.007	0.11	-9999	-0.49	5	5
p38alpha-beta/MNK1	0.007	0.11	-9999	-0.55	6	6
JUN	0.013	0.071	-9999	-0.37	1	1
PPARGC1A	-0.038	0.16	-9999	-0.42	47	47
USF1	0.003	0.11	-9999	-0.5	5	5
RAB5/GDP/GDI1	0.004	0.078	-9999	-0.38	5	5
NOS2	-0.032	0.24	-9999	-0.83	44	44
DDIT3	0.003	0.11	-9999	-0.5	5	5
RAB5A	0.011	0.023	-9999	-0.4	2	2
HSPB1	0.008	0.091	-9999	-0.43	6	6
p38alpha-beta/HBP1	0.007	0.11	-9999	-0.55	6	6
CREB1	0.005	0.11	-9999	-0.36	42	42
RAB5/GDP	0.008	0.016	-9999	-0.28	2	2
EIF4E	0.007	0.096	-9999	-0.51	5	5
RPS6KA4	0.003	0.11	-9999	-0.33	42	42
PLA2G4A	-0.022	0.12	-9999	-0.48	17	17
GDI1	0.003	0.11	-9999	-0.5	5	5
TP53	-0.002	0.13	-9999	-0.41	43	43
RPS6KA5	0.002	0.11	-9999	-0.34	42	42
ESR1	-0.025	0.15	-9999	-0.42	44	44
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.007	0.12	-9999	-0.57	9	9
MEF2A	0.003	0.11	-9999	-0.5	5	5
EIF4EBP1	0.004	0.12	-9999	-0.36	42	42
KRT19	0.002	0.11	-9999	-0.33	42	42
ELK4	0.003	0.11	-9999	-0.5	5	5
ATF6	0.003	0.11	-9999	-0.5	5	5
ATF1	0.005	0.11	-9999	-0.36	42	42
p38alpha-beta/MAPKAPK2	0.007	0.11	-9999	-0.55	6	6
p38alpha-beta/MAPKAPK3	0.007	0.11	-9999	-0.55	6	6

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.005	0.075	-9999	-0.75	6	6
GPC2	-0.011	0.13	-9999	-0.75	19	19
GPC2/Midkine	-0.005	0.12	-9999	-0.57	25	25
neuron projection morphogenesis	-0.005	0.12	-9999	-0.57	25	25

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.048	0.11	-10000	0	-0.75	1	1
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0	0.1	0.48	5	-10000	0	5
IL27/IL27R/JAK1	0.022	0.13	-10000	0	-0.65	2	2
TBX21	0.019	0.16	-10000	0	-0.53	18	18
IL12B	0.003	0.062	-10000	0	-0.76	4	4
IL12A	0.004	0.038	-10000	0	-0.31	8	8
IL6ST	0.002	0.068	-10000	0	-0.4	17	17
IL27RA/JAK1	0.023	0.023	-10000	0	-10000	0	0
IL27	-0.019	0.15	-10000	0	-0.75	24	24
TYK2	0.013	0.005	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.17	0.27	-10000	0	-0.58	173	173
T-helper 2 cell differentiation	0	0.1	0.48	5	-10000	0	5
T cell proliferation during immune response	0	0.1	0.48	5	-10000	0	5
MAPKKK cascade	0	0.1	-10000	0	-0.48	5	5
STAT3	0.013	0	-10000	0	-10000	0	0
STAT2	0.013	0	-10000	0	-10000	0	0
STAT1	0.012	0.031	-10000	0	-0.76	1	1
IL12RB1	-0.003	0.079	-10000	0	-0.41	22	22
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.023	0.15	-10000	0	-0.58	13	13
IL27/IL27R/JAK2/TYK2	0.001	0.1	-10000	0	-0.48	5	5
positive regulation of T cell mediated cytotoxicity	0	0.1	-10000	0	-0.48	5	5
STAT1 (dimer)	0.012	0.18	-10000	0	-0.68	6	6
JAK2	0.012	0.029	-10000	0	-0.4	3	3
JAK1	0.013	0.016	-10000	0	-0.39	1	1
STAT2 (dimer)	0.006	0.098	-10000	0	-0.51	3	3
T cell proliferation	-0.076	0.19	-10000	0	-0.6	38	38
IL12/IL12R/TYK2/JAK2	0.006	0.085	-10000	0	-10000	0	0
IL17A	-0.18	0.27	-10000	0	-0.58	173	173
mast cell activation	0	0.1	0.48	5	-10000	0	5
IFNG	-0.002	0.034	-10000	0	-0.09	64	64
T cell differentiation	-0.002	0.005	-10000	0	-0.019	12	12
STAT3 (dimer)	0.006	0.098	-10000	0	-0.51	3	3
STAT5A (dimer)	0.006	0.098	-10000	0	-0.51	3	3
STAT4 (dimer)	-0.003	0.11	-10000	0	-0.43	11	11
STAT4	-0.006	0.084	-10000	0	-0.4	28	28
T cell activation	-0.007	0.003	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.022	0.055	-10000	0	-10000	0	0
GATA3	0.003	0.1	-10000	0	-1.1	5	5
IL18	0.007	0.023	-10000	0	-0.28	4	4
positive regulation of mast cell cytokine production	0.006	0.096	-10000	0	-0.5	3	3
IL27/EBI3	-0.023	0.13	-10000	0	-0.39	63	63
IL27RA	0.014	0.02	-10000	0	-10000	0	0
IL6	-0.15	0.28	-10000	0	-0.78	86	86
STAT5A	0.013	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.002	-10000	0	-10000	0	0
IL2	-0.004	0.013	-10000	0	-10000	0	0
IL1B	-0.043	0.17	-10000	0	-0.56	58	58
EBI3	-0.014	0.1	-10000	0	-0.4	42	42
TNF	0.007	0.025	-10000	0	-0.28	5	5

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.025	0.093	-10000	0	-0.32	26	26
NT3 (dimer)/TRKC	-0.047	0.12	-10000	0	-0.28	135	135
NT3 (dimer)/TRKB	-0.11	0.17	-10000	0	-0.45	81	81
SHC/Grb2/SOS1/GAB1/PI3K	0.032	0.009	-10000	0	-10000	0	0
RAPGEF1	0.012	0.016	-10000	0	-0.4	1	1
BDNF	0	0.096	-10000	0	-0.75	10	10
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
DYNLT1	0.013	0	-10000	0	-10000	0	0
NTRK1	0.001	0.087	-10000	0	-0.71	9	9
NTRK2	-0.11	0.2	-10000	0	-0.41	182	182
NTRK3	-0.075	0.16	-10000	0	-0.4	131	131
NT-4/5 (dimer)/TRKB	-0.13	0.19	-10000	0	-0.47	100	100
neuron apoptosis	0.11	0.17	0.4	115	-10000	0	115
SHC 2-3/Grb2	-0.12	0.18	-10000	0	-0.43	115	115
SHC1	0.013	0	-10000	0	-10000	0	0
SHC2	-0.093	0.16	-10000	0	-0.41	88	88
SHC3	-0.12	0.18	-10000	0	-0.45	110	110
STAT3 (dimer)	0.017	0.028	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.046	0.12	-10000	0	-0.48	11	11
RIN/GDP	-0.004	0.065	-10000	0	-0.3	1	1
GIPC1	0.012	0.016	-10000	0	-0.4	1	1
KRAS	0.012	0.016	-10000	0	-0.4	1	1
DNAJA3	-0.054	0.12	-10000	0	-0.42	10	10
RIN/GTP	0	0.023	-10000	0	-0.58	1	1
CCND1	0.021	0.059	-10000	0	-0.63	5	5
MAGED1	0.013	0	-10000	0	-10000	0	0
PTPN11	0.013	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.023	0.14	-10000	0	-0.75	23	23
SHC/GRB2/SOS1	0.026	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.021	0.11	-10000	0	-0.54	11	11
TRKA/NEDD4-2	0.009	0.068	-10000	0	-0.51	10	10
ELMO1	0.011	0.028	-10000	0	-0.4	3	3
RhoG/GTP/ELMO1/DOCK1	0.016	0.019	-10000	0	-10000	0	0
NGF	-0.003	0.082	-10000	0	-0.43	21	21
HRAS	0.012	0.016	-10000	0	-0.4	1	1
DOCK1	0.012	0.016	-10000	0	-0.4	1	1
GAB2	0.013	0	-10000	0	-10000	0	0
RIT2	0	0.03	-10000	0	-0.75	1	1
RIT1	0.013	0	-10000	0	-10000	0	0
FRS2	0.013	0.001	-10000	0	-10000	0	0
DNM1	0.004	0.081	-10000	0	-0.75	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.053	0.12	-10000	0	-0.41	10	10
mol:GDP	-0.007	0.088	-10000	0	-0.31	1	1
NGF (dimer)	-0.003	0.082	-10000	0	-0.43	21	21
RhoG/GDP	0.008	0.02	-10000	0	-0.28	3	3
RIT1/GDP	0.001	0.065	-10000	0	-10000	0	0
TIAM1	-0.028	0.12	-10000	0	-0.4	62	62
PIK3R1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.058	0.14	-10000	0	-0.52	19	19
KIDINS220/CRKL/C3G	0.018	0.011	-10000	0	-0.27	1	1
SHC/RasGAP	0.019	0	-10000	0	-10000	0	0
FRS2 family/SHP2	0.025	0.021	-10000	0	-0.5	1	1
SHC/GRB2/SOS1/GAB1	0.032	0	-10000	0	-10000	0	0
RIT1/GTP	0.009	0	-10000	0	-10000	0	0
NT3 (dimer)	0.007	0.05	-10000	0	-0.44	7	7
RAP1/GDP	-0.022	0.038	-10000	0	-10000	0	0
KIDINS220/CRKL	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)	0	0.096	-10000	0	-0.75	10	10
ubiquitin-dependent protein catabolic process	0.008	0.081	-10000	0	-0.54	9	9
Schwann cell development	-0.026	0.028	-10000	0	-10000	0	0
EHD4	0.013	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.032	0.019	-10000	0	-0.45	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.034	0.013	-10000	0	-10000	0	0
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.087	0.12	-10000	0	-0.45	21	21
ABL1	0.013	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.019	0	-10000	0	-10000	0	0
Rap1/GTP	0.005	0.061	-10000	0	-10000	0	0
STAT3	0.017	0.028	-10000	0	-10000	0	0
axon guidance	-0.084	0.11	-10000	0	-0.42	22	22
MAPK3	-0.015	0.1	-10000	0	-0.49	11	11
MAPK1	-0.015	0.1	-10000	0	-0.49	11	11
CDC42/GDP	0.001	0.065	-10000	0	-0.28	1	1
NTF3	0.007	0.05	-10000	0	-0.45	7	7
NTF4	-0.023	0.14	-10000	0	-0.75	23	23
NGF (dimer)/TRKA/FAIM	0.007	0.083	-10000	0	-0.54	10	10
PI3K	0.018	0.011	-10000	0	-10000	0	0
FRS3	0.011	0.031	-10000	0	-0.75	1	1
FAIM	0.011	0.031	-10000	0	-0.75	1	1
GAB1	0.013	0	-10000	0	-10000	0	0
RASGRF1	-0.08	0.16	-10000	0	-0.45	49	49
SOS1	0.013	0	-10000	0	-10000	0	0
MCF2L	-0.032	0.1	-10000	0	-0.44	4	4
RGS19	0.012	0.016	-10000	0	-0.4	1	1
CDC42	0.011	0.023	-10000	0	-0.4	2	2
RAS family/GTP	0.01	0.066	-10000	0	-0.39	2	2
Rac1/GDP	0.001	0.065	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GRIT	0	0.08	-10000	0	-0.55	9	9
neuron projection morphogenesis	-0.045	0.13	-10000	0	-0.43	9	9
NGF (dimer)/TRKA/NEDD4-2	0.008	0.081	-10000	0	-0.54	9	9
MAP2K1	0.032	0	-10000	0	-10000	0	0
NGFR	-0.089	0.18	-10000	0	-0.4	156	156
NGF (dimer)/TRKA/GIPC/GAIP	0.016	0.059	-10000	0	-0.47	1	1
RAS family/GTP/PI3K	0.025	0.025	-10000	0	-0.49	1	1
FRS2 family/SHP2/GRB2/SOS1	0.037	0.018	-10000	0	-0.42	1	1
NRAS	0.011	0.023	-10000	0	-0.4	2	2
GRB2/SOS1	0.019	0	-10000	0	-10000	0	0
PRKCI	0.011	0.023	-10000	0	-0.4	2	2
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.039	0.12	-10000	0	-0.58	21	21
RASA1	0.013	0.001	-10000	0	-10000	0	0
TRKA/c-Abl	0.01	0.067	-10000	0	-0.57	8	8
SQSTM1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.044	0.13	-10000	0	-0.48	19	19
NGF (dimer)/TRKA/p62/Atypical PKCs	0.022	0.074	-10000	0	-0.48	9	9
MATK	-0.037	0.13	-10000	0	-0.4	76	76
NEDD4L	0.012	0.016	-10000	0	-0.4	1	1
RAS family/GDP	-0.019	0.035	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.075	0.12	-10000	0	-0.27	157	157
Rac1/GTP	-0.072	0.098	-10000	0	-0.32	38	38
FRS2 family/SHP2/CRK family	0.037	0.018	-10000	0	-0.42	1	1

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.016	0.021	-9999	-0.44	1	1
ARNO/beta Arrestin1-2	-0.005	0.065	-9999	-10000	0	0
EGFR	0.011	0.023	-9999	-0.4	2	2
EPHA2	0.01	0.043	-9999	-0.75	2	2
USP6	0.011	0.035	-9999	-0.57	2	2
IQSEC1	0.012	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.053	0.14	-9999	-0.57	20	20
ARRB2	0.008	0.002	-9999	-10000	0	0
mol:GTP	0.012	0.024	-9999	-0.35	1	1
ARRB1	0.012	0.016	-9999	-0.4	1	1
FBXO8	0.011	0.023	-9999	-0.4	2	2
TSHR	0.006	0.043	-9999	-0.75	2	2
EGF	-0.086	0.2	-9999	-0.45	131	131
somatostatin receptor activity	0	0	-9999	-0.001	24	24
ARAP2	0.011	0.023	-9999	-0.4	2	2
mol:GDP	-0.045	0.087	-9999	-0.24	53	53
mol:PI-3-4-5-P3	0	0	-9999	-0.001	5	5
ITGA2B	-0.019	0.15	-9999	-0.75	25	25
ARF6	0.012	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.031	0.028	-9999	-0.45	2	2
ADAP1	0.012	0.016	-9999	-0.4	1	1
KIF13B	0.011	0.023	-9999	-0.4	2	2
HGF/MET	0.006	0.077	-9999	-0.38	20	20
PXN	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.036	0.085	-9999	-0.25	24	24
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.036	0.12	-9999	-0.49	20	20
ADRB2	-0.052	0.15	-9999	-0.4	98	98
receptor agonist activity	0	0	-9999	0	27	27
actin filament binding	0	0	-9999	0	24	24
SRC	0.013	0	-9999	-10000	0	0
ITGB3	0.008	0.043	-9999	-0.4	7	7
GNAQ	0.01	0.028	-9999	-0.4	3	3
EFA6/PI-4-5-P2	0	0	-9999	-0.001	9	9
ARF6/GDP	0.01	0.072	-9999	-0.32	14	14
ARF6/GDP/GULP/ACAP1	-0.039	0.1	-9999	-0.4	12	12
alphaIIb/beta3 Integrin/paxillin/GIT1	0.01	0.096	-9999	-0.45	25	25
ACAP1	-0.003	0.077	-9999	-0.4	23	23
ACAP2	0.012	0.016	-9999	-0.4	1	1
LHCGR/beta Arrestin2	0.001	0.004	-9999	-10000	0	0
EFNA1	0.013	0	-9999	-10000	0	0
HGF	0.002	0.068	-9999	-0.42	15	15
CYTH3	0.009	0	-9999	-10000	0	0
CYTH2	0.009	0.002	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	6	6
endosomal lumen acidification	0	0	-9999	-0.001	5	5
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.009	0.091	-9999	-0.4	33	33
GNAQ/ARNO	0.015	0.014	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	3	3
MET	0.005	0.075	-9999	-0.75	6	6
GNA14	0.009	0.036	-9999	-0.4	5	5
GNA15	0.005	0.075	-9999	-0.75	6	6
GIT1	0.012	0.016	-9999	-0.4	1	1
mol:PI-4-5-P2	0	0	-9999	-0.001	20	20
GNA11	0.01	0.033	-9999	-0.4	4	4
LHCGR	0.001	0.004	-9999	-10000	0	0
AGTR1	-0.13	0.19	-9999	-0.4	220	220
desensitization of G-protein coupled receptor protein signaling pathway	0.001	0.004	-9999	-10000	0	0
IPCEF1/ARNO	-0.025	0.095	-9999	-0.38	20	20
alphaIIb/beta3 Integrin	-0.009	0.12	-9999	-0.5	32	32

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.004	0.081	-10000	0	-0.75	7	7
Jak2/Leptin Receptor	-0.029	0.075	-10000	0	-0.38	9	9
PTP1B/AKT1	-0.04	0.075	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.052	0.084	-10000	0	-0.3	2	2
EGFR	0.008	0.024	-10000	0	-0.41	2	2
EGF/EGFR	-0.083	0.13	-10000	0	-0.35	86	86
CSF1	0.011	0.028	-10000	0	-0.4	3	3
AKT1	0.013	0.001	-10000	0	-10000	0	0
INSR	0.013	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.056	0.091	-10000	0	-0.43	6	6
Insulin Receptor/Insulin	-0.039	0.044	-10000	0	-10000	0	0
HCK	0.003	0.062	-10000	0	-0.4	15	15
CRK	0.013	0	-10000	0	-10000	0	0
TYK2	-0.044	0.08	-10000	0	-0.28	2	2
EGF	-0.088	0.2	-10000	0	-0.46	131	131
YES1	0.012	0.016	-10000	0	-0.4	1	1
CAV1	-0.052	0.093	-10000	0	-0.33	3	3
TXN	0.011	0.003	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.036	0.078	-10000	0	-10000	0	0
cell migration	0.052	0.084	0.3	2	-10000	0	2
STAT3	0.012	0.001	-10000	0	-10000	0	0
PRLR	0.001	0.065	-10000	0	-0.4	16	16
ITGA2B	-0.02	0.15	-10000	0	-0.75	25	25
CSF1R	-0.011	0.095	-10000	0	-0.4	36	36
Prolactin Receptor/Prolactin	-0.007	0.093	-10000	0	-0.58	12	12
FGR	0.009	0.045	-10000	0	-0.47	5	5
PTP1B/p130 Cas	-0.044	0.081	-10000	0	-0.29	2	2
Crk/p130 Cas	-0.036	0.079	-10000	0	-10000	0	0
DOK1	-0.033	0.077	-10000	0	-0.37	3	3
JAK2	-0.032	0.077	-10000	0	-0.38	13	13
Jak2/Leptin Receptor/Leptin	-0.056	0.082	-10000	0	-0.46	9	9
PIK3R1	0.013	0	-10000	0	-10000	0	0
PTPN1	-0.053	0.084	-10000	0	-0.3	2	2
LYN	0.013	0	-10000	0	-10000	0	0
CDH2	-0.012	0.1	-10000	0	-0.43	34	34
SRC	-0.007	0.035	-10000	0	-10000	0	0
ITGB3	0.007	0.043	-10000	0	-0.4	7	7
CAT1/PTP1B	-0.083	0.11	-10000	0	-0.36	25	25
CAPN1	0.012	0.002	-10000	0	-10000	0	0
CSK	0.013	0	-10000	0	-10000	0	0
PI3K	-0.03	0.038	-10000	0	-10000	0	0
mol:H2O2	0.001	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.05	0.075	-10000	0	-0.45	7	7
negative regulation of transcription	-0.032	0.076	-10000	0	-0.37	13	13
FCGR2A	0.007	0.063	-10000	0	-0.68	5	5
FER	0.008	0.038	-10000	0	-0.52	3	3
alphaIIb/beta3 Integrin	-0.01	0.12	-10000	0	-0.5	32	32
BLK	-0.14	0.2	-10000	0	-0.4	236	236
Insulin Receptor/Insulin/Shc	0.017	0.001	-10000	0	-10000	0	0
RHOA	0.012	0.002	-10000	0	-10000	0	0
LEPR	0.007	0.048	-10000	0	-0.39	9	9
BCAR1	0.012	0.016	-10000	0	-0.4	1	1
p210 bcr-abl/Grb2	0.013	0	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.077	0.13	-10000	0	-0.4	37	37
PRL	-0.01	0.1	-10000	0	-0.75	12	12
SOCS3	0.013	0.034	-10000	0	-0.56	2	2
SPRY2	0.014	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.017	0.001	-10000	0	-10000	0	0
CSF1/CSF1R	-0.047	0.086	-10000	0	-0.37	5	5
Ras protein signal transduction	0.028	0.026	-10000	0	-10000	0	0
IRS1	0.013	0	-10000	0	-10000	0	0
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.034	0.14	-10000	0	-0.45	55	55
STAT5B	-0.041	0.076	-10000	0	-0.27	8	8
STAT5A	-0.041	0.076	-10000	0	-0.27	8	8
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.048	0.097	-10000	0	-0.53	8	8
CSN2	0.009	0.052	-10000	0	-0.53	3	3
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
LAT	-0.011	0.054	-10000	0	-0.38	6	6
YBX1	0.019	0.002	-10000	0	-10000	0	0
LCK	0.001	0.089	-10000	0	-0.68	10	10
SHC1	0.013	0	-10000	0	-10000	0	0
NOX4	-0.34	0.38	-10000	0	-0.75	284	284

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.012	0.17	-9999	-0.65	6	6
CRP	-0.021	0.18	-9999	-0.73	14	14
cell cycle arrest	-0.025	0.18	-9999	-0.67	16	16
TIMP1	-0.024	0.2	-9999	-0.62	29	29
IL6ST	0.004	0.067	-9999	-0.39	17	17
Rac1/GDP	-0.038	0.14	-9999	-0.44	20	20
AP1	0.023	0.065	-9999	-10000	0	0
GAB2	0.013	0.002	-9999	-10000	0	0
TNFSF11	-0.026	0.2	-9999	-0.75	16	16
HSP90B1	0.018	0.052	-9999	-0.51	1	1
GAB1	0.013	0.001	-9999	-10000	0	0
MAPK14	-0.032	0.12	-9999	-0.5	8	8
AKT1	0.045	0.015	-9999	-10000	0	0
FOXO1	0.049	0.016	-9999	-10000	0	0
MAP2K6	-0.041	0.13	-9999	-0.41	26	26
mol:GTP	0	0.002	-9999	-10000	0	0
MAP2K4	-0.027	0.15	-9999	-0.46	17	17
MITF	-0.046	0.14	-9999	-0.39	43	43
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.013	0	-9999	-10000	0	0
A2M	0.012	0.09	-9999	-1.3	3	3
CEBPB	0.009	0.082	-9999	-0.76	7	7
GRB2/SOS1/GAB family/SHP2	0.002	0.061	-9999	-10000	0	0
STAT3	-0.028	0.19	-9999	-0.7	16	16
STAT1	-0.004	0.016	-9999	-0.24	1	1
CEBPD	-0.013	0.17	-9999	-0.7	7	7
PIK3CA	0.013	0.016	-9999	-0.39	1	1
PI3K	0.021	0.012	-9999	-10000	0	0
JUN	0.012	0.001	-9999	-10000	0	0
PIAS3/MITF	-0.038	0.14	-9999	-0.43	22	22
MAPK11	-0.034	0.13	-9999	-0.5	10	10
STAT3 (dimer)/FOXO1	0.011	0.16	-9999	-0.54	5	5
GRB2/SOS1/GAB family	-0.059	0.1	-9999	-0.44	15	15
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.053	0.15	-9999	-0.42	40	40
GRB2	0.013	0.001	-9999	-10000	0	0
JAK2	0.011	0.028	-9999	-0.4	3	3
LBP	-0.071	0.25	-9999	-0.63	55	55
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.014	0.017	-9999	-0.39	1	1
MYC	-0.017	0.18	-9999	-0.66	11	11
FGG	-0.045	0.22	-9999	-0.72	24	24
macrophage differentiation	-0.025	0.18	-9999	-0.67	16	16
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.065	0.18	-9999	-0.44	86	86
JUNB	-0.013	0.17	-9999	-0.71	8	8
FOS	0.006	0.051	-9999	-0.4	10	10
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.049	0.14	-9999	-0.4	43	43
STAT1/PIAS1	-0.031	0.13	-9999	-0.39	28	28
GRB2/SOS1/GAB family/SHP2/PI3K	0.037	0.015	-9999	-10000	0	0
STAT3 (dimer)	-0.026	0.19	-9999	-0.7	16	16
PRKCD	-0.017	0.16	-9999	-0.54	9	9
IL6R	-0.071	0.16	-9999	-0.39	131	131
SOCS3	-0.029	0.12	-9999	-0.64	4	4
gp130 (dimer)/JAK1/JAK1/LMO4	0.026	0.046	-9999	-10000	0	0
Rac1/GTP	-0.036	0.14	-9999	-0.45	20	20
HCK	0.002	0.062	-9999	-0.4	15	15
MAPKKK cascade	0.018	0.048	-9999	-10000	0	0
bone resorption	-0.024	0.19	-9999	-0.71	16	16
IRF1	-0.012	0.17	-9999	-0.63	8	8
mol:GDP	-0.046	0.14	-9999	-0.41	34	34
SOS1	0.013	0.002	-9999	-10000	0	0
VAV1	-0.047	0.15	-9999	-0.41	35	35
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.068	0.17	-9999	-0.52	27	27
PTPN11	-0.003	0.013	-9999	-10000	0	0
IL6/IL6RA	-0.11	0.22	-9999	-0.59	83	83
gp130 (dimer)/TYK2/TYK2/LMO4	0.022	0.042	-9999	-10000	0	0
gp130 (dimer)/JAK2/JAK2/LMO4	0.021	0.047	-9999	-0.44	1	1
IL6	-0.085	0.26	-9999	-0.72	86	86
PIAS3	0.013	0	-9999	-10000	0	0
PTPRE	0.008	0.01	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
RAC1	0.013	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.057	0.13	-9999	-0.37	39	39
LMO4	0.015	0.018	-9999	-0.4	1	1
STAT3 (dimer)/PIAS3	-0.024	0.18	-9999	-0.67	14	14
MCL1	0.05	0.014	-9999	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.004	0.081	-9999	-0.75	7	7
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	-0.055	0.11	-9999	-0.34	32	32
GNAO1	-0.14	0.2	-9999	-0.4	234	234
S1P/S1P3/G12/G13	0.025	0.019	-9999	-0.45	1	1
AKT1	-0.011	0.056	-9999	-10000	0	0
AKT3	-0.025	0.16	-9999	-1.2	9	9
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.08	-9999	-0.75	7	7
GNAI2	0.014	0.003	-9999	-10000	0	0
GNAI3	0.014	0.002	-9999	-10000	0	0
GNAI1	-0.001	0.075	-9999	-0.4	22	22
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.012	0.031	-9999	-0.75	1	1
S1PR2	0.013	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.054	0.13	-9999	-0.38	32	32
MAPK3	-0.046	0.12	-9999	-0.36	33	33
MAPK1	-0.046	0.12	-9999	-0.36	32	32
JAK2	-0.046	0.12	-9999	-0.37	32	32
CXCR4	-0.046	0.12	-9999	-0.36	32	32
FLT1	0.015	0.002	-9999	-10000	0	0
RhoA/GDP	0.009	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
SRC	-0.046	0.12	-9999	-0.36	32	32
S1P/S1P3/Gi	-0.055	0.13	-9999	-0.38	32	32
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.044	0.12	-9999	-0.34	32	32
VEGFA	0.012	0.043	-9999	-0.75	2	2
S1P/S1P2/Gi	-0.056	0.12	-9999	-0.35	32	32
VEGFR1 homodimer/VEGFA homodimer	0.023	0.034	-9999	-0.57	2	2
RHOA	0.013	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.02	0.045	-9999	-0.44	2	2
GNAQ	0.011	0.028	-9999	-0.4	3	3
GNAZ	0.008	0.046	-9999	-0.39	8	8
G12/G13	0.019	0	-9999	-10000	0	0
GNA14	0.009	0.036	-9999	-0.4	5	5
GNA15	0.005	0.075	-9999	-0.75	6	6
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	0.01	0.033	-9999	-0.4	4	4
Rac1/GTP	-0.044	0.12	-9999	-0.34	32	32

