PARADIGM pathway analysis of mRNASeq expression data - Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Nephrin/Neph1 signaling in the kidney podocyte	133
EGFR-dependent Endothelin signaling events	113
Angiopoietin receptor Tie2-mediated signaling	97
FOXA2 and FOXA3 transcription factor networks	75
PDGFR-alpha signaling pathway	66
Thromboxane A2 receptor signaling	53
Glypican 2 network	46
Signaling mediated by p38-alpha and p38-beta	45
Arf6 signaling events	42
Glypican 1 network	40

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
Nephrin/Neph1 signaling in the kidney podocyte	0.4602	133	4537	34	-0.61	0.013	1000	-1000	-0.064	-1000
EGFR-dependent Endothelin signaling events	0.3910	113	2373	21	-0.73	0.019	1000	-1000	-0.069	-1000
Angiopoietin receptor Tie2-mediated signaling	0.3356	97	8609	88	-0.98	0.084	1000	-1000	-0.096	-1000
FOXA2 and FOXA3 transcription factor networks	0.2595	75	3461	46	-1.2	0.019	1000	-1000	-0.082	-1000
PDGFR-alpha signaling pathway	0.2284	66	2924	44	-0.32	0.028	1000	-1000	-0.054	-1000
Thromboxane A2 receptor signaling	0.1834	53	5616	105	-0.73	0.088	1000	-1000	-0.064	-1000
Glypican 2 network	0.1592	46	187	4	-0.12	-1000	1000	-1000	-0.025	-1000
Signaling mediated by p38-alpha and p38-beta	0.1557	45	1990	44	-0.2	0.013	1000	-1000	-0.045	-1000
Arf6 signaling events	0.1453	42	2615	62	-0.73	0.032	1000	-1000	-0.065	-1000
Glypican 1 network	0.1384	40	1926	48	-0.42	0.031	1000	-1000	-0.044	-1000
amb2 Integrin signaling	0.1246	36	3016	82	-0.48	0.013	1000	-1000	-0.073	-1000
Endothelins	0.1211	35	3429	96	-0.62	0.013	1000	-1000	-0.082	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1211	35	2768	78	-0.34	0.059	1000	-1000	-0.066	-1000
IL4-mediated signaling events	0.1142	33	3069	91	-0.93	0.57	1000	-1000	-0.14	-1000
BMP receptor signaling	0.1142	33	2705	81	-0.52	0.019	1000	-1000	-0.089	-1000
TCGA08_p53	0.1107	32	228	7	-0.15	0.096	1000	-1000	-0.014	-1000
TCGA08_retinoblastoma	0.1107	32	259	8	-0.23	0.061	1000	-1000	-0.015	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.1073	31	3979	125	-0.16	0.032	1000	-1000	-0.094	-1000
Effects of Botulinum toxin	0.1038	30	797	26	-0.23	0.015	1000	-1000	-0.061	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1003	29	2022	68	-0.63	0.098	1000	-1000	-0.12	-1000
S1P1 pathway	0.0865	25	904	36	-0.2	0.013	1000	-1000	-0.056	-1000
Integrins in angiogenesis	0.0865	25	2132	84	-0.54	0.037	1000	-1000	-0.088	-1000
FOXM1 transcription factor network	0.0830	24	1261	51	-0.22	0.024	1000	-1000	-0.16	-1000
Syndecan-4-mediated signaling events	0.0761	22	1495	67	-0.45	0.077	1000	-1000	-0.084	-1000
Signaling events mediated by PTP1B	0.0727	21	1661	76	-0.73	0.098	1000	-1000	-0.076	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0727	21	2633	120	-0.31	0.14	1000	-1000	-0.073	-1000
TCR signaling in naïve CD8+ T cells	0.0692	20	1866	93	-0.58	0.28	1000	-1000	-0.082	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0692	20	1531	74	-0.73	0.051	1000	-1000	-0.083	-1000
Syndecan-1-mediated signaling events	0.0588	17	603	34	-0.12	0.013	1000	-1000	-0.051	-1000
Glucocorticoid receptor regulatory network	0.0588	17	1949	114	-0.66	0.18	1000	-1000	-0.06	-1000
FoxO family signaling	0.0588	17	1122	64	-0.9	0.09	1000	-1000	-0.064	-1000
Ephrin A reverse signaling	0.0554	16	116	7	-0.048	0	1000	-1000	-0.028	-1000
Signaling events regulated by Ret tyrosine kinase	0.0554	16	1345	82	-0.13	0.013	1000	-1000	-0.076	-1000
LPA4-mediated signaling events	0.0519	15	189	12	-0.25	0.019	1000	-1000	-0.029	-1000
IL27-mediated signaling events	0.0519	15	781	51	-1.1	0.18	1000	-1000	-0.062	-1000
Coregulation of Androgen receptor activity	0.0484	14	1071	76	-0.72	0.022	1000	-1000	-0.048	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0484	14	399	28	-0.16	0.018	1000	-1000	-0.036	-1000
Nongenotropic Androgen signaling	0.0484	14	734	52	-0.087	0.023	1000	-1000	-0.071	-1000
IL6-mediated signaling events	0.0484	14	1076	75	-0.28	0.053	1000	-1000	-0.077	-1000
Plasma membrane estrogen receptor signaling	0.0484	14	1263	86	-0.17	0.024	1000	-1000	-0.09	-1000
E-cadherin signaling events	0.0484	14	72	5	-0.056	0.013	1000	-1000	-0.044	-1000
Signaling events mediated by the Hedgehog family	0.0450	13	711	52	-0.065	0.022	1000	-1000	-0.072	-1000
p75(NTR)-mediated signaling	0.0450	13	1735	125	-0.46	0.032	1000	-1000	-0.092	-1000
Calcium signaling in the CD4+ TCR pathway	0.0450	13	423	31	-0.16	0.014	1000	-1000	-0.076	-1000
HIF-1-alpha transcription factor network	0.0415	12	963	76	-0.16	0.049	1000	-1000	-0.13	-1000
Aurora B signaling	0.0415	12	855	67	-0.31	0.013	1000	-1000	-0.075	-1000
IL12-mediated signaling events	0.0381	11	991	87	-0.18	0.025	1000	-1000	-0.12	-1000
ErbB4 signaling events	0.0381	11	788	69	-0.3	0.12	1000	-1000	-0.088	-1000
Presenilin action in Notch and Wnt signaling	0.0381	11	700	61	-0.22	0.1	1000	-1000	-0.073	-1000
Reelin signaling pathway	0.0381	11	648	56	-0.18	0.019	1000	-1000	-0.075	-1000
Visual signal transduction: Rods	0.0381	11	616	52	-0.21	0.013	1000	-1000	-0.08	-1000
Regulation of nuclear SMAD2/3 signaling	0.0346	10	1450	136	-0.63	0.069	1000	-1000	-0.067	-1000
S1P3 pathway	0.0346	10	449	42	-0.16	0.02	1000	-1000	-0.036	-1000
Class IB PI3K non-lipid kinase events	0.0346	10	30	3	-0.009	-1000	1000	-1000	-0.014	-1000
Regulation of Androgen receptor activity	0.0346	10	741	70	-0.83	0.028	1000	-1000	-0.063	-1000
Osteopontin-mediated events	0.0311	9	355	38	-0.11	0.038	1000	-1000	-0.09	-1000
Syndecan-3-mediated signaling events	0.0311	9	322	35	-0.18	0.019	1000	-1000	-0.066	-1000
EPHB forward signaling	0.0311	9	827	85	-0.22	0.072	1000	-1000	-0.09	-1000
Regulation of Telomerase	0.0311	9	986	102	-0.73	0.043	1000	-1000	-0.09	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0311	9	306	33	-0.23	0.036	1000	-1000	-0.058	-1000
Syndecan-2-mediated signaling events	0.0277	8	587	69	-0.48	0.04	1000	-1000	-0.046	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0277	8	440	52	-0.34	0.057	1000	-1000	-0.072	-1000
E-cadherin signaling in the nascent adherens junction	0.0277	8	659	76	-0.056	0.03	1000	-1000	-0.081	-1000
E-cadherin signaling in keratinocytes	0.0277	8	382	43	-0.31	0.036	1000	-1000	-0.064	-1000
PLK2 and PLK4 events	0.0242	7	22	3	-0.011	0.01	1000	-1000	-0.026	-1000
Insulin-mediated glucose transport	0.0242	7	248	32	-0.14	0.07	1000	-1000	-0.07	-1000
Ceramide signaling pathway	0.0242	7	606	76	-0.73	0.25	1000	-1000	-0.053	-1000
BCR signaling pathway	0.0242	7	730	99	-0.081	0.032	1000	-1000	-0.092	-1000
IL23-mediated signaling events	0.0242	7	467	60	-0.12	0.023	1000	-1000	-0.16	-1000
PDGFR-beta signaling pathway	0.0242	7	728	97	-0.14	0.046	1000	-1000	-0.08	-1000
Caspase cascade in apoptosis	0.0208	6	515	74	-0.42	0.041	1000	-1000	-0.039	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0208	6	361	54	-0.24	0.025	1000	-1000	-0.097	-1000
Fc-epsilon receptor I signaling in mast cells	0.0208	6	663	97	-0.13	0.03	1000	-1000	-0.081	-1000
IL1-mediated signaling events	0.0208	6	420	62	-0.2	0.059	1000	-1000	-0.1	-1000
Wnt signaling	0.0208	6	47	7	-0.033	0.013	1000	-1000	-0.033	-1000
TCGA08_rtk_signaling	0.0208	6	178	26	-0.3	0.028	1000	-1000	-0.022	-1000
BARD1 signaling events	0.0173	5	336	57	-0.12	0.027	1000	-1000	-0.063	-1000
JNK signaling in the CD4+ TCR pathway	0.0173	5	100	17	-0.033	0.029	1000	-1000	-0.052	-1000
Noncanonical Wnt signaling pathway	0.0173	5	143	26	-0.16	0.013	1000	-1000	-0.065	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0173	5	500	85	-0.11	0.034	1000	-1000	-0.07	-1000
S1P5 pathway	0.0173	5	92	17	-0.059	0.03	1000	-1000	-0.044	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0173	5	486	83	-0.27	0.049	1000	-1000	-0.073	-1000
Canonical Wnt signaling pathway	0.0173	5	286	51	-0.22	0.11	1000	-1000	-0.052	-1000
Regulation of p38-alpha and p38-beta	0.0173	5	316	54	-0.2	0.062	1000	-1000	-0.06	-1000
Signaling events mediated by PRL	0.0173	5	191	34	-0.03	0.022	1000	-1000	-0.034	-1000
Ras signaling in the CD4+ TCR pathway	0.0173	5	101	17	-0.008	0.026	1000	-1000	-0.032	-1000
IFN-gamma pathway	0.0138	4	332	68	-0.32	0.068	1000	-1000	-0.094	-1000
Nectin adhesion pathway	0.0138	4	295	63	-0.085	0.049	1000	-1000	-0.077	-1000
Ephrin B reverse signaling	0.0138	4	221	48	-0.085	0.036	1000	-1000	-0.065	-1000
FAS signaling pathway (CD95)	0.0138	4	190	47	-0.11	0.022	1000	-1000	-0.05	-1000
LPA receptor mediated events	0.0138	4	438	102	-0.12	0.054	1000	-1000	-0.081	-1000
Class I PI3K signaling events	0.0138	4	333	73	-0.063	0.038	1000	-1000	-0.066	-1000
ErbB2/ErbB3 signaling events	0.0104	3	226	65	-0.12	0.034	1000	-1000	-0.068	-1000
Cellular roles of Anthrax toxin	0.0104	3	150	39	-0.2	0.018	1000	-1000	-0.029	-1000
PLK1 signaling events	0.0104	3	284	85	-0.092	0.024	1000	-1000	-0.041	-1000
IL2 signaling events mediated by PI3K	0.0104	3	208	58	-0.057	0.057	1000	-1000	-0.08	-1000
Arf6 trafficking events	0.0104	3	255	71	-0.35	0.041	1000	-1000	-0.07	-1000
IGF1 pathway	0.0104	3	193	57	-0.039	0.043	1000	-1000	-0.094	-1000
S1P4 pathway	0.0104	3	96	25	-0.059	0.027	1000	-1000	-0.056	-1000
Signaling events mediated by HDAC Class II	0.0069	2	187	75	-0.16	0.038	1000	-1000	-0.061	-1000
Aurora A signaling	0.0069	2	143	60	-0.095	0.04	1000	-1000	-0.057	-1000
Class I PI3K signaling events mediated by Akt	0.0069	2	140	68	-0.14	0.047	1000	-1000	-0.055	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0069	2	83	37	-0.03	0.032	1000	-1000	-0.051	-1000
HIF-2-alpha transcription factor network	0.0069	2	105	43	-0.22	0.13	1000	-1000	-0.079	-1000
Signaling mediated by p38-gamma and p38-delta	0.0069	2	34	15	0	0.025	1000	-1000	-0.03	-1000
Retinoic acid receptors-mediated signaling	0.0069	2	153	58	-0.059	0.034	1000	-1000	-0.069	-1000
IL2 signaling events mediated by STAT5	0.0069	2	61	22	-0.047	0.046	1000	-1000	-0.054	-1000
Visual signal transduction: Cones	0.0035	1	70	38	-0.015	0.016	1000	-1000	-0.064	-1000
Hedgehog signaling events mediated by Gli proteins	0.0035	1	100	65	-0.059	0.062	1000	-1000	-0.063	-1000
EPO signaling pathway	0.0035	1	60	55	-0.035	0.075	1000	-1000	-0.089	-1000
TRAIL signaling pathway	0.0035	1	55	48	-0.009	0.044	1000	-1000	-0.07	-1000
Signaling events mediated by HDAC Class I	0.0035	1	184	104	-0.16	0.053	1000	-1000	-0.067	-1000
Paxillin-dependent events mediated by a4b1	0.0035	1	39	36	-0.036	0.038	1000	-1000	-0.068	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0035	1	63	45	-0.027	0.059	1000	-1000	-0.085	-1000
Insulin Pathway	0.0035	1	140	74	-0.045	0.034	1000	-1000	-0.089	-1000
VEGFR1 specific signals	0.0035	1	97	56	-0.007	0.048	1000	-1000	-0.066	-1000
p38 MAPK signaling pathway	0.0035	1	62	44	-0.042	0.041	1000	-1000	-0.065	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	8	23	0	0.045	1000	-1000	-0.055	-1000
Canonical NF-kappaB pathway	0.0000	0	38	39	-0.011	0.078	1000	-1000	-0.083	-1000
Circadian rhythm pathway	0.0000	0	8	22	-0.012	0.044	1000	-1000	-0.041	-1000
a4b1 and a4b7 Integrin signaling	0.0000	0	1	5	0.011	0.018	1000	-1000	-0.02	-1000
Arf6 downstream pathway	0.0000	0	3	43	-0.025	0.026	1000	-1000	-0.037	-1000
Aurora C signaling	0.0000	0	0	7	-0.13	0.012	1000	-1000	-0.032	-1000
mTOR signaling pathway	0.0000	0	41	53	-0.006	0.033	1000	-1000	-0.063	-1000
Signaling events mediated by HDAC Class III	0.0000	0	29	40	-0.02	0.022	1000	-1000	-0.04	-1000
ceramide signaling pathway	0.0000	0	44	49	-0.011	0.046	1000	-1000	-0.043	-1000
Atypical NF-kappaB pathway	0.0000	0	25	31	0	0.046	1000	-1000	-0.038	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	3	27	-0.001	0.032	1000	-1000	-0.053	-1000
Rapid glucocorticoid signaling	0.0000	0	14	20	-0.002	0.013	1000	-1000	-0.041	-1000
Arf1 pathway	0.0000	0	12	54	-0.006	0.03	1000	-1000	-0.046	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.019	1000	-1000	-0.061	-1000
Total	NA	1845	109436	7203	-32	-2000	131000	-131000	-8.6	-131000

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.49	0.35	0.72	194	-10000	0	194
KIRREL	-0.12	0.24	-10000	0	-0.88	26	26
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.49	0.36	-10000	0	-0.72	194	194
PLCG1	0.013	0	-10000	0	-10000	0	0
ARRB2	0.011	0.018	-10000	0	-0.29	1	1
WASL	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.53	0.38	-10000	0	-0.71	215	215
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.4	0.31	-10000	0	-0.55	215	215
FYN	-0.5	0.36	-10000	0	-0.67	215	215
mol:Ca2+	-0.52	0.37	-10000	0	-0.7	215	215
mol:DAG	-0.52	0.38	-10000	0	-0.7	215	215
NPHS2	-0.36	0.4	-10000	0	-0.87	109	109
mol:IP3	-0.52	0.38	-10000	0	-0.7	215	215
regulation of endocytosis	-0.46	0.34	-10000	0	-0.63	215	215
Nephrin/NEPH1/podocin/Cholesterol	-0.53	0.38	-10000	0	-0.72	215	215
establishment of cell polarity	-0.49	0.35	-10000	0	-0.72	194	194
Nephrin/NEPH1/podocin/NCK1-2	-0.49	0.36	-10000	0	-0.66	215	215
Nephrin/NEPH1/beta Arrestin2	-0.47	0.36	-10000	0	-0.64	215	215
NPHS1	-0.56	0.4	-10000	0	-0.85	187	187
Nephrin/NEPH1/podocin	-0.5	0.36	-10000	0	-0.68	215	215
TJP1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
NCK2	0.013	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.53	0.38	-10000	0	-0.71	215	215
CD2AP	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.53	0.38	-10000	0	-0.71	215	215
GRB2	0.013	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.61	0.4	-10000	0	-0.75	234	234
cytoskeleton organization	-0.52	0.39	-10000	0	-0.71	215	215
Nephrin/NEPH1	-0.37	0.28	-10000	0	-0.55	194	194
Nephrin/NEPH1/ZO-1	-0.41	0.3	-10000	0	-0.6	194	194

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.013	0	-9999	-10000	0	0
EGFR	0.013	0	-9999	-10000	0	0
EGF/EGFR	-0.43	0.16	-9999	-0.47	263	263
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.41	0.14	-9999	-0.46	260	260
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.025	0.17	-9999	-0.81	13	13
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.73	0.25	-9999	-0.81	260	260
EGF/EGFR dimer/SHC	-0.48	0.16	-9999	-0.54	260	260
mol:GDP	-0.41	0.14	-9999	-0.45	260	260
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.008	0.054	-9999	-0.46	3	3
GRB2/SOS1	0.019	0	-9999	-10000	0	0
HRAS/GTP	-0.38	0.13	-9999	-0.42	260	260
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	-0.38	0.13	-9999	-0.42	260	260
FRAP1	-0.39	0.14	-9999	-0.44	260	260
EGF/EGFR dimer	-0.56	0.19	-9999	-0.62	260	260
SOS1	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.014	0.14	-9999	-0.62	14	14

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.56	0.56	-10000	0	-1	165	165
NCK1/PAK1/Dok-R	-0.26	0.22	-10000	0	-0.45	165	165
NCK1/Dok-R	-0.74	0.72	-10000	0	-1.3	165	165
PIK3CA	0.014	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.084	0.12	0.25	96	-10000	0	96
RELA	0.013	0	-10000	0	-10000	0	0
SHC1	0.011	0.002	-10000	0	-10000	0	0
Rac/GDP	0.009	0	-10000	0	-10000	0	0
F2	0.066	0.14	0.26	47	-0.31	13	60
TNIP2	0.013	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.68	0.61	-10000	0	-1.2	165	165
FN1	-0.01	0.079	-10000	0	-0.29	21	21
PLD2	-0.77	0.77	-10000	0	-1.4	165	165
PTPN11	0.013	0	-10000	0	-10000	0	0
GRB14	-0.045	0.21	-10000	0	-0.81	20	20
ELK1	-0.64	0.64	-10000	0	-1.2	165	165
GRB7	0.013	0	-10000	0	-10000	0	0
PAK1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.74	0.67	-10000	0	-1.3	165	165
CDKN1A	-0.36	0.38	-10000	0	-0.7	154	154
ITGA5	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.74	0.72	-10000	0	-1.3	165	165
CRK	0.013	0	-10000	0	-10000	0	0
mol:NO	-0.38	0.4	-10000	0	-0.72	165	165
PLG	-0.98	0.72	-10000	0	-1.6	165	165
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.52	0.52	-10000	0	-0.96	165	165
GRB2	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.011	0.002	-10000	0	-10000	0	0
ANGPT2	-0.28	0.34	-10000	0	-0.78	74	74
BMX	-0.77	0.77	-10000	0	-1.4	165	165
ANGPT1	-0.49	0.68	-10000	0	-1.4	98	98
tube development	-0.43	0.43	-10000	0	-0.79	163	163
ANGPT4	0.003	0.036	-10000	0	-0.29	4	4
response to hypoxia	-0.038	0.036	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.84	0.81	-10000	0	-1.5	165	165
alpha5/beta1 Integrin	0.019	0	-10000	0	-10000	0	0
FGF2	0.005	0.083	-10000	0	-0.81	3	3
STAT5A (dimer)	-0.5	0.5	-10000	0	-0.92	163	163
mol:L-citrulline	-0.38	0.4	-10000	0	-0.72	165	165
AGTR1	-0.25	0.38	-10000	0	-0.81	91	91
MAPK14	-0.76	0.74	-10000	0	-1.4	165	165
Tie2/SHP2	-0.67	0.64	-10000	0	-1.3	148	148
TEK	-0.74	0.74	-10000	0	-1.4	148	148
RPS6KB1	-0.53	0.53	-10000	0	-0.98	165	165
Angiotensin II/AT1	-0.19	0.3	-10000	0	-0.63	91	91
Tie2/Ang1/GRB2	-0.81	0.81	-10000	0	-1.5	165	165
MAPK3	-0.67	0.67	-10000	0	-1.2	165	165
MAPK1	-0.67	0.67	-10000	0	-1.2	165	165
Tie2/Ang1/GRB7	-0.81	0.81	-10000	0	-1.5	165	165
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.78	0.77	-10000	0	-1.4	165	165
PI3K	-0.68	0.67	-10000	0	-1.2	165	165
FES	-0.76	0.74	-10000	0	-1.4	165	165
Crk/Dok-R	-0.74	0.72	-10000	0	-1.3	165	165
Tie2/Ang1/ABIN2	-0.81	0.81	-10000	0	-1.5	165	165
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.48	0.48	-10000	0	-0.89	165	165
STAT5A	0.013	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.53	0.53	-10000	0	-0.98	165	165
Tie2/Ang2	-0.65	0.63	-10000	0	-1.2	163	163
Tie2/Ang1	-0.9	0.91	-10000	0	-1.6	165	165
FOXO1	-0.48	0.49	-10000	0	-0.9	165	165
ELF1	-0.036	0.055	-10000	0	-10000	0	0
ELF2	-0.79	0.78	-10000	0	-1.4	165	165
mol:Choline	-0.71	0.7	-10000	0	-1.3	165	165
cell migration	-0.14	0.12	-10000	0	-0.25	164	164
FYN	-0.5	0.5	-10000	0	-0.93	163	163
DOK2	-0.009	0.087	-10000	0	-0.32	19	19
negative regulation of cell cycle	-0.33	0.34	-10000	0	-0.62	154	154
ETS1	-0.066	0.11	-10000	0	-10000	0	0
PXN	-0.41	0.43	-10000	0	-0.78	165	165
ITGB1	0.013	0	-10000	0	-10000	0	0
NOS3	-0.45	0.46	-10000	0	-0.85	165	165
RAC1	0.013	0	-10000	0	-10000	0	0
TNF	-0.09	0.15	-10000	0	-0.54	12	12
MAPKKK cascade	-0.71	0.7	-10000	0	-1.3	165	165
RASA1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.82	0.82	-10000	0	-1.5	165	165
NCK1	0.013	0	-10000	0	-10000	0	0
vasculogenesis	-0.33	0.36	-10000	0	-0.64	165	165
mol:Phosphatidic acid	-0.71	0.7	-10000	0	-1.3	165	165
mol:Angiotensin II	0	0.003	-10000	0	-10000	0	0
mol:NADP	-0.38	0.4	-10000	0	-0.72	165	165
Rac1/GTP	-0.52	0.45	-10000	0	-0.9	165	165
MMP2	-0.77	0.77	-10000	0	-1.4	165	165

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.48	0.42	-9999	-1	80	80
PCK1	-1.1	0.72	-9999	-1.6	183	183
HNF4A	-0.57	0.56	-9999	-1.3	90	90
KCNJ11	-0.5	0.43	-9999	-1	89	89
AKT1	-0.23	0.14	-9999	-0.44	21	21
response to starvation	-0.005	0.017	-9999	-10000	0	0
DLK1	-0.52	0.44	-9999	-1.1	88	88
NKX2-1	-0.12	0.15	-9999	-10000	0	0
ACADM	-0.48	0.42	-9999	-1	87	87
TAT	-0.44	0.24	-9999	-0.71	96	96
CEBPB	-0.035	0.064	-9999	-0.35	9	9
CEBPA	-0.054	0.1	-9999	-0.36	27	27
TTR	-0.75	0.41	-9999	-0.95	180	180
PKLR	-0.63	0.62	-9999	-1.4	105	105
APOA1	-0.61	0.58	-9999	-1.3	91	91
CPT1C	-0.5	0.44	-9999	-1.1	90	90
ALAS1	-0.2	0.15	-9999	-10000	0	0
TFRC	-0.58	0.31	-9999	-0.85	127	127
FOXF1	0.005	0.069	-9999	-0.81	2	2
NF1	0.019	0	-9999	-10000	0	0
HNF1A (dimer)	-0.041	0.11	-9999	-0.86	4	4
CPT1A	-0.48	0.42	-9999	-1	87	87
HMGCS1	-0.48	0.42	-9999	-1	87	87
NR3C1	0.008	0.038	-9999	-10000	0	0
CPT1B	-0.48	0.42	-9999	-1	86	86
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.007	-9999	-10000	0	0
GCK	-0.48	0.42	-9999	-0.99	96	96
CREB1	-0.075	0.065	-9999	-10000	0	0
IGFBP1	-0.28	0.38	-9999	-1.4	26	26
PDX1	-0.25	0.21	-9999	-0.86	10	10
UCP2	-0.48	0.42	-9999	-1	88	88
ALDOB	-1.2	0.42	-9999	-1.3	274	274
AFP	-0.5	0.38	-9999	-0.9	90	90
BDH1	-0.48	0.42	-9999	-1	85	85
HADH	-0.5	0.43	-9999	-1.1	84	84
F2	-0.57	0.5	-9999	-1.2	86	86
HNF1A	-0.041	0.11	-9999	-0.86	4	4
G6PC	-1.1	0.63	-9999	-1.5	198	198
SLC2A2	-0.48	0.59	-9999	-1.7	50	50
INS	0.001	0.043	-9999	-0.31	1	1
FOXA1	-0.23	0.13	-9999	-0.46	44	44
FOXA3	-0.46	0.29	-9999	-0.54	231	231
FOXA2	-0.58	0.48	-9999	-1.1	105	105
ABCC8	-0.51	0.43	-9999	-1	96	96
ALB	-1.1	0.41	-9999	-1.2	264	264

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.3	0.4	-9999	-0.82	109	109
PDGF/PDGFRA/CRKL	-0.22	0.31	-9999	-0.62	109	109
positive regulation of JUN kinase activity	-0.18	0.23	-9999	-0.48	109	109
CRKL	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.23	0.31	-9999	-0.62	109	109
AP1	-0.32	0.48	-9999	-1.4	44	44
mol:IP3	-0.23	0.32	-9999	-0.64	109	109
PLCG1	-0.23	0.32	-9999	-0.64	109	109
PDGF/PDGFRA/alphaV Integrin	-0.22	0.31	-9999	-0.62	109	109
RAPGEF1	0.013	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.23	0.32	-9999	-0.64	109	109
CAV3	0.001	0.018	-9999	-0.29	1	1
CAV1	0.011	0.018	-9999	-0.29	1	1
SHC/Grb2/SOS1	-0.16	0.25	-9999	-0.48	109	109
PDGF/PDGFRA/Shf	-0.22	0.31	-9999	-0.62	109	109
FOS	-0.3	0.49	-9999	-1.3	44	44
JUN	-0.021	0.026	-9999	-10000	0	0
oligodendrocyte development	-0.22	0.31	-9999	-0.62	109	109
GRB2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	-0.23	0.32	-9999	-0.64	109	109
PDGF/PDGFRA	-0.3	0.4	-9999	-0.82	109	109
actin cytoskeleton reorganization	-0.22	0.31	-9999	-0.62	109	109
SRF	0.028	0.011	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
PI3K	-0.2	0.26	-9999	-0.53	109	109
PDGF/PDGFRA/Crk/C3G	-0.2	0.26	-9999	-0.53	109	109
JAK1	-0.22	0.31	-9999	-0.62	109	109
ELK1/SRF	-0.16	0.25	-9999	-0.48	109	109
SHB	0.013	0	-9999	-10000	0	0
SHF	0.013	0	-9999	-10000	0	0
CSNK2A1	0.021	0.025	-9999	-10000	0	0
GO:0007205	-0.23	0.32	-9999	-0.65	109	109
SOS1	0.013	0	-9999	-10000	0	0
Ras protein signal transduction	-0.18	0.23	-9999	-0.48	109	109
PDGF/PDGFRA/SHB	-0.22	0.31	-9999	-0.62	109	109
PDGF/PDGFRA/Caveolin-1	-0.22	0.31	-9999	-0.62	109	109
ITGAV	0.013	0	-9999	-10000	0	0
ELK1	-0.2	0.29	-9999	-0.58	109	109
PIK3CA	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.22	0.31	-9999	-0.62	109	109
JAK-STAT cascade	-0.22	0.31	-9999	-0.61	109	109
cell proliferation	-0.22	0.31	-9999	-0.62	109	109

×

Thromboxane A2 receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.012	0.077	-10000	0	-0.29	20	20
GNB1/GNG2	-0.1	0.089	-10000	0	-0.19	111	111
AKT1	-0.09	0.12	-10000	0	-0.21	43	43
EGF	-0.73	0.25	-10000	0	-0.81	260	260
mol:TXA2	-0.001	0.001	-10000	0	-10000	0	0
FGR	0.006	0.1	-10000	0	-0.36	16	16
mol:Ca2+	-0.15	0.17	-10000	0	-0.31	148	148
LYN	0.011	0.096	-10000	0	-0.43	2	2
RhoA/GTP	-0.069	0.058	-10000	0	-0.14	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.17	0.19	-10000	0	-0.34	148	148
GNG2	0.012	0	-10000	0	-10000	0	0
ARRB2	0.011	0.018	-10000	0	-0.29	1	1
TP alpha/Gq family/GDP/G beta5/gamma2	-0.027	0.12	-10000	0	-0.52	6	6
G beta5/gamma2	-0.13	0.12	-10000	0	-0.25	111	111
PRKCH	-0.18	0.19	-10000	0	-0.36	148	148
DNM1	-0.085	0.15	-10000	0	-0.3	91	91
TXA2/TP beta/beta Arrestin3	-0.026	0.043	-10000	0	-0.3	1	1
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
PTGDR	0.012	0.001	-10000	0	-10000	0	0
G12 family/GTP	-0.17	0.14	-10000	0	-0.3	148	148
ADRBK1	0.012	0	-10000	0	-10000	0	0
ADRBK2	0.012	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.004	0.008	-10000	0	-10000	0	0
mol:GDP	0.088	0.12	0.38	19	-10000	0	19
mol:NADP	-0.016	0.15	-10000	0	-0.81	10	10
RAB11A	0.013	0	-10000	0	-10000	0	0
PRKG1	-0.2	0.36	-10000	0	-0.81	73	73
mol:IP3	-0.2	0.21	-10000	0	-0.39	148	148
cell morphogenesis	0.004	0.007	-10000	0	-10000	0	0
PLCB2	-0.27	0.28	-10000	0	-0.52	148	148
mol:cGMP	-0.001	0.001	-10000	0	-10000	0	0
BLK	0.002	0.097	-10000	0	-0.34	16	16
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.002	0.11	-10000	0	-0.36	15	15
RHOA	0.013	0	-10000	0	-10000	0	0
PTGIR	0.007	0.068	-10000	0	-0.81	2	2
PRKCB1	-0.19	0.21	-10000	0	-0.38	148	148
GNAQ	0.013	0	-10000	0	-10000	0	0
mol:L-citrulline	-0.016	0.15	-10000	0	-0.81	10	10
TXA2/TXA2-R family	-0.27	0.28	-10000	0	-0.54	148	148
LCK	0.009	0.097	-10000	0	-0.52	1	1
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.03	0.11	-10000	0	-0.42	20	20
TXA2-R family/G12 family/GDP/G beta/gamma	0.022	0.034	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.03	0.11	-10000	0	-0.42	20	20
MAPK14	-0.1	0.13	-10000	0	-0.22	148	148
TGM2/GTP	-0.22	0.23	-10000	0	-0.43	148	148
MAPK11	-0.1	0.13	-10000	0	-0.22	148	148
ARHGEF1	-0.082	0.1	-10000	0	-0.18	69	69
GNAI2	0.013	0	-10000	0	-10000	0	0
JNK cascade	-0.2	0.21	-10000	0	-0.39	148	148
RAB11/GDP	0.014	0.002	-10000	0	-10000	0	0
ICAM1	-0.14	0.16	-10000	0	-0.28	149	149
cAMP biosynthetic process	-0.18	0.19	-10000	0	-0.36	148	148
Gq family/GTP/EBP50	-0.039	0.12	-10000	0	-0.37	7	7
actin cytoskeleton reorganization	0.004	0.007	-10000	0	-10000	0	0
SRC	0.011	0.096	-10000	0	-0.43	2	2
GNB5	0.012	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
EGF/EGFR	-0.1	0.083	-10000	0	-0.32	20	20
VCAM1	-0.15	0.17	-10000	0	-0.3	149	149
TP beta/Gq family/GDP/G beta5/gamma2	-0.027	0.12	-10000	0	-0.52	6	6
platelet activation	-0.14	0.18	-10000	0	-0.3	148	148
PGI2/IP	0	0.053	-10000	0	-0.63	2	2
PRKACA	0.016	0.033	-10000	0	-0.38	2	2
Gq family/GDP/G beta5/gamma2	-0.021	0.1	-10000	0	-0.45	6	6
TXA2/TP beta/beta Arrestin2	-0.034	0.06	-10000	0	-0.64	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.012	0.13	-10000	0	-0.48	21	21
mol:DAG	-0.22	0.23	-10000	0	-0.43	148	148
EGFR	0.013	0	-10000	0	-10000	0	0
TXA2/TP alpha	-0.25	0.26	-10000	0	-0.49	148	148
Gq family/GTP	-0.07	0.12	-10000	0	-0.29	66	66
YES1	0.011	0.096	-10000	0	-0.43	2	2
GNAI2/GTP	-0.028	0.1	-10000	0	-0.38	20	20
PGD2/DP	0.004	0.005	-10000	0	-10000	0	0
SLC9A3R1	0.013	0	-10000	0	-10000	0	0
FYN	0.011	0.096	-10000	0	-0.52	1	1
mol:NO	-0.016	0.15	-10000	0	-0.81	10	10
GNA15	-0.009	0.077	-10000	0	-0.29	20	20
PGK/cGMP	-0.15	0.26	-10000	0	-0.57	79	79
RhoA/GDP	0.014	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.017	0.12	-10000	0	-0.43	20	20
NOS3	-0.016	0.15	-10000	0	-0.81	10	10
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.18	0.19	-10000	0	-0.36	148	148
PRKCB	-0.18	0.2	-10000	0	-0.36	148	148
PRKCE	-0.18	0.2	-10000	0	-0.36	148	148
PRKCD	-0.19	0.21	-10000	0	-0.39	148	148
PRKCG	-0.21	0.22	-10000	0	-0.41	148	148
muscle contraction	-0.25	0.26	-10000	0	-0.49	148	148
PRKCZ	-0.17	0.19	-10000	0	-0.34	148	148
ARR3	0.003	0.005	-10000	0	-10000	0	0
TXA2/TP beta	-0.022	0.12	-10000	0	-0.43	20	20
PRKCQ	-0.19	0.2	-10000	0	-0.37	149	149
MAPKKK cascade	-0.23	0.24	-10000	0	-0.46	148	148
SELE	-0.21	0.23	-10000	0	-0.43	148	148
TP beta/GNAI2/GDP/G beta/gamma	-0.01	0.11	-10000	0	-0.41	20	20
ROCK1	0.013	0	-10000	0	-10000	0	0
GNA14	-0.16	0.34	-10000	0	-0.81	61	61
chemotaxis	-0.31	0.32	-10000	0	-0.62	148	148
GNA12	0.013	0	-10000	0	-10000	0	0
GNA13	0.011	0.018	-10000	0	-0.29	1	1
GNA11	-0.005	0.12	-10000	0	-0.81	6	6
Rac1/GTP	0.003	0.005	-10000	0	-10000	0	0

×

Glypican 2 network

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
MDK	-0.069	0.14	-9999	-0.29	77	77
GPC2	-0.12	0.15	-9999	-10000	0	0
GPC2/Midkine	-0.12	0.15	-9999	-0.37	55	55
neuron projection morphogenesis	-0.12	0.15	-9999	-0.37	55	55

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.2	0.51	-9999	-1.3	50	50
MKNK1	0.013	0	-9999	-10000	0	0
MAPK14	-0.044	0.15	-9999	-0.32	63	63
ATF2/c-Jun	-0.019	0.12	-9999	-0.43	8	8
MAPK11	-0.044	0.15	-9999	-0.32	63	63
MITF	-0.047	0.18	-9999	-0.38	64	64
MAPKAPK5	-0.045	0.18	-9999	-0.38	63	63
KRT8	-0.048	0.18	-9999	-0.38	63	63
MAPKAPK3	0.013	0	-9999	-10000	0	0
MAPKAPK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.071	0.23	-9999	-0.49	63	63
CEBPB	-0.05	0.18	-9999	-0.38	63	63
SLC9A1	-0.045	0.18	-9999	-0.38	63	63
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.038	0.18	-9999	-0.36	63	63
p38alpha-beta/MNK1	-0.046	0.19	-9999	-0.39	63	63
JUN	-0.018	0.12	-9999	-0.42	8	8
PPARGC1A	-0.058	0.2	-9999	-0.4	68	68
USF1	-0.045	0.18	-9999	-0.38	63	63
RAB5/GDP/GDI1	-0.059	0.12	-9999	-0.47	8	8
NOS2	-0.11	0.38	-9999	-1.4	21	21
DDIT3	-0.046	0.18	-9999	-0.38	63	63
RAB5A	0.013	0	-9999	-10000	0	0
HSPB1	-0.032	0.15	-9999	-0.5	9	9
p38alpha-beta/HBP1	-0.046	0.19	-9999	-0.39	63	63
CREB1	-0.047	0.19	-9999	-0.4	63	63
RAB5/GDP	0.009	0	-9999	-10000	0	0
EIF4E	-0.036	0.17	-9999	-0.62	8	8
RPS6KA4	-0.045	0.18	-9999	-0.38	63	63
PLA2G4A	-0.049	0.2	-9999	-0.74	14	14
GDI1	-0.045	0.18	-9999	-0.38	63	63
TP53	-0.063	0.22	-9999	-0.48	63	63
RPS6KA5	-0.051	0.2	-9999	-0.4	64	64
ESR1	-0.077	0.24	-9999	-0.44	73	73
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.045	0.18	-9999	-0.38	63	63
MEF2A	-0.045	0.18	-9999	-0.38	63	63
EIF4EBP1	-0.048	0.2	-9999	-0.4	63	63
KRT19	-0.1	0.24	-9999	-0.44	83	83
ELK4	-0.045	0.18	-9999	-0.38	63	63
ATF6	-0.045	0.18	-9999	-0.38	63	63
ATF1	-0.047	0.19	-9999	-0.4	63	63
p38alpha-beta/MAPKAPK2	-0.046	0.19	-9999	-0.39	63	63
p38alpha-beta/MAPKAPK3	-0.046	0.19	-9999	-0.39	63	63

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.013	0.037	-9999	-0.41	1	1
EGFR	0.012	0	-9999	-10000	0	0
EPHA2	0.011	0.018	-9999	-0.29	1	1
USP6	0	0.061	-9999	-0.29	12	12
IQSEC1	0.012	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.56	0.19	-9999	-0.62	260	260
ARRB2	-0.003	0.041	-9999	-10000	0	0
mol:GTP	0.015	0.012	-9999	-10000	0	0
ARRB1	0.01	0.048	-9999	-0.81	1	1
FBXO8	0.013	0	-9999	-10000	0	0
TSHR	0.007	0.031	-9999	-0.29	3	3
EGF	-0.73	0.25	-9999	-0.81	260	260
somatostatin receptor activity	0	0	-9999	-0.001	117	117
ARAP2	0.012	0	-9999	-10000	0	0
mol:GDP	-0.12	0.11	-9999	-0.27	90	90
mol:PI-3-4-5-P3	0	0	-9999	-0.001	80	80
ITGA2B	-0.009	0.077	-9999	-0.29	20	20
ARF6	0.012	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.032	0.009	-9999	-10000	0	0
ADAP1	0.012	0	-9999	-10000	0	0
KIF13B	0.013	0	-9999	-10000	0	0
HGF/MET	-0.046	0.17	-9999	-0.67	17	17
PXN	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.17	0.12	-9999	-0.31	117	117
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.48	0.16	-9999	-0.54	260	260
ADRB2	-0.006	0.072	-9999	-0.29	17	17
receptor agonist activity	0	0	-9999	0	117	117
actin filament binding	0	0	-9999	-0.001	117	117
SRC	0.011	0.018	-9999	-0.29	1	1
ITGB3	-0.031	0.18	-9999	-0.65	19	19
GNAQ	0.012	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	-0.001	0	-9999	-0.001	115	115
ARF6/GDP	-0.029	0.057	-9999	-10000	0	0
ARF6/GDP/GULP/ACAP1	-0.11	0.11	-9999	-0.39	12	12
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.005	0.11	-9999	-0.49	13	13
ACAP1	-0.027	0.1	-9999	-0.29	37	37
ACAP2	0.012	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.012	0.054	-9999	-10000	0	0
EFNA1	0.012	0	-9999	-10000	0	0
HGF	-0.037	0.2	-9999	-0.81	17	17
CYTH3	0.01	0	-9999	-10000	0	0
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	69	69
endosomal lumen acidification	0	0	-9999	-0.001	117	117
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	0.011	0.018	-9999	-10000	0	0
GNAQ/ARNO	0.008	0.007	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	91	91
MET	-0.026	0.1	-9999	-0.29	36	36
GNA14	-0.16	0.34	-9999	-0.81	61	61
GNA15	-0.009	0.077	-9999	-0.29	20	20
GIT1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	117	117
GNA11	-0.005	0.12	-9999	-0.81	6	6
LHCGR	-0.026	0.091	-9999	-0.29	30	30
AGTR1	-0.25	0.38	-9999	-0.81	91	91
desensitization of G-protein coupled receptor protein signaling pathway	-0.012	0.053	-9999	-10000	0	0
IPCEF1/ARNO	-0.38	0.13	-9999	-0.43	260	260
alphaIIb/beta3 Integrin	-0.029	0.14	-9999	-0.62	13	13

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.006	0.055	-10000	0	-0.54	3	3
fibroblast growth factor receptor signaling pathway	-0.006	0.055	-10000	0	-0.54	3	3
LAMA1	-0.025	0.15	-10000	0	-0.81	8	8
PRNP	0.013	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.12	0.26	-10000	0	-0.62	61	61
SMAD2	0.031	0.009	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.001	0.009	-10000	0	-10000	0	0
GPC1/Laminin alpha1	-0.01	0.12	-10000	0	-0.64	8	8
TDGF1	-0.42	0.41	-10000	0	-0.81	149	149
CRIPTO/GPC1	-0.32	0.32	-10000	0	-0.62	149	149
APP/GPC1	0.018	0.012	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.27	0.28	-10000	0	-0.54	149	149
FLT1	0.007	0.068	-10000	0	-0.81	2	2
GPC1/TGFB/TGFBR1/TGFBR2	-0.001	0.009	-10000	0	-10000	0	0
SERPINC1	-0.12	0.3	-10000	0	-0.81	44	44
FYN	-0.27	0.28	-10000	0	-0.54	149	149
FGR	-0.27	0.28	-10000	0	-0.55	149	149
positive regulation of MAPKKK cascade	-0.26	0.29	-10000	0	-0.54	149	149
SLIT2	-0.16	0.34	-10000	0	-0.81	61	61
GPC1/NRG	0.005	0.09	-10000	0	-0.65	5	5
NRG1	-0.005	0.11	-10000	0	-0.62	8	8
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.006	0.048	-10000	0	-0.54	2	2
LYN	-0.27	0.28	-10000	0	-0.54	149	149
mol:Spermine	0.01	0.012	-10000	0	-10000	0	0
cell growth	-0.006	0.055	-10000	0	-0.54	3	3
BMP signaling pathway	-0.011	0.018	0.29	1	-10000	0	1
SRC	-0.27	0.28	-10000	0	-0.54	149	149
TGFBR1	0.013	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.015	0.074	-10000	0	-0.29	19	19
GPC1	0.011	0.018	-10000	0	-0.29	1	1
TGFBR1 (dimer)	0.012	0	-10000	0	-10000	0	0
VEGFA	0.009	0.031	-10000	0	-0.29	3	3
BLK	-0.28	0.28	-10000	0	-0.55	149	149
HCK	-0.28	0.28	-10000	0	-0.55	149	149
FGF2	0.004	0.084	-10000	0	-0.81	3	3
FGFR1	0.013	0	-10000	0	-10000	0	0
VEGFR1 homodimer	0.007	0.068	-10000	0	-0.81	2	2
TGFBR2	0.013	0	-10000	0	-10000	0	0
cell death	0.018	0.012	-10000	0	-10000	0	0
ATIII/GPC1	-0.081	0.23	-10000	0	-0.62	44	44
PLA2G2A/GPC1	-0.001	0.053	-10000	0	-0.37	1	1
LCK	-0.27	0.28	-10000	0	-0.54	149	149
neuron differentiation	0.005	0.09	-10000	0	-0.65	5	5
PrPc/Cu2+	0.009	0	-10000	0	-10000	0	0
APP	0.013	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.012	0	-10000	0	-10000	0	0

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.052	0.1	-9999	-0.42	7	7
alphaM/beta2 Integrin/GPIbA	-0.049	0.1	-9999	-0.32	26	26
alphaM/beta2 Integrin/proMMP-9	-0.11	0.14	-9999	-0.38	51	51
PLAUR	-0.009	0.077	-9999	-0.29	20	20
HMGB1	0.008	0.017	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.047	0.092	-9999	-0.33	5	5
AGER	-0.014	0.081	-9999	-0.3	21	21
RAP1A	0.013	0	-9999	-10000	0	0
SELPLG	-0.02	0.094	-9999	-0.29	31	31
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.07	0.1	-9999	-0.38	7	7
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.12	0.17	-9999	-0.31	115	115
CYR61	-0.013	0.14	-9999	-0.81	9	9
TLN1	0.013	0	-9999	-10000	0	0
Rap1/GTP	-0.2	0.15	-9999	-0.47	46	46
RHOA	0.013	0	-9999	-10000	0	0
P-selectin oligomer	-0.067	0.24	-9999	-0.81	28	28
MYH2	-0.27	0.22	-9999	-0.5	97	97
MST1R	-0.02	0.11	-9999	-0.33	27	27
leukocyte activation during inflammatory response	-0.092	0.16	-9999	-0.48	32	32
APOB	-0.046	0.19	-9999	-0.81	15	15
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.004	0.062	-9999	-0.81	1	1
JAM3	0.01	0.048	-9999	-0.81	1	1
GP1BA	0.01	0.048	-9999	-0.81	1	1
alphaM/beta2 Integrin/CTGF	-0.06	0.12	-9999	-0.36	33	33
alphaM/beta2 Integrin	-0.23	0.19	-9999	-0.41	108	108
JAM3 homodimer	0.01	0.048	-9999	-0.81	1	1
ICAM2	0.013	0	-9999	-10000	0	0
ICAM1	0.009	0.031	-9999	-0.29	3	3
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.23	0.18	-9999	-0.41	109	109
cell adhesion	-0.049	0.1	-9999	-0.32	26	26
NFKB1	-0.049	0.16	-9999	-0.5	9	9
THY1	-0.29	0.4	-9999	-0.81	106	106
RhoA/GDP	0.009	0	-9999	-10000	0	0
Lipoprotein(a)	-0.063	0.17	-9999	-0.55	29	29
alphaM/beta2 Integrin/LRP/tPA	-0.087	0.16	-9999	-0.51	29	29
IL6	-0.1	0.31	-9999	-0.95	30	30
ITGB2	-0.046	0.12	-9999	-0.29	51	51
elevation of cytosolic calcium ion concentration	-0.061	0.12	-9999	-0.43	19	19
alphaM/beta2 Integrin/JAM2/JAM3	-0.048	0.1	-9999	-0.47	6	6
JAM2	0.001	0.096	-9999	-0.81	4	4
alphaM/beta2 Integrin/ICAM1	-0.051	0.093	-9999	-0.43	6	6
alphaM/beta2 Integrin/uPA/Plg	-0.33	0.27	-9999	-0.55	168	168
RhoA/GTP	-0.28	0.24	-9999	-0.5	108	108
positive regulation of phagocytosis	-0.18	0.15	-9999	-0.44	51	51
Ron/MSP	-0.007	0.087	-9999	-0.62	3	3
alphaM/beta2 Integrin/uPAR/uPA	-0.061	0.12	-9999	-0.44	19	19
alphaM/beta2 Integrin/uPAR	-0.058	0.12	-9999	-0.36	32	32
PLAU	-0.007	0.13	-9999	-0.81	7	7
PLAT	-0.068	0.24	-9999	-0.79	29	29
actin filament polymerization	-0.26	0.21	-9999	-0.47	97	97
MST1	0.008	0.054	-9999	-0.46	3	3
alphaM/beta2 Integrin/lipoprotein(a)	-0.093	0.16	-9999	-0.49	32	32
TNF	-0.049	0.18	-9999	-0.71	8	8
RAP1B	0.013	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.06	0.12	-9999	-0.46	12	12
fibrinolysis	-0.33	0.26	-9999	-0.54	168	168
HCK	-0.022	0.1	-9999	-0.31	31	31
dendritic cell antigen processing and presentation	-0.23	0.18	-9999	-0.41	109	109
VTN	-0.2	0.36	-9999	-0.76	81	81
alphaM/beta2 Integrin/CYR61	-0.064	0.13	-9999	-0.38	34	34
LPA	-0.036	0.18	-9999	-0.78	15	15
LRP1	0.013	0	-9999	-10000	0	0
cell migration	-0.085	0.15	-9999	-0.42	28	28
FN1	-0.01	0.079	-9999	-0.29	21	21
alphaM/beta2 Integrin/Thy1	-0.24	0.26	-9999	-0.52	128	128
MPO	-0.005	0.069	-9999	-10000	0	0
KNG1	-0.48	0.4	-9999	-0.81	169	169
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.26	0.22	-9999	-0.49	93	93
ELA2	0	0	-9999	-10000	0	0
PLG	-0.46	0.4	-9999	-0.81	164	164
CTGF	-0.007	0.13	-9999	-0.81	7	7
alphaM/beta2 Integrin/Hck	-0.065	0.13	-9999	-0.39	36	36
ITGAM	-0.025	0.094	-9999	-0.29	31	31
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.1	0.17	-9999	-0.46	46	46
HP	-0.033	0.11	-9999	-0.29	42	42
leukocyte adhesion	-0.22	0.23	-9999	-0.49	107	107
SELP	-0.067	0.24	-9999	-0.81	28	28

