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

Pathway.Name	Avg.Num.Perturbations
IL23-mediated signaling events	95
Ephrin A reverse signaling	92
IL4-mediated signaling events	83
Signaling mediated by p38-alpha and p38-beta	80
Wnt signaling	73
amb2 Integrin signaling	64
Syndecan-4-mediated signaling events	64
Noncanonical Wnt signaling pathway	62
Glypican 1 network	61
IL12-mediated signaling events	56

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
IL23-mediated signaling events	0.1655	95	5711	60	-0.54	0.011	1000	-1000	-0.16	-1000
Ephrin A reverse signaling	0.1603	92	649	7	-0.097	0	1000	-1000	-0.023	-1000
IL4-mediated signaling events	0.1446	83	7586	91	-0.67	0.59	1000	-1000	-0.17	-1000
Signaling mediated by p38-alpha and p38-beta	0.1394	80	3559	44	-0.19	0.011	1000	-1000	-0.045	-1000
Wnt signaling	0.1272	73	512	7	-0.14	0.004	1000	-1000	-0.028	-1000
amb2 Integrin signaling	0.1115	64	5300	82	-0.16	0.015	1000	-1000	-0.066	-1000
Syndecan-4-mediated signaling events	0.1115	64	4298	67	-0.18	0.038	1000	-1000	-0.071	-1000
Noncanonical Wnt signaling pathway	0.1080	62	1612	26	-0.14	0.011	1000	-1000	-0.046	-1000
Glypican 1 network	0.1063	61	2928	48	-0.2	0.015	1000	-1000	-0.038	-1000
IL12-mediated signaling events	0.0976	56	4908	87	-0.29	0.069	1000	-1000	-0.13	-1000
FOXA2 and FOXA3 transcription factor networks	0.0976	56	2583	46	-0.43	0.017	1000	-1000	-0.12	-1000
EGFR-dependent Endothelin signaling events	0.0976	56	1188	21	-0.18	0.016	1000	-1000	-0.055	-1000
TCR signaling in naïve CD8+ T cells	0.0958	55	5196	93	-0.12	0.056	1000	-1000	-0.073	-1000
Syndecan-1-mediated signaling events	0.0923	53	1821	34	-0.14	0.011	1000	-1000	-0.051	-1000
BCR signaling pathway	0.0906	52	5223	99	-0.17	0.014	1000	-1000	-0.08	-1000
Signaling events mediated by the Hedgehog family	0.0889	51	2656	52	-0.13	0.077	1000	-1000	-0.046	-1000
Reelin signaling pathway	0.0871	50	2817	56	-0.12	0.021	1000	-1000	-0.064	-1000
Endothelins	0.0854	49	4781	96	-0.15	0.011	1000	-1000	-0.078	-1000
HIF-1-alpha transcription factor network	0.0836	48	3688	76	-0.32	0.016	1000	-1000	-0.19	-1000
Fc-epsilon receptor I signaling in mast cells	0.0819	47	4612	97	-0.14	0.029	1000	-1000	-0.07	-1000
TCGA08_retinoblastoma	0.0819	47	379	8	-0.069	0.027	1000	-1000	-0.021	-1000
BMP receptor signaling	0.0801	46	3772	81	-0.16	0.032	1000	-1000	-0.084	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0767	44	3057	68	-0.31	0.12	1000	-1000	-0.13	-1000
Ephrin B reverse signaling	0.0749	43	2083	48	-0.14	0.044	1000	-1000	-0.058	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0732	42	1438	34	-0.057	0.011	1000	-1000	-0.04	-1000
TCGA08_p53	0.0732	42	296	7	-0.05	0.03	1000	-1000	-0.013	-1000
Calcium signaling in the CD4+ TCR pathway	0.0732	42	1323	31	-0.2	0.011	1000	-1000	-0.057	-1000
p75(NTR)-mediated signaling	0.0679	39	4988	125	-0.18	0.031	1000	-1000	-0.093	-1000
Glucocorticoid receptor regulatory network	0.0679	39	4448	114	-0.34	0.21	1000	-1000	-0.063	-1000
Thromboxane A2 receptor signaling	0.0645	37	3984	105	-0.18	0.042	1000	-1000	-0.056	-1000
Syndecan-2-mediated signaling events	0.0645	37	2595	69	-0.11	0.023	1000	-1000	-0.028	-1000
Osteopontin-mediated events	0.0627	36	1397	38	-0.16	0.011	1000	-1000	-0.094	-1000
Signaling events regulated by Ret tyrosine kinase	0.0627	36	3016	82	-0.1	0.011	1000	-1000	-0.073	-1000
IL1-mediated signaling events	0.0592	34	2150	62	-0.1	0.019	1000	-1000	-0.075	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0592	34	4111	120	-0.18	0.14	1000	-1000	-0.063	-1000
Visual signal transduction: Cones	0.0575	33	1272	38	-0.052	0.007	1000	-1000	-0.051	-1000
Effects of Botulinum toxin	0.0575	33	859	26	-0.12	0.01	1000	-1000	-0.054	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0575	33	2632	78	-0.083	0.054	1000	-1000	-0.077	-1000
LPA receptor mediated events	0.0557	32	3311	102	-0.11	0.012	1000	-1000	-0.086	-1000
JNK signaling in the CD4+ TCR pathway	0.0540	31	534	17	-0.046	0.011	1000	-1000	-0.043	-1000
Glypican 2 network	0.0540	31	127	4	-0.012	-1000	1000	-1000	-0.01	-1000
Arf6 signaling events	0.0523	30	1874	62	-0.18	0.024	1000	-1000	-0.046	-1000
Caspase cascade in apoptosis	0.0505	29	2161	74	-0.085	0.039	1000	-1000	-0.047	-1000
Cellular roles of Anthrax toxin	0.0505	29	1139	39	-0.044	0.011	1000	-1000	-0.021	-1000
Integrins in angiogenesis	0.0505	29	2462	84	-0.16	0.019	1000	-1000	-0.076	-1000
IL27-mediated signaling events	0.0505	29	1483	51	-0.2	0.025	1000	-1000	-0.051	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0505	29	2635	88	-0.12	0.045	1000	-1000	-0.096	-1000
a4b1 and a4b7 Integrin signaling	0.0488	28	141	5	-0.024	-0.004	1000	-1000	-0.02	-1000
Canonical Wnt signaling pathway	0.0488	28	1451	51	-0.18	0.089	1000	-1000	-0.066	-1000
Visual signal transduction: Rods	0.0488	28	1497	52	-0.12	0.011	1000	-1000	-0.077	-1000
Signaling events mediated by PTP1B	0.0470	27	2110	76	-0.18	0.029	1000	-1000	-0.068	-1000
FAS signaling pathway (CD95)	0.0470	27	1303	47	-0.16	0.014	1000	-1000	-0.042	-1000
Presenilin action in Notch and Wnt signaling	0.0453	26	1590	61	-0.18	0.06	1000	-1000	-0.065	-1000
Retinoic acid receptors-mediated signaling	0.0453	26	1518	58	-0.14	0.019	1000	-1000	-0.068	-1000
Ras signaling in the CD4+ TCR pathway	0.0453	26	450	17	-0.051	0.01	1000	-1000	-0.04	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0436	25	1350	54	-0.13	0.022	1000	-1000	-0.084	-1000
Plasma membrane estrogen receptor signaling	0.0436	25	2186	86	-0.071	0.02	1000	-1000	-0.072	-1000
EPHB forward signaling	0.0418	24	2084	85	-0.11	0.061	1000	-1000	-0.079	-1000
IL6-mediated signaling events	0.0418	24	1802	75	-0.11	0.042	1000	-1000	-0.065	-1000
LPA4-mediated signaling events	0.0383	22	272	12	-0.057	0.015	1000	-1000	-0.027	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0383	22	847	37	-0.12	0.025	1000	-1000	-0.042	-1000
Nongenotropic Androgen signaling	0.0366	21	1139	52	-0.052	0.012	1000	-1000	-0.053	-1000
Coregulation of Androgen receptor activity	0.0348	20	1562	76	-0.16	0.04	1000	-1000	-0.034	-1000
S1P1 pathway	0.0348	20	749	36	-0.1	0.011	1000	-1000	-0.061	-1000
IGF1 pathway	0.0348	20	1191	57	-0.071	0.023	1000	-1000	-0.079	-1000
PDGFR-alpha signaling pathway	0.0331	19	856	44	-0.066	0.017	1000	-1000	-0.059	-1000
Class I PI3K signaling events	0.0314	18	1334	73	-0.11	0.022	1000	-1000	-0.059	-1000
IL2 signaling events mediated by STAT5	0.0296	17	384	22	-0.049	0.015	1000	-1000	-0.056	-1000
Regulation of Telomerase	0.0296	17	1742	102	-0.18	0.035	1000	-1000	-0.1	-1000
FOXM1 transcription factor network	0.0279	16	863	51	-0.12	0.074	1000	-1000	-0.19	-1000
ErbB2/ErbB3 signaling events	0.0261	15	994	65	-0.068	0.016	1000	-1000	-0.061	-1000
ErbB4 signaling events	0.0261	15	1092	69	-0.16	0.036	1000	-1000	-0.08	-1000
IFN-gamma pathway	0.0261	15	1023	68	-0.063	0.02	1000	-1000	-0.09	-1000
Nectin adhesion pathway	0.0261	15	955	63	-0.031	0.021	1000	-1000	-0.068	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0261	15	515	33	-0.076	0.029	1000	-1000	-0.037	-1000
Signaling events mediated by PRL	0.0261	15	521	34	-0.025	0.026	1000	-1000	-0.032	-1000
S1P4 pathway	0.0261	15	382	25	-0.044	0.015	1000	-1000	-0.033	-1000
Regulation of nuclear SMAD2/3 signaling	0.0244	14	1920	136	-0.081	0.038	1000	-1000	-0.063	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0244	14	419	28	-0.044	0.018	1000	-1000	-0.032	-1000
Signaling events mediated by HDAC Class III	0.0244	14	573	40	-0.046	0.017	1000	-1000	-0.026	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0244	14	751	52	-0.13	0.034	1000	-1000	-0.04	-1000
PLK2 and PLK4 events	0.0226	13	39	3	-0.004	0.009	1000	-1000	-0.015	-1000
Ceramide signaling pathway	0.0226	13	1029	76	-0.18	0.059	1000	-1000	-0.053	-1000
Syndecan-3-mediated signaling events	0.0226	13	484	35	-0.11	0.031	1000	-1000	-0.044	-1000
Regulation of p38-alpha and p38-beta	0.0226	13	723	54	-0.11	0.027	1000	-1000	-0.057	-1000
Paxillin-dependent events mediated by a4b1	0.0209	12	438	36	-0.024	0.02	1000	-1000	-0.059	-1000
IL2 signaling events mediated by PI3K	0.0209	12	719	58	-0.051	0.027	1000	-1000	-0.069	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0209	12	558	45	-0.062	0.039	1000	-1000	-0.08	-1000
PDGFR-beta signaling pathway	0.0209	12	1192	97	-0.096	0.032	1000	-1000	-0.077	-1000
Regulation of Androgen receptor activity	0.0209	12	903	70	-0.19	0.027	1000	-1000	-0.059	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0192	11	939	85	-0.036	0.028	1000	-1000	-0.059	-1000
S1P5 pathway	0.0192	11	191	17	-0.044	0.011	1000	-1000	-0.031	-1000
Signaling mediated by p38-gamma and p38-delta	0.0192	11	176	15	-0.023	0.017	1000	-1000	-0.031	-1000
S1P3 pathway	0.0192	11	483	42	-0.043	0.018	1000	-1000	-0.046	-1000
Class IB PI3K non-lipid kinase events	0.0192	11	33	3	0	0	1000	-1000	-0.01	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0174	10	876	83	-0.14	0.045	1000	-1000	-0.065	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0174	10	281	27	-0.018	0.015	1000	-1000	-0.047	-1000
Signaling events mediated by HDAC Class II	0.0157	9	739	75	-0.038	0.026	1000	-1000	-0.038	-1000
Hedgehog signaling events mediated by Gli proteins	0.0157	9	604	65	-0.043	0.035	1000	-1000	-0.055	-1000
Insulin Pathway	0.0157	9	691	74	-0.12	0.027	1000	-1000	-0.079	-1000
Rapid glucocorticoid signaling	0.0157	9	188	20	-0.021	0.011	1000	-1000	-0.018	-1000
Aurora B signaling	0.0157	9	643	67	-0.11	0.028	1000	-1000	-0.058	-1000
BARD1 signaling events	0.0139	8	488	57	-0.043	0.048	1000	-1000	-0.057	-1000
TCGA08_rtk_signaling	0.0139	8	232	26	-0.044	0.035	1000	-1000	-0.018	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0139	8	650	74	-0.18	0.051	1000	-1000	-0.082	-1000
VEGFR1 specific signals	0.0139	8	485	56	-0.018	0.03	1000	-1000	-0.049	-1000
p38 MAPK signaling pathway	0.0139	8	393	44	-0.053	0.02	1000	-1000	-0.06	-1000
EPO signaling pathway	0.0122	7	438	55	-0.025	0.041	1000	-1000	-0.078	-1000
Canonical NF-kappaB pathway	0.0105	6	234	39	-0.016	0.053	1000	-1000	-0.069	-1000
Aurora A signaling	0.0105	6	369	60	-0.051	0.029	1000	-1000	-0.025	-1000
Arf6 downstream pathway	0.0105	6	258	43	-0.041	0.025	1000	-1000	-0.044	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0105	6	817	125	-0.043	0.055	1000	-1000	-0.08	-1000
Aurora C signaling	0.0087	5	37	7	-0.01	0.011	1000	-1000	-0.032	-1000
HIF-2-alpha transcription factor network	0.0087	5	252	43	-0.08	0.082	1000	-1000	-0.077	-1000
Signaling events mediated by HDAC Class I	0.0087	5	596	104	-0.022	0.04	1000	-1000	-0.065	-1000
Atypical NF-kappaB pathway	0.0087	5	159	31	-0.032	0.028	1000	-1000	-0.037	-1000
E-cadherin signaling in the nascent adherens junction	0.0087	5	448	76	-0.043	0.044	1000	-1000	-0.078	-1000
mTOR signaling pathway	0.0070	4	233	53	-0.006	0.025	1000	-1000	-0.054	-1000
Class I PI3K signaling events mediated by Akt	0.0070	4	290	68	-0.031	0.041	1000	-1000	-0.045	-1000
TRAIL signaling pathway	0.0070	4	220	48	-0.016	0.037	1000	-1000	-0.063	-1000
ceramide signaling pathway	0.0070	4	214	49	-0.016	0.029	1000	-1000	-0.057	-1000
FoxO family signaling	0.0070	4	267	64	-0.083	0.098	1000	-1000	-0.079	-1000
Arf6 trafficking events	0.0070	4	304	71	-0.039	0.027	1000	-1000	-0.069	-1000
PLK1 signaling events	0.0052	3	271	85	-0.007	0.029	1000	-1000	-0.041	-1000
Circadian rhythm pathway	0.0035	2	61	22	-0.011	0.036	1000	-1000	-0.044	-1000
Insulin-mediated glucose transport	0.0035	2	84	32	0	0.033	1000	-1000	-0.046	-1000
E-cadherin signaling in keratinocytes	0.0035	2	111	43	-0.032	0.037	1000	-1000	-0.048	-1000
Arf1 pathway	0.0035	2	140	54	-0.014	0.02	1000	-1000	-0.028	-1000
Alternative NF-kappaB pathway	0.0035	2	28	13	0	0.029	1000	-1000	-0.04	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0017	1	44	23	0.005	0.034	1000	-1000	-0.044	-1000
E-cadherin signaling events	0.0017	1	5	5	0.01	0.022	1000	-1000	-0.022	-1000
Total	NA	3267	188777	7203	-14	-1000	131000	-131000	-7.9	-131000

IL23-mediated signaling events

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
CCL2	-0.43	0.54	-10000	0	-1.2	144	144
IL23A	-0.44	0.55	-10000	0	-1.2	139	139
NF kappa B1 p50/RelA/I kappa B alpha	-0.47	0.5	-10000	0	-1.2	163	163
positive regulation of T cell mediated cytotoxicity	-0.48	0.62	-10000	0	-1.3	154	154
ITGA3	-0.41	0.52	-10000	0	-1.2	134	134
IL17F	-0.29	0.34	-10000	0	-0.72	156	156
IL12B	-0.018	0.082	-10000	0	-0.48	15	15
STAT1 (dimer)	-0.46	0.59	-10000	0	-1.3	153	153
CD4	-0.42	0.52	-10000	0	-1.1	151	151
IL23	-0.42	0.52	-10000	0	-1.2	139	139
IL23R	-0.1	0.3	-10000	0	-1.4	26	26
IL1B	-0.46	0.58	-10000	0	-1.3	146	146
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.54	0.61	-10000	0	-1.2	205	205
TYK2	-0.002	0.034	-10000	0	-0.62	1	1
STAT4	-0.028	0.14	-10000	0	-0.56	40	40
STAT3	0.011	0.002	-10000	0	-10000	0	0
IL18RAP	-0.034	0.15	-10000	0	-0.55	45	45
IL12RB1	-0.048	0.16	-10000	0	-0.57	48	48
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
IL12Rbeta1/TYK2	-0.036	0.12	-10000	0	-0.43	49	49
IL23R/JAK2	-0.12	0.3	-10000	0	-1.4	25	25
positive regulation of chronic inflammatory response	-0.48	0.62	-10000	0	-1.3	154	154
natural killer cell activation	0.008	0.017	0.069	31	-10000	0	31
JAK2	-0.02	0.11	-10000	0	-0.57	21	21
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
NFKB1	0.008	0.025	-10000	0	-0.59	1	1
RELA	0.009	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.4	0.49	-10000	0	-1.1	139	139
ALOX12B	-0.46	0.56	-10000	0	-1.2	168	168
CXCL1	-0.42	0.54	-10000	0	-1.2	142	142
T cell proliferation	-0.48	0.62	-10000	0	-1.3	154	154
NFKBIA	0.009	0.004	-10000	0	-10000	0	0
IL17A	-0.25	0.3	-10000	0	-0.6	153	153
PI3K	-0.48	0.51	-10000	0	-1.2	164	164
IFNG	-0.018	0.05	0.13	19	-0.12	48	67
STAT3 (dimer)	-0.47	0.48	-10000	0	-1.1	174	174
IL18R1	-0.014	0.12	-10000	0	-0.55	25	25
IL23/IL23R/JAK2/TYK2/SOCS3	-0.24	0.32	-10000	0	-0.73	105	105
IL18/IL18R	-0.025	0.14	-10000	0	-0.38	61	61
macrophage activation	-0.023	0.018	-10000	0	-0.045	128	128
TNF	-0.44	0.56	-10000	0	-1.3	141	141
STAT3/STAT4	-0.49	0.52	-10000	0	-1.2	160	160
STAT4 (dimer)	-0.47	0.6	-10000	0	-1.3	157	157
IL18	0.002	0.069	-10000	0	-0.54	9	9
IL19	-0.41	0.51	-10000	0	-1.1	145	145
STAT5A (dimer)	-0.46	0.59	-10000	0	-1.3	153	153
STAT1	0.006	0.052	-10000	0	-0.5	6	6
SOCS3	-0.002	0.08	-10000	0	-0.49	15	15
CXCL9	-0.47	0.58	-10000	0	-1.2	168	168
MPO	-0.44	0.54	-10000	0	-1.2	162	162
positive regulation of humoral immune response	-0.48	0.62	-10000	0	-1.3	154	154
IL23/IL23R/JAK2/TYK2	-0.53	0.75	-10000	0	-1.5	153	153
IL6	-0.48	0.58	-10000	0	-1.3	163	163
STAT5A	0.011	0	-10000	0	-10000	0	0
IL2	0.004	0.03	-10000	0	-0.46	2	2
positive regulation of tyrosine phosphorylation of STAT protein	0.008	0.017	0.069	31	-10000	0	31
CD3E	-0.42	0.53	-10000	0	-1.2	142	142
keratinocyte proliferation	-0.48	0.62	-10000	0	-1.3	154	154
NOS2	-0.48	0.58	-10000	0	-1.2	171	171

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.062	0.14	-9999	-0.32	129	129
EFNA5	-0.097	0.22	-9999	-0.52	118	118
FYN	-0.053	0.14	-9999	-0.29	131	131
neuron projection morphogenesis	-0.062	0.14	-9999	-0.32	129	129
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.062	0.14	-9999	-0.32	129	129
EPHA5	-0.004	0.069	-9999	-0.46	13	13

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.52	0.56	-10000	0	-1.3	159	159
STAT6 (cleaved dimer)	-0.57	0.55	-10000	0	-1.2	209	209
IGHG1	-0.16	0.18	-10000	0	-0.56	4	4
IGHG3	-0.5	0.54	-10000	0	-1.2	188	188
AKT1	-0.24	0.29	-10000	0	-0.76	69	69
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.19	0.26	-10000	0	-0.73	53	53
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.24	0.28	-10000	0	-0.72	66	66
THY1	-0.52	0.56	-10000	0	-1.3	162	162
MYB	0.002	0.074	-10000	0	-0.58	9	9
HMGA1	0.006	0.056	-10000	0	-0.54	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.32	0.35	-10000	0	-0.8	128	128
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.25	0.29	-10000	0	-0.73	70	70
SP1	0.015	0.025	-10000	0	-0.58	1	1
INPP5D	-0.015	0.12	-10000	0	-0.58	26	26
SOCS5	0.026	0.016	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.54	0.58	-10000	0	-1.3	176	176
SOCS1	-0.35	0.36	-10000	0	-0.81	142	142
SOCS3	-0.26	0.31	-10000	0	-0.83	70	70
FCER2	-0.51	0.56	-10000	0	-1.3	155	155
PARP14	0.009	0.021	-10000	0	-0.46	1	1
CCL17	-0.56	0.61	-10000	0	-1.3	173	173
GRB2	0.011	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.2	0.23	-10000	0	-0.71	35	35
T cell proliferation	-0.53	0.58	-10000	0	-1.3	170	170
IL4R/JAK1	-0.52	0.56	-10000	0	-1.3	165	165
EGR2	-0.57	0.6	-10000	0	-1.4	162	162
JAK2	-0.034	0.11	-10000	0	-0.58	21	21
JAK3	0.001	0.078	-10000	0	-0.53	12	12
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
JAK1	0.003	0.044	-10000	0	-0.58	3	3
COL1A2	-0.2	0.33	-10000	0	-1.2	36	36
CCL26	-0.57	0.61	-10000	0	-1.3	178	178
IL4R	-0.56	0.6	-10000	0	-1.4	164	164
PTPN6	0.023	0.012	-10000	0	-10000	0	0
IL13RA2	-0.58	0.62	-10000	0	-1.4	167	167
IL13RA1	-0.017	0.058	-10000	0	-0.59	4	4
IRF4	-0.28	0.5	-10000	0	-1.4	85	85
ARG1	-0.14	0.18	-10000	0	-0.73	20	20
CBL	-0.3	0.33	-10000	0	-0.78	110	110
GTF3A	0.012	0.039	-10000	0	-0.48	3	3
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
IL13RA1/JAK2	-0.033	0.098	-10000	0	-0.45	23	23
IRF4/BCL6	-0.24	0.46	-10000	0	-1.3	81	81
CD40LG	-0.038	0.16	-10000	0	-0.58	47	47
MAPK14	-0.29	0.34	-10000	0	-0.84	92	92
mitosis	-0.23	0.28	-10000	0	-0.71	68	68
STAT6	-0.62	0.72	-10000	0	-1.5	174	174
SPI1	-0.013	0.12	-10000	0	-0.52	27	27
RPS6KB1	-0.22	0.27	-10000	0	-0.7	65	65
STAT6 (dimer)	-0.63	0.74	-10000	0	-1.5	174	174
STAT6 (dimer)/PARP14	-0.58	0.63	-10000	0	-1.4	171	171
mast cell activation	0.012	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.25	0.3	-10000	0	-0.77	73	73
FRAP1	-0.24	0.29	-10000	0	-0.76	69	69
LTA	-0.55	0.6	-10000	0	-1.4	158	158
FES	-0.002	0.086	-10000	0	-0.56	13	13
T-helper 1 cell differentiation	0.59	0.66	1.4	174	-10000	0	174
CCL11	-0.56	0.61	-10000	0	-1.3	178	178
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.24	0.3	-10000	0	-0.78	69	69
IL2RG	0	0.085	-10000	0	-0.55	13	13
IL10	-0.56	0.61	-10000	0	-1.4	168	168
IRS1	0.002	0.074	-10000	0	-0.58	9	9
IRS2	0.003	0.069	-10000	0	-0.54	9	9
IL4	-0.11	0.12	-10000	0	-10000	0	0
IL5	-0.52	0.56	-10000	0	-1.3	165	165
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.41	0.42	-10000	0	-0.92	168	168
COL1A1	-0.24	0.38	-10000	0	-1.3	49	49
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.54	0.58	-10000	0	-1.3	153	153
IL2R gamma/JAK3	-0.003	0.084	-10000	0	-0.39	25	25
TFF3	-0.56	0.6	-10000	0	-1.3	176	176
ALOX15	-0.61	0.64	-10000	0	-1.4	198	198
MYBL1	0	0.081	-10000	0	-0.55	12	12
T-helper 2 cell differentiation	-0.43	0.44	-10000	0	-0.98	170	170
SHC1	0.011	0	-10000	0	-10000	0	0
CEBPB	0.009	0.043	-10000	0	-0.48	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.24	0.28	-10000	0	-0.75	57	57
mol:PI-3-4-5-P3	-0.24	0.29	-10000	0	-0.76	69	69
PI3K	-0.26	0.31	-10000	0	-0.82	68	68
DOK2	-0.008	0.1	-10000	0	-0.54	20	20
ETS1	0.015	0.06	-10000	0	-0.45	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.18	0.22	-10000	0	-0.68	32	32
ITGB3	-0.52	0.57	-10000	0	-1.3	164	164
PIGR	-0.67	0.7	-10000	0	-1.5	223	223
IGHE	0.04	0.052	0.26	11	-0.31	1	12
MAPKKK cascade	-0.18	0.22	-10000	0	-0.67	31	31
BCL6	0.01	0.039	-10000	0	-0.45	4	4
OPRM1	-0.52	0.56	-10000	0	-1.3	161	161
RETNLB	-0.67	0.67	-10000	0	-1.4	228	228
SELP	-0.59	0.65	-10000	0	-1.4	170	170
AICDA	-0.51	0.54	-10000	0	-1.2	156	156

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.16	0.35	-9999	-0.95	74	74
MKNK1	0.011	0	-9999	-10000	0	0
MAPK14	-0.063	0.14	-9999	-0.41	22	22
ATF2/c-Jun	-0.045	0.15	-9999	-0.52	22	22
MAPK11	-0.079	0.17	-9999	-0.36	113	113
MITF	-0.093	0.2	-9999	-0.42	125	125
MAPKAPK5	-0.074	0.18	-9999	-0.39	108	108
KRT8	-0.075	0.18	-9999	-0.4	109	109
MAPKAPK3	0.011	0	-9999	-10000	0	0
MAPKAPK2	0.011	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.11	0.23	-9999	-0.5	120	120
CEBPB	-0.075	0.18	-9999	-0.39	110	110
SLC9A1	-0.076	0.18	-9999	-0.4	110	110
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.071	0.18	-9999	-0.55	33	33
p38alpha-beta/MNK1	-0.075	0.19	-9999	-0.4	108	108
JUN	-0.045	0.14	-9999	-0.52	22	22
PPARGC1A	-0.11	0.22	-9999	-0.42	157	157
USF1	-0.074	0.18	-9999	-0.39	108	108
RAB5/GDP/GDI1	-0.073	0.12	-9999	-0.42	34	34
NOS2	-0.19	0.4	-9999	-1.1	85	85
DDIT3	-0.075	0.18	-9999	-0.39	108	108
RAB5A	0.006	0.055	-9999	-0.58	5	5
HSPB1	-0.06	0.16	-9999	-0.46	37	37
p38alpha-beta/HBP1	-0.075	0.19	-9999	-0.41	107	107
CREB1	-0.074	0.18	-9999	-0.41	109	109
RAB5/GDP	0.005	0.041	-9999	-0.43	5	5
EIF4E	-0.063	0.17	-9999	-0.56	31	31
RPS6KA4	-0.074	0.18	-9999	-0.39	109	109
PLA2G4A	-0.15	0.22	-9999	-0.46	138	138
GDI1	-0.074	0.18	-9999	-0.39	108	108
TP53	-0.12	0.24	-9999	-0.51	122	122
RPS6KA5	-0.076	0.18	-9999	-0.39	110	110
ESR1	-0.1	0.21	-9999	-0.42	132	132
HBP1	0.011	0	-9999	-10000	0	0
MEF2C	-0.079	0.18	-9999	-0.4	114	114
MEF2A	-0.075	0.18	-9999	-0.4	108	108
EIF4EBP1	-0.074	0.18	-9999	-0.41	108	108
KRT19	-0.076	0.18	-9999	-0.4	110	110
ELK4	-0.077	0.18	-9999	-0.41	108	108
ATF6	-0.074	0.18	-9999	-0.39	108	108
ATF1	-0.074	0.18	-9999	-0.41	108	108
p38alpha-beta/MAPKAPK2	-0.075	0.19	-9999	-0.41	107	107
p38alpha-beta/MAPKAPK3	-0.075	0.19	-9999	-0.41	107	107

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.13	0.21	-9999	-0.48	101	101
FZD6	0.004	0.065	-9999	-0.58	7	7
WNT6	-0.1	0.21	-9999	-0.5	128	128
WNT4	-0.056	0.18	-9999	-0.54	70	70
FZD3	-0.009	0.11	-9999	-0.58	20	20
WNT5A	-0.008	0.1	-9999	-0.55	20	20
WNT11	-0.14	0.24	-9999	-0.52	166	166

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.078	0.21	-9999	-0.46	109	109
alphaM/beta2 Integrin/GPIbA	-0.068	0.19	-9999	-0.44	103	103
alphaM/beta2 Integrin/proMMP-9	-0.095	0.23	-9999	-0.48	124	124
PLAUR	0.01	0.031	-9999	-0.52	2	2
HMGB1	-0.012	0.099	-9999	-0.59	16	16
alphaM/beta2 Integrin/Talin	-0.055	0.18	-9999	-0.43	88	88
AGER	-0.01	0.093	-9999	-0.58	14	14
RAP1A	0.01	0.025	-9999	-0.58	1	1
SELPLG	-0.006	0.098	-9999	-0.55	18	18
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.085	0.2	-9999	-0.46	98	98
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.058	0.18	-9999	-0.52	76	76
CYR61	-0.023	0.12	-9999	-0.48	40	40
TLN1	0.01	0.025	-9999	-0.58	1	1
Rap1/GTP	-0.12	0.16	-9999	-0.44	83	83
RHOA	0.01	0.025	-9999	-0.58	1	1
P-selectin oligomer	-0.078	0.21	-9999	-0.55	92	92
MYH2	-0.13	0.19	-9999	-0.46	105	105
MST1R	0.006	0.055	-9999	-0.58	5	5
leukocyte activation during inflammatory response	-0.14	0.19	-9999	-0.4	144	144
APOB	-0.12	0.22	-9999	-0.5	139	139
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.029	0.14	-9999	-0.52	43	43
JAM3	0.006	0.047	-9999	-0.46	6	6
GP1BA	-0.011	0.1	-9999	-0.52	23	23
alphaM/beta2 Integrin/CTGF	-0.065	0.19	-9999	-0.43	100	100
alphaM/beta2 Integrin	-0.13	0.2	-9999	-0.45	119	119
JAM3 homodimer	0.006	0.047	-9999	-0.45	6	6
ICAM2	0.002	0.068	-9999	-0.5	10	10
ICAM1	0.007	0.048	-9999	-0.5	5	5
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.13	0.2	-9999	-0.44	119	119
cell adhesion	-0.068	0.19	-9999	-0.44	103	103
NFKB1	-0.1	0.24	-9999	-0.62	63	63
THY1	0.004	0.064	-9999	-0.53	8	8
RhoA/GDP	0.008	0.018	-9999	-0.43	1	1
Lipoprotein(a)	-0.086	0.15	-9999	-0.31	172	172
alphaM/beta2 Integrin/LRP/tPA	-0.053	0.18	-9999	-0.44	82	82
IL6	-0.16	0.32	-9999	-0.77	97	97
ITGB2	-0.036	0.14	-9999	-0.53	43	43
elevation of cytosolic calcium ion concentration	-0.05	0.17	-9999	-0.44	75	75
alphaM/beta2 Integrin/JAM2/JAM3	-0.076	0.21	-9999	-0.48	101	101
JAM2	-0.046	0.17	-9999	-0.54	60	60
alphaM/beta2 Integrin/ICAM1	-0.062	0.18	-9999	-0.43	89	89
alphaM/beta2 Integrin/uPA/Plg	-0.076	0.2	-9999	-0.45	103	103
RhoA/GTP	-0.14	0.2	-9999	-0.48	107	107
positive regulation of phagocytosis	-0.13	0.2	-9999	-0.53	92	92
Ron/MSP	-0.02	0.12	-9999	-0.37	54	54
alphaM/beta2 Integrin/uPAR/uPA	-0.05	0.17	-9999	-0.45	75	75
alphaM/beta2 Integrin/uPAR	-0.056	0.18	-9999	-0.43	89	89
PLAU	0	0.076	-9999	-0.49	13	13
PLAT	0	0.079	-9999	-0.54	12	12
actin filament polymerization	-0.12	0.18	-9999	-0.44	105	105
MST1	-0.034	0.15	-9999	-0.51	50	50
alphaM/beta2 Integrin/lipoprotein(a)	-0.13	0.2	-9999	-0.4	144	144
TNF	-0.1	0.26	-9999	-0.73	54	54
RAP1B	0.011	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.061	0.18	-9999	-0.44	95	95
fibrinolysis	-0.076	0.2	-9999	-0.44	103	103
HCK	-0.02	0.13	-9999	-0.55	32	32
dendritic cell antigen processing and presentation	-0.13	0.2	-9999	-0.44	119	119
VTN	-0.051	0.16	-9999	-0.5	68	68
alphaM/beta2 Integrin/CYR61	-0.074	0.2	-9999	-0.43	113	113
LPA	-0.027	0.12	-9999	-0.46	41	41
LRP1	0.004	0.063	-9999	-0.56	7	7
cell migration	-0.1	0.25	-9999	-0.53	114	114
FN1	-0.087	0.21	-9999	-0.52	106	106
alphaM/beta2 Integrin/Thy1	-0.059	0.18	-9999	-0.44	91	91
MPO	-0.038	0.15	-9999	-0.52	52	52
KNG1	-0.11	0.22	-9999	-0.52	131	131
RAP1/GDP	0.015	0.016	-9999	-0.36	1	1
ROCK1	-0.13	0.2	-9999	-0.46	108	108
ELA2	0	0	-9999	-10000	0	0
PLG	-0.037	0.15	-9999	-0.58	41	41
CTGF	-0.006	0.089	-9999	-0.46	21	21
alphaM/beta2 Integrin/Hck	-0.072	0.22	-9999	-0.49	97	97
ITGAM	-0.068	0.18	-9999	-0.52	78	78
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.1	0.24	-9999	-0.47	129	129
HP	-0.078	0.19	-9999	-0.5	98	98
leukocyte adhesion	-0.12	0.21	-9999	-0.56	81	81
SELP	-0.079	0.21	-9999	-0.55	92	92

×

Syndecan-4-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.067	0.17	-9999	-0.55	55	55
Syndecan-4/Syndesmos	-0.14	0.23	-9999	-0.54	112	112
positive regulation of JNK cascade	-0.14	0.22	-9999	-0.52	118	118
Syndecan-4/ADAM12	-0.18	0.27	-9999	-0.58	141	141
CCL5	-0.037	0.15	-9999	-0.51	53	53
Rac1/GDP	0.008	0	-9999	-10000	0	0
DNM2	0.01	0.025	-9999	-0.58	1	1
ITGA5	-0.005	0.089	-9999	-0.48	19	19
SDCBP	0	0.081	-9999	-0.58	11	11
PLG	-0.033	0.14	-9999	-0.56	41	41
ADAM12	-0.077	0.2	-9999	-0.51	97	97
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.01	0.027	-9999	-0.46	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.03	0.04	-9999	-0.15	5	5
Syndecan-4/Laminin alpha1	-0.17	0.25	-9999	-0.58	125	125
Syndecan-4/CXCL12/CXCR4	-0.15	0.24	-9999	-0.55	118	118
Syndecan-4/Laminin alpha3	-0.15	0.24	-9999	-0.55	120	120
MDK	-0.008	0.1	-9999	-0.51	22	22
Syndecan-4/FZD7	-0.14	0.23	-9999	-0.55	113	113
Syndecan-4/Midkine	-0.14	0.23	-9999	-0.55	116	116
FZD7	0	0.076	-9999	-0.49	13	13
Syndecan-4/FGFR1/FGF	-0.17	0.22	-9999	-0.55	121	121
THBS1	-0.004	0.09	-9999	-0.51	17	17
integrin-mediated signaling pathway	-0.16	0.25	-9999	-0.55	129	129
positive regulation of MAPKKK cascade	-0.14	0.22	-9999	-0.52	118	118
Syndecan-4/TACI	-0.17	0.25	-9999	-0.56	127	127
CXCR4	-0.017	0.12	-9999	-0.49	32	32
cell adhesion	-0.026	0.11	-9999	-0.3	64	64
Syndecan-4/Dynamin	-0.14	0.23	-9999	-0.55	110	110
Syndecan-4/TSP1	-0.14	0.24	-9999	-0.55	116	116
Syndecan-4/GIPC	-0.14	0.23	-9999	-0.54	111	111
Syndecan-4/RANTES	-0.16	0.24	-9999	-0.57	118	118
ITGB1	0.011	0	-9999	-10000	0	0
LAMA1	-0.054	0.18	-9999	-0.54	68	68
LAMA3	-0.016	0.12	-9999	-0.5	30	30
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	0.038	0.055	-9999	-0.46	2	2
Syndecan-4/alpha-Actinin	-0.14	0.23	-9999	-0.54	110	110
TFPI	-0.008	0.1	-9999	-0.53	20	20
F2	-0.12	0.22	-9999	-0.5	143	143
alpha5/beta1 Integrin	0.005	0.064	-9999	-0.34	19	19
positive regulation of cell adhesion	-0.17	0.25	-9999	-0.57	131	131
ACTN1	0.011	0	-9999	-10000	0	0
TNC	-0.055	0.18	-9999	-0.52	72	72
Syndecan-4/CXCL12	-0.15	0.24	-9999	-0.56	118	118
FGF6	-0.001	0.019	-9999	-0.46	1	1
RHOA	0.01	0.025	-9999	-0.58	1	1
CXCL12	-0.013	0.11	-9999	-0.49	28	28
TNFRSF13B	-0.061	0.18	-9999	-0.52	76	76
FGF2	-0.037	0.15	-9999	-0.52	53	53
FGFR1	-0.009	0.1	-9999	-0.51	22	22
Syndecan-4/PI-4-5-P2	-0.14	0.23	-9999	-0.55	110	110
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.082	0.2	-9999	-0.51	106	106
cell migration	-0.006	0.017	-9999	-10000	0	0
PRKCD	0.016	0.009	-9999	-10000	0	0
vasculogenesis	-0.14	0.23	-9999	-0.53	116	116
SDC4	-0.15	0.24	-9999	-0.58	110	110
Syndecan-4/Tenascin C	-0.17	0.26	-9999	-0.58	129	129
Syndecan-4/PI-4-5-P2/PKC alpha	-0.024	0.032	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.14	0.23	-9999	-0.54	116	116
MMP9	-0.059	0.18	-9999	-0.52	76	76
Rac1/GTP	-0.027	0.12	-9999	-0.31	64	64
cytoskeleton organization	-0.13	0.22	-9999	-0.52	112	112
GIPC1	0.007	0.049	-9999	-0.58	4	4
Syndecan-4/TFPI	-0.14	0.24	-9999	-0.55	116	116

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.038	0.16	-9999	-0.56	49	49
GNB1/GNG2	-0.11	0.19	-9999	-0.49	82	82
mol:DAG	-0.097	0.18	-9999	-0.45	81	81
PLCG1	-0.1	0.18	-9999	-0.46	81	81
YES1	-0.12	0.2	-9999	-0.52	82	82
FZD3	-0.009	0.11	-9999	-0.58	20	20
FZD6	0.004	0.065	-9999	-0.58	7	7
G protein	-0.1	0.18	-9999	-0.46	81	81
MAP3K7	-0.087	0.16	-9999	-0.42	69	69
mol:Ca2+	-0.094	0.17	-9999	-0.43	81	81
mol:IP3	-0.097	0.18	-9999	-0.45	81	81
NLK	-0.005	0.009	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CAMK2A	-0.1	0.17	-9999	-0.45	75	75
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.13	0.21	-9999	-0.48	101	101
CSNK1A1	0.009	0.035	-9999	-0.58	2	2
GNAS	-0.12	0.2	-9999	-0.51	80	80
GO:0007205	-0.096	0.18	-9999	-0.44	81	81
WNT6	-0.1	0.21	-9999	-0.5	128	128
WNT4	-0.056	0.18	-9999	-0.54	70	70
NFAT1/CK1 alpha	-0.12	0.22	-9999	-0.55	84	84
GNG2	0.004	0.064	-9999	-0.53	8	8
WNT5A	-0.008	0.1	-9999	-0.55	20	20
WNT11	-0.14	0.24	-9999	-0.52	166	166
CDC42	-0.11	0.2	-9999	-0.5	83	83

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.026	0.14	-10000	0	-0.36	74	74
fibroblast growth factor receptor signaling pathway	-0.026	0.14	-10000	0	-0.36	74	74
LAMA1	-0.054	0.18	-10000	0	-0.54	68	68
PRNP	-0.003	0.09	-10000	0	-0.57	14	14
GPC1/SLIT2	-0.088	0.18	-10000	0	-0.38	150	150
SMAD2	0.015	0.063	-10000	0	-0.34	15	15
GPC1/PrPc/Cu2+	-0.001	0.075	-10000	0	-0.34	26	26
GPC1/Laminin alpha1	-0.038	0.14	-10000	0	-0.4	76	76
TDGF1	-0.072	0.2	-10000	0	-0.58	81	81
CRIPTO/GPC1	-0.053	0.16	-10000	0	-0.41	93	93
APP/GPC1	0.008	0.061	-10000	0	-0.39	13	13
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.042	0.14	-10000	0	-0.36	93	93
FLT1	0.006	0.056	-10000	0	-0.54	6	6
GPC1/TGFB/TGFBR1/TGFBR2	0.013	0.06	-10000	0	-0.33	17	17
SERPINC1	-0.011	0.089	-10000	0	-0.46	22	22
FYN	-0.041	0.14	-10000	0	-0.35	98	98
FGR	-0.058	0.16	-10000	0	-0.36	121	121
positive regulation of MAPKKK cascade	-0.095	0.21	-10000	0	-0.46	117	117
SLIT2	-0.12	0.23	-10000	0	-0.53	141	141
GPC1/NRG	-0.049	0.15	-10000	0	-0.38	94	94
NRG1	-0.068	0.19	-10000	0	-0.53	84	84
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.012	0.065	-10000	0	-0.34	18	18
LYN	-0.037	0.14	-10000	0	-0.35	93	93
mol:Spermine	0.001	0.058	-10000	0	-0.39	12	12
cell growth	-0.026	0.14	-10000	0	-0.36	74	74
BMP signaling pathway	0	0.079	0.54	12	-10000	0	12
SRC	-0.038	0.14	-10000	0	-0.35	93	93
TGFBR1	0.007	0.049	-10000	0	-0.58	4	4
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.2	0.27	-10000	0	-0.53	224	224
GPC1	0	0.079	-10000	0	-0.54	12	12
TGFBR1 (dimer)	0.007	0.049	-10000	0	-0.58	4	4
VEGFA	0.011	0.019	-10000	0	-0.46	1	1
BLK	-0.11	0.2	-10000	0	-0.37	196	196
HCK	-0.056	0.16	-10000	0	-0.36	117	117
FGF2	-0.037	0.15	-10000	0	-0.52	53	53
FGFR1	-0.009	0.1	-10000	0	-0.51	22	22
VEGFR1 homodimer	0.006	0.056	-10000	0	-0.54	6	6
TGFBR2	0.011	0.019	-10000	0	-0.46	1	1
cell death	0.008	0.061	-10000	0	-0.39	13	13
ATIII/GPC1	-0.007	0.085	-10000	0	-0.34	34	34
PLA2G2A/GPC1	-0.14	0.21	-10000	0	-0.39	228	228
LCK	-0.063	0.17	-10000	0	-0.37	124	124
neuron differentiation	-0.049	0.15	-10000	0	-0.38	94	94
PrPc/Cu2+	-0.002	0.066	-10000	0	-0.42	14	14
APP	0.01	0.025	-10000	0	-0.58	1	1
TGFBR2 (dimer)	0.011	0.019	-10000	0	-0.45	1	1

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.069	0.19	-10000	0	-0.44	83	83
TBX21	-0.24	0.51	-10000	0	-1.1	121	121
B2M	0.005	0.039	-10000	0	-0.5	3	3
TYK2	0.007	0.034	-10000	0	-0.61	1	1
IL12RB1	-0.039	0.16	-10000	0	-0.57	48	48
GADD45B	-0.15	0.37	-10000	0	-0.84	89	89
IL12RB2	-0.039	0.16	-10000	0	-0.53	53	53
GADD45G	-0.16	0.38	-10000	0	-0.83	96	96
natural killer cell activation	-0.003	0.023	-10000	0	-10000	0	0
RELB	0.009	0.037	-10000	0	-0.5	3	3
RELA	0.011	0	-10000	0	-10000	0	0
IL18	0.003	0.071	-10000	0	-0.55	9	9
IL2RA	-0.044	0.17	-10000	0	-0.55	57	57
IFNG	-0.064	0.18	-10000	0	-0.51	80	80
STAT3 (dimer)	-0.16	0.36	-10000	0	-0.75	121	121
HLA-DRB5	-0.079	0.2	-10000	0	-0.52	97	97
FASLG	-0.24	0.52	-10000	0	-1.1	118	118
NF kappa B2 p52/RelB	-0.27	0.4	-10000	0	-0.93	127	127
CD4	-0.014	0.12	-10000	0	-0.55	26	26
SOCS1	-0.029	0.14	-10000	0	-0.49	46	46
EntrezGene:6955	-0.004	0.015	-10000	0	-10000	0	0
CD3D	-0.035	0.15	-10000	0	-0.56	43	43
CD3E	-0.027	0.14	-10000	0	-0.56	36	36
CD3G	-0.053	0.18	-10000	0	-0.57	61	61
IL12Rbeta2/JAK2	-0.036	0.15	-10000	0	-0.4	72	72
CCL3	-0.24	0.5	-10000	0	-1.1	122	122
CCL4	-0.22	0.49	-10000	0	-1.1	98	98
HLA-A	-0.001	0.07	-10000	0	-0.52	10	10
IL18/IL18R	-0.012	0.15	-10000	0	-0.39	67	67
NOS2	-0.28	0.56	-10000	0	-1.2	126	126
IL12/IL12R/TYK2/JAK2/SPHK2	-0.054	0.16	-10000	0	-0.42	61	61
IL1R1	-0.21	0.46	-10000	0	-1	111	111
IL4	0.004	0.024	-10000	0	-10000	0	0
JAK2	-0.013	0.11	-10000	0	-0.57	21	21
EntrezGene:6957	-0.004	0.015	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.17	0.44	-10000	0	-0.94	111	111
RAB7A	-0.11	0.32	-10000	0	-0.79	52	52
lysosomal transport	-0.11	0.3	-10000	0	-0.73	56	56
FOS	-0.17	0.41	-10000	0	-1.1	75	75
STAT4 (dimer)	-0.17	0.41	-10000	0	-0.88	114	114
STAT5A (dimer)	-0.29	0.42	-10000	0	-0.93	145	145
GZMA	-0.24	0.5	-10000	0	-1.1	109	109
GZMB	-0.25	0.51	-10000	0	-1.1	120	120
HLX	0.006	0.056	-10000	0	-0.54	6	6
LCK	-0.24	0.51	-10000	0	-1.1	128	128
TCR/CD3/MHC II/CD4	-0.12	0.33	-10000	0	-0.74	91	91
IL2/IL2R	-0.031	0.15	-10000	0	-0.41	63	63
MAPK14	-0.15	0.38	-10000	0	-0.84	97	97
CCR5	-0.17	0.42	-10000	0	-1.1	72	72
IL1B	-0.067	0.19	-10000	0	-0.53	81	81
STAT6	-0.037	0.12	-10000	0	-0.26	19	19
STAT4	-0.028	0.14	-10000	0	-0.56	40	40
STAT3	0.011	0	-10000	0	-10000	0	0
STAT1	0.006	0.052	-10000	0	-0.5	6	6
NFKB1	0.01	0.025	-10000	0	-0.58	1	1
NFKB2	0.01	0.031	-10000	0	-0.52	2	2
IL12B	-0.007	0.079	-10000	0	-0.47	15	15
CD8A	-0.06	0.18	-10000	0	-0.54	72	72
CD8B	-0.047	0.17	-10000	0	-0.56	56	56
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.069	0.19	0.43	83	-10000	0	83
IL2RB	-0.016	0.12	-10000	0	-0.55	28	28
proteasomal ubiquitin-dependent protein catabolic process	-0.15	0.37	-10000	0	-0.78	114	114
IL2RG	-0.002	0.086	-10000	0	-0.56	13	13
IL12	-0.029	0.13	-10000	0	-0.4	58	58
STAT5A	0.011	0	-10000	0	-10000	0	0
CD247	-0.022	0.13	-10000	0	-0.55	31	31
IL2	0.001	0.027	-10000	0	-0.46	2	2
SPHK2	0.009	0.037	-10000	0	-0.5	3	3
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.037	0.16	-10000	0	-0.57	44	44
IL12/IL12R/TYK2/JAK2	-0.26	0.57	-10000	0	-1.1	131	131
MAP2K3	-0.16	0.39	-10000	0	-0.84	101	101
RIPK2	0.011	0	-10000	0	-10000	0	0
MAP2K6	-0.16	0.39	-10000	0	-0.85	102	102
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.041	0.16	-10000	0	-0.52	57	57
IL18RAP	-0.033	0.15	-10000	0	-0.56	45	45
IL12Rbeta1/TYK2	-0.023	0.13	-10000	0	-0.42	49	49
EOMES	-0.14	0.4	-10000	0	-1.3	58	58
STAT1 (dimer)	-0.18	0.38	-10000	0	-0.81	120	120
T cell proliferation	-0.12	0.3	0.4	1	-0.64	105	106
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.013	0.12	-10000	0	-0.56	25	25
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.2	0.28	-10000	0	-0.7	108	108
ATF2	-0.14	0.36	-10000	0	-0.78	93	93

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.28	0.36	-10000	0	-0.93	81	81
PCK1	-0.27	0.44	-10000	0	-1.3	73	73
HNF4A	-0.37	0.45	-10000	0	-1.1	113	113
KCNJ11	-0.27	0.38	-10000	0	-0.97	78	78
AKT1	-0.14	0.16	-10000	0	-0.47	14	14
response to starvation	-0.019	0.034	-10000	0	-10000	0	0
DLK1	-0.28	0.37	-10000	0	-0.92	92	92
NKX2-1	-0.18	0.34	-10000	0	-1.1	44	44
ACADM	-0.29	0.38	-10000	0	-0.98	84	84
TAT	-0.18	0.22	-10000	0	-0.68	43	43
CEBPB	0.004	0.043	-10000	0	-0.49	4	4
CEBPA	-0.008	0.1	-10000	0	-0.58	17	17
TTR	-0.3	0.41	-10000	0	-1	101	101
PKLR	-0.43	0.48	-10000	0	-1	187	187
APOA1	-0.38	0.49	-10000	0	-1.2	101	101
CPT1C	-0.31	0.4	-10000	0	-1	93	93
ALAS1	-0.13	0.18	-10000	0	-0.81	3	3
TFRC	-0.19	0.28	-10000	0	-0.9	32	32
FOXF1	0.013	0.1	0.27	6	-0.56	15	21
NF1	0.014	0.043	-10000	0	-0.58	3	3
HNF1A (dimer)	0.002	0.073	-10000	0	-0.58	6	6
CPT1A	-0.28	0.36	-10000	0	-0.93	82	82
HMGCS1	-0.29	0.37	-10000	0	-0.93	92	92
NR3C1	-0.039	0.13	-10000	0	-0.55	28	28
CPT1B	-0.3	0.39	-10000	0	-1	90	90
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.007	0.044	-10000	0	-0.58	1	1
GCK	-0.3	0.38	-10000	0	-0.98	92	92
CREB1	-0.007	0.061	-10000	0	-0.6	2	2
IGFBP1	-0.28	0.41	-10000	0	-1.1	93	93
PDX1	-0.18	0.36	-10000	0	-1.4	35	35
UCP2	-0.29	0.37	-10000	0	-0.96	87	87
ALDOB	-0.38	0.49	-10000	0	-1.1	130	130
AFP	-0.07	0.18	-10000	0	-0.53	41	41
BDH1	-0.29	0.37	-10000	0	-1	70	70
HADH	-0.27	0.36	-10000	0	-0.96	73	73
F2	-0.42	0.53	-10000	0	-1.3	116	116
HNF1A	0.002	0.073	-10000	0	-0.58	6	6
G6PC	-0.032	0.14	-10000	0	-0.68	10	10
SLC2A2	-0.17	0.24	-10000	0	-0.78	24	24
INS	0.017	0.063	0.22	6	-0.47	2	8
FOXA1	-0.07	0.21	0.27	2	-0.56	77	79
FOXA3	-0.033	0.13	-10000	0	-0.51	22	22
FOXA2	-0.32	0.42	-10000	0	-1	89	89
ABCC8	-0.3	0.39	-10000	0	-1	86	86
ALB	-0.078	0.18	-10000	0	-0.56	37	37

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.008	0.042	-9999	-0.49	4	4
EGFR	0.004	0.064	-9999	-0.53	8	8
EGF/EGFR	-0.12	0.15	-9999	-0.34	122	122
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.072	0.14	-9999	-0.29	90	90
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.017	0.12	-9999	-0.51	31	31
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.18	0.25	-9999	-0.5	209	209
EGF/EGFR dimer/SHC	-0.099	0.16	-9999	-0.3	216	216
mol:GDP	-0.073	0.13	-9999	-0.29	90	90
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.023	0.13	-9999	-0.51	38	38
GRB2/SOS1	0.016	0.018	-9999	-0.42	1	1
HRAS/GTP	-0.084	0.11	-9999	-0.45	3	3
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	-0.086	0.11	-9999	-0.46	3	3
FRAP1	-0.07	0.13	-9999	-0.28	90	90
EGF/EGFR dimer	-0.13	0.19	-9999	-0.36	216	216
SOS1	0.01	0.025	-9999	-0.58	1	1
GRB2	0.011	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.028	0.13	-9999	-0.38	66	66

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.092	0.19	-10000	0	-0.54	75	75
FYN	-0.087	0.28	-10000	0	-0.69	84	84
LAT/GRAP2/SLP76	-0.11	0.23	-10000	0	-0.57	91	91
IKBKB	0.011	0.019	-10000	0	-0.46	1	1
AKT1	-0.05	0.18	-10000	0	-0.45	84	84
B2M	0.008	0.037	-10000	0	-0.5	3	3
IKBKG	-0.035	0.054	-10000	0	-0.16	66	66
MAP3K8	0.01	0.031	-10000	0	-0.52	2	2
mol:Ca2+	-0.024	0.04	-10000	0	-0.1	105	105
integrin-mediated signaling pathway	0.007	0.053	-10000	0	-0.32	14	14
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.087	0.28	-10000	0	-0.67	87	87
TRPV6	-0.093	0.19	-10000	0	-0.48	113	113
CD28	-0.033	0.15	-10000	0	-0.56	45	45
SHC1	-0.084	0.27	-10000	0	-0.67	82	82
receptor internalization	-0.092	0.3	-10000	0	-0.75	79	79
PRF1	-0.097	0.32	-10000	0	-1	50	50
KRAS	0.005	0.058	-10000	0	-0.56	6	6
GRB2	0.011	0	-10000	0	-10000	0	0
COT/AKT1	-0.032	0.15	-10000	0	-0.36	78	78
LAT	-0.092	0.28	-10000	0	-0.68	86	86
EntrezGene:6955	-0.001	0.004	-10000	0	-10000	0	0
CD3D	-0.032	0.15	-10000	0	-0.56	43	43
CD3E	-0.025	0.14	-10000	0	-0.56	36	36
CD3G	-0.05	0.18	-10000	0	-0.57	61	61
RASGRP2	-0.01	0.045	-10000	0	-0.17	34	34
RASGRP1	-0.054	0.2	-10000	0	-0.48	83	83
HLA-A	0.001	0.071	-10000	0	-0.52	10	10
RASSF5	-0.001	0.081	-10000	0	-0.53	13	13
RAP1A/GTP/RAPL	0.007	0.053	-10000	0	-0.33	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.001	0.059	-10000	0	-0.12	72	72
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.064	0.095	-10000	0	-0.27	82	82
PRKCA	-0.048	0.1	-10000	0	-0.28	72	72
GRAP2	-0.023	0.14	-10000	0	-0.55	35	35
mol:IP3	-0.056	0.19	0.2	72	-0.44	81	153
EntrezGene:6957	-0.001	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.084	0.29	-10000	0	-0.75	69	69
ORAI1	0.056	0.11	0.27	110	-0.32	2	112
CSK	-0.087	0.28	-10000	0	-0.69	82	82
B7 family/CD28	-0.11	0.32	-10000	0	-0.73	101	101
CHUK	0.007	0.049	-10000	0	-0.58	4	4
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.11	0.33	-10000	0	-0.79	85	85
PTPN6	-0.088	0.28	-10000	0	-0.69	81	81
VAV1	-0.096	0.29	-10000	0	-0.7	89	89
Monovalent TCR/CD3	-0.065	0.26	-10000	0	-0.6	78	78
CBL	0.011	0	-10000	0	-10000	0	0
LCK	-0.096	0.3	-10000	0	-0.71	87	87
PAG1	-0.089	0.28	-10000	0	-0.69	83	83
RAP1A	0.01	0.025	-10000	0	-0.58	1	1
TCR/CD3/MHC I/CD8/LCK	-0.11	0.32	-10000	0	-0.79	83	83
CD80	-0.039	0.16	-10000	0	-0.57	50	50
CD86	-0.036	0.16	-10000	0	-0.54	49	49
PDK1/CARD11/BCL10/MALT1	-0.078	0.12	-10000	0	-0.32	88	88
HRAS	0.008	0.042	-10000	0	-0.49	4	4
GO:0035030	-0.088	0.25	-10000	0	-0.58	101	101
CD8A	-0.057	0.18	-10000	0	-0.54	72	72
CD8B	-0.044	0.17	-10000	0	-0.56	56	56
PTPRC	-0.041	0.16	-10000	0	-0.55	54	54
PDK1/PKC theta	-0.067	0.23	-10000	0	-0.56	85	85
CSK/PAG1	-0.082	0.27	-10000	0	-0.69	78	78
SOS1	0.01	0.025	-10000	0	-0.58	1	1
peptide-MHC class I	0.007	0.059	-10000	0	-0.37	13	13
GRAP2/SLP76	-0.12	0.27	-10000	0	-0.68	88	88
STIM1	0.03	0.053	0.2	1	-10000	0	1
RAS family/GTP	-0.002	0.082	-10000	0	-0.19	61	61
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.1	0.33	-10000	0	-0.82	79	79
mol:DAG	-0.067	0.15	0.13	1	-0.39	86	87
RAP1A/GDP	0.001	0.027	-10000	0	-0.092	3	3
PLCG1	0.01	0.025	-10000	0	-0.58	1	1
CD247	-0.019	0.13	-10000	0	-0.56	31	31
cytotoxic T cell degranulation	-0.091	0.3	-10000	0	-0.94	50	50
RAP1A/GTP	-0.006	0.015	-10000	0	-0.07	26	26
mol:PI-3-4-5-P3	-0.066	0.22	-10000	0	-0.54	87	87
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.081	0.24	0.22	64	-0.58	83	147
NRAS	0.001	0.077	-10000	0	-0.58	10	10
ZAP70	-0.037	0.16	-10000	0	-0.53	51	51
GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
LAT/GRAP2/SLP76/VAV1	-0.11	0.22	-10000	0	-0.56	91	91
MALT1	0.006	0.055	-10000	0	-0.58	5	5
TRAF6	0.01	0.025	-10000	0	-0.58	1	1
CD8 heterodimer	-0.071	0.2	-10000	0	-0.46	107	107
CARD11	-0.12	0.22	-10000	0	-0.49	148	148
PRKCB	-0.061	0.13	-10000	0	-0.33	81	81
PRKCE	-0.047	0.1	-10000	0	-0.28	71	71
PRKCQ	-0.086	0.26	-10000	0	-0.64	88	88
LCP2	-0.014	0.12	-10000	0	-0.54	26	26
BCL10	0.007	0.049	-10000	0	-0.58	4	4
regulation of survival gene product expression	-0.039	0.16	-10000	0	-0.38	84	84
IKK complex	0.006	0.056	-10000	0	-0.12	55	55
RAS family/GDP	-0.007	0.016	-10000	0	-0.091	11	11
MAP3K14	-0.017	0.12	-10000	0	-0.28	66	66
PDPK1	-0.044	0.18	-10000	0	-0.42	84	84
TCR/CD3/MHC I/CD8/Fyn	-0.1	0.33	-10000	0	-0.79	86	86

