PARADIGM pathway analysis of mRNASeq expression and copy number data - Pan-kidney cohort (KICH+KIRC+KIRP) (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Nephrin/Neph1 signaling in the kidney podocyte	424
EGFR-dependent Endothelin signaling events	278
FOXA2 and FOXA3 transcription factor networks	217
PDGFR-alpha signaling pathway	202
HIF-1-alpha transcription factor network	187
TCR signaling in naïve CD8+ T cells	167
Glypican 1 network	150
TCGA08_p53	142
Angiopoietin receptor Tie2-mediated signaling	140
TCGA08_retinoblastoma	133

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	0.4769	424	14421	34	-0.5	0.028	1000	-1000	-0.043	-1000
EGFR-dependent Endothelin signaling events	0.3127	278	5858	21	-0.54	0.037	1000	-1000	-0.054	-1000
FOXA2 and FOXA3 transcription factor networks	0.2441	217	10005	46	-1	0.031	1000	-1000	-0.092	-1000
PDGFR-alpha signaling pathway	0.2272	202	8888	44	-0.24	0.036	1000	-1000	-0.048	-1000
HIF-1-alpha transcription factor network	0.2103	187	14282	76	-0.65	0.043	1000	-1000	-0.14	-1000
TCR signaling in naïve CD8+ T cells	0.1879	167	15614	93	-0.35	0.16	1000	-1000	-0.058	-1000
Glypican 1 network	0.1687	150	7230	48	-0.41	0.048	1000	-1000	-0.041	-1000
TCGA08_p53	0.1597	142	996	7	-0.26	0.15	1000	-1000	-0.014	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1575	140	12330	88	-0.46	0.032	1000	-1000	-0.077	-1000
TCGA08_retinoblastoma	0.1496	133	1067	8	-0.37	0.097	1000	-1000	-0.007	-1000
BMP receptor signaling	0.1271	113	9205	81	-0.45	0.055	1000	-1000	-0.078	-1000
Glypican 2 network	0.1260	112	450	4	-0.023	-1000	1000	-1000	-0.005	-1000
Aurora B signaling	0.1260	112	7544	67	-0.26	0.036	1000	-1000	-0.057	-1000
amb2 Integrin signaling	0.1249	111	9114	82	-0.44	0.034	1000	-1000	-0.06	-1000
IL12-mediated signaling events	0.1080	96	8367	87	-0.22	0.07	1000	-1000	-0.1	-1000
IL4-mediated signaling events	0.0979	87	7987	91	-0.7	0.5	1000	-1000	-0.13	-1000
Syndecan-4-mediated signaling events	0.0945	84	5673	67	-0.3	0.1	1000	-1000	-0.064	-1000
Effects of Botulinum toxin	0.0900	80	2103	26	-0.2	0.028	1000	-1000	-0.029	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0832	74	5772	78	-0.27	0.05	1000	-1000	-0.066	-1000
Arf6 signaling events	0.0776	69	4308	62	-0.54	0.06	1000	-1000	-0.049	-1000
Thromboxane A2 receptor signaling	0.0742	66	6936	105	-0.54	0.034	1000	-1000	-0.061	-1000
Endothelins	0.0731	65	6262	96	-0.49	0.027	1000	-1000	-0.069	-1000
FOXM1 transcription factor network	0.0731	65	3353	51	-0.36	0.027	1000	-1000	-0.16	-1000
Syndecan-1-mediated signaling events	0.0697	62	2132	34	-0.14	0.028	1000	-1000	-0.064	-1000
Signaling mediated by p38-alpha and p38-beta	0.0697	62	2745	44	-0.087	0.027	1000	-1000	-0.041	-1000
LPA4-mediated signaling events	0.0686	61	742	12	-0.079	0.009	1000	-1000	-0.029	-1000
JNK signaling in the CD4+ TCR pathway	0.0675	60	1030	17	-0.09	0.027	1000	-1000	-0.044	-1000
S1P1 pathway	0.0675	60	2161	36	-0.11	0.026	1000	-1000	-0.05	-1000
Coregulation of Androgen receptor activity	0.0664	59	4491	76	-0.77	0.054	1000	-1000	-0.033	-1000
Signaling events mediated by the Hedgehog family	0.0630	56	2921	52	-0.12	0.042	1000	-1000	-0.058	-1000
Ephrin A reverse signaling	0.0607	54	384	7	-0.021	0	1000	-1000	-0.028	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0607	54	3705	68	-0.33	0.067	1000	-1000	-0.093	-1000
Caspase cascade in apoptosis	0.0596	53	3952	74	-0.32	0.038	1000	-1000	-0.049	-1000
Aurora C signaling	0.0596	53	375	7	-0.15	0.024	1000	-1000	-0.022	-1000
Reelin signaling pathway	0.0596	53	2981	56	-0.12	0.072	1000	-1000	-0.061	-1000
Calcium signaling in the CD4+ TCR pathway	0.0596	53	1654	31	-0.21	0.027	1000	-1000	-0.06	-1000
Integrins in angiogenesis	0.0574	51	4305	84	-0.32	0.06	1000	-1000	-0.069	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0540	48	1606	33	-0.37	0.065	1000	-1000	-0.05	-1000
Fc-epsilon receptor I signaling in mast cells	0.0529	47	4646	97	-0.13	0.047	1000	-1000	-0.071	-1000
PLK1 signaling events	0.0529	47	4030	85	-0.16	0.038	1000	-1000	-0.037	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0529	47	5914	125	-0.14	0.04	1000	-1000	-0.069	-1000
p75(NTR)-mediated signaling	0.0517	46	5784	125	-0.31	0.076	1000	-1000	-0.091	-1000
IL2 signaling events mediated by STAT5	0.0506	45	992	22	-0.14	0.03	1000	-1000	-0.053	-1000
Signaling events mediated by PTP1B	0.0495	44	3409	76	-0.54	0.055	1000	-1000	-0.054	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0495	44	3303	74	-0.54	0.067	1000	-1000	-0.085	-1000
Ceramide signaling pathway	0.0484	43	3268	76	-0.54	0.19	1000	-1000	-0.059	-1000
FoxO family signaling	0.0484	43	2764	64	-0.62	0.072	1000	-1000	-0.065	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0461	41	2240	54	-0.32	0.04	1000	-1000	-0.09	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0461	41	4941	120	-0.18	0.1	1000	-1000	-0.068	-1000
IL27-mediated signaling events	0.0450	40	2045	51	-0.7	0.087	1000	-1000	-0.065	-1000
Visual signal transduction: Rods	0.0450	40	2124	52	-0.12	0.043	1000	-1000	-0.053	-1000
IL23-mediated signaling events	0.0439	39	2358	60	-0.19	0.028	1000	-1000	-0.11	-1000
Glucocorticoid receptor regulatory network	0.0416	37	4298	114	-0.32	0.15	1000	-1000	-0.069	-1000
IL2 signaling events mediated by PI3K	0.0416	37	2191	58	-0.14	0.048	1000	-1000	-0.051	-1000
Wnt signaling	0.0405	36	252	7	-0.047	0.027	1000	-1000	-0.034	-1000
Signaling events regulated by Ret tyrosine kinase	0.0394	35	2881	82	-0.039	0.028	1000	-1000	-0.088	-1000
Plasma membrane estrogen receptor signaling	0.0394	35	3062	86	-0.083	0.048	1000	-1000	-0.078	-1000
Noncanonical Wnt signaling pathway	0.0371	33	859	26	-0.13	0.027	1000	-1000	-0.063	-1000
Nongenotropic Androgen signaling	0.0371	33	1738	52	-0.055	0.044	1000	-1000	-0.049	-1000
Syndecan-2-mediated signaling events	0.0360	32	2229	69	-0.44	0.054	1000	-1000	-0.045	-1000
HIF-2-alpha transcription factor network	0.0360	32	1394	43	-0.22	0.072	1000	-1000	-0.064	-1000
BCR signaling pathway	0.0360	32	3222	99	-0.09	0.055	1000	-1000	-0.074	-1000
PLK2 and PLK4 events	0.0349	31	94	3	0.003	0.025	1000	-1000	-0.023	-1000
Regulation of Telomerase	0.0337	30	3074	102	-0.54	0.069	1000	-1000	-0.078	-1000
VEGFR1 specific signals	0.0337	30	1684	56	-0.12	0.028	1000	-1000	-0.064	-1000
ceramide signaling pathway	0.0326	29	1457	49	-0.023	0.041	1000	-1000	-0.06	-1000
Regulation of Androgen receptor activity	0.0326	29	2044	70	-0.85	0.043	1000	-1000	-0.061	-1000
IFN-gamma pathway	0.0304	27	1857	68	-0.19	0.04	1000	-1000	-0.087	-1000
S1P3 pathway	0.0304	27	1135	42	-0.11	0.034	1000	-1000	-0.043	-1000
Regulation of nuclear SMAD2/3 signaling	0.0292	26	3618	136	-0.33	0.096	1000	-1000	-0.055	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0292	26	738	28	-0.042	0.036	1000	-1000	-0.033	-1000
Presenilin action in Notch and Wnt signaling	0.0292	26	1588	61	-0.14	0.076	1000	-1000	-0.071	-1000
Syndecan-3-mediated signaling events	0.0292	26	936	35	-0.028	0.076	1000	-1000	-0.043	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0292	26	1210	45	-0.17	0.075	1000	-1000	-0.073	-1000
LPA receptor mediated events	0.0270	24	2463	102	-0.14	0.045	1000	-1000	-0.086	-1000
E-cadherin signaling events	0.0270	24	120	5	-0.005	0.026	1000	-1000	-0.004	-1000
TCGA08_rtk_signaling	0.0259	23	602	26	-0.24	0.059	1000	-1000	-0.02	-1000
Ephrin B reverse signaling	0.0247	22	1100	48	-0.039	0.037	1000	-1000	-0.043	-1000
Regulation of p38-alpha and p38-beta	0.0247	22	1215	54	-0.044	0.059	1000	-1000	-0.061	-1000
E-cadherin signaling in keratinocytes	0.0247	22	956	43	-0.23	0.038	1000	-1000	-0.054	-1000
ErbB4 signaling events	0.0236	21	1495	69	-0.14	0.095	1000	-1000	-0.061	-1000
IL6-mediated signaling events	0.0236	21	1591	75	-0.17	0.05	1000	-1000	-0.066	-1000
Ras signaling in the CD4+ TCR pathway	0.0236	21	358	17	0	0.048	1000	-1000	-0.032	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0225	20	1736	85	-0.052	0.061	1000	-1000	-0.064	-1000
EPO signaling pathway	0.0225	20	1144	55	-0.067	0.043	1000	-1000	-0.067	-1000
Canonical Wnt signaling pathway	0.0225	20	1058	51	-0.14	0.068	1000	-1000	-0.064	-1000
Class IB PI3K non-lipid kinase events	0.0225	20	60	3	-0.014	0.014	1000	-1000	-0.009	-1000
Aurora A signaling	0.0214	19	1148	60	-0.1	0.065	1000	-1000	-0.032	-1000
FAS signaling pathway (CD95)	0.0214	19	908	47	-0.14	0.041	1000	-1000	-0.052	-1000
Class I PI3K signaling events	0.0214	19	1421	73	-0.12	0.051	1000	-1000	-0.058	-1000
Signaling events mediated by PRL	0.0214	19	667	34	-0.043	0.039	1000	-1000	-0.046	-1000
Insulin-mediated glucose transport	0.0202	18	595	32	-0.072	0.049	1000	-1000	-0.041	-1000
S1P5 pathway	0.0202	18	319	17	-0.036	0.027	1000	-1000	-0.029	-1000
EPHB forward signaling	0.0202	18	1568	85	-0.046	0.058	1000	-1000	-0.084	-1000
Osteopontin-mediated events	0.0191	17	650	38	-0.014	0.052	1000	-1000	-0.06	-1000
a4b1 and a4b7 Integrin signaling	0.0191	17	87	5	0.012	0.028	1000	-1000	-0.01	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0191	17	638	37	-0.076	0.052	1000	-1000	-0.051	-1000
Visual signal transduction: Cones	0.0180	16	641	38	-0.029	0.04	1000	-1000	-0.021	-1000
PDGFR-beta signaling pathway	0.0180	16	1559	97	-0.04	0.065	1000	-1000	-0.069	-1000
ErbB2/ErbB3 signaling events	0.0169	15	1013	65	-0.078	0.037	1000	-1000	-0.066	-1000
IL1-mediated signaling events	0.0169	15	984	62	-0.11	0.063	1000	-1000	-0.071	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0169	15	781	52	-0.068	0.088	1000	-1000	-0.054	-1000
E-cadherin signaling in the nascent adherens junction	0.0169	15	1195	76	-0.027	0.048	1000	-1000	-0.081	-1000
S1P4 pathway	0.0169	15	394	25	-0.036	0.038	1000	-1000	-0.037	-1000
Cellular roles of Anthrax toxin	0.0157	14	565	39	-0.059	0.034	1000	-1000	-0.025	-1000
Hedgehog signaling events mediated by Gli proteins	0.0146	13	849	65	-0.004	0.049	1000	-1000	-0.056	-1000
mTOR signaling pathway	0.0146	13	705	53	-0.018	0.05	1000	-1000	-0.05	-1000
Nectin adhesion pathway	0.0146	13	851	63	-0.006	0.061	1000	-1000	-0.054	-1000
BARD1 signaling events	0.0124	11	636	57	-0.066	0.063	1000	-1000	-0.056	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0124	11	956	83	-0.072	0.054	1000	-1000	-0.052	-1000
p38 MAPK signaling pathway	0.0124	11	491	44	-0.059	0.05	1000	-1000	-0.045	-1000
Canonical NF-kappaB pathway	0.0112	10	394	39	-0.053	0.062	1000	-1000	-0.053	-1000
Signaling mediated by p38-gamma and p38-delta	0.0101	9	143	15	0	0.028	1000	-1000	-0.036	-1000
Class I PI3K signaling events mediated by Akt	0.0090	8	571	68	-0.072	0.054	1000	-1000	-0.048	-1000
Retinoic acid receptors-mediated signaling	0.0090	8	481	58	-0.023	0.054	1000	-1000	-0.052	-1000
Arf6 trafficking events	0.0090	8	578	71	-0.15	0.047	1000	-1000	-0.049	-1000
Insulin Pathway	0.0090	8	633	74	-0.033	0.069	1000	-1000	-0.071	-1000
Signaling events mediated by HDAC Class I	0.0079	7	743	104	-0.053	0.066	1000	-1000	-0.061	-1000
IGF1 pathway	0.0079	7	453	57	-0.034	0.062	1000	-1000	-0.072	-1000
Signaling events mediated by HDAC Class III	0.0056	5	211	40	-0.049	0.049	1000	-1000	-0.025	-1000
Signaling events mediated by HDAC Class II	0.0045	4	369	75	-0.034	0.069	1000	-1000	-0.04	-1000
Circadian rhythm pathway	0.0045	4	103	22	-0.012	0.055	1000	-1000	-0.042	-1000
Paxillin-dependent events mediated by a4b1	0.0045	4	169	36	-0.046	0.05	1000	-1000	-0.052	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0034	3	75	23	-0.008	0.052	1000	-1000	-0.04	-1000
TRAIL signaling pathway	0.0034	3	161	48	-0.006	0.069	1000	-1000	-0.053	-1000
Atypical NF-kappaB pathway	0.0034	3	118	31	0	0.039	1000	-1000	-0.048	-1000
Rapid glucocorticoid signaling	0.0034	3	76	20	-0.016	0.035	1000	-1000	-0.007	-1000
Arf1 pathway	0.0034	3	215	54	0	0.042	1000	-1000	-0.024	-1000
Arf6 downstream pathway	0.0022	2	92	43	-0.043	0.044	1000	-1000	-0.035	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0011	1	34	27	0	0.064	1000	-1000	-0.043	-1000
Alternative NF-kappaB pathway	0.0000	0	4	13	0	0.069	1000	-1000	-0.009	-1000
Total	NA	6049	331470	7203	-25	-990	131000	-131000	-7.2	-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	0.4	0.26	0.55	647	-10000	0	647
KIRREL	-0.081	0.15	-10000	0	-0.66	46	46
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.4	0.26	-10000	0	-0.55	647	647
PLCG1	0.027	0.007	-10000	0	-10000	0	0
ARRB2	0.024	0.03	-10000	0	-0.46	3	3
WASL	0.025	0.01	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.42	0.29	-10000	0	-0.54	692	692
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.35	0.25	-10000	0	-0.47	647	647
FYN	-0.4	0.26	0.26	1	-0.52	693	694
mol:Ca2+	-0.41	0.29	-10000	0	-0.54	674	674
mol:DAG	-0.41	0.29	-10000	0	-0.54	674	674
NPHS2	-0.32	0.33	-10000	0	-0.7	374	374
mol:IP3	-0.41	0.29	-10000	0	-0.54	674	674
regulation of endocytosis	-0.37	0.26	-10000	0	-0.49	659	659
Nephrin/NEPH1/podocin/Cholesterol	-0.42	0.29	-10000	0	-0.55	695	695
establishment of cell polarity	-0.4	0.26	-10000	0	-0.55	647	647
Nephrin/NEPH1/podocin/NCK1-2	-0.38	0.28	-10000	0	-0.51	681	681
Nephrin/NEPH1/beta Arrestin2	-0.38	0.26	-10000	0	-0.5	659	659
NPHS1	-0.5	0.31	-10000	0	-0.69	638	638
Nephrin/NEPH1/podocin	-0.4	0.28	-10000	0	-0.52	693	693
TJP1	0.028	0.004	-10000	0	-10000	0	0
NCK1	0.027	0.006	-10000	0	-10000	0	0
NCK2	0.027	0.006	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.41	0.29	-10000	0	-0.55	674	674
CD2AP	0.026	0.007	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.41	0.29	-10000	0	-0.55	673	673
GRB2	0.025	0.009	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.44	0.28	0.27	1	-0.54	711	712
cytoskeleton organization	-0.43	0.3	-10000	0	-0.58	635	635
Nephrin/NEPH1	-0.3	0.19	-10000	0	-0.41	642	642
Nephrin/NEPH1/ZO-1	-0.32	0.22	-10000	0	-0.45	641	641

×

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	0.027	0.015	-9999	-0.42	1	1
EGFR	0.017	0.061	-9999	-0.45	14	14
EGF/EGFR	-0.29	0.16	-9999	-0.37	637	637
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.26	0.17	-9999	-0.37	603	603
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.007	0.11	-9999	-0.6	29	29
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.54	0.25	-9999	-0.65	731	731
EGF/EGFR dimer/SHC	-0.32	0.18	-9999	-0.42	618	618
mol:GDP	-0.26	0.16	-9999	-0.36	603	603
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.005	0.1	-9999	-0.46	38	38
GRB2/SOS1	0.037	0.014	-9999	-10000	0	0
HRAS/GTP	-0.24	0.15	-9999	-0.34	595	595
SHC1	0.026	0.016	-9999	-0.42	1	1
HRAS/GDP	-0.25	0.16	-9999	-0.34	595	595
FRAP1	-0.26	0.15	-9999	-0.35	603	603
EGF/EGFR dimer	-0.38	0.2	-9999	-0.46	727	727
SOS1	0.027	0.006	-9999	-10000	0	0
GRB2	0.025	0.009	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.007	0.12	-9999	-0.39	63	63

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.45	0.42	-10000	0	-1	222	222
PCK1	-0.97	0.71	-10000	0	-1.5	496	496
HNF4A	-0.53	0.52	-10000	0	-1.3	232	232
KCNJ11	-0.48	0.46	-10000	0	-1.1	228	228
AKT1	-0.22	0.18	-10000	0	-0.46	151	151
response to starvation	-0.008	0.018	-10000	0	-10000	0	0
DLK1	-0.52	0.49	-10000	0	-1.1	286	286
NKX2-1	-0.1	0.17	0.32	7	-0.42	53	60
ACADM	-0.45	0.42	-10000	0	-1	232	232
TAT	-0.46	0.29	-10000	0	-0.77	325	325
CEBPB	-0.029	0.084	-10000	0	-0.47	22	22
CEBPA	-0.038	0.1	-10000	0	-0.46	43	43
TTR	-0.75	0.44	-10000	0	-1	509	509
PKLR	-0.53	0.53	-10000	0	-1.2	252	252
APOA1	-0.53	0.5	-10000	0	-1.2	230	230
CPT1C	-0.46	0.43	-10000	0	-1	244	244
ALAS1	-0.2	0.2	-10000	0	-0.68	41	41
TFRC	-0.61	0.39	-10000	0	-0.95	387	387
FOXF1	0.016	0.07	-10000	0	-0.46	18	18
NF1	0.031	0.01	-10000	0	-10000	0	0
HNF1A (dimer)	-0.034	0.11	-10000	0	-0.58	22	22
CPT1A	-0.45	0.42	-10000	0	-1	224	224
HMGCS1	-0.45	0.42	-10000	0	-1	231	231
NR3C1	0.013	0.053	-10000	0	-0.28	4	4
CPT1B	-0.46	0.44	-10000	0	-1.1	230	230
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.027	0.01	-10000	0	-10000	0	0
GCK	-0.44	0.43	-10000	0	-1	231	231
CREB1	-0.054	0.085	-10000	0	-0.32	9	9
IGFBP1	-0.25	0.33	-10000	0	-1.1	71	71
PDX1	-0.23	0.23	-10000	0	-0.74	74	74
UCP2	-0.45	0.42	-10000	0	-1	235	235
ALDOB	-0.98	0.55	-10000	0	-1.2	702	702
AFP	-0.54	0.4	-10000	0	-0.79	460	460
BDH1	-0.53	0.48	-10000	0	-1.1	307	307
HADH	-0.47	0.44	-10000	0	-1.1	226	226
F2	-0.56	0.5	-10000	0	-1.2	261	261
HNF1A	-0.033	0.11	-10000	0	-0.58	22	22
G6PC	-0.83	0.64	-10000	0	-1.4	444	444
SLC2A2	-0.4	0.54	-10000	0	-1.6	129	129
INS	-0.005	0.06	0.24	2	-0.43	3	5
FOXA1	-0.25	0.19	-10000	0	-0.53	206	206
FOXA3	-0.52	0.29	-10000	0	-0.62	678	678
FOXA2	-0.54	0.5	-10000	0	-1.1	279	279
ABCC8	-0.47	0.44	-10000	0	-1.1	240	240
ALB	-1	0.45	-10000	0	-1.2	737	737

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.24	0.34	-10000	0	-0.66	347	347
PDGF/PDGFRA/CRKL	-0.16	0.25	-10000	0	-0.48	343	343
positive regulation of JUN kinase activity	-0.097	0.2	-10000	0	-0.36	305	305
CRKL	0.027	0.005	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.17	0.25	-10000	0	-0.48	346	346
AP1	-0.17	0.31	0.33	2	-1.2	56	58
mol:IP3	-0.17	0.25	-10000	0	-0.49	333	333
PLCG1	-0.17	0.25	-10000	0	-0.49	333	333
PDGF/PDGFRA/alphaV Integrin	-0.16	0.25	-10000	0	-0.48	345	345
RAPGEF1	0.028	0.004	-10000	0	-10000	0	0
CRK	0.025	0.009	-10000	0	-10000	0	0
mol:Ca2+	-0.17	0.25	-10000	0	-0.49	333	333
CAV3	-0.007	0.031	-10000	0	-0.42	3	3
CAV1	0.002	0.097	-10000	0	-0.42	44	44
SHC/Grb2/SOS1	-0.096	0.2	-10000	0	-0.37	305	305
PDGF/PDGFRA/Shf	-0.16	0.25	-10000	0	-0.48	345	345
FOS	-0.18	0.3	0.32	1	-1.1	56	57
JUN	-0.026	0.024	-10000	0	-10000	0	0
oligodendrocyte development	-0.16	0.25	-10000	0	-0.47	345	345
GRB2	0.025	0.009	-10000	0	-10000	0	0
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
mol:DAG	-0.17	0.25	-10000	0	-0.49	333	333
PDGF/PDGFRA	-0.24	0.33	-10000	0	-0.65	347	347
actin cytoskeleton reorganization	-0.16	0.25	-10000	0	-0.48	343	343
SRF	0.021	0.011	-10000	0	-10000	0	0
SHC1	0.026	0.016	-10000	0	-0.42	1	1
PI3K	-0.12	0.22	-10000	0	-0.41	317	317
PDGF/PDGFRA/Crk/C3G	-0.12	0.22	-10000	0	-0.41	313	313
JAK1	-0.18	0.24	-10000	0	-0.48	342	342
ELK1/SRF	-0.12	0.19	-10000	0	-0.38	314	314
SHB	0.028	0.004	-10000	0	-10000	0	0
SHF	0.028	0.004	-10000	0	-10000	0	0
CSNK2A1	0.036	0.019	-10000	0	-10000	0	0
GO:0007205	-0.19	0.25	-10000	0	-0.5	347	347
SOS1	0.027	0.006	-10000	0	-10000	0	0
Ras protein signal transduction	-0.097	0.2	-10000	0	-0.36	305	305
PDGF/PDGFRA/SHB	-0.16	0.25	-10000	0	-0.48	343	343
PDGF/PDGFRA/Caveolin-1	-0.17	0.24	-10000	0	-0.43	383	383
ITGAV	0.026	0.028	-10000	0	-0.53	2	2
ELK1	-0.17	0.22	-10000	0	-0.44	344	344
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	-0.16	0.25	-10000	0	-0.47	325	325
JAK-STAT cascade	-0.17	0.24	-10000	0	-0.48	342	342
cell proliferation	-0.16	0.25	-10000	0	-0.48	345	345

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.53	0.48	-10000	0	-1	309	309
HDAC7	0.026	0.008	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.37	0.37	-10000	0	-0.83	212	212
SMAD4	0.029	0.005	-10000	0	-10000	0	0
ID2	-0.52	0.48	-10000	0	-1.1	273	273
AP1	0.007	0.12	-10000	0	-0.48	53	53
ABCG2	-0.52	0.48	-10000	0	-1.1	281	281
HIF1A	-0.075	0.085	-10000	0	-0.77	2	2
TFF3	-0.56	0.49	-10000	0	-1.1	303	303
GATA2	-0.028	0.18	-10000	0	-0.64	72	72
AKT1	-0.07	0.079	-10000	0	-10000	0	0
response to hypoxia	-0.08	0.072	-10000	0	-0.26	7	7
MCL1	-0.51	0.48	-10000	0	-1.1	275	275
NDRG1	-0.52	0.48	-10000	0	-1.1	273	273
SERPINE1	-0.54	0.48	-10000	0	-1.1	281	281
FECH	-0.52	0.48	-10000	0	-1.1	278	278
FURIN	-0.52	0.48	-10000	0	-1.1	278	278
NCOA2	-0.005	0.14	-10000	0	-0.65	40	40
EP300	-0.06	0.094	0.26	1	-0.35	9	10
HMOX1	-0.53	0.49	-10000	0	-1.1	288	288
BHLHE40	-0.52	0.48	-10000	0	-1.1	275	275
BHLHE41	-0.56	0.52	-10000	0	-1.1	307	307
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.059	0.11	-10000	0	-0.54	2	2
ENG	-0.055	0.11	0.51	4	-0.5	2	6
JUN	0.027	0.009	-10000	0	-10000	0	0
RORA	-0.52	0.48	-10000	0	-1.1	277	277
ABCB1	-0.25	0.41	-10000	0	-1.2	126	126
TFRC	-0.52	0.48	-10000	0	-1.1	275	275
CXCR4	-0.56	0.52	-10000	0	-1.1	315	315
TF	-0.54	0.51	-10000	0	-1.1	287	287
CITED2	-0.52	0.48	-10000	0	-1.1	273	273
HIF1A/ARNT	-0.6	0.56	-10000	0	-1.2	316	316
LDHA	-0.063	0.13	-10000	0	-0.7	26	26
ETS1	-0.52	0.48	-10000	0	-1.1	277	277
PGK1	-0.52	0.48	-10000	0	-1.1	277	277
NOS2	-0.53	0.48	-10000	0	-1.1	276	276
ITGB2	-0.55	0.5	-10000	0	-1.1	311	311
ALDOA	-0.52	0.48	-10000	0	-1.1	270	270
Cbp/p300/CITED2	-0.5	0.48	-10000	0	-1.1	256	256
FOS	-0.015	0.16	-10000	0	-0.62	57	57
HK2	-0.62	0.53	-10000	0	-1.1	362	362
SP1	0.014	0.053	-10000	0	-0.3	2	2
GCK	-0.12	0.18	-10000	0	-0.98	10	10
HK1	-0.52	0.48	-10000	0	-1.1	273	273
NPM1	-0.51	0.48	-10000	0	-1.1	269	269
EGLN1	-0.52	0.48	-10000	0	-1.1	275	275
CREB1	0.033	0.009	-10000	0	-10000	0	0
PGM1	-0.52	0.48	-10000	0	-1.1	277	277
SMAD3	0.029	0.003	-10000	0	-10000	0	0
EDN1	-0.1	0.22	-10000	0	-0.91	34	34
IGFBP1	-0.56	0.49	-10000	0	-1.1	284	284
VEGFA	-0.39	0.38	0.55	2	-0.85	235	237
HIF1A/JAB1	-0.039	0.067	-10000	0	-0.6	2	2
CP	-0.62	0.52	-10000	0	-1.1	355	355
CXCL12	-0.54	0.49	-10000	0	-1.1	300	300
COPS5	0.026	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4	0.043	0.009	-10000	0	-10000	0	0
BNIP3	-0.52	0.48	-10000	0	-1.1	277	277
EGLN3	-0.61	0.53	-10000	0	-1.1	356	356
CA9	-0.65	0.52	-10000	0	-1.1	388	388
TERT	-0.54	0.49	-10000	0	-1.1	290	290
ENO1	-0.52	0.48	-10000	0	-1.1	277	277
PFKL	-0.52	0.48	-10000	0	-1.1	274	274
NCOA1	0.027	0.006	-10000	0	-10000	0	0
ADM	-0.54	0.5	-10000	0	-1.1	291	291
ARNT	-0.072	0.078	-10000	0	-0.31	2	2
HNF4A	-0.061	0.23	-10000	0	-0.65	117	117
ADFP	-0.53	0.48	-10000	0	-1	309	309
SLC2A1	-0.34	0.35	0.55	2	-0.82	165	167
LEP	-0.54	0.47	-10000	0	-1.1	277	277
HIF1A/ARNT/Cbp/p300	-0.39	0.37	-10000	0	-0.85	217	217
EPO	-0.31	0.29	-10000	0	-0.77	135	135
CREBBP	-0.058	0.088	-10000	0	-0.35	7	7
HIF1A/ARNT/Cbp/p300/HDAC7	-0.4	0.39	-10000	0	-0.88	217	217
PFKFB3	-0.52	0.49	-10000	0	-1.1	283	283
NT5E	-0.52	0.49	-10000	0	-1.1	274	274

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.12	0.22	0.37	6	-0.46	201	207
FYN	-0.14	0.27	0.47	22	-0.51	250	272
LAT/GRAP2/SLP76	-0.15	0.26	0.29	4	-0.52	243	247
IKBKB	0.027	0.006	-10000	0	-10000	0	0
AKT1	-0.1	0.24	0.45	49	-0.4	252	301
B2M	0.026	0.007	-10000	0	-10000	0	0
IKBKG	-0.037	0.07	0.15	14	-0.16	80	94
MAP3K8	0.026	0.022	-10000	0	-0.42	2	2
mol:Ca2+	-0.078	0.053	0.072	5	-0.12	533	538
integrin-mediated signaling pathway	0.025	0.053	-10000	0	-0.24	32	32
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.16	0.31	0.48	36	-0.55	269	305
TRPV6	-0.35	0.47	0.74	94	-0.65	578	672
CD28	-0.008	0.12	-10000	0	-0.42	66	66
SHC1	-0.16	0.27	0.41	13	-0.52	261	274
receptor internalization	-0.16	0.26	0.22	1	-0.51	274	275
PRF1	-0.16	0.3	0.43	3	-0.68	184	187
KRAS	0.027	0.006	-10000	0	-10000	0	0
GRB2	0.025	0.009	-10000	0	-10000	0	0
COT/AKT1	-0.072	0.2	0.42	46	-0.33	205	251
LAT	-0.18	0.29	0.42	13	-0.56	274	287
EntrezGene:6955	-0.001	0.005	0.048	1	-10000	0	1
CD3D	-0.12	0.21	-10000	0	-0.43	287	287
CD3E	-0.11	0.21	-10000	0	-0.43	266	266
CD3G	-0.099	0.2	-10000	0	-0.42	247	247
RASGRP2	-0.01	0.025	0.09	2	-0.17	4	6
RASGRP1	-0.095	0.24	0.52	42	-0.4	208	250
HLA-A	-0.002	0.008	0.076	3	-10000	0	3
RASSF5	0.01	0.083	-10000	0	-0.42	32	32
RAP1A/GTP/RAPL	0.025	0.053	-10000	0	-0.24	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.011	0.15	0.35	70	-0.13	8	78
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.084	0.098	-10000	0	-0.25	162	162
PRKCA	-0.073	0.13	0.18	19	-0.27	173	192
GRAP2	-0.001	0.11	-10000	0	-0.42	56	56
mol:IP3	-0.045	0.26	0.24	291	-0.41	199	490
EntrezGene:6957	-0.002	0.006	0.058	1	-10000	0	1
TCR/CD3/MHC I/CD8	-0.12	0.22	-10000	0	-0.45	245	245
ORAI1	0.16	0.29	0.67	9	-0.58	89	98
CSK	-0.16	0.26	0.32	8	-0.52	261	269
B7 family/CD28	-0.18	0.32	0.29	1	-0.66	223	224
CHUK	0.027	0.007	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.18	0.28	0.27	1	-0.57	272	273
PTPN6	-0.16	0.26	0.3	2	-0.52	260	262
VAV1	-0.19	0.3	0.45	13	-0.58	283	296
Monovalent TCR/CD3	-0.11	0.19	-10000	0	-0.38	276	276
CBL	0.027	0.023	-10000	0	-0.65	1	1
LCK	-0.15	0.28	0.46	22	-0.53	253	275
PAG1	-0.16	0.26	0.32	11	-0.52	263	274
RAP1A	0.027	0.007	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.17	0.28	0.27	7	-0.55	273	280
CD80	-0.059	0.18	-10000	0	-0.42	167	167
CD86	-0.053	0.17	-10000	0	-0.42	156	156
PDK1/CARD11/BCL10/MALT1	-0.092	0.13	-10000	0	-0.3	171	171
HRAS	0.027	0.015	-10000	0	-0.42	1	1
GO:0035030	-0.16	0.26	0.48	7	-0.54	233	240
CD8A	-0.11	0.21	-10000	0	-0.42	267	267
CD8B	-0.09	0.2	-10000	0	-0.43	226	226
PTPRC	-0.008	0.12	-10000	0	-0.43	67	67
PDK1/PKC theta	-0.13	0.3	0.55	52	-0.49	245	297
CSK/PAG1	-0.15	0.26	0.4	9	-0.54	223	232
SOS1	0.027	0.006	-10000	0	-10000	0	0
peptide-MHC class I	0.014	0.016	-10000	0	-10000	0	0
GRAP2/SLP76	-0.16	0.28	0.28	1	-0.55	254	255
STIM1	0.09	0.14	1	2	-0.77	11	13
RAS family/GTP	-0.01	0.14	0.37	47	-0.2	9	56
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.17	0.27	0.22	1	-0.54	274	275
mol:DAG	-0.1	0.19	0.14	12	-0.36	242	254
RAP1A/GDP	0.011	0.098	0.23	61	-10000	0	61
PLCG1	0.027	0.007	-10000	0	-10000	0	0
CD247	-0.079	0.19	-10000	0	-0.42	207	207
cytotoxic T cell degranulation	-0.16	0.29	0.43	3	-0.65	184	187
RAP1A/GTP	-0.003	0.01	-10000	0	-0.06	4	4
mol:PI-3-4-5-P3	-0.13	0.27	0.46	38	-0.46	259	297
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.09	0.32	0.27	217	-0.54	213	430
NRAS	0.027	0.007	-10000	0	-10000	0	0
ZAP70	-0.12	0.21	-10000	0	-0.42	299	299
GRB2/SOS1	0.037	0.014	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.17	0.26	0.27	4	-0.52	257	261
MALT1	0.027	0.005	-10000	0	-10000	0	0
TRAF6	0.028	0.003	-10000	0	-10000	0	0
CD8 heterodimer	-0.13	0.26	-10000	0	-0.49	279	279
CARD11	-0.061	0.17	-10000	0	-0.42	169	169
PRKCB	-0.077	0.13	0.17	13	-0.28	177	190
PRKCE	-0.073	0.13	0.18	20	-0.28	161	181
PRKCQ	-0.16	0.31	0.51	38	-0.55	257	295
LCP2	-0.006	0.12	-10000	0	-0.42	64	64
BCL10	0.027	0.007	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.082	0.22	0.42	52	-0.34	249	301
IKK complex	0.016	0.17	0.37	92	-0.12	14	106
RAS family/GDP	-0.008	0.012	-10000	0	-10000	0	0
MAP3K14	-0.059	0.15	0.39	20	-0.27	164	184
PDPK1	-0.091	0.24	0.48	53	-0.39	223	276
TCR/CD3/MHC I/CD8/Fyn	-0.16	0.28	-10000	0	-0.55	260	260