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.028	0.18	-10000	0	-0.58	16	16
PTK2B	0.012	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.28	0.48	-10000	0	-1	82	82
EDN1	-0.008	0.098	-10000	0	-0.58	2	2
EDN3	0.004	0.036	-10000	0	-0.29	4	4
EDN2	-0.028	0.17	-10000	0	-0.71	16	16
HRAS/GDP	-0.12	0.23	-10000	0	-0.53	46	46
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.12	0.22	-10000	0	-0.44	71	71
ADCY4	-0.046	0.2	-10000	0	-0.56	28	28
ADCY5	-0.047	0.19	-10000	0	-0.52	30	30
ADCY6	-0.018	0.14	-10000	0	-0.49	16	16
ADCY7	-0.025	0.15	-10000	0	-0.49	16	16
ADCY1	-0.25	0.28	-10000	0	-0.51	142	142
ADCY2	-0.1	0.16	-10000	0	-0.56	17	17
ADCY3	-0.018	0.14	-10000	0	-0.49	16	16
ADCY8	-0.027	0.15	-10000	0	-0.49	17	17
ADCY9	-0.018	0.14	-10000	0	-0.49	16	16
arachidonic acid secretion	-0.16	0.29	-10000	0	-0.56	77	77
ETB receptor/Endothelin-1/Gq/GTP	-0.074	0.18	-10000	0	-0.37	66	66
GNAO1	-0.059	0.23	-10000	0	-0.81	24	24
HRAS	0.012	0.003	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.036	0.17	0.34	15	-0.55	16	31
ETA receptor/Endothelin-1/Gs/GTP	-0.036	0.16	0.32	15	-0.52	17	32
mol:GTP	-0.003	0.008	-10000	0	-10000	0	0
COL3A1	-0.044	0.22	-10000	0	-0.72	20	20
EDNRB	0.01	0.053	-10000	0	-0.55	2	2
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.095	0.26	-10000	0	-0.75	28	28
CYSLTR1	-0.029	0.18	-10000	0	-0.62	15	15
SLC9A1	-0.025	0.091	0.2	4	-0.31	14	18
mol:GDP	-0.14	0.24	-10000	0	-0.55	52	52
SLC9A3	-0.62	0.36	-10000	0	-0.73	244	244
RAF1	-0.15	0.26	-10000	0	-0.55	63	63
JUN	-0.14	0.28	-10000	0	-0.65	48	48
JAK2	-0.028	0.18	-10000	0	-0.58	16	16
mol:IP3	-0.13	0.24	-10000	0	-0.5	67	67
ETA receptor/Endothelin-1	-0.052	0.21	0.4	16	-0.66	17	33
PLCB1	-0.1	0.28	-10000	0	-0.81	39	39
PLCB2	-0.028	0.1	-10000	0	-0.29	36	36
ETA receptor/Endothelin-3	-0.038	0.15	-10000	0	-0.68	13	13
FOS	-0.19	0.38	-10000	0	-0.93	52	52
Gai/GDP	-0.056	0.24	-10000	0	-0.83	24	24
CRK	0.012	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.13	0.26	-10000	0	-0.6	46	46
BCAR1	0.013	0.001	-10000	0	-10000	0	0
PRKCB1	-0.13	0.23	-10000	0	-0.47	71	71
GNAQ	0.009	0.008	-10000	0	-10000	0	0
GNAZ	0.013	0	-10000	0	-10000	0	0
GNAL	0.01	0.048	-10000	0	-0.81	1	1
Gs family/GDP	-0.15	0.19	-10000	0	-0.5	50	50
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.25	-10000	0	-0.53	53	53
MAPK14	-0.085	0.17	-10000	0	-0.4	36	36
TRPC6	-0.31	0.52	-10000	0	-1.1	81	81
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.007	0.068	-10000	0	-0.81	2	2
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.097	0.18	-10000	0	-0.36	73	73
ETB receptor/Endothelin-2	-0.016	0.14	-10000	0	-0.62	14	14
ETB receptor/Endothelin-3	0.01	0.047	-10000	0	-0.63	1	1
ETB receptor/Endothelin-1	0.001	0.083	-10000	0	-0.66	2	2
MAPK3	-0.18	0.35	-10000	0	-0.79	59	59
MAPK1	-0.18	0.35	-10000	0	-0.79	59	59
Rac1/GDP	-0.12	0.23	-10000	0	-0.53	46	46
cAMP biosynthetic process	-0.15	0.2	-10000	0	-0.55	33	33
MAPK8	-0.19	0.35	-10000	0	-0.64	85	85
SRC	0.011	0.018	-10000	0	-0.29	1	1
ETB receptor/Endothelin-1/Gi/GTP	0	0.097	-10000	0	-0.31	13	13
p130Cas/CRK/Src/PYK2	-0.18	0.3	-10000	0	-0.58	80	80
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.12	0.23	-10000	0	-0.53	46	46
COL1A2	-0.017	0.16	-10000	0	-0.54	9	9
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.064	0.2	-10000	0	-0.68	25	25
mol:DAG	-0.13	0.24	-10000	0	-0.5	67	67
MAP2K2	-0.16	0.29	-10000	0	-0.63	63	63
MAP2K1	-0.16	0.29	-10000	0	-0.62	65	65
EDNRA	-0.042	0.2	-10000	0	-0.86	13	13
positive regulation of muscle contraction	-0.018	0.15	-10000	0	-0.53	14	14
Gq family/GDP	-0.19	0.26	-10000	0	-0.63	66	66
HRAS/GTP	-0.14	0.24	-10000	0	-0.53	61	61
PRKCH	-0.12	0.23	-10000	0	-0.51	55	55
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.12	0.23	-10000	0	-0.51	57	57
PRKCB	-0.13	0.23	-10000	0	-0.5	58	58
PRKCE	-0.12	0.23	-10000	0	-0.53	50	50
PRKCD	-0.12	0.23	-10000	0	-0.53	50	50
PRKCG	-0.16	0.24	-10000	0	-0.54	63	63
regulation of vascular smooth muscle contraction	-0.22	0.44	-10000	0	-1.1	52	52
PRKCQ	-0.14	0.24	-10000	0	-0.52	62	62
PLA2G4A	-0.18	0.32	-10000	0	-0.63	76	76
GNA14	-0.16	0.34	-10000	0	-0.82	61	61
GNA15	-0.011	0.077	-10000	0	-0.29	20	20
GNA12	0.013	0	-10000	0	-10000	0	0
GNA11	-0.007	0.12	-10000	0	-0.82	6	6
Rac1/GTP	-0.036	0.17	0.34	15	-0.55	16	31
MMP1	-0.046	0.29	-10000	0	-1.1	18	18

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.045	0.17	-10000	0	-0.39	51	51
CRKL	-0.037	0.18	-10000	0	-0.42	50	50
HRAS	-0.029	0.16	-10000	0	-0.44	12	12
mol:PIP3	-0.047	0.16	-10000	0	-0.4	51	51
SPRED1	0.013	0	-10000	0	-10000	0	0
SPRED2	0.013	0	-10000	0	-10000	0	0
GAB1	-0.047	0.18	-10000	0	-0.44	51	51
FOXO3	-0.028	0.16	-10000	0	-0.37	50	50
AKT1	-0.038	0.17	-10000	0	-0.41	51	51
BAD	-0.028	0.16	-10000	0	-0.37	50	50
megakaryocyte differentiation	-0.11	0.26	-10000	0	-0.51	79	79
GSK3B	-0.028	0.16	-10000	0	-0.37	50	50
RAF1	-0.014	0.13	-10000	0	-0.42	4	4
SHC1	0.013	0	-10000	0	-10000	0	0
STAT3	-0.047	0.18	-10000	0	-0.44	51	51
STAT1	-0.13	0.41	-10000	0	-1	50	50
HRAS/SPRED1	-0.015	0.13	-10000	0	-0.42	4	4
cell proliferation	-0.051	0.19	-10000	0	-0.45	53	53
PIK3CA	0.012	0	-10000	0	-10000	0	0
TEC	0.013	0	-10000	0	-10000	0	0
RPS6KB1	-0.046	0.18	-10000	0	-0.44	51	51
HRAS/SPRED2	-0.015	0.13	-10000	0	-0.42	4	4
LYN/TEC/p62DOK	-0.073	0.16	-10000	0	-0.41	50	50
MAPK3	0.003	0.099	-10000	0	-0.28	4	4
STAP1	-0.34	0.28	-10000	0	-0.5	200	200
GRAP2	0.003	0.053	-10000	0	-0.29	9	9
JAK2	-0.14	0.33	-10000	0	-0.86	50	50
STAT1 (dimer)	-0.12	0.4	-10000	0	-1	50	50
mol:Gleevec	0	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.096	0.17	-10000	0	-0.44	52	52
actin filament polymerization	-0.046	0.18	-10000	0	-0.43	51	51
LYN	0.013	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.34	0.32	-10000	0	-0.51	199	199
PIK3R1	0.012	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.021	0.16	-10000	0	-0.37	50	50
PI3K	-0.032	0.18	-10000	0	-0.41	50	50
PTEN	0.012	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.16	0.5	-10000	0	-1.3	50	50
MAPK8	-0.053	0.2	-10000	0	-0.46	53	53
STAT3 (dimer)	-0.045	0.18	-10000	0	-0.43	51	51
positive regulation of transcription	0.006	0.084	-10000	0	-0.23	4	4
mol:GDP	-0.078	0.14	-10000	0	-0.48	12	12
PIK3C2B	-0.047	0.19	-10000	0	-0.44	51	51
CBL/CRKL	-0.028	0.17	-10000	0	-0.39	50	50
FER	-0.047	0.18	-10000	0	-0.44	51	51
SH2B3	-0.047	0.18	-10000	0	-0.44	51	51
PDPK1	-0.037	0.15	-10000	0	-0.37	50	50
SNAI2	-0.09	0.24	-10000	0	-0.49	70	70
positive regulation of cell proliferation	-0.083	0.3	-10000	0	-0.74	50	50
KITLG	0.004	0.09	-10000	0	-0.84	3	3
cell motility	-0.083	0.3	-10000	0	-0.74	50	50
PTPN6	0.013	0.01	-10000	0	-10000	0	0
EPOR	-0.001	0.12	-10000	0	-10000	0	0
STAT5A (dimer)	-0.064	0.26	-10000	0	-0.61	51	51
SOCS1	0.006	0.071	-10000	0	-0.64	3	3
cell migration	0.059	0.19	0.45	53	-10000	0	53
SOS1	0.013	0	-10000	0	-10000	0	0
EPO	0.006	0.027	-10000	0	-0.29	2	2
VAV1	-0.063	0.14	-10000	0	-0.3	70	70
GRB10	-0.047	0.18	-10000	0	-0.44	51	51
PTPN11	0.013	0.007	-10000	0	-10000	0	0
SCF/KIT	-0.057	0.19	-10000	0	-0.47	51	51
GO:0007205	0.001	0.01	-10000	0	-10000	0	0
MAP2K1	-0.002	0.11	-10000	0	-0.32	4	4
CBL	0.013	0	-10000	0	-10000	0	0
KIT	-0.19	0.53	-10000	0	-1.4	50	50
MAP2K2	-0.002	0.11	-10000	0	-0.32	4	4
SHC/Grb2/SOS1	-0.072	0.16	-10000	0	-0.41	50	50
STAT5A	-0.067	0.26	-10000	0	-0.63	50	50
GRB2	0.013	0	-10000	0	-10000	0	0
response to radiation	-0.087	0.23	-10000	0	-0.48	70	70
SHC/GRAP2	0.012	0.036	-10000	0	-10000	0	0
PTPRO	-0.11	0.26	-10000	0	-0.52	79	79
SH2B2	-0.047	0.18	-10000	0	-0.44	51	51
DOK1	0.009	0.031	-10000	0	-0.29	3	3
MATK	-0.061	0.2	-10000	0	-0.46	53	53
CREBBP	0.031	0.014	-10000	0	-10000	0	0
BCL2	0	0.12	-10000	0	-10000	0	0

×

IL4-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.51	0.44	-10000	0	-1.2	68	68
STAT6 (cleaved dimer)	-0.54	0.43	-10000	0	-1.1	92	92
IGHG1	-0.18	0.14	-10000	0	-0.38	25	25
IGHG3	-0.5	0.43	-10000	0	-1	87	87
AKT1	-0.23	0.2	-10000	0	-0.64	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.17	0.15	-10000	0	-0.6	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.24	0.2	-10000	0	-0.66	13	13
THY1	-0.79	0.68	-10000	0	-1.5	128	128
MYB	-0.059	0.13	-10000	0	-0.29	68	68
HMGA1	0.006	0.043	-10000	0	-0.29	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.3	0.23	-10000	0	-0.63	46	46
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.24	0.19	-10000	0	-0.6	12	12
SP1	0.02	0.004	-10000	0	-10000	0	0
INPP5D	0.002	0.056	-10000	0	-0.29	10	10
SOCS5	0.026	0.012	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.51	0.43	-10000	0	-1.1	74	74
SOCS1	-0.33	0.29	-10000	0	-0.75	50	50
SOCS3	-0.25	0.21	-10000	0	-0.8	7	7
FCER2	-0.39	0.32	-10000	0	-0.85	51	51
PARP14	0.013	0.003	-10000	0	-10000	0	0
CCL17	-0.54	0.44	-10000	0	-1.2	73	73
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.2	0.16	-10000	0	-0.58	5	5
T cell proliferation	-0.5	0.45	-10000	0	-1.2	69	69
IL4R/JAK1	-0.51	0.44	-10000	0	-1.1	69	69
EGR2	-0.58	0.56	-10000	0	-1.4	76	76
JAK2	-0.014	0.025	-10000	0	-10000	0	0
JAK3	-0.043	0.12	-10000	0	-0.3	11	11
PIK3R1	0.013	0	-10000	0	-10000	0	0
JAK1	0.003	0.009	-10000	0	-10000	0	0
COL1A2	-0.16	0.14	-10000	0	-10000	0	0
CCL26	-0.52	0.45	-10000	0	-1.2	68	68
IL4R	-0.54	0.47	-10000	0	-1.2	69	69
PTPN6	0.026	0.01	-10000	0	-10000	0	0
IL13RA2	-0.93	0.67	-10000	0	-1.5	165	165
IL13RA1	-0.014	0.025	-10000	0	-10000	0	0
IRF4	-0.11	0.14	-10000	0	-0.81	4	4
ARG1	-0.15	0.13	-10000	0	-10000	0	0
CBL	-0.28	0.22	-10000	0	-0.62	34	34
GTF3A	0.018	0.006	-10000	0	-10000	0	0
PIK3CA	0.013	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.021	0.034	-10000	0	-10000	0	0
IRF4/BCL6	-0.096	0.13	-10000	0	-0.82	3	3
CD40LG	0.008	0.06	-10000	0	-0.31	10	10
MAPK14	-0.28	0.22	-10000	0	-0.64	29	29
mitosis	-0.22	0.19	-10000	0	-0.61	10	10
STAT6	-0.58	0.53	-10000	0	-1.2	84	84
SPI1	-0.04	0.12	-10000	0	-0.29	52	52
RPS6KB1	-0.21	0.18	-10000	0	-0.62	6	6
STAT6 (dimer)	-0.58	0.53	-10000	0	-1.2	84	84
STAT6 (dimer)/PARP14	-0.54	0.48	-10000	0	-1.2	81	81
mast cell activation	0.014	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.24	0.19	-10000	0	-0.64	13	13
FRAP1	-0.23	0.2	-10000	0	-0.64	10	10
LTA	-0.52	0.45	-10000	0	-1.2	69	69
FES	0.01	0.048	-10000	0	-0.81	1	1
T-helper 1 cell differentiation	0.57	0.51	1.2	85	-10000	0	85
CCL11	-0.61	0.55	-10000	0	-1.3	93	93
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.23	0.19	-10000	0	-0.6	15	15
IL2RG	0.008	0.054	-10000	0	-0.29	9	9
IL10	-0.52	0.45	-10000	0	-1.2	69	69
IRS1	-0.002	0.11	-10000	0	-0.81	5	5
IRS2	0.01	0.025	-10000	0	-0.29	2	2
IL4	-0.12	0.098	-10000	0	-10000	0	0
IL5	-0.52	0.44	-10000	0	-1.2	69	69
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.42	0.34	-10000	0	-0.87	69	69
COL1A1	-0.18	0.16	-10000	0	-0.63	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.51	0.46	-10000	0	-1.2	62	62
IL2R gamma/JAK3	-0.024	0.1	-10000	0	-0.38	8	8
TFF3	-0.64	0.6	-10000	0	-1.4	87	87
ALOX15	-0.52	0.45	-10000	0	-1.2	69	69
MYBL1	-0.009	0.077	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.42	0.34	-10000	0	-0.89	68	68
SHC1	0.013	0	-10000	0	-10000	0	0
CEBPB	0.005	0.053	-10000	0	-0.29	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.23	0.19	-10000	0	-0.56	13	13
mol:PI-3-4-5-P3	-0.23	0.2	-10000	0	-0.64	10	10
PI3K	-0.24	0.21	-10000	0	-0.67	10	10
DOK2	-0.009	0.087	-10000	0	-0.32	19	19
ETS1	0.027	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.18	0.16	-10000	0	-0.56	5	5
ITGB3	-0.55	0.49	-10000	0	-1.2	75	75
PIGR	-0.56	0.49	-10000	0	-1.2	76	76
IGHE	0.041	0.044	-10000	0	-10000	0	0
MAPKKK cascade	-0.18	0.15	-10000	0	-0.55	5	5
BCL6	0.011	0.018	-10000	0	-0.29	1	1
OPRM1	-0.52	0.44	-10000	0	-1.2	68	68
RETNLB	-0.52	0.44	-10000	0	-1.2	69	69
SELP	-0.57	0.54	-10000	0	-1.4	72	72
AICDA	-0.52	0.43	-10000	0	-1.1	80	80

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.52	0.36	-9999	-0.67	226	226
SMAD6-7/SMURF1	-0.002	0.032	-9999	-0.54	1	1
NOG	0	0.089	-9999	-0.55	6	6
SMAD9	-0.072	0.12	-9999	-0.5	13	13
SMAD4	0.013	0	-9999	-10000	0	0
SMAD5	-0.2	0.2	-9999	-0.5	26	26
BMP7/USAG1	-0.33	0.36	-9999	-0.71	127	127
SMAD5/SKI	-0.18	0.19	-9999	-0.47	26	26
SMAD1	-0.011	0.046	-9999	-10000	0	0
BMP2	0.013	0	-9999	-10000	0	0
SMAD1/SMAD1/SMAD4	-0.008	0.024	-9999	-0.41	1	1
BMPR1A	0.013	0	-9999	-10000	0	0
BMPR1B	-0.48	0.4	-9999	-0.81	172	172
BMPR1A-1B/BAMBI	-0.32	0.26	-9999	-0.54	172	172
AHSG	-0.005	0.055	-9999	-0.29	10	10
CER1	0.004	0.006	-9999	-10000	0	0
BMP2-4/CER1	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.15	0.17	-9999	-0.54	22	22
BMP2-4 (homodimer)	0.019	0	-9999	-10000	0	0
RGMB	0.013	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.28	0.26	-9999	-0.5	172	172
RGMA	-0.093	0.28	-9999	-0.81	37	37
SMURF1	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.17	0.17	-9999	-0.48	24	24
BMP2-4/USAG1	-0.12	0.2	-9999	-0.54	52	52
SMAD6/SMURF1/SMAD5	-0.18	0.19	-9999	-0.47	26	26
SOSTDC1	-0.19	0.31	-9999	-0.55	104	104
BMP7/BMPR2/BMPR1A-1B	-0.44	0.31	-9999	-0.59	218	218
SKI	0.013	0	-9999	-10000	0	0
BMP6 (homodimer)	0.004	0.083	-9999	-0.81	3	3
HFE2	0.007	0.026	-9999	-0.29	2	2
ZFYVE16	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.038	0.14	-9999	-0.54	20	20
SMAD5/SMAD5/SMAD4	-0.18	0.19	-9999	-0.47	26	26
MAPK1	0.013	0	-9999	-10000	0	0
TAK1/TAB family	-0.15	0.12	-9999	-0.42	22	22
BMP7 (homodimer)	-0.25	0.38	-9999	-0.8	94	94
NUP214	0.013	0	-9999	-10000	0	0
BMP6/FETUA	0	0.078	-9999	-0.67	3	3
SMAD1/SKI	-0.004	0.044	-9999	-10000	0	0
SMAD6	0.01	0.048	-9999	-0.81	1	1
CTDSP2	0.013	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.005	0.027	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.22	0.37	-9999	-0.81	81	81
BMPR2 (homodimer)	0.012	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.36	0.31	-9999	-0.62	171	171
CHRDL1	-0.31	0.4	-9999	-0.81	114	114
ENDOFIN/SMAD1	-0.004	0.044	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.016	0.029	-9999	-0.46	1	1
SMAD6/SMURF1	0.012	0	-9999	-10000	0	0
BAMBI	0.008	0.054	-9999	-0.46	3	3
SMURF2	0.013	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.21	0.26	-9999	-0.54	114	114
BMP2-4/GREM1	-0.15	0.24	-9999	-0.54	81	81
SMAD7	0.013	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.06	0.11	-9999	-0.52	10	10
SMAD1/SMAD6	-0.004	0.044	-9999	-10000	0	0
TAK1/SMAD6	0.019	0	-9999	-10000	0	0
BMP7	-0.25	0.38	-9999	-0.81	94	94
BMP6	0.004	0.084	-9999	-0.81	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.14	0.15	-9999	-0.43	24	24
PPM1A	0.013	0	-9999	-10000	0	0
SMAD1/SMURF2	-0.004	0.044	-9999	-10000	0	0
SMAD7/SMURF1	0.019	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
PPP1CA	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
PPP1R15A	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.29	0.32	-9999	-0.78	67	67
CHRD	-0.046	0.21	-9999	-0.79	21	21
BMPR2	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.18	0.17	-9999	-0.52	24	24
BMP4	0.013	0	-9999	-10000	0	0
FST	-0.18	0.34	-9999	-0.78	70	70
BMP2-4/NOG	-0.007	0.056	-9999	-0.54	3	3
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.42	0.29	-9999	-0.56	218	218

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.15	0.085	-9999	-0.2	228	228
TP53	-0.052	0.027	-9999	-10000	0	0
Senescence	-0.051	0.027	-9999	-10000	0	0
Apoptosis	-0.051	0.027	-9999	-10000	0	0
Activated_Oncogenes	0	0	-9999	-10000	0	0
MDM2	0.096	0.05	-9999	-10000	0	0
MDM4	0.013	0	-9999	-10000	0	0

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.001	0.042	-10000	0	-0.29	6	6
CDKN2C	0.032	0.021	-10000	0	-0.26	1	1
CDKN2A	-0.23	0.12	-10000	0	-0.29	228	228
CCND2	0.047	0.036	0.18	4	-10000	0	4
RB1	-0.052	0.04	-10000	0	-0.17	5	5
CDK4	0.061	0.037	0.18	5	-10000	0	5
CDK6	0.057	0.036	0.18	5	-10000	0	5
G1/S progression	0.052	0.04	0.17	5	-10000	0	5

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.014	0.14	-9999	-0.62	13	13
AKT1	-0.042	0.27	-9999	-0.61	52	52
PTK2B	-0.12	0.32	-9999	-0.77	52	52
VEGFR2 homodimer/Frs2	-0.14	0.36	-9999	-0.91	52	52
CAV1	0.011	0.018	-9999	-0.29	1	1
CALM1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.12	0.34	-9999	-0.84	52	52
endothelial cell proliferation	-0.029	0.26	-9999	-0.58	52	52
mol:Ca2+	-0.094	0.31	-9999	-0.76	52	52
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.1	0.33	-9999	-0.8	52	52
RP11-342D11.1	-0.1	0.31	-9999	-0.77	52	52
CDH5	0.013	0	-9999	-10000	0	0
VEGFA homodimer	0.032	0.015	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
SHC2	-0.001	0.082	-9999	-0.41	9	9
HRAS/GDP	-0.12	0.25	-9999	-0.65	52	52
SH2D2A	-0.02	0.094	-9999	-0.29	31	31
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.12	0.25	-9999	-0.64	52	52
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.13	0.34	-9999	-0.85	52	52
VEGFR1 homodimer	0.007	0.068	-9999	-0.81	2	2
SHC/GRB2/SOS1	-0.13	0.28	-9999	-0.73	52	52
GRB10	-0.094	0.31	-9999	-0.76	52	52
PTPN11	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.14	0.3	-9999	-0.77	52	52
HRAS	0.013	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.042	0.17	-9999	-0.38	52	52
HIF1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.14	0.3	-9999	-0.79	52	52
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.007	0.13	-9999	-0.81	7	7
Nck/Pak	0.019	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.12	0.34	-9999	-0.84	52	52
mol:GDP	-0.13	0.27	-9999	-0.7	52	52
mol:NADP	-0.04	0.24	-9999	-0.53	54	54
eNOS/Hsp90	-0.031	0.23	-9999	-0.5	54	54
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	-0.096	0.32	-9999	-0.78	52	52
HIF1A/ARNT	0.019	0	-9999	-10000	0	0
SHB	0.013	0	-9999	-10000	0	0
VEGFA	0.011	0.031	-9999	-0.29	3	3
VEGFC	0.01	0.025	-9999	-0.29	2	2
FAK1/Vinculin	-0.095	0.32	-9999	-0.76	52	52
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.13	0.34	-9999	-0.75	64	64
PTPN6	0.013	0	-9999	-10000	0	0
EPAS1	-0.053	0.17	-9999	-0.4	52	52
mol:L-citrulline	-0.04	0.24	-9999	-0.53	54	54
ITGAV	0.013	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.1	0.33	-9999	-0.8	52	52
VEGFR2 homodimer/VEGFA homodimer	-0.11	0.34	-9999	-0.84	52	52
VEGFR2/3 heterodimer	-0.15	0.38	-9999	-0.92	55	55
VEGFB	0.013	0	-9999	-10000	0	0
MAPK11	-0.096	0.33	-9999	-0.79	52	52
VEGFR2 homodimer	-0.15	0.4	-9999	-1	52	52
FLT1	0.007	0.068	-9999	-0.81	2	2
NEDD4	0.014	0.001	-9999	-10000	0	0
MAPK3	-0.078	0.29	-9999	-0.69	52	52
MAPK1	-0.078	0.29	-9999	-0.69	52	52
VEGFA145/NRP2	-0.003	0.046	-9999	-0.62	1	1
VEGFR1/2 heterodimer	-0.14	0.37	-9999	-0.93	52	52
KDR	-0.15	0.4	-9999	-1	52	52
VEGFA165/NRP1/VEGFR2 homodimer	-0.1	0.32	-9999	-0.77	53	53
SRC	0.011	0.018	-9999	-0.29	1	1
platelet activating factor biosynthetic process	-0.08	0.3	-9999	-0.71	52	52
PI3K	-0.075	0.32	-9999	-0.75	52	52
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.12	0.34	-9999	-0.84	52	52
FES	-0.1	0.33	-9999	-0.8	52	52
GAB1	-0.14	0.3	-9999	-0.77	52	52
VEGFR2 homodimer/VEGFA homodimer/Src	-0.12	0.34	-9999	-0.84	52	52
CTNNB1	0.013	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
ARNT	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.031	0.23	-9999	-0.5	54	54
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.12	0.34	-9999	-0.84	52	52
PI3K/GAB1	-0.044	0.27	-9999	-0.63	52	52
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.14	0.3	-9999	-0.77	52	52
PRKACA	0.013	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.13	0.36	-9999	-0.86	55	55
HSP90AA1	0.013	0	-9999	-10000	0	0
CDC42	-0.099	0.32	-9999	-0.79	52	52
actin cytoskeleton reorganization	-0.16	0.32	-9999	-0.84	52	52
PTK2	-0.11	0.34	-9999	-0.83	52	52
EDG1	-0.1	0.31	-9999	-0.77	52	52
mol:DAG	-0.096	0.32	-9999	-0.78	52	52
CaM/Ca2+	-0.13	0.27	-9999	-0.71	52	52
MAP2K3	-0.089	0.32	-9999	-0.76	52	52
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.1	0.33	-9999	-0.8	52	52
PLCG1	-0.099	0.32	-9999	-0.79	52	52
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.11	0.33	-9999	-0.8	52	52
IQGAP1	0.013	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.12	0.34	-9999	-0.84	52	52
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.12	0.34	-9999	-0.84	52	52
cell migration	-0.054	0.27	-9999	-0.62	52	52
mol:PI-3-4-5-P3	-0.064	0.29	-9999	-0.68	52	52
FYN	0.013	0	-9999	-10000	0	0
VEGFB/NRP1	-0.09	0.3	-9999	-0.72	52	52
mol:NO	-0.04	0.24	-9999	-0.53	54	54
PXN	0.013	0	-9999	-10000	0	0
HRAS/GTP	-0.12	0.25	-9999	-0.65	52	52
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.1	0.33	-9999	-0.8	52	52
VHL	0.013	0	-9999	-10000	0	0
ITGB3	-0.031	0.18	-9999	-0.65	19	19
NOS3	-0.054	0.28	-9999	-0.62	54	54
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.12	0.35	-9999	-0.85	54	54
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	-0.082	0.3	-9999	-0.72	52	52
PRKCB	-0.084	0.3	-9999	-0.72	52	52
VCL	0.013	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.1	0.31	-9999	-0.77	52	52
VEGFR1/2 heterodimer/VEGFA homodimer	-0.12	0.35	-9999	-0.86	52	52
VEGFA165/NRP2	-0.003	0.046	-9999	-0.62	1	1
MAPKKK cascade	-0.058	0.28	-9999	-0.65	52	52
NRP2	0.006	0.057	-9999	-0.42	4	4
VEGFC homodimer	0.01	0.025	-9999	-0.29	2	2
NCK1	0.013	0	-9999	-10000	0	0
ROCK1	0.013	0	-9999	-10000	0	0
FAK1/Paxillin	-0.095	0.32	-9999	-0.76	52	52
MAP3K13	-0.1	0.33	-9999	-0.81	52	52
PDPK1	-0.045	0.26	-9999	-0.59	52	52

×

Effects of Botulinum toxin

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
STX1A	0.008	0.024	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.005	0.043	-9999	-10000	0	0
STXBP1	0.013	0	-9999	-10000	0	0
ACh/CHRNA1	-0.13	0.085	-9999	-0.18	202	202
RAB3GAP2/RIMS1/UNC13B	-0.007	0.031	-9999	-10000	0	0
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	-0.008	0.064	-9999	-0.29	14	14
mol:ACh	-0.016	0.029	-9999	-0.1	4	4
RAB3GAP2	0.013	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.019	0.031	-9999	-10000	0	0
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.13	0.085	-9999	-0.18	202	202
UNC13B	0.013	0	-9999	-10000	0	0
CHRNA1	-0.2	0.14	-9999	-0.29	202	202
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.18	0.27	-9999	-0.59	86	86
SNAP25	-0.045	0.06	-9999	-0.38	1	1
VAMP2	0.006	0	-9999	-10000	0	0
SYT1	-0.23	0.38	-9999	-0.81	86	86
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.015	0.02	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.019	0.031	-9999	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.008	0.074	-10000	0	-0.4	7	7
NFATC2	-0.039	0.22	-10000	0	-0.73	22	22
NFATC3	-0.03	0.11	-10000	0	-0.31	22	22
CD40LG	-0.21	0.46	-10000	0	-1	59	59
ITCH	0.038	0.05	-10000	0	-10000	0	0
CBLB	0.038	0.05	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.18	0.25	-10000	0	-0.9	13	13
JUNB	0.013	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.008	0.053	-10000	0	-0.34	7	7
T cell anergy	0.015	0.084	-10000	0	-0.44	7	7
TLE4	-0.005	0.17	-10000	0	-0.53	21	21
Jun/NFAT1-c-4/p21SNFT	-0.16	0.4	-10000	0	-0.96	49	49
AP-1/NFAT1-c-4	-0.26	0.56	-10000	0	-1.2	59	59
IKZF1	-0.019	0.18	-10000	0	-0.59	14	14
T-helper 2 cell differentiation	-0.51	0.32	-10000	0	-0.75	142	142
AP-1/NFAT1	-0.13	0.24	-10000	0	-0.58	58	58
CALM1	0.022	0.032	-10000	0	-10000	0	0
EGR2	-0.19	0.58	-10000	0	-1.6	35	35
EGR3	-0.23	0.63	-10000	0	-1.7	44	44
NFAT1/FOXP3	-0.034	0.18	-10000	0	-0.54	26	26
EGR1	-0.053	0.22	-10000	0	-0.81	23	23
JUN	0.008	0.017	-10000	0	-10000	0	0
EGR4	0.006	0.02	-10000	0	-0.29	1	1
mol:Ca2+	0.009	0.034	-10000	0	-10000	0	0
GBP3	-0.005	0.17	-10000	0	-0.58	13	13
FOSL1	0.003	0.077	-10000	0	-0.46	6	6
NFAT1-c-4/MAF/IRF4	-0.16	0.39	-10000	0	-0.93	50	50
DGKA	-0.012	0.17	-10000	0	-0.57	15	15
CREM	0.012	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.18	0.4	-10000	0	-0.97	51	51
CTLA4	-0.043	0.19	-10000	0	-0.58	14	14
NFAT1-c-4 (dimer)/EGR1	-0.18	0.48	-10000	0	-1.1	54	54
NFAT1-c-4 (dimer)/EGR4	-0.15	0.42	-10000	0	-0.98	51	51
FOS	-0.12	0.3	-10000	0	-0.83	44	44
IFNG	-0.094	0.18	-10000	0	-0.65	15	15
T cell activation	-0.1	0.28	-10000	0	-0.79	29	29
MAF	0.013	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.098	0.31	0.74	50	-10000	0	50
TNF	-0.16	0.42	-10000	0	-1	46	46
FASLG	-0.24	0.59	-10000	0	-1.4	50	50
TBX21	0.002	0.061	-10000	0	-0.31	10	10
BATF3	0.012	0.018	-10000	0	-0.29	1	1
PRKCQ	-0.011	0.14	-10000	0	-0.81	8	8
PTPN1	-0.005	0.17	-10000	0	-0.58	13	13
NFAT1-c-4/ICER1	-0.18	0.4	-10000	0	-0.97	51	51
GATA3	-0.63	0.34	-10000	0	-0.81	224	224
T-helper 1 cell differentiation	-0.063	0.2	-10000	0	-0.63	16	16
IL2RA	-0.17	0.24	-10000	0	-0.81	14	14
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.006	0.17	-10000	0	-0.54	19	19
E2F1	-0.066	0.14	-10000	0	-10000	0	0
PPARG	0.012	0.018	-10000	0	-10000	0	0
SLC3A2	-0.005	0.17	-10000	0	-0.58	13	13
IRF4	-0.01	0.089	-10000	0	-0.32	20	20
PTGS2	-0.27	0.54	-10000	0	-1.1	71	71
CSF2	-0.21	0.45	-10000	0	-1	56	56
JunB/Fra1/NFAT1-c-4	-0.15	0.4	-10000	0	-0.94	51	51
IL4	-0.53	0.34	-10000	0	-0.79	139	139
IL5	-0.21	0.45	-10000	0	-1	55	55
IL2	-0.11	0.29	-10000	0	-0.81	28	28
IL3	-0.043	0.057	-10000	0	-10000	0	0
RNF128	0.023	0.14	-10000	0	-0.87	7	7
NFATC1	-0.098	0.31	-10000	0	-0.74	50	50
CDK4	0.039	0.2	0.61	4	-10000	0	4
PTPRK	-0.005	0.17	-10000	0	-0.57	14	14
IL8	-0.24	0.46	-10000	0	-1	61	61
POU2F1	0.013	0	-10000	0	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.1	0.25	-9999	-0.63	52	52
PDGFRB	-0.018	0.15	-9999	-0.82	10	10
SPHK1	-0.067	0.061	-9999	-10000	0	0
mol:S1P	-0.064	0.061	-9999	-10000	0	0
S1P1/S1P/Gi	-0.11	0.24	-9999	-0.56	47	47
GNAO1	-0.061	0.23	-9999	-0.82	24	24
PDGFB-D/PDGFRB/PLCgamma1	-0.095	0.23	-9999	-0.58	37	37
PLCG1	-0.099	0.22	-9999	-0.62	31	31
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.018	0.15	-9999	-0.82	10	10
GNAI2	0.011	0.005	-9999	-10000	0	0
GNAI3	0.01	0.005	-9999	-10000	0	0
GNAI1	0.005	0.068	-9999	-0.81	2	2
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.088	0.22	-9999	-0.54	52	52
S1P1/S1P	-0.13	0.18	-9999	-0.5	52	52
negative regulation of cAMP metabolic process	-0.11	0.23	-9999	-0.55	47	47
MAPK3	-0.13	0.29	-9999	-0.66	57	57
calcium-dependent phospholipase C activity	-0.001	0.004	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
RhoA/GDP	0.009	0	-9999	-10000	0	0
KDR	-0.14	0.32	-9999	-0.81	52	52
PLCB2	-0.11	0.18	-9999	-0.45	52	52
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.11	0.15	-9999	-0.42	52	52
receptor internalization	-0.12	0.17	-9999	-0.46	52	52
PTGS2	-0.2	0.43	-9999	-1	57	57
Rac1/GTP	-0.11	0.15	-9999	-0.42	52	52
RHOA	0.013	0	-9999	-10000	0	0
VEGFA	0.008	0.031	-9999	-0.29	3	3
negative regulation of T cell proliferation	-0.11	0.23	-9999	-0.55	47	47
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.01	0.005	-9999	-10000	0	0
MAPK1	-0.13	0.29	-9999	-0.66	57	57
S1P1/S1P/PDGFB-D/PDGFRB	-0.12	0.22	-9999	-0.52	59	59
ABCC1	0.011	0.003	-9999	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.099	0.25	-9999	-0.62	52	52
alphaV beta3 Integrin	-0.033	0.12	-9999	-0.54	16	16
PTK2	-0.16	0.27	-9999	-0.64	41	41
IGF1R	0.013	0	-9999	-10000	0	0
PI4KB	0.013	0	-9999	-10000	0	0
MFGE8	0.013	0	-9999	-10000	0	0
SRC	0.011	0.018	-9999	-0.29	1	1
CDKN1B	-0.17	0.26	-9999	-0.6	75	75
VEGFA	0.009	0.031	-9999	-0.29	3	3
ILK	-0.17	0.26	-9999	-0.6	75	75
ROCK1	0.013	0	-9999	-10000	0	0
AKT1	-0.13	0.26	-9999	-0.56	73	73
PTK2B	-0.078	0.21	-9999	-0.46	64	64
alphaV/beta3 Integrin/JAM-A	-0.12	0.24	-9999	-0.48	87	87
CBL	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.39	0.27	-9999	-0.56	199	199
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.012	0.1	-9999	-0.49	11	11
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.12	0.22	-9999	-0.64	25	25
alphaV/beta3 Integrin/Syndecan-1	-0.03	0.12	-9999	-0.55	14	14
PI4KA	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.047	0.13	-9999	-0.47	11	11
PI4 Kinase	0.019	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.038	0.13	-9999	-0.54	16	16
RPS6KB1	0.001	0.14	-9999	-0.64	2	2
TLN1	0.013	0	-9999	-10000	0	0
MAPK3	-0.056	0.17	-9999	-0.6	16	16
GPR124	0.01	0.048	-9999	-0.81	1	1
MAPK1	-0.056	0.17	-9999	-0.6	16	16
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.055	0.17	-9999	-0.6	25	25
cell adhesion	-0.3	0.22	-9999	-0.44	199	199
ANGPTL3	-0.54	0.39	-9999	-0.81	193	193
VEGFR2 homodimer/VEGFA homodimer/Src	-0.099	0.21	-9999	-0.54	52	52
IGF-1R heterotetramer	0.012	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
TGFBR2	0.013	0	-9999	-10000	0	0
ITGB3	-0.031	0.18	-9999	-0.65	19	19
IGF1	-0.005	0.12	-9999	-0.81	6	6
RAC1	0.013	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.029	0.12	-9999	-0.54	14	14
apoptosis	0.012	0	-9999	-10000	0	0
CD47	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.027	0.11	-9999	-0.54	13	13
VCL	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.1	0.22	-9999	-0.57	49	49
CSF1	0.008	0.054	-9999	-0.81	1	1
PIK3C2A	-0.17	0.26	-9999	-0.6	75	75
PI4 Kinase/Pyk2	-0.19	0.24	-9999	-0.72	26	26
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.09	0.22	-9999	-0.5	64	64
FAK1/Vinculin	-0.12	0.21	-9999	-0.49	38	38
alphaV beta3/Integrin/ppsTEM5	-0.029	0.12	-9999	-0.54	14	14
RHOA	0.013	0	-9999	-10000	0	0
VTN	-0.2	0.36	-9999	-0.76	81	81
BCAR1	0.013	0	-9999	-10000	0	0
FGF2	0.004	0.084	-9999	-0.81	3	3
F11R	0.015	0.065	-9999	-0.62	3	3
alphaV/beta3 Integrin/Lactadherin	-0.027	0.11	-9999	-0.54	13	13
alphaV/beta3 Integrin/TGFBR2	-0.027	0.11	-9999	-0.54	13	13
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.029	0.033	-9999	-0.49	1	1
HSP90AA1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.002	0.11	-9999	-0.5	13	13
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.01	0.079	-9999	-0.29	21	21
alphaV/beta3 Integrin/Pyk2	-0.077	0.21	-9999	-0.46	64	64
SDC1	0.009	0.052	-9999	-0.55	2	2
VAV3	0.033	0.043	-9999	-0.46	2	2
PTPN11	0.013	0	-9999	-10000	0	0
IRS1	-0.002	0.11	-9999	-0.81	5	5
FAK1/Paxillin	-0.12	0.21	-9999	-0.48	40	40
cell migration	-0.096	0.19	-9999	-0.45	34	34
ITGAV	0.013	0	-9999	-10000	0	0
PI3K	-0.13	0.2	-9999	-0.43	87	87
SPP1	-0.007	0.099	-9999	-0.41	13	13
KDR	-0.14	0.32	-9999	-0.81	52	52
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.012	0	-9999	-10000	0	0
COL4A3	-0.03	0.18	-9999	-0.81	15	15
angiogenesis	-0.084	0.2	-9999	-0.58	20	20
Rac1/GTP	0.037	0.039	-9999	-0.42	2	2
EDIL3	-0.11	0.28	-9999	-0.71	49	49
cell proliferation	-0.027	0.11	-9999	-0.54	13	13

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.066	0.44	-9999	-0.97	24	24
PLK1	-0.019	0.16	-9999	-10000	0	0
BIRC5	-0.061	0.18	-9999	-10000	0	0
HSPA1B	-0.067	0.44	-9999	-0.98	23	23
MAP2K1	0.023	0.038	-9999	-10000	0	0
BRCA2	-0.07	0.45	-9999	-0.97	29	29
FOXM1	-0.096	0.5	-9999	-1.1	34	34
XRCC1	-0.066	0.44	-9999	-0.99	22	22
FOXM1B/p19	-0.16	0.39	-9999	-0.93	34	34
Cyclin D1/CDK4	-0.058	0.42	-9999	-0.93	21	21
CDC2	-0.077	0.46	-9999	-0.96	34	34
TGFA	-0.051	0.41	-9999	-0.91	23	23
SKP2	-0.066	0.44	-9999	-0.99	22	22
CCNE1	-0.005	0.078	-9999	-0.3	18	18
CKS1B	-0.066	0.44	-9999	-0.99	22	22
RB1	-0.1	0.16	-9999	-0.52	13	13
FOXM1C/SP1	-0.087	0.47	-9999	-1	32	32
AURKB	-0.092	0.19	-9999	-10000	0	0
CENPF	-0.085	0.47	-9999	-1	35	35
CDK4	0.016	0.015	-9999	-10000	0	0
MYC	-0.049	0.4	-9999	-0.86	26	26
CHEK2	0.013	0.071	-9999	-0.32	9	9
ONECUT1	-0.066	0.43	-9999	-0.95	26	26
CDKN2A	-0.22	0.12	-9999	-0.29	227	227
LAMA4	-0.075	0.44	-9999	-0.99	23	23
FOXM1B/HNF6	-0.086	0.48	-9999	-1.1	26	26
FOS	-0.18	0.59	-9999	-1.2	57	57
SP1	0.013	0.002	-9999	-10000	0	0
CDC25B	-0.067	0.44	-9999	-0.97	26	26
response to radiation	0.008	0.035	-9999	-10000	0	0
CENPB	-0.066	0.44	-9999	-0.99	22	22
CENPA	-0.11	0.48	-9999	-1	34	34
NEK2	-0.095	0.48	-9999	-1	36	36
HIST1H2BA	-0.072	0.44	-9999	-0.99	22	22
CCNA2	-0.031	0.11	-9999	-0.3	42	42
EP300	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	-0.089	0.48	-9999	-1.1	27	27
CCNB2	-0.096	0.48	-9999	-1	33	33
CCNB1	-0.075	0.46	-9999	-1	28	28
ETV5	-0.066	0.44	-9999	-0.99	22	22
ESR1	-0.11	0.51	-9999	-1.1	35	35
CCND1	-0.057	0.43	-9999	-0.95	22	22
GSK3A	0.024	0.031	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0	0.11	-9999	-0.34	15	15
CDK2	0.014	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.009	0.041	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.22	0.34	-9999	-0.96	35	35
GAS1	-0.11	0.5	-9999	-1.1	35	35
MMP2	-0.071	0.45	-9999	-1	23	23
RB1/FOXM1C	-0.062	0.44	-9999	-1	24	24
CREBBP	0.013	0	-9999	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.023	0.047	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.23	0.19	-9999	-0.59	19	19
positive regulation of JNK cascade	-0.26	0.21	-9999	-0.59	49	49
Syndecan-4/ADAM12	-0.24	0.2	-9999	-0.54	40	40
CCL5	-0.018	0.091	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
DNM2	0.013	0	-9999	-10000	0	0
ITGA5	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
PLG	-0.45	0.4	-9999	-0.8	164	164
ADAM12	-0.021	0.096	-9999	-0.29	32	32
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.061	0.041	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.25	0.21	-9999	-0.62	28	28
Syndecan-4/CXCL12/CXCR4	-0.28	0.23	-9999	-0.63	49	49
Syndecan-4/Laminin alpha3	-0.27	0.2	-9999	-0.58	35	35
MDK	-0.069	0.14	-9999	-0.29	77	77
Syndecan-4/FZD7	-0.24	0.2	-9999	-0.63	22	22
Syndecan-4/Midkine	-0.26	0.2	-9999	-0.56	40	40
FZD7	-0.01	0.14	-9999	-0.81	8	8
Syndecan-4/FGFR1/FGF	-0.22	0.17	-9999	-0.56	22	22
THBS1	-0.016	0.15	-9999	-0.81	10	10
integrin-mediated signaling pathway	-0.24	0.19	-9999	-0.55	29	29
positive regulation of MAPKKK cascade	-0.26	0.21	-9999	-0.59	49	49
Syndecan-4/TACI	-0.24	0.2	-9999	-0.6	23	23
CXCR4	-0.009	0.077	-9999	-10000	0	0
cell adhesion	0.033	0.031	-9999	-10000	0	0
Syndecan-4/Dynamin	-0.23	0.19	-9999	-0.59	19	19
Syndecan-4/TSP1	-0.24	0.21	-9999	-0.63	26	26
Syndecan-4/GIPC	-0.23	0.19	-9999	-0.59	19	19
Syndecan-4/RANTES	-0.24	0.2	-9999	-0.6	24	24
ITGB1	0.013	0	-9999	-10000	0	0
LAMA1	-0.025	0.15	-9999	-0.81	8	8
LAMA3	-0.079	0.14	-9999	-0.29	87	87
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.077	0.051	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.23	0.19	-9999	-0.53	29	29
TFPI	0.005	0.06	-9999	-0.4	5	5
F2	-0.028	0.097	-9999	-0.29	26	26
alpha5/beta1 Integrin	0.019	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.27	0.2	-9999	-0.57	46	46
ACTN1	0.013	0	-9999	-10000	0	0
TNC	-0.018	0.12	-9999	-0.39	22	22
Syndecan-4/CXCL12	-0.28	0.23	-9999	-0.66	45	45
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CXCL12	-0.09	0.27	-9999	-0.81	36	36
TNFRSF13B	-0.007	0.065	-9999	-0.29	14	14
FGF2	0.004	0.084	-9999	-0.81	3	3
FGFR1	0.013	0	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.24	0.19	-9999	-0.47	76	76
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.008	0.076	-9999	-0.29	9	9
cell migration	-0.017	0.012	-9999	-10000	0	0
PRKCD	0.014	0.012	-9999	-10000	0	0
vasculogenesis	-0.24	0.2	-9999	-0.61	26	26
SDC4	-0.25	0.2	-9999	-0.49	76	76
Syndecan-4/Tenascin C	-0.24	0.2	-9999	-0.57	29	29
Syndecan-4/PI-4-5-P2/PKC alpha	-0.048	0.033	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.23	0.19	-9999	-0.59	19	19
MMP9	-0.11	0.17	-9999	-0.3	115	115
Rac1/GTP	0.033	0.032	-9999	-10000	0	0
cytoskeleton organization	-0.22	0.19	-9999	-0.57	19	19
GIPC1	0.013	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.23	0.2	-9999	-0.59	21	21