×

Syndecan-1-mediated signaling events

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
TGFB1	-0.001	0.083	-9999	-0.54	13	13
CCL5	-0.037	0.15	-9999	-0.51	53	53
SDCBP	0	0.081	-9999	-0.58	11	11
FGFR/FGF2/Syndecan-1	-0.11	0.19	-9999	-0.51	66	66
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.12	0.2	-9999	-0.48	92	92
Syndecan-1/Syntenin	-0.11	0.18	-9999	-0.48	75	75
MAPK3	-0.083	0.17	-9999	-0.49	48	48
HGF/MET	-0.019	0.12	-9999	-0.39	51	51
TGFB1/TGF beta receptor Type II	-0.001	0.083	-9999	-0.54	13	13
BSG	0.01	0.025	-9999	-0.58	1	1
keratinocyte migration	-0.12	0.2	-9999	-0.47	92	92
Syndecan-1/RANTES	-0.12	0.2	-9999	-0.5	89	89
Syndecan-1/CD147	-0.092	0.18	-9999	-0.46	66	66
Syndecan-1/Syntenin/PIP2	-0.1	0.18	-9999	-0.46	75	75
LAMA5	-0.028	0.15	-9999	-0.57	39	39
positive regulation of cell-cell adhesion	-0.1	0.17	-9999	-0.45	75	75
MMP7	-0.14	0.24	-9999	-0.51	160	160
HGF	-0.036	0.16	-9999	-0.55	49	49
Syndecan-1/CASK	-0.11	0.18	-9999	-0.49	66	66
Syndecan-1/HGF/MET	-0.12	0.2	-9999	-0.5	88	88
regulation of cell adhesion	-0.075	0.16	-9999	-0.47	48	48
HPSE	-0.005	0.092	-9999	-0.51	18	18
positive regulation of cell migration	-0.11	0.19	-9999	-0.51	66	66
SDC1	-0.11	0.19	-9999	-0.51	66	66
Syndecan-1/Collagen	-0.11	0.19	-9999	-0.51	66	66
PPIB	0.011	0	-9999	-10000	0	0
MET	0.01	0.031	-9999	-0.52	2	2
PRKACA	0.011	0	-9999	-10000	0	0
MMP9	-0.058	0.18	-9999	-0.52	76	76
MAPK1	-0.083	0.17	-9999	-0.49	47	47
homophilic cell adhesion	-0.11	0.18	-9999	-0.5	66	66
MMP1	-0.12	0.24	-9999	-0.53	144	144

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.062	0.16	-10000	0	-0.4	76	76
IKBKB	-0.029	0.09	-10000	0	-0.25	35	35
AKT1	-0.05	0.11	0.21	1	-0.25	87	88
IKBKG	-0.03	0.096	-10000	0	-0.26	41	41
CALM1	-0.04	0.15	0.25	18	-0.45	48	66
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
MAP3K1	-0.11	0.24	-10000	0	-0.57	92	92
MAP3K7	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	-0.049	0.16	0.25	19	-0.47	51	70
DOK1	0.011	0	-10000	0	-10000	0	0
AP-1	-0.024	0.099	0.2	15	-0.24	50	65
LYN	0.011	0	-10000	0	-10000	0	0
BLNK	-0.009	0.11	-10000	0	-0.58	20	20
SHC1	0.011	0	-10000	0	-10000	0	0
BCR complex	-0.098	0.21	-10000	0	-0.46	139	139
CD22	-0.15	0.27	-10000	0	-0.68	96	96
CAMK2G	-0.032	0.14	0.25	18	-0.43	44	62
CSNK2A1	0.011	0	-10000	0	-10000	0	0
INPP5D	-0.016	0.12	-10000	0	-0.58	26	26
SHC/GRB2/SOS1	-0.076	0.14	-10000	0	-0.46	38	38
GO:0007205	-0.05	0.17	0.25	19	-0.48	51	70
SYK	0.011	0.019	-10000	0	-0.45	1	1
ELK1	-0.042	0.16	0.24	17	-0.46	48	65
NFATC1	-0.099	0.21	-10000	0	-0.49	89	89
B-cell antigen/BCR complex	-0.098	0.21	-10000	0	-0.46	139	139
PAG1/CSK	0.011	0.049	-10000	0	-0.4	8	8
NFKBIB	-0.002	0.032	0.084	11	-0.12	2	13
HRAS	-0.038	0.15	0.23	18	-0.41	53	71
NFKBIA	-0.001	0.032	0.084	11	-0.12	2	13
NF-kappa-B/RelA/I kappa B beta	0.005	0.027	0.085	11	-0.17	1	12
RasGAP/Csk	-0.1	0.22	-10000	0	-0.43	135	135
mol:GDP	-0.045	0.16	0.26	18	-0.45	50	68
PTEN	0.005	0.06	-10000	0	-0.58	6	6
CD79B	-0.026	0.14	-10000	0	-0.51	41	41
NF-kappa-B/RelA/I kappa B alpha	0.005	0.027	0.085	11	-0.17	1	12
GRB2	0.011	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.11	0.22	-10000	0	-0.52	96	96
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
mol:IP3	-0.05	0.17	0.26	19	-0.48	51	70
CSK	0.01	0.025	-10000	0	-0.58	1	1
FOS	-0.052	0.16	0.24	16	-0.42	64	80
CHUK	-0.031	0.099	-10000	0	-0.29	30	30
IBTK	0.001	0.078	-10000	0	-0.58	10	10
CARD11/BCL10/MALT1/TAK1	-0.1	0.16	-10000	0	-0.46	72	72
PTPN6	-0.12	0.26	-10000	0	-0.64	93	93
RELA	0.011	0	-10000	0	-10000	0	0
BCL2A1	-0.002	0.036	-10000	0	-0.1	33	33
VAV2	-0.15	0.28	-10000	0	-0.65	107	107
ubiquitin-dependent protein catabolic process	0.002	0.032	0.086	11	-0.11	2	13
BTK	-0.05	0.26	0.36	23	-1.1	31	54
CD19	-0.16	0.27	-10000	0	-0.63	111	111
MAP4K1	-0.043	0.17	-10000	0	-0.55	56	56
CD72	-0.007	0.095	-10000	0	-0.5	20	20
PAG1	0.005	0.061	-10000	0	-0.55	7	7
MAPK14	-0.087	0.2	-10000	0	-0.48	88	88
SH3BP5	0.004	0.065	-10000	0	-0.58	7	7
PIK3AP1	-0.053	0.17	0.3	2	-0.48	56	58
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.076	0.22	-10000	0	-0.52	90	90
RAF1	-0.03	0.14	0.22	18	-0.42	38	56
RasGAP/p62DOK/SHIP	-0.13	0.2	-10000	0	-0.59	64	64
CD79A	-0.11	0.23	-10000	0	-0.54	132	132
re-entry into mitotic cell cycle	-0.024	0.099	0.2	15	-0.25	50	65
RASA1	0.009	0.035	-10000	0	-0.58	2	2
MAPK3	-0.015	0.12	0.21	17	-0.4	24	41
MAPK1	-0.015	0.12	0.21	16	-0.4	24	40
CD72/SHP1	-0.12	0.26	-10000	0	-0.62	94	94
NFKB1	0.01	0.025	-10000	0	-0.58	1	1
MAPK8	-0.088	0.2	-10000	0	-0.48	90	90
actin cytoskeleton organization	-0.12	0.23	-10000	0	-0.54	105	105
NF-kappa-B/RelA	0.014	0.053	0.17	11	-0.22	2	13
Calcineurin	-0.05	0.12	-10000	0	-0.45	29	29
PI3K	-0.14	0.2	-10000	0	-0.52	106	106
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.054	0.17	0.31	2	-0.49	52	54
SOS1	0.01	0.025	-10000	0	-0.58	1	1
Bam32/HPK1	-0.15	0.33	-10000	0	-0.84	91	91
DAPP1	-0.17	0.36	-10000	0	-1.1	69	69
cytokine secretion	-0.091	0.19	-10000	0	-0.45	89	89
mol:DAG	-0.05	0.17	0.26	19	-0.48	51	70
PLCG2	-0.01	0.11	-10000	0	-0.54	22	22
MAP2K1	-0.023	0.13	0.22	17	-0.42	31	48
B-cell antigen/BCR complex/FcgammaRIIB	-0.13	0.24	-10000	0	-0.42	198	198
mol:PI-3-4-5-P3	-0.1	0.14	0.28	1	-0.36	105	106
ETS1	-0.027	0.14	0.24	18	-0.45	33	51
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.064	0.18	-10000	0	-0.36	122	122
B-cell antigen/BCR complex/LYN	-0.12	0.24	-10000	0	-0.52	110	110
MALT1	0.006	0.055	-10000	0	-0.58	5	5
TRAF6	0.01	0.025	-10000	0	-0.58	1	1
RAC1	-0.13	0.25	-10000	0	-0.58	104	104
B-cell antigen/BCR complex/LYN/SYK	-0.14	0.25	-10000	0	-0.64	92	92
CARD11	-0.1	0.21	0.25	15	-0.5	91	106
FCGR2B	-0.082	0.21	-10000	0	-0.53	99	99
PPP3CA	0.011	0	-10000	0	-10000	0	0
BCL10	0.007	0.049	-10000	0	-0.58	4	4
IKK complex	-0.006	0.04	0.091	11	-0.11	11	22
PTPRC	-0.041	0.16	-10000	0	-0.54	54	54
PDPK1	-0.052	0.11	0.19	1	-0.25	88	89
PPP3CB	0.011	0	-10000	0	-10000	0	0
PPP3CC	0.007	0.049	-10000	0	-0.58	4	4
POU2F2	0.004	0.028	-10000	0	-0.099	16	16

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.048	0.22	-10000	0	-0.63	48	48
IHH	-0.039	0.17	-10000	0	-0.62	42	42
SHH Np/Cholesterol/GAS1	-0.077	0.16	-10000	0	-0.3	173	173
LRPAP1	0.01	0.025	-10000	0	-0.58	1	1
dorsoventral neural tube patterning	0.077	0.15	0.3	173	-10000	0	173
SMO/beta Arrestin2	-0.036	0.19	-10000	0	-0.63	33	33
SMO	-0.044	0.2	-10000	0	-0.64	37	37
AKT1	-0.005	0.11	-10000	0	-0.49	12	12
ARRB2	0.011	0	-10000	0	-10000	0	0
BOC	-0.034	0.14	-10000	0	-0.48	53	53
ADRBK1	0.009	0.037	-10000	0	-0.5	3	3
heart looping	-0.043	0.2	-10000	0	-0.63	37	37
STIL	-0.025	0.16	-10000	0	-0.59	27	27
DHH N/PTCH2	-0.04	0.15	-10000	0	-0.43	73	73
DHH N/PTCH1	-0.045	0.17	-10000	0	-0.53	29	29
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
DHH	-0.03	0.14	-10000	0	-0.54	42	42
PTHLH	-0.073	0.29	-10000	0	-0.91	48	48
determination of left/right symmetry	-0.043	0.2	-10000	0	-0.63	37	37
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
skeletal system development	-0.071	0.28	-10000	0	-0.9	48	48
IHH N/Hhip	-0.082	0.2	-10000	0	-0.46	120	120
DHH N/Hhip	-0.077	0.18	-10000	0	-0.41	125	125
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.043	0.2	-10000	0	-0.63	37	37
pancreas development	-0.077	0.2	-10000	0	-0.54	92	92
HHAT	0.005	0.06	-10000	0	-0.58	6	6
PI3K	0.013	0.041	-10000	0	-0.42	5	5
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.13	0.23	-10000	0	-0.52	150	150
somite specification	-0.043	0.2	-10000	0	-0.63	37	37
SHH Np/Cholesterol/PTCH1	-0.031	0.17	-10000	0	-0.62	28	28
SHH Np/Cholesterol/PTCH2	-0.022	0.11	-10000	0	-0.31	73	73
SHH Np/Cholesterol/Megalin	-0.022	0.11	-10000	0	-0.29	72	72
SHH	-0.008	0.1	-10000	0	-0.41	35	35
catabolic process	-0.031	0.16	-10000	0	-0.43	51	51
SMO/Vitamin D3	-0.038	0.19	-10000	0	-0.64	36	36
SHH Np/Cholesterol/Hhip	-0.05	0.15	-10000	0	-0.32	117	117
LRP2	-0.028	0.12	-10000	0	-0.46	42	42
receptor-mediated endocytosis	-0.042	0.19	-10000	0	-0.61	37	37
SHH Np/Cholesterol/BOC	-0.025	0.11	-10000	0	-0.29	83	83
SHH Np/Cholesterol/CDO	-0.007	0.096	-10000	0	-0.33	44	44
mesenchymal cell differentiation	0.05	0.14	0.32	117	-10000	0	117
mol:Vitamin D3	-0.029	0.17	-10000	0	-0.62	28	28
IHH N/PTCH2	-0.043	0.16	-10000	0	-0.43	75	75
CDON	-0.001	0.079	-10000	0	-0.51	13	13
IHH N/PTCH1	-0.031	0.16	-10000	0	-0.44	51	51
Megalin/LRPAP1	-0.012	0.087	-10000	0	-0.32	43	43
PTCH2	-0.027	0.14	-10000	0	-0.54	40	40
SHH Np/Cholesterol	-0.007	0.08	-10000	0	-0.32	35	35
PTCH1	-0.031	0.16	-10000	0	-0.44	51	51
HHIP	-0.077	0.2	-10000	0	-0.54	92	92

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.015	0.024	-9999	-0.32	3	3
VLDLR	-0.042	0.16	-9999	-0.54	55	55
CRKL	0.011	0	-9999	-10000	0	0
LRPAP1	0.01	0.025	-9999	-0.58	1	1
FYN	0.005	0.061	-9999	-0.55	7	7
ITGA3	0.008	0.044	-9999	-0.52	4	4
RELN/VLDLR/Fyn	-0.077	0.17	-9999	-0.34	157	157
MAPK8IP1/MKK7/MAP3K11/JNK1	0.021	0.068	-9999	-0.34	13	13
AKT1	-0.069	0.15	-9999	-0.32	92	92
MAP2K7	0.01	0.025	-9999	-0.58	1	1
RAPGEF1	0.01	0.025	-9999	-0.58	1	1
DAB1	-0.081	0.2	-9999	-0.51	99	99
RELN/LRP8/DAB1	-0.089	0.17	-9999	-0.31	187	187
LRPAP1/LRP8	0.014	0.036	-9999	-0.42	4	4
RELN/LRP8/DAB1/Fyn	-0.081	0.16	-9999	-0.36	108	108
DAB1/alpha3/beta1 Integrin	-0.11	0.16	-9999	-0.5	47	47
long-term memory	-0.11	0.19	-9999	-0.4	114	114
DAB1/LIS1	-0.11	0.16	-9999	-0.51	45	45
DAB1/CRLK/C3G	-0.11	0.16	-9999	-0.5	46	46
PIK3CA	0.009	0.035	-9999	-0.58	2	2
DAB1/NCK2	-0.11	0.16	-9999	-0.52	46	46
ARHGEF2	0.011	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.02	0.11	-9999	-0.47	33	33
CDK5R1	0.009	0.034	-9999	-0.46	3	3
RELN	-0.091	0.21	-9999	-0.52	110	110
PIK3R1	0.008	0.043	-9999	-0.58	3	3
RELN/LRP8/Fyn	-0.047	0.14	-9999	-0.31	119	119
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.091	0.18	-9999	-0.37	124	124
MAPK8	0.01	0.025	-9999	-0.58	1	1
RELN/VLDLR/DAB1	-0.12	0.19	-9999	-0.34	219	219
ITGB1	0.011	0	-9999	-10000	0	0
MAP1B	-0.11	0.19	-9999	-0.38	148	148
RELN/LRP8	-0.043	0.13	-9999	-0.31	114	114
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.1	0.19	-9999	-0.37	143	143
PI3K	0.013	0.041	-9999	-0.42	5	5
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.014	0.032	-9999	-0.37	4	4
RAP1A	-0.074	0.16	-9999	-0.46	46	46
PAFAH1B1	0.011	0	-9999	-10000	0	0
MAPK8IP1	-0.01	0.1	-9999	-0.52	23	23
CRLK/C3G	0.016	0.018	-9999	-0.42	1	1
GRIN2B	-0.041	0.16	-9999	-0.56	52	52
NCK2	0.01	0.025	-9999	-0.58	1	1
neuron differentiation	-0.036	0.12	-9999	-0.38	26	26
neuron adhesion	-0.062	0.16	-9999	-0.44	47	47
LRP8	0.008	0.043	-9999	-0.58	3	3
GSK3B	-0.061	0.14	-9999	-0.44	35	35
RELN/VLDLR/DAB1/Fyn	-0.11	0.18	-9999	-0.38	137	137
MAP3K11	0.01	0.025	-9999	-0.58	1	1
RELN/VLDLR/DAB1/P13K	-0.079	0.15	-9999	-0.32	136	136
CDK5	0.011	0	-9999	-10000	0	0
MAPT	-0.062	0.18	-9999	-0.46	96	96
neuron migration	-0.064	0.16	-9999	-0.46	38	38
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.036	0.12	-9999	-0.38	26	26
RELN/VLDLR	-0.061	0.16	-9999	-0.36	91	91

×

Endothelins

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
AKT1	-0.031	0.22	0.27	34	-0.6	49	83
PTK2B	0.009	0.035	-10000	0	-0.58	2	2
mol:Ca2+	-0.02	0.24	-10000	0	-0.87	33	33
EDN1	-0.022	0.17	0.22	20	-0.44	54	74
EDN3	-0.098	0.22	-10000	0	-0.55	111	111
EDN2	-0.064	0.19	-10000	0	-0.52	80	80
HRAS/GDP	-0.042	0.18	-10000	0	-0.49	53	53
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.021	0.16	-10000	0	-0.45	45	45
ADCY4	-0.046	0.2	-10000	0	-0.52	56	56
ADCY5	-0.1	0.23	-10000	0	-0.52	88	88
ADCY6	-0.042	0.19	-10000	0	-0.5	56	56
ADCY7	-0.044	0.19	-10000	0	-0.51	55	55
ADCY1	-0.069	0.21	-10000	0	-0.52	68	68
ADCY2	-0.068	0.23	-10000	0	-0.58	66	66
ADCY3	-0.042	0.19	-10000	0	-0.5	55	55
ADCY8	-0.055	0.19	-10000	0	-0.52	55	55
ADCY9	-0.044	0.19	-10000	0	-0.52	52	52
arachidonic acid secretion	-0.065	0.2	-10000	0	-0.54	51	51
ETB receptor/Endothelin-1/Gq/GTP	-0.011	0.14	-10000	0	-0.45	31	31
GNAO1	-0.044	0.16	-10000	0	-0.49	63	63
HRAS	0.008	0.042	-10000	0	-0.49	4	4
ETA receptor/Endothelin-1/G12/GTP	-0.027	0.23	0.3	95	-0.58	45	140
ETA receptor/Endothelin-1/Gs/GTP	-0.043	0.23	0.28	92	-0.53	56	148
mol:GTP	0.001	0.004	-10000	0	-10000	0	0
COL3A1	-0.049	0.27	-10000	0	-0.73	58	58
EDNRB	-0.009	0.1	-10000	0	-0.57	19	19
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.063	0.28	-10000	0	-0.67	76	76
CYSLTR1	-0.063	0.29	-10000	0	-0.7	73	73
SLC9A1	-0.023	0.12	0.19	47	-0.31	44	91
mol:GDP	-0.05	0.2	-10000	0	-0.51	58	58
SLC9A3	-0.15	0.31	-10000	0	-0.62	144	144
RAF1	-0.047	0.18	-10000	0	-0.5	45	45
JUN	-0.006	0.2	-10000	0	-0.75	24	24
JAK2	-0.043	0.24	-10000	0	-0.59	59	59
mol:IP3	-0.023	0.17	-10000	0	-0.47	41	41
ETA receptor/Endothelin-1	-0.041	0.28	0.35	98	-0.64	56	154
PLCB1	-0.033	0.15	-10000	0	-0.56	44	44
PLCB2	0.004	0.063	-10000	0	-0.52	8	8
ETA receptor/Endothelin-3	-0.095	0.21	-10000	0	-0.44	128	128
FOS	-0.053	0.24	-10000	0	-0.87	31	31
Gai/GDP	-0.024	0.16	-10000	0	-0.83	17	17
CRK	0.011	0.02	-10000	0	-0.46	1	1
mol:Ca ++	-0.049	0.25	-10000	0	-0.64	62	62
BCAR1	0.008	0.044	-10000	0	-0.52	4	4
PRKCB1	-0.022	0.16	-10000	0	-0.46	40	40
GNAQ	0.006	0.061	-10000	0	-0.58	6	6
GNAZ	-0.012	0.11	-10000	0	-0.54	24	24
GNAL	-0.021	0.13	-10000	0	-0.5	36	36
Gs family/GDP	-0.089	0.16	-10000	0	-0.46	67	67
ETA receptor/Endothelin-1/Gq/GTP	-0.013	0.18	-10000	0	-0.5	39	39
MAPK14	-0.012	0.13	-10000	0	-0.46	26	26
TRPC6	-0.025	0.26	-10000	0	-0.94	33	33
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.088	-10000	0	-0.55	14	14
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.019	0.14	-10000	0	-0.42	37	37
ETB receptor/Endothelin-2	-0.052	0.15	-10000	0	-0.38	98	98
ETB receptor/Endothelin-3	-0.077	0.18	-10000	0	-0.41	127	127
ETB receptor/Endothelin-1	-0.019	0.15	-10000	0	-0.39	60	60
MAPK3	-0.052	0.22	-10000	0	-0.71	38	38
MAPK1	-0.052	0.22	-10000	0	-0.7	39	39
Rac1/GDP	-0.04	0.18	-10000	0	-0.48	54	54
cAMP biosynthetic process	-0.071	0.21	-10000	0	-0.52	68	68
MAPK8	-0.016	0.22	-10000	0	-0.67	39	39
SRC	0.01	0.025	-10000	0	-0.58	1	1
ETB receptor/Endothelin-1/Gi/GTP	-0.018	0.12	-10000	0	-0.41	27	27
p130Cas/CRK/Src/PYK2	-0.05	0.21	-10000	0	-0.6	45	45
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.04	0.18	-10000	0	-0.49	48	48
COL1A2	-0.055	0.3	-10000	0	-0.8	60	60
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.07	0.18	-10000	0	-0.41	103	103
mol:DAG	-0.023	0.17	-10000	0	-0.47	41	41
MAP2K2	-0.046	0.19	-10000	0	-0.55	43	43
MAP2K1	-0.046	0.19	-10000	0	-0.55	44	44
EDNRA	-0.019	0.18	-10000	0	-0.51	46	46
positive regulation of muscle contraction	-0.021	0.2	-10000	0	-0.54	45	45
Gq family/GDP	-0.079	0.17	-10000	0	-0.56	43	43
HRAS/GTP	-0.05	0.18	-10000	0	-0.47	56	56
PRKCH	-0.02	0.16	-10000	0	-0.47	42	42
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.018	0.16	-10000	0	-0.47	36	36
PRKCB	-0.041	0.2	-10000	0	-0.5	61	61
PRKCE	-0.016	0.16	-10000	0	-0.48	33	33
PRKCD	-0.017	0.16	-10000	0	-0.47	35	35
PRKCG	-0.093	0.2	-10000	0	-0.47	70	70
regulation of vascular smooth muscle contraction	-0.064	0.27	-10000	0	-1	31	31
PRKCQ	-0.045	0.19	-10000	0	-0.5	50	50
PLA2G4A	-0.072	0.21	-10000	0	-0.59	51	51
GNA14	-0.007	0.1	-10000	0	-0.56	19	19
GNA15	-0.008	0.1	-10000	0	-0.54	21	21
GNA12	0.011	0	-10000	0	-10000	0	0
GNA11	0.007	0.051	-10000	0	-0.53	5	5
Rac1/GTP	-0.027	0.23	0.3	96	-0.57	46	142
MMP1	-0.15	0.36	0.34	1	-0.75	131	132

×

HIF-1-alpha transcription factor network

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
PKM2	-0.23	0.46	-9999	-1.1	65	65
HDAC7	0.011	0.025	-9999	-0.58	1	1
HIF1A/ARNT/Cbp/p300/Src-1	-0.2	0.33	-9999	-0.9	49	49
SMAD4	0.006	0.06	-9999	-0.58	6	6
ID2	-0.24	0.46	-9999	-1.1	64	64
AP1	-0.017	0.11	-9999	-0.38	48	48
ABCG2	-0.26	0.49	-9999	-1.1	81	81
HIF1A	-0.031	0.11	-9999	-0.68	9	9
TFF3	-0.26	0.49	-9999	-1.2	78	78
GATA2	-0.014	0.12	-9999	-0.55	26	26
AKT1	-0.024	0.087	-9999	-0.72	1	1
response to hypoxia	-0.039	0.085	-9999	-0.25	5	5
MCL1	-0.23	0.46	-9999	-1.1	64	64
NDRG1	-0.24	0.46	-9999	-1.1	67	67
SERPINE1	-0.25	0.48	-9999	-1.2	75	75
FECH	-0.23	0.46	-9999	-1.1	66	66
FURIN	-0.24	0.46	-9999	-1.1	67	67
NCOA2	0.004	0.068	-9999	-0.56	8	8
EP300	-0.016	0.12	-9999	-0.37	17	17
HMOX1	-0.24	0.47	-9999	-1.2	64	64
BHLHE40	-0.24	0.46	-9999	-1.1	66	66
BHLHE41	-0.25	0.48	-9999	-1.2	71	71
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.039	0.11	-9999	-0.51	13	13
ENG	-0.006	0.12	-9999	-0.52	11	11
JUN	0.006	0.053	-9999	-0.56	5	5
RORA	-0.24	0.48	-9999	-1.2	72	72
ABCB1	-0.23	0.41	-9999	-1.1	95	95
TFRC	-0.24	0.47	-9999	-1.2	64	64
CXCR4	-0.25	0.48	-9999	-1.2	75	75
TF	-0.29	0.5	-9999	-1.1	88	88
CITED2	-0.24	0.46	-9999	-1.2	63	63
HIF1A/ARNT	-0.3	0.51	-9999	-1.3	76	76
LDHA	-0.037	0.078	-9999	-1.1	2	2
ETS1	-0.24	0.47	-9999	-1.2	64	64
PGK1	-0.23	0.46	-9999	-1.1	64	64
NOS2	-0.29	0.5	-9999	-1.2	88	88
ITGB2	-0.25	0.48	-9999	-1.2	75	75
ALDOA	-0.23	0.46	-9999	-1.1	69	69
Cbp/p300/CITED2	-0.22	0.47	-9999	-1.2	62	62
FOS	-0.03	0.14	-9999	-0.53	44	44
HK2	-0.24	0.46	-9999	-1.1	65	65
SP1	0.003	0.044	-9999	-0.58	1	1
GCK	-0.052	0.28	-9999	-1.3	19	19
HK1	-0.23	0.46	-9999	-1.1	64	64
NPM1	-0.24	0.47	-9999	-1.2	65	65
EGLN1	-0.23	0.46	-9999	-1.1	64	64
CREB1	0.016	0.035	-9999	-0.58	2	2
PGM1	-0.24	0.46	-9999	-1.1	64	64
SMAD3	0.005	0.063	-9999	-0.56	7	7
EDN1	-0.061	0.27	-9999	-1.1	24	24
IGFBP1	-0.29	0.5	-9999	-1.1	96	96
VEGFA	-0.12	0.34	-9999	-0.85	28	28
HIF1A/JAB1	-0.026	0.07	-9999	-0.49	10	10
CP	-0.3	0.51	-9999	-1.2	93	93
CXCL12	-0.24	0.48	-9999	-1.1	74	74
COPS5	0.011	0.02	-9999	-0.46	1	1
SMAD3/SMAD4	0.009	0.064	-9999	-0.41	13	13
BNIP3	-0.26	0.49	-9999	-1.1	80	80
EGLN3	-0.24	0.47	-9999	-1.2	67	67
CA9	-0.32	0.52	-9999	-1.1	118	118
TERT	-0.26	0.48	-9999	-1.1	80	80
ENO1	-0.23	0.46	-9999	-1.1	66	66
PFKL	-0.24	0.47	-9999	-1.2	64	64
NCOA1	0.01	0.025	-9999	-0.58	1	1
ADM	-0.24	0.47	-9999	-1.1	68	68
ARNT	-0.022	0.078	-9999	-0.64	1	1
HNF4A	0.004	0.067	-9999	-0.58	7	7
ADFP	-0.24	0.46	-9999	-1.1	71	71
SLC2A1	-0.12	0.34	-9999	-0.88	31	31
LEP	-0.25	0.47	-9999	-1.2	68	68
HIF1A/ARNT/Cbp/p300	-0.21	0.34	-9999	-0.94	46	46
EPO	-0.099	0.3	-9999	-0.98	13	13
CREBBP	-0.013	0.12	-9999	-0.36	14	14
HIF1A/ARNT/Cbp/p300/HDAC7	-0.2	0.33	-9999	-0.94	42	42
PFKFB3	-0.23	0.46	-9999	-1.1	64	64
NT5E	-0.25	0.48	-9999	-1.2	69	69

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.01	0.031	-10000	0	-0.52	2	2
LAT2	-0.061	0.16	-10000	0	-0.4	77	77
AP1	-0.1	0.19	-10000	0	-0.57	67	67
mol:PIP3	-0.079	0.21	-10000	0	-0.57	65	65
IKBKB	-0.033	0.13	0.15	12	-0.31	67	79
AKT1	-0.05	0.16	-10000	0	-0.45	42	42
IKBKG	-0.033	0.13	0.15	12	-0.31	68	80
MS4A2	-0.079	0.2	-10000	0	-0.54	94	94
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
MAP3K1	-0.05	0.18	-10000	0	-0.49	60	60
mol:Ca2+	-0.055	0.16	-10000	0	-0.41	65	65
LYN	0.009	0.006	-10000	0	-10000	0	0
CBLB	-0.058	0.16	-10000	0	-0.39	76	76
SHC1	0.011	0	-10000	0	-10000	0	0
RasGAP/p62DOK	0.01	0.056	-10000	0	-0.25	25	25
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	-0.015	0.12	-10000	0	-0.58	26	26
PLD2	-0.073	0.17	-10000	0	-0.37	99	99
PTPN13	-0.091	0.19	-10000	0	-0.56	51	51
PTPN11	0.003	0.057	-10000	0	-0.6	5	5
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.025	0.13	-10000	0	-0.36	38	38
SYK	0.008	0.02	-10000	0	-0.45	1	1
GRB2	0.011	0.001	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.2	-10000	0	-0.58	67	67
LAT	-0.067	0.17	-10000	0	-0.4	82	82
PAK2	-0.06	0.19	-10000	0	-0.53	63	63
NFATC2	-0.081	0.18	-10000	0	-0.65	45	45
HRAS	-0.072	0.21	-10000	0	-0.57	66	66
GAB2	0.009	0.035	-10000	0	-0.58	2	2
PLA2G1B	0.029	0.026	-10000	0	-10000	0	0
Fc epsilon R1	-0.12	0.19	-10000	0	-0.38	175	175
Antigen/IgE/Fc epsilon R1	-0.1	0.18	-10000	0	-0.35	175	175
mol:GDP	-0.083	0.23	-10000	0	-0.62	68	68
JUN	0.006	0.053	-10000	0	-0.56	5	5
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
FOS	-0.03	0.14	-10000	0	-0.53	44	44
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.065	0.16	-10000	0	-0.38	87	87
CHUK	-0.034	0.13	0.15	12	-0.31	67	79
KLRG1	-0.062	0.15	-10000	0	-0.39	67	67
VAV1	-0.074	0.19	-10000	0	-0.43	93	93
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.056	0.15	-10000	0	-0.43	56	56
negative regulation of mast cell degranulation	-0.065	0.16	-10000	0	-0.41	67	67
BTK	-0.086	0.24	-10000	0	-0.68	63	63
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.11	0.24	-10000	0	-0.48	119	119
GAB2/PI3K/SHP2	-0.088	0.15	-10000	0	-0.5	42	42
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.058	0.16	-10000	0	-0.33	102	102
RAF1	0.023	0.025	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.14	0.24	-10000	0	-0.47	154	154
FCER1G	-0.017	0.12	-10000	0	-0.53	31	31
FCER1A	-0.077	0.2	-10000	0	-0.55	88	88
Antigen/IgE/Fc epsilon R1/Fyn	-0.084	0.18	-10000	0	-0.37	127	127
MAPK3	0.029	0.025	-10000	0	-10000	0	0
MAPK1	0.029	0.026	-10000	0	-10000	0	0
NFKB1	0.01	0.025	-10000	0	-0.58	1	1
MAPK8	-0.005	0.073	-10000	0	-0.5	5	5
DUSP1	-0.008	0.095	-10000	0	-0.47	23	23
NF-kappa-B/RelA	-0.038	0.062	-10000	0	-0.22	22	22
actin cytoskeleton reorganization	-0.057	0.17	-10000	0	-0.56	36	36
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.094	0.18	-10000	0	-0.53	63	63
FER	-0.061	0.16	-10000	0	-0.39	78	78
RELA	0.011	0	-10000	0	-10000	0	0
ITK	-0.049	0.12	-10000	0	-0.45	43	43
SOS1	0.01	0.025	-10000	0	-0.58	1	1
PLCG1	-0.08	0.23	-10000	0	-0.62	68	68
cytokine secretion	-0.027	0.045	-10000	0	-10000	0	0
SPHK1	-0.076	0.18	-10000	0	-0.41	94	94
PTK2	-0.06	0.18	-10000	0	-0.6	34	34
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.12	0.2	-10000	0	-0.53	86	86
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.071	0.2	-10000	0	-0.54	65	65
MAP2K2	0.026	0.026	-10000	0	-10000	0	0
MAP2K1	0.026	0.03	-10000	0	-10000	0	0
MAP2K7	0.01	0.025	-10000	0	-0.58	1	1
KLRG1/SHP2	-0.058	0.14	-10000	0	-0.39	60	60
MAP2K4	0.007	0.08	-10000	0	-0.94	4	4
Fc epsilon R1/FcgammaRIIB	-0.14	0.25	-10000	0	-0.49	152	152
mol:Choline	-0.072	0.17	-10000	0	-0.37	99	99
SHC/Grb2/SOS1	-0.044	0.15	-10000	0	-0.47	38	38
FYN	0.005	0.061	-10000	0	-0.55	7	7
DOK1	0.011	0	-10000	0	-10000	0	0
PXN	-0.05	0.16	-10000	0	-0.55	34	34
HCLS1	-0.062	0.17	-10000	0	-0.4	82	82
PRKCB	-0.058	0.18	-10000	0	-0.43	74	74
FCGR2B	-0.082	0.21	-10000	0	-0.53	99	99
IGHE	-0.003	0.007	-10000	0	-10000	0	0
KLRG1/SHIP	-0.066	0.16	-10000	0	-0.42	67	67
LCP2	-0.014	0.12	-10000	0	-0.54	26	26
PLA2G4A	-0.13	0.21	-10000	0	-0.42	147	147
RASA1	0.009	0.035	-10000	0	-0.58	2	2
mol:Phosphatidic acid	-0.072	0.17	-10000	0	-0.37	99	99
IKK complex	-0.014	0.1	0.15	12	-0.24	53	65
WIPF1	-0.001	0.083	-10000	0	-0.54	13	13

×

TCGA08_retinoblastoma

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
CDKN2B	-0.012	0.1	-10000	0	-0.51	24	24
CDKN2C	0.018	0.017	-10000	0	-10000	0	0
CDKN2A	-0.069	0.19	-10000	0	-0.5	90	90
CCND2	0.019	0.072	0.21	46	-0.13	25	71
RB1	-0.016	0.077	-10000	0	-0.22	51	51
CDK4	0.027	0.075	0.23	46	-10000	0	46
CDK6	0.026	0.076	0.23	46	-10000	0	46
G1/S progression	0.016	0.077	0.22	51	-10000	0	51

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.13	0.2	-9999	-0.38	181	181
SMAD6-7/SMURF1	0.019	0.043	-9999	-0.38	6	6
NOG	-0.025	0.12	-9999	-0.47	40	40
SMAD9	-0.062	0.16	-9999	-0.53	52	52
SMAD4	0.005	0.06	-9999	-0.58	6	6
SMAD5	-0.044	0.14	-9999	-0.46	28	28
BMP7/USAG1	-0.16	0.24	-9999	-0.44	226	226
SMAD5/SKI	-0.036	0.13	-9999	-0.44	26	26
SMAD1	0.021	0.046	-9999	-0.47	3	3
BMP2	-0.001	0.081	-9999	-0.53	13	13
SMAD1/SMAD1/SMAD4	-0.007	0.046	-9999	-0.48	3	3
BMPR1A	0.01	0.025	-9999	-0.58	1	1
BMPR1B	-0.094	0.21	-9999	-0.51	115	115
BMPR1A-1B/BAMBI	-0.079	0.16	-9999	-0.32	169	169
AHSG	-0.041	0.14	-9999	-0.46	60	60
CER1	-0.005	0.063	-9999	-0.46	11	11
BMP2-4/CER1	-0.009	0.094	-9999	-0.31	47	47
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.049	0.14	-9999	-0.42	44	44
BMP2-4 (homodimer)	-0.009	0.1	-9999	-0.38	37	37
RGMB	-0.012	0.1	-9999	-0.46	29	29
BMP6/BMPR2/BMPR1A-1B	-0.045	0.14	-9999	-0.34	66	66
RGMA	-0.071	0.2	-9999	-0.54	86	86
SMURF1	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.048	0.13	-9999	-0.39	41	41
BMP2-4/USAG1	-0.07	0.17	-9999	-0.35	144	144
SMAD6/SMURF1/SMAD5	-0.036	0.13	-9999	-0.44	26	26
SOSTDC1	-0.1	0.23	-9999	-0.56	116	116
BMP7/BMPR2/BMPR1A-1B	-0.11	0.18	-9999	-0.38	144	144
SKI	0.011	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.01	0.1	-9999	-0.51	23	23
HFE2	0	0.033	-9999	-0.46	3	3
ZFYVE16	-0.006	0.1	-9999	-0.58	17	17
MAP3K7	0.011	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.018	0.12	-9999	-0.34	65	65
SMAD5/SMAD5/SMAD4	-0.04	0.13	-9999	-0.44	27	27
MAPK1	0.01	0.025	-9999	-0.58	1	1
TAK1/TAB family	-0.056	0.097	-9999	-0.38	26	26
BMP7 (homodimer)	-0.13	0.24	-9999	-0.54	144	144
NUP214	0.011	0	-9999	-10000	0	0
BMP6/FETUA	-0.036	0.12	-9999	-0.34	82	82
SMAD1/SKI	0.026	0.044	-9999	-0.44	3	3
SMAD6	0.007	0.051	-9999	-0.53	5	5
CTDSP2	0.011	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.031	0.12	-9999	-0.3	93	93
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.08	0.21	-9999	-0.54	96	96
BMPR2 (homodimer)	0.006	0.055	-9999	-0.58	5	5
GADD34/PP1CA	0.012	0.064	-9999	-0.35	17	17
BMPR1A-1B (homodimer)	-0.06	0.15	-9999	-0.36	116	116
CHRDL1	-0.16	0.25	-9999	-0.52	182	182
ENDOFIN/SMAD1	0.017	0.073	-9999	-0.62	3	3
SMAD6-7/SMURF1/SMAD1	0.032	0.056	-9999	-0.54	3	3
SMAD6/SMURF1	0.011	0	-9999	-10000	0	0
BAMBI	-0.049	0.17	-9999	-0.52	65	65
SMURF2	0.007	0.051	-9999	-0.53	5	5
BMP2-4/CHRDL1	-0.1	0.18	-9999	-0.33	207	207
BMP2-4/GREM1	-0.056	0.16	-9999	-0.33	127	127
SMAD7	0.009	0.035	-9999	-0.58	2	2
SMAD8A/SMAD8A/SMAD4	-0.056	0.16	-9999	-0.48	57	57
SMAD1/SMAD6	0.026	0.044	-9999	-0.44	3	3
TAK1/SMAD6	0.017	0	-9999	-10000	0	0
BMP7	-0.13	0.24	-9999	-0.54	144	144
BMP6	-0.01	0.1	-9999	-0.52	23	23
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.039	0.12	-9999	-0.36	42	42
PPM1A	0.011	0	-9999	-10000	0	0
SMAD1/SMURF2	0.024	0.055	-9999	-0.48	4	4
SMAD7/SMURF1	0.015	0.026	-9999	-0.42	2	2
CTDSPL	0.011	0	-9999	-10000	0	0
PPP1CA	0.011	0	-9999	-10000	0	0
XIAP	0.01	0.025	-9999	-0.58	1	1
CTDSP1	0.01	0.025	-9999	-0.58	1	1
PPP1R15A	0.011	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.081	0.19	-9999	-0.5	67	67
CHRD	-0.021	0.13	-9999	-0.55	33	33
BMPR2	0.006	0.055	-9999	-0.58	5	5
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.055	0.14	-9999	-0.43	41	41
BMP4	-0.012	0.11	-9999	-0.5	26	26
FST	-0.052	0.18	-9999	-0.52	68	68
BMP2-4/NOG	-0.021	0.11	-9999	-0.3	74	74
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.099	0.18	-9999	-0.35	144	144

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.038	0.17	-10000	0	-0.61	45	45
NFATC2	-0.093	0.26	-10000	0	-0.67	65	65
NFATC3	-0.02	0.077	-10000	0	-0.29	2	2
CD40LG	-0.28	0.42	-10000	0	-1	101	101
ITCH	0.027	0.086	-10000	0	-0.8	5	5
CBLB	0.028	0.082	-10000	0	-0.84	4	4
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.28	0.45	-10000	0	-1.2	89	89
JUNB	0.007	0.051	-10000	0	-0.53	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.009	0.06	-10000	0	-0.37	14	14
T cell anergy	0.004	0.1	-10000	0	-0.55	14	14
TLE4	-0.058	0.21	-10000	0	-0.7	36	36
Jun/NFAT1-c-4/p21SNFT	-0.18	0.37	-10000	0	-1	58	58
AP-1/NFAT1-c-4	-0.3	0.48	-10000	0	-1.1	98	98
IKZF1	-0.075	0.26	-10000	0	-0.75	53	53
T-helper 2 cell differentiation	-0.13	0.26	-10000	0	-0.84	46	46
AP-1/NFAT1	-0.097	0.21	-10000	0	-0.56	62	62
CALM1	0.018	0.034	-10000	0	-0.3	3	3
EGR2	-0.14	0.36	-10000	0	-1.2	39	39
EGR3	-0.15	0.38	-10000	0	-1.3	41	41
NFAT1/FOXP3	-0.094	0.27	-10000	0	-0.76	61	61
EGR1	-0.012	0.11	-10000	0	-0.5	27	27
JUN	-0.009	0.06	-10000	0	-0.58	5	5
EGR4	-0.055	0.17	-10000	0	-0.51	71	71
mol:Ca2+	0.007	0.035	-10000	0	-0.32	3	3
GBP3	-0.12	0.31	-10000	0	-0.8	85	85
FOSL1	-0.024	0.13	-10000	0	-0.51	39	39
NFAT1-c-4/MAF/IRF4	-0.19	0.38	-10000	0	-1.1	62	62
DGKA	-0.053	0.2	-10000	0	-0.64	36	36
CREM	0.01	0.019	-10000	0	-0.46	1	1
NFAT1-c-4/PPARG	-0.15	0.35	-10000	0	-1.1	48	48
CTLA4	-0.096	0.29	-10000	0	-0.83	61	61
NFAT1-c-4 (dimer)/EGR1	-0.16	0.36	-10000	0	-1.1	52	52
NFAT1-c-4 (dimer)/EGR4	-0.18	0.36	-10000	0	-1	59	59
FOS	-0.046	0.15	-10000	0	-0.54	44	44
IFNG	-0.23	0.4	-10000	0	-0.97	104	104
T cell activation	-0.11	0.2	-10000	0	-0.71	21	21
MAF	0.001	0.075	-10000	0	-0.54	11	11
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.12	0.3	1	37	-10000	0	37
TNF	-0.18	0.35	-10000	0	-0.96	65	65
FASLG	-0.24	0.51	-10000	0	-1.4	73	73
TBX21	-0.059	0.18	-10000	0	-0.56	67	67
BATF3	-0.005	0.089	-10000	0	-0.5	18	18
PRKCQ	-0.047	0.17	-10000	0	-0.58	54	54
PTPN1	-0.05	0.19	-10000	0	-0.64	30	30
NFAT1-c-4/ICER1	-0.15	0.35	-10000	0	-1	51	51
GATA3	-0.017	0.12	-10000	0	-0.52	31	31
T-helper 1 cell differentiation	-0.21	0.4	-10000	0	-0.93	105	105
IL2RA	-0.27	0.42	-10000	0	-1.1	93	93
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.051	0.19	-10000	0	-0.64	32	32
E2F1	0.014	0.037	-10000	0	-0.49	3	3
PPARG	0.004	0.065	-10000	0	-0.58	7	7
SLC3A2	-0.049	0.19	-10000	0	-0.63	30	30
IRF4	-0.079	0.2	-10000	0	-0.54	95	95
PTGS2	-0.3	0.44	-10000	0	-0.98	125	125
CSF2	-0.31	0.44	-10000	0	-0.98	128	128
JunB/Fra1/NFAT1-c-4	-0.16	0.34	-10000	0	-1	51	51
IL4	-0.14	0.27	-10000	0	-0.91	44	44
IL5	-0.26	0.4	-10000	0	-0.98	93	93
IL2	-0.11	0.21	-10000	0	-0.74	20	20
IL3	-0.064	0.1	-10000	0	-0.8	7	7
RNF128	0.024	0.093	-10000	0	-0.62	11	11
NFATC1	-0.12	0.3	-10000	0	-1	36	36
CDK4	0.083	0.18	0.66	14	-10000	0	14
PTPRK	-0.05	0.19	-10000	0	-0.63	32	32
IL8	-0.31	0.45	-10000	0	-1	125	125
POU2F1	0.002	0.073	-10000	0	-0.54	10	10

×

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	0.01	0.031	-10000	0	-0.52	2	2
EPHB2	0	0.081	-10000	0	-0.55	12	12
EFNB1	0.006	0.066	-10000	0	-0.36	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.062	0.15	-10000	0	-0.48	32	32
Ephrin B2/EPHB1-2	-0.051	0.13	-10000	0	-0.32	54	54
neuron projection morphogenesis	-0.083	0.13	-10000	0	-0.46	32	32
Ephrin B1/EPHB1-2/Tiam1	-0.071	0.16	-10000	0	-0.49	35	35
DNM1	-0.004	0.087	-10000	0	-0.5	17	17
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.077	0.23	-10000	0	-0.66	74	74
YES1	-0.12	0.3	-10000	0	-0.89	73	73
Ephrin B1/EPHB1-2/NCK2	-0.043	0.13	-10000	0	-0.44	14	14
PI3K	-0.077	0.23	-10000	0	-0.65	77	77
mol:GDP	-0.071	0.16	-10000	0	-0.49	35	35
ITGA2B	-0.047	0.16	-10000	0	-0.5	64	64
endothelial cell proliferation	0.014	0.02	-10000	0	-0.31	2	2
FYN	-0.12	0.3	-10000	0	-0.89	73	73
MAP3K7	-0.086	0.24	-10000	0	-0.7	73	73
FGR	-0.12	0.3	-10000	0	-0.88	74	74
TIAM1	-0.043	0.16	-10000	0	-0.52	59	59
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
RGS3	0.011	0	-10000	0	-10000	0	0
cell adhesion	-0.096	0.24	-10000	0	-0.62	82	82
LYN	-0.12	0.3	-10000	0	-0.89	73	73
Ephrin B1/EPHB1-2/Src Family Kinases	-0.11	0.28	-10000	0	-0.83	73	73
Ephrin B1/EPHB1-2	-0.1	0.25	-10000	0	-0.76	73	73
SRC	-0.12	0.3	-10000	0	-0.88	73	73
ITGB3	-0.005	0.093	-10000	0	-0.54	17	17
EPHB1	-0.11	0.22	-10000	0	-0.49	135	135
EPHB4	0.011	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.014	0.02	-10000	0	-0.32	2	2
alphaIIb/beta3 Integrin	-0.037	0.13	-10000	0	-0.37	80	80
BLK	-0.14	0.31	-10000	0	-0.91	74	74
HCK	-0.12	0.3	-10000	0	-0.89	74	74
regulation of stress fiber formation	0.044	0.13	0.43	14	-10000	0	14
MAPK8	-0.068	0.22	-10000	0	-0.62	75	75
Ephrin B1/EPHB1-2/RGS3	-0.043	0.13	-10000	0	-0.35	29	29
endothelial cell migration	-0.07	0.21	-10000	0	-0.6	74	74
NCK2	0.01	0.025	-10000	0	-0.58	1	1
PTPN13	-0.089	0.24	-10000	0	-0.65	88	88
regulation of focal adhesion formation	0.044	0.13	0.43	14	-10000	0	14
chemotaxis	0.043	0.13	0.35	29	-10000	0	29
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
Rac1/GTP	-0.084	0.14	-10000	0	-0.47	32	32
angiogenesis	-0.1	0.25	-10000	0	-0.75	73	73
LCK	-0.12	0.3	-10000	0	-0.91	73	73

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.057	0.16	0.4	97	-10000	0	97
KIRREL	-0.029	0.14	-10000	0	-0.58	34	34
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.057	0.16	-10000	0	-0.4	97	97
PLCG1	0.01	0.025	-10000	0	-0.58	1	1
ARRB2	0.011	0	-10000	0	-10000	0	0
WASL	0.011	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.056	0.16	-10000	0	-0.38	84	84
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.022	0.11	-10000	0	-0.35	35	35
FYN	-0.041	0.13	-10000	0	-0.34	62	62
mol:Ca2+	-0.039	0.13	-10000	0	-0.36	58	58
mol:DAG	-0.039	0.13	-10000	0	-0.37	58	58
NPHS2	-0.021	0.091	-10000	0	-0.46	22	22
mol:IP3	-0.039	0.13	-10000	0	-0.37	58	58
regulation of endocytosis	-0.031	0.12	-10000	0	-0.32	58	58
Nephrin/NEPH1/podocin/Cholesterol	-0.046	0.13	-10000	0	-0.37	58	58
establishment of cell polarity	-0.057	0.16	-10000	0	-0.4	97	97
Nephrin/NEPH1/podocin/NCK1-2	-0.029	0.12	-10000	0	-0.48	17	17
Nephrin/NEPH1/beta Arrestin2	-0.031	0.12	-10000	0	-0.33	58	58
NPHS1	-0.057	0.17	-10000	0	-0.51	70	70
Nephrin/NEPH1/podocin	-0.04	0.13	-10000	0	-0.34	62	62
TJP1	0.01	0.025	-10000	0	-0.58	1	1
NCK1	0.009	0.035	-10000	0	-0.58	2	2
NCK2	0.01	0.025	-10000	0	-0.58	1	1
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.039	0.13	-10000	0	-0.37	58	58
CD2AP	-0.018	0.13	-10000	0	-0.58	29	29
Nephrin/NEPH1/podocin/GRB2	-0.038	0.13	-10000	0	-0.36	58	58
GRB2	0.011	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.049	0.15	-10000	0	-0.38	69	69
cytoskeleton organization	-0.026	0.13	-10000	0	-0.4	39	39
Nephrin/NEPH1	-0.039	0.12	-10000	0	-0.28	97	97
Nephrin/NEPH1/ZO-1	-0.037	0.14	-10000	0	-0.38	58	58

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.05	0.14	-10000	0	-0.37	90	90
TP53	-0.047	0.11	0.21	2	-0.36	52	54
Senescence	-0.047	0.11	0.21	2	-0.35	52	54
Apoptosis	-0.047	0.11	0.21	2	-0.35	52	54
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.03	0.084	0.26	38	-0.34	4	42
MDM4	0.01	0.031	-10000	0	-0.52	2	2

×

Calcium signaling in the CD4+ TCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.019	0.084	-9999	-0.34	30	30
NFATC2	-0.034	0.11	-9999	-0.38	49	49
NFATC3	-0.001	0.032	-9999	-10000	0	0
CD40LG	-0.18	0.32	-9999	-0.73	104	104
PTGS2	-0.2	0.33	-9999	-0.7	128	128
JUNB	0.007	0.051	-9999	-0.53	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.009	0.016	-9999	-10000	0	0
CaM/Ca2+	-0.009	0.015	-9999	-10000	0	0
CALM1	0.006	0.011	-9999	-10000	0	0
JUN	0.001	0.054	-9999	-0.56	5	5
mol:Ca2+	-0.009	0.013	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.004	0.007	-9999	-10000	0	0
FOSL1	-0.024	0.13	-9999	-0.51	39	39
CREM	0.01	0.019	-9999	-0.46	1	1
Jun/NFAT1-c-4/p21SNFT	-0.098	0.2	-9999	-0.52	66	66
FOS	-0.036	0.15	-9999	-0.54	44	44
IFNG	-0.19	0.32	-9999	-0.7	127	127
AP-1/NFAT1-c-4	-0.19	0.35	-9999	-0.76	118	118
FASLG	-0.18	0.32	-9999	-0.72	115	115
NFAT1-c-4/ICER1	-0.061	0.14	-9999	-0.41	53	53
IL2RA	-0.18	0.32	-9999	-0.77	95	95
FKBP12/FK506	0.008	0	-9999	-10000	0	0
CSF2	-0.2	0.34	-9999	-0.68	150	150
JunB/Fra1/NFAT1-c-4	-0.073	0.15	-9999	-0.4	69	69
IL4	-0.16	0.28	-9999	-0.68	88	88
IL2	-0.007	0.025	-9999	-0.36	2	2
IL3	-0.031	0.096	-9999	-0.85	7	7
FKBP1A	0.011	0	-9999	-10000	0	0
BATF3	-0.005	0.089	-9999	-0.5	18	18
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.002	0.073	-9999	-0.54	10	10

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.015	0.026	-9999	-0.42	2	2
Necdin/E2F1	0.008	0.057	-9999	-0.36	13	13
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.053	0.16	-9999	-0.49	27	27
NGF (dimer)/p75(NTR)/BEX1	-0.099	0.2	-9999	-0.45	109	109
NT-4/5 (dimer)/p75(NTR)	-0.067	0.16	-9999	-0.37	118	118
IKBKB	0.011	0.019	-9999	-0.46	1	1
AKT1	-0.04	0.14	-9999	-0.33	85	85
IKBKG	0.01	0.025	-9999	-0.58	1	1
BDNF	-0.02	0.13	-9999	-0.52	34	34
MGDIs/NGR/p75(NTR)/LINGO1	-0.062	0.16	-9999	-0.41	61	61
FURIN	0.01	0.031	-9999	-0.52	2	2
proBDNF (dimer)/p75(NTR)/Sortilin	-0.052	0.15	-9999	-0.4	58	58
LINGO1	-0.024	0.12	-9999	-0.47	42	42
Sortilin/TRAF6/NRIF	-0.008	0.051	-9999	-0.79	1	1
proBDNF (dimer)	-0.02	0.13	-9999	-0.52	34	34
NTRK1	-0.039	0.16	-9999	-0.53	52	52
RTN4R	-0.003	0.083	-9999	-0.48	17	17
neuron apoptosis	-0.059	0.17	-9999	-0.58	24	24
IRAK1	0.01	0.031	-9999	-0.52	2	2
SHC1	-0.057	0.16	-9999	-0.35	123	123
ARHGDIA	0.008	0.043	-9999	-0.58	3	3
RhoA/GTP	0.008	0.018	-9999	-0.43	1	1
Gamma Secretase	0.031	0.033	-9999	-0.3	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.049	0.15	-9999	-0.36	85	85
MAGEH1	0.003	0.068	-9999	-0.56	8	8
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.05	0.16	-9999	-0.37	84	84
Mammalian IAPs/DIABLO	0.006	0.1	-9999	-0.46	20	20
proNGF (dimer)	-0.029	0.14	-9999	-0.52	43	43
MAGED1	0.011	0	-9999	-10000	0	0
APP	0.01	0.025	-9999	-0.58	1	1
NT-4/5 (dimer)	-0.014	0.091	-9999	-0.46	23	23
ZNF274	0.001	0.077	-9999	-0.58	10	10
RhoA/GDP/RHOGDI	-0.044	0.14	-9999	-0.34	83	83
NGF	-0.029	0.14	-9999	-0.52	43	43
cell cycle arrest	-0.048	0.14	-9999	-0.48	21	21
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.023	0.11	-9999	-0.28	30	30
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.049	0.14	-9999	-0.38	48	48
NCSTN	0.011	0	-9999	-10000	0	0
mol:GTP	-0.077	0.18	-9999	-0.37	145	145
PSENEN	0.01	0.025	-9999	-0.58	1	1
mol:ceramide	-0.046	0.14	-9999	-0.36	79	79
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.012	0.096	-9999	-0.44	6	6
p75(NTR)/beta APP	-0.05	0.14	-9999	-0.36	101	101
BEX1	-0.06	0.18	-9999	-0.5	77	77
mol:GDP	-0.065	0.16	-9999	-0.35	123	123
NGF (dimer)	-0.1	0.18	-9999	-0.38	130	130
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.05	0.15	-9999	-0.38	62	62
PIK3R1	0.008	0.043	-9999	-0.58	3	3
RAC1/GTP	-0.049	0.14	-9999	-0.3	123	123
MYD88	0.011	0	-9999	-10000	0	0
CHUK	0.007	0.049	-9999	-0.58	4	4
NGF (dimer)/p75(NTR)/PKA	-0.077	0.18	-9999	-0.37	145	145
RHOB	0.008	0.04	-9999	-0.54	3	3
RHOA	0.01	0.025	-9999	-0.58	1	1
MAGE-G1/E2F1	0.015	0.027	-9999	-0.35	3	3
NT3 (dimer)	-0.02	0.13	-9999	-0.53	33	33
TP53	-0.06	0.16	-9999	-0.55	19	19
PRDM4	-0.046	0.15	-9999	-0.36	79	79
BDNF (dimer)	-0.18	0.22	-9999	-0.42	194	194
PIK3CA	0.009	0.035	-9999	-0.58	2	2
SORT1	0.01	0.025	-9999	-0.58	1	1
activation of caspase activity	-0.055	0.15	-9999	-0.48	27	27
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.045	0.15	-9999	-0.36	80	80
RHOC	0.011	0	-9999	-10000	0	0
XIAP	0.01	0.025	-9999	-0.58	1	1
MAPK10	-0.041	0.16	-9999	-0.5	29	29
DIABLO	0.011	0	-9999	-10000	0	0
SMPD2	-0.046	0.15	-9999	-0.36	79	79
APH1B	0.006	0.055	-9999	-0.58	5	5
APH1A	0.011	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.058	0.16	-9999	-0.4	79	79
PSEN1	0.011	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0.014	0.036	-9999	-0.42	4	4
NT3 (dimer)/p75(NTR)	-0.071	0.18	-9999	-0.39	123	123
MAPK8	-0.025	0.14	-9999	-0.51	15	15
MAPK9	-0.025	0.14	-9999	-0.51	15	15
APAF1	0.008	0.043	-9999	-0.58	3	3
NTF3	-0.02	0.13	-9999	-0.54	33	33
NTF4	-0.014	0.091	-9999	-0.46	23	23
NDN	0.002	0.07	-9999	-0.52	10	10
RAC1/GDP	0.008	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.073	0.13	-9999	-0.46	30	30
p75 CTF/Sortilin/TRAF6/NRIF	0.021	0.062	-9999	-0.37	12	12
RhoA-B-C/GTP	-0.076	0.18	-9999	-0.37	145	145
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.038	0.14	-9999	-0.57	14	14
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.041	0.14	-9999	-0.36	59	59
PRKACB	-0.021	0.13	-9999	-0.57	32	32
proBDNF (dimer)/p75 ECD	-0.008	0.096	-9999	-0.38	36	36
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.016	0.12	-9999	-0.52	29	29
BIRC2	-0.002	0.088	-9999	-0.58	13	13
neuron projection morphogenesis	-0.061	0.15	-9999	-0.37	78	78
BAD	-0.026	0.14	-9999	-0.48	20	20
RIPK2	0.011	0	-9999	-10000	0	0
NGFR	-0.079	0.2	-9999	-0.51	100	100
CYCS	-0.047	0.15	-9999	-0.49	26	26
ADAM17	0.009	0.035	-9999	-0.58	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.045	0.15	-9999	-0.36	80	80
BCL2L11	-0.026	0.14	-9999	-0.48	20	20
BDNF (dimer)/p75(NTR)	-0.071	0.17	-9999	-0.39	124	124
PI3K	-0.047	0.15	-9999	-0.36	84	84
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.045	0.15	-9999	-0.36	79	79
NDNL2	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
PRKCI	0.008	0.043	-9999	-0.58	3	3
NGF (dimer)/p75(NTR)	-0.076	0.18	-9999	-0.42	123	123
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.045	0.15	-9999	-0.36	79	79
TRAF6	0.01	0.025	-9999	-0.58	1	1
RAC1	0.011	0	-9999	-10000	0	0
PRKCZ	0.01	0.031	-9999	-0.52	2	2
PLG	-0.037	0.15	-9999	-0.58	41	41
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.055	0.16	-9999	-0.4	63	63
SQSTM1	0.011	0	-9999	-10000	0	0
NGFRAP1	-0.02	0.13	-9999	-0.58	30	30
CASP3	-0.022	0.14	-9999	-0.43	21	21
E2F1	0.009	0.037	-9999	-0.5	3	3
CASP9	0.01	0.025	-9999	-0.58	1	1
IKK complex	-0.06	0.12	-9999	-0.51	18	18
NGF (dimer)/TRKA	-0.048	0.16	-9999	-0.41	86	86
MMP7	-0.14	0.24	-9999	-0.51	160	160
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.042	0.15	-9999	-0.43	34	34
MMP3	-0.13	0.24	-9999	-0.53	147	147
APAF-1/Caspase 9	-0.066	0.14	-9999	-0.58	23	23