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.016	0.017	-10000	0	-10000	0	0
HSPA8	0.012	0.004	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.007	0.11	-10000	0	-0.38	13	13
AKT1	-0.013	0.038	-10000	0	-10000	0	0
GSC	-0.05	0.18	-10000	0	-0.55	67	67
NKX2-5	-0.025	0.14	-10000	0	-0.75	22	22
muscle cell differentiation	0.033	0.072	0.44	3	-10000	0	3
SMAD2-3/SMAD4/SP1	-0.018	0.094	-10000	0	-0.39	1	1
SMAD4	-0.005	0.048	-10000	0	-0.47	2	2
CBFB	0.013	0	-10000	0	-10000	0	0
SAP18	0.012	0.002	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.083	0.22	-10000	0	-0.49	139	139
SMAD3/SMAD4/VDR	0.041	0.04	-10000	0	-10000	0	0
MYC	0.024	0.11	-10000	0	-0.72	11	11
CDKN2B	-0.42	0.62	-10000	0	-1.3	219	219
AP1	0.031	0.052	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.032	0.036	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.097	0.18	-10000	0	-0.5	42	42
SP3	0.015	0	-10000	0	-10000	0	0
CREB1	0.013	0	-10000	0	-10000	0	0
FOXH1	-0.009	0.093	-10000	0	-0.49	19	19
SMAD3/SMAD4/GR	-0.001	0.097	-10000	0	-0.39	10	10
GATA3	0.004	0.055	-10000	0	-0.48	5	5
SKI/SIN3/HDAC complex/NCoR1	0.037	0.013	-10000	0	-10000	0	0
MEF2C/TIF2	-0.021	0.13	-10000	0	-0.55	9	9
endothelial cell migration	0.092	0.24	0.54	139	-10000	0	139
MAX	0.019	0.016	-10000	0	-10000	0	0
RBBP7	0.012	0.002	-10000	0	-10000	0	0
RBBP4	0.012	0.002	-10000	0	-10000	0	0
RUNX2	0.013	0	-10000	0	-10000	0	0
RUNX3	0.012	0.016	-10000	0	-0.4	1	1
RUNX1	0.013	0	-10000	0	-10000	0	0
CTBP1	0.013	0	-10000	0	-10000	0	0
NR3C1	-0.011	0.11	-10000	0	-0.4	46	46
VDR	0.013	0	-10000	0	-10000	0	0
CDKN1A	0.023	0.083	-10000	0	-1.2	1	1
KAT2B	-0.004	0.081	-10000	0	-0.38	27	27
SMAD2/SMAD2/SMAD4/FOXH1	-0.022	0.089	-10000	0	-0.48	6	6
DCP1A	0.013	0	-10000	0	-10000	0	0
SKI	0.012	0.002	-10000	0	-10000	0	0
SERPINE1	-0.092	0.24	-10000	0	-0.54	139	139
SMAD3/SMAD4/ATF2	0.012	0.051	-10000	0	-0.36	2	2
SMAD3/SMAD4/ATF3	0.01	0.058	-10000	0	-0.44	4	4
SAP30	0.012	0.002	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.039	0.039	-10000	0	-10000	0	0
JUN	0.028	0.051	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	0.012	0.051	-10000	0	-0.36	2	2
TFE3	0.009	0.017	-10000	0	-10000	0	0
COL1A2	-0.026	0.15	-10000	0	-0.6	40	40
mesenchymal cell differentiation	-0.012	0.049	0.36	2	-10000	0	2
DLX1	-0.013	0.13	-10000	0	-0.71	19	19
TCF3	0.013	0	-10000	0	-10000	0	0
FOS	0.009	0.053	-10000	0	-0.4	10	10
SMAD3/SMAD4/Max	0.017	0.056	-10000	0	-0.36	2	2
Cbp/p300/SNIP1	0.027	0.015	-10000	0	-10000	0	0
ZBTB17	0.031	0.033	-10000	0	-0.4	1	1
LAMC1	0.017	0.043	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.007	0.072	-10000	0	-0.48	8	8
IRF7	0.012	0.016	-10000	0	-0.4	1	1
ESR1	-0.026	0.12	-10000	0	-0.4	59	59
HNF4A	0.012	0.016	-10000	0	-0.4	1	1
MEF2C	-0.029	0.13	-10000	0	-0.52	15	15
SMAD2-3/SMAD4	-0.015	0.077	-10000	0	-0.4	3	3
Cbp/p300/Src-1	0.032	0.025	-10000	0	-10000	0	0
IGHV3OR16-13	0.002	0.008	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.005	0.074	-10000	0	-0.75	6	6
CREBBP	0.015	0.012	-10000	0	-10000	0	0
SKIL	0.012	0.016	-10000	0	-0.4	1	1
HDAC1	0.012	0.002	-10000	0	-10000	0	0
HDAC2	0.012	0.002	-10000	0	-10000	0	0
SNIP1	0.012	0.004	-10000	0	-10000	0	0
GCN5L2	0.003	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.015	0.053	-10000	0	-0.35	2	2
MSG1/HSC70	-0.12	0.24	-10000	0	-0.57	139	139
SMAD2	-0.019	0.049	-10000	0	-0.42	2	2
SMAD3	0.007	0.044	-10000	0	-0.44	2	2
SMAD3/E2F4-5/DP1/p107/SMAD4	0.02	0.052	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.008	0.064	-10000	0	-0.28	29	29
NCOR1	0.012	0.002	-10000	0	-10000	0	0
NCOA2	0.011	0.028	-10000	0	-0.4	3	3
NCOA1	0.013	0	-10000	0	-10000	0	0
MYOD/E2A	0.009	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	-0.009	0.094	-10000	0	-10000	0	0
IFNB1	0.016	0.045	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.03	0.13	-10000	0	-0.56	8	8
CITED1	-0.16	0.32	-10000	0	-0.75	139	139
SMAD2-3/SMAD4/ARC105	-0.005	0.069	-10000	0	-10000	0	0
RBL1	0.011	0.031	-10000	0	-0.75	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.13	0.26	-10000	0	-0.48	219	219
RUNX1-3/PEBPB2	0.025	0.01	-10000	0	-10000	0	0
SMAD7	0.012	0.078	-10000	0	-0.62	1	1
MYC/MIZ-1	0.052	0.1	-10000	0	-0.53	11	11
SMAD3/SMAD4	0.023	0.14	0.32	11	-10000	0	11
IL10	0.001	0.13	-10000	0	-0.48	26	26
PIASy/HDAC complex	0.011	0.012	-10000	0	-10000	0	0
PIAS3	0.014	0.006	-10000	0	-10000	0	0
CDK2	0.015	0.011	-10000	0	-10000	0	0
IL5	0.007	0.1	-10000	0	-0.63	8	8
CDK4	0.015	0.032	-10000	0	-0.73	1	1
PIAS4	0.011	0.012	-10000	0	-10000	0	0
ATF3	0.01	0.043	-10000	0	-0.75	2	2
SMAD3/SMAD4/SP1	0	0.07	-10000	0	-0.38	2	2
FOXG1	-0.099	0.26	-10000	0	-0.75	83	83
FOXO3	-0.013	0.049	-10000	0	-10000	0	0
FOXO1	-0.013	0.05	-10000	0	-0.35	1	1
FOXO4	-0.012	0.048	-10000	0	-10000	0	0
heart looping	-0.028	0.13	-10000	0	-0.5	18	18
CEBPB	-0.01	0.084	-10000	0	-0.77	7	7
SMAD3/SMAD4/DLX1	-0.005	0.098	-10000	0	-0.49	19	19
MYOD1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.012	0.05	-10000	0	-0.36	2	2
SMAD3/SMAD4/GATA3	0.004	0.087	-10000	0	-0.48	4	4
SnoN/SIN3/HDAC complex/NCoR1	0.012	0.016	-10000	0	-0.39	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.022	0.045	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.015	0.064	-10000	0	-10000	0	0
MED15	0.012	0.016	-10000	0	-0.4	1	1
SP1	0.003	0.035	-10000	0	-10000	0	0
SIN3B	0.012	0.002	-10000	0	-10000	0	0
SIN3A	0.012	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.028	0.13	-10000	0	-0.5	26	26
ITGB5	0.024	0.058	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.039	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.008	0.089	-10000	0	-0.41	8	8
AR	-0.021	0.11	-10000	0	-0.4	47	47
negative regulation of cell growth	0.019	0.066	-10000	0	-0.38	2	2
SMAD3/SMAD4/MYOD	0.005	0.049	-10000	0	-0.36	2	2
E2F5	-0.002	0.1	-10000	0	-0.72	12	12
E2F4	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.003	0.073	-10000	0	-0.43	5	5
SMAD2-3/SMAD4/FOXO1-3a-4	-0.079	0.18	-10000	0	-0.39	26	26
TFDP1	0.013	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.023	0.055	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.012	0.05	-10000	0	-0.36	2	2
TGIF2	0.005	0.075	-10000	0	-0.75	6	6
TGIF1	0.013	0	-10000	0	-10000	0	0
ATF2	0.012	0.016	-10000	0	-0.4	1	1

×

Aurora A 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.023	0.001	-9999	-10000	0	0
BIRC5	0.01	0.043	-9999	-0.75	2	2
NFKBIA	0.024	0.002	-9999	-10000	0	0
CPEB1	-0.1	0.18	-9999	-0.4	174	174
AKT1	0.024	0.002	-9999	-10000	0	0
NDEL1	0.013	0	-9999	-10000	0	0
Aurora A/BRCA1	0.021	0.001	-9999	-10000	0	0
NDEL1/TACC3	0.027	0.018	-9999	-0.42	1	1
GADD45A	0.013	0	-9999	-10000	0	0
GSK3B	0.011	0.001	-9999	-10000	0	0
PAK1/Aurora A	0.023	0.001	-9999	-10000	0	0
MDM2	0.012	0.016	-9999	-0.4	1	1
JUB	-0.24	0.36	-9999	-0.75	204	204
TPX2	0.013	0.058	-9999	-0.57	6	6
TP53	0.024	0.012	-9999	-0.27	1	1
DLG7	0.016	0.002	-9999	-10000	0	0
AURKAIP1	0.011	0.031	-9999	-0.75	1	1
ARHGEF7	0.013	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.029	0.019	-9999	-0.44	1	1
G2/M transition of mitotic cell cycle	0.021	0.001	-9999	-10000	0	0
AURKA	0.02	0.002	-9999	-10000	0	0
AURKB	0.013	0.003	-9999	-10000	0	0
CDC25B	-0.04	0.095	-9999	-0.29	44	44
G2/M transition checkpoint	-0.13	0.22	-9999	-0.45	204	204
mRNA polyadenylation	-0.043	0.094	-9999	-10000	0	0
Aurora A/CPEB	-0.043	0.094	-9999	-10000	0	0
Aurora A/TACC1/TRAP/chTOG	0.035	0.012	-9999	-10000	0	0
BRCA1	0.013	0	-9999	-10000	0	0
centrosome duplication	0.023	0.001	-9999	-10000	0	0
regulation of centrosome cycle	0.026	0.018	-9999	-0.42	1	1
spindle assembly	0.034	0.012	-9999	-10000	0	0
TDRD7	0.013	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	0.032	0.025	-9999	-0.4	2	2
CENPA	0.016	0.005	-9999	-10000	0	0
Aurora A/PP2A	0.023	0.001	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.028	0.007	-9999	-10000	0	0
negative regulation of DNA binding	0.024	0.012	-9999	-0.27	1	1
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.018	0.011	-9999	-10000	0	0
RASA1	0.013	0.001	-9999	-10000	0	0
Ajuba/Aurora A	-0.13	0.22	-9999	-0.45	204	204
mitotic prometaphase	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.002	-9999	-10000	0	0
TACC1	0.011	0.023	-9999	-0.4	2	2
TACC3	0.011	0.031	-9999	-0.75	1	1
Aurora A/Antizyme1	0.029	0.019	-9999	-0.44	1	1
Aurora A/RasGAP	0.023	0.002	-9999	-10000	0	0
OAZ1	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.011	0.001	-9999	-10000	0	0
GIT1	0.012	0.016	-9999	-0.4	1	1
GIT1/beta-PIX/PAK1	0.025	0.01	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.013	0.057	-9999	-0.57	6	6
PPP2R5D	0.013	0	-9999	-10000	0	0
Aurora A/TPX2	0.024	0.046	-9999	-0.44	6	6
PAK1	0.013	0	-9999	-10000	0	0
CKAP5	0.013	0	-9999	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.016	0.035	-9999	-0.47	3	3
alphaV beta3 Integrin	0.005	0.07	-9999	-0.43	3	3
PTK2	0.012	0.092	-9999	-0.41	5	5
IGF1R	0.013	0	-9999	-10000	0	0
PI4KB	0.013	0	-9999	-10000	0	0
MFGE8	0.013	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
CDKN1B	0.004	0.068	-9999	-0.33	19	19
VEGFA	0.01	0.043	-9999	-0.75	2	2
ILK	0.004	0.068	-9999	-0.33	19	19
ROCK1	0.012	0.016	-9999	-0.4	1	1
AKT1	0.01	0.063	-9999	-10000	0	0
PTK2B	0.027	0.036	-9999	-0.41	2	2
alphaV/beta3 Integrin/JAM-A	0.004	0.096	-9999	-0.41	22	22
CBL	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.015	0.044	-9999	-0.49	3	3
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.018	0.093	-9999	-10000	0	0
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.026	0.046	-9999	-0.42	1	1
alphaV/beta3 Integrin/Syndecan-1	0.023	0.026	-9999	-10000	0	0
PI4KA	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.068	0.12	-9999	-0.54	7	7
PI4 Kinase	0.019	0	-9999	-10000	0	0
PIK3CA	0.012	0.016	-9999	-0.4	1	1
alphaV/beta3 Integrin/Osteopontin	-0.2	0.25	-9999	-0.49	263	263
RPS6KB1	-0.032	0.13	-9999	-0.51	7	7
TLN1	0.013	0	-9999	-10000	0	0
MAPK3	-0.026	0.15	-9999	-0.49	49	49
GPR124	0.012	0.016	-9999	-0.4	1	1
MAPK1	-0.026	0.15	-9999	-0.53	38	38
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.002	0.088	-9999	-0.49	9	9
cell adhesion	0.024	0.036	-9999	-0.35	3	3
ANGPTL3	0.001	0.053	-9999	-0.75	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	0.024	0.031	-9999	-0.49	2	2
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
TGFBR2	0.013	0	-9999	-10000	0	0
ITGB3	0.008	0.043	-9999	-0.4	7	7
IGF1	-0.08	0.17	-9999	-0.4	142	142
RAC1	0.013	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.022	0.027	-9999	-10000	0	0
apoptosis	0.012	0	-9999	-10000	0	0
CD47	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	0.023	0.026	-9999	-10000	0	0
VCL	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.021	0.1	-9999	-0.43	7	7
CSF1	0.011	0.028	-9999	-0.4	3	3
PIK3C2A	0.003	0.071	-9999	-0.34	21	21
PI4 Kinase/Pyk2	-0.023	0.073	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.028	0.037	-9999	-0.45	2	2
FAK1/Vinculin	0.018	0.079	-9999	-0.34	3	3
alphaV beta3/Integrin/ppsTEM5	0.022	0.027	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
VTN	-0.013	0.13	-9999	-0.75	19	19
BCAR1	0.012	0.016	-9999	-0.4	1	1
FGF2	-0.017	0.1	-9999	-0.4	45	45
F11R	-0.002	0.074	-9999	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	0.023	0.026	-9999	-10000	0	0
alphaV/beta3 Integrin/TGFBR2	0.023	0.026	-9999	-10000	0	0
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.031	0.018	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	0.022	0.023	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.028	0.17	-9999	-0.67	37	37
alphaV/beta3 Integrin/Pyk2	0.031	0.036	-9999	-0.41	2	2
SDC1	0.013	0	-9999	-10000	0	0
VAV3	0.014	0.058	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
IRS1	0.013	0	-9999	-10000	0	0
FAK1/Paxillin	0.018	0.079	-9999	-0.34	3	3
cell migration	0.024	0.075	-9999	-10000	0	0
ITGAV	0.013	0	-9999	-10000	0	0
PI3K	0.01	0.088	-9999	-0.38	19	19
SPP1	-0.31	0.38	-9999	-0.75	267	267
KDR	0.012	0.016	-9999	-0.4	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.013	0	-9999	-10000	0	0
COL4A3	-0.028	0.13	-9999	-0.46	51	51
angiogenesis	-0.023	0.15	-9999	-0.53	37	37
Rac1/GTP	0.019	0.054	-9999	-10000	0	0
EDIL3	-0.061	0.16	-9999	-0.4	113	113
cell proliferation	0.023	0.025	-9999	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.003	0.075	-10000	0	-0.41	4	4
regulation of S phase of mitotic cell cycle	0.009	0.057	-10000	0	-10000	0	0
GNAO1	-0.14	0.2	-10000	0	-0.4	234	234
HRAS	0.012	0.016	-10000	0	-0.39	1	1
SHBG/T-DHT	0.001	0.054	-10000	0	-0.5	7	7
PELP1	0.013	0	-10000	0	-10000	0	0
AKT1	0.009	0	-10000	0	-10000	0	0
MAP2K1	0.023	0.052	-10000	0	-0.35	1	1
T-DHT/AR	-0.014	0.078	-10000	0	-0.28	47	47
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.007	10	10
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.075	-10000	0	-0.4	22	22
mol:GDP	-0.025	0.088	-10000	0	-0.33	47	47
cell proliferation	0.024	0.074	-10000	0	-0.4	4	4
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
FOS	0.023	0.11	-10000	0	-0.77	10	10
mol:Ca2+	-0.021	0.027	-10000	0	-0.084	55	55
MAPK3	0.022	0.063	-10000	0	-0.39	1	1
MAPK1	0.018	0.041	-10000	0	-0.34	2	2
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.005	10	10
cAMP biosynthetic process	0.002	0.054	-10000	0	-0.46	7	7
GNG2	-0.004	0.081	-10000	0	-0.4	26	26
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	10	10
HRAS/GTP	0.01	0.054	-10000	0	-0.4	1	1
actin cytoskeleton reorganization	-0.001	0.015	-10000	0	-0.35	1	1
SRC	0.013	0	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	10	10
PI3K	0.017	0.01	-10000	0	-10000	0	0
apoptosis	-0.025	0.065	0.39	10	-10000	0	10
T-DHT/AR/PELP1	-0.003	0.066	-10000	0	-0.5	1	1
HRAS/GDP	-0.024	0.082	-10000	0	-0.31	47	47
CREB1	0.025	0.069	-10000	0	-0.41	10	10
RAC1-CDC42/GTP	0.024	0.017	-10000	0	-0.35	1	1
AR	-0.021	0.11	-10000	0	-0.4	47	47
GNB1	0.013	0	-10000	0	-10000	0	0
RAF1	0.017	0.053	-10000	0	-0.38	1	1
RAC1-CDC42/GDP	0.006	0.087	-10000	0	-0.32	1	1
T-DHT/AR/PELP1/Src	0.007	0.06	-10000	0	-0.45	1	1
MAP2K2	0.022	0.053	-10000	0	-0.35	1	1
T-DHT/AR/PELP1/Src/PI3K	0.009	0.058	-10000	0	-10000	0	0
GNAZ	0.007	0.046	-10000	0	-0.4	8	8
SHBG	0.001	0.08	-10000	0	-0.75	7	7
Gi family/GNB1/GNG2/GDP	-0.096	0.18	-10000	0	-0.45	63	63
mol:T-DHT	0	0	-10000	0	-0.003	9	9
RAC1	0.013	0	-10000	0	-10000	0	0
GNRH1	0.009	0.012	-10000	0	-0.28	1	1
Gi family/GTP	-0.058	0.12	-10000	0	-0.34	52	52
CDC42	0.011	0.023	-10000	0	-0.4	2	2

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.004	0.1	0.56	19	-10000	0	19
KIRREL	0.005	0.055	-10000	0	-0.45	8	8
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.004	0.1	-10000	0	-0.56	19	19
PLCG1	0.013	0	-10000	0	-10000	0	0
ARRB2	0.013	0	-10000	0	-10000	0	0
WASL	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.001	0.1	-10000	0	-0.45	23	23
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.016	0.06	-10000	0	-0.52	2	2
FYN	0.001	0.083	-10000	0	-0.4	23	23
mol:Ca2+	0.006	0.092	-10000	0	-0.44	23	23
mol:DAG	0.006	0.092	-10000	0	-0.44	23	23
NPHS2	-0.003	0.076	-10000	0	-0.76	6	6
mol:IP3	0.006	0.092	-10000	0	-0.44	23	23
regulation of endocytosis	0.011	0.079	-10000	0	-0.37	23	23
Nephrin/NEPH1/podocin/Cholesterol	-0.002	0.092	-10000	0	-0.45	23	23
establishment of cell polarity	-0.004	0.1	-10000	0	-0.56	19	19
Nephrin/NEPH1/podocin/NCK1-2	0.014	0.086	-10000	0	-0.41	23	23
Nephrin/NEPH1/beta Arrestin2	0.012	0.08	-10000	0	-0.38	23	23
NPHS1	-0.01	0.12	-10000	0	-0.75	17	17
Nephrin/NEPH1/podocin	0.003	0.084	-10000	0	-0.4	23	23
TJP1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
NCK2	0.013	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.007	0.093	-10000	0	-0.44	23	23
CD2AP	0	0.07	-10000	0	-0.4	19	19
Nephrin/NEPH1/podocin/GRB2	0.007	0.093	-10000	0	-0.44	23	23
GRB2	0.013	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.005	0.095	-10000	0	-0.4	26	26
cytoskeleton organization	0.017	0.075	-10000	0	-0.35	15	15
Nephrin/NEPH1	-0.001	0.076	-10000	0	-0.41	19	19
Nephrin/NEPH1/ZO-1	0.007	0.085	-10000	0	-0.46	18	18