×

Glypican 1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.042	0.066	-10000	0	-0.42	15	15
fibroblast growth factor receptor signaling pathway	0.042	0.066	-10000	0	-0.42	15	15
LAMA1	0.006	0.12	-10000	0	-0.57	32	32
PRNP	0.027	0.006	-10000	0	-10000	0	0
GPC1/SLIT2	-0.042	0.19	-10000	0	-0.47	137	137
SMAD2	0.025	0.031	-10000	0	-0.38	1	1
GPC1/PrPc/Cu2+	0.034	0.019	-10000	0	-0.42	1	1
GPC1/Laminin alpha1	0.021	0.092	-10000	0	-0.44	31	31
TDGF1	-0.41	0.31	-10000	0	-0.63	574	574
CRIPTO/GPC1	-0.3	0.24	-10000	0	-0.47	570	570
APP/GPC1	0.037	0.024	-10000	0	-0.39	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.26	0.2	-10000	0	-0.42	523	523
FLT1	0.018	0.067	-10000	0	-0.48	15	15
GPC1/TGFB/TGFBR1/TGFBR2	0.048	0.027	-10000	0	-0.42	1	1
SERPINC1	-0.015	0.15	-10000	0	-0.6	52	52
FYN	-0.25	0.21	-10000	0	-0.42	526	526
FGR	-0.26	0.21	-10000	0	-0.42	530	530
positive regulation of MAPKKK cascade	-0.28	0.24	0.4	11	-0.45	539	550
SLIT2	-0.075	0.24	-10000	0	-0.62	139	139
GPC1/NRG	0.016	0.1	-10000	0	-0.47	35	35
NRG1	-0.001	0.13	-10000	0	-0.6	39	39
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.046	0.15	-10000	0	-0.26	268	268
LYN	-0.25	0.21	-10000	0	-0.42	520	520
mol:Spermine	0.009	0.02	-10000	0	-0.39	2	2
cell growth	0.042	0.066	-10000	0	-0.42	15	15
BMP signaling pathway	-0.025	0.028	0.53	2	-10000	0	2
SRC	-0.25	0.2	-10000	0	-0.42	511	511
TGFBR1	0.028	0.004	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.032	0.13	-10000	0	-0.42	82	82
GPC1	0.025	0.028	-10000	0	-0.53	2	2
TGFBR1 (dimer)	0.028	0.004	-10000	0	-10000	0	0
VEGFA	-0.11	0.2	-10000	0	-0.42	269	269
BLK	-0.26	0.22	-10000	0	-0.44	523	523
HCK	-0.27	0.21	-10000	0	-0.43	514	514
FGF2	0.016	0.087	-10000	0	-0.62	16	16
FGFR1	0.026	0.016	-10000	0	-0.42	1	1
VEGFR1 homodimer	0.018	0.067	-10000	0	-0.48	15	15
TGFBR2	0.026	0.008	-10000	0	-10000	0	0
cell death	0.037	0.024	-10000	0	-0.39	2	2
ATIII/GPC1	0.008	0.12	-10000	0	-0.44	53	53
PLA2G2A/GPC1	0.004	0.098	-10000	0	-0.3	82	82
LCK	-0.27	0.21	-10000	0	-0.43	530	530
neuron differentiation	0.016	0.1	-10000	0	-0.47	35	35
PrPc/Cu2+	0.02	0.005	-10000	0	-10000	0	0
APP	0.027	0.007	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.026	0.008	-10000	0	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.26	0.1	0.2	2	-0.3	772	774
TP53	-0.071	0.062	-10000	0	-0.28	54	54
Senescence	-0.071	0.062	-10000	0	-0.28	54	54
Apoptosis	-0.071	0.062	-10000	0	-0.28	54	54
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.15	0.095	0.41	60	-10000	0	60
MDM4	0.027	0.007	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.26	0.46	-10000	0	-1	224	224
NCK1/PAK1/Dok-R	-0.13	0.18	-10000	0	-0.44	216	216
NCK1/Dok-R	-0.28	0.61	-10000	0	-1.3	224	224
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
mol:beta2-estradiol	0.032	0.087	0.24	124	-10000	0	124
RELA	0.028	0.003	-10000	0	-10000	0	0
SHC1	0.025	0.016	-10000	0	-0.42	1	1
Rac/GDP	0.018	0.007	-10000	0	-10000	0	0
F2	-0.06	0.23	0.26	121	-0.42	228	349
TNIP2	0.028	0.004	-10000	0	-10000	0	0
NF kappa B/RelA	-0.23	0.56	-10000	0	-1.2	223	223
FN1	-0.01	0.12	-10000	0	-0.42	72	72
PLD2	-0.3	0.63	-10000	0	-1.3	224	224
PTPN11	0.027	0.006	-10000	0	-10000	0	0
GRB14	-0.01	0.15	-10000	0	-0.65	48	48
ELK1	-0.24	0.54	0.48	4	-1.1	223	227
GRB7	0.018	0.069	-10000	0	-0.65	9	9
PAK1	0.028	0.003	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.28	0.59	-10000	0	-1.3	222	222
CDKN1A	-0.18	0.31	-10000	0	-0.68	214	214
ITGA5	0.004	0.098	-10000	0	-0.42	45	45
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.29	0.61	-10000	0	-1.3	224	224
CRK	0.025	0.009	-10000	0	-10000	0	0
mol:NO	-0.17	0.33	0.49	6	-0.69	223	229
PLG	-0.46	0.63	-10000	0	-1.5	224	224
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.23	0.43	-10000	0	-0.94	224	224
GRB2	0.025	0.009	-10000	0	-10000	0	0
PIK3R1	0.026	0.005	-10000	0	-10000	0	0
ANGPT2	-0.16	0.27	-10000	0	-0.75	95	95
BMX	-0.33	0.64	-10000	0	-1.4	224	224
ANGPT1	-0.18	0.5	-10000	0	-1.4	124	124
tube development	-0.21	0.35	-10000	0	-0.78	222	222
ANGPT4	0.01	0.062	-10000	0	-0.42	17	17
response to hypoxia	-0.018	0.03	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.33	0.68	-10000	0	-1.4	223	223
alpha5/beta1 Integrin	0.021	0.074	-10000	0	-0.29	45	45
FGF2	0.019	0.088	-10000	0	-0.62	16	16
STAT5A (dimer)	-0.24	0.41	-10000	0	-0.9	213	213
mol:L-citrulline	-0.17	0.33	0.49	6	-0.69	223	229
AGTR1	-0.081	0.24	-10000	0	-0.65	128	128
MAPK14	-0.34	0.63	-10000	0	-1.4	226	226
Tie2/SHP2	-0.26	0.55	-10000	0	-1.2	212	212
TEK	-0.31	0.62	-10000	0	-1.4	212	212
RPS6KB1	-0.23	0.44	-10000	0	-0.95	224	224
Angiotensin II/AT1	-0.068	0.18	-10000	0	-0.49	128	128
Tie2/Ang1/GRB2	-0.31	0.67	-10000	0	-1.4	224	224
MAPK3	-0.26	0.55	-10000	0	-1.2	222	222
MAPK1	-0.26	0.55	-10000	0	-1.2	224	224
Tie2/Ang1/GRB7	-0.31	0.67	-10000	0	-1.4	224	224
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
MAPK8	-0.31	0.64	-10000	0	-1.4	224	224
PI3K	-0.31	0.56	-10000	0	-1.2	224	224
FES	-0.32	0.63	-10000	0	-1.4	224	224
Crk/Dok-R	-0.28	0.61	-10000	0	-1.3	223	223
Tie2/Ang1/ABIN2	-0.32	0.68	-10000	0	-1.4	224	224
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.22	0.4	-10000	0	-0.89	224	224
STAT5A	0.026	0.009	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.24	0.44	0.46	3	-0.97	224	227
Tie2/Ang2	-0.32	0.52	-10000	0	-1.2	221	221
Tie2/Ang1	-0.36	0.74	-10000	0	-1.6	224	224
FOXO1	-0.23	0.41	-10000	0	-0.9	224	224
ELF1	0.001	0.064	-10000	0	-0.65	1	1
ELF2	-0.31	0.65	-10000	0	-1.4	224	224
mol:Choline	-0.28	0.58	-10000	0	-1.2	224	224
cell migration	-0.079	0.1	-10000	0	-0.24	220	220
FYN	-0.25	0.41	-10000	0	-0.92	221	221
DOK2	-0.004	0.11	-10000	0	-0.42	59	59
negative regulation of cell cycle	-0.16	0.28	-10000	0	-0.61	214	214
ETS1	-0.008	0.096	-10000	0	-0.25	108	108
PXN	-0.18	0.36	0.56	6	-0.77	222	228
ITGB1	0.027	0.007	-10000	0	-10000	0	0
NOS3	-0.2	0.38	0.5	6	-0.8	223	229
RAC1	0.025	0.01	-10000	0	-10000	0	0
TNF	-0.025	0.13	-10000	0	-0.51	26	26
MAPKKK cascade	-0.28	0.58	-10000	0	-1.2	224	224
RASA1	0.027	0.023	-10000	0	-0.65	1	1
Tie2/Ang1/Shc	-0.32	0.68	-10000	0	-1.4	224	224
NCK1	0.027	0.006	-10000	0	-10000	0	0
vasculogenesis	-0.14	0.29	0.45	8	-0.62	223	231
mol:Phosphatidic acid	-0.28	0.58	-10000	0	-1.2	224	224
mol:Angiotensin II	-0.006	0.009	-10000	0	-10000	0	0
mol:NADP	-0.17	0.33	0.49	6	-0.69	223	229
Rac1/GTP	-0.21	0.4	-10000	0	-0.86	224	224
MMP2	-0.31	0.63	-10000	0	-1.3	224	224

×

TCGA08_retinoblastoma

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
CDKN2B	0.025	0.054	-10000	0	-0.42	12	12
CDKN2C	0.06	0.031	-10000	0	-0.38	2	2
CDKN2A	-0.37	0.15	-10000	0	-0.43	772	772
CCND2	0.081	0.048	0.21	41	-10000	0	41
RB1	-0.093	0.057	-10000	0	-0.26	38	38
CDK4	0.097	0.058	0.22	79	-10000	0	79
CDK6	0.093	0.057	0.22	68	-0.16	1	69
G1/S progression	0.097	0.057	0.24	54	-10000	0	54

×

BMP receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.43	0.3	-10000	0	-0.56	676	676
SMAD6-7/SMURF1	0.048	0.031	-10000	0	-0.42	2	2
NOG	-0.026	0.14	-10000	0	-0.45	90	90
SMAD9	-0.076	0.18	-10000	0	-0.61	75	75
SMAD4	0.028	0.005	-10000	0	-10000	0	0
SMAD5	-0.16	0.16	-10000	0	-0.44	69	69
BMP7/USAG1	-0.45	0.35	-10000	0	-0.64	624	624
SMAD5/SKI	-0.15	0.17	0.32	7	-0.45	54	61
SMAD1	-0.018	0.068	-10000	0	-0.49	6	6
BMP2	0.025	0.033	-10000	0	-0.65	2	2
SMAD1/SMAD1/SMAD4	-0.01	0.062	-10000	0	-0.45	3	3
BMPR1A	0.026	0.024	-10000	0	-0.65	1	1
BMPR1B	-0.38	0.33	-10000	0	-0.64	535	535
BMPR1A-1B/BAMBI	-0.24	0.23	-10000	0	-0.42	526	526
AHSG	-0.006	0.063	-10000	0	-0.42	18	18
CER1	-0.004	0.025	-10000	0	-0.42	1	1
BMP2-4/CER1	0.043	0.047	-10000	0	-0.42	7	7
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.11	0.13	-10000	0	-0.44	33	33
BMP2-4 (homodimer)	0.034	0.049	-10000	0	-0.49	7	7
RGMB	0.026	0.022	-10000	0	-0.42	2	2
BMP6/BMPR2/BMPR1A-1B	-0.21	0.22	-10000	0	-0.39	522	522
RGMA	-0.001	0.14	-10000	0	-0.64	38	38
SMURF1	0.025	0.01	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.14	0.14	-10000	0	-0.38	72	72
BMP2-4/USAG1	-0.18	0.23	-10000	0	-0.42	412	412
SMAD6/SMURF1/SMAD5	-0.14	0.16	0.34	2	-0.44	58	60
SOSTDC1	-0.3	0.33	-10000	0	-0.64	426	426
BMP7/BMPR2/BMPR1A-1B	-0.4	0.29	-10000	0	-0.54	657	657
SKI	0.026	0.007	-10000	0	-10000	0	0
BMP6 (homodimer)	0.012	0.098	-10000	0	-0.62	20	20
HFE2	0.004	0.072	-10000	0	-0.42	23	23
ZFYVE16	0.028	0.005	-10000	0	-10000	0	0
MAP3K7	0.027	0.007	-10000	0	-10000	0	0
BMP2-4/CHRD	0.033	0.097	-10000	0	-0.45	30	30
SMAD5/SMAD5/SMAD4	-0.16	0.16	0.31	4	-0.43	66	70
MAPK1	0.027	0.005	-10000	0	-10000	0	0
TAK1/TAB family	-0.1	0.12	-10000	0	-0.37	33	33
BMP7 (homodimer)	-0.34	0.33	-10000	0	-0.65	462	462
NUP214	0.028	0.004	-10000	0	-10000	0	0
BMP6/FETUA	0.016	0.088	-10000	0	-0.39	37	37
SMAD1/SKI	-0.005	0.084	0.41	6	-0.47	6	12
SMAD6	0.027	0.033	-10000	0	-0.65	2	2
CTDSP2	0.027	0.006	-10000	0	-10000	0	0
BMP2-4/FETUA	0.038	0.061	-10000	0	-0.43	7	7
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.18	0.31	-10000	0	-0.64	277	277
BMPR2 (homodimer)	0.027	0.006	-10000	0	-10000	0	0
GADD34/PP1CA	0.055	0.012	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	-0.28	0.25	-10000	0	-0.48	533	533
CHRDL1	-0.31	0.34	-10000	0	-0.65	430	430
ENDOFIN/SMAD1	-0.008	0.082	0.41	4	-0.48	6	10
SMAD6-7/SMURF1/SMAD1	-0.005	0.075	-10000	0	-0.47	5	5
SMAD6/SMURF1	0.025	0.01	-10000	0	-10000	0	0
BAMBI	0.018	0.075	-10000	0	-0.58	13	13
SMURF2	0.024	0.025	-10000	0	-0.65	1	1
BMP2-4/CHRDL1	-0.18	0.24	-10000	0	-0.42	408	408
BMP2-4/GREM1	-0.091	0.22	-10000	0	-0.42	244	244
SMAD7	0.028	0.005	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.068	0.18	-10000	0	-0.58	79	79
SMAD1/SMAD6	-0.013	0.07	-10000	0	-0.49	6	6
TAK1/SMAD6	0.034	0.017	-10000	0	-10000	0	0
BMP7	-0.34	0.33	-10000	0	-0.65	462	462
BMP6	0.012	0.098	-10000	0	-0.62	20	20
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.11	0.12	-10000	0	-0.38	48	48
PPM1A	0.027	0.005	-10000	0	-10000	0	0
SMAD1/SMURF2	-0.01	0.079	0.41	6	-0.49	6	12
SMAD7/SMURF1	0.036	0.015	-10000	0	-10000	0	0
CTDSPL	0.026	0.008	-10000	0	-10000	0	0
PPP1CA	0.028	0.003	-10000	0	-10000	0	0
XIAP	0.028	0.001	-10000	0	-10000	0	0
CTDSP1	0.027	0.007	-10000	0	-10000	0	0
PPP1R15A	0.028	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.19	0.22	-10000	0	-0.56	158	158
CHRD	0.005	0.12	-10000	0	-0.63	30	30
BMPR2	0.027	0.006	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.14	0.14	-10000	0	-0.4	75	75
BMP4	0.023	0.056	-10000	0	-0.65	6	6
FST	-0.079	0.24	-10000	0	-0.61	139	139
BMP2-4/NOG	0.012	0.1	-10000	0	-0.41	19	19
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.37	0.28	-10000	0	-0.52	609	609

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.02	0.14	-9999	-0.42	94	94
GPC2	-0.02	0.13	-9999	-0.42	88	88
GPC2/Midkine	-0.023	0.14	-9999	-0.34	134	134
neuron projection morphogenesis	-0.023	0.14	-9999	-0.34	134	134

×

Aurora B signaling

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
Condensin I complex	-0.064	0.13	-10000	0	-0.3	135	135
STMN1	-0.099	0.16	0.21	1	-0.29	353	354
Aurora B/RasGAP/Survivin	-0.12	0.22	-10000	0	-0.45	239	239
Chromosomal passenger complex/Cul3 protein complex	-0.055	0.12	0.2	7	-0.39	48	55
BIRC5	-0.11	0.2	-10000	0	-0.43	256	256
DES	-0.26	0.34	-10000	0	-0.67	326	326
Aurora C/Aurora B/INCENP	-0.058	0.13	-10000	0	-0.32	9	9
Aurora B/TACC1	-0.076	0.14	-10000	0	-0.24	351	351
Aurora B/PP2A	-0.091	0.16	-10000	0	-0.29	348	348
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.015	0.038	-10000	0	-0.17	7	7
mitotic metaphase/anaphase transition	0.002	0.004	-10000	0	-10000	0	0
NDC80	-0.15	0.23	-10000	0	-0.41	365	365
Cul3 protein complex	0.036	0.089	-10000	0	-0.42	31	31
KIF2C	-0.069	0.14	-10000	0	-0.38	101	101
PEBP1	0.023	0.009	-10000	0	-10000	0	0
KIF20A	-0.16	0.22	-10000	0	-0.42	358	358
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	-0.09	0.16	-10000	0	-0.29	344	344
SEPT1	-0.004	0.11	-10000	0	-0.42	60	60
SMC2	0.028	0.004	-10000	0	-10000	0	0
SMC4	0.027	0.006	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.054	0.18	0.39	1	-0.74	44	45
PSMA3	0.027	0.005	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.003	-10000	0	-10000	0	0
H3F3B	-0.049	0.085	-10000	0	-0.36	7	7
AURKB	-0.15	0.22	-10000	0	-0.42	353	353
AURKC	0.024	0.042	-10000	0	-0.42	8	8
CDCA8	-0.007	0.11	-10000	0	-0.43	53	53
cytokinesis	-0.12	0.16	-10000	0	-0.46	81	81
Aurora B/Septin1	-0.1	0.19	0.33	1	-0.47	92	93
AURKA	0.022	0.05	-10000	0	-0.42	11	11
INCENP	0.019	0.018	-10000	0	-10000	0	0
KLHL13	0.004	0.13	-10000	0	-0.65	32	32
BUB1	-0.18	0.22	-10000	0	-0.42	400	400
hSgo1/Aurora B/Survivin	-0.12	0.22	-10000	0	-0.44	250	250
EVI5	0.027	0.008	-10000	0	-10000	0	0
RhoA/GTP	-0.079	0.16	-10000	0	-0.42	59	59
SGOL1	0.003	0.098	-10000	0	-0.42	44	44
CENPA	-0.086	0.15	0.22	13	-0.3	202	215
NCAPG	-0.12	0.21	-10000	0	-0.42	301	301
Aurora B/HC8 Proteasome	-0.092	0.16	-10000	0	-0.29	352	352
NCAPD2	0.027	0.006	-10000	0	-10000	0	0
Aurora B/PP1-gamma	-0.089	0.16	-10000	0	-0.29	342	342
RHOA	0.026	0.008	-10000	0	-10000	0	0
NCAPH	-0.042	0.16	-10000	0	-0.42	136	136
NPM1	-0.055	0.12	-10000	0	-0.57	15	15
RASA1	0.027	0.023	-10000	0	-0.65	1	1
KLHL9	0.027	0.013	-10000	0	-0.35	1	1
mitotic prometaphase	-0.004	0.007	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.092	0.16	-10000	0	-0.29	352	352
PPP1CC	0.027	0.006	-10000	0	-10000	0	0
Centraspindlin	-0.091	0.17	-10000	0	-0.42	83	83
RhoA/GDP	0.019	0.006	-10000	0	-10000	0	0
NSUN2	-0.055	0.11	-10000	0	-0.39	43	43
MYLK	-0.056	0.1	-10000	0	-0.38	27	27
KIF23	0.022	0.046	-10000	0	-0.43	9	9
VIM	-0.12	0.19	-10000	0	-0.33	359	359
RACGAP1	0.024	0.023	-10000	0	-0.43	2	2
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.077	0.19	-10000	0	-0.82	40	40
Chromosomal passenger complex	-0.11	0.16	0.21	3	-0.34	244	247
Chromosomal passenger complex/EVI5	-0.093	0.23	-10000	0	-0.43	243	243
TACC1	0.026	0.024	-10000	0	-0.65	1	1
PPP2R5D	0.026	0.007	-10000	0	-10000	0	0
CUL3	0.027	0.007	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	-0.036	0.16	-10000	0	-0.44	73	73
alphaM/beta2 Integrin/GPIbA	-0.037	0.16	-10000	0	-0.44	71	71
alphaM/beta2 Integrin/proMMP-9	-0.13	0.21	-10000	0	-0.5	144	144
PLAUR	0.006	0.096	-10000	0	-0.42	43	43
HMGB1	0.018	0.03	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.034	0.15	-10000	0	-0.43	71	71
AGER	-0.03	0.14	-10000	0	-0.42	92	92
RAP1A	0.027	0.007	-10000	0	-10000	0	0
SELPLG	-0.014	0.13	-10000	0	-0.42	82	82
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.061	0.18	-10000	0	-0.42	107	107
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.14	0.22	-10000	0	-0.42	332	332
CYR61	-0.002	0.13	-10000	0	-0.54	45	45
TLN1	0.028	0.004	-10000	0	-10000	0	0
Rap1/GTP	-0.18	0.17	-10000	0	-0.43	179	179
RHOA	0.026	0.008	-10000	0	-10000	0	0
P-selectin oligomer	-0.025	0.18	-10000	0	-0.61	72	72
MYH2	-0.25	0.21	-10000	0	-0.47	287	287
MST1R	0.006	0.098	-10000	0	-0.46	35	35
leukocyte activation during inflammatory response	-0.093	0.18	-10000	0	-0.44	122	122
APOB	-0.1	0.21	-10000	0	-0.45	234	234
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.022	0.048	-10000	0	-0.44	9	9
JAM3	0.026	0.04	-10000	0	-0.65	3	3
GP1BA	0.023	0.037	-10000	0	-0.57	3	3
alphaM/beta2 Integrin/CTGF	-0.046	0.16	-10000	0	-0.45	85	85
alphaM/beta2 Integrin	-0.21	0.2	-10000	0	-0.39	366	366
JAM3 homodimer	0.026	0.04	-10000	0	-0.65	3	3
ICAM2	0.025	0.009	-10000	0	-10000	0	0
ICAM1	0.021	0.058	-10000	0	-0.42	15	15
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.21	0.19	-10000	0	-0.38	366	366
cell adhesion	-0.037	0.15	-10000	0	-0.44	71	71
NFKB1	-0.094	0.2	0.37	3	-0.66	41	44
THY1	-0.035	0.2	-10000	0	-0.64	82	82
RhoA/GDP	0.019	0.006	-10000	0	-10000	0	0
Lipoprotein(a)	-0.053	0.14	-10000	0	-0.28	238	238
alphaM/beta2 Integrin/LRP/tPA	-0.044	0.18	-10000	0	-0.43	104	104
IL6	-0.13	0.27	-10000	0	-0.76	107	107
ITGB2	-0.063	0.17	-10000	0	-0.42	158	158
elevation of cytosolic calcium ion concentration	-0.046	0.18	-10000	0	-0.46	88	88
alphaM/beta2 Integrin/JAM2/JAM3	-0.022	0.16	-10000	0	-0.43	70	70
JAM2	0.018	0.077	-10000	0	-0.63	12	12
alphaM/beta2 Integrin/ICAM1	-0.025	0.16	-10000	0	-0.42	70	70
alphaM/beta2 Integrin/uPA/Plg	-0.23	0.26	-10000	0	-0.46	432	432
RhoA/GTP	-0.26	0.22	-10000	0	-0.48	311	311
positive regulation of phagocytosis	-0.17	0.18	-10000	0	-0.46	176	176
Ron/MSP	0.02	0.084	-10000	0	-0.34	43	43
alphaM/beta2 Integrin/uPAR/uPA	-0.045	0.18	-10000	0	-0.46	88	88
alphaM/beta2 Integrin/uPAR	-0.046	0.17	-10000	0	-0.46	81	81
PLAU	-0.004	0.13	-10000	0	-0.55	47	47
PLAT	-0.022	0.18	-10000	0	-0.63	66	66
actin filament polymerization	-0.24	0.2	-10000	0	-0.46	280	280
MST1	0.02	0.054	-10000	0	-0.5	9	9
alphaM/beta2 Integrin/lipoprotein(a)	-0.092	0.18	-10000	0	-0.44	122	122
TNF	-0.092	0.2	0.39	1	-0.64	48	49
RAP1B	0.027	0.006	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.052	0.17	-10000	0	-0.43	101	101
fibrinolysis	-0.23	0.25	-10000	0	-0.46	432	432
HCK	-0.006	0.12	-10000	0	-0.42	63	63
dendritic cell antigen processing and presentation	-0.21	0.19	-10000	0	-0.38	366	366
VTN	-0.078	0.23	-10000	0	-0.58	148	148
alphaM/beta2 Integrin/CYR61	-0.051	0.17	-10000	0	-0.44	93	93
LPA	-0.003	0.049	-10000	0	-0.43	9	9
LRP1	0.027	0.006	-10000	0	-10000	0	0
cell migration	-0.12	0.2	-10000	0	-0.5	127	127
FN1	-0.01	0.12	-10000	0	-0.42	72	72
alphaM/beta2 Integrin/Thy1	-0.07	0.19	-10000	0	-0.43	137	137
MPO	0.006	0.085	-10000	0	-0.42	33	33
KNG1	-0.44	0.3	-10000	0	-0.65	587	587
RAP1/GDP	0.034	0.012	-10000	0	-10000	0	0
ROCK1	-0.24	0.21	-10000	0	-0.47	278	278
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.31	0.32	-10000	0	-0.63	441	441
CTGF	0.008	0.11	-10000	0	-0.56	28	28
alphaM/beta2 Integrin/Hck	-0.05	0.19	-10000	0	-0.53	88	88
ITGAM	-0.018	0.12	-10000	0	-0.42	71	71
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.063	0.21	-10000	0	-0.47	142	142
HP	-0.067	0.18	-10000	0	-0.42	181	181
leukocyte adhesion	-0.08	0.19	-10000	0	-0.56	58	58
SELP	-0.025	0.18	-10000	0	-0.61	72	72

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.071	0.13	-10000	0	-0.36	58	58
TBX21	-0.2	0.37	0.6	2	-0.85	137	139
B2M	0.023	0.013	-10000	0	-10000	0	0
TYK2	0.009	0.035	-10000	0	-10000	0	0
IL12RB1	-0.087	0.2	-10000	0	-0.45	200	200
GADD45B	-0.12	0.26	-10000	0	-0.65	53	53
IL12RB2	-0.11	0.2	-10000	0	-0.43	233	233
GADD45G	-0.13	0.28	-10000	0	-0.73	46	46
natural killer cell activation	-0.005	0.023	0.042	3	-0.038	123	126
RELB	0.028	0.003	-10000	0	-10000	0	0
RELA	0.028	0.003	-10000	0	-10000	0	0
IL18	0.006	0.095	-10000	0	-0.42	40	40
IL2RA	-0.045	0.16	-10000	0	-0.42	140	140
IFNG	-0.11	0.2	-10000	0	-0.42	257	257
STAT3 (dimer)	-0.17	0.3	-10000	0	-0.63	183	183
HLA-DRB5	-0.001	0.006	-10000	0	-0.024	43	43
FASLG	-0.22	0.37	-10000	0	-0.83	170	170
NF kappa B2 p52/RelB	-0.17	0.33	-10000	0	-0.71	164	164
CD4	0.01	0.081	-10000	0	-0.42	30	30
SOCS1	0.018	0.068	-10000	0	-0.52	13	13
EntrezGene:6955	-0.003	0.009	-10000	0	-0.025	52	52
CD3D	-0.12	0.21	-10000	0	-0.43	287	287
CD3E	-0.12	0.21	-10000	0	-0.43	266	266
CD3G	-0.1	0.2	-10000	0	-0.43	247	247
IL12Rbeta2/JAK2	-0.073	0.15	-10000	0	-0.34	127	127
CCL3	-0.18	0.36	0.6	2	-0.85	119	121
CCL4	-0.19	0.37	0.6	2	-0.86	137	139
HLA-A	-0.003	0.007	-10000	0	-0.022	19	19
IL18/IL18R	-0.02	0.15	-10000	0	-0.3	83	83
NOS2	-0.17	0.34	-10000	0	-0.82	111	111
IL12/IL12R/TYK2/JAK2/SPHK2	-0.068	0.13	-10000	0	-0.36	50	50
IL1R1	-0.18	0.34	0.6	2	-0.77	139	141
IL4	0.01	0.038	-10000	0	-10000	0	0
JAK2	0.008	0.034	-10000	0	-10000	0	0
EntrezGene:6957	-0.003	0.008	-10000	0	-0.023	45	45
TCR/CD3/MHC I/CD8	-0.17	0.27	-10000	0	-0.58	236	236
RAB7A	-0.093	0.26	0.59	4	-0.78	14	18
lysosomal transport	-0.088	0.25	0.59	4	-0.72	15	19
FOS	-0.18	0.38	-10000	0	-0.93	118	118
STAT4 (dimer)	-0.16	0.33	0.58	5	-0.71	152	157
STAT5A (dimer)	-0.22	0.37	-10000	0	-0.8	203	203
GZMA	-0.21	0.37	-10000	0	-0.82	173	173
GZMB	-0.2	0.36	-10000	0	-0.82	158	158
HLX	-0.01	0.12	-10000	0	-0.42	71	71
LCK	-0.2	0.36	-10000	0	-0.79	175	175
TCR/CD3/MHC II/CD4	-0.1	0.16	-10000	0	-0.33	270	270
IL2/IL2R	-0.098	0.2	-10000	0	-0.48	129	129
MAPK14	-0.12	0.29	0.51	3	-0.68	80	83
CCR5	-0.18	0.33	0.61	2	-0.72	150	152
IL1B	-0.003	0.086	-10000	0	-0.54	18	18
STAT6	-0.038	0.1	-10000	0	-10000	0	0
STAT4	0.003	0.1	-10000	0	-0.42	47	47
STAT3	0.025	0.009	-10000	0	-10000	0	0
STAT1	0.026	0.022	-10000	0	-0.42	2	2
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
NFKB2	0.027	0.007	-10000	0	-10000	0	0
IL12B	-0.037	0.14	-10000	0	-0.44	90	90
CD8A	-0.11	0.21	-10000	0	-0.43	267	267
CD8B	-0.093	0.2	-10000	0	-0.43	226	226
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.07	0.13	0.36	58	-10000	0	58
IL2RB	-0.14	0.22	-10000	0	-0.42	328	328
proteasomal ubiquitin-dependent protein catabolic process	-0.15	0.31	0.57	5	-0.65	151	156
IL2RG	0.003	0.11	-10000	0	-0.44	47	47
IL12	-0.019	0.11	-10000	0	-0.32	88	88
STAT5A	0.025	0.009	-10000	0	-10000	0	0
CD247	-0.085	0.19	-10000	0	-0.43	207	207
IL2	-0.004	0.061	-10000	0	-0.42	16	16
SPHK2	0.027	0.033	-10000	0	-0.65	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.007	0.034	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	-0.2	0.36	-10000	0	-0.78	185	185
MAP2K3	-0.12	0.29	0.5	3	-0.67	86	89
RIPK2	0.027	0.016	-10000	0	-0.42	1	1
MAP2K6	-0.12	0.29	0.5	3	-0.67	86	89
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.001	0.006	-10000	0	-0.027	44	44
IL18RAP	-0.058	0.18	-10000	0	-0.42	164	164
IL12Rbeta1/TYK2	-0.053	0.16	-10000	0	-0.34	189	189
EOMES	-0.099	0.17	-10000	0	-0.72	20	20
STAT1 (dimer)	-0.18	0.32	-10000	0	-0.68	170	170
T cell proliferation	-0.12	0.26	0.46	5	-0.54	132	137
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.019	0.06	-10000	0	-0.48	11	11
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.16	0.26	-10000	0	-0.62	103	103
ATF2	-0.11	0.28	0.64	4	-0.66	63	67

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.44	0.43	-10000	0	-1.2	133	133
STAT6 (cleaved dimer)	-0.47	0.44	-10000	0	-1.1	211	211
IGHG1	-0.16	0.15	-10000	0	-0.42	23	23
IGHG3	-0.43	0.42	-10000	0	-1	191	191
AKT1	-0.22	0.24	0.56	2	-0.78	47	49
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.16	0.18	-10000	0	-0.8	15	15
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.24	0.26	-10000	0	-0.93	51	51
THY1	-0.51	0.53	-10000	0	-1.4	175	175
MYB	-0.093	0.2	-10000	0	-0.42	233	233
HMGA1	0.022	0.043	-10000	0	-0.42	8	8
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.29	0.26	-10000	0	-0.69	127	127
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.24	0.26	-10000	0	-0.96	44	44
SP1	0.025	0.026	-10000	0	-10000	0	0
INPP5D	0.022	0.048	-10000	0	-0.42	10	10
SOCS5	0.038	0.02	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.46	0.44	-10000	0	-1.1	188	188
SOCS1	-0.31	0.29	-10000	0	-0.76	110	110
SOCS3	-0.24	0.24	-10000	0	-0.84	24	24
FCER2	-0.36	0.34	-10000	0	-0.97	92	92
PARP14	0.027	0.008	-10000	0	-10000	0	0
CCL17	-0.45	0.44	-10000	0	-1.1	154	154
GRB2	0.025	0.009	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.2	0.24	-10000	0	-0.86	50	50
T cell proliferation	-0.45	0.44	-10000	0	-1.2	157	157
IL4R/JAK1	-0.44	0.43	-10000	0	-1.1	145	145
EGR2	-0.48	0.48	-10000	0	-1.3	151	151
JAK2	-0.024	0.039	-10000	0	-10000	0	0
JAK3	-0.054	0.18	-10000	0	-0.42	165	165
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
JAK1	0.006	0.021	-10000	0	-10000	0	0
COL1A2	-0.15	0.17	-10000	0	-0.56	13	13
CCL26	-0.43	0.44	-10000	0	-1.1	147	147
IL4R	-0.47	0.46	-10000	0	-1.2	140	140
PTPN6	0.038	0.014	-10000	0	-10000	0	0
IL13RA2	-0.64	0.61	-10000	0	-1.4	282	282
IL13RA1	-0.024	0.039	-10000	0	-10000	0	0
IRF4	-0.15	0.22	-10000	0	-0.72	58	58
ARG1	-0.14	0.17	-10000	0	-0.84	6	6
CBL	-0.27	0.25	-10000	0	-0.68	104	104
GTF3A	0.011	0.04	-10000	0	-0.41	1	1
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.028	0.055	-10000	0	-10000	0	0
IRF4/BCL6	-0.14	0.21	-10000	0	-0.72	46	46
CD40LG	-0.029	0.15	-10000	0	-0.45	101	101
MAPK14	-0.27	0.25	-10000	0	-0.69	92	92
mitosis	-0.21	0.23	0.56	2	-0.73	47	49
STAT6	-0.5	0.5	-10000	0	-1.3	179	179
SPI1	-0.036	0.16	-10000	0	-0.41	130	130
RPS6KB1	-0.19	0.23	0.54	2	-0.74	38	40
STAT6 (dimer)	-0.5	0.51	-10000	0	-1.3	179	179
STAT6 (dimer)/PARP14	-0.46	0.46	-10000	0	-1.2	167	167
mast cell activation	0.012	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.22	0.22	-10000	0	-0.71	42	42
FRAP1	-0.22	0.24	0.56	2	-0.78	47	49
LTA	-0.48	0.44	-10000	0	-1.1	179	179
FES	0.026	0.04	-10000	0	-0.65	3	3
T-helper 1 cell differentiation	0.5	0.49	1.2	179	-10000	0	179
CCL11	-0.61	0.58	-10000	0	-1.3	294	294
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.21	0.22	-10000	0	-0.72	32	32
IL2RG	0.006	0.11	-10000	0	-0.45	47	47
IL10	-0.46	0.44	-10000	0	-1.2	150	150
IRS1	0.019	0.072	-10000	0	-0.65	10	10
IRS2	0.018	0.064	-10000	0	-0.42	18	18
IL4	-0.11	0.13	-10000	0	-0.96	7	7
IL5	-0.44	0.44	-10000	0	-1.1	150	150
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.38	0.36	-10000	0	-0.93	145	145
COL1A1	-0.24	0.27	-10000	0	-0.82	71	71
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.44	0.44	-10000	0	-1.2	117	117
IL2R gamma/JAK3	-0.039	0.17	-10000	0	-0.36	176	176
TFF3	-0.53	0.55	-10000	0	-1.4	194	194
ALOX15	-0.44	0.43	-10000	0	-1.2	132	132
MYBL1	-0.001	0.11	-10000	0	-0.42	56	56
T-helper 2 cell differentiation	-0.39	0.38	-10000	0	-0.94	174	174
SHC1	0.026	0.016	-10000	0	-0.42	1	1
CEBPB	0.018	0.071	-10000	0	-0.42	22	22
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.23	0.26	0.44	1	-0.9	53	54
mol:PI-3-4-5-P3	-0.22	0.24	0.57	2	-0.78	47	49
PI3K	-0.23	0.26	0.57	2	-0.84	47	49
DOK2	-0.004	0.11	-10000	0	-0.42	59	59
ETS1	0.038	0.019	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.2	0.24	-10000	0	-0.82	59	59
ITGB3	-0.46	0.46	-10000	0	-1.2	140	140
PIGR	-0.7	0.64	-10000	0	-1.4	358	358
IGHE	0.034	0.062	0.23	15	-0.27	1	16
MAPKKK cascade	-0.19	0.24	-10000	0	-0.8	59	59
BCL6	0.027	0.006	-10000	0	-10000	0	0
OPRM1	-0.46	0.43	-10000	0	-1.1	158	158
RETNLB	-0.45	0.43	-10000	0	-1.2	136	136
SELP	-0.5	0.52	-10000	0	-1.3	178	178
AICDA	-0.47	0.43	-10000	0	-1.1	184	184

×

Syndecan-4-mediated signaling events

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
PTK2	-0.042	0.11	-10000	0	-0.65	12	12
Syndecan-4/Syndesmos	-0.2	0.19	-10000	0	-0.53	107	107
positive regulation of JNK cascade	-0.25	0.22	-10000	0	-0.55	181	181
Syndecan-4/ADAM12	-0.24	0.23	-10000	0	-0.61	145	145
CCL5	-0.1	0.2	-10000	0	-0.42	253	253
Rac1/GDP	0.018	0.007	-10000	0	-10000	0	0
DNM2	0.028	0.003	-10000	0	-10000	0	0
ITGA5	0.004	0.098	-10000	0	-0.42	45	45
SDCBP	0.027	0.005	-10000	0	-10000	0	0
PLG	-0.3	0.32	-10000	0	-0.62	442	442
ADAM12	-0.068	0.18	-10000	0	-0.42	187	187
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.026	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.075	0.054	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.21	0.2	-10000	0	-0.55	123	123
Syndecan-4/CXCL12/CXCR4	-0.26	0.23	-10000	0	-0.58	181	181
Syndecan-4/Laminin alpha3	-0.22	0.2	-10000	0	-0.54	123	123
MDK	-0.02	0.14	-10000	0	-0.42	94	94
Syndecan-4/FZD7	-0.21	0.2	-10000	0	-0.54	112	112
Syndecan-4/Midkine	-0.22	0.21	0.41	1	-0.56	123	124
FZD7	0.015	0.086	-10000	0	-0.61	16	16
Syndecan-4/FGFR1/FGF	-0.19	0.19	-10000	0	-0.52	106	106
THBS1	0.006	0.12	-10000	0	-0.64	29	29
integrin-mediated signaling pathway	-0.2	0.2	-10000	0	-0.53	119	119
positive regulation of MAPKKK cascade	-0.25	0.22	-10000	0	-0.55	181	181
Syndecan-4/TACI	-0.21	0.2	-10000	0	-0.55	121	121
CXCR4	-0.086	0.19	-10000	0	-0.42	223	223
cell adhesion	0.018	0.055	0.22	11	-0.25	1	12
Syndecan-4/Dynamin	-0.2	0.2	-10000	0	-0.53	107	107
Syndecan-4/TSP1	-0.21	0.2	-10000	0	-0.55	120	120
Syndecan-4/GIPC	-0.2	0.2	-10000	0	-0.53	108	108
Syndecan-4/RANTES	-0.25	0.22	-10000	0	-0.6	156	156
ITGB1	0.027	0.007	-10000	0	-10000	0	0
LAMA1	0.006	0.12	-10000	0	-0.57	32	32
LAMA3	-0.011	0.13	-10000	0	-0.42	75	75
RAC1	0.025	0.01	-10000	0	-10000	0	0
PRKCA	0.1	0.19	0.83	52	-10000	0	52
Syndecan-4/alpha-Actinin	-0.2	0.2	-10000	0	-0.53	108	108
TFPI	0.012	0.092	-10000	0	-0.5	26	26
F2	-0.1	0.2	-10000	0	-0.41	251	251
alpha5/beta1 Integrin	0.021	0.074	-10000	0	-0.29	45	45
positive regulation of cell adhesion	-0.22	0.2	-10000	0	-0.53	140	140
ACTN1	0.027	0.024	-10000	0	-0.65	1	1
TNC	0.003	0.12	-10000	0	-0.58	35	35
Syndecan-4/CXCL12	-0.22	0.21	-10000	0	-0.55	133	133
FGF6	-0.016	0.008	-10000	0	-10000	0	0
RHOA	0.026	0.008	-10000	0	-10000	0	0
CXCL12	-0.024	0.17	-10000	0	-0.56	77	77
TNFRSF13B	-0.007	0.1	-10000	0	-0.42	48	48
FGF2	0.016	0.087	-10000	0	-0.62	16	16
FGFR1	0.026	0.016	-10000	0	-0.42	1	1
Syndecan-4/PI-4-5-P2	-0.21	0.19	-10000	0	-0.53	108	108
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.004	0.12	-10000	0	-0.4	72	72
cell migration	-0.027	0.018	-10000	0	-10000	0	0
PRKCD	0.028	0.049	-10000	0	-0.41	9	9
vasculogenesis	-0.2	0.2	-10000	0	-0.52	120	120
SDC4	-0.21	0.2	-10000	0	-0.56	107	107
Syndecan-4/Tenascin C	-0.21	0.2	-10000	0	-0.55	119	119
Syndecan-4/PI-4-5-P2/PKC alpha	-0.06	0.042	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.2	0.2	-10000	0	-0.53	106	106
MMP9	-0.14	0.21	-10000	0	-0.41	332	332
Rac1/GTP	0.018	0.056	0.22	9	-0.25	1	10
cytoskeleton organization	-0.19	0.19	-10000	0	-0.51	107	107
GIPC1	0.027	0.023	-10000	0	-0.65	1	1
Syndecan-4/TFPI	-0.21	0.2	-10000	0	-0.54	115	115

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.008	0.029	0.2	4	-0.33	5	9
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.01	0.1	-10000	0	-0.34	66	66
STXBP1	0.027	0.023	-10000	0	-0.65	1	1
ACh/CHRNA1	-0.12	0.14	-10000	0	-0.26	421	421
RAB3GAP2/RIMS1/UNC13B	0.028	0.088	-10000	0	-0.32	32	32
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	-0.023	0.13	-10000	0	-0.47	67	67
mol:ACh	0.004	0.054	0.13	83	-0.14	16	99
RAB3GAP2	0.027	0.007	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.005	0.092	-10000	0	-0.36	10	10
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.12	0.14	-10000	0	-0.26	421	421
UNC13B	0.028	0.004	-10000	0	-10000	0	0
CHRNA1	-0.2	0.22	-10000	0	-0.42	430	430
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.077	0.18	-10000	0	-0.44	174	174
SNAP25	-0.024	0.064	-10000	0	-0.14	183	183
VAMP2	0.006	0.002	-10000	0	-10000	0	0
SYT1	-0.11	0.27	-10000	0	-0.65	174	174
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.022	0.03	-10000	0	-0.3	6	6
STX1A/SNAP25 fragment 1/VAMP2	0.005	0.092	-10000	0	-0.36	10	10