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.021	0.074	0.35	5	-10000	0	5
SMARCC2	0.012	0.006	-10000	0	-10000	0	0
SMARCC1	0.012	0.006	-10000	0	-10000	0	0
TBX21	-0.11	0.26	-10000	0	-0.67	85	85
SUMO2	0.01	0.026	-10000	0	-0.58	1	1
STAT1 (dimer)	0.012	0.055	-10000	0	-0.52	6	6
FKBP4	0.009	0.034	-10000	0	-0.46	3	3
FKBP5	0.008	0.04	-10000	0	-0.54	3	3
GR alpha/HSP90/FKBP51/HSP90	0.074	0.12	0.3	37	-0.44	7	44
PRL	-0.064	0.14	-10000	0	-0.55	18	18
cortisol/GR alpha (dimer)/TIF2	0.18	0.23	0.52	115	-0.5	5	120
RELA	-0.036	0.093	-10000	0	-0.31	16	16
FGG	0.12	0.2	0.48	58	-0.44	14	72
GR beta/TIF2	0.074	0.13	0.31	49	-0.46	12	61
IFNG	-0.27	0.37	-10000	0	-0.93	99	99
apoptosis	0.004	0.16	0.47	19	-0.62	5	24
CREB1	0.009	0.042	-10000	0	-0.58	2	2
histone acetylation	-0.028	0.12	0.34	3	-0.36	35	38
BGLAP	-0.051	0.14	-10000	0	-0.7	7	7
GR/PKAc	0.056	0.13	0.29	31	-0.36	18	49
NF kappa B1 p50/RelA	-0.067	0.18	-10000	0	-0.49	45	45
SMARCD1	0.011	0.026	-10000	0	-0.58	1	1
MDM2	0.073	0.086	0.25	54	-0.28	3	57
GATA3	-0.017	0.12	-10000	0	-0.52	31	31
AKT1	0.003	0.025	-10000	0	-0.59	1	1
CSF2	-0.18	0.38	-10000	0	-1	79	79
GSK3B	0.009	0.036	-10000	0	-0.58	2	2
NR1I3	0.018	0.18	0.47	13	-0.82	13	26
CSN2	0.12	0.15	0.39	57	-0.36	4	61
BRG1/BAF155/BAF170/BAF60A	0.032	0.029	-10000	0	-0.31	2	2
NFATC1	-0.015	0.12	-10000	0	-0.5	30	30
POU2F1	0	0.076	-10000	0	-0.55	10	10
CDKN1A	-0.017	0.16	-10000	0	-1.5	3	3
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0	0.006	-10000	0	-10000	0	0
SFN	0.005	0.057	-10000	0	-0.47	8	8
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.075	0.11	0.3	31	-0.45	6	37
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.015	0.17	0.44	16	-0.79	11	27
JUN	-0.16	0.19	-10000	0	-0.48	85	85
IL4	-0.075	0.14	-10000	0	-0.53	12	12
CDK5R1	0.009	0.034	-10000	0	-0.46	3	3
PRKACA	0.011	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.13	0.2	0.22	26	-0.47	89	115
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.078	0.11	0.3	32	-0.42	6	38
cortisol/GR alpha (monomer)	0.21	0.28	0.63	117	-0.46	4	121
NCOA2	0.003	0.068	-10000	0	-0.56	8	8
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.083	0.16	-10000	0	-0.58	44	44
AP-1/NFAT1-c-4	-0.28	0.31	-10000	0	-0.7	136	136
AFP	-0.12	0.17	-10000	0	-0.71	15	15
SUV420H1	0.01	0.025	-10000	0	-0.58	1	1
IRF1	0.12	0.14	0.44	34	-0.58	1	35
TP53	-0.03	0.18	-10000	0	-0.57	56	56
PPP5C	0.011	0	-10000	0	-10000	0	0
KRT17	-0.34	0.45	-10000	0	-1	147	147
KRT14	-0.12	0.22	-10000	0	-0.68	45	45
TBP	0.017	0.026	-10000	0	-0.37	2	2
CREBBP	0.037	0.06	0.3	6	-10000	0	6
HDAC1	0.01	0.008	-10000	0	-10000	0	0
HDAC2	0.022	0.027	-10000	0	-10000	0	0
AP-1	-0.28	0.31	-10000	0	-0.71	136	136
MAPK14	0.011	0.006	-10000	0	-10000	0	0
MAPK10	-0.032	0.15	-10000	0	-0.55	44	44
MAPK11	-0.003	0.083	-10000	0	-0.48	17	17
KRT5	-0.32	0.42	-10000	0	-0.91	148	148
interleukin-1 receptor activity	0.011	0.028	-10000	0	-10000	0	0
NCOA1	0.013	0.025	-10000	0	-0.58	1	1
STAT1	0.012	0.055	-10000	0	-0.52	6	6
CGA	-0.062	0.13	-10000	0	-0.44	31	31
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.2	0.46	106	-0.52	5	111
MAPK3	0.01	0.026	-10000	0	-0.58	1	1
MAPK1	0.01	0.025	-10000	0	-0.58	1	1
ICAM1	-0.13	0.22	-10000	0	-0.68	44	44
NFKB1	-0.037	0.098	-10000	0	-0.39	10	10
MAPK8	-0.12	0.16	-10000	0	-0.42	80	80
MAPK9	0.011	0.006	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.004	0.16	0.47	19	-0.66	5	24
BAX	-0.012	0.13	-10000	0	-0.93	2	2
POMC	-0.14	0.3	-10000	0	-1.3	26	26
EP300	0.034	0.078	0.28	9	-0.48	5	14
cortisol/GR alpha (dimer)/p53	0.15	0.26	0.54	101	-0.41	15	116
proteasomal ubiquitin-dependent protein catabolic process	0.049	0.068	0.23	20	-0.24	3	23
SGK1	0.067	0.14	0.42	1	-1.4	3	4
IL13	-0.18	0.23	-10000	0	-0.67	53	53
IL6	-0.24	0.4	-10000	0	-0.91	122	122
PRKACG	0.002	0.027	-10000	0	-0.46	2	2
IL5	-0.15	0.18	-10000	0	-0.63	31	31
IL2	-0.2	0.23	-10000	0	-0.63	77	77
CDK5	0.011	0.003	-10000	0	-10000	0	0
PRKACB	-0.021	0.13	-10000	0	-0.57	32	32
HSP90AA1	0.009	0.035	-10000	0	-0.58	2	2
IL8	-0.24	0.41	-10000	0	-0.87	136	136
CDK5R1/CDK5	0.014	0.026	-10000	0	-0.32	3	3
NF kappa B1 p50/RelA/PKAc	-0.049	0.16	-10000	0	-0.48	40	40
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.18	0.21	0.51	107	-0.4	1	108
SMARCA4	0.011	0.025	-10000	0	-0.58	1	1
chromatin remodeling	0.12	0.14	0.38	63	-0.44	3	66
NF kappa B1 p50/RelA/Cbp	-0.013	0.17	0.32	7	-0.51	26	33
JUN (dimer)	-0.16	0.19	-10000	0	-0.48	85	85
YWHAH	0.011	0	-10000	0	-10000	0	0
VIPR1	-0.077	0.21	-10000	0	-0.7	44	44
NR3C1	0.12	0.18	0.43	76	-0.45	12	88
NR4A1	-0.037	0.15	-10000	0	-0.47	59	59
TIF2/SUV420H1	0.01	0.053	-10000	0	-0.41	9	9
MAPKKK cascade	0.004	0.16	0.47	19	-0.62	5	24
cortisol/GR alpha (dimer)/Src-1	0.19	0.23	0.54	115	-0.42	4	119
PBX1	-0.004	0.092	-10000	0	-0.57	14	14
POU1F1	0	0.032	-10000	0	-0.57	1	1
SELE	-0.23	0.39	-10000	0	-0.89	111	111
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.12	0.14	0.38	62	-0.44	3	65
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.18	0.21	0.51	107	-0.4	1	108
mol:cortisol	0.12	0.16	0.37	119	-10000	0	119
MMP1	-0.27	0.45	-10000	0	-1.1	115	115

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.004	0.088	-10000	0	-0.54	15	15
GNB1/GNG2	-0.052	0.068	-10000	0	-0.2	76	76
AKT1	-0.021	0.092	-10000	0	-0.21	49	49
EGF	-0.18	0.25	-10000	0	-0.5	209	209
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.031	0.12	-10000	0	-0.4	25	25
mol:Ca2+	-0.045	0.13	-10000	0	-0.3	78	78
LYN	-0.016	0.092	-10000	0	-0.41	9	9
RhoA/GTP	-0.03	0.045	-10000	0	-0.14	26	26
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.049	0.14	-10000	0	-0.35	73	73
GNG2	0.004	0.064	-10000	0	-0.53	8	8
ARRB2	0.011	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.007	0.11	-10000	0	-0.48	23	23
G beta5/gamma2	-0.066	0.091	-10000	0	-0.26	79	79
PRKCH	-0.051	0.14	-10000	0	-0.36	74	74
DNM1	-0.004	0.087	-10000	0	-0.5	17	17
TXA2/TP beta/beta Arrestin3	-0.015	0.034	-10000	0	-0.25	6	6
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.12	0.23	-10000	0	-0.5	145	145
G12 family/GTP	-0.071	0.11	-10000	0	-0.3	76	76
ADRBK1	0.009	0.037	-10000	0	-0.5	3	3
ADRBK2	-0.001	0.083	-10000	0	-0.57	12	12
RhoA/GTP/ROCK1	0.006	0.057	-10000	0	-0.39	11	11
mol:GDP	0.042	0.11	0.31	38	-10000	0	38
mol:NADP	-0.007	0.099	-10000	0	-0.52	20	20
RAB11A	0.011	0	-10000	0	-10000	0	0
PRKG1	-0.024	0.14	-10000	0	-0.56	36	36
mol:IP3	-0.059	0.16	-10000	0	-0.38	78	78
cell morphogenesis	0.006	0.057	-10000	0	-0.39	11	11
PLCB2	-0.083	0.2	-10000	0	-0.52	78	78
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.072	0.14	-10000	0	-0.39	49	49
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.03	0.12	-10000	0	-0.43	20	20
RHOA	0.01	0.025	-10000	0	-0.58	1	1
PTGIR	-0.005	0.091	-10000	0	-0.5	19	19
PRKCB1	-0.056	0.15	-10000	0	-0.37	76	76
GNAQ	0.005	0.06	-10000	0	-0.58	6	6
mol:L-citrulline	-0.007	0.099	-10000	0	-0.52	20	20
TXA2/TXA2-R family	-0.086	0.21	-10000	0	-0.53	77	77
LCK	-0.035	0.12	-10000	0	-0.42	23	23
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.048	0.091	-10000	0	-0.46	8	8
TXA2-R family/G12 family/GDP/G beta/gamma	0.006	0.04	-10000	0	-0.3	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.045	0.089	-10000	0	-0.45	8	8
MAPK14	-0.026	0.1	-10000	0	-0.23	66	66
TGM2/GTP	-0.071	0.18	-10000	0	-0.45	76	76
MAPK11	-0.031	0.1	-10000	0	-0.24	71	71
ARHGEF1	-0.022	0.079	-10000	0	-0.19	52	52
GNAI2	0.011	0	-10000	0	-10000	0	0
JNK cascade	-0.06	0.16	-10000	0	-0.39	79	79
RAB11/GDP	0.012	0.001	-10000	0	-10000	0	0
ICAM1	-0.038	0.12	-10000	0	-0.29	68	68
cAMP biosynthetic process	-0.062	0.15	-10000	0	-0.37	77	77
Gq family/GTP/EBP50	0.004	0.08	-10000	0	-0.34	19	19
actin cytoskeleton reorganization	0.006	0.057	-10000	0	-0.39	11	11
SRC	-0.017	0.094	-10000	0	-0.42	10	10
GNB5	0.007	0.049	-10000	0	-0.58	4	4
GNB1	0.011	0	-10000	0	-10000	0	0
EGF/EGFR	-0.062	0.12	-10000	0	-0.32	57	57
VCAM1	-0.047	0.13	-10000	0	-0.32	79	79
TP beta/Gq family/GDP/G beta5/gamma2	-0.007	0.11	-10000	0	-0.48	23	23
platelet activation	-0.038	0.13	-10000	0	-0.3	75	75
PGI2/IP	-0.004	0.066	-10000	0	-0.36	19	19
PRKACA	-0.046	0.11	-10000	0	-0.3	62	62
Gq family/GDP/G beta5/gamma2	-0.01	0.11	-10000	0	-0.45	24	24
TXA2/TP beta/beta Arrestin2	-0.015	0.062	-10000	0	-0.48	8	8
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.04	0.11	-10000	0	-0.29	65	65
mol:DAG	-0.063	0.17	-10000	0	-0.42	76	76
EGFR	0.004	0.064	-10000	0	-0.53	8	8
TXA2/TP alpha	-0.085	0.2	-10000	0	-0.51	76	76
Gq family/GTP	-0.012	0.08	-10000	0	-0.28	34	34
YES1	-0.019	0.099	-10000	0	-0.43	11	11
GNAI2/GTP	-0.048	0.09	-10000	0	-0.45	11	11
PGD2/DP	-0.086	0.16	-10000	0	-0.36	145	145
SLC9A3R1	0.011	0	-10000	0	-10000	0	0
FYN	-0.019	0.096	-10000	0	-0.42	10	10
mol:NO	-0.007	0.099	-10000	0	-0.52	20	20
GNA15	-0.009	0.1	-10000	0	-0.54	21	21
PGK/cGMP	-0.019	0.11	-10000	0	-0.34	55	55
RhoA/GDP	0.011	0.024	-10000	0	-0.57	1	1
TP alpha/TGM2/GDP/G beta/gamma	-0.028	0.12	-10000	0	-0.46	14	14
NOS3	-0.007	0.099	-10000	0	-0.52	20	20
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCA	-0.049	0.14	-10000	0	-0.34	74	74
PRKCB	-0.062	0.16	-10000	0	-0.39	87	87
PRKCE	-0.046	0.14	-10000	0	-0.35	72	72
PRKCD	-0.053	0.15	-10000	0	-0.37	74	74
PRKCG	-0.085	0.18	-10000	0	-0.41	99	99
muscle contraction	-0.079	0.2	-10000	0	-0.5	78	78
PRKCZ	-0.049	0.14	-10000	0	-0.35	74	74
ARR3	-0.001	0.043	-10000	0	-0.46	5	5
TXA2/TP beta	-0.035	0.11	-10000	0	-0.51	11	11
PRKCQ	-0.065	0.16	-10000	0	-0.37	85	85
MAPKKK cascade	-0.075	0.19	-10000	0	-0.47	79	79
SELE	-0.06	0.16	-10000	0	-0.36	93	93
TP beta/GNAI2/GDP/G beta/gamma	-0.021	0.11	-10000	0	-0.46	10	10
ROCK1	0	0.081	-10000	0	-0.58	11	11
GNA14	-0.008	0.1	-10000	0	-0.56	19	19
chemotaxis	-0.095	0.23	-10000	0	-0.6	76	76
GNA12	0.011	0	-10000	0	-10000	0	0
GNA13	0.009	0.035	-10000	0	-0.58	2	2
GNA11	0.007	0.051	-10000	0	-0.53	5	5
Rac1/GTP	0.007	0.003	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.05	0.15	-9999	-0.34	114	114
EPHB2	0	0.081	-9999	-0.55	12	12
Syndecan-2/TACI	-0.035	0.13	-9999	-0.32	92	92
LAMA1	-0.054	0.18	-9999	-0.54	68	68
Syndecan-2/alpha2 ITGB1	0.005	0.089	-9999	-0.31	30	30
HRAS	0.008	0.042	-9999	-0.49	4	4
Syndecan-2/CASK	0.001	0.061	-9999	-0.33	18	18
ITGA5	-0.005	0.089	-9999	-0.48	19	19
BAX	0.02	0.074	-9999	-1.1	1	1
EPB41	0.007	0.049	-9999	-0.58	4	4
positive regulation of cell-cell adhesion	0.002	0.074	-9999	-0.32	27	27
LAMA3	-0.016	0.12	-9999	-0.5	30	30
EZR	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.004	0.088	-9999	-0.51	17	17
Syndecan-2/MMP2	-0.014	0.12	-9999	-0.38	49	49
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.012	0.045	-9999	-0.42	6	6
dendrite morphogenesis	0.002	0.079	-9999	-0.34	29	29
Syndecan-2/GM-CSF	-0.058	0.14	-9999	-0.32	132	132
determination of left/right symmetry	0.003	0.072	-9999	-0.39	18	18
Syndecan-2/PKC delta	0.01	0.061	-9999	-0.34	17	17
GNB2L1	0.011	0.019	-9999	-0.46	1	1
MAPK3	-0.046	0.13	-9999	-0.32	74	74
MAPK1	-0.046	0.13	-9999	-0.32	74	74
Syndecan-2/RACK1	0.014	0.061	-9999	-0.32	16	16
NF1	0.008	0.043	-9999	-0.58	3	3
FGFR/FGF/Syndecan-2	0.003	0.072	-9999	-0.39	18	18
ITGA2	0.005	0.06	-9999	-0.58	6	6
MAPK8	0.015	0.065	-9999	-0.34	19	19
Syndecan-2/alpha2/beta1 Integrin	-0.015	0.12	-9999	-0.31	62	62
Syndecan-2/Kininogen	-0.067	0.15	-9999	-0.32	145	145
ITGB1	0.011	0	-9999	-10000	0	0
SRC	0.018	0.062	-9999	-0.31	16	16
Syndecan-2/CASK/Protein 4.1	0.007	0.062	-9999	-0.31	21	21
extracellular matrix organization	0.002	0.085	-9999	-0.36	28	28
actin cytoskeleton reorganization	-0.05	0.15	-9999	-0.33	114	114
Syndecan-2/Caveolin-2/Ras	0.006	0.084	-9999	-0.37	19	19
Syndecan-2/Laminin alpha3	-0.007	0.092	-9999	-0.31	47	47
Syndecan-2/RasGAP	0.018	0.063	-9999	-0.31	18	18
alpha5/beta1 Integrin	0.005	0.064	-9999	-0.34	19	19
PRKCD	0.011	0	-9999	-10000	0	0
Syndecan-2 dimer	0.002	0.08	-9999	-0.34	29	29
GO:0007205	0.003	0.006	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.023	0.065	-9999	-0.31	18	18
RHOA	0.01	0.025	-9999	-0.58	1	1
SDCBP	0	0.081	-9999	-0.58	11	11
TNFRSF13B	-0.061	0.18	-9999	-0.52	76	76
RASA1	0.009	0.035	-9999	-0.58	2	2
alpha2/beta1 Integrin	0.012	0.045	-9999	-0.42	6	6
Syndecan-2/Synbindin	0.01	0.061	-9999	-0.34	17	17
TGFB1	-0.001	0.083	-9999	-0.54	13	13
CASP3	0.015	0.059	-9999	-0.31	16	16
FN1	-0.087	0.21	-9999	-0.52	106	106
Syndecan-2/IL8	-0.063	0.16	-9999	-0.33	138	138
SDC2	0.003	0.072	-9999	-0.39	18	18
KNG1	-0.11	0.22	-9999	-0.52	131	131
Syndecan-2/Neurofibromin	0.008	0.067	-9999	-0.34	20	20
TRAPPC4	0.011	0	-9999	-10000	0	0
CSF2	-0.097	0.22	-9999	-0.52	117	117
Syndecan-2/TGFB1	0.002	0.085	-9999	-0.36	28	28
Syndecan-2/Syntenin/PI-4-5-P2	0.002	0.074	-9999	-0.32	27	27
Syndecan-2/Ezrin	0.016	0.058	-9999	-0.32	15	15
PRKACA	0.014	0.061	-9999	-0.31	17	17
angiogenesis	-0.063	0.16	-9999	-0.33	138	138
MMP2	-0.029	0.14	-9999	-0.52	43	43
IL8	-0.11	0.22	-9999	-0.52	129	129
calcineurin-NFAT signaling pathway	-0.035	0.12	-9999	-0.32	92	92

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.064	0.16	-9999	-0.54	18	18
NF kappa B1 p50/RelA/I kappa B alpha	-0.038	0.15	-9999	-0.51	16	16
alphaV/beta3 Integrin/Osteopontin/Src	-0.11	0.19	-9999	-0.36	198	198
AP1	-0.073	0.2	-9999	-0.59	40	40
ILK	-0.073	0.16	-9999	-0.46	24	24
bone resorption	-0.051	0.16	-9999	-0.54	20	20
PTK2B	0.009	0.035	-9999	-0.58	2	2
PYK2/p130Cas	-0.058	0.15	-9999	-0.5	19	19
ITGAV	0.003	0.081	-9999	-0.57	11	11
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.006	0.073	-9999	-0.45	14	14
alphaV/beta3 Integrin/Osteopontin	-0.089	0.18	-9999	-0.37	112	112
MAP3K1	-0.078	0.17	-9999	-0.35	110	110
JUN	0.006	0.053	-9999	-0.56	5	5
MAPK3	-0.061	0.16	-9999	-0.49	21	21
MAPK1	-0.061	0.16	-9999	-0.5	21	21
Rac1/GDP	0.008	0	-9999	-10000	0	0
NFKB1	0.01	0.025	-9999	-0.58	1	1
MAPK8	-0.067	0.16	-9999	-0.46	35	35
ITGB3	-0.002	0.094	-9999	-0.54	17	17
NFKBIA	-0.052	0.16	-9999	-0.52	20	20
FOS	-0.03	0.14	-9999	-0.53	44	44
CD44	0.007	0.049	-9999	-0.58	4	4
CHUK	0.007	0.049	-9999	-0.58	4	4
PLAU	-0.048	0.18	-9999	-0.68	20	20
NF kappa B1 p50/RelA	-0.076	0.12	-9999	-0.52	18	18
BCAR1	0.008	0.044	-9999	-0.52	4	4
RELA	0.011	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.002	0.093	-9999	-0.41	27	27
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.075	0.16	-9999	-0.34	109	109
VAV3	-0.1	0.19	-9999	-0.49	57	57
MAP3K14	-0.073	0.16	-9999	-0.34	112	112
ROCK2	0	0.081	-9999	-0.58	11	11
SPP1	-0.16	0.25	-9999	-0.51	188	188
RAC1	0.011	0	-9999	-10000	0	0
Rac1/GTP	-0.092	0.18	-9999	-0.49	45	45
MMP2	-0.072	0.2	-9999	-0.6	50	50

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.025	0.051	-9999	-0.56	2	2
Crk/p130 Cas/Paxillin	-0.059	0.11	-9999	-0.39	29	29
JUN	-0.029	0.12	-9999	-0.44	24	24
HRAS	0.008	0.042	-9999	-0.49	4	4
RET51/GFRalpha1/GDNF/GRB10	-0.072	0.17	-9999	-0.41	81	81
RAP1A	0.01	0.025	-9999	-0.58	1	1
FRS2	0.009	0.035	-9999	-0.58	2	2
RAP1A/GDP	0.008	0.018	-9999	-0.43	1	1
RET51/GFRalpha1/GDNF/DOK1	-0.069	0.17	-9999	-0.4	80	80
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.006	0.055	-9999	-0.58	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0.019	-9999	-0.46	1	1
RET9/GFRalpha1/GDNF/Enigma	-0.029	0.12	-9999	-0.29	90	90
RHOA	0.01	0.025	-9999	-0.58	1	1
RAP1A/GTP	-0.08	0.14	-9999	-0.4	54	54
GRB7	0.002	0.067	-9999	-0.46	12	12
RET51/GFRalpha1/GDNF	-0.069	0.17	-9999	-0.4	80	80
MAPKKK cascade	-0.072	0.13	-9999	-0.47	31	31
BCAR1	0.008	0.044	-9999	-0.52	4	4
RET9/GFRalpha1/GDNF/IRS1	-0.031	0.12	-9999	-0.3	92	92
lamellipodium assembly	-0.054	0.098	-9999	-0.3	58	58
RET51/GFRalpha1/GDNF/SHC	-0.069	0.17	-9999	-0.4	80	80
PIK3CA	0.009	0.035	-9999	-0.58	2	2
RET9/GFRalpha1/GDNF/SHC	-0.026	0.11	-9999	-0.29	85	85
RET9/GFRalpha1/GDNF/Shank3	-0.028	0.12	-9999	-0.3	86	86
MAPK3	-0.051	0.14	-9999	-0.49	26	26
DOK1	0.011	0	-9999	-10000	0	0
DOK6	-0.032	0.15	-9999	-0.55	44	44
PXN	0.011	0	-9999	-10000	0	0
neurite development	-0.048	0.15	-9999	-0.48	32	32
DOK5	-0.05	0.17	-9999	-0.54	64	64
GFRA1	-0.067	0.19	-9999	-0.53	83	83
MAPK8	-0.034	0.12	-9999	-0.45	21	21
HRAS/GTP	-0.08	0.14	-9999	-0.38	82	82
tube development	-0.021	0.11	-9999	-0.32	53	53
MAPK1	-0.051	0.14	-9999	-0.49	26	26
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.013	0.093	-9999	-0.27	57	57
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	0.01	0.025	-9999	-0.58	1	1
PDLIM7	0.005	0.053	-9999	-0.47	7	7
RET51/GFRalpha1/GDNF/Dok6	-0.082	0.19	-9999	-0.41	106	106
SHC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.07	0.17	-9999	-0.4	80	80
RET51/GFRalpha1/GDNF/Dok5	-0.1	0.2	-9999	-0.44	113	113
PRKCA	0.01	0.031	-9999	-0.52	2	2
HRAS/GDP	0.006	0.03	-9999	-0.35	4	4
CREB1	-0.027	0.12	-9999	-0.35	53	53
PIK3R1	0.008	0.043	-9999	-0.58	3	3
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.01	0.086	-9999	-0.26	51	51
RET51/GFRalpha1/GDNF/Grb7	-0.075	0.17	-9999	-0.41	81	81
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.081	0.2	-9999	-0.5	104	104
DOK4	0.01	0.025	-9999	-0.58	1	1
JNK cascade	-0.028	0.12	-9999	-0.43	24	24
RET9/GFRalpha1/GDNF/FRS2	-0.027	0.11	-9999	-0.33	53	53
SHANK3	0.007	0.051	-9999	-0.53	5	5
RASA1	0.009	0.035	-9999	-0.58	2	2
NCK1	0.009	0.035	-9999	-0.58	2	2
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.01	0.087	-9999	-0.26	52	52
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.044	0.13	-9999	-0.42	31	31
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.042	0.13	-9999	-0.34	55	55
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.044	0.14	-9999	-0.33	81	81
PI3K	-0.044	0.17	-9999	-0.46	58	58
SOS1	0.01	0.025	-9999	-0.58	1	1
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.02	0.11	-9999	-0.32	53	53
GRB10	0.007	0.049	-9999	-0.58	4	4
activation of MAPKK activity	-0.034	0.12	-9999	-0.42	22	22
RET51/GFRalpha1/GDNF/FRS2	-0.071	0.17	-9999	-0.4	82	82
GAB1	0.011	0	-9999	-10000	0	0
IRS1	0.002	0.074	-9999	-0.58	9	9
IRS2	0.003	0.069	-9999	-0.54	9	9
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.043	0.14	-9999	-0.34	80	80
RET51/GFRalpha1/GDNF/PKC alpha	-0.07	0.17	-9999	-0.4	80	80
GRB2	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GDNF	0.006	0.037	-9999	-0.5	3	3
RAC1	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.074	0.18	-9999	-0.42	83	83
Rac1/GTP	-0.063	0.12	-9999	-0.36	58	58
RET9/GFRalpha1/GDNF	-0.037	0.12	-9999	-0.33	85	85
GFRalpha1/GDNF	-0.044	0.14	-9999	-0.38	85	85

×

IL1-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.038	0.12	-10000	0	-0.32	84	84
PRKCZ	0.01	0.031	-10000	0	-0.52	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.009	0.034	-10000	0	-0.46	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.015	0.083	-10000	0	-0.28	23	23
IRAK/TOLLIP	-0.016	0.097	-10000	0	-0.41	7	7
IKBKB	0.011	0.019	-10000	0	-0.46	1	1
IKBKG	0.01	0.025	-10000	0	-0.58	1	1
IL1 alpha/IL1R2	-0.1	0.2	-10000	0	-0.4	163	163
IL1A	-0.09	0.21	-10000	0	-0.51	111	111
IL1B	-0.058	0.17	-10000	0	-0.4	105	105
IRAK/TRAF6/p62/Atypical PKCs	0.001	0.097	-10000	0	-0.58	5	5
IL1R2	-0.055	0.18	-10000	0	-0.52	72	72
IL1R1	-0.007	0.097	-10000	0	-0.51	20	20
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.011	0.092	0.2	7	-0.3	24	31
TOLLIP	0.01	0.025	-10000	0	-0.58	1	1
TICAM2	-0.011	0.11	-10000	0	-0.58	20	20
MAP3K3	0.009	0.035	-10000	0	-0.58	2	2
TAK1/TAB1/TAB2	0.008	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.019	0.088	-10000	0	-0.61	4	4
JUN	-0.003	0.09	-10000	0	-0.55	4	4
MAP3K7	0.011	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.034	0.14	-10000	0	-0.54	19	19
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.044	0.14	-10000	0	-0.34	67	67
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.035	0.13	-10000	0	-0.32	67	67
IL1 beta fragment/IL1R1/IL1RAP	-0.048	0.15	-10000	0	-0.38	72	72
NFKB1	0.01	0.025	-10000	0	-0.58	1	1
MAPK8	-0.007	0.09	-10000	0	-0.53	4	4
IRAK1	-0.025	0.1	-10000	0	-0.27	85	85
IL1RN/IL1R1	-0.04	0.15	-10000	0	-0.39	81	81
IRAK4	0.011	0	-10000	0	-10000	0	0
PRKCI	0.008	0.043	-10000	0	-0.58	3	3
TRAF6	0.01	0.025	-10000	0	-0.58	1	1
PI3K	0.013	0.041	-10000	0	-0.42	5	5
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.015	0.099	-10000	0	-0.31	31	31
CHUK	0.007	0.049	-10000	0	-0.58	4	4
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.048	0.15	-10000	0	-0.38	72	72
IL1 beta/IL1R2	-0.082	0.2	-10000	0	-0.38	151	151
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.018	0.082	-10000	0	-0.36	7	7
NF kappa B1 p50/RelA	-0.057	0.12	-10000	0	-0.5	20	20
IRAK3	-0.024	0.13	-10000	0	-0.53	37	37
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.042	0.15	-10000	0	-0.35	74	74
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.023	0.11	-10000	0	-0.27	68	68
IL1 alpha/IL1R1/IL1RAP	-0.057	0.15	-10000	0	-0.32	134	134
RELA	0.011	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.011	0	-10000	0	-10000	0	0
MYD88	0.011	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	-0.008	0.095	-10000	0	-0.36	9	9
IL1RAP	0.001	0.077	-10000	0	-0.58	10	10
UBE2N	0.01	0.025	-10000	0	-0.58	1	1
IRAK/TRAF6	-0.084	0.14	-10000	0	-0.45	47	47
CASP1	-0.02	0.13	-10000	0	-0.54	33	33
IL1RN/IL1R2	-0.073	0.19	-10000	0	-0.42	118	118
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.038	0.14	-10000	0	-0.35	72	72
TMEM189-UBE2V1	-0.064	0.16	-10000	0	-0.46	84	84
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.026	0.11	-10000	0	-0.4	22	22
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
IL1RN	-0.05	0.17	-10000	0	-0.52	67	67
TRAF6/TAK1/TAB1/TAB2	-0.031	0.08	-10000	0	-0.38	5	5
MAP2K6	-0.012	0.092	-10000	0	-0.33	15	15

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.011	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.028	0.12	-10000	0	-0.33	47	47
NT3 (dimer)/TRKC	-0.045	0.15	-10000	0	-0.39	85	85
NT3 (dimer)/TRKB	-0.16	0.21	-10000	0	-0.35	286	286
SHC/Grb2/SOS1/GAB1/PI3K	0.028	0.033	-10000	0	-0.3	5	5
RAPGEF1	0.01	0.025	-10000	0	-0.58	1	1
BDNF	-0.02	0.13	-10000	0	-0.52	34	34
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
DYNLT1	0.011	0	-10000	0	-10000	0	0
NTRK1	-0.039	0.16	-10000	0	-0.53	52	52
NTRK2	-0.18	0.25	-10000	0	-0.5	209	209
NTRK3	-0.042	0.16	-10000	0	-0.51	57	57
NT-4/5 (dimer)/TRKB	-0.16	0.2	-10000	0	-0.34	284	284
neuron apoptosis	0.14	0.19	0.45	115	-10000	0	115
SHC 2-3/Grb2	-0.15	0.21	-10000	0	-0.5	113	113
SHC1	0.011	0	-10000	0	-10000	0	0
SHC2	-0.13	0.2	-10000	0	-0.55	78	78
SHC3	-0.14	0.21	-10000	0	-0.57	87	87
STAT3 (dimer)	0.018	0.015	-10000	0	-0.35	1	1
NT3 (dimer)/TRKA	-0.082	0.18	-10000	0	-0.43	94	94
RIN/GDP	-0.003	0.07	-10000	0	-0.27	10	10
GIPC1	0.007	0.049	-10000	0	-0.58	4	4
KRAS	0.005	0.058	-10000	0	-0.56	6	6
DNAJA3	-0.057	0.14	-10000	0	-0.35	68	68
RIN/GTP	-0.001	0.019	-10000	0	-0.32	2	2
CCND1	0.024	0.035	-10000	0	-0.81	1	1
MAGED1	0.011	0	-10000	0	-10000	0	0
PTPN11	0.006	0.055	-10000	0	-0.58	5	5
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.014	0.091	-10000	0	-0.46	23	23
SHC/GRB2/SOS1	0.023	0.016	-10000	0	-0.35	1	1
GRB2	0.011	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.078	0.18	-10000	0	-0.37	145	145
TRKA/NEDD4-2	-0.02	0.12	-10000	0	-0.38	53	53
ELMO1	0.004	0.059	-10000	0	-0.49	8	8
RhoG/GTP/ELMO1/DOCK1	0.011	0.039	-10000	0	-0.3	9	9
NGF	-0.029	0.14	-10000	0	-0.52	43	43
HRAS	0.008	0.042	-10000	0	-0.49	4	4
DOCK1	0.01	0.025	-10000	0	-0.58	1	1
GAB2	0.009	0.035	-10000	0	-0.58	2	2
RIT2	-0.001	0.027	-10000	0	-0.46	2	2
RIT1	0.011	0	-10000	0	-10000	0	0
FRS2	0.009	0.035	-10000	0	-0.58	2	2
DNM1	-0.004	0.087	-10000	0	-0.5	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.011	0.019	-10000	0	-0.46	1	1
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.07	0.13	-10000	0	-0.34	72	72
mol:GDP	-0.006	0.1	-10000	0	-0.39	12	12
NGF (dimer)	-0.029	0.14	-10000	0	-0.52	43	43
RhoG/GDP	0.003	0.042	-10000	0	-0.35	8	8
RIT1/GDP	0.002	0.07	-10000	0	-0.27	8	8
TIAM1	-0.043	0.16	-10000	0	-0.52	59	59
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
BDNF (dimer)/TRKB	-0.11	0.18	-10000	0	-0.32	226	226
KIDINS220/CRKL/C3G	0.016	0.018	-10000	0	-0.42	1	1
SHC/RasGAP	0.015	0.026	-10000	0	-0.42	2	2
FRS2 family/SHP2	0.018	0.052	-10000	0	-0.44	7	7
SHC/GRB2/SOS1/GAB1	0.029	0.014	-10000	0	-0.32	1	1
RIT1/GTP	0.008	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.02	0.13	-10000	0	-0.53	33	33
RAP1/GDP	-0.021	0.047	-10000	0	-0.27	5	5
KIDINS220/CRKL	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.02	0.13	-10000	0	-0.52	34	34
ubiquitin-dependent protein catabolic process	-0.034	0.13	-10000	0	-0.38	61	61
Schwann cell development	-0.032	0.032	-10000	0	-10000	0	0
EHD4	0.011	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.027	0.031	-10000	0	-0.32	4	4
FRS2 family/SHP2/CRK family/C3G/GAB2	0.028	0.05	-10000	0	-0.5	4	4
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.01	0.025	-10000	0	-0.58	1	1
CDC42/GTP	-0.13	0.16	-10000	0	-0.47	65	65
ABL1	0.01	0.025	-10000	0	-0.58	1	1
SH2B family/GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
Rap1/GTP	-0.017	0.08	-10000	0	-0.43	2	2
STAT3	0.018	0.015	-10000	0	-0.35	1	1
axon guidance	-0.12	0.16	-10000	0	-0.45	65	65
MAPK3	-0.066	0.17	-10000	0	-0.38	101	101
MAPK1	-0.066	0.17	-10000	0	-0.38	101	101
CDC42/GDP	0	0.074	-10000	0	-0.3	10	10
NTF3	-0.02	0.13	-10000	0	-0.54	33	33
NTF4	-0.014	0.091	-10000	0	-0.46	23	23
NGF (dimer)/TRKA/FAIM	-0.036	0.14	-10000	0	-0.34	91	91
PI3K	0.013	0.041	-10000	0	-0.42	5	5
FRS3	0.01	0.031	-10000	0	-0.52	2	2
FAIM	0.005	0.058	-10000	0	-0.56	6	6
GAB1	0.011	0	-10000	0	-10000	0	0
RASGRF1	-0.092	0.16	-10000	0	-0.37	104	104
SOS1	0.01	0.025	-10000	0	-0.58	1	1
MCF2L	-0.033	0.13	-10000	0	-0.33	89	89
RGS19	0	0.079	-10000	0	-0.54	12	12
CDC42	0.006	0.055	-10000	0	-0.58	5	5
RAS family/GTP	-0.003	0.096	-10000	0	-0.54	9	9
Rac1/GDP	0.002	0.07	-10000	0	-0.26	9	9
NGF (dimer)/TRKA/GRIT	-0.04	0.13	-10000	0	-0.35	86	86
neuron projection morphogenesis	-0.04	0.13	-10000	0	-0.56	8	8
NGF (dimer)/TRKA/NEDD4-2	-0.033	0.14	-10000	0	-0.38	61	61
MAP2K1	0.03	0.023	-10000	0	-0.29	3	3
NGFR	-0.079	0.2	-10000	0	-0.51	100	100
NGF (dimer)/TRKA/GIPC/GAIP	-0.02	0.11	-10000	0	-0.5	8	8
RAS family/GTP/PI3K	0.013	0.081	-10000	0	-0.42	15	15
FRS2 family/SHP2/GRB2/SOS1	0.028	0.048	-10000	0	-0.56	2	2
NRAS	0.001	0.077	-10000	0	-0.58	10	10
GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
PRKCI	0.008	0.043	-10000	0	-0.58	3	3
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.031	-10000	0	-0.52	2	2
MAPKKK cascade	-0.089	0.18	-10000	0	-0.62	56	56
RASA1	0.009	0.035	-10000	0	-0.58	2	2
TRKA/c-Abl	-0.02	0.12	-10000	0	-0.38	53	53
SQSTM1	0.011	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.096	0.16	-10000	0	-0.36	97	97
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.017	0.12	-10000	0	-0.33	61	61
MATK	-0.064	0.19	-10000	0	-0.52	81	81
NEDD4L	0.01	0.025	-10000	0	-0.58	1	1
RAS family/GDP	-0.021	0.049	-10000	0	-0.27	8	8
NGF (dimer)/TRKA	-0.076	0.14	-10000	0	-0.32	111	111
Rac1/GTP	-0.079	0.11	-10000	0	-0.32	62	62
FRS2 family/SHP2/CRK family	0.029	0.05	-10000	0	-0.54	3	3

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.016	0.098	-9999	-0.31	44	44
RGS9BP	-0.01	0.1	-9999	-0.54	21	21
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.003	0.047	-9999	-0.46	6	6
mol:Na +	-0.046	0.12	-9999	-0.3	102	102
mol:ADP	-0.002	0.058	-9999	-0.34	16	16
GNAT2	-0.008	0.097	-9999	-0.53	19	19
RGS9-1/Gbeta5/R9AP	-0.021	0.12	-9999	-0.33	70	70
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.004	0.061	-9999	-0.32	20	20
GRK7	-0.002	0.064	-9999	-0.46	11	11
CNGB3	-0.029	0.12	-9999	-0.46	41	41
Cone Metarhodopsin II/X-Arrestin	-0.001	0.03	-9999	-0.32	5	5
mol:Ca2+	-0.049	0.12	-9999	-0.28	119	119
Cone PDE6	-0.016	0.1	-9999	-0.32	43	43
Cone Metarhodopsin II	-0.002	0.045	-9999	-0.26	16	16
Na + (4 Units)	-0.048	0.12	-9999	-0.28	119	119
GNAT2/GDP	-0.021	0.11	-9999	-0.32	53	53
GNB5	0.007	0.049	-9999	-0.58	4	4
mol:GMP (4 units)	-0.003	0.057	-9999	-0.29	22	22
Cone Transducin	-0.016	0.1	-9999	-0.32	47	47
SLC24A2	-0.013	0.095	-9999	-0.48	23	23
GNB3/GNGT2	-0.018	0.12	-9999	-0.39	49	49
GNB3	-0.017	0.12	-9999	-0.53	30	30
GNAT2/GTP	-0.005	0.071	-9999	-0.38	19	19
CNGA3	-0.048	0.16	-9999	-0.52	62	62
ARR3	-0.001	0.043	-9999	-0.46	5	5
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.047	0.12	-9999	-0.3	102	102
mol:Pi	-0.021	0.12	-9999	-0.33	70	70
Cone CNG Channel	-0.052	0.1	-9999	-0.31	41	41
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.013	0.095	-9999	-0.48	23	23
RGS9	-0.033	0.15	-9999	-0.53	47	47
PDE6C	0.001	0.027	-9999	-0.46	2	2
GNGT2	-0.008	0.1	-9999	-0.56	20	20
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0	0.019	-9999	-0.46	1	1

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.001	0.052	-9999	-0.34	13	13
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.03	0.12	-9999	-0.36	67	67
STXBP1	-0.006	0.099	-9999	-0.55	18	18
ACh/CHRNA1	-0.028	0.11	-9999	-0.36	50	50
RAB3GAP2/RIMS1/UNC13B	-0.019	0.11	-9999	-0.36	32	32
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	-0.052	0.16	-9999	-0.51	66	66
mol:ACh	-0.007	0.035	-9999	-0.088	81	81
RAB3GAP2	0.008	0.043	-9999	-0.58	3	3
STX1A/SNAP25/VAMP2	-0.05	0.1	-9999	-0.33	34	34
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.028	0.11	-9999	-0.36	50	50
UNC13B	0.01	0.031	-9999	-0.52	2	2
CHRNA1	-0.036	0.15	-9999	-0.53	50	50
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.081	0.16	-9999	-0.38	125	125
SNAP25	-0.022	0.074	-9999	-0.2	78	78
VAMP2	0.005	0	-9999	-10000	0	0
SYT1	-0.12	0.24	-9999	-0.57	125	125
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.002	0.075	-9999	-0.31	31	31
STX1A/SNAP25 fragment 1/VAMP2	-0.05	0.1	-9999	-0.33	34	34

×

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

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
MAP4K1	-0.031	0.14	-10000	0	-0.41	42	42
CRKL	-0.011	0.12	-10000	0	-0.42	36	36
HRAS	-0.024	0.15	-10000	0	-0.43	49	49
mol:PIP3	-0.02	0.12	-10000	0	-0.41	37	37
SPRED1	0.005	0.06	-10000	0	-0.58	6	6
SPRED2	0.008	0.043	-10000	0	-0.58	3	3
GAB1	-0.017	0.13	-10000	0	-0.44	37	37
FOXO3	-0.006	0.12	-10000	0	-0.38	38	38
AKT1	-0.013	0.13	-10000	0	-0.42	38	38
BAD	-0.007	0.12	-10000	0	-0.39	38	38
megakaryocyte differentiation	-0.082	0.18	-10000	0	-0.36	129	129
GSK3B	-0.007	0.12	-10000	0	-0.39	39	39
RAF1	-0.011	0.13	-10000	0	-0.39	30	30
SHC1	0.011	0	-10000	0	-10000	0	0
STAT3	-0.017	0.13	-10000	0	-0.44	38	38
STAT1	-0.061	0.32	-10000	0	-1	49	49
HRAS/SPRED1	-0.015	0.13	-10000	0	-0.4	35	35
cell proliferation	-0.017	0.13	-10000	0	-0.43	39	39
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
TEC	0.011	0	-10000	0	-10000	0	0
RPS6KB1	-0.019	0.14	-10000	0	-0.44	43	43
HRAS/SPRED2	-0.014	0.13	-10000	0	-0.39	34	34
LYN/TEC/p62DOK	-0.005	0.12	-10000	0	-0.41	36	36
MAPK3	0.002	0.095	-10000	0	-0.28	29	29
STAP1	-0.05	0.17	-10000	0	-0.43	72	72
GRAP2	-0.023	0.14	-10000	0	-0.55	35	35
JAK2	-0.054	0.29	-10000	0	-0.89	48	48
STAT1 (dimer)	-0.058	0.31	-10000	0	-0.96	49	49
mol:Gleevec	0	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.041	0.16	-10000	0	-0.47	49	49
actin filament polymerization	-0.03	0.14	-10000	0	-0.41	53	53
LYN	0.011	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.056	0.22	-10000	0	-0.65	53	53
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
CBL/CRKL/GRB2	0.002	0.12	-10000	0	-0.38	32	32
PI3K	-0.01	0.14	-10000	0	-0.46	38	38
PTEN	0.005	0.06	-10000	0	-0.58	6	6
SCF/KIT/EPO/EPOR	-0.062	0.34	-10000	0	-1.3	35	35
MAPK8	-0.018	0.13	-10000	0	-0.43	39	39
STAT3 (dimer)	-0.017	0.13	-10000	0	-0.43	39	39
positive regulation of transcription	0.005	0.08	-10000	0	-0.24	17	17
mol:GDP	-0.034	0.16	-10000	0	-0.45	54	54
PIK3C2B	-0.017	0.13	-10000	0	-0.44	37	37
CBL/CRKL	-0.003	0.12	-10000	0	-0.39	36	36
FER	-0.022	0.14	-10000	0	-0.47	39	39
SH2B3	-0.017	0.13	-10000	0	-0.44	37	37
PDPK1	-0.013	0.11	-10000	0	-0.38	36	36
SNAI2	-0.025	0.14	-10000	0	-0.43	45	45
positive regulation of cell proliferation	-0.038	0.23	-10000	0	-0.72	48	48
KITLG	-0.005	0.1	-10000	0	-0.6	17	17
cell motility	-0.038	0.23	-10000	0	-0.72	48	48
PTPN6	0.011	0.007	-10000	0	-10000	0	0
EPOR	0.002	0.13	-10000	0	-1.1	3	3
STAT5A (dimer)	-0.03	0.19	-10000	0	-0.61	46	46
SOCS1	-0.029	0.14	-10000	0	-0.49	46	46
cell migration	0.054	0.16	0.38	82	-0.21	1	83
SOS1	0.01	0.025	-10000	0	-0.58	1	1
EPO	0	0.055	-10000	0	-0.46	8	8
VAV1	-0.024	0.14	-10000	0	-0.57	35	35
GRB10	-0.02	0.13	-10000	0	-0.44	40	40
PTPN11	0.006	0.055	-10000	0	-0.57	5	5
SCF/KIT	-0.025	0.14	0.22	1	-0.44	44	45
GO:0007205	0	0.007	-10000	0	-10000	0	0
MAP2K1	-0.002	0.1	-10000	0	-0.31	29	29
CBL	0.011	0	-10000	0	-10000	0	0
KIT	-0.064	0.33	-10000	0	-1.4	31	31
MAP2K2	-0.001	0.1	-10000	0	-0.31	27	27
SHC/Grb2/SOS1	-0.006	0.12	-10000	0	-0.42	36	36
STAT5A	-0.031	0.2	-10000	0	-0.64	44	44
GRB2	0.011	0	-10000	0	-10000	0	0
response to radiation	-0.024	0.14	-10000	0	-0.42	45	45
SHC/GRAP2	-0.008	0.1	-10000	0	-0.4	35	35
PTPRO	-0.083	0.18	-10000	0	-0.36	129	129
SH2B2	-0.031	0.14	-10000	0	-0.42	53	53
DOK1	0.011	0	-10000	0	-10000	0	0
MATK	-0.055	0.16	-10000	0	-0.39	82	82
CREBBP	0.022	0.031	-10000	0	-10000	0	0
BCL2	-0.019	0.23	-10000	0	-1.2	17	17

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.013	0.12	-9999	-0.4	36	36
NF kappa B1 p50/RelA/I kappa B alpha	-0.015	0.11	-9999	-0.4	12	12
AP1	-0.087	0.14	-9999	-0.51	32	32
mol:PIP3	-0.065	0.12	-9999	-0.49	23	23
AKT1	0.011	0.091	-9999	-0.42	12	12
PTK2B	-0.013	0.093	-9999	-0.33	22	22
RHOA	0.011	0.05	-9999	-0.35	3	3
PIK3CB	0.007	0.047	-9999	-0.55	4	4
mol:Ca2+	-0.019	0.11	-9999	-0.44	13	13
MAGI3	0.008	0.043	-9999	-0.58	3	3
RELA	0.011	0	-9999	-10000	0	0
apoptosis	-0.052	0.14	-9999	-0.35	72	72
HRAS/GDP	0.006	0.03	-9999	-0.35	4	4
positive regulation of microtubule depolymerization	-0.042	0.13	-9999	-0.35	39	39
NF kappa B1 p50/RelA	-0.064	0.12	-9999	-0.47	27	27
endothelial cell migration	-0.041	0.18	-9999	-0.51	69	69
ADCY4	-0.036	0.16	-9999	-0.5	44	44
ADCY5	-0.068	0.19	-9999	-0.56	56	56
ADCY6	-0.034	0.16	-9999	-0.51	41	41
ADCY7	-0.035	0.16	-9999	-0.52	41	41
ADCY1	-0.046	0.16	-9999	-0.5	47	47
ADCY2	-0.052	0.18	-9999	-0.52	58	58
ADCY3	-0.034	0.16	-9999	-0.51	41	41
ADCY8	-0.039	0.16	-9999	-0.52	41	41
ADCY9	-0.035	0.16	-9999	-0.51	42	42
GSK3B	-0.008	0.091	-9999	-0.38	14	14
arachidonic acid secretion	-0.03	0.15	-9999	-0.48	42	42
GNG2	0.004	0.064	-9999	-0.53	8	8
TRIP6	-0.014	0.12	-9999	-0.42	39	39
GNAO1	-0.051	0.16	-9999	-0.34	108	108
HRAS	0.008	0.042	-9999	-0.49	4	4
NFKBIA	-0.021	0.12	-9999	-0.43	16	16
GAB1	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.03	0.2	-9999	-0.91	28	28
JUN	0.006	0.053	-9999	-0.56	5	5
LPA/LPA2/NHERF2	0.007	0.046	-9999	-0.32	7	7
TIAM1	-0.057	0.23	-9999	-1.1	28	28
PIK3R1	0.008	0.043	-9999	-0.58	3	3
mol:IP3	-0.02	0.12	-9999	-0.45	13	13
PLCB3	0.012	0.056	-9999	-0.57	3	3
FOS	-0.03	0.14	-9999	-0.53	44	44
positive regulation of mitosis	-0.03	0.15	-9999	-0.48	42	42
LPA/LPA1-2-3	-0.062	0.15	-9999	-0.38	72	72
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0.001	-9999	-10000	0	0
BCAR1	0.008	0.044	-9999	-0.52	4	4
stress fiber formation	-0.022	0.11	-9999	-0.36	25	25
GNAZ	-0.032	0.14	-9999	-0.36	72	72
EGFR/PI3K-beta/Gab1	-0.067	0.13	-9999	-0.51	23	23
positive regulation of dendritic cell cytokine production	-0.062	0.15	-9999	-0.38	72	72
LPA/LPA2/MAGI-3	0.006	0.05	-9999	-0.33	9	9
ARHGEF1	-0.005	0.1	-9999	-0.35	35	35
GNAI2	-0.018	0.12	-9999	-0.36	52	52
GNAI3	-0.018	0.12	-9999	-0.36	52	52
GNAI1	-0.026	0.14	-9999	-0.39	60	60
LPA/LPA3	-0.057	0.14	-9999	-0.37	90	90
LPA/LPA2	-0.001	0.046	-9999	-0.34	7	7
LPA/LPA1	-0.031	0.14	-9999	-0.42	52	52
HB-EGF/EGFR	-0.035	0.12	-9999	-0.31	93	93
HBEGF	-0.04	0.14	-9999	-0.37	87	87
mol:DAG	-0.02	0.12	-9999	-0.45	13	13
cAMP biosynthetic process	-0.048	0.17	-9999	-0.49	54	54
NFKB1	0.01	0.025	-9999	-0.58	1	1
SRC	0.01	0.025	-9999	-0.58	1	1
GNB1	0.011	0.001	-9999	-10000	0	0
LYN	-0.021	0.12	-9999	-0.43	16	16
GNAQ	-0.032	0.1	-9999	-0.32	47	47
LPAR2	0.005	0.053	-9999	-0.47	7	7
LPAR3	-0.072	0.19	-9999	-0.51	90	90
LPAR1	-0.032	0.15	-9999	-0.61	34	34
IL8	-0.11	0.21	-9999	-0.46	115	115
PTK2	-0.05	0.14	-9999	-0.35	73	73
Rac1/GDP	0.008	0	-9999	-10000	0	0
CASP3	-0.052	0.14	-9999	-0.35	72	72
EGFR	0.003	0.064	-9999	-0.53	8	8
PLCG1	-0.033	0.12	-9999	-0.34	50	50
PLD2	-0.05	0.14	-9999	-0.35	72	72
G12/G13	-0.01	0.11	-9999	-0.37	35	35
PI3K-beta	-0.03	0.087	-9999	-0.44	15	15
cell migration	-0.018	0.088	-9999	-0.26	37	37
SLC9A3R2	0.01	0.025	-9999	-0.58	1	1
PXN	-0.023	0.11	-9999	-0.37	25	25
HRAS/GTP	-0.032	0.16	-9999	-0.5	42	42
RAC1	0.011	0	-9999	-10000	0	0
MMP9	-0.059	0.18	-9999	-0.52	76	76
PRKCE	0.011	0	-9999	-10000	0	0
PRKCD	-0.013	0.11	-9999	-0.46	10	10
Gi(beta/gamma)	-0.031	0.15	-9999	-0.49	42	42
mol:LPA	-0.008	0.042	-9999	-0.19	18	18
TRIP6/p130 Cas/FAK1/Paxillin	-0.074	0.14	-9999	-0.5	28	28
MAPKKK cascade	-0.03	0.15	-9999	-0.48	42	42
contractile ring contraction involved in cytokinesis	0.011	0.05	-9999	-0.34	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.039	0.12	-9999	-0.34	57	57
GNA15	-0.039	0.12	-9999	-0.33	54	54
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.009	0.035	-9999	-0.58	2	2
MAPT	-0.043	0.13	-9999	-0.37	38	38
GNA11	-0.031	0.1	-9999	-0.32	45	45
Rac1/GTP	-0.033	0.21	-9999	-0.97	28	28
MMP2	-0.041	0.19	-9999	-0.51	69	69

×

JNK signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.046	0.19	-9999	-0.49	70	70
MAP4K1	-0.043	0.17	-9999	-0.55	56	56
MAP3K8	0.01	0.031	-9999	-0.52	2	2
PRKCB	-0.039	0.16	-9999	-0.54	52	52
DBNL	0.01	0.025	-9999	-0.58	1	1
CRKL	0.011	0	-9999	-10000	0	0
MAP3K1	-0.02	0.15	-9999	-0.56	32	32
JUN	-0.029	0.19	-9999	-0.72	37	37
MAP3K7	-0.017	0.15	-9999	-0.55	30	30
GRAP2	-0.023	0.14	-9999	-0.55	35	35
CRK	0.011	0.019	-9999	-0.46	1	1
MAP2K4	-0.013	0.15	-9999	-0.54	32	32
LAT	-0.01	0.1	-9999	-0.51	24	24
LCP2	-0.014	0.12	-9999	-0.54	26	26
MAPK8	-0.034	0.2	-9999	-0.76	36	36
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.024	0.16	-9999	-0.59	30	30
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.038	0.18	-9999	-0.46	70	70

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.008	0.1	-9999	-0.51	22	22
GPC2	-0.009	0.1	-9999	-0.55	21	21
GPC2/Midkine	-0.012	0.11	-9999	-0.38	42	42
neuron projection morphogenesis	-0.012	0.1	-9999	-0.38	42	42

×

Arf6 signaling 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
CENTA1/KIF3B	0.013	0.035	-9999	-0.44	3	3
ARNO/beta Arrestin1-2	-0.003	0.069	-9999	-10000	0	0
EGFR	0.004	0.064	-9999	-0.53	8	8
EPHA2	0.006	0.056	-9999	-0.54	6	6
USP6	0.008	0.042	-9999	-0.49	4	4
IQSEC1	0.011	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.13	0.19	-9999	-0.36	216	216
ARRB2	0.007	0.008	-9999	-0.19	1	1
mol:GTP	0.004	0.047	-9999	-0.26	12	12
ARRB1	0.009	0.035	-9999	-0.58	2	2
FBXO8	0.009	0.035	-9999	-0.58	2	2
TSHR	-0.014	0.1	-9999	-0.46	27	27
EGF	-0.18	0.25	-9999	-0.5	209	209
somatostatin receptor activity	0	0	-9999	-0.001	47	47
ARAP2	-0.006	0.1	-9999	-0.58	17	17
mol:GDP	-0.034	0.088	-9999	-0.28	42	42
mol:PI-3-4-5-P3	0	0	-9999	-0.001	22	22
ITGA2B	-0.047	0.16	-9999	-0.5	64	64
ARF6	0.01	0.025	-9999	-0.58	1	1
Ephrin A1/EPHA2/NCK1/GIT1	0.024	0.046	-9999	-0.37	6	6
ADAP1	0.01	0.031	-9999	-0.52	2	2
KIF13B	0.009	0.035	-9999	-0.58	2	2
HGF/MET	-0.019	0.12	-9999	-0.39	51	51
PXN	0.011	0	-9999	-10000	0	0
ARF6/GTP	-0.039	0.094	-9999	-0.27	45	45
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.099	0.16	-9999	-0.3	216	216
ADRB2	-0.029	0.14	-9999	-0.54	42	42
receptor agonist activity	0	0	-9999	0	46	46
actin filament binding	0	0	-9999	-0.001	45	45
SRC	0.01	0.025	-9999	-0.58	1	1
ITGB3	-0.005	0.093	-9999	-0.54	17	17
GNAQ	0.005	0.06	-9999	-0.58	6	6
EFA6/PI-4-5-P2	0	0	-9999	-0.001	38	38
ARF6/GDP	-0.003	0.1	-9999	-0.36	28	28
ARF6/GDP/GULP/ACAP1	-0.06	0.14	-9999	-0.37	64	64
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.013	0.11	-9999	-0.32	37	37
ACAP1	-0.025	0.14	-9999	-0.53	38	38
ACAP2	0.001	0.078	-9999	-0.58	10	10
LHCGR/beta Arrestin2	0.001	0.012	-9999	-0.26	1	1
EFNA1	0.011	0.019	-9999	-0.46	1	1
HGF	-0.036	0.16	-9999	-0.55	49	49
CYTH3	0.007	0.029	-9999	-0.39	3	3
CYTH2	0.008	0.002	-9999	-10000	0	0
NCK1	0.009	0.035	-9999	-0.58	2	2
fibronectin binding	0	0	-9999	0	33	33
endosomal lumen acidification	0	0	-9999	0	35	35
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.05	0.17	-9999	-0.53	65	65
GNAQ/ARNO	0.01	0.032	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	24	24
MET	0.009	0.031	-9999	-0.52	2	2
GNA14	-0.008	0.1	-9999	-0.56	19	19
GNA15	-0.009	0.1	-9999	-0.54	21	21
GIT1	0.01	0.025	-9999	-0.58	1	1
mol:PI-4-5-P2	0	0	-9999	-0.001	39	39
GNA11	0.007	0.051	-9999	-0.53	5	5
LHCGR	0	0.019	-9999	-0.46	1	1
AGTR1	-0.095	0.21	-9999	-0.52	114	114
desensitization of G-protein coupled receptor protein signaling pathway	0.001	0.012	-9999	-0.26	1	1
IPCEF1/ARNO	-0.074	0.12	-9999	-0.47	1	1
alphaIIb/beta3 Integrin	-0.037	0.13	-9999	-0.37	80	80