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.064	0.18	-9999	-0.59	57	57
RAD9A	0.013	0	-9999	-10000	0	0
AP1	0.014	0.036	-9999	-10000	0	0
IFNAR2	0.013	0.004	-9999	-10000	0	0
AKT1	-0.002	0.052	-9999	-10000	0	0
ER alpha/Oestrogen	-0.018	0.084	-9999	-0.28	59	59
NFX1/SIN3/HDAC complex	0.038	0.012	-9999	-10000	0	0
EGF	-0.086	0.2	-9999	-0.45	131	131
SMG5	0.013	0	-9999	-10000	0	0
SMG6	0.013	0	-9999	-10000	0	0
SP3/HDAC2	0.02	0.008	-9999	-10000	0	0
TERT/c-Abl	-0.054	0.17	-9999	-0.57	48	48
SAP18	0.013	0.001	-9999	-10000	0	0
MRN complex	0.025	0.01	-9999	-10000	0	0
WT1	-0.37	0.38	-9999	-0.75	309	309
WRN	0.012	0.016	-9999	-0.4	1	1
SP1	0.013	0.006	-9999	-10000	0	0
SP3	0.012	0.003	-9999	-10000	0	0
TERF2IP	0.013	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.063	0.15	-9999	-0.54	36	36
Mad/Max	0.018	0.017	-9999	-0.27	2	2
TERT	-0.066	0.19	-9999	-0.62	51	51
CCND1	-0.054	0.17	-9999	-0.57	40	40
MAX	0.012	0.003	-9999	-10000	0	0
RBBP7	0.013	0.001	-9999	-10000	0	0
RBBP4	0.013	0.001	-9999	-10000	0	0
TERF2	0.012	0.003	-9999	-10000	0	0
PTGES3	0.013	0	-9999	-10000	0	0
SIN3A	0.013	0.001	-9999	-10000	0	0
Telomerase/911	0.024	0.027	-9999	-10000	0	0
CDKN1B	-0.021	0.15	-9999	-0.48	63	63
RAD1	0.011	0.031	-9999	-0.75	1	1
XRCC5	0.013	0	-9999	-10000	0	0
XRCC6	0.013	0	-9999	-10000	0	0
SAP30	0.013	0.001	-9999	-10000	0	0
TRF2/PARP2	0.019	0.002	-9999	-10000	0	0
UBE3A	0.012	0.017	-9999	-0.39	1	1
JUN	0.012	0.003	-9999	-10000	0	0
E6	0	0.003	-9999	-10000	0	0
HPV-16 E6/E6AP	0.009	0.012	-9999	-0.28	1	1
FOS	0.006	0.051	-9999	-0.39	10	10
IFN-gamma/IRF1	-0.034	0.18	-9999	-0.56	63	63
PARP2	0.013	0	-9999	-10000	0	0
BLM	0.011	0.031	-9999	-0.75	1	1
Telomerase	0	0.061	-9999	-0.35	6	6
IRF1	0.017	0.003	-9999	-10000	0	0
ESR1	-0.027	0.12	-9999	-0.4	59	59
KU/TER	0.019	0	-9999	-10000	0	0
ATM/TRF2	0.019	0.011	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.042	0.015	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.042	0.015	-9999	-10000	0	0
HDAC1	0.013	0.001	-9999	-10000	0	0
HDAC2	0.013	0.006	-9999	-10000	0	0
ATM	-0.001	0.014	-9999	-0.34	1	1
SMAD3	0.017	0.029	-9999	-0.37	3	3
ABL1	0.013	0	-9999	-10000	0	0
MXD1	0.011	0.023	-9999	-0.39	2	2
MRE11A	0.013	0.001	-9999	-10000	0	0
HUS1	0.013	0	-9999	-10000	0	0
RPS6KB1	0.012	0.016	-9999	-0.4	1	1
TERT/NF kappa B1/14-3-3	-0.038	0.17	-9999	-0.57	38	38
NR2F2	0.013	0.006	-9999	-10000	0	0
MAPK3	0.012	0.013	-9999	-0.29	1	1
MAPK1	0.012	0.013	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.011	0.031	-9999	-0.75	1	1
NFKB1	0.013	0	-9999	-10000	0	0
HNRNPC	0.013	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.014	-9999	-0.34	1	1
NBN	0.012	0.016	-9999	-0.4	1	1
EGFR	0.011	0.023	-9999	-0.4	2	2
mol:Oestrogen	0	0.002	-9999	-10000	0	0
EGF/EGFR	-0.053	0.14	-9999	-0.44	36	36
MYC	-0.001	0.1	-9999	-0.75	11	11
IL2	0.004	0.01	-9999	-10000	0	0
KU	0.019	0	-9999	-10000	0	0
RAD50	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
TGFB1	0.011	0.031	-9999	-0.75	1	1
TRF2/BLM	0.018	0.022	-9999	-0.54	1	1
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.049	0.17	-9999	-0.58	44	44
SP1/HDAC2	0.021	0.011	-9999	-10000	0	0
PINX1	0.013	0	-9999	-10000	0	0
Telomerase/EST1A	-0.063	0.15	-9999	-0.54	36	36
Smad3/Myc	0.013	0.072	-9999	-0.49	12	12
911 complex	0.025	0.021	-9999	-0.49	1	1
IFNG	-0.062	0.23	-9999	-0.75	63	63
Telomerase/PinX1	-0.063	0.15	-9999	-0.54	36	36
Telomerase/AKT1/mTOR/p70S6K	0.008	0.049	-9999	-10000	0	0
SIN3B	0.013	0.001	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
Telomerase/EST1B	-0.063	0.15	-9999	-0.54	36	36
response to DNA damage stimulus	0.003	0.005	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.036	0.008	-9999	-10000	0	0
TRF2/WRN	0.018	0.011	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.063	0.15	-9999	-0.54	35	35
E2F1	-0.003	0.11	-9999	-0.76	13	13
ZNFX1	0.013	0.001	-9999	-10000	0	0
PIF1	-0.008	0.12	-9999	-0.75	17	17
NCL	0.013	0	-9999	-10000	0	0
DKC1	0.013	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.008	0.075	-9999	-0.47	5	5
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
DOCK1	0.012	0.016	-9999	-0.4	1	1
ITGA4	-0.002	0.075	-9999	-0.4	22	22
alpha4/beta7 Integrin/MAdCAM1	-0.085	0.13	-9999	-0.42	31	31
EPO	-0.002	0.08	-9999	-0.75	7	7
alpha4/beta7 Integrin	-0.002	0.08	-9999	-0.51	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.009	0.053	-9999	-10000	0	0
EPO/EPOR (dimer)	0.007	0.066	-9999	-0.57	8	8
lamellipodium assembly	0.031	0.01	-9999	-10000	0	0
PIK3CA	0.012	0.016	-9999	-0.4	1	1
PI3K	0.018	0.011	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
JAK2	0.014	0.06	-9999	-0.42	3	3
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
MADCAM1	-0.18	0.2	-9999	-0.4	287	287
cell adhesion	-0.085	0.13	-9999	-0.42	31	31
CRKL/CBL	0.019	0	-9999	-10000	0	0
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.016	0.06	-9999	-0.39	9	9
ITGB7	-0.003	0.077	-9999	-0.4	23	23
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.012	0.067	-9999	-0.43	9	9
p130Cas/Crk/Dock1	0.033	0.054	-9999	-10000	0	0
VCAM1	0.004	0.058	-9999	-0.4	13	13
RHOA	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.024	0.042	-9999	-10000	0	0
BCAR1	0.02	0.057	-9999	-10000	0	0
EPOR	0.011	0.031	-9999	-0.75	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
GIT1	0.012	0.016	-9999	-0.4	1	1
Rac1/GTP	0.031	0.01	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.023	0	-9999	-10000	0	0
SNTA1	0.012	0.016	-9999	-0.4	1	1
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.023	0.01	-9999	-10000	0	0
MAPK12	0.016	0.063	-9999	-0.48	9	9
CCND1	0.014	0.03	-9999	-0.18	14	14
p38 gamma/SNTA1	0.022	0.06	-9999	-0.45	9	9
MAP2K3	0.013	0	-9999	-10000	0	0
PKN1	0.013	0	-9999	-10000	0	0
G2/M transition checkpoint	0.016	0.062	-9999	-0.48	9	9
MAP2K6	0.018	0.019	-9999	-10000	0	0
MAPT	-0.042	0.12	-9999	-0.26	146	146
MAPK13	0.019	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.015	0	-9999	-10000	0	0

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.018	0.004	-9999	-10000	0	0
SMARCC1	0.004	0.008	-9999	-10000	0	0
REL	0.015	0.007	-9999	-10000	0	0
HDAC7	0.02	0.082	-9999	-10000	0	0
JUN	0.011	0.005	-9999	-10000	0	0
EP300	0.012	0.001	-9999	-10000	0	0
KAT2B	-0.006	0.083	-9999	-0.4	27	27
KAT5	0.013	0.001	-9999	-10000	0	0
MAPK14	0.015	0.027	-9999	-0.29	3	3
FOXO1	0.012	0.016	-9999	-0.39	1	1
T-DHT/AR	0.019	0.088	-9999	-0.44	2	2
MAP2K6	0.008	0.034	-9999	-0.41	4	4
BRM/BAF57	0.014	0.017	-9999	-10000	0	0
MAP2K4	0.009	0.029	-9999	-0.4	3	3
SMARCA2	0.01	0.018	-9999	-0.42	1	1
PDE9A	-0.14	0.37	-9999	-0.96	104	104
NCOA2	0.01	0.028	-9999	-0.39	3	3
CEBPA	0.011	0.028	-9999	-0.39	3	3
EHMT2	0.01	0.031	-9999	-0.75	1	1
cell proliferation	0.024	0.1	-9999	-0.42	1	1
NR0B1	-0.002	0.068	-9999	-0.75	5	5
EGR1	0.01	0.023	-9999	-0.39	2	2
RXRs/9cRA	-0.074	0.11	-9999	-10000	0	0
AR/RACK1/Src	0.019	0.056	-9999	-10000	0	0
AR/GR	-0.006	0.088	-9999	-0.39	9	9
GNB2L1	0.013	0.001	-9999	-10000	0	0
PKN1	0.012	0.001	-9999	-10000	0	0
RCHY1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.002	-9999	-10000	0	0
MAPK8	0.015	0.024	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.025	0.054	-9999	-10000	0	0
SRC	0.023	0.036	-9999	-10000	0	0
NR3C1	-0.018	0.11	-9999	-0.4	46	46
KLK3	-0.2	0.43	-9999	-1.1	105	105
APPBP2	0.011	0.017	-9999	-0.39	1	1
TRIM24	0.011	0.006	-9999	-10000	0	0
T-DHT/AR/TIP60	0.02	0.05	-9999	-10000	0	0
TMPRSS2	-0.007	0.11	-9999	-1.1	4	4
RXRG	-0.16	0.2	-9999	-0.4	262	262
mol:9cRA	-0.001	0.002	-9999	-10000	0	0
RXRA	0.011	0.016	-9999	-0.39	1	1
RXRB	0.012	0.001	-9999	-10000	0	0
CARM1	0.013	0.002	-9999	-10000	0	0
NR2C2	0.012	0.016	-9999	-0.39	1	1
KLK2	0.011	0.12	-9999	-0.5	29	29
AR	0.005	0.073	-9999	-0.33	9	9
SENP1	0.012	0.001	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
MDM2	0.016	0.02	-9999	-0.4	1	1
SRY	0.003	0.032	-9999	-0.75	1	1
GATA2	0.005	0.054	-9999	-0.4	11	11
MYST2	0.013	0.001	-9999	-10000	0	0
HOXB13	-0.02	0.11	-9999	-0.4	45	45
T-DHT/AR/RACK1/Src	0.024	0.051	-9999	-10000	0	0
positive regulation of transcription	0.005	0.054	-9999	-0.39	11	11
DNAJA1	0.011	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.013	-9999	-0.27	1	1
NCOA1	0.014	0.006	-9999	-10000	0	0
SPDEF	-0.08	0.17	-9999	-0.4	140	140
T-DHT/AR/TIF2	0.021	0.057	-9999	-10000	0	0
T-DHT/AR/Hsp90	0.019	0.05	-9999	-10000	0	0
GSK3B	0.012	0.003	-9999	-10000	0	0
NR2C1	0.013	0.003	-9999	-10000	0	0
mol:T-DHT	0.019	0.038	-9999	-10000	0	0
SIRT1	0.012	0.001	-9999	-10000	0	0
ZMIZ2	0.017	0.012	-9999	-10000	0	0
POU2F1	0.01	0.048	-9999	-0.74	1	1
T-DHT/AR/DAX-1	0.01	0.062	-9999	-0.41	5	5
CREBBP	0.012	0.001	-9999	-10000	0	0
SMARCE1	0.01	0.007	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.018	0.06	0.36	5	-10000	0	5
RFC1	0.018	0.06	0.36	5	-10000	0	5
PRKDC	0.017	0.063	0.36	5	-0.48	1	6
RIPK1	0.013	0.003	-10000	0	-10000	0	0
CASP7	0.016	0.052	0.22	17	-0.54	1	18
FASLG/FAS/FADD/FAF1	0.008	0.076	0.22	20	-0.29	7	27
MAP2K4	0.01	0.093	-10000	0	-0.36	6	6
mol:ceramide	0.006	0.082	-10000	0	-0.37	7	7
GSN	0.014	0.061	0.36	4	-10000	0	4
FASLG/FAS/FADD/FAF1/Caspase 8	0.013	0.077	0.28	1	-0.36	5	6
FAS	0.006	0.049	-10000	0	-0.4	9	9
BID	0.019	0.059	0.27	29	-0.5	1	30
MAP3K1	0.02	0.065	0.25	3	-0.32	1	4
MAP3K7	0.012	0.003	-10000	0	-10000	0	0
RB1	0.018	0.06	0.36	5	-10000	0	5
CFLAR	0.013	0.003	-10000	0	-10000	0	0
HGF/MET	-0.006	0.12	-10000	0	-0.5	31	31
ARHGDIB	0.018	0.06	0.36	5	-10000	0	5
FADD	0.012	0.005	-10000	0	-10000	0	0
actin filament polymerization	-0.014	0.061	-10000	0	-0.36	4	4
NFKB1	-0.023	0.051	-10000	0	-10000	0	0
MAPK8	0.003	0.12	-10000	0	-0.44	10	10
DFFA	0.018	0.06	0.36	5	-10000	0	5
DNA fragmentation during apoptosis	0.018	0.06	0.36	5	-10000	0	5
FAS/FADD/MET	0.015	0.059	-10000	0	-0.49	6	6
CFLAR/RIP1	0.016	0.006	-10000	0	-10000	0	0
FAIM3	-0.006	0.086	-10000	0	-0.39	29	29
FAF1	0.012	0.005	-10000	0	-10000	0	0
PARP1	0.018	0.06	0.36	5	-10000	0	5
DFFB	0.018	0.06	0.36	5	-10000	0	5
CHUK	-0.017	0.045	-10000	0	-10000	0	0
FASLG	-0.011	0.096	-10000	0	-0.41	34	34
FAS/FADD	0.013	0.035	-10000	0	-0.27	9	9
HGF	0.002	0.067	-10000	0	-0.42	15	15
LMNA	0.027	0.052	0.32	5	-10000	0	5
CASP6	0.018	0.06	0.36	5	-10000	0	5
CASP10	0.012	0.005	-10000	0	-10000	0	0
CASP3	0.021	0.071	0.26	32	-10000	0	32
PTPN13	-0.018	0.15	-10000	0	-0.68	28	28
CASP8	0.015	0.069	0.33	29	-10000	0	29
IL6	-0.055	0.23	-10000	0	-0.6	83	83
MET	0.005	0.075	-10000	0	-0.75	6	6
ICAD/CAD	0.017	0.055	0.33	5	-10000	0	5
FASLG/FAS/FADD/FAF1/Caspase 10	0.006	0.083	-10000	0	-0.37	7	7
activation of caspase activity by cytochrome c	0.019	0.059	0.27	29	-0.5	1	30
PAK2	0.018	0.06	0.36	5	-10000	0	5
BCL2	-0.008	0.09	-10000	0	-0.4	32	32

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.065	0.16	-9999	-0.4	118	118
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0.043	-9999	-0.75	2	2
TCEB1	0.013	0	-9999	-10000	0	0
HIF1A/p53	0.027	0.007	-9999	-10000	0	0
HIF1A	0.02	0.007	-9999	-10000	0	0
COPS5	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.036	0.027	-9999	-0.42	2	2
FIH (dimer)	0.013	0	-9999	-10000	0	0
CDKN2A	-0.14	0.3	-9999	-0.75	120	120
ARNT/IPAS	-0.036	0.11	-9999	-10000	0	0
HIF1AN	0.013	0	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
HIF1A/ARNT	0.027	0.01	-9999	-10000	0	0
CUL2	0.013	0	-9999	-10000	0	0
OS9	0.013	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.024	0.029	-9999	-0.49	2	2
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.027	0.007	-9999	-10000	0	0
PHD1-3/OS9	0.03	0.023	-9999	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	0.036	0.023	-9999	-0.36	2	2
VHL	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
HIF1A/JAB1	0.027	0.007	-9999	-10000	0	0
EGLN3	0.009	0.04	-9999	-0.4	6	6
EGLN2	0.012	0.016	-9999	-0.4	1	1
EGLN1	0.013	0	-9999	-10000	0	0
TP53	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.033	0.015	-9999	-10000	0	0
ARNT	0.012	0.016	-9999	-0.4	1	1
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.012	0.016	-9999	-0.4	1	1
HIF1A/p19ARF	-0.053	0.16	-9999	-0.39	120	120

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0	0.036	-9999	-0.39	2	2
SVIL	0.002	0.029	-9999	-0.39	1	1
ZNF318	0.036	0.058	-9999	-10000	0	0
JMJD2C	0.002	0.028	-9999	-0.12	29	29
T-DHT/AR/Ubc9	0.006	0.07	-9999	-0.33	5	5
CARM1	0.011	0.003	-9999	-10000	0	0
PRDX1	0.014	0.004	-9999	-10000	0	0
PELP1	0.017	0.01	-9999	-10000	0	0
CTNNB1	0.004	0.02	-9999	-10000	0	0
AKT1	0.019	0.016	-9999	-10000	0	0
PTK2B	0.004	0.029	-9999	-0.39	2	2
MED1	0.018	0.046	-9999	-0.72	2	2
MAK	0.009	0.15	-9999	-0.74	22	22
response to oxidative stress	0.002	0.004	-9999	-10000	0	0
HIP1	0.002	0.029	-9999	-0.39	1	1
GSN	-0.007	0.065	-9999	-0.41	13	13
NCOA2	0.009	0.028	-9999	-0.39	3	3
NCOA6	0.003	0.024	-9999	-10000	0	0
DNA-PK	0.047	0.059	-9999	-0.49	1	1
NCOA4	0.011	0.017	-9999	-0.4	1	1
PIAS3	0.004	0.02	-9999	-10000	0	0
cell proliferation	0.007	0.093	-9999	-0.38	21	21
XRCC5	0.018	0.013	-9999	-10000	0	0
UBE3A	-0.004	0.041	-9999	-0.4	1	1
T-DHT/AR/SNURF	-0.025	0.11	-9999	-0.41	22	22
FHL2	0.043	0.053	-9999	-10000	0	0
RANBP9	0.002	0.029	-9999	-0.4	1	1
JMJD1A	0.007	0.025	-9999	-0.13	18	18
CDK6	0.014	0.003	-9999	-10000	0	0
TGFB1I1	0.003	0.025	-9999	-10000	0	0
T-DHT/AR/CyclinD1	-0.006	0.086	-9999	-0.42	10	10
XRCC6	0.018	0.013	-9999	-10000	0	0
T-DHT/AR	0.018	0.083	-9999	-0.38	5	5
CTDSP1	0.009	0.009	-9999	-10000	0	0
CTDSP2	0.029	0.039	-9999	-10000	0	0
BRCA1	0.003	0.025	-9999	-10000	0	0
TCF4	0.022	0.04	-9999	-0.37	3	3
CDKN2A	-0.13	0.3	-9999	-0.74	120	120
SRF	0.027	0.018	-9999	-10000	0	0
NKX3-1	-0.001	0.12	-9999	-0.78	14	14
KLK3	-0.19	0.49	-9999	-1.3	104	104
TMF1	0.01	0.017	-9999	-0.4	1	1
HNRNPA1	0.021	0.021	-9999	-10000	0	0
AOF2	-0.01	0.025	-9999	-0.068	100	100
APPL1	0.032	0.042	-9999	-10000	0	0
T-DHT/AR/Caspase 8	0.014	0.075	-9999	-0.33	5	5
AR	-0.018	0.11	-9999	-0.4	47	47
UBA3	0.009	0.009	-9999	-10000	0	0
PATZ1	0.021	0.021	-9999	-10000	0	0
PAWR	0.011	0.005	-9999	-10000	0	0
PRKDC	0.017	0.033	-9999	-0.75	1	1
PA2G4	0.023	0.026	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.013	0.067	-9999	-0.3	5	5
RPS6KA3	0.001	0.028	-9999	-10000	0	0
T-DHT/AR/ARA70	0	0.07	-9999	-0.33	5	5
LATS2	0.021	0.021	-9999	-10000	0	0
T-DHT/AR/PRX1	0.018	0.073	-9999	-0.3	5	5
Cyclin D3/CDK11 p58	0.011	0.005	-9999	-10000	0	0
VAV3	-0.029	0.11	-9999	-0.4	52	52
KLK2	-0.016	0.13	-9999	-0.58	29	29
CASP8	0.016	0.008	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.006	0.068	-9999	-0.44	1	1
TMPRSS2	0.008	0.081	-9999	-0.81	4	4
CCND1	0.001	0.069	-9999	-0.75	5	5
PIAS1	-0.003	0.038	-9999	-10000	0	0
mol:T-DHT	0.003	0.017	-9999	-0.059	38	38
CDC2L1	0.001	0.002	-9999	-10000	0	0
PIAS4	-0.011	0.057	-9999	-10000	0	0
T-DHT/AR/CDK6	0.009	0.072	-9999	-0.33	5	5
CMTM2	-0.014	0.14	-9999	-0.75	23	23
SNURF	-0.038	0.14	-9999	-0.42	68	68
ZMIZ1	0.015	0.016	-9999	-10000	0	0
CCND3	0.013	0.002	-9999	-10000	0	0
TGIF1	0.021	0.021	-9999	-10000	0	0
FKBP4	0.002	0.038	-9999	-0.75	1	1

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	-0.003	0.077	-9999	-0.4	23	23
ITGA4	-0.002	0.075	-9999	-0.4	22	22
alpha4/beta7 Integrin	-0.002	0.08	-9999	-0.51	5	5
alpha4/beta1 Integrin	0.009	0.053	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.002	0.087	-10000	0	-0.71	9	9
ANTXR2	0.011	0.023	-10000	0	-0.4	2	2
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.001	0.011	-10000	0	-0.08	11	11
monocyte activation	0.003	0.065	-10000	0	-0.37	18	18
MAP2K2	0.009	0.029	-10000	0	-0.69	1	1
MAP2K1	-0.001	0.009	-10000	0	-10000	0	0
MAP2K7	-0.002	0.012	-10000	0	-10000	0	0
MAP2K6	-0.002	0.018	-10000	0	-0.19	4	4
CYAA	0.005	0.052	-10000	0	-0.43	8	8
MAP2K4	-0.002	0.016	-10000	0	-0.19	3	3
IL1B	-0.028	0.12	-10000	0	-0.42	57	57
Channel	0.009	0.055	-10000	0	-0.46	8	8
NLRP1	-0.004	0.029	-10000	0	-0.29	5	5
CALM1	0.013	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.01	0.014	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.001	0.011	0.08	11	-10000	0	11
MAPK3	-0.002	0.012	-10000	0	-0.19	1	1
MAPK1	-0.002	0.012	-10000	0	-0.19	1	1
PGR	-0.053	0.085	-10000	0	-0.19	168	168
PA/Cellular Receptors	0.009	0.06	-10000	0	-0.5	8	8
apoptosis	-0.001	0.011	-10000	0	-0.08	11	11
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.009	0.05	-10000	0	-0.41	8	8
macrophage activation	0.013	0.015	-10000	0	-10000	0	0
TNF	0.009	0.036	-10000	0	-0.4	5	5
VCAM1	0.003	0.065	-10000	0	-0.37	18	18
platelet activation	0.01	0.014	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.013	0.12	1	-10000	0	1
IL18	0.01	0.023	-10000	0	-0.18	6	6
negative regulation of macrophage activation	-0.001	0.011	-10000	0	-0.08	11	11
LEF	-0.001	0.011	-10000	0	-0.081	11	11
CASP1	-0.002	0.016	-10000	0	-0.14	5	5
mol:cAMP	0.01	0.014	-10000	0	-10000	0	0
necrosis	-0.001	0.011	-10000	0	-0.08	11	11
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.009	0.052	-10000	0	-0.43	8	8
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.006	0.12	-9999	-0.37	63	63
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.019	0.11	-9999	-0.67	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.016	0.034	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.022	0.047	-9999	-0.27	1	1
CaM/Ca2+	-0.003	0.11	-9999	-0.34	57	57
RAP1A	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.001	0.12	-9999	-0.75	1	1
AKT1	0.007	0.1	-9999	-10000	0	0
MAP2K1	0.003	0.11	-9999	-10000	0	0
MAP3K11	-0.004	0.12	-9999	-0.35	57	57
IFNGR1	0.01	0.013	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.025	0.13	-9999	-0.45	20	20
Rap1/GTP	-0.027	0.079	-9999	-10000	0	0
CRKL/C3G	0.018	0.011	-9999	-0.27	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.007	0.13	-9999	-0.4	63	63
CEBPB	0.017	0.13	-9999	-0.5	2	2
STAT3	0.013	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.016	0.16	-9999	-0.54	22	22
STAT1	-0.003	0.12	-9999	-0.75	1	1
CALM1	0.013	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.065	0.23	-9999	-0.74	63	63
PIK3CA	0.012	0.016	-9999	-0.4	1	1
STAT1 (dimer)/PIAS1	0.005	0.11	-9999	-0.7	1	1
CEBPB/PTGES2/Cbp/p300	-0.027	0.066	-9999	-10000	0	0
mol:Ca2+	-0.007	0.12	-9999	-0.36	63	63
MAPK3	0.013	0.11	-9999	-0.9	1	1
STAT1 (dimer)	-0.029	0.061	-9999	-0.37	1	1
MAPK1	0.013	0.1	-9999	-0.7	1	1
JAK2	0.008	0.031	-9999	-0.4	3	3
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.009	0.021	-9999	-0.39	1	1
CAMK2D	0.011	0.023	-9999	-0.4	2	2
DAPK1	0.014	0.14	-9999	-0.57	26	26
SMAD7	0.026	0.045	-9999	-0.22	1	1
CBL/CRKL/C3G	0.009	0.11	-9999	-10000	0	0
PI3K	-0.034	0.099	-9999	-10000	0	0
IFNG	-0.065	0.23	-9999	-0.74	63	63
apoptosis	0.009	0.11	-9999	-0.42	26	26
CAMK2G	0.013	0	-9999	-10000	0	0
STAT3 (dimer)	0.013	0	-9999	-10000	0	0
CAMK2A	-0.021	0.11	-9999	-0.4	50	50
CAMK2B	-0.028	0.13	-9999	-0.45	52	52
FRAP1	0.007	0.098	-9999	-10000	0	0
PRKCD	0.008	0.11	-9999	-10000	0	0
RAP1B	0.013	0	-9999	-10000	0	0
negative regulation of cell growth	-0.022	0.047	-9999	-0.27	1	1
PTPN2	0.013	0.001	-9999	-10000	0	0
EP300	0.013	0.001	-9999	-10000	0	0
IRF1	0.021	0.1	-9999	-0.46	7	7
STAT1 (dimer)/PIASy	0.004	0.11	-9999	-0.7	1	1
SOCS1	-0.016	0.1	-9999	-0.55	22	22
mol:GDP	0.005	0.1	-9999	-10000	0	0
CASP1	0.025	0.047	-9999	-0.23	3	3
PTGES2	0.013	0	-9999	-10000	0	0
IRF9	0.031	0.046	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.033	0.097	-9999	-10000	0	0
RAP1/GDP	-0.027	0.079	-9999	-10000	0	0
CBL	-0.004	0.12	-9999	-10000	0	0
MAP3K1	-0.003	0.12	-9999	-0.35	1	1
PIAS1	0.013	0	-9999	-10000	0	0
PIAS4	0.012	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.022	0.047	-9999	-0.27	1	1
PTPN11	-0.01	0.12	-9999	-0.36	63	63
CREBBP	0.013	0.001	-9999	-10000	0	0
RAPGEF1	0.012	0.016	-9999	-0.4	1	1