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.079	0.17	0.43	2	-0.47	93	95
CRKL	-0.033	0.16	-10000	0	-0.47	93	93
HRAS	-0.034	0.15	-10000	0	-0.48	39	39
mol:PIP3	-0.024	0.16	-10000	0	-0.44	84	84
SPRED1	0.028	0.004	-10000	0	-10000	0	0
SPRED2	0.026	0.024	-10000	0	-0.65	1	1
GAB1	-0.035	0.18	-10000	0	-0.49	96	96
FOXO3	-0.009	0.17	0.29	7	-0.43	82	89
AKT1	-0.013	0.18	0.3	7	-0.46	88	95
BAD	-0.009	0.17	0.3	10	-0.44	82	92
megakaryocyte differentiation	-0.096	0.22	-10000	0	-0.43	232	232
GSK3B	-0.003	0.17	0.39	19	-0.43	81	100
RAF1	-0.024	0.12	0.28	8	-0.39	29	37
SHC1	0.026	0.016	-10000	0	-0.42	1	1
STAT3	-0.033	0.17	-10000	0	-0.49	87	87
STAT1	-0.084	0.34	-10000	0	-1	96	96
HRAS/SPRED1	-0.018	0.13	-10000	0	-0.39	33	33
cell proliferation	-0.034	0.17	-10000	0	-0.48	98	98
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
TEC	0.028	0.005	-10000	0	-10000	0	0
RPS6KB1	-0.03	0.18	-10000	0	-0.48	97	97
HRAS/SPRED2	-0.017	0.13	-10000	0	-0.39	32	32
LYN/TEC/p62DOK	0	0.18	-10000	0	-0.46	93	93
MAPK3	0	0.12	0.37	28	-0.3	12	40
STAP1	-0.27	0.23	-10000	0	-0.39	603	603
GRAP2	-0.002	0.11	-10000	0	-0.42	56	56
JAK2	-0.073	0.3	-10000	0	-0.89	96	96
STAT1 (dimer)	-0.082	0.33	-10000	0	-1	97	97
mol:Gleevec	0	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.05	0.18	-10000	0	-0.49	82	82
actin filament polymerization	-0.037	0.16	0.24	1	-0.49	83	84
LYN	0.026	0.024	-10000	0	-0.65	1	1
STAP1/STAT5A (dimer)	-0.27	0.26	-10000	0	-0.74	133	133
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.005	0.15	0.4	1	-0.44	62	63
PI3K	-0.005	0.18	-10000	0	-0.47	79	79
PTEN	0.026	0.007	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.12	0.4	-10000	0	-1.2	96	96
MAPK8	-0.035	0.18	-10000	0	-0.49	98	98
STAT3 (dimer)	-0.031	0.16	-10000	0	-0.48	87	87
positive regulation of transcription	0.005	0.1	0.35	30	-0.27	5	35
mol:GDP	-0.045	0.16	-10000	0	-0.5	41	41
PIK3C2B	-0.032	0.17	-10000	0	-0.49	93	93
CBL/CRKL	-0.017	0.16	0.4	1	-0.44	90	91
FER	-0.036	0.17	-10000	0	-0.49	96	96
SH2B3	-0.033	0.17	-10000	0	-0.48	96	96
PDPK1	-0.012	0.14	0.33	11	-0.4	77	88
SNAI2	-0.053	0.2	-10000	0	-0.54	106	106
positive regulation of cell proliferation	-0.054	0.26	-10000	0	-0.76	97	97
KITLG	0.013	0.092	-10000	0	-0.67	15	15
cell motility	-0.054	0.26	-10000	0	-0.76	97	97
PTPN6	0.027	0.011	-10000	0	-10000	0	0
EPOR	0.013	0.12	-10000	0	-1	4	4
STAT5A (dimer)	-0.048	0.23	-10000	0	-0.64	97	97
SOCS1	0.018	0.068	-10000	0	-0.52	13	13
cell migration	0.05	0.18	0.5	97	-10000	0	97
SOS1	0.027	0.006	-10000	0	-10000	0	0
EPO	-0.073	0.18	-10000	0	-0.41	184	184
VAV1	-0.069	0.18	-10000	0	-0.42	191	191
GRB10	-0.037	0.16	-10000	0	-0.49	84	84
PTPN11	0.027	0.008	-10000	0	-10000	0	0
SCF/KIT	-0.037	0.18	-10000	0	-0.51	102	102
GO:0007205	0.001	0.008	-10000	0	-10000	0	0
MAP2K1	-0.008	0.12	0.37	22	-0.33	14	36
CBL	0.027	0.023	-10000	0	-0.65	1	1
KIT	-0.11	0.43	-10000	0	-1.3	98	98
MAP2K2	-0.009	0.12	0.35	25	-0.33	16	41
SHC/Grb2/SOS1	0.002	0.17	-10000	0	-0.46	80	80
STAT5A	-0.051	0.23	-10000	0	-0.67	97	97
GRB2	0.025	0.009	-10000	0	-10000	0	0
response to radiation	-0.052	0.2	-10000	0	-0.52	107	107
SHC/GRAP2	0.016	0.084	-10000	0	-0.3	57	57
PTPRO	-0.098	0.22	-10000	0	-0.44	231	231
SH2B2	-0.038	0.17	-10000	0	-0.5	83	83
DOK1	0.026	0.022	-10000	0	-0.42	2	2
MATK	-0.051	0.19	-10000	0	-0.52	97	97
CREBBP	0.031	0.045	-10000	0	-10000	0	0
BCL2	0.005	0.16	-10000	0	-1.1	10	10

×

Arf6 signaling events

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
CENTA1/KIF3B	0.029	0.037	-10000	0	-0.42	5	5
ARNO/beta Arrestin1-2	0.021	0.066	-10000	0	-0.82	2	2
EGFR	0.017	0.061	-10000	0	-0.45	14	14
EPHA2	0.026	0.024	-10000	0	-0.65	1	1
USP6	0.02	0.05	-10000	0	-0.42	11	11
IQSEC1	0.026	0.008	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.38	0.2	-10000	0	-0.46	727	727
ARRB2	-0.002	0.048	-10000	0	-0.51	1	1
mol:GTP	0.017	0.065	0.2	58	-0.22	8	66
ARRB1	0.027	0.023	-10000	0	-0.65	1	1
FBXO8	0.028	0.005	-10000	0	-10000	0	0
TSHR	-0.015	0.13	-10000	0	-0.42	78	78
EGF	-0.54	0.25	-10000	0	-0.65	731	731
somatostatin receptor activity	0	0	0.001	33	-0.001	71	104
ARAP2	0.026	0.033	-10000	0	-0.65	2	2
mol:GDP	-0.049	0.11	0.26	16	-0.29	71	87
mol:PI-3-4-5-P3	0	0	0.001	27	-0.001	37	64
ITGA2B	0.015	0.068	-10000	0	-0.46	17	17
ARF6	0.027	0.005	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.06	0.032	-10000	0	-0.38	1	1
ADAP1	0.021	0.052	-10000	0	-0.65	5	5
KIF13B	0.027	0.007	-10000	0	-10000	0	0
HGF/MET	0.01	0.11	-10000	0	-0.46	46	46
PXN	0.027	0.006	-10000	0	-10000	0	0
ARF6/GTP	-0.077	0.13	0.33	31	-0.32	78	109
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.32	0.18	-10000	0	-0.42	624	624
ADRB2	0.016	0.069	-10000	0	-0.43	20	20
receptor agonist activity	0	0	0.001	33	0	59	92
actin filament binding	0	0	0.001	31	-0.001	77	108
SRC	0.027	0.007	-10000	0	-10000	0	0
ITGB3	0.007	0.11	-10000	0	-0.61	25	25
GNAQ	0.028	0.004	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.002	54	-0.001	40	94
ARF6/GDP	-0.03	0.11	0.34	6	-0.45	19	25
ARF6/GDP/GULP/ACAP1	-0.078	0.14	-10000	0	-0.42	48	48
alphaIIb/beta3 Integrin/paxillin/GIT1	0.046	0.083	-10000	0	-0.4	20	20
ACAP1	-0.089	0.19	-10000	0	-0.42	225	225
ACAP2	0.027	0.006	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	-0.001	0.068	-10000	0	-0.23	69	69
EFNA1	0.026	0.016	-10000	0	-0.42	1	1
HGF	-0.007	0.14	-10000	0	-0.6	45	45
CYTH3	0.009	0.003	-10000	0	-10000	0	0
CYTH2	0.016	0.049	-10000	0	-1	2	2
NCK1	0.027	0.006	-10000	0	-10000	0	0
fibronectin binding	0	0	0.001	56	0	47	103
endosomal lumen acidification	0	0	0.001	23	-0.001	114	137
microtubule-based process	0	0	-10000	0	-0.001	8	8
GULP1	0.017	0.08	-10000	0	-0.63	13	13
GNAQ/ARNO	0.032	0.047	-10000	0	-0.93	2	2
mol:Phosphatidic acid	0	0	0.001	10	-10000	0	10
PIP3-E	0	0	0.001	9	0	2	11
MET	0.021	0.04	-10000	0	-0.42	7	7
GNA14	-0.042	0.21	-10000	0	-0.64	92	92
GNA15	0.01	0.088	-10000	0	-0.42	34	34
GIT1	0.025	0.009	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0.001	0.002	47	-0.001	47	94
GNA11	0.022	0.065	-10000	0	-0.65	8	8
LHCGR	-0.03	0.12	-10000	0	-0.42	69	69
AGTR1	-0.072	0.24	-10000	0	-0.65	128	128
desensitization of G-protein coupled receptor protein signaling pathway	-0.001	0.068	-10000	0	-0.23	69	69
IPCEF1/ARNO	-0.24	0.14	-10000	0	-0.57	13	13
alphaIIb/beta3 Integrin	0.016	0.098	-10000	0	-0.42	40	40

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.015	0.07	-10000	0	-0.42	22	22
GNB1/GNG2	-0.055	0.076	-10000	0	-0.19	117	117
AKT1	-0.017	0.13	0.35	18	-0.35	13	31
EGF	-0.54	0.25	-10000	0	-0.65	731	731
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.013	0.087	0.55	8	-0.69	1	9
mol:Ca2+	-0.042	0.16	0.42	9	-0.31	160	169
LYN	0.012	0.069	0.47	4	-0.45	1	5
RhoA/GTP	-0.014	0.063	-10000	0	-10000	0	0
mol:PGI2	0	0.001	-10000	0	-10000	0	0
SYK	-0.053	0.18	0.44	11	-0.34	186	197
GNG2	0.027	0.005	-10000	0	-10000	0	0
ARRB2	0.024	0.03	-10000	0	-0.46	3	3
TP alpha/Gq family/GDP/G beta5/gamma2	-0.001	0.09	-10000	0	-0.48	13	13
G beta5/gamma2	-0.071	0.1	-10000	0	-0.26	116	116
PRKCH	-0.056	0.18	0.46	7	-0.36	167	174
DNM1	-0.039	0.16	-10000	0	-0.42	129	129
TXA2/TP beta/beta Arrestin3	-0.008	0.053	-10000	0	-0.3	1	1
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.012	0.13	-10000	0	-0.42	78	78
G12 family/GTP	-0.049	0.14	-10000	0	-0.3	135	135
ADRBK1	0.028	0.003	-10000	0	-10000	0	0
ADRBK2	0.027	0.005	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.034	0.012	-10000	0	-10000	0	0
mol:GDP	0.019	0.13	0.43	32	-0.34	11	43
mol:NADP	0.017	0.072	-10000	0	-0.65	10	10
RAB11A	0.028	0.003	-10000	0	-10000	0	0
PRKG1	-0.044	0.21	-10000	0	-0.64	92	92
mol:IP3	-0.059	0.2	0.46	8	-0.38	167	175
cell morphogenesis	0.033	0.012	-10000	0	-10000	0	0
PLCB2	-0.091	0.25	0.46	6	-0.52	170	176
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	0.002	0.083	0.45	5	-0.45	1	6
mol:PDG2	0	0.001	-10000	0	-10000	0	0
HCK	-0.004	0.079	0.38	2	-0.59	2	4
RHOA	0.026	0.008	-10000	0	-10000	0	0
PTGIR	0.024	0.053	-10000	0	-0.61	6	6
PRKCB1	-0.06	0.2	0.48	8	-0.38	182	190
GNAQ	0.028	0.004	-10000	0	-10000	0	0
mol:L-citrulline	0.017	0.072	-10000	0	-0.65	10	10
TXA2/TXA2-R family	-0.094	0.26	0.55	8	-0.52	209	217
LCK	0.007	0.097	0.55	8	-0.49	3	11
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.016	0.071	-10000	0	-0.33	16	16
TXA2-R family/G12 family/GDP/G beta/gamma	-0.001	0.12	-10000	0	-0.44	54	54
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.016	0.067	-10000	0	-0.42	1	1
MAPK14	-0.029	0.13	0.36	12	-0.26	8	20
TGM2/GTP	-0.069	0.21	0.4	4	-0.44	117	121
MAPK11	-0.027	0.13	0.41	12	-0.26	19	31
ARHGEF1	-0.022	0.087	-10000	0	-0.2	4	4
GNAI2	0.026	0.008	-10000	0	-10000	0	0
JNK cascade	-0.061	0.2	0.49	9	-0.38	208	217
RAB11/GDP	0.028	0.005	-10000	0	-10000	0	0
ICAM1	-0.038	0.15	0.42	9	-0.28	113	122
cAMP biosynthetic process	-0.056	0.18	0.48	9	-0.37	125	134
Gq family/GTP/EBP50	-0.005	0.076	0.24	1	-0.3	16	17
actin cytoskeleton reorganization	0.033	0.012	-10000	0	-10000	0	0
SRC	0.009	0.057	0.38	2	-0.45	1	3
GNB5	0.028	0.003	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
EGF/EGFR	-0.089	0.11	0.6	10	-0.34	13	23
VCAM1	-0.049	0.17	0.43	9	-0.31	187	196
TP beta/Gq family/GDP/G beta5/gamma2	-0.001	0.09	-10000	0	-0.48	13	13
platelet activation	-0.037	0.17	0.42	17	-0.31	99	116
PGI2/IP	0.017	0.04	-10000	0	-0.46	6	6
PRKACA	0.008	0.05	-10000	0	-0.31	5	5
Gq family/GDP/G beta5/gamma2	0	0.085	-10000	0	-0.41	16	16
TXA2/TP beta/beta Arrestin2	-0.012	0.072	-10000	0	-0.42	13	13
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.003	0.07	-10000	0	-0.36	22	22
mol:DAG	-0.07	0.22	0.49	7	-0.43	180	187
EGFR	0.017	0.061	-10000	0	-0.45	14	14
TXA2/TP alpha	-0.081	0.24	0.56	8	-0.5	128	136
Gq family/GTP	-0.016	0.09	-10000	0	-0.26	99	99
YES1	0.013	0.072	0.49	5	-0.45	1	6
GNAI2/GTP	0.009	0.063	-10000	0	-0.52	1	1
PGD2/DP	-0.008	0.089	-10000	0	-0.29	78	78
SLC9A3R1	0.025	0.009	-10000	0	-10000	0	0
FYN	0.015	0.083	0.55	8	-0.45	1	9
mol:NO	0.017	0.072	-10000	0	-0.65	10	10
GNA15	0.011	0.088	-10000	0	-0.42	34	34
PGK/cGMP	-0.012	0.13	-10000	0	-0.36	97	97
RhoA/GDP	0.026	0.009	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.026	0.082	-10000	0	-0.73	1	1
NOS3	0.017	0.072	-10000	0	-0.65	10	10
RAC1	0.025	0.01	-10000	0	-10000	0	0
PRKCA	-0.049	0.18	0.4	15	-0.36	143	158
PRKCB	-0.051	0.19	0.4	14	-0.37	157	171
PRKCE	-0.055	0.18	0.47	8	-0.36	154	162
PRKCD	-0.063	0.2	0.46	10	-0.38	196	206
PRKCG	-0.072	0.21	0.49	8	-0.42	190	198
muscle contraction	-0.083	0.24	0.56	8	-0.48	207	215
PRKCZ	-0.053	0.18	0.44	10	-0.34	184	194
ARR3	-0.007	0.02	-10000	0	-10000	0	0
TXA2/TP beta	0.021	0.073	-10000	0	-0.58	1	1
PRKCQ	-0.067	0.19	0.42	8	-0.38	187	195
MAPKKK cascade	-0.075	0.23	0.5	9	-0.45	172	181
SELE	-0.071	0.2	0.43	9	-0.41	218	227
TP beta/GNAI2/GDP/G beta/gamma	0.03	0.076	-10000	0	-0.56	1	1
ROCK1	0.028	0.005	-10000	0	-10000	0	0
GNA14	-0.042	0.21	-10000	0	-0.64	92	92
chemotaxis	-0.12	0.3	0.56	8	-0.61	217	225
GNA12	0.025	0.009	-10000	0	-10000	0	0
GNA13	0.025	0.009	-10000	0	-10000	0	0
GNA11	0.022	0.065	-10000	0	-0.65	8	8
Rac1/GTP	0.018	0.007	-10000	0	-10000	0	0

×

Endothelins

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.025	0.17	-10000	0	-0.52	39	39
PTK2B	0.027	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.12	0.38	0.62	4	-0.93	136	140
EDN1	-0.008	0.14	0.47	1	-0.46	40	41
EDN3	0	0.065	-10000	0	-0.43	17	17
EDN2	-0.04	0.18	-10000	0	-0.5	111	111
HRAS/GDP	-0.051	0.21	0.32	9	-0.55	76	85
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.056	0.19	0.25	2	-0.47	104	106
ADCY4	-0.027	0.16	0.34	1	-0.6	30	31
ADCY5	-0.038	0.17	0.42	3	-0.56	40	43
ADCY6	-0.021	0.14	-10000	0	-0.52	24	24
ADCY7	-0.027	0.14	0.34	1	-0.51	21	22
ADCY1	-0.059	0.17	0.45	1	-0.51	58	59
ADCY2	-0.09	0.18	0.34	2	-0.54	49	51
ADCY3	-0.019	0.14	0.35	3	-0.52	24	27
ADCY8	-0.061	0.16	0.34	1	-0.46	55	56
ADCY9	-0.02	0.13	-10000	0	-0.5	21	21
arachidonic acid secretion	-0.069	0.26	0.48	12	-0.59	117	129
ETB receptor/Endothelin-1/Gq/GTP	-0.024	0.13	-10000	0	-0.36	76	76
GNAO1	0.011	0.095	-10000	0	-0.56	23	23
HRAS	0.027	0.015	-10000	0	-0.42	1	1
ETA receptor/Endothelin-1/G12/GTP	0.008	0.18	0.37	39	-0.49	32	71
ETA receptor/Endothelin-1/Gs/GTP	0.009	0.18	0.34	48	-0.51	31	79
mol:GTP	0	0.006	-10000	0	-10000	0	0
COL3A1	-0.043	0.21	-10000	0	-0.56	73	73
EDNRB	0.015	0.068	-10000	0	-0.57	9	9
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.074	0.24	0.52	1	-0.69	69	70
CYSLTR1	-0.025	0.18	0.52	1	-0.64	24	25
SLC9A1	-0.005	0.11	0.37	1	-0.37	33	34
mol:GDP	-0.062	0.22	0.41	14	-0.56	91	105
SLC9A3	-0.49	0.39	-10000	0	-0.81	400	400
RAF1	-0.062	0.21	0.45	11	-0.55	93	104
JUN	-0.065	0.26	0.51	3	-0.67	87	90
JAK2	-0.024	0.17	0.52	1	-0.53	39	40
mol:IP3	-0.062	0.19	0.23	1	-0.48	114	115
ETA receptor/Endothelin-1	-0.008	0.23	0.43	55	-0.59	42	97
PLCB1	-0.042	0.2	-10000	0	-0.65	90	90
PLCB2	-0.018	0.13	-10000	0	-0.42	89	89
ETA receptor/Endothelin-3	0.002	0.13	-10000	0	-0.5	30	30
FOS	-0.067	0.28	0.5	11	-0.85	75	86
Gai/GDP	-0.027	0.21	-10000	0	-0.74	51	51
CRK	0.025	0.009	-10000	0	-10000	0	0
mol:Ca ++	-0.076	0.22	0.3	2	-0.62	76	78
BCAR1	0.026	0.024	-10000	0	-0.65	1	1
PRKCB1	-0.062	0.19	-10000	0	-0.47	113	113
GNAQ	0.025	0.016	-10000	0	-10000	0	0
GNAZ	0.025	0.04	-10000	0	-0.65	3	3
GNAL	0.026	0.028	-10000	0	-0.53	2	2
Gs family/GDP	-0.05	0.2	0.33	9	-0.53	76	85
ETA receptor/Endothelin-1/Gq/GTP	-0.036	0.19	0.52	1	-0.53	71	72
MAPK14	-0.041	0.14	-10000	0	-0.44	63	63
TRPC6	-0.14	0.41	0.63	4	-1	136	140
GNAI2	0.026	0.008	-10000	0	-10000	0	0
GNAI3	0.027	0.007	-10000	0	-10000	0	0
GNAI1	0.022	0.041	-10000	0	-0.65	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.048	0.16	-10000	0	-0.43	84	84
ETB receptor/Endothelin-2	-0.021	0.15	-10000	0	-0.39	106	106
ETB receptor/Endothelin-3	0.019	0.07	-10000	0	-0.34	26	26
ETB receptor/Endothelin-1	0.005	0.13	0.34	1	-0.49	21	22
MAPK3	-0.067	0.27	0.5	11	-0.76	82	93
MAPK1	-0.071	0.28	0.49	12	-0.78	85	97
Rac1/GDP	-0.045	0.19	0.52	2	-0.53	71	73
cAMP biosynthetic process	-0.059	0.17	0.42	14	-0.51	49	63
MAPK8	-0.087	0.31	0.54	3	-0.77	113	116
SRC	0.027	0.007	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.006	0.086	-10000	0	-0.36	26	26
p130Cas/CRK/Src/PYK2	-0.071	0.25	0.48	15	-0.62	98	113
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.046	0.19	0.52	2	-0.52	73	75
COL1A2	-0.031	0.19	0.5	1	-0.5	69	70
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.038	0.18	-10000	0	-0.44	108	108
mol:DAG	-0.062	0.19	0.23	1	-0.48	114	115
MAP2K2	-0.062	0.23	0.48	12	-0.62	87	99
MAP2K1	-0.061	0.23	0.5	11	-0.62	86	97
EDNRA	-0.008	0.16	-10000	0	-0.61	33	33
positive regulation of muscle contraction	0.002	0.16	0.35	21	-0.5	24	45
Gq family/GDP	-0.053	0.22	0.31	5	-0.58	89	94
HRAS/GTP	-0.064	0.21	0.4	11	-0.51	107	118
PRKCH	-0.061	0.19	-10000	0	-0.49	99	99
RAC1	0.025	0.01	-10000	0	-10000	0	0
PRKCA	-0.048	0.18	0.31	6	-0.49	82	88
PRKCB	-0.054	0.19	0.28	9	-0.5	92	101
PRKCE	-0.057	0.18	-10000	0	-0.49	96	96
PRKCD	-0.06	0.18	0.25	1	-0.5	93	94
PRKCG	-0.085	0.21	-10000	0	-0.54	115	115
regulation of vascular smooth muscle contraction	-0.084	0.32	0.53	11	-1	73	84
PRKCQ	-0.073	0.21	-10000	0	-0.5	126	126
PLA2G4A	-0.079	0.28	0.51	11	-0.66	117	128
GNA14	-0.045	0.21	-10000	0	-0.65	92	92
GNA15	0.009	0.088	-10000	0	-0.42	34	34
GNA12	0.025	0.009	-10000	0	-10000	0	0
GNA11	0.02	0.066	-10000	0	-0.65	8	8
Rac1/GTP	0.008	0.18	0.37	39	-0.49	32	71
MMP1	-0.1	0.3	0.51	2	-0.73	131	133

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.12	0.45	0.94	5	-1.1	53	58
PLK1	-0.029	0.18	-10000	0	-1.2	2	2
BIRC5	-0.084	0.24	-10000	0	-0.98	19	19
HSPA1B	-0.13	0.44	0.85	3	-1.1	56	59
MAP2K1	0.019	0.048	-10000	0	-10000	0	0
BRCA2	-0.13	0.45	0.8	4	-1.1	62	66
FOXM1	-0.16	0.51	0.97	3	-1.2	88	91
XRCC1	-0.13	0.44	1	3	-1.1	53	56
FOXM1B/p19	-0.21	0.43	0.66	2	-1.1	67	69
Cyclin D1/CDK4	-0.13	0.41	-10000	0	-1	44	44
CDC2	-0.14	0.46	0.91	3	-1.1	83	86
TGFA	-0.14	0.43	0.93	2	-1	56	58
SKP2	-0.12	0.44	0.95	3	-1.1	45	48
CCNE1	0.017	0.072	-10000	0	-0.43	22	22
CKS1B	-0.13	0.44	0.84	3	-1	85	88
RB1	-0.039	0.25	-10000	0	-0.9	22	22
FOXM1C/SP1	-0.15	0.47	-10000	0	-1.1	80	80
AURKB	-0.12	0.26	-10000	0	-0.94	39	39
CENPF	-0.14	0.47	0.85	3	-1.1	85	88
CDK4	0.02	0.024	-10000	0	-10000	0	0
MYC	-0.12	0.4	-10000	0	-0.94	55	55
CHEK2	0.017	0.058	-10000	0	-0.44	5	5
ONECUT1	-0.13	0.43	0.74	1	-1	61	62
CDKN2A	-0.36	0.14	-10000	0	-0.42	772	772
LAMA4	-0.16	0.45	0.85	3	-1.1	73	76
FOXM1B/HNF6	-0.16	0.49	0.75	1	-1.3	62	63
FOS	-0.17	0.5	1.1	3	-1.2	96	99
SP1	0.027	0.008	-10000	0	-10000	0	0
CDC25B	-0.12	0.44	1	4	-1.1	53	57
response to radiation	0.002	0.031	-10000	0	-10000	0	0
CENPB	-0.12	0.44	1	4	-1.1	47	51
CENPA	-0.17	0.48	0.86	4	-1.1	86	90
NEK2	-0.16	0.48	0.85	3	-1.1	84	87
HIST1H2BA	-0.13	0.44	0.84	3	-1.1	57	60
CCNA2	-0.057	0.18	-10000	0	-0.43	166	166
EP300	0.027	0.024	-10000	0	-0.65	1	1
CCNB1/CDK1	-0.15	0.48	0.9	3	-1.2	57	60
CCNB2	-0.16	0.49	1	3	-1.1	98	101
CCNB1	-0.14	0.46	0.95	3	-1.1	55	58
ETV5	-0.12	0.44	0.77	5	-1.1	55	60
ESR1	-0.15	0.48	0.85	3	-1.2	74	77
CCND1	-0.13	0.42	-10000	0	-1	45	45
GSK3A	0.02	0.042	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.009	0.15	-10000	0	-0.48	22	22
CDK2	0.027	0.01	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.001	0.037	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.14	0.46	-10000	0	-1.1	77	77
GAS1	-0.17	0.5	0.95	3	-1.1	92	95
MMP2	-0.12	0.45	1	4	-1.1	53	57
RB1/FOXM1C	-0.14	0.44	-10000	0	-1.1	62	62
CREBBP	0.027	0.007	-10000	0	-10000	0	0

×

Syndecan-1-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.026	0.03	-10000	0	-0.42	4	4
CCL5	-0.1	0.2	-10000	0	-0.42	253	253
SDCBP	0.027	0.005	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.094	0.15	0.26	3	-0.42	81	84
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.087	0.14	0.27	1	-0.46	51	52
Syndecan-1/Syntenin	-0.084	0.15	0.28	2	-0.46	51	53
MAPK3	-0.075	0.13	-10000	0	-0.43	47	47
HGF/MET	0.01	0.11	-10000	0	-0.46	46	46
TGFB1/TGF beta receptor Type II	0.026	0.03	-10000	0	-0.42	4	4
BSG	0.027	0.021	-10000	0	-0.42	2	2
keratinocyte migration	-0.086	0.14	0.27	1	-0.45	51	52
Syndecan-1/RANTES	-0.14	0.16	0.33	3	-0.43	99	102
Syndecan-1/CD147	-0.075	0.15	-10000	0	-0.46	49	49
Syndecan-1/Syntenin/PIP2	-0.082	0.14	-10000	0	-0.44	51	51
LAMA5	0.025	0.028	-10000	0	-0.53	2	2
positive regulation of cell-cell adhesion	-0.081	0.14	-10000	0	-0.43	51	51
MMP7	-0.068	0.22	-10000	0	-0.58	139	139
HGF	-0.007	0.14	-10000	0	-0.59	45	45
Syndecan-1/CASK	-0.096	0.14	0.2	1	-0.4	82	83
Syndecan-1/HGF/MET	-0.084	0.16	-10000	0	-0.49	65	65
regulation of cell adhesion	-0.074	0.13	0.32	1	-0.47	25	26
HPSE	0.007	0.11	-10000	0	-0.6	29	29
positive regulation of cell migration	-0.094	0.15	0.26	3	-0.42	81	84
SDC1	-0.095	0.15	0.25	2	-0.43	81	83
Syndecan-1/Collagen	-0.094	0.15	0.26	3	-0.42	81	84
PPIB	0.028	0.003	-10000	0	-10000	0	0
MET	0.021	0.04	-10000	0	-0.42	7	7
PRKACA	0.028	0.003	-10000	0	-10000	0	0
MMP9	-0.14	0.22	-10000	0	-0.42	332	332
MAPK1	-0.077	0.14	0.24	1	-0.43	49	50
homophilic cell adhesion	-0.094	0.15	0.25	3	-0.42	81	84
MMP1	-0.08	0.22	-10000	0	-0.52	169	169

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.087	0.37	-10000	0	-1.2	90	90
MKNK1	0.027	0.007	-10000	0	-10000	0	0
MAPK14	0.001	0.12	-10000	0	-0.52	12	12
ATF2/c-Jun	0.001	0.095	-10000	0	-0.43	12	12
MAPK11	0.004	0.12	-10000	0	-0.33	82	82
MITF	-0.004	0.13	-10000	0	-0.38	83	83
MAPKAPK5	0	0.13	-10000	0	-0.38	80	80
KRT8	-0.001	0.13	-10000	0	-0.38	75	75
MAPKAPK3	0.026	0.008	-10000	0	-10000	0	0
MAPKAPK2	0.027	0.007	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.005	0.18	-10000	0	-0.5	87	87
CEBPB	-0.006	0.13	-10000	0	-0.39	78	78
SLC9A1	-0.006	0.14	-10000	0	-0.38	91	91
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0	0.13	-10000	0	-0.37	89	89
p38alpha-beta/MNK1	0.015	0.15	-10000	0	-0.68	13	13
JUN	0	0.094	-10000	0	-0.43	12	12
PPARGC1A	-0.028	0.16	-10000	0	-0.38	134	134
USF1	-0.006	0.14	-10000	0	-0.38	97	97
RAB5/GDP/GDI1	0.001	0.099	-10000	0	-0.4	12	12
NOS2	-0.019	0.22	-10000	0	-1.1	25	25
DDIT3	-0.004	0.13	-10000	0	-0.39	82	82
RAB5A	0.026	0.008	-10000	0	-10000	0	0
HSPB1	0.019	0.12	0.29	58	-0.47	13	71
p38alpha-beta/HBP1	0.018	0.13	-10000	0	-0.42	56	56
CREB1	-0.008	0.15	-10000	0	-0.4	95	95
RAB5/GDP	0.019	0.006	-10000	0	-10000	0	0
EIF4E	-0.008	0.13	-10000	0	-0.67	11	11
RPS6KA4	-0.006	0.14	-10000	0	-0.38	90	90
PLA2G4A	-0.016	0.15	-10000	0	-0.63	27	27
GDI1	-0.006	0.14	-10000	0	-0.38	92	92
TP53	-0.013	0.15	-10000	0	-0.49	69	69
RPS6KA5	-0.009	0.14	-10000	0	-0.39	92	92
ESR1	-0.018	0.17	-10000	0	-0.44	99	99
HBP1	0.025	0.01	-10000	0	-10000	0	0
MEF2C	-0.005	0.13	-10000	0	-0.38	89	89
MEF2A	-0.006	0.14	-10000	0	-0.38	89	89
EIF4EBP1	-0.009	0.15	-10000	0	-0.41	96	96
KRT19	-0.066	0.21	-10000	0	-0.42	184	184
ELK4	-0.006	0.14	-10000	0	-0.38	90	90
ATF6	-0.006	0.14	-10000	0	-0.38	91	91
ATF1	-0.007	0.14	-10000	0	-0.4	95	95
p38alpha-beta/MAPKAPK2	0.015	0.15	-10000	0	-0.41	81	81
p38alpha-beta/MAPKAPK3	0.015	0.14	-10000	0	-0.4	74	74

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.002	0.064	-10000	0	-0.42	20	20
ADCY5	-0.018	0.1	-10000	0	-0.42	52	52
ADCY6	0.007	0.027	-10000	0	-0.79	1	1
ADCY7	-0.002	0.05	0.19	1	-0.25	32	33
ADCY1	-0.038	0.13	0.19	4	-0.4	101	105
ADCY2	-0.079	0.13	0.19	12	-0.26	297	309
ADCY3	0.007	0.017	-10000	0	-0.33	2	2
ADCY8	-0.044	0.1	0.19	5	-0.25	170	175
PRKCE	0.009	0.017	-10000	0	-0.49	1	1
ADCY9	0.007	0.015	-10000	0	-0.42	1	1
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.046	0.11	0.35	25	-0.32	18	43

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.077	0.23	-10000	0	-0.57	119	119
MAP4K1	-0.09	0.2	-10000	0	-0.42	234	234
MAP3K8	0.026	0.022	-10000	0	-0.42	2	2
PRKCB	0.019	0.066	-10000	0	-0.58	10	10
DBNL	0.025	0.009	-10000	0	-10000	0	0
CRKL	0.027	0.005	-10000	0	-10000	0	0
MAP3K1	-0.022	0.1	-10000	0	-0.35	32	32
JUN	-0.003	0.16	0.36	2	-0.6	51	53
MAP3K7	-0.02	0.1	-10000	0	-0.35	32	32
GRAP2	-0.002	0.11	-10000	0	-0.42	56	56
CRK	0.025	0.009	-10000	0	-10000	0	0
MAP2K4	-0.002	0.11	0.3	26	-0.33	33	59
LAT	-0.047	0.16	-10000	0	-0.42	145	145
LCP2	-0.006	0.12	-10000	0	-0.42	64	64
MAPK8	-0.01	0.17	-10000	0	-0.64	52	52
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.023	0.11	-10000	0	-0.33	60	60
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.065	0.22	-10000	0	-0.56	112	112

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.1	0.18	-10000	0	-0.33	331	331
PDGFRB	0.017	0.081	-10000	0	-0.64	13	13
SPHK1	-0.027	0.13	-10000	0	-0.62	35	35
mol:S1P	-0.019	0.11	0.29	1	-0.53	34	35
S1P1/S1P/Gi	-0.049	0.15	-10000	0	-0.46	65	65
GNAO1	0.01	0.096	-10000	0	-0.56	23	23
PDGFB-D/PDGFRB/PLCgamma1	-0.036	0.15	0.39	7	-0.48	45	52
PLCG1	-0.043	0.14	0.26	1	-0.48	44	45
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.017	0.081	-10000	0	-0.64	13	13
GNAI2	0.024	0.014	-10000	0	-10000	0	0
GNAI3	0.024	0.014	-10000	0	-10000	0	0
GNAI1	0.021	0.041	-10000	0	-0.65	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.1	0.14	0.16	1	-0.28	331	332
S1P1/S1P	-0.082	0.13	-10000	0	-0.38	79	79
negative regulation of cAMP metabolic process	-0.047	0.14	-10000	0	-0.45	65	65
MAPK3	-0.057	0.18	0.32	2	-0.58	71	73
calcium-dependent phospholipase C activity	-0.001	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.019	0.006	-10000	0	-10000	0	0
KDR	-0.023	0.18	-10000	0	-0.65	64	64
PLCB2	-0.083	0.14	0.36	11	-0.34	107	118
RAC1	0.025	0.01	-10000	0	-10000	0	0
RhoA/GTP	-0.073	0.11	-10000	0	-0.33	72	72
receptor internalization	-0.079	0.12	-10000	0	-0.35	84	84
PTGS2	-0.098	0.33	0.56	17	-0.97	96	113
Rac1/GTP	-0.068	0.11	-10000	0	-0.32	67	67
RHOA	0.026	0.008	-10000	0	-10000	0	0
VEGFA	-0.11	0.2	-10000	0	-0.42	269	269
negative regulation of T cell proliferation	-0.047	0.14	-10000	0	-0.45	65	65
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.023	0.042	-10000	0	-0.65	3	3
MAPK1	-0.072	0.21	-10000	0	-0.62	91	91
S1P1/S1P/PDGFB-D/PDGFRB	-0.076	0.15	0.29	3	-0.45	48	51
ABCC1	0.026	0.008	-10000	0	-10000	0	0

×

Coregulation of Androgen receptor activity

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
NRIP1	0.023	0.015	-9999	-10000	0	0
SVIL	0.024	0.014	-9999	-10000	0	0
ZNF318	0.029	0.015	-9999	-10000	0	0
JMJD2C	-0.004	0.02	-9999	-0.066	82	82
T-DHT/AR/Ubc9	-0.083	0.11	-9999	-0.44	53	53
CARM1	0.028	0.003	-9999	-10000	0	0
PRDX1	0.027	0.007	-9999	-10000	0	0
PELP1	0.026	0.009	-9999	-10000	0	0
CTNNB1	0.023	0.013	-9999	-10000	0	0
AKT1	0.029	0.007	-9999	-10000	0	0
PTK2B	0.026	0.008	-9999	-10000	0	0
MED1	0.026	0.01	-9999	-10000	0	0
MAK	0.023	0.051	-9999	-0.41	11	11
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.017	0.053	-9999	-0.66	5	5
GSN	0.023	0.016	-9999	-10000	0	0
NCOA2	-0.004	0.14	-9999	-0.65	40	40
NCOA6	0.023	0.015	-9999	-10000	0	0
DNA-PK	0.054	0.023	-9999	-10000	0	0
NCOA4	0.027	0.007	-9999	-10000	0	0
PIAS3	0.024	0.013	-9999	-10000	0	0
cell proliferation	-0.054	0.12	-9999	-0.51	51	51
XRCC5	0.028	0.007	-9999	-10000	0	0
UBE3A	0.022	0.02	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.1	0.14	-9999	-0.48	85	85
FHL2	-0.057	0.14	-9999	-0.77	24	24
RANBP9	0.024	0.014	-9999	-10000	0	0
JMJD1A	-0.11	0.066	-9999	-0.14	652	652
CDK6	0.024	0.025	-9999	-0.65	1	1
TGFB1I1	0.018	0.055	-9999	-0.61	6	6
T-DHT/AR/CyclinD1	-0.096	0.12	-9999	-0.4	86	86
XRCC6	0.028	0.006	-9999	-10000	0	0
T-DHT/AR	-0.15	0.12	-9999	-0.42	77	77
CTDSP1	0.026	0.007	-9999	-10000	0	0
CTDSP2	0.03	0.013	-9999	-10000	0	0
BRCA1	0.02	0.033	-9999	-0.42	4	4
TCF4	0.026	0.049	-9999	-0.6	5	5
CDKN2A	-0.36	0.15	-9999	-0.42	772	772
SRF	0.032	0.019	-9999	-10000	0	0
NKX3-1	-0.19	0.1	-9999	-0.24	684	684
KLK3	0.001	0.088	-9999	-10000	0	0
TMF1	0.025	0.024	-9999	-0.65	1	1
HNRNPA1	0.028	0.008	-9999	-10000	0	0
AOF2	-0.002	0.006	-9999	-10000	0	0
APPL1	0.02	0.012	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.084	0.11	-9999	-0.45	53	53
AR	-0.087	0.15	-9999	-0.67	53	53
UBA3	0.026	0.007	-9999	-10000	0	0
PATZ1	0.029	0.007	-9999	-10000	0	0
PAWR	0.026	0.024	-9999	-0.65	1	1
PRKDC	0.028	0.007	-9999	-10000	0	0
PA2G4	0.029	0.009	-9999	-10000	0	0
UBE2I	0.026	0.007	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.075	0.099	-9999	-0.42	53	53
RPS6KA3	0.023	0.016	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.085	0.11	-9999	-0.47	50	50
LATS2	0.028	0.008	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.075	0.099	-9999	-0.42	53	53
Cyclin D3/CDK11 p58	0.02	0.005	-9999	-10000	0	0
VAV3	0.015	0.079	-9999	-0.65	12	12
KLK2	-0.087	0.1	-9999	-0.42	40	40
CASP8	0.027	0.007	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.089	0.14	-9999	-0.48	80	80
TMPRSS2	-0.77	0.44	-9999	-1	657	657
CCND1	0.01	0.088	-9999	-0.42	34	34
PIAS1	0.022	0.02	-9999	-10000	0	0
mol:T-DHT	-0.054	0.03	-9999	-0.071	648	648
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.02	0.025	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.078	0.11	-9999	-0.45	52	52
CMTM2	0.012	0.078	-9999	-0.42	28	28
SNURF	-0.004	0.13	-9999	-0.63	38	38
ZMIZ1	-0.045	0.04	-9999	-10000	0	0
CCND3	0.026	0.007	-9999	-10000	0	0
TGIF1	0.029	0.007	-9999	-10000	0	0
FKBP4	0.022	0.015	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.08	0.16	-10000	0	-0.56	32	32
IHH	-0.056	0.2	-10000	0	-0.66	78	78
SHH Np/Cholesterol/GAS1	-0.01	0.12	-10000	0	-0.38	68	68
LRPAP1	0.028	0.004	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.01	0.11	0.38	68	-10000	0	68
SMO/beta Arrestin2	-0.046	0.14	-10000	0	-0.51	37	37
SMO	-0.058	0.14	-10000	0	-0.47	66	66
AKT1	-0.011	0.098	-10000	0	-0.57	11	11
ARRB2	0.024	0.03	-10000	0	-0.46	3	3
BOC	0.026	0.024	-10000	0	-0.65	1	1
ADRBK1	0.028	0.003	-10000	0	-10000	0	0
heart looping	-0.057	0.14	-10000	0	-0.47	66	66
STIL	-0.032	0.14	-10000	0	-0.43	43	43
DHH N/PTCH2	0.007	0.12	-10000	0	-0.43	57	57
DHH N/PTCH1	-0.063	0.15	-10000	0	-0.44	72	72
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
DHH	-0.006	0.14	-10000	0	-0.65	41	41
PTHLH	-0.12	0.21	-10000	0	-0.72	38	38
determination of left/right symmetry	-0.057	0.14	-10000	0	-0.47	66	66
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
skeletal system development	-0.12	0.21	-10000	0	-0.72	38	38
IHH N/Hhip	-0.095	0.22	-10000	0	-0.5	187	187
DHH N/Hhip	-0.055	0.2	-10000	0	-0.47	160	160
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.057	0.14	-10000	0	-0.47	66	66
pancreas development	-0.067	0.22	-10000	0	-0.61	125	125
HHAT	0.027	0.007	-10000	0	-10000	0	0
PI3K	0.039	0.011	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.01	0.16	-10000	0	-0.64	50	50
somite specification	-0.057	0.14	-10000	0	-0.47	66	66
SHH Np/Cholesterol/PTCH1	-0.054	0.13	-10000	0	-0.44	48	48
SHH Np/Cholesterol/PTCH2	0.005	0.086	-10000	0	-0.37	35	35
SHH Np/Cholesterol/Megalin	-0.036	0.16	-10000	0	-0.46	102	102
SHH	-0.005	0.1	0.21	2	-0.46	39	41
catabolic process	-0.058	0.14	-10000	0	-0.42	71	71
SMO/Vitamin D3	-0.057	0.14	-10000	0	-0.49	50	50
SHH Np/Cholesterol/Hhip	-0.042	0.16	-10000	0	-0.42	117	117
LRP2	-0.055	0.21	-10000	0	-0.57	121	121
receptor-mediated endocytosis	-0.085	0.19	-10000	0	-0.57	76	76
SHH Np/Cholesterol/BOC	0.009	0.081	-10000	0	-0.38	35	35
SHH Np/Cholesterol/CDO	-0.014	0.1	-10000	0	-0.38	35	35
mesenchymal cell differentiation	0.042	0.16	0.42	117	-10000	0	117
mol:Vitamin D3	-0.035	0.15	-10000	0	-0.44	48	48
IHH N/PTCH2	-0.029	0.14	-10000	0	-0.42	88	88
CDON	-0.016	0.13	-10000	0	-0.42	87	87
IHH N/PTCH1	-0.056	0.14	-10000	0	-0.43	71	71
Megalin/LRPAP1	-0.022	0.16	-10000	0	-0.47	92	92
PTCH2	0.018	0.062	-10000	0	-0.42	17	17
SHH Np/Cholesterol	-0.001	0.079	-10000	0	-0.38	35	35
PTCH1	-0.058	0.14	-10000	0	-0.43	71	71
HHIP	-0.067	0.23	-10000	0	-0.61	125	125