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.016	0.15	-10000	0	-0.81	10	10
Jak2/Leptin Receptor	-0.15	0.15	-10000	0	-0.42	29	29
PTP1B/AKT1	-0.08	0.076	-10000	0	-0.33	9	9
FYN	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.098	0.084	-10000	0	-0.34	24	24
EGFR	0.001	0.004	-10000	0	-10000	0	0
EGF/EGFR	-0.44	0.14	-10000	0	-0.48	260	260
CSF1	0.008	0.054	-10000	0	-0.81	1	1
AKT1	0.012	0.001	-10000	0	-10000	0	0
INSR	0.012	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.11	0.14	-10000	0	-0.47	31	31
Insulin Receptor/Insulin	-0.054	0.057	-10000	0	-0.35	1	1
HCK	-0.022	0.1	-10000	0	-0.31	31	31
CRK	0.013	0	-10000	0	-10000	0	0
TYK2	-0.086	0.081	-10000	0	-0.32	23	23
EGF	-0.73	0.25	-10000	0	-0.82	260	260
YES1	0.013	0	-10000	0	-10000	0	0
CAV1	-0.18	0.084	-10000	0	-0.36	30	30
TXN	-0.002	0.03	-10000	0	-0.3	3	3
PTP1B/IRS1/GRB2	-0.084	0.1	-10000	0	-0.42	14	14
cell migration	0.098	0.084	0.34	24	-10000	0	24
STAT3	0.012	0.001	-10000	0	-10000	0	0
PRLR	-0.3	0.4	-10000	0	-0.81	110	110
ITGA2B	-0.011	0.077	-10000	0	-0.29	20	20
CSF1R	-0.001	0.073	-10000	0	-0.34	11	11
Prolactin Receptor/Prolactin	-0.24	0.31	-10000	0	-0.63	110	110
FGR	-0.001	0.073	-10000	0	-0.34	11	11
PTP1B/p130 Cas	-0.086	0.081	-10000	0	-0.32	23	23
Crk/p130 Cas	-0.076	0.078	-10000	0	-0.34	9	9
DOK1	-0.078	0.088	-10000	0	-0.33	19	19
JAK2	-0.16	0.16	-10000	0	-0.36	109	109
Jak2/Leptin Receptor/Leptin	-0.1	0.098	-10000	0	-0.47	6	6
PIK3R1	0.013	0	-10000	0	-10000	0	0
PTPN1	-0.099	0.085	-10000	0	-0.34	24	24
LYN	0.013	0	-10000	0	-10000	0	0
CDH2	-0.027	0.17	-10000	0	-0.74	15	15
SRC	-0.026	0.032	-10000	0	-10000	0	0
ITGB3	-0.032	0.18	-10000	0	-0.65	19	19
CAT1/PTP1B	-0.25	0.14	-10000	0	-0.43	55	55
CAPN1	0.011	0.001	-10000	0	-10000	0	0
CSK	0.013	0	-10000	0	-10000	0	0
PI3K	-0.038	0.053	-10000	0	-10000	0	0
mol:H2O2	-0.007	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.09	0.092	-10000	0	-0.51	4	4
negative regulation of transcription	-0.16	0.16	-10000	0	-0.35	109	109
FCGR2A	-0.002	0.065	-10000	0	-0.29	14	14
FER	0.001	0.004	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.044	0.14	-10000	0	-0.63	13	13
BLK	-0.004	0.065	-10000	0	-0.29	14	14
Insulin Receptor/Insulin/Shc	0.001	0.009	-10000	0	-10000	0	0
RHOA	0.011	0.001	-10000	0	-10000	0	0
LEPR	0.01	0.048	-10000	0	-0.81	1	1
BCAR1	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.012	0	-10000	0	-10000	0	0
mol:NADPH	-0.007	0.002	-10000	0	-10000	0	0
TRPV6	-0.19	0.14	-10000	0	-0.4	31	31
PRL	0	0.018	-10000	0	-10000	0	0
SOCS3	0.023	0.091	-10000	0	-1.4	1	1
SPRY2	0.006	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.009	0.073	-10000	0	-0.55	5	5
CSF1/CSF1R	-0.085	0.096	-10000	0	-0.42	10	10
Ras protein signal transduction	0.046	0.022	-10000	0	-10000	0	0
IRS1	-0.002	0.11	-10000	0	-0.81	5	5
INS	0	0.017	-10000	0	-0.29	1	1
LEP	-0.024	0.093	-10000	0	-0.29	31	31
STAT5B	-0.12	0.098	-10000	0	-0.33	30	30
STAT5A	-0.12	0.098	-10000	0	-0.33	29	29
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.1	0.12	-10000	0	-0.4	32	32
CSN2	-0.058	0.1	-10000	0	-10000	0	0
PIK3CA	0.013	0	-10000	0	-10000	0	0
LAT	-0.04	0.048	-10000	0	-0.24	3	3
YBX1	0.015	0.002	-10000	0	-10000	0	0
LCK	0.005	0.047	-10000	0	-0.29	7	7
SHC1	0.013	0	-10000	0	-10000	0	0
NOX4	-0.081	0.25	-10000	0	-0.82	30	30

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.013	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.036	0.12	-10000	0	-0.34	6	6
NT3 (dimer)/TRKC	-0.15	0.3	-10000	0	-0.66	73	73
NT3 (dimer)/TRKB	-0.28	0.32	-10000	0	-0.59	136	136
SHC/Grb2/SOS1/GAB1/PI3K	0.036	0	-10000	0	-10000	0	0
RAPGEF1	0.013	0	-10000	0	-10000	0	0
BDNF	-0.029	0.1	-10000	0	-0.29	39	39
PIK3CA	0.013	0	-10000	0	-10000	0	0
DYNLT1	0.013	0	-10000	0	-10000	0	0
NTRK1	-0.15	0.32	-10000	0	-0.81	56	56
NTRK2	-0.31	0.4	-10000	0	-0.81	112	112
NTRK3	-0.12	0.31	-10000	0	-0.81	48	48
NT-4/5 (dimer)/TRKB	-0.24	0.27	-10000	0	-0.56	118	118
neuron apoptosis	0.14	0.19	0.5	36	-10000	0	36
SHC 2-3/Grb2	-0.15	0.21	-10000	0	-0.56	36	36
SHC1	0.013	0	-10000	0	-10000	0	0
SHC2	-0.14	0.17	-10000	0	-0.52	33	33
SHC3	-0.15	0.2	-10000	0	-0.59	35	35
STAT3 (dimer)	0.019	0.024	-10000	0	-0.38	1	1
NT3 (dimer)/TRKA	-0.18	0.3	-10000	0	-0.62	82	82
RIN/GDP	-0.019	0.092	-10000	0	-0.27	5	5
GIPC1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
DNAJA3	-0.081	0.15	-10000	0	-0.55	10	10
RIN/GTP	0	0.012	-10000	0	-10000	0	0
CCND1	0.026	0.061	-10000	0	-1	1	1
MAGED1	0.013	0	-10000	0	-10000	0	0
PTPN11	0.013	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.019	0.084	-10000	0	-0.29	25	25
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.14	0.23	-10000	0	-0.56	66	66
TRKA/NEDD4-2	-0.11	0.26	-10000	0	-0.62	57	57
ELMO1	0.013	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.013	0.14	-10000	0	-0.71	10	10
HRAS	0.013	0	-10000	0	-10000	0	0
DOCK1	0.013	0	-10000	0	-10000	0	0
GAB2	0.013	0	-10000	0	-10000	0	0
RIT2	0	0.018	-10000	0	-0.29	1	1
RIT1	0.013	0	-10000	0	-10000	0	0
FRS2	0.013	0	-10000	0	-10000	0	0
DNM1	-0.085	0.15	-10000	0	-0.3	91	91
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.078	0.15	-10000	0	-0.54	10	10
mol:GDP	-0.03	0.13	-10000	0	-0.39	7	7
NGF (dimer)	-0.013	0.14	-10000	0	-0.71	10	10
RhoG/GDP	0.009	0	-10000	0	-10000	0	0
RIT1/GDP	-0.014	0.093	-10000	0	-0.26	5	5
TIAM1	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.23	0.26	-10000	0	-0.55	112	112
KIDINS220/CRKL/C3G	0.019	0	-10000	0	-10000	0	0
SHC/RasGAP	0.019	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.002	0.015	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.032	0	-10000	0	-10000	0	0
RIT1/GTP	0.009	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.076	0.25	-10000	0	-0.81	31	31
RAP1/GDP	-0.036	0.062	-10000	0	-0.25	1	1
KIDINS220/CRKL	0.012	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.029	0.1	-10000	0	-0.29	39	39
ubiquitin-dependent protein catabolic process	-0.12	0.23	-10000	0	-0.55	64	64
Schwann cell development	-0.044	0.037	-10000	0	-10000	0	0
EHD4	0.013	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.031	0.016	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.038	0.01	-10000	0	-10000	0	0
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.28	0.28	-10000	0	-0.5	157	157
ABL1	0.013	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.019	0	-10000	0	-10000	0	0
Rap1/GTP	-0.075	0.09	-10000	0	-10000	0	0
STAT3	0.019	0.024	-10000	0	-0.38	1	1
axon guidance	-0.27	0.26	-10000	0	-0.48	157	157
MAPK3	-0.1	0.22	-10000	0	-0.5	66	66
MAPK1	-0.1	0.22	-10000	0	-0.5	66	66
CDC42/GDP	-0.014	0.093	-10000	0	-0.27	3	3
NTF3	-0.077	0.26	-10000	0	-0.81	31	31
NTF4	-0.019	0.084	-10000	0	-0.29	25	25
NGF (dimer)/TRKA/FAIM	-0.12	0.23	-10000	0	-0.55	63	63
PI3K	0.019	0	-10000	0	-10000	0	0
FRS3	0.009	0.031	-10000	0	-0.29	3	3
FAIM	0.01	0.025	-10000	0	-0.29	2	2
GAB1	0.013	0	-10000	0	-10000	0	0
RASGRF1	-0.083	0.16	-10000	0	-0.56	12	12
SOS1	0.013	0	-10000	0	-10000	0	0
MCF2L	-0.13	0.27	-10000	0	-0.58	73	73
RGS19	0.009	0.031	-10000	0	-10000	0	0
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	0.024	0.063	-10000	0	-10000	0	0
Rac1/GDP	-0.014	0.093	-10000	0	-0.26	5	5
NGF (dimer)/TRKA/GRIT	-0.12	0.23	-10000	0	-0.56	63	63
neuron projection morphogenesis	-0.044	0.15	-10000	0	-0.52	9	9
NGF (dimer)/TRKA/NEDD4-2	-0.12	0.23	-10000	0	-0.55	64	64
MAP2K1	0.037	0	-10000	0	-10000	0	0
NGFR	-0.01	0.14	-10000	0	-0.81	8	8
NGF (dimer)/TRKA/GIPC/GAIP	-0.081	0.17	-10000	0	-0.38	63	63
RAS family/GTP/PI3K	0.03	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.011	-10000	0	-10000	0	0
NRAS	0.013	0	-10000	0	-10000	0	0
GRB2/SOS1	0.019	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.15	0.26	-10000	0	-0.63	63	63
RASA1	0.013	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.11	0.25	-10000	0	-0.62	56	56
SQSTM1	0.003	0.053	-10000	0	-0.29	9	9
BDNF (dimer)/TRKB/GIPC	-0.19	0.25	-10000	0	-0.5	112	112
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.11	0.2	-10000	0	-0.47	63	63
MATK	-0.018	0.11	-10000	0	-0.36	24	24
NEDD4L	0.01	0.048	-10000	0	-0.81	1	1
RAS family/GDP	-0.034	0.06	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.086	0.16	-10000	0	-0.36	68	68
Rac1/GTP	-0.07	0.1	-10000	0	-0.37	10	10
FRS2 family/SHP2/CRK family	-0.001	0.011	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.028	0.093	-10000	0	-0.47	6	6
FYN	0.016	0.13	-10000	0	-0.53	9	9
LAT/GRAP2/SLP76	0.004	0.14	-10000	0	-0.49	13	13
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	0.005	0.12	-10000	0	-0.38	15	15
B2M	0.014	0.003	-10000	0	-10000	0	0
IKBKG	-0.015	0.034	-10000	0	-10000	0	0
MAP3K8	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	-0.088	0.056	-10000	0	-0.12	205	205
integrin-mediated signaling pathway	-0.004	0.024	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.006	0.16	-10000	0	-0.55	15	15
TRPV6	-0.58	0.37	-10000	0	-0.82	207	207
CD28	-0.006	0.083	-10000	0	-0.33	16	16
SHC1	0.012	0.13	-10000	0	-0.51	10	10
receptor internalization	0.008	0.13	-10000	0	-0.47	12	12
PRF1	0.014	0.12	-10000	0	-0.62	5	5
KRAS	0.013	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	0.013	0.099	-10000	0	-0.32	11	11
LAT	0	0.14	-10000	0	-0.53	12	12
EntrezGene:6955	0.001	0.002	-10000	0	-10000	0	0
CD3D	-0.035	0.11	-10000	0	-0.29	46	46
CD3E	-0.016	0.1	-10000	0	-0.32	27	27
CD3G	-0.002	0.067	-10000	0	-0.3	14	14
RASGRP2	-0.002	0.022	-10000	0	-0.18	2	2
RASGRP1	0.011	0.12	-10000	0	-0.38	16	16
HLA-A	0.012	0.026	-10000	0	-0.3	2	2
RASSF5	0.005	0.047	-10000	0	-0.29	7	7
RAP1A/GTP/RAPL	-0.004	0.024	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.026	0.044	-10000	0	-0.11	3	3
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.03	0.058	-10000	0	-0.24	7	7
PRKCA	0.008	0.083	-10000	0	-0.26	11	11
GRAP2	0.003	0.053	-10000	0	-0.29	9	9
mol:IP3	0.14	0.19	0.26	185	-0.39	13	198
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.005	0.11	-10000	0	-0.37	15	15
ORAI1	0.28	0.17	0.38	205	-10000	0	205
CSK	0.01	0.13	-10000	0	-0.52	10	10
B7 family/CD28	-0.062	0.15	-10000	0	-0.59	15	15
CHUK	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.004	0.15	-10000	0	-0.53	13	13
PTPN6	0.01	0.13	-10000	0	-0.51	10	10
VAV1	-0.018	0.17	-10000	0	-0.51	22	22
Monovalent TCR/CD3	-0.008	0.094	-10000	0	-0.33	16	16
CBL	0.013	0	-10000	0	-10000	0	0
LCK	0.012	0.14	-10000	0	-0.54	10	10
PAG1	0.01	0.13	-10000	0	-0.52	10	10
RAP1A	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.005	0.14	-10000	0	-0.53	12	12
CD80	-0.024	0.099	-10000	0	-0.3	31	31
CD86	-0.047	0.12	-10000	0	-0.29	57	57
PDK1/CARD11/BCL10/MALT1	-0.037	0.07	-10000	0	-0.27	12	12
HRAS	0.013	0	-10000	0	-10000	0	0
GO:0035030	-0.007	0.15	-10000	0	-0.5	15	15
CD8A	-0.013	0.087	-10000	0	-0.3	9	9
CD8B	-0.007	0.079	-10000	0	-0.3	20	20
PTPRC	0.002	0.068	-10000	0	-0.56	2	2
PDK1/PKC theta	0.003	0.14	-10000	0	-0.46	15	15
CSK/PAG1	0.014	0.13	-10000	0	-0.52	9	9
SOS1	0.013	0	-10000	0	-10000	0	0
peptide-MHC class I	0.018	0.019	-10000	0	-10000	0	0
GRAP2/SLP76	0.006	0.15	-10000	0	-0.53	14	14
STIM1	0.14	0.088	-10000	0	-10000	0	0
RAS family/GTP	0.03	0.055	-10000	0	-0.16	1	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.007	0.13	-10000	0	-0.5	12	12
mol:DAG	0.034	0.13	-10000	0	-0.36	14	14
RAP1A/GDP	0.013	0.019	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
CD247	0	0.065	-10000	0	-0.3	13	13
cytotoxic T cell degranulation	0.015	0.11	-10000	0	-0.57	6	6
RAP1A/GTP	-0.001	0.007	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.14	-10000	0	-0.45	15	15
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.13	0.22	0.28	160	-0.51	14	174
NRAS	0.013	0	-10000	0	-10000	0	0
ZAP70	-0.025	0.1	-10000	0	-0.29	36	36
GRB2/SOS1	0.019	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.017	0.15	-10000	0	-0.54	14	14
MALT1	0.013	0	-10000	0	-10000	0	0
TRAF6	0.013	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.01	0.097	-10000	0	-0.38	15	15
CARD11	-0.073	0.14	-10000	0	-0.29	81	81
PRKCB	0.007	0.085	-10000	0	-0.26	12	12
PRKCE	0.008	0.083	-10000	0	-0.26	9	9
PRKCQ	-0.006	0.16	-10000	0	-0.53	15	15
LCP2	0.004	0.05	-10000	0	-10000	0	0
BCL10	0.013	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.008	0.11	-10000	0	-0.33	15	15
IKK complex	0.03	0.045	-10000	0	-0.11	2	2
RAS family/GDP	-0.002	0.005	-10000	0	-10000	0	0
MAP3K14	0.019	0.079	-10000	0	-0.26	7	7
PDPK1	0.008	0.12	-10000	0	-0.37	14	14
TCR/CD3/MHC I/CD8/Fyn	0.005	0.14	-10000	0	-0.52	11	11

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0	0.099	-10000	0	-0.33	24	24
epithelial cell differentiation	-0.038	0.13	-10000	0	-0.46	24	24
CYFIP2	0.01	0.048	-10000	0	-0.81	1	1
ENAH	0.034	0.091	-10000	0	-10000	0	0
EGFR	0.013	0	-10000	0	-10000	0	0
EPHA2	0.011	0.018	-10000	0	-0.29	1	1
MYO6	-0.003	0.13	-10000	0	-0.44	24	24
CTNNB1	0.013	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.002	0.032	-10000	0	-0.54	1	1
AQP5	-0.098	0.21	-10000	0	-0.61	33	33
CTNND1	0.013	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.003	0.13	-10000	0	-0.43	24	24
regulation of calcium-dependent cell-cell adhesion	-0.041	0.19	-10000	0	-0.48	43	43
EGF	-0.73	0.25	-10000	0	-0.81	260	260
NCKAP1	0.013	0	-10000	0	-10000	0	0
AQP3	-0.24	0.31	-10000	0	-0.63	106	106
cortical microtubule organization	-0.038	0.13	-10000	0	-0.46	24	24
GO:0000145	-0.003	0.12	-10000	0	-0.41	24	24
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.039	0.13	-10000	0	-0.47	24	24
MLLT4	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.03	0.099	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.032	0.009	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.009	0.12	-10000	0	-0.4	24	24
PVRL2	0.013	0	-10000	0	-10000	0	0
ZYX	-0.003	0.13	-10000	0	-0.44	24	24
ARF6/GTP	0	0.006	-10000	0	-10000	0	0
CDH1	-0.056	0.23	-10000	0	-0.81	24	24
EGFR/EGFR/EGF/EGF	-0.42	0.16	-10000	0	-0.45	265	265
RhoA/GDP	-0.036	0.12	-10000	0	-0.43	24	24
actin cytoskeleton organization	0.003	0.12	-10000	0	-0.41	24	24
IGF-1R heterotetramer	0.012	0	-10000	0	-10000	0	0
GIT1	0.013	0	-10000	0	-10000	0	0
IGF1R	0.013	0	-10000	0	-10000	0	0
IGF1	-0.005	0.12	-10000	0	-0.81	6	6
DIAPH1	-0.004	0.039	-10000	0	-0.65	1	1
Wnt receptor signaling pathway	0.038	0.13	0.46	24	-10000	0	24
RHOA	0.013	0	-10000	0	-10000	0	0
RhoA/GTP	-0.031	0.1	-10000	0	-10000	0	0
CTNNA1	0.013	0	-10000	0	-10000	0	0
VCL	0.003	0.13	-10000	0	-0.42	24	24
EFNA1	0.013	0	-10000	0	-10000	0	0
LPP	0.004	0.12	-10000	0	-0.41	24	24
Ephrin A1/EPHA2	-0.035	0.12	-10000	0	-0.42	24	24
SEC6/SEC8	-0.032	0.11	-10000	0	-10000	0	0
MGAT3	-0.043	0.2	-10000	0	-0.49	43	43
HGF/MET	-0.072	0.16	-10000	0	-0.47	38	38
HGF	-0.037	0.2	-10000	0	-0.81	17	17
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0	0.1	-10000	0	-0.33	24	24
actin cable formation	0.051	0.088	-10000	0	-10000	0	0
KIAA1543	0.003	0.13	-10000	0	-0.41	25	25
KIFC3	-0.003	0.13	-10000	0	-0.44	24	24
NCK1	0.013	0	-10000	0	-10000	0	0
EXOC3	0.013	0	-10000	0	-10000	0	0
ACTN1	-0.003	0.13	-10000	0	-0.44	24	24
NCK1/GIT1	0.019	0	-10000	0	-10000	0	0
mol:GDP	-0.038	0.13	-10000	0	-0.46	24	24
EXOC4	0.013	0	-10000	0	-10000	0	0
STX4	-0.003	0.13	-10000	0	-0.44	24	24
PIP5K1C	-0.003	0.13	-10000	0	-0.44	24	24
LIMA1	0.013	0	-10000	0	-10000	0	0
ABI1	0.013	0	-10000	0	-10000	0	0
ROCK1	0.027	0.1	-10000	0	-10000	0	0
adherens junction assembly	0.02	0.12	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.043	0.13	-10000	0	-0.42	30	30
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.019	0	-10000	0	-10000	0	0
MET	-0.025	0.1	-10000	0	-0.29	36	36
PLEKHA7	-0.005	0.13	-10000	0	-0.44	25	25
mol:GTP	0	0.007	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.023	0.12	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0	0.099	-10000	0	-0.33	24	24
regulation of cell-cell adhesion	0.003	0.12	-10000	0	-0.41	24	24
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0	0.1	-10000	0	-0.33	24	24

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.025	-9999	-0.29	2	2
CCL5	-0.018	0.091	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.076	0.15	-9999	-0.43	25	25
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.065	0.14	-9999	-0.52	12	12
Syndecan-1/Syntenin	-0.065	0.14	-9999	-0.52	12	12
MAPK3	-0.046	0.13	-9999	-0.51	9	9
HGF/MET	-0.044	0.17	-9999	-0.67	17	17
TGFB1/TGF beta receptor Type II	0.01	0.025	-9999	-0.29	2	2
BSG	0.013	0	-9999	-10000	0	0
keratinocyte migration	-0.064	0.14	-9999	-0.51	12	12
Syndecan-1/RANTES	-0.079	0.15	-9999	-0.49	16	16
Syndecan-1/CD147	-0.056	0.14	-9999	-0.53	10	10
Syndecan-1/Syntenin/PIP2	-0.063	0.13	-9999	-0.5	12	12
LAMA5	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.076	0.12	-9999	-0.49	12	12
MMP7	-0.083	0.16	-9999	-0.32	82	82
HGF	-0.037	0.2	-9999	-0.81	17	17
Syndecan-1/CASK	-0.073	0.14	-9999	-0.41	25	25
Syndecan-1/HGF/MET	-0.099	0.19	-9999	-0.56	29	29
regulation of cell adhesion	-0.038	0.12	-9999	-0.6	5	5
HPSE	-0.026	0.17	-9999	-0.78	14	14
positive regulation of cell migration	-0.076	0.15	-9999	-0.43	25	25
SDC1	-0.076	0.15	-9999	-0.43	25	25
Syndecan-1/Collagen	-0.076	0.15	-9999	-0.43	25	25
PPIB	0.013	0	-9999	-10000	0	0
MET	-0.025	0.1	-9999	-0.29	36	36
PRKACA	0.013	0	-9999	-10000	0	0
MMP9	-0.12	0.17	-9999	-0.31	115	115
MAPK1	-0.046	0.13	-9999	-0.51	9	9
homophilic cell adhesion	-0.075	0.14	-9999	-0.42	25	25
MMP1	-0.052	0.2	-9999	-0.6	30	30

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.005	0.12	-10000	0	-1.1	3	3
SMARCC2	0.014	0	-10000	0	-10000	0	0
SMARCC1	0.014	0	-10000	0	-10000	0	0
TBX21	-0.028	0.095	-10000	0	-0.38	8	8
SUMO2	0.01	0.006	-10000	0	-10000	0	0
STAT1 (dimer)	0.015	0.04	-10000	0	-0.28	5	5
FKBP4	0.013	0	-10000	0	-10000	0	0
FKBP5	-0.005	0.12	-10000	0	-0.81	6	6
GR alpha/HSP90/FKBP51/HSP90	0.06	0.1	0.34	2	-0.48	6	8
PRL	-0.026	0.084	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.11	0.24	0.51	18	-0.49	21	39
RELA	-0.094	0.098	-10000	0	-10000	0	0
FGG	0.1	0.16	0.48	6	-10000	0	6
GR beta/TIF2	0.018	0.2	0.37	2	-0.59	25	27
IFNG	-0.14	0.19	-10000	0	-0.71	7	7
apoptosis	-0.071	0.21	0.38	1	-0.57	25	26
CREB1	0.004	0.053	-10000	0	-0.34	6	6
histone acetylation	-0.01	0.072	-10000	0	-0.4	2	2
BGLAP	-0.014	0.072	-10000	0	-10000	0	0
GR/PKAc	0.071	0.063	0.32	2	-10000	0	2
NF kappa B1 p50/RelA	-0.17	0.18	-10000	0	-0.43	48	48
SMARCD1	0.014	0	-10000	0	-10000	0	0
MDM2	0.058	0.059	0.25	5	-10000	0	5
GATA3	-0.62	0.34	-10000	0	-0.81	224	224
AKT1	0.002	0.018	-10000	0	-10000	0	0
CSF2	-0.029	0.068	-10000	0	-10000	0	0
GSK3B	0.01	0.006	-10000	0	-10000	0	0
NR1I3	-0.036	0.25	-10000	0	-0.91	13	13
CSN2	0.1	0.11	0.41	3	-10000	0	3
BRG1/BAF155/BAF170/BAF60A	0.04	0	-10000	0	-10000	0	0
NFATC1	0.015	0.004	-10000	0	-10000	0	0
POU2F1	0.013	0.006	-10000	0	-10000	0	0
CDKN1A	0.024	0.051	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.14	0.18	-10000	0	-0.31	135	135
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.011	0.14	-10000	0	-0.49	10	10
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.059	0.3	-10000	0	-0.89	25	25
JUN	-0.095	0.17	-10000	0	-0.52	25	25
IL4	-0.028	0.077	-10000	0	-10000	0	0
CDK5R1	0.007	0.031	-10000	0	-0.29	3	3
PRKACA	0.013	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.098	0.21	0.24	6	-0.52	46	52
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.065	0.096	0.32	2	-0.43	6	8
cortisol/GR alpha (monomer)	0.18	0.19	0.56	25	-10000	0	25
NCOA2	-0.059	0.23	-10000	0	-0.81	25	25
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.13	0.3	-10000	0	-0.83	44	44
AP-1/NFAT1-c-4	-0.19	0.3	-10000	0	-0.74	50	50
AFP	-0.2	0.46	-10000	0	-1.4	35	35
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.1	0.094	0.47	2	-10000	0	2
TP53	0.029	0.024	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
KRT17	-0.23	0.36	-10000	0	-1.2	27	27
KRT14	-0.07	0.11	-10000	0	-0.46	3	3
TBP	0.022	0	-10000	0	-10000	0	0
CREBBP	0.023	0.028	-10000	0	-10000	0	0
HDAC1	0.011	0.003	-10000	0	-10000	0	0
HDAC2	0.012	0.003	-10000	0	-10000	0	0
AP-1	-0.19	0.3	-10000	0	-0.74	50	50
MAPK14	0.01	0.005	-10000	0	-10000	0	0
MAPK10	0.01	0.006	-10000	0	-10000	0	0
MAPK11	0.01	0.006	-10000	0	-10000	0	0
KRT5	-0.17	0.27	-10000	0	-1.1	13	13
interleukin-1 receptor activity	-0.001	0.003	-10000	0	-10000	0	0
NCOA1	0.014	0.009	-10000	0	-10000	0	0
STAT1	0.015	0.04	-10000	0	-0.28	5	5
CGA	-0.06	0.21	-10000	0	-1.3	7	7
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.034	0.077	0.34	4	-10000	0	4
MAPK3	0.01	0.006	-10000	0	-10000	0	0
MAPK1	0.01	0.005	-10000	0	-10000	0	0
ICAM1	-0.17	0.18	-10000	0	-0.49	31	31
NFKB1	-0.094	0.098	-10000	0	-0.26	16	16
MAPK8	-0.082	0.15	-10000	0	-0.43	23	23
MAPK9	0.01	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.079	0.22	0.39	1	-0.6	26	27
BAX	0.027	0.037	-10000	0	-10000	0	0
POMC	-0.23	0.29	-10000	0	-0.86	19	19
EP300	0.023	0.028	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.17	0.17	0.5	21	-10000	0	21
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.046	0.22	2	-10000	0	2
SGK1	0.068	0.041	-10000	0	-10000	0	0
IL13	-0.48	0.28	-10000	0	-0.72	134	134
IL6	-0.27	0.42	-10000	0	-1.3	34	34
PRKACG	0.001	0.018	-10000	0	-0.29	1	1
IL5	-0.4	0.22	-10000	0	-0.65	90	90
IL2	-0.14	0.18	-10000	0	-0.67	6	6
CDK5	0.01	0.005	-10000	0	-10000	0	0
PRKACB	0.013	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0	-10000	0	-10000	0	0
IL8	-0.22	0.21	-10000	0	-0.53	53	53
CDK5R1/CDK5	0.008	0.022	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.1	0.13	-10000	0	-0.37	8	8
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.16	0.15	0.49	17	-10000	0	17
SMARCA4	0.014	0	-10000	0	-10000	0	0
chromatin remodeling	0.12	0.094	0.4	5	-10000	0	5
NF kappa B1 p50/RelA/Cbp	-0.1	0.15	-10000	0	-0.38	16	16
JUN (dimer)	-0.095	0.17	-10000	0	-0.52	25	25
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.065	0.25	-10000	0	-1	16	16
NR3C1	0.095	0.1	0.42	8	-10000	0	8
NR4A1	-0.33	0.41	-10000	0	-0.81	123	123
TIF2/SUV420H1	-0.037	0.18	-10000	0	-0.62	25	25
MAPKKK cascade	-0.071	0.21	0.38	1	-0.57	25	26
cortisol/GR alpha (dimer)/Src-1	0.17	0.16	0.52	17	-10000	0	17
PBX1	-0.004	0.12	-10000	0	-0.81	6	6
POU1F1	0.006	0.009	-10000	0	-10000	0	0
SELE	-0.66	0.63	-10000	0	-1.3	148	148
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.12	0.095	0.4	5	-10000	0	5
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.16	0.15	0.49	17	-10000	0	17
mol:cortisol	0.084	0.11	0.3	26	-10000	0	26
MMP1	-0.13	0.34	-10000	0	-1.4	18	18

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.9	0.65	-9999	-1.4	196	196
PLK1	0.037	0.13	-9999	-10000	0	0
CDKN1B	-0.032	0.1	-9999	-10000	0	0
FOXO3	0.059	0.095	-9999	-10000	0	0
KAT2B	0.02	0.012	-9999	-10000	0	0
FOXO1/SIRT1	-0.25	0.18	-9999	-0.38	196	196
CAT	0.062	0.087	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
AKT1	-0.015	0.027	-9999	-10000	0	0
FOXO1	-0.27	0.21	-9999	-0.42	196	196
MAPK10	0.021	0.012	-9999	-10000	0	0
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.068	0.042	-9999	-10000	0	0
response to oxidative stress	-0.031	0.03	-9999	-10000	0	0
FOXO3A/SIRT1	0.055	0.09	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
EP300	-0.024	0.026	-9999	-10000	0	0
BCL2L11	0.028	0.019	-9999	-10000	0	0
FOXO1/SKP2	-0.24	0.2	-9999	-0.38	196	196
mol:GDP	-0.031	0.03	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
GADD45A	0.09	0.05	-9999	-10000	0	0
YWHAQ	0.013	0	-9999	-10000	0	0
FOXO1/14-3-3 family	-0.03	0.063	-9999	-10000	0	0
MST1	0.015	0.057	-9999	-0.46	3	3
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.009	0.061	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
MAPK8	0.015	0.061	-9999	-0.49	4	4
MAPK9	0.021	0.012	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
SIRT1	0.014	0.01	-9999	-10000	0	0
SOD2	-0.037	0.13	-9999	-10000	0	0
RBL2	0.073	0.071	-9999	-10000	0	0
RAL/GDP	0.005	0.016	-9999	-10000	0	0
CHUK	0.02	0.012	-9999	-10000	0	0
Ran/GTP	0.013	0.003	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
RAL/GTP	0.012	0.017	-9999	-10000	0	0
CSNK1G1	0.013	0	-9999	-10000	0	0
FASLG	-0.002	0.095	-9999	-10000	0	0
SKP2	0.013	0	-9999	-10000	0	0
USP7	0.014	0	-9999	-10000	0	0
IKBKB	0.02	0.012	-9999	-10000	0	0
CCNB1	0.061	0.094	-9999	-10000	0	0
FOXO1-3a-4/beta catenin	-0.025	0.12	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.24	0.2	-9999	-0.38	196	196
CSNK1A1	0.013	0	-9999	-10000	0	0
SGK1	0.02	0.012	-9999	-10000	0	0
CSNK1G3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.023	0.005	-9999	-10000	0	0
ZFAND5	0.071	0.037	-9999	-10000	0	0
SFN	-0.14	0.18	-9999	-0.31	135	135
CDK2	-0.045	0.041	-9999	-10000	0	0
FOXO3A/14-3-3	0.02	0.055	-9999	-10000	0	0
CREBBP	-0.045	0.041	-9999	-10000	0	0
FBXO32	0.059	0.095	-9999	-10000	0	0
BCL6	0.072	0.073	-9999	-10000	0	0
RALB	0.014	0	-9999	-10000	0	0
RALA	0.014	0	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.046	0.15	-9999	-0.56	21	21
EFNA5	-0.048	0.21	-9999	-0.79	22	22
FYN	-0.025	0.14	-9999	-0.51	21	21
neuron projection morphogenesis	-0.046	0.15	-9999	-0.56	21	21
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.046	0.15	-9999	-0.56	21	21
EPHA5	-0.007	0.054	-9999	-0.29	10	10

×

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	-0.017	0.042	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.046	0.12	-9999	-0.36	23	23
JUN	-0.009	0.13	-9999	-0.56	6	6
HRAS	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.045	0.18	-9999	-0.51	36	36
RAP1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
RAP1A/GDP	0.009	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.046	0.18	-9999	-0.52	36	36
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.027	0.14	-9999	-0.5	23	23
RHOA	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.06	0.15	-9999	-0.46	36	36
GRB7	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF	-0.045	0.18	-9999	-0.51	36	36
MAPKKK cascade	-0.054	0.14	-9999	-0.42	36	36
BCAR1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.036	0.16	-9999	-0.54	26	26
lamellipodium assembly	-0.042	0.1	-9999	-0.34	23	23
RET51/GFRalpha1/GDNF/SHC	-0.045	0.18	-9999	-0.51	36	36
PIK3CA	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.027	0.14	-9999	-0.5	23	23
RET9/GFRalpha1/GDNF/Shank3	-0.027	0.14	-9999	-0.5	23	23
MAPK3	-0.025	0.16	-9999	-0.43	36	36
DOK1	0.009	0.031	-9999	-0.29	3	3
DOK6	-0.11	0.29	-9999	-0.81	43	43
PXN	0.013	0	-9999	-10000	0	0
neurite development	-0.039	0.17	-9999	-0.56	9	9
DOK5	0.002	0.087	-9999	-0.6	5	5
GFRA1	-0.06	0.23	-9999	-0.69	30	30
MAPK8	-0.017	0.14	-9999	-0.35	38	38
HRAS/GTP	-0.062	0.16	-9999	-0.48	36	36
tube development	-0.034	0.13	-9999	-0.47	23	23
MAPK1	-0.025	0.16	-9999	-0.43	36	36
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.006	0.098	-9999	-0.34	23	23
Rac1/GDP	0.009	0	-9999	-10000	0	0
SRC	0.011	0.018	-9999	-0.29	1	1
PDLIM7	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.13	0.24	-9999	-0.52	72	72
SHC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.045	0.18	-9999	-0.51	36	36
RET51/GFRalpha1/GDNF/Dok5	-0.051	0.19	-9999	-0.51	39	39
PRKCA	0.013	0	-9999	-10000	0	0
HRAS/GDP	0.009	0	-9999	-10000	0	0
CREB1	-0.01	0.12	-9999	-0.37	23	23
PIK3R1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.006	0.098	-9999	-0.34	23	23
RET51/GFRalpha1/GDNF/Grb7	-0.045	0.18	-9999	-0.51	36	36
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.029	0.18	-9999	-0.78	15	15
DOK4	0.013	0	-9999	-10000	0	0
JNK cascade	-0.008	0.13	-9999	-0.55	6	6
RET9/GFRalpha1/GDNF/FRS2	-0.027	0.14	-9999	-0.5	23	23
SHANK3	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.006	0.099	-9999	-0.34	23	23
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.018	0.12	-9999	-0.34	36	36
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.019	0.13	-9999	-0.35	36	36
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.019	0.13	-9999	-0.35	36	36
PI3K	-0.017	0.18	-9999	-0.51	26	26
SOS1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.04	0.13	-9999	-0.47	23	23
GRB10	0.013	0	-9999	-10000	0	0
activation of MAPKK activity	-0.013	0.11	-9999	-0.33	23	23
RET51/GFRalpha1/GDNF/FRS2	-0.045	0.18	-9999	-0.51	36	36
GAB1	0.013	0	-9999	-10000	0	0
IRS1	-0.002	0.11	-9999	-0.81	5	5
IRS2	0.01	0.025	-9999	-0.29	2	2
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.019	0.13	-9999	-0.35	36	36
RET51/GFRalpha1/GDNF/PKC alpha	-0.045	0.18	-9999	-0.51	36	36
GRB2	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GDNF	0.003	0.005	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.054	0.2	-9999	-0.53	39	39
Rac1/GTP	-0.05	0.13	-9999	-0.41	23	23
RET9/GFRalpha1/GDNF	-0.048	0.15	-9999	-0.55	23	23
GFRalpha1/GDNF	-0.044	0.18	-9999	-0.63	23	23

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.015	0.13	-9999	-0.55	17	17
ADCY5	-0.015	0.13	-9999	-0.55	17	17
ADCY6	0.019	0	-9999	-10000	0	0
ADCY7	0.011	0.036	-9999	-10000	0	0
ADCY1	-0.25	0.28	-9999	-0.55	139	139
ADCY2	-0.085	0.089	-9999	-0.55	1	1
ADCY3	0.019	0	-9999	-10000	0	0
ADCY8	0.01	0.031	-9999	-10000	0	0
PRKCE	0.011	0	-9999	-10000	0	0
ADCY9	0.019	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.083	0.093	-9999	-0.34	15	15

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.012	0.026	-10000	0	-0.29	2	2
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.027	0.14	0.4	13	-10000	0	13
IL27/IL27R/JAK1	0.037	0.25	-10000	0	-0.54	23	23
TBX21	-0.006	0.19	-10000	0	-0.5	11	11
IL12B	0.003	0.031	-10000	0	-0.3	1	1
IL12A	0.009	0.004	-10000	0	-10000	0	0
IL6ST	-0.11	0.3	-10000	0	-0.82	43	43
IL27RA/JAK1	0.025	0.027	-10000	0	-10000	0	0
IL27	-0.001	0.057	-10000	0	-0.3	10	10
TYK2	0.013	0.004	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.029	0.12	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.027	0.14	0.4	13	-10000	0	13
T cell proliferation during immune response	0.027	0.14	0.4	13	-10000	0	13
MAPKKK cascade	-0.027	0.14	-10000	0	-0.4	13	13
STAT3	0.013	0	-10000	0	-10000	0	0
STAT2	0.013	0	-10000	0	-10000	0	0
STAT1	0.01	0.04	-10000	0	-0.29	5	5
IL12RB1	-0.007	0.074	-10000	0	-0.29	18	18
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.064	0.21	-10000	0	-0.51	25	25
IL27/IL27R/JAK2/TYK2	-0.027	0.14	-10000	0	-0.41	13	13
positive regulation of T cell mediated cytotoxicity	-0.027	0.14	-10000	0	-0.4	13	13
STAT1 (dimer)	0.18	0.35	0.5	86	-0.63	10	96
JAK2	0.013	0.004	-10000	0	-10000	0	0
JAK1	0.015	0.004	-10000	0	-10000	0	0
STAT2 (dimer)	-0.019	0.13	-10000	0	-0.42	8	8
T cell proliferation	-0.072	0.2	-10000	0	-0.5	36	36
IL12/IL12R/TYK2/JAK2	0.014	0.048	-10000	0	-10000	0	0
IL17A	-0.029	0.12	-10000	0	-10000	0	0
mast cell activation	0.027	0.14	0.4	13	-10000	0	13
IFNG	-0.002	0.027	-10000	0	-0.088	3	3
T cell differentiation	-0.003	0.005	-10000	0	-0.019	2	2
STAT3 (dimer)	-0.019	0.13	-10000	0	-0.4	10	10
STAT5A (dimer)	-0.019	0.13	-10000	0	-0.42	7	7
STAT4 (dimer)	-0.031	0.14	-10000	0	-0.48	9	9
STAT4	-0.013	0.084	-10000	0	-0.29	24	24
T cell activation	-0.01	0.006	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.053	0.17	-10000	0	-0.46	43	43
GATA3	-1.1	0.59	-10000	0	-1.4	224	224
IL18	0.007	0.027	-10000	0	-0.2	5	5
positive regulation of mast cell cytokine production	-0.019	0.13	-10000	0	-0.4	10	10
IL27/EBI3	-0.017	0.098	-10000	0	-0.41	8	8
IL27RA	0.011	0.023	-10000	0	-10000	0	0
IL6	-0.082	0.25	-10000	0	-0.81	29	29
STAT5A	0.013	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	-0.001	0.016	-10000	0	-10000	0	0
IL1B	-0.001	0.085	-10000	0	-0.63	5	5
EBI3	-0.031	0.12	-10000	0	-0.32	30	30
TNF	-0.006	0.078	-10000	0	-0.63	3	3

×

Coregulation of Androgen receptor activity

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
NRIP1	0.012	0.003	-9999	-10000	0	0
SVIL	0.012	0.003	-9999	-10000	0	0
ZNF318	0.014	0.011	-9999	-10000	0	0
JMJD2C	-0.002	0.017	-9999	-0.061	22	22
T-DHT/AR/Ubc9	-0.064	0.12	-9999	-0.57	12	12
CARM1	0.012	0	-9999	-10000	0	0
PRDX1	0.013	0.001	-9999	-10000	0	0
PELP1	0.013	0.002	-9999	-10000	0	0
CTNNB1	0.012	0.003	-9999	-10000	0	0
AKT1	0.013	0.003	-9999	-10000	0	0
PTK2B	0.012	0.003	-9999	-10000	0	0
MED1	0.013	0.003	-9999	-10000	0	0
MAK	0.003	0.057	-9999	-0.29	10	10
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.007	0.068	-9999	-0.81	2	2
GSN	0.012	0.003	-9999	-10000	0	0
NCOA2	-0.059	0.23	-9999	-0.81	25	25
NCOA6	0.012	0.003	-9999	-10000	0	0
DNA-PK	0.004	0.017	-9999	-10000	0	0
NCOA4	0.012	0	-9999	-10000	0	0
PIAS3	0.012	0.003	-9999	-10000	0	0
cell proliferation	-0.034	0.035	-9999	-10000	0	0
XRCC5	0.013	0.002	-9999	-10000	0	0
UBE3A	0.012	0.006	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.094	0.16	-9999	-0.58	27	27
FHL2	-0.032	0.081	-9999	-1.1	1	1
RANBP9	0.012	0.003	-9999	-10000	0	0
JMJD1A	-0.089	0.078	-9999	-0.15	185	185
CDK6	0.013	0	-9999	-10000	0	0
TGFB1I1	-0.002	0.11	-9999	-0.81	5	5
T-DHT/AR/CyclinD1	-0.066	0.12	-9999	-0.58	13	13
XRCC6	0.013	0.002	-9999	-10000	0	0
T-DHT/AR	-0.12	0.14	-9999	-0.59	12	12
CTDSP1	0.012	0.002	-9999	-10000	0	0
CTDSP2	0.013	0.007	-9999	-10000	0	0
BRCA1	0.009	0.032	-9999	-0.3	3	3
TCF4	0.013	0.005	-9999	-10000	0	0
CDKN2A	-0.23	0.12	-9999	-0.29	228	228
SRF	0.02	0.01	-9999	-10000	0	0
NKX3-1	-0.15	0.12	-9999	-0.37	4	4
KLK3	0.005	0.069	-9999	-10000	0	0
TMF1	0.012	0.002	-9999	-10000	0	0
HNRNPA1	0.013	0.004	-9999	-10000	0	0
AOF2	0	0.005	-9999	-10000	0	0
APPL1	0.022	0.006	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.064	0.12	-9999	-0.57	12	12
AR	-0.065	0.16	-9999	-0.83	12	12
UBA3	0.012	0.002	-9999	-10000	0	0
PATZ1	0.013	0.004	-9999	-10000	0	0
PAWR	0.012	0.002	-9999	-10000	0	0
PRKDC	0.013	0.002	-9999	-10000	0	0
PA2G4	0.013	0.005	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.059	0.11	-9999	-0.53	12	12
RPS6KA3	0.012	0.003	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.064	0.12	-9999	-0.57	12	12
LATS2	0.013	0.004	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.057	0.11	-9999	-0.53	12	12
Cyclin D3/CDK11 p58	0.007	0.021	-9999	-10000	0	0
VAV3	0.009	0.048	-9999	-0.81	1	1
KLK2	-0.072	0.084	-9999	-0.36	13	13
CASP8	0.013	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.093	0.2	-9999	-0.61	33	33
TMPRSS2	-0.72	0.55	-9999	-1.1	185	185
CCND1	0.01	0.048	-9999	-0.81	1	1
PIAS1	0.012	0.006	-9999	-10000	0	0
mol:T-DHT	-0.047	0.039	-9999	-0.076	182	182
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.011	0.009	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.064	0.12	-9999	-0.57	12	12
CMTM2	-0.006	0.071	-9999	-0.29	17	17
SNURF	-0.032	0.18	-9999	-0.81	15	15
ZMIZ1	-0.029	0.035	-9999	-10000	0	0
CCND3	0.009	0.031	-9999	-0.29	3	3
TGIF1	0.013	0.004	-9999	-10000	0	0
FKBP4	0.012	0.003	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.013	0	-9999	-10000	0	0
SPHK1	-0.14	0.15	-9999	-0.29	144	144
GNAI2	0.013	0	-9999	-10000	0	0
mol:S1P	-0.035	0.057	-9999	-10000	0	0
GNAO1	-0.059	0.23	-9999	-0.81	24	24
mol:Sphinganine-1-P	-0.082	0.1	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.003	0.041	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0.018	0.012	-9999	-10000	0	0
S1PR3	-0.053	0.22	-9999	-0.81	23	23
S1PR2	0.013	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.039	0.039	-9999	-10000	0	0
S1PR5	-0.002	0.094	-9999	-0.46	9	9
S1PR4	0.006	0.043	-9999	-0.29	6	6
GNAI1	0.007	0.068	-9999	-0.81	2	2
S1P/S1P5/G12	-0.02	0.069	-9999	-0.53	3	3
S1P/S1P3/Gq	-0.1	0.2	-9999	-0.4	76	76
S1P/S1P4/Gi	-0.015	0.1	-9999	-0.33	24	24
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNA14	-0.16	0.34	-9999	-0.81	61	61
GNA15	-0.009	0.077	-9999	-0.29	20	20
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.011	0.018	-9999	-0.29	1	1
GNA11	-0.005	0.12	-9999	-0.81	6	6
ABCC1	0.013	0	-9999	-10000	0	0

×

Nongenotropic Androgen signaling

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
PTK2	0.011	0	-10000	0	-10000	0	0
GNB1/GNG2	0.001	0.1	-10000	0	-0.5	12	12
regulation of S phase of mitotic cell cycle	0.012	0.074	-10000	0	-0.34	12	12
GNAO1	-0.059	0.23	-10000	0	-0.81	24	24
HRAS	0.012	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.016	0.096	-10000	0	-0.55	9	9
PELP1	0.012	0.001	-10000	0	-10000	0	0
AKT1	0.011	0	-10000	0	-10000	0	0
MAP2K1	0.008	0.1	-10000	0	-0.42	12	12
T-DHT/AR	-0.019	0.13	-10000	0	-0.63	12	12
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.008	44	44
GNAI2	0.012	0	-10000	0	-10000	0	0
GNAI3	0.012	0	-10000	0	-10000	0	0
GNAI1	0.007	0.068	-10000	0	-0.81	2	2
mol:GDP	-0.026	0.12	-10000	0	-0.61	12	12
cell proliferation	-0.016	0.17	-10000	0	-0.44	14	14
PIK3CA	0.013	0	-10000	0	-10000	0	0
FOS	-0.087	0.33	-10000	0	-0.85	44	44
mol:Ca2+	-0.011	0.024	-10000	0	-0.075	28	28
MAPK3	-0.003	0.13	-10000	0	-0.57	3	3
MAPK1	-0.003	0.087	-10000	0	-0.28	3	3
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	0	0.002	-10000	0	-0.005	44	44
cAMP biosynthetic process	-0.008	0.095	-10000	0	-0.53	9	9
GNG2	0.013	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.002	-10000	0	-0.005	44	44
HRAS/GTP	-0.024	0.093	-10000	0	-0.46	12	12
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.011	0.018	-10000	0	-0.29	1	1
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.005	44	44
PI3K	0.002	0.006	-10000	0	-10000	0	0
apoptosis	0.023	0.17	0.4	44	-10000	0	44
T-DHT/AR/PELP1	-0.023	0.11	-10000	0	-0.55	12	12
HRAS/GDP	-0.023	0.12	-10000	0	-0.57	12	12
CREB1	-0.026	0.18	-10000	0	-0.43	44	44
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.024	0.17	-10000	0	-0.81	12	12
GNB1	0.013	0	-10000	0	-10000	0	0
RAF1	0.005	0.1	-10000	0	-0.44	12	12
RAC1-CDC42/GDP	-0.02	0.11	-10000	0	-0.55	12	12
T-DHT/AR/PELP1/Src	-0.001	0.11	-10000	0	-0.51	12	12
MAP2K2	0.008	0.1	-10000	0	-0.42	12	12
T-DHT/AR/PELP1/Src/PI3K	0.012	0.075	-10000	0	-0.34	12	12
GNAZ	0.012	0	-10000	0	-10000	0	0
SHBG	-0.013	0.14	-10000	0	-0.81	9	9
Gi family/GNB1/GNG2/GDP	0	0.12	-10000	0	-0.39	24	24
mol:T-DHT	0	0.001	0.001	2	-0.003	41	43
RAC1	0.013	0	-10000	0	-10000	0	0
GNRH1	-0.035	0.086	-10000	0	-0.2	63	63
Gi family/GTP	-0.011	0.092	-10000	0	-0.27	26	26
CDC42	0.013	0	-10000	0	-10000	0	0