×

Caspase cascade in apoptosis

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
TOP1	-0.025	0.12	0.19	2	-0.33	57	59
ACTA1	-0.046	0.15	0.23	2	-0.42	58	60
NUMA1	-0.025	0.12	0.19	2	-0.32	57	59
SPTAN1	-0.038	0.15	0.23	2	-0.4	57	59
LIMK1	-0.038	0.15	0.23	2	-0.41	55	57
BIRC3	-0.016	0.12	-10000	0	-0.52	29	29
BIRC2	-0.002	0.088	-10000	0	-0.58	13	13
BAX	0.01	0.025	-10000	0	-0.58	1	1
CASP10	-0.052	0.16	-10000	0	-0.42	59	59
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.01	0.025	-10000	0	-0.58	1	1
PTK2	-0.025	0.12	0.19	2	-0.33	55	57
DIABLO	0.011	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.037	0.14	0.23	2	-0.4	57	59
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.01	0.025	-10000	0	-0.58	1	1
GSN	-0.043	0.15	0.23	2	-0.41	59	61
MADD	0.011	0	-10000	0	-10000	0	0
TFAP2A	-0.085	0.2	-10000	0	-0.56	82	82
BID	-0.021	0.084	-10000	0	-0.23	60	60
MAP3K1	-0.013	0.07	-10000	0	-0.33	12	12
TRADD	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.014	0.036	-10000	0	-0.42	4	4
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.039	0.15	0.23	2	-0.41	57	59
CASP9	0.01	0.025	-10000	0	-0.58	1	1
DNA repair	0.003	0.048	-10000	0	-0.19	8	8
neuron apoptosis	0.012	0.037	-10000	0	-0.49	2	2
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.03	0.14	0.22	2	-0.39	55	57
APAF1	0.008	0.043	-10000	0	-0.58	3	3
CASP6	-0.004	0.083	-10000	0	-0.53	4	4
TRAF2	0.01	0.025	-10000	0	-0.58	1	1
ICAD/CAD	-0.031	0.14	-10000	0	-0.39	55	55
CASP7	0.008	0.058	0.26	19	-10000	0	19
KRT18	0.006	0.033	-10000	0	-0.55	1	1
apoptosis	-0.036	0.14	0.25	2	-0.36	63	65
DFFA	-0.038	0.15	0.23	2	-0.41	55	57
DFFB	-0.038	0.15	0.23	2	-0.41	55	57
PARP1	-0.003	0.048	0.19	8	-10000	0	8
actin filament polymerization	0.039	0.14	0.38	57	-10000	0	57
TNF	-0.016	0.12	-10000	0	-0.54	28	28
CYCS	-0.021	0.086	-10000	0	-0.28	32	32
SATB1	-0.018	0.11	-10000	0	-0.41	19	19
SLK	-0.049	0.16	0.23	2	-0.41	72	74
p15 BID/BAX	-0.013	0.076	-10000	0	-0.29	11	11
CASP2	0.022	0.06	-10000	0	-0.4	2	2
JNK cascade	0.013	0.069	0.32	12	-10000	0	12
CASP3	-0.046	0.15	0.24	2	-0.43	58	60
LMNB2	0.017	0.06	-10000	0	-0.53	2	2
RIPK1	0.011	0	-10000	0	-10000	0	0
CASP4	0.008	0.04	-10000	0	-0.54	3	3
Mammalian IAPs/DIABLO	0.006	0.1	-10000	0	-0.46	20	20
negative regulation of DNA binding	-0.085	0.2	-10000	0	-0.55	82	82
stress fiber formation	-0.049	0.16	0.23	2	-0.4	72	74
GZMB	-0.069	0.18	-10000	0	-0.4	120	120
CASP1	-0.006	0.079	-10000	0	-0.3	36	36
LMNB1	0.018	0.052	-10000	0	-0.27	3	3
APP	0.012	0.037	-10000	0	-0.5	2	2
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.008	0.018	-10000	0	-0.43	1	1
VIM	-0.028	0.13	0.23	5	-0.35	52	57
LMNA	0.017	0.058	-10000	0	-0.37	4	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.017	0.063	-10000	0	-0.43	2	2
LRDD	0.008	0.043	-10000	0	-0.58	3	3
SREBF1	-0.039	0.15	0.23	2	-0.4	58	60
APAF-1/Caspase 9	-0.003	0.066	0.4	7	-0.75	1	8
nuclear fragmentation during apoptosis	-0.024	0.12	0.19	2	-0.32	57	59
CFL2	-0.041	0.15	-10000	0	-0.39	57	57
GAS2	-0.07	0.17	0.23	1	-0.4	88	89
positive regulation of apoptosis	0.02	0.058	-10000	0	-0.62	1	1
PRF1	-0.036	0.15	-10000	0	-0.5	53	53

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.044	0.16	-10000	0	-0.53	59	59
ANTXR2	0.005	0.059	-10000	0	-0.53	7	7
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.008	0.022	-10000	0	-0.068	65	65
monocyte activation	-0.023	0.13	-10000	0	-0.49	34	34
MAP2K2	-0.004	0.033	-10000	0	-0.76	1	1
MAP2K1	-0.008	0.027	-10000	0	-0.35	2	2
MAP2K7	-0.007	0.022	-10000	0	-0.31	1	1
MAP2K6	-0.012	0.046	-10000	0	-0.33	10	10
CYAA	-0.021	0.093	-10000	0	-0.28	65	65
MAP2K4	-0.008	0.029	-10000	0	-0.31	3	3
IL1B	-0.04	0.11	-10000	0	-0.28	89	89
Channel	-0.021	0.1	-10000	0	-0.3	65	65
NLRP1	-0.018	0.062	-10000	0	-0.28	26	26
CALM1	0.011	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.009	0.025	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.008	0.022	0.068	65	-10000	0	65
MAPK3	-0.007	0.022	-10000	0	-0.31	1	1
MAPK1	-0.007	0.024	-10000	0	-0.38	1	1
PGR	-0.04	0.097	-10000	0	-0.29	73	73
PA/Cellular Receptors	-0.023	0.11	-10000	0	-0.33	65	65
apoptosis	-0.008	0.022	-10000	0	-0.068	65	65
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.018	0.092	-10000	0	-0.27	65	65
macrophage activation	0.007	0.028	-10000	0	-0.33	2	2
TNF	-0.016	0.12	-10000	0	-0.54	28	28
VCAM1	-0.023	0.13	-10000	0	-0.49	34	34
platelet activation	-0.009	0.025	-10000	0	-10000	0	0
MAPKKK cascade	-0.002	0.028	0.14	5	-10000	0	5
IL18	-0.007	0.054	-10000	0	-0.24	19	19
negative regulation of macrophage activation	-0.008	0.022	-10000	0	-0.068	65	65
LEF	-0.008	0.022	-10000	0	-0.068	65	65
CASP1	-0.015	0.039	-10000	0	-0.15	29	29
mol:cAMP	-0.009	0.025	-10000	0	-10000	0	0
necrosis	-0.008	0.022	-10000	0	-0.068	65	65
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.019	0.094	-10000	0	-0.28	65	65
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.012	0.042	-9999	-0.36	7	7
alphaV beta3 Integrin	-0.024	0.13	-9999	-0.37	69	69
PTK2	-0.024	0.15	-9999	-0.53	26	26
IGF1R	0.01	0.025	-9999	-0.58	1	1
PI4KB	0.011	0	-9999	-10000	0	0
MFGE8	0	0.076	-9999	-0.49	13	13
SRC	0.01	0.025	-9999	-0.58	1	1
CDKN1B	-0.034	0.13	-9999	-0.5	28	28
VEGFA	0.011	0.019	-9999	-0.46	1	1
ILK	-0.033	0.13	-9999	-0.49	27	27
ROCK1	0	0.081	-9999	-0.58	11	11
AKT1	-0.023	0.12	-9999	-0.46	26	26
PTK2B	0.012	0.078	-9999	-0.31	25	25
alphaV/beta3 Integrin/JAM-A	-0.039	0.15	-9999	-0.37	70	70
CBL	0.011	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.001	0.08	-9999	-0.35	28	28
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.026	0.12	-9999	-0.33	60	60
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.005	0.11	-9999	-0.62	11	11
alphaV/beta3 Integrin/Syndecan-1	0.005	0.081	-9999	-0.34	28	28
PI4KA	0.011	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.12	0.19	-9999	-0.57	63	63
PI4 Kinase	0.017	0	-9999	-10000	0	0
PIK3CA	0.009	0.035	-9999	-0.58	2	2
alphaV/beta3 Integrin/Osteopontin	-0.1	0.17	-9999	-0.32	204	204
RPS6KB1	-0.081	0.2	-9999	-0.54	66	66
TLN1	0.01	0.025	-9999	-0.58	1	1
MAPK3	-0.063	0.2	-9999	-0.64	48	48
GPR124	0.005	0.061	-9999	-0.55	7	7
MAPK1	-0.063	0.2	-9999	-0.64	48	48
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.008	0.043	-9999	-0.58	3	3
alphaV/beta3 Integrin/Tumstatin	-0.045	0.14	-9999	-0.32	114	114
cell adhesion	0.003	0.091	-9999	-0.37	26	26
ANGPTL3	0.003	0.02	-9999	-0.46	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.019	0.039	-9999	-0.31	8	8
IGF-1R heterotetramer	0.01	0.025	-9999	-0.58	1	1
Rac1/GDP	0.008	0	-9999	-10000	0	0
TGFBR2	0.011	0.019	-9999	-0.46	1	1
ITGB3	-0.005	0.093	-9999	-0.54	17	17
IGF1	-0.071	0.19	-9999	-0.52	88	88
RAC1	0.011	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.002	0.093	-9999	-0.37	31	31
apoptosis	0	0.081	-9999	-0.58	11	11
CD47	0.009	0.035	-9999	-0.58	2	2
alphaV/beta3 Integrin/CD47	0.005	0.085	-9999	-0.36	28	28
VCL	0.009	0.035	-9999	-0.58	2	2
alphaV/beta3 Integrin/Del1	-0.025	0.15	-9999	-0.41	63	63
CSF1	0.006	0.056	-9999	-0.54	6	6
PIK3C2A	-0.054	0.18	-9999	-0.58	49	49
PI4 Kinase/Pyk2	-0.056	0.12	-9999	-0.46	24	24
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.01	0.082	-9999	-0.34	23	23
FAK1/Vinculin	-0.013	0.12	-9999	-0.42	26	26
alphaV beta3/Integrin/ppsTEM5	0.002	0.093	-9999	-0.37	31	31
RHOA	0.01	0.025	-9999	-0.58	1	1
VTN	-0.051	0.16	-9999	-0.5	68	68
BCAR1	0.008	0.044	-9999	-0.52	4	4
FGF2	-0.037	0.15	-9999	-0.52	53	53
F11R	-0.017	0.11	-9999	-0.37	53	53
alphaV/beta3 Integrin/Lactadherin	-0.001	0.096	-9999	-0.35	37	37
alphaV/beta3 Integrin/TGFBR2	0.005	0.08	-9999	-0.34	28	28
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.017	0.066	-9999	-0.34	17	17
HSP90AA1	0.009	0.035	-9999	-0.58	2	2
alphaV/beta3 Integrin/Talin	0.006	0.074	-9999	-0.31	28	28
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.087	0.21	-9999	-0.52	106	106
alphaV/beta3 Integrin/Pyk2	0.014	0.079	-9999	-0.32	25	25
SDC1	0.01	0.025	-9999	-0.58	1	1
VAV3	-0.023	0.13	-9999	-0.31	89	89
PTPN11	0.006	0.055	-9999	-0.58	5	5
IRS1	0.002	0.074	-9999	-0.58	9	9
FAK1/Paxillin	-0.012	0.12	-9999	-0.41	26	26
cell migration	-0.005	0.11	-9999	-0.38	25	25
ITGAV	0	0.081	-9999	-0.58	11	11
PI3K	-0.06	0.13	-9999	-0.5	25	25
SPP1	-0.16	0.25	-9999	-0.51	188	188
KDR	0.006	0.054	-9999	-0.52	6	6
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0	0.081	-9999	-0.58	11	11
COL4A3	-0.071	0.19	-9999	-0.5	90	90
angiogenesis	-0.062	0.2	-9999	-0.64	47	47
Rac1/GTP	-0.015	0.12	-9999	-0.56	4	4
EDIL3	-0.039	0.16	-9999	-0.57	49	49
cell proliferation	0.005	0.08	-9999	-0.34	28	28

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.043	0.14	-10000	0	-0.42	59	59
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.025	0.13	0.48	18	-0.25	1	19
IL27/IL27R/JAK1	-0.025	0.17	-10000	0	-0.56	28	28
TBX21	-0.046	0.23	-10000	0	-0.55	73	73
IL12B	-0.005	0.074	-10000	0	-0.46	15	15
IL12A	-0.024	0.11	-10000	0	-0.41	44	44
IL6ST	-0.005	0.095	-10000	0	-0.58	15	15
IL27RA/JAK1	0.004	0.11	-10000	0	-0.94	6	6
IL27	-0.007	0.082	-10000	0	-0.46	18	18
TYK2	0.01	0.026	-10000	0	-0.58	1	1
T-helper cell lineage commitment	-0.19	0.41	-10000	0	-1.3	59	59
T-helper 2 cell differentiation	0.025	0.13	0.48	18	-0.25	1	19
T cell proliferation during immune response	0.025	0.13	0.48	18	-0.25	1	19
MAPKKK cascade	-0.025	0.13	0.25	1	-0.48	18	19
STAT3	0.011	0	-10000	0	-10000	0	0
STAT2	0.011	0.019	-10000	0	-0.46	1	1
STAT1	0.006	0.052	-10000	0	-0.5	6	6
IL12RB1	-0.036	0.15	-10000	0	-0.54	48	48
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.043	0.22	-10000	0	-0.57	56	56
IL27/IL27R/JAK2/TYK2	-0.025	0.13	0.26	1	-0.49	18	19
positive regulation of T cell mediated cytotoxicity	-0.025	0.13	0.25	1	-0.48	18	19
STAT1 (dimer)	-0.057	0.24	0.4	21	-0.73	37	58
JAK2	-0.008	0.11	-10000	0	-0.55	21	21
JAK1	0.009	0.043	-10000	0	-0.58	3	3
STAT2 (dimer)	-0.019	0.13	-10000	0	-0.48	17	17
T cell proliferation	-0.098	0.18	-10000	0	-0.46	69	69
IL12/IL12R/TYK2/JAK2	-0.044	0.14	-10000	0	-0.55	15	15
IL17A	-0.2	0.41	-10000	0	-1.3	59	59
mast cell activation	0.025	0.13	0.48	18	-0.25	1	19
IFNG	-0.011	0.043	0.066	1	-0.11	62	63
T cell differentiation	-0.004	0.007	0.014	2	-0.021	64	66
STAT3 (dimer)	-0.019	0.12	-10000	0	-0.48	16	16
STAT5A (dimer)	-0.019	0.12	-10000	0	-0.48	16	16
STAT4 (dimer)	-0.039	0.16	-10000	0	-0.49	43	43
STAT4	-0.028	0.14	-10000	0	-0.56	40	40
T cell activation	-0.006	0.011	0.12	4	-10000	0	4
IL27R/JAK2/TYK2	-0.015	0.14	-10000	0	-0.77	10	10
GATA3	-0.028	0.22	-10000	0	-1.3	16	16
IL18	0.003	0.05	-10000	0	-0.39	9	9
positive regulation of mast cell cytokine production	-0.018	0.12	-10000	0	-0.47	16	16
IL27/EBI3	-0.027	0.13	-10000	0	-0.39	59	59
IL27RA	-0.004	0.11	-10000	0	-1.3	4	4
IL6	-0.15	0.25	-10000	0	-0.53	161	161
STAT5A	0.011	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.006	0.044	0.48	4	-10000	0	4
IL1B	-0.045	0.14	-10000	0	-0.38	81	81
EBI3	-0.031	0.15	-10000	0	-0.56	43	43
TNF	-0.011	0.088	-10000	0	-0.4	28	28

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.025	0.26	-10000	0	-0.87	37	37
NCK1/PAK1/Dok-R	-0.038	0.11	-10000	0	-0.41	39	39
NCK1/Dok-R	-0.025	0.29	-10000	0	-1.1	37	37
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
mol:beta2-estradiol	0.006	0.056	0.24	29	-10000	0	29
RELA	0.011	0	-10000	0	-10000	0	0
SHC1	0.012	0.001	-10000	0	-10000	0	0
Rac/GDP	0.008	0	-10000	0	-10000	0	0
F2	-0.11	0.23	0.25	23	-0.5	139	162
TNIP2	0.01	0.025	-10000	0	-0.58	1	1
NF kappa B/RelA	-0.04	0.26	-10000	0	-0.98	37	37
FN1	-0.087	0.21	-10000	0	-0.52	106	106
PLD2	-0.006	0.3	-10000	0	-1.1	37	37
PTPN11	0.006	0.055	-10000	0	-0.58	5	5
GRB14	-0.12	0.24	-10000	0	-0.54	138	138
ELK1	0.005	0.27	-10000	0	-0.97	37	37
GRB7	0.002	0.067	-10000	0	-0.46	12	12
PAK1	0.011	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.085	0.29	-10000	0	-1	40	40
CDKN1A	0.042	0.2	-10000	0	-0.68	20	20
ITGA5	-0.005	0.089	-10000	0	-0.48	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.025	0.29	-10000	0	-1.1	37	37
CRK	0.011	0.019	-10000	0	-0.46	1	1
mol:NO	0.033	0.21	-10000	0	-0.64	39	39
PLG	-0.031	0.3	-10000	0	-1.1	39	39
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.02	0.24	-10000	0	-0.83	37	37
GRB2	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.009	0.043	-10000	0	-0.58	3	3
ANGPT2	0.019	0.19	-10000	0	-0.86	9	9
BMX	-0.052	0.32	-10000	0	-1.1	39	39
ANGPT1	-0.017	0.31	-10000	0	-1.2	31	31
tube development	0.036	0.22	-10000	0	-0.67	33	33
ANGPT4	0.001	0.043	-10000	0	-0.45	5	5
response to hypoxia	-0.001	0.019	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.077	0.32	-10000	0	-1.1	38	38
alpha5/beta1 Integrin	0.005	0.064	-10000	0	-0.34	19	19
FGF2	-0.038	0.15	-10000	0	-0.52	53	53
STAT5A (dimer)	0.037	0.24	-10000	0	-0.83	20	20
mol:L-citrulline	0.033	0.21	-10000	0	-0.64	39	39
AGTR1	-0.094	0.21	-10000	0	-0.51	114	114
MAPK14	0.001	0.3	-10000	0	-1.1	36	36
Tie2/SHP2	-0.037	0.18	-10000	0	-0.98	17	17
TEK	-0.015	0.2	-10000	0	-1.2	14	14
RPS6KB1	0.025	0.25	-10000	0	-0.85	37	37
Angiotensin II/AT1	-0.066	0.15	-10000	0	-0.37	114	114
Tie2/Ang1/GRB2	-0.01	0.31	-10000	0	-1.1	37	37
MAPK3	0.002	0.28	-10000	0	-1	37	37
MAPK1	0.002	0.28	-10000	0	-1	37	37
Tie2/Ang1/GRB7	-0.014	0.31	-10000	0	-1.1	37	37
NFKB1	0.01	0.025	-10000	0	-0.58	1	1
MAPK8	-0.007	0.3	-10000	0	-1.1	37	37
PI3K	0.014	0.29	-10000	0	-1	37	37
FES	-0.006	0.31	-10000	0	-1.1	37	37
Crk/Dok-R	-0.024	0.29	-10000	0	-1.1	37	37
Tie2/Ang1/ABIN2	-0.011	0.31	-10000	0	-1.1	37	37
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.031	0.23	-10000	0	-0.77	37	37
STAT5A	0.012	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.026	0.25	-10000	0	-0.83	37	37
Tie2/Ang2	0.022	0.27	-10000	0	-0.89	33	33
Tie2/Ang1	-0.014	0.33	-10000	0	-1.2	37	37
FOXO1	0.033	0.24	-10000	0	-0.77	39	39
ELF1	0.013	0.047	-10000	0	-0.59	3	3
ELF2	-0.007	0.3	-10000	0	-1.1	37	37
mol:Choline	-0.003	0.28	-10000	0	-1	37	37
cell migration	-0.03	0.067	-10000	0	-0.23	47	47
FYN	0.031	0.24	-10000	0	-0.76	33	33
DOK2	-0.008	0.1	-10000	0	-0.54	20	20
negative regulation of cell cycle	0.045	0.19	-10000	0	-0.6	22	22
ETS1	-0.003	0.084	-10000	0	-0.44	12	12
PXN	0.037	0.21	-10000	0	-0.68	37	37
ITGB1	0.011	0	-10000	0	-10000	0	0
NOS3	0.028	0.23	-10000	0	-0.73	39	39
RAC1	0.011	0	-10000	0	-10000	0	0
TNF	-0.021	0.14	-10000	0	-0.53	31	31
MAPKKK cascade	-0.003	0.28	-10000	0	-1	37	37
RASA1	0.009	0.035	-10000	0	-0.58	2	2
Tie2/Ang1/Shc	-0.009	0.31	-10000	0	-1.1	37	37
NCK1	0.009	0.035	-10000	0	-0.58	2	2
vasculogenesis	0.037	0.19	-10000	0	-0.57	39	39
mol:Phosphatidic acid	-0.003	0.28	-10000	0	-1	37	37
mol:Angiotensin II	0.001	0.004	-10000	0	-10000	0	0
mol:NADP	0.033	0.21	-10000	0	-0.64	39	39
Rac1/GTP	-0.06	0.2	-10000	0	-0.77	37	37
MMP2	-0.025	0.32	-10000	0	-1.1	38	38

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.011	0	-9999	-10000	0	0
ITGB7	-0.017	0.12	-9999	-0.53	30	30
ITGA4	-0.018	0.13	-9999	-0.56	29	29
alpha4/beta7 Integrin	-0.024	0.14	-9999	-0.43	53	53
alpha4/beta1 Integrin	-0.004	0.093	-9999	-0.41	29	29

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.015	0.026	-10000	0	-10000	0	0
AES	0.013	0.033	-10000	0	-0.58	1	1
FBXW11	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.013	0.039	-10000	0	-0.4	5	5
SMAD4	0.005	0.06	-10000	0	-0.58	6	6
DKK2	-0.085	0.21	-10000	0	-0.54	101	101
TLE1	0.01	0.054	-10000	0	-0.58	4	4
MACF1	0.012	0.001	-10000	0	-10000	0	0
CTNNB1	0.05	0.1	0.25	13	-0.95	2	15
WIF1	-0.18	0.25	-10000	0	-0.5	211	211
beta catenin/RanBP3	0.025	0.13	0.39	56	-0.7	2	58
KREMEN2	-0.039	0.15	-10000	0	-0.48	59	59
DKK1	-0.15	0.24	-10000	0	-0.51	174	174
beta catenin/beta TrCP1	0.054	0.091	0.25	9	-0.8	2	11
FZD1	0.009	0.04	-10000	0	-0.54	3	3
AXIN2	-0.12	0.42	-10000	0	-1.4	53	53
AXIN1	0.011	0.025	-10000	0	-0.58	1	1
RAN	0.012	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.014	0.083	-10000	0	-0.95	3	3
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.05	0.1	-10000	0	-0.63	6	6
Axin1/APC/GSK3	0.046	0.08	0.22	17	-0.78	2	19
Axin1/APC/GSK3/beta catenin/Macf1	0.036	0.095	-10000	0	-0.71	4	4
HNF1A	0.008	0.059	-10000	0	-0.53	6	6
CTBP1	0.013	0.034	-10000	0	-0.58	1	1
MYC	-0.014	0.16	-10000	0	-1.5	5	5
RANBP3	0.01	0.025	-10000	0	-0.58	1	1
DKK2/LRP6/Kremen 2	-0.069	0.16	-10000	0	-0.38	81	81
NKD1	-0.13	0.24	-10000	0	-0.52	155	155
TCF4	0.002	0.083	-10000	0	-0.52	13	13
TCF3	0.013	0.033	-10000	0	-0.58	1	1
WNT1/LRP6/FZD1/Axin1	0.016	0.061	-10000	0	-0.36	6	6
Ran/GTP	0.009	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.029	0.16	0.46	50	-0.64	5	55
LEF1	-0.009	0.11	-10000	0	-0.52	25	25
DVL1	0.045	0.062	0.21	1	-0.5	4	5
CSNK2A1	0.012	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.042	0.11	-10000	0	-0.58	7	7
DKK1/LRP6/Kremen 2	-0.11	0.18	-10000	0	-0.4	93	93
LRP6	0.01	0.035	-10000	0	-0.58	2	2
CSNK1A1	0.013	0.044	-10000	0	-0.59	2	2
NLK	0.011	0.004	-10000	0	-10000	0	0
CCND1	-0.005	0.094	-10000	0	-0.73	4	4
WNT1	-0.008	0.086	-10000	0	-0.46	20	20
GSK3A	0.012	0.001	-10000	0	-10000	0	0
GSK3B	0.009	0.035	-10000	0	-0.58	2	2
FRAT1	0.01	0.025	-10000	0	-0.58	1	1
PPP2R5D	0.089	0.11	0.27	151	-10000	0	151
APC	0.009	0.084	-10000	0	-0.54	4	4
WNT1/LRP6/FZD1	0.07	0.1	0.23	74	-0.69	3	77
CREBBP	0.014	0.022	-10000	0	-10000	0	0

×

Visual signal transduction: Rods

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.009	0.035	-9999	-0.58	2	2
GNAT1/GTP	0	0.019	-9999	-0.32	2	2
Metarhodopsin II/Arrestin	0	0.023	-9999	-0.27	4	4
PDE6G/GNAT1/GTP	-0.015	0.088	-9999	-0.33	41	41
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.001	0.027	-9999	-0.46	2	2
GRK1	-0.003	0.047	-9999	-0.46	6	6
CNG Channel	-0.12	0.17	-9999	-0.56	46	46
mol:Na +	-0.066	0.13	-9999	-0.5	22	22
mol:ADP	-0.003	0.047	-9999	-0.45	6	6
RGS9-1/Gbeta5/R9AP	-0.021	0.12	-9999	-0.33	70	70
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.068	0.14	-9999	-0.52	22	22
CNGB1	-0.005	0.069	-9999	-0.46	13	13
RDH5	-0.002	0.084	-9999	-0.53	14	14
SAG	0.001	0.02	-9999	-0.46	1	1
mol:Ca2+	-0.043	0.14	-9999	-0.49	22	22
Na + (4 Units)	-0.063	0.12	-9999	-0.47	22	22
RGS9	-0.033	0.15	-9999	-0.53	47	47
GNB1/GNGT1	-0.022	0.11	-9999	-0.37	54	54
GNAT1/GDP	-0.017	0.1	-9999	-0.32	44	44
GUCY2D	-0.014	0.099	-9999	-0.46	27	27
GNGT1	-0.042	0.16	-9999	-0.52	54	54
GUCY2F	0	0.019	-9999	-0.46	1	1
GNB5	0.007	0.049	-9999	-0.58	4	4
mol:GMP (4 units)	-0.082	0.17	-9999	-0.36	118	118
mol:11-cis-retinal	-0.002	0.083	-9999	-0.53	14	14
mol:cGMP	-0.024	0.1	-9999	-0.37	15	15
GNB1	0.011	0	-9999	-10000	0	0
Rhodopsin	-0.002	0.065	-9999	-0.37	17	17
SLC24A1	0.009	0.035	-9999	-0.58	2	2
CNGA1	-0.052	0.18	-9999	-0.53	67	67
Metarhodopsin II	-0.002	0.034	-9999	-0.27	8	8
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.026	0.11	-9999	-0.35	34	34
RGS9BP	-0.01	0.1	-9999	-0.54	21	21
Metarhodopsin II/Transducin	-0.012	0.07	-9999	-0.28	31	31
GCAP Family/Ca ++	-0.019	0.094	-9999	-0.33	30	30
PDE6A/B	-0.095	0.2	-9999	-0.41	149	149
mol:Pi	-0.021	0.12	-9999	-0.33	70	70
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.015	0.091	-9999	-0.29	51	51
PDE6B	-0.029	0.14	-9999	-0.52	43	43
PDE6A	-0.1	0.22	-9999	-0.54	120	120
PDE6G	-0.026	0.14	-9999	-0.54	39	39
RHO	-0.002	0.033	-9999	-0.46	3	3
PDE6	-0.12	0.17	-9999	-0.56	46	46
GUCA1A	-0.021	0.12	-9999	-0.49	33	33
GC2/GCAP Family	-0.019	0.095	-9999	-0.34	31	31
GUCA1C	-0.001	0.027	-9999	-0.46	2	2
GUCA1B	-0.015	0.12	-9999	-0.54	27	27

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.087	-10000	0	-0.53	15	15
Jak2/Leptin Receptor	-0.055	0.13	0.19	1	-0.41	50	51
PTP1B/AKT1	-0.02	0.076	-10000	0	-0.3	16	16
FYN	0.005	0.061	-10000	0	-0.55	7	7
p210 bcr-abl/PTP1B	-0.029	0.082	0.17	1	-0.29	23	24
EGFR	0.001	0.065	-10000	0	-0.54	8	8
EGF/EGFR	-0.096	0.15	-10000	0	-0.33	115	115
CSF1	0.006	0.056	-10000	0	-0.54	6	6
AKT1	0.01	0.025	-10000	0	-0.59	1	1
INSR	0.009	0.035	-10000	0	-0.58	2	2
PTP1B/N-cadherin	-0.068	0.14	-10000	0	-0.34	101	101
Insulin Receptor/Insulin	-0.026	0.058	-10000	0	-0.36	7	7
HCK	-0.02	0.13	-10000	0	-0.55	32	32
CRK	0.011	0.019	-10000	0	-0.46	1	1
TYK2	-0.022	0.08	-10000	0	-0.32	16	16
EGF	-0.18	0.25	-10000	0	-0.51	209	209
YES1	0.004	0.065	-10000	0	-0.58	7	7
CAV1	-0.041	0.1	0.16	1	-0.29	36	37
TXN	0.009	0.004	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.019	0.084	-10000	0	-0.3	23	23
cell migration	0.029	0.082	0.29	23	-0.17	1	24
STAT3	0.011	0.001	-10000	0	-10000	0	0
PRLR	-0.043	0.17	-10000	0	-0.57	53	53
ITGA2B	-0.047	0.16	-10000	0	-0.5	64	64
CSF1R	-0.029	0.14	-10000	0	-0.53	43	43
Prolactin Receptor/Prolactin	-0.042	0.14	-10000	0	-0.42	69	69
FGR	-0.023	0.13	-10000	0	-0.53	36	36
PTP1B/p130 Cas	-0.023	0.083	-10000	0	-0.32	19	19
Crk/p130 Cas	-0.017	0.082	-10000	0	-0.34	15	15
DOK1	-0.017	0.086	-10000	0	-0.36	17	17
JAK2	-0.047	0.13	-10000	0	-0.41	50	50
Jak2/Leptin Receptor/Leptin	-0.054	0.12	-10000	0	-0.45	28	28
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
PTPN1	-0.029	0.082	0.17	1	-0.29	23	24
LYN	0.011	0	-10000	0	-10000	0	0
CDH2	-0.081	0.2	-10000	0	-0.53	98	98
SRC	0	0.06	-10000	0	-1.2	1	1
ITGB3	-0.006	0.094	-10000	0	-0.54	17	17
CAT1/PTP1B	-0.081	0.17	-10000	0	-0.48	53	53
CAPN1	0.01	0.025	-10000	0	-0.59	1	1
CSK	0.01	0.025	-10000	0	-0.58	1	1
PI3K	-0.021	0.064	-10000	0	-0.42	8	8
mol:H2O2	-0.001	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.049	0.11	-10000	0	-0.45	25	25
negative regulation of transcription	-0.046	0.13	-10000	0	-0.4	50	50
FCGR2A	-0.02	0.13	-10000	0	-0.54	33	33
FER	-0.001	0.072	-10000	0	-0.54	10	10
alphaIIb/beta3 Integrin	-0.039	0.13	-10000	0	-0.37	80	80
BLK	-0.11	0.23	-10000	0	-0.53	132	132
Insulin Receptor/Insulin/Shc	0.014	0.027	-10000	0	-0.31	4	4
RHOA	0.01	0.025	-10000	0	-0.59	1	1
LEPR	0	0.081	-10000	0	-0.55	12	12
BCAR1	0.008	0.044	-10000	0	-0.52	4	4
p210 bcr-abl/Grb2	0.011	0	-10000	0	-10000	0	0
mol:NADPH	-0.002	0.003	-10000	0	-10000	0	0
TRPV6	-0.083	0.19	-10000	0	-0.51	61	61
PRL	-0.013	0.088	-10000	0	-0.45	22	22
SOCS3	-0.002	0.12	-10000	0	-1.3	4	4
SPRY2	0.007	0.043	-10000	0	-0.59	3	3
Insulin Receptor/Insulin/IRS1	0.008	0.054	-10000	0	-0.35	13	13
CSF1/CSF1R	-0.037	0.12	-10000	0	-0.37	47	47
Ras protein signal transduction	0.021	0.025	-10000	0	-10000	0	0
IRS1	0.002	0.074	-10000	0	-0.58	9	9
INS	-0.001	0.027	-10000	0	-0.45	2	2
LEP	-0.025	0.12	-10000	0	-0.46	38	38
STAT5B	-0.033	0.09	-10000	0	-0.29	32	32
STAT5A	-0.033	0.09	-10000	0	-0.29	32	32
GRB2	0.011	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.028	0.1	-10000	0	-0.38	26	26
CSN2	-0.008	0.06	-10000	0	-10000	0	0
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
LAT	-0.032	0.14	-10000	0	-0.57	30	30
YBX1	0.016	0.016	-10000	0	-0.36	1	1
LCK	-0.032	0.14	-10000	0	-0.51	48	48
SHC1	0.011	0	-10000	0	-10000	0	0
NOX4	-0.07	0.19	-10000	0	-0.52	87	87

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.011	0.058	0.24	21	-0.3	4	25
RFC1	0.011	0.062	0.23	25	-0.38	4	29
PRKDC	0.01	0.061	0.24	21	-0.3	6	27
RIPK1	0.013	0.003	-10000	0	-10000	0	0
CASP7	-0.01	0.051	0.24	6	-0.43	1	7
FASLG/FAS/FADD/FAF1	0.002	0.11	0.22	60	-0.3	30	90
MAP2K4	-0.027	0.13	-10000	0	-0.42	21	21
mol:ceramide	-0.027	0.12	-10000	0	-0.38	43	43
GSN	0.006	0.068	0.23	24	-0.29	12	36
FASLG/FAS/FADD/FAF1/Caspase 8	-0.001	0.12	-10000	0	-0.35	34	34
FAS	-0.001	0.075	-10000	0	-0.56	10	10
BID	0.008	0.051	0.29	13	-0.32	2	15
MAP3K1	-0.005	0.087	0.22	5	-0.32	10	15
MAP3K7	0.01	0.004	-10000	0	-10000	0	0
RB1	0	0.086	0.23	24	-0.35	21	45
CFLAR	0.013	0.003	-10000	0	-10000	0	0
HGF/MET	-0.062	0.17	-10000	0	-0.37	125	125
ARHGDIB	0.01	0.06	0.24	20	-0.31	5	25
FADD	0.009	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.006	0.068	0.29	12	-0.23	24	36
NFKB1	-0.043	0.085	-10000	0	-0.73	2	2
MAPK8	-0.045	0.17	-10000	0	-0.45	67	67
DFFA	0.012	0.056	0.23	25	-0.28	3	28
DNA fragmentation during apoptosis	0.012	0.056	0.24	21	-0.28	3	24
FAS/FADD/MET	0.012	0.052	-10000	0	-0.34	12	12
CFLAR/RIP1	0.013	0.007	-10000	0	-10000	0	0
FAIM3	-0.012	0.11	-10000	0	-0.52	26	26
FAF1	0.009	0.008	-10000	0	-10000	0	0
PARP1	0.012	0.056	0.23	26	-0.28	3	29
DFFB	0.012	0.056	0.24	21	-0.28	3	24
CHUK	-0.039	0.081	-10000	0	-0.77	2	2
FASLG	-0.054	0.18	-10000	0	-0.54	66	66
FAS/FADD	0.006	0.056	-10000	0	-0.41	10	10
HGF	-0.036	0.16	-10000	0	-0.55	49	49
LMNA	0.009	0.052	0.23	14	-0.3	3	17
CASP6	0.011	0.054	0.22	24	-0.28	3	27
CASP10	0.008	0.025	-10000	0	-0.58	1	1
CASP3	0.014	0.068	0.27	29	-0.33	3	32
PTPN13	-0.076	0.21	-10000	0	-0.56	88	88
CASP8	0.013	0.067	0.3	26	-0.44	1	27
IL6	-0.16	0.41	-10000	0	-1.2	65	65
MET	0.01	0.031	-10000	0	-0.52	2	2
ICAD/CAD	0.011	0.052	0.24	15	-0.29	2	17
FASLG/FAS/FADD/FAF1/Caspase 10	-0.027	0.12	-10000	0	-0.39	43	43
activation of caspase activity by cytochrome c	0.008	0.051	0.29	13	-0.32	2	15
PAK2	0.011	0.06	0.23	25	-0.39	3	28
BCL2	-0.007	0.1	-10000	0	-0.55	19	19

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.018	0.093	-10000	0	-0.63	10	10
HDAC1	0.008	0.004	-10000	0	-10000	0	0
AES	0.01	0.025	-10000	0	-0.58	1	1
FBXW11	0.011	0	-10000	0	-10000	0	0
DTX1	-0.01	0.11	-10000	0	-0.54	22	22
LRP6/FZD1	0.013	0.039	-10000	0	-0.4	5	5
TLE1	0.007	0.049	-10000	0	-0.58	4	4
AP1	-0.063	0.14	-10000	0	-0.31	105	105
NCSTN	0.011	0	-10000	0	-10000	0	0
ADAM10	0.006	0.055	-10000	0	-0.58	5	5
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.036	0.069	-10000	0	-1.3	1	1
NICD/RBPSUH	0.015	0.087	-10000	0	-0.65	9	9
WIF1	-0.18	0.25	-10000	0	-0.5	211	211
NOTCH1	-0.012	0.08	-10000	0	-0.63	9	9
PSENEN	0.01	0.025	-10000	0	-0.58	1	1
KREMEN2	-0.039	0.15	-10000	0	-0.48	59	59
DKK1	-0.15	0.24	-10000	0	-0.51	174	174
beta catenin/beta TrCP1	0.051	0.068	0.25	2	-10000	0	2
APH1B	0.006	0.055	-10000	0	-0.58	5	5
APH1A	0.011	0	-10000	0	-10000	0	0
AXIN1	-0.014	0.047	-10000	0	-0.36	5	5
CtBP/CBP/TCF1/TLE1/AES	0.013	0.054	-10000	0	-0.93	1	1
PSEN1	0.011	0	-10000	0	-10000	0	0
FOS	-0.03	0.14	-10000	0	-0.53	44	44
JUN	0.006	0.053	-10000	0	-0.56	5	5
MAP3K7	0.01	0.002	-10000	0	-10000	0	0
CTNNB1	0.047	0.072	0.25	3	-10000	0	3
MAPK3	0.01	0.025	-10000	0	-0.58	1	1
DKK2/LRP6/Kremen 2	-0.069	0.16	-10000	0	-0.38	81	81
HNF1A	0.005	0.058	-10000	0	-0.56	6	6
CTBP1	0.01	0.025	-10000	0	-0.58	1	1
MYC	0.009	0.13	-10000	0	-1.4	5	5
NKD1	-0.13	0.24	-10000	0	-0.52	155	155
FZD1	0.009	0.04	-10000	0	-0.54	3	3
NOTCH1 precursor/Deltex homolog 1	0.005	0.098	-10000	0	-0.59	10	10
apoptosis	-0.063	0.13	-10000	0	-0.31	105	105
Delta 1/NOTCHprecursor	0.009	0.097	-10000	0	-0.63	10	10
DLL1	-0.003	0.088	-10000	0	-0.52	16	16
PPARD	0.019	0.059	-10000	0	-1.4	1	1
Gamma Secretase	0.031	0.033	-10000	0	-0.3	1	1
APC	-0.029	0.1	-10000	0	-0.49	22	22
DVL1	-0.01	0.053	-10000	0	-0.5	4	4
CSNK2A1	0.012	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.11	0.18	-10000	0	-0.4	93	93
LRP6	0.009	0.035	-10000	0	-0.58	2	2
CSNK1A1	0.01	0.035	-10000	0	-0.58	2	2
NLK	0.011	0.005	-10000	0	-10000	0	0
CCND1	0.019	0.059	-10000	0	-1.4	1	1
WNT1	-0.009	0.086	-10000	0	-0.46	20	20
Axin1/APC/beta catenin	0.025	0.08	-10000	0	-0.42	8	8
DKK2	-0.085	0.21	-10000	0	-0.54	101	101
NOTCH1 precursor/DVL1	-0.018	0.092	-10000	0	-0.66	10	10
GSK3B	0.009	0.035	-10000	0	-0.58	2	2
FRAT1	0.01	0.025	-10000	0	-0.58	1	1
NOTCH/Deltex homolog 1	-0.021	0.093	-10000	0	-0.6	10	10
PPP2R5D	0.06	0.12	0.25	151	-10000	0	151
MAPK1	0.01	0.025	-10000	0	-0.58	1	1
WNT1/LRP6/FZD1	-0.093	0.15	-10000	0	-0.34	84	84
RBPJ	0.01	0.031	-10000	0	-0.52	2	2
CREBBP	0.014	0.002	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC3	0.011	0	-10000	0	-10000	0	0
VDR	0.01	0.025	-10000	0	-0.58	1	1
Cbp/p300/PCAF	0.01	0.073	-10000	0	-0.37	20	20
EP300	0.007	0.049	-10000	0	-0.58	4	4
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.002	0.08	-10000	0	-0.38	12	12
KAT2B	-0.006	0.1	-10000	0	-0.58	17	17
MAPK14	0.011	0	-10000	0	-10000	0	0
AKT1	0.006	0.086	0.21	12	-0.3	15	27
RAR alpha/9cRA/Cyclin H	-0.045	0.083	-10000	0	-0.5	4	4
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.006	0.087	-10000	0	-0.38	17	17
CDC2	0	0.002	-10000	0	-10000	0	0
response to UV	0.001	0.003	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.029	0.08	-10000	0	-0.47	1	1
NCOR2	0.007	0.047	-10000	0	-0.55	4	4
VDR/VDR/Vit D3	0.008	0.018	-10000	0	-0.43	1	1
RXRs/RARs/NRIP1/9cRA	-0.048	0.17	-10000	0	-0.42	85	85
NCOA2	0.003	0.068	-10000	0	-0.56	8	8
NCOA3	0.01	0.025	-10000	0	-0.58	1	1
NCOA1	0.01	0.025	-10000	0	-0.58	1	1
VDR/VDR/DNA	0.01	0.025	-10000	0	-0.58	1	1
RARG	0.006	0.06	-10000	0	-0.58	6	6
RAR gamma1/9cRA	0.012	0.038	-10000	0	-0.36	6	6
MAPK3	0.011	0.025	-10000	0	-0.58	1	1
MAPK1	0.01	0.025	-10000	0	-0.58	1	1
MAPK8	0.011	0.025	-10000	0	-0.58	1	1
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.056	0.16	-10000	0	-0.43	77	77
RARA	-0.037	0.099	-10000	0	-0.25	79	79
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.009	0.095	-10000	0	-0.4	19	19
PRKCA	0.011	0.032	-10000	0	-0.52	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.056	0.17	-10000	0	-0.43	84	84
RXRG	-0.07	0.14	-10000	0	-0.34	78	78
RXRA	-0.027	0.091	-10000	0	-0.26	5	5
RXRB	-0.059	0.13	-10000	0	-0.34	76	76
VDR/Vit D3/DNA	0.008	0.018	-10000	0	-0.43	1	1
RBP1	-0.086	0.2	-10000	0	-0.48	113	113
CRBP1/9-cic-RA	-0.062	0.14	-10000	0	-0.35	113	113
RARB	-0.004	0.097	-10000	0	-0.54	18	18
PRKCG	-0.14	0.24	-10000	0	-0.51	171	171
MNAT1	0.007	0.047	-10000	0	-0.55	4	4
RAR alpha/RXRs	-0.04	0.18	-10000	0	-0.43	80	80
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.039	0.15	-10000	0	-0.37	79	79
proteasomal ubiquitin-dependent protein catabolic process	-0.017	0.096	-10000	0	-0.36	18	18
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.056	0.17	-10000	0	-0.43	84	84
positive regulation of DNA binding	-0.043	0.079	-10000	0	-0.47	4	4
NRIP1	-0.059	0.2	-10000	0	-0.93	14	14
RXRs/RARs	-0.059	0.16	-10000	0	-0.42	84	84
RXRs/RXRs/DNA/9cRA	-0.064	0.16	-10000	0	-0.44	82	82
PRKACA	0.011	0	-10000	0	-10000	0	0
CDK7	0.008	0.043	-10000	0	-0.58	3	3
TFIIH	0.019	0.045	-10000	0	-0.39	6	6
RAR alpha/9cRA	-0.033	0.061	-10000	0	-0.39	4	4
CCNH	0.011	0	-10000	0	-10000	0	0
CREBBP	0.011	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	-0.006	0.042	-10000	0	-0.55	1	1

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.026	0.17	-9999	-0.5	51	51
MAP3K8	0.009	0.031	-9999	-0.52	2	2
FOS	-0.026	0.16	-9999	-0.6	30	30
PRKCA	0.01	0.032	-9999	-0.52	2	2
PTPN7	-0.051	0.17	-9999	-0.5	71	71
HRAS	0.008	0.042	-9999	-0.49	4	4
PRKCB	-0.039	0.16	-9999	-0.54	52	52
NRAS	0.001	0.077	-9999	-0.58	10	10
RAS family/GTP	0.01	0.07	-9999	-0.38	16	16
MAPK3	-0.022	0.14	-9999	-0.59	26	26
MAP2K1	-0.006	0.12	-9999	-0.42	38	38
ELK1	0.01	0.025	-9999	-0.58	1	1
BRAF	-0.012	0.12	-9999	-0.43	37	37
mol:GTP	0	0.001	-9999	-0.005	42	42
MAPK1	-0.022	0.14	-9999	-0.59	26	26
RAF1	-0.011	0.11	-9999	-0.42	36	36
KRAS	0.005	0.058	-9999	-0.56	6	6

×

Lissencephaly gene (LIS1) in neuronal migration and development

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.011	0	-9999	-10000	0	0
VLDLR	-0.042	0.16	-9999	-0.54	55	55
LRPAP1	0.01	0.025	-9999	-0.58	1	1
NUDC	0.011	0.019	-9999	-0.46	1	1
RELN/LRP8	-0.043	0.13	-9999	-0.31	114	114
CaM/Ca2+	0.008	0	-9999	-10000	0	0
KATNA1	0.01	0.025	-9999	-0.58	1	1
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.034	0.12	-9999	-0.32	60	60
IQGAP1/CaM	0.015	0.029	-9999	-0.39	3	3
DAB1	-0.081	0.2	-9999	-0.51	99	99
IQGAP1	0.008	0.04	-9999	-0.54	3	3
PLA2G7	-0.02	0.13	-9999	-0.56	32	32
CALM1	0.011	0	-9999	-10000	0	0
DYNLT1	0.011	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.014	0.036	-9999	-0.42	4	4
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.009	0.035	-9999	-0.58	2	2
CDK5R1	0.009	0.034	-9999	-0.46	3	3
LIS1/Poliovirus Protein 3A	0.014	0	-9999	-10000	0	0
CDK5R2	-0.048	0.16	-9999	-0.5	65	65
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.13	0.21	-9999	-0.37	219	219
YWHAE	0.011	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.023	0.12	-9999	-0.42	15	15
MAP1B	-0.012	0.049	-9999	-0.31	9	9
RAC1	0.017	0.013	-9999	-0.18	2	2
p35/CDK5	-0.019	0.11	-9999	-0.48	3	3
RELN	-0.091	0.21	-9999	-0.52	110	110
PAFAH/LIS1	0.002	0.083	-9999	-0.35	26	26
LIS1/CLIP170	0.021	0.022	-9999	-0.35	2	2
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.043	0.08	-9999	-0.37	8	8
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.071	0.16	-9999	-0.32	131	131
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.031	0.13	-9999	-0.41	22	22
LIS1/IQGAP1	0.02	0.025	-9999	-0.32	3	3
RHOA	0.016	0.036	-9999	-0.49	2	2
PAFAH1B1	0.018	0	-9999	-10000	0	0
PAFAH1B3	0.008	0.044	-9999	-0.52	4	4
PAFAH1B2	0.007	0.049	-9999	-0.58	4	4
MAP1B/LIS1/Dynein heavy chain	0.013	0.035	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.018	0.12	-9999	-0.4	16	16
LRP8	0.008	0.043	-9999	-0.58	3	3
NDEL1/Katanin 60	-0.023	0.12	-9999	-0.42	16	16
P39/CDK5	-0.047	0.14	-9999	-0.48	22	22
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.022	0.012	-9999	-0.26	1	1
CDK5	-0.025	0.12	-9999	-0.29	60	60
PPP2R5D	0.011	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.018	0.019	-9999	-0.3	2	2
CSNK2A1	0.011	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.097	0.18	-9999	-0.37	131	131
RELN/VLDLR	-0.061	0.16	-9999	-0.36	91	91
CDC42	0.012	0.058	-9999	-0.58	5	5

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.013	0.11	-10000	0	-0.32	49	49
ER alpha/Gai/GDP/Gbeta gamma	-0.022	0.14	-10000	0	-0.44	37	37
AKT1	-0.022	0.18	-10000	0	-0.72	33	33
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.024	0.18	-10000	0	-0.77	30	30
mol:Ca2+	-0.026	0.13	-10000	0	-0.43	32	32
IGF1R	0.01	0.025	-10000	0	-0.58	1	1
E2/ER alpha (dimer)/Striatin	-0.018	0.1	-10000	0	-0.32	56	56
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	0.02	0.17	0.69	33	-10000	0	33
RhoA/GTP	-0.029	0.088	-10000	0	-0.57	5	5
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.048	0.12	-10000	0	-0.46	33	33
regulation of stress fiber formation	-0.007	0.096	0.47	10	-10000	0	10
E2/ERA-ERB (dimer)	-0.026	0.12	-10000	0	-0.34	67	67
KRAS	0.005	0.058	-10000	0	-0.56	6	6
G13/GTP	-0.013	0.088	-10000	0	-0.29	52	52
pseudopodium formation	0.007	0.096	-10000	0	-0.47	10	10
E2/ER alpha (dimer)/PELP1	-0.015	0.096	-10000	0	-0.32	51	51
GRB2	0.011	0	-10000	0	-10000	0	0
GNG2	0.004	0.064	-10000	0	-0.53	8	8
GNAO1	-0.044	0.16	-10000	0	-0.49	63	63
HRAS	0.008	0.042	-10000	0	-0.49	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.02	0.14	-10000	0	-0.49	36	36
E2/ER beta (dimer)	-0.006	0.075	-10000	0	-0.4	20	20
mol:GDP	-0.041	0.11	-10000	0	-0.38	48	48
mol:NADP	-0.02	0.14	-10000	0	-0.49	36	36
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
mol:IP3	-0.027	0.14	-10000	0	-0.45	32	32
IGF-1R heterotetramer	0.01	0.025	-10000	0	-0.58	1	1
PLCB1	-0.03	0.14	-10000	0	-0.47	30	30
PLCB2	-0.011	0.12	-10000	0	-0.45	26	26
IGF1	-0.071	0.19	-10000	0	-0.52	88	88
mol:L-citrulline	-0.02	0.14	-10000	0	-0.49	36	36
RHOA	0.01	0.025	-10000	0	-0.58	1	1
Gai/GDP	-0.02	0.15	-10000	0	-0.76	17	17
JNK cascade	-0.006	0.075	-10000	0	-0.4	20	20
BCAR1	0.008	0.044	-10000	0	-0.52	4	4
ESR2	-0.008	0.1	-10000	0	-0.54	20	20
GNAQ	0.005	0.06	-10000	0	-0.58	6	6
ESR1	-0.036	0.15	-10000	0	-0.52	50	50
Gq family/GDP/Gbeta gamma	0.002	0.12	-10000	0	-0.52	20	20
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.008	0.071	-10000	0	-0.3	7	7
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.046	0.12	-10000	0	-0.46	32	32
GNAZ	-0.012	0.11	-10000	0	-0.54	24	24
E2/ER alpha (dimer)	-0.026	0.11	-10000	0	-0.38	50	50
STRN	0.005	0.06	-10000	0	-0.58	6	6
GNAL	-0.021	0.13	-10000	0	-0.5	36	36
PELP1	0.01	0.025	-10000	0	-0.58	1	1
MAPK11	-0.006	0.084	-10000	0	-0.32	35	35
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.088	-10000	0	-0.55	14	14
HBEGF	-0.035	0.15	-10000	0	-0.44	49	49
cAMP biosynthetic process	-0.046	0.11	-10000	0	-0.28	96	96
SRC	-0.016	0.13	-10000	0	-0.42	34	34
PI3K	0.013	0.041	-10000	0	-0.42	5	5
GNB1	0.011	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.039	0.1	-10000	0	-0.37	37	37
SOS1	0.01	0.025	-10000	0	-0.58	1	1
IGF-1R heterotetramer/IGF1	-0.065	0.13	-10000	0	-0.41	51	51
Gs family/GTP	-0.047	0.11	-10000	0	-0.28	96	96
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.011	0.07	-10000	0	-0.38	16	16
vasodilation	-0.019	0.14	-10000	0	-0.46	36	36
mol:DAG	-0.027	0.14	-10000	0	-0.45	32	32
Gs family/GDP/Gbeta gamma	-0.048	0.11	-10000	0	-0.38	37	37
MSN	0.006	0.1	-10000	0	-0.52	10	10
Gq family/GTP	-0.015	0.12	-10000	0	-0.49	24	24
mol:PI-3-4-5-P3	-0.023	0.18	-10000	0	-0.74	30	30
NRAS	0.001	0.077	-10000	0	-0.58	10	10
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.019	0.14	0.46	36	-10000	0	36
GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
RhoA/GDP	-0.039	0.1	-10000	0	-0.37	45	45
NOS3	-0.022	0.15	-10000	0	-0.51	36	36
GNA11	0.007	0.051	-10000	0	-0.53	5	5
MAPKKK cascade	-0.008	0.15	-10000	0	-0.56	34	34
E2/ER alpha (dimer)/PELP1/Src	-0.049	0.12	-10000	0	-0.47	35	35
ruffle organization	0.007	0.096	-10000	0	-0.47	10	10
ROCK2	0.001	0.11	-10000	0	-0.62	9	9
GNA14	-0.008	0.1	-10000	0	-0.56	19	19
GNA15	-0.009	0.1	-10000	0	-0.54	21	21
GNA13	0.009	0.035	-10000	0	-0.58	2	2
MMP9	-0.042	0.16	-10000	0	-0.46	47	47
MMP2	-0.028	0.15	-10000	0	-0.45	41	41

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.059	0.15	-10000	0	-0.33	124	124
cell-cell adhesion	0.061	0.1	0.42	15	-10000	0	15
Ephrin B/EPHB2/RasGAP	0.009	0.088	-10000	0	-0.32	28	28
ITSN1	0.01	0.025	-10000	0	-0.58	1	1
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
SHC1	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.002	0.079	-10000	0	-0.34	28	28
Ephrin B1/EPHB1	-0.058	0.13	-10000	0	-0.29	136	136
HRAS/GDP	-0.058	0.1	-10000	0	-0.43	13	13
Ephrin B/EPHB1/GRB7	-0.051	0.14	-10000	0	-0.35	62	62
Endophilin/SYNJ1	0.006	0.082	-10000	0	-0.3	28	28
KRAS	0.005	0.058	-10000	0	-0.56	6	6
Ephrin B/EPHB1/Src	-0.047	0.14	-10000	0	-0.34	57	57
endothelial cell migration	0.021	0.038	-10000	0	-0.36	5	5
GRB2	0.011	0	-10000	0	-10000	0	0
GRB7	0.002	0.067	-10000	0	-0.46	12	12
PAK1	0.01	0.092	-10000	0	-0.6	5	5
HRAS	0.008	0.042	-10000	0	-0.49	4	4
RRAS	0.007	0.086	-10000	0	-0.32	26	26
DNM1	-0.004	0.087	-10000	0	-0.5	17	17
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.046	0.13	-10000	0	-0.32	57	57
lamellipodium assembly	-0.061	0.1	-10000	0	-0.42	15	15
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.023	0.1	-10000	0	-0.42	8	8
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
EPHB2	0	0.081	-10000	0	-0.55	12	12
EPHB3	-0.016	0.12	-10000	0	-0.55	28	28
EPHB1	-0.11	0.21	-10000	0	-0.49	135	135
EPHB4	0.011	0	-10000	0	-10000	0	0
mol:GDP	-0.024	0.11	-10000	0	-0.36	21	21
Ephrin B/EPHB2	0.003	0.086	-10000	0	-0.33	26	26
Ephrin B/EPHB3	-0.005	0.1	-10000	0	-0.34	35	35
JNK cascade	-0.038	0.12	-10000	0	-0.3	50	50
Ephrin B/EPHB1	-0.053	0.13	-10000	0	-0.34	57	57
RAP1/GDP	-0.011	0.1	-10000	0	-0.41	8	8
EFNB2	0.01	0.031	-10000	0	-0.52	2	2
EFNB3	-0.019	0.12	-10000	0	-0.52	33	33
EFNB1	0.01	0.025	-10000	0	-0.58	1	1
Ephrin B2/EPHB1-2	-0.052	0.13	-10000	0	-0.33	49	49
RAP1B	0.011	0	-10000	0	-10000	0	0
RAP1A	0.01	0.025	-10000	0	-0.58	1	1
CDC42/GTP	-0.066	0.12	-10000	0	-0.47	19	19
Rap1/GTP	-0.061	0.1	-10000	0	-0.43	17	17
axon guidance	-0.059	0.15	-10000	0	-0.33	124	124
MAPK3	-0.011	0.094	-10000	0	-0.39	9	9
MAPK1	-0.011	0.095	-10000	0	-0.39	10	10
Rac1/GDP	-0.016	0.1	-10000	0	-0.38	12	12
actin cytoskeleton reorganization	-0.053	0.091	-10000	0	-0.39	17	17
CDC42/GDP	-0.019	0.11	-10000	0	-0.39	15	15
PI3K	0.023	0.039	-10000	0	-0.36	5	5
EFNA5	-0.097	0.22	-10000	0	-0.52	118	118
Ephrin B2/EPHB4	0.014	0.02	-10000	0	-0.31	2	2
Ephrin B/EPHB2/Intersectin/N-WASP	0.011	0.073	-10000	0	-0.29	26	26
CDC42	0.006	0.055	-10000	0	-0.58	5	5
RAS family/GTP	-0.067	0.12	-10000	0	-0.46	23	23
PTK2	0.016	0.038	-10000	0	-0.57	1	1
MAP4K4	-0.039	0.12	-10000	0	-0.48	4	4
SRC	0.01	0.025	-10000	0	-0.58	1	1
KALRN	0.006	0.055	-10000	0	-0.58	5	5
Intersectin/N-WASP	0.016	0.018	-10000	0	-0.42	1	1
neuron projection morphogenesis	-0.009	0.11	-10000	0	-0.4	17	17
MAP2K1	-0.017	0.097	-10000	0	-0.4	10	10
WASL	0.011	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.045	0.13	-10000	0	-0.33	49	49
cell migration	-0.014	0.11	-10000	0	-0.44	10	10
NRAS	0.001	0.077	-10000	0	-0.58	10	10
SYNJ1	0.006	0.084	-10000	0	-0.31	28	28
PXN	0.011	0	-10000	0	-10000	0	0
TF	-0.044	0.13	-10000	0	-0.45	19	19
HRAS/GTP	-0.067	0.11	-10000	0	-0.47	17	17
Ephrin B1/EPHB1-2	-0.051	0.13	-10000	0	-0.27	145	145
cell adhesion mediated by integrin	0.01	0.079	0.32	22	-10000	0	22
RAC1	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.045	0.13	-10000	0	-0.49	15	15
RAC1-CDC42/GTP	-0.072	0.12	-10000	0	-0.47	29	29
RASA1	0.009	0.035	-10000	0	-0.58	2	2
RAC1-CDC42/GDP	-0.013	0.1	-10000	0	-0.4	11	11
ruffle organization	-0.026	0.12	-10000	0	-0.43	16	16
NCK1	0.009	0.035	-10000	0	-0.58	2	2
receptor internalization	0.004	0.094	-10000	0	-0.5	7	7
Ephrin B/EPHB2/KALRN	0.007	0.098	-10000	0	-0.35	28	28
ROCK1	-0.002	0.091	-10000	0	-0.35	35	35
RAS family/GDP	-0.048	0.088	-10000	0	-0.4	16	16
Rac1/GTP	-0.064	0.11	-10000	0	-0.45	15	15
Ephrin B/EPHB1/Src/Paxillin	-0.027	0.1	-10000	0	-0.28	57	57