×

Ephrin A reverse 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
MAPKKK cascade	-0.007	0.12	-9999	-0.39	80	80
EFNA5	-0.021	0.17	-9999	-0.64	63	63
FYN	-0.018	0.11	-9999	-0.4	61	61
neuron projection morphogenesis	-0.007	0.12	-9999	-0.39	80	80
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.007	0.12	-9999	-0.39	80	80
EPHA5	-0.013	0.066	-9999	-0.42	20	20

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.052	0.16	-10000	0	-0.54	76	76
NFATC2	-0.049	0.18	-10000	0	-0.57	29	29
NFATC3	-0.017	0.083	-10000	0	-0.33	19	19
CD40LG	-0.17	0.34	0.52	1	-0.92	84	85
ITCH	0.019	0.08	-10000	0	-0.46	1	1
CBLB	0.019	0.079	-10000	0	-0.46	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.18	0.31	-10000	0	-0.79	107	107
JUNB	0.027	0.032	-10000	0	-0.65	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.017	0.095	-10000	0	-0.31	64	64
T cell anergy	0.002	0.12	-10000	0	-0.42	64	64
TLE4	-0.022	0.12	-10000	0	-0.49	8	8
Jun/NFAT1-c-4/p21SNFT	-0.1	0.29	-10000	0	-0.95	48	48
AP-1/NFAT1-c-4	-0.17	0.38	-10000	0	-1.1	66	66
IKZF1	-0.061	0.18	-10000	0	-0.47	59	59
T-helper 2 cell differentiation	-0.32	0.29	0.46	1	-0.75	147	148
AP-1/NFAT1	-0.048	0.17	-10000	0	-0.49	44	44
CALM1	0.024	0.058	-10000	0	-0.28	1	1
EGR2	-0.12	0.37	-10000	0	-1.4	52	52
EGR3	-0.14	0.41	-10000	0	-1.5	68	68
NFAT1/FOXP3	-0.081	0.22	-10000	0	-0.6	85	85
EGR1	-0.01	0.15	-10000	0	-0.65	48	48
JUN	0.01	0.032	-10000	0	-10000	0	0
EGR4	0.019	0.046	-10000	0	-0.41	9	9
mol:Ca2+	-0.003	0.056	-10000	0	-0.28	6	6
GBP3	-0.03	0.14	-10000	0	-0.6	17	17
FOSL1	0.012	0.084	-10000	0	-0.42	31	31
NFAT1-c-4/MAF/IRF4	-0.11	0.29	-10000	0	-0.87	57	57
DGKA	-0.024	0.13	-10000	0	-0.52	15	15
CREM	0.026	0.007	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.086	0.28	-10000	0	-0.9	55	55
CTLA4	-0.13	0.26	-10000	0	-0.6	152	152
NFAT1-c-4 (dimer)/EGR1	-0.099	0.32	-10000	0	-1	61	61
NFAT1-c-4 (dimer)/EGR4	-0.088	0.28	-10000	0	-0.92	56	56
FOS	-0.031	0.16	-10000	0	-0.64	57	57
IFNG	-0.13	0.22	-10000	0	-0.71	12	12
T cell activation	-0.049	0.19	0.57	2	-0.72	16	18
MAF	0.026	0.007	-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	0.067	0.21	0.75	52	-10000	0	52
TNF	-0.1	0.28	-10000	0	-0.98	49	49
FASLG	-0.19	0.43	-10000	0	-1.4	76	76
TBX21	-0.094	0.2	-10000	0	-0.46	200	200
BATF3	0.01	0.085	-10000	0	-0.42	33	33
PRKCQ	-0.028	0.14	-10000	0	-0.55	51	51
PTPN1	-0.022	0.12	-10000	0	-0.5	7	7
NFAT1-c-4/ICER1	-0.088	0.28	-10000	0	-0.91	56	56
GATA3	-0.32	0.34	-10000	0	-0.65	458	458
T-helper 1 cell differentiation	-0.13	0.22	-10000	0	-0.69	13	13
IL2RA	-0.14	0.28	-10000	0	-0.71	100	100
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.023	0.12	-10000	0	-0.49	8	8
E2F1	-0.051	0.17	-10000	0	-0.41	163	163
PPARG	0.025	0.017	-10000	0	-0.42	1	1
SLC3A2	-0.022	0.12	-10000	0	-0.5	7	7
IRF4	-0.051	0.17	-10000	0	-0.42	152	152
PTGS2	-0.18	0.36	0.52	1	-1	83	84
CSF2	-0.16	0.32	-10000	0	-0.97	66	66
JunB/Fra1/NFAT1-c-4	-0.078	0.28	-10000	0	-0.89	55	55
IL4	-0.33	0.3	-10000	0	-0.8	135	135
IL5	-0.16	0.32	-10000	0	-0.96	63	63
IL2	-0.05	0.19	0.57	2	-0.73	16	18
IL3	-0.039	0.13	-10000	0	-0.81	18	18
RNF128	-0.017	0.2	-10000	0	-0.68	73	73
NFATC1	-0.067	0.21	-10000	0	-0.76	51	51
CDK4	0.035	0.15	0.65	7	-10000	0	7
PTPRK	-0.024	0.12	-10000	0	-0.54	9	9
IL8	-0.17	0.34	-10000	0	-0.96	79	79
POU2F1	0.027	0.007	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.027	0.12	-10000	0	-0.39	12	12
ACTA1	-0.057	0.13	-10000	0	-0.33	100	100
NUMA1	-0.027	0.12	-10000	0	-0.48	10	10
SPTAN1	-0.056	0.13	0.27	2	-0.33	100	102
LIMK1	-0.035	0.15	0.3	17	-0.33	100	117
BIRC3	-0.023	0.14	-10000	0	-0.42	100	100
BIRC2	0.028	0.004	-10000	0	-10000	0	0
BAX	0.028	0.015	-10000	0	-0.42	1	1
CASP10	-0.091	0.18	-10000	0	-0.46	134	134
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.028	0.001	-10000	0	-10000	0	0
PTK2	-0.029	0.13	-10000	0	-0.43	19	19
DIABLO	0.027	0.006	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.055	0.12	0.27	2	-0.33	100	102
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.027	0.006	-10000	0	-10000	0	0
GSN	-0.056	0.13	0.27	2	-0.33	100	102
MADD	0.028	0.004	-10000	0	-10000	0	0
TFAP2A	-0.32	0.29	-10000	0	-0.55	464	464
BID	-0.034	0.082	-10000	0	-0.2	134	134
MAP3K1	-0.011	0.061	-10000	0	-0.46	5	5
TRADD	0.026	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.038	0.014	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.048	0.14	0.3	14	-0.33	102	116
CASP9	0.027	0.007	-10000	0	-10000	0	0
DNA repair	0.019	0.088	0.34	45	-10000	0	45
neuron apoptosis	-0.007	0.15	-10000	0	-0.64	41	41
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.041	0.13	-10000	0	-0.46	9	9
APAF1	0.027	0.006	-10000	0	-10000	0	0
CASP6	0.001	0.14	-10000	0	-0.94	10	10
TRAF2	0.028	0.004	-10000	0	-10000	0	0
ICAD/CAD	-0.052	0.12	-10000	0	-0.32	100	100
CASP7	0.005	0.091	-10000	0	-0.29	36	36
KRT18	0.018	0.038	-10000	0	-0.48	1	1
apoptosis	-0.053	0.14	0.49	4	-0.46	25	29
DFFA	-0.053	0.13	-10000	0	-0.33	100	100
DFFB	-0.052	0.13	-10000	0	-0.33	100	100
PARP1	-0.019	0.088	-10000	0	-0.34	45	45
actin filament polymerization	0.029	0.15	0.39	5	-0.35	18	23
TNF	0.012	0.082	-10000	0	-0.46	25	25
CYCS	-0.018	0.078	0.21	16	-0.2	1	17
SATB1	0.006	0.14	0.42	15	-0.87	10	25
SLK	-0.052	0.13	0.33	4	-0.33	101	105
p15 BID/BAX	-0.021	0.085	-10000	0	-0.27	2	2
CASP2	0.006	0.06	-10000	0	-0.36	7	7
JNK cascade	0.011	0.061	0.46	5	-10000	0	5
CASP3	-0.06	0.13	0.25	1	-0.35	101	102
LMNB2	0.038	0.11	0.35	31	-0.59	7	38
RIPK1	0.027	0.007	-10000	0	-10000	0	0
CASP4	0.028	0.004	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.035	0.093	-10000	0	-0.39	1	1
negative regulation of DNA binding	-0.31	0.29	-10000	0	-0.55	465	465
stress fiber formation	-0.054	0.13	0.33	4	-0.33	101	105
GZMB	-0.1	0.21	0.21	1	-0.43	237	238
CASP1	0.018	0.012	-10000	0	-10000	0	0
LMNB1	0.036	0.11	0.31	46	-0.42	11	57
APP	-0.007	0.15	-10000	0	-0.65	41	41
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.01	0.002	-10000	0	-10000	0	0
VIM	-0.053	0.14	0.33	4	-0.44	31	35
LMNA	0.025	0.14	0.32	46	-0.46	41	87
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.016	0.053	-10000	0	-0.42	3	3
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.043	0.14	0.29	8	-0.33	100	108
APAF-1/Caspase 9	-0.024	0.15	-10000	0	-0.6	52	52
nuclear fragmentation during apoptosis	-0.026	0.12	-10000	0	-0.46	10	10
CFL2	-0.03	0.15	0.35	18	-0.4	5	23
GAS2	-0.063	0.14	0.34	4	-0.34	115	119
positive regulation of apoptosis	0.037	0.12	0.32	46	-0.47	16	62
PRF1	-0.056	0.17	-10000	0	-0.42	163	163

×

Aurora C signaling

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
INCENP	0.028	0.003	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.063	0.13	-9999	-0.31	9	9
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.016	0.05	-9999	-0.47	5	5
AURKB	-0.15	0.22	-9999	-0.42	353	353
AURKC	0.024	0.042	-9999	-0.42	8	8

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.033	0.027	-10000	0	-0.32	3	3
VLDLR	0.027	0.016	-10000	0	-0.42	1	1
CRKL	0.027	0.005	-10000	0	-10000	0	0
LRPAP1	0.028	0.004	-10000	0	-10000	0	0
FYN	0.026	0.007	-10000	0	-10000	0	0
ITGA3	0.02	0.048	-10000	0	-0.42	10	10
RELN/VLDLR/Fyn	-0.053	0.18	-10000	0	-0.42	162	162
MAPK8IP1/MKK7/MAP3K11/JNK1	0.072	0.056	-10000	0	-0.4	9	9
AKT1	-0.039	0.12	-10000	0	-0.28	90	90
MAP2K7	0.028	0.003	-10000	0	-10000	0	0
RAPGEF1	0.028	0.004	-10000	0	-10000	0	0
DAB1	-0.003	0.07	-10000	0	-0.42	22	22
RELN/LRP8/DAB1	-0.056	0.17	-10000	0	-0.39	161	161
LRPAP1/LRP8	0.037	0.025	-10000	0	-0.29	3	3
RELN/LRP8/DAB1/Fyn	-0.044	0.17	-10000	0	-0.37	161	161
DAB1/alpha3/beta1 Integrin	-0.04	0.16	-10000	0	-0.51	2	2
long-term memory	-0.092	0.2	-10000	0	-0.4	201	201
DAB1/LIS1	-0.029	0.17	-10000	0	-0.53	2	2
DAB1/CRLK/C3G	-0.037	0.16	-10000	0	-0.51	2	2
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
DAB1/NCK2	-0.025	0.17	-10000	0	-0.53	2	2
ARHGEF2	0.027	0.007	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.084	0.22	-10000	0	-0.52	174	174
CDK5R1	0.023	0.036	-10000	0	-0.44	5	5
RELN	-0.12	0.27	-10000	0	-0.61	195	195
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
RELN/LRP8/Fyn	-0.053	0.18	-10000	0	-0.42	161	161
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.092	0.21	-10000	0	-0.41	215	215
MAPK8	0.022	0.058	-10000	0	-0.61	7	7
RELN/VLDLR/DAB1	-0.055	0.17	-10000	0	-0.39	162	162
ITGB1	0.027	0.007	-10000	0	-10000	0	0
MAP1B	-0.063	0.16	-10000	0	-0.37	159	159
RELN/LRP8	-0.053	0.18	-10000	0	-0.42	160	160
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.034	0.18	-10000	0	-0.37	159	159
PI3K	0.039	0.011	-10000	0	-10000	0	0
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.033	0.037	-10000	0	-0.29	10	10
RAP1A	-0.032	0.16	0.46	11	-0.48	2	13
PAFAH1B1	0.025	0.009	-10000	0	-10000	0	0
MAPK8IP1	0.026	0.04	-10000	0	-0.65	3	3
CRLK/C3G	0.04	0.009	-10000	0	-10000	0	0
GRIN2B	0.005	0.05	-10000	0	-0.42	10	10
NCK2	0.027	0.006	-10000	0	-10000	0	0
neuron differentiation	-0.027	0.15	-10000	0	-0.47	50	50
neuron adhesion	-0.019	0.17	0.36	48	-0.47	2	50
LRP8	0.025	0.031	-10000	0	-0.42	4	4
GSK3B	-0.038	0.11	-10000	0	-0.34	13	13
RELN/VLDLR/DAB1/Fyn	-0.044	0.17	-10000	0	-0.37	162	162
MAP3K11	0.027	0.023	-10000	0	-0.65	1	1
RELN/VLDLR/DAB1/P13K	-0.039	0.13	-10000	0	-0.29	161	161
CDK5	0.025	0.01	-10000	0	-10000	0	0
MAPT	0.028	0.16	0.66	42	-0.58	14	56
neuron migration	-0.038	0.16	0.35	8	-0.42	5	13
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.027	0.15	-10000	0	-0.49	47	47
RELN/VLDLR	-0.037	0.18	-10000	0	-0.38	160	160

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.013	0.041	-10000	0	-10000	0	0
NFATC2	-0.023	0.078	-10000	0	-0.42	24	24
NFATC3	-0.012	0.04	-10000	0	-10000	0	0
CD40LG	-0.17	0.28	0.4	3	-0.63	155	158
PTGS2	-0.19	0.28	0.39	4	-0.61	187	191
JUNB	0.027	0.032	-10000	0	-0.65	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.03	-10000	0	-10000	0	0
CaM/Ca2+	-0.005	0.03	-10000	0	-10000	0	0
CALM1	0.01	0.025	-10000	0	-10000	0	0
JUN	0.009	0.026	-10000	0	-10000	0	0
mol:Ca2+	-0.011	0.014	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.012	0.012	-10000	0	-10000	0	0
FOSL1	0.012	0.084	-10000	0	-0.42	31	31
CREM	0.027	0.007	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.079	0.16	-10000	0	-0.46	28	28
FOS	-0.033	0.16	-10000	0	-0.63	57	57
IFNG	-0.2	0.3	0.4	3	-0.65	187	190
AP-1/NFAT1-c-4	-0.18	0.29	-10000	0	-0.68	140	140
FASLG	-0.21	0.31	0.4	5	-0.6	280	285
NFAT1-c-4/ICER1	-0.042	0.1	-10000	0	-0.44	10	10
IL2RA	-0.18	0.28	0.39	3	-0.64	158	161
FKBP12/FK506	0.02	0.005	-10000	0	-10000	0	0
CSF2	-0.16	0.25	0.39	3	-0.58	139	142
JunB/Fra1/NFAT1-c-4	-0.039	0.12	-10000	0	-0.42	16	16
IL4	-0.16	0.24	0.39	3	-0.57	133	136
IL2	-0.003	0.1	-10000	0	-0.88	9	9
IL3	-0.023	0.14	-10000	0	-0.59	41	41
FKBP1A	0.027	0.006	-10000	0	-10000	0	0
BATF3	0.01	0.085	-10000	0	-0.42	33	33
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.027	0.007	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.1	0.18	-10000	0	-0.33	331	331
alphaV beta3 Integrin	0.029	0.099	-10000	0	-0.43	34	34
PTK2	-0.091	0.2	0.45	17	-0.56	56	73
IGF1R	0.028	0.003	-10000	0	-10000	0	0
PI4KB	0.027	0.007	-10000	0	-10000	0	0
MFGE8	0.027	0.028	-10000	0	-0.53	2	2
SRC	0.027	0.007	-10000	0	-10000	0	0
CDKN1B	-0.058	0.19	-10000	0	-0.51	124	124
VEGFA	-0.11	0.2	-10000	0	-0.42	269	269
ILK	-0.059	0.19	-10000	0	-0.52	126	126
ROCK1	0.028	0.005	-10000	0	-10000	0	0
AKT1	-0.057	0.18	-10000	0	-0.48	125	125
PTK2B	-0.07	0.15	0.36	4	-0.37	63	67
alphaV/beta3 Integrin/JAM-A	-0.02	0.16	-10000	0	-0.38	132	132
CBL	0.027	0.023	-10000	0	-0.65	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.19	0.23	-10000	0	-0.43	397	397
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.049	0.081	-10000	0	-0.38	19	19
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.073	0.15	-10000	0	-0.42	98	98
alphaV/beta3 Integrin/Syndecan-1	0.034	0.09	-10000	0	-0.44	28	28
PI4KA	0.027	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.008	0.12	-10000	0	-0.53	15	15
PI4 Kinase	0.038	0.012	-10000	0	-10000	0	0
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.029	0.1	-10000	0	-0.46	29	29
RPS6KB1	-0.011	0.12	0.5	8	-0.55	11	19
TLN1	0.028	0.004	-10000	0	-10000	0	0
MAPK3	-0.03	0.14	-10000	0	-0.59	35	35
GPR124	0.025	0.032	-10000	0	-0.5	3	3
MAPK1	-0.031	0.14	-10000	0	-0.61	32	32
PXN	0.027	0.006	-10000	0	-10000	0	0
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0	0.15	-10000	0	-0.44	83	83
cell adhesion	-0.14	0.19	-10000	0	-0.35	382	382
ANGPTL3	-0.32	0.33	-10000	0	-0.62	467	467
VEGFR2 homodimer/VEGFA homodimer/Src	-0.071	0.16	-10000	0	-0.42	50	50
IGF-1R heterotetramer	0.028	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.007	-10000	0	-10000	0	0
TGFBR2	0.026	0.008	-10000	0	-10000	0	0
ITGB3	0.007	0.11	-10000	0	-0.61	25	25
IGF1	0.008	0.098	-10000	0	-0.48	32	32
RAC1	0.025	0.01	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.035	0.078	-10000	0	-0.42	21	21
apoptosis	0.026	0.028	-10000	0	-0.53	2	2
CD47	0.027	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.037	0.076	-10000	0	-0.42	20	20
VCL	0.027	0.007	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.004	0.15	-10000	0	-0.46	73	73
CSF1	0.023	0.049	-10000	0	-0.6	5	5
PIK3C2A	-0.06	0.2	-10000	0	-0.52	127	127
PI4 Kinase/Pyk2	-0.11	0.17	-10000	0	-0.53	62	62
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.066	0.16	-10000	0	-0.4	65	65
FAK1/Vinculin	-0.065	0.17	0.43	20	-0.46	42	62
alphaV beta3/Integrin/ppsTEM5	0.035	0.079	-10000	0	-0.42	21	21
RHOA	0.026	0.008	-10000	0	-10000	0	0
VTN	-0.078	0.23	-10000	0	-0.58	148	148
BCAR1	0.026	0.024	-10000	0	-0.65	1	1
FGF2	0.016	0.087	-10000	0	-0.62	16	16
F11R	0.01	0.065	-10000	0	-0.47	15	15
alphaV/beta3 Integrin/Lactadherin	0.036	0.08	-10000	0	-0.42	22	22
alphaV/beta3 Integrin/TGFBR2	0.034	0.076	-10000	0	-0.42	20	20
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.06	0.049	-10000	0	-0.47	4	4
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.035	0.071	-10000	0	-0.38	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.01	0.12	-10000	0	-0.42	72	72
alphaV/beta3 Integrin/Pyk2	-0.066	0.14	-10000	0	-0.37	63	63
SDC1	0.021	0.062	-10000	0	-0.62	8	8
VAV3	0.027	0.077	0.38	11	-0.39	14	25
PTPN11	0.027	0.006	-10000	0	-10000	0	0
IRS1	0.019	0.072	-10000	0	-0.65	10	10
FAK1/Paxillin	-0.071	0.16	0.35	14	-0.45	42	56
cell migration	-0.064	0.14	0.35	13	-0.43	28	41
ITGAV	0.026	0.028	-10000	0	-0.53	2	2
PI3K	-0.006	0.16	-10000	0	-0.57	11	11
SPP1	0.016	0.085	-10000	0	-0.58	17	17
KDR	-0.021	0.18	-10000	0	-0.64	64	64
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.026	0.028	-10000	0	-0.53	2	2
COL4A3	-0.028	0.18	-10000	0	-0.64	72	72
angiogenesis	-0.038	0.17	-10000	0	-0.6	36	36
Rac1/GTP	0.028	0.057	-10000	0	-0.36	14	14
EDIL3	-0.036	0.19	-10000	0	-0.6	89	89
cell proliferation	0.034	0.076	-10000	0	-0.42	20	20

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.021	0.18	-10000	0	-0.63	66	66
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.024	0.038	-10000	0	-0.46	5	5
TCEB1	0.027	0.005	-10000	0	-10000	0	0
HIF1A/p53	-0.024	0.078	0.32	6	-0.41	9	15
HIF1A	-0.035	0.07	-10000	0	-0.35	16	16
COPS5	0.027	0.005	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.065	0.042	-10000	0	-0.36	1	1
FIH (dimer)	0.027	0.007	-10000	0	-10000	0	0
CDKN2A	-0.37	0.15	-10000	0	-0.42	772	772
ARNT/IPAS	0.001	0.14	-10000	0	-0.47	65	65
HIF1AN	0.027	0.007	-10000	0	-10000	0	0
GNB2L1	0.027	0.007	-10000	0	-10000	0	0
HIF1A/ARNT	-0.021	0.081	0.32	6	-0.41	9	15
CUL2	0.027	0.007	-10000	0	-10000	0	0
OS9	0.027	0.006	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.048	0.032	-10000	0	-0.28	5	5
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.022	0.076	-10000	0	-0.41	9	9
PHD1-3/OS9	-0.094	0.14	-10000	0	-0.33	10	10
HIF1A/RACK1/Elongin B/Elongin C	-0.015	0.08	-10000	0	-0.42	8	8
VHL	0.026	0.008	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
HIF1A/JAB1	-0.022	0.078	0.35	1	-0.41	9	10
EGLN3	-0.22	0.22	-10000	0	-0.42	484	484
EGLN2	0.028	0.003	-10000	0	-10000	0	0
EGLN1	0.027	0.007	-10000	0	-10000	0	0
TP53	0.025	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.006	0.15	-10000	0	-0.55	62	62
ARNT	0.027	0.007	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.027	0.005	-10000	0	-10000	0	0
HIF1A/p19ARF	-0.19	0.11	0.3	3	-0.41	60	63

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.028	0.005	-10000	0	-10000	0	0
LAT2	-0.056	0.12	-10000	0	-0.34	75	75
AP1	-0.047	0.17	-10000	0	-0.54	53	53
mol:PIP3	-0.061	0.24	0.49	57	-0.5	88	145
IKBKB	-0.012	0.16	0.4	66	-0.27	40	106
AKT1	-0.065	0.14	0.37	16	-0.49	5	21
IKBKG	-0.014	0.16	0.4	63	-0.28	35	98
MS4A2	-0.087	0.2	-10000	0	-0.42	224	224
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
MAP3K1	-0.036	0.15	0.36	44	-0.4	15	59
mol:Ca2+	-0.039	0.2	0.45	59	-0.37	87	146
LYN	0.024	0.025	-10000	0	-0.68	1	1
CBLB	-0.042	0.093	-10000	0	-0.41	15	15
SHC1	0.026	0.016	-10000	0	-0.42	1	1
RasGAP/p62DOK	0.047	0.032	-10000	0	-0.38	2	2
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.022	0.048	-10000	0	-0.42	10	10
PLD2	-0.085	0.14	0.32	10	-0.4	64	74
PTPN13	-0.021	0.15	0.44	8	-0.66	26	34
PTPN11	0.025	0.012	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.008	0.16	0.5	43	-0.38	10	53
SYK	0.022	0.049	-10000	0	-0.6	5	5
GRB2	0.025	0.009	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.18	-10000	0	-0.48	117	117
LAT	-0.071	0.13	0.23	2	-0.33	109	111
PAK2	-0.045	0.16	0.36	38	-0.39	29	67
NFATC2	-0.044	0.12	-10000	0	-0.64	25	25
HRAS	-0.06	0.15	0.28	15	-0.39	42	57
GAB2	0.027	0.015	-10000	0	-0.42	1	1
PLA2G1B	-0.017	0.2	-10000	0	-0.82	52	52
Fc epsilon R1	-0.11	0.18	-10000	0	-0.42	96	96
Antigen/IgE/Fc epsilon R1	-0.096	0.17	-10000	0	-0.34	138	138
mol:GDP	-0.074	0.15	-10000	0	-0.41	49	49
JUN	0.027	0.007	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
FOS	-0.015	0.16	-10000	0	-0.62	57	57
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.041	0.099	-10000	0	-0.37	25	25
CHUK	-0.013	0.16	0.41	62	-0.28	35	97
KLRG1	-0.044	0.095	-10000	0	-0.4	16	16
VAV1	-0.083	0.14	-10000	0	-0.32	163	163
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.043	0.095	-10000	0	-0.42	16	16
negative regulation of mast cell degranulation	-0.035	0.1	-10000	0	-0.42	14	14
BTK	-0.046	0.11	-10000	0	-0.44	21	21
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.062	0.12	-10000	0	-0.35	72	72
GAB2/PI3K/SHP2	-0.089	0.13	-10000	0	-0.4	44	44
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.043	0.099	-10000	0	-0.34	33	33
RAF1	-0.024	0.22	-10000	0	-0.91	52	52
Fc epsilon R1/FcgammaRIIB/SHIP	-0.12	0.21	-10000	0	-0.45	184	184
FCER1G	-0.07	0.19	-10000	0	-0.42	189	189
FCER1A	-0.003	0.12	-10000	0	-0.55	41	41
Antigen/IgE/Fc epsilon R1/Fyn	-0.082	0.16	-10000	0	-0.42	67	67
MAPK3	-0.018	0.21	-10000	0	-0.83	52	52
MAPK1	-0.02	0.21	-10000	0	-0.84	52	52
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
MAPK8	-0.025	0.22	-10000	0	-0.84	54	54
DUSP1	0.025	0.036	-10000	0	-0.57	3	3
NF-kappa-B/RelA	-0.022	0.07	-10000	0	-0.23	1	1
actin cytoskeleton reorganization	-0.016	0.14	0.42	2	-0.76	16	18
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.068	0.16	-10000	0	-0.42	37	37
FER	-0.042	0.096	-10000	0	-0.43	16	16
RELA	0.028	0.003	-10000	0	-10000	0	0
ITK	-0.025	0.062	-10000	0	-0.26	2	2
SOS1	0.027	0.006	-10000	0	-10000	0	0
PLCG1	-0.057	0.18	0.37	29	-0.39	65	94
cytokine secretion	-0.022	0.045	-10000	0	-10000	0	0
SPHK1	-0.06	0.13	0.23	7	-0.36	60	67
PTK2	-0.017	0.15	0.42	2	-0.81	16	18
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.091	0.18	-10000	0	-0.47	97	97
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.049	0.22	0.45	57	-0.45	77	134
MAP2K2	-0.023	0.21	-10000	0	-0.85	52	52
MAP2K1	-0.023	0.21	-10000	0	-0.85	52	52
MAP2K7	0.028	0.003	-10000	0	-10000	0	0
KLRG1/SHP2	-0.044	0.097	-10000	0	-0.45	9	9
MAP2K4	-0.012	0.2	-10000	0	-0.86	46	46
Fc epsilon R1/FcgammaRIIB	-0.13	0.22	-10000	0	-0.47	183	183
mol:Choline	-0.084	0.14	0.32	10	-0.39	64	74
SHC/Grb2/SOS1	-0.018	0.11	-10000	0	-0.55	5	5
FYN	0.026	0.007	-10000	0	-10000	0	0
DOK1	0.026	0.022	-10000	0	-0.42	2	2
PXN	-0.007	0.15	0.42	22	-0.75	15	37
HCLS1	-0.048	0.1	-10000	0	-0.35	42	42
PRKCB	-0.031	0.2	0.44	62	-0.35	82	144
FCGR2B	-0.065	0.18	-10000	0	-0.42	180	180
IGHE	-0.003	0.009	-10000	0	-10000	0	0
KLRG1/SHIP	-0.036	0.1	-10000	0	-0.43	14	14
LCP2	-0.006	0.12	-10000	0	-0.42	64	64
PLA2G4A	-0.043	0.1	-10000	0	-0.43	27	27
RASA1	0.027	0.023	-10000	0	-0.65	1	1
mol:Phosphatidic acid	-0.084	0.14	0.32	10	-0.39	64	74
IKK complex	0.001	0.14	0.39	66	-0.28	1	67
WIPF1	0.026	0.016	-10000	0	-0.42	1	1

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	0.004	0.049	0.13	90	-0.13	22	112
BUB1B	-0.001	0.064	0.2	20	-0.19	48	68
PLK1	0.002	0.042	0.14	30	-0.12	16	46
PLK1S1	0.01	0.033	0.14	24	-0.23	2	26
KIF2A	0.006	0.056	0.23	27	-0.23	7	34
regulation of mitotic centrosome separation	0.002	0.042	0.14	30	-0.12	16	46
GOLGA2	0.028	0.004	-10000	0	-10000	0	0
Hec1/SPC24	-0.047	0.16	0.19	1	-0.34	158	159
WEE1	0.012	0.057	0.26	5	-0.38	9	14
cytokinesis	-0.048	0.12	0.26	19	-0.33	21	40
PP2A-alpha B56	-0.009	0.13	-10000	0	-0.58	34	34
AURKA	0.008	0.031	0.15	12	-0.22	2	14
PICH/PLK1	-0.012	0.08	-10000	0	-0.38	22	22
CENPE	-0.02	0.097	0.36	10	-0.25	99	109
RhoA/GTP	0.019	0.006	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.006	0.056	0.23	27	-0.22	7	34
PPP2CA	0.027	0.007	-10000	0	-10000	0	0
FZR1	0.027	0.023	-10000	0	-0.65	1	1
TPX2	-0.009	0.055	0.14	33	-0.18	5	38
PAK1	0.028	0.004	-10000	0	-10000	0	0
SPC24	-0.033	0.15	-10000	0	-0.42	117	117
FBXW11	0.027	0.007	-10000	0	-10000	0	0
CLSPN	-0.016	0.075	0.15	5	-0.26	57	62
GORASP1	0.026	0.008	-10000	0	-10000	0	0
metaphase	0.001	0.005	0.017	54	-0.017	2	56
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0	0.024	0.081	32	-0.061	16	48
G2 phase of mitotic cell cycle	0	0.002	0.013	14	-10000	0	14
STAG2	0.028	0.002	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.007	0.12	-10000	0	-0.48	55	55
spindle elongation	0.002	0.042	0.14	30	-0.12	16	46
ODF2	0.028	0.005	-10000	0	-10000	0	0
BUB1	-0.032	0.13	-10000	0	-0.63	34	34
TPT1	0	0.053	0.13	15	-0.22	39	54
CDC25C	-0.022	0.068	0.18	7	-0.28	9	16
CDC25B	0.025	0.034	-10000	0	-0.42	5	5
SGOL1	-0.004	0.049	0.13	22	-0.13	90	112
RHOA	0.026	0.008	-10000	0	-10000	0	0
CCNB1/CDK1	0.031	0.045	-10000	0	-0.39	3	3
CDC14B	0.01	0.002	-10000	0	-10000	0	0
CDC20	-0.015	0.13	-10000	0	-0.42	82	82
PLK1/PBIP1	-0.01	0.064	0.12	6	-0.23	53	59
mitosis	-0.002	0.003	0.019	3	-10000	0	3
FBXO5	0.001	0.044	0.17	15	-0.17	5	20
CDC2	0	0.002	-10000	0	-0.014	5	5
NDC80	-0.07	0.18	-10000	0	-0.42	192	192
metaphase plate congression	-0.006	0.073	0.16	5	-0.26	56	61
ERCC6L	-0.001	0.078	-10000	0	-0.38	21	21
NLP/gamma Tubulin	0.002	0.037	0.11	34	-0.12	35	69
microtubule cytoskeleton organization	0	0.053	0.13	15	-0.22	39	54
G2/M transition DNA damage checkpoint	0	0.002	0.014	7	-10000	0	7
PPP1R12A	0.027	0.006	-10000	0	-10000	0	0
interphase	0	0.002	0.014	7	-10000	0	7
PLK1/PRC1-2	-0.068	0.14	0.2	2	-0.26	169	171
GRASP65/GM130/RAB1/GTP/PLK1	0.032	0.042	-10000	0	-10000	0	0
RAB1A	0.027	0.006	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.005	0.033	0.12	39	-0.1	10	49
mitotic prometaphase	-0.001	0.005	0.017	46	-10000	0	46
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.05	-10000	0	-0.46	5	5
microtubule-based process	-0.078	0.13	0.16	9	-0.23	356	365
Golgi organization	0.002	0.042	0.14	30	-0.12	16	46
Cohesin/SA2	0.014	0.038	0.18	5	-10000	0	5
PPP1CB/MYPT1	0.038	0.012	-10000	0	-10000	0	0
KIF20A	-0.16	0.22	-10000	0	-0.42	358	358
APC/C/CDC20	-0.002	0.087	0.2	5	-0.26	76	81
PPP2R1A	0.028	0.003	-10000	0	-10000	0	0
chromosome segregation	-0.009	0.064	0.12	6	-0.23	53	59
PRC1	0.02	0.058	-10000	0	-0.42	15	15
ECT2	0.011	0.065	0.26	42	-0.27	1	43
C13orf34	0.003	0.033	0.12	31	-0.099	13	44
NUDC	-0.006	0.073	0.16	5	-0.26	56	61
regulation of attachment of spindle microtubules to kinetochore	0	0.063	0.2	20	-0.19	48	68
spindle assembly	0.005	0.044	0.14	53	-0.12	8	61
spindle stabilization	0.01	0.033	0.16	18	-0.23	2	20
APC/C/HCDH1	0.027	0.016	-10000	0	-0.42	1	1
MKLP2/PLK1	-0.078	0.13	0.17	9	-0.23	356	365
CCNB1	0.022	0.054	-10000	0	-0.42	13	13
PPP1CB	0.027	0.006	-10000	0	-10000	0	0
BTRC	0.027	0.007	-10000	0	-10000	0	0
ROCK2	-0.004	0.091	0.26	7	-0.35	42	49
TUBG1	0.002	0.054	0.14	16	-0.23	35	51
G2/M transition of mitotic cell cycle	-0.003	0.04	-10000	0	-0.38	3	3
MLF1IP	-0.01	0.074	-10000	0	-0.3	52	52
INCENP	0.027	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.022	0.085	-10000	0	-0.45	26	26
AKT1	-0.023	0.17	0.37	13	-0.56	58	71
PTK2B	-0.081	0.19	-10000	0	-0.65	58	58
VEGFR2 homodimer/Frs2	-0.018	0.21	-10000	0	-0.77	61	61
CAV1	0.002	0.097	-10000	0	-0.42	44	44
CALM1	0.027	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.081	0.21	-10000	0	-0.72	61	61
endothelial cell proliferation	0.008	0.2	0.56	42	-0.52	49	91
mol:Ca2+	-0.079	0.18	-10000	0	-0.64	60	60
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.065	0.2	-10000	0	-0.64	60	60
RP11-342D11.1	-0.088	0.19	-10000	0	-0.67	60	60
CDH5	0.025	0.032	-10000	0	-0.5	3	3
VEGFA homodimer	-0.025	0.13	-10000	0	-0.38	2	2
SHC1	0.026	0.016	-10000	0	-0.42	1	1
SHC2	0.017	0.075	-10000	0	-0.46	20	20
HRAS/GDP	-0.059	0.16	-10000	0	-0.55	59	59
SH2D2A	-0.071	0.18	-10000	0	-0.42	193	193
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.019	0.18	0.33	4	-0.58	53	57
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.14	0.23	-10000	0	-0.56	134	134
VEGFR1 homodimer	0.018	0.067	-10000	0	-0.48	15	15
SHC/GRB2/SOS1	-0.05	0.19	-10000	0	-0.61	58	58
GRB10	-0.077	0.18	0.36	1	-0.61	59	60
PTPN11	0.027	0.006	-10000	0	-10000	0	0
GRB2	0.025	0.009	-10000	0	-10000	0	0
PAK1	0.028	0.003	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.058	0.2	-10000	0	-0.66	59	59
HRAS	0.027	0.015	-10000	0	-0.42	1	1
VEGF/Rho/ROCK1/Integrin Complex	-0.031	0.12	-10000	0	-0.39	48	48
HIF1A	0.026	0.033	-10000	0	-0.65	2	2
FRS2	0.027	0.006	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.065	0.19	-10000	0	-0.63	60	60
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.02	0.069	-10000	0	-0.65	9	9
Nck/Pak	0.04	0.01	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.082	0.22	-10000	0	-0.73	61	61
mol:GDP	-0.056	0.18	-10000	0	-0.59	58	58
mol:NADP	-0.013	0.17	0.5	17	-0.5	52	69
eNOS/Hsp90	-0.008	0.15	0.37	9	-0.47	49	58
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
mol:IP3	-0.08	0.19	-10000	0	-0.65	60	60
HIF1A/ARNT	0.037	0.028	-10000	0	-0.49	2	2
SHB	0.028	0.004	-10000	0	-10000	0	0
VEGFA	-0.11	0.2	-10000	0	-0.41	269	269
VEGFC	0.026	0.03	-10000	0	-0.42	4	4
FAK1/Vinculin	-0.054	0.2	0.44	7	-0.64	68	75
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.026	0.008	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.077	0.21	-10000	0	-0.68	59	59
PTPN6	0.027	0.006	-10000	0	-10000	0	0
EPAS1	0.005	0.11	-10000	0	-0.4	61	61
mol:L-citrulline	-0.013	0.17	0.5	17	-0.5	52	69
ITGAV	0.026	0.028	-10000	0	-0.53	2	2
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.066	0.2	-10000	0	-0.64	60	60
VEGFR2 homodimer/VEGFA homodimer	-0.078	0.22	-10000	0	-0.72	61	61
VEGFR2/3 heterodimer	-0.024	0.22	-10000	0	-0.79	66	66
VEGFB	0.028	0.003	-10000	0	-10000	0	0
MAPK11	-0.077	0.19	0.44	3	-0.67	61	64
VEGFR2 homodimer	-0.036	0.23	-10000	0	-0.84	66	66
FLT1	0.018	0.067	-10000	0	-0.48	15	15
NEDD4	0.029	0.023	-10000	0	-0.65	1	1
MAPK3	-0.073	0.16	0.53	2	-0.56	60	62
MAPK1	-0.073	0.17	0.47	3	-0.56	60	63
VEGFA145/NRP2	-0.069	0.16	-10000	0	-0.3	282	282
VEGFR1/2 heterodimer	-0.024	0.22	-10000	0	-0.78	65	65
KDR	-0.036	0.23	-10000	0	-0.84	66	66
VEGFA165/NRP1/VEGFR2 homodimer	-0.07	0.2	-10000	0	-0.66	65	65
SRC	0.027	0.007	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.058	0.19	0.46	22	-0.57	60	82
PI3K	-0.045	0.19	-10000	0	-0.68	57	57
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.081	0.21	-10000	0	-0.71	61	61
FES	-0.083	0.2	0.37	1	-0.69	61	62
GAB1	-0.055	0.19	-10000	0	-0.68	60	60
VEGFR2 homodimer/VEGFA homodimer/Src	-0.08	0.21	-10000	0	-0.7	61	61
CTNNB1	0.026	0.008	-10000	0	-10000	0	0
SOS1	0.027	0.006	-10000	0	-10000	0	0
ARNT	0.027	0.007	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.025	0.14	0.42	4	-0.48	35	39
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.082	0.21	-10000	0	-0.73	61	61
PI3K/GAB1	-0.021	0.17	-10000	0	-0.57	59	59
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.057	0.2	-10000	0	-0.66	59	59
PRKACA	0.028	0.003	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.009	0.21	-10000	0	-0.76	63	63
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
CDC42	-0.082	0.2	0.37	1	-0.69	60	61
actin cytoskeleton reorganization	-0.13	0.22	-10000	0	-0.56	134	134
PTK2	-0.064	0.2	0.33	2	-0.7	63	65
EDG1	-0.088	0.19	-10000	0	-0.67	60	60
mol:DAG	-0.08	0.19	-10000	0	-0.65	60	60
CaM/Ca2+	-0.066	0.18	-10000	0	-0.6	60	60
MAP2K3	-0.076	0.18	0.37	5	-0.62	58	63
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.051	0.21	-10000	0	-0.63	59	59
PLCG1	-0.081	0.19	-10000	0	-0.66	60	60
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.066	0.2	-10000	0	-0.67	60	60
IQGAP1	0.028	0.003	-10000	0	-10000	0	0
YES1	0.028	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.081	0.21	-10000	0	-0.72	61	61
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.081	0.21	-10000	0	-0.72	61	61
cell migration	-0.037	0.18	0.39	2	-0.54	57	59
mol:PI-3-4-5-P3	-0.041	0.18	-10000	0	-0.62	58	58
FYN	0.026	0.007	-10000	0	-10000	0	0
VEGFB/NRP1	-0.073	0.18	-10000	0	-0.64	60	60
mol:NO	-0.013	0.17	0.5	17	-0.5	52	69
PXN	0.027	0.006	-10000	0	-10000	0	0
HRAS/GTP	-0.07	0.16	-10000	0	-0.55	59	59
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.071	0.19	-10000	0	-0.64	59	59
VHL	0.026	0.008	-10000	0	-10000	0	0
ITGB3	0.007	0.11	-10000	0	-0.61	25	25
NOS3	-0.019	0.18	0.53	15	-0.57	52	67
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.087	0.22	-10000	0	-0.73	66	66
RAC1	0.025	0.01	-10000	0	-10000	0	0
PRKCA	-0.073	0.17	0.37	1	-0.58	55	56
PRKCB	-0.078	0.17	-10000	0	-0.6	56	56
VCL	0.027	0.007	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.08	0.19	-10000	0	-0.67	60	60
VEGFR1/2 heterodimer/VEGFA homodimer	-0.086	0.22	-10000	0	-0.71	71	71
VEGFA165/NRP2	-0.069	0.16	-10000	0	-0.3	282	282
MAPKKK cascade	-0.05	0.16	0.36	1	-0.58	33	34
NRP2	0.016	0.069	-10000	0	-0.43	20	20
VEGFC homodimer	0.026	0.03	-10000	0	-0.42	4	4
NCK1	0.027	0.006	-10000	0	-10000	0	0
ROCK1	0.028	0.005	-10000	0	-10000	0	0
FAK1/Paxillin	-0.059	0.2	0.45	3	-0.63	67	70
MAP3K13	-0.082	0.19	0.37	1	-0.68	60	61
PDPK1	-0.042	0.15	0.28	1	-0.55	53	54