×

IL6-mediated signaling 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
BCL2L1	-0.049	0.19	-9999	-0.62	6	6
CRP	-0.061	0.2	-9999	-0.62	11	11
cell cycle arrest	-0.067	0.2	-9999	-0.64	11	11
TIMP1	-0.082	0.2	-9999	-0.56	12	12
IL6ST	-0.11	0.29	-9999	-0.81	43	43
Rac1/GDP	-0.076	0.19	-9999	-0.5	25	25
AP1	-0.065	0.17	-9999	-0.46	30	30
GAB2	0.013	0.003	-9999	-10000	0	0
TNFSF11	-0.064	0.2	-9999	-0.64	8	8
HSP90B1	0.012	0.049	-9999	-10000	0	0
GAB1	0.013	0.001	-9999	-10000	0	0
MAPK14	-0.04	0.17	-9999	-0.68	8	8
AKT1	0.048	0.013	-9999	-10000	0	0
FOXO1	0.053	0.013	-9999	-10000	0	0
MAP2K6	-0.051	0.18	-9999	-0.58	12	12
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.064	0.18	-9999	-0.57	13	13
MITF	-0.059	0.19	-9999	-0.47	27	27
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.013	0	-9999	-10000	0	0
A2M	0.011	0.12	-9999	-1.4	2	2
CEBPB	0.006	0.053	-9999	-0.29	9	9
GRB2/SOS1/GAB family/SHP2	-0.008	0.074	-9999	-10000	0	0
STAT3	-0.071	0.21	-9999	-0.68	11	11
STAT1	-0.01	0.025	-9999	-10000	0	0
CEBPD	-0.049	0.19	-9999	-0.6	8	8
PIK3CA	0.014	0	-9999	-10000	0	0
PI3K	0.021	0.001	-9999	-10000	0	0
JUN	0.012	0.001	-9999	-10000	0	0
PIAS3/MITF	-0.046	0.18	-9999	-0.68	9	9
MAPK11	-0.04	0.17	-9999	-0.68	8	8
STAT3 (dimer)/FOXO1	-0.019	0.18	-9999	-0.54	8	8
GRB2/SOS1/GAB family	-0.075	0.15	-9999	-0.64	8	8
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.07	0.19	-9999	-0.41	50	50
GRB2	0.013	0.001	-9999	-10000	0	0
JAK2	0.013	0	-9999	-10000	0	0
LBP	-0.28	0.45	-9999	-0.95	82	82
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.014	0.003	-9999	-10000	0	0
MYC	-0.051	0.19	-9999	-0.6	8	8
FGG	-0.066	0.2	-9999	-0.61	10	10
macrophage differentiation	-0.067	0.2	-9999	-0.64	11	11
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.11	0.22	-9999	-0.49	67	67
JUNB	-0.049	0.18	-9999	-0.58	8	8
FOS	-0.11	0.3	-9999	-0.81	44	44
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.068	0.19	-9999	-0.42	45	45
STAT1/PIAS1	-0.059	0.18	-9999	-0.42	33	33
GRB2/SOS1/GAB family/SHP2/PI3K	0.032	0.021	-9999	-10000	0	0
STAT3 (dimer)	-0.069	0.21	-9999	-0.66	11	11
PRKCD	-0.052	0.18	-9999	-0.61	8	8
IL6R	0.014	0.003	-9999	-10000	0	0
SOCS3	-0.034	0.18	-9999	-0.77	7	7
gp130 (dimer)/JAK1/JAK1/LMO4	-0.059	0.2	-9999	-0.54	43	43
Rac1/GTP	-0.078	0.19	-9999	-0.52	22	22
HCK	-0.022	0.1	-9999	-0.31	31	31
MAPKKK cascade	0.008	0.058	-9999	-10000	0	0
bone resorption	-0.061	0.19	-9999	-0.61	8	8
IRF1	-0.049	0.19	-9999	-0.6	8	8
mol:GDP	-0.089	0.2	-9999	-0.48	34	34
SOS1	0.012	0.003	-9999	-10000	0	0
VAV1	-0.091	0.2	-9999	-0.49	34	34
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.048	0.18	-9999	-0.71	8	8
PTPN11	-0.007	0.016	-9999	-10000	0	0
IL6/IL6RA	-0.054	0.19	-9999	-0.62	29	29
gp130 (dimer)/TYK2/TYK2/LMO4	-0.064	0.2	-9999	-0.54	43	43
gp130 (dimer)/JAK2/JAK2/LMO4	-0.064	0.2	-9999	-0.54	43	43
IL6	-0.082	0.25	-9999	-0.66	41	41
PIAS3	0.013	0	-9999	-10000	0	0
PTPRE	0.009	0.009	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
RAC1	0.013	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.076	0.19	-9999	-0.39	67	67
LMO4	0.013	0.019	-9999	-0.28	1	1
STAT3 (dimer)/PIAS3	-0.11	0.18	-9999	-0.68	11	11
MCL1	0.053	0.012	-9999	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.028	0.11	-10000	0	-0.47	17	17
ER alpha/Gai/GDP/Gbeta gamma	-0.02	0.18	-10000	0	-0.59	17	17
AKT1	-0.018	0.21	-10000	0	-0.85	17	17
PIK3CA	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.021	0.21	-10000	0	-0.86	17	17
mol:Ca2+	-0.16	0.28	-10000	0	-0.54	91	91
IGF1R	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.04	0.14	-10000	0	-0.55	21	21
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.016	0.2	0.8	17	-10000	0	17
RhoA/GTP	-0.024	0.096	-10000	0	-0.41	17	17
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.052	0.15	-10000	0	-0.61	17	17
regulation of stress fiber formation	-0.02	0.097	-10000	0	-10000	0	0
E2/ERA-ERB (dimer)	-0.033	0.13	-10000	0	-0.55	17	17
KRAS	0.013	0	-10000	0	-10000	0	0
G13/GTP	-0.015	0.12	-10000	0	-0.5	17	17
pseudopodium formation	0.02	0.097	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1	-0.032	0.13	-10000	0	-0.55	17	17
GRB2	0.013	0	-10000	0	-10000	0	0
GNG2	0.013	0	-10000	0	-10000	0	0
GNAO1	-0.059	0.23	-10000	0	-0.81	24	24
HRAS	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.011	0.18	-10000	0	-0.63	19	19
E2/ER beta (dimer)	0.009	0.012	-10000	0	-10000	0	0
mol:GDP	-0.033	0.13	-10000	0	-0.55	17	17
mol:NADP	-0.011	0.18	-10000	0	-0.63	19	19
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.17	0.3	-10000	0	-0.57	91	91
IGF-1R heterotetramer	0.012	0	-10000	0	-10000	0	0
PLCB1	-0.17	0.3	-10000	0	-0.58	91	91
PLCB2	-0.12	0.26	-10000	0	-0.58	63	63
IGF1	-0.005	0.12	-10000	0	-0.81	6	6
mol:L-citrulline	-0.011	0.18	-10000	0	-0.63	19	19
RHOA	0.013	0	-10000	0	-10000	0	0
Gai/GDP	-0.065	0.21	-10000	0	-0.74	24	24
JNK cascade	0.009	0.012	-10000	0	-10000	0	0
BCAR1	0.013	0	-10000	0	-10000	0	0
ESR2	0.011	0.018	-10000	0	-0.29	1	1
GNAQ	0.013	0	-10000	0	-10000	0	0
ESR1	-0.036	0.19	-10000	0	-0.81	17	17
Gq family/GDP/Gbeta gamma	-0.05	0.16	-10000	0	-0.57	7	7
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.014	0.087	-10000	0	-0.36	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.052	0.15	-10000	0	-0.61	17	17
GNAZ	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.028	0.15	-10000	0	-0.63	17	17
STRN	0.001	0.096	-10000	0	-0.81	4	4
GNAL	0.01	0.048	-10000	0	-0.81	1	1
PELP1	0.013	0	-10000	0	-10000	0	0
MAPK11	0.017	0.01	-10000	0	-10000	0	0
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.007	0.068	-10000	0	-0.81	2	2
HBEGF	-0.034	0.17	-10000	0	-0.61	13	13
cAMP biosynthetic process	-0.028	0.11	-10000	0	-0.44	18	18
SRC	-0.011	0.17	-10000	0	-0.55	17	17
PI3K	0.019	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.029	0.11	-10000	0	-0.48	17	17
SOS1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.046	0.13	-10000	0	-0.49	19	19
Gs family/GTP	-0.029	0.11	-10000	0	-0.45	18	18
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.024	0	-10000	0	-10000	0	0
vasodilation	-0.008	0.17	-10000	0	-0.59	19	19
mol:DAG	-0.17	0.3	-10000	0	-0.57	91	91
Gs family/GDP/Gbeta gamma	-0.028	0.11	-10000	0	-0.44	17	17
MSN	0.02	0.1	-10000	0	-10000	0	0
Gq family/GTP	-0.12	0.27	-10000	0	-0.6	63	63
mol:PI-3-4-5-P3	-0.019	0.2	-10000	0	-0.82	17	17
NRAS	0.013	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.008	0.17	0.59	19	-10000	0	19
GRB2/SOS1	0.019	0	-10000	0	-10000	0	0
RhoA/GDP	-0.03	0.12	-10000	0	-0.51	17	17
NOS3	-0.013	0.19	-10000	0	-0.67	19	19
GNA11	-0.005	0.12	-10000	0	-0.81	6	6
MAPKKK cascade	-0.003	0.18	-10000	0	-0.63	21	21
E2/ER alpha (dimer)/PELP1/Src	-0.055	0.16	-10000	0	-0.64	17	17
ruffle organization	0.02	0.097	-10000	0	-10000	0	0
ROCK2	0.013	0.11	-10000	0	-0.38	22	22
GNA14	-0.16	0.34	-10000	0	-0.81	61	61
GNA15	-0.009	0.077	-10000	0	-0.29	20	20
GNA13	0.011	0.018	-10000	0	-0.29	1	1
MMP9	-0.058	0.18	-10000	0	-0.57	19	19
MMP2	-0.007	0.17	-10000	0	-0.83	6	6

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.045	0.15	-9999	-0.54	24	24
E-cadherin/beta catenin	-0.035	0.18	-9999	-0.62	24	24
CTNNB1	0.013	0	-9999	-10000	0	0
JUP	0.013	0	-9999	-10000	0	0
CDH1	-0.056	0.23	-9999	-0.81	24	24

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.005	0.15	-10000	0	-0.6	3	3
IHH	-0.062	0.25	-10000	0	-0.83	28	28
SHH Np/Cholesterol/GAS1	-0.014	0.13	-10000	0	-0.5	19	19
LRPAP1	0.013	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.014	0.13	0.5	19	-10000	0	19
SMO/beta Arrestin2	0.003	0.16	-10000	0	-0.57	7	7
SMO	-0.003	0.17	-10000	0	-0.5	29	29
AKT1	0.022	0.078	-10000	0	-10000	0	0
ARRB2	0.011	0.018	-10000	0	-0.29	1	1
BOC	0.013	0	-10000	0	-10000	0	0
ADRBK1	0.013	0	-10000	0	-10000	0	0
heart looping	-0.003	0.17	-10000	0	-0.5	29	29
STIL	0.005	0.14	-10000	0	-0.46	8	8
DHH N/PTCH2	-0.026	0.16	-10000	0	-0.62	19	19
DHH N/PTCH1	-0.037	0.19	-10000	0	-0.47	46	46
PIK3CA	0.013	0	-10000	0	-10000	0	0
DHH	-0.043	0.2	-10000	0	-0.81	19	19
PTHLH	-0.003	0.18	-10000	0	-0.77	3	3
determination of left/right symmetry	-0.003	0.17	-10000	0	-0.5	29	29
PIK3R1	0.013	0	-10000	0	-10000	0	0
skeletal system development	-0.002	0.17	-10000	0	-0.76	3	3
IHH N/Hhip	-0.063	0.21	-10000	0	-0.59	39	39
DHH N/Hhip	-0.052	0.21	-10000	0	-0.68	27	27
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.003	0.17	-10000	0	-0.5	29	29
pancreas development	-0.026	0.16	-10000	0	-0.63	17	17
HHAT	0.013	0	-10000	0	-10000	0	0
PI3K	0.019	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.033	0.19	-10000	0	-0.81	16	16
somite specification	-0.003	0.17	-10000	0	-0.5	29	29
SHH Np/Cholesterol/PTCH1	0	0.14	-10000	0	-0.46	8	8
SHH Np/Cholesterol/PTCH2	0.013	0.058	-10000	0	-0.5	3	3
SHH Np/Cholesterol/Megalin	-0.033	0.16	-10000	0	-0.52	29	29
SHH	0.011	0.071	-10000	0	-0.62	3	3
catabolic process	-0.008	0.16	-10000	0	-0.49	28	28
SMO/Vitamin D3	0	0.16	-10000	0	-0.55	6	6
SHH Np/Cholesterol/Hhip	-0.009	0.12	-10000	0	-0.5	14	14
LRP2	-0.065	0.24	-10000	0	-0.81	27	27
receptor-mediated endocytosis	-0.023	0.2	-10000	0	-0.66	15	15
SHH Np/Cholesterol/BOC	0.015	0.056	-10000	0	-0.5	3	3
SHH Np/Cholesterol/CDO	0.013	0.059	-10000	0	-0.5	3	3
mesenchymal cell differentiation	0.009	0.11	0.49	14	-10000	0	14
mol:Vitamin D3	0.002	0.14	-10000	0	-0.47	8	8
IHH N/PTCH2	-0.034	0.17	-10000	0	-0.55	28	28
CDON	0.008	0.036	-10000	0	-10000	0	0
IHH N/PTCH1	-0.008	0.16	-10000	0	-0.49	28	28
Megalin/LRPAP1	-0.041	0.19	-10000	0	-0.62	27	27
PTCH2	0.009	0.031	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.008	0.054	-10000	0	-0.5	3	3
PTCH1	-0.008	0.16	-10000	0	-0.49	28	28
HHIP	-0.026	0.16	-10000	0	-0.63	17	17

×

p75(NTR)-mediated signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.019	0	-9999	-10000	0	0
Necdin/E2F1	-0.088	0.19	-9999	-0.65	23	23
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.026	0.11	-9999	-0.49	15	15
NGF (dimer)/p75(NTR)/BEX1	-0.068	0.18	-9999	-0.56	34	34
NT-4/5 (dimer)/p75(NTR)	-0.021	0.12	-9999	-0.64	8	8
IKBKB	0.013	0	-9999	-10000	0	0
AKT1	0.009	0.12	-9999	-0.48	15	15
IKBKG	0.013	0	-9999	-10000	0	0
BDNF	-0.029	0.1	-9999	-0.29	39	39
MGDIs/NGR/p75(NTR)/LINGO1	-0.027	0.12	-9999	-0.58	12	12
FURIN	0.013	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.034	0.11	-9999	-0.59	8	8
LINGO1	-0.002	0.11	-9999	-0.81	5	5
Sortilin/TRAF6/NRIF	-0.001	0.023	-9999	-10000	0	0
proBDNF (dimer)	-0.029	0.1	-9999	-0.29	39	39
NTRK1	-0.15	0.32	-9999	-0.81	56	56
RTN4R	0.007	0.04	-9999	-0.29	5	5
neuron apoptosis	-0.005	0.12	-9999	-0.55	8	8
IRAK1	0.013	0	-9999	-10000	0	0
SHC1	-0.006	0.14	-9999	-0.57	15	15
ARHGDIA	0.013	0	-9999	-10000	0	0
RhoA/GTP	0.009	0	-9999	-10000	0	0
Gamma Secretase	-0.002	0.027	-9999	-0.46	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.002	0.13	-9999	-0.52	15	15
MAGEH1	0.011	0.018	-9999	-0.29	1	1
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.038	0.21	-9999	-0.57	33	33
Mammalian IAPs/DIABLO	0.022	0.039	-9999	-10000	0	0
proNGF (dimer)	-0.013	0.14	-9999	-0.71	10	10
MAGED1	0.013	0	-9999	-10000	0	0
APP	0.013	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.019	0.084	-9999	-0.29	25	25
ZNF274	0.013	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	0.002	0.12	-9999	-0.49	15	15
NGF	-0.013	0.14	-9999	-0.71	10	10
cell cycle arrest	-0.012	0.12	-9999	-0.48	15	15
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.015	0.088	-9999	-0.35	15	15
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.028	0.099	-9999	-0.56	8	8
NCSTN	0.013	0	-9999	-10000	0	0
mol:GTP	-0.03	0.13	-9999	-0.57	15	15
PSENEN	0.013	0	-9999	-10000	0	0
mol:ceramide	0.002	0.12	-9999	-0.51	15	15
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.022	0.073	-9999	-0.54	1	1
p75(NTR)/beta APP	0.001	0.1	-9999	-0.62	8	8
BEX1	-0.046	0.21	-9999	-0.72	23	23
mol:GDP	-0.015	0.14	-9999	-0.58	15	15
NGF (dimer)	-0.33	0.28	-9999	-0.55	167	167
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.006	0.12	-9999	-0.53	12	12
PIK3R1	0.013	0	-9999	-10000	0	0
RAC1/GTP	-0.027	0.11	-9999	-0.5	15	15
MYD88	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.031	0.13	-9999	-0.57	15	15
RHOB	0.013	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.038	0.092	-9999	-10000	0	0
NT3 (dimer)	-0.076	0.25	-9999	-0.81	31	31
TP53	0.011	0.094	-9999	-0.48	8	8
PRDM4	0.002	0.12	-9999	-0.52	15	15
BDNF (dimer)	-0.35	0.27	-9999	-0.56	167	167
PIK3CA	0.013	0	-9999	-10000	0	0
SORT1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.026	0.11	-9999	-0.48	15	15
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.002	0.13	-9999	-0.52	15	15
RHOC	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
MAPK10	0.024	0.11	-9999	-0.47	9	9
DIABLO	0.013	0	-9999	-10000	0	0
SMPD2	0.002	0.12	-9999	-0.52	15	15
APH1B	0.01	0.048	-9999	-0.81	1	1
APH1A	0.013	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.031	0.13	-9999	-0.57	15	15
PSEN1	0.013	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0.019	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.067	0.23	-9999	-0.65	37	37
MAPK8	0.019	0.12	-9999	-0.47	9	9
MAPK9	0.024	0.11	-9999	-0.47	9	9
APAF1	0.013	0	-9999	-10000	0	0
NTF3	-0.077	0.26	-9999	-0.81	31	31
NTF4	-0.019	0.084	-9999	-0.29	25	25
NDN	-0.053	0.22	-9999	-0.81	23	23
RAC1/GDP	0.009	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.024	0.1	-9999	-0.45	15	15
p75 CTF/Sortilin/TRAF6/NRIF	0.032	0	-9999	-10000	0	0
RhoA-B-C/GTP	-0.03	0.13	-9999	-0.56	15	15
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.027	0.089	-9999	-0.51	8	8
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.003	0.1	-9999	-0.54	8	8
PRKACB	0.013	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.009	0.07	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.009	0.077	-9999	-0.29	20	20
BIRC2	0.013	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.03	0.16	-9999	-0.59	15	15
BAD	0.029	0.11	-9999	-0.46	9	9
RIPK2	0.013	0	-9999	-10000	0	0
NGFR	-0.01	0.14	-9999	-0.81	8	8
CYCS	0.009	0.12	-9999	-0.48	15	15
ADAM17	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.002	0.13	-9999	-0.52	15	15
BCL2L11	0.029	0.11	-9999	-0.46	9	9
BDNF (dimer)/p75(NTR)	-0.026	0.13	-9999	-0.68	8	8
PI3K	0.002	0.13	-9999	-0.52	15	15
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.002	0.13	-9999	-0.52	15	15
NDNL2	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.018	0.15	-9999	-0.66	15	15
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.002	0.13	-9999	-0.52	15	15
TRAF6	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
PLG	-0.46	0.4	-9999	-0.81	164	164
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.009	0.13	-9999	-0.52	15	15
SQSTM1	0.003	0.053	-9999	-0.29	9	9
NGFRAP1	0.013	0	-9999	-10000	0	0
CASP3	0.03	0.1	-9999	-0.42	9	9
E2F1	-0.072	0.14	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
IKK complex	-0.093	0.17	-9999	-0.53	12	12
NGF (dimer)/TRKA	-0.13	0.27	-9999	-0.63	63	63
MMP7	-0.083	0.16	-9999	-0.32	82	82
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.026	0.11	-9999	-0.49	15	15
MMP3	-0.015	0.071	-9999	-0.29	18	18
APAF-1/Caspase 9	-0.023	0.083	-9999	-0.55	2	2

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.014	0.023	-9999	-10000	0	0
NFATC2	-0.027	0.15	-9999	-0.55	21	21
NFATC3	0.014	0.023	-9999	-10000	0	0
CD40LG	-0.093	0.26	-9999	-0.64	33	33
PTGS2	-0.16	0.37	-9999	-0.85	52	52
JUNB	0.013	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.009	-9999	-10000	0	0
CaM/Ca2+	-0.003	0.008	-9999	-10000	0	0
CALM1	0.012	0.006	-9999	-10000	0	0
JUN	0.012	0.007	-9999	-10000	0	0
mol:Ca2+	-0.004	0.009	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.001	0.003	-9999	-10000	0	0
FOSL1	0.003	0.077	-9999	-0.46	6	6
CREM	0.012	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.057	0.12	-9999	-0.5	10	10
FOS	-0.12	0.3	-9999	-0.82	44	44
IFNG	-0.1	0.27	-9999	-0.63	38	38
AP-1/NFAT1-c-4	-0.12	0.3	-9999	-0.74	37	37
FASLG	-0.1	0.27	-9999	-0.63	38	38
NFAT1-c-4/ICER1	-0.029	0.12	-9999	-0.44	21	21
IL2RA	-0.1	0.26	-9999	-0.63	35	35
FKBP12/FK506	0.009	0	-9999	-10000	0	0
CSF2	-0.095	0.26	-9999	-0.64	32	32
JunB/Fra1/NFAT1-c-4	-0.044	0.12	-9999	-0.43	23	23
IL4	-0.095	0.26	-9999	-0.64	32	32
IL2	-0.006	0.025	-9999	-10000	0	0
IL3	-0.015	0.021	-9999	-10000	0	0
FKBP1A	0.013	0	-9999	-10000	0	0
BATF3	0.011	0.018	-9999	-0.29	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.013	0	-9999	-10000	0	0

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.059	0.37	-9999	-1	14	14
HDAC7	0.014	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.076	0.24	-9999	-0.77	8	8
SMAD4	0.014	0	-9999	-10000	0	0
ID2	-0.059	0.37	-9999	-1	14	14
AP1	-0.077	0.23	-9999	-0.62	44	44
ABCG2	-0.063	0.37	-9999	-1	14	14
HIF1A	0.002	0.069	-9999	-10000	0	0
TFF3	-0.14	0.45	-9999	-1.1	23	23
GATA2	-0.16	0.34	-9999	-0.81	60	60
AKT1	0.006	0.072	-9999	-10000	0	0
response to hypoxia	-0.01	0.077	-9999	-10000	0	0
MCL1	-0.059	0.37	-9999	-1	14	14
NDRG1	-0.059	0.37	-9999	-1	14	14
SERPINE1	-0.08	0.4	-9999	-1.1	18	18
FECH	-0.059	0.37	-9999	-1	14	14
FURIN	-0.059	0.37	-9999	-1	14	14
NCOA2	-0.058	0.23	-9999	-0.81	25	25
EP300	0.029	0.097	-9999	-10000	0	0
HMOX1	-0.071	0.38	-9999	-1.1	14	14
BHLHE40	-0.059	0.37	-9999	-1	14	14
BHLHE41	-0.082	0.38	-9999	-1	16	16
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.009	0.048	-9999	-10000	0	0
ENG	0.049	0.088	-9999	-10000	0	0
JUN	0.013	0.001	-9999	-10000	0	0
RORA	-0.061	0.37	-9999	-1	14	14
ABCB1	-0.099	0.3	-9999	-1.3	16	16
TFRC	-0.06	0.37	-9999	-1	14	14
CXCR4	-0.069	0.37	-9999	-1.1	14	14
TF	-0.07	0.38	-9999	-1	16	16
CITED2	-0.059	0.37	-9999	-1	14	14
HIF1A/ARNT	-0.11	0.38	-9999	-1.1	15	15
LDHA	-0.016	0.032	-9999	-10000	0	0
ETS1	-0.059	0.37	-9999	-1	14	14
PGK1	-0.059	0.37	-9999	-1	14	14
NOS2	-0.091	0.42	-9999	-1.2	21	21
ITGB2	-0.083	0.38	-9999	-1.1	14	14
ALDOA	-0.059	0.37	-9999	-1	14	14
Cbp/p300/CITED2	-0.046	0.36	-9999	-1.1	11	11
FOS	-0.11	0.3	-9999	-0.81	44	44
HK2	-0.14	0.39	-9999	-1.1	17	17
SP1	0.017	0.022	-9999	-10000	0	0
GCK	0.014	0.17	-9999	-0.51	4	4
HK1	-0.059	0.37	-9999	-1	14	14
NPM1	-0.059	0.37	-9999	-1	14	14
EGLN1	-0.059	0.37	-9999	-1	14	14
CREB1	0.02	0	-9999	-10000	0	0
PGM1	-0.059	0.37	-9999	-1	14	14
SMAD3	0.014	0	-9999	-10000	0	0
EDN1	-0.08	0.28	-9999	-0.85	21	21
IGFBP1	-0.1	0.41	-9999	-1.1	21	21
VEGFA	0.012	0.28	-9999	-0.81	4	4
HIF1A/JAB1	-0.007	0.026	-9999	-10000	0	0
CP	-0.1	0.41	-9999	-1	22	22
CXCL12	-0.12	0.46	-9999	-1	38	38
COPS5	0.013	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.059	0.37	-9999	-1	14	14
EGLN3	-0.064	0.37	-9999	-1	14	14
CA9	-0.14	0.39	-9999	-1	19	19
TERT	-0.085	0.38	-9999	-1	16	16
ENO1	-0.059	0.37	-9999	-1	14	14
PFKL	-0.059	0.37	-9999	-1	14	14
NCOA1	0.013	0.001	-9999	-10000	0	0
ADM	-0.063	0.37	-9999	-1.1	14	14
ARNT	0.002	0.069	-9999	-10000	0	0
HNF4A	-0.073	0.26	-9999	-0.81	31	31
ADFP	-0.07	0.36	-9999	-1	14	14
SLC2A1	0.009	0.28	-9999	-0.8	6	6
LEP	-0.076	0.38	-9999	-1.1	14	14
HIF1A/ARNT/Cbp/p300	-0.05	0.28	-9999	-0.78	10	10
EPO	-0.02	0.26	-9999	-0.84	5	5
CREBBP	0.029	0.097	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/HDAC7	-0.077	0.24	-9999	-0.76	12	12
PFKFB3	-0.059	0.37	-9999	-1	14	14
NT5E	-0.061	0.37	-9999	-1.1	14	14

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.048	0.1	-9999	-10000	0	0
STMN1	-0.073	0.1	-9999	-10000	0	0
Aurora B/RasGAP/Survivin	-0.11	0.14	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.059	0.12	-9999	-0.43	11	11
BIRC5	-0.099	0.15	-9999	-0.3	102	102
DES	-0.31	0.3	-9999	-0.65	122	122
Aurora C/Aurora B/INCENP	-0.049	0.076	-9999	-10000	0	0
Aurora B/TACC1	-0.063	0.082	-9999	-10000	0	0
Aurora B/PP2A	-0.079	0.1	-9999	-0.37	1	1
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.014	0.032	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.002	0.003	-9999	-10000	0	0
NDC80	-0.095	0.14	-9999	-0.37	34	34
Cul3 protein complex	-0.039	0.14	-9999	-0.54	21	21
KIF2C	-0.048	0.086	-9999	-0.24	32	32
PEBP1	0.008	0.006	-9999	-10000	0	0
KIF20A	-0.092	0.14	-9999	-0.29	89	89
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.078	0.1	-9999	-10000	0	0
SEPT1	0.007	0.04	-9999	-0.29	5	5
SMC2	0.013	0	-9999	-10000	0	0
SMC4	0.013	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.042	0.075	-9999	-10000	0	0
PSMA3	0.013	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.002	-9999	-10000	0	0
H3F3B	-0.045	0.068	-9999	-10000	0	0
AURKB	-0.13	0.16	-9999	-0.3	1	1
AURKC	0.012	0.001	-9999	-10000	0	0
CDCA8	-0.026	0.099	-9999	-0.3	32	32
cytokinesis	-0.12	0.12	-9999	-0.4	11	11
Aurora B/Septin1	-0.097	0.13	-9999	-0.44	3	3
AURKA	0.008	0.04	-9999	-0.29	5	5
INCENP	0.008	0.006	-9999	-10000	0	0
KLHL13	-0.045	0.21	-9999	-0.81	20	20
BUB1	-0.098	0.15	-9999	-0.29	105	105
hSgo1/Aurora B/Survivin	-0.11	0.15	-9999	-0.42	28	28
EVI5	0.012	0.002	-9999	-10000	0	0
RhoA/GTP	-0.08	0.1	-9999	-0.42	1	1
SGOL1	-0.017	0.09	-9999	-0.29	28	28
CENPA	-0.079	0.12	-9999	-0.25	65	65
NCAPG	-0.075	0.14	-9999	-10000	0	0
Aurora B/HC8 Proteasome	-0.078	0.1	-9999	-10000	0	0
NCAPD2	0.013	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.078	0.1	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
NCAPH	-0.046	0.12	-9999	-0.29	56	56
NPM1	-0.055	0.07	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
KLHL9	0.01	0.048	-9999	-0.81	1	1
mitotic prometaphase	-0.004	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.078	0.1	-9999	-10000	0	0
PPP1CC	0.013	0	-9999	-10000	0	0
Centraspindlin	-0.09	0.11	-9999	-0.36	4	4
RhoA/GDP	0.009	0	-9999	-10000	0	0
NSUN2	-0.055	0.07	-9999	-10000	0	0
MYLK	-0.059	0.11	-9999	-0.52	9	9
KIF23	0.008	0.026	-9999	-0.3	2	2
VIM	-0.075	0.1	-9999	-0.37	1	1
RACGAP1	0.01	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.055	0.07	-9999	-10000	0	0
Chromosomal passenger complex	-0.088	0.14	-9999	-0.3	65	65
Chromosomal passenger complex/EVI5	-0.087	0.16	-9999	-10000	0	0
TACC1	0.013	0	-9999	-10000	0	0
PPP2R5D	0.011	0.018	-9999	-0.29	1	1
CUL3	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.018	0.094	-10000	0	-0.37	4	4
TBX21	-0.027	0.27	-10000	0	-0.77	19	19
B2M	0.013	0.004	-10000	0	-10000	0	0
TYK2	0.016	0.017	-10000	0	-10000	0	0
IL12RB1	-0.003	0.083	-10000	0	-0.32	18	18
GADD45B	-0.004	0.23	-10000	0	-0.75	5	5
IL12RB2	-0.13	0.17	-10000	0	-0.3	137	137
GADD45G	-0.008	0.24	-10000	0	-0.77	9	9
natural killer cell activation	0.006	0.02	-10000	0	-10000	0	0
RELB	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL18	0.01	0.041	-10000	0	-0.3	5	5
IL2RA	-0.018	0.091	-10000	0	-10000	0	0
IFNG	-0.013	0.076	-10000	0	-0.29	20	20
STAT3 (dimer)	-0.01	0.24	-10000	0	-0.61	21	21
HLA-DRB5	-0.01	0.096	-10000	0	-0.36	17	17
FASLG	-0.037	0.28	-10000	0	-0.79	20	20
NF kappa B2 p52/RelB	-0.1	0.21	-10000	0	-0.68	23	23
CD4	-0.001	0.061	-10000	0	-0.29	12	12
SOCS1	0.006	0.071	-10000	0	-0.64	3	3
EntrezGene:6955	-0.003	0.011	-10000	0	-10000	0	0
CD3D	-0.037	0.11	-10000	0	-0.3	46	46
CD3E	-0.019	0.1	-10000	0	-0.32	27	27
CD3G	-0.003	0.068	-10000	0	-0.3	14	14
IL12Rbeta2/JAK2	-0.077	0.12	-10000	0	-0.64	3	3
CCL3	-0.039	0.29	-10000	0	-0.86	15	15
CCL4	-0.034	0.28	-10000	0	-0.86	15	15
HLA-A	0.011	0.026	-10000	0	-0.3	2	2
IL18/IL18R	0.025	0.086	-10000	0	-0.52	1	1
NOS2	-0.07	0.4	-10000	0	-1.1	31	31
IL12/IL12R/TYK2/JAK2/SPHK2	-0.015	0.09	-10000	0	-0.41	2	2
IL1R1	-0.023	0.26	-10000	0	-0.77	15	15
IL4	-0.002	0.021	-10000	0	-10000	0	0
JAK2	0.016	0.017	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.01	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.011	0.14	-10000	0	-0.48	18	18
RAB7A	0.017	0.21	-10000	0	-0.64	3	3
lysosomal transport	0.019	0.2	-10000	0	-0.59	4	4
FOS	-0.18	0.5	-10000	0	-1.2	52	52
STAT4 (dimer)	-0.008	0.24	-10000	0	-0.68	16	16
STAT5A (dimer)	-0.11	0.22	-10000	0	-0.7	25	25
GZMA	-0.031	0.27	-10000	0	-0.83	16	16
GZMB	-0.029	0.27	-10000	0	-0.82	15	15
HLX	0.011	0.018	-10000	0	-0.29	1	1
LCK	-0.03	0.28	-10000	0	-0.74	25	25
TCR/CD3/MHC II/CD4	-0.03	0.13	-10000	0	-0.4	16	16
IL2/IL2R	-0.011	0.089	-10000	0	-0.44	4	4
MAPK14	0.004	0.24	-10000	0	-0.62	13	13
CCR5	-0.021	0.25	-10000	0	-0.69	16	16
IL1B	0.001	0.11	-10000	0	-0.74	6	6
STAT6	0.01	0.093	-10000	0	-10000	0	0
STAT4	-0.013	0.084	-10000	0	-0.29	24	24
STAT3	0.013	0	-10000	0	-10000	0	0
STAT1	0.007	0.04	-10000	0	-0.29	5	5
NFKB1	0.013	0	-10000	0	-10000	0	0
NFKB2	0.013	0	-10000	0	-10000	0	0
IL12B	0.011	0.036	-10000	0	-0.34	1	1
CD8A	-0.014	0.089	-10000	0	-0.31	17	17
CD8B	-0.008	0.079	-10000	0	-0.3	20	20
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.018	0.093	0.37	4	-10000	0	4
IL2RB	-0.022	0.097	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.23	-10000	0	-0.63	16	16
IL2RG	0.003	0.053	-10000	0	-0.29	9	9
IL12	0.022	0.037	-10000	0	-10000	0	0
STAT5A	0.013	0	-10000	0	-10000	0	0
CD247	-0.002	0.065	-10000	0	-0.3	13	13
IL2	0.003	0.018	-10000	0	-0.29	1	1
SPHK2	0.013	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.015	0.018	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	-0.034	0.29	-10000	0	-0.74	27	27
MAP2K3	-0.001	0.23	-10000	0	-0.6	17	17
RIPK2	0.013	0	-10000	0	-10000	0	0
MAP2K6	-0.001	0.23	-10000	0	-0.6	17	17
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.004	0.063	-10000	0	-0.38	6	6
IL18RAP	-0.024	0.1	-10000	0	-0.29	38	38
IL12Rbeta1/TYK2	0.009	0.064	-10000	0	-10000	0	0
EOMES	-0.01	0.079	-10000	0	-10000	0	0
STAT1 (dimer)	-0.013	0.24	-10000	0	-0.64	19	19
T cell proliferation	0.012	0.21	-10000	0	-0.51	17	17
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.013	0.049	-10000	0	-0.8	1	1
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.084	0.17	-10000	0	-0.56	16	16
ATF2	0.012	0.22	-10000	0	-0.61	9	9

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.11	0.1	-10000	0	-0.68	2	2
epithelial cell differentiation	-0.18	0.19	-10000	0	-0.43	84	84
ITCH	0.046	0.022	-10000	0	-10000	0	0
WWP1	-0.094	0.085	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
EGFR	0.013	0	-10000	0	-10000	0	0
PRL	0.001	0.018	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.033	0.077	-10000	0	-0.48	2	2
PTPRZ1	-0.013	0.11	-10000	0	-0.55	10	10
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.065	0.065	-10000	0	-0.48	4	4
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.082	0.094	-10000	0	-0.54	5	5
ADAM17	0.046	0.022	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.13	0.11	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.12	0.11	-10000	0	-0.68	3	3
NCOR1	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.069	0.088	-10000	0	-0.51	5	5
GRIN2B	-0.063	0.086	-10000	0	-0.48	5	5
ErbB4/ErbB2/betacellulin	-0.08	0.12	-10000	0	-0.58	12	12
STAT1	0.007	0.04	-10000	0	-0.29	5	5
HBEGF	0.007	0.068	-10000	0	-0.81	2	2
PRLR	-0.3	0.4	-10000	0	-0.81	110	110
E4ICDs/ETO2	-0.1	0.092	-10000	0	-10000	0	0
axon guidance	-0.036	0.053	-10000	0	-10000	0	0
NEDD4	0.046	0.022	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.23	0.31	-10000	0	-0.63	110	110
CBFA2T3	0.011	0.018	-10000	0	-0.29	1	1
ErbB4/ErbB2/HBEGF	-0.063	0.08	-10000	0	-0.59	2	2
MAPK3	-0.041	0.079	-10000	0	-0.5	2	2
STAT1 (dimer)	-0.11	0.095	-10000	0	-0.31	5	5
MAPK1	-0.041	0.079	-10000	0	-0.5	2	2
JAK2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.069	0.088	-10000	0	-0.51	5	5
NRG1	0.028	0.091	-10000	0	-0.63	5	5
NRG3	-0.009	0.1	-10000	0	-0.4	15	15
NRG2	0.003	0.085	-10000	0	-0.68	4	4
NRG4	0.005	0.057	-10000	0	-0.42	4	4
heart development	-0.036	0.053	-10000	0	-10000	0	0
neural crest cell migration	-0.069	0.088	-10000	0	-0.5	5	5
ERBB2	0.042	0.013	-10000	0	-10000	0	0
WWOX/E4ICDs	-0.1	0.092	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.092	0.088	-10000	0	-0.63	1	1
apoptosis	0.12	0.088	0.55	3	-10000	0	3
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.11	0.1	-10000	0	-0.56	3	3
ErbB4/ErbB2/epiregulin	-0.13	0.1	-10000	0	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	-0.13	0.14	-10000	0	-0.66	12	12
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.26	0.23	-10000	0	-0.54	112	112
MDM2	-0.1	0.093	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.057	0.074	-10000	0	-0.51	5	5
STAT5A	-0.027	0.05	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.069	0.088	-10000	0	-0.51	5	5
DLG4	0.013	0	-10000	0	-10000	0	0
GRB2/SHC	0.019	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.1	0.069	-10000	0	-10000	0	0
STAT5A (dimer)	-0.19	0.21	-10000	0	-0.47	84	84
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.027	0.049	-10000	0	-10000	0	0
LRIG1	0.011	0.018	-10000	0	-0.29	1	1
EREG	-0.13	0.15	-10000	0	-0.29	137	137
BTC	-0.022	0.16	-10000	0	-0.81	12	12
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.037	0.053	-10000	0	-10000	0	0
ERBB4	-0.13	0.11	-10000	0	-10000	0	0
STAT5B	0.013	0	-10000	0	-10000	0	0
YAP1	-0.035	0.023	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.064	0.072	-10000	0	-0.59	1	1
glial cell differentiation	0.1	0.069	-10000	0	-10000	0	0
WWOX	0.013	0	-10000	0	-10000	0	0
cell proliferation	-0.046	0.11	-10000	0	-0.47	3	3

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	-0.037	0.12	-10000	0	-0.45	22	22
HDAC1	0.009	0.003	-10000	0	-10000	0	0
AES	0.012	0.001	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
DTX1	-0.005	0.12	-10000	0	-0.81	6	6
LRP6/FZD1	0.012	0.036	-10000	0	-10000	0	0
TLE1	0.012	0.001	-10000	0	-10000	0	0
AP1	-0.16	0.26	-10000	0	-0.43	113	113
NCSTN	0.013	0	-10000	0	-10000	0	0
ADAM10	0.011	0.018	-10000	0	-0.29	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.05	0.044	-10000	0	-10000	0	0
NICD/RBPSUH	-0.001	0.009	-10000	0	-10000	0	0
WIF1	0.002	0.043	-10000	0	-10000	0	0
NOTCH1	-0.001	0.01	-10000	0	-10000	0	0
PSENEN	0.013	0	-10000	0	-10000	0	0
KREMEN2	-0.024	0.098	-10000	0	-0.29	34	34
DKK1	-0.004	0.065	-10000	0	-0.29	14	14
beta catenin/beta TrCP1	0.083	0.089	0.24	1	-10000	0	1
APH1B	0.01	0.048	-10000	0	-0.81	1	1
APH1A	0.013	0	-10000	0	-10000	0	0
AXIN1	-0.016	0.037	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.016	0.044	-10000	0	-0.34	4	4
PSEN1	0.013	0	-10000	0	-10000	0	0
FOS	-0.11	0.3	-10000	0	-0.81	44	44
JUN	0.013	0	-10000	0	-10000	0	0
MAP3K7	0.011	0.001	-10000	0	-10000	0	0
CTNNB1	0.081	0.097	0.24	72	-10000	0	72
MAPK3	0.013	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.02	0.06	-10000	0	-0.38	3	3
HNF1A	0	0.096	-10000	0	-0.81	4	4
CTBP1	0.012	0.001	-10000	0	-10000	0	0
MYC	0.022	0.039	-10000	0	-10000	0	0
NKD1	-0.22	0.37	-10000	0	-0.81	82	82
FZD1	0.003	0.053	-10000	0	-0.29	9	9
NOTCH1 precursor/Deltex homolog 1	-0.01	0.065	-10000	0	-0.45	6	6
apoptosis	-0.15	0.25	-10000	0	-0.43	113	113
Delta 1/NOTCHprecursor	-0.037	0.12	-10000	0	-0.45	22	22
DLL1	-0.056	0.22	-10000	0	-0.72	27	27
PPARD	0.026	0.009	-10000	0	-10000	0	0
Gamma Secretase	-0.002	0.027	-10000	0	-0.46	1	1
APC	-0.016	0.037	-10000	0	-10000	0	0
DVL1	0.001	0.008	-10000	0	-10000	0	0
CSNK2A1	0.013	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.024	0.057	-10000	0	-0.3	2	2
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.013	0.001	-10000	0	-10000	0	0
NLK	0.012	0.004	-10000	0	-10000	0	0
CCND1	0.021	0.086	-10000	0	-1.4	1	1
WNT1	-0.017	0.088	-10000	0	-0.29	27	27
Axin1/APC/beta catenin	0.069	0.047	-10000	0	-10000	0	0
DKK2	0.007	0.054	-10000	0	-0.46	3	3
NOTCH1 precursor/DVL1	0.002	0.01	-10000	0	-10000	0	0
GSK3B	0.012	0	-10000	0	-10000	0	0
FRAT1	0.012	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.01	0.065	-10000	0	-0.45	6	6
PPP2R5D	0.1	0.16	0.37	82	-10000	0	82
MAPK1	0.013	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.006	0.057	-10000	0	-10000	0	0
RBPJ	0.013	0	-10000	0	-10000	0	0
CREBBP	0.016	0.002	-10000	0	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.017	0.021	-9999	-10000	0	0
VLDLR	0.013	0	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
LRPAP1	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
ITGA3	-0.003	0.068	-9999	-0.29	15	15
RELN/VLDLR/Fyn	-0.079	0.13	-9999	-0.54	15	15
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.006	0.054	-9999	-0.46	4	4
AKT1	-0.021	0.083	-9999	-0.4	1	1
MAP2K7	0.013	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
DAB1	-0.004	0.052	-9999	-0.29	9	9
RELN/LRP8/DAB1	-0.069	0.13	-9999	-0.53	15	15
LRPAP1/LRP8	0.014	0.032	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.072	0.12	-9999	-0.5	15	15
DAB1/alpha3/beta1 Integrin	-0.063	0.1	-9999	-0.45	15	15
long-term memory	-0.16	0.22	-9999	-0.51	79	79
DAB1/LIS1	-0.062	0.1	-9999	-0.46	15	15
DAB1/CRLK/C3G	-0.058	0.1	-9999	-0.45	15	15
PIK3CA	0.013	0	-9999	-10000	0	0
DAB1/NCK2	-0.063	0.11	-9999	-0.46	15	15
ARHGEF2	0.013	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.18	0.35	-9999	-0.8	69	69
CDK5R1	0.009	0.031	-9999	-0.29	3	3
RELN	-0.14	0.21	-9999	-0.36	116	116
PIK3R1	0.013	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.082	0.13	-9999	-0.56	15	15
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.18	0.23	-9999	-0.53	79	79
MAPK8	0.001	0.096	-9999	-0.81	4	4
RELN/VLDLR/DAB1	-0.066	0.13	-9999	-0.51	15	15
ITGB1	0.013	0	-9999	-10000	0	0
MAP1B	-0.05	0.12	-9999	-0.49	15	15
RELN/LRP8	-0.082	0.13	-9999	-0.56	15	15
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.072	0.11	-9999	-0.49	15	15
PI3K	0.019	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.008	0.046	-9999	-10000	0	0
RAP1A	-0.025	0.11	-9999	-0.5	3	3
PAFAH1B1	0.013	0	-9999	-10000	0	0
MAPK8IP1	0.013	0	-9999	-10000	0	0
CRLK/C3G	0.019	0	-9999	-10000	0	0
GRIN2B	0.002	0.035	-9999	-0.29	4	4
NCK2	0.013	0	-9999	-10000	0	0
neuron differentiation	-0.005	0.07	-9999	-0.3	2	2
neuron adhesion	-0.017	0.11	-9999	-0.48	3	3
LRP8	0.005	0.047	-9999	-0.29	7	7
GSK3B	-0.013	0.079	-9999	-0.37	1	1
RELN/VLDLR/DAB1/Fyn	-0.069	0.11	-9999	-0.48	15	15
MAP3K11	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.031	0.088	-9999	-0.34	15	15
CDK5	0.013	0	-9999	-10000	0	0
MAPT	-0.014	0.14	-9999	-0.76	10	10
neuron migration	-0.007	0.11	-9999	-0.42	12	12
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.006	0.07	-9999	-0.3	2	2
RELN/VLDLR	-0.052	0.13	-9999	-0.51	15	15

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.012	0	-9999	-10000	0	0
GNAT1/GTP	0	0.021	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.002	0.019	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.015	0.081	-9999	-0.55	6	6
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0	0.03	-9999	-0.29	3	3
GRK1	0.002	0.018	-9999	-10000	0	0
CNG Channel	-0.14	0.21	-9999	-0.45	87	87
mol:Na +	-0.14	0.2	-9999	-0.45	78	78
mol:ADP	0.002	0.018	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.015	0.079	-9999	-0.57	5	5
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.14	0.2	-9999	-0.47	78	78
CNGB1	-0.001	0.053	-9999	-0.29	9	9
RDH5	-0.016	0.1	-9999	-0.34	24	24
SAG	0.001	0.003	-9999	-10000	0	0
mol:Ca2+	-0.11	0.21	-9999	-0.49	30	30
Na + (4 Units)	-0.13	0.19	-9999	-0.47	30	30
RGS9	-0.01	0.11	-9999	-0.43	15	15
GNB1/GNGT1	-0.014	0.071	-9999	-10000	0	0
GNAT1/GDP	-0.014	0.07	-9999	-0.49	5	5
GUCY2D	-0.032	0.1	-9999	-0.29	40	40
GNGT1	-0.035	0.11	-9999	-0.29	42	42
GUCY2F	0.001	0.003	-9999	-10000	0	0
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.001	0.088	-9999	-0.47	8	8
mol:11-cis-retinal	-0.016	0.1	-9999	-0.34	24	24
mol:cGMP	-0.004	0.059	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
Rhodopsin	-0.009	0.08	-9999	-0.54	3	3
SLC24A1	0.013	0	-9999	-10000	0	0
CNGA1	-0.21	0.37	-9999	-0.81	78	78
Metarhodopsin II	0.003	0.023	-9999	-0.28	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.005	0.063	-9999	-10000	0	0
RGS9BP	0.008	0.052	-9999	-0.81	1	1
Metarhodopsin II/Transducin	-0.002	0.04	-9999	-10000	0	0
GCAP Family/Ca ++	0.009	0.033	-9999	-10000	0	0
PDE6A/B	0.004	0.066	-9999	-0.63	2	2
mol:Pi	-0.015	0.078	-9999	-0.56	5	5
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.008	0.057	-9999	-10000	0	0
PDE6B	0.004	0.075	-9999	-0.5	5	5
PDE6A	0.001	0.05	-9999	-0.29	8	8
PDE6G	-0.008	0.12	-9999	-0.64	9	9
RHO	0.002	0.035	-9999	-0.29	4	4
PDE6	-0.029	0.1	-9999	-0.5	12	12
GUCA1A	-0.004	0.052	-9999	-10000	0	0
GC2/GCAP Family	0.01	0.033	-9999	-10000	0	0
GUCA1C	0.006	0.019	-9999	-0.29	1	1
GUCA1B	0.009	0.031	-9999	-0.29	3	3