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.013	0	-10000	0	-10000	0	0
NFATC1	0.045	0.027	-10000	0	-10000	0	0
NFATC2	0.03	0.025	-10000	0	-10000	0	0
NFATC3	0.021	0.003	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.071	0.12	-10000	0	-0.35	53	53
Exportin 1/Ran/NUP214	0.026	0.001	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.076	0.1	-10000	0	-0.46	11	11
BCL2/BAX	0.004	0.063	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.01	0.003	-10000	0	-10000	0	0
BAX	0.013	0	-10000	0	-10000	0	0
MAPK14	0.013	0.001	-10000	0	-10000	0	0
BAD	0.012	0.016	-10000	0	-0.4	1	1
CABIN1/MEF2D	-0.061	0.11	-10000	0	-0.33	53	53
Calcineurin A alpha-beta B1/BCL2	-0.008	0.09	-10000	0	-0.39	32	32
FKBP8	0.012	0.016	-10000	0	-0.4	1	1
activation-induced cell death of T cells	0.061	0.11	0.32	53	-10000	0	53
KPNB1	0.013	0	-10000	0	-10000	0	0
KPNA2	0.011	0.031	-10000	0	-0.75	1	1
XPO1	0.013	0	-10000	0	-10000	0	0
SFN	0.011	0.023	-10000	0	-0.4	2	2
MAP3K8	0.013	0.001	-10000	0	-10000	0	0
NFAT4/CK1 alpha	0.03	0.009	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.051	0.049	-10000	0	-0.4	1	1
CABIN1	-0.072	0.12	-10000	0	-0.35	53	53
CALM1	0.013	0.001	-10000	0	-10000	0	0
RAN	0.013	0	-10000	0	-10000	0	0
MAP3K1	0.012	0.016	-10000	0	-0.4	1	1
CAMK4	-0.011	0.095	-10000	0	-0.4	36	36
mol:Ca2+	0.001	0.002	-10000	0	-10000	0	0
MAPK3	0.012	0.016	-10000	0	-0.4	1	1
YWHAH	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.004	0.063	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
MAPK8	0.013	0.002	-10000	0	-10000	0	0
MAPK9	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
FKBP1A	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.06	0.026	-10000	0	-10000	0	0
PRKCH	0.012	0.016	-10000	0	-0.4	1	1
CABIN1/Cbp/p300	0.019	0.004	-10000	0	-10000	0	0
CASP3	0.013	0.001	-10000	0	-10000	0	0
PIM1	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.009	0.001	-10000	0	-10000	0	0
apoptosis	-0.004	0.017	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.036	0.017	-10000	0	-0.36	1	1
PRKCB	-0.084	0.17	-10000	0	-0.4	147	147
PRKCE	0.013	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.026	0.002	-10000	0	-10000	0	0
BAD/BCL-XL	0.018	0.011	-10000	0	-0.27	1	1
PRKCD	0.013	0	-10000	0	-10000	0	0
NUP214	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0.002	-10000	0	-10000	0	0
PRKCA	0.013	0	-10000	0	-10000	0	0
PRKCG	-0.25	0.36	-10000	0	-0.75	217	217
PRKCQ	0.006	0.051	-10000	0	-0.4	10	10
FKBP38/BCL2	0.003	0.064	-10000	0	-10000	0	0
EP300	0.013	0.002	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.013	0	-10000	0	-10000	0	0
NFATc/JNK1	0.051	0.026	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.018	0.01	-10000	0	-0.23	1	1
FKBP12/FK506	0.009	0	-10000	0	-10000	0	0
CSNK1A1	0.017	0.003	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.004	0.056	-10000	0	-10000	0	0
NFATc/ERK1	0.051	0.026	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.077	0.1	-10000	0	-0.46	11	11
NR4A1	0.045	0.085	-10000	0	-0.6	10	10
GSK3B	0.013	0.002	-10000	0	-10000	0	0
positive T cell selection	0.021	0.003	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.028	0.02	-10000	0	-10000	0	0
RCH1/ KPNB1	0.018	0.024	-10000	0	-0.57	1	1
YWHAQ	0.013	0	-10000	0	-10000	0	0
PRKACA	0.013	0.001	-10000	0	-10000	0	0
AKAP5	-0.008	0.09	-10000	0	-0.4	32	32
MEF2D	0.013	0.002	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.013	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.051	0.026	-10000	0	-10000	0	0
CREBBP	0.013	0.002	-10000	0	-10000	0	0
BCL2	-0.008	0.09	-10000	0	-0.4	32	32

×

Class I PI3K 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.031	0.017	-9999	-10000	0	0
DAPP1	-0.036	0.11	-9999	-0.39	23	23
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.049	0.14	-9999	-0.48	21	21
mol:DAG	-0.007	0.079	-9999	-0.25	10	10
HRAS	0.013	0.016	-9999	-0.39	1	1
RAP1A	0.013	0.001	-9999	-10000	0	0
ARF5/GDP	0.007	0.094	-9999	-0.4	20	20
PLCG2	-0.019	0.11	-9999	-0.4	49	49
PLCG1	0.013	0	-9999	-10000	0	0
ARF5	0.013	0	-9999	-10000	0	0
mol:GTP	0	0.017	-9999	-10000	0	0
ARF1/GTP	0.031	0.018	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
YES1	0.012	0.016	-9999	-0.4	1	1
RAP1A/GTP	0.022	0.018	-9999	-10000	0	0
ADAP1	-0.001	0.02	-9999	-10000	0	0
ARAP3	0	0.017	-9999	-10000	0	0
INPPL1	0.013	0	-9999	-10000	0	0
PREX1	0.011	0.023	-9999	-0.4	2	2
ARHGEF6	0.004	0.058	-9999	-0.4	13	13
ARHGEF7	0.013	0	-9999	-10000	0	0
ARF1	0.013	0	-9999	-10000	0	0
NRAS	0.012	0.023	-9999	-0.39	2	2
FYN	0.013	0	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
FGR	0.009	0.045	-9999	-0.47	5	5
mol:Ca2+	0.002	0.045	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	-0.028	0.12	-9999	-0.4	62	62
ZAP70	0.002	0.07	-9999	-0.45	14	14
mol:IP3	0	0.06	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
ARF1/GDP	0.007	0.094	-9999	-0.4	20	20
RhoA/GDP	0.028	0.045	-9999	-10000	0	0
PDK1/Src/Hsp90	0.026	0	-9999	-10000	0	0
BLNK	0.007	0.049	-9999	-0.4	9	9
actin cytoskeleton reorganization	0.031	0.066	-9999	-0.42	1	1
SRC	0.013	0	-9999	-10000	0	0
PLEKHA2	0.023	0.01	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
PTEN	0.008	0.022	-9999	-0.37	2	2
HSP90AA1	0.013	0	-9999	-10000	0	0
ARF6/GTP	0.031	0.017	-9999	-10000	0	0
RhoA/GTP	0.027	0.017	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.033	0.11	-9999	-0.44	9	9
BLK	-0.14	0.2	-9999	-0.4	236	236
PDPK1	0.013	0	-9999	-10000	0	0
CYTH1	0	0.017	-9999	-10000	0	0
HCK	0.003	0.062	-9999	-0.4	15	15
CYTH3	0	0.017	-9999	-10000	0	0
CYTH2	0	0.017	-9999	-10000	0	0
KRAS	0.013	0.016	-9999	-0.39	1	1
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0.019	0.084	-9999	-0.39	25	25
SGK1	-0.017	0.083	-9999	-0.42	25	25
INPP5D	0.012	0.016	-9999	-0.4	1	1
mol:GDP	-0.001	0.097	-9999	-0.42	20	20
SOS1	0.013	0	-9999	-10000	0	0
SYK	0.013	0	-9999	-10000	0	0
ARF6/GDP	0.027	0.045	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0.018	-9999	-10000	0	0
ARAP3/RAP1A/GTP	0.022	0.018	-9999	-10000	0	0
VAV1	-0.004	0.081	-9999	-0.4	26	26
mol:PI-3-4-P2	0.019	0.011	-9999	-10000	0	0
RAS family/GTP/PI3K Class I	0.027	0.016	-9999	-10000	0	0
PLEKHA1	0.023	0.01	-9999	-10000	0	0
Rac1/GDP	0.007	0.094	-9999	-0.4	20	20
LAT	0.009	0.049	-9999	-0.57	4	4
Rac1/GTP	-0.005	0.12	-9999	-0.5	21	21
ITK	-0.008	0.036	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.015	0.1	-9999	-0.35	11	11
LCK	0.001	0.089	-9999	-0.68	10	10
BTK	-0.019	0.053	-9999	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.031	0.018	-9999	-0.36	1	1
STMN1	0.023	0.012	-9999	-10000	0	0
Aurora B/RasGAP/Survivin	0.034	0.029	-9999	-0.47	2	2
Chromosomal passenger complex/Cul3 protein complex	0.007	0.068	-9999	-0.42	1	1
BIRC5	0.013	0.043	-9999	-0.74	2	2
DES	-0.36	0.24	-9999	-0.52	427	427
Aurora C/Aurora B/INCENP	0.032	0.019	-9999	-10000	0	0
Aurora B/TACC1	0.022	0.014	-9999	-10000	0	0
Aurora B/PP2A	0.025	0.004	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.015	0.001	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0	0	-9999	-10000	0	0
NDC80	0.023	0.003	-9999	-10000	0	0
Cul3 protein complex	-0.01	0.089	-9999	-0.49	3	3
KIF2C	0.026	0.006	-9999	-10000	0	0
PEBP1	0.014	0	-9999	-10000	0	0
KIF20A	0.012	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.025	0.004	-9999	-10000	0	0
SEPT1	0.008	0.043	-9999	-0.4	7	7
SMC2	0.012	0.016	-9999	-0.4	1	1
SMC4	0.011	0.023	-9999	-0.4	2	2
NSUN2/NPM1/Nucleolin	0.01	0.016	-9999	-10000	0	0
PSMA3	0.013	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.001	-9999	-10000	0	0
H3F3B	0.018	0.002	-9999	-10000	0	0
AURKB	0.021	0.006	-9999	-10000	0	0
AURKC	0.009	0.033	-9999	-0.4	4	4
CDCA8	0.015	0.001	-9999	-10000	0	0
cytokinesis	0.012	0.026	-9999	-10000	0	0
Aurora B/Septin1	0.041	0.026	-9999	-10000	0	0
AURKA	0.012	0.001	-9999	-10000	0	0
INCENP	0.015	0.001	-9999	-10000	0	0
KLHL13	-0.046	0.15	-9999	-0.41	87	87
BUB1	0.012	0	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	0.032	0.039	-9999	-0.44	4	4
EVI5	0.014	0.001	-9999	-10000	0	0
RhoA/GTP	0.012	0.025	-9999	-0.33	1	1
SGOL1	0.01	0.043	-9999	-0.75	2	2
CENPA	0.03	0.009	-9999	-10000	0	0
NCAPG	0.012	0.001	-9999	-10000	0	0
Aurora B/HC8 Proteasome	0.025	0.004	-9999	-10000	0	0
NCAPD2	0.013	0	-9999	-10000	0	0
Aurora B/PP1-gamma	0.025	0.004	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
NCAPH	0.013	0	-9999	-10000	0	0
NPM1	0.006	0.009	-9999	-10000	0	0
RASA1	0.013	0.001	-9999	-10000	0	0
KLHL9	0.013	0	-9999	-10000	0	0
mitotic prometaphase	0.001	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.004	-9999	-10000	0	0
PPP1CC	0.013	0	-9999	-10000	0	0
Centraspindlin	0.048	0.02	-9999	-0.36	1	1
RhoA/GDP	0.009	0	-9999	-10000	0	0
NSUN2	0.006	0.009	-9999	-10000	0	0
MYLK	-0.036	0.11	-9999	-0.26	118	118
KIF23	0.013	0.03	-9999	-0.74	1	1
VIM	0.023	0.003	-9999	-10000	0	0
RACGAP1	0.014	0.001	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.006	0.009	-9999	-10000	0	0
Chromosomal passenger complex	0.038	0.011	-9999	-10000	0	0
Chromosomal passenger complex/EVI5	0.075	0.039	-9999	-0.39	2	2
TACC1	0.011	0.023	-9999	-0.4	2	2
PPP2R5D	0.013	0	-9999	-10000	0	0
CUL3	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.013	-10000	0	-10000	0	0
RAS family/GTP	0.016	0.074	-10000	0	-10000	0	0
NFATC4	0.015	0.068	-10000	0	-0.37	2	2
ERBB2IP	0.007	0.045	-10000	0	-0.39	8	8
HSP90 (dimer)	0.013	0	-10000	0	-10000	0	0
mammary gland morphogenesis	0.005	0.084	-10000	0	-0.5	2	2
JUN	0.032	0.07	-10000	0	-0.29	11	11
HRAS	0.012	0.016	-10000	0	-0.39	1	1
DOCK7	0.009	0.081	-10000	0	-0.48	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.006	0.091	-10000	0	-0.46	11	11
AKT1	0.01	0.002	-10000	0	-10000	0	0
BAD	0.015	0.01	-10000	0	-10000	0	0
MAPK10	0.007	0.063	-10000	0	-0.31	2	2
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.006	0.09	-10000	0	-0.55	2	2
RAF1	0.024	0.08	-10000	0	-0.36	1	1
ErbB2/ErbB3/neuregulin 2	-0.025	0.098	-10000	0	-0.47	12	12
STAT3	0.019	0.005	-10000	0	-10000	0	0
cell migration	0.011	0.067	0.16	4	-0.27	2	6
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	0.009	0.21	-10000	0	-0.6	57	57
FOS	0.025	0.14	-10000	0	-0.4	28	28
NRAS	0.011	0.023	-10000	0	-0.39	2	2
mol:Ca2+	0.005	0.084	-10000	0	-0.5	2	2
MAPK3	0.014	0.17	-10000	0	-0.47	56	56
MAPK1	0.015	0.16	-10000	0	-0.46	56	56
JAK2	0.008	0.082	-10000	0	-0.48	2	2
NF2	-0.001	0.003	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.002	0.078	-10000	0	-0.34	2	2
NRG1	-0.035	0.13	-10000	0	-0.4	73	73
GRB2/SOS1	0.019	0.001	-10000	0	-10000	0	0
MAPK8	0.009	0.087	-10000	0	-0.39	2	2
MAPK9	0.017	0.046	-10000	0	-10000	0	0
ERBB2	-0.006	0.086	0.33	8	-0.58	11	19
ERBB3	0.012	0.002	-10000	0	-10000	0	0
SHC1	0.013	0.001	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
apoptosis	-0.011	0.014	-10000	0	-10000	0	0
STAT3 (dimer)	0.018	0.005	-10000	0	-10000	0	0
RNF41	0.019	0.012	-10000	0	-10000	0	0
FRAP1	0.008	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.018	0.049	-10000	0	-0.33	2	2
ErbB2/ErbB2/HSP90 (dimer)	0.003	0.072	0.23	4	-0.5	11	15
CHRNA1	0.001	0.2	-10000	0	-0.62	57	57
myelination	0.015	0.067	-10000	0	-0.36	2	2
PPP3CB	0.009	0.076	-10000	0	-0.44	2	2
KRAS	0.012	0.016	-10000	0	-0.39	1	1
RAC1-CDC42/GDP	0.011	0.07	-10000	0	-0.3	1	1
NRG2	-0.049	0.14	-10000	0	-0.4	89	89
mol:GDP	-0.002	0.078	-10000	0	-0.34	2	2
SOS1	0.013	0.001	-10000	0	-10000	0	0
MAP2K2	0.026	0.088	-10000	0	-0.38	1	1
SRC	0.013	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.009	0.081	-10000	0	-0.48	2	2
MAP2K1	0.011	0.15	-10000	0	-0.55	18	18
heart morphogenesis	0.005	0.084	-10000	0	-0.5	2	2
RAS family/GDP	0.017	0.071	-10000	0	-10000	0	0
GRB2	0.013	0.001	-10000	0	-10000	0	0
PRKACA	-0.002	0.005	-10000	0	-10000	0	0
CHRNE	0.014	0.033	-10000	0	-0.21	11	11
HSP90AA1	0.013	0	-10000	0	-10000	0	0
activation of caspase activity	-0.01	0.002	-10000	0	-10000	0	0
nervous system development	0.005	0.084	-10000	0	-0.5	2	2
CDC42	0.011	0.023	-10000	0	-0.4	2	2

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.001	0.1	-9999	-0.37	40	40
PDGFB-D/PDGFRB/SLAP	0.009	0.068	-9999	-0.57	7	7
PDGFB-D/PDGFRB/APS/CBL	0.012	0.084	-9999	-0.49	17	17
AKT1	0.04	0.041	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.004	0.11	-9999	-0.39	40	40
PIK3CA	0.012	0.016	-9999	-0.4	1	1
FGR	-0.006	0.059	-9999	-0.42	11	11
mol:Ca2+	0.007	0.047	-9999	-0.33	5	5
MYC	0.012	0.081	-9999	-0.46	11	11
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	0.026	0.046	-9999	-0.4	7	7
LRP1/PDGFRB/PDGFB	0.019	0.056	-9999	-0.48	7	7
GRB10	0.013	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
GO:0007205	0.007	0.047	-9999	-0.34	5	5
PTEN	0.011	0.023	-9999	-0.4	2	2
GRB2	0.013	0	-9999	-10000	0	0
GRB7	-0.006	0.12	-9999	-0.75	15	15
PDGFB-D/PDGFRB/SHP2	0.012	0.062	-9999	-0.57	7	7
PDGFB-D/PDGFRB/GRB10	0.012	0.062	-9999	-0.57	7	7
cell cycle arrest	0.009	0.067	-9999	-0.56	7	7
HRAS	0.012	0.016	-9999	-0.4	1	1
HIF1A	0.043	0.037	-9999	-10000	0	0
GAB1	0	0.064	-9999	-0.4	5	5
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.004	0.066	-9999	-0.41	5	5
PDGFB-D/PDGFRB	0.02	0.056	-9999	-0.5	7	7
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.012	0.062	-9999	-0.57	7	7
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.017	0.097	-9999	-0.44	16	16
positive regulation of MAPKKK cascade	0.012	0.061	-9999	-0.56	7	7
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.007	0.047	-9999	-0.34	5	5
E5	0	0.001	-9999	-10000	0	0
CSK	0.012	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.002	0.11	-9999	-0.57	22	22
SHB	0.009	0.053	-9999	-0.75	3	3
BLK	-0.18	0.23	-9999	-0.47	241	241
PTPN2	0.013	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.012	0.062	-9999	-0.57	7	7
BCAR1	0.012	0.016	-9999	-0.4	1	1
VAV2	0.002	0.068	-9999	-0.39	5	5
CBL	0.013	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.012	0.062	-9999	-0.57	7	7
LCK	-0.007	0.058	-9999	-0.41	9	9
PDGFRB	0.004	0.081	-9999	-0.75	7	7
ACP1	0.013	0	-9999	-10000	0	0
HCK	-0.007	0.085	-9999	-0.44	22	22
ABL1	-0.006	0.063	-9999	-0.41	5	5
PDGFB-D/PDGFRB/CBL	-0.003	0.063	-9999	-0.37	5	5
PTPN1	0.013	0.002	-9999	-10000	0	0
SNX15	0.013	0	-9999	-10000	0	0
STAT3	0.013	0	-9999	-10000	0	0
STAT1	0.011	0.031	-9999	-0.75	1	1
cell proliferation	0.013	0.076	-9999	-0.42	11	11
SLA	0.009	0.04	-9999	-0.4	6	6
actin cytoskeleton reorganization	0.034	0.054	-9999	-0.38	8	8
SRC	-0.002	0.043	-9999	-0.39	7	7
PI3K	-0.005	0.039	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.007	0.095	-9999	-0.49	22	22
SH2B2	0	0.096	-9999	-0.75	10	10
PLCgamma1/SPHK1	-0.005	0.11	-9999	-0.4	40	40
LYN	-0.001	0.043	-9999	-0.39	7	7
LRP1	0.011	0.023	-9999	-0.4	2	2
SOS1	0.013	0	-9999	-10000	0	0
STAT5B	0.013	0	-9999	-10000	0	0
STAT5A	0.013	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0.033	0.047	-9999	-0.39	7	7
SPHK1	-0.036	0.19	-9999	-0.75	40	40
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.007	0.047	-9999	-0.34	5	5
PLCG1	0.007	0.048	-9999	-0.35	5	5
NHERF/PDGFRB	0.02	0.055	-9999	-0.48	7	7
YES1	-0.003	0.047	-9999	-0.4	8	8
cell migration	0.019	0.054	-9999	-0.48	7	7
SHC/Grb2/SOS1	0.034	0.046	-9999	-0.39	7	7
SLC9A3R2	0.012	0.016	-9999	-0.4	1	1
SLC9A3R1	0.013	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.026	0.052	-9999	-0.44	7	7
FYN	-0.001	0.043	-9999	-0.39	7	7
DOK1	0.022	0.049	-9999	-0.44	7	7
HRAS/GTP	0.009	0.011	-9999	-0.28	1	1
PDGFB	0.013	0	-9999	-10000	0	0
RAC1	0.012	0.072	-9999	-0.39	2	2
PRKCD	0.021	0.05	-9999	-0.45	7	7
FER	0.02	0.055	-9999	-0.45	8	8
MAPKKK cascade	-0.004	0.041	-9999	-0.39	7	7
RASA1	0.021	0.05	-9999	-0.45	7	7
NCK1	0.013	0	-9999	-10000	0	0
NCK2	0.013	0	-9999	-10000	0	0
p62DOK/Csk	0.028	0.046	-9999	-0.4	7	7
PDGFB-D/PDGFRB/SHB	0.009	0.074	-9999	-0.57	10	10
chemotaxis	-0.005	0.062	-9999	-0.36	7	7
STAT1-3-5/STAT1-3-5	-0.004	0.043	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.003	0.062	-9999	-0.58	7	7
PTPRJ	0.013	0	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.002	0.066	-10000	0	-0.37	6	6
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.002	0.033	-10000	0	-0.58	2	2
GNB1/GNG2	0.007	0.048	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0	-10000	0	-10000	0	0
Gs family/GTP	-0.004	0.05	-10000	0	-0.21	35	35
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	0.003	0.013	0.058	35	-10000	0	35
GNAL	-0.01	0.094	-10000	0	-0.4	35	35
GNG2	-0.004	0.081	-10000	0	-0.4	26	26
CRH	-0.002	0.043	-10000	0	-0.75	2	2
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0	-10000	0	-10000	0	0
MAPK11	0.006	0.019	-10000	0	-0.33	2	2

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.012	0	-9999	-10000	0	0
HDAC2	0.012	0	-9999	-10000	0	0
GNB1/GNG2	0.016	0.049	-9999	-10000	0	0
forebrain development	0.012	0.072	-9999	-0.48	5	5
GNAO1	-0.14	0.2	-9999	-0.39	234	234
SMO/beta Arrestin2	0.021	0.004	-9999	-10000	0	0
SMO	0.014	0.002	-9999	-10000	0	0
ARRB2	0.013	0.002	-9999	-10000	0	0
GLI3/SPOP	0.018	0.072	-9999	-10000	0	0
mol:GTP	0.001	0.001	-9999	-10000	0	0
GSK3B	0.013	0	-9999	-10000	0	0
GNAI2	0.013	0.001	-9999	-10000	0	0
SIN3/HDAC complex	0.032	0.002	-9999	-10000	0	0
GNAI1	-0.001	0.075	-9999	-0.4	22	22
XPO1	0.015	0.003	-9999	-10000	0	0
GLI1/Su(fu)	0.023	0.06	-9999	-0.46	3	3
SAP30	0.012	0	-9999	-10000	0	0
mol:GDP	0.014	0.002	-9999	-10000	0	0
MIM/GLI2A	0.014	0.042	-9999	-0.39	6	6
IFT88	0.013	0.001	-9999	-10000	0	0
GNAI3	0.013	0.001	-9999	-10000	0	0
GLI2	0.037	0.016	-9999	-10000	0	0
GLI3	0.012	0.075	-9999	-10000	0	0
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
SAP18	0.012	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.012	0.001	-9999	-10000	0	0
GNG2	-0.004	0.081	-9999	-0.4	26	26
Gi family/GTP	-0.056	0.12	-9999	-0.36	26	26
SIN3B	0.012	0	-9999	-10000	0	0
SIN3A	0.012	0	-9999	-10000	0	0
GLI3/Su(fu)	0.035	0.055	-9999	-10000	0	0
GLI2/Su(fu)	0.051	0.016	-9999	-10000	0	0
FOXA2	-0.016	0.12	-9999	-0.65	22	22
neural tube patterning	0.012	0.072	-9999	-0.48	5	5
SPOP	0.013	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.03	0.003	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CSNK1G2	0.012	0.016	-9999	-0.4	1	1
CSNK1G3	0.013	0	-9999	-10000	0	0
MTSS1	0.014	0.042	-9999	-0.39	6	6
embryonic limb morphogenesis	0.012	0.072	-9999	-0.48	5	5
SUFU	0.026	0.005	-9999	-10000	0	0
LGALS3	0.012	0.016	-9999	-0.4	1	1
catabolic process	0.041	0.066	-9999	-10000	0	0
GLI3A/CBP	0.019	0.022	-9999	-0.3	1	1
KIF3A	0.013	0.001	-9999	-10000	0	0
GLI1	0.012	0.074	-9999	-0.5	5	5
RAB23	0.011	0.023	-9999	-0.4	2	2
CSNK1A1	0.013	0	-9999	-10000	0	0
IFT172	0.013	0	-9999	-10000	0	0
RBBP7	0.012	0	-9999	-10000	0	0
Su(fu)/Galectin3	0.03	0.009	-9999	-10000	0	0
GNAZ	0.008	0.046	-9999	-0.39	8	8
RBBP4	0.012	0	-9999	-10000	0	0
CSNK1G1	0.012	0.016	-9999	-0.4	1	1
PIAS1	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GLI2/SPOP	0.041	0.015	-9999	-10000	0	0
STK36	0.015	0.003	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.051	0.13	-9999	-0.39	37	37
PTCH1	0.017	0.088	-9999	-0.92	3	3
MIM/GLI1	0.019	0.098	-9999	-0.51	10	10
CREBBP	0.019	0.022	-9999	-0.3	1	1
Su(fu)/SIN3/HDAC complex	0.042	0.002	-9999	-10000	0	0