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.02	0.2	-9999	-0.74	11	11
CRP	-0.028	0.2	-9999	-0.69	17	17
cell cycle arrest	-0.034	0.22	-9999	-0.69	26	26
TIMP1	-0.01	0.18	-9999	-0.63	11	11
IL6ST	-0.001	0.094	-9999	-0.58	15	15
Rac1/GDP	-0.038	0.17	-9999	-0.49	44	44
AP1	-0.001	0.12	-9999	-0.53	11	11
GAB2	0.01	0.035	-9999	-0.58	2	2
TNFSF11	-0.076	0.33	-9999	-1	52	52
HSP90B1	0.008	0.14	-9999	-1.3	6	6
GAB1	0.012	0.001	-9999	-10000	0	0
MAPK14	-0.028	0.16	-9999	-0.54	28	28
AKT1	0.037	0.073	-9999	-0.73	4	4
FOXO1	0.041	0.07	-9999	-0.68	4	4
MAP2K6	-0.035	0.16	-9999	-0.48	39	39
mol:GTP	0	0.002	-9999	-10000	0	0
MAP2K4	-0.029	0.18	-9999	-0.52	39	39
MITF	-0.046	0.17	-9999	-0.47	47	47
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.01	0.025	-9999	-0.58	1	1
A2M	0.011	0.071	-9999	-1.4	1	1
CEBPB	0.012	0.042	-9999	-0.48	4	4
GRB2/SOS1/GAB family/SHP2	0	0.09	-9999	-0.61	5	5
STAT3	-0.038	0.23	-9999	-0.73	27	27
STAT1	-0.009	0.069	-9999	-1.1	2	2
CEBPD	-0.022	0.2	-9999	-0.76	14	14
PIK3CA	0.011	0.035	-9999	-0.58	2	2
PI3K	0.015	0.041	-9999	-0.42	5	5
JUN	0.006	0.053	-9999	-0.56	5	5
PIAS3/MITF	-0.039	0.16	-9999	-0.48	41	41
MAPK11	-0.036	0.17	-9999	-0.58	32	32
STAT3 (dimer)/FOXO1	0.011	0.19	-9999	-0.63	13	13
GRB2/SOS1/GAB family	-0.059	0.13	-9999	-0.54	28	28
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.047	0.17	-9999	-0.44	58	58
GRB2	0.012	0.001	-9999	-10000	0	0
JAK2	-0.009	0.1	-9999	-0.55	21	21
LBP	-0.096	0.32	-9999	-0.87	62	62
PIK3R1	0.009	0.043	-9999	-0.58	3	3
JAK1	0.01	0.043	-9999	-0.58	3	3
MYC	-0.026	0.21	-9999	-0.85	15	15
FGG	-0.035	0.21	-9999	-0.75	16	16
macrophage differentiation	-0.034	0.22	-9999	-0.69	26	26
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.061	0.17	-9999	-0.41	66	66
JUNB	-0.023	0.2	-9999	-0.79	13	13
FOS	-0.03	0.14	-9999	-0.53	44	44
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.038	0.16	-9999	-0.45	44	44
STAT1/PIAS1	-0.028	0.15	-9999	-0.49	31	31
GRB2/SOS1/GAB family/SHP2/PI3K	0.027	0.076	-9999	-0.56	7	7
STAT3 (dimer)	-0.037	0.23	-9999	-0.74	25	25
PRKCD	-0.02	0.19	-9999	-0.56	32	32
IL6R	-0.005	0.099	-9999	-0.55	18	18
SOCS3	-0.032	0.18	-9999	-0.77	16	16
gp130 (dimer)/JAK1/JAK1/LMO4	0.013	0.081	-9999	-0.34	26	26
Rac1/GTP	-0.037	0.18	-9999	-0.5	45	45
HCK	-0.02	0.13	-9999	-0.55	32	32
MAPKKK cascade	0.012	0.094	-9999	-0.8	5	5
bone resorption	-0.067	0.31	-9999	-0.93	53	53
IRF1	-0.021	0.2	-9999	-0.7	14	14
mol:GDP	-0.047	0.18	-9999	-0.5	46	46
SOS1	0.01	0.025	-9999	-0.58	1	1
VAV1	-0.048	0.18	-9999	-0.52	46	46
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.038	0.17	-9999	-0.56	34	34
PTPN11	-0.011	0.088	-9999	-0.91	5	5
IL6/IL6RA	-0.079	0.18	-9999	-0.38	143	143
gp130 (dimer)/TYK2/TYK2/LMO4	0.011	0.074	-9999	-0.33	25	25
gp130 (dimer)/JAK2/JAK2/LMO4	-0.001	0.1	-9999	-0.36	41	41
IL6	-0.11	0.22	-9999	-0.52	130	130
PIAS3	0.01	0.031	-9999	-0.52	2	2
PTPRE	0.006	0.026	-9999	-0.57	1	1
PIAS1	0.011	0	-9999	-10000	0	0
RAC1	0.012	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.042	0.14	-9999	-0.33	78	78
LMO4	0.006	0.063	-9999	-0.49	9	9
STAT3 (dimer)/PIAS3	-0.033	0.22	-9999	-0.7	27	27
MCL1	0.042	0.064	-9999	-0.7	3	3

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.01	0.041	-9999	-0.31	9	9
ADCY5	-0.057	0.14	-9999	-0.32	124	124
ADCY6	0.015	0	-9999	-10000	0	0
ADCY7	0.014	0.023	-9999	-0.3	3	3
ADCY1	-0.018	0.095	-9999	-0.29	63	63
ADCY2	-0.017	0.1	-9999	-0.34	52	52
ADCY3	0.015	0	-9999	-10000	0	0
ADCY8	0.002	0.043	-9999	-0.27	14	14
PRKCE	0.009	0	-9999	-10000	0	0
ADCY9	0.014	0.025	-9999	-0.33	3	3
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.014	0.067	-9999	-0.36	4	4

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.009	0.12	-9999	-0.41	39	39
CRKL	0.011	0	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
DOCK1	0.01	0.025	-9999	-0.58	1	1
ITGA4	-0.018	0.13	-9999	-0.56	29	29
alpha4/beta7 Integrin/MAdCAM1	-0.081	0.17	-9999	-0.36	115	115
EPO	0	0.054	-9999	-0.46	8	8
alpha4/beta7 Integrin	-0.024	0.14	-9999	-0.43	53	53
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.011	0.019	-9999	-0.46	1	1
alpha4/beta1 Integrin	-0.004	0.093	-9999	-0.41	29	29
EPO/EPOR (dimer)	0.004	0.059	-9999	-0.35	15	15
lamellipodium assembly	0.025	0.05	-9999	-0.44	5	5
PIK3CA	0.009	0.035	-9999	-0.58	2	2
PI3K	0.013	0.041	-9999	-0.42	5	5
ARF6	0.01	0.025	-9999	-0.58	1	1
JAK2	-0.006	0.11	-9999	-0.36	39	39
PXN	0.011	0	-9999	-10000	0	0
PIK3R1	0.008	0.043	-9999	-0.58	3	3
MADCAM1	-0.12	0.23	-9999	-0.52	146	146
cell adhesion	-0.081	0.17	-9999	-0.36	115	115
CRKL/CBL	0.017	0	-9999	-10000	0	0
ITGB1	0.011	0	-9999	-10000	0	0
SRC	-0.007	0.12	-9999	-0.42	37	37
ITGB7	-0.017	0.12	-9999	-0.53	30	30
RAC1	0.011	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.013	0.13	-9999	-0.42	46	46
p130Cas/Crk/Dock1	0.01	0.11	-9999	-0.51	17	17
VCAM1	-0.019	0.12	-9999	-0.53	32	32
RHOA	0.01	0.025	-9999	-0.58	1	1
alpha4/beta1 Integrin/Paxillin/GIT1	0.012	0.075	-9999	-0.32	26	26
BCAR1	-0.002	0.12	-9999	-0.4	38	38
EPOR	0.004	0.059	-9999	-0.49	8	8
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.011	0	-9999	-10000	0	0
GIT1	0.01	0.025	-9999	-0.58	1	1
Rac1/GTP	-0.002	0.052	-9999	-0.46	5	5

×

Nongenotropic Androgen 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
PTK2	0.008	0.018	-10000	0	-0.43	1	1
GNB1/GNG2	-0.018	0.1	-10000	0	-0.34	27	27
regulation of S phase of mitotic cell cycle	-0.002	0.074	-10000	0	-0.27	27	27
GNAO1	-0.044	0.16	-10000	0	-0.49	63	63
HRAS	0.008	0.042	-10000	0	-0.49	4	4
SHBG/T-DHT	-0.008	0.062	-10000	0	-0.27	30	30
PELP1	0.01	0.025	-10000	0	-0.58	1	1
AKT1	0.008	0.018	-10000	0	-0.43	1	1
MAP2K1	-0.001	0.091	-10000	0	-0.42	5	5
T-DHT/AR	-0.037	0.12	-10000	0	-0.36	70	70
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.006	42	42
GNAI2	0.011	0	-10000	0	-10000	0	0
GNAI3	0.011	0	-10000	0	-10000	0	0
GNAI1	-0.002	0.088	-10000	0	-0.55	14	14
mol:GDP	-0.034	0.098	-10000	0	-0.44	23	23
cell proliferation	-0.003	0.12	-10000	0	-0.39	28	28
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
FOS	-0.019	0.19	-10000	0	-0.74	31	31
mol:Ca2+	-0.011	0.021	-10000	0	-0.062	63	63
MAPK3	-0.001	0.1	-10000	0	-0.46	6	6
MAPK1	0.003	0.064	-10000	0	-0.31	4	4
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
mol:IP3	0	0.001	-10000	0	-0.004	44	44
cAMP biosynthetic process	-0.003	0.062	-10000	0	-0.25	30	30
GNG2	0.004	0.064	-10000	0	-0.53	8	8
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	44	44
HRAS/GTP	-0.032	0.084	-10000	0	-0.31	24	24
actin cytoskeleton reorganization	-0.005	0.047	-10000	0	-0.4	7	7
SRC	0.01	0.025	-10000	0	-0.58	1	1
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	44	44
PI3K	0.012	0.035	-10000	0	-0.36	5	5
apoptosis	0.002	0.11	0.39	33	-10000	0	33
T-DHT/AR/PELP1	-0.024	0.1	-10000	0	-0.3	71	71
HRAS/GDP	-0.033	0.095	-10000	0	-0.42	24	24
CREB1	-0.004	0.12	-10000	0	-0.41	33	33
RAC1-CDC42/GTP	-0.004	0.048	-10000	0	-0.41	7	7
AR	-0.052	0.17	-10000	0	-0.49	70	70
GNB1	0.011	0	-10000	0	-10000	0	0
RAF1	-0.005	0.09	-10000	0	-0.48	3	3
RAC1-CDC42/GDP	-0.031	0.094	-10000	0	-0.4	26	26
T-DHT/AR/PELP1/Src	-0.015	0.097	-10000	0	-0.32	27	27
MAP2K2	-0.001	0.092	-10000	0	-0.54	3	3
T-DHT/AR/PELP1/Src/PI3K	-0.002	0.074	-10000	0	-0.27	27	27
GNAZ	-0.012	0.11	-10000	0	-0.54	24	24
SHBG	-0.015	0.1	-10000	0	-0.46	30	30
Gi family/GNB1/GNG2/GDP	-0.007	0.097	-10000	0	-0.37	18	18
mol:T-DHT	0	0.001	-10000	0	-0.003	23	23
RAC1	0.011	0	-10000	0	-10000	0	0
GNRH1	0.001	0.056	-10000	0	-0.4	11	11
Gi family/GTP	-0.022	0.088	-10000	0	-0.24	52	52
CDC42	0.006	0.055	-10000	0	-0.58	5	5

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.006	0.073	-10000	0	-0.59	8	8
SVIL	0	0.045	-10000	0	-0.48	4	4
ZNF318	0.031	0.048	-10000	0	-10000	0	0
JMJD2C	0.003	0.02	-10000	0	-0.077	26	26
T-DHT/AR/Ubc9	-0.023	0.11	-10000	0	-0.3	70	70
CARM1	0.009	0.025	-10000	0	-0.58	1	1
PRDX1	0.012	0.025	-10000	0	-0.58	1	1
PELP1	0.014	0.026	-10000	0	-0.58	1	1
CTNNB1	0.005	0.016	-10000	0	-10000	0	0
AKT1	0.016	0.028	-10000	0	-0.58	1	1
PTK2B	0.004	0.037	-10000	0	-0.58	2	2
MED1	0.014	0.046	-10000	0	-0.5	4	4
MAK	0.008	0.12	0.2	1	-0.46	27	28
response to oxidative stress	0.001	0.004	-10000	0	-10000	0	0
HIP1	0	0.052	-10000	0	-0.58	4	4
GSN	-0.008	0.077	-10000	0	-0.51	12	12
NCOA2	0.002	0.068	-10000	0	-0.57	8	8
NCOA6	0.004	0.031	-10000	0	-0.58	1	1
DNA-PK	0.04	0.056	-10000	0	-0.64	1	1
NCOA4	0.008	0.035	-10000	0	-0.58	2	2
PIAS3	0.004	0.035	-10000	0	-0.52	2	2
cell proliferation	-0.004	0.099	-10000	0	-0.47	14	14
XRCC5	0.015	0.027	-10000	0	-0.57	1	1
UBE3A	-0.005	0.058	-10000	0	-0.59	4	4
T-DHT/AR/SNURF	-0.079	0.16	-10000	0	-0.33	152	152
FHL2	0.022	0.09	-10000	0	-1.1	2	2
RANBP9	0.004	0.031	-10000	0	-0.58	1	1
JMJD1A	-0.006	0.043	-10000	0	-0.11	71	71
CDK6	0.011	0.02	-10000	0	-0.46	1	1
TGFB1I1	-0.001	0.053	-10000	0	-0.53	5	5
T-DHT/AR/CyclinD1	-0.031	0.11	-10000	0	-0.31	71	71
XRCC6	0.016	0.011	-10000	0	-10000	0	0
T-DHT/AR	-0.02	0.12	-10000	0	-0.37	34	34
CTDSP1	0.007	0.026	-10000	0	-0.58	1	1
CTDSP2	0.025	0.032	-10000	0	-10000	0	0
BRCA1	0.003	0.031	-10000	0	-0.59	1	1
TCF4	0.009	0.084	-10000	0	-0.52	13	13
CDKN2A	-0.063	0.19	-10000	0	-0.5	90	90
SRF	0.022	0.033	-10000	0	-0.45	2	2
NKX3-1	-0.074	0.24	-10000	0	-0.82	44	44
KLK3	-0.16	0.41	-10000	0	-1.4	52	52
TMF1	0.003	0.06	-10000	0	-0.58	6	6
HNRNPA1	0.018	0.017	-10000	0	-10000	0	0
AOF2	-0.008	0.021	-10000	0	-0.069	50	50
APPL1	0.022	0.071	-10000	0	-0.42	12	12
T-DHT/AR/Caspase 8	-0.017	0.11	-10000	0	-0.3	67	67
AR	-0.054	0.17	-10000	0	-0.5	70	70
UBA3	0.007	0.026	-10000	0	-0.59	1	1
PATZ1	0.018	0.017	-10000	0	-10000	0	0
PAWR	0.008	0.025	-10000	0	-0.58	1	1
PRKDC	0.013	0.04	-10000	0	-0.52	3	3
PA2G4	0.02	0.021	-10000	0	-10000	0	0
UBE2I	0.011	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.017	0.1	-10000	0	-0.28	66	66
RPS6KA3	-0.002	0.054	-10000	0	-0.59	4	4
T-DHT/AR/ARA70	-0.03	0.11	-10000	0	-0.31	71	71
LATS2	0.017	0.035	-10000	0	-0.49	2	2
T-DHT/AR/PRX1	-0.011	0.11	-10000	0	-0.27	67	67
Cyclin D3/CDK11 p58	0.007	0.031	-10000	0	-0.32	5	5
VAV3	-0.073	0.2	-10000	0	-0.58	77	77
KLK2	-0.027	0.093	-10000	0	-0.4	26	26
CASP8	0.013	0.026	-10000	0	-0.58	1	1
T-DHT/AR/TIF2/CARM1	-0.026	0.11	-10000	0	-0.33	41	41
TMPRSS2	-0.019	0.11	-10000	0	-0.95	4	4
CCND1	0.007	0.027	-10000	0	-0.59	1	1
PIAS1	-0.001	0.03	-10000	0	-10000	0	0
mol:T-DHT	-0.003	0.023	-10000	0	-0.07	34	34
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.009	0.052	-10000	0	-0.58	1	1
T-DHT/AR/CDK6	-0.021	0.11	-10000	0	-0.3	71	71
CMTM2	-0.03	0.14	-10000	0	-0.52	46	46
SNURF	-0.079	0.2	-10000	0	-0.54	91	91
ZMIZ1	0.008	0.028	-10000	0	-0.44	1	1
CCND3	0.008	0.043	-10000	0	-0.46	5	5
TGIF1	0.018	0.017	-10000	0	-10000	0	0
FKBP4	0.003	0.038	-10000	0	-0.46	3	3

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.01	0.043	-9999	-0.36	7	7
PDGFRB	-0.004	0.087	-9999	-0.53	15	15
SPHK1	-0.043	0.15	-9999	-0.78	20	20
mol:S1P	-0.043	0.13	-9999	-0.66	21	21
S1P1/S1P/Gi	-0.044	0.15	-9999	-0.39	57	57
GNAO1	-0.045	0.16	-9999	-0.49	63	63
PDGFB-D/PDGFRB/PLCgamma1	-0.039	0.15	-9999	-0.48	22	22
PLCG1	-0.039	0.14	-9999	-0.37	58	58
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.003	0.087	-9999	-0.53	15	15
GNAI2	0.01	0.005	-9999	-10000	0	0
GNAI3	0.01	0.005	-9999	-10000	0	0
GNAI1	-0.004	0.088	-9999	-0.56	14	14
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.008	0.037	-9999	-0.31	7	7
S1P1/S1P	-0.018	0.12	-9999	-0.47	24	24
negative regulation of cAMP metabolic process	-0.043	0.15	-9999	-0.38	57	57
MAPK3	-0.057	0.19	-9999	-0.56	52	52
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0.008	0	-9999	-10000	0	0
RhoA/GDP	0.008	0.018	-9999	-0.43	1	1
KDR	0.005	0.054	-9999	-0.52	6	6
PLCB2	-0.013	0.11	-9999	-0.42	27	27
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.036	0.088	-9999	-0.39	24	24
receptor internalization	-0.039	0.098	-9999	-0.44	24	24
PTGS2	-0.1	0.31	-9999	-1	48	48
Rac1/GTP	-0.035	0.087	-9999	-0.39	24	24
RHOA	0.01	0.025	-9999	-0.58	1	1
VEGFA	0.01	0.02	-9999	-0.46	1	1
negative regulation of T cell proliferation	-0.043	0.15	-9999	-0.38	57	57
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.013	0.11	-9999	-0.55	24	24
MAPK1	-0.057	0.19	-9999	-0.56	52	52
S1P1/S1P/PDGFB-D/PDGFRB	-0.018	0.12	-9999	-0.44	27	27
ABCC1	0.01	0.025	-9999	-0.59	1	1

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.01	0.025	-10000	0	-0.58	1	1
PTK2	0.01	0.025	-10000	0	-0.58	1	1
CRKL	-0.021	0.1	-10000	0	-0.3	47	47
GRB2/SOS1/SHC	0.023	0.016	-10000	0	-0.35	1	1
HRAS	0.008	0.042	-10000	0	-0.49	4	4
IRS1/Crk	-0.021	0.1	-10000	0	-0.3	47	47
IGF-1R heterotetramer/IGF1/PTP1B	-0.027	0.12	-10000	0	-0.34	48	48
AKT1	-0.004	0.092	-10000	0	-0.48	3	3
BAD	0.001	0.091	-10000	0	-0.46	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.021	0.1	-10000	0	-0.3	47	47
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.024	0.1	-10000	0	-0.3	53	53
RAF1	0.006	0.085	-10000	0	-0.43	3	3
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.012	0.099	-10000	0	-0.29	47	47
YWHAZ	0.008	0.043	-10000	0	-0.58	3	3
IGF-1R heterotetramer/IGF1/IRS1	-0.029	0.11	-10000	0	-0.32	55	55
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
RPS6KB1	-0.007	0.099	-10000	0	-0.51	6	6
GNB2L1	0.011	0.019	-10000	0	-0.46	1	1
positive regulation of MAPKKK cascade	0.004	0.076	-10000	0	-0.37	3	3
PXN	0.011	0	-10000	0	-10000	0	0
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
HRAS/GTP	-0.033	0.078	-10000	0	-0.49	3	3
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.006	0.095	-10000	0	-0.48	3	3
IGF-1R heterotetramer	0	0.037	-10000	0	-0.66	1	1
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.02	0.1	-10000	0	-0.3	48	48
Crk/p130 Cas/Paxillin	-0.009	0.095	-10000	0	-0.39	4	4
IGF1R	0	0.038	-10000	0	-0.67	1	1
IGF1	-0.071	0.2	-10000	0	-0.53	88	88
IRS2/Crk	-0.018	0.1	-10000	0	-0.28	52	52
PI3K	-0.015	0.1	-10000	0	-0.28	51	51
apoptosis	-0.006	0.087	0.44	7	-10000	0	7
HRAS/GDP	0.006	0.03	-10000	0	-0.35	4	4
PRKCD	-0.013	0.12	-10000	0	-0.39	47	47
RAF1/14-3-3 E	0.013	0.077	-10000	0	-0.37	3	3
BAD/14-3-3	0.006	0.092	-10000	0	-0.48	7	7
PRKCZ	-0.005	0.093	-10000	0	-0.48	4	4
Crk/p130 Cas/Paxillin/FAK1	-0.031	0.076	-10000	0	-0.44	8	8
PTPN1	0.01	0.025	-10000	0	-0.58	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.02	0.13	-10000	0	-0.41	47	47
BCAR1	0.008	0.044	-10000	0	-0.52	4	4
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.017	0.1	-10000	0	-0.3	50	50
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.01	0.025	-10000	0	-0.58	1	1
IRS1/NCK2	-0.021	0.1	-10000	0	-0.3	48	48
GRB10	0.007	0.049	-10000	0	-0.58	4	4
PTPN11	-0.024	0.1	-10000	0	-0.3	53	53
IRS1	-0.03	0.11	-10000	0	-0.32	55	55
IRS2	-0.026	0.11	-10000	0	-0.31	52	52
IGF-1R heterotetramer/IGF1	-0.046	0.15	-10000	0	-0.38	88	88
GRB2	0.011	0	-10000	0	-10000	0	0
PDPK1	-0.01	0.096	-10000	0	-0.38	7	7
YWHAE	0.011	0	-10000	0	-10000	0	0
PRKD1	-0.033	0.16	-10000	0	-0.42	69	69
SHC1	0.011	0	-10000	0	-10000	0	0

×

PDGFR-alpha signaling 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
PDGFRA	-0.011	0.11	-9999	-0.57	21	21
PDGF/PDGFRA/CRKL	0.001	0.079	-9999	-0.4	21	21
positive regulation of JUN kinase activity	0.016	0.062	-9999	-0.3	20	20
CRKL	0.011	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.009	0.086	-9999	-0.41	25	25
AP1	-0.066	0.21	-9999	-0.9	30	30
mol:IP3	0.001	0.086	-9999	-0.42	22	22
PLCG1	0.001	0.086	-9999	-0.42	22	22
PDGF/PDGFRA/alphaV Integrin	-0.007	0.1	-9999	-0.42	31	31
RAPGEF1	0.01	0.025	-9999	-0.58	1	1
CRK	0.011	0.019	-9999	-0.46	1	1
mol:Ca2+	0.001	0.085	-9999	-0.42	22	22
CAV3	-0.002	0.043	-9999	-0.46	5	5
CAV1	-0.002	0.08	-9999	-0.49	15	15
SHC/Grb2/SOS1	0.017	0.063	-9999	-0.3	20	20
PDGF/PDGFRA/Shf	-0.032	0.13	-9999	-0.37	71	71
FOS	-0.034	0.22	-9999	-0.89	30	30
JUN	-0.009	0.043	-9999	-0.44	5	5
oligodendrocyte development	-0.007	0.1	-9999	-0.42	31	31
GRB2	0.011	0	-9999	-10000	0	0
PIK3R1	0.008	0.043	-9999	-0.58	3	3
mol:DAG	0.001	0.086	-9999	-0.42	22	22
PDGF/PDGFRA	-0.011	0.11	-9999	-0.57	21	21
actin cytoskeleton reorganization	0	0.08	-9999	-0.4	22	22
SRF	0.017	0.02	-9999	-0.31	2	2
SHC1	0.011	0	-9999	-10000	0	0
PI3K	0.006	0.075	-9999	-0.35	24	24
PDGF/PDGFRA/Crk/C3G	0.009	0.07	-9999	-0.34	21	21
JAK1	0	0.085	-9999	-0.4	24	24
ELK1/SRF	0.015	0.069	-9999	-0.32	21	21
SHB	0.011	0.019	-9999	-0.46	1	1
SHF	-0.033	0.14	-9999	-0.48	52	52
CSNK2A1	0.005	0.015	-9999	-10000	0	0
GO:0007205	0	0.089	-9999	-0.44	22	22
SOS1	0.01	0.025	-9999	-0.58	1	1
Ras protein signal transduction	0.016	0.062	-9999	-0.3	20	20
PDGF/PDGFRA/SHB	0	0.08	-9999	-0.4	22	22
PDGF/PDGFRA/Caveolin-1	-0.008	0.1	-9999	-0.4	34	34
ITGAV	0	0.081	-9999	-0.58	11	11
ELK1	0.004	0.082	-9999	-0.39	21	21
PIK3CA	0.009	0.035	-9999	-0.58	2	2
PDGF/PDGFRA/Crk	0	0.08	-9999	-0.4	22	22
JAK-STAT cascade	0	0.085	-9999	-0.4	24	24
cell proliferation	-0.031	0.13	-9999	-0.37	71	71

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.011	0.071	0.25	6	-0.56	4	10
DAPP1	-0.065	0.19	-10000	0	-0.51	64	64
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.07	0.22	-10000	0	-0.6	64	64
mol:DAG	-0.015	0.11	0.18	2	-0.28	49	51
HRAS	0.008	0.042	-10000	0	-0.49	4	4
RAP1A	0.01	0.027	-10000	0	-0.62	1	1
ARF5/GDP	0.001	0.1	-10000	0	-0.43	24	24
PLCG2	-0.01	0.11	-10000	0	-0.54	22	22
PLCG1	0.01	0.025	-10000	0	-0.58	1	1
ARF5	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.011	0.073	0.23	6	-0.6	4	10
ARF1/GTP	-0.011	0.071	0.24	6	-0.56	4	10
RHOA	0.01	0.025	-10000	0	-0.58	1	1
YES1	0.004	0.065	-10000	0	-0.58	7	7
RAP1A/GTP	0.01	0.075	0.22	6	-0.37	13	19
ADAP1	-0.011	0.072	0.22	6	-0.55	5	11
ARAP3	-0.011	0.072	0.23	6	-0.58	4	10
INPPL1	0.01	0.025	-10000	0	-0.58	1	1
PREX1	0.006	0.056	-10000	0	-0.54	6	6
ARHGEF6	-0.005	0.093	-10000	0	-0.54	17	17
ARHGEF7	0.011	0	-10000	0	-10000	0	0
ARF1	0.011	0.019	-10000	0	-0.46	1	1
NRAS	0.001	0.079	-10000	0	-0.59	10	10
FYN	0.005	0.061	-10000	0	-0.55	7	7
ARF6	0.01	0.025	-10000	0	-0.58	1	1
FGR	-0.023	0.13	-10000	0	-0.53	36	36
mol:Ca2+	-0.001	0.055	-10000	0	-0.21	1	1
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.043	0.16	-10000	0	-0.52	59	59
ZAP70	-0.037	0.16	-10000	0	-0.53	51	51
mol:IP3	-0.005	0.076	-10000	0	-0.23	18	18
LYN	0.011	0	-10000	0	-10000	0	0
ARF1/GDP	0.001	0.11	-10000	0	-0.44	24	24
RhoA/GDP	-0.021	0.083	0.24	3	-0.47	10	13
PDK1/Src/Hsp90	0.021	0.027	-10000	0	-0.35	3	3
BLNK	-0.009	0.11	-10000	0	-0.58	20	20
actin cytoskeleton reorganization	0.014	0.11	0.23	3	-0.48	15	18
SRC	0.01	0.025	-10000	0	-0.58	1	1
PLEKHA2	0.003	0.087	-10000	0	-0.36	30	30
RAC1	0.011	0	-10000	0	-10000	0	0
PTEN	0.003	0.058	-10000	0	-0.56	6	6
HSP90AA1	0.009	0.035	-10000	0	-0.58	2	2
ARF6/GTP	-0.01	0.073	0.25	6	-0.62	4	10
RhoA/GTP	0.015	0.077	0.22	6	-0.63	4	10
Src family/SYK family/BLNK-LAT	-0.066	0.2	-10000	0	-0.57	60	60
BLK	-0.11	0.23	-10000	0	-0.53	132	132
PDPK1	0.011	0	-10000	0	-10000	0	0
CYTH1	-0.01	0.069	0.22	6	-0.56	4	10
HCK	-0.02	0.13	-10000	0	-0.55	32	32
CYTH3	-0.011	0.071	0.22	6	-0.56	4	10
CYTH2	-0.01	0.069	0.22	6	-0.56	4	10
KRAS	0.005	0.06	-10000	0	-0.57	6	6
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.022	0.076	-10000	0	-0.62	5	5
SGK1	-0.012	0.08	0.19	6	-0.7	5	11
INPP5D	-0.015	0.12	-10000	0	-0.58	26	26
mol:GDP	-0.006	0.11	-10000	0	-0.44	25	25
SOS1	0.01	0.025	-10000	0	-0.58	1	1
SYK	0.011	0.019	-10000	0	-0.46	1	1
ARF6/GDP	-0.021	0.082	0.24	3	-0.46	10	13
mol:PI-3-4-5-P3	-0.01	0.075	0.29	6	-0.59	4	10
ARAP3/RAP1A/GTP	0.01	0.076	0.22	6	-0.37	13	19
VAV1	-0.024	0.14	-10000	0	-0.57	35	35
mol:PI-3-4-P2	-0.002	0.095	-10000	0	-0.44	26	26
RAS family/GTP/PI3K Class I	0.011	0.075	-10000	0	-0.38	13	13
PLEKHA1	0.004	0.086	-10000	0	-0.36	29	29
Rac1/GDP	0.001	0.1	-10000	0	-0.43	24	24
LAT	-0.01	0.1	-10000	0	-0.51	24	24
Rac1/GTP	-0.013	0.14	-10000	0	-0.47	36	36
ITK	-0.03	0.098	0.22	5	-0.55	7	12
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.028	0.15	0.21	2	-0.4	51	53
LCK	-0.032	0.14	-10000	0	-0.51	48	48
BTK	-0.028	0.092	0.22	3	-0.55	6	9

×

IL2 signaling events mediated by STAT5

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
GAB2	0.01	0.035	-9999	-0.58	2	2
ELF1	-0.017	0.11	-9999	-0.36	45	45
CCNA2	0.01	0.025	-9999	-0.58	1	1
PIK3CA	0.01	0.035	-9999	-0.58	2	2
JAK3	0.001	0.078	-9999	-0.53	12	12
PIK3R1	0.009	0.043	-9999	-0.58	3	3
JAK1	0.009	0.043	-9999	-0.58	3	3
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.008	0.14	-9999	-0.46	31	31
SHC1	0.012	0.001	-9999	-10000	0	0
SP1	-0.008	0.094	-9999	-0.35	38	38
IL2RA	-0.049	0.23	-9999	-0.69	60	60
IL2RB	-0.015	0.12	-9999	-0.55	28	28
SOS1	0.011	0.025	-9999	-0.58	1	1
IL2RG	-0.001	0.086	-9999	-0.56	13	13
G1/S transition of mitotic cell cycle	-0.016	0.18	-9999	-0.69	39	39
PTPN11	0.007	0.055	-9999	-0.58	5	5
CCND2	-0.032	0.21	-9999	-0.77	41	41
LCK	-0.031	0.14	-9999	-0.51	48	48
GRB2	0.012	0.001	-9999	-10000	0	0
IL2	0.002	0.027	-9999	-0.45	2	2
CDK6	0.011	0.019	-9999	-0.46	1	1
CCND3	0.015	0.13	-9999	-0.59	9	9

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.1	0.29	-9999	-1.1	38	38
RAD9A	0.01	0.025	-9999	-0.58	1	1
AP1	-0.017	0.11	-9999	-0.38	48	48
IFNAR2	0.011	0.025	-9999	-0.58	1	1
AKT1	-0.006	0.061	-9999	-0.22	29	29
ER alpha/Oestrogen	-0.026	0.11	-9999	-0.38	50	50
NFX1/SIN3/HDAC complex	0.033	0.028	-9999	-10000	0	0
EGF	-0.18	0.25	-9999	-0.51	209	209
SMG5	0.01	0.025	-9999	-0.58	1	1
SMG6	0.011	0	-9999	-10000	0	0
SP3/HDAC2	0.016	0.02	-9999	-0.42	1	1
TERT/c-Abl	-0.089	0.27	-9999	-0.96	40	40
SAP18	0.01	0.019	-9999	-0.45	1	1
MRN complex	0.007	0.092	-9999	-0.46	19	19
WT1	-0.18	0.26	-9999	-0.52	199	199
WRN	0.004	0.063	-9999	-0.56	7	7
SP1	0.01	0.026	-9999	-0.58	1	1
SP3	0.01	0.025	-9999	-0.58	1	1
TERF2IP	0.01	0.025	-9999	-0.58	1	1
Telomerase/Nucleolin	-0.096	0.22	-9999	-0.89	37	37
Mad/Max	0.014	0.031	-9999	-0.34	4	4
TERT	-0.1	0.3	-9999	-1.1	38	38
CCND1	-0.082	0.25	-9999	-0.96	35	35
MAX	0.011	0.004	-9999	-10000	0	0
RBBP7	0.01	0.025	-9999	-0.58	1	1
RBBP4	0.01	0.025	-9999	-0.58	1	1
TERF2	0.012	0.009	-9999	-10000	0	0
PTGES3	0.009	0.035	-9999	-0.58	2	2
SIN3A	0.01	0.025	-9999	-0.58	1	1
Telomerase/911	0.018	0.054	-9999	-0.7	2	2
CDKN1B	-0.019	0.12	-9999	-0.36	41	41
RAD1	0.011	0.019	-9999	-0.46	1	1
XRCC5	0.01	0.025	-9999	-0.58	1	1
XRCC6	0.011	0	-9999	-10000	0	0
SAP30	0.009	0.035	-9999	-0.58	2	2
TRF2/PARP2	0.017	0.018	-9999	-0.38	1	1
UBE3A	0.007	0.049	-9999	-0.58	4	4
JUN	0.006	0.053	-9999	-0.56	5	5
E6	0	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.006	0.037	-9999	-0.43	4	4
FOS	-0.03	0.14	-9999	-0.53	44	44
IFN-gamma/IRF1	-0.032	0.14	-9999	-0.36	81	81
PARP2	0.01	0.025	-9999	-0.58	1	1
BLM	0.005	0.058	-9999	-0.56	6	6
Telomerase	0	0.07	-9999	-0.52	6	6
IRF1	0.012	0.035	-9999	-0.45	3	3
ESR1	-0.036	0.15	-9999	-0.53	50	50
KU/TER	0.016	0.018	-9999	-0.42	1	1
ATM/TRF2	0.012	0.049	-9999	-0.38	9	9
ubiquitin-dependent protein catabolic process	0.035	0.037	-9999	-0.38	2	2
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.035	0.038	-9999	-0.39	2	2
HDAC1	0.011	0.001	-9999	-10000	0	0
HDAC2	0.011	0.008	-9999	-10000	0	0
ATM	-0.007	0.054	-9999	-0.44	9	9
SMAD3	0.004	0.076	-9999	-0.39	20	20
ABL1	0.01	0.025	-9999	-0.58	1	1
MXD1	0.008	0.042	-9999	-0.48	4	4
MRE11A	0.003	0.069	-9999	-0.58	8	8
HUS1	0.011	0	-9999	-10000	0	0
RPS6KB1	0.005	0.058	-9999	-0.56	6	6
TERT/NF kappa B1/14-3-3	-0.092	0.25	-9999	-1	33	33
NR2F2	0.012	0.007	-9999	-10000	0	0
MAPK3	0.009	0.027	-9999	-0.35	3	3
MAPK1	0.009	0.027	-9999	-0.35	3	3
TGFB1/TGF beta receptor Type II	-0.001	0.083	-9999	-0.54	13	13
NFKB1	0.01	0.025	-9999	-0.58	1	1
HNRNPC	0.011	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.007	0.054	-9999	-0.44	9	9
NBN	-0.005	0.098	-9999	-0.58	16	16
EGFR	0.004	0.064	-9999	-0.54	8	8
mol:Oestrogen	0	0.002	-9999	-10000	0	0
EGF/EGFR	-0.13	0.19	-9999	-0.36	216	216
MYC	0.005	0.059	-9999	-0.56	6	6
IL2	0.001	0.029	-9999	-0.45	2	2
KU	0.016	0.018	-9999	-0.42	1	1
RAD50	0.01	0.025	-9999	-0.58	1	1
HSP90AA1	0.009	0.035	-9999	-0.58	2	2
TGFB1	-0.001	0.083	-9999	-0.54	13	13
TRF2/BLM	0.014	0.04	-9999	-0.37	6	6
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.083	0.27	-9999	-0.99	38	38
SP1/HDAC2	0.017	0.023	-9999	-0.42	1	1
PINX1	0.004	0.065	-9999	-0.58	7	7
Telomerase/EST1A	-0.096	0.22	-9999	-0.89	37	37
Smad3/Myc	0.007	0.074	-9999	-0.33	25	25
911 complex	0.022	0.02	-9999	-0.31	2	2
IFNG	-0.06	0.18	-9999	-0.51	80	80
Telomerase/PinX1	-0.099	0.23	-9999	-0.88	39	39
Telomerase/AKT1/mTOR/p70S6K	-0.003	0.084	-9999	-0.99	2	2
SIN3B	0.01	0.025	-9999	-0.58	1	1
YWHAE	0.011	0	-9999	-10000	0	0
Telomerase/EST1B	-0.097	0.23	-9999	-0.88	38	38
response to DNA damage stimulus	0.001	0.017	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.019	0.082	-9999	-0.62	6	6
TRF2/WRN	0.013	0.042	-9999	-0.36	7	7
Telomerase/hnRNP C1/C2	-0.096	0.22	-9999	-0.89	37	37
E2F1	0.009	0.037	-9999	-0.5	3	3
ZNFX1	0.011	0.001	-9999	-10000	0	0
PIF1	0.006	0.056	-9999	-0.54	6	6
NCL	0.011	0	-9999	-10000	0	0
DKC1	0.011	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.073	0.32	-9999	-0.98	16	16
PLK1	0.042	0.074	-9999	-1.4	1	1
BIRC5	0.044	0.047	-9999	-0.41	1	1
HSPA1B	0.059	0.34	-9999	-1	22	22
MAP2K1	0.028	0.049	-9999	-0.63	2	2
BRCA2	0.055	0.37	-9999	-1.2	28	28
FOXM1	0.062	0.37	-9999	-1.3	17	17
XRCC1	0.072	0.32	-9999	-1	17	17
FOXM1B/p19	-0.12	0.27	-9999	-1	33	33
Cyclin D1/CDK4	0.07	0.3	-9999	-0.9	16	16
CDC2	0.068	0.33	-9999	-1	17	17
TGFA	0.071	0.31	-9999	-0.89	19	19
SKP2	0.072	0.32	-9999	-1	16	16
CCNE1	0.013	0.035	-9999	-0.45	3	3
CKS1B	0.072	0.32	-9999	-0.98	17	17
RB1	-0.064	0.18	-9999	-0.96	18	18
FOXM1C/SP1	0.062	0.34	-9999	-1.1	18	18
AURKB	0.044	0.043	-9999	-10000	0	0
CENPF	0.061	0.36	-9999	-1.1	24	24
CDK4	0.018	0.012	-9999	-10000	0	0
MYC	0.074	0.3	-9999	-0.89	19	19
CHEK2	0.029	0.041	-9999	-0.63	1	1
ONECUT1	0.067	0.31	-9999	-0.95	17	17
CDKN2A	-0.074	0.19	-9999	-0.51	90	90
LAMA4	0.071	0.32	-9999	-1	16	16
FOXM1B/HNF6	0.062	0.34	-9999	-1.1	17	17
FOS	0.032	0.39	-9999	-1	39	39
SP1	0.011	0.025	-9999	-0.58	1	1
CDC25B	0.072	0.32	-9999	-0.98	16	16
response to radiation	0.016	0.028	-9999	-10000	0	0
CENPB	0.072	0.32	-9999	-1	18	18
CENPA	0.072	0.32	-9999	-1	16	16
NEK2	0.073	0.32	-9999	-0.99	16	16
HIST1H2BA	0.066	0.32	-9999	-0.99	16	16
CCNA2	0.014	0.026	-9999	-0.59	1	1
EP300	0.007	0.049	-9999	-0.58	4	4
CCNB1/CDK1	0.063	0.35	-9999	-1.1	17	17
CCNB2	0.07	0.32	-9999	-0.99	18	18
CCNB1	0.07	0.33	-9999	-1	17	17
ETV5	0.057	0.35	-9999	-1.1	23	23
ESR1	0.03	0.4	-9999	-1.1	40	40
CCND1	0.073	0.31	-9999	-0.91	17	17
GSK3A	0.028	0.026	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.037	0.049	-9999	-0.5	2	2
CDK2	0.014	0.026	-9999	-0.59	1	1
G2/M transition of mitotic cell cycle	0.018	0.033	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.089	0.24	-9999	-1.1	17	17
GAS1	-0.048	0.5	-9999	-1.1	83	83
MMP2	0.039	0.4	-9999	-1.2	34	34
RB1/FOXM1C	0.069	0.33	-9999	-0.98	22	22
CREBBP	0.011	0	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	0.011	0.038	-10000	0	-0.36	6	6
RAS family/GTP	-0.002	0.097	-10000	0	-0.36	12	12
NFATC4	0.003	0.088	0.19	5	-0.42	4	9
ERBB2IP	-0.009	0.11	-10000	0	-0.58	20	20
HSP90 (dimer)	0.009	0.035	-10000	0	-0.58	2	2
mammary gland morphogenesis	-0.011	0.1	0.22	6	-0.45	3	9
JUN	0.005	0.1	0.16	3	-0.28	44	47
HRAS	0.008	0.042	-10000	0	-0.49	4	4
DOCK7	-0.004	0.1	0.21	3	-0.4	4	7
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.019	0.12	0.23	14	-0.31	50	64
AKT1	0.008	0.019	-10000	0	-0.44	1	1
BAD	0.014	0.032	-10000	0	-0.48	2	2
MAPK10	-0.007	0.081	-10000	0	-0.27	23	23
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.01	0.11	0.24	6	-0.49	3	9
RAF1	0.007	0.099	-10000	0	-0.36	11	11
ErbB2/ErbB3/neuregulin 2	0.001	0.073	0.23	12	-0.29	5	17
STAT3	0	0.045	-10000	0	-1.1	1	1
cell migration	0.008	0.075	0.16	10	-0.24	18	28
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	-0.009	0.19	-10000	0	-0.59	40	40
FOS	-0.003	0.16	-10000	0	-0.41	57	57
NRAS	0.001	0.078	-10000	0	-0.58	10	10
mol:Ca2+	-0.011	0.1	0.22	6	-0.45	3	9
MAPK3	-0.002	0.16	-10000	0	-0.5	33	33
MAPK1	-0.002	0.16	-10000	0	-0.49	33	33
JAK2	-0.011	0.11	-10000	0	-0.43	10	10
NF2	-0.001	0.004	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.01	0.093	-10000	0	-0.28	49	49
NRG1	-0.068	0.19	-10000	0	-0.53	84	84
GRB2/SOS1	0.016	0.018	-10000	0	-0.42	1	1
MAPK8	0	0.097	0.2	6	-0.27	52	58
MAPK9	0.007	0.059	-10000	0	-0.23	6	6
ERBB2	0.005	0.087	0.39	19	-0.34	13	32
ERBB3	0.01	0.025	-10000	0	-0.58	1	1
SHC1	0.011	0.001	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
apoptosis	-0.002	0.036	0.82	1	-10000	0	1
STAT3 (dimer)	0.014	0.044	-10000	0	-1	1	1
RNF41	0.016	0.035	-10000	0	-0.32	6	6
FRAP1	0.007	0.016	-10000	0	-0.37	1	1
RAC1-CDC42/GTP	-0.027	0.065	-10000	0	-0.33	7	7
ErbB2/ErbB2/HSP90 (dimer)	0.008	0.062	0.26	17	-0.28	13	30
CHRNA1	-0.009	0.18	-10000	0	-0.61	37	37
myelination	0.005	0.086	0.19	6	-0.4	4	10
PPP3CB	-0.003	0.094	-10000	0	-0.4	3	3
KRAS	0.005	0.058	-10000	0	-0.56	6	6
RAC1-CDC42/GDP	-0.001	0.084	-10000	0	-0.31	6	6
NRG2	-0.015	0.1	-10000	0	-0.46	29	29
mol:GDP	-0.009	0.093	-10000	0	-0.28	49	49
SOS1	0.01	0.025	-10000	0	-0.58	1	1
MAP2K2	0.011	0.1	-10000	0	-0.39	11	11
SRC	0.01	0.025	-10000	0	-0.58	1	1
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.006	0.1	-10000	0	-0.42	5	5
MAP2K1	-0.005	0.15	-10000	0	-0.53	17	17
heart morphogenesis	-0.011	0.1	0.22	6	-0.45	3	9
RAS family/GDP	-0.002	0.097	-10000	0	-0.42	7	7
GRB2	0.011	0.001	-10000	0	-10000	0	0
PRKACA	-0.003	0.006	-10000	0	-10000	0	0
CHRNE	0	0.055	-10000	0	-0.18	45	45
HSP90AA1	0.009	0.035	-10000	0	-0.58	2	2
activation of caspase activity	-0.008	0.019	0.44	1	-10000	0	1
nervous system development	-0.011	0.1	0.22	6	-0.45	3	9
CDC42	0.006	0.055	-10000	0	-0.58	5	5

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.013	0.1	-10000	0	-0.98	4	4
epithelial cell differentiation	-0.049	0.12	-10000	0	-0.54	16	16
ITCH	0.007	0.057	-10000	0	-0.59	5	5
WWP1	0.016	0.12	-10000	0	-1.5	3	3
FYN	0.005	0.061	-10000	0	-0.55	7	7
EGFR	0.004	0.064	-10000	0	-0.53	8	8
PRL	-0.013	0.088	-10000	0	-0.46	22	22
neuron projection morphogenesis	0.006	0.12	-10000	0	-0.79	4	4
PTPRZ1	-0.077	0.19	-10000	0	-0.5	96	96
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.005	0.13	-10000	0	-1.1	3	3
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.024	0.14	-10000	0	-1.2	3	3
ADAM17	0.011	0.038	-10000	0	-0.63	2	2
ErbB4/ErbB4	0.017	0.1	-10000	0	-1.1	4	4
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0	0.1	-10000	0	-1	4	4
NCOR1	0.01	0.025	-10000	0	-0.58	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.02	0.14	-10000	0	-1	4	4
GRIN2B	-0.039	0.16	-10000	0	-0.66	16	16
ErbB4/ErbB2/betacellulin	0.013	0.11	-10000	0	-0.96	4	4
STAT1	0.006	0.052	-10000	0	-0.5	6	6
HBEGF	0.001	0.069	-10000	0	-0.46	13	13
PRLR	-0.043	0.17	-10000	0	-0.57	53	53
E4ICDs/ETO2	-0.036	0.15	-10000	0	-0.38	51	51
axon guidance	0.014	0.13	-10000	0	-1.1	4	4
NEDD4	0.008	0.049	-10000	0	-0.57	4	4
Prolactin receptor/Prolactin receptor/Prolactin	-0.04	0.14	-10000	0	-0.42	69	69
CBFA2T3	-0.082	0.2	-10000	0	-0.5	104	104
ErbB4/ErbB2/HBEGF	0.014	0.1	-10000	0	-1.1	3	3
MAPK3	0.001	0.12	-10000	0	-0.83	4	4
STAT1 (dimer)	0.016	0.11	-10000	0	-1.1	4	4
MAPK1	0.001	0.12	-10000	0	-0.94	3	3
JAK2	-0.009	0.1	-10000	0	-0.55	21	21
ErbB4/ErbB2/neuregulin 1 beta	-0.023	0.14	-10000	0	-0.91	5	5
NRG1	-0.041	0.15	-10000	0	-0.39	85	85
NRG3	-0.004	0.066	-10000	0	-0.46	12	12
NRG2	-0.015	0.1	-10000	0	-0.46	29	29
NRG4	-0.022	0.12	-10000	0	-0.47	36	36
heart development	0.014	0.13	-10000	0	-1.1	4	4
neural crest cell migration	-0.022	0.14	-10000	0	-0.87	5	5
ERBB2	0.009	0.061	-10000	0	-0.34	16	16
WWOX/E4ICDs	0.018	0.097	-10000	0	-0.76	6	6
SHC1	0.011	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.003	0.12	-10000	0	-0.87	6	6
apoptosis	0.036	0.097	0.99	4	-10000	0	4
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.002	0.12	-10000	0	-1.1	4	4
ErbB4/ErbB2/epiregulin	-0.074	0.17	-10000	0	-0.54	15	15
ErbB4/ErbB4/betacellulin/betacellulin	0.011	0.11	-10000	0	-0.48	17	17
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.02	0.16	-10000	0	-0.61	20	20
MDM2	0.019	0.1	-10000	0	-0.9	5	5
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.022	0.14	-10000	0	-0.78	6	6
STAT5A	0.019	0.12	-10000	0	-1.1	4	4
ErbB4/EGFR/neuregulin 1 beta	-0.02	0.15	-10000	0	-1.1	4	4
DLG4	0.007	0.048	-10000	0	-0.5	5	5
GRB2/SHC	0.017	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.016	0.091	-10000	0	-0.81	5	5
STAT5A (dimer)	-0.053	0.13	-10000	0	-0.61	16	16
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.018	0.12	-10000	0	-1.1	4	4
LRIG1	-0.002	0.088	-10000	0	-0.58	13	13
EREG	-0.16	0.26	-10000	0	-0.55	179	179
BTC	-0.002	0.088	-10000	0	-0.58	13	13
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.014	0.14	-10000	0	-1.2	4	4
ERBB4	0.017	0.1	-10000	0	-1.1	4	4
STAT5B	0.011	0	-10000	0	-10000	0	0
YAP1	0.003	0.088	-10000	0	-1.1	3	3
GRB2	0.011	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.001	0.11	-10000	0	-0.96	4	4
glial cell differentiation	-0.016	0.089	0.79	5	-10000	0	5
WWOX	0.009	0.035	-10000	0	-0.58	2	2
cell proliferation	-0.017	0.15	-10000	0	-0.78	7	7

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.018	0.12	-9999	-0.31	53	53
positive regulation of NF-kappaB transcription factor activity	0	0.002	-9999	-10000	0	0
CRKL	0.011	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.003	0.12	-9999	-0.56	12	12
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.08	-9999	-0.37	22	22
antigen processing and presentation of peptide antigen via MHC class I	-0.039	0.074	-9999	-0.28	19	19
CaM/Ca2+	-0.017	0.11	-9999	-0.45	9	9
RAP1A	0.01	0.025	-9999	-0.58	1	1
STAT1 (dimer)/SHP2	-0.012	0.12	-9999	-0.54	11	11
AKT1	-0.003	0.11	-9999	-0.46	12	12
MAP2K1	-0.009	0.12	-9999	-0.56	11	11
MAP3K11	-0.013	0.11	-9999	-0.42	12	12
IFNGR1	0.008	0.012	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.053	0.12	-9999	-0.48	31	31
Rap1/GTP	-0.031	0.073	-9999	-0.42	5	5
CRKL/C3G	0.016	0.018	-9999	-0.42	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.02	0.12	-9999	-0.48	10	10
CEBPB	-0.008	0.16	-9999	-0.5	26	26
STAT3	0.011	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.052	0.22	-9999	-0.85	26	26
STAT1	-0.012	0.12	-9999	-0.53	11	11
CALM1	0.011	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.063	0.18	-9999	-0.51	80	80
PIK3CA	0.009	0.035	-9999	-0.58	2	2
STAT1 (dimer)/PIAS1	-0.005	0.11	-9999	-0.5	11	11
CEBPB/PTGES2/Cbp/p300	-0.039	0.087	-9999	-0.42	13	13
mol:Ca2+	-0.02	0.11	-9999	-0.31	53	53
MAPK3	-0.005	0.13	-9999	-0.71	7	7
STAT1 (dimer)	-0.051	0.1	-9999	-0.4	19	19
MAPK1	-0.005	0.12	-9999	-0.66	8	8
JAK2	-0.012	0.11	-9999	-0.56	21	21
PIK3R1	0.008	0.043	-9999	-0.58	3	3
JAK1	0.005	0.045	-9999	-0.6	3	3
CAMK2D	0.007	0.049	-9999	-0.58	4	4
DAPK1	-0.012	0.16	-9999	-0.54	36	36
SMAD7	0.012	0.059	-9999	-0.29	2	2
CBL/CRKL/C3G	-0.001	0.1	-9999	-0.47	6	6
PI3K	-0.041	0.1	-9999	-0.5	12	12
IFNG	-0.063	0.18	-9999	-0.51	80	80
apoptosis	-0.012	0.12	-9999	-0.4	34	34
CAMK2G	0.011	0	-9999	-10000	0	0
STAT3 (dimer)	0.011	0	-9999	-10000	0	0
CAMK2A	-0.023	0.13	-9999	-0.53	35	35
CAMK2B	-0.053	0.17	-9999	-0.49	72	72
FRAP1	-0.002	0.1	-9999	-0.42	12	12
PRKCD	-0.002	0.11	-9999	-0.46	12	12
RAP1B	0.011	0	-9999	-10000	0	0
negative regulation of cell growth	-0.039	0.074	-9999	-0.28	19	19
PTPN2	0.008	0.043	-9999	-0.58	3	3
EP300	0.007	0.049	-9999	-0.58	4	4
IRF1	0.001	0.13	-9999	-0.51	15	15
STAT1 (dimer)/PIASy	-0.004	0.12	-9999	-0.51	10	10
SOCS1	-0.046	0.22	-9999	-1.4	13	13
mol:GDP	-0.03	0.087	-9999	-0.41	8	8
CASP1	0.002	0.085	-9999	-0.28	33	33
PTGES2	0.007	0.046	-9999	-0.48	5	5
IRF9	0.02	0.054	-9999	-0.27	2	2
mol:PI-3-4-5-P3	-0.04	0.1	-9999	-0.48	12	12
RAP1/GDP	-0.031	0.074	-9999	-0.43	5	5
CBL	-0.012	0.11	-9999	-0.46	9	9
MAP3K1	-0.016	0.12	-9999	-0.49	14	14
PIAS1	0.011	0	-9999	-10000	0	0
PIAS4	0.011	0.024	-9999	-0.56	1	1
antigen processing and presentation of peptide antigen via MHC class II	-0.039	0.074	-9999	-0.28	19	19
PTPN11	-0.019	0.11	-9999	-0.31	53	53
CREBBP	0.012	0.001	-9999	-10000	0	0
RAPGEF1	0.01	0.025	-9999	-0.58	1	1

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.003	0.087	-9999	-0.53	15	15
alphaV beta3 Integrin	-0.003	0.092	-9999	-0.41	27	27
PTK2	-0.027	0.1	-9999	-0.43	27	27
positive regulation of JNK cascade	-0.017	0.068	-9999	-0.31	27	27
CDC42/GDP	0.018	0.11	-9999	-0.42	27	27
Rac1/GDP	0.021	0.1	-9999	-0.42	26	26
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.01	0.025	-9999	-0.58	1	1
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	-0.021	0.083	-9999	-0.38	27	27
nectin-3/I-afadin	-0.003	0.09	-9999	-0.42	26	26
RAPGEF1	0.019	0.11	-9999	-0.46	26	26
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0.12	-9999	-0.52	26	26
PDGFB-D/PDGFRB	-0.003	0.087	-9999	-0.53	15	15
TLN1	0.013	0.059	-9999	-0.54	3	3
Rap1/GTP	-0.016	0.069	-9999	-0.32	26	26
IQGAP1	0.008	0.04	-9999	-0.54	3	3
Rap1/GTP/I-afadin	0.02	0.025	-9999	-0.32	3	3
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.003	0.09	-9999	-0.42	26	26
PVR	0.011	0	-9999	-10000	0	0
Necl-5(dimer)	0.011	0	-9999	-10000	0	0
mol:GDP	0.014	0.13	-9999	-0.53	26	26
MLLT4	0.009	0.035	-9999	-0.58	2	2
PIK3CA	0.009	0.035	-9999	-0.58	2	2
PI3K	0.009	0.089	-9999	-0.31	37	37
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.014	0.036	-9999	-0.42	4	4
positive regulation of lamellipodium assembly	-0.025	0.083	-9999	-0.3	46	46
PVRL1	0.009	0.035	-9999	-0.58	2	2
PVRL3	-0.013	0.12	-9999	-0.58	24	24
PVRL2	0.01	0.031	-9999	-0.52	2	2
PIK3R1	0.008	0.043	-9999	-0.58	3	3
CDH1	0.01	0.025	-9999	-0.58	1	1
CLDN1	-0.013	0.12	-9999	-0.56	24	24
JAM-A/CLDN1	0	0.095	-9999	-0.32	45	45
SRC	0.006	0.13	-9999	-0.58	26	26
ITGB3	-0.005	0.093	-9999	-0.54	17	17
nectin-1(dimer)/I-afadin/I-afadin	0.014	0.036	-9999	-0.42	4	4
FARP2	0.016	0.12	-9999	-0.5	26	26
RAC1	0.011	0	-9999	-10000	0	0
CTNNA1	0.009	0.035	-9999	-0.58	2	2
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.006	0.078	-9999	-0.35	26	26
nectin-1/I-afadin	0.014	0.036	-9999	-0.42	4	4
nectin-2/I-afadin	0.014	0.034	-9999	-0.4	4	4
RAC1/GTP/IQGAP1/filamentous actin	0.014	0.025	-9999	-0.33	3	3
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.005	0.081	-9999	-0.35	28	28
CDC42/GTP/IQGAP1/filamentous actin	0.011	0.051	-9999	-0.45	6	6
F11R	0.011	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.017	0.068	-9999	-0.31	27	27
alphaV/beta3 Integrin/Talin	0.012	0.09	-9999	-0.52	7	7
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.014	0.034	-9999	-0.4	4	4
nectin-2(dimer)/I-afadin/I-afadin	0.014	0.034	-9999	-0.4	4	4
PIP5K1C	0.008	0.059	-9999	-0.47	3	3
VAV2	-0.003	0.16	-9999	-0.51	46	46
RAP1/GDP	-0.021	0.083	-9999	-0.39	26	26
ITGAV	0	0.081	-9999	-0.58	11	11
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.005	0.08	-9999	-0.35	28	28
nectin-3(dimer)/I-afadin/I-afadin	-0.003	0.09	-9999	-0.42	26	26
Rac1/GTP	-0.031	0.1	-9999	-0.36	46	46
PTPRM	0.002	0.062	-9999	-0.25	26	26
E-cadherin/beta catenin/alpha catenin	-0.004	0.037	-9999	-0.57	1	1
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.006	0.055	-9999	-0.58	5	5