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.011	0.007	-10000	0	-10000	0	0
HSPA8	0.01	0.048	-10000	0	-0.8	1	1
SMAD3/SMAD4/ER alpha	-0.033	0.13	-10000	0	-0.56	17	17
AKT1	0.015	0.004	-10000	0	-10000	0	0
GSC	0.016	0.048	-10000	0	-10000	0	0
NKX2-5	-0.014	0.071	-10000	0	-0.29	18	18
muscle cell differentiation	0.003	0.026	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.063	0.043	-10000	0	-10000	0	0
SMAD4	0.018	0.026	-10000	0	-10000	0	0
CBFB	0.013	0	-10000	0	-10000	0	0
SAP18	0.013	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.006	0.022	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	-0.006	0.061	-10000	0	-0.46	5	5
MYC	0.005	0.04	-10000	0	-0.3	5	5
CDKN2B	0.033	0.046	-10000	0	-10000	0	0
AP1	-0.014	0.17	-10000	0	-0.41	44	44
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.062	0.013	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.046	0.028	-10000	0	-10000	0	0
SP3	0.015	0	-10000	0	-10000	0	0
CREB1	0.013	0	-10000	0	-10000	0	0
FOXH1	-0.006	0.079	-10000	0	-0.29	21	21
SMAD3/SMAD4/GR	-0.002	0.02	-10000	0	-10000	0	0
GATA3	-0.63	0.34	-10000	0	-0.81	224	224
SKI/SIN3/HDAC complex/NCoR1	0.046	0.008	-10000	0	-10000	0	0
MEF2C/TIF2	-0.004	0.16	-10000	0	-0.5	20	20
endothelial cell migration	0.058	0.29	1.4	13	-10000	0	13
MAX	0.013	0.011	-10000	0	-10000	0	0
RBBP7	0.013	0.001	-10000	0	-10000	0	0
RBBP4	0.013	0.001	-10000	0	-10000	0	0
RUNX2	0.005	0.047	-10000	0	-10000	0	0
RUNX3	-0.028	0.1	-10000	0	-0.29	38	38
RUNX1	-0.011	0.081	-10000	0	-0.29	22	22
CTBP1	0.013	0	-10000	0	-10000	0	0
NR3C1	0.013	0.011	-10000	0	-10000	0	0
VDR	-0.002	0.11	-10000	0	-0.81	5	5
CDKN1A	0.05	0.055	-10000	0	-10000	0	0
KAT2B	0.012	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.021	0.052	-10000	0	-10000	0	0
DCP1A	0.013	0	-10000	0	-10000	0	0
SKI	0.013	0.001	-10000	0	-10000	0	0
SERPINE1	-0.061	0.3	-10000	0	-1.4	13	13
SMAD3/SMAD4/ATF2	0	0.02	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.027	0.12	-10000	0	-0.57	13	13
SAP30	0.011	0.025	-10000	0	-0.29	1	1
Cbp/p300/PIAS3	0.007	0.017	-10000	0	-10000	0	0
JUN	-0.013	0.16	-10000	0	-0.4	44	44
SMAD3/SMAD4/IRF7	-0.001	0.025	-10000	0	-10000	0	0
TFE3	0.016	0.013	-10000	0	-10000	0	0
COL1A2	0.005	0.07	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.004	0.029	-10000	0	-10000	0	0
DLX1	-0.015	0.084	-10000	0	-10000	0	0
TCF3	0.013	0	-10000	0	-10000	0	0
FOS	-0.11	0.3	-10000	0	-0.8	44	44
SMAD3/SMAD4/Max	-0.002	0.02	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.001	0.007	-10000	0	-10000	0	0
ZBTB17	0.011	0.004	-10000	0	-10000	0	0
LAMC1	0.045	0.038	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0	0.02	-10000	0	-10000	0	0
IRF7	0.013	0.008	-10000	0	-10000	0	0
ESR1	-0.037	0.19	-10000	0	-0.81	17	17
HNF4A	-0.076	0.26	-10000	0	-0.81	31	31
MEF2C	0.031	0.055	-10000	0	-10000	0	0
SMAD2-3/SMAD4	0.021	0.035	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.008	0.014	-10000	0	-10000	0	0
IGHV3OR16-13	-0.004	0.013	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.012	0	-10000	0	-10000	0	0
CREBBP	0.012	0.005	-10000	0	-10000	0	0
SKIL	0.013	0	-10000	0	-10000	0	0
HDAC1	0.013	0.001	-10000	0	-10000	0	0
HDAC2	0.013	0.001	-10000	0	-10000	0	0
SNIP1	0.013	0.002	-10000	0	-10000	0	0
GCN5L2	-0.001	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.043	0.038	-10000	0	-10000	0	0
MSG1/HSC70	0.014	0.043	-10000	0	-0.61	1	1
SMAD2	0.019	0.006	-10000	0	-10000	0	0
SMAD3	0.016	0.026	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.04	0.023	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.014	0.014	-10000	0	-10000	0	0
NCOR1	0.013	0.001	-10000	0	-10000	0	0
NCOA2	-0.059	0.23	-10000	0	-0.81	25	25
NCOA1	0.013	0	-10000	0	-10000	0	0
MYOD/E2A	0.007	0.026	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.069	0.041	-10000	0	-10000	0	0
IFNB1	0.031	0.042	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.039	0.061	-10000	0	-10000	0	0
CITED1	0.009	0.031	-10000	0	-0.29	3	3
SMAD2-3/SMAD4/ARC105	0.046	0.033	-10000	0	-10000	0	0
RBL1	0.013	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.053	0.033	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.03	0.067	-10000	0	-10000	0	0
SMAD7	0.033	0.14	-10000	0	-10000	0	0
MYC/MIZ-1	-0.002	0.028	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.016	0.092	-10000	0	-0.42	13	13
IL10	-0.38	0.23	-10000	0	-0.5	224	224
PIASy/HDAC complex	0.014	0.007	-10000	0	-10000	0	0
PIAS3	0.012	0.003	-10000	0	-10000	0	0
CDK2	0.012	0.003	-10000	0	-10000	0	0
IL5	-0.38	0.22	-10000	0	-0.49	224	224
CDK4	0.012	0.004	-10000	0	-10000	0	0
PIAS4	0.014	0.007	-10000	0	-10000	0	0
ATF3	-0.027	0.17	-10000	0	-0.74	15	15
SMAD3/SMAD4/SP1	0.047	0.042	-10000	0	-10000	0	0
FOXG1	-0.009	0.059	-10000	0	-0.29	12	12
FOXO3	0.025	0.006	-10000	0	-10000	0	0
FOXO1	0.025	0.006	-10000	0	-10000	0	0
FOXO4	0.025	0.006	-10000	0	-10000	0	0
heart looping	0.031	0.055	-10000	0	-10000	0	0
CEBPB	0.004	0.053	-10000	0	-0.29	9	9
SMAD3/SMAD4/DLX1	-0.014	0.051	-10000	0	-10000	0	0
MYOD1	-0.004	0.038	-10000	0	-0.29	5	5
SMAD3/SMAD4/HNF4	-0.061	0.18	-10000	0	-0.57	31	31
SMAD3/SMAD4/GATA3	-0.44	0.23	-10000	0	-0.56	224	224
SnoN/SIN3/HDAC complex/NCoR1	0.012	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.009	0.07	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.057	0.04	-10000	0	-10000	0	0
MED15	0.013	0	-10000	0	-10000	0	0
SP1	0.02	0.013	-10000	0	-10000	0	0
SIN3B	0.013	0.001	-10000	0	-10000	0	0
SIN3A	0.013	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.017	0.061	-10000	0	-10000	0	0
ITGB5	0.059	0.032	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.045	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.025	0.12	-10000	0	-0.56	12	12
AR	-0.024	0.17	-10000	0	-0.81	12	12
negative regulation of cell growth	0.034	0.058	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.005	0.031	-10000	0	-10000	0	0
E2F5	0.013	0	-10000	0	-10000	0	0
E2F4	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.031	0.045	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.052	0.027	-10000	0	-10000	0	0
TFDP1	0.013	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.011	0.17	-10000	0	-0.41	44	44
SMAD3/SMAD4/RUNX2	-0.004	0.03	-10000	0	-10000	0	0
TGIF2	0.013	0	-10000	0	-10000	0	0
TGIF1	0.013	0	-10000	0	-10000	0	0
ATF2	0.013	0	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.016	0.15	-9999	-0.81	10	10
mol:S1P	0.001	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.005	0.089	-9999	-0.28	26	26
GNAO1	-0.057	0.23	-9999	-0.81	24	24
S1P/S1P3/G12/G13	-0.015	0.14	-9999	-0.5	23	23
AKT1	-0.011	0.15	-9999	-0.7	10	10
AKT3	0.014	0.089	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.016	0.15	-9999	-0.81	10	10
GNAI2	0.014	0	-9999	-10000	0	0
GNAI3	0.014	0	-9999	-10000	0	0
GNAI1	0.008	0.068	-9999	-0.81	2	2
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.051	0.22	-9999	-0.81	23	23
S1PR2	0.013	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.022	0.18	-9999	-0.4	41	41
MAPK3	-0.015	0.17	-9999	-0.87	6	6
MAPK1	-0.015	0.17	-9999	-0.87	6	6
JAK2	-0.017	0.17	-9999	-0.8	7	7
CXCR4	-0.024	0.17	-9999	-0.81	7	7
FLT1	0.01	0.068	-9999	-0.81	2	2
RhoA/GDP	0.009	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
SRC	-0.015	0.17	-9999	-0.87	6	6
S1P/S1P3/Gi	-0.023	0.18	-9999	-0.41	41	41
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.016	0.16	-9999	-0.84	6	6
VEGFA	0.012	0.031	-9999	-0.29	3	3
S1P/S1P2/Gi	0.007	0.1	-9999	-0.32	24	24
VEGFR1 homodimer/VEGFA homodimer	0.02	0.058	-9999	-0.62	2	2
RHOA	0.013	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.089	0.2	-9999	-0.4	76	76
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.014	0	-9999	-10000	0	0
G12/G13	0.018	0.012	-9999	-10000	0	0
GNA14	-0.16	0.34	-9999	-0.81	61	61
GNA15	-0.009	0.077	-9999	-0.29	20	20
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.011	0.018	-9999	-0.29	1	1
GNA11	-0.005	0.12	-9999	-0.81	6	6
Rac1/GTP	-0.016	0.16	-9999	-0.84	6	6

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.009	0.12	0.6	10	-10000	0	10
PI3K Class IB/PDE3B	-0.009	0.12	-10000	0	-0.6	10	10
PDE3B	-0.009	0.12	-10000	0	-0.6	10	10

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.022	0.001	-9999	-10000	0	0
SMARCC1	0.011	0.008	-9999	-10000	0	0
REL	0	0.098	-9999	-0.71	5	5
HDAC7	-0.083	0.12	-9999	-0.7	3	3
JUN	0.012	0.003	-9999	-10000	0	0
EP300	0.012	0	-9999	-10000	0	0
KAT2B	0.012	0	-9999	-10000	0	0
KAT5	0.013	0	-9999	-10000	0	0
MAPK14	0.003	0.017	-9999	-10000	0	0
FOXO1	0.012	0	-9999	-10000	0	0
T-DHT/AR	-0.092	0.13	-9999	-0.68	4	4
MAP2K6	0.004	0.008	-9999	-10000	0	0
BRM/BAF57	0.018	0.005	-9999	-10000	0	0
MAP2K4	0.004	0.008	-9999	-10000	0	0
SMARCA2	0.012	0.002	-9999	-10000	0	0
PDE9A	-0.18	0.2	-9999	-0.6	37	37
NCOA2	-0.059	0.23	-9999	-0.81	25	25
CEBPA	-0.018	0.099	-9999	-0.31	27	27
EHMT2	0.012	0.003	-9999	-10000	0	0
cell proliferation	-0.15	0.18	-9999	-0.5	38	38
NR0B1	-0.054	0.12	-9999	-0.29	59	59
EGR1	-0.054	0.22	-9999	-0.81	23	23
RXRs/9cRA	0.018	0.011	-9999	-10000	0	0
AR/RACK1/Src	-0.029	0.076	-9999	-0.57	4	4
AR/GR	-0.007	0.087	-9999	-0.54	4	4
GNB2L1	0.012	0.001	-9999	-10000	0	0
PKN1	0.012	0	-9999	-10000	0	0
RCHY1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-9999	-10000	0	0
MAPK8	-0.006	0.078	-9999	-0.65	4	4
T-DHT/AR/TIF2/CARM1	-0.057	0.18	-9999	-0.6	23	23
SRC	-0.01	0.069	-9999	-0.5	4	4
NR3C1	0.013	0	-9999	-10000	0	0
KLK3	-0.1	0.2	-9999	-0.52	26	26
APPBP2	0.004	0.008	-9999	-10000	0	0
TRIM24	0.012	0.003	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.024	0.085	-9999	-0.6	4	4
TMPRSS2	-0.83	0.58	-9999	-1.2	185	185
RXRG	0.003	0.018	-9999	-10000	0	0
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.012	0	-9999	-10000	0	0
RXRB	0.012	0	-9999	-10000	0	0
CARM1	0.012	0.001	-9999	-10000	0	0
NR2C2	0.007	0.068	-9999	-0.81	2	2
KLK2	-0.042	0.14	-9999	-0.61	9	9
AR	-0.015	0.096	-9999	-0.41	12	12
SENP1	0.012	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
MDM2	0.013	0.004	-9999	-10000	0	0
SRY	0.001	0.004	-9999	-10000	0	0
GATA2	-0.16	0.33	-9999	-0.81	60	60
MYST2	0.013	0	-9999	-10000	0	0
HOXB13	-0.074	0.14	-9999	-0.29	80	80
T-DHT/AR/RACK1/Src	-0.017	0.084	-9999	-0.58	4	4
positive regulation of transcription	-0.16	0.33	-9999	-0.81	60	60
DNAJA1	0.004	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.001	-9999	-10000	0	0
NCOA1	0.019	0.005	-9999	-10000	0	0
SPDEF	-0.011	0.08	-9999	-0.3	21	21
T-DHT/AR/TIF2	-0.013	0.11	-9999	-0.56	6	6
T-DHT/AR/Hsp90	-0.024	0.085	-9999	-0.6	4	4
GSK3B	0.009	0.004	-9999	-10000	0	0
NR2C1	0.013	0.001	-9999	-10000	0	0
mol:T-DHT	-0.019	0.073	-9999	-0.54	4	4
SIRT1	0.012	0	-9999	-10000	0	0
ZMIZ2	0.013	0.004	-9999	-10000	0	0
POU2F1	-0.036	0.049	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.059	0.099	-9999	-0.67	4	4
CREBBP	0.012	0	-9999	-10000	0	0
SMARCE1	0.012	0.002	-9999	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.017	0.12	-9999	-0.43	16	16
NF kappa B1 p50/RelA/I kappa B alpha	0.038	0.11	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin/Src	-0.013	0.07	-9999	-0.61	3	3
AP1	-0.03	0.22	-9999	-0.66	16	16
ILK	0.01	0.12	-9999	-0.46	16	16
bone resorption	0.016	0.14	-9999	-0.69	3	3
PTK2B	0.013	0	-9999	-10000	0	0
PYK2/p130Cas	-0.029	0.1	-9999	-0.42	17	17
ITGAV	0.016	0.004	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.006	0.096	-9999	-0.62	5	5
alphaV/beta3 Integrin/Osteopontin	-0.037	0.12	-9999	-0.52	16	16
MAP3K1	0.009	0.12	-9999	-0.47	16	16
JUN	0.013	0.001	-9999	-10000	0	0
MAPK3	0.02	0.12	-9999	-0.43	16	16
MAPK1	0.02	0.12	-9999	-0.43	16	16
Rac1/GDP	0.009	0	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	0.012	0.13	-9999	-0.46	19	19
ITGB3	-0.027	0.17	-9999	-0.64	19	19
NFKBIA	0.028	0.12	-9999	-0.41	16	16
FOS	-0.11	0.3	-9999	-0.81	44	44
CD44	-0.008	0.075	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
PLAU	0.011	0.22	-9999	-1.2	7	7
NF kappa B1 p50/RelA	-0.029	0.09	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.031	0.13	-9999	-0.61	13	13
mol:GDP	0	0	-9999	-10000	0	0
SYK	0.006	0.13	-9999	-0.47	17	17
VAV3	0.013	0.12	-9999	-0.44	18	18
MAP3K14	0.011	0.12	-9999	-0.47	16	16
ROCK2	-0.002	0.11	-9999	-0.81	5	5
SPP1	-0.003	0.099	-9999	-0.41	13	13
RAC1	0.013	0	-9999	-10000	0	0
Rac1/GTP	0.017	0.11	-9999	-0.4	18	18
MMP2	-0.016	0.19	-9999	-0.61	10	10

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.013	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.099	0.18	-9999	-0.42	65	65
Syndecan-3/Neurocan	-0.014	0.037	-9999	-10000	0	0
POMC	0	0.098	-9999	-0.71	5	5
EGFR	0.013	0	-9999	-10000	0	0
Syndecan-3/EGFR	-0.002	0.013	-9999	-10000	0	0
AGRP	0.008	0.019	-9999	-0.29	1	1
NCSTN	0.013	0	-9999	-10000	0	0
PSENEN	0.013	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.01	0.048	-9999	-0.81	1	1
APH1A	0.013	0	-9999	-10000	0	0
NCAN	-0.024	0.095	-9999	-0.29	32	32
long-term memory	-0.001	0.011	-9999	-10000	0	0
Syndecan-3/IL8	-0.03	0.056	-9999	-0.46	1	1
PSEN1	0.013	0	-9999	-10000	0	0
Src/Cortactin	0.018	0.012	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
limb bud formation	-0.002	0.014	-9999	-10000	0	0
MC4R	0	0.03	-9999	-0.29	3	3
SRC	0.011	0.018	-9999	-0.29	1	1
PTN	-0.18	0.34	-9999	-0.76	73	73
FGFR/FGF/Syndecan-3	-0.002	0.014	-9999	-10000	0	0
neuron projection morphogenesis	-0.1	0.17	-9999	-0.42	65	65
Syndecan-3/AgRP	-0.002	0.014	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.003	0.017	-9999	-10000	0	0
Fyn/Cortactin	0.019	0	-9999	-10000	0	0
SDC3	-0.002	0.014	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.03	0.055	-9999	-0.45	1	1
IL8	-0.062	0.14	-9999	-0.3	69	69
Syndecan-3/Fyn/Cortactin	-0.001	0.011	-9999	-10000	0	0
Syndecan-3/CASK	-0.002	0.013	-9999	-10000	0	0
alpha-MSH/MC4R	0	0.078	-9999	-0.63	4	4
Gamma Secretase	-0.002	0.027	-9999	-0.46	1	1

×

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	-0.042	0.14	-10000	0	-0.55	21	21
cell-cell adhesion	0.025	0.08	0.47	1	-10000	0	1
Ephrin B/EPHB2/RasGAP	-0.025	0.087	-10000	0	-0.46	10	10
ITSN1	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.013	0	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.15	0.24	-10000	0	-0.55	81	81
Ephrin B1/EPHB1	-0.01	0.061	-10000	0	-0.55	3	3
HRAS/GDP	-0.022	0.078	-10000	0	-0.43	7	7
Ephrin B/EPHB1/GRB7	-0.032	0.1	-10000	0	-0.47	13	13
Endophilin/SYNJ1	0.007	0.091	-10000	0	-0.43	10	10
KRAS	0.013	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.032	0.1	-10000	0	-0.47	13	13
endothelial cell migration	0	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
GRB7	0.013	0	-10000	0	-10000	0	0
PAK1	0.014	0.093	-10000	0	-0.43	10	10
HRAS	0.013	0	-10000	0	-10000	0	0
RRAS	0.007	0.093	-10000	0	-0.44	10	10
DNM1	-0.085	0.15	-10000	0	-0.3	91	91
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0	0.11	-10000	0	-0.45	13	13
lamellipodium assembly	-0.025	0.08	-10000	0	-0.47	1	1
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.015	0.07	-10000	0	-0.33	4	4
PIK3R1	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.036	-10000	0	-0.29	4	4
EPHB3	-0.22	0.37	-10000	0	-0.81	81	81
EPHB1	-0.006	0.098	-10000	0	-0.42	12	12
EPHB4	0.013	0	-10000	0	-10000	0	0
mol:GDP	0.055	0.12	-10000	0	-0.44	7	7
Ephrin B/EPHB2	-0.026	0.089	-10000	0	-0.47	10	10
Ephrin B/EPHB3	-0.16	0.23	-10000	0	-0.49	88	88
JNK cascade	0.026	0.058	-10000	0	-0.45	3	3
Ephrin B/EPHB1	-0.033	0.1	-10000	0	-0.48	13	13
RAP1/GDP	0.03	0.11	-10000	0	-0.45	1	1
EFNB2	0.013	0	-10000	0	-10000	0	0
EFNB3	-0.039	0.17	-10000	0	-0.45	32	32
EFNB1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.012	0.062	-10000	0	-0.44	4	4
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.027	0.088	-10000	0	-0.52	1	1
Rap1/GTP	-0.025	0.08	-10000	0	-0.48	1	1
axon guidance	-0.042	0.14	-10000	0	-0.54	21	21
MAPK3	0.028	0.064	-10000	0	-10000	0	0
MAPK1	0.028	0.064	-10000	0	-10000	0	0
Rac1/GDP	0.06	0.12	-10000	0	-0.41	7	7
actin cytoskeleton reorganization	-0.016	0.059	-10000	0	-0.38	1	1
CDC42/GDP	0.06	0.12	-10000	0	-0.41	7	7
PI3K	0	0	-10000	0	-10000	0	0
EFNA5	-0.048	0.21	-10000	0	-0.79	22	22
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.014	0.071	-10000	0	-0.33	10	10
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	-0.024	0.078	-10000	0	-0.46	1	1
PTK2	0.003	0.014	-10000	0	-10000	0	0
MAP4K4	0.026	0.059	-10000	0	-0.46	3	3
SRC	0.011	0.018	-10000	0	-0.29	1	1
KALRN	0.013	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0.019	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.039	0.084	-10000	0	-10000	0	0
MAP2K1	0.021	0.067	-10000	0	-0.33	1	1
WASL	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.02	0.062	-10000	0	-0.49	3	3
cell migration	0.038	0.081	-10000	0	-0.36	2	2
NRAS	0.013	0	-10000	0	-10000	0	0
SYNJ1	0.007	0.093	-10000	0	-0.44	10	10
PXN	0.013	0	-10000	0	-10000	0	0
TF	0.003	0.1	-10000	0	-0.41	13	13
HRAS/GTP	-0.028	0.086	-10000	0	-0.4	13	13
Ephrin B1/EPHB1-2	0.012	0.062	-10000	0	-0.5	3	3
cell adhesion mediated by integrin	0.072	0.12	0.43	17	-10000	0	17
RAC1	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.03	0.093	-10000	0	-0.43	13	13
RAC1-CDC42/GTP	-0.13	0.19	-10000	0	-0.56	15	15
RASA1	0.013	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.03	0.11	-10000	0	-0.45	1	1
ruffle organization	0.024	0.097	-10000	0	-0.48	1	1
NCK1	0.013	0	-10000	0	-10000	0	0
receptor internalization	-0.029	0.11	-10000	0	-0.42	11	11
Ephrin B/EPHB2/KALRN	-0.025	0.087	-10000	0	-0.46	10	10
ROCK1	-0.12	0.23	-10000	0	-0.5	81	81
RAS family/GDP	-0.016	0.059	-10000	0	-0.39	1	1
Rac1/GTP	-0.027	0.085	-10000	0	-0.5	1	1
Ephrin B/EPHB1/Src/Paxillin	0.008	0.081	-10000	0	-0.33	13	13

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.19	0.14	-9999	-0.5	21	21
RAD9A	0.011	0.018	-9999	-0.29	1	1
AP1	-0.08	0.23	-9999	-0.62	44	44
IFNAR2	0.012	0.005	-9999	-10000	0	0
AKT1	-0.002	0.073	-9999	-0.31	2	2
ER alpha/Oestrogen	-0.029	0.15	-9999	-0.63	17	17
NFX1/SIN3/HDAC complex	0.038	0.017	-9999	-10000	0	0
EGF	-0.73	0.25	-9999	-0.81	260	260
SMG5	0.013	0	-9999	-10000	0	0
SMG6	0.013	0	-9999	-10000	0	0
SP3/HDAC2	0.018	0.007	-9999	-10000	0	0
TERT/c-Abl	-0.18	0.13	-9999	-0.47	19	19
SAP18	0.012	0.001	-9999	-10000	0	0
MRN complex	-0.002	0.032	-9999	-0.54	1	1
WT1	-0.45	0.4	-9999	-0.81	162	162
WRN	0.013	0	-9999	-10000	0	0
SP1	0.012	0.005	-9999	-10000	0	0
SP3	0.012	0.003	-9999	-10000	0	0
TERF2IP	0.013	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.15	0.12	-9999	-0.45	6	6
Mad/Max	0.017	0.007	-9999	-10000	0	0
TERT	-0.2	0.14	-9999	-0.51	19	19
CCND1	-0.18	0.14	-9999	-1.2	1	1
MAX	0.012	0.002	-9999	-10000	0	0
RBBP7	0.012	0.001	-9999	-10000	0	0
RBBP4	0.012	0.001	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.013	0	-9999	-10000	0	0
SIN3A	0.012	0.001	-9999	-10000	0	0
Telomerase/911	0.003	0.021	-9999	-10000	0	0
CDKN1B	0.021	0.043	-9999	-10000	0	0
RAD1	0.013	0	-9999	-10000	0	0
XRCC5	0.013	0	-9999	-10000	0	0
XRCC6	0.013	0	-9999	-10000	0	0
SAP30	0.01	0.025	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.012	0.002	-9999	-10000	0	0
JUN	0.012	0.002	-9999	-10000	0	0
E6	0	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP	0.009	0.004	-9999	-10000	0	0
FOS	-0.11	0.3	-9999	-0.81	44	44
IFN-gamma/IRF1	-0.006	0.047	-9999	-10000	0	0
PARP2	0.013	0	-9999	-10000	0	0
BLM	-0.009	0.077	-9999	-0.29	20	20
Telomerase	-0.026	0.039	-9999	-10000	0	0
IRF1	0.017	0.002	-9999	-10000	0	0
ESR1	-0.036	0.19	-9999	-0.81	17	17
KU/TER	0.019	0	-9999	-10000	0	0
ATM/TRF2	0.02	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.043	0.018	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.043	0.018	-9999	-10000	0	0
HDAC1	0.012	0.001	-9999	-10000	0	0
HDAC2	0.012	0.005	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.021	0.018	-9999	-10000	0	0
ABL1	0.013	0	-9999	-10000	0	0
MXD1	0.012	0.002	-9999	-10000	0	0
MRE11A	0.013	0	-9999	-10000	0	0
HUS1	0.013	0	-9999	-10000	0	0
RPS6KB1	0.013	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.14	0.12	-9999	-0.55	2	2
NR2F2	0.013	0.004	-9999	-10000	0	0
MAPK3	0.013	0.014	-9999	-10000	0	0
MAPK1	0.013	0.014	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.011	0.025	-9999	-0.29	2	2
NFKB1	0.013	0	-9999	-10000	0	0
HNRNPC	0.013	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.013	0	-9999	-10000	0	0
EGFR	0.012	0.001	-9999	-10000	0	0
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.56	0.19	-9999	-0.62	260	260
MYC	0.006	0.04	-9999	-0.29	5	5
IL2	0.003	0.019	-9999	-10000	0	0
KU	0.019	0	-9999	-10000	0	0
RAD50	0.01	0.048	-9999	-0.81	1	1
HSP90AA1	0.013	0	-9999	-10000	0	0
TGFB1	0.011	0.025	-9999	-0.29	2	2
TRF2/BLM	-0.012	0.043	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.17	0.13	-9999	-0.49	10	10
SP1/HDAC2	0.019	0.008	-9999	-10000	0	0
PINX1	0.013	0	-9999	-10000	0	0
Telomerase/EST1A	-0.15	0.12	-9999	-0.46	4	4
Smad3/Myc	0.022	0.026	-9999	-10000	0	0
911 complex	-0.001	0.009	-9999	-10000	0	0
IFNG	-0.008	0.076	-9999	-0.28	20	20
Telomerase/PinX1	-0.15	0.12	-9999	-0.45	7	7
Telomerase/AKT1/mTOR/p70S6K	-0.021	0.043	-9999	-10000	0	0
SIN3B	0.012	0.001	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
Telomerase/EST1B	-0.15	0.12	-9999	-0.46	4	4
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	-0.002	0.026	-9999	-0.45	1	1
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.15	0.12	-9999	-0.46	4	4
E2F1	-0.072	0.14	-9999	-0.3	1	1
ZNFX1	0.012	0.001	-9999	-10000	0	0
PIF1	-0.018	0.091	-9999	-0.29	29	29
NCL	0.013	0	-9999	-10000	0	0
DKC1	0.013	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.079	0.26	-9999	-0.77	34	34
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0.025	-9999	-0.29	2	2
TCEB1	0.013	0	-9999	-10000	0	0
HIF1A/p53	0.029	0.009	-9999	-10000	0	0
HIF1A	0.022	0.009	-9999	-10000	0	0
COPS5	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.009	-9999	-10000	0	0
FIH (dimer)	0.012	0	-9999	-10000	0	0
CDKN2A	-0.23	0.12	-9999	-0.29	228	228
ARNT/IPAS	-0.052	0.2	-9999	-0.62	31	31
HIF1AN	0.013	0	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
HIF1A/ARNT	0.029	0.009	-9999	-10000	0	0
CUL2	0.013	0	-9999	-10000	0	0
OS9	0.013	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.001	0.012	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.029	0.009	-9999	-10000	0	0
PHD1-3/OS9	0.027	0.029	-9999	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	0	0.007	-9999	-10000	0	0
VHL	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
HIF1A/JAB1	0.029	0.009	-9999	-10000	0	0
EGLN3	0.001	0.058	-9999	-0.29	11	11
EGLN2	0.013	0	-9999	-10000	0	0
EGLN1	0.013	0	-9999	-10000	0	0
TP53	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.036	0.008	-9999	-10000	0	0
ARNT	0.013	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.013	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.074	0.055	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.011	0.045	-9999	-10000	0	0
EPHB2	0.008	0.036	-9999	-0.29	4	4
Syndecan-2/TACI	0.006	0.037	-9999	-10000	0	0
LAMA1	-0.025	0.15	-9999	-0.81	8	8
Syndecan-2/alpha2 ITGB1	-0.012	0.08	-9999	-0.46	3	3
HRAS	0.013	0	-9999	-10000	0	0
Syndecan-2/CASK	0	0.006	-9999	-10000	0	0
ITGA5	0.013	0	-9999	-10000	0	0
BAX	0.029	0.065	-9999	-0.48	4	4
EPB41	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0	0.005	-9999	-10000	0	0
LAMA3	-0.079	0.14	-9999	-0.29	87	87
EZR	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.007	0.04	-9999	-0.29	5	5
Syndecan-2/MMP2	0.018	0.04	-9999	-0.54	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.012	0.065	-9999	-0.62	3	3
dendrite morphogenesis	0.02	0.021	-9999	-10000	0	0
Syndecan-2/GM-CSF	0.008	0.023	-9999	-10000	0	0
determination of left/right symmetry	0.018	0.009	-9999	-10000	0	0
Syndecan-2/PKC delta	0.023	0.007	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
MAPK3	0.024	0.019	-9999	-10000	0	0
MAPK1	0.024	0.019	-9999	-10000	0	0
Syndecan-2/RACK1	0.028	0.006	-9999	-10000	0	0
NF1	0.013	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.018	0.009	-9999	-10000	0	0
ITGA2	0.004	0.084	-9999	-0.81	3	3
MAPK8	0.023	0.068	-9999	-0.53	4	4
Syndecan-2/alpha2/beta1 Integrin	0.01	0.099	-9999	-0.46	11	11
Syndecan-2/Kininogen	-0.32	0.27	-9999	-0.54	169	169
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.034	0.01	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	0	0.005	-9999	-10000	0	0
extracellular matrix organization	0.022	0.016	-9999	-10000	0	0
actin cytoskeleton reorganization	0.01	0.045	-9999	-10000	0	0
Syndecan-2/Caveolin-2/Ras	0.027	0.021	-9999	-10000	0	0
Syndecan-2/Laminin alpha3	-0.028	0.078	-9999	-10000	0	0
Syndecan-2/RasGAP	0	0.005	-9999	-10000	0	0
alpha5/beta1 Integrin	0.019	0	-9999	-10000	0	0
PRKCD	0.013	0	-9999	-10000	0	0
Syndecan-2 dimer	0.021	0.021	-9999	-10000	0	0
GO:0007205	0.003	0.006	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.04	0.01	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
TNFRSF13B	-0.007	0.065	-9999	-0.29	14	14
RASA1	0.013	0	-9999	-10000	0	0
alpha2/beta1 Integrin	0.012	0.065	-9999	-0.62	3	3
Syndecan-2/Synbindin	0.023	0.007	-9999	-10000	0	0
TGFB1	0.01	0.025	-9999	-0.29	2	2
CASP3	0.03	0.011	-9999	-10000	0	0
FN1	-0.01	0.079	-9999	-0.29	21	21
Syndecan-2/IL8	-0.019	0.079	-9999	-0.54	1	1
SDC2	0.018	0.009	-9999	-10000	0	0
KNG1	-0.48	0.4	-9999	-0.81	169	169
Syndecan-2/Neurofibromin	0.023	0.007	-9999	-10000	0	0
TRAPPC4	0.013	0	-9999	-10000	0	0
CSF2	0.001	0.035	-9999	-0.29	4	4
Syndecan-2/TGFB1	0.022	0.016	-9999	-10000	0	0
Syndecan-2/Syntenin/PI-4-5-P2	0	0.005	-9999	-10000	0	0
Syndecan-2/Ezrin	0.029	0.007	-9999	-10000	0	0
PRKACA	0.03	0.007	-9999	-10000	0	0
angiogenesis	-0.019	0.079	-9999	-0.54	1	1
MMP2	0.004	0.062	-9999	-0.81	1	1
IL8	-0.062	0.14	-9999	-0.3	69	69
calcineurin-NFAT signaling pathway	0.006	0.037	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.001	0.024	-9999	-10000	0	0
VDR	-0.002	0.11	-9999	-0.81	5	5
FAM120B	0.013	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.047	0.042	-9999	-10000	0	0
RXRs/LXRs/DNA/Oxysterols	0.052	0.06	-9999	-0.38	3	3
MED1	0.013	0	-9999	-10000	0	0
mol:9cRA	0.005	0.009	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.022	0.069	-9999	-10000	0	0
RXRs/NUR77	-0.18	0.26	-9999	-0.49	122	122
RXRs/PPAR	0.037	0.014	-9999	-10000	0	0
NCOR2	0.013	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.083	-9999	-0.63	5	5
RARs/VDR/DNA/Vit D3	-0.008	0.061	-9999	-0.47	5	5
RARA	0.013	0	-9999	-10000	0	0
NCOA1	0.013	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.002	0.11	-9999	-0.81	5	5
RARs/RARs/DNA/9cRA	0.024	0.011	-9999	-10000	0	0
RARG	0.011	0.018	-9999	-10000	0	0
RPS6KB1	0.002	0.016	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.022	0.069	-9999	-10000	0	0
THRA	0.013	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.083	-9999	-0.63	5	5
RXRs/PPAR/9cRA/PGJ2/DNA	0.034	0.026	-9999	-10000	0	0
NR1H4	0	0.098	-9999	-0.71	5	5
RXRs/LXRs/DNA	0.055	0.031	-9999	-10000	0	0
NR1H2	0.018	0.006	-9999	-10000	0	0
NR1H3	0.018	0.007	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.027	0.069	-9999	-0.48	5	5
NR4A1	-0.34	0.41	-9999	-0.81	122	122
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.027	0.047	-9999	-0.34	4	4
RXRG	0.008	0.02	-9999	-10000	0	0
RXR alpha/CCPG	0.022	0.006	-9999	-10000	0	0
RXRA	0.017	0.006	-9999	-10000	0	0
RXRB	0.018	0.007	-9999	-10000	0	0
THRB	-0.019	0.16	-9999	-0.81	11	11
PPARG	0.011	0.018	-9999	-10000	0	0
PPARD	0.013	0	-9999	-10000	0	0
TNF	0.042	0.14	-9999	-1.2	3	3
mol:Oxysterols	0.005	0.008	-9999	-10000	0	0
cholesterol transport	0.052	0.059	-9999	-0.38	3	3
PPARA	0.013	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.013	0	-9999	-10000	0	0
RXRs/NUR77/BCL2	-0.12	0.18	-9999	-0.34	122	122
SREBF1	0.056	0.057	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	0.035	0.026	-9999	-10000	0	0
ABCA1	0.057	0.055	-9999	-10000	0	0
RARs/THRs	-0.018	0.088	-9999	-0.46	11	11
RXRs/FXR	0.031	0.065	-9999	-0.49	4	4
BCL2	0.013	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.01	0.17	-9999	-0.57	24	24
KLHL20	-0.014	0.048	-9999	-0.35	1	1
CYFIP2	0.01	0.048	-9999	-0.81	1	1
Rac1/GDP	0.025	0.11	-9999	-0.34	24	24
ENAH	-0.01	0.17	-9999	-0.57	24	24
AP1M1	0.013	0	-9999	-10000	0	0
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	-0.024	0.079	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.01	0.033	-9999	-0.22	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.011	0.14	-9999	-0.49	24	24
RAPGEF1	0.007	0.15	-9999	-0.48	24	24
CTNND1	0.013	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.049	0.16	-9999	-0.59	24	24
CRK	-0.002	0.16	-9999	-0.53	24	24
E-cadherin/gamma catenin/alpha catenin	-0.045	0.15	-9999	-0.54	24	24
alphaE/beta7 Integrin	0.019	0	-9999	-10000	0	0
IQGAP1	0.013	0	-9999	-10000	0	0
NCKAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.024	0.001	-9999	-10000	0	0
DLG1	-0.01	0.17	-9999	-0.57	24	24
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.017	0.057	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.023	0.016	-9999	-10000	0	0
PI3K	-0.022	0.073	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.035	0.18	-9999	-0.62	24	24
TIAM1	0.013	0	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	-0.039	0.13	-9999	-0.47	24	24
AKT1	-0.012	0.041	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	-0.056	0.23	-9999	-0.81	24	24
RhoA/GDP	0.024	0.11	-9999	-0.34	24	24
actin cytoskeleton organization	0.03	0.048	-9999	-0.24	1	1
CDC42/GDP	0.024	0.11	-9999	-0.36	1	1
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.006	0.1	-9999	-0.34	24	24
ITGB7	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.011	0.14	-9999	-0.49	24	24
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.019	0.14	-9999	-0.47	24	24
mol:GDP	0.017	0.13	-9999	-0.41	24	24
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.013	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	-0.029	0.097	-9999	-0.35	24	24
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.019	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.025	0.036	-9999	-0.29	1	1
NME1	0.009	0.031	-9999	-0.29	3	3
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.01	0.17	-9999	-0.57	24	24
regulation of cell-cell adhesion	-0.021	0.069	-9999	-10000	0	0
WASF2	-0.005	0.017	-9999	-10000	0	0
Rap1/GTP	-0.027	0.091	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.038	0.13	-9999	-0.46	24	24
CCND1	0.028	0.043	-9999	-0.38	1	1
VAV2	0.004	0.15	-9999	-0.5	24	24
RAP1/GDP	0.021	0.11	-9999	-10000	0	0
adherens junction assembly	-0.009	0.16	-9999	-0.55	24	24
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
PIP5K1C	0.013	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.004	0.13	-9999	-0.44	24	24
E-cadherin/beta catenin	-0.041	0.14	-9999	-0.5	24	24
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.01	0.17	-9999	-0.57	24	24
PIK3CA	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.023	0.079	-9999	-0.65	1	1
E-cadherin/beta catenin/alpha catenin	-0.045	0.15	-9999	-0.54	24	24
ITGAE	0.013	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.05	0.17	-9999	-0.61	24	24

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.031	0.056	-9999	-10000	0	0
adherens junction organization	0.007	0.1	-9999	-0.31	24	24
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.036	0.055	-9999	-10000	0	0
FMN1	-0.014	0.15	-9999	-0.47	17	17
mol:IP3	0.023	0.057	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.007	0.098	-9999	-0.32	24	24
CTNNB1	0.013	0.004	-9999	-10000	0	0
AKT1	0.027	0.066	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.037	0.16	-9999	-0.56	24	24
CTNND1	0.013	0.001	-9999	-10000	0	0
mol:PI-4-5-P2	0.014	0.092	-9999	-10000	0	0
VASP	0.014	0.094	-9999	-10000	0	0
ZYX	0.014	0.094	-9999	-10000	0	0
JUB	0.014	0.094	-9999	-10000	0	0
EGFR(dimer)	0.014	0.094	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin	-0.043	0.14	-9999	-0.52	24	24
mol:PI-3-4-5-P3	-0.017	0.057	-9999	-10000	0	0
PIK3CA	0.013	0.001	-9999	-10000	0	0
PI3K	0.02	0.069	-9999	-10000	0	0
FYN	-0.25	0.17	-9999	-0.49	15	15
mol:Ca2+	0.023	0.056	-9999	-10000	0	0
JUP	0.013	0.004	-9999	-10000	0	0
PIK3R1	0.013	0.001	-9999	-10000	0	0
mol:DAG	0.023	0.057	-9999	-10000	0	0
CDH1	-0.056	0.23	-9999	-0.81	24	24
RhoA/GDP	0.036	0.055	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.014	0.092	-9999	-10000	0	0
SRC	0.011	0.018	-9999	-0.29	1	1
RAC1	0.013	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
EGFR	0.013	0	-9999	-10000	0	0
CASR	-0.31	0.2	-9999	-0.42	212	212
RhoA/GTP	-0.012	0.04	-9999	-10000	0	0
AKT2	0.027	0.066	-9999	-10000	0	0
actin cable formation	-0.007	0.14	-9999	-0.45	17	17
apoptosis	-0.025	0.064	-9999	-10000	0	0
CTNNA1	0.013	0.001	-9999	-10000	0	0
mol:GDP	0.03	0.058	-9999	-10000	0	0
PIP5K1A	0.014	0.094	-9999	-10000	0	0
PLCG1	0.023	0.058	-9999	-10000	0	0
Rac1/GTP	-0.022	0.074	-9999	-10000	0	0
homophilic cell adhesion	0.001	0.001	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.011	0.081	-9999	-0.29	22	22
PLK4	0.01	0.025	-9999	-10000	0	0
regulation of centriole replication	0.004	0.058	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.006	0.022	-9999	-10000	0	0
CaM/Ca2+	0.009	0	-9999	-10000	0	0
AKT1	0.013	0	-9999	-10000	0	0
AKT2	0.013	0	-9999	-10000	0	0
STXBP4	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.068	0.066	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
YWHAQ	0.013	0	-9999	-10000	0	0
TBC1D4	0.022	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
SNARE/Synip	0	0	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
ASIP	-0.11	0.15	-9999	-0.29	113	113
PRKCI	0.013	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0.009	0	-9999	-10000	0	0
RHOQ	0.013	0	-9999	-10000	0	0
GYS1	0.03	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
TRIP10	0.013	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	0.003	0.052	-9999	-10000	0	0
VAMP2	0.013	0	-9999	-10000	0	0
SLC2A4	0.07	0.069	-9999	-10000	0	0
STX4	0.013	0	-9999	-10000	0	0
GSK3B	0.025	0	-9999	-10000	0	0
SFN	-0.14	0.18	-9999	-0.31	135	135
LNPEP	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.015	0.036	-10000	0	-10000	0	0
MAP4K4	0.034	0.039	-10000	0	-10000	0	0
BAG4	0.013	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.099	0.036	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.009	0.077	-10000	0	-0.29	20	20
BAX	-0.045	0.019	-10000	0	-0.15	2	2
RIPK1	0.013	0	-10000	0	-10000	0	0
AKT1	0.037	0.007	-10000	0	-10000	0	0
BAD	-0.1	0.036	-10000	0	-10000	0	0
SMPD1	0.021	0.033	-10000	0	-0.24	3	3
RB1	-0.1	0.036	-10000	0	-10000	0	0
FADD/Caspase 8	0.044	0.037	-10000	0	-10000	0	0
MAP2K4	-0.088	0.034	-10000	0	-10000	0	0
NSMAF	0.013	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.088	0.035	-10000	0	-0.23	1	1
EGF	-0.73	0.25	-10000	0	-0.81	260	260
mol:ceramide	-0.11	0.038	-10000	0	-10000	0	0
MADD	0.013	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.015	0.036	-10000	0	-10000	0	0
ASAH1	0.013	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.099	0.036	-10000	0	-10000	0	0
cell proliferation	-0.064	0.063	-10000	0	-0.44	6	6
BID	-0.006	0.03	-10000	0	-10000	0	0
MAP3K1	-0.1	0.036	-10000	0	-10000	0	0
EIF2A	-0.077	0.033	-10000	0	-10000	0	0
TRADD	0.013	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
MAPK3	-0.073	0.033	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.073	0.033	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.1	0.038	-10000	0	-0.25	1	1
FADD	0.034	0.039	-10000	0	-10000	0	0
KSR1	-0.1	0.037	-10000	0	-0.25	1	1
MAPK8	-0.085	0.048	-10000	0	-0.37	4	4
PRKRA	-0.1	0.036	-10000	0	-10000	0	0
PDGFA	0.003	0.053	-10000	0	-0.29	9	9
TRAF2	0.013	0	-10000	0	-10000	0	0
IGF1	-0.005	0.12	-10000	0	-0.81	6	6
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.11	0.038	-10000	0	-10000	0	0
CTSD	0.011	0.018	-10000	0	-0.29	1	1
regulation of nitric oxide biosynthetic process	0.019	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.067	0.068	-10000	0	-0.48	6	6
PRKCD	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.015	0.036	-10000	0	-10000	0	0
RelA/NF kappa B1	0.019	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.013	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.028	0.042	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.062	-10000	0	-0.54	3	3
mol:Sphingosine-1-phosphate	0.015	0.036	-10000	0	-10000	0	0
MAP2K1	-0.077	0.034	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
CYCS	-0.066	0.025	-10000	0	-10000	0	0
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
NFKB1	0.013	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.019	0	-10000	0	-10000	0	0
EIF2AK2	-0.088	0.034	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.013	0.062	-10000	0	-0.54	3	3
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.035	0.025	-10000	0	-10000	0	0
MAP2K2	-0.077	0.034	-10000	0	-10000	0	0
SMPD3	0.023	0.035	-10000	0	-0.24	3	3
TNF	-0.011	0.1	-10000	0	-0.38	17	17
PKC zeta/PAR4	0.019	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.25	0.089	0.28	260	-10000	0	260
NF kappa B1/RelA/I kappa B alpha	0	0	-10000	0	-10000	0	0
AIFM1	-0.066	0.025	-10000	0	-10000	0	0
BCL2	0.013	0	-10000	0	-10000	0	0