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.039	0.021	-10000	0	-0.49	1	1
Necdin/E2F1	-0.035	0.15	-10000	0	-0.32	183	183
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.026	0.12	-10000	0	-0.39	30	30
NGF (dimer)/p75(NTR)/BEX1	-0.11	0.22	-10000	0	-0.44	241	241
NT-4/5 (dimer)/p75(NTR)	-0.005	0.11	-10000	0	-0.33	90	90
IKBKB	0.027	0.006	-10000	0	-10000	0	0
AKT1	0.003	0.12	0.37	19	-0.4	24	43
IKBKG	0.028	0.002	-10000	0	-10000	0	0
BDNF	-0.039	0.16	-10000	0	-0.42	130	130
MGDIs/NGR/p75(NTR)/LINGO1	0.007	0.12	-10000	0	-0.38	32	32
FURIN	0.028	0.003	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.02	0.14	-10000	0	-0.43	42	42
LINGO1	0.008	0.096	-10000	0	-0.45	36	36
Sortilin/TRAF6/NRIF	0.035	0.024	-10000	0	-10000	0	0
proBDNF (dimer)	-0.039	0.16	-10000	0	-0.42	130	130
NTRK1	-0.032	0.18	-10000	0	-0.61	75	75
RTN4R	0.022	0.05	-10000	0	-0.44	10	10
neuron apoptosis	-0.02	0.15	0.43	10	-0.53	22	32
IRAK1	0.028	0.002	-10000	0	-10000	0	0
SHC1	-0.024	0.12	-10000	0	-0.4	44	44
ARHGDIA	0.025	0.009	-10000	0	-10000	0	0
RhoA/GTP	0.019	0.006	-10000	0	-10000	0	0
Gamma Secretase	0.076	0.033	-10000	0	-0.36	2	2
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.015	0.12	-10000	0	-0.42	29	29
MAGEH1	0.028	0.015	-10000	0	-0.42	1	1
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.005	0.14	-10000	0	-0.45	42	42
Mammalian IAPs/DIABLO	0.035	0.093	-10000	0	-0.38	1	1
proNGF (dimer)	-0.011	0.13	-10000	0	-0.46	67	67
MAGED1	0.028	0.002	-10000	0	-10000	0	0
APP	0.027	0.007	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.011	0.074	-10000	0	-0.42	25	25
ZNF274	0.028	0.003	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.002	0.1	-10000	0	-0.39	27	27
NGF	-0.011	0.13	-10000	0	-0.46	67	67
cell cycle arrest	0.01	0.14	0.34	10	-0.41	28	38
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.003	0.082	-10000	0	-0.36	19	19
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.013	0.1	-10000	0	-0.37	24	24
NCSTN	0.027	0.007	-10000	0	-10000	0	0
mol:GTP	0	0.13	-10000	0	-0.4	44	44
PSENEN	0.028	0.003	-10000	0	-10000	0	0
mol:ceramide	-0.008	0.12	-10000	0	-0.41	29	29
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.006	0.085	-10000	0	-0.46	19	19
p75(NTR)/beta APP	0.006	0.1	-10000	0	-0.33	72	72
BEX1	-0.14	0.29	-10000	0	-0.64	216	216
mol:GDP	-0.035	0.11	-10000	0	-0.3	120	120
NGF (dimer)	-0.23	0.25	-10000	0	-0.44	472	472
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.023	0.11	-10000	0	-0.4	16	16
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
RAC1/GTP	0	0.1	-10000	0	-0.34	40	40
MYD88	0.026	0.008	-10000	0	-10000	0	0
CHUK	0.027	0.007	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.001	0.13	-10000	0	-0.4	44	44
RHOB	0.027	0.006	-10000	0	-10000	0	0
RHOA	0.026	0.008	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.022	0.13	-10000	0	-0.29	162	162
NT3 (dimer)	-0.007	0.15	-10000	0	-0.64	44	44
TP53	-0.024	0.12	0.44	6	-0.41	22	28
PRDM4	-0.012	0.12	-10000	0	-0.41	29	29
BDNF (dimer)	-0.26	0.26	-10000	0	-0.47	477	477
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
SORT1	0.026	0.024	-10000	0	-0.65	1	1
activation of caspase activity	0.021	0.12	-10000	0	-0.39	30	30
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.015	0.12	-10000	0	-0.42	29	29
RHOC	0.027	0.007	-10000	0	-10000	0	0
XIAP	0.028	0.001	-10000	0	-10000	0	0
MAPK10	-0.007	0.14	0.32	37	-0.46	14	51
DIABLO	0.027	0.006	-10000	0	-10000	0	0
SMPD2	-0.008	0.12	-10000	0	-0.41	29	29
APH1B	0.026	0.033	-10000	0	-0.65	2	2
APH1A	0.027	0.007	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0	0.13	-10000	0	-0.4	45	45
PSEN1	0.027	0.005	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.037	0.013	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.017	0.15	-10000	0	-0.39	111	111
MAPK8	-0.004	0.13	0.33	35	-0.48	7	42
MAPK9	-0.003	0.13	0.47	12	-0.47	7	19
APAF1	0.027	0.006	-10000	0	-10000	0	0
NTF3	-0.007	0.15	-10000	0	-0.64	44	44
NTF4	-0.011	0.074	-10000	0	-0.42	25	25
NDN	0.008	0.11	-10000	0	-0.62	27	27
RAC1/GDP	0.018	0.007	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.02	0.11	-10000	0	-0.4	15	15
p75 CTF/Sortilin/TRAF6/NRIF	0.066	0.026	-10000	0	-0.38	1	1
RhoA-B-C/GTP	0	0.13	-10000	0	-0.4	44	44
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.007	0.13	-10000	0	-0.41	29	29
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.004	0.14	-10000	0	-0.44	29	29
PRKACB	0.027	0.007	-10000	0	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.011	0.12	-10000	0	-0.3	128	128
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.023	0.14	-10000	0	-0.42	100	100
BIRC2	0.028	0.004	-10000	0	-10000	0	0
neuron projection morphogenesis	0.011	0.14	0.34	6	-0.42	30	36
BAD	-0.001	0.14	0.42	20	-0.47	10	30
RIPK2	0.027	0.016	-10000	0	-0.42	1	1
NGFR	-0.015	0.14	-10000	0	-0.47	73	73
CYCS	-0.012	0.1	0.36	2	-0.39	25	27
ADAM17	0.027	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.015	0.12	-10000	0	-0.42	28	28
BCL2L11	-0.001	0.14	0.41	23	-0.44	19	42
BDNF (dimer)/p75(NTR)	-0.04	0.16	-10000	0	-0.34	178	178
PI3K	0.015	0.12	-10000	0	-0.42	25	25
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.016	0.12	-10000	0	-0.42	29	29
NDNL2	0.028	0.004	-10000	0	-10000	0	0
YWHAE	0.025	0.009	-10000	0	-10000	0	0
PRKCI	0.027	0.006	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.019	0.14	-10000	0	-0.35	125	125
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.016	0.12	-10000	0	-0.42	29	29
TRAF6	0.028	0.003	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
PRKCZ	0.024	0.04	-10000	0	-0.65	3	3
PLG	-0.31	0.32	-10000	0	-0.63	441	441
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.037	0.12	-10000	0	-0.42	34	34
SQSTM1	0.024	0.034	-10000	0	-0.42	5	5
NGFRAP1	0.027	0.032	-10000	0	-0.65	2	2
CASP3	0.001	0.14	0.33	44	-0.45	10	54
E2F1	-0.056	0.17	-10000	0	-0.42	163	163
CASP9	0.026	0.007	-10000	0	-10000	0	0
IKK complex	0.005	0.15	-10000	0	-0.49	20	20
NGF (dimer)/TRKA	-0.031	0.17	-10000	0	-0.41	129	129
MMP7	-0.068	0.22	-10000	0	-0.58	139	139
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.026	0.12	-10000	0	-0.4	28	28
MMP3	-0.031	0.11	-10000	0	-0.42	68	68
APAF-1/Caspase 9	-0.03	0.091	-10000	0	-0.43	1	1

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.028	0.015	-10000	0	-0.42	1	1
ELF1	-0.003	0.085	-10000	0	-0.44	3	3
CCNA2	-0.057	0.18	-10000	0	-0.42	166	166
PIK3CA	0.028	0.006	-10000	0	-10000	0	0
JAK3	-0.055	0.17	-10000	0	-0.42	165	165
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
JAK1	0.027	0.007	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.024	0.14	-10000	0	-0.5	42	42
SHC1	0.027	0.016	-10000	0	-0.42	1	1
SP1	0.03	0.032	-10000	0	-0.34	2	2
IL2RA	-0.035	0.14	-10000	0	-0.35	141	141
IL2RB	-0.14	0.22	-10000	0	-0.42	328	328
SOS1	0.028	0.006	-10000	0	-10000	0	0
IL2RG	0.004	0.11	-10000	0	-0.44	47	47
G1/S transition of mitotic cell cycle	0.02	0.11	0.41	24	-0.46	3	27
PTPN11	0.028	0.006	-10000	0	-10000	0	0
CCND2	0.02	0.043	-10000	0	-10000	0	0
LCK	0.004	0.1	-10000	0	-0.44	44	44
GRB2	0.026	0.009	-10000	0	-10000	0	0
IL2	0.015	0.059	-10000	0	-0.42	16	16
CDK6	0.024	0.025	-10000	0	-0.65	1	1
CCND3	-0.01	0.13	0.37	1	-0.54	7	8

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.017	0.08	-10000	0	-0.63	13	13
Jak2/Leptin Receptor	-0.072	0.14	-10000	0	-0.5	36	36
PTP1B/AKT1	-0.046	0.089	0.25	4	-0.43	14	18
FYN	0.026	0.007	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.055	0.098	0.28	13	-0.38	29	42
EGFR	-0.015	0.061	-10000	0	-0.47	14	14
EGF/EGFR	-0.28	0.16	-10000	0	-0.37	614	614
CSF1	0.023	0.049	-10000	0	-0.6	5	5
AKT1	0.028	0.006	-10000	0	-10000	0	0
INSR	0.029	0.003	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.081	0.14	0.25	3	-0.45	82	85
Insulin Receptor/Insulin	-0.026	0.088	0.27	1	-0.41	9	10
HCK	-0.006	0.12	-10000	0	-0.42	63	63
CRK	0.025	0.009	-10000	0	-10000	0	0
TYK2	-0.051	0.098	0.36	10	-0.46	13	23
EGF	-0.54	0.26	-10000	0	-0.65	731	731
YES1	0.028	0.005	-10000	0	-10000	0	0
CAV1	-0.12	0.13	0.34	20	-0.39	34	54
TXN	0.022	0.016	-10000	0	-0.42	1	1
PTP1B/IRS1/GRB2	-0.055	0.094	0.3	6	-0.48	19	25
cell migration	0.055	0.098	0.38	29	-0.28	13	42
STAT3	0.025	0.009	-10000	0	-10000	0	0
PRLR	-0.083	0.25	-10000	0	-0.65	143	143
ITGA2B	0.014	0.068	-10000	0	-0.46	17	17
CSF1R	0.013	0.079	-10000	0	-0.44	26	26
Prolactin Receptor/Prolactin	-0.054	0.19	-10000	0	-0.49	143	143
FGR	0.021	0.053	-10000	0	-0.44	11	11
PTP1B/p130 Cas	-0.055	0.084	0.27	1	-0.42	18	19
Crk/p130 Cas	-0.051	0.081	0.27	1	-0.45	13	14
DOK1	-0.038	0.11	0.34	17	-0.41	23	40
JAK2	-0.073	0.15	0.3	4	-0.48	48	52
Jak2/Leptin Receptor/Leptin	-0.058	0.097	-10000	0	-0.52	11	11
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
PTPN1	-0.055	0.099	0.29	12	-0.38	29	41
LYN	0.026	0.024	-10000	0	-0.65	1	1
CDH2	-0.033	0.19	-10000	0	-0.64	80	80
SRC	0.003	0.067	0.31	3	-0.58	7	10
ITGB3	0.006	0.11	-10000	0	-0.61	25	25
CAT1/PTP1B	-0.19	0.19	0.38	27	-0.44	136	163
CAPN1	0.027	0.004	-10000	0	-10000	0	0
CSK	0.028	0.003	-10000	0	-10000	0	0
PI3K	0.012	0.082	-10000	0	-0.44	4	4
mol:H2O2	-0.005	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.046	0.093	-10000	0	-0.47	13	13
negative regulation of transcription	-0.072	0.15	0.3	4	-0.47	48	52
FCGR2A	0.002	0.1	-10000	0	-0.42	48	48
FER	0.02	0.033	-10000	0	-0.66	2	2
alphaIIb/beta3 Integrin	0.014	0.098	-10000	0	-0.42	40	40
BLK	-0.001	0.1	-10000	0	-0.42	48	48
Insulin Receptor/Insulin/Shc	0.046	0.024	-10000	0	-10000	0	0
RHOA	0.025	0.008	-10000	0	-10000	0	0
LEPR	0.025	0.032	-10000	0	-0.64	2	2
BCAR1	0.026	0.024	-10000	0	-0.65	1	1
p210 bcr-abl/Grb2	0.025	0.009	-10000	0	-10000	0	0
mol:NADPH	-0.005	0.004	-10000	0	-10000	0	0
TRPV6	-0.17	0.19	0.31	14	-0.44	142	156
PRL	-0.002	0.021	-10000	0	-10000	0	0
SOCS3	-0.014	0.23	-10000	0	-1.1	37	37
SPRY2	0.023	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.041	0.055	-10000	0	-0.43	10	10
CSF1/CSF1R	-0.052	0.1	0.28	5	-0.51	16	21
Ras protein signal transduction	0.051	0.12	0.46	63	-10000	0	63
IRS1	0.019	0.072	-10000	0	-0.65	10	10
INS	0.012	0.029	-10000	0	-0.41	3	3
LEP	-0.025	0.12	-10000	0	-0.42	78	78
STAT5B	-0.06	0.11	0.28	11	-0.42	36	47
STAT5A	-0.06	0.11	0.28	12	-0.42	36	48
GRB2	0.025	0.009	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.055	0.099	0.28	5	-0.42	28	33
CSN2	-0.016	0.085	-10000	0	-0.64	4	4
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
LAT	-0.032	0.12	0.29	2	-0.48	41	43
YBX1	0.03	0.009	-10000	0	-10000	0	0
LCK	0.003	0.1	-10000	0	-0.44	44	44
SHC1	0.026	0.016	-10000	0	-0.42	1	1
NOX4	0.002	0.12	-10000	0	-0.66	29	29

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.013	0.066	-10000	0	-0.28	39	39
epithelial cell differentiation	0.032	0.088	-10000	0	-0.36	39	39
CYFIP2	0.018	0.076	-10000	0	-0.65	11	11
ENAH	0.039	0.13	0.5	44	-10000	0	44
EGFR	0.017	0.061	-10000	0	-0.45	14	14
EPHA2	0.026	0.024	-10000	0	-0.65	1	1
MYO6	0.027	0.11	0.37	29	-0.36	38	67
CTNNB1	0.026	0.008	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.044	0.056	-10000	0	-0.42	11	11
AQP5	-0.12	0.24	0.34	1	-0.53	211	212
CTNND1	0.028	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.028	0.1	0.36	26	-0.34	38	64
regulation of calcium-dependent cell-cell adhesion	0.01	0.12	0.35	18	-0.38	50	68
EGF	-0.54	0.25	-10000	0	-0.65	731	731
NCKAP1	0.027	0.006	-10000	0	-10000	0	0
AQP3	-0.073	0.22	0.34	1	-0.55	144	145
cortical microtubule organization	0.032	0.088	-10000	0	-0.36	39	39
GO:0000145	0.017	0.1	0.35	26	-0.32	38	64
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.036	0.09	-10000	0	-0.36	39	39
MLLT4	0.026	0.007	-10000	0	-10000	0	0
ARF6/GDP	-0.007	0.06	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.06	0.032	-10000	0	-0.38	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.013	0.079	0.35	4	-10000	0	4
PVRL2	0.028	0.003	-10000	0	-10000	0	0
ZYX	0.014	0.087	0.34	6	-0.34	36	42
ARF6/GTP	0.065	0.036	-10000	0	-0.36	1	1
CDH1	-0.005	0.14	-10000	0	-0.65	40	40
EGFR/EGFR/EGF/EGF	-0.26	0.17	-10000	0	-0.36	559	559
RhoA/GDP	0.034	0.084	-10000	0	-0.34	39	39
actin cytoskeleton organization	0.021	0.11	0.36	27	-0.63	2	29
IGF-1R heterotetramer	0.028	0.003	-10000	0	-10000	0	0
GIT1	0.025	0.009	-10000	0	-10000	0	0
IGF1R	0.028	0.003	-10000	0	-10000	0	0
IGF1	0.008	0.098	-10000	0	-0.48	32	32
DIAPH1	0.017	0.14	-10000	0	-0.69	9	9
Wnt receptor signaling pathway	-0.032	0.088	0.36	39	-10000	0	39
RHOA	0.026	0.008	-10000	0	-10000	0	0
RhoA/GTP	-0.008	0.061	-10000	0	-10000	0	0
CTNNA1	0.027	0.007	-10000	0	-10000	0	0
VCL	0.021	0.11	0.36	27	-0.65	2	29
EFNA1	0.026	0.016	-10000	0	-0.42	1	1
LPP	0.013	0.087	0.35	6	-10000	0	6
Ephrin A1/EPHA2	0.025	0.082	-10000	0	-10000	0	0
SEC6/SEC8	-0.002	0.066	-10000	0	-10000	0	0
MGAT3	0.009	0.12	0.35	18	-0.38	50	68
HGF/MET	0.009	0.11	-10000	0	-0.37	59	59
HGF	-0.007	0.14	-10000	0	-0.59	45	45
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.013	0.067	-10000	0	-0.29	39	39
actin cable formation	0.067	0.16	0.55	60	-10000	0	60
KIAA1543	0.015	0.11	0.36	25	-0.36	41	66
KIFC3	0.011	0.089	-10000	0	-0.34	44	44
NCK1	0.027	0.006	-10000	0	-10000	0	0
EXOC3	0.027	0.005	-10000	0	-10000	0	0
ACTN1	0.026	0.1	0.35	23	-0.34	38	61
NCK1/GIT1	0.037	0.014	-10000	0	-10000	0	0
mol:GDP	0.032	0.088	-10000	0	-0.36	39	39
EXOC4	0.025	0.01	-10000	0	-10000	0	0
STX4	0.013	0.086	0.35	1	-0.34	39	40
PIP5K1C	0.028	0.11	0.36	26	-0.34	38	64
LIMA1	0.027	0.006	-10000	0	-10000	0	0
ABI1	0.027	0.007	-10000	0	-10000	0	0
ROCK1	0.049	0.14	0.51	47	-10000	0	47
adherens junction assembly	0.034	0.14	0.49	33	-0.56	8	41
IGF-1R heterotetramer/IGF1	0.018	0.094	-10000	0	-0.38	7	7
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.039	0.012	-10000	0	-10000	0	0
MET	0.021	0.04	-10000	0	-0.42	7	7
PLEKHA7	0.026	0.12	0.37	25	-0.38	41	66
mol:GTP	0.058	0.032	-10000	0	-0.38	1	1
establishment of epithelial cell apical/basal polarity	0.035	0.1	0.38	23	-10000	0	23
cortical actin cytoskeleton stabilization	0.013	0.066	-10000	0	-0.28	39	39
regulation of cell-cell adhesion	0.021	0.11	0.36	27	-0.63	2	29
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.013	0.067	-10000	0	-0.29	39	39

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0.037	-10000	0	-0.44	4	4
MAP4K4	0.014	0.049	-10000	0	-0.4	3	3
BAG4	0.025	0.033	-10000	0	-0.65	2	2
PKC zeta/ceramide	-0.099	0.086	0.17	1	-0.29	111	112
NFKBIA	0.027	0.005	-10000	0	-10000	0	0
BIRC3	-0.023	0.14	-10000	0	-0.42	100	100
BAX	-0.036	0.039	-10000	0	-0.3	6	6
RIPK1	0.027	0.007	-10000	0	-10000	0	0
AKT1	0.029	0.088	0.83	10	-10000	0	10
BAD	-0.1	0.079	0.17	1	-0.28	110	111
SMPD1	0.018	0.06	0.23	22	-0.28	7	29
RB1	-0.1	0.08	-10000	0	-0.29	99	99
FADD/Caspase 8	0.015	0.084	-10000	0	-0.46	7	7
MAP2K4	-0.079	0.071	0.2	2	-0.27	62	64
NSMAF	0.027	0.005	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.079	0.077	0.2	2	-0.28	67	69
EGF	-0.54	0.25	-10000	0	-0.65	731	731
mol:ceramide	-0.11	0.086	0.18	2	-0.3	109	111
MADD	0.028	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.017	0.027	0.21	7	-0.39	2	9
ASAH1	0.027	0.007	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.099	0.079	-10000	0	-0.28	99	99
cell proliferation	-0.067	0.076	-10000	0	-0.37	15	15
BID	-0.015	0.12	-10000	0	-0.68	24	24
MAP3K1	-0.098	0.079	0.19	3	-0.28	104	107
EIF2A	-0.079	0.075	0.25	7	-0.46	5	12
TRADD	0.026	0.007	-10000	0	-10000	0	0
CRADD	0.027	0.006	-10000	0	-10000	0	0
MAPK3	-0.07	0.071	-10000	0	-0.31	16	16
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.072	0.074	-10000	0	-0.31	19	19
Cathepsin D/ceramide	-0.098	0.084	-10000	0	-0.28	111	111
FADD	0.01	0.055	-10000	0	-0.41	3	3
KSR1	-0.092	0.077	0.19	5	-0.29	75	80
MAPK8	-0.09	0.078	-10000	0	-0.26	110	110
PRKRA	-0.099	0.081	0.18	3	-0.28	102	105
PDGFA	0.023	0.029	-10000	0	-0.53	2	2
TRAF2	0.028	0.004	-10000	0	-10000	0	0
IGF1	0.008	0.098	-10000	0	-0.48	32	32
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.11	0.085	0.18	2	-0.3	109	111
CTSD	0.026	0.031	-10000	0	-0.5	3	3
regulation of nitric oxide biosynthetic process	0.04	0.019	-10000	0	-0.49	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.07	0.081	-10000	0	-0.4	15	15
PRKCD	0.021	0.045	-10000	0	-0.42	9	9
PRKCZ	0.024	0.04	-10000	0	-0.65	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.017	0.027	0.21	7	-0.39	2	9
RelA/NF kappa B1	0.04	0.019	-10000	0	-0.49	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.026	0.024	-10000	0	-0.65	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.018	0.051	-10000	0	-0.48	3	3
TNFR1A/BAG4/TNF-alpha	0.04	0.06	-10000	0	-0.42	7	7
mol:Sphingosine-1-phosphate	0.017	0.037	-10000	0	-0.44	4	4
MAP2K1	-0.075	0.074	-10000	0	-0.32	17	17
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.028	0.003	-10000	0	-10000	0	0
CYCS	-0.051	0.04	0.17	1	-0.26	9	10
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
TNFR1A/BAG4	0.037	0.028	-10000	0	-0.49	2	2
EIF2AK2	-0.092	0.08	0.32	2	-0.28	92	94
TNF-alpha/TNFR1A/FAN	0.041	0.056	-10000	0	-0.42	5	5
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.018	0.1	-10000	0	-0.45	33	33
MAP2K2	-0.076	0.072	-10000	0	-0.31	16	16
SMPD3	0.012	0.048	-10000	0	-0.33	6	6
TNF	0.012	0.082	-10000	0	-0.46	25	25
PKC zeta/PAR4	0.035	0.038	-10000	0	-0.49	4	4
mol:PHOSPHOCHOLINE	0.19	0.11	0.25	639	-0.27	5	644
NF kappa B1/RelA/I kappa B alpha	0.071	0.04	-10000	0	-0.36	3	3
AIFM1	-0.06	0.054	0.17	1	-0.2	37	38
BCL2	0.027	0.023	-10000	0	-0.65	1	1

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.62	0.68	0.58	6	-1.3	438	444
PLK1	-0.027	0.18	0.53	1	-0.64	6	7
CDKN1B	-0.02	0.16	0.5	13	-0.38	3	16
FOXO3	0.001	0.13	-10000	0	-0.6	6	6
KAT2B	0.023	0.033	-10000	0	-0.69	1	1
FOXO1/SIRT1	-0.19	0.28	0.35	3	-0.44	413	416
CAT	-0.011	0.15	-10000	0	-1.2	4	4
CTNNB1	0.026	0.008	-10000	0	-10000	0	0
AKT1	-0.015	0.052	-10000	0	-0.31	2	2
FOXO1	-0.22	0.3	0.44	10	-0.48	420	430
MAPK10	0.028	0.076	0.33	5	-0.36	13	18
mol:GTP	0.002	0.001	-10000	0	-10000	0	0
FOXO4	0.072	0.096	0.4	29	-0.4	2	31
response to oxidative stress	-0.028	0.041	-10000	0	-0.24	5	5
FOXO3A/SIRT1	0.032	0.14	-10000	0	-0.55	7	7
XPO1	0.028	0.006	-10000	0	-10000	0	0
EP300	-0.018	0.056	-10000	0	-0.43	3	3
BCL2L11	-0.001	0.14	-10000	0	-0.74	32	32
FOXO1/SKP2	-0.19	0.28	0.39	4	-0.45	399	403
mol:GDP	-0.028	0.041	-10000	0	-0.23	5	5
RAN	0.028	0.006	-10000	0	-10000	0	0
GADD45A	0.048	0.2	0.43	4	-0.67	48	52
YWHAQ	0.027	0.006	-10000	0	-10000	0	0
FOXO1/14-3-3 family	-0.019	0.15	-10000	0	-0.57	43	43
MST1	0.018	0.058	-10000	0	-0.5	9	9
CSNK1D	0.025	0.009	-10000	0	-10000	0	0
CSNK1E	0.027	0.005	-10000	0	-10000	0	0
FOXO4/14-3-3 family	-0.004	0.15	-10000	0	-0.59	37	37
YWHAB	0.027	0.007	-10000	0	-10000	0	0
MAPK8	0.033	0.064	0.27	11	-10000	0	11
MAPK9	0.033	0.058	0.33	5	-10000	0	5
YWHAG	0.025	0.009	-10000	0	-10000	0	0
YWHAE	0.025	0.009	-10000	0	-10000	0	0
YWHAZ	0.027	0.005	-10000	0	-10000	0	0
SIRT1	0.035	0.015	-10000	0	-10000	0	0
SOD2	-0.048	0.19	0.53	8	-0.52	45	53
RBL2	0.027	0.13	-10000	0	-0.91	6	6
RAL/GDP	0.017	0.031	-10000	0	-10000	0	0
CHUK	0.024	0.023	-10000	0	-10000	0	0
Ran/GTP	0.024	0.005	-10000	0	-10000	0	0
CSNK1G2	0.027	0.023	-10000	0	-0.65	1	1
RAL/GTP	0.022	0.031	-10000	0	-10000	0	0
CSNK1G1	0.028	0.003	-10000	0	-10000	0	0
FASLG	-0.11	0.2	-10000	0	-0.73	41	41
SKP2	0.027	0.005	-10000	0	-10000	0	0
USP7	0.028	0.008	-10000	0	-10000	0	0
IKBKB	0.025	0.022	-10000	0	-10000	0	0
CCNB1	-0.008	0.14	-10000	0	-0.67	2	2
FOXO1-3a-4/beta catenin	-0.028	0.15	0.35	8	-0.43	1	9
proteasomal ubiquitin-dependent protein catabolic process	-0.19	0.27	0.39	4	-0.44	399	403
CSNK1A1	0.027	0.007	-10000	0	-10000	0	0
SGK1	0.021	0.043	-10000	0	-0.49	4	4
CSNK1G3	0.027	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.041	0.013	-10000	0	-10000	0	0
ZFAND5	0.07	0.092	0.48	16	-10000	0	16
SFN	-0.072	0.2	-10000	0	-0.44	185	185
CDK2	-0.029	0.065	-10000	0	-0.29	4	4
FOXO3A/14-3-3	-0.007	0.14	-10000	0	-0.55	41	41
CREBBP	-0.028	0.061	-10000	0	-0.24	1	1
FBXO32	-0.006	0.14	0.53	1	-0.71	3	4
BCL6	0.028	0.13	-10000	0	-0.79	7	7
RALB	0.028	0.006	-10000	0	-10000	0	0
RALA	0.026	0.01	-10000	0	-10000	0	0
YWHAH	0.027	0.005	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.027	0.005	-10000	0	-10000	0	0
VLDLR	0.027	0.016	-10000	0	-0.42	1	1
LRPAP1	0.028	0.004	-10000	0	-10000	0	0
NUDC	0.027	0.007	-10000	0	-10000	0	0
RELN/LRP8	-0.053	0.18	-10000	0	-0.42	160	160
CaM/Ca2+	0.02	0.004	-10000	0	-10000	0	0
KATNA1	0.026	0.007	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.042	0.18	-10000	0	-0.38	160	160
IQGAP1/CaM	0.04	0.008	-10000	0	-10000	0	0
DAB1	-0.003	0.07	-10000	0	-0.42	22	22
IQGAP1	0.028	0.003	-10000	0	-10000	0	0
PLA2G7	-0.32	0.19	-10000	0	-0.42	683	683
CALM1	0.027	0.005	-10000	0	-10000	0	0
DYNLT1	0.026	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.037	0.025	-10000	0	-0.29	3	3
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.027	0.006	-10000	0	-10000	0	0
CDK5R1	0.023	0.036	-10000	0	-0.44	5	5
LIS1/Poliovirus Protein 3A	0.013	0.005	-10000	0	-10000	0	0
CDK5R2	-0.049	0.15	-10000	0	-0.42	128	128
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.062	0.19	-10000	0	-0.43	162	162
YWHAE	0.025	0.009	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.03	0.17	0.32	55	-0.41	14	69
MAP1B	0.006	0.013	-10000	0	-10000	0	0
RAC1	0.016	0.008	-10000	0	-10000	0	0
p35/CDK5	-0.047	0.15	0.37	2	-10000	0	2
RELN	-0.12	0.27	-10000	0	-0.61	195	195
PAFAH/LIS1	-0.17	0.12	-10000	0	-0.32	29	29
LIS1/CLIP170	0.03	0.013	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.037	0.12	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.035	0.13	-10000	0	-0.46	14	14
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.059	0.14	0.31	8	-0.43	18	26
LIS1/IQGAP1	0.031	0.013	-10000	0	-10000	0	0
RHOA	0.016	0.008	-10000	0	-10000	0	0
PAFAH1B1	0.017	0.007	-10000	0	-10000	0	0
PAFAH1B3	0.027	0.028	-10000	0	-0.53	2	2
PAFAH1B2	0.026	0.035	-10000	0	-0.55	3	3
MAP1B/LIS1/Dynein heavy chain	0.029	0.021	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.025	0.16	0.33	31	-0.47	1	32
LRP8	0.025	0.031	-10000	0	-0.42	4	4
NDEL1/Katanin 60	-0.03	0.17	0.33	53	-0.49	1	54
P39/CDK5	-0.073	0.16	0.35	1	-0.47	22	23
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.03	0.013	-10000	0	-10000	0	0
CDK5	-0.061	0.15	0.38	1	-0.36	144	145
PPP2R5D	0.026	0.007	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.026	0.011	-10000	0	-10000	0	0
CSNK2A1	0.027	0.006	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.042	0.16	-10000	0	-0.37	158	158
RELN/VLDLR	-0.037	0.18	-10000	0	-0.38	160	160
CDC42	0.017	0.008	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor 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
CRKL	0.027	0.005	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	0.002	0.08	-10000	0	-0.31	16	16
NT3 (dimer)/TRKC	-0.03	0.18	-10000	0	-0.5	114	114
NT3 (dimer)/TRKB	-0.12	0.24	-10000	0	-0.47	244	244
SHC/Grb2/SOS1/GAB1/PI3K	0.033	0.016	-10000	0	-10000	0	0
RAPGEF1	0.028	0.004	-10000	0	-10000	0	0
BDNF	-0.039	0.16	-10000	0	-0.42	130	130
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
DYNLT1	0.026	0.007	-10000	0	-10000	0	0
NTRK1	-0.032	0.18	-10000	0	-0.61	75	75
NTRK2	-0.18	0.31	-10000	0	-0.64	268	268
NTRK3	-0.033	0.19	-10000	0	-0.65	78	78
NT-4/5 (dimer)/TRKB	-0.11	0.23	-10000	0	-0.46	230	230
neuron apoptosis	0.1	0.2	0.49	125	-10000	0	125
SHC 2-3/Grb2	-0.11	0.22	-10000	0	-0.58	105	105
SHC1	0.026	0.016	-10000	0	-0.42	1	1
SHC2	-0.082	0.18	-10000	0	-0.52	87	87
SHC3	-0.13	0.25	-10000	0	-0.64	133	133
STAT3 (dimer)	0.023	0.045	-10000	0	-0.37	1	1
NT3 (dimer)/TRKA	-0.033	0.18	-10000	0	-0.45	108	108
RIN/GDP	0.018	0.12	0.34	35	-0.32	37	72
GIPC1	0.027	0.023	-10000	0	-0.65	1	1
KRAS	0.027	0.006	-10000	0	-10000	0	0
DNAJA3	-0.037	0.12	-10000	0	-0.45	34	34
RIN/GTP	0.013	0.018	-10000	0	-0.29	3	3
CCND1	0.008	0.077	-10000	0	-0.89	1	1
MAGED1	0.028	0.002	-10000	0	-10000	0	0
PTPN11	0.027	0.006	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.011	0.074	-10000	0	-0.42	25	25
SHC/GRB2/SOS1	0.05	0.022	-10000	0	-10000	0	0
GRB2	0.025	0.009	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.033	0.17	-10000	0	-0.44	80	80
TRKA/NEDD4-2	-0.005	0.14	-10000	0	-0.49	67	67
ELMO1	0.023	0.031	-10000	0	-0.42	4	4
RhoG/GTP/ELMO1/DOCK1	0.03	0.028	-10000	0	-0.28	5	5
NGF	-0.011	0.13	-10000	0	-0.46	67	67
HRAS	0.027	0.015	-10000	0	-0.42	1	1
DOCK1	0.026	0.024	-10000	0	-0.65	1	1
GAB2	0.027	0.015	-10000	0	-0.42	1	1
RIT2	-0.01	0.03	-10000	0	-0.42	3	3
RIT1	0.027	0.007	-10000	0	-10000	0	0
FRS2	0.027	0.006	-10000	0	-10000	0	0
DNM1	-0.039	0.16	-10000	0	-0.42	129	129
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.009	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.026	0.12	-10000	0	-0.43	34	34
mol:GDP	0.013	0.17	0.41	41	-0.49	44	85
NGF (dimer)	-0.011	0.13	-10000	0	-0.46	67	67
RhoG/GDP	0.017	0.022	-10000	0	-0.29	4	4
RIT1/GDP	0.025	0.12	0.34	41	-0.31	37	78
TIAM1	0.026	0.024	-10000	0	-0.65	1	1
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.13	0.22	-10000	0	-0.44	258	258
KIDINS220/CRKL/C3G	0.04	0.009	-10000	0	-10000	0	0
SHC/RasGAP	0.038	0.024	-10000	0	-0.39	2	2
FRS2 family/SHP2	0.051	0.019	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.062	0.028	-10000	0	-10000	0	0
RIT1/GTP	0.02	0.005	-10000	0	-10000	0	0
NT3 (dimer)	-0.007	0.15	-10000	0	-0.64	44	44
RAP1/GDP	0.006	0.082	-10000	0	-0.26	36	36
KIDINS220/CRKL	0.027	0.005	-10000	0	-10000	0	0
BDNF (dimer)	-0.039	0.16	-10000	0	-0.42	130	130
ubiquitin-dependent protein catabolic process	-0.011	0.15	-10000	0	-0.44	74	74
Schwann cell development	-0.028	0.032	-10000	0	-10000	0	0
EHD4	0.028	0.004	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.061	0.027	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.036	0.035	-10000	0	-10000	0	0
RAP1B	0.027	0.006	-10000	0	-10000	0	0
RAP1A	0.027	0.007	-10000	0	-10000	0	0
CDC42/GTP	-0.13	0.23	-10000	0	-0.62	88	88
ABL1	0.028	0.004	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.037	0.014	-10000	0	-10000	0	0
Rap1/GTP	-0.039	0.13	-10000	0	-0.46	41	41
STAT3	0.023	0.045	-10000	0	-0.37	1	1
axon guidance	-0.13	0.21	-10000	0	-0.59	88	88
MAPK3	-0.046	0.14	-10000	0	-0.4	74	74
MAPK1	-0.047	0.14	-10000	0	-0.4	80	80
CDC42/GDP	0.027	0.12	0.34	44	-0.31	37	81
NTF3	-0.007	0.15	-10000	0	-0.64	44	44
NTF4	-0.011	0.074	-10000	0	-0.42	25	25
NGF (dimer)/TRKA/FAIM	-0.01	0.15	-10000	0	-0.44	69	69
PI3K	0.039	0.011	-10000	0	-10000	0	0
FRS3	0.026	0.007	-10000	0	-10000	0	0
FAIM	0.027	0.006	-10000	0	-10000	0	0
GAB1	0.028	0.004	-10000	0	-10000	0	0
RASGRF1	-0.043	0.12	-10000	0	-0.45	42	42
SOS1	0.027	0.006	-10000	0	-10000	0	0
MCF2L	-0.036	0.16	-10000	0	-0.44	105	105
RGS19	0.025	0.027	-10000	0	-0.42	3	3
CDC42	0.027	0.007	-10000	0	-10000	0	0
RAS family/GTP	0.019	0.14	0.31	3	-0.56	36	39
Rac1/GDP	0.012	0.1	0.26	14	-0.32	37	51
NGF (dimer)/TRKA/GRIT	-0.024	0.14	-10000	0	-0.35	129	129
neuron projection morphogenesis	-0.042	0.23	0.4	1	-1	39	40
NGF (dimer)/TRKA/NEDD4-2	-0.011	0.15	-10000	0	-0.44	74	74
MAP2K1	0.039	0.058	0.38	11	-10000	0	11
NGFR	-0.015	0.14	-10000	0	-0.47	73	73
NGF (dimer)/TRKA/GIPC/GAIP	-0.023	0.12	-10000	0	-0.43	33	33
RAS family/GTP/PI3K	0.028	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.07	0.032	-10000	0	-10000	0	0
NRAS	0.027	0.007	-10000	0	-10000	0	0
GRB2/SOS1	0.037	0.014	-10000	0	-10000	0	0
PRKCI	0.027	0.006	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
PRKCZ	0.024	0.04	-10000	0	-0.65	3	3
MAPKKK cascade	-0.086	0.26	-10000	0	-0.69	125	125
RASA1	0.027	0.023	-10000	0	-0.65	1	1
TRKA/c-Abl	-0.004	0.14	-10000	0	-0.48	66	66
SQSTM1	0.024	0.034	-10000	0	-0.42	5	5
BDNF (dimer)/TRKB/GIPC	-0.11	0.21	-10000	0	-0.4	259	259
NGF (dimer)/TRKA/p62/Atypical PKCs	0.012	0.14	-10000	0	-0.38	69	69
MATK	-0.008	0.12	-10000	0	-0.42	71	71
NEDD4L	0.026	0.033	-10000	0	-0.65	2	2
RAS family/GDP	-0.023	0.058	-10000	0	-0.26	11	11
NGF (dimer)/TRKA	-0.036	0.13	-10000	0	-0.36	90	90
Rac1/GTP	-0.03	0.087	-10000	0	-0.32	26	26
FRS2 family/SHP2/CRK family	0.07	0.033	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.027	0.03	-10000	0	-0.42	4	4
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.028	0.12	0.43	10	-0.37	1	11
IL27/IL27R/JAK1	0.018	0.23	0.71	4	-0.55	37	41
TBX21	-0.071	0.24	0.6	9	-0.55	74	83
IL12B	-0.026	0.13	-10000	0	-0.42	90	90
IL12A	0.006	0.006	-10000	0	-10000	0	0
IL6ST	-0.032	0.19	-10000	0	-0.66	71	71
IL27RA/JAK1	0.019	0.05	-10000	0	-10000	0	0
IL27	-0.008	0.11	-10000	0	-0.43	51	51
TYK2	0.017	0.021	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.016	0.12	-10000	0	-0.49	9	9
T-helper 2 cell differentiation	0.028	0.12	0.43	10	-0.37	1	11
T cell proliferation during immune response	0.028	0.12	0.43	10	-0.37	1	11
MAPKKK cascade	-0.028	0.12	0.37	1	-0.43	10	11
STAT3	0.025	0.009	-10000	0	-10000	0	0
STAT2	0.027	0.006	-10000	0	-10000	0	0
STAT1	0.028	0.023	-10000	0	-0.42	2	2
IL12RB1	-0.074	0.19	-10000	0	-0.42	200	200
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.079	0.24	0.56	13	-0.53	72	85
IL27/IL27R/JAK2/TYK2	-0.028	0.12	0.37	1	-0.44	9	10
positive regulation of T cell mediated cytotoxicity	-0.028	0.12	0.37	1	-0.43	10	11
STAT1 (dimer)	0.087	0.36	0.52	209	-0.65	35	244
JAK2	0.021	0.017	-10000	0	-10000	0	0
JAK1	0.028	0.01	-10000	0	-10000	0	0
STAT2 (dimer)	-0.012	0.12	0.4	1	-0.43	7	8
T cell proliferation	-0.061	0.14	0.54	1	-0.51	24	25
IL12/IL12R/TYK2/JAK2	-0.024	0.12	-10000	0	-0.71	8	8
IL17A	-0.017	0.11	-10000	0	-0.49	9	9
mast cell activation	0.028	0.12	0.43	10	-0.37	1	11
IFNG	-0.009	0.039	0.13	4	-0.095	1	5
T cell differentiation	-0.004	0.008	0.016	2	-0.022	31	33
STAT3 (dimer)	-0.014	0.12	0.37	2	-0.44	6	8
STAT5A (dimer)	-0.014	0.12	0.37	2	-0.47	4	6
STAT4 (dimer)	-0.024	0.14	0.38	3	-0.46	19	22
STAT4	0.003	0.1	-10000	0	-0.42	47	47
T cell activation	-0.008	0.005	0.048	1	-10000	0	1
IL27R/JAK2/TYK2	-0.005	0.13	-10000	0	-0.47	1	1
GATA3	-0.7	0.69	0.6	4	-1.4	458	462
IL18	-0.004	0.067	0.2	5	-0.3	40	45
positive regulation of mast cell cytokine production	-0.014	0.12	0.37	2	-0.43	6	8
IL27/EBI3	-0.025	0.15	-10000	0	-0.36	131	131
IL27RA	0.003	0.036	-10000	0	-10000	0	0
IL6	-0.053	0.2	-10000	0	-0.55	117	117
STAT5A	0.025	0.009	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	-0.014	0.037	-10000	0	-10000	0	0
IL1B	0.001	0.057	-10000	0	-0.38	18	18
EBI3	-0.031	0.15	-10000	0	-0.43	110	110
TNF	-0.001	0.058	-10000	0	-0.33	25	25