×

Ceramide signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.019	0.012	-10000	0	-10000	0	0
MAP4K4	0.036	0.029	-10000	0	-10000	0	0
BAG4	0.012	0.001	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.012	0.03	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	0.005	0.057	-10000	0	-0.43	10	10
BAX	-0.003	0.014	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AKT1	0.017	0.006	-10000	0	-10000	0	0
BAD	-0.015	0.028	-10000	0	-10000	0	0
SMPD1	0.021	0.028	-10000	0	-0.23	5	5
RB1	-0.014	0.029	-10000	0	-10000	0	0
FADD/Caspase 8	0.044	0.028	-10000	0	-10000	0	0
MAP2K4	-0.009	0.031	-10000	0	-10000	0	0
NSMAF	0.013	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.008	0.027	-10000	0	-10000	0	0
EGF	-0.086	0.2	-10000	0	-0.45	131	131
mol:ceramide	-0.022	0.031	-10000	0	-10000	0	0
MADD	0.013	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.019	0	-10000	0	-10000	0	0
ASAH1	0.013	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.014	0.028	-10000	0	-10000	0	0
cell proliferation	-0.025	0.074	-10000	0	-10000	0	0
BID	0.024	0.028	-10000	0	-0.31	1	1
MAP3K1	-0.015	0.03	-10000	0	-0.2	1	1
EIF2A	-0.003	0.028	-10000	0	-10000	0	0
TRADD	0.013	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
MAPK3	0.001	0.026	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.001	0.026	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.012	0.029	-10000	0	-10000	0	0
FADD	0.036	0.029	-10000	0	-10000	0	0
KSR1	-0.014	0.029	-10000	0	-10000	0	0
MAPK8	-0.004	0.028	-10000	0	-10000	0	0
PRKRA	-0.014	0.029	-10000	0	-10000	0	0
PDGFA	0.013	0	-10000	0	-10000	0	0
TRAF2	0.012	0.016	-10000	0	-0.4	1	1
IGF1	-0.08	0.17	-10000	0	-0.4	142	142
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.022	0.031	-10000	0	-10000	0	0
CTSD	0.012	0.016	-10000	0	-0.4	1	1
regulation of nitric oxide biosynthetic process	0.019	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.026	0.079	-10000	0	-10000	0	0
PRKCD	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.019	0	-10000	0	-10000	0	0
RelA/NF kappa B1	0.019	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.013	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.032	0.03	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.024	0.022	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.019	0.011	-10000	0	-10000	0	0
MAP2K1	-0.002	0.026	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
CYCS	-0.001	0.036	0.14	26	-10000	0	26
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
NFKB1	0.013	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.019	0.001	-10000	0	-10000	0	0
EIF2AK2	-0.009	0.029	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	0.024	0.022	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.036	0.019	-10000	0	-10000	0	0
MAP2K2	-0.002	0.026	-10000	0	-10000	0	0
SMPD3	0.019	0.049	-10000	0	-0.28	14	14
TNF	0.009	0.036	-10000	0	-0.4	5	5
PKC zeta/PAR4	0.019	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.034	0.082	0.19	128	-10000	0	128
NF kappa B1/RelA/I kappa B alpha	0.037	0	-10000	0	-10000	0	0
AIFM1	0	0.037	0.14	27	-10000	0	27
BCL2	-0.008	0.09	-10000	0	-0.4	32	32

×

FoxO family signaling

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
G6PC	-0.056	0.32	-9999	-1.2	44	44
PLK1	0.049	0.13	-9999	-0.77	4	4
CDKN1B	0.083	0.077	-9999	-10000	0	0
FOXO3	0.046	0.14	-9999	-0.57	8	8
KAT2B	0.004	0.084	-9999	-0.39	27	27
FOXO1/SIRT1	-0.013	0.1	-9999	-0.37	44	44
CAT	0.05	0.12	-9999	-0.7	1	1
CTNNB1	0.012	0	-9999	-10000	0	0
AKT1	0.02	0.016	-9999	-10000	0	0
FOXO1	0.003	0.11	-9999	-0.4	44	44
MAPK10	0.007	0.069	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.069	0.05	-9999	-10000	0	0
response to oxidative stress	0.009	0.017	-9999	-10000	0	0
FOXO3A/SIRT1	0.035	0.11	-9999	-0.54	8	8
XPO1	0.013	0	-9999	-10000	0	0
EP300	0.01	0.015	-9999	-10000	0	0
BCL2L11	0.026	0.026	-9999	-10000	0	0
FOXO1/SKP2	0.008	0.1	-9999	-0.37	44	44
mol:GDP	0.008	0.017	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
GADD45A	0.079	0.058	-9999	-10000	0	0
YWHAQ	0.013	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.056	0.031	-9999	-10000	0	0
MST1	-0.099	0.28	-9999	-0.74	99	99
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.049	0.015	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
MAPK8	0.033	0.007	-9999	-10000	0	0
MAPK9	0.033	0.007	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
SIRT1	0.013	0.014	-9999	-10000	0	0
SOD2	0.084	0.087	-9999	-10000	0	0
RBL2	0.064	0.095	-9999	-10000	0	0
RAL/GDP	0.028	0.011	-9999	-10000	0	0
CHUK	0.022	0.008	-9999	-10000	0	0
Ran/GTP	0.013	0	-9999	-10000	0	0
CSNK1G2	0.012	0.016	-9999	-0.4	1	1
RAL/GTP	0.034	0.01	-9999	-10000	0	0
CSNK1G1	0.012	0.016	-9999	-0.4	1	1
FASLG	-0.041	0.3	-9999	-1.3	34	34
SKP2	0.013	0	-9999	-10000	0	0
USP7	0.014	0	-9999	-10000	0	0
IKBKB	0.022	0.008	-9999	-10000	0	0
CCNB1	0.05	0.12	-9999	-0.7	1	1
FOXO1-3a-4/beta catenin	0.091	0.093	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.008	0.1	-9999	-0.37	44	44
CSNK1A1	0.013	0	-9999	-10000	0	0
SGK1	0.006	0.081	-9999	-0.39	25	25
CSNK1G3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.023	0	-9999	-10000	0	0
ZFAND5	0.071	0.045	-9999	-10000	0	0
SFN	0.011	0.023	-9999	-0.4	2	2
CDK2	0.007	0.023	-9999	-10000	0	0
FOXO3A/14-3-3	0.053	0.029	-9999	-10000	0	0
CREBBP	0.007	0.023	-9999	-10000	0	0
FBXO32	0.049	0.13	-9999	-1.4	1	1
BCL6	0.064	0.095	-9999	-10000	0	0
RALB	0.014	0	-9999	-10000	0	0
RALA	0.014	0	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0.017	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.01	0.033	-9999	-0.4	4	4
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.011	0.028	-9999	-0.4	3	3
RAC1-CDC42/GTP/PAK family	0.021	0.011	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.012	0.016	-9999	-0.4	1	1
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
MAP3K12	0.013	0	-9999	-10000	0	0
FGR	0.009	0.045	-9999	-0.47	5	5
p38 alpha/TAB1	-0.032	0.046	-9999	-0.3	2	2
PRKG1	-0.003	0.078	-9999	-0.4	24	24
DUSP8	0.011	0.023	-9999	-0.4	2	2
PGK/cGMP/p38 alpha	-0.035	0.056	-9999	-0.31	7	7
apoptosis	-0.031	0.044	-9999	-0.28	2	2
RAL/GTP	0.017	0	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
DUSP1	0.011	0.028	-9999	-0.4	3	3
PAK1	0.013	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.032	0.009	-9999	-10000	0	0
TRAF6	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.012	0.016	-9999	-0.4	1	1
RAC1-CDC42/GTP	0.016	0.014	-9999	-10000	0	0
MAPK11	-0.017	0.092	-9999	-0.33	9	9
BLK	-0.14	0.2	-9999	-0.4	236	236
HCK	0.003	0.062	-9999	-0.4	15	15
MAP2K3	0.013	0	-9999	-10000	0	0
DUSP16	0.013	0	-9999	-10000	0	0
DUSP10	0.008	0.061	-9999	-0.75	4	4
TRAF6/MEKK3	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.004	0.072	-9999	-0.32	2	2
positive regulation of innate immune response	-0.012	0.098	-9999	-0.35	9	9
LCK	0.001	0.089	-9999	-0.68	10	10
p38alpha-beta/MKP7	-0.006	0.096	-9999	-0.44	2	2
p38alpha-beta/MKP5	-0.009	0.1	-9999	-0.45	4	4
PGK/cGMP	-0.002	0.055	-9999	-0.28	24	24
PAK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.007	0.097	-9999	-0.44	2	2
CDC42	0.011	0.023	-9999	-0.4	2	2
RALB	0.013	0	-9999	-10000	0	0
RALA	0.013	0	-9999	-10000	0	0
PAK3	0.008	0.006	-9999	-10000	0	0

×

TCGA08_rtk_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
PDGFRA	0.003	0.062	-10000	0	-0.4	15	15
HRAS	0.012	0.016	-10000	0	-0.4	1	1
EGFR	0.011	0.023	-10000	0	-0.4	2	2
AKT	0.029	0.038	-10000	0	-0.34	2	2
FOXO3	0.013	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
FOXO1	0.012	0.016	-10000	0	-0.4	1	1
AKT3	0.007	0.049	-10000	0	-0.4	9	9
FOXO4	0.013	0	-10000	0	-10000	0	0
MET	0.005	0.075	-10000	0	-0.75	6	6
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
PIK3CB	0.011	0.031	-10000	0	-0.75	1	1
NRAS	0.011	0.023	-10000	0	-0.4	2	2
PIK3CG	-0.053	0.15	-10000	0	-0.4	100	100
PIK3R3	0.013	0	-10000	0	-10000	0	0
PIK3R2	0.013	0	-10000	0	-10000	0	0
NF1	0.013	0	-10000	0	-10000	0	0
RAS	0.015	0.036	-10000	0	-0.26	2	2
ERBB2	-0.001	0.1	-10000	0	-0.75	11	11
proliferation/survival/translation	-0.018	0.041	0.2	9	-10000	0	9
PI3K	0.018	0.043	-10000	0	-0.21	13	13
PIK3R1	0.013	0	-10000	0	-10000	0	0
KRAS	0.012	0.016	-10000	0	-0.4	1	1
FOXO	0.039	0.019	-10000	0	-10000	0	0
AKT2	0.013	0	-10000	0	-10000	0	0
PTEN	0.011	0.023	-10000	0	-0.4	2	2

×

EPO signaling pathway

Figure S93. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S93. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.044	0.085	-9999	-0.53	1	1
CRKL	0.028	0.051	-9999	-0.36	8	8
mol:DAG	0.033	0.052	-9999	-0.44	1	1
HRAS	0.045	0.045	-9999	-10000	0	0
MAPK8	0.022	0.051	-9999	-0.42	8	8
RAP1A	0.028	0.051	-9999	-0.36	8	8
GAB1	0.028	0.051	-9999	-0.36	8	8
MAPK14	0.022	0.051	-9999	-0.42	8	8
EPO	0.001	0.08	-9999	-0.75	7	7
PLCG1	0.033	0.052	-9999	-0.45	1	1
EPOR/TRPC2/IP3 Receptors	0.013	0.031	-9999	-0.74	1	1
RAPGEF1	0.012	0.016	-9999	-0.4	1	1
EPO/EPOR (dimer)/SOCS3	0.017	0.064	-9999	-0.48	10	10
GAB1/SHC/GRB2/SOS1	0.012	0.046	-9999	-0.4	1	1
EPO/EPOR (dimer)	0.011	0.066	-9999	-0.57	8	8
IRS2	0.028	0.051	-9999	-0.36	8	8
STAT1	0.036	0.07	-9999	-0.54	1	1
STAT5B	0.035	0.061	-9999	-0.5	1	1
cell proliferation	0.027	0.048	-9999	-0.39	8	8
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.006	0.035	-9999	-10000	0	0
TEC	0.028	0.054	-9999	-0.36	9	9
SOCS3	0.01	0.043	-9999	-0.75	2	2
STAT1 (dimer)	0.036	0.069	-9999	-0.53	1	1
JAK2	0.011	0.029	-9999	-0.4	3	3
PIK3R1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.038	0.057	-9999	-0.38	8	8
EPO/EPOR	0.011	0.066	-9999	-0.57	8	8
LYN	0.013	0.004	-9999	-10000	0	0
TEC/VAV2	0.033	0.058	-9999	-0.41	2	2
elevation of cytosolic calcium ion concentration	0.013	0.031	-9999	-0.74	1	1
SHC1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.024	0.058	-9999	-0.47	8	8
mol:IP3	0.033	0.052	-9999	-0.44	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.039	0.049	-9999	-0.41	1	1
SH2B3	0.013	0.006	-9999	-10000	0	0
NFKB1	0.022	0.051	-9999	-0.42	8	8
EPO/EPOR (dimer)/JAK2/SOCS3	-0.004	0.033	-9999	-0.25	7	7
PTPN6	0.023	0.053	-9999	-0.38	8	8
TEC/VAV2/GRB2	0.038	0.056	-9999	-0.43	1	1
EPOR	0.013	0.031	-9999	-0.74	1	1
INPP5D	0.012	0.016	-9999	-0.4	1	1
mol:GDP	-0.007	0.038	-9999	-0.4	1	1
SOS1	0.013	0	-9999	-10000	0	0
PLCG2	-0.019	0.11	-9999	-0.4	49	49
CRKL/CBL/C3G	0.041	0.05	-9999	-0.42	1	1
VAV2	0.026	0.056	-9999	-0.36	8	8
CBL	0.028	0.051	-9999	-0.36	8	8
SHC/Grb2/SOS1	-0.007	0.04	-9999	-0.42	1	1
STAT5A	0.035	0.061	-9999	-0.5	1	1
GRB2	0.013	0	-9999	-10000	0	0
STAT5 (dimer)	0.045	0.083	-9999	-0.62	1	1
LYN/PLCgamma2	-0.003	0.078	-9999	-0.27	49	49
PTPN11	0.013	0	-9999	-10000	0	0
BTK	0.006	0.083	-9999	-0.36	10	10
BCL2	0.019	0.19	-9999	-0.78	32	32

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.013	0	-9999	-10000	0	0
PTK2	0.013	0	-9999	-10000	0	0
CRKL	-0.024	0.086	-9999	-10000	0	0
GRB2/SOS1/SHC	0.026	0	-9999	-10000	0	0
HRAS	0.012	0.016	-9999	-0.4	1	1
IRS1/Crk	-0.024	0.087	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/PTP1B	-0.028	0.096	-9999	-10000	0	0
AKT1	-0.005	0.075	-9999	-10000	0	0
BAD	0	0.072	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	-0.024	0.086	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.024	0.087	-9999	-10000	0	0
RAF1	0.006	0.071	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.014	0.084	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.033	0.095	-9999	-10000	0	0
PIK3CA	0.012	0.016	-9999	-0.4	1	1
RPS6KB1	-0.005	0.076	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.003	0.064	-9999	-10000	0	0
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0.019	0	-9999	-10000	0	0
HRAS/GTP	-0.033	0.06	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.005	0.077	-9999	-10000	0	0
IGF-1R heterotetramer	0	0.024	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.022	0.088	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.008	0.08	-9999	-10000	0	0
IGF1R	0	0.024	-9999	-10000	0	0
IGF1	-0.082	0.18	-9999	-0.41	142	142
IRS2/Crk	-0.016	0.082	-9999	-10000	0	0
PI3K	-0.014	0.085	-9999	-0.36	1	1
apoptosis	-0.007	0.066	-9999	-10000	0	0
HRAS/GDP	0.009	0.011	-9999	-0.28	1	1
PRKCD	-0.037	0.13	-9999	-10000	0	0
RAF1/14-3-3 E	0.012	0.065	-9999	-10000	0	0
BAD/14-3-3	0.007	0.069	-9999	-10000	0	0
PRKCZ	-0.005	0.075	-9999	-10000	0	0
Crk/p130 Cas/Paxillin/FAK1	-0.026	0.047	-9999	-10000	0	0
PTPN1	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.045	0.14	-9999	-0.3	142	142
BCAR1	0.012	0.016	-9999	-0.4	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.014	0.084	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
IRS1/NCK2	-0.023	0.087	-9999	-10000	0	0
GRB10	0.013	0	-9999	-10000	0	0
PTPN11	-0.024	0.086	-9999	-10000	0	0
IRS1	-0.034	0.094	-9999	-10000	0	0
IRS2	-0.024	0.086	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.051	0.13	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
PDPK1	-0.011	0.079	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
PRKD1	-0.04	0.14	-9999	-0.46	8	8
SHC1	0.013	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.029	0	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.02	0	-9999	-10000	0	0
mol:DAG	0.018	0.083	-9999	-0.44	20	20
VEGFR1 homodimer/NRP1/VEGFR 121	0.025	0.027	-9999	-0.45	2	2
CaM/Ca2+	0.024	0.079	-9999	-0.41	20	20
HIF1A	0.02	0	-9999	-10000	0	0
GAB1	0.013	0	-9999	-10000	0	0
AKT1	0.035	0.068	-9999	-10000	0	0
PLCG1	0.018	0.083	-9999	-0.44	20	20
NOS3	0.036	0.072	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
mol:NO	0.036	0.07	-9999	-10000	0	0
FLT1	0.026	0	-9999	-10000	0	0
PGF	-0.012	0.14	-9999	-0.75	20	20
VEGFR1 homodimer/NRP2/VEGFR121	0.032	0.031	-9999	-0.44	2	2
CALM1	0.013	0	-9999	-10000	0	0
PIK3CA	0.012	0.016	-9999	-0.4	1	1
eNOS/Hsp90	0.042	0.069	-9999	-10000	0	0
endothelial cell proliferation	-0.011	0.098	-9999	-0.5	1	1
mol:Ca2+	0.018	0.082	-9999	-0.43	20	20
MAPK3	0.026	0.074	-9999	-10000	0	0
MAPK1	0.026	0.074	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
PLGF homodimer	-0.012	0.13	-9999	-0.75	20	20
PRKACA	0.013	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0.004	0.058	-9999	-0.4	13	13
VEGFA homodimer	0.01	0.043	-9999	-0.75	2	2
VEGFR1 homodimer/VEGFA homodimer	0.027	0.029	-9999	-0.49	2	2
platelet activating factor biosynthetic process	0.03	0.072	-9999	-10000	0	0
PI3K	0.026	0.08	-9999	-0.41	20	20
PRKCA	0.022	0.077	-9999	-0.4	20	20
PRKCB	-0.026	0.11	-9999	-0.41	20	20
VEGFR1 homodimer/PLGF homodimer	0.012	0.091	-9999	-0.49	20	20
VEGFA	0.01	0.043	-9999	-0.75	2	2
VEGFB	0.013	0	-9999	-10000	0	0
mol:IP3	0.018	0.083	-9999	-0.44	20	20
RASA1	0.033	0	-9999	-10000	0	0
NRP2	0.011	0.028	-9999	-0.4	3	3
VEGFR1 homodimer	0.026	0	-9999	-10000	0	0
VEGFB homodimer	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.041	0.069	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.025	0.079	-9999	-0.41	20	20
mol:L-citrulline	0.036	0.07	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.034	0.044	-9999	-0.41	2	2
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.033	0.027	-9999	-0.44	2	2
CD2AP	0	0.07	-9999	-0.4	19	19
PI3K/GAB1	0.031	0.076	-9999	-10000	0	0
PDPK1	0.027	0.075	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.033	0.027	-9999	-0.44	2	2
mol:NADP	0.036	0.07	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.032	0.043	-9999	-0.41	2	2
VEGFR1 homodimer/NRP2	0.028	0.017	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.009	0.036	0.39	5	-10000	0	5
PI3K Class IB/PDE3B	0.009	0.036	-10000	0	-0.39	5	5
PDE3B	0.009	0.036	-10000	0	-0.4	5	5

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.13	0.26	-9999	-0.99	2	2
PLK1	0.052	0.06	-9999	-0.55	2	2
BIRC5	0.052	0.057	-9999	-0.56	2	2
HSPA1B	0.1	0.29	-9999	-0.98	5	5
MAP2K1	0.035	0.03	-9999	-10000	0	0
BRCA2	0.12	0.27	-9999	-1.1	1	1
FOXM1	0.12	0.28	-9999	-1.2	2	2
XRCC1	0.13	0.26	-9999	-1.1	1	1
FOXM1B/p19	-0.12	0.21	-9999	-1	9	9
Cyclin D1/CDK4	0.12	0.25	-9999	-0.92	3	3
CDC2	0.12	0.27	-9999	-1	2	2
TGFA	0.12	0.25	-9999	-1	2	2
SKP2	0.13	0.26	-9999	-0.99	2	2
CCNE1	0.011	0.069	-9999	-0.75	5	5
CKS1B	0.12	0.26	-9999	-0.99	2	2
RB1	-0.024	0.071	-9999	-10000	0	0
FOXM1C/SP1	0.12	0.26	-9999	-1.1	2	2
AURKB	0.054	0.045	-9999	-10000	0	0
CENPF	0.13	0.26	-9999	-0.99	2	2
CDK4	0.02	0.033	-9999	-0.75	1	1
MYC	0.12	0.25	-9999	-0.92	1	1
CHEK2	0.035	0.03	-9999	-10000	0	0
ONECUT1	0.12	0.26	-9999	-1	2	2
CDKN2A	-0.14	0.3	-9999	-0.76	120	120
LAMA4	0.13	0.26	-9999	-0.99	2	2
FOXM1B/HNF6	0.12	0.27	-9999	-1.2	2	2
FOS	0.11	0.29	-9999	-1	9	9
SP1	0.013	0.005	-9999	-10000	0	0
CDC25B	0.11	0.29	-9999	-1.1	3	3
response to radiation	0.02	0.027	-9999	-10000	0	0
CENPB	0.13	0.26	-9999	-0.99	2	2
CENPA	0.13	0.26	-9999	-0.99	2	2
NEK2	0.13	0.26	-9999	-0.99	2	2
HIST1H2BA	0.12	0.26	-9999	-0.99	2	2
CCNA2	0.017	0.007	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	0.12	0.27	-9999	-1.1	2	2
CCNB2	0.13	0.26	-9999	-0.99	2	2
CCNB1	0.13	0.27	-9999	-1	2	2
ETV5	0.12	0.26	-9999	-1.1	1	1
ESR1	0.058	0.41	-9999	-1.2	34	34
CCND1	0.12	0.26	-9999	-0.95	3	3
GSK3A	0.033	0.026	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.043	0.057	-9999	-0.48	5	5
CDK2	0.017	0.007	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.023	0.031	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.056	0.16	-9999	-1.1	2	2
GAS1	0.012	0.48	-9999	-1.1	50	50
MMP2	0.12	0.27	-9999	-1.2	3	3
RB1/FOXM1C	0.13	0.26	-9999	-1	2	2
CREBBP	0.013	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.023	0.045	-9999	-10000	0	0
HDAC3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0.015	0.004	-9999	-10000	0	0
GATA1/HDAC5	0.015	0.012	-9999	-10000	0	0
GATA2/HDAC5	0.013	0.039	-9999	-10000	0	0
HDAC5/BCL6/BCoR	0.025	0.01	-9999	-10000	0	0
HDAC9	-0.046	0.14	-9999	-0.4	90	90
Glucocorticoid receptor/Hsp90/HDAC6	0.008	0.063	-9999	-10000	0	0
HDAC4/ANKRA2	0.019	0	-9999	-10000	0	0
HDAC5/YWHAB	0.018	0.011	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0.014	-9999	-10000	0	0
GATA2	0.005	0.054	-9999	-0.4	11	11
HDAC4/RFXANK	0.018	0.024	-9999	-0.57	1	1
BCOR	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.012	0.016	-9999	-0.4	1	1
HDAC5	0.012	0.016	-9999	-0.4	1	1
GNB1/GNG2	0.007	0.057	-9999	-10000	0	0
Histones	0.006	0.069	-9999	-0.36	1	1
ADRBK1	0.013	0	-9999	-10000	0	0
HDAC4	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.018	0.011	-9999	-10000	0	0
HDAC4/Ubc9	0.019	0	-9999	-10000	0	0
HDAC7	0.013	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.018	0.011	-9999	-0.27	1	1
TUBA1B	0.013	0	-9999	-10000	0	0
HDAC6	0.013	0	-9999	-10000	0	0
HDAC5/RFXANK	0.017	0.026	-9999	-0.57	1	1
CAMK4	-0.011	0.095	-9999	-0.4	36	36
Tubulin/HDAC6	0.02	0.054	-9999	-0.49	7	7
SUMO1	0.011	0.023	-9999	-0.4	2	2
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
GATA1	0.008	0.006	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
NR3C1	-0.018	0.11	-9999	-0.4	46	46
SUMO1/HDAC4	0.026	0.018	-9999	-0.26	2	2
SRF	0.013	0	-9999	-10000	0	0
HDAC4/YWHAB	0.019	0	-9999	-10000	0	0
Tubulin	0.012	0.062	-9999	-0.57	7	7
HDAC4/14-3-3 E	0.019	0	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
RANGAP1	0.011	0.031	-9999	-0.75	1	1
BCL6/BCoR	0.019	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.025	0.01	-9999	-10000	0	0
HDAC4/SRF	0.011	0.057	-9999	-10000	0	0
HDAC4/ER alpha	-0.009	0.084	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.006	0.069	-9999	-0.36	1	1
cell motility	0.02	0.054	-9999	-0.49	7	7
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
HDAC7/HDAC3	0.019	0	-9999	-10000	0	0
BCL6	0.013	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.013	0	-9999	-10000	0	0
Hsp90/HDAC6	0.019	0	-9999	-10000	0	0
ESR1	-0.027	0.12	-9999	-0.4	59	59
HDAC6/HDAC11	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.029	0.012	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
MEF2C	-0.002	0.075	-9999	-0.4	22	22
RAN	0.013	0	-9999	-10000	0	0
HDAC4/MEF2C	0.03	0.039	-9999	-10000	0	0
GNG2	-0.004	0.081	-9999	-0.4	26	26
NCOR2	0.012	0.016	-9999	-0.4	1	1
TUBB2A	0.004	0.081	-9999	-0.75	7	7
HDAC11	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
ANKRA2	0.013	0	-9999	-10000	0	0
RFXANK	0.011	0.031	-9999	-0.75	1	1
nuclear import	-0.026	0.01	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.042	0.045	-10000	0	-10000	0	0
UGCG	0.02	0.043	-10000	0	-0.67	2	2
AKT1/mTOR/p70S6K/Hsp90/TERT	0.037	0.091	-10000	0	-0.36	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.02	0.043	-10000	0	-0.66	2	2
mol:DAG	0.001	0.017	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.025	0.082	-10000	0	-0.45	6	6
FRAP1	0.044	0.12	-10000	0	-0.39	32	32
FOXO3	0.055	0.08	-10000	0	-0.42	1	1
AKT1	0.051	0.084	-10000	0	-0.39	3	3
GAB2	0.013	0.002	-10000	0	-10000	0	0
SMPD1	0.017	0.06	-10000	0	-0.62	5	5
SGMS1	0.022	0.018	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.011	-10000	0	-10000	0	0
CALM1	0.013	0	-10000	0	-10000	0	0
cell proliferation	0.036	0.049	-10000	0	-0.38	2	2
EIF3A	0.013	0	-10000	0	-10000	0	0
PI3K	0.022	0.013	-10000	0	-10000	0	0
RPS6KB1	0.022	0.035	-10000	0	-0.73	1	1
mol:sphingomyelin	0.001	0.017	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-10000	0	0
JAK3	0.014	0.031	-10000	0	-0.75	1	1
PIK3R1	0.015	0.002	-10000	0	-10000	0	0
JAK1	0.014	0.016	-10000	0	-0.39	1	1
NFKB1	0.013	0	-10000	0	-10000	0	0
MYC	0.051	0.095	-10000	0	-0.45	11	11
MYB	0.022	0.073	-10000	0	-1.2	2	2
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.049	0.068	-10000	0	-0.39	3	3
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.034	0.037	-10000	0	-0.52	2	2
mol:PI-3-4-5-P3	0.049	0.067	-10000	0	-0.38	3	3
Rac1/GDP	0.023	0.011	-10000	0	-10000	0	0
T cell proliferation	0.052	0.063	-10000	0	-0.36	3	3
SHC1	0.013	0.002	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.004	-10000	0	-0.065	2	2
PRKCZ	0.053	0.065	-10000	0	-0.37	3	3
NF kappa B1 p50/RelA	0.051	0.1	-10000	0	-0.44	6	6
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.036	0.049	-10000	0	-0.37	2	2
HSP90AA1	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL2RA	0.004	0.058	-10000	0	-0.39	13	13
IL2RB	0.004	0.067	-10000	0	-0.39	17	17
TERT	-0.056	0.22	-10000	0	-0.74	57	57
E2F1	0.021	0.043	-10000	0	-0.42	3	3
SOS1	0.013	0.002	-10000	0	-10000	0	0
RPS6	0.011	0.031	-10000	0	-0.75	1	1
mol:cAMP	-0.002	0.002	0.031	2	-10000	0	2
PTPN11	0.013	0.003	-10000	0	-10000	0	0
IL2RG	0.013	0.028	-10000	0	-0.4	3	3
actin cytoskeleton organization	0.052	0.063	-10000	0	-0.36	3	3
GRB2	0.013	0.002	-10000	0	-10000	0	0
IL2	0.006	0.006	-10000	0	-10000	0	0
PIK3CA	0.014	0.016	-10000	0	-0.39	1	1
Rac1/GTP	0.032	0.012	-10000	0	-10000	0	0
LCK	0.004	0.089	-10000	0	-0.68	10	10
BCL2	0.024	0.2	-10000	0	-0.82	32	32