×

BCR signaling pathway

Figure S68. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S68. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.013	0.076	-10000	0	-0.36	5	5
IKBKB	0.002	0.057	-10000	0	-0.26	1	1
AKT1	0.007	0.06	-10000	0	-0.24	2	2
IKBKG	0.003	0.06	-10000	0	-0.28	1	1
CALM1	-0.016	0.11	-10000	0	-0.48	9	9
PIK3CA	0.012	0	-10000	0	-10000	0	0
MAP3K1	0.005	0.094	-10000	0	-0.5	4	4
MAP3K7	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	-0.024	0.12	0.24	8	-0.52	9	17
DOK1	0.009	0.031	-10000	0	-0.29	3	3
AP-1	-0.013	0.092	0.19	5	-0.25	12	17
LYN	0.012	0	-10000	0	-10000	0	0
BLNK	-0.016	0.15	-10000	0	-0.81	10	10
SHC1	0.013	0	-10000	0	-10000	0	0
BCR complex	-0.018	0.11	-10000	0	-0.58	6	6
CD22	-0.041	0.096	-10000	0	-0.52	7	7
CAMK2G	-0.008	0.1	-10000	0	-0.49	7	7
CSNK2A1	0.013	0	-10000	0	-10000	0	0
INPP5D	0.002	0.056	-10000	0	-0.29	10	10
SHC/GRB2/SOS1	-0.031	0.098	-10000	0	-0.8	1	1
GO:0007205	-0.024	0.12	0.24	8	-0.53	9	17
SYK	0.01	0.048	-10000	0	-0.81	1	1
ELK1	-0.016	0.11	-10000	0	-0.49	9	9
NFATC1	0	0.086	-10000	0	-0.45	5	5
B-cell antigen/BCR complex	-0.018	0.11	-10000	0	-0.58	6	6
PAG1/CSK	0.019	0	-10000	0	-10000	0	0
NFKBIB	0.009	0.024	0.085	7	-10000	0	7
HRAS	-0.007	0.11	-10000	0	-0.48	9	9
NFKBIA	0.01	0.023	0.085	7	-10000	0	7
NF-kappa-B/RelA/I kappa B beta	0.014	0.021	-10000	0	-10000	0	0
RasGAP/Csk	-0.056	0.09	-10000	0	-0.46	6	6
mol:GDP	-0.023	0.11	0.23	8	-0.51	9	17
PTEN	0.013	0	-10000	0	-10000	0	0
CD79B	0.003	0.085	-10000	0	-0.68	4	4
NF-kappa-B/RelA/I kappa B alpha	0.014	0.021	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.006	0.11	-10000	0	-0.55	5	5
PIK3R1	0.012	0	-10000	0	-10000	0	0
mol:IP3	-0.025	0.12	0.24	8	-0.54	9	17
CSK	0.013	0	-10000	0	-10000	0	0
FOS	-0.075	0.19	-10000	0	-0.47	47	47
CHUK	0.003	0.06	-10000	0	-0.28	1	1
IBTK	0.013	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.051	0.09	-10000	0	-0.48	6	6
PTPN6	-0.034	0.091	-10000	0	-0.58	4	4
RELA	0.013	0	-10000	0	-10000	0	0
BCL2A1	-0.004	0.031	-10000	0	-10000	0	0
VAV2	-0.036	0.097	-10000	0	-0.58	5	5
ubiquitin-dependent protein catabolic process	0.014	0.023	0.088	7	-10000	0	7
BTK	-0.033	0.064	-10000	0	-10000	0	0
CD19	-0.041	0.1	-10000	0	-0.52	7	7
MAP4K1	-0.028	0.1	-10000	0	-0.29	38	38
CD72	-0.009	0.077	-10000	0	-0.29	20	20
PAG1	0.013	0	-10000	0	-10000	0	0
MAPK14	0.013	0.083	-10000	0	-0.42	4	4
SH3BP5	-0.022	0.16	-10000	0	-0.81	12	12
PIK3AP1	-0.014	0.12	0.27	8	-0.53	10	18
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.026	0.14	-10000	0	-0.67	10	10
RAF1	0	0.1	-10000	0	-0.45	9	9
RasGAP/p62DOK/SHIP	-0.056	0.089	-10000	0	-0.43	6	6
CD79A	-0.03	0.12	-10000	0	-0.32	37	37
re-entry into mitotic cell cycle	-0.014	0.092	0.19	5	-0.24	15	20
RASA1	0.013	0	-10000	0	-10000	0	0
MAPK3	0.015	0.086	-10000	0	-0.41	6	6
MAPK1	0.015	0.086	-10000	0	-0.41	6	6
CD72/SHP1	-0.015	0.11	-10000	0	-0.53	5	5
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	0.007	0.097	-10000	0	-0.42	8	8
actin cytoskeleton organization	-0.003	0.096	-10000	0	-0.49	5	5
NF-kappa-B/RelA	0.032	0.04	0.17	7	-10000	0	7
Calcineurin	-0.022	0.078	-10000	0	-0.46	6	6
PI3K	-0.035	0.083	-10000	0	-0.44	5	5
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.027	0.12	0.27	8	-0.57	9	17
SOS1	0.013	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.019	0.12	-10000	0	-0.64	5	5
DAPP1	-0.028	0.1	-10000	0	-0.77	4	4
cytokine secretion	0.001	0.081	-10000	0	-0.42	5	5
mol:DAG	-0.025	0.12	0.24	8	-0.54	9	17
PLCG2	-0.035	0.19	-10000	0	-0.75	18	18
MAP2K1	0.008	0.094	-10000	0	-0.46	6	6
B-cell antigen/BCR complex/FcgammaRIIB	-0.073	0.11	-10000	0	-0.54	6	6
mol:PI-3-4-5-P3	-0.028	0.062	-10000	0	-0.32	5	5
ETS1	0.001	0.094	-10000	0	-0.46	6	6
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.037	0.12	-10000	0	-0.49	15	15
B-cell antigen/BCR complex/LYN	-0.033	0.088	-10000	0	-0.55	6	6
MALT1	0.013	0	-10000	0	-10000	0	0
TRAF6	0.012	0	-10000	0	-10000	0	0
RAC1	-0.004	0.1	-10000	0	-0.53	5	5
B-cell antigen/BCR complex/LYN/SYK	-0.034	0.095	-10000	0	-0.54	5	5
CARD11	-0.053	0.12	-10000	0	-0.45	12	12
FCGR2B	-0.081	0.15	-10000	0	-0.3	87	87
PPP3CA	0.013	0	-10000	0	-10000	0	0
BCL10	0.013	0	-10000	0	-10000	0	0
IKK complex	0.011	0.027	-10000	0	-10000	0	0
PTPRC	0.002	0.067	-10000	0	-0.81	1	1
PDPK1	0.003	0.055	-10000	0	-0.23	1	1
PPP3CB	0.013	0	-10000	0	-10000	0	0
PPP3CC	0.013	0	-10000	0	-10000	0	0
POU2F2	0.014	0.019	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.035	0.3	-10000	0	-1	9	9
IL23A	-0.035	0.3	-10000	0	-1	8	8
NF kappa B1 p50/RelA/I kappa B alpha	-0.11	0.21	-10000	0	-0.85	11	11
positive regulation of T cell mediated cytotoxicity	-0.038	0.3	-10000	0	-0.94	11	11
ITGA3	-0.033	0.28	-10000	0	-0.91	8	8
IL17F	-0.005	0.22	-10000	0	-0.64	6	6
IL12B	0.011	0.042	-10000	0	-0.34	1	1
STAT1 (dimer)	-0.038	0.29	-10000	0	-0.91	11	11
CD4	-0.031	0.28	-10000	0	-0.92	7	7
IL23	-0.047	0.29	-10000	0	-1	8	8
IL23R	0.011	0.092	-10000	0	-10000	0	0
IL1B	-0.042	0.32	-10000	0	-1.2	9	9
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.03	0.28	-10000	0	-0.9	9	9
TYK2	0.016	0.018	-10000	0	-10000	0	0
STAT4	-0.013	0.084	-10000	0	-0.29	24	24
STAT3	0.013	0.001	-10000	0	-10000	0	0
IL18RAP	-0.028	0.1	-10000	0	-0.29	38	38
IL12RB1	-0.003	0.08	-10000	0	-0.31	18	18
PIK3CA	0.013	0.001	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.007	0.059	-10000	0	-10000	0	0
IL23R/JAK2	0.019	0.1	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.038	0.3	-10000	0	-0.94	11	11
natural killer cell activation	0	0.009	0.037	5	-10000	0	5
JAK2	0.023	0.023	-10000	0	-10000	0	0
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
NFKB1	0.013	0.003	-10000	0	-10000	0	0
RELA	0.013	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.044	0.28	-10000	0	-0.96	8	8
ALOX12B	-0.03	0.28	-10000	0	-0.9	8	8
CXCL1	-0.088	0.35	-10000	0	-1.1	16	16
T cell proliferation	-0.038	0.3	-10000	0	-0.94	11	11
NFKBIA	0.013	0.003	-10000	0	-10000	0	0
IL17A	0.016	0.19	-10000	0	-0.52	2	2
PI3K	-0.1	0.22	-10000	0	-0.87	11	11
IFNG	0	0.027	0.087	2	-10000	0	2
STAT3 (dimer)	-0.11	0.21	-10000	0	-0.83	11	11
IL18R1	0.009	0.049	-10000	0	-0.81	1	1
IL23/IL23R/JAK2/TYK2/SOCS3	-0.001	0.2	-10000	0	-0.63	4	4
IL18/IL18R	-0.005	0.069	-10000	0	-0.54	1	1
macrophage activation	-0.009	0.013	-10000	0	-0.043	8	8
TNF	-0.041	0.31	-10000	0	-1.1	9	9
STAT3/STAT4	-0.11	0.23	-10000	0	-0.91	11	11
STAT4 (dimer)	-0.046	0.29	-10000	0	-0.95	11	11
IL18	0.007	0.04	-10000	0	-0.29	5	5
IL19	-0.033	0.28	-10000	0	-0.89	8	8
STAT5A (dimer)	-0.036	0.28	-10000	0	-0.91	11	11
STAT1	0.007	0.04	-10000	0	-0.29	5	5
SOCS3	0.006	0.057	-10000	0	-0.42	4	4
CXCL9	-0.037	0.3	-10000	0	-0.95	11	11
MPO	-0.033	0.28	-10000	0	-0.92	7	7
positive regulation of humoral immune response	-0.038	0.3	-10000	0	-0.94	11	11
IL23/IL23R/JAK2/TYK2	-0.04	0.3	-10000	0	-0.97	11	11
IL6	-0.12	0.45	-10000	0	-1.2	34	34
STAT5A	0.013	0	-10000	0	-10000	0	0
IL2	0.003	0.02	-10000	0	-0.3	1	1
positive regulation of tyrosine phosphorylation of STAT protein	0	0.009	0.037	5	-10000	0	5
CD3E	-0.039	0.3	-10000	0	-1	8	8
keratinocyte proliferation	-0.038	0.3	-10000	0	-0.94	11	11
NOS2	-0.088	0.41	-10000	0	-1.2	27	27

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.055	0.11	-9999	-0.59	10	10
PDGFB-D/PDGFRB/SLAP	-0.021	0.12	-9999	-0.63	10	10
PDGFB-D/PDGFRB/APS/CBL	-0.017	0.099	-9999	-0.53	10	10
AKT1	0.041	0.074	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.044	0.13	-9999	-0.62	10	10
PIK3CA	0.013	0	-9999	-10000	0	0
FGR	-0.019	0.1	-9999	-0.53	11	11
mol:Ca2+	-0.003	0.12	-9999	-0.63	10	10
MYC	0.013	0.089	-9999	-0.38	10	10
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	0.017	0.086	-9999	-0.44	10	10
LRP1/PDGFRB/PDGFB	-0.018	0.1	-9999	-0.53	11	11
GRB10	0.013	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
GO:0007205	-0.004	0.12	-9999	-0.64	10	10
PTEN	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
GRB7	0.013	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHP2	-0.012	0.12	-9999	-0.62	10	10
PDGFB-D/PDGFRB/GRB10	-0.012	0.12	-9999	-0.62	10	10
cell cycle arrest	-0.021	0.12	-9999	-0.63	10	10
HRAS	0.013	0	-9999	-10000	0	0
HIF1A	0.046	0.067	-9999	-10000	0	0
GAB1	-0.011	0.12	-9999	-0.61	10	10
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.011	0.11	-9999	-0.57	10	10
PDGFB-D/PDGFRB	-0.015	0.1	-9999	-0.55	10	10
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.012	0.12	-9999	-0.62	10	10
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.053	0.11	-9999	-0.57	10	10
positive regulation of MAPKKK cascade	-0.012	0.12	-9999	-0.62	10	10
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	-0.004	0.12	-9999	-0.65	10	10
E5	0	0.001	-9999	-10000	0	0
CSK	0.012	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.012	0.12	-9999	-0.62	10	10
SHB	0.013	0	-9999	-10000	0	0
BLK	-0.018	0.097	-9999	-0.51	10	10
PTPN2	0.012	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.012	0.12	-9999	-0.62	10	10
BCAR1	0.013	0	-9999	-10000	0	0
VAV2	-0.007	0.12	-9999	-0.57	11	11
CBL	0.013	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.012	0.12	-9999	-0.62	10	10
LCK	-0.016	0.096	-9999	-0.51	10	10
PDGFRB	-0.017	0.15	-9999	-0.82	10	10
ACP1	0.013	0	-9999	-10000	0	0
HCK	-0.026	0.11	-9999	-0.54	11	11
ABL1	-0.005	0.11	-9999	-0.56	10	10
PDGFB-D/PDGFRB/CBL	-0.01	0.13	-9999	-0.66	10	10
PTPN1	0.012	0.002	-9999	-10000	0	0
SNX15	0.013	0	-9999	-10000	0	0
STAT3	0.013	0	-9999	-10000	0	0
STAT1	0.007	0.04	-9999	-0.29	5	5
cell proliferation	0.013	0.083	-9999	-0.36	10	10
SLA	-0.001	0.063	-9999	-0.29	13	13
actin cytoskeleton reorganization	0.03	0.085	-9999	-0.42	10	10
SRC	-0.013	0.095	-9999	-0.51	10	10
PI3K	-0.013	0.071	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.016	0.098	-9999	-0.53	10	10
SH2B2	0.011	0.018	-9999	-0.29	1	1
PLCgamma1/SPHK1	-0.045	0.13	-9999	-0.65	10	10
LYN	-0.013	0.095	-9999	-0.51	10	10
LRP1	0.013	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
STAT5B	0.013	0	-9999	-10000	0	0
STAT5A	0.013	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.014	0.08	-9999	-0.43	10	10
SPHK1	-0.14	0.15	-9999	-0.29	144	144
EDG1	-0.001	0.002	-9999	-10000	0	0
mol:DAG	-0.004	0.12	-9999	-0.65	10	10
PLCG1	-0.005	0.13	-9999	-0.67	10	10
NHERF/PDGFRB	-0.016	0.098	-9999	-0.53	10	10
YES1	-0.013	0.095	-9999	-0.51	10	10
cell migration	-0.018	0.097	-9999	-0.53	10	10
SHC/Grb2/SOS1	-0.014	0.08	-9999	-0.43	10	10
SLC9A3R2	0.013	0	-9999	-10000	0	0
SLC9A3R1	0.013	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	-0.001	0.093	-9999	-0.48	10	10
FYN	-0.013	0.095	-9999	-0.51	10	10
DOK1	0.011	0.096	-9999	-0.49	10	10
HRAS/GTP	0.009	0	-9999	-10000	0	0
PDGFB	0.01	0.048	-9999	-0.81	1	1
RAC1	0.001	0.11	-9999	-0.53	10	10
PRKCD	0.012	0.095	-9999	-0.49	10	10
FER	0.012	0.095	-9999	-0.49	10	10
MAPKKK cascade	-0.015	0.077	-9999	-0.42	10	10
RASA1	0.012	0.095	-9999	-0.49	10	10
NCK1	0.013	0	-9999	-10000	0	0
NCK2	0.013	0	-9999	-10000	0	0
p62DOK/Csk	0.019	0.09	-9999	-0.45	10	10
PDGFB-D/PDGFRB/SHB	-0.012	0.12	-9999	-0.62	10	10
chemotaxis	-0.004	0.11	-9999	-0.54	10	10
STAT1-3-5/STAT1-3-5	-0.016	0.076	-9999	-0.41	10	10
Bovine Papilomavirus E5/PDGFRB	-0.017	0.12	-9999	-0.63	10	10
PTPRJ	0.013	0	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.023	0.038	-9999	-10000	0	0
ACTA1	0.017	0.045	-9999	-10000	0	0
NUMA1	0.023	0.038	-9999	-10000	0	0
SPTAN1	0.018	0.045	-9999	-10000	0	0
LIMK1	0.016	0.049	-9999	-10000	0	0
BIRC3	-0.009	0.077	-9999	-0.29	20	20
BIRC2	0.013	0	-9999	-10000	0	0
BAX	0.01	0.025	-9999	-0.29	2	2
CASP10	0.011	0.059	-9999	-10000	0	0
CRMA	0	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
PTK2	0.023	0.038	-9999	-10000	0	0
DIABLO	0.012	0	-9999	-10000	0	0
apoptotic nuclear changes	0.018	0.044	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
CRADD	0.013	0	-9999	-10000	0	0
GSN	0.018	0.045	-9999	-10000	0	0
MADD	0.013	0	-9999	-10000	0	0
TFAP2A	-0.42	0.24	-9999	-0.53	229	229
BID	0.015	0.031	-9999	-10000	0	0
MAP3K1	0.013	0.02	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0.019	0.001	-9999	-10000	0	0
mol:Activated DNA	0	0	-9999	-10000	0	0
ARHGDIB	0.017	0.049	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
DNA repair	-0.01	0.022	-9999	-10000	0	0
neuron apoptosis	0.024	0.007	-9999	-10000	0	0
mol:NAD	0	0	-9999	-10000	0	0
DNA fragmentation during apoptosis	0.025	0.043	-9999	-10000	0	0
APAF1	0.012	0	-9999	-10000	0	0
CASP6	0.031	0.027	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
ICAD/CAD	0.024	0.043	-9999	-10000	0	0
CASP7	-0.002	0.037	-9999	-10000	0	0
KRT18	0.015	0.02	-9999	-10000	0	0
apoptosis	0.029	0.044	-9999	-10000	0	0
DFFA	0.018	0.045	-9999	-10000	0	0
DFFB	0.018	0.045	-9999	-10000	0	0
PARP1	0.01	0.022	-9999	-10000	0	0
actin filament polymerization	-0.022	0.046	-9999	-10000	0	0
TNF	-0.011	0.1	-9999	-0.38	17	17
CYCS	0.014	0.026	-9999	-10000	0	0
SATB1	0.035	0.037	-9999	-0.42	1	1
SLK	0.018	0.045	-9999	-10000	0	0
p15 BID/BAX	0.019	0.03	-9999	-10000	0	0
CASP2	0.037	0.038	-9999	-10000	0	0
JNK cascade	-0.013	0.02	-9999	-10000	0	0
CASP3	0.011	0.048	-9999	-10000	0	0
LMNB2	0.04	0.027	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
CASP4	0.013	0	-9999	-10000	0	0
Mammalian IAPs/DIABLO	0.02	0.039	-9999	-10000	0	0
negative regulation of DNA binding	-0.41	0.23	-9999	-0.52	229	229
stress fiber formation	0.018	0.044	-9999	-10000	0	0
GZMB	0.002	0.07	-9999	-0.37	5	5
CASP1	0.015	0.014	-9999	-10000	0	0
LMNB1	0.037	0.031	-9999	-10000	0	0
APP	0.024	0.007	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
CASP8	0.011	0	-9999	-10000	0	0
VIM	0.023	0.044	-9999	-10000	0	0
LMNA	0.04	0.027	-9999	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.031	0.04	-9999	-10000	0	0
LRDD	0.011	0.018	-9999	-0.29	1	1
SREBF1	0.018	0.046	-9999	-10000	0	0
APAF-1/Caspase 9	0.002	0.015	-9999	-10000	0	0
nuclear fragmentation during apoptosis	0.023	0.038	-9999	-10000	0	0
CFL2	0.022	0.046	-9999	-10000	0	0
GAS2	0.011	0.078	-9999	-0.53	4	4
positive regulation of apoptosis	0.041	0.029	-9999	-10000	0	0
PRF1	0.005	0.047	-9999	-0.29	7	7

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.013	0	-9999	-10000	0	0
VLDLR	0.013	0	-9999	-10000	0	0
LRPAP1	0.013	0	-9999	-10000	0	0
NUDC	0.013	0	-9999	-10000	0	0
RELN/LRP8	-0.082	0.13	-9999	-0.56	15	15
CaM/Ca2+	0.009	0	-9999	-10000	0	0
KATNA1	0.013	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.052	0.13	-9999	-0.51	15	15
IQGAP1/CaM	0.019	0	-9999	-10000	0	0
DAB1	-0.004	0.052	-9999	-0.29	9	9
IQGAP1	0.013	0	-9999	-10000	0	0
PLA2G7	-0.24	0.12	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
DYNLT1	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.014	0.032	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.013	0	-9999	-10000	0	0
CDK5R1	0.009	0.031	-9999	-0.29	3	3
LIS1/Poliovirus Protein 3A	0.016	0	-9999	-10000	0	0
CDK5R2	-0.064	0.13	-9999	-0.29	71	71
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.085	0.13	-9999	-0.55	15	15
YWHAE	0.013	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.036	0.11	-9999	-0.46	4	4
MAP1B	0	0.009	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.033	0.12	-9999	-0.44	15	15
RELN	-0.14	0.21	-9999	-0.36	116	116
PAFAH/LIS1	-0.11	0.065	-9999	-10000	0	0
LIS1/CLIP170	0.025	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.037	0.071	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.022	0.089	-9999	-0.33	16	16
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.045	0.11	-9999	-0.5	4	4
LIS1/IQGAP1	0.025	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.022	0	-9999	-10000	0	0
PAFAH1B3	0.011	0.018	-9999	-0.29	1	1
PAFAH1B2	0.01	0.048	-9999	-0.81	1	1
MAP1B/LIS1/Dynein heavy chain	0.024	0.006	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.048	0.092	-9999	-0.44	4	4
LRP8	0.005	0.047	-9999	-0.29	7	7
NDEL1/Katanin 60	-0.036	0.11	-9999	-0.46	4	4
P39/CDK5	-0.066	0.12	-9999	-0.46	15	15
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.025	0	-9999	-10000	0	0
CDK5	-0.041	0.12	-9999	-0.47	15	15
PPP2R5D	0.011	0.018	-9999	-0.29	1	1
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.047	0.12	-9999	-0.47	15	15
RELN/VLDLR	-0.052	0.13	-9999	-0.51	15	15
CDC42	0	0	-9999	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.013	0	-9999	-10000	0	0
LAT2	-0.039	0.1	-9999	-0.34	3	3
AP1	-0.11	0.15	-9999	-0.41	45	45
mol:PIP3	-0.06	0.15	-9999	-0.46	8	8
IKBKB	-0.022	0.086	-9999	-0.27	3	3
AKT1	-0.022	0.1	-9999	-10000	0	0
IKBKG	-0.022	0.086	-9999	-0.27	3	3
MS4A2	-0.073	0.14	-9999	-0.3	80	80
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
MAP3K1	-0.029	0.11	-9999	-0.45	1	1
mol:Ca2+	-0.044	0.12	-9999	-0.34	8	8
LYN	0.01	0.004	-9999	-10000	0	0
CBLB	-0.023	0.076	-9999	-0.32	1	1
SHC1	0.012	0	-9999	-10000	0	0
RasGAP/p62DOK	0.021	0.034	-9999	-0.5	1	1
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.002	0.056	-9999	-0.29	10	10
PLD2	-0.052	0.11	-9999	-0.42	11	11
PTPN13	-0.012	0.071	-9999	-10000	0	0
PTPN11	0.012	0.003	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.003	0.081	-9999	-10000	0	0
SYK	0.008	0.049	-9999	-0.82	1	1
GRB2	0.012	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.089	0.12	-9999	-0.46	8	8
LAT	-0.036	0.086	-9999	-0.34	3	3
PAK2	-0.039	0.12	-9999	-0.51	1	1
NFATC2	-0.079	0.18	-9999	-0.72	21	21
HRAS	-0.049	0.12	-9999	-0.46	2	2
GAB2	0.013	0	-9999	-10000	0	0
PLA2G1B	0.03	0.012	-9999	-10000	0	0
Fc epsilon R1	-0.1	0.13	-9999	-0.39	30	30
Antigen/IgE/Fc epsilon R1	-0.09	0.12	-9999	-0.45	13	13
mol:GDP	-0.061	0.13	-9999	-0.5	2	2
JUN	0.013	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.012	0.001	-9999	-10000	0	0
FOS	-0.11	0.3	-9999	-0.81	44	44
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.032	0.08	-9999	-0.34	1	1
CHUK	-0.022	0.086	-9999	-0.27	3	3
KLRG1	-0.027	0.077	-9999	-10000	0	0
VAV1	-0.055	0.12	-9999	-0.43	4	4
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.023	0.076	-9999	-0.32	1	1
negative regulation of mast cell degranulation	-0.023	0.079	-9999	-0.34	1	1
BTK	-0.05	0.11	-9999	-0.32	2	2
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.059	0.12	-9999	-0.38	13	13
GAB2/PI3K/SHP2	-0.058	0.086	-9999	-0.41	1	1
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.03	0.08	-9999	-0.33	1	1
RAF1	0.019	0.015	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.15	-9999	-0.42	35	35
FCER1G	-0.071	0.14	-9999	-0.29	80	80
FCER1A	-0.018	0.14	-9999	-0.62	13	13
Antigen/IgE/Fc epsilon R1/Fyn	-0.079	0.11	-9999	-0.45	11	11
MAPK3	0.028	0.012	-9999	-10000	0	0
MAPK1	0.028	0.012	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	-0.004	0.088	-9999	-0.67	4	4
DUSP1	0.01	0.048	-9999	-0.81	1	1
NF-kappa-B/RelA	-0.025	0.04	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.019	0.073	-9999	-10000	0	0
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.071	0.1	-9999	-0.6	1	1
FER	-0.023	0.076	-9999	-0.32	1	1
RELA	0.013	0	-9999	-10000	0	0
ITK	-0.014	0.029	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
PLCG1	-0.057	0.14	-9999	-0.51	2	2
cytokine secretion	-0.019	0.029	-9999	-10000	0	0
SPHK1	-0.09	0.1	-9999	-0.35	7	7
PTK2	-0.02	0.075	-9999	-10000	0	0
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.09	0.13	-9999	-0.47	7	7
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.05	0.14	-9999	-0.44	6	6
MAP2K2	0.025	0.013	-9999	-10000	0	0
MAP2K1	0.025	0.013	-9999	-10000	0	0
MAP2K7	0.013	0	-9999	-10000	0	0
KLRG1/SHP2	-0.043	0.059	-9999	-10000	0	0
MAP2K4	0.016	0.008	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.13	0.16	-9999	-0.45	31	31
mol:Choline	-0.052	0.11	-9999	-0.41	11	11
SHC/Grb2/SOS1	-0.035	0.055	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
DOK1	0.009	0.031	-9999	-0.29	3	3
PXN	-0.012	0.071	-9999	-10000	0	0
HCLS1	-0.026	0.081	-9999	-0.32	1	1
PRKCB	-0.039	0.11	-9999	-0.34	7	7
FCGR2B	-0.081	0.15	-9999	-0.3	87	87
IGHE	-0.002	0.005	-9999	-10000	0	0
KLRG1/SHIP	-0.023	0.08	-9999	-0.35	1	1
LCP2	0.004	0.05	-9999	-0.29	8	8
PLA2G4A	-0.036	0.11	-9999	-0.51	9	9
RASA1	0.013	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.052	0.11	-9999	-0.41	11	11
IKK complex	-0.005	0.07	-9999	-10000	0	0
WIPF1	0.011	0.018	-9999	-10000	0	0

×

IL1-mediated signaling events

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
UBC13/UEV1A	0.011	0.004	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.005	0.031	-9999	-10000	0	0
IRAK/TOLLIP	0.026	0.003	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
IKBKG	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.18	0.28	-9999	-0.63	76	76
IL1A	-0.029	0.1	-9999	-0.29	38	38
IL1B	0.008	0.087	-9999	-0.62	5	5
IRAK/TRAF6/p62/Atypical PKCs	-0.003	0.015	-9999	-10000	0	0
IL1R2	-0.2	0.36	-9999	-0.8	77	77
IL1R1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.032	0.032	-9999	-10000	0	0
TOLLIP	0.013	0	-9999	-10000	0	0
TICAM2	0.01	0.048	-9999	-0.81	1	1
MAP3K3	0.013	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.059	0.007	-9999	-10000	0	0
JUN	0.035	0.05	-9999	-0.39	4	4
MAP3K7	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.031	0.065	-9999	-0.44	5	5
IL1 alpha/IL1R1/IL1RAP/MYD88	0.01	0.055	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.015	0.039	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP	0.019	0.072	-9999	-0.49	5	5
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	0.029	0.053	-9999	-0.42	4	4
IRAK1	0.02	0.004	-9999	-10000	0	0
IL1RN/IL1R1	0.005	0.06	-9999	-0.62	1	1
IRAK4	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
TRAF6	0.013	0	-9999	-10000	0	0
PI3K	0.019	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.032	0.04	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.019	0.072	-9999	-0.49	5	5
IL1 beta/IL1R2	-0.14	0.26	-9999	-0.55	80	80
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.009	0.052	-9999	-10000	0	0
IRAK3	0.01	0.025	-9999	-0.29	2	2
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.029	0.08	-9999	-0.52	5	5
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.021	0.036	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP	-0.021	0.052	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.003	0.053	-9999	-0.29	9	9
MYD88	0.013	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.033	0.003	-9999	-10000	0	0
IL1RAP	0.009	0.031	-9999	-0.29	3	3
UBE2N	0.013	0	-9999	-10000	0	0
IRAK/TRAF6	-0.009	0.06	-9999	-0.72	1	1
CASP1	0.009	0.031	-9999	-10000	0	0
IL1RN/IL1R2	-0.16	0.28	-9999	-0.63	77	77
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.026	0.068	-9999	-0.46	5	5
TMEM189-UBE2V1	0.003	0.005	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.029	0.028	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
IL1RN	-0.007	0.084	-9999	-0.32	17	17
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.03	0.003	-9999	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.011	0.1	-9999	-0.34	22	22
FZD6	0.013	0	-9999	-10000	0	0
WNT6	0.008	0.052	-9999	-0.55	2	2
WNT4	-0.015	0.14	-9999	-0.72	11	11
FZD3	0.013	0	-9999	-10000	0	0
WNT5A	-0.033	0.11	-9999	-10000	0	0
WNT11	-0.029	0.17	-9999	-0.81	12	12

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.3	0.4	-9999	-0.81	109	109
HRAS	0.013	0	-9999	-10000	0	0
EGFR	0.013	0	-9999	-10000	0	0
AKT	0.023	0.022	-9999	-10000	0	0
FOXO3	0.013	0	-9999	-10000	0	0
AKT1	0.013	0	-9999	-10000	0	0
FOXO1	0.013	0	-9999	-10000	0	0
AKT3	0.013	0	-9999	-10000	0	0
FOXO4	0.013	0	-9999	-10000	0	0
MET	-0.025	0.1	-9999	-0.29	36	36
PIK3CA	0.013	0	-9999	-10000	0	0
PIK3CB	0.011	0.018	-9999	-0.29	1	1
NRAS	0.013	0	-9999	-10000	0	0
PIK3CG	0.004	0.075	-9999	-0.5	5	5
PIK3R3	0.013	0	-9999	-10000	0	0
PIK3R2	0.013	0	-9999	-10000	0	0
NF1	0.013	0	-9999	-10000	0	0
RAS	-0.056	0.098	-9999	-0.25	12	12
ERBB2	0.013	0	-9999	-10000	0	0
proliferation/survival/translation	-0.027	0.013	-9999	-10000	0	0
PI3K	-0.04	0.093	-9999	-0.22	15	15
PIK3R1	0.013	0	-9999	-10000	0	0
KRAS	0.013	0	-9999	-10000	0	0
FOXO	0.028	0.025	-9999	-10000	0	0
AKT2	0.013	0	-9999	-10000	0	0
PTEN	0.013	0	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.003	0.099	-10000	0	-0.62	7	7
ATM	0.013	0	-10000	0	-10000	0	0
UBE2D3	0.013	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
ATR	0.013	0	-10000	0	-10000	0	0
UBE2L3	0.013	0	-10000	0	-10000	0	0
FANCD2	0.024	0.011	-10000	0	-10000	0	0
protein ubiquitination	-0.019	0.075	-10000	0	-0.45	7	7
XRCC5	0.013	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
M/R/N Complex	-0.002	0.032	-10000	0	-0.54	1	1
MRE11A	0.013	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.011	0.022	-10000	0	-10000	0	0
FANCF	0.013	0	-10000	0	-10000	0	0
BRCA1	0.009	0.031	-10000	0	-0.29	3	3
CCNE1	-0.006	0.074	-10000	0	-0.29	18	18
CDK2/Cyclin E1	0.006	0.05	-10000	0	-10000	0	0
FANCG	0.013	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.001	0.1	-10000	0	-0.62	7	7
FANCE	0.013	0	-10000	0	-10000	0	0
FANCC	0.013	0	-10000	0	-10000	0	0
NBN	0.013	0	-10000	0	-10000	0	0
FANCA	-0.12	0.15	-10000	0	-0.29	124	124
DNA repair	0.014	0.094	-10000	0	-0.42	6	6
BRCA1/BARD1/ubiquitin	0.001	0.1	-10000	0	-0.62	7	7
BARD1/DNA-PK	0.019	0.08	-10000	0	-0.49	7	7
FANCL	0.013	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.003	0.098	0.62	7	-10000	0	7
BRCA1/BARD1/CTIP/M/R/N Complex	0.027	0.061	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.015	0.084	-10000	0	-0.54	7	7
BRCA1/BARD1/P53	0.018	0.082	-10000	0	-0.49	7	7
BARD1/CSTF1/BRCA1	-0.015	0.084	-10000	0	-0.54	7	7
BRCA1/BACH1	0.009	0.031	-10000	0	-0.29	3	3
BARD1	-0.008	0.13	-10000	0	-0.81	7	7
PCNA	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.015	0.084	-10000	0	-0.54	7	7
BRCA1/BARD1/UbcH7	-0.015	0.084	-10000	0	-0.54	7	7
BRCA1/BARD1/RAD51/PCNA	0.001	0.094	-10000	0	-0.49	7	7
BARD1/DNA-PK/P53	-0.011	0.071	-10000	0	-0.46	7	7
BRCA1/BARD1/Ubiquitin	0.001	0.1	-10000	0	-0.62	7	7
BRCA1/BARD1/CTIP	0.015	0.087	-10000	0	-0.49	8	8
FA complex	-0.004	0.05	-10000	0	-10000	0	0
BARD1/EWS	0.003	0.099	-10000	0	-0.62	7	7
RBBP8	0.019	0.038	-10000	0	-0.62	1	1
TP53	0.013	0	-10000	0	-10000	0	0
TOPBP1	0.013	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.013	0.076	0.49	7	-10000	0	7
BRCA1/BARD1	-0.019	0.076	-10000	0	-0.46	7	7
CSTF1	0.013	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.006	0.098	-10000	0	-0.63	7	7
CDK2	0.013	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.02	0.094	-10000	0	-0.29	31	31
RAD50	0.01	0.048	-10000	0	-0.81	1	1
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.001	0.1	-10000	0	-0.62	7	7
EWSR1	0.013	0	-10000	0	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.011	0.096	-9999	-0.46	5	5
MAP4K1	-0.028	0.1	-9999	-0.29	38	38
MAP3K8	0.013	0	-9999	-10000	0	0
PRKCB	0.007	0.04	-9999	-0.29	5	5
DBNL	0.013	0	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
MAP3K1	0.02	0.054	-9999	-10000	0	0
JUN	0.021	0.075	-9999	-0.58	4	4
MAP3K7	0.02	0.054	-9999	-10000	0	0
GRAP2	0.003	0.053	-9999	-0.29	9	9
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.029	0.052	-9999	-10000	0	0
LAT	-0.017	0.09	-9999	-0.29	28	28
LCP2	0.004	0.05	-9999	-10000	0	0
MAPK8	0.015	0.079	-9999	-0.62	4	4
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.014	0.057	-9999	-0.32	2	2
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.033	0.077	-9999	-0.43	5	5

×

Noncanonical Wnt signaling 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
NFATC2	-0.048	0.21	-9999	-0.81	21	21
GNB1/GNG2	0.004	0.093	-9999	-0.4	2	2
mol:DAG	0.011	0.087	-9999	-10000	0	0
PLCG1	0.011	0.089	-9999	-10000	0	0
YES1	-0.003	0.096	-9999	-0.42	2	2
FZD3	0.013	0	-9999	-10000	0	0
FZD6	0.013	0	-9999	-10000	0	0
G protein	0.011	0.089	-9999	-10000	0	0
MAP3K7	-0.15	0.21	-9999	-0.47	28	28
mol:Ca2+	0.011	0.085	-9999	-10000	0	0
mol:IP3	0.011	0.087	-9999	-10000	0	0
NLK	-0.009	0.012	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CAMK2A	-0.16	0.23	-9999	-0.49	36	36
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.011	0.1	-9999	-0.34	22	22
CSNK1A1	0.013	0	-9999	-10000	0	0
GNAS	-0.003	0.096	-9999	-0.42	2	2
GO:0007205	0.011	0.085	-9999	-10000	0	0
WNT6	0.008	0.052	-9999	-0.55	2	2
WNT4	-0.015	0.14	-9999	-0.72	11	11
NFAT1/CK1 alpha	-0.017	0.14	-9999	-0.54	3	3
GNG2	0.013	0	-9999	-10000	0	0
WNT5A	-0.033	0.11	-9999	-10000	0	0
WNT11	-0.029	0.17	-9999	-0.81	12	12
CDC42	0.005	0.092	-9999	-0.39	2	2

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.007	0.068	-9999	-10000	0	0
CRKL	0.01	0.077	-9999	-0.33	5	5
mol:PIP3	-0.019	0.004	-9999	-10000	0	0
AKT1	0.001	0.003	-9999	-10000	0	0
PTK2B	0.013	0	-9999	-10000	0	0
RAPGEF1	0.017	0.074	-9999	-10000	0	0
RANBP10	0.013	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.05	0.14	-9999	-0.58	17	17
MAP3K5	0.017	0.071	-9999	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.018	0.14	-9999	-0.53	17	17
AP1	-0.077	0.2	-9999	-0.56	44	44
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
apoptosis	-0.098	0.27	-9999	-0.72	44	44
STAT3 (dimer)	0.008	0.09	-9999	-0.33	17	17
GAB1/CRKL/SHP2/PI3K	-0.017	0.056	-9999	-10000	0	0
INPP5D	0.002	0.056	-9999	-0.29	10	10
CBL/CRK	0.017	0.074	-9999	-0.31	5	5
PTPN11	0.013	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.013	0	-9999	-10000	0	0
PTEN	0.013	0	-9999	-10000	0	0
ELK1	-0.014	0.04	-9999	-10000	0	0
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.016	0.048	-9999	-0.25	5	5
PAK1	0.008	0.003	-9999	-10000	0	0
HGF/MET/RANBP10	-0.05	0.14	-9999	-0.58	17	17
HRAS	-0.003	0.11	-9999	-0.5	5	5
DOCK1	0.017	0.074	-9999	-0.31	5	5
GAB1	0.003	0.081	-9999	-0.3	17	17
CRK	0.01	0.077	-9999	-0.33	5	5
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.044	0.14	-9999	-0.59	17	17
JUN	0.013	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.014	0.075	-9999	-0.28	17	17
PIK3R1	0.013	0	-9999	-10000	0	0
cell morphogenesis	0.034	0.091	-9999	-10000	0	0
GRB2/SHC	0.003	0.068	-9999	-0.3	5	5
FOS	-0.11	0.3	-9999	-0.81	44	44
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.014	0.04	-9999	-10000	0	0
HGF/MET/MUC20	-0.052	0.14	-9999	-0.59	17	17
cell migration	0.002	0.067	-9999	-0.3	5	5
GRB2	0.013	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
MET/RANBP10	-0.007	0.068	-9999	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.002	0.095	-9999	-0.35	17	17
MET/MUC20	-0.016	0.068	-9999	-10000	0	0
RAP1B	0.023	0.071	-9999	-10000	0	0
RAP1A	0.023	0.071	-9999	-10000	0	0
HGF/MET/RANBP9	-0.05	0.14	-9999	-0.58	17	17
RAF1	0.005	0.11	-9999	-0.47	5	5
STAT3	0.008	0.091	-9999	-0.34	17	17
cell proliferation	0.012	0.12	-9999	-0.44	17	17
RPS6KB1	0.002	0.028	-9999	-10000	0	0
MAPK3	-0.018	0.036	-9999	-10000	0	0
MAPK1	-0.018	0.036	-9999	-10000	0	0
RANBP9	0.013	0	-9999	-10000	0	0
MAPK8	0.026	0.091	-9999	-0.54	4	4
SRC	0.009	0.09	-9999	-0.39	5	5
PI3K	0.003	0.068	-9999	-0.3	5	5
MET/Glomulin	-0.01	0.059	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
MAP2K1	0.012	0.1	-9999	-0.43	5	5
MET	-0.025	0.1	-9999	-0.29	36	36
MAP4K1	0.01	0.074	-9999	-0.31	5	5
PTK2	0.013	0	-9999	-10000	0	0
MAP2K2	0.012	0.1	-9999	-0.43	5	5
BAD	0.008	0.003	-9999	-10000	0	0
MAP2K4	0.023	0.067	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.022	0.063	-9999	-10000	0	0
INPPL1	0.013	0	-9999	-10000	0	0
PXN	0.013	0	-9999	-10000	0	0
SH3KBP1	0.013	0	-9999	-10000	0	0
HGS	-0.005	0.071	-9999	-0.32	5	5
PLCgamma1/PKC	0.009	0	-9999	-10000	0	0
HGF	-0.037	0.2	-9999	-0.81	17	17
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
PTPRJ	0.013	0	-9999	-10000	0	0
NCK/PLCgamma1	0.003	0.074	-9999	-0.33	5	5
PDPK1	-0.008	0.004	-9999	-10000	0	0
HGF/MET/SHIP	-0.055	0.14	-9999	-0.58	17	17

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	0.03	0.085	-9999	-10000	0	0
GNAI2	0.013	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.009	0.059	-9999	-0.55	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	-0.059	0.23	-9999	-0.81	24	24
RhoA/GTP	-0.03	0.087	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.005	0.11	-9999	-0.32	27	27
GNAZ	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
GNA12	0.013	0	-9999	-10000	0	0
S1PR5	-0.002	0.094	-9999	-0.46	9	9
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.006	0.11	-9999	-0.33	27	27
RhoA/GDP	0.009	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
GNAI1	0.007	0.068	-9999	-0.81	2	2

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.013	0	-9999	-10000	0	0
NFATC1	0.043	0.015	-9999	-10000	0	0
NFATC2	-0.013	0.072	-9999	-0.25	13	13
NFATC3	0.013	0.011	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.013	0.049	-9999	-10000	0	0
Exportin 1/Ran/NUP214	0	0	-9999	-10000	0	0
mol:DAG	-0.003	0.004	-9999	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.011	0.032	-9999	-10000	0	0
BCL2/BAX	0.017	0.017	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.011	-9999	-10000	0	0
CaM/Ca2+	0.001	0.011	-9999	-10000	0	0
BAX	0.01	0.025	-9999	-0.29	2	2
MAPK14	0.007	0.006	-9999	-10000	0	0
BAD	0.013	0	-9999	-10000	0	0
CABIN1/MEF2D	0.015	0.047	-9999	-10000	0	0
Calcineurin A alpha-beta B1/BCL2	0.012	0	-9999	-10000	0	0
FKBP8	0.013	0	-9999	-10000	0	0
activation-induced cell death of T cells	-0.015	0.046	-9999	-10000	0	0
KPNB1	0.013	0	-9999	-10000	0	0
KPNA2	0.013	0	-9999	-10000	0	0
XPO1	0.012	0.001	-9999	-10000	0	0
SFN	-0.14	0.18	-9999	-0.31	135	135
MAP3K8	0.008	0.006	-9999	-10000	0	0
NFAT4/CK1 alpha	0	0	-9999	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.11	0.2	-9999	-0.34	122	122
CABIN1	0.013	0.049	-9999	-10000	0	0
CALM1	0.008	0.006	-9999	-10000	0	0
RAN	0.012	0.001	-9999	-10000	0	0
MAP3K1	0.013	0	-9999	-10000	0	0
CAMK4	0.012	0.002	-9999	-10000	0	0
mol:Ca2+	-0.008	0.01	-9999	-10000	0	0
MAPK3	0.013	0	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.01	0.015	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
MAPK8	-0.004	0.097	-9999	-0.82	4	4
MAPK9	0.013	0	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
FKBP1A	0.013	0	-9999	-10000	0	0
NFAT1-c-4/YWHAQ	0.038	0.042	-9999	-10000	0	0
PRKCH	0.013	0	-9999	-10000	0	0
CABIN1/Cbp/p300	0.007	0.016	-9999	-10000	0	0
CASP3	0.006	0.019	-9999	-0.29	1	1
PIM1	0.009	0.031	-9999	-0.29	3	3
Calcineurin A alpha-beta B1/FKBP12/FK506	0.005	0.005	-9999	-10000	0	0
apoptosis	-0.001	0.008	-9999	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.045	-9999	-10000	0	0
PRKCB	0.007	0.04	-9999	-0.29	5	5
PRKCE	0.013	0	-9999	-10000	0	0
JNK2/NFAT4	0.021	0.008	-9999	-10000	0	0
BAD/BCL-XL	0.019	0	-9999	-10000	0	0
PRKCD	0.013	0	-9999	-10000	0	0
NUP214	0.012	0.001	-9999	-10000	0	0
PRKCZ	0.008	0.006	-9999	-10000	0	0
PRKCA	0.013	0	-9999	-10000	0	0
PRKCG	-0.061	0.13	-9999	-0.29	66	66
PRKCQ	-0.01	0.14	-9999	-0.81	8	8
FKBP38/BCL2	0.019	0	-9999	-10000	0	0
EP300	0.006	0.008	-9999	-10000	0	0
PRKCB1	0	0	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
NFATc/JNK1	0.028	0.061	-9999	-0.42	4	4
CaM/Ca2+/FKBP38	0.011	0.009	-9999	-10000	0	0
FKBP12/FK506	0.009	0	-9999	-10000	0	0
CSNK1A1	0.008	0.014	-9999	-10000	0	0
CaM/Ca2+/CAMK IV	0.01	0.01	-9999	-10000	0	0
NFATc/ERK1	0.049	0.014	-9999	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.009	0.029	-9999	-10000	0	0
NR4A1	-0.27	0.39	-9999	-0.73	122	122
GSK3B	0.008	0.006	-9999	-10000	0	0
positive T cell selection	0.013	0.011	-9999	-10000	0	0
NFAT1/CK1 alpha	-0.029	0.047	-9999	-0.34	1	1
RCH1/ KPNB1	0.019	0	-9999	-10000	0	0
YWHAQ	0.013	0	-9999	-10000	0	0
PRKACA	0.007	0.006	-9999	-10000	0	0
AKAP5	0.011	0.018	-9999	-10000	0	0
MEF2D	0.006	0.008	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
NFATc/p38 alpha	0.034	0.03	-9999	-10000	0	0
CREBBP	0.006	0.008	-9999	-10000	0	0
BCL2	0.013	0	-9999	-10000	0	0

×

Canonical Wnt 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
HDAC1	0.001	0.007	-10000	0	-10000	0	0
AES	0.008	0.005	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.013	0.036	-10000	0	-10000	0	0
SMAD4	0.013	0	-10000	0	-10000	0	0
DKK2	0.007	0.054	-10000	0	-0.46	3	3
TLE1	0.008	0.005	-10000	0	-10000	0	0
MACF1	0.013	0	-10000	0	-10000	0	0
CTNNB1	0.05	0.056	-10000	0	-10000	0	0
WIF1	0.001	0.043	-10000	0	-10000	0	0
beta catenin/RanBP3	-0.002	0.035	0.35	1	-10000	0	1
KREMEN2	-0.024	0.098	-10000	0	-0.29	34	34
DKK1	-0.005	0.065	-10000	0	-0.29	14	14
beta catenin/beta TrCP1	0.054	0.053	-10000	0	-10000	0	0
FZD1	0.004	0.053	-10000	0	-0.29	9	9
AXIN2	0.022	0.025	-10000	0	-10000	0	0
AXIN1	0.013	0.001	-10000	0	-10000	0	0
RAN	0.012	0	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.003	0.01	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.032	0.09	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.042	0.073	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.047	0.048	-10000	0	-10000	0	0
HNF1A	-0.01	0.096	-10000	0	-0.82	4	4
CTBP1	0.002	0.006	-10000	0	-10000	0	0
MYC	0.018	0.046	-10000	0	-10000	0	0
RANBP3	0.012	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.02	0.06	-10000	0	-0.38	3	3
NKD1	-0.22	0.37	-10000	0	-0.81	82	82
TCF4	0.001	0.006	-10000	0	-10000	0	0
TCF3	0.002	0.006	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.015	0.043	-10000	0	-10000	0	0
Ran/GTP	0.009	0	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.019	0.08	0.44	1	-10000	0	1
LEF1	-0.064	0.22	-10000	0	-0.82	23	23
DVL1	0.026	0.014	-10000	0	-10000	0	0
CSNK2A1	0.013	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.045	0.091	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.024	0.058	-10000	0	-0.3	2	2
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.001	0.007	-10000	0	-10000	0	0
NLK	0.013	0.001	-10000	0	-10000	0	0
CCND1	0.017	0.091	-10000	0	-1.5	1	1
WNT1	-0.017	0.088	-10000	0	-0.29	27	27
GSK3A	0.013	0.001	-10000	0	-10000	0	0
GSK3B	0.013	0	-10000	0	-10000	0	0
FRAT1	0.012	0	-10000	0	-10000	0	0
PPP2R5D	0.11	0.16	0.36	82	-10000	0	82
APC	0.02	0.049	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.005	0.034	-10000	0	-10000	0	0
CREBBP	0.002	0.006	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.024	0.007	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
MAP3K12	0.011	0.018	-9999	-0.29	1	1
FGR	-0.001	0.073	-9999	-0.34	11	11
p38 alpha/TAB1	-0.003	0.017	-9999	-10000	0	0
PRKG1	-0.2	0.36	-9999	-0.81	73	73
DUSP8	0.013	0	-9999	-10000	0	0
PGK/cGMP/p38 alpha	-0.1	0.17	-9999	-0.39	73	73
apoptosis	-0.002	0.016	-9999	-10000	0	0
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
DUSP1	0.01	0.048	-9999	-0.81	1	1
PAK1	0.013	0	-9999	-10000	0	0
SRC	0.011	0.018	-9999	-0.29	1	1
RAC1/OSM/MEKK3/MKK3	0.032	0	-9999	-10000	0	0
TRAF6	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.048	0.04	-9999	-0.35	1	1
BLK	-0.004	0.065	-9999	-0.29	14	14
HCK	-0.022	0.1	-9999	-0.31	31	31
MAP2K3	0.013	0	-9999	-10000	0	0
DUSP16	0.013	0	-9999	-10000	0	0
DUSP10	-0.014	0.086	-9999	-0.29	25	25
TRAF6/MEKK3	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.047	0.031	-9999	-10000	0	0
positive regulation of innate immune response	0.058	0.043	-9999	-0.38	1	1
LCK	0.005	0.047	-9999	-0.29	7	7
p38alpha-beta/MKP7	0.062	0.041	-9999	-0.36	1	1
p38alpha-beta/MKP5	0.052	0.057	-9999	-10000	0	0
PGK/cGMP	-0.15	0.28	-9999	-0.63	73	73
PAK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.061	0.047	-9999	-0.36	1	1
CDC42	0.013	0	-9999	-10000	0	0
RALB	0.013	0	-9999	-10000	0	0
RALA	0.013	0	-9999	-10000	0	0
PAK3	0.008	0.026	-9999	-0.29	2	2

×

Signaling events mediated by PRL

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
CCNE1	-0.006	0.074	-9999	-0.29	18	18
mol:Halofuginone	0.005	0.001	-9999	-10000	0	0
ITGA1	0.007	0.068	-9999	-0.81	2	2
CDKN1A	0.013	0.06	-9999	-0.29	1	1
PRL-3/alpha Tubulin	0.019	0	-9999	-10000	0	0
mol:Ca2+	-0.03	0.13	-9999	-0.64	13	13
AGT	-0.027	0.17	-9999	-0.74	15	15
CCNA2	-0.02	0.14	-9999	-0.45	23	23
TUBA1B	0.013	0	-9999	-10000	0	0
EGR1	-0.028	0.17	-9999	-0.62	23	23
CDK2/Cyclin E1	0.016	0.06	-9999	-10000	0	0
MAPK3	0.022	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.019	0	-9999	-10000	0	0
MAPK1	0.022	0	-9999	-10000	0	0
PTP4A1	-0.006	0.14	-9999	-0.48	23	23
PTP4A3	0.013	0	-9999	-10000	0	0
PTP4A2	0.013	0	-9999	-10000	0	0
ITGB1	0.022	0	-9999	-10000	0	0
SRC	0.011	0.018	-9999	-0.29	1	1
RAC1	0.015	0.057	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.019	0	-9999	-10000	0	0
PRL-1/ATF-5	0	0.13	-9999	-0.45	23	23
RABGGTA	0.013	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	0.015	0.057	-9999	-10000	0	0
RHOA	0.015	0.057	-9999	-10000	0	0
cell motility	0.018	0.061	-9999	-10000	0	0
PRL-1/alpha Tubulin	0	0.13	-9999	-0.44	23	23
PRL-3/alpha1 Integrin	0.014	0.053	-9999	-0.62	2	2
ROCK1	0.018	0.062	-9999	-10000	0	0
RABGGTB	0.013	0	-9999	-10000	0	0
CDK2	0.013	0	-9999	-10000	0	0
mitosis	-0.006	0.14	-9999	-0.48	23	23
ATF5	0.011	0.018	-9999	-0.29	1	1