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.028	0.003	-10000	0	-10000	0	0
GNAT1/GTP	0.011	0.033	-10000	0	-0.29	10	10
Metarhodopsin II/Arrestin	0.021	0.038	-10000	0	-0.25	16	16
PDE6G/GNAT1/GTP	0.017	0.063	-10000	0	-0.34	23	23
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	-0.007	0.049	-10000	0	-0.42	10	10
GRK1	-0.009	0.032	-10000	0	-0.46	3	3
CNG Channel	-0.063	0.17	-10000	0	-0.37	172	172
mol:Na +	-0.061	0.17	-10000	0	-0.38	157	157
mol:ADP	-0.009	0.032	-10000	0	-0.46	3	3
RGS9-1/Gbeta5/R9AP	0.025	0.1	-10000	0	-0.36	48	48
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.056	0.18	-10000	0	-0.39	157	157
CNGB1	-0.012	0.098	-10000	0	-0.42	46	46
RDH5	-0.003	0.12	-10000	0	-0.45	55	55
SAG	-0.012	0.02	-10000	0	-0.42	1	1
mol:Ca2+	-0.075	0.17	0.41	21	-0.51	29	50
Na + (4 Units)	-0.06	0.16	-10000	0	-0.47	35	35
RGS9	0.001	0.11	-10000	0	-0.49	41	41
GNB1/GNGT1	-0.05	0.14	-10000	0	-0.29	221	221
GNAT1/GDP	0.027	0.094	-10000	0	-0.37	32	32
GUCY2D	-0.011	0.11	-10000	0	-0.42	54	54
GNGT1	-0.096	0.19	-10000	0	-0.42	221	221
GUCY2F	-0.013	0.014	-10000	0	-10000	0	0
GNB5	0.028	0.003	-10000	0	-10000	0	0
mol:GMP (4 units)	0.005	0.085	-10000	0	-0.42	24	24
mol:11-cis-retinal	-0.003	0.12	-10000	0	-0.45	55	55
mol:cGMP	0.021	0.079	-10000	0	-0.41	3	3
GNB1	0.026	0.007	-10000	0	-10000	0	0
Rhodopsin	0.009	0.093	-10000	0	-0.31	65	65
SLC24A1	0.028	0.003	-10000	0	-10000	0	0
CNGA1	-0.12	0.28	-10000	0	-0.64	199	199
Metarhodopsin II	0.02	0.04	-10000	0	-0.24	18	18
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.028	0.084	-10000	0	-0.36	6	6
RGS9BP	0.014	0.093	-10000	0	-0.63	18	18
Metarhodopsin II/Transducin	-0.022	0.077	-10000	0	-0.25	38	38
GCAP Family/Ca ++	0.033	0.048	-10000	0	-0.36	2	2
PDE6A/B	0.022	0.079	-10000	0	-0.34	37	37
mol:Pi	0.025	0.1	-10000	0	-0.36	48	48
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	-0.032	0.12	-10000	0	-0.24	115	115
PDE6B	0.02	0.071	-10000	0	-0.6	11	11
PDE6A	0.006	0.076	-10000	0	-0.42	26	26
PDE6G	0.014	0.084	-10000	0	-0.58	16	16
RHO	0	0.061	-10000	0	-0.42	16	16
PDE6	0.03	0.13	-10000	0	-0.43	45	45
GUCA1A	-0.009	0.064	-10000	0	-0.42	18	18
GC2/GCAP Family	0.043	0.052	-10000	0	-0.37	2	2
GUCA1C	-0.004	0.029	-10000	0	-0.42	2	2
GUCA1B	0.024	0.034	-10000	0	-0.42	5	5

×

IL23-mediated signaling events

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
CCL2	-0.14	0.36	-10000	0	-1.2	36	36
IL23A	-0.14	0.34	-10000	0	-1.2	29	29
NF kappa B1 p50/RelA/I kappa B alpha	-0.12	0.34	-10000	0	-1	46	46
positive regulation of T cell mediated cytotoxicity	-0.15	0.36	-10000	0	-1.1	56	56
ITGA3	-0.13	0.33	-10000	0	-1.1	29	29
IL17F	-0.085	0.25	0.51	10	-0.72	24	34
IL12B	-0.038	0.14	-10000	0	-0.43	90	90
STAT1 (dimer)	-0.15	0.35	-10000	0	-1	52	52
CD4	-0.13	0.33	-10000	0	-1	34	34
IL23	-0.14	0.34	-10000	0	-1.1	33	33
IL23R	-0.042	0.2	-10000	0	-0.91	31	31
IL1B	-0.15	0.35	-10000	0	-1.3	29	29
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.14	0.33	-10000	0	-1.1	28	28
TYK2	0.011	0.033	-10000	0	-10000	0	0
STAT4	0.003	0.1	-10000	0	-0.42	47	47
STAT3	0.025	0.009	-10000	0	-10000	0	0
IL18RAP	-0.06	0.18	-10000	0	-0.42	164	164
IL12RB1	-0.085	0.19	-10000	0	-0.44	200	200
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.051	0.15	-10000	0	-0.32	187	187
IL23R/JAK2	-0.036	0.19	-10000	0	-0.84	28	28
positive regulation of chronic inflammatory response	-0.15	0.36	-10000	0	-1.1	56	56
natural killer cell activation	0.002	0.009	0.039	11	-0.037	1	12
JAK2	0.01	0.042	-10000	0	-10000	0	0
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
RELA	0.028	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.14	0.32	-10000	0	-1	33	33
ALOX12B	-0.14	0.33	-10000	0	-1.1	27	27
CXCL1	-0.19	0.4	-10000	0	-1.2	70	70
T cell proliferation	-0.15	0.36	-10000	0	-1.1	56	56
NFKBIA	0.027	0.006	-10000	0	-10000	0	0
IL17A	-0.059	0.21	0.4	9	-0.57	17	26
PI3K	-0.13	0.34	-10000	0	-1	42	42
IFNG	-0.02	0.043	0.11	2	-0.12	6	8
STAT3 (dimer)	-0.12	0.32	-10000	0	-1	35	35
IL18R1	0.018	0.059	-10000	0	-0.48	11	11
IL23/IL23R/JAK2/TYK2/SOCS3	-0.089	0.25	-10000	0	-0.88	20	20
IL18/IL18R	-0.036	0.14	-10000	0	-0.29	104	104
macrophage activation	-0.01	0.017	-10000	0	-0.045	18	18
TNF	-0.15	0.35	-10000	0	-1.2	30	30
STAT3/STAT4	-0.14	0.34	-10000	0	-1.1	41	41
STAT4 (dimer)	-0.16	0.36	-10000	0	-1	54	54
IL18	0.004	0.094	-10000	0	-0.42	40	40
IL19	-0.14	0.33	-10000	0	-1.1	29	29
STAT5A (dimer)	-0.15	0.34	-10000	0	-1.1	43	43
STAT1	0.026	0.022	-10000	0	-0.42	2	2
SOCS3	0.02	0.052	-10000	0	-0.44	10	10
CXCL9	-0.18	0.35	-10000	0	-1.1	35	35
MPO	-0.13	0.33	-10000	0	-1.1	24	24
positive regulation of humoral immune response	-0.15	0.36	-10000	0	-1.1	56	56
IL23/IL23R/JAK2/TYK2	-0.16	0.37	-10000	0	-1.1	55	55
IL6	-0.19	0.46	-10000	0	-1.2	103	103
STAT5A	0.025	0.009	-10000	0	-10000	0	0
IL2	-0.003	0.062	-10000	0	-0.42	16	16
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.009	0.039	11	-0.037	1	12
CD3E	-0.18	0.36	-10000	0	-1.1	34	34
keratinocyte proliferation	-0.15	0.36	-10000	0	-1.1	56	56
NOS2	-0.15	0.37	-10000	0	-1.2	46	46

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.043	0.082	-10000	0	-1.1	2	2
SMARCC2	0.028	0.009	-10000	0	-10000	0	0
SMARCC1	0.027	0.011	-10000	0	-10000	0	0
TBX21	-0.1	0.16	0.5	1	-0.44	73	74
SUMO2	0.021	0.014	-10000	0	-10000	0	0
STAT1 (dimer)	0.033	0.026	-10000	0	-0.48	2	2
FKBP4	0.027	0.006	-10000	0	-10000	0	0
FKBP5	0.012	0.087	-10000	0	-0.49	24	24
GR alpha/HSP90/FKBP51/HSP90	0.072	0.098	0.32	9	-0.34	14	23
PRL	-0.025	0.079	-10000	0	-0.57	1	1
cortisol/GR alpha (dimer)/TIF2	0.12	0.21	0.51	50	-0.43	8	58
RELA	-0.034	0.11	-10000	0	-0.31	29	29
FGG	0.028	0.22	0.51	17	-0.43	26	43
GR beta/TIF2	0.047	0.14	0.32	11	-0.43	40	51
IFNG	-0.18	0.2	-10000	0	-0.74	17	17
apoptosis	-0.071	0.22	0.62	3	-0.58	81	84
CREB1	0.01	0.08	-10000	0	-0.36	36	36
histone acetylation	-0.012	0.088	0.26	1	-0.4	8	9
BGLAP	-0.026	0.086	-10000	0	-0.53	2	2
GR/PKAc	0.088	0.079	0.35	4	-10000	0	4
NF kappa B1 p50/RelA	-0.062	0.2	-10000	0	-0.51	82	82
SMARCD1	0.028	0.01	-10000	0	-10000	0	0
MDM2	0.043	0.065	0.28	14	-10000	0	14
GATA3	-0.32	0.34	-10000	0	-0.64	458	458
AKT1	0.021	0.008	-10000	0	-10000	0	0
CSF2	-0.028	0.074	-10000	0	-0.48	2	2
GSK3B	0.022	0.013	-10000	0	-10000	0	0
NR1I3	-0.046	0.22	0.57	4	-0.72	32	36
CSN2	0.061	0.13	0.41	18	-10000	0	18
BRG1/BAF155/BAF170/BAF60A	0.069	0.032	-10000	0	-10000	0	0
NFATC1	0.029	0.006	-10000	0	-10000	0	0
POU2F1	0.028	0.008	-10000	0	-10000	0	0
CDKN1A	0.022	0.061	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.007	-10000	0	-10000	0	0
SFN	-0.072	0.2	-10000	0	-0.44	185	185
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.024	0.15	0.35	1	-0.35	27	28
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.063	0.27	0.55	4	-0.79	61	65
JUN	-0.14	0.18	0.31	1	-0.51	102	103
IL4	-0.038	0.083	-10000	0	-10000	0	0
CDK5R1	0.021	0.037	-10000	0	-0.45	5	5
PRKACA	0.028	0.003	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.13	0.19	0.22	46	-0.44	135	181
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.084	0.097	0.35	5	-0.33	9	14
cortisol/GR alpha (monomer)	0.15	0.22	0.57	69	-10000	0	69
NCOA2	-0.004	0.14	-10000	0	-0.65	40	40
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.063	0.16	-10000	0	-0.64	57	57
AP-1/NFAT1-c-4	-0.21	0.24	-10000	0	-0.66	102	102
AFP	-0.28	0.5	-10000	0	-1.4	137	137
SUV420H1	0.028	0.004	-10000	0	-10000	0	0
IRF1	0.081	0.1	0.45	6	-10000	0	6
TP53	0.042	0.018	-10000	0	-10000	0	0
PPP5C	0.028	0.003	-10000	0	-10000	0	0
KRT17	-0.2	0.35	-10000	0	-1.1	87	87
KRT14	-0.078	0.13	-10000	0	-0.53	5	5
TBP	0.034	0.011	-10000	0	-10000	0	0
CREBBP	0.042	0.045	-10000	0	-10000	0	0
HDAC1	0.025	0.007	-10000	0	-10000	0	0
HDAC2	0.026	0.008	-10000	0	-10000	0	0
AP-1	-0.21	0.24	-10000	0	-0.66	103	103
MAPK14	0.023	0.012	-10000	0	-10000	0	0
MAPK10	0.013	0.086	-10000	0	-0.66	14	14
MAPK11	0.022	0.02	-10000	0	-0.43	1	1
KRT5	-0.16	0.2	-10000	0	-0.71	17	17
interleukin-1 receptor activity	0	0.004	-10000	0	-10000	0	0
NCOA1	0.029	0.008	-10000	0	-10000	0	0
STAT1	0.033	0.026	-10000	0	-0.48	2	2
CGA	-0.095	0.26	-10000	0	-1.1	50	50
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.05	0.092	0.38	10	-0.46	2	12
MAPK3	0.023	0.011	-10000	0	-10000	0	0
MAPK1	0.024	0.011	-10000	0	-10000	0	0
ICAM1	-0.093	0.19	-10000	0	-0.58	50	50
NFKB1	-0.034	0.11	-10000	0	-0.34	18	18
MAPK8	-0.11	0.14	-10000	0	-0.41	62	62
MAPK9	0.023	0.011	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.075	0.23	0.63	3	-0.6	85	88
BAX	0.028	0.042	-10000	0	-10000	0	0
POMC	-0.097	0.22	0.56	1	-1.1	18	19
EP300	0.042	0.049	-10000	0	-0.43	2	2
cortisol/GR alpha (dimer)/p53	0.14	0.19	0.52	51	-10000	0	51
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.063	0.35	14	-10000	0	14
SGK1	0.058	0.13	0.59	2	-1.4	4	6
IL13	-0.32	0.27	-10000	0	-0.68	230	230
IL6	-0.17	0.38	-10000	0	-1.2	101	101
PRKACG	-0.007	0.024	-10000	0	-0.42	1	1
IL5	-0.26	0.22	-10000	0	-0.6	140	140
IL2	-0.13	0.17	-10000	0	-0.72	14	14
CDK5	0.023	0.01	-10000	0	-10000	0	0
PRKACB	0.027	0.007	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
IL8	-0.12	0.26	-10000	0	-0.71	89	89
CDK5R1/CDK5	0.03	0.027	-10000	0	-0.32	3	3
NF kappa B1 p50/RelA/PKAc	-0.017	0.17	-10000	0	-0.47	31	31
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.14	0.18	0.5	48	-10000	0	48
SMARCA4	0.029	0.008	-10000	0	-10000	0	0
chromatin remodeling	0.084	0.11	0.37	22	-0.4	2	24
NF kappa B1 p50/RelA/Cbp	0.001	0.18	-10000	0	-0.53	23	23
JUN (dimer)	-0.14	0.18	0.31	1	-0.51	101	102
YWHAH	0.027	0.005	-10000	0	-10000	0	0
VIPR1	-0.059	0.17	-10000	0	-0.85	27	27
NR3C1	0.08	0.13	0.39	34	-0.43	1	35
NR4A1	-0.065	0.24	-10000	0	-0.65	126	126
TIF2/SUV420H1	0.016	0.11	-10000	0	-0.49	40	40
MAPKKK cascade	-0.071	0.22	0.62	3	-0.58	81	84
cortisol/GR alpha (dimer)/Src-1	0.14	0.19	0.52	58	-10000	0	58
PBX1	0.018	0.085	-10000	0	-0.65	14	14
POU1F1	0.006	0.023	-10000	0	-10000	0	0
SELE	-0.29	0.51	-10000	0	-1.2	212	212
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.084	0.11	0.38	21	-0.4	2	23
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.14	0.18	0.5	48	-10000	0	48
mol:cortisol	0.059	0.12	0.31	72	-0.25	7	79
MMP1	-0.17	0.37	-10000	0	-1.2	84	84

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.016	0.1	-10000	0	-0.5	1	1
UGCG	0	0.11	-10000	0	-0.68	19	19
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.008	0.16	0.34	14	-0.51	43	57
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.001	0.11	-10000	0	-0.67	19	19
mol:DAG	-0.038	0.2	-10000	0	-0.86	47	47
CaM/Ca2+/Calcineurin A alpha-beta B1	0.005	0.13	0.29	7	-0.46	17	24
FRAP1	-0.002	0.15	0.36	13	-0.46	38	51
FOXO3	-0.002	0.15	0.35	14	-0.46	38	52
AKT1	-0.007	0.15	0.32	8	-0.5	40	48
GAB2	0.028	0.015	-10000	0	-0.42	1	1
SMPD1	0.007	0.078	-10000	0	-0.69	9	9
SGMS1	-0.026	0.18	-10000	0	-0.79	47	47
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	0.013	0.005	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
cell proliferation	-0.011	0.16	0.33	8	-0.61	50	58
EIF3A	0.027	0.007	-10000	0	-10000	0	0
PI3K	0.043	0.012	-10000	0	-10000	0	0
RPS6KB1	-0.034	0.18	-10000	0	-0.9	35	35
mol:sphingomyelin	-0.038	0.2	-10000	0	-0.86	47	47
natural killer cell activation	0	0.001	-10000	0	-10000	0	0
JAK3	-0.053	0.17	-10000	0	-0.42	165	165
PIK3R1	0.03	0.005	-10000	0	-10000	0	0
JAK1	0.029	0.008	-10000	0	-10000	0	0
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
MYC	0.002	0.15	0.48	9	-0.55	14	23
MYB	-0.064	0.14	-10000	0	-0.5	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.023	0.14	-10000	0	-0.48	45	45
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.008	0.18	-10000	0	-0.82	35	35
mol:PI-3-4-5-P3	-0.022	0.14	-10000	0	-0.46	45	45
Rac1/GDP	0.027	0.012	-10000	0	-10000	0	0
T cell proliferation	-0.011	0.13	0.29	4	-0.44	39	43
SHC1	0.027	0.016	-10000	0	-0.42	1	1
RAC1	0.025	0.01	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.005	0.015	-10000	0	-0.03	233	233
PRKCZ	-0.015	0.13	-10000	0	-0.46	39	39
NF kappa B1 p50/RelA	0.016	0.14	0.31	7	-0.48	14	21
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.024	0.1	-10000	0	-0.36	34	34
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
RELA	0.028	0.003	-10000	0	-10000	0	0
IL2RA	-0.044	0.16	-10000	0	-0.42	140	140
IL2RB	-0.14	0.22	-10000	0	-0.42	328	328
TERT	-0.057	0.15	-10000	0	-0.42	122	122
E2F1	-0.036	0.1	-10000	0	-0.46	3	3
SOS1	0.027	0.006	-10000	0	-10000	0	0
RPS6	0.027	0.022	-10000	0	-0.42	2	2
mol:cAMP	0.002	0.007	0.014	232	-10000	0	232
PTPN11	0.028	0.006	-10000	0	-10000	0	0
IL2RG	0.005	0.11	-10000	0	-0.44	47	47
actin cytoskeleton organization	-0.011	0.13	0.29	4	-0.44	39	43
GRB2	0.026	0.009	-10000	0	-10000	0	0
IL2	0.016	0.059	-10000	0	-0.42	16	16
PIK3CA	0.029	0.007	-10000	0	-10000	0	0
Rac1/GTP	0.048	0.024	-10000	0	-10000	0	0
LCK	0.005	0.1	-10000	0	-0.44	44	44
BCL2	0.006	0.13	0.48	5	-0.54	8	13

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.031	0.14	-9999	-0.46	40	40
FZD6	0.027	0.005	-9999	-10000	0	0
WNT6	0.016	0.067	-9999	-0.44	18	18
WNT4	-0.021	0.17	-9999	-0.62	64	64
FZD3	0.027	0.007	-9999	-10000	0	0
WNT5A	0.01	0.088	-9999	-0.46	29	29
WNT11	-0.047	0.21	-9999	-0.62	101	101

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.005	0.098	-10000	0	-0.52	14	14
Crk/p130 Cas/Paxillin	-0.039	0.094	-10000	0	-0.4	11	11
JUN	-0.009	0.094	-10000	0	-0.41	17	17
HRAS	0.027	0.015	-10000	0	-0.42	1	1
RET51/GFRalpha1/GDNF/GRB10	0.008	0.13	-10000	0	-0.4	63	63
RAP1A	0.027	0.007	-10000	0	-10000	0	0
FRS2	0.027	0.006	-10000	0	-10000	0	0
RAP1A/GDP	0.02	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.008	0.14	-10000	0	-0.41	81	81
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.027	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.009	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	0.006	0.12	-10000	0	-0.39	55	55
RHOA	0.026	0.008	-10000	0	-10000	0	0
RAP1A/GTP	0.011	0.12	-10000	0	-0.36	71	71
GRB7	0.018	0.069	-10000	0	-0.65	9	9
RET51/GFRalpha1/GDNF	0.009	0.14	-10000	0	-0.4	79	79
MAPKKK cascade	-0.001	0.12	-10000	0	-0.36	60	60
BCAR1	0.026	0.024	-10000	0	-0.65	1	1
RET9/GFRalpha1/GDNF/IRS1	0.003	0.13	-10000	0	-0.41	62	62
lamellipodium assembly	-0.01	0.1	-10000	0	-0.31	51	51
RET51/GFRalpha1/GDNF/SHC	0.008	0.14	-10000	0	-0.4	81	81
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	0.008	0.12	-10000	0	-0.39	55	55
RET9/GFRalpha1/GDNF/Shank3	0.008	0.11	-10000	0	-0.39	52	52
MAPK3	-0.015	0.11	0.41	2	-0.35	63	65
DOK1	0.026	0.022	-10000	0	-0.42	2	2
DOK6	-0.031	0.19	-10000	0	-0.63	78	78
PXN	0.027	0.006	-10000	0	-10000	0	0
neurite development	-0.024	0.12	0.33	1	-0.47	18	19
DOK5	0.002	0.13	-10000	0	-0.64	32	32
GFRA1	-0.034	0.18	-10000	0	-0.54	95	95
MAPK8	-0.007	0.099	-10000	0	-0.42	18	18
HRAS/GTP	0.005	0.14	-10000	0	-0.39	74	74
tube development	0.019	0.11	-10000	0	-0.37	45	45
MAPK1	-0.009	0.12	0.39	9	-0.35	47	56
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.002	0.087	-10000	0	-0.29	60	60
Rac1/GDP	0.018	0.007	-10000	0	-10000	0	0
SRC	0.027	0.007	-10000	0	-10000	0	0
PDLIM7	0.025	0.027	-10000	0	-0.42	3	3
RET51/GFRalpha1/GDNF/Dok6	-0.012	0.18	-10000	0	-0.43	127	127
SHC1	0.026	0.016	-10000	0	-0.42	1	1
RET51/GFRalpha1/GDNF/Dok4	0.009	0.14	-10000	0	-0.4	71	71
RET51/GFRalpha1/GDNF/Dok5	-0.005	0.17	-10000	0	-0.44	95	95
PRKCA	0.025	0.009	-10000	0	-10000	0	0
HRAS/GDP	0.02	0.011	-10000	0	-0.29	1	1
CREB1	-0.002	0.1	-10000	0	-0.35	59	59
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.007	0.1	-10000	0	-0.32	70	70
RET51/GFRalpha1/GDNF/Grb7	0.005	0.15	-10000	0	-0.43	73	73
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.002	0.12	-10000	0	-0.59	35	35
DOK4	0.026	0.007	-10000	0	-10000	0	0
JNK cascade	-0.005	0.094	-10000	0	-0.4	17	17
RET9/GFRalpha1/GDNF/FRS2	0.008	0.11	-10000	0	-0.39	51	51
SHANK3	0.027	0.005	-10000	0	-10000	0	0
RASA1	0.027	0.023	-10000	0	-0.65	1	1
NCK1	0.027	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.008	0.1	-10000	0	-0.33	73	73
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.007	0.11	-10000	0	-0.35	29	29
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.011	0.12	-10000	0	-0.32	100	100
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.013	0.12	-10000	0	-0.34	92	92
PI3K	-0.016	0.15	-10000	0	-0.45	62	62
SOS1	0.027	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.02	0.11	-10000	0	-0.37	45	45
GRB10	0.025	0.009	-10000	0	-10000	0	0
activation of MAPKK activity	-0.007	0.095	-10000	0	-0.35	21	21
RET51/GFRalpha1/GDNF/FRS2	0.009	0.14	-10000	0	-0.4	75	75
GAB1	0.028	0.004	-10000	0	-10000	0	0
IRS1	0.019	0.072	-10000	0	-0.65	10	10
IRS2	0.018	0.064	-10000	0	-0.42	18	18
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.013	0.12	-10000	0	-0.34	92	92
RET51/GFRalpha1/GDNF/PKC alpha	0.009	0.14	-10000	0	-0.4	68	68
GRB2	0.025	0.009	-10000	0	-10000	0	0
PRKACA	0.028	0.003	-10000	0	-10000	0	0
GDNF	-0.005	0.035	-10000	0	-0.42	4	4
RAC1	0.025	0.01	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.003	0.15	-10000	0	-0.41	88	88
Rac1/GTP	-0.008	0.12	-10000	0	-0.37	51	51
RET9/GFRalpha1/GDNF	-0.009	0.12	-10000	0	-0.39	71	71
GFRalpha1/GDNF	-0.013	0.14	-10000	0	-0.45	71	71

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.045	0.075	-10000	0	-0.36	22	22
ER alpha/Gai/GDP/Gbeta gamma	-0.025	0.19	-10000	0	-0.58	75	75
AKT1	-0.038	0.25	-10000	0	-0.8	83	83
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.037	0.26	-10000	0	-0.82	83	83
mol:Ca2+	-0.079	0.19	-10000	0	-0.51	103	103
IGF1R	0.028	0.003	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.016	0.092	-10000	0	-0.42	34	34
SHC1	0.026	0.016	-10000	0	-0.42	1	1
apoptosis	0.034	0.24	0.76	83	-10000	0	83
RhoA/GTP	0.015	0.047	-10000	0	-0.33	10	10
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	0.004	0.16	-10000	0	-0.58	39	39
regulation of stress fiber formation	-0.026	0.08	-10000	0	-0.35	24	24
E2/ERA-ERB (dimer)	0.019	0.079	-10000	0	-0.38	29	29
KRAS	0.027	0.006	-10000	0	-10000	0	0
G13/GTP	0.02	0.062	-10000	0	-0.32	23	23
pseudopodium formation	0.026	0.08	0.35	24	-10000	0	24
E2/ER alpha (dimer)/PELP1	0.021	0.068	-10000	0	-0.36	23	23
GRB2	0.025	0.009	-10000	0	-10000	0	0
GNG2	0.027	0.005	-10000	0	-10000	0	0
GNAO1	0.011	0.095	-10000	0	-0.56	23	23
HRAS	0.027	0.015	-10000	0	-0.42	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0	0.21	0.35	20	-0.58	78	98
E2/ER beta (dimer)	0.018	0.031	-10000	0	-0.31	7	7
mol:GDP	0.008	0.079	-10000	0	-0.38	29	29
mol:NADP	0	0.21	0.35	20	-0.58	78	98
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
mol:IP3	-0.083	0.2	-10000	0	-0.53	103	103
IGF-1R heterotetramer	0.028	0.003	-10000	0	-10000	0	0
PLCB1	-0.064	0.2	-10000	0	-0.46	150	150
PLCB2	-0.052	0.17	-10000	0	-0.5	92	92
IGF1	0.008	0.098	-10000	0	-0.48	32	32
mol:L-citrulline	0	0.21	0.35	20	-0.58	78	98
RHOA	0.026	0.008	-10000	0	-10000	0	0
Gai/GDP	-0.015	0.19	-10000	0	-0.61	72	72
JNK cascade	0.018	0.031	-10000	0	-0.31	7	7
BCAR1	0.026	0.024	-10000	0	-0.65	1	1
ESR2	0.023	0.043	-10000	0	-0.44	7	7
GNAQ	0.028	0.004	-10000	0	-10000	0	0
ESR1	0.005	0.11	-10000	0	-0.56	32	32
Gq family/GDP/Gbeta gamma	-0.013	0.13	-10000	0	-0.54	23	23
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.015	0.25	-10000	0	-1.1	44	44
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.005	0.16	-10000	0	-0.57	39	39
GNAZ	0.025	0.04	-10000	0	-0.65	3	3
E2/ER alpha (dimer)	0.004	0.084	-10000	0	-0.41	32	32
STRN	0.018	0.079	-10000	0	-0.65	12	12
GNAL	0.026	0.028	-10000	0	-0.53	2	2
PELP1	0.025	0.009	-10000	0	-10000	0	0
MAPK11	0.016	0.027	-10000	0	-0.26	8	8
GNAI2	0.026	0.008	-10000	0	-10000	0	0
GNAI3	0.027	0.007	-10000	0	-10000	0	0
GNAI1	0.022	0.041	-10000	0	-0.65	3	3
HBEGF	-0.032	0.2	0.4	37	-0.57	64	101
cAMP biosynthetic process	0.016	0.066	-10000	0	-0.34	23	23
SRC	-0.021	0.18	-10000	0	-0.58	64	64
PI3K	0.039	0.011	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.032	0.081	-10000	0	-0.41	13	13
SOS1	0.027	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.044	0.12	-10000	0	-0.48	44	44
Gs family/GTP	0.023	0.069	-10000	0	-0.35	23	23
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.048	0.02	-10000	0	-10000	0	0
vasodilation	0.003	0.2	0.34	21	-0.55	78	99
mol:DAG	-0.083	0.2	-10000	0	-0.53	103	103
Gs family/GDP/Gbeta gamma	0.012	0.073	-10000	0	-0.39	12	12
MSN	0.026	0.083	0.36	24	-10000	0	24
Gq family/GTP	-0.031	0.17	-10000	0	-0.51	94	94
mol:PI-3-4-5-P3	-0.033	0.25	-10000	0	-0.78	83	83
NRAS	0.027	0.007	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.003	0.2	0.55	78	-0.34	21	99
GRB2/SOS1	0.037	0.014	-10000	0	-10000	0	0
RhoA/GDP	0.021	0.085	-10000	0	-0.38	20	20
NOS3	-0.003	0.22	0.36	19	-0.63	77	96
GNA11	0.022	0.065	-10000	0	-0.65	8	8
MAPKKK cascade	0.001	0.23	0.42	23	-0.67	74	97
E2/ER alpha (dimer)/PELP1/Src	0.002	0.17	0.26	1	-0.52	63	64
ruffle organization	0.026	0.08	0.35	24	-10000	0	24
ROCK2	0.031	0.087	0.37	24	-10000	0	24
GNA14	-0.042	0.21	-10000	0	-0.64	92	92
GNA15	0.011	0.088	-10000	0	-0.42	34	34
GNA13	0.025	0.009	-10000	0	-10000	0	0
MMP9	-0.078	0.19	0.38	14	-0.59	64	78
MMP2	-0.009	0.18	0.3	16	-0.58	55	71

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.008	0.11	-10000	0	-0.63	24	24
GNB1/GNG2	-0.012	0.14	-10000	0	-0.47	29	29
mol:DAG	-0.024	0.12	-10000	0	-0.43	28	28
PLCG1	-0.025	0.12	-10000	0	-0.45	28	28
YES1	-0.034	0.13	-10000	0	-0.46	36	36
FZD3	0.027	0.007	-10000	0	-10000	0	0
FZD6	0.027	0.005	-10000	0	-10000	0	0
G protein	-0.008	0.14	0.28	2	-0.45	28	30
MAP3K7	-0.12	0.18	-10000	0	-0.45	106	106
mol:Ca2+	-0.023	0.12	-10000	0	-0.42	28	28
mol:IP3	-0.024	0.12	-10000	0	-0.43	28	28
NLK	-0.029	0.17	-10000	0	-0.85	37	37
GNB1	0.026	0.007	-10000	0	-10000	0	0
CAMK2A	-0.13	0.19	-10000	0	-0.48	111	111
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.031	0.14	-10000	0	-0.46	40	40
CSNK1A1	0.027	0.007	-10000	0	-10000	0	0
GNAS	-0.031	0.13	-10000	0	-0.45	38	38
GO:0007205	-0.03	0.12	-10000	0	-0.42	29	29
WNT6	0.016	0.067	-10000	0	-0.44	18	18
WNT4	-0.021	0.17	-10000	0	-0.62	64	64
NFAT1/CK1 alpha	-0.019	0.14	-10000	0	-0.48	23	23
GNG2	0.027	0.005	-10000	0	-10000	0	0
WNT5A	0.01	0.088	-10000	0	-0.46	29	29
WNT11	-0.047	0.21	-10000	0	-0.62	101	101
CDC42	-0.031	0.12	-10000	0	-0.45	32	32

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.025	0.1	-10000	0	-0.38	49	49
regulation of S phase of mitotic cell cycle	0.011	0.075	-10000	0	-0.3	44	44
GNAO1	0.011	0.095	-10000	0	-0.56	23	23
HRAS	0.027	0.016	-10000	0	-0.42	1	1
SHBG/T-DHT	-0.01	0.1	-10000	0	-0.4	57	57
PELP1	0.025	0.009	-10000	0	-10000	0	0
AKT1	0.01	0.002	-10000	0	-10000	0	0
MAP2K1	0.007	0.095	0.35	7	-0.42	7	14
T-DHT/AR	-0.01	0.12	-10000	0	-0.48	53	53
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-0.01	58	58
GNAI2	0.026	0.008	-10000	0	-10000	0	0
GNAI3	0.027	0.007	-10000	0	-10000	0	0
GNAI1	0.022	0.041	-10000	0	-0.65	3	3
mol:GDP	-0.016	0.12	-10000	0	-0.5	48	48
cell proliferation	0.012	0.15	0.43	29	-0.46	35	64
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
FOS	-0.02	0.23	0.43	17	-0.8	58	75
mol:Ca2+	0	0.019	-10000	0	-0.072	31	31
MAPK3	0.017	0.13	0.4	36	-0.47	12	48
MAPK1	0.009	0.1	0.29	18	-0.43	24	42
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.005	56	56
cAMP biosynthetic process	-0.022	0.1	0.25	11	-0.39	55	66
GNG2	0.027	0.005	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	56	56
HRAS/GTP	0.024	0.094	-10000	0	-0.35	46	46
actin cytoskeleton reorganization	0.035	0.018	-10000	0	-10000	0	0
SRC	0.027	0.007	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	56	56
PI3K	0.036	0.01	-10000	0	-10000	0	0
apoptosis	-0.006	0.15	0.47	46	-0.36	24	70
T-DHT/AR/PELP1	0.008	0.11	-10000	0	-0.41	53	53
HRAS/GDP	-0.001	0.12	-10000	0	-0.47	48	48
CREB1	0.004	0.16	0.4	19	-0.51	46	65
RAC1-CDC42/GTP	0.044	0.023	-10000	0	-10000	0	0
AR	-0.013	0.16	-10000	0	-0.64	53	53
GNB1	0.026	0.007	-10000	0	-10000	0	0
RAF1	0.011	0.099	0.35	9	-0.34	43	52
RAC1-CDC42/GDP	0.015	0.12	-10000	0	-0.46	45	45
T-DHT/AR/PELP1/Src	0.023	0.1	-10000	0	-0.38	46	46
MAP2K2	0.006	0.095	0.35	7	-0.42	7	14
T-DHT/AR/PELP1/Src/PI3K	0.011	0.075	-10000	0	-0.3	44	44
GNAZ	0.025	0.04	-10000	0	-0.65	3	3
SHBG	-0.017	0.16	-10000	0	-0.62	57	57
Gi family/GNB1/GNG2/GDP	-0.002	0.12	-10000	0	-0.48	33	33
mol:T-DHT	0	0.002	0.002	1	-0.007	50	51
RAC1	0.025	0.01	-10000	0	-10000	0	0
GNRH1	-0.055	0.13	0.19	2	-0.3	184	186
Gi family/GTP	-0.001	0.068	-10000	0	-0.28	28	28
CDC42	0.027	0.007	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.009	0.074	-10000	0	-0.24	70	70
EPHB2	0.02	0.058	-10000	0	-0.45	12	12
Syndecan-2/TACI	0.013	0.062	-10000	0	-0.24	49	49
LAMA1	0.006	0.12	-10000	0	-0.57	32	32
Syndecan-2/alpha2 ITGB1	0.032	0.085	-10000	0	-0.36	9	9
HRAS	0.027	0.015	-10000	0	-0.42	1	1
Syndecan-2/CASK	0.012	0.009	-10000	0	-0.24	1	1
ITGA5	0.004	0.098	-10000	0	-0.42	45	45
BAX	0.013	0.035	-10000	0	-10000	0	0
EPB41	0.027	0.007	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.029	0.011	-10000	0	-10000	0	0
LAMA3	-0.011	0.13	-10000	0	-0.42	75	75
EZR	0.026	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.016	0.062	-10000	0	-0.42	17	17
Syndecan-2/MMP2	0.028	0.034	-10000	0	-0.29	8	8
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.033	0.054	-10000	0	-0.49	9	9
dendrite morphogenesis	0.027	0.038	-10000	0	-0.3	9	9
Syndecan-2/GM-CSF	0.021	0.04	-10000	0	-0.24	18	18
determination of left/right symmetry	0.016	0.011	-10000	0	-0.28	1	1
Syndecan-2/PKC delta	0.027	0.031	-10000	0	-0.24	10	10
GNB2L1	0.027	0.007	-10000	0	-10000	0	0
MAPK3	0.015	0.039	-10000	0	-0.29	1	1
MAPK1	0.016	0.04	-10000	0	-0.29	1	1
Syndecan-2/RACK1	0.043	0.019	-10000	0	-10000	0	0
NF1	0.025	0.009	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.016	0.011	-10000	0	-0.28	1	1
ITGA2	0.021	0.069	-10000	0	-0.65	9	9
MAPK8	0.016	0.038	-10000	0	-0.41	6	6
Syndecan-2/alpha2/beta1 Integrin	0.042	0.08	-10000	0	-0.35	27	27
Syndecan-2/Kininogen	-0.27	0.21	-10000	0	-0.42	570	570
ITGB1	0.027	0.007	-10000	0	-10000	0	0
SRC	0.032	0.037	0.34	1	-10000	0	1
Syndecan-2/CASK/Protein 4.1	0.028	0.012	-10000	0	-10000	0	0
extracellular matrix organization	0.031	0.022	-10000	0	-0.24	5	5
actin cytoskeleton reorganization	0.009	0.074	-10000	0	-0.24	70	70
Syndecan-2/Caveolin-2/Ras	0.037	0.042	-10000	0	-0.42	1	1
Syndecan-2/Laminin alpha3	0.009	0.077	-10000	0	-0.24	72	72
Syndecan-2/RasGAP	0.054	0.029	-10000	0	-0.53	1	1
alpha5/beta1 Integrin	0.021	0.074	-10000	0	-0.29	45	45
PRKCD	0.021	0.045	-10000	0	-0.42	9	9
Syndecan-2 dimer	0.027	0.038	-10000	0	-0.3	9	9
GO:0007205	0.003	0.002	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.046	0.034	-10000	0	-0.52	1	1
RHOA	0.026	0.008	-10000	0	-10000	0	0
SDCBP	0.027	0.005	-10000	0	-10000	0	0
TNFRSF13B	-0.007	0.1	-10000	0	-0.42	48	48
RASA1	0.027	0.023	-10000	0	-0.65	1	1
alpha2/beta1 Integrin	0.033	0.054	-10000	0	-0.49	9	9
Syndecan-2/Synbindin	0.032	0.012	-10000	0	-0.24	1	1
TGFB1	0.026	0.03	-10000	0	-0.42	4	4
CASP3	0.022	0.034	-10000	0	-10000	0	0
FN1	-0.01	0.12	-10000	0	-0.42	72	72
Syndecan-2/IL8	0.005	0.092	-10000	0	-0.28	77	77
SDC2	0.016	0.011	-10000	0	-0.28	1	1
KNG1	-0.44	0.3	-10000	0	-0.65	587	587
Syndecan-2/Neurofibromin	0.029	0.015	-10000	0	-10000	0	0
TRAPPC4	0.028	0.004	-10000	0	-10000	0	0
CSF2	-0.006	0.063	-10000	0	-0.42	17	17
Syndecan-2/TGFB1	0.031	0.022	-10000	0	-0.24	5	5
Syndecan-2/Syntenin/PI-4-5-P2	0.029	0.011	-10000	0	-10000	0	0
Syndecan-2/Ezrin	0.042	0.021	-10000	0	-10000	0	0
PRKACA	0.024	0.024	-10000	0	-10000	0	0
angiogenesis	0.005	0.092	-10000	0	-0.28	77	77
MMP2	0.022	0.048	-10000	0	-0.44	9	9
IL8	-0.016	0.14	-10000	0	-0.48	77	77
calcineurin-NFAT signaling pathway	0.013	0.062	-10000	0	-0.24	49	49