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.024	0.026	-9999	-10000	0	0
epithelial cell differentiation	0.027	0	-9999	-10000	0	0
CYFIP2	0.012	0.016	-9999	-0.4	1	1
ENAH	0.049	0.018	-9999	-10000	0	0
EGFR	0.011	0.023	-9999	-0.4	2	2
EPHA2	0.01	0.043	-9999	-0.75	2	2
MYO6	0.031	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	0.025	0.01	-9999	-10000	0	0
AQP5	-0.015	0.11	-9999	-10000	0	0
CTNND1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.03	0.008	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.022	0.038	-9999	-10000	0	0
EGF	-0.086	0.2	-9999	-0.45	131	131
NCKAP1	0.013	0	-9999	-10000	0	0
AQP3	0.028	0.062	-9999	-0.38	2	2
cortical microtubule organization	0.027	0	-9999	-10000	0	0
GO:0000145	0.028	0.007	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.03	0	-9999	-10000	0	0
MLLT4	0.012	0.016	-9999	-0.4	1	1
ARF6/GDP	-0.001	0.02	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.031	0.028	-9999	-0.45	2	2
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.039	0.002	-9999	-10000	0	0
PVRL2	0.013	0	-9999	-10000	0	0
ZYX	0.031	0	-9999	-10000	0	0
ARF6/GTP	0.034	0.027	-9999	-0.41	2	2
CDH1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.04	0.086	-9999	-0.38	20	20
RhoA/GDP	0	0	-9999	-10000	0	0
actin cytoskeleton organization	0.034	0	-9999	-10000	0	0
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
GIT1	0.012	0.016	-9999	-0.4	1	1
IGF1R	0.013	0	-9999	-10000	0	0
IGF1	-0.08	0.17	-9999	-0.4	142	142
DIAPH1	-0.001	0.021	-9999	-0.52	1	1
Wnt receptor signaling pathway	-0.027	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.001	0.019	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
VCL	0.035	0	-9999	-10000	0	0
EFNA1	0.013	0	-9999	-10000	0	0
LPP	0.034	0.008	-9999	-10000	0	0
Ephrin A1/EPHA2	-0.001	0.022	-9999	-0.38	2	2
SEC6/SEC8	0	0.005	-9999	-10000	0	0
MGAT3	0.023	0.039	-9999	-10000	0	0
HGF/MET	-0.008	0.049	-9999	-0.41	7	7
HGF	0.002	0.067	-9999	-0.42	15	15
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.024	0.026	-9999	-10000	0	0
actin cable formation	0.063	0.016	-9999	-10000	0	0
KIAA1543	0.034	0.011	-9999	-10000	0	0
KIFC3	0.018	0.073	-9999	-0.4	18	18
NCK1	0.013	0	-9999	-10000	0	0
EXOC3	0.013	0	-9999	-10000	0	0
ACTN1	0.031	0	-9999	-10000	0	0
NCK1/GIT1	0.018	0.011	-9999	-10000	0	0
mol:GDP	0.027	0	-9999	-10000	0	0
EXOC4	0.013	0	-9999	-10000	0	0
STX4	0.031	0	-9999	-10000	0	0
PIP5K1C	0.03	0.008	-9999	-10000	0	0
LIMA1	0.007	0.049	-9999	-0.4	9	9
ABI1	0.013	0	-9999	-10000	0	0
ROCK1	0.047	0.02	-9999	-10000	0	0
adherens junction assembly	0.038	0.054	-9999	-0.5	1	1
IGF-1R heterotetramer/IGF1	-0.035	0.064	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.018	0.011	-9999	-0.27	1	1
MET	0.005	0.075	-9999	-0.75	6	6
PLEKHA7	0.03	0.008	-9999	-10000	0	0
mol:GTP	0.029	0.028	-9999	-0.44	2	2
establishment of epithelial cell apical/basal polarity	0.048	0.007	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.024	0.026	-9999	-10000	0	0
regulation of cell-cell adhesion	0.034	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.024	0.026	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.041	0.011	-9999	-10000	0	0
adherens junction organization	-0.006	0.064	-9999	-0.32	1	1
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.045	0.013	-9999	-10000	0	0
FMN1	0.036	0.012	-9999	-10000	0	0
mol:IP3	0.035	0.009	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.032	0.01	-9999	-10000	0	0
CTNNB1	0.012	0	-9999	-10000	0	0
AKT1	0.04	0.01	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.034	0.011	-9999	-10000	0	0
CTNND1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.036	0.009	-9999	-10000	0	0
VASP	0.036	0.01	-9999	-10000	0	0
ZYX	0.036	0.01	-9999	-10000	0	0
JUB	-0.1	0.2	-9999	-0.39	204	204
EGFR(dimer)	0.037	0.014	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin	0.024	0.009	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.036	0.01	-9999	-10000	0	0
PIK3CA	0.013	0.016	-9999	-0.4	1	1
PI3K	0.037	0.01	-9999	-10000	0	0
FYN	0.018	0.06	-9999	-10000	0	0
mol:Ca2+	0.034	0.009	-9999	-10000	0	0
JUP	0.012	0.016	-9999	-0.39	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	0.035	0.009	-9999	-10000	0	0
CDH1	0.012	0	-9999	-10000	0	0
RhoA/GDP	0.045	0.013	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.036	0.009	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
EGFR	0.011	0.023	-9999	-0.4	2	2
CASR	0.011	0.063	-9999	-0.37	1	1
RhoA/GTP	0.038	0.009	-9999	-10000	0	0
AKT2	0.04	0.01	-9999	-10000	0	0
actin cable formation	0.04	0.012	-9999	-10000	0	0
apoptosis	-0.038	0.01	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
mol:GDP	0.04	0.014	-9999	-10000	0	0
PIP5K1A	0.036	0.01	-9999	-10000	0	0
PLCG1	0.035	0.009	-9999	-10000	0	0
Rac1/GTP	0.039	0.013	-9999	-10000	0	0
homophilic cell adhesion	0.001	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.006	0.068	-9999	-0.75	5	5
PLK4	0.012	0.001	-9999	-10000	0	0
regulation of centriole replication	0.014	0.053	-9999	-0.57	5	5

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.008	0.012	0.2	2	-10000	0	2
BUB1B	0.015	0.024	-10000	0	-0.25	1	1
PLK1	0.014	0.011	-10000	0	-10000	0	0
PLK1S1	0.012	0.007	-10000	0	-10000	0	0
KIF2A	0.018	0.01	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.014	0.011	-10000	0	-10000	0	0
GOLGA2	0.013	0	-10000	0	-10000	0	0
Hec1/SPC24	0.019	0.06	-10000	0	-0.42	11	11
WEE1	0.015	0.025	-10000	0	-10000	0	0
cytokinesis	0.026	0.015	-10000	0	-0.22	1	1
PP2A-alpha B56	0.03	0.015	-10000	0	-10000	0	0
AURKA	0.012	0.007	-10000	0	-10000	0	0
PICH/PLK1	0.001	0.1	-10000	0	-0.35	50	50
CENPE	0.018	0.021	-10000	0	-0.44	1	1
RhoA/GTP	0.009	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.018	0.01	-10000	0	-10000	0	0
PPP2CA	0.013	0	-10000	0	-10000	0	0
FZR1	0.012	0.016	-10000	0	-0.4	1	1
TPX2	0.011	0.017	-10000	0	-0.15	6	6
PAK1	0.012	0.001	-10000	0	-10000	0	0
SPC24	-0.001	0.1	-10000	0	-0.75	11	11
FBXW11	0.013	0	-10000	0	-10000	0	0
CLSPN	0.013	0.01	-10000	0	-0.17	1	1
GORASP1	0.013	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-0.011	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.007	0.007	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0.001	-10000	0	-10000	0	0
STAG2	0.013	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.017	0.014	-10000	0	-10000	0	0
spindle elongation	0.014	0.011	-10000	0	-10000	0	0
ODF2	0.012	0.001	-10000	0	-10000	0	0
BUB1	-0.003	0.011	-10000	0	-10000	0	0
TPT1	0.012	0.007	-10000	0	-10000	0	0
CDC25C	0.014	0.006	-10000	0	-10000	0	0
CDC25B	-0.04	0.19	-10000	0	-0.75	44	44
SGOL1	0.008	0.012	-10000	0	-0.2	2	2
RHOA	0.013	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.024	0.087	-10000	0	-0.34	44	44
CDC14B	0.009	0.012	-10000	0	-0.28	1	1
CDC20	0.011	0.031	-10000	0	-0.75	1	1
PLK1/PBIP1	0.015	0.012	-10000	0	-10000	0	0
mitosis	0	0.001	-10000	0	-10000	0	0
FBXO5	0.014	0.019	-10000	0	-10000	0	0
CDC2	0	0.004	-10000	0	-0.015	44	44
NDC80	0.013	0.001	-10000	0	-10000	0	0
metaphase plate congression	0.013	0.007	-10000	0	-10000	0	0
ERCC6L	0.001	0.098	-10000	0	-0.33	50	50
NLP/gamma Tubulin	0.01	0.007	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.012	0.006	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-10000	0	-10000	0	0
PPP1R12A	0.011	0.023	-10000	0	-0.4	2	2
interphase	0	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	0.027	0.009	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0.03	0.008	-10000	0	-10000	0	0
RAB1A	0.013	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.015	0.008	-10000	0	-10000	0	0
mitotic prometaphase	0	0.001	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.012	-10000	0	-10000	0	0
microtubule-based process	0.019	0.01	-10000	0	-10000	0	0
Golgi organization	0.014	0.011	-10000	0	-10000	0	0
Cohesin/SA2	0.017	0.009	-10000	0	-10000	0	0
PPP1CB/MYPT1	0.017	0.024	-10000	0	-0.51	1	1
KIF20A	0.013	0	-10000	0	-10000	0	0
APC/C/CDC20	0.019	0.021	-10000	0	-0.44	1	1
PPP2R1A	0.013	0	-10000	0	-10000	0	0
chromosome segregation	0.015	0.011	-10000	0	-10000	0	0
PRC1	0.013	0	-10000	0	-10000	0	0
ECT2	0.015	0.04	-10000	0	-0.4	5	5
C13orf34	0.016	0.009	-10000	0	-10000	0	0
NUDC	0.013	0.007	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.015	0.024	-10000	0	-0.24	1	1
spindle assembly	0.013	0.009	-10000	0	-10000	0	0
spindle stabilization	0.012	0.006	-10000	0	-10000	0	0
APC/C/HCDH1	0.016	0.014	-10000	0	-0.23	1	1
MKLP2/PLK1	0.02	0.01	-10000	0	-10000	0	0
CCNB1	0.012	0.003	-10000	0	-10000	0	0
PPP1CB	0.012	0.017	-10000	0	-0.4	1	1
BTRC	0.013	0	-10000	0	-10000	0	0
ROCK2	0.019	0.025	-10000	0	-0.41	2	2
TUBG1	0.012	0.007	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.024	0.085	-10000	0	-0.33	44	44
MLF1IP	0.009	0.012	-10000	0	-0.28	1	1
INCENP	0.012	0.001	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.004	0.063	-9999	-0.39	15	15
PDGF/PDGFRA/CRKL	0.013	0.043	-9999	-10000	0	0
positive regulation of JUN kinase activity	0.027	0.032	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	0.002	0.059	-9999	-0.58	3	3
AP1	0.016	0.11	-9999	-0.8	10	10
mol:IP3	0.014	0.045	-9999	-10000	0	0
PLCG1	0.014	0.045	-9999	-10000	0	0
PDGF/PDGFRA/alphaV Integrin	0.013	0.043	-9999	-10000	0	0
RAPGEF1	0.012	0.016	-9999	-0.4	1	1
CRK	0.013	0	-9999	-10000	0	0
mol:Ca2+	0.014	0.045	-9999	-10000	0	0
CAV3	-0.002	0.052	-9999	-0.75	3	3
CAV1	0.004	0.058	-9999	-0.4	13	13
SHC/Grb2/SOS1	0.028	0.032	-9999	-10000	0	0
PDGF/PDGFRA/Shf	-0.001	0.098	-9999	-0.58	14	14
FOS	0.018	0.11	-9999	-0.79	10	10
JUN	-0.001	0.008	-9999	-10000	0	0
oligodendrocyte development	0.013	0.043	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	0.014	0.045	-9999	-10000	0	0
PDGF/PDGFRA	0.004	0.063	-9999	-0.39	15	15
actin cytoskeleton reorganization	0.01	0.059	-9999	-0.58	3	3
SRF	0.017	0.004	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
PI3K	0.02	0.037	-9999	-10000	0	0
PDGF/PDGFRA/Crk/C3G	0.02	0.037	-9999	-10000	0	0
JAK1	0.013	0.044	-9999	-10000	0	0
ELK1/SRF	0.027	0.034	-9999	-10000	0	0
SHB	0.009	0.053	-9999	-0.75	3	3
SHF	-0.005	0.11	-9999	-0.73	15	15
CSNK2A1	0.009	0.007	-9999	-10000	0	0
GO:0007205	0.014	0.05	-9999	-0.3	15	15
SOS1	0.013	0	-9999	-10000	0	0
Ras protein signal transduction	0.027	0.032	-9999	-10000	0	0
PDGF/PDGFRA/SHB	0.01	0.059	-9999	-0.58	3	3
PDGF/PDGFRA/Caveolin-1	0.007	0.065	-9999	-0.34	13	13
ITGAV	0.013	0	-9999	-10000	0	0
ELK1	0.019	0.043	-9999	-10000	0	0
PIK3CA	0.012	0.016	-9999	-0.4	1	1
PDGF/PDGFRA/Crk	0.013	0.043	-9999	-10000	0	0
JAK-STAT cascade	0.013	0.044	-9999	-10000	0	0
cell proliferation	-0.001	0.098	-9999	-0.58	14	14

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.009	0.036	-9999	-0.4	5	5
positive regulation of NF-kappaB transcription factor activity	0.016	0.026	-9999	-10000	0	0
MAP2K4	0.036	0.025	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
TNFRSF10B	0.013	0	-9999	-10000	0	0
TNFRSF10A	0.013	0	-9999	-10000	0	0
SMPD1	0.013	0.037	-9999	-0.36	5	5
IKBKG	0.012	0.016	-9999	-0.4	1	1
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR2	0.016	0.026	-9999	-0.27	5	5
TRAIL/TRAILR3	-0.022	0.15	-9999	-0.57	41	41
TRAIL/TRAILR1	0.016	0.026	-9999	-0.27	5	5
TRAIL/TRAILR4	0.016	0.026	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP	0.023	0.02	-9999	-10000	0	0
IKK complex	-0.001	0.014	-9999	-0.3	1	1
RIPK1	0.013	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.009	0	-9999	-10000	0	0
MAPK3	0.016	0.028	-9999	-0.27	6	6
MAP3K1	0.033	0.022	-9999	-10000	0	0
TRAILR4 (trimer)	0.013	0	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.03	0.021	-9999	-10000	0	0
CFLAR	0.013	0	-9999	-10000	0	0
MAPK1	0.016	0.028	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	0.036	0.019	-9999	-10000	0	0
mol:ceramide	0.013	0.037	-9999	-0.36	5	5
FADD	0.013	0	-9999	-10000	0	0
MAPK8	0.04	0.024	-9999	-10000	0	0
TRAF2	0.012	0.016	-9999	-0.4	1	1
TRAILR3 (trimer)	-0.038	0.19	-9999	-0.75	41	41
CHUK	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	0.024	0.022	-9999	-10000	0	0
DAP3	0.013	0	-9999	-10000	0	0
CASP10	-0.002	0.021	-9999	-10000	0	0
JNK cascade	0.016	0.026	-9999	-10000	0	0
TRAIL (trimer)	0.009	0.036	-9999	-0.39	5	5
TNFRSF10C	-0.038	0.19	-9999	-0.75	41	41
TRAIL/TRAILR1/DAP3/GTP/FADD	0.028	0.018	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	0.024	0.022	-9999	-10000	0	0
cell death	0.013	0.037	-9999	-0.36	5	5
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.03	0.021	-9999	-10000	0	0
TRAILR2 (trimer)	0.013	0	-9999	-10000	0	0
CASP8	0.001	0.011	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.036	0.019	-9999	-10000	0	0

×

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

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
BAG4	0.012	0.001	-9999	-10000	0	0
Caspase 8 (4 units)	0.025	0.055	-9999	-0.35	2	2
NEF	-0.004	0.034	-9999	-10000	0	0
NFKBIA	0.014	0.012	-9999	-10000	0	0
BIRC3	0.029	0.062	-9999	-0.45	10	10
CYCS	0.025	0.064	-9999	-0.37	3	3
RIPK1	0.013	0	-9999	-10000	0	0
CD247	-0.002	0.083	-9999	-0.47	16	16
MAP2K7	0.033	0.056	-9999	-0.64	1	1
protein ubiquitination	0.055	0.021	-9999	-10000	0	0
CRADD	0.013	0	-9999	-10000	0	0
DAXX	0.013	0	-9999	-10000	0	0
FAS	0.007	0.049	-9999	-0.4	9	9
BID	0.021	0.066	-9999	-0.4	3	3
NF-kappa-B/RelA/I kappa B alpha	0.031	0.033	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
MAP3K5	0.013	0	-9999	-10000	0	0
CFLAR	0.013	0	-9999	-10000	0	0
FADD	0.013	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.031	0.034	-9999	-10000	0	0
MAPK8	0.037	0.053	-9999	-0.59	1	1
APAF1	0.013	0.001	-9999	-10000	0	0
TRAF1	0.013	0	-9999	-10000	0	0
TRAF2	0.012	0.016	-9999	-0.4	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.016	0.067	-9999	-0.37	3	3
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.05	0.024	-9999	-10000	0	0
CHUK	0.056	0.022	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.034	0.025	-9999	-10000	0	0
TCRz/NEF	-0.004	0.086	-9999	-0.31	41	41
TNF	0.009	0.036	-9999	-0.4	5	5
FASLG	-0.009	0.13	-9999	-0.54	34	34
NFKB1	0.014	0.012	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.024	0.022	-9999	-10000	0	0
CASP6	0.039	0.04	-9999	-10000	0	0
CASP7	0.052	0.075	-9999	-0.42	9	9
RELA	0.014	0.012	-9999	-10000	0	0
CASP2	0.013	0	-9999	-10000	0	0
CASP3	0.052	0.074	-9999	-0.42	9	9
TNFRSF1A	0.013	0	-9999	-10000	0	0
TNFR1A/BAG4	0.019	0.001	-9999	-10000	0	0
CASP8	0.013	0	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
MAP3K14	0.054	0.023	-9999	-10000	0	0
APAF-1/Caspase 9	-0.013	0.048	-9999	-0.44	2	2
BCL2	0.032	0.066	-9999	-0.46	2	2

×

IL2 signaling events mediated by STAT5

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
GAB2	0.013	0	-9999	-10000	0	0
ELF1	0.014	0.046	-9999	-0.3	13	13
CCNA2	0.013	0	-9999	-10000	0	0
PIK3CA	0.013	0.016	-9999	-0.39	1	1
JAK3	0.012	0.031	-9999	-0.75	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.013	0.016	-9999	-0.39	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.054	0.057	-9999	-0.45	2	2
SHC1	0.013	0	-9999	-10000	0	0
SP1	0.016	0.034	-9999	-0.3	7	7
IL2RA	0.013	0.095	-9999	-0.64	13	13
IL2RB	0.002	0.066	-9999	-0.39	17	17
SOS1	0.013	0	-9999	-10000	0	0
IL2RG	0.011	0.028	-9999	-0.39	3	3
G1/S transition of mitotic cell cycle	0.033	0.064	-9999	-0.6	6	6
PTPN11	0.013	0	-9999	-10000	0	0
CCND2	0.019	0.07	-9999	-0.64	7	7
LCK	0.002	0.089	-9999	-0.68	10	10
GRB2	0.013	0	-9999	-10000	0	0
IL2	0.004	0.006	-9999	-10000	0	0
CDK6	0.013	0	-9999	-10000	0	0
CCND3	0.058	0.051	-9999	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.01	0.055	-9999	-0.39	10	10
TC10/GTP	-0.01	0.053	-9999	-0.38	10	10
Insulin Receptor/Insulin/IRS1/Shp2	0.027	0	-9999	-10000	0	0
HRAS	0.012	0.016	-9999	-0.4	1	1
APS homodimer	0	0.096	-9999	-0.75	10	10
GRB14	-0.024	0.14	-9999	-0.5	42	42
FOXO3	-0.001	0.11	-9999	-0.52	25	25
AKT1	0.023	0.066	-9999	-10000	0	0
INSR	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.032	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.013	0	-9999	-10000	0	0
SORBS1	0.002	0.064	-9999	-0.4	16	16
CRK	0.013	0	-9999	-10000	0	0
PTPN1	0.027	0	-9999	-10000	0	0
CAV1	0.018	0.03	-9999	-10000	0	0
CBL/APS/CAP/Crk-II/C3G	0.024	0.066	-9999	-0.42	10	10
Insulin Receptor/Insulin/IRS1/NCK2	0.027	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0.007	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.033	0	-9999	-10000	0	0
RPS6KB1	0.027	0.062	-9999	-10000	0	0
PARD6A	0.01	0.043	-9999	-0.75	2	2
CBL	0.013	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.012	0.05	-9999	-10000	0	0
HRAS/GTP	0	0.008	-9999	-10000	0	0
Insulin Receptor	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.033	0	-9999	-10000	0	0
PRKCI	-0.005	0.027	-9999	-0.42	2	2
Insulin Receptor/Insulin/GRB14/PDK1	-0.015	0.062	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.024	0.001	-9999	-10000	0	0
PI3K	0.027	0.008	-9999	-10000	0	0
NCK2	0.013	0	-9999	-10000	0	0
RHOQ	0.013	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.009	0.011	-9999	-0.28	1	1
AKT2	0.023	0.066	-9999	-10000	0	0
PRKCZ	-0.003	0.014	-9999	-10000	0	0
SH2B2	0	0.096	-9999	-0.75	10	10
SHC/SHIP	0.029	0.008	-9999	-10000	0	0
F2RL2	-0.027	0.17	-9999	-0.71	34	34
TRIP10	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0.019	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.017	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.033	0	-9999	-10000	0	0
RAPGEF1	0.012	0.016	-9999	-0.4	1	1
RASA1	0.013	0.001	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	0.019	0.069	-9999	-0.45	10	10
TC10/GDP	0.009	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.027	0	-9999	-10000	0	0
INPP5D	0.022	0.008	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
SGK1	-0.032	0.15	-9999	-0.78	25	25
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
IRS1	0.013	0	-9999	-10000	0	0
p62DOK/RasGAP	0.024	0.001	-9999	-10000	0	0
INS	0.002	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.022	0.008	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
EIF4EBP1	0.025	0.069	-9999	-10000	0	0
PTPRA	0.014	0	-9999	-10000	0	0
PIK3CA	0.012	0.016	-9999	-0.4	1	1
TC10/GTP/CIP4	0.017	0	-9999	-10000	0	0
PDPK1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.029	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.012	0	-9999	-10000	0	0
Par3/Par6	0.005	0.1	-9999	-0.42	32	32