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.076	0.19	-9999	-0.5	97	97
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.005	0.057	-9999	-0.47	8	8
TCEB1	0.011	0.019	-9999	-0.46	1	1
HIF1A/p53	-0.007	0.095	-9999	-0.28	53	53
HIF1A	0.014	0.036	-9999	-0.25	9	9
COPS5	0.011	0.019	-9999	-0.46	1	1
VHL/Elongin B/Elongin C/RBX1/CUL2	0.029	0.043	-9999	-0.38	4	4
FIH (dimer)	0.011	0	-9999	-10000	0	0
CDKN2A	-0.07	0.19	-9999	-0.51	90	90
ARNT/IPAS	-0.047	0.14	-9999	-0.36	98	98
HIF1AN	0.011	0	-9999	-10000	0	0
GNB2L1	0.011	0.019	-9999	-0.46	1	1
HIF1A/ARNT	0.019	0.04	-9999	-0.4	2	2
CUL2	0.011	0	-9999	-10000	0	0
OS9	0.011	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.018	0.041	-9999	-0.3	9	9
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.019	0.045	-9999	-0.44	3	3
PHD1-3/OS9	0.02	0.052	-9999	-0.32	8	8
HIF1A/RACK1/Elongin B/Elongin C	0.026	0.055	-9999	-0.4	8	8
VHL	0.01	0.025	-9999	-0.58	1	1
HSP90AA1	0.009	0.035	-9999	-0.58	2	2
HIF1A/JAB1	0.02	0.036	-9999	-0.29	1	1
EGLN3	-0.002	0.084	-9999	-0.51	15	15
EGLN2	0.009	0.037	-9999	-0.5	3	3
EGLN1	0.011	0	-9999	-10000	0	0
TP53	-0.043	0.17	-9999	-0.58	53	53
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.026	0.046	-9999	-0.86	1	1
ARNT	0.01	0.025	-9999	-0.58	1	1
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.01	0.031	-9999	-0.52	2	2
HIF1A/p19ARF	-0.02	0.1	-9999	-0.28	44	44

×

Signaling events mediated by PRL

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
CCNE1	0.009	0.034	-10000	0	-0.46	3	3
mol:Halofuginone	0.004	0.01	-10000	0	-0.23	1	1
ITGA1	0.006	0.055	-10000	0	-0.58	5	5
CDKN1A	0.018	0.049	-10000	0	-0.44	4	4
PRL-3/alpha Tubulin	-0.006	0.093	-10000	0	-0.37	35	35
mol:Ca2+	-0.009	0.12	0.29	33	-0.39	37	70
AGT	-0.025	0.14	-10000	0	-0.53	39	39
CCNA2	0.018	0.07	-10000	0	-0.89	1	1
TUBA1B	0.011	0	-10000	0	-10000	0	0
EGR1	0.002	0.08	-10000	0	-0.35	28	28
CDK2/Cyclin E1	0.026	0.048	-10000	0	-0.43	3	3
MAPK3	-0.006	0.095	-10000	0	-0.37	36	36
PRL-2 /Rab GGTase beta	0.015	0.032	-10000	0	-0.42	3	3
MAPK1	-0.006	0.095	-10000	0	-0.37	36	36
PTP4A1	0.014	0.073	-10000	0	-0.94	1	1
PTP4A3	-0.021	0.13	-10000	0	-0.52	35	35
PTP4A2	0.011	0	-10000	0	-10000	0	0
ITGB1	-0.005	0.093	-10000	0	-0.37	35	35
SRC	0.01	0.025	-10000	0	-0.58	1	1
RAC1	0.004	0.086	-10000	0	-0.41	19	19
Rab GGTase beta/Rab GGTase alpha	0.014	0.036	-10000	0	-0.42	4	4
PRL-1/ATF-5	0.018	0.069	-10000	0	-0.89	1	1
RABGGTA	0.01	0.025	-10000	0	-0.58	1	1
BCAR1	0.015	0.075	0.29	33	-0.33	2	35
RHOC	0.004	0.086	-10000	0	-0.42	18	18
RHOA	0.003	0.087	-10000	0	-0.41	20	20
cell motility	0.003	0.092	-10000	0	-0.42	20	20
PRL-1/alpha Tubulin	0.019	0.069	-10000	0	-0.89	1	1
PRL-3/alpha1 Integrin	-0.01	0.1	-10000	0	-0.37	40	40
ROCK1	0.003	0.093	-10000	0	-0.43	20	20
RABGGTB	0.008	0.043	-10000	0	-0.58	3	3
CDK2	0.01	0.025	-10000	0	-0.58	1	1
mitosis	0.014	0.073	-10000	0	-0.93	1	1
ATF5	0.011	0.019	-10000	0	-0.46	1	1

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.044	0.16	-9999	-0.49	63	63
CDC42/GTP	-0.016	0.1	-9999	-0.4	16	16
PLCG1	-0.014	0.11	-9999	-0.45	12	12
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.011	0	-9999	-10000	0	0
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.015	0.026	-9999	-0.42	2	2
cell migration	-0.016	0.1	-9999	-0.39	16	16
S1PR5	0.001	0.075	-9999	-0.54	11	11
S1PR4	-0.025	0.14	-9999	-0.53	38	38
MAPK3	-0.014	0.11	-9999	-0.47	12	12
MAPK1	-0.014	0.11	-9999	-0.47	12	12
S1P/S1P5/Gi	-0.01	0.095	-9999	-0.3	27	27
GNAI1	-0.002	0.088	-9999	-0.55	14	14
CDC42/GDP	0.005	0.041	-9999	-0.43	5	5
S1P/S1P5/G12	0.009	0.047	-9999	-0.33	11	11
RHOA	0.005	0.076	-9999	-0.3	26	26
S1P/S1P4/Gi	-0.021	0.11	-9999	-0.31	46	46
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.012	0.11	-9999	-0.54	24	24
S1P/S1P4/G12/G13	0	0.08	-9999	-0.29	40	40
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.009	0.035	-9999	-0.58	2	2
CDC42	0.006	0.055	-9999	-0.58	5	5

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.007	0.049	-10000	0	-0.57	4	4
HSPA8	0.009	0.035	-10000	0	-0.58	2	2
SMAD3/SMAD4/ER alpha	-0.036	0.12	0.21	6	-0.36	45	51
AKT1	0.01	0.028	-10000	0	-0.58	1	1
GSC	-0.018	0.14	-10000	0	-1.1	6	6
NKX2-5	-0.012	0.08	-10000	0	-0.46	18	18
muscle cell differentiation	0.038	0.091	0.47	13	-10000	0	13
SMAD2-3/SMAD4/SP1	0.025	0.098	-10000	0	-0.42	5	5
SMAD4	0	0.072	-10000	0	-0.56	6	6
CBFB	0.007	0.049	-10000	0	-0.58	4	4
SAP18	0.011	0.019	-10000	0	-0.46	1	1
Cbp/p300/MSG1	-0.037	0.12	-10000	0	-0.29	90	90
SMAD3/SMAD4/VDR	-0.007	0.058	-10000	0	-0.45	2	2
MYC	0.005	0.059	-10000	0	-0.55	6	6
CDKN2B	-0.01	0.22	-10000	0	-1.4	13	13
AP1	0.009	0.11	-10000	0	-0.48	13	13
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.038	0.055	-10000	0	-0.44	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.008	0.082	-10000	0	-0.34	10	10
SP3	0.012	0.025	-10000	0	-0.58	1	1
CREB1	0.009	0.035	-10000	0	-0.58	2	2
FOXH1	-0.056	0.17	-10000	0	-0.5	75	75
SMAD3/SMAD4/GR	-0.012	0.1	-10000	0	-0.38	30	30
GATA3	-0.027	0.13	-10000	0	-0.54	31	31
SKI/SIN3/HDAC complex/NCoR1	0.036	0.024	-10000	0	-10000	0	0
MEF2C/TIF2	-0.019	0.13	-10000	0	-0.48	21	21
endothelial cell migration	0.038	0.2	1.3	11	-10000	0	11
MAX	0.013	0.01	-10000	0	-10000	0	0
RBBP7	0.01	0.025	-10000	0	-0.58	1	1
RBBP4	0.01	0.025	-10000	0	-0.58	1	1
RUNX2	-0.006	0.095	-10000	0	-0.53	18	18
RUNX3	-0.019	0.12	-10000	0	-0.51	33	33
RUNX1	0.011	0	-10000	0	-10000	0	0
CTBP1	0.01	0.025	-10000	0	-0.58	1	1
NR3C1	-0.014	0.12	-10000	0	-0.52	28	28
VDR	0.01	0.025	-10000	0	-0.58	1	1
CDKN1A	0.028	0.13	-10000	0	-1.2	4	4
KAT2B	-0.007	0.1	-10000	0	-0.58	17	17
SMAD2/SMAD2/SMAD4/FOXH1	-0.023	0.13	-10000	0	-0.36	43	43
DCP1A	0.011	0	-10000	0	-10000	0	0
SKI	0.011	0.001	-10000	0	-10000	0	0
SERPINE1	-0.038	0.21	-10000	0	-1.3	11	11
SMAD3/SMAD4/ATF2	0.012	0.075	-10000	0	-0.35	10	10
SMAD3/SMAD4/ATF3	0.004	0.091	-10000	0	-0.35	19	19
SAP30	0.009	0.035	-10000	0	-0.58	2	2
Cbp/p300/PIAS3	0.019	0.041	-10000	0	-0.33	6	6
JUN	0.008	0.11	-10000	0	-0.47	13	13
SMAD3/SMAD4/IRF7	0.009	0.085	-10000	0	-0.36	15	15
TFE3	0.014	0.013	-10000	0	-10000	0	0
COL1A2	-0.042	0.21	-10000	0	-0.76	36	36
mesenchymal cell differentiation	-0.002	0.095	0.36	25	-10000	0	25
DLX1	-0.044	0.15	-10000	0	-0.46	64	64
TCF3	0.01	0.025	-10000	0	-0.58	1	1
FOS	-0.028	0.15	-10000	0	-0.53	44	44
SMAD3/SMAD4/Max	0.006	0.07	-10000	0	-0.32	11	11
Cbp/p300/SNIP1	0.02	0.032	-10000	0	-0.35	4	4
ZBTB17	0.01	0.027	-10000	0	-0.58	1	1
LAMC1	0.023	0.066	-10000	0	-0.43	1	1
TGIF2/HDAC complex/SMAD3/SMAD4	0.01	0.08	-10000	0	-0.34	16	16
IRF7	0.005	0.058	-10000	0	-0.56	6	6
ESR1	-0.034	0.15	-10000	0	-0.52	50	50
HNF4A	0.004	0.065	-10000	0	-0.58	7	7
MEF2C	-0.022	0.13	-10000	0	-0.48	22	22
SMAD2-3/SMAD4	0.013	0.084	-10000	0	-0.37	11	11
Cbp/p300/Src-1	0.019	0.041	-10000	0	-0.43	4	4
IGHV3OR16-13	-0.009	0.051	-10000	0	-0.8	2	2
TGIF2/HDAC complex	0.006	0.055	-10000	0	-0.58	5	5
CREBBP	0.011	0.006	-10000	0	-10000	0	0
SKIL	0	0.081	-10000	0	-0.58	11	11
HDAC1	0.011	0.001	-10000	0	-10000	0	0
HDAC2	0.011	0.001	-10000	0	-10000	0	0
SNIP1	0.012	0.002	-10000	0	-10000	0	0
GCN5L2	-0.001	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.023	0.075	-10000	0	-0.37	3	3
MSG1/HSC70	-0.052	0.14	-10000	0	-0.34	109	109
SMAD2	0.007	0.053	-10000	0	-0.57	4	4
SMAD3	0.001	0.076	-10000	0	-0.57	7	7
SMAD3/E2F4-5/DP1/p107/SMAD4	0.019	0.069	-10000	0	-0.32	6	6
SMAD2/SMAD2/SMAD4	-0.004	0.076	-10000	0	-0.35	23	23
NCOR1	0.01	0.025	-10000	0	-0.58	1	1
NCOA2	0.003	0.068	-10000	0	-0.56	8	8
NCOA1	0.01	0.025	-10000	0	-0.58	1	1
MYOD/E2A	0.007	0.026	-10000	0	-0.35	3	3
SMAD2-3/SMAD4/SP1/MIZ-1	0.032	0.094	-10000	0	-0.41	4	4
IFNB1	0.009	0.082	-10000	0	-0.45	8	8
SMAD3/SMAD4/MEF2C	-0.018	0.14	-10000	0	-0.48	22	22
CITED1	-0.081	0.2	-10000	0	-0.48	107	107
SMAD2-3/SMAD4/ARC105	0.021	0.078	-10000	0	-0.4	5	5
RBL1	0.008	0.04	-10000	0	-0.54	3	3
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.025	0.099	-10000	0	-0.48	15	15
RUNX1-3/PEBPB2	0.002	0.081	-10000	0	-0.3	37	37
SMAD7	0.026	0.12	-10000	0	-0.85	3	3
MYC/MIZ-1	0.012	0.051	-10000	0	-0.4	7	7
SMAD3/SMAD4	-0.016	0.1	0.31	4	-0.43	14	18
IL10	-0.036	0.2	-10000	0	-0.58	56	56
PIASy/HDAC complex	0.011	0.026	-10000	0	-0.58	1	1
PIAS3	0.009	0.032	-10000	0	-0.52	2	2
CDK2	0.01	0.025	-10000	0	-0.58	1	1
IL5	-0.013	0.13	-10000	0	-0.49	17	17
CDK4	0.011	0.006	-10000	0	-10000	0	0
PIAS4	0.011	0.026	-10000	0	-0.58	1	1
ATF3	-0.003	0.083	-10000	0	-0.46	18	18
SMAD3/SMAD4/SP1	0.016	0.094	-10000	0	-0.37	8	8
FOXG1	-0.059	0.16	-10000	0	-0.48	72	72
FOXO3	0.018	0.025	-10000	0	-0.42	1	1
FOXO1	0.017	0.031	-10000	0	-0.42	2	2
FOXO4	0.017	0.031	-10000	0	-0.42	2	2
heart looping	-0.022	0.13	-10000	0	-0.47	22	22
CEBPB	0.008	0.042	-10000	0	-0.48	4	4
SMAD3/SMAD4/DLX1	-0.022	0.12	-10000	0	-0.35	22	22
MYOD1	-0.001	0.027	-10000	0	-0.46	2	2
SMAD3/SMAD4/HNF4	0.009	0.087	-10000	0	-0.38	18	18
SMAD3/SMAD4/GATA3	-0.025	0.14	-10000	0	-0.45	27	27
SnoN/SIN3/HDAC complex/NCoR1	0	0.081	-10000	0	-0.58	11	11
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.009	0.097	-10000	0	-0.41	9	9
SMAD3/SMAD4/SP1-3	0.028	0.085	-10000	0	-0.4	1	1
MED15	0.01	0.025	-10000	0	-0.58	1	1
SP1	0.009	0.043	-10000	0	-0.57	1	1
SIN3B	0.01	0.025	-10000	0	-0.58	1	1
SIN3A	0.01	0.025	-10000	0	-0.58	1	1
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.024	0.13	-10000	0	-0.36	38	38
ITGB5	0.029	0.075	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.036	0.029	-10000	0	-0.46	1	1
SMAD3/SMAD4/AR	-0.028	0.13	-10000	0	-0.37	41	41
AR	-0.052	0.17	-10000	0	-0.49	70	70
negative regulation of cell growth	0.02	0.08	-10000	0	-0.35	15	15
SMAD3/SMAD4/MYOD	0.005	0.072	-10000	0	-0.33	11	11
E2F5	-0.002	0.088	-10000	0	-0.58	13	13
E2F4	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.007	0.11	-10000	0	-0.4	14	14
SMAD2-3/SMAD4/FOXO1-3a-4	0.026	0.079	-10000	0	-0.34	15	15
TFDP1	0.011	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.01	0.11	-10000	0	-0.48	13	13
SMAD3/SMAD4/RUNX2	0.002	0.095	-10000	0	-0.36	25	25
TGIF2	0.006	0.055	-10000	0	-0.58	5	5
TGIF1	0.011	0	-10000	0	-10000	0	0
ATF2	0.009	0.035	-10000	0	-0.58	2	2

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.009	0.037	-9999	-0.5	3	3
SPHK1	-0.03	0.14	-9999	-0.51	45	45
GNAI2	0.011	0	-9999	-10000	0	0
mol:S1P	-0.001	0.068	-9999	-0.3	22	22
GNAO1	-0.044	0.16	-9999	-0.49	63	63
mol:Sphinganine-1-P	-0.013	0.11	-9999	-0.36	48	48
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.018	0.054	-9999	-0.29	2	2
GNAI3	0.011	0	-9999	-10000	0	0
G12/G13	0.015	0.026	-9999	-0.42	2	2
S1PR3	0.005	0.059	-9999	-0.53	7	7
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.004	0.058	-9999	-0.25	22	22
S1PR5	0.001	0.075	-9999	-0.54	11	11
S1PR4	-0.025	0.14	-9999	-0.53	38	38
GNAI1	-0.002	0.088	-9999	-0.55	14	14
S1P/S1P5/G12	0.006	0.068	-9999	-0.32	9	9
S1P/S1P3/Gq	-0.002	0.11	-9999	-0.35	36	36
S1P/S1P4/Gi	-0.021	0.12	-9999	-0.44	19	19
GNAQ	0.005	0.06	-9999	-0.58	6	6
GNAZ	-0.012	0.11	-9999	-0.54	24	24
GNA14	-0.008	0.1	-9999	-0.56	19	19
GNA15	-0.009	0.1	-9999	-0.54	21	21
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.009	0.035	-9999	-0.58	2	2
GNA11	0.007	0.051	-9999	-0.53	5	5
ABCC1	0.01	0.025	-9999	-0.58	1	1

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.007	0.049	-10000	0	-0.58	4	4
HDAC4	0.011	0.019	-10000	0	-0.46	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.008	0.094	0.36	37	-10000	0	37
CDKN1A	0.006	0.068	-10000	0	-0.58	5	5
KAT2B	-0.006	0.1	-10000	0	-0.58	17	17
BAX	0.01	0.025	-10000	0	-0.58	1	1
FOXO3	0.004	0.042	0.49	4	-10000	0	4
FOXO1	0.01	0.025	-10000	0	-0.58	1	1
FOXO4	0.016	0.029	-10000	0	-0.3	5	5
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.011	0	-10000	0	-10000	0	0
TAT	-0.018	0.11	-10000	0	-0.46	32	32
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.005	0.076	-10000	0	-0.42	19	19
PPARGC1A	-0.046	0.17	-10000	0	-0.56	57	57
FHL2	0.009	0.035	-10000	0	-0.58	2	2
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.011	0.042	-10000	0	-0.42	5	5
HIST2H4A	-0.008	0.095	-10000	0	-0.36	37	37
SIRT1/FOXO3a	0	0.032	0.29	2	-0.36	3	5
SIRT1	0.003	0.056	0.2	2	-0.58	5	7
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.017	0.041	-10000	0	-0.34	7	7
SIRT1/Histone H1b	0.003	0.068	-10000	0	-0.31	19	19
apoptosis	-0.017	0.039	0.35	6	-10000	0	6
SIRT1/PGC1A	-0.036	0.11	-10000	0	-0.35	62	62
p53/SIRT1	-0.04	0.13	0.32	4	-0.43	56	60
SIRT1/FOXO4	0.014	0.049	-10000	0	-0.37	8	8
FOXO1/FHL2/SIRT1	0.015	0.041	-10000	0	-0.32	8	8
HIST1H1E	0.002	0.062	-10000	0	-0.31	16	16
SIRT1/p300	0.008	0.062	-10000	0	-0.52	7	7
muscle cell differentiation	0.001	0.081	0.41	19	-10000	0	19
TP53	-0.046	0.17	-10000	0	-0.58	53	53
KU70/SIRT1/BAX	0.017	0.039	-10000	0	-0.35	6	6
CREBBP	0.011	0	-10000	0	-10000	0	0
MEF2D	0.01	0.025	-10000	0	-0.58	1	1
HIV-1 Tat/SIRT1	-0.011	0.085	-10000	0	-0.33	37	37
ACSS2	0.012	0.045	-10000	0	-0.42	6	6
SIRT1/PCAF/MYOD	-0.001	0.081	-10000	0	-0.41	19	19

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.022	0.16	-10000	0	-1.2	9	9
VDR	0.01	0.025	-10000	0	-0.58	1	1
FAM120B	0.01	0.025	-10000	0	-0.58	1	1
RXRs/LXRs/DNA/9cRA	0.026	0.084	-10000	0	-0.58	3	3
RXRs/LXRs/DNA/Oxysterols	0.025	0.11	-10000	0	-0.43	26	26
MED1	0.008	0.044	-10000	0	-0.52	4	4
mol:9cRA	0.003	0.013	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.021	0.12	-10000	0	-0.54	7	7
RXRs/NUR77	0.004	0.095	-10000	0	-0.39	9	9
RXRs/PPAR	0.021	0.059	-10000	0	-0.52	2	2
NCOR2	0.007	0.047	-10000	0	-0.55	4	4
VDR/VDR/Vit D3	0.008	0.018	-10000	0	-0.43	1	1
RARs/VDR/DNA/Vit D3	0.012	0.071	-10000	0	-0.33	18	18
RARA	0.007	0.046	-10000	0	-0.48	5	5
NCOA1	0.01	0.025	-10000	0	-0.58	1	1
VDR/VDR/DNA	0.01	0.025	-10000	0	-0.58	1	1
RARs/RARs/DNA/9cRA	0.007	0.068	-10000	0	-0.31	20	20
RARG	0.005	0.06	-10000	0	-0.58	6	6
RPS6KB1	-0.008	0.079	-10000	0	-0.46	15	15
RARs/THRs/DNA/SMRT	-0.022	0.12	-10000	0	-0.57	7	7
THRA	0.008	0.042	-10000	0	-0.49	4	4
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.008	0.018	-10000	0	-0.43	1	1
RXRs/PPAR/9cRA/PGJ2/DNA	0.02	0.072	0.28	6	-0.32	4	10
NR1H4	-0.13	0.23	-10000	0	-0.5	151	151
RXRs/LXRs/DNA	0.034	0.078	-10000	0	-0.41	4	4
NR1H2	0.013	0.028	-10000	0	-0.6	1	1
NR1H3	0.013	0.024	-10000	0	-0.48	1	1
RXRs/VDR/DNA/Vit D3	0.021	0.058	-10000	0	-0.3	3	3
NR4A1	-0.024	0.12	-10000	0	-0.46	43	43
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.034	0.1	-10000	0	-0.26	67	67
RXRG	-0.01	0.096	-10000	0	-0.46	25	25
RXR alpha/CCPG	0.018	0.027	-10000	0	-0.42	2	2
RXRA	0.013	0.027	-10000	0	-0.59	1	1
RXRB	0.014	0.012	-10000	0	-10000	0	0
THRB	-0.071	0.2	-10000	0	-0.56	83	83
PPARG	0.004	0.065	-10000	0	-0.58	7	7
PPARD	0.01	0.025	-10000	0	-0.58	1	1
TNF	0.005	0.22	-10000	0	-1.1	20	20
mol:Oxysterols	0.003	0.011	-10000	0	-10000	0	0
cholesterol transport	0.025	0.11	-10000	0	-0.43	26	26
PPARA	0.009	0.035	-10000	0	-0.58	2	2
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	-0.006	0.096	-10000	0	-0.54	18	18
RXRs/NUR77/BCL2	-0.001	0.072	-10000	0	-0.28	21	21
SREBF1	0.029	0.12	-10000	0	-0.82	4	4
RXRs/RXRs/DNA/9cRA	0.02	0.072	0.28	6	-0.32	4	10
ABCA1	0.021	0.16	-10000	0	-1	10	10
RARs/THRs	-0.027	0.13	-10000	0	-0.54	9	9
RXRs/FXR	-0.055	0.14	-10000	0	-0.33	68	68
BCL2	-0.007	0.1	-10000	0	-0.55	19	19

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.004	0.085	-9999	-0.48	18	18
PLK4	0.009	0.035	-9999	-0.58	2	2
regulation of centriole replication	0.006	0.07	-9999	-0.36	19	19

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.012	0.047	-10000	0	-0.34	10	10
MAP4K4	0.02	0.065	-10000	0	-0.51	2	2
BAG4	0.009	0.035	-10000	0	-0.58	2	2
PKC zeta/ceramide	-0.023	0.041	0.15	1	-0.2	2	3
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	-0.016	0.12	-10000	0	-0.52	29	29
BAX	-0.009	0.023	-10000	0	-0.31	1	1
RIPK1	0.011	0	-10000	0	-10000	0	0
AKT1	0.018	0.023	-10000	0	-0.51	1	1
BAD	-0.024	0.041	0.16	1	-0.2	2	3
SMPD1	0.012	0.046	-10000	0	-0.2	20	20
RB1	-0.034	0.068	0.16	2	-0.32	20	22
FADD/Caspase 8	0.028	0.061	-10000	0	-0.5	1	1
MAP2K4	-0.021	0.053	-10000	0	-0.33	8	8
NSMAF	0.011	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.018	0.042	-10000	0	-0.31	2	2
EGF	-0.18	0.25	-10000	0	-0.5	209	209
mol:ceramide	-0.032	0.043	0.14	9	-10000	0	9
MADD	0.011	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.014	0.039	-10000	0	-0.33	7	7
ASAH1	0.011	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.034	0.067	0.16	2	-0.32	20	22
cell proliferation	-0.035	0.089	-10000	0	-0.26	52	52
BID	0.01	0.047	-10000	0	-0.33	2	2
MAP3K1	-0.026	0.051	0.16	2	-0.33	6	8
EIF2A	-0.021	0.064	-10000	0	-0.32	17	17
TRADD	0.011	0	-10000	0	-10000	0	0
CRADD	0.01	0.025	-10000	0	-0.58	1	1
MAPK3	-0.009	0.039	-10000	0	-0.28	2	2
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.009	0.039	-10000	0	-0.28	2	2
Cathepsin D/ceramide	-0.024	0.041	0.15	1	-0.23	2	3
FADD	0.02	0.062	-10000	0	-0.52	1	1
KSR1	-0.024	0.044	0.16	2	-0.33	2	4
MAPK8	-0.016	0.045	0.15	1	-0.22	9	10
PRKRA	-0.024	0.04	0.16	2	-0.2	1	3
PDGFA	0.005	0.053	-10000	0	-0.47	7	7
TRAF2	0.01	0.025	-10000	0	-0.58	1	1
IGF1	-0.071	0.19	-10000	0	-0.52	88	88
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.031	0.042	0.14	9	-10000	0	9
CTSD	0.009	0.037	-10000	0	-0.5	3	3
regulation of nitric oxide biosynthetic process	0.016	0.018	-10000	0	-0.42	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.036	0.095	-10000	0	-0.28	52	52
PRKCD	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.01	0.031	-10000	0	-0.52	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.014	0.039	-10000	0	-0.33	7	7
RelA/NF kappa B1	0.016	0.018	-10000	0	-0.42	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.01	0.025	-10000	0	-0.58	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.015	0.065	-10000	0	-0.56	1	1
TNFR1A/BAG4/TNF-alpha	0.005	0.078	-10000	0	-0.32	30	30
mol:Sphingosine-1-phosphate	0.012	0.047	-10000	0	-0.34	10	10
MAP2K1	-0.012	0.042	-10000	0	-0.29	3	3
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.011	0	-10000	0	-10000	0	0
CYCS	-0.016	0.049	0.16	7	-0.23	13	20
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
NFKB1	0.01	0.025	-10000	0	-0.58	1	1
TNFR1A/BAG4	0.015	0.026	-10000	0	-0.42	2	2
EIF2AK2	-0.027	0.062	-10000	0	-0.3	19	19
TNF-alpha/TNFR1A/FAN	0.006	0.075	-10000	0	-0.32	28	28
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.024	0.047	-10000	0	-0.43	2	2
MAP2K2	-0.012	0.04	-10000	0	-0.29	2	2
SMPD3	0.006	0.071	-10000	0	-0.35	14	14
TNF	-0.016	0.12	-10000	0	-0.54	28	28
PKC zeta/PAR4	0.015	0.029	-10000	0	-0.39	3	3
mol:PHOSPHOCHOLINE	0.059	0.094	0.18	201	-10000	0	201
NF kappa B1/RelA/I kappa B alpha	0.032	0.03	-10000	0	-0.36	3	3
AIFM1	-0.01	0.038	0.14	14	-0.26	1	15
BCL2	-0.007	0.1	-10000	0	-0.55	19	19

×

Syndecan-3-mediated signaling events

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
CTTN	0.011	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.012	0.077	-9999	-0.48	3	3
Syndecan-3/Neurocan	0.002	0.049	-9999	-0.6	2	2
POMC	-0.024	0.13	-9999	-0.51	38	38
EGFR	0.004	0.064	-9999	-0.53	8	8
Syndecan-3/EGFR	0.015	0.05	-9999	-0.38	7	7
AGRP	-0.001	0.051	-9999	-0.46	7	7
NCSTN	0.011	0	-9999	-10000	0	0
PSENEN	0.01	0.025	-9999	-0.58	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.006	0.055	-9999	-0.58	5	5
APH1A	0.011	0	-9999	-10000	0	0
NCAN	-0.004	0.066	-9999	-0.46	12	12
long-term memory	0.021	0.048	-9999	-0.37	7	7
Syndecan-3/IL8	-0.043	0.12	-9999	-0.31	67	67
PSEN1	0.011	0	-9999	-10000	0	0
Src/Cortactin	0.016	0.018	-9999	-0.42	1	1
FYN	0.005	0.061	-9999	-0.55	7	7
limb bud formation	-0.003	0.037	-9999	-0.62	2	2
MC4R	-0.005	0.057	-9999	-0.46	9	9
SRC	0.01	0.025	-9999	-0.58	1	1
PTN	-0.024	0.14	-9999	-0.54	37	37
FGFR/FGF/Syndecan-3	-0.003	0.038	-9999	-0.63	2	2
neuron projection morphogenesis	-0.006	0.076	-9999	-0.46	3	3
Syndecan-3/AgRP	0.002	0.045	-9999	-0.6	2	2
Syndecan-3/AgRP/MC4R	-0.005	0.051	-9999	-0.46	4	4
Fyn/Cortactin	0.012	0.045	-9999	-0.39	7	7
SDC3	-0.003	0.038	-9999	-0.64	2	2
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.042	0.12	-9999	-0.31	67	67
IL8	-0.11	0.22	-9999	-0.52	129	129
Syndecan-3/Fyn/Cortactin	0.021	0.049	-9999	-0.38	7	7
Syndecan-3/CASK	-0.003	0.036	-9999	-0.6	2	2
alpha-MSH/MC4R	-0.02	0.11	-9999	-0.38	44	44
Gamma Secretase	0.031	0.033	-9999	-0.3	1	1

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.014	0.022	-9999	-0.36	2	2
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.011	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.001	0.077	-9999	-0.58	10	10
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.008	0.043	-9999	-0.58	3	3
RAC1-CDC42/GTP/PAK family	0.016	0.035	-9999	-0.29	5	5
response to UV	0	0	-9999	-10000	0	0
YES1	0.004	0.065	-9999	-0.58	7	7
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.009	0.035	-9999	-0.58	2	2
FYN	0.005	0.061	-9999	-0.55	7	7
MAP3K12	0.003	0.069	-9999	-0.54	9	9
FGR	-0.023	0.13	-9999	-0.53	36	36
p38 alpha/TAB1	-0.038	0.087	-9999	-0.34	28	28
PRKG1	-0.024	0.14	-9999	-0.56	36	36
DUSP8	0.006	0.053	-9999	-0.56	5	5
PGK/cGMP/p38 alpha	-0.05	0.11	-9999	-0.36	45	45
apoptosis	-0.037	0.083	-9999	-0.32	28	28
RAL/GTP	0.015	0	-9999	-10000	0	0
LYN	0.011	0	-9999	-10000	0	0
DUSP1	-0.008	0.095	-9999	-0.47	23	23
PAK1	0.011	0	-9999	-10000	0	0
SRC	0.01	0.025	-9999	-0.58	1	1
RAC1/OSM/MEKK3/MKK3	0.027	0.035	-9999	-0.37	4	4
TRAF6	0.01	0.025	-9999	-0.58	1	1
RAC1	0.011	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.01	0.031	-9999	-0.52	2	2
RAC1-CDC42/GTP	0.012	0.035	-9999	-0.36	5	5
MAPK11	-0.025	0.14	-9999	-0.43	38	38
BLK	-0.11	0.23	-9999	-0.53	132	132
HCK	-0.02	0.13	-9999	-0.55	32	32
MAP2K3	0.01	0.025	-9999	-0.58	1	1
DUSP16	0.011	0	-9999	-10000	0	0
DUSP10	0.01	0.031	-9999	-0.52	2	2
TRAF6/MEKK3	0.013	0.025	-9999	-0.33	3	3
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.01	0.11	-9999	-0.37	27	27
positive regulation of innate immune response	-0.022	0.15	-9999	-0.46	36	36
LCK	-0.032	0.14	-9999	-0.51	48	48
p38alpha-beta/MKP7	-0.015	0.14	-9999	-0.47	29	29
p38alpha-beta/MKP5	-0.016	0.14	-9999	-0.51	24	24
PGK/cGMP	-0.018	0.1	-9999	-0.41	36	36
PAK2	0.01	0.025	-9999	-0.58	1	1
p38alpha-beta/MKP1	-0.023	0.15	-9999	-0.44	41	41
CDC42	0.006	0.055	-9999	-0.58	5	5
RALB	0.011	0	-9999	-10000	0	0
RALA	0.011	0	-9999	-10000	0	0
PAK3	0	0.058	-9999	-0.46	9	9

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.011	0	-10000	0	-10000	0	0
Rac1/GDP	0.003	0.011	-10000	0	-10000	0	0
DOCK1	0.01	0.025	-10000	0	-0.58	1	1
ITGA4	-0.018	0.13	-10000	0	-0.56	29	29
RAC1	0.011	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.024	0.14	-10000	0	-0.43	53	53
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.011	0.019	-10000	0	-0.46	1	1
alpha4/beta1 Integrin	0.005	0.08	-10000	0	-0.34	29	29
alpha4/beta7 Integrin/Paxillin	-0.005	0.11	-10000	0	-0.36	39	39
lamellipodium assembly	-0.003	0.052	-10000	0	-0.5	5	5
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
PI3K	0.013	0.041	-10000	0	-0.42	5	5
ARF6	0.01	0.025	-10000	0	-0.58	1	1
TLN1	0.01	0.025	-10000	0	-0.58	1	1
PXN	0.018	0	-10000	0	-10000	0	0
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
ARF6/GTP	-0.014	0.058	-10000	0	-10000	0	0
cell adhesion	0.017	0.069	-10000	0	-0.29	26	26
CRKL/CBL	0.017	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.011	0.073	-10000	0	-0.32	25	25
ITGB1	0.011	0	-10000	0	-10000	0	0
ITGB7	-0.017	0.12	-10000	0	-0.53	30	30
ARF6/GDP	0.002	0.027	-10000	0	-0.57	1	1
alpha4/beta1 Integrin/Paxillin/VCAM1	0.003	0.11	-10000	0	-0.4	36	36
p130Cas/Crk/Dock1	0.02	0.038	-10000	0	-0.36	5	5
VCAM1	-0.019	0.12	-10000	0	-0.53	32	32
alpha4/beta1 Integrin/Paxillin/Talin	0.018	0.07	-10000	0	-0.29	26	26
alpha4/beta1 Integrin/Paxillin/GIT1	0.018	0.07	-10000	0	-0.29	26	26
BCAR1	0.008	0.044	-10000	0	-0.52	4	4
mol:GDP	-0.017	0.069	0.29	26	-10000	0	26
CBL	0.011	0	-10000	0	-10000	0	0
PRKACA	0.011	0	-10000	0	-10000	0	0
GIT1	0.01	0.025	-10000	0	-0.58	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.018	0.07	-10000	0	-0.29	26	26
Rac1/GTP	-0.004	0.059	-10000	0	-0.56	5	5

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.014	0.1	-10000	0	-0.52	11	11
UGCG	0.01	0.07	-10000	0	-0.84	3	3
AKT1/mTOR/p70S6K/Hsp90/TERT	0.007	0.13	-10000	0	-0.44	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.01	0.069	-10000	0	-0.82	3	3
mol:DAG	-0.001	0.01	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.039	0.11	-10000	0	-0.43	31	31
FRAP1	0.017	0.15	-10000	0	-0.5	32	32
FOXO3	0.023	0.13	-10000	0	-0.44	25	25
AKT1	0.017	0.14	-10000	0	-0.47	28	28
GAB2	0.01	0.035	-10000	0	-0.58	2	2
SMPD1	0.013	0.039	-10000	0	-0.6	1	1
SGMS1	0.014	0.028	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0.035	-10000	0	-0.36	5	5
CALM1	0.011	0	-10000	0	-10000	0	0
cell proliferation	0.018	0.081	-10000	0	-0.41	7	7
EIF3A	0.01	0.025	-10000	0	-0.58	1	1
PI3K	0.017	0.041	-10000	0	-0.42	5	5
RPS6KB1	0.007	0.097	-10000	0	-0.96	5	5
mol:sphingomyelin	-0.001	0.01	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-0.012	2	2
JAK3	0.002	0.078	-10000	0	-0.53	12	12
PIK3R1	0.011	0.043	-10000	0	-0.58	3	3
JAK1	0.011	0.043	-10000	0	-0.58	3	3
NFKB1	0.01	0.025	-10000	0	-0.58	1	1
MYC	0.021	0.15	-10000	0	-0.67	13	13
MYB	0.005	0.16	-10000	0	-1.2	9	9
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.011	0.14	-10000	0	-0.42	37	37
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.017	0.093	-10000	0	-0.87	5	5
mol:PI-3-4-5-P3	0.012	0.13	-10000	0	-0.4	37	37
Rac1/GDP	0.02	0.032	-10000	0	-0.32	5	5
T cell proliferation	0.017	0.13	-10000	0	-0.43	25	25
SHC1	0.012	0.002	-10000	0	-10000	0	0
RAC1	0.011	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.009	-10000	0	-0.065	9	9
PRKCZ	0.016	0.13	-10000	0	-0.45	25	25
NF kappa B1 p50/RelA	-0.038	0.11	-10000	0	-0.45	27	27
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.007	0.11	-10000	0	-0.5	18	18
HSP90AA1	0.009	0.035	-10000	0	-0.58	2	2
RELA	0.011	0	-10000	0	-10000	0	0
IL2RA	-0.044	0.17	-10000	0	-0.55	57	57
IL2RB	-0.013	0.12	-10000	0	-0.54	28	28
TERT	-0.051	0.17	-10000	0	-0.51	68	68
E2F1	0.014	0.066	-10000	0	-0.44	11	11
SOS1	0.011	0.025	-10000	0	-0.58	1	1
RPS6	0.007	0.046	-10000	0	-0.48	5	5
mol:cAMP	-0.002	0.004	0.031	9	-10000	0	9
PTPN11	0.007	0.055	-10000	0	-0.58	5	5
IL2RG	0.001	0.086	-10000	0	-0.56	13	13
actin cytoskeleton organization	0.017	0.13	-10000	0	-0.43	25	25
GRB2	0.012	0.002	-10000	0	-10000	0	0
IL2	0.004	0.027	-10000	0	-0.45	2	2
PIK3CA	0.012	0.035	-10000	0	-0.58	2	2
Rac1/GTP	0.027	0.032	-10000	0	-0.3	5	5
LCK	-0.03	0.14	-10000	0	-0.5	48	48
BCL2	0.014	0.18	-10000	0	-0.72	23	23

×

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

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
BAG4	0.009	0.035	-9999	-0.58	2	2
Caspase 8 (4 units)	0.006	0.087	-9999	-0.48	6	6
NEF	-0.013	0.051	-9999	-0.19	28	28
NFKBIA	0.009	0.023	-9999	-10000	0	0
BIRC3	0.007	0.12	-9999	-0.51	29	29
CYCS	-0.001	0.11	-9999	-0.51	10	10
RIPK1	0.011	0	-9999	-10000	0	0
CD247	-0.034	0.15	-9999	-0.64	31	31
MAP2K7	0.013	0.084	-9999	-0.49	5	5
protein ubiquitination	0.038	0.057	-9999	-0.4	3	3
CRADD	0.01	0.025	-9999	-0.58	1	1
DAXX	0.011	0	-9999	-10000	0	0
FAS	0.001	0.074	-9999	-0.56	10	10
BID	0.001	0.098	-9999	-0.3	31	31
NF-kappa-B/RelA/I kappa B alpha	0.017	0.065	-9999	-0.29	16	16
TRADD	0.011	0	-9999	-10000	0	0
MAP3K5	0.009	0.035	-9999	-0.58	2	2
CFLAR	0.011	0	-9999	-10000	0	0
FADD	0.011	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.017	0.065	-9999	-0.29	16	16
MAPK8	0.018	0.083	-9999	-0.56	4	4
APAF1	0.008	0.043	-9999	-0.58	3	3
TRAF1	0.008	0.039	-9999	-0.46	4	4
TRAF2	0.01	0.025	-9999	-0.58	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.005	0.1	-9999	-0.3	46	46
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.033	0.057	-9999	-10000	0	0
CHUK	0.039	0.061	-9999	-0.43	3	3
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.027	0.05	-9999	-0.32	10	10
TCRz/NEF	-0.039	0.15	-9999	-0.39	79	79
TNF	-0.016	0.12	-9999	-0.54	28	28
FASLG	-0.062	0.23	-9999	-0.6	77	77
NFKB1	0.008	0.033	-9999	-0.58	1	1
TNFR1A/BAG4/TNF-alpha	0.005	0.078	-9999	-0.32	30	30
CASP6	-0.017	0.059	-9999	-0.5	4	4
CASP7	0.022	0.13	-9999	-0.54	19	19
RELA	0.009	0.023	-9999	-10000	0	0
CASP2	0.011	0	-9999	-10000	0	0
CASP3	0.021	0.13	-9999	-0.54	20	20
TNFRSF1A	0.011	0	-9999	-10000	0	0
TNFR1A/BAG4	0.015	0.026	-9999	-0.42	2	2
CASP8	0.01	0.025	-9999	-0.58	1	1
CASP9	0.01	0.025	-9999	-0.58	1	1
MAP3K14	0.037	0.057	-9999	-0.42	1	1
APAF-1/Caspase 9	-0.038	0.1	-9999	-0.44	25	25
BCL2	0.015	0.094	-9999	-0.46	9	9

×

PDGFR-beta 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.013	0.12	-9999	-0.45	25	25
PDGFB-D/PDGFRB/SLAP	-0.011	0.11	-9999	-0.4	38	38
PDGFB-D/PDGFRB/APS/CBL	-0.003	0.09	-9999	-0.34	27	27
AKT1	0.031	0.065	-9999	-0.48	3	3
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.013	0.12	-9999	-0.48	24	24
PIK3CA	0.009	0.035	-9999	-0.58	2	2
FGR	-0.037	0.15	-9999	-0.56	34	34
mol:Ca2+	-0.004	0.1	-9999	-0.58	14	14
MYC	0.001	0.12	-9999	-0.6	14	14
SHC1	0.011	0	-9999	-10000	0	0
HRAS/GDP	0.018	0.065	-9999	-0.32	15	15
LRP1/PDGFRB/PDGFB	0.008	0.077	-9999	-0.39	17	17
GRB10	0.007	0.049	-9999	-0.58	4	4
PTPN11	0.006	0.055	-9999	-0.58	5	5
GO:0007205	-0.004	0.11	-9999	-0.59	14	14
PTEN	0.005	0.06	-9999	-0.58	6	6
GRB2	0.011	0	-9999	-10000	0	0
GRB7	0.002	0.067	-9999	-0.46	12	12
PDGFB-D/PDGFRB/SHP2	0.002	0.076	-9999	-0.39	20	20
PDGFB-D/PDGFRB/GRB10	0.003	0.073	-9999	-0.39	19	19
cell cycle arrest	-0.011	0.11	-9999	-0.4	38	38
HRAS	0.008	0.042	-9999	-0.49	4	4
HIF1A	0.032	0.078	-9999	-0.5	7	7
GAB1	-0.014	0.12	-9999	-0.63	14	14
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.01	0.12	-9999	-0.56	14	14
PDGFB-D/PDGFRB	0.013	0.066	-9999	-0.36	15	15
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.006	0.064	-9999	-0.38	15	15
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.037	0.12	-9999	-0.47	25	25
positive regulation of MAPKKK cascade	0.002	0.075	-9999	-0.39	20	20
PIK3R1	0.008	0.043	-9999	-0.58	3	3
mol:IP3	-0.004	0.11	-9999	-0.6	14	14
E5	0	0.001	-9999	-10000	0	0
CSK	0.01	0.024	-9999	-0.57	1	1
PDGFB-D/PDGFRB/GRB7	-0.001	0.081	-9999	-0.36	26	26
SHB	0.011	0.019	-9999	-0.46	1	1
BLK	-0.096	0.2	-9999	-0.56	85	85
PTPN2	0.008	0.043	-9999	-0.58	3	3
PDGFB-D/PDGFRB/SNX15	0.006	0.064	-9999	-0.38	15	15
BCAR1	0.008	0.044	-9999	-0.52	4	4
VAV2	-0.018	0.14	-9999	-0.6	20	20
CBL	0.011	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.006	0.067	-9999	-0.38	16	16
LCK	-0.036	0.13	-9999	-0.5	34	34
PDGFRB	-0.003	0.088	-9999	-0.54	15	15
ACP1	0.011	0	-9999	-10000	0	0
HCK	-0.034	0.16	-9999	-0.61	33	33
ABL1	-0.015	0.12	-9999	-0.54	17	17
PDGFB-D/PDGFRB/CBL	-0.017	0.13	-9999	-0.7	13	13
PTPN1	0.01	0.025	-9999	-0.59	1	1
SNX15	0.011	0	-9999	-10000	0	0
STAT3	0.011	0	-9999	-10000	0	0
STAT1	0.006	0.052	-9999	-0.5	6	6
cell proliferation	0.003	0.11	-9999	-0.53	14	14
SLA	-0.013	0.11	-9999	-0.52	26	26
actin cytoskeleton reorganization	0.027	0.066	-9999	-0.5	3	3
SRC	-0.011	0.066	-9999	-0.4	14	14
PI3K	-0.013	0.058	-9999	-0.52	2	2
PDGFB-D/PDGFRB/GRB7/SHC	0.008	0.069	-9999	-0.35	12	12
SH2B2	-0.015	0.12	-9999	-0.52	29	29
PLCgamma1/SPHK1	-0.014	0.13	-9999	-0.5	24	24
LYN	-0.009	0.062	-9999	-0.38	13	13
LRP1	0.004	0.063	-9999	-0.56	7	7
SOS1	0.01	0.025	-9999	-0.58	1	1
STAT5B	0.011	0	-9999	-10000	0	0
STAT5A	0.011	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0	0.063	-9999	-0.54	2	2
SPHK1	-0.029	0.14	-9999	-0.51	45	45
EDG1	0	0.003	-9999	-10000	0	0
mol:DAG	-0.004	0.11	-9999	-0.6	14	14
PLCG1	-0.005	0.11	-9999	-0.62	14	14
NHERF/PDGFRB	0.013	0.057	-9999	-0.36	10	10
YES1	-0.017	0.098	-9999	-0.52	17	17
cell migration	0.013	0.057	-9999	-0.35	10	10
SHC/Grb2/SOS1	0.003	0.053	-9999	-10000	0	0
SLC9A3R2	0.01	0.025	-9999	-0.58	1	1
SLC9A3R1	0.011	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.017	0.062	-9999	-0.32	16	16
FYN	-0.015	0.086	-9999	-0.46	17	17
DOK1	0.016	0.058	-9999	-0.32	13	13
HRAS/GTP	0.006	0.03	-9999	-0.35	4	4
PDGFB	0.008	0.042	-9999	-0.49	4	4
RAC1	-0.008	0.13	-9999	-0.59	19	19
PRKCD	0.016	0.059	-9999	-0.33	13	13
FER	0.01	0.076	-9999	-0.36	17	17
MAPKKK cascade	-0.008	0.047	-9999	-10000	0	0
RASA1	0.015	0.065	-9999	-0.35	14	14
NCK1	0.009	0.035	-9999	-0.58	2	2
NCK2	0.01	0.025	-9999	-0.58	1	1
p62DOK/Csk	0.021	0.055	-9999	-0.29	12	12
PDGFB-D/PDGFRB/SHB	0.006	0.065	-9999	-0.38	16	16
chemotaxis	-0.014	0.11	-9999	-0.52	17	17
STAT1-3-5/STAT1-3-5	-0.009	0.052	-9999	-0.55	1	1
Bovine Papilomavirus E5/PDGFRB	-0.002	0.064	-9999	-0.39	15	15
PTPRJ	0.01	0.025	-9999	-0.58	1	1

×

Regulation of Androgen receptor activity

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
HDAC1	0.016	0.019	-9999	-0.43	1	1
SMARCC1	0.002	0.019	-9999	-10000	0	0
REL	0.011	0.043	-9999	-0.58	3	3
HDAC7	0.027	0.093	-9999	-0.54	7	7
JUN	0.004	0.053	-9999	-0.56	5	5
EP300	0.007	0.049	-9999	-0.58	4	4
KAT2B	-0.007	0.1	-9999	-0.58	17	17
KAT5	0.011	0.025	-9999	-0.58	1	1
MAPK14	0.011	0.061	-9999	-0.44	10	10
FOXO1	0.01	0.025	-9999	-0.58	1	1
T-DHT/AR	0.024	0.099	-9999	-0.55	8	8
MAP2K6	0.001	0.079	-9999	-0.59	10	10
BRM/BAF57	0.009	0.042	-9999	-0.43	5	5
MAP2K4	0.008	0.043	-9999	-0.58	3	3
SMARCA2	0.005	0.05	-9999	-0.59	4	4
PDE9A	-0.08	0.28	-9999	-1	42	42
NCOA2	0.003	0.068	-9999	-0.56	8	8
CEBPA	-0.005	0.099	-9999	-0.57	17	17
EHMT2	0.007	0.032	-9999	-0.52	2	2
cell proliferation	0.023	0.12	-9999	-0.49	17	17
NR0B1	-0.001	0.051	-9999	-0.46	7	7
EGR1	-0.015	0.11	-9999	-0.5	27	27
RXRs/9cRA	0.004	0.055	-9999	-0.24	26	26
AR/RACK1/Src	0.015	0.075	-9999	-0.42	8	8
AR/GR	-0.011	0.1	-9999	-0.35	31	31
GNB2L1	0.011	0.02	-9999	-0.46	1	1
PKN1	0.008	0.043	-9999	-0.58	3	3
RCHY1	0.01	0.025	-9999	-0.58	1	1
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.016	0.038	-9999	-0.42	4	4
T-DHT/AR/TIF2/CARM1	0.02	0.086	-9999	-0.43	11	11
SRC	0.023	0.061	-9999	-0.36	10	10
NR3C1	-0.015	0.12	-9999	-0.54	28	28
KLK3	-0.19	0.36	-9999	-0.97	78	78
APPBP2	0.008	0.049	-9999	-0.58	4	4
TRIM24	0.009	0.006	-9999	-10000	0	0
T-DHT/AR/TIP60	0.018	0.078	-9999	-0.48	8	8
TMPRSS2	-0.024	0.14	-9999	-0.84	10	10
RXRG	-0.013	0.096	-9999	-0.46	25	25
mol:9cRA	-0.001	0.002	-9999	-10000	0	0
RXRA	0.01	0.025	-9999	-0.58	1	1
RXRB	0.011	0.001	-9999	-10000	0	0
CARM1	0.01	0.025	-9999	-0.58	1	1
NR2C2	0.01	0.025	-9999	-0.58	1	1
KLK2	0.015	0.11	-9999	-0.45	11	11
AR	-0.001	0.084	-9999	-0.33	14	14
SENP1	0.01	0.025	-9999	-0.58	1	1
HSP90AA1	0.009	0.035	-9999	-0.58	2	2
MDM2	0.012	0.046	-9999	-0.52	4	4
SRY	0.001	0.039	-9999	-0.45	4	4
GATA2	-0.014	0.12	-9999	-0.55	26	26
MYST2	0.011	0.025	-9999	-0.58	1	1
HOXB13	-0.095	0.21	-9999	-0.5	117	117
T-DHT/AR/RACK1/Src	0.021	0.074	-9999	-0.42	8	8
positive regulation of transcription	-0.014	0.12	-9999	-0.55	26	26
DNAJA1	0.012	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.042	-9999	-0.47	3	3
NCOA1	0.011	0.027	-9999	-0.62	1	1
SPDEF	-0.16	0.25	-9999	-0.53	178	178
T-DHT/AR/TIF2	0.013	0.11	-9999	-0.75	6	6
T-DHT/AR/Hsp90	0.016	0.076	-9999	-0.45	9	9
GSK3B	0.009	0.035	-9999	-0.58	2	2
NR2C1	0.011	0.025	-9999	-0.58	1	1
mol:T-DHT	0.02	0.064	-9999	-0.37	13	13
SIRT1	0.006	0.055	-9999	-0.58	5	5
ZMIZ2	0.014	0.027	-9999	-0.58	1	1
POU2F1	0.01	0.078	-9999	-0.54	10	10
T-DHT/AR/DAX-1	0.008	0.076	-9999	-0.43	9	9
CREBBP	0.011	0.001	-9999	-10000	0	0
SMARCE1	0.008	0.025	-9999	-0.58	1	1

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.015	0.036	-10000	0	-0.54	2	2
CRKL	0.014	0.061	-10000	0	-0.27	1	1
mol:PIP3	-0.01	0.055	0.52	6	-10000	0	6
AKT1	0.004	0.039	0.36	6	-0.3	1	7
PTK2B	0.009	0.035	-10000	0	-0.58	2	2
RAPGEF1	0.018	0.061	-10000	0	-0.37	1	1
RANBP10	0.011	0	-10000	0	-10000	0	0
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
HGF/MET/SHIP2	-0.008	0.1	-10000	0	-0.33	52	52
MAP3K5	0.004	0.099	-10000	0	-0.4	14	14
HGF/MET/CIN85/CBL/ENDOPHILINS	0	0.094	-10000	0	-0.32	38	38
AP1	-0.014	0.098	-10000	0	-0.33	48	48
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.011	0	-10000	0	-10000	0	0
apoptosis	-0.026	0.17	-10000	0	-0.74	29	29
STAT3 (dimer)	0.011	0.075	-10000	0	-0.25	41	41
GAB1/CRKL/SHP2/PI3K	-0.017	0.067	-10000	0	-0.68	3	3
INPP5D	-0.015	0.12	-10000	0	-0.58	26	26
CBL/CRK	0.019	0.061	-10000	0	-0.44	1	1
PTPN11	0.006	0.055	-10000	0	-0.58	5	5
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.01	0.025	-10000	0	-0.58	1	1
PTEN	0.005	0.06	-10000	0	-0.58	6	6
ELK1	-0.001	0.025	0.23	2	-0.31	2	4
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.013	0.046	-10000	0	-0.36	3	3
PAK1	0.009	0.036	0.34	6	-0.28	1	7
HGF/MET/RANBP10	-0.008	0.1	-10000	0	-0.33	51	51
HRAS	0.004	0.096	-10000	0	-1.1	1	1
DOCK1	0.018	0.062	-10000	0	-0.53	1	1
GAB1	0.008	0.064	-10000	0	-0.28	2	2
CRK	0.013	0.063	-10000	0	-0.37	2	2
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.008	0.13	-10000	0	-0.49	36	36
JUN	0.006	0.053	-10000	0	-0.56	5	5
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.004	0.057	-10000	0	-0.21	37	37
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
cell morphogenesis	0.028	0.092	-10000	0	-0.59	4	4
GRB2/SHC	0.01	0.051	-10000	0	-0.24	2	2
FOS	-0.03	0.14	-10000	0	-0.53	44	44
GLMN	-0.008	0.047	-10000	0	-0.27	18	18
cell motility	-0.001	0.025	0.23	2	-0.31	2	4
HGF/MET/MUC20	-0.015	0.1	-10000	0	-0.33	51	51
cell migration	0.01	0.051	-10000	0	-0.24	2	2
GRB2	0.011	0	-10000	0	-10000	0	0
CBL	0.011	0	-10000	0	-10000	0	0
MET/RANBP10	0.016	0.023	-10000	0	-0.37	2	2
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.007	0.076	-10000	0	-0.25	41	41
MET/MUC20	0.007	0.023	-10000	0	-0.38	2	2
RAP1B	0.023	0.058	-10000	0	-0.34	1	1
RAP1A	0.023	0.059	-10000	0	-0.34	1	1
HGF/MET/RANBP9	-0.008	0.1	-10000	0	-0.33	51	51
RAF1	0.01	0.09	-10000	0	-1	1	1
STAT3	0.011	0.076	-10000	0	-0.31	3	3
cell proliferation	0.015	0.097	-10000	0	-0.34	37	37
RPS6KB1	-0.001	0.043	-10000	0	-0.33	5	5
MAPK3	-0.004	0.031	0.67	1	-0.24	1	2
MAPK1	-0.004	0.031	0.67	1	-0.24	1	2
RANBP9	0.01	0.025	-10000	0	-0.58	1	1
MAPK8	0.019	0.089	-10000	0	-0.37	13	13
SRC	0.012	0.074	-10000	0	-0.53	1	1
PI3K	0.007	0.063	-10000	0	-0.39	5	5
MET/Glomulin	0.003	0.043	-10000	0	-0.22	20	20
SOS1	0.01	0.025	-10000	0	-0.58	1	1
MAP2K1	0.015	0.089	-10000	0	-1.1	1	1
MET	0.01	0.031	-10000	0	-0.52	2	2
MAP4K1	-0.001	0.1	-10000	0	-0.42	13	13
PTK2	0.01	0.025	-10000	0	-0.58	1	1
MAP2K2	0.015	0.087	-10000	0	-0.7	2	2
BAD	0.008	0.043	0.34	6	-0.58	1	7
MAP2K4	0.009	0.094	-10000	0	-0.38	12	12
SHP2/GRB2/SOS1/GAB1	-0.016	0.057	-10000	0	-0.47	3	3
INPPL1	0.01	0.025	-10000	0	-0.58	1	1
PXN	0.011	0	-10000	0	-10000	0	0
SH3KBP1	0.009	0.035	-10000	0	-0.58	2	2
HGS	0.002	0.054	-10000	0	-0.25	3	3
PLCgamma1/PKC	0.008	0.018	-10000	0	-0.43	1	1
HGF	-0.036	0.16	-10000	0	-0.55	49	49
RASA1	0.009	0.035	-10000	0	-0.58	2	2
NCK1	0.009	0.035	-10000	0	-0.58	2	2
PTPRJ	0.01	0.025	-10000	0	-0.58	1	1
NCK/PLCgamma1	0.008	0.063	-10000	0	-0.32	4	4
PDPK1	-0.003	0.043	0.41	6	-10000	0	6
HGF/MET/SHIP	-0.025	0.12	-10000	0	-0.34	76	76

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.004	0.086	0.46	6	-10000	0	6
GNAI2	0.011	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.009	0.047	-10000	0	-0.33	11	11
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.044	0.16	-10000	0	-0.49	63	63
RhoA/GTP	-0.004	0.088	-10000	0	-0.48	6	6
negative regulation of cAMP metabolic process	-0.01	0.094	-10000	0	-0.3	27	27
GNAZ	-0.012	0.11	-10000	0	-0.54	24	24
GNAI3	0.011	0	-10000	0	-10000	0	0
GNA12	0.011	0	-10000	0	-10000	0	0
S1PR5	0.001	0.075	-10000	0	-0.54	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.01	0.095	-10000	0	-0.3	27	27
RhoA/GDP	0.008	0.018	-10000	0	-0.43	1	1
RHOA	0.01	0.025	-10000	0	-0.58	1	1
GNAI1	-0.002	0.088	-10000	0	-0.55	14	14

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.022	0.022	-9999	-0.35	2	2
SNTA1	0.006	0.056	-9999	-0.54	6	6
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.012	0.067	-9999	-0.38	16	16
MAPK12	-0.002	0.092	-9999	-0.37	22	22
CCND1	0.006	0.042	-9999	-0.22	8	8
p38 gamma/SNTA1	0.001	0.093	-9999	-0.38	21	21
MAP2K3	0.01	0.025	-9999	-0.58	1	1
PKN1	0.008	0.043	-9999	-0.58	3	3
G2/M transition checkpoint	-0.002	0.091	-9999	-0.37	22	22
MAP2K6	0.009	0.06	-9999	-0.32	18	18
MAPT	-0.023	0.11	-9999	-0.33	47	47
MAPK13	0.017	0.026	-9999	-0.42	2	2
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.009	0.043	-9999	-0.35	8	8