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.008	0.16	-9999	-0.37	44	44
MAP3K8	0.011	0.005	-9999	-10000	0	0
FOS	0.01	0.096	-9999	-0.72	1	1
PRKCA	0.012	0.005	-9999	-10000	0	0
PTPN7	0.005	0.061	-9999	-0.4	5	5
HRAS	0.012	0.001	-9999	-10000	0	0
PRKCB	0.006	0.04	-9999	-0.3	5	5
NRAS	0.012	0.001	-9999	-10000	0	0
RAS family/GTP	0.022	0.009	-9999	-10000	0	0
MAPK3	0.016	0.057	-9999	-0.55	1	1
MAP2K1	0.026	0.04	-9999	-10000	0	0
ELK1	0.009	0.01	-9999	-10000	0	0
BRAF	0.022	0.028	-9999	-10000	0	0
mol:GTP	-0.001	0.002	-9999	-0.006	44	44
MAPK1	0.016	0.057	-9999	-0.55	1	1
RAF1	0.022	0.028	-9999	-10000	0	0
KRAS	0.012	0.001	-9999	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.029	0.032	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.055	0.034	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.061	0.079	-9999	-0.31	2	2
CaM/Ca2+	-0.005	0.019	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.033	0.036	-9999	-10000	0	0
AKT1	0.044	0.028	-9999	-10000	0	0
MAP2K1	0.043	0.029	-9999	-10000	0	0
MAP3K11	0.034	0.03	-9999	-10000	0	0
IFNGR1	0.014	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.21	0.25	-9999	-0.51	116	116
Rap1/GTP	-0.003	0.01	-9999	-10000	0	0
CRKL/C3G	0.019	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.029	0.034	-9999	-10000	0	0
CEBPB	0.068	0.031	-9999	-10000	0	0
STAT3	0.013	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.026	0.11	-9999	-1.2	2	2
STAT1	0.033	0.036	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.011	0.075	-9999	-0.29	20	20
PIK3CA	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.039	0.035	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	0.001	0.005	-9999	-10000	0	0
mol:Ca2+	0.026	0.031	-9999	-10000	0	0
MAPK3	0.051	0.027	-9999	-10000	0	0
STAT1 (dimer)	-0.077	0.11	-9999	-0.43	2	2
MAPK1	0.051	0.027	-9999	-10000	0	0
JAK2	0.014	0.002	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.014	0.002	-9999	-10000	0	0
CAMK2D	0.013	0	-9999	-10000	0	0
DAPK1	0.064	0.024	-9999	-10000	0	0
SMAD7	-0.002	0.065	-9999	-10000	0	0
CBL/CRKL/C3G	0.043	0.028	-9999	-10000	0	0
PI3K	-0.005	0.017	-9999	-10000	0	0
IFNG	-0.011	0.075	-9999	-0.29	20	20
apoptosis	0.04	0.026	-9999	-10000	0	0
CAMK2G	0.013	0	-9999	-10000	0	0
STAT3 (dimer)	0.012	0	-9999	-10000	0	0
CAMK2A	-0.32	0.4	-9999	-0.81	116	116
CAMK2B	-0.042	0.14	-9999	-0.34	45	45
FRAP1	0.043	0.026	-9999	-10000	0	0
PRKCD	0.046	0.028	-9999	-10000	0	0
RAP1B	0.013	0	-9999	-10000	0	0
negative regulation of cell growth	-0.061	0.079	-9999	-0.31	2	2
PTPN2	0.013	0	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
IRF1	0.061	0.041	-9999	-10000	0	0
STAT1 (dimer)/PIASy	0.036	0.037	-9999	-10000	0	0
SOCS1	-0.009	0.12	-9999	-1.4	2	2
mol:GDP	-0.004	0.014	-9999	-10000	0	0
CASP1	-0.003	0.068	-9999	-0.24	3	3
PTGES2	0.013	0	-9999	-10000	0	0
IRF9	0.053	0.013	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.016	-9999	-10000	0	0
RAP1/GDP	-0.003	0.01	-9999	-10000	0	0
CBL	0.033	0.03	-9999	-10000	0	0
MAP3K1	0.035	0.03	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
PIAS4	0.012	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.061	0.079	-9999	-0.31	2	2
PTPN11	0.027	0.031	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.016	0.15	-9999	-0.81	10	10
alphaV beta3 Integrin	-0.014	0.14	-9999	-0.62	13	13
PTK2	-0.015	0.074	-9999	-0.61	3	3
positive regulation of JNK cascade	-0.005	0.036	-9999	-0.34	3	3
CDC42/GDP	0.048	0.057	-9999	-0.46	3	3
Rac1/GDP	0.049	0.057	-9999	-0.46	3	3
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	-0.006	0.044	-9999	-0.42	3	3
nectin-3/I-afadin	0.012	0.065	-9999	-0.62	3	3
RAPGEF1	0.043	0.064	-9999	-0.53	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.037	0.073	-9999	-0.62	3	3
PDGFB-D/PDGFRB	-0.016	0.15	-9999	-0.81	10	10
TLN1	0.029	0.027	-9999	-10000	0	0
Rap1/GTP	-0.006	0.038	-9999	-0.37	3	3
IQGAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.024	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.012	0.065	-9999	-0.62	3	3
PVR	0.011	0.018	-9999	-10000	0	0
Necl-5(dimer)	0.011	0.018	-9999	-10000	0	0
mol:GDP	0.046	0.069	-9999	-0.58	3	3
MLLT4	0.013	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
PI3K	-0.021	0.095	-9999	-0.46	13	13
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.018	0.012	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.005	0.037	-9999	-0.36	3	3
PVRL1	0.011	0.018	-9999	-0.29	1	1
PVRL3	0.004	0.084	-9999	-0.81	3	3
PVRL2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	-0.056	0.23	-9999	-0.81	24	24
CLDN1	-0.085	0.14	-9999	-0.29	93	93
JAM-A/CLDN1	-0.023	0.089	-9999	-0.53	3	3
SRC	-0.011	0.074	-9999	-0.7	3	3
ITGB3	-0.031	0.18	-9999	-0.65	19	19
nectin-1(dimer)/I-afadin/I-afadin	0.018	0.012	-9999	-10000	0	0
FARP2	0.041	0.068	-9999	-0.57	3	3
RAC1	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.006	0.055	-9999	-0.54	3	3
nectin-1/I-afadin	0.018	0.012	-9999	-10000	0	0
nectin-2/I-afadin	0.019	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.006	0.055	-9999	-0.54	3	3
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.013	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.005	0.036	-9999	-0.34	3	3
alphaV/beta3 Integrin/Talin	0.017	0.1	-9999	-0.44	13	13
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.019	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.019	0	-9999	-10000	0	0
PIP5K1C	0.023	0.028	-9999	-10000	0	0
VAV2	0.04	0.069	-9999	-0.58	3	3
RAP1/GDP	-0.006	0.044	-9999	-0.43	3	3
ITGAV	0.013	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.006	0.055	-9999	-0.54	3	3
nectin-3(dimer)/I-afadin/I-afadin	0.012	0.065	-9999	-0.62	3	3
Rac1/GTP	-0.007	0.046	-9999	-0.44	3	3
PTPRM	0.016	0.031	-9999	-0.29	3	3
E-cadherin/beta catenin/alpha catenin	-0.037	0.12	-9999	-0.44	24	24
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.036	-10000	0	-0.29	4	4
EFNB1	-0.045	0.1	-10000	0	-0.62	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.038	0.072	-10000	0	-0.48	4	4
Ephrin B2/EPHB1-2	0.012	0.062	-10000	0	-0.44	4	4
neuron projection morphogenesis	-0.037	0.068	-10000	0	-0.46	4	4
Ephrin B1/EPHB1-2/Tiam1	-0.019	0.093	-10000	0	-0.52	4	4
DNM1	-0.085	0.15	-10000	0	-0.3	91	91
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.022	0.006	-10000	0	-10000	0	0
YES1	0.005	0.006	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK2	-0.019	0.093	-10000	0	-0.52	4	4
PI3K	0.023	0.005	-10000	0	-10000	0	0
mol:GDP	-0.036	0.083	-10000	0	-0.51	4	4
ITGA2B	-0.009	0.077	-10000	0	-0.29	20	20
endothelial cell proliferation	0.002	0.005	-10000	0	-10000	0	0
FYN	0.005	0.006	-10000	0	-10000	0	0
MAP3K7	0.006	0.007	-10000	0	-10000	0	0
FGR	0.003	0.015	-10000	0	-10000	0	0
TIAM1	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
RGS3	0.013	0	-10000	0	-10000	0	0
cell adhesion	0.003	0.1	-10000	0	-0.43	13	13
LYN	0.005	0.006	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/Src Family Kinases	0.003	0.004	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2	0.002	0.005	-10000	0	-10000	0	0
SRC	0.005	0.006	-10000	0	-10000	0	0
ITGB3	-0.031	0.18	-10000	0	-0.65	19	19
EPHB1	-0.006	0.098	-10000	0	-0.42	12	12
EPHB4	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.002	0.006	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.029	0.14	-10000	0	-0.62	13	13
BLK	0.003	0.01	-10000	0	-10000	0	0
HCK	0	0.017	-10000	0	-10000	0	0
regulation of stress fiber formation	0.036	0.083	0.51	4	-10000	0	4
MAPK8	0.022	0.056	-10000	0	-0.45	4	4
Ephrin B1/EPHB1-2/RGS3	-0.019	0.093	-10000	0	-0.52	4	4
endothelial cell migration	0.008	0.009	-10000	0	-10000	0	0
NCK2	0.013	0	-10000	0	-10000	0	0
PTPN13	0.007	0.008	-10000	0	-10000	0	0
regulation of focal adhesion formation	0.036	0.083	0.51	4	-10000	0	4
chemotaxis	0.036	0.083	0.51	4	-10000	0	4
PIK3CA	0.013	0	-10000	0	-10000	0	0
Rac1/GTP	-0.038	0.07	-10000	0	-0.47	4	4
angiogenesis	0.002	0.005	-10000	0	-10000	0	0
LCK	0.004	0.009	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.006	0.02	-9999	-10000	0	0
RFC1	0.006	0.02	-9999	-10000	0	0
PRKDC	0.006	0.02	-9999	-10000	0	0
RIPK1	0.013	0.003	-9999	-10000	0	0
CASP7	0.001	0.035	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.006	0.038	-9999	-10000	0	0
MAP2K4	0.016	0.094	-9999	-0.32	2	2
mol:ceramide	0.013	0.066	-9999	-10000	0	0
GSN	0.006	0.02	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	0.011	0.047	-9999	-10000	0	0
FAS	0.012	0.005	-9999	-10000	0	0
BID	0.009	0.03	-9999	-10000	0	0
MAP3K1	0.022	0.058	-9999	-10000	0	0
MAP3K7	0.011	0.004	-9999	-10000	0	0
RB1	0.006	0.02	-9999	-10000	0	0
CFLAR	0.013	0.003	-9999	-10000	0	0
HGF/MET	-0.05	0.14	-9999	-0.58	17	17
ARHGDIB	0.005	0.021	-9999	-10000	0	0
FADD	0.012	0.005	-9999	-10000	0	0
actin filament polymerization	-0.006	0.02	-9999	-10000	0	0
NFKB1	-0.025	0.061	-9999	-10000	0	0
MAPK8	-0.003	0.16	-9999	-0.45	31	31
DFFA	0.006	0.02	-9999	-10000	0	0
DNA fragmentation during apoptosis	0.006	0.02	-9999	-10000	0	0
FAS/FADD/MET	0.001	0.056	-9999	-10000	0	0
CFLAR/RIP1	0.015	0.006	-9999	-10000	0	0
FAIM3	-0.013	0.086	-9999	-0.29	25	25
FAF1	0.012	0.005	-9999	-10000	0	0
PARP1	0.006	0.02	-9999	-10000	0	0
DFFB	0.006	0.02	-9999	-10000	0	0
CHUK	-0.021	0.054	-9999	-10000	0	0
FASLG	-0.023	0.098	-9999	-0.29	33	33
FAS/FADD	0.017	0.009	-9999	-10000	0	0
HGF	-0.037	0.2	-9999	-0.81	17	17
LMNA	0.006	0.02	-9999	-10000	0	0
CASP6	0.006	0.02	-9999	-10000	0	0
CASP10	0.012	0.005	-9999	-10000	0	0
CASP3	0.006	0.022	-9999	-10000	0	0
PTPN13	0.013	0	-9999	-10000	0	0
CASP8	0.013	0.044	-9999	-10000	0	0
IL6	-0.11	0.4	-9999	-1.3	29	29
MET	-0.025	0.1	-9999	-0.29	36	36
ICAD/CAD	0.006	0.021	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	0.012	0.067	-9999	-10000	0	0
activation of caspase activity by cytochrome c	0.009	0.03	-9999	-10000	0	0
PAK2	0.006	0.02	-9999	-10000	0	0
BCL2	0.013	0.001	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.003	0.021	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.043	-9999	-10000	0	0
AP1	-0.069	0.16	-9999	-0.43	44	44
mol:PIP3	-0.004	0.02	-9999	-10000	0	0
AKT1	0.054	0.02	-9999	-10000	0	0
PTK2B	0.019	0.027	-9999	-10000	0	0
RHOA	0.028	0.015	-9999	-10000	0	0
PIK3CB	0.011	0.018	-9999	-0.29	1	1
mol:Ca2+	0.001	0.064	-9999	-10000	0	0
MAGI3	0.012	0	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
apoptosis	0.018	0.029	-9999	-10000	0	0
HRAS/GDP	0.009	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.015	0.09	-9999	-0.45	10	10
NF kappa B1 p50/RelA	-0.016	0.034	-9999	-10000	0	0
endothelial cell migration	0.018	0.066	-9999	-0.88	1	1
ADCY4	-0.003	0.12	-9999	-0.66	5	5
ADCY5	-0.002	0.11	-9999	-0.64	3	3
ADCY6	0.013	0.089	-9999	-0.54	1	1
ADCY7	0.011	0.09	-9999	-0.54	1	1
ADCY1	-0.11	0.18	-9999	-0.61	20	20
ADCY2	-0.026	0.1	-9999	-0.36	17	17
ADCY3	0.013	0.089	-9999	-0.54	1	1
ADCY8	0.01	0.09	-9999	-0.44	2	2
ADCY9	0.013	0.089	-9999	-0.54	1	1
GSK3B	0.025	0.026	-9999	-10000	0	0
arachidonic acid secretion	0.013	0.1	-9999	-0.56	1	1
GNG2	0.012	0	-9999	-10000	0	0
TRIP6	0.022	0.015	-9999	-10000	0	0
GNAO1	-0.026	0.16	-9999	-0.55	24	24
HRAS	0.013	0	-9999	-10000	0	0
NFKBIA	0.019	0.053	-9999	-10000	0	0
GAB1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.001	0.004	-9999	-10000	0	0
JUN	0.012	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.001	0.011	-9999	-10000	0	0
TIAM1	0.001	0.003	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
mol:IP3	0.001	0.065	-9999	-10000	0	0
PLCB3	0.025	0.013	-9999	-10000	0	0
FOS	-0.11	0.3	-9999	-0.81	44	44
positive regulation of mitosis	0.013	0.1	-9999	-0.56	1	1
LPA/LPA1-2-3	-0.005	0.03	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
stress fiber formation	0.028	0.027	-9999	-10000	0	0
GNAZ	0.023	0.027	-9999	-0.31	1	1
EGFR/PI3K-beta/Gab1	-0.004	0.021	-9999	-10000	0	0
positive regulation of dendritic cell cytokine production	-0.005	0.03	-9999	-10000	0	0
LPA/LPA2/MAGI-3	-0.001	0.011	-9999	-10000	0	0
ARHGEF1	0.033	0.024	-9999	-10000	0	0
GNAI2	0.023	0.027	-9999	-0.31	1	1
GNAI3	0.023	0.027	-9999	-0.31	1	1
GNAI1	0.019	0.054	-9999	-0.46	3	3
LPA/LPA3	-0.005	0.028	-9999	-10000	0	0
LPA/LPA2	-0.002	0.015	-9999	-10000	0	0
LPA/LPA1	-0.004	0.03	-9999	-0.37	1	1
HB-EGF/EGFR	-0.053	0.11	-9999	-0.54	6	6
HBEGF	-0.072	0.13	-9999	-0.62	6	6
mol:DAG	0.001	0.065	-9999	-10000	0	0
cAMP biosynthetic process	-0.026	0.14	-9999	-0.46	24	24
NFKB1	0.012	0	-9999	-10000	0	0
SRC	0.011	0.018	-9999	-0.29	1	1
GNB1	0.012	0	-9999	-10000	0	0
LYN	0.019	0.053	-9999	-10000	0	0
GNAQ	0.016	0.023	-9999	-10000	0	0
LPAR2	0.011	0.018	-9999	-0.29	1	1
LPAR3	-0.001	0.039	-9999	-0.29	5	5
LPAR1	0.014	0.018	-9999	-10000	0	0
IL8	-0.057	0.13	-9999	-0.4	10	10
PTK2	0.027	0.032	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
CASP3	0.018	0.029	-9999	-10000	0	0
EGFR	0.012	0.001	-9999	-10000	0	0
PLCG1	-0.016	0.074	-9999	-0.3	2	2
PLD2	0.027	0.032	-9999	-10000	0	0
G12/G13	-0.003	0.022	-9999	-10000	0	0
PI3K-beta	-0.002	0.014	-9999	-10000	0	0
cell migration	0.008	0.019	-9999	-10000	0	0
SLC9A3R2	0.012	0	-9999	-10000	0	0
PXN	0.028	0.027	-9999	-10000	0	0
HRAS/GTP	0.013	0.1	-9999	-0.58	1	1
RAC1	0.013	0	-9999	-10000	0	0
MMP9	-0.12	0.17	-9999	-0.31	115	115
PRKCE	0.012	0	-9999	-10000	0	0
PRKCD	0.007	0.062	-9999	-10000	0	0
Gi(beta/gamma)	0.016	0.089	-9999	-0.53	1	1
mol:LPA	0.002	0.019	-9999	-0.22	1	1
TRIP6/p130 Cas/FAK1/Paxillin	0.008	0.03	-9999	-10000	0	0
MAPKKK cascade	0.013	0.1	-9999	-0.56	1	1
contractile ring contraction involved in cytokinesis	0.028	0.015	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.078	0.18	-9999	-0.43	61	61
GNA15	0.007	0.046	-9999	-0.34	1	1
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.011	0.018	-9999	-0.29	1	1
MAPT	0.015	0.093	-9999	-0.46	10	10
GNA11	0.006	0.067	-9999	-0.43	6	6
Rac1/GTP	0.001	0.004	-9999	-10000	0	0
MMP2	0.018	0.067	-9999	-0.89	1	1

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.006	0.049	-9999	-10000	0	0
DAPP1	0.026	0.067	-9999	-0.79	1	1
Src family/SYK family/BLNK-LAT/BTK-ITK	0.013	0.095	-9999	-0.51	3	3
mol:DAG	0.014	0.071	-9999	-0.28	2	2
HRAS	0.013	0.003	-9999	-10000	0	0
RAP1A	0.013	0.003	-9999	-10000	0	0
ARF5/GDP	0.025	0.04	-9999	-0.32	2	2
PLCG2	-0.035	0.19	-9999	-0.75	18	18
PLCG1	0.013	0	-9999	-10000	0	0
ARF5	0.013	0	-9999	-10000	0	0
mol:GTP	-0.007	0.053	-9999	-0.41	5	5
ARF1/GTP	-0.007	0.051	-9999	-0.39	5	5
RHOA	0.013	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.007	0.052	-9999	-0.4	5	5
ADAP1	-0.007	0.05	-9999	-0.38	5	5
ARAP3	-0.007	0.053	-9999	-0.41	5	5
INPPL1	0.013	0	-9999	-10000	0	0
PREX1	0.007	0.068	-9999	-0.81	2	2
ARHGEF6	0.013	0	-9999	-10000	0	0
ARHGEF7	0.013	0	-9999	-10000	0	0
ARF1	0.013	0	-9999	-10000	0	0
NRAS	0.013	0.003	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
FGR	-0.001	0.073	-9999	-0.34	11	11
mol:Ca2+	0.016	0.039	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.013	0	-9999	-10000	0	0
ZAP70	-0.025	0.1	-9999	-0.29	36	36
mol:IP3	0.018	0.051	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
ARF1/GDP	0.025	0.04	-9999	-0.32	2	2
RhoA/GDP	-0.002	0.051	-9999	-0.45	1	1
PDK1/Src/Hsp90	-0.001	0.009	-9999	-10000	0	0
BLNK	-0.016	0.15	-9999	-0.81	10	10
actin cytoskeleton reorganization	0.038	0.068	-9999	-0.48	2	2
SRC	0.011	0.018	-9999	-0.29	1	1
PLEKHA2	0.022	0.032	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
PTEN	0.001	0.006	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.006	0.049	-9999	-10000	0	0
RhoA/GTP	-0.007	0.05	-9999	-0.38	5	5
Src family/SYK family/BLNK-LAT	0.01	0.086	-9999	-0.38	3	3
BLK	-0.004	0.065	-9999	-0.29	14	14
PDPK1	0.013	0	-9999	-10000	0	0
CYTH1	-0.007	0.05	-9999	-0.38	5	5
HCK	-0.022	0.1	-9999	-0.31	31	31
CYTH3	-0.007	0.05	-9999	-0.38	5	5
CYTH2	-0.007	0.05	-9999	-0.38	5	5
KRAS	0.013	0.003	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0.038	0.03	-9999	-10000	0	0
SGK1	-0.004	0.026	-9999	-10000	0	0
INPP5D	0.002	0.056	-9999	-0.29	10	10
mol:GDP	0.019	0.042	-9999	-0.34	2	2
SOS1	0.013	0	-9999	-10000	0	0
SYK	0.01	0.048	-9999	-0.81	1	1
ARF6/GDP	-0.002	0.051	-9999	-0.45	1	1
mol:PI-3-4-5-P3	-0.007	0.053	-9999	-0.4	5	5
ARAP3/RAP1A/GTP	-0.007	0.053	-9999	-0.41	5	5
VAV1	-0.063	0.14	-9999	-0.3	70	70
mol:PI-3-4-P2	0.014	0.038	-9999	-10000	0	0
RAS family/GTP/PI3K Class I	0.022	0.057	-9999	-0.41	5	5
PLEKHA1	0.022	0.032	-9999	-10000	0	0
Rac1/GDP	0.025	0.04	-9999	-0.32	2	2
LAT	-0.017	0.09	-9999	-0.29	28	28
Rac1/GTP	0.018	0.056	-9999	-0.69	1	1
ITK	-0.01	0.052	-9999	-0.38	5	5
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.012	0.092	-9999	-0.41	2	2
LCK	0.005	0.047	-9999	-0.29	7	7
BTK	-0.037	0.064	-9999	-0.38	5	5

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.019	0.003	-9999	-10000	0	0
RAS family/GTP	-0.001	0.053	-9999	-10000	0	0
NFATC4	0.023	0.066	-9999	-0.38	2	2
ERBB2IP	0.013	0.001	-9999	-10000	0	0
HSP90 (dimer)	0.012	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.005	0.068	-9999	-0.39	8	8
JUN	-0.001	0.051	-9999	-0.26	1	1
HRAS	0.012	0.001	-9999	-10000	0	0
DOCK7	-0.001	0.066	-9999	-0.37	8	8
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.009	0.08	-9999	-0.47	8	8
AKT1	0.011	0.002	-9999	-10000	0	0
BAD	0.019	0.001	-9999	-10000	0	0
MAPK10	0.02	0.038	-9999	-10000	0	0
mol:GTP	-0.002	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.003	0.074	-9999	-0.42	8	8
RAF1	0.003	0.057	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.011	0.072	-9999	-0.5	6	6
STAT3	0	0.007	-9999	-10000	0	0
cell migration	0.034	0.043	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	-0.11	0.14	-9999	-0.44	22	22
FOS	-0.11	0.19	-9999	-0.53	44	44
NRAS	0.012	0.001	-9999	-10000	0	0
mol:Ca2+	-0.005	0.068	-9999	-0.39	8	8
MAPK3	-0.08	0.11	-9999	-0.39	1	1
MAPK1	-0.08	0.11	-9999	-0.39	1	1
JAK2	-0.001	0.066	-9999	-0.37	8	8
NF2	-0.001	0.008	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.013	0.063	-9999	-0.36	8	8
NRG1	-0.006	0.11	-9999	-0.62	8	8
GRB2/SOS1	0.016	0.005	-9999	-10000	0	0
MAPK8	-0.004	0.074	-9999	-0.34	12	12
MAPK9	0.02	0.038	-9999	-10000	0	0
ERBB2	0	0	-9999	-10000	0	0
ERBB3	0.003	0.084	-9999	-0.81	3	3
SHC1	0.011	0.001	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
apoptosis	0	0.005	-9999	-10000	0	0
STAT3 (dimer)	0.019	0.009	-9999	-10000	0	0
RNF41	0.025	0.004	-9999	-10000	0	0
FRAP1	0.01	0.001	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.008	0.044	-9999	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	0	0	-9999	-10000	0	0
CHRNA1	-0.12	0.12	-9999	-0.35	24	24
myelination	0.027	0.063	-9999	-10000	0	0
PPP3CB	-0.001	0.062	-9999	-0.35	4	4
KRAS	0.012	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	0.026	0.056	-9999	-10000	0	0
NRG2	0.003	0.085	-9999	-0.68	4	4
mol:GDP	0.013	0.063	-9999	-0.35	8	8
SOS1	0.012	0.001	-9999	-10000	0	0
MAP2K2	0.003	0.059	-9999	-10000	0	0
SRC	0.011	0.018	-9999	-0.29	1	1
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	-0.001	0.066	-9999	-0.37	8	8
MAP2K1	-0.07	0.1	-9999	-0.41	4	4
heart morphogenesis	-0.005	0.068	-9999	-0.39	8	8
RAS family/GDP	0.002	0.054	-9999	-10000	0	0
GRB2	0.012	0.001	-9999	-10000	0	0
PRKACA	-0.001	0.004	-9999	-10000	0	0
CHRNE	0.003	0.015	-9999	-0.13	1	1
HSP90AA1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.011	0.002	-9999	-10000	0	0
nervous system development	-0.005	0.068	-9999	-0.39	8	8
CDC42	0.013	0	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.013	0	-9999	-10000	0	0
ANTXR2	0.013	0	-9999	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0	-9999	-10000	0	0
monocyte activation	-0.007	0.067	-9999	-0.44	4	4
MAP2K2	0	0	-9999	-10000	0	0
MAP2K1	0	0	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
MAP2K6	0	0	-9999	-10000	0	0
CYAA	0.014	0	-9999	-10000	0	0
MAP2K4	0	0	-9999	-10000	0	0
IL1B	0.007	0.064	-9999	-0.47	5	5
Channel	0.016	0	-9999	-10000	0	0
NLRP1	-0.001	0.011	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
negative regulation of phagocytosis	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
regulation of endothelial cell proliferation	0	0	-9999	-10000	0	0
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
PGR	-0.2	0.24	-9999	-0.48	120	120
PA/Cellular Receptors	0	0	-9999	-10000	0	0
apoptosis	0	0	-9999	-10000	0	0
LOC728358	0	0	-9999	-10000	0	0
Lethal toxin (unfolded)	0.016	0	-9999	-10000	0	0
macrophage activation	0.018	0	-9999	-10000	0	0
TNF	-0.011	0.1	-9999	-0.38	17	17
VCAM1	-0.007	0.067	-9999	-0.45	4	4
platelet activation	0	0	-9999	-10000	0	0
MAPKKK cascade	-0.016	0	-9999	-10000	0	0
IL18	0.014	0.019	-9999	-10000	0	0
negative regulation of macrophage activation	0	0	-9999	-10000	0	0
LEF	0	0	-9999	-10000	0	0
CASP1	-0.001	0.006	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
necrosis	0	0	-9999	-10000	0	0
intracellular pH reduction	0	0	-9999	-10000	0	0
PAGA	0	0	-9999	-10000	0	0
Edema toxin (unfolded)	0.016	0	-9999	-10000	0	0
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-9999	-10000	0	0

×

PLK1 signaling 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	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	0.032	0.1	8	-10000	0	8
BUB1B	-0.001	0.053	-10000	0	-0.19	3	3
PLK1	0.007	0.02	-10000	0	-10000	0	0
PLK1S1	0.009	0.011	-10000	0	-10000	0	0
KIF2A	0.014	0.018	-10000	0	-10000	0	0
regulation of mitotic centrosome separation	0.007	0.02	-10000	0	-10000	0	0
GOLGA2	0.013	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.022	0.1	-10000	0	-0.31	6	6
WEE1	0.014	0.019	-10000	0	-10000	0	0
cytokinesis	-0.027	0.083	-10000	0	-0.33	1	1
PP2A-alpha B56	-0.006	0.054	-10000	0	-10000	0	0
AURKA	0.008	0.017	-10000	0	-10000	0	0
PICH/PLK1	0.01	0.062	-10000	0	-0.37	1	1
CENPE	0.003	0.052	-10000	0	-0.21	1	1
RhoA/GTP	0.009	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.014	0.018	-10000	0	-10000	0	0
PPP2CA	0.013	0	-10000	0	-10000	0	0
FZR1	0.013	0	-10000	0	-10000	0	0
TPX2	-0.01	0.042	-10000	0	-10000	0	0
PAK1	0.012	0	-10000	0	-10000	0	0
SPC24	-0.046	0.12	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
CLSPN	-0.004	0.038	-10000	0	-0.12	5	5
GORASP1	0.013	0	-10000	0	-10000	0	0
metaphase	-0.001	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.004	0.011	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0.001	-10000	0	-10000	0	0
STAG2	0.013	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.007	0.01	-10000	0	-10000	0	0
spindle elongation	0.007	0.02	-10000	0	-10000	0	0
ODF2	0.012	0.001	-10000	0	-10000	0	0
BUB1	-0.036	0.049	-10000	0	-10000	0	0
TPT1	0.009	0.011	-10000	0	-10000	0	0
CDC25C	-0.017	0.052	-10000	0	-10000	0	0
CDC25B	0.011	0.026	-10000	0	-0.3	2	2
SGOL1	0	0.032	-10000	0	-0.1	8	8
RHOA	0.013	0	-10000	0	-10000	0	0
CCNB1/CDK1	0.002	0.024	-10000	0	-10000	0	0
CDC14B	0.011	0	-10000	0	-10000	0	0
CDC20	-0.022	0.097	-10000	0	-0.29	33	33
PLK1/PBIP1	-0.016	0.048	-10000	0	-0.16	24	24
mitosis	0	0.002	-10000	0	-10000	0	0
FBXO5	0.014	0.015	-10000	0	-10000	0	0
CDC2	0.001	0.002	-10000	0	-0.013	1	1
NDC80	-0.023	0.098	-10000	0	-10000	0	0
metaphase plate congression	0.008	0.014	-10000	0	-10000	0	0
ERCC6L	-0.011	0.052	-10000	0	-0.36	1	1
NLP/gamma Tubulin	0.007	0.012	-10000	0	-10000	0	0
microtubule cytoskeleton organization	0.009	0.011	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0	0	-10000	0	-10000	0	0
PPP1R12A	0.013	0	-10000	0	-10000	0	0
interphase	0	0	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.032	0.09	-10000	0	-0.29	10	10
GRASP65/GM130/RAB1/GTP/PLK1	0.005	0.011	-10000	0	-10000	0	0
RAB1A	0.013	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.014	0.014	-10000	0	-10000	0	0
mitotic prometaphase	-0.001	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.023	-10000	0	-10000	0	0
microtubule-based process	-0.037	0.083	-10000	0	-0.21	2	2
Golgi organization	0.007	0.02	-10000	0	-10000	0	0
Cohesin/SA2	-0.005	0.01	-10000	0	-10000	0	0
PPP1CB/MYPT1	0.018	0.003	-10000	0	-10000	0	0
KIF20A	-0.092	0.14	-10000	0	-0.29	99	99
APC/C/CDC20	-0.003	0.061	-10000	0	-0.21	2	2
PPP2R1A	0.013	0	-10000	0	-10000	0	0
chromosome segregation	-0.016	0.047	-10000	0	-0.16	24	24
PRC1	0.002	0.056	-10000	0	-0.29	10	10
ECT2	0.013	0.023	-10000	0	-10000	0	0
C13orf34	0.013	0.015	-10000	0	-10000	0	0
NUDC	0.008	0.014	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.001	0.052	-10000	0	-0.19	3	3
spindle assembly	0.009	0.016	-10000	0	-10000	0	0
spindle stabilization	0.009	0.011	-10000	0	-10000	0	0
APC/C/HCDH1	0.017	0	-10000	0	-10000	0	0
MKLP2/PLK1	-0.037	0.084	-10000	0	-0.21	2	2
CCNB1	0.009	0.036	-10000	0	-0.3	4	4
PPP1CB	0.013	0	-10000	0	-10000	0	0
BTRC	0.013	0	-10000	0	-10000	0	0
ROCK2	0.007	0.068	-10000	0	-0.5	5	5
TUBG1	0.009	0.011	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.004	0.022	-10000	0	-10000	0	0
MLF1IP	-0.011	0.064	-10000	0	-0.2	29	29
INCENP	0.012	0.001	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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	0.031	0.059	-10000	0	-10000	0	0
UGCG	0.017	0.041	-10000	0	-0.62	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.038	0.063	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.019	0.04	-10000	0	-0.61	1	1
mol:DAG	0.001	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.009	0.035	-10000	0	-10000	0	0
FRAP1	0.053	0.066	-10000	0	-10000	0	0
FOXO3	0.057	0.062	-10000	0	-10000	0	0
AKT1	0.052	0.065	-10000	0	-10000	0	0
GAB2	0.013	0.002	-10000	0	-10000	0	0
SMPD1	0.019	0.018	-10000	0	-10000	0	0
SGMS1	0.019	0.018	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.021	0.003	-10000	0	-10000	0	0
CALM1	0.013	0	-10000	0	-10000	0	0
cell proliferation	0.035	0.039	-10000	0	-0.29	1	1
EIF3A	0.013	0	-10000	0	-10000	0	0
PI3K	0.024	0.003	-10000	0	-10000	0	0
RPS6KB1	0.005	0.041	-10000	0	-10000	0	0
mol:sphingomyelin	0.001	0.002	-10000	0	-10000	0	0
natural killer cell activation	0.001	0.001	-10000	0	-10000	0	0
JAK3	-0.045	0.12	-10000	0	-0.29	1	1
PIK3R1	0.015	0.001	-10000	0	-10000	0	0
JAK1	0.015	0.001	-10000	0	-10000	0	0
NFKB1	0.013	0	-10000	0	-10000	0	0
MYC	0.055	0.067	-10000	0	-10000	0	0
MYB	-0.057	0.13	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.044	0.065	-10000	0	-0.36	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.019	0.038	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.044	0.065	-10000	0	-0.35	1	1
Rac1/GDP	0.027	0.004	-10000	0	-10000	0	0
T cell proliferation	0.049	0.062	-10000	0	-10000	0	0
SHC1	0.013	0.002	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.003	0.014	-10000	0	-0.028	68	68
PRKCZ	0.049	0.063	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.005	0.042	-10000	0	-10000	0	0
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.024	0.064	-10000	0	-0.36	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL2RA	-0.018	0.092	-10000	0	-10000	0	0
IL2RB	-0.019	0.097	-10000	0	-0.3	1	1
TERT	-0.038	0.1	-10000	0	-0.29	40	40
E2F1	-0.04	0.094	-10000	0	-0.26	8	8
SOS1	0.013	0.002	-10000	0	-10000	0	0
RPS6	0.013	0	-10000	0	-10000	0	0
mol:cAMP	0.001	0.007	0.014	68	-10000	0	68
PTPN11	0.013	0.002	-10000	0	-10000	0	0
IL2RG	0.006	0.053	-10000	0	-0.29	9	9
actin cytoskeleton organization	0.049	0.062	-10000	0	-10000	0	0
GRB2	0.013	0.002	-10000	0	-10000	0	0
IL2	0.006	0.018	-10000	0	-10000	0	0
PIK3CA	0.015	0.001	-10000	0	-10000	0	0
Rac1/GTP	0.029	0.013	-10000	0	-10000	0	0
LCK	0.008	0.047	-10000	0	-0.29	7	7
BCL2	0.057	0.058	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.003	0.077	-10000	0	-0.81	2	2
CLTC	0.03	0.01	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.026	0.001	-10000	0	-10000	0	0
Dynamin 2/GTP	0.022	0.015	-10000	0	-10000	0	0
EXOC4	0.013	0	-10000	0	-10000	0	0
CD59	0.027	0.007	-10000	0	-10000	0	0
CPE	0.015	0.022	-10000	0	-10000	0	0
CTNNB1	0.013	0	-10000	0	-10000	0	0
membrane fusion	0.025	0	-10000	0	-10000	0	0
CTNND1	0.029	0.014	-10000	0	-10000	0	0
DNM2	0.013	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.031	0.005	-10000	0	-10000	0	0
TSHR	0.014	0.018	-10000	0	-10000	0	0
INS	0.011	0.006	-10000	0	-10000	0	0
BIN1	0.007	0.068	-10000	0	-0.81	2	2
mol:Choline	0.025	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.016	0.017	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0.021	0.015	-10000	0	-10000	0	0
JUP	0.027	0.007	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.019	0.053	-10000	0	-0.5	3	3
ARF6/GTP	0.009	0	-10000	0	-10000	0	0
CDH1	0.002	0.082	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.009	0	-10000	0	-10000	0	0
MAPK8IP3	0.005	0.047	-10000	0	-0.29	7	7
positive regulation of endocytosis	0.009	0	-10000	0	-10000	0	0
EXOC2	0.013	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.041	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.013	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.016	0.051	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.018	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	-0.004	0.024	-10000	0	-10000	0	0
ACAP1	0.021	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.022	0.007	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.034	0.009	-10000	0	-10000	0	0
JIP4/KLC1	0.024	0	-10000	0	-10000	0	0
EXOC1	0.013	0	-10000	0	-10000	0	0
exocyst	0.041	0	-10000	0	-10000	0	0
RALA/GTP	0.009	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0.009	0	-10000	0	-10000	0	0
CTNNA1	0.029	0.014	-10000	0	-10000	0	0
NME1	0.016	0.017	-10000	0	-10000	0	0
clathrin coat assembly	0.03	0.01	-10000	0	-10000	0	0
IL2RA	0.018	0.027	-10000	0	-10000	0	0
VAMP3	0.018	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.004	0.035	-10000	0	-0.4	2	2
EXOC6	0.013	0	-10000	0	-10000	0	0
PLD1	0.021	0	-10000	0	-10000	0	0
PLD2	0.021	0	-10000	0	-10000	0	0
EXOC5	0.013	0	-10000	0	-10000	0	0
PIP5K1C	0.031	0.005	-10000	0	-10000	0	0
SDC1	0.026	0.019	-10000	0	-10000	0	0
ARF6/GDP	0.016	0.017	-10000	0	-10000	0	0
EXOC7	0.013	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.017	0.053	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.025	0	-10000	0	-10000	0	0
endocytosis	0.005	0.05	0.49	3	-10000	0	3
SCAMP2	0.013	0	-10000	0	-10000	0	0
ADRB2	0.027	0.033	-10000	0	-10000	0	0
EXOC3	0.013	0	-10000	0	-10000	0	0
ASAP2	0.01	0.048	-10000	0	-0.81	1	1
Dynamin 2/GDP	0.023	0.015	-10000	0	-10000	0	0
KLC1	0.013	0	-10000	0	-10000	0	0
AVPR2	-0.35	0.18	-10000	0	-0.43	235	235
RALA	0.013	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.015	0.046	-10000	0	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.013	0	-9999	-10000	0	0
PTK2	0.013	0	-9999	-10000	0	0
CRKL	0.009	0.082	-9999	-0.4	11	11
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0.013	0	-9999	-10000	0	0
IRS1/Crk	0.009	0.082	-9999	-0.4	11	11
IGF-1R heterotetramer/IGF1/PTP1B	-0.012	0.073	-9999	-0.51	6	6
AKT1	0.029	0.072	-9999	-10000	0	0
BAD	0.035	0.068	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.009	0.082	-9999	-0.4	11	11
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.009	0.082	-9999	-0.4	11	11
RAF1	0.039	0.065	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.017	0.079	-9999	-0.41	6	6
YWHAZ	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.002	0.088	-9999	-0.44	11	11
PIK3CA	0.013	0	-9999	-10000	0	0
RPS6KB1	0.029	0.072	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.033	0.057	-9999	-10000	0	0
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0.019	0	-9999	-10000	0	0
HRAS/GTP	-0.013	0.064	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.026	0.063	-9999	-0.4	6	6
IGF-1R heterotetramer	0.009	0.019	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.01	0.083	-9999	-0.4	11	11
Crk/p130 Cas/Paxillin	0.022	0.076	-9999	-0.39	6	6
IGF1R	0.009	0.019	-9999	-10000	0	0
IGF1	-0.006	0.12	-9999	-0.82	6	6
IRS2/Crk	0.016	0.079	-9999	-0.38	11	11
PI3K	0.017	0.079	-9999	-0.41	6	6
apoptosis	-0.039	0.061	-9999	-10000	0	0
HRAS/GDP	0.009	0	-9999	-10000	0	0
PRKCD	0.026	0.079	-9999	-0.49	6	6
RAF1/14-3-3 E	0.043	0.058	-9999	-10000	0	0
BAD/14-3-3	0.04	0.064	-9999	-10000	0	0
PRKCZ	0.029	0.072	-9999	-10000	0	0
Crk/p130 Cas/Paxillin/FAK1	-0.01	0.053	-9999	-10000	0	0
PTPN1	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.02	0.083	-9999	-0.52	6	6
BCAR1	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.01	0.063	-9999	-0.44	6	6
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
IRS1/NCK2	0.009	0.082	-9999	-0.4	11	11
GRB10	0.013	0	-9999	-10000	0	0
PTPN11	0.009	0.082	-9999	-0.4	11	11
IRS1	0.002	0.088	-9999	-0.44	11	11
IRS2	0.008	0.083	-9999	-0.4	11	11
IGF-1R heterotetramer/IGF1	0.002	0.094	-9999	-0.64	6	6
GRB2	0.013	0	-9999	-10000	0	0
PDPK1	0.022	0.075	-9999	-0.38	6	6
YWHAE	0.013	0	-9999	-10000	0	0
PRKD1	0.026	0.079	-9999	-0.49	6	6
SHC1	0.013	0	-9999	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.059	0.23	-9999	-0.81	24	24
CDC42/GTP	-0.027	0.083	-9999	-10000	0	0
PLCG1	0.006	0.097	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0.018	0.012	-9999	-10000	0	0
cell migration	-0.027	0.081	-9999	-10000	0	0
S1PR5	-0.002	0.094	-9999	-0.46	9	9
S1PR4	0.006	0.043	-9999	-0.29	6	6
MAPK3	0.006	0.097	-9999	-10000	0	0
MAPK1	0.006	0.097	-9999	-10000	0	0
S1P/S1P5/Gi	-0.006	0.11	-9999	-0.33	27	27
GNAI1	0.007	0.068	-9999	-0.81	2	2
CDC42/GDP	0.009	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.009	0.059	-9999	-0.55	3	3
RHOA	0.027	0.022	-9999	-10000	0	0
S1P/S1P4/Gi	-0.002	0.1	-9999	-0.33	24	24
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
S1P/S1P4/G12/G13	0.021	0.024	-9999	-10000	0	0
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.011	0.018	-9999	-0.29	1	1
CDC42	0.013	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.032	0	-10000	0	-10000	0	0
HDAC3	0.013	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.024	-10000	0	-0.41	1	1
GATA1/HDAC4	0.003	0.061	-10000	0	-0.63	1	1
GATA1/HDAC5	0.005	0.048	-10000	0	-10000	0	0
GATA2/HDAC5	-0.12	0.26	-10000	0	-0.62	60	60
HDAC5/BCL6/BCoR	-0.001	0.009	-10000	0	-10000	0	0
HDAC9	0.013	0	-10000	0	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
HDAC4/ANKRA2	0.016	0.038	-10000	0	-0.62	1	1
HDAC5/YWHAB	0.019	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.021	0	-10000	0	-10000	0	0
GATA2	-0.16	0.33	-10000	0	-0.81	60	60
HDAC4/RFXANK	0.016	0.038	-10000	0	-0.62	1	1
BCOR	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.013	0	-10000	0	-10000	0	0
HDAC5	0.013	0	-10000	0	-10000	0	0
GNB1/GNG2	0.019	0	-10000	0	-10000	0	0
Histones	0.038	0.018	-10000	0	-10000	0	0
ADRBK1	0.013	0	-10000	0	-10000	0	0
HDAC4	0.01	0.048	-10000	0	-0.81	1	1
XPO1	0.013	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.019	0	-10000	0	-10000	0	0
HDAC4/Ubc9	0.016	0.038	-10000	0	-0.62	1	1
HDAC7	0.013	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.019	0	-10000	0	-10000	0	0
TUBA1B	0.013	0	-10000	0	-10000	0	0
HDAC6	0.013	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.019	0	-10000	0	-10000	0	0
CAMK4	0.012	0.002	-10000	0	-10000	0	0
Tubulin/HDAC6	0	0	-10000	0	-10000	0	0
SUMO1	0.013	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
GATA1	-0.008	0.071	-10000	0	-0.29	17	17
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0
NR3C1	0.013	0	-10000	0	-10000	0	0
SUMO1/HDAC4	0.027	0.028	-10000	0	-0.45	1	1
SRF	0.013	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.016	0.038	-10000	0	-0.62	1	1
Tubulin	0.019	0	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.016	0.038	-10000	0	-0.62	1	1
GNB1	0.013	0	-10000	0	-10000	0	0
RANGAP1	0.013	0	-10000	0	-10000	0	0
BCL6/BCoR	0.018	0.012	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	-0.002	0.032	-10000	0	-0.54	1	1
HDAC4/SRF	-0.002	0.032	-10000	0	-0.54	1	1
HDAC4/ER alpha	-0.021	0.16	-10000	0	-0.62	18	18
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.037	0.017	-10000	0	-10000	0	0
cell motility	0	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.013	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.019	0	-10000	0	-10000	0	0
BCL6	0.011	0.018	-10000	0	-0.29	1	1
HDAC4/CaMK II delta B	0.01	0.048	-10000	0	-0.81	1	1
Hsp90/HDAC6	0.019	0	-10000	0	-10000	0	0
ESR1	-0.036	0.19	-10000	0	-0.81	17	17
HDAC6/HDAC11	0.019	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.032	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	0.013	0	-10000	0	-10000	0	0
RAN	0.013	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.002	0.027	-10000	0	-0.46	1	1
GNG2	0.013	0	-10000	0	-10000	0	0
NCOR2	0.013	0	-10000	0	-10000	0	0
TUBB2A	0.013	0	-10000	0	-10000	0	0
HDAC11	0.013	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0	-10000	0	-10000	0	0
RANBP2	0.013	0	-10000	0	-10000	0	0
ANKRA2	0.013	0	-10000	0	-10000	0	0
RFXANK	0.013	0	-10000	0	-10000	0	0
nuclear import	-0.026	0.027	0.44	1	-10000	0	1