×

LPA4-mediated signaling events

Figure S109. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S109. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.016	0	-9999	-10000	0	0
ADCY5	-0.094	0.12	-9999	-10000	0	0
ADCY6	0.016	0	-9999	-10000	0	0
ADCY7	0.016	0	-9999	-10000	0	0
ADCY1	0.004	0.075	-9999	-0.5	13	13
ADCY2	-0.02	0.086	-9999	-0.5	1	1
ADCY3	0.016	0	-9999	-10000	0	0
ADCY8	0.002	0.061	-9999	-0.5	9	9
PRKCE	0.01	0	-9999	-10000	0	0
ADCY9	0.015	0.014	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.019	0.059	-9999	-0.26	3	3

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.013	0.059	-10000	0	-0.53	7	7
CRKL	0.027	0.038	-10000	0	-0.36	1	1
mol:PIP3	-0.015	0.022	0.37	2	-10000	0	2
AKT1	0.001	0.016	0.27	2	-10000	0	2
PTK2B	0.011	0.023	-10000	0	-0.4	2	2
RAPGEF1	0.031	0.037	-10000	0	-0.34	1	1
RANBP10	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
HGF/MET/SHIP2	0.014	0.067	-10000	0	-0.52	7	7
MAP3K5	0.019	0.077	-10000	0	-0.35	6	6
HGF/MET/CIN85/CBL/ENDOPHILINS	0.022	0.062	-10000	0	-0.47	7	7
AP1	0.012	0.035	-10000	0	-10000	0	0
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.007	0.094	-10000	0	-0.72	10	10
STAT3 (dimer)	0.028	0.044	-10000	0	-0.4	1	1
GAB1/CRKL/SHP2/PI3K	0.041	0.036	-10000	0	-10000	0	0
INPP5D	0.012	0.016	-10000	0	-0.4	1	1
CBL/CRK	0.033	0.036	-10000	0	-0.34	1	1
PTPN11	0.013	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
PTEN	0.011	0.023	-10000	0	-0.4	2	2
ELK1	-0.002	0.029	0.23	2	-0.27	6	8
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.022	0.028	-10000	0	-0.27	1	1
PAK1	0.006	0.014	0.27	1	-10000	0	1
HGF/MET/RANBP10	0.014	0.067	-10000	0	-0.52	7	7
HRAS	0.024	0.054	-10000	0	-0.48	2	2
DOCK1	0.031	0.037	-10000	0	-0.34	1	1
GAB1	0.022	0.039	-10000	0	-0.39	1	1
CRK	0.027	0.038	-10000	0	-0.36	1	1
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.076	-10000	0	-0.42	15	15
JUN	0.013	0	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.007	0.039	-10000	0	-0.27	7	7
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell morphogenesis	0.049	0.045	-10000	0	-0.38	1	1
GRB2/SHC	0.021	0.035	-10000	0	-0.36	1	1
FOS	0.006	0.051	-10000	0	-0.4	10	10
GLMN	-0.001	0.012	-10000	0	-0.22	2	2
cell motility	-0.002	0.029	0.23	2	-0.26	6	8
HGF/MET/MUC20	0.006	0.067	-10000	0	-0.52	7	7
cell migration	0.021	0.035	-10000	0	-0.36	1	1
GRB2	0.013	0	-10000	0	-10000	0	0
CBL	0.013	0	-10000	0	-10000	0	0
MET/RANBP10	0.013	0.057	-10000	0	-0.57	6	6
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.024	0.045	-10000	0	-0.43	1	1
MET/MUC20	0.004	0.057	-10000	0	-0.58	6	6
RAP1B	0.036	0.036	-10000	0	-0.32	1	1
RAP1A	0.036	0.036	-10000	0	-10000	0	0
HGF/MET/RANBP9	0.014	0.068	-10000	0	-0.52	7	7
RAF1	0.029	0.052	-10000	0	-0.45	2	2
STAT3	0.028	0.044	-10000	0	-0.41	1	1
cell proliferation	0.035	0.056	-10000	0	-0.52	1	1
RPS6KB1	0.009	0.019	-10000	0	-0.28	1	1
MAPK3	-0.006	0.036	0.65	1	-0.25	6	7
MAPK1	-0.006	0.036	0.65	1	-0.25	6	7
RANBP9	0.012	0.016	-10000	0	-0.4	1	1
MAPK8	0.034	0.061	-10000	0	-10000	0	0
SRC	0.028	0.043	-10000	0	-0.4	1	1
PI3K	0.021	0.036	-10000	0	-0.36	1	1
MET/Glomulin	0.006	0.052	-10000	0	-0.52	6	6
SOS1	0.013	0	-10000	0	-10000	0	0
MAP2K1	0.033	0.049	-10000	0	-0.42	2	2
MET	0.005	0.075	-10000	0	-0.75	6	6
MAP4K1	0.013	0.081	-10000	0	-0.38	6	6
PTK2	0.013	0	-10000	0	-10000	0	0
MAP2K2	0.033	0.05	-10000	0	-0.39	3	3
BAD	0.006	0.016	0.26	2	-10000	0	2
MAP2K4	0.023	0.073	-10000	0	-0.34	1	1
SHP2/GRB2/SOS1/GAB1	-0.006	0.036	-10000	0	-0.45	1	1
INPPL1	0.013	0	-10000	0	-10000	0	0
PXN	0.013	0	-10000	0	-10000	0	0
SH3KBP1	0.013	0	-10000	0	-10000	0	0
HGS	0.012	0.036	-10000	0	-0.26	6	6
PLCgamma1/PKC	0.009	0	-10000	0	-10000	0	0
HGF	0.002	0.067	-10000	0	-0.42	15	15
RASA1	0.013	0.001	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
PTPRJ	0.013	0	-10000	0	-10000	0	0
NCK/PLCgamma1	0.023	0.037	-10000	0	-0.38	1	1
PDPK1	-0.007	0.018	0.3	2	-10000	0	2
HGF/MET/SHIP	0.014	0.068	-10000	0	-0.52	7	7

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.031	0.017	-10000	0	-10000	0	0
regulation of axonogenesis	-0.024	0.009	-10000	0	-10000	0	0
myoblast fusion	-0.022	0.016	-10000	0	-10000	0	0
mol:GTP	0.01	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.001	0.095	0.5	10	-10000	0	10
ARF1/GTP	0.016	0.006	-10000	0	-10000	0	0
mol:GM1	0.009	0.003	-10000	0	-10000	0	0
mol:Choline	0.023	0.013	-10000	0	-10000	0	0
lamellipodium assembly	0.009	0.025	-10000	0	-10000	0	0
MAPK3	0.022	0.013	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.002	0.096	-10000	0	-0.5	10	10
ARF1	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	0.022	0.016	-10000	0	-10000	0	0
ARF1/GDP	0.03	0.016	-10000	0	-10000	0	0
ARF6	0.013	0.001	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
TIAM1	-0.027	0.12	-10000	0	-0.39	62	62
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.022	0.013	-10000	0	-10000	0	0
actin filament bundle formation	-0.021	0.009	-10000	0	-10000	0	0
KALRN	0.007	0.023	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0.019	0	-10000	0	-10000	0	0
RhoA/GDP	0.021	0.009	-10000	0	-10000	0	0
NME1	0.002	0.096	-10000	0	-0.75	10	10
Rac1/GDP	0.021	0.009	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.01	0.004	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.009	0.025	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
liver development	0.01	0.004	-10000	0	-10000	0	0
ARF6/GTP	0.01	0.004	-10000	0	-10000	0	0
RhoA/GTP	0.016	0.006	-10000	0	-10000	0	0
mol:GDP	0.009	0.026	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.023	0.008	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
PLD1	0.018	0.015	-10000	0	-0.24	2	2
RAB11FIP3	0.013	0	-10000	0	-10000	0	0
tube morphogenesis	0.009	0.025	-10000	0	-10000	0	0
ruffle organization	0.024	0.009	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.01	0.004	-10000	0	-10000	0	0
PLD2	0.019	0.001	-10000	0	-10000	0	0
PIP5K1A	0.024	0.009	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.023	0.013	-10000	0	-10000	0	0
Rac1/GTP	0.009	0.025	-10000	0	-10000	0	0

×

ceramide signaling pathway

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
MAP4K4	0.039	0.037	-10000	0	-10000	0	0
BAG4	0.012	0.001	-10000	0	-10000	0	0
BAD	0.025	0.021	-10000	0	-0.35	1	1
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	0.005	0.057	-10000	0	-0.43	10	10
BAX	0.025	0.017	-10000	0	-0.18	1	1
EnzymeConsortium:3.1.4.12	0.013	0.01	-10000	0	-10000	0	0
IKBKB	0.043	0.035	-10000	0	-10000	0	0
MAP2K2	0.034	0.019	-10000	0	-0.29	1	1
MAP2K1	0.034	0.015	-10000	0	-10000	0	0
SMPD1	0.016	0.021	-10000	0	-0.19	5	5
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.045	0.036	-10000	0	-10000	0	0
MAP2K4	0.029	0.022	-10000	0	-10000	0	0
protein ubiquitination	0.044	0.036	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.038	0.018	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.031	0.016	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
mol:ceramide	0.02	0.018	-10000	0	-0.19	1	1
I-kappa-B-alpha/RELA/p50/ubiquitin	0.017	0	-10000	0	-10000	0	0
MADD	0.013	0	-10000	0	-10000	0	0
MAP3K1	0.025	0.019	-10000	0	-0.23	1	1
TRADD	0.013	0	-10000	0	-10000	0	0
RELA/p50	0.013	0	-10000	0	-10000	0	0
MAPK3	0.036	0.017	-10000	0	-10000	0	0
MAPK1	0.036	0.017	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.019	0	-10000	0	-10000	0	0
FADD	0.039	0.037	-10000	0	-10000	0	0
KSR1	0.026	0.017	-10000	0	-10000	0	0
MAPK8	0.033	0.021	-10000	0	-10000	0	0
TRAF2	0.012	0.016	-10000	0	-0.4	1	1
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.043	0.035	-10000	0	-10000	0	0
TNF R/SODD	0.019	0.001	-10000	0	-10000	0	0
TNF	0.009	0.036	-10000	0	-0.4	5	5
CYCS	0.03	0.027	0.12	28	-0.26	1	29
IKBKG	0.043	0.038	-10000	0	-0.4	1	1
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.035	0.038	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
RIPK1	0.012	0	-10000	0	-10000	0	0
AIFM1	0.03	0.027	0.12	29	-0.26	1	30
TNF/TNF R/SODD	0.024	0.022	-10000	0	-10000	0	0
TNFRSF1A	0.012	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.027	0.01	-10000	0	-10000	0	0
NSMAF	0.039	0.036	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	-0.008	0.09	-10000	0	-0.4	32	32

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.001	0.007	-9999	-10000	0	0
DOCK1	0.012	0.016	-9999	-0.4	1	1
ITGA4	-0.002	0.075	-9999	-0.4	22	22
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.002	0.08	-9999	-0.51	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.017	0.045	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.014	0.062	-9999	-0.39	5	5
lamellipodium assembly	0.001	0.019	-9999	-10000	0	0
PIK3CA	0.012	0.016	-9999	-0.4	1	1
PI3K	0.018	0.011	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
TLN1	0.013	0	-9999	-10000	0	0
PXN	0.019	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
ARF6/GTP	0.027	0.035	-9999	-10000	0	0
cell adhesion	0.028	0.038	-9999	-10000	0	0
CRKL/CBL	0.019	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.022	0.04	-9999	-10000	0	0
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	-0.003	0.077	-9999	-0.4	23	23
ARF6/GDP	0.001	0.007	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.025	0.058	-9999	-0.36	9	9
p130Cas/Crk/Dock1	0.025	0.014	-9999	-10000	0	0
VCAM1	0.004	0.058	-9999	-0.4	13	13
alpha4/beta1 Integrin/Paxillin/Talin	0.029	0.038	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.029	0.039	-9999	-10000	0	0
BCAR1	0.012	0.016	-9999	-0.4	1	1
mol:GDP	-0.028	0.039	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GIT1	0.012	0.016	-9999	-0.4	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.029	0.038	-9999	-10000	0	0
Rac1/GTP	0.001	0.02	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.035	0.003	-9999	-10000	0	0
KLHL20	0.03	0.05	-9999	-0.23	5	5
CYFIP2	0.012	0.016	-9999	-0.4	1	1
Rac1/GDP	0.051	0.018	-9999	-10000	0	0
ENAH	0.035	0.008	-9999	-10000	0	0
AP1M1	0.013	0	-9999	-10000	0	0
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	-0.001	0.008	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.007	0.025	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.024	0.042	-9999	-10000	0	0
RAPGEF1	0.043	0.008	-9999	-10000	0	0
CTNND1	0.013	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.03	0.003	-9999	-10000	0	0
CRK	0.04	0.003	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0.025	0.01	-9999	-10000	0	0
alphaE/beta7 Integrin	0.008	0.054	-9999	-10000	0	0
IQGAP1	0.013	0	-9999	-10000	0	0
NCKAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.024	0.009	-9999	-10000	0	0
DLG1	0.035	0.008	-9999	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0.005	-9999	-10000	0	0
MLLT4	0.012	0.016	-9999	-0.4	1	1
ARF6/GTP/NME1/Tiam1	-0.005	0.09	-9999	-0.49	10	10
PI3K	0	0.006	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.018	0.011	-9999	-10000	0	0
TIAM1	-0.028	0.12	-9999	-0.4	62	62
E-cadherin(dimer)/Ca2+	0.03	0.001	-9999	-10000	0	0
AKT1	0	0.004	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
RhoA/GDP	0.05	0.018	-9999	-10000	0	0
actin cytoskeleton organization	0.025	0.038	-9999	-0.17	5	5
CDC42/GDP	0.05	0.021	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.021	0.009	-9999	-10000	0	0
ITGB7	-0.003	0.077	-9999	-0.4	23	23
RAC1	0.013	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.033	0.001	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0.023	0	-9999	-10000	0	0
mol:GDP	0.048	0.02	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0.016	0.014	-9999	-10000	0	0
JUP	0.012	0.016	-9999	-0.4	1	1
p120 catenin/RhoA/GDP	0.049	0.018	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0.017	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.018	0.011	-9999	-0.27	1	1
RHOA	0.013	0	-9999	-10000	0	0
CDC42	0.011	0.023	-9999	-0.4	2	2
CTNNA1	0.013	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.02	0.034	-9999	-0.24	5	5
NME1	0	0.096	-9999	-0.75	10	10
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.035	0.003	-9999	-10000	0	0
regulation of cell-cell adhesion	-0.001	0.007	-9999	-10000	0	0
WASF2	-0.004	0.013	-9999	-10000	0	0
Rap1/GTP	0	0.005	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.029	0.04	-9999	-10000	0	0
CCND1	0.023	0.041	-9999	-0.31	5	5
VAV2	0.035	0.081	-9999	-0.63	9	9
RAP1/GDP	0.042	0.018	-9999	-10000	0	0
adherens junction assembly	0.035	0.003	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
PIP5K1C	0.012	0.016	-9999	-0.4	1	1
regulation of heterotypic cell-cell adhesion	0.033	0.038	-9999	-10000	0	0
E-cadherin/beta catenin	0	0.006	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.035	0.004	-9999	-10000	0	0
PIK3CA	0.012	0.016	-9999	-0.4	1	1
Rac1/GTP	-0.017	0.059	-9999	-0.35	11	11
E-cadherin/beta catenin/alpha catenin	0.026	0	-9999	-10000	0	0
ITGAE	0.013	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.031	0.003	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.037	0.13	-10000	0	-0.4	76	76
CLTC	0.023	0.034	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.022	0.008	-10000	0	-10000	0	0
Dynamin 2/GTP	0.014	0.059	-10000	0	-0.45	10	10
EXOC4	0.013	0	-10000	0	-10000	0	0
CD59	0.021	0.021	-10000	0	-10000	0	0
CPE	-0.002	0.065	-10000	0	-0.5	1	1
CTNNB1	0.013	0	-10000	0	-10000	0	0
membrane fusion	0.022	0.008	-10000	0	-10000	0	0
CTNND1	0.019	0.056	-10000	0	-0.42	10	10
DNM2	0.013	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.025	0.017	-10000	0	-10000	0	0
TSHR	0.012	0.029	-10000	0	-0.5	2	2
INS	0.009	0.006	-10000	0	-10000	0	0
BIN1	0.012	0.016	-10000	0	-0.4	1	1
mol:Choline	0.022	0.008	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.008	0.064	-10000	0	-0.5	10	10
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0.014	0.059	-10000	0	-0.45	10	10
JUP	0.021	0.022	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.024	0.009	-10000	0	-10000	0	0
ARF6/GTP	0.009	0	-10000	0	-10000	0	0
CDH1	0.021	0.021	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.009	0	-10000	0	-10000	0	0
MAPK8IP3	0.011	0.035	-10000	0	-0.57	2	2
positive regulation of endocytosis	0.009	0	-10000	0	-10000	0	0
EXOC2	0.012	0.016	-10000	0	-0.4	1	1
substrate adhesion-dependent cell spreading	0.035	0.029	-10000	0	-0.61	1	1
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.013	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.005	0.043	0.34	10	-10000	0	10
positive regulation of phagocytosis	0.016	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.016	0.023	-10000	0	-0.5	1	1
ACAP1	0.017	0.025	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.026	0.079	-10000	0	-0.4	2	2
clathrin heavy chain/ACAP1	0.026	0.031	-10000	0	-10000	0	0
JIP4/KLC1	0.024	0	-10000	0	-10000	0	0
EXOC1	0.012	0.016	-10000	0	-0.4	1	1
exocyst	0.035	0.029	-10000	0	-0.62	1	1
RALA/GTP	0.009	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.017	0	-10000	0	-10000	0	0
receptor recycling	0.009	0	-10000	0	-10000	0	0
CTNNA1	0.019	0.056	-10000	0	-0.42	10	10
NME1	0.008	0.065	-10000	0	-0.5	10	10
clathrin coat assembly	0.023	0.034	-10000	0	-10000	0	0
IL2RA	0.018	0.032	-10000	0	-10000	0	0
VAMP3	0.016	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.021	0.056	-10000	0	-0.36	3	3
EXOC6	0.013	0	-10000	0	-10000	0	0
PLD1	0.018	0.014	-10000	0	-0.23	2	2
PLD2	0.019	0	-10000	0	-10000	0	0
EXOC5	0.01	0.033	-10000	0	-0.4	4	4
PIP5K1C	0.025	0.017	-10000	0	-10000	0	0
SDC1	0.021	0.021	-10000	0	-10000	0	0
ARF6/GDP	0.008	0.064	-10000	0	-0.5	10	10
EXOC7	0.013	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.028	0.049	-10000	0	-0.35	10	10
mol:Phosphatidic acid	0.022	0.008	-10000	0	-10000	0	0
endocytosis	-0.023	0.009	-10000	0	-10000	0	0
SCAMP2	0.013	0	-10000	0	-10000	0	0
ADRB2	-0.002	0.079	-10000	0	-0.4	5	5
EXOC3	0.013	0	-10000	0	-10000	0	0
ASAP2	0.013	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.015	0.059	-10000	0	-0.45	10	10
KLC1	0.013	0	-10000	0	-10000	0	0
AVPR2	0.01	0.071	-10000	0	-0.39	8	8
RALA	0.013	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.005	0.041	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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
TRAF6/ASK1	0.013	0	-10000	0	-10000	0	0
TRAF2/ASK1	0.017	0.01	-10000	0	-0.22	1	1
ATM	0.012	0.016	-10000	0	-0.4	1	1
MAP2K3	0.028	0.028	-10000	0	-0.3	2	2
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.034	0.028	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.005	0.076	-10000	0	-0.7	7	7
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.013	0	-10000	0	-10000	0	0
GADD45A	0.013	0	-10000	0	-10000	0	0
GADD45B	0.013	0	-10000	0	-10000	0	0
MAP3K1	0.012	0.016	-10000	0	-0.4	1	1
MAP3K6	0.011	0.023	-10000	0	-0.4	2	2
MAP3K7	0.013	0	-10000	0	-10000	0	0
MAP3K4	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.018	0.016	-10000	0	-10000	0	0
TAK1/TAB family	0.001	0.01	0.18	2	-10000	0	2
RAC1/OSM/MEKK3	0.024	0.009	-10000	0	-10000	0	0
TRAF2	0.012	0.016	-10000	0	-0.4	1	1
RAC1/OSM/MEKK3/MKK3	-0.002	0.016	-10000	0	-10000	0	0
TRAF6	0.007	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.028	0.13	-10000	0	-0.45	52	52
CCM2	0.012	0.016	-10000	0	-0.4	1	1
CaM/Ca2+/CAMKIIB	-0.008	0.083	-10000	0	-0.5	8	8
MAPK11	0.01	0.043	-10000	0	-0.75	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.002	0.076	-10000	0	-0.45	8	8
OSM/MEKK3	0.018	0.011	-10000	0	-10000	0	0
TAOK1	0.014	0.011	-10000	0	-0.27	1	1
TAOK2	0.014	0.011	-10000	0	-0.27	1	1
TAOK3	0.014	0.011	-10000	0	-0.27	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.013	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.013	0	-10000	0	-10000	0	0
MAP3K10	0.011	0.031	-10000	0	-0.75	1	1
MAP3K3	0.013	0	-10000	0	-10000	0	0
TRX/ASK1	0.015	0	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.025	0.045	-10000	0	-0.42	6	6

×

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	0.015	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.067	0.027	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
RIP2/NOD2	0.003	0.094	-9999	-0.57	16	16
NFKBIA	0.037	0	-9999	-10000	0	0
BIRC2	0.012	0.016	-9999	-0.4	1	1
IKBKB	0.013	0	-9999	-10000	0	0
RIPK2	0.013	0	-9999	-10000	0	0
IKBKG	0.032	0.044	-9999	-0.39	3	3
IKK complex/A20	0.045	0.043	-9999	-0.4	1	1
NEMO/A20/RIP2	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
NEMO/ATM	0.037	0.043	-9999	-0.4	2	2
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.017	0	-9999	-10000	0	0
IKK complex/ELKS	-0.005	0.031	-9999	-0.39	1	1
BCL10/MALT1/TRAF6	0.025	0.014	-9999	-10000	0	0
NOD2	-0.008	0.12	-9999	-0.73	17	17
NFKB1	0.015	0	-9999	-10000	0	0
RELA	0.015	0	-9999	-10000	0	0
MALT1	0.012	0.016	-9999	-0.4	1	1
cIAP1/UbcH5C	0.018	0.011	-9999	-10000	0	0
ATM	0.012	0.016	-9999	-0.4	1	1
TNF/TNFR1A	0.016	0.026	-9999	-10000	0	0
TRAF6	0.013	0	-9999	-10000	0	0
PRKCA	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
UBE2D3	0.013	0	-9999	-10000	0	0
TNF	0.009	0.036	-9999	-0.4	5	5
NF kappa B1 p50/RelA	0.035	0	-9999	-10000	0	0
BCL10	0.012	0.016	-9999	-0.4	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.036	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
IKK complex	0.043	0.041	-9999	-0.42	1	1
CYLD	0.012	0.016	-9999	-0.4	1	1
IKK complex/PKC alpha	0.047	0.04	-9999	-0.4	1	1

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.043	0.009	-10000	0	-10000	0	0
CLOCK	0.015	0.002	-10000	0	-10000	0	0
TIMELESS/CRY2	0.038	0.01	-10000	0	-10000	0	0
DEC1/BMAL1	0.004	0.077	-10000	0	-0.57	11	11
ATR	0.013	0	-10000	0	-10000	0	0
NR1D1	0.035	0.023	-10000	0	-0.54	1	1
ARNTL	0.015	0.002	-10000	0	-10000	0	0
TIMELESS	0.035	0.011	-10000	0	-10000	0	0
NPAS2	0.015	0.002	-10000	0	-10000	0	0
CRY2	0.013	0	-10000	0	-10000	0	0
mol:CO	-0.012	0.004	0.097	1	-10000	0	1
CHEK1	0.013	0	-10000	0	-10000	0	0
mol:HEME	0.012	0.004	-10000	0	-0.097	1	1
PER1	0.011	0.023	-10000	0	-0.4	2	2
BMAL/CLOCK/NPAS2	0.04	0.005	-10000	0	-10000	0	0
BMAL1/CLOCK	0.04	0.035	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.043	0.009	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.043	0.009	-10000	0	-10000	0	0
mol:NADPH	0.012	0.004	-10000	0	-0.097	1	1
PER1/TIMELESS	0.037	0.015	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.009	0.1	-10000	0	-0.75	11	11