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.001	0.093	-10000	0	-0.68	10	10
oxygen homeostasis	0.001	0.014	-10000	0	-10000	0	0
TCEB2	0.024	0.038	-10000	0	-0.46	5	5
TCEB1	0.027	0.005	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.038	0.12	-10000	0	-0.43	3	3
EPO	-0.1	0.24	-10000	0	-0.58	73	73
FIH (dimer)	0.023	0.022	-10000	0	-10000	0	0
APEX1	0.023	0.024	-10000	0	-10000	0	0
SERPINE1	-0.098	0.25	-10000	0	-0.67	59	59
FLT1	-0.018	0.15	-10000	0	-0.66	31	31
ADORA2A	-0.083	0.23	0.46	3	-0.62	38	41
germ cell development	-0.11	0.27	-10000	0	-0.65	60	60
SLC11A2	-0.073	0.23	-10000	0	-0.71	13	13
BHLHE40	-0.073	0.23	-10000	0	-0.62	31	31
HIF1AN	0.023	0.022	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.061	0.18	-10000	0	-0.46	9	9
ETS1	0.03	0.037	-10000	0	-10000	0	0
CITED2	-0.023	0.14	-10000	0	-0.66	23	23
KDR	-0.07	0.31	-10000	0	-1.1	67	67
PGK1	-0.071	0.23	-10000	0	-0.62	34	34
SIRT1	0.026	0.007	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	-0.074	0.27	-10000	0	-0.72	35	35
EPAS1	-0.057	0.12	-10000	0	-0.39	10	10
SP1	0.031	0.015	-10000	0	-10000	0	0
ABCG2	-0.075	0.24	-10000	0	-0.65	38	38
EFNA1	-0.071	0.23	-10000	0	-0.62	33	33
FXN	-0.077	0.23	0.49	8	-0.62	35	43
POU5F1	-0.12	0.28	-10000	0	-0.68	60	60
neuron apoptosis	0.072	0.26	0.69	35	-10000	0	35
EP300	0.027	0.024	-10000	0	-0.65	1	1
EGLN3	-0.22	0.23	-10000	0	-0.43	484	484
EGLN2	0.025	0.021	-10000	0	-10000	0	0
EGLN1	0.023	0.022	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.047	0.033	-10000	0	-0.42	1	1
VHL	0.026	0.008	-10000	0	-10000	0	0
ARNT	0.022	0.024	-10000	0	-10000	0	0
SLC2A1	-0.084	0.24	0.5	7	-0.66	50	57
TWIST1	-0.088	0.22	0.52	3	-0.63	33	36
ELK1	0.035	0.003	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.046	0.16	-10000	0	-0.47	4	4
VEGFA	-0.12	0.28	-10000	0	-0.63	98	98
CREBBP	0.027	0.007	-10000	0	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.016	0.15	0.34	19	-0.51	42	61
IKBKB	0.007	0.1	0.32	33	-0.3	13	46
AKT1	-0.001	0.12	0.36	56	-0.24	3	59
IKBKG	0.017	0.094	0.32	29	-0.3	4	33
CALM1	-0.004	0.087	0.31	6	-0.43	12	18
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
MAP3K1	-0.016	0.16	0.39	19	-0.49	38	57
MAP3K7	0.026	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.007	0.09	0.32	3	-0.42	16	19
DOK1	0.026	0.022	-10000	0	-0.42	2	2
AP-1	-0.005	0.1	0.3	19	-0.28	41	60
LYN	0.026	0.024	-10000	0	-0.65	1	1
BLNK	0.017	0.079	-10000	0	-0.65	12	12
SHC1	0.026	0.016	-10000	0	-0.42	1	1
BCR complex	-0.031	0.14	-10000	0	-0.3	172	172
CD22	-0.057	0.12	-10000	0	-0.45	39	39
CAMK2G	-0.001	0.084	0.32	6	-0.4	11	17
CSNK2A1	0.027	0.006	-10000	0	-10000	0	0
INPP5D	0.022	0.048	-10000	0	-0.42	10	10
SHC/GRB2/SOS1	-0.016	0.097	-10000	0	-0.43	7	7
GO:0007205	-0.008	0.091	0.32	3	-0.42	16	19
SYK	0.024	0.048	-10000	0	-0.59	5	5
ELK1	-0.005	0.088	0.3	3	-0.44	12	15
NFATC1	-0.022	0.11	0.38	10	-0.43	7	17
B-cell antigen/BCR complex	-0.031	0.14	-10000	0	-0.3	172	172
PAG1/CSK	0.039	0.024	-10000	0	-0.29	4	4
NFKBIB	0.022	0.049	0.16	40	-0.13	11	51
HRAS	0.002	0.083	0.32	6	-0.49	3	9
NFKBIA	0.022	0.048	0.16	40	-0.13	8	48
NF-kappa-B/RelA/I kappa B beta	0.025	0.044	0.16	33	-0.18	1	34
RasGAP/Csk	-0.037	0.16	-10000	0	-0.41	68	68
mol:GDP	-0.005	0.09	0.31	3	-0.4	18	21
PTEN	0.027	0.007	-10000	0	-10000	0	0
CD79B	0.022	0.045	-10000	0	-0.5	6	6
NF-kappa-B/RelA/I kappa B alpha	0.026	0.045	0.16	34	-0.18	1	35
GRB2	0.025	0.009	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.016	0.14	0.4	11	-0.46	20	31
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
mol:IP3	-0.006	0.09	0.32	3	-0.43	16	19
CSK	0.028	0.003	-10000	0	-10000	0	0
FOS	-0.023	0.12	0.31	8	-0.48	28	36
CHUK	0.003	0.12	0.31	30	-0.33	43	73
IBTK	0.027	0.007	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.007	0.12	0.29	3	-0.43	4	7
PTPN6	-0.055	0.12	-10000	0	-0.47	27	27
RELA	0.028	0.003	-10000	0	-10000	0	0
BCL2A1	0.007	0.048	0.17	16	-0.13	1	17
VAV2	-0.047	0.12	-10000	0	-0.44	25	25
ubiquitin-dependent protein catabolic process	0.025	0.048	0.16	40	-0.13	9	49
BTK	-0.01	0.092	-10000	0	-0.85	8	8
CD19	-0.058	0.13	-10000	0	-0.42	54	54
MAP4K1	-0.09	0.2	-10000	0	-0.42	234	234
CD72	-0.04	0.16	-10000	0	-0.42	134	134
PAG1	0.025	0.03	-10000	0	-0.42	4	4
MAPK14	-0.009	0.15	0.34	26	-0.41	35	61
SH3BP5	0.012	0.097	-10000	0	-0.64	19	19
PIK3AP1	-0.002	0.097	0.34	3	-0.47	17	20
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.022	0.11	-10000	0	-0.5	22	22
RAF1	0.006	0.084	0.31	12	-0.45	3	15
RasGAP/p62DOK/SHIP	-0.037	0.16	-10000	0	-0.4	74	74
CD79A	-0.06	0.18	-10000	0	-0.42	172	172
re-entry into mitotic cell cycle	-0.005	0.1	0.3	19	-0.28	38	57
RASA1	0.027	0.023	-10000	0	-0.65	1	1
MAPK3	0.022	0.1	0.38	36	-0.4	1	37
MAPK1	0.014	0.087	0.42	13	-0.4	2	15
CD72/SHP1	-0.065	0.16	0.34	2	-0.46	49	51
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
MAPK8	-0.011	0.15	0.37	25	-0.41	37	62
actin cytoskeleton organization	-0.022	0.13	0.35	7	-0.45	9	16
NF-kappa-B/RelA	0.055	0.082	0.29	37	-10000	0	37
Calcineurin	0.02	0.082	0.3	1	-0.42	4	5
PI3K	-0.056	0.12	-10000	0	-0.44	19	19
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.007	0.099	0.28	11	-0.49	18	29
SOS1	0.027	0.006	-10000	0	-10000	0	0
Bam32/HPK1	-0.064	0.18	-10000	0	-0.67	20	20
DAPP1	-0.032	0.16	-10000	0	-0.75	20	20
cytokine secretion	-0.02	0.11	0.36	11	-0.4	7	18
mol:DAG	-0.006	0.09	0.32	3	-0.43	16	19
PLCG2	0.005	0.11	-10000	0	-0.51	35	35
MAP2K1	0.011	0.084	0.34	13	-0.42	3	16
B-cell antigen/BCR complex/FcgammaRIIB	-0.066	0.17	-10000	0	-0.47	69	69
mol:PI-3-4-5-P3	-0.044	0.085	-10000	0	-0.31	17	17
ETS1	0.001	0.085	0.41	8	-0.38	9	17
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.006	0.12	-10000	0	-0.41	16	16
B-cell antigen/BCR complex/LYN	-0.038	0.1	-10000	0	-0.48	9	9
MALT1	0.027	0.005	-10000	0	-10000	0	0
TRAF6	0.028	0.003	-10000	0	-10000	0	0
RAC1	-0.03	0.13	0.32	2	-0.48	9	11
B-cell antigen/BCR complex/LYN/SYK	-0.043	0.14	-10000	0	-0.44	34	34
CARD11	-0.022	0.14	0.36	19	-0.41	15	34
FCGR2B	-0.065	0.18	-10000	0	-0.42	180	180
PPP3CA	0.028	0.004	-10000	0	-10000	0	0
BCL10	0.026	0.007	-10000	0	-10000	0	0
IKK complex	0.016	0.067	0.2	58	-0.13	3	61
PTPRC	-0.007	0.12	-10000	0	-0.42	67	67
PDPK1	-0.024	0.076	0.32	10	-0.23	4	14
PPP3CB	0.027	0.007	-10000	0	-10000	0	0
PPP3CC	0.027	0.007	-10000	0	-10000	0	0
POU2F2	0.016	0.045	0.18	16	-10000	0	16

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.006	0.095	-9999	-0.42	42	42
PLK4	0.025	0.034	-9999	-0.42	5	5
regulation of centriole replication	0.003	0.071	-9999	-0.29	47	47

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.16	0.17	0.53	6	-0.61	26	32
RAD9A	0.027	0.021	-10000	0	-0.42	2	2
AP1	0.005	0.12	-10000	0	-0.46	57	57
IFNAR2	0.026	0.008	-10000	0	-10000	0	0
AKT1	0.007	0.051	-10000	0	-0.24	21	21
ER alpha/Oestrogen	0.003	0.084	-10000	0	-0.41	32	32
NFX1/SIN3/HDAC complex	0.013	0.091	-10000	0	-0.37	32	32
EGF	-0.54	0.25	-10000	0	-0.65	731	731
SMG5	0.027	0.007	-10000	0	-10000	0	0
SMG6	0.025	0.009	-10000	0	-10000	0	0
SP3/HDAC2	0.037	0.015	-10000	0	-10000	0	0
TERT/c-Abl	-0.15	0.16	0.5	5	-0.6	19	24
SAP18	0.027	0.006	-10000	0	-10000	0	0
MRN complex	0.051	0.024	-10000	0	-0.42	1	1
WT1	-0.3	0.34	-10000	0	-0.65	425	425
WRN	0.027	0.007	-10000	0	-10000	0	0
SP1	0.024	0.012	-10000	0	-10000	0	0
SP3	0.027	0.007	-10000	0	-10000	0	0
TERF2IP	0.026	0.007	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.14	0.15	-10000	0	-0.62	8	8
Mad/Max	0.037	0.017	-10000	0	-0.29	1	1
TERT	-0.17	0.18	0.54	6	-0.65	20	26
CCND1	-0.16	0.18	0.69	6	-0.75	9	15
MAX	0.027	0.006	-10000	0	-10000	0	0
RBBP7	0.028	0.002	-10000	0	-10000	0	0
RBBP4	0.026	0.024	-10000	0	-0.65	1	1
TERF2	0.023	0.008	-10000	0	-10000	0	0
PTGES3	0.027	0.006	-10000	0	-10000	0	0
SIN3A	0.028	0.003	-10000	0	-10000	0	0
Telomerase/911	0.019	0.039	-10000	0	-10000	0	0
CDKN1B	-0.046	0.12	-10000	0	-0.45	2	2
RAD1	0.027	0.005	-10000	0	-10000	0	0
XRCC5	0.027	0.006	-10000	0	-10000	0	0
XRCC6	0.027	0.005	-10000	0	-10000	0	0
SAP30	-0.004	0.11	-10000	0	-0.42	62	62
TRF2/PARP2	0.037	0.012	-10000	0	-10000	0	0
UBE3A	0.028	0.004	-10000	0	-10000	0	0
JUN	0.026	0.007	-10000	0	-10000	0	0
E6	0	0.002	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.019	0.007	-10000	0	-10000	0	0
FOS	-0.015	0.16	-10000	0	-0.62	57	57
IFN-gamma/IRF1	-0.049	0.15	-10000	0	-0.53	2	2
PARP2	0.027	0.005	-10000	0	-10000	0	0
BLM	0.012	0.082	-10000	0	-0.42	31	31
Telomerase	-0.007	0.085	0.29	1	-0.74	5	6
IRF1	0.029	0.022	-10000	0	-0.41	2	2
ESR1	0.005	0.11	-10000	0	-0.56	32	32
KU/TER	0.039	0.012	-10000	0	-10000	0	0
ATM/TRF2	0.039	0.02	-10000	0	-0.44	1	1
ubiquitin-dependent protein catabolic process	0.03	0.061	-10000	0	-0.4	6	6
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.03	0.062	-10000	0	-0.41	6	6
HDAC1	0.026	0.007	-10000	0	-10000	0	0
HDAC2	0.024	0.012	-10000	0	-10000	0	0
ATM	0.01	0.017	-10000	0	-0.47	1	1
SMAD3	0.019	0.022	0.22	1	-0.29	4	5
ABL1	0.028	0.004	-10000	0	-10000	0	0
MXD1	0.026	0.016	-10000	0	-0.42	1	1
MRE11A	0.028	0.004	-10000	0	-10000	0	0
HUS1	0.025	0.009	-10000	0	-10000	0	0
RPS6KB1	0.025	0.009	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.12	0.16	-10000	0	-0.65	10	10
NR2F2	0.028	0.024	-10000	0	-0.65	1	1
MAPK3	0.005	0.042	-10000	0	-0.29	16	16
MAPK1	0.006	0.042	-10000	0	-0.29	16	16
TGFB1/TGF beta receptor Type II	0.026	0.03	-10000	0	-0.41	4	4
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
HNRNPC	0.027	0.005	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.01	0.017	-10000	0	-0.47	1	1
NBN	0.027	0.005	-10000	0	-10000	0	0
EGFR	0.017	0.061	-10000	0	-0.45	14	14
mol:Oestrogen	0	0.001	-10000	0	-10000	0	0
EGF/EGFR	-0.38	0.2	-10000	0	-0.46	728	728
MYC	0.014	0.076	-10000	0	-0.43	25	25
IL2	0.009	0.061	-10000	0	-0.42	16	16
KU	0.039	0.012	-10000	0	-10000	0	0
RAD50	0.026	0.024	-10000	0	-0.65	1	1
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
TGFB1	0.026	0.03	-10000	0	-0.42	4	4
TRF2/BLM	0.027	0.058	-10000	0	-0.27	29	29
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	-0.15	0.16	-10000	0	-0.61	17	17
SP1/HDAC2	0.033	0.022	-10000	0	-10000	0	0
PINX1	0.027	0.007	-10000	0	-10000	0	0
Telomerase/EST1A	-0.13	0.15	-10000	0	-0.62	8	8
Smad3/Myc	0.026	0.053	-10000	0	-0.44	2	2
911 complex	0.048	0.025	-10000	0	-10000	0	0
IFNG	-0.1	0.2	-10000	0	-0.41	257	257
Telomerase/PinX1	-0.14	0.15	-10000	0	-0.62	8	8
Telomerase/AKT1/mTOR/p70S6K	-0.015	0.075	-10000	0	-0.54	5	5
SIN3B	0.028	0.003	-10000	0	-10000	0	0
YWHAE	0.025	0.009	-10000	0	-10000	0	0
Telomerase/EST1B	-0.14	0.15	-10000	0	-0.6	8	8
response to DNA damage stimulus	0.004	0.015	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.069	0.033	-10000	0	-0.36	1	1
TRF2/WRN	0.036	0.014	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	-0.14	0.15	-10000	0	-0.6	10	10
E2F1	-0.057	0.17	-10000	0	-0.42	163	163
ZNFX1	0.027	0.007	-10000	0	-10000	0	0
PIF1	-0.026	0.15	-10000	0	-0.42	107	107
NCL	0.027	0.006	-10000	0	-10000	0	0
DKC1	0.028	0.002	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.029	0.071	-10000	0	-0.67	6	6
VEGFR1 homodimer/NRP1	0.01	0.068	-10000	0	-0.67	6	6
mol:DAG	-0.064	0.13	-10000	0	-0.52	15	15
VEGFR1 homodimer/NRP1/VEGFR 121	-0.052	0.13	-10000	0	-0.52	17	17
CaM/Ca2+	-0.049	0.13	-10000	0	-0.5	15	15
HIF1A	0.028	0.049	-10000	0	-0.46	6	6
GAB1	0.028	0.004	-10000	0	-10000	0	0
AKT1	-0.038	0.11	-10000	0	-0.6	6	6
PLCG1	-0.064	0.13	-10000	0	-0.53	15	15
NOS3	-0.034	0.1	0.46	1	-0.62	6	7
CBL	0.027	0.023	-10000	0	-0.65	1	1
mol:NO	-0.022	0.11	0.44	2	-0.59	6	8
FLT1	0.014	0.078	-10000	0	-0.49	17	17
PGF	-0.12	0.21	-10000	0	-0.42	298	298
VEGFR1 homodimer/NRP2/VEGFR121	-0.046	0.14	-10000	0	-0.49	23	23
CALM1	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
eNOS/Hsp90	-0.003	0.13	0.46	7	-0.57	6	13
endothelial cell proliferation	-0.039	0.11	0.36	1	-0.56	6	7
mol:Ca2+	-0.063	0.13	-10000	0	-0.52	15	15
MAPK3	-0.06	0.11	0.36	2	-0.45	12	14
MAPK1	-0.06	0.11	0.36	2	-0.45	13	15
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
PLGF homodimer	-0.12	0.21	-10000	0	-0.42	298	298
PRKACA	0.028	0.003	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.002	0.097	-10000	0	-0.42	44	44
VEGFA homodimer	-0.11	0.2	-10000	0	-0.42	269	269
VEGFR1 homodimer/VEGFA homodimer	-0.057	0.14	-10000	0	-0.54	19	19
platelet activating factor biosynthetic process	-0.058	0.1	0.35	2	-0.44	12	14
PI3K	-0.034	0.14	-10000	0	-0.52	15	15
PRKCA	-0.062	0.11	-10000	0	-0.46	15	15
PRKCB	-0.066	0.12	-10000	0	-0.46	20	20
VEGFR1 homodimer/PLGF homodimer	-0.066	0.15	-10000	0	-0.6	15	15
VEGFA	-0.11	0.2	-10000	0	-0.42	269	269
VEGFB	0.028	0.003	-10000	0	-10000	0	0
mol:IP3	-0.064	0.13	-10000	0	-0.52	15	15
RASA1	0.017	0.069	-10000	0	-0.68	6	6
NRP2	0.016	0.069	-10000	0	-0.43	20	20
VEGFR1 homodimer	0.014	0.077	-10000	0	-0.49	17	17
VEGFB homodimer	0.028	0.003	-10000	0	-10000	0	0
NCK1	0.027	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.031	0.12	0.43	2	-0.52	7	9
PTPN11	0.027	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.035	0.14	-10000	0	-0.52	15	15
mol:L-citrulline	-0.022	0.11	0.44	2	-0.59	6	8
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.027	0.14	-10000	0	-0.52	16	16
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.041	0.14	-10000	0	-0.52	17	17
CD2AP	0.026	0.007	-10000	0	-10000	0	0
PI3K/GAB1	-0.025	0.14	-10000	0	-0.5	15	15
PDPK1	-0.048	0.12	0.34	2	-0.5	14	16
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.041	0.14	-10000	0	-0.51	17	17
mol:NADP	-0.022	0.11	0.44	2	-0.59	6	8
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.028	0.14	-10000	0	-0.52	16	16
VEGFR1 homodimer/NRP2	0.022	0.081	-10000	0	-0.63	7	7

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.016	0.083	0.28	1	-0.45	16	17
BAG4	0.025	0.033	-10000	0	-0.65	2	2
BAD	0.02	0.061	0.26	28	-0.26	2	30
NFKBIA	0.027	0.005	-10000	0	-10000	0	0
BIRC3	-0.023	0.14	-10000	0	-0.42	100	100
BAX	0.021	0.059	0.27	24	-0.2	1	25
EnzymeConsortium:3.1.4.12	0.012	0.036	0.13	42	-0.1	13	55
IKBKB	0.022	0.089	0.29	8	-0.46	10	18
MAP2K2	0.032	0.09	0.31	59	-0.3	1	60
MAP2K1	0.033	0.089	0.31	59	-10000	0	59
SMPD1	0.016	0.042	0.17	27	-0.18	5	32
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.019	0.099	0.32	1	-0.49	13	14
MAP2K4	0.035	0.08	0.28	69	-10000	0	69
protein ubiquitination	0.029	0.11	0.38	21	-0.44	15	36
EnzymeConsortium:2.7.1.37	0.038	0.1	0.36	61	-10000	0	61
response to UV	0	0.002	0.005	72	-10000	0	72
RAF1	0.032	0.089	0.29	67	-10000	0	67
CRADD	0.027	0.006	-10000	0	-10000	0	0
mol:ceramide	0.019	0.053	0.19	41	-0.18	8	49
I-kappa-B-alpha/RELA/p50/ubiquitin	0.037	0.007	-10000	0	-10000	0	0
MADD	0.028	0.004	-10000	0	-10000	0	0
MAP3K1	0.024	0.061	0.23	43	-0.2	1	44
TRADD	0.027	0.007	-10000	0	-10000	0	0
RELA/p50	0.028	0.003	-10000	0	-10000	0	0
MAPK3	0.035	0.087	0.3	63	-10000	0	63
MAPK1	0.034	0.09	0.3	64	-10000	0	64
p50/RELA/I-kappa-B-alpha	0.041	0.008	-10000	0	-10000	0	0
FADD	0.011	0.089	0.32	1	-0.45	14	15
KSR1	0.029	0.075	0.26	62	-0.19	2	64
MAPK8	0.033	0.08	0.28	66	-0.26	3	69
TRAF2	0.028	0.004	-10000	0	-10000	0	0
response to radiation	0	0.001	0.004	39	-10000	0	39
CHUK	0.027	0.084	0.3	10	-0.45	11	21
TNF R/SODD	0.037	0.028	-10000	0	-0.49	2	2
TNF	0.013	0.082	-10000	0	-0.46	25	25
CYCS	0.028	0.071	0.25	46	-10000	0	46
IKBKG	0.021	0.092	0.29	10	-0.44	12	22
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.011	0.092	-10000	0	-0.47	16	16
RELA	0.028	0.003	-10000	0	-10000	0	0
RIPK1	0.027	0.007	-10000	0	-10000	0	0
AIFM1	0.02	0.06	0.24	31	-10000	0	31
TNF/TNF R/SODD	0.04	0.06	-10000	0	-0.42	7	7
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
response to heat	0	0.001	0.004	39	-10000	0	39
CASP8	0.007	0.14	-10000	0	-0.67	36	36
NSMAF	0.014	0.089	-10000	0	-0.44	15	15
response to hydrogen peroxide	0	0.002	0.005	72	-10000	0	72
BCL2	0.027	0.023	-10000	0	-0.65	1	1

×

Regulation of Androgen receptor activity

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
HDAC1	0.017	0.006	-10000	0	-10000	0	0
SMARCC1	0.009	0.048	-10000	0	-0.66	4	4
REL	0.02	0.071	-10000	0	-0.6	11	11
HDAC7	-0.12	0.1	-10000	0	-0.53	6	6
JUN	0.026	0.007	-10000	0	-10000	0	0
EP300	0.027	0.024	-10000	0	-0.65	1	1
KAT2B	0.025	0.024	-10000	0	-0.65	1	1
KAT5	0.028	0.003	-10000	0	-10000	0	0
MAPK14	-0.017	0.036	0.24	1	-0.51	3	4
FOXO1	0.027	0.006	-10000	0	-10000	0	0
T-DHT/AR	-0.13	0.11	-10000	0	-0.5	12	12
MAP2K6	-0.008	0.045	-10000	0	-0.58	4	4
BRM/BAF57	0.036	0.015	-10000	0	-10000	0	0
MAP2K4	-0.005	0.02	-10000	0	-10000	0	0
SMARCA2	0.027	0.005	-10000	0	-10000	0	0
PDE9A	-0.15	0.19	-10000	0	-0.78	41	41
NCOA2	-0.004	0.14	-10000	0	-0.65	40	40
CEBPA	0.007	0.095	-10000	0	-0.42	41	41
EHMT2	0.026	0.007	-10000	0	-10000	0	0
cell proliferation	-0.13	0.19	0.51	34	-0.5	56	90
NR0B1	-0.044	0.13	-10000	0	-0.42	95	95
EGR1	-0.011	0.16	-10000	0	-0.65	48	48
RXRs/9cRA	0.043	0.036	-10000	0	-0.29	3	3
AR/RACK1/Src	-0.047	0.086	0.34	2	-0.44	7	9
AR/GR	-0.023	0.12	0.26	24	-0.37	48	72
GNB2L1	0.026	0.007	-10000	0	-10000	0	0
PKN1	0.028	0.003	-10000	0	-10000	0	0
RCHY1	0.028	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.002	-10000	0	-0.019	7	7
MAPK8	-0.019	0.041	-10000	0	-0.4	7	7
T-DHT/AR/TIF2/CARM1	-0.059	0.13	0.36	8	-0.49	39	47
SRC	-0.039	0.042	0.21	1	-0.39	3	4
NR3C1	0.026	0.016	-10000	0	-0.42	1	1
KLK3	-0.06	0.19	0.4	1	-0.59	51	52
APPBP2	-0.005	0.02	-10000	0	-10000	0	0
TRIM24	0.024	0.01	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.046	0.095	0.35	11	-0.47	9	20
TMPRSS2	-0.85	0.47	-10000	0	-1.1	685	685
RXRG	0.009	0.056	-10000	0	-0.45	11	11
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	0.028	0.004	-10000	0	-10000	0	0
RXRB	0.026	0.007	-10000	0	-10000	0	0
CARM1	0.028	0.003	-10000	0	-10000	0	0
NR2C2	0.023	0.046	-10000	0	-0.65	4	4
KLK2	-0.052	0.16	0.39	23	-0.51	41	64
AR	-0.03	0.083	-10000	0	-0.37	44	44
SENP1	0.027	0.006	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
MDM2	0.028	0.008	-10000	0	-10000	0	0
SRY	0.001	0.005	0.014	95	-10000	0	95
GATA2	-0.028	0.18	-10000	0	-0.64	72	72
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	-0.073	0.17	-10000	0	-0.42	171	171
T-DHT/AR/RACK1/Src	-0.039	0.099	0.4	12	-0.44	7	19
positive regulation of transcription	-0.028	0.18	-10000	0	-0.64	72	72
DNAJA1	-0.005	0.023	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.009	-10000	0	-10000	0	0
NCOA1	0.036	0.02	-10000	0	-10000	0	0
SPDEF	-0.034	0.15	-10000	0	-0.42	111	111
T-DHT/AR/TIF2	-0.018	0.098	0.3	11	-0.46	16	27
T-DHT/AR/Hsp90	-0.046	0.095	0.35	11	-0.45	10	21
GSK3B	0.023	0.007	-10000	0	-10000	0	0
NR2C1	0.027	0.006	-10000	0	-10000	0	0
mol:T-DHT	-0.044	0.046	-10000	0	-0.44	5	5
SIRT1	0.027	0.007	-10000	0	-10000	0	0
ZMIZ2	0.026	0.011	-10000	0	-10000	0	0
POU2F1	-0.061	0.06	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.072	0.11	0.35	9	-0.49	14	23
CREBBP	0.026	0.007	-10000	0	-10000	0	0
SMARCE1	0.025	0.009	-10000	0	-10000	0	0

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.006	0.11	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-10000	0	-10000	0	0
CRKL	0.027	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.006	0.1	0.31	1	-0.54	1	2
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.028	0.053	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.05	0.088	-10000	0	-0.35	3	3
CaM/Ca2+	-0.003	0.1	-10000	0	-10000	0	0
RAP1A	0.027	0.007	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.019	0.095	-10000	0	-0.44	1	1
AKT1	-0.003	0.11	0.36	30	-10000	0	30
MAP2K1	-0.017	0.1	0.3	29	-10000	0	29
MAP3K11	-0.018	0.11	0.3	30	-0.5	1	31
IFNGR1	0.014	0.026	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.16	0.25	-10000	0	-0.51	254	254
Rap1/GTP	-0.022	0.071	-10000	0	-10000	0	0
CRKL/C3G	0.04	0.009	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.007	0.12	-10000	0	-10000	0	0
CEBPB	0.015	0.13	0.42	26	-0.54	5	31
STAT3	0.025	0.009	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.005	0.15	-10000	0	-1	9	9
STAT1	-0.017	0.11	0.3	30	-0.44	1	31
CALM1	0.027	0.005	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.1	0.2	-10000	0	-0.41	257	257
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	-0.006	0.11	0.3	27	-0.42	1	28
CEBPB/PTGES2/Cbp/p300	0.013	0.076	-10000	0	-0.38	2	2
mol:Ca2+	-0.009	0.11	-10000	0	-10000	0	0
MAPK3	-0.002	0.094	0.42	1	-0.71	3	4
STAT1 (dimer)	-0.062	0.12	-10000	0	-0.51	3	3
MAPK1	-0.01	0.14	0.42	2	-0.68	20	22
JAK2	0.015	0.026	-10000	0	-10000	0	0
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
JAK1	0.014	0.026	-10000	0	-10000	0	0
CAMK2D	0.028	0.004	-10000	0	-10000	0	0
DAPK1	0.013	0.14	0.37	31	-0.62	22	53
SMAD7	-0.006	0.08	0.25	33	-10000	0	33
CBL/CRKL/C3G	0.003	0.11	0.3	27	-10000	0	27
PI3K	-0.004	0.1	-10000	0	-10000	0	0
IFNG	-0.1	0.2	-10000	0	-0.41	257	257
apoptosis	-0.015	0.13	0.37	18	-0.41	51	69
CAMK2G	0.027	0.007	-10000	0	-10000	0	0
STAT3 (dimer)	0.025	0.009	-10000	0	-10000	0	0
CAMK2A	-0.19	0.31	-10000	0	-0.65	275	275
CAMK2B	-0.059	0.2	-10000	0	-0.54	129	129
FRAP1	-0.01	0.1	0.34	31	-10000	0	31
PRKCD	-0.012	0.1	0.32	24	-10000	0	24
RAP1B	0.027	0.006	-10000	0	-10000	0	0
negative regulation of cell growth	-0.05	0.088	-10000	0	-0.35	3	3
PTPN2	0.028	0.005	-10000	0	-10000	0	0
EP300	0.027	0.024	-10000	0	-0.65	1	1
IRF1	0.007	0.11	0.49	18	-0.5	2	20
STAT1 (dimer)/PIASy	-0.008	0.11	0.3	28	-0.42	1	29
SOCS1	0.016	0.14	-10000	0	-1.3	9	9
mol:GDP	0.001	0.1	0.28	27	-10000	0	27
CASP1	-0.007	0.081	0.26	32	-0.26	4	36
PTGES2	0.026	0.033	-10000	0	-0.65	2	2
IRF9	0.029	0.062	0.25	31	-10000	0	31
mol:PI-3-4-5-P3	-0.014	0.091	-10000	0	-10000	0	0
RAP1/GDP	-0.008	0.082	-10000	0	-10000	0	0
CBL	-0.019	0.11	0.3	30	-0.35	1	31
MAP3K1	-0.017	0.11	0.3	30	-10000	0	30
PIAS1	0.028	0.003	-10000	0	-10000	0	0
PIAS4	0.028	0.003	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.05	0.088	-10000	0	-0.35	3	3
PTPN11	-0.031	0.091	-10000	0	-10000	0	0
CREBBP	0.027	0.007	-10000	0	-10000	0	0
RAPGEF1	0.028	0.004	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.017	0.08	-9999	-0.63	13	13
mol:S1P	0.001	0.001	-9999	-10000	0	0
S1P1/S1P/Gi	0.015	0.054	-9999	-0.28	18	18
GNAO1	0.013	0.095	-9999	-0.56	23	23
S1P/S1P3/G12/G13	0.03	0.08	-9999	-0.38	24	24
AKT1	0.012	0.11	-9999	-0.55	25	25
AKT3	-0.008	0.12	-9999	-0.62	13	13
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.017	0.08	-9999	-0.63	13	13
GNAI2	0.027	0.009	-9999	-10000	0	0
GNAI3	0.028	0.008	-9999	-10000	0	0
GNAI1	0.024	0.041	-9999	-0.65	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.008	0.16	-9999	-0.64	49	49
S1PR2	0.028	0.015	-9999	-0.42	1	1
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.016	0.094	-9999	-0.46	15	15
MAPK3	0.014	0.087	-9999	-0.46	13	13
MAPK1	0.014	0.086	-9999	-0.46	13	13
JAK2	-0.011	0.1	-9999	-0.46	17	17
CXCR4	-0.04	0.12	-9999	-0.44	16	16
FLT1	0.021	0.067	-9999	-0.48	15	15
RhoA/GDP	0.019	0.006	-9999	-10000	0	0
Rac1/GDP	0.018	0.007	-9999	-10000	0	0
SRC	0.013	0.086	-9999	-0.46	13	13
S1P/S1P3/Gi	0.016	0.094	-9999	-0.46	15	15
RAC1	0.025	0.01	-9999	-10000	0	0
RhoA/GTP	0.022	0.093	-9999	-0.45	13	13
VEGFA	-0.11	0.2	-9999	-0.42	269	269
S1P/S1P2/Gi	0.026	0.063	-9999	-0.32	13	13
VEGFR1 homodimer/VEGFA homodimer	-0.064	0.16	-9999	-0.3	273	273
RHOA	0.026	0.008	-9999	-10000	0	0
S1P/S1P3/Gq	-0.025	0.15	-9999	-0.37	119	119
GNAQ	0.028	0.004	-9999	-10000	0	0
GNAZ	0.026	0.04	-9999	-0.65	3	3
G12/G13	0.034	0.017	-9999	-10000	0	0
GNA14	-0.042	0.21	-9999	-0.64	92	92
GNA15	0.011	0.088	-9999	-0.42	34	34
GNA12	0.025	0.009	-9999	-10000	0	0
GNA13	0.025	0.009	-9999	-10000	0	0
GNA11	0.022	0.065	-9999	-0.65	8	8
Rac1/GTP	0.018	0.086	-9999	-0.44	12	12