×

S1P3 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
PDGFRB	-0.003	0.087	-9999	-0.53	15	15
mol:S1P	0	0.005	-9999	-10000	0	0
S1P1/S1P/Gi	-0.008	0.087	-9999	-0.26	46	46
GNAO1	-0.043	0.16	-9999	-0.49	63	63
S1P/S1P3/G12/G13	0.018	0.041	-9999	-0.3	9	9
AKT1	0.002	0.09	-9999	-0.56	10	10
AKT3	-0.011	0.2	-9999	-1.2	12	12
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.003	0.087	-9999	-0.53	15	15
GNAI2	0.012	0.004	-9999	-10000	0	0
GNAI3	0.012	0.004	-9999	-10000	0	0
GNAI1	-0.002	0.088	-9999	-0.56	14	14
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.005	0.061	-9999	-0.54	7	7
S1PR2	0.011	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.008	0.11	-9999	-0.44	17	17
MAPK3	-0.002	0.11	-9999	-0.51	12	12
MAPK1	-0.002	0.11	-9999	-0.51	12	12
JAK2	-0.011	0.13	-9999	-0.46	24	24
CXCR4	-0.016	0.13	-9999	-0.49	25	25
FLT1	0.007	0.057	-9999	-0.54	6	6
RhoA/GDP	0.008	0.018	-9999	-0.43	1	1
Rac1/GDP	0.008	0	-9999	-10000	0	0
SRC	-0.002	0.11	-9999	-0.49	12	12
S1P/S1P3/Gi	-0.008	0.11	-9999	-0.44	17	17
RAC1	0.011	0	-9999	-10000	0	0
RhoA/GTP	-0.003	0.1	-9999	-0.48	12	12
VEGFA	0.012	0.02	-9999	-0.45	1	1
S1P/S1P2/Gi	-0.004	0.09	-9999	-0.31	19	19
VEGFR1 homodimer/VEGFA homodimer	0.017	0.046	-9999	-0.38	7	7
RHOA	0.01	0.025	-9999	-0.58	1	1
S1P/S1P3/Gq	0	0.099	-9999	-0.34	36	36
GNAQ	0.005	0.06	-9999	-0.58	6	6
GNAZ	-0.011	0.11	-9999	-0.54	24	24
G12/G13	0.015	0.026	-9999	-0.42	2	2
GNA14	-0.008	0.1	-9999	-0.56	19	19
GNA15	-0.009	0.1	-9999	-0.54	21	21
GNA12	0.011	0	-9999	-10000	0	0
GNA13	0.009	0.035	-9999	-0.58	2	2
GNA11	0.007	0.051	-9999	-0.53	5	5
Rac1/GTP	-0.002	0.1	-9999	-0.5	11	11

×

Class IB PI3K non-lipid kinase events

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	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	0.081	0.58	11	-10000	0	11
PI3K Class IB/PDE3B	0.081	-10000	0	-0.58	11	11
PDE3B	0.081	-10000	0	-0.58	11	11

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.011	0	-10000	0	-10000	0	0
NFATC1	0.031	0.06	-10000	0	-0.3	14	14
NFATC2	0.015	0.057	-10000	0	-0.24	12	12
NFATC3	0.017	0.02	-10000	0	-0.41	1	1
YWHAE	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.054	0.14	-10000	0	-0.46	34	34
Exportin 1/Ran/NUP214	0.015	0.052	-10000	0	-0.35	11	11
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.067	0.13	-10000	0	-0.47	37	37
BCL2/BAX	0.003	0.076	-10000	0	-0.4	20	20
CaM/Ca2+/Calcineurin A alpha-beta B1	0.009	0.004	-10000	0	-10000	0	0
CaM/Ca2+	0.009	0.004	-10000	0	-10000	0	0
BAX	0.01	0.025	-10000	0	-0.58	1	1
MAPK14	0.011	0.003	-10000	0	-10000	0	0
BAD	0.01	0.031	-10000	0	-0.52	2	2
CABIN1/MEF2D	-0.046	0.13	-10000	0	-0.44	35	35
Calcineurin A alpha-beta B1/BCL2	-0.007	0.1	-10000	0	-0.55	19	19
FKBP8	0.009	0.035	-10000	0	-0.58	2	2
activation-induced cell death of T cells	0.045	0.13	0.43	35	-10000	0	35
KPNB1	0.011	0	-10000	0	-10000	0	0
KPNA2	0.011	0	-10000	0	-10000	0	0
XPO1	0	0.081	-10000	0	-0.58	11	11
SFN	0.005	0.057	-10000	0	-0.47	8	8
MAP3K8	0.009	0.032	-10000	0	-0.52	2	2
NFAT4/CK1 alpha	0.022	0.047	-10000	0	-0.38	6	6
MEF2D/NFAT1/Cbp/p300	0.022	0.097	-10000	0	-0.42	12	12
CABIN1	-0.054	0.14	-10000	0	-0.47	34	34
CALM1	0.011	0.002	-10000	0	-10000	0	0
RAN	0.011	0	-10000	0	-10000	0	0
MAP3K1	0.005	0.06	-10000	0	-0.58	6	6
CAMK4	-0.013	0.11	-10000	0	-0.55	25	25
mol:Ca2+	0	0.004	-10000	0	-10000	0	0
MAPK3	0.01	0.025	-10000	0	-0.58	1	1
YWHAH	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.008	0.094	-10000	0	-0.37	35	35
YWHAB	0.011	0	-10000	0	-10000	0	0
MAPK8	0.01	0.025	-10000	0	-0.58	1	1
MAPK9	0.011	0	-10000	0	-10000	0	0
YWHAG	0.011	0	-10000	0	-10000	0	0
FKBP1A	0.011	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.04	0.061	-10000	0	-0.34	4	4
PRKCH	0.005	0.06	-10000	0	-0.58	6	6
CABIN1/Cbp/p300	0.013	0.037	-10000	0	-0.42	4	4
CASP3	0.009	0.035	-10000	0	-0.58	2	2
PIM1	0.011	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.008	0.002	-10000	0	-10000	0	0
apoptosis	-0.005	0.037	0.23	1	-0.65	1	2
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.032	0.03	-10000	0	-0.38	2	2
PRKCB	-0.039	0.16	-10000	0	-0.54	52	52
PRKCE	0.011	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.023	0.018	-10000	0	-0.37	1	1
BAD/BCL-XL	0.016	0.023	-10000	0	-0.37	2	2
PRKCD	0.011	0	-10000	0	-10000	0	0
NUP214	0.011	0	-10000	0	-10000	0	0
PRKCZ	0.009	0.032	-10000	0	-0.52	2	2
PRKCA	0.01	0.031	-10000	0	-0.52	2	2
PRKCG	-0.14	0.24	-10000	0	-0.51	171	171
PRKCQ	-0.044	0.17	-10000	0	-0.58	54	54
FKBP38/BCL2	0.002	0.078	-10000	0	-0.4	21	21
EP300	0.007	0.049	-10000	0	-0.58	4	4
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.011	0	-10000	0	-10000	0	0
NFATc/JNK1	0.034	0.06	-10000	0	-0.32	4	4
CaM/Ca2+/FKBP38	0.014	0.023	-10000	0	-0.36	2	2
FKBP12/FK506	0.008	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0.023	-10000	0	-0.36	2	2
CaM/Ca2+/CAMK IV	0	0.072	-10000	0	-0.33	25	25
NFATc/ERK1	0.035	0.058	-10000	0	-0.31	2	2
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.067	0.13	-10000	0	-0.47	36	36
NR4A1	0.011	0.13	-10000	0	-0.41	45	45
GSK3B	0.009	0.035	-10000	0	-0.58	2	2
positive T cell selection	0.017	0.02	-10000	0	-0.41	1	1
NFAT1/CK1 alpha	-0.012	0.045	-10000	0	-0.42	4	4
RCH1/ KPNB1	0.017	0	-10000	0	-10000	0	0
YWHAQ	0.011	0	-10000	0	-10000	0	0
PRKACA	0.011	0.003	-10000	0	-10000	0	0
AKAP5	-0.021	0.13	-10000	0	-0.52	35	35
MEF2D	0.01	0.025	-10000	0	-0.59	1	1
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.008	0.043	-10000	0	-0.58	3	3
NFATc/p38 alpha	0.034	0.058	-10000	0	-0.31	2	2
CREBBP	0.011	0.002	-10000	0	-10000	0	0
BCL2	-0.007	0.1	-10000	0	-0.55	19	19

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.018	0.094	-9999	-0.5	19	19
MDM2/SUMO1	0.003	0.11	-9999	-0.58	19	19
HDAC4	0.011	0.019	-9999	-0.46	1	1
Ran/GTP/Exportin 1/HDAC1	-0.018	0.094	-9999	-0.5	19	19
SUMO1	-0.008	0.11	-9999	-0.58	19	19
NPC/RanGAP1/SUMO1	-0.005	0.097	-9999	-0.44	24	24
mol:GTP	0	0	-9999	-10000	0	0
XPO1	-0.001	0.12	-9999	-0.54	24	24
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	-0.008	0.1	-9999	-0.57	19	19
SUMO1/HDAC4	0.004	0.11	-9999	-0.55	19	19
SUMO1/HDAC1	0.005	0.11	-9999	-0.55	19	19
RANGAP1	0.01	0.031	-9999	-0.52	2	2
MDM2/SUMO1/SUMO1	0.015	0.073	-9999	-0.35	19	19
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	-0.001	0.097	-9999	-0.43	24	24
Ran/GTP	0.005	0.089	-9999	-0.53	14	14
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.008	0.044	-9999	-0.52	4	4
UBE2I	0.011	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.005	0.12	-9999	-0.68	15	15
NPC	-0.004	0.057	-9999	-0.31	19	19
PIAS2	0.01	0.027	-9999	-0.46	2	2
PIAS1	0.011	0	-9999	-10000	0	0
EntrezGene:9972	0	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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.023	0.049	-10000	0	-0.37	6	6
HDAC3	0.011	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.014	0.077	-10000	0	-0.4	19	19
GATA1/HDAC4	0.005	0.054	-10000	0	-0.32	15	15
GATA1/HDAC5	0.004	0.057	-10000	0	-0.33	16	16
GATA2/HDAC5	-0.003	0.092	-10000	0	-0.41	27	27
HDAC5/BCL6/BCoR	0.02	0.031	-10000	0	-0.28	6	6
HDAC9	-0.038	0.16	-10000	0	-0.54	51	51
Glucocorticoid receptor/Hsp90/HDAC6	0.005	0.08	-10000	0	-0.37	19	19
HDAC4/ANKRA2	0.016	0.023	-10000	0	-0.37	2	2
HDAC5/YWHAB	0.016	0.023	-10000	0	-0.37	2	2
NPC/RanGAP1/SUMO1/Ubc9	-0.001	0.097	-10000	0	-0.43	24	24
GATA2	-0.014	0.12	-10000	0	-0.55	26	26
HDAC4/RFXANK	0.014	0.032	-10000	0	-0.37	4	4
BCOR	0.011	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.007	0.047	-10000	0	-0.55	4	4
HDAC5	0.01	0.031	-10000	0	-0.52	2	2
GNB1/GNG2	0.011	0.047	-10000	0	-0.38	8	8
Histones	0.011	0.081	-10000	0	-1.2	1	1
ADRBK1	0.009	0.037	-10000	0	-0.5	3	3
HDAC4	0.011	0.019	-10000	0	-0.46	1	1
XPO1	0	0.081	-10000	0	-0.58	11	11
HDAC5/ANKRA2	0.015	0.029	-10000	0	-0.39	3	3
HDAC4/Ubc9	0.016	0.014	-10000	0	-0.32	1	1
HDAC7	0.01	0.025	-10000	0	-0.58	1	1
HDAC5/14-3-3 E	0.016	0.023	-10000	0	-0.37	2	2
TUBA1B	0.011	0	-10000	0	-10000	0	0
HDAC6	0.011	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.014	0.042	-10000	0	-0.46	4	4
CAMK4	-0.013	0.11	-10000	0	-0.55	25	25
Tubulin/HDAC6	0.006	0.072	-10000	0	-0.29	32	32
SUMO1	-0.008	0.11	-10000	0	-0.58	19	19
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.011	0	-10000	0	-10000	0	0
GATA1	-0.004	0.073	-10000	0	-0.46	14	14
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.011	0	-10000	0	-10000	0	0
NR3C1	-0.015	0.12	-10000	0	-0.54	28	28
SUMO1/HDAC4	0.004	0.11	-10000	0	-0.55	19	19
SRF	0.01	0.027	-10000	0	-0.46	2	2
HDAC4/YWHAB	0.016	0.014	-10000	0	-0.32	1	1
Tubulin	-0.003	0.085	-10000	0	-0.35	32	32
HDAC4/14-3-3 E	0.016	0.014	-10000	0	-0.32	1	1
GNB1	0.011	0	-10000	0	-10000	0	0
RANGAP1	0.01	0.031	-10000	0	-0.52	2	2
BCL6/BCoR	0.015	0.028	-10000	0	-0.32	4	4
HDAC4/HDAC3/SMRT (N-CoR2)	0.02	0.032	-10000	0	-0.32	5	5
HDAC4/SRF	0.006	0.076	-10000	0	-0.33	27	27
HDAC4/ER alpha	-0.018	0.11	-10000	0	-0.37	51	51
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.011	0.08	-10000	0	-1.2	1	1
cell motility	0.006	0.072	-10000	0	-0.29	32	32
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.011	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.016	0.018	-10000	0	-0.42	1	1
BCL6	0.008	0.039	-10000	0	-0.46	4	4
HDAC4/CaMK II delta B	0.011	0.019	-10000	0	-0.45	1	1
Hsp90/HDAC6	0.015	0.026	-10000	0	-0.42	2	2
ESR1	-0.036	0.15	-10000	0	-0.52	50	50
HDAC6/HDAC11	0.015	0.026	-10000	0	-0.42	2	2
Ran/GTP/Exportin 1	0.006	0.12	-10000	0	-0.68	15	15
NPC	-0.004	0.057	-10000	0	-0.31	19	19
MEF2C	0.001	0.074	-10000	0	-0.52	11	11
RAN	0.011	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.026	0.048	-10000	0	-0.29	9	9
GNG2	0.004	0.064	-10000	0	-0.53	8	8
NCOR2	0.007	0.047	-10000	0	-0.55	4	4
TUBB2A	-0.017	0.12	-10000	0	-0.49	32	32
HDAC11	0.009	0.035	-10000	0	-0.58	2	2
HSP90AA1	0.009	0.035	-10000	0	-0.58	2	2
RANBP2	-0.008	0.1	-10000	0	-0.57	19	19
ANKRA2	0.01	0.025	-10000	0	-0.58	1	1
RFXANK	0.008	0.04	-10000	0	-0.54	3	3
nuclear import	-0.023	0.019	0.32	1	-10000	0	1

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0	-9999	-10000	0	0
HDAC2	0.011	0.001	-9999	-10000	0	0
GNB1/GNG2	0.001	0.089	-9999	-0.34	35	35
forebrain development	0	0.15	-9999	-0.57	23	23
GNAO1	-0.043	0.16	-9999	-0.49	63	63
SMO/beta Arrestin2	-0.001	0.091	-9999	-0.4	28	28
SMO	-0.015	0.12	-9999	-0.56	28	28
ARRB2	0.012	0.002	-9999	-10000	0	0
GLI3/SPOP	0.015	0.099	-9999	-0.67	5	5
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0.009	0.035	-9999	-0.58	2	2
GNAI2	0.012	0.002	-9999	-10000	0	0
SIN3/HDAC complex	0.026	0.031	-9999	-0.32	4	4
GNAI1	-0.002	0.088	-9999	-0.55	14	14
XPO1	0.002	0.081	-9999	-0.58	11	11
GLI1/Su(fu)	-0.037	0.13	-9999	-0.64	14	14
SAP30	0.009	0.035	-9999	-0.58	2	2
mol:GDP	-0.015	0.12	-9999	-0.56	28	28
MIM/GLI2A	0.002	0.091	-9999	-0.54	15	15
IFT88	0.007	0.049	-9999	-0.58	4	4
GNAI3	0.012	0.002	-9999	-10000	0	0
GLI2	0.023	0.058	-9999	-0.57	2	2
GLI3	0.009	0.1	-9999	-0.71	5	5
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
SAP18	0.01	0.019	-9999	-0.46	1	1
embryonic digit morphogenesis	0.007	0.049	-9999	-0.58	4	4
GNG2	0.004	0.064	-9999	-0.53	8	8
Gi family/GTP	-0.016	0.11	-9999	-0.34	39	39
SIN3B	0.01	0.025	-9999	-0.58	1	1
SIN3A	0.01	0.025	-9999	-0.58	1	1
GLI3/Su(fu)	0.025	0.081	-9999	-0.55	5	5
GLI2/Su(fu)	0.03	0.066	-9999	-0.37	6	6
FOXA2	-0.037	0.18	-9999	-0.96	21	21
neural tube patterning	0	0.15	-9999	-0.57	23	23
SPOP	0.011	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.019	0.043	-9999	-10000	0	0
GNB1	0.011	0	-9999	-10000	0	0
CSNK1G2	0.009	0.035	-9999	-0.58	2	2
CSNK1G3	0.01	0.025	-9999	-0.58	1	1
MTSS1	0.002	0.091	-9999	-0.55	15	15
embryonic limb morphogenesis	0	0.15	-9999	-0.57	23	23
SUFU	0.014	0.048	-9999	-10000	0	0
LGALS3	0.009	0.037	-9999	-0.5	3	3
catabolic process	0.028	0.11	-9999	-0.42	17	17
GLI3A/CBP	0.008	0.06	-9999	-0.35	14	14
KIF3A	0	0.081	-9999	-0.58	11	11
GLI1	-0.001	0.15	-9999	-0.59	23	23
RAB23	0.006	0.056	-9999	-0.54	6	6
CSNK1A1	0.009	0.035	-9999	-0.58	2	2
IFT172	0.011	0	-9999	-10000	0	0
RBBP7	0.01	0.025	-9999	-0.58	1	1
Su(fu)/Galectin3	0.017	0.049	-9999	-0.36	2	2
GNAZ	-0.012	0.11	-9999	-0.54	24	24
RBBP4	0.01	0.025	-9999	-0.58	1	1
CSNK1G1	0.01	0.025	-9999	-0.58	1	1
PIAS1	0.011	0	-9999	-10000	0	0
PRKACA	0.011	0	-9999	-10000	0	0
GLI2/SPOP	0.028	0.055	-9999	-0.54	2	2
STK36	0.014	0.003	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.008	0.1	-9999	-0.45	13	13
PTCH1	0	0.17	-9999	-0.97	11	11
MIM/GLI1	0.001	0.17	-9999	-0.61	26	26
CREBBP	0.008	0.06	-9999	-0.35	14	14
Su(fu)/SIN3/HDAC complex	0.035	0.027	-9999	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.028	0.084	-9999	-0.5	5	5
TC10/GTP	-0.022	0.071	-9999	-0.47	2	2
Insulin Receptor/Insulin/IRS1/Shp2	0.014	0.06	-9999	-0.33	16	16
HRAS	0.008	0.042	-9999	-0.49	4	4
APS homodimer	-0.015	0.12	-9999	-0.52	29	29
GRB14	-0.12	0.24	-9999	-0.54	138	138
FOXO3	0.001	0.058	-9999	-0.66	3	3
AKT1	-0.031	0.12	-9999	-0.38	2	2
INSR	0.01	0.035	-9999	-0.58	2	2
Insulin Receptor/Insulin	0.027	0.034	-9999	-0.6	1	1
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.007	0.049	-9999	-0.58	4	4
SORBS1	-0.013	0.11	-9999	-0.51	27	27
CRK	0.011	0.019	-9999	-0.46	1	1
PTPN1	0.025	0.033	-9999	-0.59	1	1
CAV1	0.008	0.064	-9999	-0.32	15	15
CBL/APS/CAP/Crk-II/C3G	0.006	0.088	-9999	-0.31	27	27
Insulin Receptor/Insulin/IRS1/NCK2	0.017	0.052	-9999	-0.32	12	12
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.048	-9999	-0.28	16	16
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.025	0.045	-9999	-0.51	2	2
RPS6KB1	-0.026	0.12	-9999	-0.57	2	2
PARD6A	0.007	0.046	-9999	-0.48	5	5
CBL	0.011	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.001	0.008	-9999	-10000	0	0
PIK3R1	0.008	0.043	-9999	-0.58	3	3
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.055	0.093	-9999	-0.53	2	2
HRAS/GTP	-0.018	0.066	-9999	-0.47	3	3
Insulin Receptor	0.01	0.035	-9999	-0.58	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.023	0.046	-9999	-0.3	11	11
PRKCI	-0.019	0.055	-9999	-0.59	4	4
Insulin Receptor/Insulin/GRB14/PDK1	-0.064	0.11	-9999	-0.42	2	2
SHC1	0.011	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.019	0.028	-9999	-0.31	1	1
PI3K	-0.009	0.048	-9999	-0.29	16	16
NCK2	0.01	0.025	-9999	-0.58	1	1
RHOQ	0.011	0	-9999	-10000	0	0
mol:H2O2	0	0.004	-9999	-10000	0	0
HRAS/GDP	0.006	0.03	-9999	-0.35	4	4
AKT2	-0.032	0.12	-9999	-0.4	4	4
PRKCZ	-0.017	0.042	-9999	-0.78	1	1
SH2B2	-0.015	0.12	-9999	-0.52	29	29
SHC/SHIP	0.007	0.08	-9999	-0.3	36	36
F2RL2	-0.036	0.16	-9999	-0.56	47	47
TRIP10	0.01	0.025	-9999	-0.58	1	1
Insulin Receptor/Insulin/Shc	0.015	0.023	-9999	-0.31	2	2
TC10/GTP/CIP4/Exocyst	0.015	0.016	-9999	-0.36	1	1
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.027	0.026	-9999	-0.3	1	1
RAPGEF1	0.01	0.025	-9999	-0.58	1	1
RASA1	0.009	0.035	-9999	-0.58	2	2
NCK1	0.009	0.035	-9999	-0.58	2	2
CBL/APS/CAP/Crk-II	0	0.093	-9999	-0.33	26	26
TC10/GDP	0.008	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.02	0.038	-9999	-0.32	6	6
INPP5D	0	0.084	-9999	-0.32	36	36
SOS1	0.01	0.025	-9999	-0.58	1	1
SGK1	-0.012	0.07	-9999	-0.93	3	3
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.006	0.055	-9999	-0.58	5	5
IRS1	0.002	0.074	-9999	-0.58	9	9
p62DOK/RasGAP	0.02	0.028	-9999	-0.31	1	1
INS	0.001	0.027	-9999	-0.45	2	2
mol:PI-3-4-P2	0	0.084	-9999	-0.32	36	36
GRB2	0.011	0	-9999	-10000	0	0
EIF4EBP1	-0.024	0.11	-9999	-0.5	3	3
PTPRA	0.012	0.003	-9999	-10000	0	0
PIK3CA	0.009	0.035	-9999	-0.58	2	2
TC10/GTP/CIP4	0.015	0.016	-9999	-0.36	1	1
PDPK1	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.021	0.041	-9999	-0.25	12	12
Insulin Receptor/Insulin/IRS1	0.01	0.049	-9999	-0.31	13	13
Insulin Receptor/Insulin/IRS3	0.009	0.032	-9999	-0.37	4	4
Par3/Par6	-0.001	0.093	-9999	-0.31	41	41

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.001	0.078	-10000	0	-0.27	42	42
MAPK9	0.007	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.001	0.019	-10000	0	-0.32	2	2
GNB1/GNG2	0.011	0.04	-10000	0	-0.32	8	8
GNB1	0.011	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	-0.011	0.071	-10000	0	-0.28	36	36
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	0.005	0.018	0.074	36	-10000	0	36
GNAL	-0.021	0.13	-10000	0	-0.5	36	36
GNG2	0.004	0.064	-10000	0	-0.53	8	8
CRH	-0.001	0.027	-10000	0	-0.46	2	2
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.015	-10000	0	-0.36	1	1
MAPK11	0	0.04	-10000	0	-0.22	17	17

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.016	0.088	-9999	-0.47	15	15
STMN1	0.008	0.072	-9999	-0.43	15	15
Aurora B/RasGAP/Survivin	0.025	0.031	-9999	-0.48	2	2
Chromosomal passenger complex/Cul3 protein complex	-0.012	0.078	-9999	-0.39	2	2
BIRC5	0.012	0.02	-9999	-0.46	1	1
DES	-0.11	0.19	-9999	-0.55	90	90
Aurora C/Aurora B/INCENP	0.013	0.063	-9999	-0.3	21	21
Aurora B/TACC1	0.012	0.046	-9999	-0.35	9	9
Aurora B/PP2A	0.019	0.004	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.013	0.012	-9999	-0.28	1	1
mitotic metaphase/anaphase transition	0	0.001	-9999	-10000	0	0
NDC80	0.009	0.069	-9999	-0.43	14	14
Cul3 protein complex	-0.056	0.14	-9999	-0.3	142	142
KIF2C	0.02	0.02	-9999	-0.42	1	1
PEBP1	0.012	0.001	-9999	-10000	0	0
KIF20A	0.009	0.035	-9999	-0.58	2	2
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.018	0.027	-9999	-0.43	2	2
SEPT1	-0.008	0.1	-9999	-0.53	21	21
SMC2	0.002	0.074	-9999	-0.58	9	9
SMC4	-0.004	0.094	-9999	-0.58	15	15
NSUN2/NPM1/Nucleolin	0.024	0.032	-9999	-0.33	1	1
PSMA3	0.011	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.001	-9999	-10000	0	0
H3F3B	0.015	0.002	-9999	-10000	0	0
AURKB	0.015	0.005	-9999	-10000	0	0
AURKC	-0.01	0.11	-9999	-0.55	21	21
CDCA8	0.012	0.001	-9999	-10000	0	0
cytokinesis	0.014	0.04	-9999	-0.32	1	1
Aurora B/Septin1	0.005	0.057	-9999	-0.32	1	1
AURKA	0.011	0.001	-9999	-10000	0	0
INCENP	0.012	0.001	-9999	-10000	0	0
KLHL13	-0.11	0.22	-9999	-0.5	141	141
BUB1	0.01	0.025	-9999	-0.59	1	1
hSgo1/Aurora B/Survivin	0.022	0.035	-9999	-0.31	6	6
EVI5	0.004	0.07	-9999	-0.58	8	8
RhoA/GTP	-0.001	0.019	-9999	-0.34	1	1
SGOL1	0.006	0.055	-9999	-0.58	5	5
CENPA	0.023	0.021	-9999	-0.26	3	3
NCAPG	0.008	0.043	-9999	-0.58	3	3
Aurora B/HC8 Proteasome	0.019	0.004	-9999	-10000	0	0
NCAPD2	0.011	0	-9999	-10000	0	0
Aurora B/PP1-gamma	0.018	0.019	-9999	-0.43	1	1
RHOA	0.01	0.025	-9999	-0.58	1	1
NCAPH	0.01	0.025	-9999	-0.58	1	1
NPM1	0.011	0.055	-9999	-0.48	7	7
RASA1	0.009	0.035	-9999	-0.58	2	2
KLHL9	0.01	0.025	-9999	-0.58	1	1
mitotic prometaphase	0.001	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.004	-9999	-10000	0	0
PPP1CC	0.01	0.025	-9999	-0.58	1	1
Centraspindlin	0.027	0.02	-9999	-10000	0	0
RhoA/GDP	0.008	0.018	-9999	-0.43	1	1
NSUN2	0.017	0.004	-9999	-10000	0	0
MYLK	-0.005	0.072	-9999	-0.24	47	47
KIF23	0.012	0.001	-9999	-10000	0	0
VIM	0.016	0.042	-9999	-0.39	6	6
RACGAP1	0.012	0.001	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.017	0.004	-9999	-10000	0	0
Chromosomal passenger complex	0.028	0.017	-9999	-0.22	2	2
Chromosomal passenger complex/EVI5	0.02	0.053	-9999	-0.3	8	8
TACC1	0.002	0.072	-9999	-0.57	9	9
PPP2R5D	0.011	0	-9999	-10000	0	0
CUL3	0.009	0.035	-9999	-0.58	2	2
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

BARD1 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
BARD1/CSTF1	0.012	0.048	-10000	0	-0.42	7	7
ATM	0.002	0.074	-10000	0	-0.58	9	9
UBE2D3	0.011	0	-10000	0	-10000	0	0
PRKDC	0.008	0.04	-10000	0	-0.54	3	3
ATR	0.009	0.035	-10000	0	-0.58	2	2
UBE2L3	0.011	0	-10000	0	-10000	0	0
FANCD2	0.013	0.066	-10000	0	-0.44	10	10
protein ubiquitination	0.02	0.063	-10000	0	-0.33	16	16
XRCC5	0.01	0.025	-10000	0	-0.58	1	1
XRCC6	0.011	0	-10000	0	-10000	0	0
M/R/N Complex	0.007	0.092	-10000	0	-0.46	19	19
MRE11A	0.003	0.069	-10000	0	-0.58	8	8
DNA-PK	0.021	0.035	-10000	0	-0.52	2	2
FA complex/FANCD2/Ubiquitin	0.034	0.059	-10000	0	-0.54	4	4
FANCF	0.005	0.06	-10000	0	-0.58	6	6
BRCA1	0.01	0.025	-10000	0	-0.58	1	1
CCNE1	0.009	0.034	-10000	0	-0.46	3	3
CDK2/Cyclin E1	0.014	0.03	-10000	0	-0.34	4	4
FANCG	0.011	0.019	-10000	0	-0.46	1	1
BRCA1/BACH1/BARD1	0.011	0.051	-10000	0	-0.42	8	8
FANCE	0.011	0	-10000	0	-10000	0	0
FANCC	0.011	0	-10000	0	-10000	0	0
NBN	-0.005	0.098	-10000	0	-0.58	16	16
FANCA	0.011	0	-10000	0	-10000	0	0
DNA repair	0.048	0.068	-10000	0	-0.58	4	4
BRCA1/BARD1/ubiquitin	0.011	0.051	-10000	0	-0.42	8	8
BARD1/DNA-PK	0.023	0.05	-10000	0	-0.35	9	9
FANCL	0.008	0.043	-10000	0	-0.58	3	3
mRNA polyadenylation	-0.012	0.048	0.42	7	-10000	0	7
BRCA1/BARD1/CTIP/M/R/N Complex	0.004	0.16	-10000	0	-0.74	18	18
BRCA1/BACH1/BARD1/TopBP1	0.017	0.047	-10000	0	-0.35	9	9
BRCA1/BARD1/P53	-0.008	0.11	-10000	0	-0.33	60	60
BARD1/CSTF1/BRCA1	0.018	0.044	-10000	0	-0.35	8	8
BRCA1/BACH1	0.01	0.025	-10000	0	-0.58	1	1
BARD1	0.004	0.065	-10000	0	-0.58	7	7
PCNA	0.011	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.018	0.044	-10000	0	-0.35	8	8
BRCA1/BARD1/UbcH7	0.018	0.044	-10000	0	-0.35	8	8
BRCA1/BARD1/RAD51/PCNA	0.025	0.04	-10000	0	-0.32	8	8
BARD1/DNA-PK/P53	-0.002	0.11	-10000	0	-0.6	3	3
BRCA1/BARD1/Ubiquitin	0.011	0.051	-10000	0	-0.42	8	8
BRCA1/BARD1/CTIP	0.009	0.098	-10000	0	-0.41	25	25
FA complex	0.028	0.053	-10000	0	-1	1	1
BARD1/EWS	0.012	0.048	-10000	0	-0.42	7	7
RBBP8	0	0.1	-10000	0	-0.53	19	19
TP53	-0.043	0.17	-10000	0	-0.58	53	53
TOPBP1	0.01	0.025	-10000	0	-0.58	1	1
G1/S transition of mitotic cell cycle	0.009	0.11	0.33	60	-10000	0	60
BRCA1/BARD1	0.022	0.064	-10000	0	-0.33	16	16
CSTF1	0.011	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.003	0.048	-10000	0	-0.43	7	7
CDK2	0.01	0.025	-10000	0	-0.58	1	1
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.011	0	-10000	0	-10000	0	0
RAD50	0.01	0.025	-10000	0	-0.58	1	1
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.011	0.051	-10000	0	-0.42	8	8
EWSR1	0.011	0	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.01	0.11	-10000	0	-0.57	21	21
HRAS	0.008	0.042	-10000	0	-0.49	4	4
EGFR	0.004	0.064	-10000	0	-0.53	8	8
AKT	0.017	0.076	-10000	0	-0.34	18	18
FOXO3	0.011	0	-10000	0	-10000	0	0
AKT1	0.01	0.025	-10000	0	-0.58	1	1
FOXO1	0.01	0.025	-10000	0	-0.58	1	1
AKT3	-0.011	0.11	-10000	0	-0.51	25	25
FOXO4	0.01	0.025	-10000	0	-0.58	1	1
MET	0.01	0.031	-10000	0	-0.52	2	2
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
PIK3CB	0.007	0.047	-10000	0	-0.55	4	4
NRAS	0.001	0.077	-10000	0	-0.58	10	10
PIK3CG	-0.044	0.17	-10000	0	-0.55	57	57
PIK3R3	0.008	0.043	-10000	0	-0.58	3	3
PIK3R2	0.01	0.025	-10000	0	-0.58	1	1
NF1	0.008	0.043	-10000	0	-0.58	3	3
RAS	0.008	0.055	0.21	1	-0.31	8	9
ERBB2	0	0.073	-10000	0	-0.46	14	14
proliferation/survival/translation	-0.02	0.045	0.26	7	-0.15	1	8
PI3K	0.009	0.064	0.18	2	-0.26	18	20
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
KRAS	0.005	0.058	-10000	0	-0.56	6	6
FOXO	0.035	0.026	0.16	2	-10000	0	2
AKT2	0.009	0.037	-10000	0	-0.5	3	3
PTEN	0.005	0.06	-10000	0	-0.58	6	6

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.021	0.037	-10000	0	-0.26	10	10
epithelial cell differentiation	0.023	0.023	-10000	0	-0.3	3	3
CYFIP2	0.001	0.077	-10000	0	-0.58	10	10
ENAH	0.037	0.067	-10000	0	-0.42	6	6
EGFR	0.004	0.064	-10000	0	-0.53	8	8
EPHA2	0.006	0.056	-10000	0	-0.54	6	6
MYO6	0.029	0.022	-10000	0	-10000	0	0
CTNNB1	0.011	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.015	0.059	-10000	0	-0.38	12	12
AQP5	-0.038	0.1	-10000	0	-0.47	24	24
CTNND1	0.011	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.028	0.025	-10000	0	-0.27	4	4
regulation of calcium-dependent cell-cell adhesion	-0.003	0.093	-10000	0	-0.28	43	43
EGF	-0.18	0.25	-10000	0	-0.5	209	209
NCKAP1	0.009	0.035	-10000	0	-0.58	2	2
AQP3	-0.023	0.07	-10000	0	-0.47	9	9
cortical microtubule organization	0.023	0.023	-10000	0	-0.3	3	3
GO:0000145	0.026	0.024	-10000	0	-0.26	4	4
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.025	0.023	-10000	0	-0.3	3	3
MLLT4	0.009	0.035	-10000	0	-0.58	2	2
ARF6/GDP	-0.005	0.039	-10000	0	-0.48	2	2
ARF6	0.01	0.025	-10000	0	-0.58	1	1
Ephrin A1/EPHA2/NCK1/GIT1	0.024	0.046	-10000	0	-0.37	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.036	0.026	-10000	0	-10000	0	0
PVRL2	0.01	0.031	-10000	0	-0.52	2	2
ZYX	0.028	0.026	-10000	0	-0.28	1	1
ARF6/GTP	0.027	0.048	-10000	0	-0.59	2	2
CDH1	0.01	0.025	-10000	0	-0.58	1	1
EGFR/EGFR/EGF/EGF	-0.084	0.11	-10000	0	-0.48	1	1
RhoA/GDP	-0.002	0.023	-10000	0	-0.28	1	1
actin cytoskeleton organization	0.032	0.027	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.01	0.025	-10000	0	-0.58	1	1
GIT1	0.01	0.025	-10000	0	-0.58	1	1
IGF1R	0.01	0.025	-10000	0	-0.58	1	1
IGF1	-0.071	0.19	-10000	0	-0.52	88	88
DIAPH1	-0.013	0.091	-10000	0	-0.62	12	12
Wnt receptor signaling pathway	-0.023	0.023	0.3	3	-10000	0	3
RHOA	0.01	0.025	-10000	0	-0.58	1	1
RhoA/GTP	-0.005	0.039	-10000	0	-0.48	2	2
CTNNA1	0.009	0.035	-10000	0	-0.58	2	2
VCL	0.032	0.028	-10000	0	-10000	0	0
EFNA1	0.011	0.019	-10000	0	-0.46	1	1
LPP	0.032	0.028	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.004	0.032	-10000	0	-10000	0	0
SEC6/SEC8	-0.003	0.025	-10000	0	-10000	0	0
MGAT3	-0.003	0.094	-10000	0	-0.29	43	43
HGF/MET	-0.023	0.072	-10000	0	-10000	0	0
HGF	-0.036	0.16	-10000	0	-0.55	49	49
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.021	0.037	-10000	0	-0.26	10	10
actin cable formation	0.051	0.057	-10000	0	-0.4	3	3
KIAA1543	0.031	0.033	-10000	0	-10000	0	0
KIFC3	0.024	0.042	-10000	0	-10000	0	0
NCK1	0.009	0.035	-10000	0	-0.58	2	2
EXOC3	0.011	0	-10000	0	-10000	0	0
ACTN1	0.029	0.022	-10000	0	-10000	0	0
NCK1/GIT1	0.015	0.032	-10000	0	-0.42	3	3
mol:GDP	0.023	0.023	-10000	0	-0.3	3	3
EXOC4	0.011	0	-10000	0	-10000	0	0
STX4	0.029	0.022	-10000	0	-10000	0	0
PIP5K1C	0.028	0.026	-10000	0	-0.28	4	4
LIMA1	0.004	0.065	-10000	0	-0.58	7	7
ABI1	0.01	0.025	-10000	0	-0.58	1	1
ROCK1	0.038	0.06	-10000	0	-0.47	4	4
adherens junction assembly	0.038	0.067	-10000	0	-1.1	1	1
IGF-1R heterotetramer/IGF1	-0.037	0.088	-10000	0	-0.55	1	1
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.014	0.034	-10000	0	-0.4	4	4
MET	0.01	0.031	-10000	0	-0.52	2	2
PLEKHA7	0.028	0.026	-10000	0	-10000	0	0
mol:GTP	0.023	0.046	-10000	0	-0.37	6	6
establishment of epithelial cell apical/basal polarity	0.045	0.029	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.021	0.037	-10000	0	-0.26	10	10
regulation of cell-cell adhesion	0.032	0.027	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.021	0.037	-10000	0	-0.26	10	10

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.015	0.082	-9999	-0.46	14	14
VEGFR1 homodimer/NRP1	0.007	0.081	-9999	-0.47	14	14
mol:DAG	0.014	0.091	-9999	-0.64	7	7
VEGFR1 homodimer/NRP1/VEGFR 121	0.013	0.076	-9999	-0.45	12	12
CaM/Ca2+	0.019	0.086	-9999	-0.6	7	7
HIF1A	0.006	0.083	-9999	-0.54	12	12
GAB1	0.011	0	-9999	-10000	0	0
AKT1	0.028	0.096	-9999	-0.62	10	10
PLCG1	0.014	0.092	-9999	-0.65	7	7
NOS3	0.025	0.11	-9999	-0.59	11	11
CBL	0.011	0	-9999	-10000	0	0
mol:NO	0.025	0.1	-9999	-0.56	11	11
FLT1	0.012	0.093	-9999	-0.54	14	14
PGF	-0.001	0.077	-9999	-0.47	15	15
VEGFR1 homodimer/NRP2/VEGFR121	0.008	0.1	-9999	-0.73	5	5
CALM1	0.011	0	-9999	-10000	0	0
PIK3CA	0.009	0.035	-9999	-0.58	2	2
eNOS/Hsp90	0.03	0.1	-9999	-0.59	11	11
endothelial cell proliferation	0.004	0.12	-9999	-0.73	7	7
mol:Ca2+	0.014	0.09	-9999	-0.63	7	7
MAPK3	0.022	0.083	-9999	-0.56	7	7
MAPK1	0.022	0.083	-9999	-0.56	7	7
PIK3R1	0.008	0.043	-9999	-0.58	3	3
PLGF homodimer	-0.001	0.077	-9999	-0.47	15	15
PRKACA	0.011	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.002	0.08	-9999	-0.49	15	15
VEGFA homodimer	0.011	0.019	-9999	-0.45	1	1
VEGFR1 homodimer/VEGFA homodimer	0.015	0.082	-9999	-0.46	14	14
platelet activating factor biosynthetic process	0.026	0.081	-9999	-0.54	7	7
PI3K	0.019	0.1	-9999	-0.67	9	9
PRKCA	0.018	0.086	-9999	-0.59	7	7
PRKCB	-0.008	0.12	-9999	-0.6	10	10
VEGFR1 homodimer/PLGF homodimer	0.008	0.096	-9999	-0.48	16	16
VEGFA	0.011	0.019	-9999	-0.46	1	1
VEGFB	0.011	0	-9999	-10000	0	0
mol:IP3	0.014	0.091	-9999	-0.64	7	7
RASA1	0.02	0.08	-9999	-0.69	5	5
NRP2	-0.013	0.11	-9999	-0.5	27	27
VEGFR1 homodimer	0.012	0.093	-9999	-0.54	14	14
VEGFB homodimer	0.011	0	-9999	-10000	0	0
NCK1	0.009	0.035	-9999	-0.58	2	2
eNOS/Caveolin-1	0.025	0.11	-9999	-0.64	9	9
PTPN11	0.006	0.055	-9999	-0.58	5	5
mol:PI-3-4-5-P3	0.018	0.098	-9999	-0.66	9	9
mol:L-citrulline	0.025	0.1	-9999	-0.56	11	11
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.012	0.12	-9999	-0.67	12	12
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.02	0.083	-9999	-0.68	6	6
CD2AP	-0.018	0.13	-9999	-0.58	29	29
PI3K/GAB1	0.023	0.095	-9999	-0.64	9	9
PDPK1	0.022	0.093	-9999	-0.62	9	9
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.018	0.093	-9999	-0.71	7	7
mol:NADP	0.025	0.1	-9999	-0.56	11	11
HSP90AA1	0.009	0.035	-9999	-0.58	2	2
ubiquitin-dependent protein catabolic process	0.011	0.12	-9999	-0.66	12	12
VEGFR1 homodimer/NRP2	0.001	0.11	-9999	-0.45	21	21

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.01	0.027	-10000	0	-0.44	2	2
TRAF2/ASK1	0.014	0.027	-10000	0	-0.36	3	3
ATM	0.002	0.074	-10000	0	-0.58	9	9
MAP2K3	0.013	0.097	-10000	0	-0.58	12	12
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.015	0.094	-10000	0	-0.54	12	12
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.004	0.085	-10000	0	-0.46	19	19
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.011	0	-10000	0	-10000	0	0
GADD45A	0.009	0.035	-10000	0	-0.58	2	2
GADD45B	0.008	0.039	-10000	0	-0.46	4	4
MAP3K1	0.005	0.06	-10000	0	-0.58	6	6
MAP3K6	0.003	0.068	-10000	0	-0.56	8	8
MAP3K7	0.011	0	-10000	0	-10000	0	0
MAP3K4	0.011	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.009	0.056	-10000	0	-0.41	10	10
TAK1/TAB family	0.004	0.022	0.18	3	-10000	0	3
RAC1/OSM/MEKK3	0.02	0.031	-10000	0	-0.4	3	3
TRAF2	0.01	0.025	-10000	0	-0.58	1	1
RAC1/OSM/MEKK3/MKK3	-0.012	0.069	-10000	0	-0.46	12	12
TRAF6	0.006	0.015	-10000	0	-0.36	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.053	0.17	-10000	0	-0.49	72	72
CCM2	0.01	0.031	-10000	0	-0.52	2	2
CaM/Ca2+/CAMKIIB	-0.024	0.1	-10000	0	-0.29	72	72
MAPK11	-0.003	0.083	-10000	0	-0.48	17	17
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.015	0.097	-10000	0	-0.26	73	73
OSM/MEKK3	0.014	0.039	-10000	0	-0.51	3	3
TAOK1	0.003	0.079	-10000	0	-0.46	14	14
TAOK2	0.008	0.048	-10000	0	-0.35	10	10
TAOK3	0.008	0.045	-10000	0	-0.35	9	9
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.011	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.009	0.035	-10000	0	-0.58	2	2
MAP3K10	0.007	0.051	-10000	0	-0.53	5	5
MAP3K3	0.009	0.035	-10000	0	-0.58	2	2
TRX/ASK1	0.012	0.022	-10000	0	-0.35	2	2
GADD45/MTK1/MTK1	0.016	0.054	-10000	0	-0.37	3	3

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.041	0.083	-9999	-0.45	3	3
CRKL	0.02	0.068	-9999	-0.42	4	4
mol:DAG	0.026	0.061	-9999	-0.33	7	7
HRAS	0.036	0.065	-9999	-0.41	4	4
MAPK8	0.019	0.047	-9999	-0.33	5	5
RAP1A	0.019	0.071	-9999	-0.45	5	5
GAB1	0.02	0.068	-9999	-0.42	4	4
MAPK14	0.02	0.045	-9999	-0.33	4	4
EPO	0.001	0.055	-9999	-0.46	8	8
PLCG1	0.026	0.063	-9999	-0.34	7	7
EPOR/TRPC2/IP3 Receptors	0.005	0.06	-9999	-0.49	8	8
RAPGEF1	0.01	0.025	-9999	-0.58	1	1
EPO/EPOR (dimer)/SOCS3	0.006	0.074	-9999	-0.34	19	19
GAB1/SHC/GRB2/SOS1	-0.013	0.052	-9999	-0.45	3	3
EPO/EPOR (dimer)	0.007	0.061	-9999	-0.35	15	15
IRS2	0.016	0.076	-9999	-0.41	5	5
STAT1	0.029	0.08	-9999	-0.45	6	6
STAT5B	0.029	0.066	-9999	-0.36	6	6
cell proliferation	0.024	0.044	-9999	-0.32	4	4
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.025	0.082	-9999	-0.52	8	8
TEC	0.02	0.068	-9999	-0.42	4	4
SOCS3	-0.002	0.08	-9999	-0.49	15	15
STAT1 (dimer)	0.029	0.079	-9999	-0.44	6	6
JAK2	-0.008	0.11	-9999	-0.55	21	21
PIK3R1	0.008	0.043	-9999	-0.58	3	3
EPO/EPOR (dimer)/JAK2	0.026	0.074	-9999	-0.31	18	18
EPO/EPOR	0.007	0.061	-9999	-0.35	15	15
LYN	0.012	0.003	-9999	-10000	0	0
TEC/VAV2	0.014	0.089	-9999	-0.4	6	6
elevation of cytosolic calcium ion concentration	0.005	0.06	-9999	-0.49	8	8
SHC1	0.011	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.02	0.051	-9999	-0.28	15	15
mol:IP3	0.026	0.061	-9999	-0.33	7	7
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.011	0.098	-9999	-0.48	6	6
SH2B3	0.011	0.007	-9999	-10000	0	0
NFKB1	0.019	0.047	-9999	-0.34	4	4
EPO/EPOR (dimer)/JAK2/SOCS3	-0.016	0.061	-9999	-0.3	20	20
PTPN6	0.014	0.071	-9999	-0.31	18	18
TEC/VAV2/GRB2	0.019	0.087	-9999	-0.4	5	5
EPOR	0.005	0.06	-9999	-0.49	8	8
INPP5D	-0.015	0.12	-9999	-0.58	26	26
mol:GDP	-0.013	0.053	-9999	-0.46	3	3
SOS1	0.01	0.025	-9999	-0.58	1	1
PLCG2	-0.01	0.11	-9999	-0.54	22	22
CRKL/CBL/C3G	0.031	0.066	-9999	-0.46	2	2
VAV2	0.007	0.091	-9999	-0.41	6	6
CBL	0.02	0.068	-9999	-0.42	4	4
SHC/Grb2/SOS1	-0.014	0.056	-9999	-0.41	5	5
STAT5A	0.029	0.066	-9999	-0.36	6	6
GRB2	0.011	0	-9999	-10000	0	0
STAT5 (dimer)	0.041	0.082	-9999	-0.46	4	4
LYN/PLCgamma2	0.002	0.078	-9999	-0.39	22	22
PTPN11	0.006	0.055	-9999	-0.58	5	5
BTK	0	0.1	-9999	-0.42	11	11
BCL2	0.025	0.16	-9999	-0.83	16	16

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.014	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.053	0.059	-9999	-0.34	5	5
ERC1	0.009	0.034	-9999	-0.46	3	3
RIP2/NOD2	-0.001	0.085	-9999	-0.4	24	24
NFKBIA	0.036	0.014	-9999	-10000	0	0
BIRC2	-0.002	0.088	-9999	-0.58	13	13
IKBKB	0.011	0.019	-9999	-0.46	1	1
RIPK2	0.011	0	-9999	-10000	0	0
IKBKG	0.019	0.073	-9999	-0.46	5	5
IKK complex/A20	0.02	0.088	-9999	-0.45	6	6
NEMO/A20/RIP2	0.011	0	-9999	-10000	0	0
XPO1	0	0.081	-9999	-0.58	11	11
NEMO/ATM	0.02	0.092	-9999	-0.53	11	11
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.008	0.051	-9999	-0.36	11	11
IKK complex/ELKS	-0.016	0.066	-9999	-0.49	6	6
BCL10/MALT1/TRAF6	0.017	0.062	-9999	-0.49	7	7
NOD2	-0.013	0.12	-9999	-0.56	24	24
NFKB1	0.013	0.025	-9999	-0.58	1	1
RELA	0.014	0	-9999	-10000	0	0
MALT1	0.006	0.055	-9999	-0.58	5	5
cIAP1/UbcH5C	0.007	0.065	-9999	-0.42	13	13
ATM	0.002	0.074	-9999	-0.58	9	9
TNF/TNFR1A	-0.003	0.088	-9999	-0.39	28	28
TRAF6	0.01	0.025	-9999	-0.58	1	1
PRKCA	0.01	0.031	-9999	-0.52	2	2
CHUK	0.007	0.049	-9999	-0.58	4	4
UBE2D3	0.011	0	-9999	-10000	0	0
TNF	-0.016	0.12	-9999	-0.54	28	28
NF kappa B1 p50/RelA	0.032	0.016	-9999	-0.34	1	1
BCL10	0.007	0.049	-9999	-0.58	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.014	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.014	0	-9999	-10000	0	0
TNFRSF1A	0.011	0	-9999	-10000	0	0
IKK complex	0.028	0.08	-9999	-0.56	5	5
CYLD	0.01	0.025	-9999	-0.58	1	1
IKK complex/PKC alpha	0.031	0.078	-9999	-0.53	5	5

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.02	0.026	-9999	-0.35	2	2
BIRC5	0.011	0.019	-9999	-0.46	1	1
NFKBIA	0.023	0.013	-9999	-10000	0	0
CPEB1	-0.051	0.17	-9999	-0.54	63	63
AKT1	0.022	0.02	-9999	-0.35	1	1
NDEL1	0.011	0	-9999	-10000	0	0
Aurora A/BRCA1	0.018	0.023	-9999	-0.49	1	1
NDEL1/TACC3	0.025	0.015	-9999	-10000	0	0
GADD45A	0.009	0.035	-9999	-0.58	2	2
GSK3B	0.008	0.033	-9999	-0.55	2	2
PAK1/Aurora A	0.021	0.013	-9999	-10000	0	0
MDM2	0.008	0.044	-9999	-0.52	4	4
JUB	0.011	0	-9999	-10000	0	0
TPX2	0.017	0.026	-9999	-0.42	2	2
TP53	-0.01	0.11	-9999	-0.33	54	54
DLG7	0.015	0.013	-9999	-0.2	2	2
AURKAIP1	0.01	0.031	-9999	-0.52	2	2
ARHGEF7	0.011	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.026	0.016	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.018	0.023	-9999	-0.49	1	1
AURKA	0.018	0.016	-9999	-0.24	2	2
AURKB	0.011	0.019	-9999	-0.24	3	3
CDC25B	0.022	0.016	-9999	-10000	0	0
G2/M transition checkpoint	0.019	0.011	-9999	-10000	0	0
mRNA polyadenylation	-0.018	0.097	-9999	-0.29	63	63
Aurora A/CPEB	-0.018	0.097	-9999	-0.29	63	63
Aurora A/TACC1/TRAP/chTOG	0.028	0.043	-9999	-0.31	8	8
BRCA1	0.01	0.025	-9999	-0.58	1	1
centrosome duplication	0.021	0.013	-9999	-10000	0	0
regulation of centrosome cycle	0.024	0.015	-9999	-10000	0	0
spindle assembly	0.027	0.042	-9999	-0.31	8	8
TDRD7	0.011	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	0.029	0.033	-9999	-0.4	3	3
CENPA	0.013	0.033	-9999	-0.42	3	3
Aurora A/PP2A	0.021	0.013	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.013	0.049	-9999	-0.57	1	1
negative regulation of DNA binding	-0.01	0.11	-9999	-0.33	54	54
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.016	0.018	-9999	-0.42	1	1
RASA1	0.009	0.035	-9999	-0.58	2	2
Ajuba/Aurora A	0.019	0.012	-9999	-10000	0	0
mitotic prometaphase	0	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.016	-9999	-0.24	2	2
TACC1	0.002	0.072	-9999	-0.57	9	9
TACC3	0.011	0.019	-9999	-0.46	1	1
Aurora A/Antizyme1	0.026	0.021	-9999	-0.32	1	1
Aurora A/RasGAP	0.02	0.026	-9999	-0.35	2	2
OAZ1	0.011	0	-9999	-10000	0	0
RAN	0.011	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.011	0.004	-9999	-10000	0	0
GIT1	0.01	0.025	-9999	-0.58	1	1
GIT1/beta-PIX/PAK1	0.023	0.016	-9999	-0.35	1	1
Importin alpha/Importin beta/TPX2	0.017	0.026	-9999	-0.42	2	2
PPP2R5D	0.011	0	-9999	-10000	0	0
Aurora A/TPX2	0.025	0.022	-9999	-0.32	1	1
PAK1	0.011	0	-9999	-10000	0	0
CKAP5	0.011	0	-9999	-10000	0	0

×

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	0.026	0.055	-10000	0	-1.1	1	1
regulation of axonogenesis	-0.02	0.045	0.6	2	-10000	0	2
myoblast fusion	-0.016	0.032	0.4	2	-10000	0	2
mol:GTP	0.007	0.023	-10000	0	-0.33	2	2
regulation of calcium-dependent cell-cell adhesion	0.004	0.098	0.28	61	-10000	0	61
ARF1/GTP	-0.002	0.02	-10000	0	-0.31	2	2
mol:GM1	0.007	0.017	-10000	0	-0.34	1	1
mol:Choline	0.02	0.035	-10000	0	-0.43	3	3
lamellipodium assembly	0.006	0.041	-10000	0	-0.46	2	2
MAPK3	0.019	0.029	-10000	0	-0.34	3	3
ARF6/GTP/NME1/Tiam1	-0.004	0.099	-10000	0	-0.28	61	61
ARF1	0.011	0.019	-10000	0	-0.46	1	1
ARF6/GDP	0.016	0.033	-10000	0	-0.4	2	2
ARF1/GDP	0.025	0.033	-10000	0	-0.36	2	2
ARF6	0.01	0.029	-10000	0	-0.67	1	1
RAB11A	0.011	0	-10000	0	-10000	0	0
TIAM1	-0.041	0.16	-10000	0	-0.51	59	59
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.019	0.029	-10000	0	-0.34	3	3
actin filament bundle formation	-0.017	0.036	0.52	2	-10000	0	2
KALRN	0.003	0.043	-10000	0	-0.33	7	7
RAB11FIP3/RAB11A	0.016	0.023	-10000	0	-0.37	2	2
RhoA/GDP	0.017	0.036	-10000	0	-0.52	2	2
NME1	0.012	0.019	-10000	0	-0.45	1	1
Rac1/GDP	0.018	0.028	-10000	0	-0.37	2	2
substrate adhesion-dependent cell spreading	0.007	0.022	-10000	0	-0.33	2	2
cortical actin cytoskeleton organization	0.006	0.041	-10000	0	-0.46	2	2
RAC1	0.011	0	-10000	0	-10000	0	0
liver development	0.007	0.022	-10000	0	-0.33	2	2
ARF6/GTP	0.007	0.023	-10000	0	-0.33	2	2
RhoA/GTP	-0.002	0.03	-10000	0	-0.68	1	1
mol:GDP	0.005	0.038	-10000	0	-0.4	2	2
ARF6/GTP/RAB11FIP3/RAB11A	0.018	0.025	-10000	0	-0.29	3	3
RHOA	0.01	0.025	-10000	0	-0.58	1	1
PLD1	0.014	0.039	-10000	0	-0.49	3	3
RAB11FIP3	0.01	0.031	-10000	0	-0.52	2	2
tube morphogenesis	0.006	0.041	-10000	0	-0.46	2	2
ruffle organization	0.02	0.045	-10000	0	-0.6	2	2
regulation of epithelial cell migration	0.007	0.022	-10000	0	-0.33	2	2
PLD2	0.016	0.018	-10000	0	-0.34	1	1
PIP5K1A	0.02	0.046	-10000	0	-0.6	2	2
mol:Phosphatidic acid	0.02	0.035	-10000	0	-0.43	3	3
Rac1/GTP	0.006	0.041	-10000	0	-0.46	2	2