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.015	0.03	-9999	-0.27	7	7
AKT1	0.068	0.034	-9999	-0.45	1	1
PTK2B	0.041	0.041	-9999	-0.44	1	1
VEGFR2 homodimer/Frs2	0.031	0.025	-9999	-0.55	1	1
CAV1	0.004	0.058	-9999	-0.4	13	13
CALM1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.038	0.035	-9999	-0.46	3	3
endothelial cell proliferation	0.045	0.066	-9999	-0.47	1	1
mol:Ca2+	0.044	0.033	-9999	-0.41	3	3
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.044	0.034	-9999	-0.43	3	3
RP11-342D11.1	0.036	0.033	-9999	-0.42	3	3
CDH5	0.013	0	-9999	-10000	0	0
VEGFA homodimer	0.032	0.028	-9999	-0.44	2	2
SHC1	0.013	0	-9999	-10000	0	0
SHC2	0.001	0.087	-9999	-0.62	11	11
HRAS/GDP	-0.002	0.025	-9999	-10000	0	0
SH2D2A	0.011	0.031	-9999	-0.75	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.063	0.041	-9999	-0.55	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.037	0.04	-9999	-0.45	4	4
VEGFR1 homodimer	0.013	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.002	0.027	-9999	-0.42	1	1
GRB10	0.044	0.033	-9999	-0.45	1	1
PTPN11	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.048	0.033	-9999	-0.44	1	1
HRAS	0.012	0.016	-9999	-0.4	1	1
VEGF/Rho/ROCK1/Integrin Complex	0.04	0.041	-9999	-0.76	1	1
HIF1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0.001	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.043	0.033	-9999	-0.42	3	3
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.01	0.033	-9999	-0.4	4	4
Nck/Pak	0.019	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.038	0.035	-9999	-0.46	3	3
mol:GDP	-0.002	0.026	-9999	-0.41	1	1
mol:NADP	0.058	0.039	-9999	-0.5	1	1
eNOS/Hsp90	0.062	0.037	-9999	-0.47	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.044	0.033	-9999	-0.42	3	3
HIF1A/ARNT	0.018	0.011	-9999	-10000	0	0
SHB	0.009	0.053	-9999	-0.75	3	3
VEGFA	0.012	0.043	-9999	-0.75	2	2
VEGFC	0.006	0.051	-9999	-0.4	10	10
FAK1/Vinculin	0.057	0.042	-9999	-0.62	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.042	0.041	-9999	-0.43	3	3
PTPN6	0.013	0	-9999	-10000	0	0
EPAS1	0.02	0.021	-9999	-0.34	2	2
mol:L-citrulline	0.058	0.039	-9999	-0.5	1	1
ITGAV	0.013	0	-9999	-10000	0	0
PIK3CA	0.012	0.016	-9999	-0.4	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.044	0.034	-9999	-0.43	3	3
VEGFR2 homodimer/VEGFA homodimer	0.043	0.036	-9999	-0.45	3	3
VEGFR2/3 heterodimer	0.029	0.031	-9999	-0.55	1	1
VEGFB	0.013	0	-9999	-10000	0	0
MAPK11	0.045	0.034	-9999	-0.48	1	1
VEGFR2 homodimer	0.029	0.029	-9999	-0.63	1	1
FLT1	0.013	0	-9999	-10000	0	0
NEDD4	0.014	0.001	-9999	-10000	0	0
MAPK3	0.024	0.049	-9999	-0.41	1	1
MAPK1	0.024	0.049	-9999	-0.41	1	1
VEGFA145/NRP2	0.017	0.039	-9999	-0.57	2	2
VEGFR1/2 heterodimer	0.031	0.025	-9999	-0.55	1	1
KDR	0.029	0.029	-9999	-0.63	1	1
VEGFA165/NRP1/VEGFR2 homodimer	0.045	0.035	-9999	-0.41	3	3
SRC	0.013	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.027	0.048	-9999	-0.42	1	1
PI3K	0.061	0.038	-9999	-0.48	1	1
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.038	0.035	-9999	-0.46	3	3
FES	0.043	0.036	-9999	-0.46	1	1
GAB1	0.054	0.031	-9999	-0.5	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.038	0.035	-9999	-0.46	3	3
CTNNB1	0.013	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
ARNT	0.012	0.016	-9999	-0.4	1	1
eNOS/Caveolin-1	0.06	0.041	-9999	-0.47	1	1
VEGFR2 homodimer/VEGFA homodimer/Yes	0.038	0.04	-9999	-0.52	3	3
PI3K/GAB1	0.071	0.033	-9999	-0.46	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.048	0.033	-9999	-0.44	1	1
PRKACA	0.013	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.032	0.041	-9999	-0.44	2	2
HSP90AA1	0.013	0	-9999	-10000	0	0
CDC42	0.044	0.035	-9999	-0.42	3	3
actin cytoskeleton reorganization	0.037	0.04	-9999	-0.45	4	4
PTK2	0.052	0.044	-9999	-0.67	1	1
EDG1	0.036	0.033	-9999	-0.42	3	3
mol:DAG	0.044	0.033	-9999	-0.42	3	3
CaM/Ca2+	0.046	0.031	-9999	-0.42	1	1
MAP2K3	0.047	0.033	-9999	-0.44	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.049	0.034	-9999	-0.47	1	1
PLCG1	0.044	0.033	-9999	-0.42	3	3
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.042	0.046	-9999	-0.42	6	6
IQGAP1	0.013	0	-9999	-10000	0	0
YES1	0.012	0.016	-9999	-0.4	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.038	0.035	-9999	-0.46	3	3
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.038	0.035	-9999	-0.46	3	3
cell migration	0.073	0.037	-9999	-0.53	1	1
mol:PI-3-4-5-P3	0.06	0.036	-9999	-0.45	1	1
FYN	0.013	0	-9999	-10000	0	0
VEGFB/NRP1	0.042	0.031	-9999	-0.43	1	1
mol:NO	0.058	0.039	-9999	-0.5	1	1
PXN	0.013	0	-9999	-10000	0	0
HRAS/GTP	-0.002	0.025	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.047	0.034	-9999	-0.47	1	1
VHL	0.013	0	-9999	-10000	0	0
ITGB3	0.008	0.043	-9999	-0.4	7	7
NOS3	0.06	0.043	-9999	-0.58	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	0.031	0.064	-9999	-0.44	10	10
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.047	0.031	-9999	-0.43	1	1
PRKCB	0.001	0.088	-9999	-0.43	1	1
VCL	0.013	0	-9999	-10000	0	0
VEGFA165/NRP1	0.038	0.033	-9999	-0.43	3	3
VEGFR1/2 heterodimer/VEGFA homodimer	0.038	0.035	-9999	-0.46	3	3
VEGFA165/NRP2	0.017	0.039	-9999	-0.57	2	2
MAPKKK cascade	0.061	0.03	-9999	-10000	0	0
NRP2	0.011	0.028	-9999	-0.4	3	3
VEGFC homodimer	0.006	0.051	-9999	-0.39	10	10
NCK1	0.013	0	-9999	-10000	0	0
ROCK1	0.012	0.016	-9999	-0.4	1	1
FAK1/Paxillin	0.057	0.042	-9999	-0.62	1	1
MAP3K13	0.044	0.034	-9999	-0.42	3	3
PDPK1	0.062	0.033	-9999	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 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
SMAD4	0.011	0.023	-9999	-0.4	2	2
SMAD2	0.012	0.012	-9999	-10000	0	0
SMAD3	0.033	0.016	-9999	-10000	0	0
SMAD3/SMAD4	0.039	0.016	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0.025	0.014	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.034	0.021	-9999	-0.38	1	1
PPM1A	0.013	0	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
SMAD2/SMAD4	0.018	0.016	-9999	-10000	0	0
MAP3K1	0.012	0.016	-9999	-0.4	1	1
TRAP-1/SMAD4	0.017	0.02	-9999	-10000	0	0
MAPK3	0.012	0.016	-9999	-0.4	1	1
MAPK1	0.012	0.016	-9999	-0.4	1	1
NUP214	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
KPNB1	0.013	0	-9999	-10000	0	0
TGFBRAP1	0.012	0.016	-9999	-0.4	1	1
UBE2I	0.013	0	-9999	-10000	0	0
NUP153	0.013	0.001	-9999	-10000	0	0
KPNA2	0.011	0.031	-9999	-0.75	1	1
PIAS4	0.013	0	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.019	0	-9999	-10000	0	0
ATM	0.012	0.016	-9999	-0.4	1	1
UBE2D3	0.013	0	-9999	-10000	0	0
PRKDC	0.011	0.031	-9999	-0.75	1	1
ATR	0.013	0	-9999	-10000	0	0
UBE2L3	0.013	0	-9999	-10000	0	0
FANCD2	0.021	0.016	-9999	-0.26	2	2
protein ubiquitination	0.03	0.041	-9999	-0.41	5	5
XRCC5	0.013	0	-9999	-10000	0	0
XRCC6	0.013	0	-9999	-10000	0	0
M/R/N Complex	0.025	0.01	-9999	-10000	0	0
MRE11A	0.013	0.001	-9999	-10000	0	0
DNA-PK	0.025	0.021	-9999	-0.49	1	1
FA complex/FANCD2/Ubiquitin	0.043	0.014	-9999	-10000	0	0
FANCF	0.013	0	-9999	-10000	0	0
BRCA1	0.013	0	-9999	-10000	0	0
CCNE1	0.006	0.068	-9999	-0.75	5	5
CDK2/Cyclin E1	0.014	0.053	-9999	-0.57	5	5
FANCG	0.011	0.031	-9999	-0.75	1	1
BRCA1/BACH1/BARD1	0.019	0	-9999	-10000	0	0
FANCE	0.013	0	-9999	-10000	0	0
FANCC	0.013	0	-9999	-10000	0	0
NBN	0.012	0.016	-9999	-0.4	1	1
FANCA	0.013	0	-9999	-10000	0	0
DNA repair	0.059	0.015	-9999	-10000	0	0
BRCA1/BARD1/ubiquitin	0.019	0	-9999	-10000	0	0
BARD1/DNA-PK	0.032	0.019	-9999	-0.45	1	1
FANCL	0.013	0	-9999	-10000	0	0
mRNA polyadenylation	-0.019	0	-9999	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.032	0.02	-9999	-0.29	2	2
BRCA1/BACH1/BARD1/TopBP1	0.026	0	-9999	-10000	0	0
BRCA1/BARD1/P53	0.032	0	-9999	-10000	0	0
BARD1/CSTF1/BRCA1	0.026	0	-9999	-10000	0	0
BRCA1/BACH1	0.013	0	-9999	-10000	0	0
BARD1	0.013	0	-9999	-10000	0	0
PCNA	0.013	0	-9999	-10000	0	0
BRCA1/BARD1/UbcH5C	0.026	0	-9999	-10000	0	0
BRCA1/BARD1/UbcH7	0.026	0	-9999	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.032	0	-9999	-10000	0	0
BARD1/DNA-PK/P53	0.037	0.018	-9999	-0.42	1	1
BRCA1/BARD1/Ubiquitin	0.019	0	-9999	-10000	0	0
BRCA1/BARD1/CTIP	0.029	0.017	-9999	-10000	0	0
FA complex	0.034	0.01	-9999	-10000	0	0
BARD1/EWS	0.019	0	-9999	-10000	0	0
RBBP8	0.017	0.023	-9999	-10000	0	0
TP53	0.013	0	-9999	-10000	0	0
TOPBP1	0.013	0	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	-0.031	0	-9999	-10000	0	0
BRCA1/BARD1	0.033	0.041	-9999	-0.42	5	5
CSTF1	0.013	0	-9999	-10000	0	0
BARD1/EWS-Fli1	0.009	0	-9999	-10000	0	0
CDK2	0.013	0	-9999	-10000	0	0
UniProt:Q9BZD1	0	0	-9999	-10000	0	0
RAD51	0.013	0	-9999	-10000	0	0
RAD50	0.013	0	-9999	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.019	0	-9999	-10000	0	0
EWSR1	0.013	0	-9999	-10000	0	0

×

Aurora C signaling

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
INCENP	0.013	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.023	0.018	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0	0.006	-9999	-10000	0	0
AURKB	0.013	0	-9999	-10000	0	0
AURKC	0.009	0.033	-9999	-0.4	4	4

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.02	0.061	-10000	0	-10000	0	0
CaM/Ca2+	0.009	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
AKT2	0.013	0	-10000	0	-10000	0	0
STXBP4	0.012	0.016	-10000	0	-0.4	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.018	0.069	0.27	6	-10000	0	6
YWHAZ	0.013	0	-10000	0	-10000	0	0
CALM1	0.013	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
TBC1D4	0.019	0.012	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
SNARE/Synip	0.025	0.01	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
ASIP	-0.002	0.086	-10000	0	-0.75	8	8
PRKCI	0.011	0.023	-10000	0	-0.4	2	2
AS160/CaM/Ca2+	0.009	0	-10000	0	-10000	0	0
RHOQ	0.013	0	-10000	0	-10000	0	0
GYS1	0.026	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
TRIP10	0.013	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.017	0	-10000	0	-10000	0	0
AS160/14-3-3	0.038	0.012	-10000	0	-10000	0	0
VAMP2	0.013	0	-10000	0	-10000	0	0
SLC2A4	0.018	0.074	0.28	6	-10000	0	6
STX4	0.013	0	-10000	0	-10000	0	0
GSK3B	0.022	0	-10000	0	-10000	0	0
SFN	0.011	0.023	-10000	0	-0.4	2	2
LNPEP	0.012	0.001	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0

×

mTOR signaling 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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.013	0	-10000	0	-10000	0	0
mol:PIP3	0	0.015	0.23	2	-10000	0	2
FRAP1	0.013	0.007	-10000	0	-10000	0	0
AKT1	0.023	0.014	0.2	2	-10000	0	2
INSR	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.008	0	-10000	0	-10000	0	0
mol:GTP	0.03	0.008	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.011	-10000	0	-0.25	1	1
TSC2	0.012	0	-10000	0	-10000	0	0
RHEB/GDP	0	0.006	-10000	0	-10000	0	0
TSC1	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.015	0	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.013	-10000	0	-0.29	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.013	0	-10000	0	-10000	0	0
RPS6KB1	0.023	0.016	-10000	0	-0.3	1	1
MAP3K5	0.009	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.009	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-10000	0	0
EIF4B	0.027	0.015	-10000	0	-0.26	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.03	0.019	-10000	0	-0.32	1	1
eIF4E/eIF4G1/eIF4A1	0	0.006	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.023	0.008	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.025	0.009	0.15	2	-10000	0	2
FKBP1A	0.013	0	-10000	0	-10000	0	0
RHEB/GTP	0	0.006	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-10000	0	0
FKBP12/Rapamycin	0.01	0.001	-10000	0	-10000	0	0
PDPK1	0.019	0.013	-10000	0	-10000	0	0
EIF4E	0.011	0.023	-10000	0	-0.4	2	2
ASK1/PP5C	0.021	0.004	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.014	0.023	-10000	0	-0.4	2	2
TSC1/TSC2	0.033	0.009	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RPS6	0.011	0.031	-10000	0	-0.75	1	1
PPP5C	0.013	0	-10000	0	-10000	0	0
EIF4G1	0.013	0	-10000	0	-10000	0	0
IRS1	0.007	0.001	-10000	0	-10000	0	0
INS	0	0	-10000	0	-10000	0	0
PTEN	0.011	0.023	-10000	0	-0.39	2	2
PDK2	0.019	0.015	0.21	2	-10000	0	2
EIF4EBP1	0.01	0.023	-10000	0	-0.28	4	4
PIK3CA	0.012	0.016	-10000	0	-0.4	1	1
PPP2R5D	0.017	0.006	-10000	0	-10000	0	0
peptide biosynthetic process	0.014	0.019	-10000	0	-0.46	1	1
RHEB	0.013	0	-10000	0	-10000	0	0
EIF4A1	0.013	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	2	-10000	0	2
EEF2	0.014	0.019	-10000	0	-0.46	1	1
eIF4E/4E-BP1	0.016	0.024	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.019	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0.03	0.009	-9999	-10000	0	0
CDKN1B	0.03	0.011	-9999	-10000	0	0
CDKN1A	0.03	0.014	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.011	0.031	-9999	-0.75	1	1
FOXO3	0.03	0.011	-9999	-10000	0	0
AKT1	0.025	0.012	-9999	-10000	0	0
BAD	0.012	0.016	-9999	-0.4	1	1
AKT3	0.011	0.034	-9999	-0.27	9	9
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.03	0.011	-9999	-10000	0	0
AKT1/ASK1	0.03	0.011	-9999	-10000	0	0
BAD/YWHAZ	0.025	0.01	-9999	-10000	0	0
RICTOR	0.009	0.036	-9999	-0.4	5	5
RAF1	0.013	0	-9999	-10000	0	0
JNK cascade	-0.029	0.011	-9999	-10000	0	0
TSC1	0.03	0.011	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
AKT1/RAF1	0.031	0.012	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
mol:GDP	0.025	0.012	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.03	0.011	-9999	-10000	0	0
YWHAQ	0.013	0	-9999	-10000	0	0
TBC1D4	0.019	0.009	-9999	-10000	0	0
MAP3K5	0.013	0	-9999	-10000	0	0
MAPKAP1	0.013	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.037	0.009	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0
AKT1S1	0.03	0.011	-9999	-10000	0	0
CASP9	0.03	0.011	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.036	0.011	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.026	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
AKT2/p21CIP1	0.033	0.013	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0.004	-9999	-10000	0	0
CHUK	0.03	0.011	-9999	-10000	0	0
BAD/BCL-XL	0.042	0.013	-9999	-10000	0	0
mTORC2	0.014	0.019	-9999	-10000	0	0
AKT2	0.015	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.049	0.012	-9999	-10000	0	0
PDPK1	0.013	0	-9999	-10000	0	0
MDM2	0.03	0.014	-9999	-10000	0	0
MAPKKK cascade	-0.031	0.011	-9999	-10000	0	0
MDM2/Cbp/p300	0.042	0.013	-9999	-10000	0	0
TSC1/TSC2	0.034	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.013	-9999	-10000	0	0
glucose import	-0.002	0.069	-9999	-10000	0	0
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.026	0.009	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.002	0.07	-9999	-10000	0	0
GSK3A	0.03	0.011	-9999	-10000	0	0
FOXO1	0.03	0.014	-9999	-10000	0	0
GSK3B	0.03	0.011	-9999	-10000	0	0
SFN	0.011	0.023	-9999	-0.4	2	2
G1/S transition of mitotic cell cycle	0.034	0.011	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.041	0.01	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
KPNA1	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
RHEB	0.013	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.002	0.02	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.039	0.024	-9999	-10000	0	0
SUMO1	0.011	0.023	-9999	-0.4	2	2
ZFPM1	-0.002	0.1	-9999	-0.75	12	12
NPC/RanGAP1/SUMO1/Ubc9	0.017	0.014	-9999	-10000	0	0
FKBP3	0.011	0.023	-9999	-0.4	2	2
Histones	0.04	0.013	-9999	-10000	0	0
YY1/LSF	0.018	0.044	-9999	-10000	0	0
SMG5	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.028	0.019	-9999	-10000	0	0
I kappa B alpha/HDAC1	0.028	0.014	-9999	-10000	0	0
SAP18	0.013	0	-9999	-10000	0	0
RELA	0.031	0.019	-9999	-10000	0	0
HDAC1/Smad7	0.025	0.01	-9999	-10000	0	0
RANGAP1	0.011	0.031	-9999	-0.75	1	1
HDAC3/TR2	0.028	0.014	-9999	-10000	0	0
NuRD/MBD3 Complex	0.04	0.01	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.034	0.017	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.005	0.054	-9999	-0.4	11	11
GATA1	0.008	0.006	-9999	-10000	0	0
Mad/Max	0.018	0.016	-9999	-0.27	2	2
NuRD/MBD3 Complex/GATA1/Fog1	0.044	0.028	-9999	-10000	0	0
RBBP7	0.013	0	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
RBBP4	0.013	0	-9999	-10000	0	0
MAX	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NFKBIA	0.023	0.015	-9999	-10000	0	0
KAT2B	-0.005	0.083	-9999	-0.4	27	27
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.037	0	-9999	-10000	0	0
SIN3 complex	0.032	0	-9999	-10000	0	0
SMURF1	0.013	0	-9999	-10000	0	0
CHD3	0.013	0	-9999	-10000	0	0
SAP30	0.013	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.013	0	-9999	-10000	0	0
YY1/HDAC3	0.028	0.039	-9999	-10000	0	0
YY1/HDAC2	0.018	0.043	-9999	-10000	0	0
YY1/HDAC1	0.018	0.043	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.04	0	-9999	-10000	0	0
PPARG	0.03	0.029	-9999	-10000	0	0
HDAC8/hEST1B	0.026	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.027	0.016	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.025	0.01	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.043	0.01	-9999	-10000	0	0
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	0.023	0.015	-9999	-10000	0	0
HDAC2	0.013	0	-9999	-10000	0	0
YY1	0.015	0.051	-9999	-10000	0	0
HDAC8	0.013	0	-9999	-10000	0	0
SMAD7	0.012	0.016	-9999	-0.4	1	1
NCOR2	0.012	0.016	-9999	-0.4	1	1
MXD1	0.011	0.023	-9999	-0.4	2	2
STAT3	0.022	0	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.025	0.041	-9999	-10000	0	0
YY1/SAP30/HDAC1	0.025	0.04	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.022	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.015	-9999	-10000	0	0
histone deacetylation	0.04	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.034	0.013	-9999	-10000	0	0
nuclear export	-0.025	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GATAD2B	0.013	0	-9999	-10000	0	0
GATAD2A	0.013	0	-9999	-10000	0	0
GATA2/HDAC3	0.024	0.033	-9999	-0.33	1	1
GATA1/HDAC1	0.015	0.004	-9999	-10000	0	0
GATA1/HDAC3	0.025	0.014	-9999	-10000	0	0
CHD4	0.013	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	0.016	0.026	-9999	-10000	0	0
SIN3/HDAC complex/Mad/Max	0.04	0.01	-9999	-10000	0	0
NuRD Complex	0.047	0.01	-9999	-10000	0	0
positive regulation of chromatin silencing	0.039	0.012	-9999	-10000	0	0
SIN3B	0.013	0	-9999	-10000	0	0
MTA2	0.013	0	-9999	-10000	0	0
SIN3A	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC1	0.026	0.018	-9999	-0.26	2	2
HDAC complex	0.032	0	-9999	-10000	0	0
GATA1/Fog1	0.004	0.081	-9999	-0.57	12	12
FKBP25/HDAC1/HDAC2	0.025	0.014	-9999	-10000	0	0
TNF	0.009	0.036	-9999	-0.4	5	5
negative regulation of cell growth	0.04	0.01	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.04	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.029	0.012	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.034	0.025	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.039	0	-9999	-10000	0	0
TFCP2	0.012	0.016	-9999	-0.4	1	1
NR2C1	0.013	0	-9999	-10000	0	0
MBD3	0.011	0.035	-9999	-0.57	2	2
MBD2	0.013	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.019	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.023	0.001	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.038	0.023	-9999	-10000	0	0
NFKBIA	0.021	0.026	-9999	-10000	0	0
MAPK14	0.013	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.024	0	-9999	-10000	0	0
ARRB2	0.015	0	-9999	-10000	0	0
REL	0.012	0.001	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.024	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.024	0	-9999	-10000	0	0
PIK3CA	0.012	0.016	-9999	-0.4	1	1
NF kappa B1 p50 dimer	0.018	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
NFKB1	0.019	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.027	0.025	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.041	0.023	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
PI3K	0.018	0.011	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.027	0.025	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
SYK	0.013	0	-9999	-10000	0	0
I kappa B alpha/PIK3R1	0.027	0.025	-9999	-10000	0	0
cell death	0.039	0.022	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.023	0.001	-9999	-10000	0	0
LCK	0.001	0.089	-9999	-0.68	10	10
BCL3	0.013	0	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.005	-9999	-10000	0	0
MDM2/SUMO1	0.026	0.024	-9999	-0.35	2	2
HDAC4	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0.005	-9999	-10000	0	0
SUMO1	0.011	0.023	-9999	-0.4	2	2
NPC/RanGAP1/SUMO1	0.014	0.015	-9999	-0.2	3	3
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.022	0.013	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
SUMO1/HDAC4	0.026	0.018	-9999	-0.26	2	2
SUMO1/HDAC1	0.026	0.018	-9999	-0.26	2	2
RANGAP1	0.011	0.031	-9999	-0.75	1	1
MDM2/SUMO1/SUMO1	0.031	0.019	-9999	-0.4	1	1
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	0.014	-9999	-0.18	3	3
Ran/GTP	0.023	0.013	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.012	0.016	-9999	-0.4	1	1
UBE2I	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.028	0.012	-9999	-10000	0	0
NPC	0.007	0	-9999	-10000	0	0
PIAS2	0.013	0.001	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	0.025	0.01	-9999	-10000	0	0
E-cadherin/beta catenin	0.019	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
JUP	0.012	0.016	-9999	-0.4	1	1
CDH1	0.013	0	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	-0.002	0.024	-9999	-0.35	3	3
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.018	0	-9999	-10000	0	0
AP2	0.018	0.011	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.018	0	-9999	-10000	0	0
CLTB	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.022	0	-9999	-10000	0	0
CD4	0.001	0.066	-9999	-0.4	17	17
CLTA	0.013	0	-9999	-10000	0	0
mol:GTP	0.001	0	-9999	-10000	0	0
ARFGAP1	0.007	0.035	-9999	-0.48	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0.015	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.021	0.026	-9999	-0.39	2	2
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.013	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0.005	0.026	-9999	-0.36	3	3
AP2M1	0.013	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.014	0	-9999	-10000	0	0
Rac/GTP	0.01	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.021	0.027	-9999	-0.43	2	2
ARFIP2	0.011	0	-9999	-10000	0	0
COPA	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.022	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.009	0	-9999	-10000	0	0
GGA3	0.013	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.017	0	-9999	-10000	0	0
AP2A1	0.012	0.016	-9999	-0.4	1	1
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.022	0.015	-9999	-10000	0	0
ARF1/GDP/Membrin	0.017	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.016	0	-9999	-10000	0	0
CYTH2	0.013	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.018	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.009	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.025	0.032	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.007	0.035	-9999	-0.48	3	3
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.019	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.007	0.035	-9999	-0.48	3	3
GOSR2	0.013	0	-9999	-10000	0	0
USO1	0.013	0	-9999	-10000	0	0
GBF1	0.013	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0.018	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.019	0.041	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.019	-9999	-9999
FBXW11	0.013	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.013	-9999	-9999
CHUK	0.013	-9999	-9999
NF kappa B2 p100/RelB	0.037	-9999	-9999
NFKB1	0.013	-9999	-9999
MAP3K14	0.013	-9999	-9999
NF kappa B1 p50/RelB	0.019	-9999	-9999
RELB	0.013	-9999	-9999
NFKB2	0.013	-9999	-9999
NF kappa B2 p52/RelB	0.017	-9999	-9999
regulation of B cell activation	0.017	-9999	-9999

pid_entity	TCGA.WS.AB45	TCGA.T9.A92H	TCGA.SS.A7HO	TCGA.RU.A8FL
109_MAP3K5	0.045	0.045	-0.19	-0.19
47_PPARGC1A	0.013	0.013	0.013	0.013
105_BMP4	0.013	0.013	0.013	0.013
105_BMP6	0.013	0.013	0.013	0.013
105_BMP7	-0.39	0.013	0.013	-0.75
105_BMP2	0.013	0.013	-0.39	-0.39
131_RELN/VLDLR	-0.44	-0.63	-0.45	-0.63
30_TGFB1/TGF beta receptor Type II	0.012	0.012	0.017	0.018
84_STAT5B	-0.039	0.04	-0.033	-0.021
84_STAT5A	-0.039	0.04	-0.033	-0.021