×

Aurora A 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.028	0.015	-9999	-10000	0	0
BIRC5	-0.095	0.14	-9999	-0.29	102	102
NFKBIA	0.031	0.016	-9999	-10000	0	0
CPEB1	-0.02	0.12	-9999	-0.38	24	24
AKT1	0.031	0.016	-9999	-10000	0	0
NDEL1	0.013	0	-9999	-10000	0	0
Aurora A/BRCA1	0.012	0.025	-9999	-10000	0	0
NDEL1/TACC3	0.015	0.029	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GSK3B	0.015	0.006	-9999	-10000	0	0
PAK1/Aurora A	0.028	0.015	-9999	-10000	0	0
MDM2	0.013	0	-9999	-10000	0	0
JUB	0.013	0	-9999	-10000	0	0
TPX2	-0.034	0.092	-9999	-10000	0	0
TP53	0.03	0.011	-9999	-10000	0	0
DLG7	0.022	0.016	-9999	-10000	0	0
AURKAIP1	0.013	0	-9999	-10000	0	0
ARHGEF7	0.013	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.031	0.027	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.009	0.025	-9999	-10000	0	0
AURKA	0.027	0.02	-9999	-10000	0	0
AURKB	-0.044	0.047	-9999	-10000	0	0
CDC25B	0.03	0.019	-9999	-10000	0	0
G2/M transition checkpoint	0.011	0.019	-9999	-10000	0	0
mRNA polyadenylation	-0.007	0.068	-9999	-0.48	4	4
Aurora A/CPEB	-0.004	0.069	-9999	-0.49	4	4
Aurora A/TACC1/TRAP/chTOG	0.04	0.013	-9999	-10000	0	0
BRCA1	0.009	0.031	-9999	-0.29	3	3
centrosome duplication	0.028	0.015	-9999	-10000	0	0
regulation of centrosome cycle	0.01	0.029	-9999	-10000	0	0
spindle assembly	0.021	0.024	-9999	-10000	0	0
TDRD7	0.013	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.032	0.056	-9999	-10000	0	0
CENPA	-0.026	0.05	-9999	-10000	0	0
Aurora A/PP2A	0.027	0.018	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.036	0.014	-9999	-10000	0	0
negative regulation of DNA binding	0.03	0.011	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.019	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
Ajuba/Aurora A	0.014	0.019	-9999	-10000	0	0
mitotic prometaphase	0.014	0.015	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.02	-9999	-10000	0	0
TACC1	0.013	0	-9999	-10000	0	0
TACC3	0.007	0.04	-9999	-0.29	5	5
Aurora A/Antizyme1	0.034	0.014	-9999	-10000	0	0
Aurora A/RasGAP	0.028	0.015	-9999	-10000	0	0
OAZ1	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.015	0.006	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.034	0.092	-9999	-10000	0	0
PPP2R5D	0.011	0.018	-9999	-0.29	1	1
Aurora A/TPX2	-0.007	0.068	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
CKAP5	0.013	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.022	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0.032	0	-9999	-10000	0	0
CDKN1B	0.035	0.003	-9999	-10000	0	0
CDKN1A	0.032	0.021	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.013	0	-9999	-10000	0	0
FOXO3	0.035	0.003	-9999	-10000	0	0
AKT1	0	0.002	-9999	-10000	0	0
BAD	0.013	0	-9999	-10000	0	0
AKT3	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.035	0.003	-9999	-10000	0	0
AKT1/ASK1	0.033	0.003	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.013	0	-9999	-10000	0	0
RAF1	0.013	0	-9999	-10000	0	0
JNK cascade	0	0.001	-9999	-10000	0	0
TSC1	0.035	0.003	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
AKT1/RAF1	0.035	0.003	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
mol:GDP	0.029	0.003	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.035	0.003	-9999	-10000	0	0
YWHAQ	0.013	0	-9999	-10000	0	0
TBC1D4	0.023	0	-9999	-10000	0	0
MAP3K5	0.013	0	-9999	-10000	0	0
MAPKAP1	0.013	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.015	0.034	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0
AKT1S1	0.035	0.003	-9999	-10000	0	0
CASP9	0.035	0.003	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.041	0.003	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.009	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
SRC	0.011	0.018	-9999	-0.29	1	1
AKT2/p21CIP1	-0.002	0.014	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.001	-9999	-10000	0	0
CHUK	0.035	0.003	-9999	-10000	0	0
BAD/BCL-XL	0.047	0.003	-9999	-10000	0	0
mTORC2	0.016	0	-9999	-10000	0	0
AKT2	0.016	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.027	0.038	-9999	-10000	0	0
PDPK1	0.013	0	-9999	-10000	0	0
MDM2	0.035	0.003	-9999	-10000	0	0
MAPKKK cascade	-0.035	0.003	-9999	-10000	0	0
MDM2/Cbp/p300	0.047	0.003	-9999	-10000	0	0
TSC1/TSC2	0.041	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.044	0.003	-9999	-10000	0	0
glucose import	0.023	0.046	-9999	-0.48	2	2
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.03	0.002	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.023	0.046	-9999	-0.49	2	2
GSK3A	0.035	0.003	-9999	-10000	0	0
FOXO1	0.035	0.003	-9999	-10000	0	0
GSK3B	0.035	0.003	-9999	-10000	0	0
SFN	-0.14	0.18	-9999	-0.31	135	135
G1/S transition of mitotic cell cycle	0.041	0.003	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.007	0.049	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
KPNA1	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
RHEB	0.013	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.029	0.009	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
DOCK1	0.013	0	-9999	-10000	0	0
ITGA4	0.011	0.018	-9999	-0.29	1	1
alpha4/beta7 Integrin/MAdCAM1	0.01	0.053	-9999	-10000	0	0
EPO	0.007	0.026	-9999	-0.29	2	2
alpha4/beta7 Integrin	0.018	0.012	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.018	0.012	-9999	-10000	0	0
EPO/EPOR (dimer)	0.014	0.017	-9999	-10000	0	0
lamellipodium assembly	0.003	0.008	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
PI3K	0.019	0	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
JAK2	0.03	0.012	-9999	-10000	0	0
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
MADCAM1	-0.03	0.1	-9999	-0.29	39	39
cell adhesion	-0.017	0.042	-9999	-10000	0	0
CRKL/CBL	0.019	0	-9999	-10000	0	0
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.01	0.059	-9999	-0.49	1	1
ITGB7	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.02	0.057	-9999	-0.54	1	1
p130Cas/Crk/Dock1	0.03	0.051	-9999	-0.41	1	1
VCAM1	-0.028	0.11	-9999	-0.31	37	37
RHOA	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.032	0.009	-9999	-10000	0	0
BCAR1	0.017	0.056	-9999	-0.45	1	1
EPOR	0.013	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
Rac1/GTP	0.003	0.008	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.013	0.05	-10000	0	-10000	0	0
oxygen homeostasis	0.009	0.013	-10000	0	-10000	0	0
TCEB2	0.01	0.025	-10000	0	-0.29	2	2
TCEB1	0.013	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.002	0.041	-10000	0	-0.41	1	1
EPO	0.12	0.16	-10000	0	-0.54	2	2
FIH (dimer)	0.022	0.012	-10000	0	-10000	0	0
APEX1	0.02	0.013	-10000	0	-10000	0	0
SERPINE1	0.095	0.24	-10000	0	-0.76	13	13
FLT1	-0.033	0.12	-10000	0	-1.4	2	2
ADORA2A	0.12	0.16	-10000	0	-0.59	1	1
germ cell development	0.092	0.2	-10000	0	-0.59	1	1
SLC11A2	0.12	0.17	-10000	0	-0.61	1	1
BHLHE40	0.12	0.17	-10000	0	-0.61	1	1
HIF1AN	0.022	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.007	0.063	-10000	0	-0.5	1	1
ETS1	0.015	0.033	-10000	0	-10000	0	0
CITED2	-0.001	0.009	-10000	0	-10000	0	0
KDR	-0.22	0.47	-10000	0	-1.2	52	52
PGK1	0.12	0.17	-10000	0	-0.61	1	1
SIRT1	0.013	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.13	0.19	-10000	0	-0.71	1	1
EPAS1	0.073	0.086	-10000	0	-0.48	1	1
SP1	0.019	0.004	-10000	0	-10000	0	0
ABCG2	0.11	0.18	-10000	0	-0.78	3	3
EFNA1	0.12	0.17	-10000	0	-0.61	1	1
FXN	0.12	0.16	-10000	0	-0.59	1	1
POU5F1	0.092	0.2	-10000	0	-0.61	1	1
neuron apoptosis	-0.12	0.18	0.69	1	-10000	0	1
EP300	0.013	0	-10000	0	-10000	0	0
EGLN3	0.01	0.06	-10000	0	-0.28	11	11
EGLN2	0.022	0.012	-10000	0	-10000	0	0
EGLN1	0.022	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.001	0.012	-10000	0	-10000	0	0
VHL	0.013	0	-10000	0	-10000	0	0
ARNT	0.02	0.013	-10000	0	-10000	0	0
SLC2A1	0.11	0.17	-10000	0	-0.57	2	2
TWIST1	0.11	0.17	-10000	0	-0.69	3	3
ELK1	0.02	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.006	0.061	-10000	0	-0.5	1	1
VEGFA	0.12	0.17	-10000	0	-0.61	1	1
CREBBP	0.013	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.021	0.059	-9999	-0.54	3	3
SNTA1	0.003	0.085	-9999	-0.68	4	4
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.022	0.057	-9999	-0.54	3	3
MAPK12	0.025	0.034	-9999	-0.49	1	1
CCND1	0.018	0.031	-9999	-0.32	2	2
p38 gamma/SNTA1	0.025	0.059	-9999	-0.46	4	4
MAP2K3	0.013	0	-9999	-10000	0	0
PKN1	0.013	0	-9999	-10000	0	0
G2/M transition checkpoint	0.025	0.034	-9999	-0.48	1	1
MAP2K6	0.023	0	-9999	-10000	0	0
MAPT	0.011	0.085	-9999	-0.38	13	13
MAPK13	0.015	0.065	-9999	-0.62	3	3
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.016	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	0.013	0	-9999	-10000	0	0
VDR	-0.002	0.11	-9999	-0.81	5	5
Cbp/p300/PCAF	0	0	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.034	0.023	-9999	-10000	0	0
KAT2B	0.013	0	-9999	-10000	0	0
MAPK14	0.013	0	-9999	-10000	0	0
AKT1	0.013	0.028	-9999	-10000	0	0
RAR alpha/9cRA/Cyclin H	-0.01	0.039	-9999	-0.35	3	3
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.032	0.023	-9999	-10000	0	0
CDC2	0.001	0	-9999	-10000	0	0
response to UV	0.001	0	-9999	-10000	0	0
RAR alpha/Jnk1	-0.003	0.089	-9999	-0.7	4	4
NCOR2	0.013	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.002	0.083	-9999	-0.63	5	5
RXRs/RARs/NRIP1/9cRA	0.03	0.054	-9999	-10000	0	0
NCOA2	-0.059	0.23	-9999	-0.81	25	25
NCOA3	0.013	0	-9999	-10000	0	0
NCOA1	0.013	0	-9999	-10000	0	0
VDR/VDR/DNA	-0.002	0.11	-9999	-0.81	5	5
RARG	0.012	0.018	-9999	-10000	0	0
RAR gamma1/9cRA	0.017	0.01	-9999	-10000	0	0
MAPK3	0.013	0	-9999	-10000	0	0
MAPK1	0.013	0	-9999	-10000	0	0
MAPK8	0.002	0.096	-9999	-0.81	4	4
mol:Vit D3	0	0	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.025	0.069	-9999	-0.45	5	5
RARA	0.001	0.06	-9999	-0.38	4	4
negative regulation of phosphoinositide 3-kinase cascade	0	0	-9999	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.007	0.092	-9999	-0.32	12	12
PRKCA	0.016	0	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.024	0.054	-9999	-10000	0	0
RXRG	-0.01	0.057	-9999	-10000	0	0
RXRA	0.011	0.055	-9999	-0.35	4	4
RXRB	-0.005	0.057	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.002	0.083	-9999	-0.63	5	5
RBP1	0.013	0	-9999	-10000	0	0
CRBP1/9-cic-RA	0.009	0	-9999	-10000	0	0
RARB	0.015	0	-9999	-10000	0	0
PRKCG	-0.057	0.13	-9999	-0.29	66	66
MNAT1	0.013	0	-9999	-10000	0	0
RAR alpha/RXRs	0.022	0.057	-9999	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.028	0.052	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.043	-9999	-0.27	3	3
RXRs/RARs/NRIP1/9cRA/HDAC3	0.024	0.054	-9999	-10000	0	0
positive regulation of DNA binding	-0.01	0.037	-9999	-0.33	3	3
NRIP1	0.025	0.051	-9999	-10000	0	0
RXRs/RARs	0.018	0.054	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.007	0.052	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
CDK7	0.013	0	-9999	-10000	0	0
TFIIH	0	0	-9999	-10000	0	0
RAR alpha/9cRA	-0.007	0.029	-9999	-10000	0	0
CCNH	0.013	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
RAR gamma2/9cRA	0	0.005	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.013	0.001	-9999	-10000	0	0
ELF1	0.004	0.05	-9999	-10000	0	0
CCNA2	-0.032	0.11	-9999	-0.29	42	42
PIK3CA	0.013	0.001	-9999	-10000	0	0
JAK3	-0.047	0.12	-9999	-0.3	1	1
PIK3R1	0.013	0.001	-9999	-10000	0	0
JAK1	0.013	0.001	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.042	0.065	-9999	-10000	0	0
SHC1	0.013	0.001	-9999	-10000	0	0
SP1	-0.005	0.06	-9999	-10000	0	0
IL2RA	0	0.09	-9999	-10000	0	0
IL2RB	-0.022	0.097	-9999	-0.3	1	1
SOS1	0.013	0.001	-9999	-10000	0	0
IL2RG	0.004	0.053	-9999	-0.29	9	9
G1/S transition of mitotic cell cycle	-0.004	0.077	-9999	-10000	0	0
PTPN11	0.013	0.001	-9999	-10000	0	0
CCND2	-0.016	0.11	-9999	-10000	0	0
LCK	0.006	0.047	-9999	-0.29	7	7
GRB2	0.013	0.001	-9999	-10000	0	0
IL2	0.004	0.018	-9999	-0.29	1	1
CDK6	0.013	0	-9999	-10000	0	0
CCND3	0.046	0.064	-9999	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.005	0.035	-9999	-0.47	1	1
RGS9BP	0.008	0.052	-9999	-0.81	1	1
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.002	0.018	-9999	-10000	0	0
mol:Na +	-0.007	0.033	-9999	-10000	0	0
mol:ADP	0.005	0.027	-9999	-10000	0	0
GNAT2	0.01	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.015	0.079	-9999	-0.57	5	5
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	0.002	0.035	-9999	-0.29	4	4
CNGB3	-0.006	0.052	-9999	-0.29	9	9
Cone Metarhodopsin II/X-Arrestin	0.002	0.004	-9999	-10000	0	0
mol:Ca2+	-0.002	0.032	-9999	-10000	0	0
Cone PDE6	-0.013	0.068	-9999	-0.49	5	5
Cone Metarhodopsin II	0.003	0.02	-9999	-10000	0	0
Na + (4 Units)	-0.006	0.031	-9999	-10000	0	0
GNAT2/GDP	-0.013	0.067	-9999	-0.49	5	5
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.011	0.006	-9999	-10000	0	0
Cone Transducin	0.016	0.041	-9999	-0.5	1	1
SLC24A2	-0.001	0.025	-9999	-0.29	2	2
GNB3/GNGT2	0.01	0.052	-9999	-0.62	1	1
GNB3	0.004	0.05	-9999	-0.29	8	8
GNAT2/GTP	0.007	0.004	-9999	-10000	0	0
CNGA3	0	0.035	-9999	-0.29	4	4
ARR3	0.003	0.005	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.007	0.033	-9999	-10000	0	0
mol:Pi	-0.015	0.078	-9999	-0.56	5	5
Cone CNG Channel	-0.005	0.024	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.001	0.025	-9999	-0.29	2	2
RGS9	-0.01	0.11	-9999	-0.43	15	15
PDE6C	0.004	0.006	-9999	-10000	0	0
GNGT2	0.009	0.052	-9999	-0.55	2	2
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.005	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.012	0	-9999	-10000	0	0
HDAC2	0.012	0	-9999	-10000	0	0
GNB1/GNG2	0.02	0.048	-9999	-0.54	2	2
forebrain development	0.031	0.073	-9999	-0.41	4	4
GNAO1	-0.059	0.23	-9999	-0.81	24	24
SMO/beta Arrestin2	0.015	0.056	-9999	-0.62	2	2
SMO	0.006	0.071	-9999	-0.81	2	2
ARRB2	0.012	0.018	-9999	-0.29	1	1
GLI3/SPOP	0.046	0.024	-9999	-10000	0	0
mol:GTP	0	0.001	-9999	-10000	0	0
GSK3B	0.013	0	-9999	-10000	0	0
GNAI2	0.013	0.001	-9999	-10000	0	0
SIN3/HDAC complex	0.003	0.015	-9999	-10000	0	0
GNAI1	0.007	0.068	-9999	-0.81	2	2
XPO1	0.014	0.004	-9999	-10000	0	0
GLI1/Su(fu)	-0.012	0.045	-9999	-10000	0	0
SAP30	0.01	0.025	-9999	-0.29	2	2
mol:GDP	0.006	0.07	-9999	-0.81	2	2
MIM/GLI2A	0.013	0.049	-9999	-0.81	1	1
IFT88	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0.001	-9999	-10000	0	0
GLI2	0.032	0.054	-9999	-10000	0	0
GLI3	0.041	0.025	-9999	-0.3	1	1
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
SAP18	0.012	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.012	0	-9999	-10000	0	0
GNG2	0.013	0	-9999	-10000	0	0
Gi family/GTP	0	0.11	-9999	-0.32	26	26
SIN3B	0.012	0	-9999	-10000	0	0
SIN3A	0.012	0	-9999	-10000	0	0
GLI3/Su(fu)	0.059	0.016	-9999	-10000	0	0
GLI2/Su(fu)	0.044	0.053	-9999	-10000	0	0
FOXA2	-0.018	0.077	-9999	-0.82	1	1
neural tube patterning	0.031	0.073	-9999	-0.41	4	4
SPOP	0.013	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.029	0.025	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
CSNK1G3	0.013	0	-9999	-10000	0	0
MTSS1	0.013	0.049	-9999	-0.81	1	1
embryonic limb morphogenesis	0.031	0.073	-9999	-0.41	4	4
SUFU	0.025	0.027	-9999	-10000	0	0
LGALS3	0.003	0.065	-9999	-0.37	7	7
catabolic process	0.062	0.043	-9999	-10000	0	0
GLI3A/CBP	0.015	0.048	-9999	-0.38	4	4
KIF3A	0.013	0	-9999	-10000	0	0
GLI1	0.031	0.074	-9999	-0.42	4	4
RAB23	0.013	0	-9999	-10000	0	0
CSNK1A1	0.013	0	-9999	-10000	0	0
IFT172	0.013	0	-9999	-10000	0	0
RBBP7	0.012	0	-9999	-10000	0	0
Su(fu)/Galectin3	0.024	0.047	-9999	-0.43	2	2
GNAZ	0.013	0.001	-9999	-10000	0	0
RBBP4	0.012	0	-9999	-10000	0	0
CSNK1G1	0.013	0	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GLI2/SPOP	0.036	0.051	-9999	-10000	0	0
STK36	0.014	0.004	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.012	0.089	-9999	-10000	0	0
PTCH1	0.037	0.068	-9999	-10000	0	0
MIM/GLI1	0.034	0.087	-9999	-10000	0	0
CREBBP	0.015	0.048	-9999	-0.38	4	4
Su(fu)/SIN3/HDAC complex	0.046	0.01	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.075	0.014	-9999	-10000	0	0
CRKL	0.046	0.01	-9999	-10000	0	0
mol:DAG	0.051	0.01	-9999	-10000	0	0
HRAS	0.065	0.009	-9999	-10000	0	0
MAPK8	0.027	0.064	-9999	-0.5	4	4
RAP1A	0.046	0.01	-9999	-10000	0	0
GAB1	0.046	0.01	-9999	-10000	0	0
MAPK14	0.034	0.012	-9999	-10000	0	0
EPO	0.01	0.025	-9999	-0.28	2	2
PLCG1	0.052	0.01	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.016	0.001	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.024	0.041	-9999	-0.56	1	1
GAB1/SHC/GRB2/SOS1	0	0.004	-9999	-10000	0	0
EPO/EPOR (dimer)	0.021	0.017	-9999	-10000	0	0
IRS2	0.045	0.015	-9999	-10000	0	0
STAT1	0.06	0.02	-9999	-10000	0	0
STAT5B	0.057	0.01	-9999	-10000	0	0
cell proliferation	0.033	0.06	-9999	-0.46	4	4
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.002	0.01	-9999	-10000	0	0
TEC	0.046	0.01	-9999	-10000	0	0
SOCS3	0.006	0.057	-9999	-0.42	4	4
STAT1 (dimer)	0.059	0.019	-9999	-10000	0	0
JAK2	0.015	0.001	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.053	0.012	-9999	-10000	0	0
EPO/EPOR	0.021	0.017	-9999	-10000	0	0
LYN	0.014	0	-9999	-10000	0	0
TEC/VAV2	0.053	0.01	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.016	0.001	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.035	0.014	-9999	-10000	0	0
mol:IP3	0.051	0.01	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.05	0.027	-9999	-10000	0	0
SH2B3	0.015	0.001	-9999	-10000	0	0
NFKB1	0.034	0.012	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.002	0.019	-9999	-0.28	1	1
PTPN6	0.04	0.011	-9999	-10000	0	0
TEC/VAV2/GRB2	0.057	0.01	-9999	-10000	0	0
EPOR	0.016	0.001	-9999	-10000	0	0
INPP5D	0.002	0.056	-9999	-0.29	10	10
mol:GDP	0	0.004	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
PLCG2	-0.035	0.19	-9999	-0.75	18	18
CRKL/CBL/C3G	0.057	0.01	-9999	-10000	0	0
VAV2	0.046	0.01	-9999	-10000	0	0
CBL	0.046	0.01	-9999	-10000	0	0
SHC/Grb2/SOS1	0	0.004	-9999	-10000	0	0
STAT5A	0.057	0.01	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
STAT5 (dimer)	0.075	0.01	-9999	-10000	0	0
LYN/PLCgamma2	-0.017	0.15	-9999	-0.62	16	16
PTPN11	0.013	0	-9999	-10000	0	0
BTK	0.004	0.063	-9999	-10000	0	0
BCL2	0.075	0.014	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.009	0.031	-9999	-0.29	3	3
positive regulation of NF-kappaB transcription factor activity	0.016	0.021	-9999	-10000	0	0
MAP2K4	0.044	0.011	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
TNFRSF10B	0.009	0.031	-9999	-0.29	3	3
TNFRSF10A	0.013	0	-9999	-10000	0	0
SMPD1	0.017	0.014	-9999	-10000	0	0
IKBKG	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR2	0.014	0.029	-9999	-10000	0	0
TRAIL/TRAILR3	0.001	0.065	-9999	-0.62	1	1
TRAIL/TRAILR1	0.017	0.021	-9999	-10000	0	0
TRAIL/TRAILR4	0.017	0.021	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP	0.023	0.016	-9999	-10000	0	0
IKK complex	0	0.003	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.009	0	-9999	-10000	0	0
MAPK3	0.019	0.021	-9999	-10000	0	0
MAP3K1	0.038	0.011	-9999	-10000	0	0
TRAILR4 (trimer)	0.012	0	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.012	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.035	0.01	-9999	-10000	0	0
CFLAR	0.013	0	-9999	-10000	0	0
MAPK1	0.019	0.021	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.001	0.011	-9999	-10000	0	0
mol:ceramide	0.017	0.014	-9999	-10000	0	0
FADD	0.013	0	-9999	-10000	0	0
MAPK8	0.042	0.055	-9999	-0.42	4	4
TRAF2	0.013	0	-9999	-10000	0	0
TRAILR3 (trimer)	-0.009	0.087	-9999	-0.32	19	19
CHUK	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.002	0.015	-9999	-10000	0	0
DAP3	0.013	0	-9999	-10000	0	0
CASP10	-0.002	0.013	-9999	-10000	0	0
JNK cascade	0.016	0.021	-9999	-10000	0	0
TRAIL (trimer)	0.009	0.031	-9999	-0.29	3	3
TNFRSF10C	-0.009	0.087	-9999	-0.32	19	19
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.001	0.011	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	-0.003	0.021	-9999	-10000	0	0
cell death	0.017	0.014	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.034	0.014	-9999	-10000	0	0
TRAILR2 (trimer)	0.009	0.031	-9999	-0.29	3	3
CASP8	0.001	0.007	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.002	0.015	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.01	0.054	-9999	-0.5	3	3
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.035	0.052	-9999	-0.41	3	3
SUMO1	0.013	0	-9999	-10000	0	0
ZFPM1	0.013	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.021	0	-9999	-10000	0	0
FKBP3	0.013	0	-9999	-10000	0	0
Histones	0.037	0.03	-9999	-10000	0	0
YY1/LSF	0.03	0	-9999	-10000	0	0
SMG5	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.023	0.046	-9999	-0.36	3	3
I kappa B alpha/HDAC1	0.024	0.033	-9999	-10000	0	0
SAP18	0.013	0	-9999	-10000	0	0
RELA	0.028	0.041	-9999	-0.32	3	3
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
HDAC3/TR2	0.024	0.033	-9999	-10000	0	0
NuRD/MBD3 Complex	0.045	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.031	0.038	-9999	-0.28	3	3
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.16	0.33	-9999	-0.81	60	60
GATA1	-0.008	0.071	-9999	-0.29	17	17
Mad/Max	0.019	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.051	0.018	-9999	-10000	0	0
RBBP7	0.013	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.013	0	-9999	-10000	0	0
MAX	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NFKBIA	0.019	0.037	-9999	-0.28	3	3
KAT2B	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.041	0.007	-9999	-10000	0	0
SIN3 complex	0.031	0.013	-9999	-10000	0	0
SMURF1	0.013	0	-9999	-10000	0	0
CHD3	0.013	0	-9999	-10000	0	0
SAP30	0.01	0.025	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.013	0	-9999	-10000	0	0
YY1/HDAC3	0.036	0.031	-9999	-10000	0	0
YY1/HDAC2	0.03	0	-9999	-10000	0	0
YY1/HDAC1	0.03	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.045	0	-9999	-10000	0	0
PPARG	0.026	0.055	-9999	-0.44	3	3
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.024	0.033	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.049	0	-9999	-10000	0	0
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	0.019	0.037	-9999	-10000	0	0
HDAC2	0.013	0	-9999	-10000	0	0
YY1	0.029	0	-9999	-10000	0	0
HDAC8	0.013	0	-9999	-10000	0	0
SMAD7	0.013	0	-9999	-10000	0	0
NCOR2	0.013	0	-9999	-10000	0	0
MXD1	0.013	0	-9999	-10000	0	0
STAT3	0.025	0	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.035	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0.034	0.012	-9999	-10000	0	0
EP300	0.013	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.025	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.037	-9999	-0.28	3	3
histone deacetylation	0.045	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.033	0.031	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GATAD2B	0.013	0	-9999	-10000	0	0
GATAD2A	0.013	0	-9999	-10000	0	0
GATA2/HDAC3	-0.083	0.21	-9999	-0.49	60	60
GATA1/HDAC1	0.005	0.048	-9999	-10000	0	0
GATA1/HDAC3	0.01	0.048	-9999	-10000	0	0
CHD4	0.013	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	0.002	0.078	-9999	-0.62	3	3
SIN3/HDAC complex/Mad/Max	0.045	0.006	-9999	-10000	0	0
NuRD Complex	0.053	0	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.004	0.022	-9999	-10000	0	0
SIN3B	0.013	0	-9999	-10000	0	0
MTA2	0.013	0	-9999	-10000	0	0
SIN3A	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC1	0.029	0	-9999	-10000	0	0
HDAC complex	0.032	0	-9999	-10000	0	0
GATA1/Fog1	0.005	0.048	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.011	0.1	-9999	-0.38	17	17
negative regulation of cell growth	0.045	0.006	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.045	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.032	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.03	0.054	-9999	-0.43	3	3
SIN3/HDAC complex/NCoR1	0.043	0.006	-9999	-10000	0	0
TFCP2	0.013	0	-9999	-10000	0	0
NR2C1	0.013	0	-9999	-10000	0	0
MBD3	0.013	0	-9999	-10000	0	0
MBD2	0.013	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0.002	-9999	-10000	0	0
DOCK1	0.013	0	-9999	-10000	0	0
ITGA4	0.011	0.018	-9999	-0.29	1	1
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.018	0.012	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.001	0.009	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.031	0.009	-9999	-10000	0	0
lamellipodium assembly	0	0.003	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
PI3K	0.019	0	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
TLN1	0.013	0	-9999	-10000	0	0
PXN	0.022	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
ARF6/GTP	0	0.005	-9999	-10000	0	0
cell adhesion	0.036	0.008	-9999	-10000	0	0
CRKL/CBL	0.019	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.031	0.009	-9999	-10000	0	0
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	0.013	0	-9999	-10000	0	0
ARF6/GDP	0	0.002	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.018	0.056	-9999	-0.46	1	1
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.028	0.11	-9999	-0.31	37	37
alpha4/beta1 Integrin/Paxillin/Talin	0.038	0.008	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.038	0.008	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
mol:GDP	-0.036	0.008	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.038	0.008	-9999	-10000	0	0
Rac1/GTP	0	0.003	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.013	0	-9999	-10000	0	0
Caspase 8 (4 units)	-0.008	0.027	-9999	-10000	0	0
NEF	-0.007	0.033	-9999	-10000	0	0
NFKBIA	0.011	0.017	-9999	-10000	0	0
BIRC3	0.021	0.077	-9999	-10000	0	0
CYCS	0.034	0.045	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
CD247	-0.008	0.085	-9999	-0.38	13	13
MAP2K7	0.038	0.036	-9999	-10000	0	0
protein ubiquitination	0.057	0.033	-9999	-10000	0	0
CRADD	0.013	0	-9999	-10000	0	0
DAXX	0.013	0	-9999	-10000	0	0
FAS	0.013	0	-9999	-10000	0	0
BID	0.029	0.046	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.01	0.036	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
MAP3K5	0.013	0	-9999	-10000	0	0
CFLAR	0.013	0	-9999	-10000	0	0
FADD	0.013	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.01	0.036	-9999	-10000	0	0
MAPK8	0.037	0.066	-9999	-0.44	4	4
APAF1	0.013	0	-9999	-10000	0	0
TRAF1	0.011	0.018	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.022	0.049	-9999	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.049	0.038	-9999	-10000	0	0
CHUK	0.059	0.034	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0	0	-9999	-10000	0	0
TCRz/NEF	-0.027	0.081	-9999	-0.37	11	11
TNF	-0.011	0.1	-9999	-0.38	17	17
FASLG	-0.015	0.12	-9999	-0.45	11	11
NFKB1	0.011	0.017	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.062	-9999	-0.54	3	3
CASP6	-0.002	0.013	-9999	-10000	0	0
CASP7	0.057	0.064	-9999	-10000	0	0
RELA	0.011	0.017	-9999	-10000	0	0
CASP2	0.013	0	-9999	-10000	0	0
CASP3	0.057	0.065	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
TNFR1A/BAG4	0.019	0	-9999	-10000	0	0
CASP8	0.013	0	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
MAP3K14	0.054	0.036	-9999	-10000	0	0
APAF-1/Caspase 9	-0.013	0.039	-9999	-10000	0	0
BCL2	0.043	0.062	-9999	-0.4	4	4

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.008	0.056	-9999	-0.43	5	5
TC10/GTP	0	0.005	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.009	0.066	-9999	-0.51	5	5
HRAS	0.013	0	-9999	-10000	0	0
APS homodimer	0.011	0.018	-9999	-0.29	1	1
GRB14	-0.045	0.21	-9999	-0.81	20	20
FOXO3	-0.005	0.018	-9999	-10000	0	0
AKT1	0.011	0.13	-9999	-0.75	2	2
INSR	0.014	0.001	-9999	-10000	0	0
Insulin Receptor/Insulin	0.034	0.007	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.013	0	-9999	-10000	0	0
SORBS1	0.013	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
PTPN1	0.033	0.007	-9999	-10000	0	0
CAV1	0.016	0.066	-9999	-0.47	5	5
CBL/APS/CAP/Crk-II/C3G	0	0.006	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.009	0.066	-9999	-0.51	5	5
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.058	-9999	-0.44	5	5
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.031	0.042	-9999	-10000	0	0
RPS6KB1	0.019	0.12	-9999	-0.66	2	2
PARD6A	0.013	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	-0.001	0.015	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.03	0.1	-9999	-0.69	2	2
HRAS/GTP	-0.01	0.054	-9999	-0.49	1	1
Insulin Receptor	0.014	0.001	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.008	0.062	-9999	-0.47	5	5
PRKCI	-0.008	0.028	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.036	0.13	-9999	-0.45	23	23
SHC1	0.013	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	-0.001	0.011	-9999	-10000	0	0
PI3K	-0.008	0.059	-9999	-0.45	5	5
NCK2	0.013	0	-9999	-10000	0	0
RHOQ	0.013	0	-9999	-10000	0	0
mol:H2O2	0	0.001	-9999	-10000	0	0
HRAS/GDP	0.009	0	-9999	-10000	0	0
AKT2	0.011	0.13	-9999	-0.75	2	2
PRKCZ	-0.008	0.028	-9999	-10000	0	0
SH2B2	0.011	0.018	-9999	-0.29	1	1
SHC/SHIP	0.019	0.07	-9999	-0.47	5	5
F2RL2	-0.034	0.16	-9999	-0.81	9	9
TRIP10	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0.007	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0.005	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	0.032	0.009	-9999	-10000	0	0
TC10/GDP	0.009	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0.006	-9999	-10000	0	0
INPP5D	0.012	0.073	-9999	-0.5	5	5
SOS1	0.013	0	-9999	-10000	0	0
SGK1	-0.002	0.008	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.013	0	-9999	-10000	0	0
IRS1	-0.002	0.11	-9999	-0.81	5	5
p62DOK/RasGAP	-0.001	0.011	-9999	-10000	0	0
INS	0.002	0.017	-9999	-0.29	1	1
mol:PI-3-4-P2	0.012	0.073	-9999	-0.5	5	5
GRB2	0.013	0	-9999	-10000	0	0
EIF4EBP1	0.017	0.12	-9999	-0.71	2	2
PTPRA	0.014	0.001	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.026	0.047	-9999	-0.33	5	5
Insulin Receptor/Insulin/IRS1	-0.009	0.067	-9999	-0.51	5	5
Insulin Receptor/Insulin/IRS3	-0.001	0.011	-9999	-10000	0	0
Par3/Par6	-0.022	0.084	-9999	-0.47	9	9

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.025	0.078	-9999	-0.91	2	2
VEGFR1 homodimer/NRP1	0.015	0.077	-9999	-0.91	2	2
mol:DAG	0.029	0.074	-9999	-0.83	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	-0.007	0.072	-9999	-0.85	2	2
CaM/Ca2+	0.034	0.071	-9999	-0.79	2	2
HIF1A	0.017	0.033	-9999	-0.38	2	2
GAB1	0.013	0	-9999	-10000	0	0
AKT1	0.048	0.066	-9999	-0.72	2	2
PLCG1	0.029	0.075	-9999	-0.84	2	2
NOS3	0.038	0.1	-9999	-0.71	2	2
CBL	0.013	0	-9999	-10000	0	0
mol:NO	0.038	0.097	-9999	-0.67	2	2
FLT1	0.022	0.086	-9999	-1	2	2
PGF	0.007	0.04	-9999	-0.29	5	5
VEGFR1 homodimer/NRP2/VEGFR121	0.026	0.082	-9999	-0.73	3	3
CALM1	0.013	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
eNOS/Hsp90	0.044	0.095	-9999	-0.65	2	2
endothelial cell proliferation	0.042	0.072	-9999	-0.78	2	2
mol:Ca2+	0.029	0.074	-9999	-0.82	2	2
MAPK3	0.041	0.066	-9999	-0.72	2	2
MAPK1	0.041	0.066	-9999	-0.72	2	2
PIK3R1	0.013	0	-9999	-10000	0	0
PLGF homodimer	0.007	0.04	-9999	-0.29	5	5
PRKACA	0.013	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0.011	0.018	-9999	-0.29	1	1
VEGFA homodimer	0.009	0.031	-9999	-0.29	3	3
VEGFR1 homodimer/VEGFA homodimer	0.023	0.079	-9999	-0.91	2	2
platelet activating factor biosynthetic process	0.046	0.064	-9999	-0.7	2	2
PI3K	0.035	0.072	-9999	-0.8	2	2
PRKCA	0.035	0.07	-9999	-0.77	2	2
PRKCB	0.033	0.072	-9999	-0.77	2	2
VEGFR1 homodimer/PLGF homodimer	0.022	0.081	-9999	-0.91	2	2
VEGFA	0.009	0.031	-9999	-0.29	3	3
VEGFB	0.013	0	-9999	-10000	0	0
mol:IP3	0.029	0.074	-9999	-0.83	2	2
RASA1	0.032	0.073	-9999	-0.84	2	2
NRP2	0.006	0.057	-9999	-0.42	4	4
VEGFR1 homodimer	0.022	0.086	-9999	-1	2	2
VEGFB homodimer	0.012	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.044	0.095	-9999	-0.65	2	2
PTPN11	0.013	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.007	0.066	-9999	-0.78	2	2
mol:L-citrulline	0.038	0.097	-9999	-0.67	2	2
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.036	0.072	-9999	-0.8	2	2
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.029	0.075	-9999	-0.85	2	2
CD2AP	0.013	0	-9999	-10000	0	0
PI3K/GAB1	-0.007	0.063	-9999	-0.75	2	2
PDPK1	0.04	0.067	-9999	-0.74	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.029	0.075	-9999	-0.85	2	2
mol:NADP	0.038	0.097	-9999	-0.67	2	2
HSP90AA1	0.013	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.007	0.066	-9999	-0.79	2	2
VEGFR1 homodimer/NRP2	0.021	0.086	-9999	-0.78	3	3

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.013	0	-9999	-10000	0	0
TRAF2/ASK1	0	0	-9999	-10000	0	0
ATM	0.013	0	-9999	-10000	0	0
MAP2K3	0.032	0.02	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.041	0.019	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.005	0.073	-9999	-0.55	4	4
TXN	0.007	0.014	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GADD45B	0.01	0.048	-9999	-0.81	1	1
MAP3K1	0.013	0	-9999	-10000	0	0
MAP3K6	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
MAP3K4	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.019	0	-9999	-10000	0	0
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0.024	0	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.001	0.007	-9999	-10000	0	0
TRAF6	0.008	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.042	0.14	-9999	-0.34	45	45
CCM2	0.013	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.029	0.081	-9999	-0.55	4	4
MAPK11	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.005	0.079	-9999	-0.5	4	4
OSM/MEKK3	0.019	0	-9999	-10000	0	0
TAOK1	0.015	0.027	-9999	-0.44	1	1
TAOK2	0.016	0	-9999	-10000	0	0
TAOK3	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.013	0	-9999	-10000	0	0
MAP3K10	0.013	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
TRX/ASK1	0.014	0.012	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.006	0.048	-9999	-0.47	3	3

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.013	0	-9999	-10000	0	0
SMAD2	0.013	0	-9999	-10000	0	0
SMAD3	0.039	0	-9999	-10000	0	0
SMAD3/SMAD4	0.045	0	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0	0	-9999	-10000	0	0
PPM1A	0.013	0	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
SMAD2/SMAD4	0.02	0	-9999	-10000	0	0
MAP3K1	0.013	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.01	0.075	-9999	-0.62	4	4
MAPK3	0.013	0	-9999	-10000	0	0
MAPK1	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
KPNB1	0.013	0	-9999	-10000	0	0
TGFBRAP1	0.001	0.096	-9999	-0.81	4	4
UBE2I	0.013	0	-9999	-10000	0	0
NUP153	0.013	0	-9999	-10000	0	0
KPNA2	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.078	0.014	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
RIP2/NOD2	0.006	0.05	-9999	-10000	0	0
NFKBIA	0.044	0	-9999	-10000	0	0
BIRC2	0.013	0	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
RIPK2	0.013	0	-9999	-10000	0	0
IKBKG	-0.002	0.009	-9999	-10000	0	0
IKK complex/A20	-0.008	0.042	-9999	-10000	0	0
NEMO/A20/RIP2	0.012	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
NEMO/ATM	0.044	0.019	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.001	0.003	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.006	0.074	-9999	-0.29	18	18
NFKB1	0.016	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
MALT1	0.013	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.019	0	-9999	-10000	0	0
ATM	0.013	0	-9999	-10000	0	0
TNF/TNFR1A	0.002	0.078	-9999	-0.62	3	3
TRAF6	0.013	0	-9999	-10000	0	0
PRKCA	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
UBE2D3	0.013	0	-9999	-10000	0	0
TNF	-0.011	0.1	-9999	-0.38	17	17
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.043	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
IKK complex	0.05	0.018	-9999	-10000	0	0
CYLD	0.013	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.001	0.004	-9999	-10000	0	0

×

Circadian rhythm 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
chromatin modification	0.043	0.02	-9999	-10000	0	0
CLOCK	0.007	0.083	-9999	-0.81	3	3
TIMELESS/CRY2	0.038	0.021	-9999	-10000	0	0
DEC1/BMAL1	0.013	0.004	-9999	-10000	0	0
ATR	0.013	0	-9999	-10000	0	0
NR1D1	0.035	0.041	-9999	-10000	0	0
ARNTL	0.015	0.002	-9999	-10000	0	0
TIMELESS	0.037	0.024	-9999	-10000	0	0
NPAS2	0.013	0.048	-9999	-0.81	1	1
CRY2	0.013	0	-9999	-10000	0	0
mol:CO	-0.012	0.009	-9999	-10000	0	0
CHEK1	0.013	0	-9999	-10000	0	0
mol:HEME	0.012	0.009	-9999	-10000	0	0
PER1	0.013	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.033	0.067	-9999	-0.53	4	4
BMAL1/CLOCK	0.041	0.055	-9999	-10000	0	0
S phase of mitotic cell cycle	0.043	0.02	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.044	0.02	-9999	-10000	0	0
mol:NADPH	0.012	0.009	-9999	-10000	0	0
PER1/TIMELESS	0.038	0.021	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.003	0.005	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	0.013	0	-9999	-10000	0	0
ITGA4	0.011	0.018	-9999	-0.29	1	1
alpha4/beta7 Integrin	0.018	0.012	-9999	-10000	0	0
alpha4/beta1 Integrin	0.018	0.012	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.021	0.075	-9999	-10000	0	0
regulation of axonogenesis	-0.023	0.018	-9999	-10000	0	0
myoblast fusion	-0.008	0.041	-9999	-10000	0	0
mol:GTP	-0.007	0.025	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.025	0.031	-9999	-10000	0	0
ARF1/GTP	-0.004	0.015	-9999	-10000	0	0
mol:GM1	0.005	0.02	-9999	-10000	0	0
mol:Choline	0.023	0.018	-9999	-10000	0	0
lamellipodium assembly	-0.009	0.036	-9999	-10000	0	0
MAPK3	0.018	0.039	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.026	0.031	-9999	-10000	0	0
ARF1	0.013	0	-9999	-10000	0	0
ARF6/GDP	0.008	0.041	-9999	-10000	0	0
ARF1/GDP	0.017	0.037	-9999	-10000	0	0
ARF6	0.008	0.015	-9999	-10000	0	0
RAB11A	0.013	0	-9999	-10000	0	0
TIAM1	0.013	0.004	-9999	-10000	0	0
fibronectin binding	0	0	-9999	-10000	0	0
MAPK1	0.018	0.039	-9999	-10000	0	0
actin filament bundle formation	-0.015	0.037	-9999	-10000	0	0
KALRN	-0.007	0.028	-9999	-10000	0	0
RAB11FIP3/RAB11A	0.019	0	-9999	-10000	0	0
RhoA/GDP	0.016	0.037	-9999	-10000	0	0
NME1	0.01	0.031	-9999	-0.29	3	3
Rac1/GDP	0.016	0.037	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	-0.007	0.025	-9999	-10000	0	0
cortical actin cytoskeleton organization	-0.009	0.036	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
liver development	-0.007	0.025	-9999	-10000	0	0
ARF6/GTP	-0.007	0.025	-9999	-10000	0	0
RhoA/GTP	-0.004	0.015	-9999	-10000	0	0
mol:GDP	-0.009	0.037	-9999	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.003	0.011	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
PLD1	0.015	0.02	-9999	-10000	0	0
RAB11FIP3	0.013	0	-9999	-10000	0	0
tube morphogenesis	-0.009	0.036	-9999	-10000	0	0
ruffle organization	0.023	0.018	-9999	-10000	0	0
regulation of epithelial cell migration	-0.007	0.025	-9999	-10000	0	0
PLD2	0.015	0.02	-9999	-10000	0	0
PIP5K1A	0.023	0.018	-9999	-10000	0	0
mol:Phosphatidic acid	0.023	0.018	-9999	-10000	0	0
Rac1/GTP	-0.009	0.036	-9999	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
INCENP	0.013	0	-9999	-9999
Aurora C/Aurora B/INCENP	-0.049	0.077	-9999	-9999
metaphase	0	0	-9999	-9999
mitosis	0	0	-9999	-9999
H3F3B	-0.017	0.018	-9999	-9999
AURKB	-0.13	0.15	-9999	-9999
AURKC	0.012	0.001	-9999	-9999

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.013	0	-10000	0	-10000	0	0
mol:PIP3	-0.006	0.045	-10000	0	-0.34	5	5
FRAP1	0.013	0.008	-10000	0	-10000	0	0
AKT1	0.022	0.04	-10000	0	-10000	0	0
INSR	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	-0.001	0.009	-10000	0	-10000	0	0
mol:GTP	-0.004	0.027	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.008	-10000	0	-10000	0	0
TSC2	0.012	0	-10000	0	-10000	0	0
RHEB/GDP	-0.003	0.023	-10000	0	-10000	0	0
TSC1	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.008	0.056	-10000	0	-0.42	5	5
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.009	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.013	0	-10000	0	-10000	0	0
RPS6KB1	0.024	0.021	-10000	0	-10000	0	0
MAP3K5	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.01	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.002	5	5
EIF4B	0.029	0.019	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.002	0.014	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.004	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.017	0.052	-10000	0	-0.37	5	5
mTOR/RHEB/GTP/Raptor/GBL	0.028	0.013	-10000	0	-10000	0	0
FKBP1A	0.013	0	-10000	0	-10000	0	0
RHEB/GTP	-0.003	0.023	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.002	5	5
FKBP12/Rapamycin	0.01	0.001	-10000	0	-10000	0	0
PDPK1	-0.005	0.04	-10000	0	-0.31	5	5
EIF4E	0.013	0	-10000	0	-10000	0	0
ASK1/PP5C	0.02	0.006	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.016	0	-10000	0	-10000	0	0
TSC1/TSC2	0.033	0.034	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.002	5	-10000	0	5
RPS6	0.013	0	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
EIF4G1	0.013	0	-10000	0	-10000	0	0
IRS1	0	0.059	-10000	0	-0.45	5	5
INS	-0.001	0.017	-10000	0	-0.29	1	1
PTEN	0.012	0	-10000	0	-10000	0	0
PDK2	-0.005	0.04	-10000	0	-10000	0	0
EIF4EBP1	0.01	0.018	-10000	0	-10000	0	0
PIK3CA	0.013	0	-10000	0	-10000	0	0
PPP2R5D	0.019	0.011	-10000	0	-10000	0	0
peptide biosynthetic process	0.016	0.009	-10000	0	-10000	0	0
RHEB	0.013	0	-10000	0	-10000	0	0
EIF4A1	0.013	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.016	0.009	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.016	0.016	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.013	0	-9999	-10000	0	0
HDAC4	0.01	0.048	-9999	-0.81	1	1
induction of apoptosis	0	0	-9999	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.02	0.005	-9999	-10000	0	0
CDKN1A	-0.005	0.033	-9999	-10000	0	0
KAT2B	0.013	0	-9999	-10000	0	0
BAX	0.01	0.025	-9999	-0.29	2	2
FOXO3	0	0	-9999	-10000	0	0
FOXO1	0.013	0	-9999	-10000	0	0
FOXO4	0.022	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
XRCC6	0.013	0	-9999	-10000	0	0
TAT	0.001	0.053	-9999	-0.29	9	9
mol:Lysophosphatidic acid	0	0	-9999	-10000	0	0
MYOD1	0.009	0.026	-9999	-10000	0	0
PPARGC1A	-0.007	0.13	-9999	-0.81	7	7
FHL2	0.01	0.048	-9999	-0.81	1	1
response to nutrient levels	0	0	-9999	-10000	0	0
KU70/SIRT1	0.002	0.01	-9999	-10000	0	0
HIST2H4A	0.02	0.005	-9999	-10000	0	0
SIRT1/FOXO3a	0.001	0.008	-9999	-10000	0	0
SIRT1	0.002	0.012	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.033	-9999	-0.54	1	1
SIRT1/Histone H1b	0.001	0.013	-9999	-10000	0	0
apoptosis	-0.001	0.016	-9999	-10000	0	0
SIRT1/PGC1A	-0.012	0.085	-9999	-0.55	7	7
p53/SIRT1	0.004	0.028	-9999	-10000	0	0
SIRT1/FOXO4	0.002	0.011	-9999	-10000	0	0
FOXO1/FHL2/SIRT1	0	0.031	-9999	-0.5	1	1
HIST1H1E	0.02	0.012	-9999	-10000	0	0
SIRT1/p300	0.002	0.01	-9999	-10000	0	0
muscle cell differentiation	0.001	0.022	-9999	-10000	0	0
TP53	0.002	0.012	-9999	-10000	0	0
KU70/SIRT1/BAX	0.001	0.016	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
MEF2D	0.013	0	-9999	-10000	0	0
HIV-1 Tat/SIRT1	-0.004	0.034	-9999	-10000	0	0
ACSS2	0.02	0.005	-9999	-10000	0	0
SIRT1/PCAF/MYOD	-0.001	0.022	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.039	0.038	-9999	-10000	0	0
BAG4	0.013	0	-9999	-10000	0	0
BAD	0.028	0.016	-9999	-10000	0	0
NFKBIA	0.013	0	-9999	-10000	0	0
BIRC3	-0.009	0.077	-9999	-0.29	20	20
BAX	0.027	0.019	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.013	0.012	-9999	-10000	0	0
IKBKB	0.045	0.037	-9999	-10000	0	0
MAP2K2	0.038	0.019	-9999	-10000	0	0
MAP2K1	0.038	0.019	-9999	-10000	0	0
SMPD1	0.018	0.012	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.046	0.037	-9999	-10000	0	0
MAP2K4	0.034	0.016	-9999	-10000	0	0
protein ubiquitination	0.046	0.037	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.043	0.021	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.034	0.019	-9999	-10000	0	0
CRADD	0.013	0	-9999	-10000	0	0
mol:ceramide	0.022	0.017	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.013	0	-9999	-10000	0	0
MAP3K1	0.028	0.016	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
RELA/p50	0.012	0	-9999	-10000	0	0
MAPK3	0.041	0.019	-9999	-10000	0	0
MAPK1	0.041	0.019	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.019	0	-9999	-10000	0	0
FADD	0.039	0.038	-9999	-10000	0	0
KSR1	0.028	0.018	-9999	-10000	0	0
MAPK8	0.033	0.052	-9999	-0.39	4	4
TRAF2	0.012	0	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.045	0.037	-9999	-10000	0	0
TNF R/SODD	0.019	0	-9999	-10000	0	0
TNF	-0.011	0.1	-9999	-0.38	17	17
CYCS	0.028	0.017	-9999	-10000	0	0
IKBKG	0.045	0.037	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.033	0.04	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
RIPK1	0.012	0	-9999	-10000	0	0
AIFM1	0.028	0.017	-9999	-10000	0	0
TNF/TNF R/SODD	-0.011	0.063	-9999	-0.54	3	3
TNFRSF1A	0.012	0	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.027	0.012	-9999	-10000	0	0
NSMAF	0.039	0.038	-9999	-10000	0	0
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	0.013	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.017	0.017	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.017	0.067	-9999	-0.54	4	4
NF kappa B1 p50/RelA/I kappa B alpha	0.043	0.02	-9999	-10000	0	0
NFKBIA	0.025	0.023	-9999	-0.27	1	1
MAPK14	0.013	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.025	0	-9999	-10000	0	0
ARRB2	0.016	0.008	-9999	-10000	0	0
REL	0	0.098	-9999	-0.71	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.024	0.014	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.025	0	-9999	-10000	0	0
PIK3CA	0.013	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.019	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
NFKB1	0.022	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.031	0.022	-9999	-0.26	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.046	0.02	-9999	-10000	0	0
SRC	0.011	0.018	-9999	-0.29	1	1
PI3K	0.019	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.031	0.022	-9999	-0.26	1	1
IKBKB	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-10000	0	0
SYK	0.01	0.048	-9999	-0.81	1	1
I kappa B alpha/PIK3R1	0.03	0.021	-9999	-10000	0	0
cell death	0.044	0.019	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.017	0.067	-9999	-0.54	4	4
LCK	0.005	0.047	-9999	-0.29	7	7
BCL3	0.01	0.025	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.022	-9999	-0.38	1	1
MDM2/SUMO1	0.029	0	-9999	-10000	0	0
HDAC4	0.01	0.048	-9999	-0.81	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0.013	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.027	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
SUMO1/HDAC4	0.027	0.028	-9999	-0.45	1	1
SUMO1/HDAC1	0.029	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.032	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.021	0	-9999	-10000	0	0
Ran/GTP	0.026	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.013	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.032	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0.013	0	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.002	0.028	-10000	0	-0.47	1	1
MAPK9	0.008	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.029	-10000	0	-10000	0	0
GNB1/GNG2	0	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.008	0	-10000	0	-10000	0	0
Gs family/GTP	0.006	0.031	-10000	0	-0.51	1	1
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0	0.007	0.12	1	-10000	0	1
GNAL	0.01	0.048	-10000	0	-0.81	1	1
GNG2	0.013	0	-10000	0	-10000	0	0
CRH	-0.001	0.043	-10000	0	-0.29	6	6
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.002	0.054	-10000	0	-0.45	4	4
MAPK11	0.008	0	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.02	0	-9999	-10000	0	0
AP2	0.019	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.024	0	-9999	-10000	0	0
CD4	0	0.061	-9999	-0.29	12	12
CLTA	0.013	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.011	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.026	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.013	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0.013	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.016	0	-9999	-10000	0	0
Rac/GTP	0.011	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.024	0	-9999	-10000	0	0
ARFIP2	0.011	0	-9999	-10000	0	0
COPA	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.025	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.013	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.026	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.018	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0.013	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.009	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.03	0.017	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.011	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.011	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.006	0.029	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

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

pid_entity	TCGA.Y8.A8S1	TCGA.Y8.A8S0	TCGA.Y8.A8RZ	TCGA.Y8.A8RY
109_MAP3K5	-0.017	0.052	0.052	0.052
47_PPARGC1A	0.013	0.013	0.013	0.013
105_BMP4	0.013	0.013	0.013	0.013
105_BMP6	0.013	0.013	0.013	0.013
105_BMP7	0.013	0.013	-0.81	0.013
105_BMP2	0.013	0.013	0.013	0.013
131_RELN/VLDLR	0.032	-0.12	0.032	-0.12
30_TGFB1/TGF beta receptor Type II	0.012	0.012	0.012	0.012
84_STAT5B	-0.05	-0.17	-0.15	-0.17
84_STAT5A	-0.05	-0.17	-0.15	-0.17