×

Signaling events mediated by VEGFR1 and VEGFR2

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.003	0.092	-9999	-0.41	27	27
AKT1	0.052	0.087	-9999	-0.54	8	8
PTK2B	0.024	0.093	-9999	-0.66	5	5
VEGFR2 homodimer/Frs2	0.022	0.073	-9999	-0.85	3	3
CAV1	-0.002	0.08	-9999	-0.49	15	15
CALM1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.03	0.072	-9999	-0.81	3	3
endothelial cell proliferation	0.046	0.096	-9999	-0.51	7	7
mol:Ca2+	0.035	0.07	-9999	-0.69	3	3
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.035	0.069	-9999	-0.77	3	3
RP11-342D11.1	0.028	0.068	-9999	-0.69	3	3
CDH5	0.006	0.05	-9999	-0.48	6	6
VEGFA homodimer	0.023	0.055	-9999	-0.38	9	9
SHC1	0.011	0	-9999	-10000	0	0
SHC2	-0.043	0.16	-9999	-0.53	57	57
HRAS/GDP	-0.009	0.059	-9999	-0.54	5	5
SH2D2A	0.011	0.019	-9999	-0.46	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.016	0.075	-9999	-0.61	4	4
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.03	0.064	-9999	-0.71	3	3
VEGFR1 homodimer	0.006	0.056	-9999	-0.54	6	6
SHC/GRB2/SOS1	-0.009	0.062	-9999	-0.63	4	4
GRB10	0.033	0.086	-9999	-0.7	6	6
PTPN11	0.006	0.055	-9999	-0.58	5	5
GRB2	0.011	0	-9999	-10000	0	0
PAK1	0.011	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.036	0.076	-9999	-0.6	6	6
HRAS	0.008	0.042	-9999	-0.49	4	4
VEGF/Rho/ROCK1/Integrin Complex	0.017	0.12	-9999	-0.79	10	10
HIF1A	0.002	0.074	-9999	-0.58	9	9
FRS2	0.009	0.035	-9999	-0.58	2	2
oxygen and reactive oxygen species metabolic process	0.034	0.068	-9999	-0.76	3	3
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.004	0.091	-9999	-0.52	17	17
Nck/Pak	0.015	0.026	-9999	-0.42	2	2
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.027	0.073	-9999	-0.65	4	4
mol:GDP	-0.009	0.06	-9999	-0.6	4	4
mol:NADP	0.042	0.084	-9999	-0.41	14	14
eNOS/Hsp90	0.045	0.083	-9999	-0.39	15	15
PIK3R1	0.008	0.043	-9999	-0.58	3	3
mol:IP3	0.035	0.071	-9999	-0.7	3	3
HIF1A/ARNT	0.009	0.061	-9999	-0.46	9	9
SHB	0.011	0.019	-9999	-0.46	1	1
VEGFA	0.012	0.02	-9999	-0.45	1	1
VEGFC	-0.012	0.11	-9999	-0.54	24	24
FAK1/Vinculin	0.036	0.11	-9999	-0.68	9	9
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.01	0.025	-9999	-0.58	1	1
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.022	0.096	-9999	-0.7	5	5
PTPN6	0.011	0	-9999	-10000	0	0
EPAS1	0.015	0.04	-9999	-0.41	4	4
mol:L-citrulline	0.042	0.084	-9999	-0.41	14	14
ITGAV	0	0.081	-9999	-0.58	11	11
PIK3CA	0.009	0.035	-9999	-0.58	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.035	0.069	-9999	-0.77	3	3
VEGFR2 homodimer/VEGFA homodimer	0.032	0.075	-9999	-0.76	3	3
VEGFR2/3 heterodimer	0.014	0.093	-9999	-0.49	15	15
VEGFB	0.011	0	-9999	-10000	0	0
MAPK11	0.033	0.082	-9999	-0.61	6	6
VEGFR2 homodimer	0.021	0.072	-9999	-0.58	7	7
FLT1	0.006	0.056	-9999	-0.54	6	6
NEDD4	0.009	0.049	-9999	-0.58	4	4
MAPK3	0.028	0.073	-9999	-0.52	5	5
MAPK1	0.028	0.073	-9999	-0.52	5	5
VEGFA145/NRP2	0	0.08	-9999	-0.35	28	28
VEGFR1/2 heterodimer	0.02	0.075	-9999	-0.51	9	9
KDR	0.021	0.073	-9999	-0.59	7	7
VEGFA165/NRP1/VEGFR2 homodimer	0.024	0.091	-9999	-0.59	6	6
SRC	0.01	0.025	-9999	-0.58	1	1
platelet activating factor biosynthetic process	0.03	0.075	-9999	-0.5	6	6
PI3K	0.044	0.096	-9999	-0.64	7	7
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.03	0.066	-9999	-0.71	3	3
FES	0.029	0.085	-9999	-0.68	4	4
GAB1	-0.01	0.067	-9999	-0.67	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	0.03	0.064	-9999	-0.71	3	3
CTNNB1	0.011	0	-9999	-10000	0	0
SOS1	0.01	0.025	-9999	-0.58	1	1
ARNT	0.01	0.025	-9999	-0.58	1	1
eNOS/Caveolin-1	0.04	0.089	-9999	-0.38	15	15
VEGFR2 homodimer/VEGFA homodimer/Yes	0.027	0.078	-9999	-0.81	3	3
PI3K/GAB1	0.055	0.085	-9999	-0.58	6	6
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.038	0.071	-9999	-0.7	4	4
PRKACA	0.011	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.007	0.12	-9999	-0.62	12	12
HSP90AA1	0.009	0.035	-9999	-0.58	2	2
CDC42	0.033	0.084	-9999	-0.75	4	4
actin cytoskeleton reorganization	0.03	0.063	-9999	-0.71	3	3
PTK2	0.031	0.12	-9999	-0.68	10	10
EDG1	0.028	0.068	-9999	-0.69	3	3
mol:DAG	0.035	0.071	-9999	-0.7	3	3
CaM/Ca2+	0.037	0.065	-9999	-0.64	3	3
MAP2K3	0.039	0.071	-9999	-0.64	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.035	0.089	-9999	-0.72	6	6
PLCG1	0.035	0.072	-9999	-0.71	3	3
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.036	0.062	-9999	-0.68	3	3
IQGAP1	0.008	0.04	-9999	-0.54	3	3
YES1	0.004	0.065	-9999	-0.58	7	7
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.028	0.076	-9999	-0.81	3	3
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.031	0.063	-9999	-0.71	3	3
cell migration	0.054	0.095	-9999	-0.65	6	6
mol:PI-3-4-5-P3	0.043	0.089	-9999	-0.58	7	7
FYN	0.005	0.061	-9999	-0.55	7	7
VEGFB/NRP1	0.033	0.065	-9999	-0.65	3	3
mol:NO	0.042	0.084	-9999	-0.41	14	14
PXN	0.011	0	-9999	-10000	0	0
HRAS/GTP	-0.009	0.059	-9999	-0.54	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.035	0.089	-9999	-0.72	6	6
VHL	0.01	0.025	-9999	-0.58	1	1
ITGB3	-0.005	0.093	-9999	-0.54	17	17
NOS3	0.043	0.094	-9999	-0.46	14	14
VEGFR2 homodimer/VEGFA homodimer/Sck	0	0.11	-9999	-0.67	4	4
RAC1	0.011	0	-9999	-10000	0	0
PRKCA	0.038	0.068	-9999	-0.65	3	3
PRKCB	0.013	0.11	-9999	-0.59	6	6
VCL	0.009	0.035	-9999	-0.58	2	2
VEGFA165/NRP1	0.029	0.069	-9999	-0.69	3	3
VEGFR1/2 heterodimer/VEGFA homodimer	0.028	0.073	-9999	-0.62	5	5
VEGFA165/NRP2	0	0.08	-9999	-0.35	28	28
MAPKKK cascade	0.049	0.08	-9999	-0.54	8	8
NRP2	-0.013	0.11	-9999	-0.5	27	27
VEGFC homodimer	-0.012	0.11	-9999	-0.54	24	24
NCK1	0.009	0.035	-9999	-0.58	2	2
ROCK1	0	0.081	-9999	-0.58	11	11
FAK1/Paxillin	0.037	0.1	-9999	-0.64	9	9
MAP3K13	0.035	0.074	-9999	-0.68	4	4
PDPK1	0.047	0.08	-9999	-0.51	7	7

×

Aurora C signaling

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
INCENP	0.011	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.01	0.061	-9999	-0.32	16	16
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.003	0.017	-9999	-10000	0	0
AURKB	0.011	0	-9999	-10000	0	0
AURKC	-0.01	0.11	-9999	-0.55	21	21

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.01	0.066	-10000	0	-0.86	1	1
oxygen homeostasis	0.005	0.014	-10000	0	-10000	0	0
TCEB2	0.005	0.057	-10000	0	-0.47	8	8
TCEB1	0.011	0.019	-10000	0	-0.46	1	1
VHL/Elongin B/Elongin C/HIF2A	-0.015	0.055	-10000	0	-0.46	4	4
EPO	0.074	0.18	-10000	0	-0.6	8	8
FIH (dimer)	0.017	0.012	-10000	0	-10000	0	0
APEX1	0.017	0.014	-10000	0	-10000	0	0
SERPINE1	0.054	0.23	-10000	0	-0.69	19	19
FLT1	-0.014	0.11	-10000	0	-0.99	6	6
ADORA2A	0.07	0.19	-10000	0	-0.7	8	8
germ cell development	0.065	0.21	-10000	0	-0.69	12	12
SLC11A2	0.075	0.19	-10000	0	-0.67	7	7
BHLHE40	0.075	0.19	-10000	0	-0.69	7	7
HIF1AN	0.017	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.021	0.12	-10000	0	-0.44	6	6
ETS1	0.015	0.064	-10000	0	-0.48	9	9
CITED2	-0.005	0.067	-10000	0	-1.1	2	2
KDR	-0.012	0.1	-10000	0	-0.88	6	6
PGK1	0.075	0.19	-10000	0	-0.67	7	7
SIRT1	0.006	0.055	-10000	0	-0.58	5	5
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.082	0.22	-10000	0	-0.77	8	8
EPAS1	0.05	0.091	-10000	0	-0.37	5	5
SP1	0.016	0.025	-10000	0	-0.58	1	1
ABCG2	0.043	0.24	-10000	0	-0.76	13	13
EFNA1	0.075	0.19	-10000	0	-0.67	7	7
FXN	0.072	0.19	-10000	0	-0.65	8	8
POU5F1	0.064	0.22	-10000	0	-0.72	12	12
neuron apoptosis	-0.08	0.21	0.74	8	-10000	0	8
EP300	0.007	0.049	-10000	0	-0.58	4	4
EGLN3	0.004	0.085	-10000	0	-0.51	15	15
EGLN2	0.015	0.039	-10000	0	-0.49	3	3
EGLN1	0.017	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.018	0.043	-10000	0	-0.31	9	9
VHL	0.01	0.025	-10000	0	-0.58	1	1
ARNT	0.016	0.029	-10000	0	-0.6	1	1
SLC2A1	0.067	0.2	-10000	0	-0.72	8	8
TWIST1	0.046	0.24	-10000	0	-0.68	21	21
ELK1	0.017	0.025	-10000	0	-0.58	1	1
HIF2A/ARNT/Cbp/p300	0.066	0.12	-10000	0	-0.43	4	4
VEGFA	0.075	0.19	-10000	0	-0.67	7	7
CREBBP	0.011	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.015	0.067	-10000	0	-0.35	20	20
Ran/GTP/Exportin 1/HDAC1	-0.014	0.076	-10000	0	-0.4	19	19
NF kappa B1 p50/RelA/I kappa B alpha	0.024	0.069	-10000	0	-0.32	20	20
SUMO1	-0.008	0.11	-10000	0	-0.58	19	19
ZFPM1	-0.004	0.086	-10000	0	-0.49	17	17
NPC/RanGAP1/SUMO1/Ubc9	-0.001	0.097	-10000	0	-0.43	24	24
FKBP3	-0.003	0.091	-10000	0	-0.58	14	14
Histones	0.03	0.037	-10000	0	-10000	0	0
YY1/LSF	0.015	0.061	-10000	0	-0.51	3	3
SMG5	0.01	0.025	-10000	0	-0.58	1	1
RAN	0.011	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.016	0.057	-10000	0	-10000	0	0
I kappa B alpha/HDAC1	0.018	0.041	-10000	0	-10000	0	0
SAP18	0.011	0.019	-10000	0	-0.46	1	1
RELA	0.018	0.056	-10000	0	-10000	0	0
HDAC1/Smad7	0.022	0.022	-10000	0	-0.35	2	2
RANGAP1	0.01	0.031	-10000	0	-0.52	2	2
HDAC3/TR2	0.018	0.043	-10000	0	-0.31	1	1
NuRD/MBD3 Complex	0.036	0.033	-10000	0	-0.34	3	3
NF kappa B1 p50/RelA	0.021	0.055	-10000	0	-0.51	1	1
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.014	0.12	-10000	0	-0.55	26	26
GATA1	-0.004	0.073	-10000	0	-0.46	14	14
Mad/Max	0.014	0.03	-10000	0	-0.34	4	4
NuRD/MBD3 Complex/GATA1/Fog1	0.036	0.053	-10000	0	-0.44	4	4
RBBP7	0.01	0.025	-10000	0	-0.58	1	1
NPC	-0.004	0.057	-10000	0	-0.31	19	19
RBBP4	0.01	0.025	-10000	0	-0.58	1	1
MAX	0.011	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.011	0	-10000	0	-10000	0	0
NFKBIA	0.013	0.045	-10000	0	-10000	0	0
KAT2B	-0.006	0.1	-10000	0	-0.58	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.033	0.025	-10000	0	-10000	0	0
SIN3 complex	0.027	0.031	-10000	0	-0.32	4	4
SMURF1	0.011	0	-10000	0	-10000	0	0
CHD3	0.009	0.035	-10000	0	-0.58	2	2
SAP30	0.009	0.035	-10000	0	-0.58	2	2
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.01	0.025	-10000	0	-0.58	1	1
YY1/HDAC3	0.019	0.059	-10000	0	-0.54	1	1
YY1/HDAC2	0.016	0.055	-10000	0	-0.26	20	20
YY1/HDAC1	0.016	0.055	-10000	0	-0.61	1	1
NuRD/MBD2 Complex (MeCP1)	0.035	0.03	-10000	0	-0.36	1	1
PPARG	0.011	0.079	-10000	0	-0.32	27	27
HDAC8/hEST1B	0.023	0.016	-10000	0	-0.35	1	1
UBE2I	0.011	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-10000	0	-10000	0	0
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.016	0.048	-10000	0	-0.31	3	3
MBD3L2	-0.001	0.019	-10000	0	-0.46	1	1
ubiquitin-dependent protein catabolic process	0.022	0.022	-10000	0	-0.35	2	2
CREBBP	0.011	0	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.038	0.034	-10000	0	-0.34	3	3
HDAC1	0.011	0	-10000	0	-10000	0	0
HDAC3	0.013	0.045	-10000	0	-10000	0	0
HDAC2	0.011	0	-10000	0	-10000	0	0
YY1	0.013	0.063	-10000	0	-0.31	20	20
HDAC8	0.011	0	-10000	0	-10000	0	0
SMAD7	0.009	0.035	-10000	0	-0.58	2	2
NCOR2	0.007	0.047	-10000	0	-0.55	4	4
MXD1	0.008	0.042	-10000	0	-0.49	4	4
STAT3	0.019	0.03	-10000	0	-0.34	4	4
NFKB1	0.01	0.025	-10000	0	-0.58	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	-0.008	0.1	-10000	0	-0.57	19	19
YY1/LSF/HDAC1	0.021	0.056	-10000	0	-0.47	3	3
YY1/SAP30/HDAC1	0.021	0.054	-10000	0	-0.39	3	3
EP300	0.007	0.049	-10000	0	-0.58	4	4
STAT3 (dimer non-phopshorylated)	0.019	0.03	-10000	0	-0.34	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.045	-10000	0	-10000	0	0
histone deacetylation	0.035	0.029	-10000	0	-0.36	1	1
STAT3 (dimer non-phopshorylated)/HDAC3	0.024	0.044	-10000	0	-10000	0	0
nuclear export	-0.022	0.016	0.35	1	-10000	0	1
PRKACA	0.011	0	-10000	0	-10000	0	0
GATAD2B	0.011	0	-10000	0	-10000	0	0
GATAD2A	0.01	0.025	-10000	0	-0.58	1	1
GATA2/HDAC3	0.004	0.079	-10000	0	-0.32	21	21
GATA1/HDAC1	0.006	0.052	-10000	0	-0.32	14	14
GATA1/HDAC3	0.003	0.056	-10000	0	-0.33	2	2
CHD4	0.011	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	-0.003	0.088	-10000	0	-0.39	28	28
SIN3/HDAC complex/Mad/Max	0.036	0.027	-10000	0	-0.36	1	1
NuRD Complex	0.04	0.042	-10000	0	-0.47	2	2
positive regulation of chromatin silencing	0.029	0.036	-10000	0	-10000	0	0
SIN3B	0.01	0.025	-10000	0	-0.58	1	1
MTA2	0.011	0	-10000	0	-10000	0	0
SIN3A	0.01	0.025	-10000	0	-0.58	1	1
XPO1	0	0.081	-10000	0	-0.58	11	11
SUMO1/HDAC1	0.005	0.11	-10000	0	-0.55	19	19
HDAC complex	0.028	0.02	-10000	0	-0.32	2	2
GATA1/Fog1	-0.005	0.082	-10000	0	-0.35	30	30
FKBP25/HDAC1/HDAC2	0.014	0.058	-10000	0	-0.35	14	14
TNF	-0.016	0.12	-10000	0	-0.54	28	28
negative regulation of cell growth	0.036	0.027	-10000	0	-0.36	1	1
NuRD/MBD2/PRMT5 Complex	0.035	0.03	-10000	0	-0.36	1	1
Ran/GTP/Exportin 1	0.006	0.12	-10000	0	-0.68	15	15
NF kappa B/RelA/I kappa B alpha	0.019	0.069	-10000	0	-0.33	19	19
SIN3/HDAC complex/NCoR1	0.034	0.024	-10000	0	-10000	0	0
TFCP2	0.009	0.035	-10000	0	-0.58	2	2
NR2C1	0.01	0.025	-10000	0	-0.58	1	1
MBD3	0.007	0.051	-10000	0	-0.53	5	5
MBD2	0.006	0.055	-10000	0	-0.58	5	5

×

Atypical NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.015	0.029	-9999	-0.39	3	3
FBXW11	0.011	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.019	0.033	-9999	-0.33	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.025	0.049	-9999	-10000	0	0
NFKBIA	0.009	0.052	-9999	-0.22	21	21
MAPK14	0.011	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.021	0.02	-9999	-0.35	1	1
ARRB2	0.014	0	-9999	-10000	0	0
REL	0.008	0.043	-9999	-0.58	3	3
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.019	0.032	-9999	-0.32	5	5
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.021	0.02	-9999	-0.31	2	2
PIK3CA	0.009	0.035	-9999	-0.58	2	2
NF kappa B1 p50 dimer	0.015	0.023	-9999	-0.37	2	2
PIK3R1	0.008	0.043	-9999	-0.58	3	3
NFKB1	0.017	0.023	-9999	-0.37	2	2
RELA	0.011	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.014	0.053	-9999	-0.22	21	21
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.028	0.047	-9999	-10000	0	0
SRC	0.01	0.025	-9999	-0.58	1	1
PI3K	0.013	0.041	-9999	-0.42	5	5
NF kappa B1 p50/RelA	0.014	0.053	-9999	-0.22	21	21
IKBKB	0.011	0.019	-9999	-0.46	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
SYK	0.011	0.019	-9999	-0.46	1	1
I kappa B alpha/PIK3R1	0.013	0.054	-9999	-0.28	4	4
cell death	0.027	0.046	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.019	0.033	-9999	-0.33	5	5
LCK	-0.032	0.14	-9999	-0.51	48	48
BCL3	0.008	0.04	-9999	-0.54	3	3

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.032	0.026	-9999	-0.46	1	1
KLHL20	-0.018	0.052	-9999	-0.23	25	25
CYFIP2	0.001	0.077	-9999	-0.58	10	10
Rac1/GDP	0.044	0.04	-9999	-0.49	1	1
ENAH	0.026	0.051	-9999	-0.48	2	2
AP1M1	0.01	0.025	-9999	-0.58	1	1
RAP1B	0.011	0	-9999	-10000	0	0
RAP1A	0.01	0.025	-9999	-0.58	1	1
CTNNB1	0.011	0	-9999	-10000	0	0
CDC42/GTP	-0.004	0.033	-9999	-0.41	2	2
ABI1/Sra1/Nap1	-0.014	0.039	-9999	-0.21	9	9
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.012	0.073	-9999	-0.32	20	20
RAPGEF1	0.04	0.033	-9999	-0.44	2	2
CTNND1	0.011	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.027	0.027	-9999	-0.48	1	1
CRK	0.036	0.029	-9999	-0.43	1	1
E-cadherin/gamma catenin/alpha catenin	0.021	0.031	-9999	-0.35	4	4
alphaE/beta7 Integrin	-0.004	0.091	-9999	-0.39	30	30
IQGAP1	0.008	0.04	-9999	-0.54	3	3
NCKAP1	0.009	0.035	-9999	-0.58	2	2
Rap1/GTP/I-afadin	0.02	0.025	-9999	-0.32	3	3
DLG1	0.031	0.034	-9999	-0.46	1	1
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.027	-9999	-0.26	5	5
MLLT4	0.009	0.035	-9999	-0.58	2	2
ARF6/GTP/NME1/Tiam1	-0.009	0.093	-9999	-0.28	61	61
PI3K	-0.005	0.035	-9999	-0.34	5	5
ARF6	0.01	0.025	-9999	-0.58	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.015	0.026	-9999	-0.42	2	2
TIAM1	-0.043	0.16	-9999	-0.52	59	59
E-cadherin(dimer)/Ca2+	0.026	0.023	-9999	-0.3	3	3
AKT1	-0.003	0.023	-9999	-0.23	4	4
PIK3R1	0.008	0.043	-9999	-0.58	3	3
CDH1	0.01	0.025	-9999	-0.58	1	1
RhoA/GDP	0.043	0.041	-9999	-0.49	1	1
actin cytoskeleton organization	0.018	0.05	-9999	-0.17	25	25
CDC42/GDP	0.041	0.048	-9999	-0.42	2	2
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.019	0.024	-9999	-0.26	4	4
ITGB7	-0.017	0.12	-9999	-0.53	30	30
RAC1	0.011	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.028	0.025	-9999	-0.32	3	3
E-cadherin/Ca2+/beta catenin/alpha catenin	0.019	0.023	-9999	-0.3	3	3
mol:GDP	0.04	0.045	-9999	-0.6	1	1
CDC42/GTP/IQGAP1	0.011	0.051	-9999	-0.45	6	6
JUP	0.01	0.025	-9999	-0.58	1	1
p120 catenin/RhoA/GDP	0.035	0.041	-9999	-0.49	1	1
RAC1/GTP/IQGAP1	0.014	0.025	-9999	-0.33	3	3
PIP5K1C/AP1M1	0.016	0.033	-9999	-0.77	1	1
RHOA	0.01	0.025	-9999	-0.58	1	1
CDC42	0.006	0.055	-9999	-0.58	5	5
CTNNA1	0.009	0.035	-9999	-0.58	2	2
positive regulation of S phase of mitotic cell cycle	0.016	0.034	-9999	-0.27	1	1
NME1	0.011	0.019	-9999	-0.46	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.032	0.029	-9999	-0.46	1	1
regulation of cell-cell adhesion	-0.004	0.029	-9999	-0.35	2	2
WASF2	-0.007	0.02	-9999	-10000	0	0
Rap1/GTP	-0.003	0.026	-9999	-0.44	1	1
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.016	0.072	-9999	-0.3	23	23
CCND1	0.019	0.041	-9999	-0.35	1	1
VAV2	0.01	0.15	-9999	-0.68	25	25
RAP1/GDP	0.036	0.036	-9999	-0.49	1	1
adherens junction assembly	0.031	0.028	-9999	-0.45	1	1
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.01	0.025	-9999	-0.58	1	1
PIP5K1C	0.01	0.025	-9999	-0.58	1	1
regulation of heterotypic cell-cell adhesion	0.021	0.07	-9999	-0.41	1	1
E-cadherin/beta catenin	0	0.022	-9999	-0.35	2	2
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.032	0.029	-9999	-0.46	1	1
PIK3CA	0.009	0.035	-9999	-0.58	2	2
Rac1/GTP	-0.029	0.083	-9999	-0.37	24	24
E-cadherin/beta catenin/alpha catenin	0.021	0.027	-9999	-0.35	3	3
ITGAE	0.011	0.019	-9999	-0.46	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.027	0.027	-9999	-0.49	1	1

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.011	0	-10000	0	-10000	0	0
mol:PIP3	-0.004	0.051	0.28	5	-0.29	13	18
FRAP1	0.012	0.017	-10000	0	-10000	0	0
AKT1	0.017	0.049	0.22	5	-0.26	14	19
INSR	0.009	0.035	-10000	0	-0.58	2	2
Insulin Receptor/Insulin	0.006	0.027	-10000	0	-0.32	4	4
mol:GTP	-0.006	0.038	-10000	0	-0.54	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.004	0.027	-10000	0	-0.3	3	3
TSC2	0.009	0.031	-10000	0	-0.52	2	2
RHEB/GDP	-0.005	0.034	-10000	0	-0.49	1	1
TSC1	0.011	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.007	0.049	-10000	0	-0.34	11	11
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.004	0.03	-10000	0	-0.35	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.01	0.025	-10000	0	-0.58	1	1
RPS6KB1	0.017	0.049	-10000	0	-0.4	5	5
MAP3K5	0.007	0.023	-10000	0	-0.38	2	2
PIK3R1	0.008	0.043	-10000	0	-0.58	3	3
apoptosis	0.007	0.023	-10000	0	-0.38	2	2
mol:LY294002	0	0	0.001	1	-0.002	9	10
EIF4B	0.021	0.043	-10000	0	-0.34	5	5
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.021	0.044	-10000	0	-0.34	4	4
eIF4E/eIF4G1/eIF4A1	-0.001	0.015	-10000	0	-0.25	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.013	0.05	-10000	0	-0.3	14	14
mTOR/RHEB/GTP/Raptor/GBL	0.023	0.024	0.16	5	-0.2	1	6
FKBP1A	0.012	0	-10000	0	-10000	0	0
RHEB/GTP	-0.005	0.033	-10000	0	-0.48	1	1
mol:Amino Acids	0	0	0.001	1	-0.002	9	10
FKBP12/Rapamycin	0.009	0.001	-10000	0	-10000	0	0
PDPK1	-0.004	0.045	0.23	5	-0.26	13	18
EIF4E	0.009	0.035	-10000	0	-0.58	2	2
ASK1/PP5C	0.017	0.04	-10000	0	-0.62	2	2
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.012	0.031	-10000	0	-0.51	2	2
TSC1/TSC2	0.025	0.046	-10000	0	-0.6	1	1
tumor necrosis factor receptor activity	0	0	0.002	9	-0.001	1	10
RPS6	0.007	0.046	-10000	0	-0.48	5	5
PPP5C	0.011	0	-10000	0	-10000	0	0
EIF4G1	0.011	0	-10000	0	-10000	0	0
IRS1	0.001	0.048	-10000	0	-0.38	9	9
INS	-0.001	0.027	-10000	0	-0.46	2	2
PTEN	0.005	0.06	-10000	0	-0.58	6	6
PDK2	-0.005	0.048	0.23	5	-0.27	15	20
EIF4EBP1	0.009	0.045	-10000	0	-1	1	1
PIK3CA	0.009	0.035	-10000	0	-0.58	2	2
PPP2R5D	0.017	0.016	-10000	0	-10000	0	0
peptide biosynthetic process	0.01	0.034	-10000	0	-0.27	8	8
RHEB	0.011	0	-10000	0	-10000	0	0
EIF4A1	0.011	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	6	-0.003	1	7
EEF2	0.01	0.034	-10000	0	-0.27	8	8
eIF4E/4E-BP1	0.013	0.046	-10000	0	-0.96	1	1

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.018	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.025	0.031	-10000	0	-0.32	4	4
CDKN1B	0.023	0.049	-10000	0	-0.52	4	4
CDKN1A	0.021	0.052	-10000	0	-0.41	6	6
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.008	0.04	-10000	0	-0.54	3	3
FOXO3	0.024	0.045	-10000	0	-0.54	3	3
AKT1	-0.006	0.044	-10000	0	-0.57	3	3
BAD	0.01	0.031	-10000	0	-0.52	2	2
AKT3	0.002	0.058	-10000	0	-0.26	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.023	0.047	-10000	0	-0.47	4	4
AKT1/ASK1	0.022	0.054	-10000	0	-0.58	4	4
BAD/YWHAZ	0.02	0.033	-10000	0	-0.34	5	5
RICTOR	-0.009	0.11	-10000	0	-0.58	20	20
RAF1	0.011	0	-10000	0	-10000	0	0
JNK cascade	-0.021	0.052	0.55	4	-10000	0	4
TSC1	0.024	0.045	-10000	0	-0.54	3	3
YWHAZ	0.008	0.043	-10000	0	-0.58	3	3
AKT1/RAF1	0.024	0.046	-10000	0	-0.54	3	3
EP300	0.007	0.049	-10000	0	-0.58	4	4
mol:GDP	0.019	0.047	-10000	0	-0.56	3	3
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.023	0.054	-10000	0	-0.54	4	4
YWHAQ	0.011	0	-10000	0	-10000	0	0
TBC1D4	0.016	0.035	-10000	0	-0.34	5	5
MAP3K5	0.009	0.035	-10000	0	-0.58	2	2
MAPKAP1	0.011	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.031	0.031	0.3	4	-10000	0	4
YWHAH	0.011	0	-10000	0	-10000	0	0
AKT1S1	0.023	0.053	-10000	0	-0.63	3	3
CASP9	0.023	0.047	-10000	0	-0.54	3	3
YWHAB	0.011	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.028	0.059	-10000	0	-0.63	4	4
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.021	0.027	-10000	0	-0.35	3	3
YWHAE	0.011	0	-10000	0	-10000	0	0
SRC	0.01	0.025	-10000	0	-0.58	1	1
AKT2/p21CIP1	0.025	0.052	-10000	0	-0.47	4	4
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.013	0.014	-10000	0	-10000	0	0
CHUK	0.022	0.059	-10000	0	-0.55	5	5
BAD/BCL-XL	0.034	0.051	-10000	0	-0.58	3	3
mTORC2	0.003	0.063	-10000	0	-0.33	20	20
AKT2	0.013	0.019	-10000	0	-0.24	3	3
FOXO1-3a-4/14-3-3 family	0.041	0.048	-10000	0	-0.46	4	4
PDPK1	0.011	0	-10000	0	-10000	0	0
MDM2	0.022	0.053	-10000	0	-0.49	5	5
MAPKKK cascade	-0.024	0.045	0.52	3	-10000	0	3
MDM2/Cbp/p300	0.031	0.059	-10000	0	-0.54	4	4
TSC1/TSC2	0.028	0.053	-10000	0	-0.6	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.056	-10000	0	-0.51	4	4
glucose import	0.006	0.07	-10000	0	-0.26	35	35
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.02	0.032	-10000	0	-0.34	3	3
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.006	0.07	-10000	0	-0.26	35	35
GSK3A	0.024	0.045	-10000	0	-0.54	3	3
FOXO1	0.023	0.047	-10000	0	-0.54	3	3
GSK3B	0.023	0.056	-10000	0	-0.59	4	4
SFN	0.005	0.057	-10000	0	-0.47	8	8
G1/S transition of mitotic cell cycle	0.028	0.054	-10000	0	-0.57	4	4
p27Kip1/14-3-3 family	0.036	0.03	-10000	0	-0.39	1	1
PRKACA	0.011	0	-10000	0	-10000	0	0
KPNA1	0.009	0.035	-10000	0	-0.58	2	2
HSP90AA1	0.009	0.035	-10000	0	-0.58	2	2
YWHAG	0.011	0	-10000	0	-10000	0	0
RHEB	0.011	0	-10000	0	-10000	0	0
CREBBP	0.011	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.007	0.049	-9999	-0.58	4	4
positive regulation of NF-kappaB transcription factor activity	0.011	0.048	-9999	-0.36	9	9
MAP2K4	0.033	0.037	-9999	-10000	0	0
IKBKB	0.011	0.019	-9999	-0.46	1	1
TNFRSF10B	0.01	0.025	-9999	-0.58	1	1
TNFRSF10A	0.011	0	-9999	-10000	0	0
SMPD1	0.013	0.029	-9999	-0.24	7	7
IKBKG	0.01	0.025	-9999	-0.58	1	1
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.007	0.043	-9999	-0.46	5	5
TRAIL/TRAILR2	0.013	0.041	-9999	-0.42	5	5
TRAIL/TRAILR3	-0.006	0.089	-9999	-0.35	35	35
TRAIL/TRAILR1	0.014	0.036	-9999	-0.42	4	4
TRAIL/TRAILR4	0.011	0.048	-9999	-0.36	9	9
TRAIL/TRAILR1/DAP3/GTP	0.02	0.029	-9999	-0.32	4	4
IKK complex	-0.005	0.039	-9999	-0.4	5	5
RIPK1	0.011	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.008	0	-9999	-10000	0	0
MAPK3	0.015	0.041	-9999	-0.42	5	5
MAP3K1	0.03	0.031	-9999	-10000	0	0
TRAILR4 (trimer)	0.007	0.043	-9999	-0.45	5	5
TRADD	0.011	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.011	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.028	0.026	-9999	-10000	0	0
CFLAR	0.011	0	-9999	-10000	0	0
MAPK1	0.015	0.041	-9999	-0.42	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP	0.032	0.027	-9999	-10000	0	0
mol:ceramide	0.013	0.029	-9999	-0.24	7	7
FADD	0.011	0	-9999	-10000	0	0
MAPK8	0.037	0.039	-9999	-0.39	1	1
TRAF2	0.01	0.025	-9999	-0.58	1	1
TRAILR3 (trimer)	-0.016	0.11	-9999	-0.49	31	31
CHUK	0.007	0.049	-9999	-0.58	4	4
TRAIL/TRAILR1/FADD	0.021	0.031	-9999	-0.35	4	4
DAP3	0.011	0	-9999	-10000	0	0
CASP10	-0.002	0.037	-9999	-0.34	5	5
JNK cascade	0.011	0.048	-9999	-0.36	9	9
TRAIL (trimer)	0.007	0.049	-9999	-0.58	4	4
TNFRSF10C	-0.016	0.11	-9999	-0.49	31	31
TRAIL/TRAILR1/DAP3/GTP/FADD	0.025	0.027	-9999	-0.3	4	4
TRAIL/TRAILR2/FADD	0.02	0.035	-9999	-0.35	5	5
cell death	0.013	0.029	-9999	-0.24	7	7
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.028	0.029	-9999	-10000	0	0
TRAILR2 (trimer)	0.01	0.025	-9999	-0.58	1	1
CASP8	0	0.036	-9999	-0.8	1	1
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.031	0.03	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.022	0.071	-10000	0	-0.51	2	2
BAG4	0.009	0.035	-10000	0	-0.58	2	2
BAD	0.018	0.036	-10000	0	-0.4	2	2
NFKBIA	0.011	0	-10000	0	-10000	0	0
BIRC3	-0.016	0.12	-10000	0	-0.52	29	29
BAX	0.019	0.034	-10000	0	-0.52	1	1
EnzymeConsortium:3.1.4.12	0.008	0.019	-10000	0	-0.097	2	2
IKBKB	0.027	0.068	-10000	0	-0.48	2	2
MAP2K2	0.027	0.036	-10000	0	-0.43	1	1
MAP2K1	0.026	0.037	-10000	0	-0.31	2	2
SMPD1	0.012	0.024	-10000	0	-0.24	2	2
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.028	0.067	-10000	0	-0.44	1	1
MAP2K4	0.02	0.048	-10000	0	-0.29	10	10
protein ubiquitination	0.027	0.071	-10000	0	-0.44	4	4
EnzymeConsortium:2.7.1.37	0.029	0.041	-10000	0	-0.3	2	2
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.023	0.033	-10000	0	-0.24	3	3
CRADD	0.011	0.025	-10000	0	-0.58	1	1
mol:ceramide	0.014	0.029	-10000	0	-0.2	2	2
I-kappa-B-alpha/RELA/p50/ubiquitin	0.015	0	-10000	0	-10000	0	0
MADD	0.012	0	-10000	0	-10000	0	0
MAP3K1	0.016	0.045	-10000	0	-0.32	7	7
TRADD	0.012	0	-10000	0	-10000	0	0
RELA/p50	0.011	0	-10000	0	-10000	0	0
MAPK3	0.028	0.036	-10000	0	-0.28	2	2
MAPK1	0.028	0.036	-10000	0	-0.28	2	2
p50/RELA/I-kappa-B-alpha	0.017	0	-10000	0	-10000	0	0
FADD	0.023	0.068	-10000	0	-0.46	1	1
KSR1	0.018	0.033	-10000	0	-0.26	3	3
MAPK8	0.024	0.047	-10000	0	-0.28	10	10
TRAF2	0.01	0.025	-10000	0	-0.58	1	1
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.025	0.074	-10000	0	-0.51	3	3
TNF R/SODD	0.015	0.026	-10000	0	-0.42	2	2
TNF	-0.015	0.12	-10000	0	-0.54	28	28
CYCS	0.018	0.046	0.13	10	-0.25	8	18
IKBKG	0.027	0.071	-10000	0	-0.51	3	3
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.018	0.071	-10000	0	-0.38	3	3
RELA	0.011	0	-10000	0	-10000	0	0
RIPK1	0.011	0	-10000	0	-10000	0	0
AIFM1	0.022	0.037	0.13	10	-0.35	2	12
TNF/TNF R/SODD	0.005	0.078	-10000	0	-0.32	30	30
TNFRSF1A	0.011	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.02	0.032	-10000	0	-0.58	1	1
NSMAF	0.023	0.067	-10000	0	-0.46	1	1
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	-0.007	0.1	-10000	0	-0.55	19	19

×

FoxO family 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
G6PC	0.015	0.072	-9999	-10000	0	0
PLK1	0.053	0.13	-9999	-1	2	2
CDKN1B	0.094	0.073	-9999	-0.43	4	4
FOXO3	0.051	0.13	-9999	-0.65	4	4
KAT2B	0.002	0.1	-9999	-0.58	17	17
FOXO1/SIRT1	0.002	0.054	-9999	-0.45	2	2
CAT	0.055	0.12	-9999	-0.73	2	2
CTNNB1	0.011	0	-9999	-10000	0	0
AKT1	0.019	0.027	-9999	-0.57	1	1
FOXO1	0.022	0.047	-9999	-0.28	2	2
MAPK10	0.009	0.083	-9999	-0.29	34	34
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.067	0.066	-9999	-0.58	2	2
response to oxidative stress	0.009	0.013	-9999	-10000	0	0
FOXO3A/SIRT1	-0.003	0.089	-9999	-0.64	4	4
XPO1	0.001	0.081	-9999	-0.58	11	11
EP300	0.008	0.05	-9999	-0.58	4	4
BCL2L11	0.026	0.027	-9999	-10000	0	0
FOXO1/SKP2	0.023	0.053	-9999	-0.51	2	2
mol:GDP	0.009	0.013	-9999	-10000	0	0
RAN	0.013	0.001	-9999	-10000	0	0
GADD45A	0.079	0.09	-9999	-0.88	3	3
YWHAQ	0.011	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.053	0.054	-9999	-0.59	3	3
MST1	-0.026	0.15	-9999	-0.5	50	50
CSNK1D	0.011	0	-9999	-10000	0	0
CSNK1E	0.011	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.042	0.044	-9999	-0.45	3	3
YWHAB	0.011	0	-9999	-10000	0	0
MAPK8	0.032	0.017	-9999	-0.34	1	1
MAPK9	0.032	0.007	-9999	-10000	0	0
YWHAG	0.011	0	-9999	-10000	0	0
YWHAE	0.011	0	-9999	-10000	0	0
YWHAZ	0.008	0.043	-9999	-0.58	3	3
SIRT1	0.008	0.057	-9999	-0.57	5	5
SOD2	0.094	0.088	-9999	-0.63	2	2
RBL2	0.063	0.12	-9999	-1.4	2	2
RAL/GDP	0.026	0.01	-9999	-10000	0	0
CHUK	0.015	0.05	-9999	-0.58	4	4
Ran/GTP	0.012	0.002	-9999	-10000	0	0
CSNK1G2	0.009	0.035	-9999	-0.58	2	2
RAL/GTP	0.032	0.01	-9999	-10000	0	0
CSNK1G1	0.01	0.025	-9999	-0.58	1	1
FASLG	-0.083	0.36	-9999	-1.4	40	40
SKP2	0.008	0.043	-9999	-0.58	3	3
USP7	0.013	0.001	-9999	-10000	0	0
IKBKB	0.018	0.021	-9999	-0.44	1	1
CCNB1	0.055	0.12	-9999	-0.73	2	2
FOXO1-3a-4/beta catenin	0.098	0.09	-9999	-0.44	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.053	-9999	-0.5	2	2
CSNK1A1	0.009	0.035	-9999	-0.58	2	2
SGK1	0.007	0.077	-9999	-0.48	14	14
CSNK1G3	0.01	0.025	-9999	-0.58	1	1
Ran/GTP/Exportin 1	0.014	0.052	-9999	-0.36	11	11
ZFAND5	0.068	0.068	-9999	-0.72	2	2
SFN	0.005	0.057	-9999	-0.47	8	8
CDK2	0.009	0.026	-9999	-0.58	1	1
FOXO3A/14-3-3	0.048	0.052	-9999	-0.42	4	4
CREBBP	0.01	0.009	-9999	-10000	0	0
FBXO32	0.053	0.12	-9999	-0.73	2	2
BCL6	0.064	0.1	-9999	-0.65	2	2
RALB	0.012	0.001	-9999	-10000	0	0
RALA	0.012	0.001	-9999	-10000	0	0
YWHAH	0.011	0	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.015	0.12	-10000	0	-0.5	30	30
CLTC	0.024	0.033	-10000	0	-0.7	1	1
calcium ion-dependent exocytosis	0.02	0.023	-10000	0	-0.46	1	1
Dynamin 2/GTP	0.019	0.023	-10000	0	-0.29	3	3
EXOC4	0.011	0	-10000	0	-10000	0	0
CD59	0.022	0.031	-10000	0	-0.7	1	1
CPE	-0.039	0.12	-10000	0	-0.32	92	92
CTNNB1	0.011	0	-10000	0	-10000	0	0
membrane fusion	0.02	0.022	-10000	0	-0.45	1	1
CTNND1	0.024	0.021	-10000	0	-0.3	2	2
DNM2	0.01	0.025	-10000	0	-0.58	1	1
mol:PI-4-5-P2	0.024	0.032	-10000	0	-0.5	2	2
TSHR	-0.001	0.065	-10000	0	-0.29	27	27
INS	0.009	0.011	-10000	0	-10000	0	0
BIN1	0.006	0.055	-10000	0	-0.58	5	5
mol:Choline	0.02	0.022	-10000	0	-0.45	1	1
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0.019	-10000	0	-0.31	2	2
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.01	0.025	-10000	0	-0.58	1	1
mol:Ca2+	0.018	0.023	-10000	0	-0.29	3	3
JUP	0.021	0.032	-10000	0	-0.7	1	1
ASAP2/amphiphysin II	0.017	0.04	-10000	0	-0.32	8	8
ARF6/GTP	0.008	0.018	-10000	0	-0.43	1	1
CDH1	0.021	0.032	-10000	0	-0.7	1	1
clathrin-independent pinocytosis	0.008	0.018	-10000	0	-0.43	1	1
MAPK8IP3	0.005	0.058	-10000	0	-0.51	7	7
positive regulation of endocytosis	0.008	0.018	-10000	0	-0.43	1	1
EXOC2	0.01	0.025	-10000	0	-0.58	1	1
substrate adhesion-dependent cell spreading	0.026	0.066	-10000	0	-0.61	4	4
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.01	0.025	-10000	0	-0.58	1	1
regulation of calcium-dependent cell-cell adhesion	0.002	0.029	0.62	1	-10000	0	1
positive regulation of phagocytosis	0.015	0.016	-10000	0	-0.36	1	1
ARF6/GTP/JIP3	0.011	0.039	-10000	0	-0.31	8	8
ACAP1	0.014	0.032	-10000	0	-0.36	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.008	0.071	-10000	0	-0.7	1	1
clathrin heavy chain/ACAP1	0.027	0.033	-10000	0	-0.66	1	1
JIP4/KLC1	0.021	0.02	-10000	0	-0.32	2	2
EXOC1	0.01	0.025	-10000	0	-0.58	1	1
exocyst	0.026	0.067	-10000	0	-0.62	4	4
RALA/GTP	0.008	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.014	0.022	-10000	0	-0.36	2	2
receptor recycling	0.008	0.018	-10000	0	-0.43	1	1
CTNNA1	0.023	0.029	-10000	0	-0.3	4	4
NME1	0.014	0.02	-10000	0	-0.31	2	2
clathrin coat assembly	0.024	0.032	-10000	0	-0.69	1	1
IL2RA	0.001	0.07	-10000	0	-0.5	2	2
VAMP3	0.015	0.016	-10000	0	-0.36	1	1
GLUT4/clathrin heavy chain/ACAP1	-0.013	0.054	-10000	0	-0.45	2	2
EXOC6	0.008	0.043	-10000	0	-0.58	3	3
PLD1	0.016	0.03	-10000	0	-0.37	3	3
PLD2	0.018	0.008	-10000	0	-10000	0	0
EXOC5	-0.006	0.1	-10000	0	-0.58	17	17
PIP5K1C	0.024	0.033	-10000	0	-0.51	2	2
SDC1	0.021	0.032	-10000	0	-0.7	1	1
ARF6/GDP	0.014	0.02	-10000	0	-0.31	2	2
EXOC7	0.011	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.002	0.03	-10000	0	-0.64	1	1
mol:Phosphatidic acid	0.02	0.022	-10000	0	-0.45	1	1
endocytosis	-0.016	0.04	0.32	8	-10000	0	8
SCAMP2	0.011	0	-10000	0	-10000	0	0
ADRB2	0.008	0.079	-10000	0	-0.65	1	1
EXOC3	0.011	0	-10000	0	-10000	0	0
ASAP2	0.009	0.035	-10000	0	-0.58	2	2
Dynamin 2/GDP	0.02	0.023	-10000	0	-0.29	3	3
KLC1	0.011	0	-10000	0	-10000	0	0
AVPR2	0.002	0.084	-10000	0	-0.29	25	25
RALA	0.011	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.003	0.031	-10000	0	-0.59	1	1

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.007	0.025	0.26	5	-10000	0	5
BUB1B	0.017	0.029	-10000	0	-0.32	4	4
PLK1	0.015	0.007	-10000	0	-10000	0	0
PLK1S1	0.011	0.019	-10000	0	-0.27	2	2
KIF2A	0.02	0.015	-10000	0	-0.32	1	1
regulation of mitotic centrosome separation	0.015	0.007	-10000	0	-10000	0	0
GOLGA2	0.009	0.035	-10000	0	-0.58	2	2
Hec1/SPC24	0.011	0.068	-10000	0	-0.29	28	28
WEE1	0.017	0.045	-10000	0	-0.51	4	4
cytokinesis	0.021	0.049	-10000	0	-0.51	3	3
PP2A-alpha B56	0.029	0.036	-10000	0	-0.78	1	1
AURKA	0.014	0.004	-10000	0	-10000	0	0
PICH/PLK1	0.021	0.058	-10000	0	-0.3	15	15
CENPE	0.01	0.06	-10000	0	-0.32	18	18
RhoA/GTP	0.008	0.018	-10000	0	-0.43	1	1
positive regulation of microtubule depolymerization	0.02	0.015	-10000	0	-0.31	1	1
PPP2CA	0.011	0	-10000	0	-10000	0	0
FZR1	0.01	0.025	-10000	0	-0.58	1	1
TPX2	0.012	0.017	-10000	0	-0.26	2	2
PAK1	0.011	0	-10000	0	-10000	0	0
SPC24	-0.002	0.088	-10000	0	-0.55	14	14
FBXW11	0.011	0	-10000	0	-10000	0	0
CLSPN	0.013	0.02	-10000	0	-0.32	2	2
GORASP1	0.011	0	-10000	0	-10000	0	0
metaphase	0	0.001	-10000	0	-0.016	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.008	0.004	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0.001	0.011	1	-10000	0	1
STAG2	0.007	0.049	-10000	0	-0.58	4	4
GRASP65/GM130/RAB1/GTP	-0.001	0.018	-10000	0	-10000	0	0
spindle elongation	0.015	0.007	-10000	0	-10000	0	0
ODF2	0.011	0.001	-10000	0	-10000	0	0
BUB1	-0.002	0.036	-10000	0	-0.86	1	1
TPT1	0.013	0.005	-10000	0	-10000	0	0
CDC25C	0.015	0.004	-10000	0	-10000	0	0
CDC25B	0.01	0.027	-10000	0	-0.45	2	2
SGOL1	0.007	0.025	-10000	0	-0.26	5	5
RHOA	0.01	0.025	-10000	0	-0.58	1	1
CCNB1/CDK1	-0.003	0.026	-10000	0	-0.27	4	4
CDC14B	0.007	0.032	-10000	0	-0.43	3	3
CDC20	0.011	0	-10000	0	-10000	0	0
PLK1/PBIP1	0.01	0.047	-10000	0	-0.3	13	13
mitosis	0	0	-10000	0	-10000	0	0
FBXO5	0.016	0.028	-10000	0	-0.31	4	4
CDC2	0.001	0.001	-10000	0	-10000	0	0
NDC80	-0.003	0.091	-10000	0	-0.58	14	14
metaphase plate congression	0.014	0.006	-10000	0	-10000	0	0
ERCC6L	0.019	0.061	-10000	0	-0.32	16	16
NLP/gamma Tubulin	0.012	0.004	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.013	0.005	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0	-10000	0	-10000	0	0
PPP1R12A	0.007	0.05	-10000	0	-0.58	4	4
interphase	0	0	-10000	0	-10000	0	0
PLK1/PRC1-2	0.025	0.02	-10000	0	-0.3	2	2
GRASP65/GM130/RAB1/GTP/PLK1	0.028	0.024	-10000	0	-0.29	3	3
RAB1A	0.01	0.025	-10000	0	-0.58	1	1
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.017	0.005	-10000	0	-10000	0	0
mitotic prometaphase	0	0.001	0.012	1	-0.008	1	2
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.026	-10000	0	-0.4	1	1
microtubule-based process	0.019	0.021	-10000	0	-0.32	2	2
Golgi organization	0.015	0.007	-10000	0	-10000	0	0
Cohesin/SA2	0.015	0.028	-10000	0	-0.31	4	4
PPP1CB/MYPT1	0.011	0.052	-10000	0	-0.48	6	6
KIF20A	0.009	0.035	-10000	0	-0.58	2	2
APC/C/CDC20	0.02	0.006	-10000	0	-10000	0	0
PPP2R1A	0.01	0.025	-10000	0	-0.58	1	1
chromosome segregation	0.01	0.046	-10000	0	-0.29	13	13
PRC1	0.011	0	-10000	0	-10000	0	0
ECT2	0.013	0.052	-10000	0	-0.33	13	13
C13orf34	0.017	0.005	-10000	0	-10000	0	0
NUDC	0.014	0.006	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.017	0.029	-10000	0	-0.32	4	4
spindle assembly	0.015	0.005	-10000	0	-10000	0	0
spindle stabilization	0.011	0.019	-10000	0	-0.27	2	2
APC/C/HCDH1	0.013	0.031	-10000	0	-0.36	4	4
MKLP2/PLK1	0.019	0.021	-10000	0	-0.32	2	2
CCNB1	0.012	0.001	-10000	0	-10000	0	0
PPP1CB	0.008	0.043	-10000	0	-0.59	3	3
BTRC	0.01	0.025	-10000	0	-0.58	1	1
ROCK2	0.011	0.071	-10000	0	-0.48	11	11
TUBG1	0.013	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.025	-10000	0	-0.27	4	4
MLF1IP	-0.001	0.066	-10000	0	-0.44	13	13
INCENP	0.011	0.001	-10000	0	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.036	0.058	-10000	0	-1.1	1	1
CLOCK	0.012	0.032	-10000	0	-0.51	2	2
TIMELESS/CRY2	0.032	0.055	-10000	0	-1.2	1	1
DEC1/BMAL1	0.007	0.048	-10000	0	-0.33	11	11
ATR	0.009	0.035	-10000	0	-0.58	2	2
NR1D1	0.03	0.061	-10000	0	-1.3	1	1
ARNTL	0.012	0.035	-10000	0	-0.58	2	2
TIMELESS	0.031	0.059	-10000	0	-1.3	1	1
NPAS2	0.012	0.032	-10000	0	-0.51	2	2
CRY2	0.011	0	-10000	0	-10000	0	0
mol:CO	-0.011	0.009	0.12	3	-10000	0	3
CHEK1	0.01	0.025	-10000	0	-0.58	1	1
mol:HEME	0.011	0.009	-10000	0	-0.12	3	3
PER1	0.003	0.064	-10000	0	-0.5	9	9
BMAL/CLOCK/NPAS2	0.033	0.037	-10000	0	-0.34	4	4
BMAL1/CLOCK	0.034	0.068	-10000	0	-0.88	2	2
S phase of mitotic cell cycle	0.036	0.058	-10000	0	-1.1	1	1
TIMELESS/CHEK1/ATR	0.036	0.059	-10000	0	-1.2	1	1
mol:NADPH	0.011	0.009	-10000	0	-0.12	3	3
PER1/TIMELESS	0.028	0.068	-10000	0	-0.93	2	2
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.003	0.057	-10000	0	-0.46	9	9

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.009	0.059	-10000	0	-0.35	6	6
CaM/Ca2+	0.008	0	-10000	0	-10000	0	0
AKT1	0.01	0.025	-10000	0	-0.58	1	1
AKT2	0.009	0.037	-10000	0	-0.5	3	3
STXBP4	0.005	0.06	-10000	0	-0.58	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.028	0.057	0.2	6	-0.36	4	10
YWHAZ	0.008	0.043	-10000	0	-0.58	3	3
CALM1	0.011	0	-10000	0	-10000	0	0
YWHAQ	0.011	0	-10000	0	-10000	0	0
TBC1D4	0.015	0.041	-10000	0	-0.42	5	5
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.011	0	-10000	0	-10000	0	0
YWHAB	0.011	0	-10000	0	-10000	0	0
SNARE/Synip	0.019	0.038	-10000	0	-0.35	6	6
YWHAG	0.011	0	-10000	0	-10000	0	0
ASIP	0	0.054	-10000	0	-0.46	8	8
PRKCI	0.008	0.043	-10000	0	-0.58	3	3
AS160/CaM/Ca2+	0.008	0	-10000	0	-10000	0	0
RHOQ	0.011	0	-10000	0	-10000	0	0
GYS1	0.021	0.044	-10000	0	-0.47	4	4
PRKCZ	0.01	0.031	-10000	0	-0.52	2	2
TRIP10	0.01	0.025	-10000	0	-0.58	1	1
TC10/GTP/CIP4/Exocyst	0.015	0.016	-10000	0	-0.36	1	1
AS160/14-3-3	0.033	0.033	-10000	0	-0.34	2	2
VAMP2	0.011	0	-10000	0	-10000	0	0
SLC2A4	0.028	0.061	-10000	0	-0.4	4	4
STX4	0.011	0	-10000	0	-10000	0	0
GSK3B	0.018	0.046	-10000	0	-0.58	3	3
SFN	0.005	0.057	-10000	0	-0.47	8	8
LNPEP	0.003	0.069	-10000	0	-0.58	8	8
YWHAE	0.011	0	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.034	0.052	-10000	0	-0.41	6	6
adherens junction organization	0.032	0.033	-10000	0	-0.46	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.037	0.052	-10000	0	-0.48	3	3
FMN1	0.027	0.049	-10000	0	-0.3	9	9
mol:IP3	0.03	0.038	-10000	0	-0.38	2	2
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.028	0.031	-10000	0	-0.37	2	2
CTNNB1	0.011	0.001	-10000	0	-10000	0	0
AKT1	0.034	0.044	-10000	0	-0.69	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.032	0.04	-10000	0	-0.56	2	2
CTNND1	0.012	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.031	0.037	-10000	0	-0.39	3	3
VASP	0.032	0.029	-10000	0	-0.46	1	1
ZYX	0.032	0.039	-10000	0	-0.74	1	1
JUB	0.032	0.029	-10000	0	-0.46	1	1
EGFR(dimer)	0.029	0.046	-10000	0	-0.33	6	6
E-cadherin/beta catenin-gamma catenin	0.021	0.021	-10000	0	-0.34	2	2
mol:PI-3-4-5-P3	0.03	0.038	-10000	0	-0.3	6	6
PIK3CA	0.01	0.035	-10000	0	-0.58	2	2
PI3K	0.031	0.039	-10000	0	-0.31	6	6
FYN	0.031	0.055	-10000	0	-0.33	7	7
mol:Ca2+	0.029	0.038	-10000	0	-0.37	2	2
JUP	0.01	0.025	-10000	0	-0.59	1	1
PIK3R1	0.009	0.043	-10000	0	-0.58	3	3
mol:DAG	0.03	0.038	-10000	0	-0.38	2	2
CDH1	0.01	0.025	-10000	0	-0.58	1	1
RhoA/GDP	0.037	0.055	-10000	0	-0.49	4	4
establishment of polarity of embryonic epithelium	0.032	0.029	-10000	0	-0.45	1	1
SRC	0.01	0.025	-10000	0	-0.58	1	1
RAC1	0.011	0	-10000	0	-10000	0	0
RHOA	0.01	0.025	-10000	0	-0.58	1	1
EGFR	0.004	0.064	-10000	0	-0.53	8	8
CASR	0.028	0.045	-10000	0	-0.45	1	1
RhoA/GTP	0.032	0.04	-10000	0	-0.47	2	2
AKT2	0.034	0.048	-10000	0	-0.58	2	2
actin cable formation	0.032	0.047	-10000	0	-0.4	2	2
apoptosis	-0.032	0.048	0.37	6	-10000	0	6
CTNNA1	0.01	0.035	-10000	0	-0.58	2	2
mol:GDP	0.032	0.055	-10000	0	-0.52	3	3
PIP5K1A	0.031	0.037	-10000	0	-0.4	3	3
PLCG1	0.03	0.039	-10000	0	-0.39	2	2
Rac1/GTP	-0.005	0.037	-10000	0	-0.37	3	3
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	-0.002	0.03	-9999	-0.63	1	1
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.015	0.021	-9999	-0.23	3	3
AP2	0.014	0.03	-9999	-0.34	4	4
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.016	0.002	-9999	-10000	0	0
CLTB	0.009	0.037	-9999	-0.5	3	3
coatomer protein complex/ARF1/GTP/ER cargo protein	0.02	0.016	-9999	-0.26	1	1
CD4	-0.014	0.12	-9999	-0.55	26	26
CLTA	0.011	0	-9999	-10000	0	0
mol:GTP	0.001	0.001	-9999	-10000	0	0
ARFGAP1	0.007	0.027	-9999	-0.36	3	3
mol:PI-4-5-P2	-0.001	0.019	-9999	-0.32	2	2
ARF1/GTP	-0.001	0.012	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.02	0.026	-9999	-0.3	3	3
mol:Choline	-0.001	0.019	-9999	-0.32	2	2
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.011	0.019	-9999	-0.45	1	1
DDEF1	-0.001	0.02	-9999	-0.33	2	2
ARF1/GDP	0.005	0.021	-9999	-0.26	3	3
AP2M1	0.011	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.013	0.01	-9999	-0.22	1	1
Rac/GTP	0.009	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.019	0.022	-9999	-0.25	3	3
ARFIP2	0.01	0.003	-9999	-10000	0	0
COPA	0.011	0	-9999	-10000	0	0
RAC1	0.011	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.02	0.011	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.008	0.011	-9999	-0.26	1	1
GGA3	0.011	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.015	0.011	-9999	-0.2	1	1
AP2A1	0.008	0.042	-9999	-0.49	4	4
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.02	0.029	-9999	-0.61	1	1
ARF1/GDP/Membrin	0.015	0.011	-9999	-0.19	1	1
Arfaptin 2/Rac/GDP	0.015	0.002	-9999	-10000	0	0
CYTH2	0.012	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3	0.016	0.011	-9999	-0.25	1	1
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.008	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	0.017	0.051	-9999	-0.22	21	21
PLD2	-0.001	0.019	-9999	-0.32	2	2
ARF-GAP1/v-SNARE	0.007	0.027	-9999	-0.36	3	3
PIP5K1A	-0.001	0.02	-9999	-0.33	2	2
ARF1/GTP/Membrin/GBF1/p115	-0.002	0.019	-9999	-0.28	2	2
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.001	0.019	-9999	-0.32	2	2
KDEL Receptor/Ligand/ARF-GAP1	0.007	0.027	-9999	-0.36	3	3
GOSR2	-0.001	0.008	-9999	-10000	0	0
USO1	-0.005	0.05	-9999	-0.48	6	6
GBF1	-0.001	0.019	-9999	-0.42	1	1
ARF1/GTP/Arfaptin 2	0.016	0.011	-9999	-0.24	1	1
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.005	0.078	-9999	-0.32	30	30

×

Alternative NF-kappaB pathway

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
IKK alpha homodimer	0.013	0.041	-9999	-0.42	5	5
FBXW11	0.011	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.011	0	-9999	-10000	0	0
CHUK	0.007	0.049	-9999	-0.58	4	4
NF kappa B2 p100/RelB	0.029	0.052	-9999	-0.66	2	2
NFKB1	0.01	0.025	-9999	-0.58	1	1
MAP3K14	0.01	0.025	-9999	-0.58	1	1
NF kappa B1 p50/RelB	0.014	0.032	-9999	-0.37	4	4
RELB	0.009	0.037	-9999	-0.5	3	3
NFKB2	0.01	0.031	-9999	-0.52	2	2
NF kappa B2 p52/RelB	0.013	0.038	-9999	-0.49	3	3
regulation of B cell activation	0.013	0.038	-9999	-0.49	3	3

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.005	0.06	-10000	0	-0.58	6	6
SMAD2	0.013	0.024	0.24	1	-0.25	2	3
SMAD3	0.029	0.031	-10000	0	-0.25	1	1
SMAD3/SMAD4	0.034	0.029	-10000	0	-10000	0	0
SMAD4/Ubc9/PIASy	0.019	0.041	-10000	0	-0.35	7	7
SMAD2/SMAD2/SMAD4	0.029	0.033	-10000	0	-10000	0	0
PPM1A	0.011	0	-10000	0	-10000	0	0
CALM1	0.011	0	-10000	0	-10000	0	0
SMAD2/SMAD4	0.015	0.039	0.19	1	-0.31	6	7
MAP3K1	0.005	0.06	-10000	0	-0.58	6	6
TRAP-1/SMAD4	0.011	0.051	-10000	0	-0.42	8	8
MAPK3	0.01	0.025	-10000	0	-0.58	1	1
MAPK1	0.01	0.025	-10000	0	-0.58	1	1
NUP214	0.011	0	-10000	0	-10000	0	0
CTDSP1	0.01	0.025	-10000	0	-0.58	1	1
CTDSP2	0.011	0	-10000	0	-10000	0	0
CTDSPL	0.011	0	-10000	0	-10000	0	0
KPNB1	0.011	0	-10000	0	-10000	0	0
TGFBRAP1	0.009	0.035	-10000	0	-0.58	2	2
UBE2I	0.011	0	-10000	0	-10000	0	0
NUP153	0.011	0	-10000	0	-10000	0	0
KPNA2	0.011	0	-10000	0	-10000	0	0
PIAS4	0.01	0.025	-10000	0	-0.58	1	1

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.022	0.022	-9999	-0.35	2	2
E-cadherin/beta catenin	0.016	0.018	-9999	-0.42	1	1
CTNNB1	0.011	0	-9999	-10000	0	0
JUP	0.01	0.025	-9999	-0.58	1	1
CDH1	0.01	0.025	-9999	-0.58	1	1

pid_entity	TCGA.QG.A5Z2	TCGA.QG.A5Z1	TCGA.QG.A5YX	TCGA.QG.A5YW
109_MAP3K5	0.044	0.044	0.044	0.044
47_PPARGC1A	0.011	0.011	0.011	0.011
105_BMP4	0.011	0.011	-0.58	0.011
105_BMP6	0.011	0.011	-0.58	0.011
105_BMP7	0.011	0.011	0.011	0.011
105_BMP2	0.011	0.011	0.011	0.011
131_RELN/VLDLR	0.029	0.029	-0.32	0.029
30_TGFB1/TGF beta receptor Type II	0.011	0.011	-0.58	0.011
84_STAT5B	-0.14	-0.0065	-0.18	0.037
84_STAT5A	-0.14	-0.0065	-0.18	0.037