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.021	0.029	-10000	0	-0.64	1	1
HSPA8	0.028	0.023	-10000	0	-0.63	1	1
SMAD3/SMAD4/ER alpha	0.053	0.094	-10000	0	-0.43	20	20
AKT1	0.029	0.009	-10000	0	-10000	0	0
GSC	0.001	0.093	-10000	0	-0.61	2	2
NKX2-5	0.002	0.002	-10000	0	-10000	0	0
muscle cell differentiation	-0.054	0.057	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.092	0.067	-10000	0	-10000	0	0
SMAD4	0.035	0.033	-10000	0	-10000	0	0
CBFB	0.026	0.007	-10000	0	-10000	0	0
SAP18	0.027	0.006	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.044	0.04	-10000	0	-0.41	1	1
SMAD3/SMAD4/VDR	0.079	0.056	-10000	0	-10000	0	0
MYC	0.012	0.076	-10000	0	-0.43	25	25
CDKN2B	0.024	0.093	-10000	0	-0.57	1	1
AP1	0.039	0.093	-10000	0	-0.32	24	24
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.027	0.097	-10000	0	-0.38	30	30
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.036	0.037	-10000	0	-10000	0	0
SP3	0.029	0.007	-10000	0	-10000	0	0
CREB1	0.027	0.006	-10000	0	-10000	0	0
FOXH1	-0.006	0.12	-10000	0	-0.42	66	66
SMAD3/SMAD4/GR	0.068	0.049	-10000	0	-10000	0	0
GATA3	-0.33	0.33	-10000	0	-0.64	458	458
SKI/SIN3/HDAC complex/NCoR1	0.028	0.064	0.2	1	-0.43	13	14
MEF2C/TIF2	0.019	0.12	0.32	2	-0.52	21	23
endothelial cell migration	0.053	0.26	1.3	31	-10000	0	31
MAX	0.03	0.014	-10000	0	-10000	0	0
RBBP7	0.028	0.003	-10000	0	-10000	0	0
RBBP4	0.026	0.024	-10000	0	-0.65	1	1
RUNX2	0.009	0.088	-10000	0	-0.42	35	35
RUNX3	-0.11	0.2	-10000	0	-0.42	271	271
RUNX1	-0.006	0.12	-10000	0	-0.42	65	65
CTBP1	0.028	0.004	-10000	0	-10000	0	0
NR3C1	0.029	0.021	-10000	0	-0.42	1	1
VDR	0.024	0.046	-10000	0	-0.65	4	4
CDKN1A	0.04	0.087	-10000	0	-0.51	1	1
KAT2B	0.024	0.025	-10000	0	-0.65	1	1
SMAD2/SMAD2/SMAD4/FOXH1	0.048	0.09	-10000	0	-0.33	10	10
DCP1A	0.026	0.008	-10000	0	-10000	0	0
SKI	0.027	0.007	-10000	0	-10000	0	0
SERPINE1	-0.054	0.27	-10000	0	-1.4	31	31
SMAD3/SMAD4/ATF2	0.063	0.048	-10000	0	-0.43	1	1
SMAD3/SMAD4/ATF3	0.051	0.088	-10000	0	-0.43	21	21
SAP30	-0.004	0.11	-10000	0	-0.42	62	62
Cbp/p300/PIAS3	0.041	0.037	-10000	0	-0.41	1	1
JUN	0.03	0.09	0.3	6	-0.32	13	19
SMAD3/SMAD4/IRF7	0.064	0.057	-10000	0	-0.44	1	1
TFE3	0.027	0.023	-10000	0	-10000	0	0
COL1A2	0.001	0.11	0.48	4	-10000	0	4
mesenchymal cell differentiation	-0.05	0.075	0.33	8	-10000	0	8
DLX1	-0.16	0.22	-10000	0	-0.42	355	355
TCF3	0.028	0.003	-10000	0	-10000	0	0
FOS	-0.008	0.16	-10000	0	-0.61	57	57
SMAD3/SMAD4/Max	0.071	0.048	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.046	0.028	-10000	0	-0.41	1	1
ZBTB17	0.023	0.032	-10000	0	-0.64	2	2
LAMC1	0.04	0.038	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.065	0.045	-10000	0	-10000	0	0
IRF7	0.023	0.051	-10000	0	-0.44	10	10
ESR1	0.006	0.11	-10000	0	-0.56	32	32
HNF4A	-0.064	0.23	-10000	0	-0.65	117	117
MEF2C	0.026	0.076	0.44	5	-0.38	1	6
SMAD2-3/SMAD4	0.074	0.045	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.046	0.029	-10000	0	-0.41	1	1
IGHV3OR16-13	-0.008	0.049	-10000	0	-0.35	10	10
TGIF2/HDAC complex	0.027	0.007	-10000	0	-10000	0	0
CREBBP	0.024	0.012	-10000	0	-10000	0	0
SKIL	0.027	0.006	-10000	0	-10000	0	0
HDAC1	0.027	0.007	-10000	0	-10000	0	0
HDAC2	0.027	0.007	-10000	0	-10000	0	0
SNIP1	0.027	0.007	-10000	0	-10000	0	0
GCN5L2	-0.002	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.072	0.049	-10000	0	-10000	0	0
MSG1/HSC70	0.039	0.037	-10000	0	-0.31	9	9
SMAD2	0.031	0.017	-10000	0	-10000	0	0
SMAD3	0.035	0.033	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.043	0.029	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.009	0.054	0.29	3	-0.44	3	6
NCOR1	0.026	0.009	-10000	0	-10000	0	0
NCOA2	-0.004	0.14	-10000	0	-0.65	40	40
NCOA1	0.027	0.006	-10000	0	-10000	0	0
MYOD/E2A	0.026	0.055	-10000	0	-0.29	25	25
SMAD2-3/SMAD4/SP1/MIZ-1	0.096	0.073	-10000	0	-0.38	2	2
IFNB1	0.028	0.05	-10000	0	-0.38	3	3
SMAD3/SMAD4/MEF2C	0.059	0.079	-10000	0	-10000	0	0
CITED1	0.023	0.045	-10000	0	-0.42	9	9
SMAD2-3/SMAD4/ARC105	0.089	0.041	-10000	0	-10000	0	0
RBL1	0.027	0.007	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.046	0.04	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.062	0.15	-10000	0	-0.46	28	28
SMAD7	0.061	0.082	-10000	0	-10000	0	0
MYC/MIZ-1	0.024	0.062	-10000	0	-0.32	26	26
SMAD3/SMAD4	0.004	0.1	-10000	0	-0.43	28	28
IL10	-0.19	0.22	-10000	0	-0.4	325	325
PIASy/HDAC complex	0.03	0.009	-10000	0	-10000	0	0
PIAS3	0.025	0.011	-10000	0	-10000	0	0
CDK2	0.025	0.011	-10000	0	-10000	0	0
IL5	-0.18	0.2	-10000	0	-0.38	404	404
CDK4	0.024	0.012	-10000	0	-10000	0	0
PIAS4	0.03	0.009	-10000	0	-10000	0	0
ATF3	0.009	0.11	-10000	0	-0.61	24	24
SMAD3/SMAD4/SP1	0.066	0.07	-10000	0	-10000	0	0
FOXG1	-0.011	0.082	-10000	0	-0.42	32	32
FOXO3	0.021	0.01	-10000	0	-10000	0	0
FOXO1	0.021	0.009	-10000	0	-10000	0	0
FOXO4	0.022	0.008	-10000	0	-10000	0	0
heart looping	0.026	0.075	0.44	5	-0.38	1	6
CEBPB	0.016	0.07	-10000	0	-0.42	22	22
SMAD3/SMAD4/DLX1	-0.065	0.16	-10000	0	-0.31	47	47
MYOD1	-0.017	0.071	-10000	0	-0.42	25	25
SMAD3/SMAD4/HNF4	-0.001	0.17	-10000	0	-0.44	114	114
SMAD3/SMAD4/GATA3	-0.19	0.24	-10000	0	-0.42	446	446
SnoN/SIN3/HDAC complex/NCoR1	0.027	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.025	0.15	-10000	0	-0.42	27	27
SMAD3/SMAD4/SP1-3	0.081	0.067	-10000	0	-10000	0	0
MED15	0.027	0.005	-10000	0	-10000	0	0
SP1	0.024	0.036	-10000	0	-10000	0	0
SIN3B	0.028	0.003	-10000	0	-10000	0	0
SIN3A	0.028	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.051	0.082	-10000	0	-0.31	3	3
ITGB5	0.046	0.064	0.41	5	-10000	0	5
TGIF/SIN3/HDAC complex/CtBP	0.031	0.054	-10000	0	-0.54	5	5
SMAD3/SMAD4/AR	0.039	0.12	-10000	0	-0.44	49	49
AR	-0.012	0.16	-10000	0	-0.64	53	53
negative regulation of cell growth	0.04	0.048	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	0.052	0.068	-10000	0	-0.31	6	6
E2F5	0.027	0.024	-10000	0	-0.65	1	1
E2F4	0.026	0.007	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.061	0.088	-10000	0	-0.61	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	0.046	0.026	-10000	0	-10000	0	0
TFDP1	0.027	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.062	0.097	-10000	0	-0.33	13	13
SMAD3/SMAD4/RUNX2	0.05	0.076	-10000	0	-0.33	8	8
TGIF2	0.027	0.007	-10000	0	-10000	0	0
TGIF1	0.028	0.005	-10000	0	-10000	0	0
ATF2	0.026	0.024	-10000	0	-0.65	1	1

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.027	0.033	-10000	0	-0.65	2	2
SPHK1	-0.041	0.16	-10000	0	-0.42	131	131
GNAI2	0.026	0.008	-10000	0	-10000	0	0
mol:S1P	0.002	0.055	-10000	0	-0.29	3	3
GNAO1	0.011	0.095	-10000	0	-0.56	23	23
mol:Sphinganine-1-P	-0.02	0.12	-10000	0	-0.3	131	131
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.036	0.056	-10000	0	-10000	0	0
GNAI3	0.027	0.007	-10000	0	-10000	0	0
G12/G13	0.034	0.017	-10000	0	-10000	0	0
S1PR3	-0.01	0.16	-10000	0	-0.65	49	49
S1PR2	0.028	0.015	-10000	0	-0.42	1	1
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	-0.007	0.044	-10000	0	-0.24	4	4
S1PR5	-0.036	0.16	-10000	0	-0.42	125	125
S1PR4	0.014	0.077	-10000	0	-0.42	27	27
GNAI1	0.022	0.041	-10000	0	-0.65	3	3
S1P/S1P5/G12	-0.01	0.098	-10000	0	-0.3	14	14
S1P/S1P3/Gq	-0.024	0.15	-10000	0	-0.44	74	74
S1P/S1P4/Gi	0.014	0.078	0.24	1	-0.36	13	14
GNAQ	0.028	0.004	-10000	0	-10000	0	0
GNAZ	0.025	0.04	-10000	0	-0.65	3	3
GNA14	-0.042	0.21	-10000	0	-0.64	92	92
GNA15	0.011	0.088	-10000	0	-0.42	34	34
GNA12	0.025	0.009	-10000	0	-10000	0	0
GNA13	0.025	0.009	-10000	0	-10000	0	0
GNA11	0.022	0.065	-10000	0	-0.65	8	8
ABCC1	0.026	0.007	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.029	0.086	-10000	0	-0.59	2	2
HDAC1	0.024	0.008	-10000	0	-10000	0	0
AES	0.027	0.003	-10000	0	-10000	0	0
FBXW11	0.027	0.007	-10000	0	-10000	0	0
DTX1	-0.029	0.19	-10000	0	-0.65	72	72
LRP6/FZD1	0.035	0.026	-10000	0	-0.39	2	2
TLE1	0.027	0.004	-10000	0	-10000	0	0
AP1	-0.079	0.18	-10000	0	-0.35	235	235
NCSTN	0.027	0.007	-10000	0	-10000	0	0
ADAM10	0.027	0.023	-10000	0	-0.65	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.04	0.064	-10000	0	-0.64	2	2
NICD/RBPSUH	0.042	0.06	-10000	0	-0.65	1	1
WIF1	0.018	0.044	-10000	0	-0.45	7	7
NOTCH1	0.028	0.055	-10000	0	-0.68	1	1
PSENEN	0.028	0.003	-10000	0	-10000	0	0
KREMEN2	-0.023	0.14	-10000	0	-0.42	92	92
DKK1	0.005	0.093	-10000	0	-0.44	36	36
beta catenin/beta TrCP1	0.055	0.11	0.3	21	-0.41	5	26
APH1B	0.026	0.033	-10000	0	-0.65	2	2
APH1A	0.027	0.007	-10000	0	-10000	0	0
AXIN1	0.005	0.054	0.3	6	-10000	0	6
CtBP/CBP/TCF1/TLE1/AES	0.02	0.05	-10000	0	-0.32	15	15
PSEN1	0.027	0.005	-10000	0	-10000	0	0
FOS	-0.015	0.16	-10000	0	-0.62	57	57
JUN	0.027	0.007	-10000	0	-10000	0	0
MAP3K7	0.025	0.007	-10000	0	-10000	0	0
CTNNB1	0.049	0.12	0.29	35	-0.4	8	43
MAPK3	0.026	0.007	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.006	0.11	-10000	0	-0.42	15	15
HNF1A	0.014	0.091	-10000	0	-0.65	16	16
CTBP1	0.027	0.004	-10000	0	-10000	0	0
MYC	0.018	0.1	-10000	0	-0.79	10	10
NKD1	-0.14	0.29	-10000	0	-0.65	213	213
FZD1	0.023	0.029	-10000	0	-0.53	2	2
NOTCH1 precursor/Deltex homolog 1	0.009	0.12	-10000	0	-0.66	2	2
apoptosis	-0.078	0.18	-10000	0	-0.35	235	235
Delta 1/NOTCHprecursor	0.028	0.085	-10000	0	-0.58	2	2
DLL1	0.005	0.11	-10000	0	-0.57	31	31
PPARD	-0.017	0.2	-10000	0	-0.76	58	58
Gamma Secretase	0.076	0.033	-10000	0	-0.36	2	2
APC	0.002	0.067	0.3	6	-0.44	6	12
DVL1	0.02	0.029	-10000	0	-0.45	2	2
CSNK2A1	0.027	0.006	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.008	0.11	-10000	0	-0.42	8	8
LRP6	0.027	0.006	-10000	0	-10000	0	0
CSNK1A1	0.027	0.007	-10000	0	-10000	0	0
NLK	0.014	0.007	-10000	0	-10000	0	0
CCND1	0.02	0.095	-10000	0	-0.85	6	6
WNT1	-0.004	0.11	-10000	0	-0.42	58	58
Axin1/APC/beta catenin	0.067	0.11	0.38	37	-0.45	5	42
DKK2	0.002	0.11	-10000	0	-0.49	42	42
NOTCH1 precursor/DVL1	0.033	0.086	-10000	0	-0.59	3	3
GSK3B	0.027	0.006	-10000	0	-10000	0	0
FRAT1	0.026	0.007	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.011	0.12	-10000	0	-0.67	2	2
PPP2R5D	0.068	0.17	0.34	192	-0.45	33	225
MAPK1	0.027	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.038	0.077	-10000	0	-0.39	2	2
RBPJ	0.028	0.004	-10000	0	-10000	0	0
CREBBP	0.029	0.009	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.028	0.004	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.004	0.14	-9999	-0.49	19	19
Syndecan-3/Neurocan	0	0.1	-9999	-0.35	55	55
POMC	0.02	0.065	-9999	-0.6	9	9
EGFR	0.017	0.061	-9999	-0.45	14	14
Syndecan-3/EGFR	0.003	0.097	-9999	-0.35	54	54
AGRP	0.011	0.03	-9999	-0.42	2	2
NCSTN	0.027	0.007	-9999	-10000	0	0
PSENEN	0.028	0.003	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.026	0.033	-9999	-0.65	2	2
APH1A	0.027	0.007	-9999	-10000	0	0
NCAN	-0.003	0.088	-9999	-0.42	35	35
long-term memory	0.027	0.091	-9999	-0.32	53	53
Syndecan-3/IL8	-0.011	0.12	-9999	-0.37	70	70
PSEN1	0.027	0.005	-9999	-10000	0	0
Src/Cortactin	0.039	0.011	-9999	-10000	0	0
FYN	0.026	0.007	-9999	-10000	0	0
limb bud formation	-0.005	0.091	-9999	-0.36	53	53
MC4R	-0.009	0.046	-9999	-0.42	9	9
SRC	0.027	0.007	-9999	-10000	0	0
PTN	-0.028	0.18	-9999	-0.63	70	70
FGFR/FGF/Syndecan-3	-0.005	0.092	-9999	-0.36	53	53
neuron projection morphogenesis	-0.008	0.14	-9999	-0.54	17	17
Syndecan-3/AgRP	0.007	0.092	-9999	-0.35	51	51
Syndecan-3/AgRP/MC4R	0.016	0.096	-9999	-0.35	45	45
Fyn/Cortactin	0.039	0.012	-9999	-10000	0	0
SDC3	-0.006	0.092	-9999	-0.37	53	53
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.011	0.12	-9999	-0.36	70	70
IL8	-0.016	0.14	-9999	-0.48	77	77
Syndecan-3/Fyn/Cortactin	0.028	0.093	-9999	-0.33	51	51
Syndecan-3/CASK	-0.007	0.088	-9999	-0.35	55	55
alpha-MSH/MC4R	0.025	0.06	-9999	-0.38	17	17
Gamma Secretase	0.076	0.033	-9999	-0.36	2	2

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.025	0.033	-10000	0	-0.65	2	2
Caspase 8 (4 units)	-0.023	0.095	-10000	0	-10000	0	0
NEF	-0.032	0.053	-10000	0	-0.36	3	3
NFKBIA	0.018	0.036	-10000	0	-10000	0	0
BIRC3	-0.014	0.14	-10000	0	-0.38	99	99
CYCS	-0.037	0.08	-10000	0	-0.35	1	1
RIPK1	0.027	0.007	-10000	0	-10000	0	0
CD247	-0.12	0.23	-10000	0	-0.53	207	207
MAP2K7	-0.029	0.18	0.34	1	-0.71	41	42
protein ubiquitination	0.05	0.12	0.38	54	-0.42	7	61
CRADD	0.027	0.006	-10000	0	-10000	0	0
DAXX	0.027	0.007	-10000	0	-10000	0	0
FAS	0.026	0.024	-10000	0	-0.65	1	1
BID	-0.035	0.087	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	0.032	0.09	-10000	0	-0.4	2	2
TRADD	0.026	0.007	-10000	0	-10000	0	0
MAP3K5	0.026	0.007	-10000	0	-10000	0	0
CFLAR	0.027	0.006	-10000	0	-10000	0	0
FADD	0.028	0.004	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.032	0.09	-10000	0	-0.41	2	2
MAPK8	-0.025	0.16	0.34	3	-0.64	41	44
APAF1	0.027	0.006	-10000	0	-10000	0	0
TRAF1	0.027	0.022	-10000	0	-0.42	2	2
TRAF2	0.028	0.004	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.036	0.092	-10000	0	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.007	0.098	-10000	0	-0.5	13	13
CHUK	0.041	0.096	0.32	33	-0.46	6	39
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.075	0.031	-10000	0	-0.36	1	1
TCRz/NEF	-0.12	0.21	-10000	0	-0.47	207	207
TNF	0.012	0.082	-10000	0	-0.46	25	25
FASLG	-0.17	0.26	-10000	0	-0.51	314	314
NFKB1	0.017	0.042	-10000	0	-0.65	1	1
TNFR1A/BAG4/TNF-alpha	0.04	0.06	-10000	0	-0.42	7	7
CASP6	-0.013	0.14	-10000	0	-0.55	37	37
CASP7	-0.03	0.14	0.42	4	-0.44	29	33
RELA	0.018	0.036	-10000	0	-10000	0	0
CASP2	0.025	0.01	-10000	0	-10000	0	0
CASP3	-0.022	0.12	0.34	2	-0.59	3	5
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
TNFR1A/BAG4	0.037	0.028	-10000	0	-0.49	2	2
CASP8	0.027	0.006	-10000	0	-10000	0	0
CASP9	0.026	0.007	-10000	0	-10000	0	0
MAP3K14	0.02	0.082	-10000	0	-0.47	11	11
APAF-1/Caspase 9	-0.047	0.12	-10000	0	-0.47	2	2
BCL2	-0.021	0.15	0.38	6	-0.58	41	47

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.04	0.076	-10000	0	-0.38	23	23
NF kappa B1 p50/RelA/I kappa B alpha	0.037	0.082	0.32	8	-10000	0	8
AP1	0.007	0.12	-10000	0	-0.36	69	69
mol:PIP3	0.001	0.062	-10000	0	-0.4	2	2
AKT1	0.042	0.096	0.38	23	-0.4	2	25
PTK2B	0.009	0.072	0.3	4	-0.38	10	14
RHOA	0.009	0.077	0.26	4	-0.36	8	12
PIK3CB	0.027	0.006	-10000	0	-10000	0	0
mol:Ca2+	0.011	0.064	0.35	5	-0.36	2	7
MAGI3	0.025	0.033	-10000	0	-0.65	2	2
RELA	0.028	0.003	-10000	0	-10000	0	0
apoptosis	0.009	0.07	-10000	0	-0.34	30	30
HRAS/GDP	0.02	0.011	-10000	0	-0.29	1	1
positive regulation of microtubule depolymerization	0.024	0.1	0.35	30	-0.34	20	50
NF kappa B1 p50/RelA	0.016	0.079	0.24	3	-0.48	2	5
endothelial cell migration	0.009	0.081	-10000	0	-0.4	30	30
ADCY4	0.009	0.096	-10000	0	-0.47	25	25
ADCY5	0	0.11	-10000	0	-0.44	35	35
ADCY6	0.012	0.089	-10000	0	-0.46	23	23
ADCY7	0.009	0.09	-10000	0	-0.45	24	24
ADCY1	-0.017	0.12	-10000	0	-0.47	36	36
ADCY2	-0.012	0.1	-10000	0	-0.45	31	31
ADCY3	0.012	0.093	-10000	0	-0.47	24	24
ADCY8	-0.001	0.093	-10000	0	-0.45	25	25
ADCY9	0.012	0.089	-10000	0	-0.45	23	23
GSK3B	0.016	0.079	0.27	22	-0.36	10	32
arachidonic acid secretion	0.011	0.088	-10000	0	-0.42	25	25
GNG2	0.027	0.005	-10000	0	-10000	0	0
TRIP6	0.023	0.025	-10000	0	-0.44	2	2
GNAO1	0.002	0.091	-10000	0	-0.4	35	35
HRAS	0.027	0.015	-10000	0	-0.42	1	1
NFKBIA	0.017	0.091	0.41	14	-0.42	2	16
GAB1	0.028	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.017	0.23	-10000	0	-0.87	53	53
JUN	0.027	0.007	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.037	0.023	-10000	0	-0.33	2	2
TIAM1	-0.037	0.27	-10000	0	-1	60	60
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	0.009	0.063	0.38	4	-0.37	2	6
PLCB3	0.031	0.04	-10000	0	-0.38	1	1
FOS	-0.015	0.16	-10000	0	-0.62	57	57
positive regulation of mitosis	0.011	0.088	-10000	0	-0.42	25	25
LPA/LPA1-2-3	0.036	0.082	-10000	0	-0.38	25	25
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	-10000	0	-10000	0	0
BCAR1	0.026	0.024	-10000	0	-0.65	1	1
stress fiber formation	0.019	0.076	0.38	4	-0.38	9	13
GNAZ	0.01	0.08	-10000	0	-0.41	28	28
EGFR/PI3K-beta/Gab1	0.011	0.068	-10000	0	-0.42	2	2
positive regulation of dendritic cell cytokine production	0.035	0.081	-10000	0	-0.38	25	25
LPA/LPA2/MAGI-3	0.036	0.03	-10000	0	-0.36	3	3
ARHGEF1	0.045	0.1	0.36	37	-0.35	20	57
GNAI2	0.011	0.072	-10000	0	-0.4	22	22
GNAI3	0.011	0.076	-10000	0	-0.4	26	26
GNAI1	0.009	0.075	-10000	0	-0.4	24	24
LPA/LPA3	0.014	0.038	-10000	0	-0.28	12	12
LPA/LPA2	0.022	0.019	-10000	0	-0.23	3	3
LPA/LPA1	0.011	0.088	-10000	0	-0.46	27	27
HB-EGF/EGFR	-0.07	0.14	-10000	0	-0.48	11	11
HBEGF	-0.097	0.15	-10000	0	-0.3	322	322
mol:DAG	0.009	0.063	0.38	4	-0.37	2	6
cAMP biosynthetic process	0.015	0.13	0.38	39	-0.43	31	70
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
SRC	0.027	0.007	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
LYN	0.018	0.091	0.39	15	-0.4	5	20
GNAQ	0.017	0.03	-10000	0	-0.3	4	4
LPAR2	0.028	0.015	-10000	0	-0.42	1	1
LPAR3	0.015	0.049	-10000	0	-0.43	10	10
LPAR1	0.012	0.11	-10000	0	-0.59	26	26
IL8	-0.033	0.13	0.37	3	-0.51	24	27
PTK2	0.012	0.07	0.3	1	-0.36	21	22
Rac1/GDP	0.018	0.007	-10000	0	-10000	0	0
CASP3	0.009	0.07	-10000	0	-0.34	30	30
EGFR	0.017	0.061	-10000	0	-0.45	14	14
PLCG1	0.001	0.056	-10000	0	-0.31	7	7
PLD2	0.011	0.07	0.3	1	-0.36	22	23
G12/G13	0.036	0.073	-10000	0	-0.38	20	20
PI3K-beta	0.006	0.066	-10000	0	-0.46	2	2
cell migration	0.017	0.076	-10000	0	-0.27	25	25
SLC9A3R2	0.026	0.024	-10000	0	-0.65	1	1
PXN	0.019	0.077	0.39	4	-0.38	9	13
HRAS/GTP	0.004	0.086	-10000	0	-0.43	25	25
RAC1	0.025	0.01	-10000	0	-10000	0	0
MMP9	-0.14	0.22	-10000	0	-0.42	332	332
PRKCE	0.026	0.024	-10000	0	-0.65	1	1
PRKCD	0.013	0.084	0.37	21	-0.4	1	22
Gi(beta/gamma)	0.015	0.092	-10000	0	-0.44	27	27
mol:LPA	0.001	0.021	-10000	0	-0.25	4	4
TRIP6/p130 Cas/FAK1/Paxillin	0.035	0.079	-10000	0	-10000	0	0
MAPKKK cascade	0.011	0.088	-10000	0	-0.42	25	25
contractile ring contraction involved in cytokinesis	0.013	0.083	0.26	12	-0.34	9	21
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.021	0.12	-10000	0	-0.35	95	95
GNA15	0.011	0.047	-10000	0	-0.32	7	7
GNA12	0.025	0.009	-10000	0	-10000	0	0
GNA13	0.025	0.009	-10000	0	-10000	0	0
MAPT	0.023	0.1	0.36	29	-0.35	20	49
GNA11	0.014	0.043	-10000	0	-0.34	10	10
Rac1/GTP	-0.019	0.24	-10000	0	-0.93	53	53
MMP2	0.009	0.082	-10000	0	-0.41	30	30

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.024	0.1	-9999	-0.43	37	37
E-cadherin/beta catenin	0.012	0.11	-9999	-0.49	40	40
CTNNB1	0.026	0.008	-9999	-10000	0	0
JUP	0.023	0.04	-9999	-0.65	3	3
CDH1	-0.005	0.14	-9999	-0.65	40	40

×

TCGA08_rtk_signaling

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
PDGFRA	-0.24	0.33	-10000	0	-0.65	347	347
HRAS	0.027	0.015	-10000	0	-0.42	1	1
EGFR	0.017	0.061	-10000	0	-0.45	14	14
AKT	0.03	0.1	0.28	60	-0.39	1	61
FOXO3	0.026	0.007	-10000	0	-10000	0	0
AKT1	0.027	0.005	-10000	0	-10000	0	0
FOXO1	0.027	0.006	-10000	0	-10000	0	0
AKT3	0.026	0.024	-10000	0	-0.65	1	1
FOXO4	0.028	0.001	-10000	0	-10000	0	0
MET	0.021	0.04	-10000	0	-0.42	7	7
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
PIK3CB	0.027	0.006	-10000	0	-10000	0	0
NRAS	0.027	0.007	-10000	0	-10000	0	0
PIK3CG	0.017	0.066	-10000	0	-0.51	13	13
PIK3R3	0.026	0.024	-10000	0	-0.65	1	1
PIK3R2	0.028	0.003	-10000	0	-10000	0	0
NF1	0.025	0.009	-10000	0	-10000	0	0
RAS	-0.032	0.081	-10000	0	-0.27	9	9
ERBB2	0.025	0.024	-10000	0	-0.65	1	1
proliferation/survival/translation	-0.044	0.048	0.24	5	-0.24	11	16
PI3K	-0.001	0.11	0.29	52	-0.23	12	64
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
KRAS	0.027	0.006	-10000	0	-10000	0	0
FOXO	0.059	0.082	0.27	67	-10000	0	67
AKT2	0.028	0.003	-10000	0	-10000	0	0
PTEN	0.027	0.007	-10000	0	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.027	0.006	-10000	0	-10000	0	0
EPHB2	0.02	0.057	-10000	0	-0.45	12	12
EFNB1	-0.027	0.11	-10000	0	-0.3	127	127
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.028	0.095	-10000	0	-0.39	14	14
Ephrin B2/EPHB1-2	0.037	0.066	-10000	0	-0.43	11	11
neuron projection morphogenesis	0.013	0.084	-10000	0	-0.37	14	14
Ephrin B1/EPHB1-2/Tiam1	0.013	0.11	-10000	0	-0.43	18	18
DNM1	-0.039	0.16	-10000	0	-0.42	129	129
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	0	0.12	-10000	0	-0.56	32	32
YES1	-0.011	0.16	-10000	0	-0.81	32	32
Ephrin B1/EPHB1-2/NCK2	0.015	0.11	-10000	0	-0.43	17	17
PI3K	0.022	0.12	-10000	0	-0.59	30	30
mol:GDP	0.012	0.11	-10000	0	-0.43	18	18
ITGA2B	0.015	0.068	-10000	0	-0.46	17	17
endothelial cell proliferation	0.031	0.014	-10000	0	-10000	0	0
FYN	-0.014	0.16	-10000	0	-0.83	32	32
MAP3K7	-0.012	0.12	-10000	0	-0.63	29	29
FGR	-0.012	0.16	-10000	0	-0.82	32	32
TIAM1	0.026	0.024	-10000	0	-0.65	1	1
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
RGS3	0.028	0.004	-10000	0	-10000	0	0
cell adhesion	0.003	0.13	-10000	0	-0.59	27	27
LYN	-0.01	0.16	-10000	0	-0.81	32	32
Ephrin B1/EPHB1-2/Src Family Kinases	-0.015	0.14	-10000	0	-0.75	32	32
Ephrin B1/EPHB1-2	-0.015	0.13	-10000	0	-0.67	31	31
SRC	-0.009	0.15	-10000	0	-0.79	32	32
ITGB3	0.007	0.11	-10000	0	-0.61	25	25
EPHB1	0.015	0.083	-10000	0	-0.53	19	19
EPHB4	0.025	0.009	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.031	0.015	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.016	0.098	-10000	0	-0.42	40	40
BLK	-0.012	0.16	-10000	0	-0.8	32	32
HCK	-0.012	0.16	-10000	0	-0.8	32	32
regulation of stress fiber formation	-0.013	0.11	0.42	17	-10000	0	17
MAPK8	0.001	0.12	0.37	3	-0.54	31	34
Ephrin B1/EPHB1-2/RGS3	0.014	0.11	-10000	0	-0.43	17	17
endothelial cell migration	0.009	0.12	0.4	2	-0.54	28	30
NCK2	0.027	0.006	-10000	0	-10000	0	0
PTPN13	0.008	0.13	-10000	0	-0.76	23	23
regulation of focal adhesion formation	-0.013	0.11	0.42	17	-10000	0	17
chemotaxis	-0.013	0.11	0.43	17	-10000	0	17
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
Rac1/GTP	0.021	0.09	-10000	0	-0.38	14	14
angiogenesis	-0.015	0.13	-10000	0	-0.66	32	32
LCK	-0.014	0.16	-10000	0	-0.82	32	32

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.033	0.013	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.027	0.007	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.022	0.042	-10000	0	-0.58	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.025	0.009	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.019	0.016	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.028	0.005	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.025	0.009	-10000	0	-10000	0	0
FYN	0.026	0.007	-10000	0	-10000	0	0
MAP3K12	0.026	0.024	-10000	0	-0.65	1	1
FGR	0.021	0.053	-10000	0	-0.44	11	11
p38 alpha/TAB1	-0.038	0.14	-10000	0	-0.58	46	46
PRKG1	-0.044	0.2	-10000	0	-0.64	92	92
DUSP8	0.026	0.031	-10000	0	-0.5	3	3
PGK/cGMP/p38 alpha	-0.016	0.16	-10000	0	-0.51	62	62
apoptosis	-0.036	0.13	-10000	0	-0.55	46	46
RAL/GTP	0.032	0.014	-10000	0	-10000	0	0
LYN	0.026	0.024	-10000	0	-0.65	1	1
DUSP1	0.025	0.036	-10000	0	-0.57	3	3
PAK1	0.028	0.003	-10000	0	-10000	0	0
SRC	0.027	0.007	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.059	0.029	-10000	0	-10000	0	0
TRAF6	0.028	0.003	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.025	0.009	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.031	0.015	-10000	0	-10000	0	0
MAPK11	0.047	0.18	0.4	77	-0.47	44	121
BLK	-0.001	0.1	-10000	0	-0.42	48	48
HCK	-0.006	0.12	-10000	0	-0.42	63	63
MAP2K3	0.025	0.009	-10000	0	-10000	0	0
DUSP16	0.027	0.006	-10000	0	-10000	0	0
DUSP10	0.021	0.052	-10000	0	-0.42	12	12
TRAF6/MEKK3	0.032	0.012	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.033	0.19	0.35	74	-0.64	46	120
positive regulation of innate immune response	0.051	0.21	0.44	79	-0.63	44	123
LCK	0.003	0.1	-10000	0	-0.44	44	44
p38alpha-beta/MKP7	0.043	0.18	0.4	48	-0.61	41	89
p38alpha-beta/MKP5	0.059	0.2	0.45	71	-0.61	40	111
PGK/cGMP	-0.033	0.15	-10000	0	-0.48	92	92
PAK2	0.027	0.006	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.054	0.2	0.44	66	-0.61	41	107
CDC42	0.027	0.007	-10000	0	-10000	0	0
RALB	0.027	0.006	-10000	0	-10000	0	0
RALA	0.025	0.009	-10000	0	-10000	0	0
PAK3	0.014	0.063	-10000	0	-0.43	16	16

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.026	0.055	-10000	0	-0.44	1	1
adherens junction organization	0.004	0.091	0.25	8	-0.38	10	18
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.027	0.062	-10000	0	-0.5	1	1
FMN1	-0.011	0.11	-10000	0	-0.37	37	37
mol:IP3	0.02	0.049	-10000	0	-0.51	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.006	0.082	-10000	0	-0.42	5	5
CTNNB1	0.026	0.009	-10000	0	-10000	0	0
AKT1	0.026	0.061	0.28	3	-0.4	1	4
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.021	0.13	-10000	0	-0.52	38	38
CTNND1	0.03	0.008	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.009	0.073	-10000	0	-0.48	3	3
VASP	0.005	0.079	-10000	0	-0.58	2	2
ZYX	0.003	0.076	-10000	0	-0.58	2	2
JUB	0.004	0.079	-10000	0	-0.4	5	5
EGFR(dimer)	0.013	0.088	-10000	0	-0.47	5	5
E-cadherin/beta catenin-gamma catenin	0.024	0.097	-10000	0	-0.41	37	37
mol:PI-3-4-5-P3	0.037	0.069	0.26	6	-0.44	2	8
PIK3CA	0.029	0.007	-10000	0	-10000	0	0
PI3K	0.038	0.071	0.26	6	-0.46	2	8
FYN	-0.2	0.14	-10000	0	-0.42	91	91
mol:Ca2+	0.02	0.049	-10000	0	-0.5	1	1
JUP	0.024	0.041	-10000	0	-0.65	3	3
PIK3R1	0.03	0.008	-10000	0	-10000	0	0
mol:DAG	0.02	0.049	-10000	0	-0.51	1	1
CDH1	-0.004	0.14	-10000	0	-0.65	40	40
RhoA/GDP	0.035	0.068	-10000	0	-0.5	1	1
establishment of polarity of embryonic epithelium	0.006	0.078	-10000	0	-0.56	2	2
SRC	0.027	0.007	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
RHOA	0.026	0.008	-10000	0	-10000	0	0
EGFR	0.017	0.061	-10000	0	-0.45	14	14
CASR	-0.23	0.15	0.23	2	-0.33	577	579
RhoA/GTP	0.031	0.049	-10000	0	-0.46	1	1
AKT2	0.027	0.064	0.27	5	-0.55	1	6
actin cable formation	-0.009	0.11	-10000	0	-0.5	10	10
apoptosis	-0.032	0.081	0.48	1	-0.4	20	21
CTNNA1	0.029	0.009	-10000	0	-10000	0	0
mol:GDP	0.012	0.056	-10000	0	-0.41	3	3
PIP5K1A	0.009	0.075	-10000	0	-0.49	3	3
PLCG1	0.02	0.05	-10000	0	-0.53	1	1
Rac1/GTP	0.022	0.086	-10000	0	-0.47	4	4
homophilic cell adhesion	0.002	0.007	-10000	0	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.095	0.094	-10000	0	-0.47	4	4
epithelial cell differentiation	-0.076	0.12	-10000	0	-0.41	22	22
ITCH	0.057	0.023	-10000	0	-10000	0	0
WWP1	-0.083	0.077	-10000	0	-10000	0	0
FYN	0.026	0.007	-10000	0	-10000	0	0
EGFR	0.017	0.061	-10000	0	-0.45	14	14
PRL	-0.004	0.02	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.05	0.096	0.34	6	-0.5	2	8
PTPRZ1	-0.007	0.1	-10000	0	-0.58	26	26
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.058	0.096	-10000	0	-0.43	18	18
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.082	0.097	-10000	0	-0.45	31	31
ADAM17	0.057	0.023	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.11	0.098	-10000	0	-0.45	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.11	0.11	-10000	0	-0.42	32	32
NCOR1	0.025	0.009	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.074	0.096	-10000	0	-0.46	20	20
GRIN2B	-0.073	0.092	0.28	1	-0.45	19	20
ErbB4/ErbB2/betacellulin	-0.095	0.13	-10000	0	-0.46	67	67
STAT1	0.026	0.022	-10000	0	-0.42	2	2
HBEGF	0.023	0.048	-10000	0	-0.59	5	5
PRLR	-0.083	0.25	-10000	0	-0.65	143	143
E4ICDs/ETO2	-0.096	0.09	-10000	0	-0.38	4	4
axon guidance	-0.046	0.064	-10000	0	-10000	0	0
NEDD4	0.058	0.031	-10000	0	-0.63	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.053	0.19	-10000	0	-0.49	143	143
CBFA2T3	0.025	0.027	-10000	0	-0.42	3	3
ErbB4/ErbB2/HBEGF	-0.055	0.073	-10000	0	-0.43	3	3
MAPK3	-0.059	0.085	-10000	0	-0.43	9	9
STAT1 (dimer)	-0.093	0.092	-10000	0	-0.43	2	2
MAPK1	-0.059	0.085	-10000	0	-0.43	9	9
JAK2	0.028	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.07	0.098	-10000	0	-0.46	21	21
NRG1	0.015	0.1	-10000	0	-0.47	33	33
NRG3	-0.005	0.12	-10000	0	-0.48	55	55
NRG2	0.001	0.11	-10000	0	-0.43	49	49
NRG4	-0.015	0.14	-10000	0	-0.52	63	63
heart development	-0.046	0.064	-10000	0	-10000	0	0
neural crest cell migration	-0.069	0.097	-10000	0	-0.46	21	21
ERBB2	0.034	0.024	-10000	0	-0.48	1	1
WWOX/E4ICDs	-0.094	0.089	-10000	0	-0.38	2	2
SHC1	0.026	0.016	-10000	0	-0.42	1	1
ErbB4/EGFR/neuregulin 4	-0.099	0.12	-10000	0	-0.48	27	27
apoptosis	0.095	0.11	0.51	30	-10000	0	30
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.11	0.1	-10000	0	-0.37	30	30
ErbB4/ErbB2/epiregulin	-0.088	0.1	-10000	0	-0.44	2	2
ErbB4/ErbB4/betacellulin/betacellulin	-0.14	0.15	-10000	0	-0.5	94	94
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.13	0.16	-10000	0	-0.47	104	104
MDM2	-0.09	0.087	-10000	0	-0.4	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.056	0.087	-10000	0	-0.41	30	30
STAT5A	-0.037	0.06	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.074	0.1	-10000	0	-0.48	21	21
DLG4	0.025	0.009	-10000	0	-10000	0	0
GRB2/SHC	0.036	0.018	-10000	0	-0.29	1	1
E4ICDs/TAB2/NCoR1	-0.085	0.082	-10000	0	-0.37	1	1
STAT5A (dimer)	-0.076	0.14	-10000	0	-0.49	6	6
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.035	0.068	0.33	2	-10000	0	2
LRIG1	0.026	0.007	-10000	0	-10000	0	0
EREG	-0.053	0.17	-10000	0	-0.42	153	153
BTC	-0.045	0.21	-10000	0	-0.65	94	94
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.046	0.063	-10000	0	-10000	0	0
ERBB4	-0.11	0.098	-10000	0	-0.45	1	1
STAT5B	0.025	0.009	-10000	0	-10000	0	0
YAP1	-0.022	0.059	-10000	0	-0.53	9	9
GRB2	0.025	0.009	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.078	0.1	-10000	0	-0.46	26	26
glial cell differentiation	0.085	0.081	0.37	1	-10000	0	1
WWOX	0.026	0.017	-10000	0	-0.42	1	1
cell proliferation	-0.085	0.16	0.54	2	-0.61	26	28

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.049	0.19	0.58	4	-0.64	3	7
CRP	-0.075	0.21	-10000	0	-0.67	9	9
cell cycle arrest	-0.07	0.19	-10000	0	-0.66	8	8
TIMP1	-0.057	0.2	-10000	0	-0.59	10	10
IL6ST	-0.028	0.18	-10000	0	-0.65	71	71
Rac1/GDP	-0.068	0.15	-10000	0	-0.45	41	41
AP1	-0.001	0.16	-10000	0	-0.65	20	20
GAB2	0.027	0.015	-10000	0	-0.42	1	1
TNFSF11	-0.071	0.2	0.63	1	-0.68	8	9
HSP90B1	0.026	0.049	-10000	0	-10000	0	0
GAB1	0.028	0.004	-10000	0	-10000	0	0
MAPK14	-0.016	0.11	-10000	0	-0.6	10	10
AKT1	0.041	0.027	-10000	0	-10000	0	0
FOXO1	0.045	0.032	-10000	0	-10000	0	0
MAP2K6	-0.026	0.12	-10000	0	-0.49	21	21
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.071	0.15	-10000	0	-0.49	24	24
MITF	-0.038	0.12	-10000	0	-0.45	31	31
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.028	0.003	-10000	0	-10000	0	0
A2M	0.021	0.12	-10000	0	-1.2	7	7
CEBPB	0.019	0.07	-10000	0	-0.41	22	22
GRB2/SOS1/GAB family/SHP2	0.003	0.11	-10000	0	-0.63	17	17
STAT3	-0.081	0.19	-10000	0	-0.69	8	8
STAT1	-0.01	0.13	-10000	0	-0.68	30	30
CEBPD	-0.053	0.18	0.48	4	-0.61	5	9
PIK3CA	0.028	0.006	-10000	0	-10000	0	0
PI3K	0.041	0.011	-10000	0	-10000	0	0
JUN	0.026	0.007	-10000	0	-10000	0	0
PIAS3/MITF	-0.02	0.13	-10000	0	-0.5	17	17
MAPK11	-0.018	0.11	-10000	0	-0.54	16	16
STAT3 (dimer)/FOXO1	-0.039	0.16	-10000	0	-0.57	2	2
GRB2/SOS1/GAB family	0.001	0.14	-10000	0	-0.5	19	19
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.035	0.14	-10000	0	-0.5	37	37
GRB2	0.025	0.009	-10000	0	-10000	0	0
JAK2	0.028	0.005	-10000	0	-10000	0	0
LBP	-0.17	0.37	0.48	8	-0.88	155	163
PIK3R1	0.029	0.005	-10000	0	-10000	0	0
JAK1	0.027	0.009	-10000	0	-10000	0	0
MYC	-0.057	0.19	0.5	2	-0.72	6	8
FGG	-0.089	0.22	-10000	0	-0.7	5	5
macrophage differentiation	-0.07	0.19	-10000	0	-0.66	8	8
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.011	0.16	-10000	0	-0.42	46	46
JUNB	-0.055	0.18	-10000	0	-0.8	5	5
FOS	-0.015	0.16	-10000	0	-0.62	57	57
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.039	0.13	-10000	0	-0.45	36	36
STAT1/PIAS1	-0.032	0.13	-10000	0	-0.46	18	18
GRB2/SOS1/GAB family/SHP2/PI3K	0.04	0.027	-10000	0	-10000	0	0
STAT3 (dimer)	-0.076	0.19	-10000	0	-0.68	8	8
PRKCD	-0.066	0.17	0.4	11	-0.52	17	28
IL6R	0.026	0.033	-10000	0	-0.65	2	2
SOCS3	-0.005	0.14	-10000	0	-0.83	11	11
gp130 (dimer)/JAK1/JAK1/LMO4	0.015	0.13	-10000	0	-0.41	71	71
Rac1/GTP	-0.071	0.15	-10000	0	-0.46	36	36
HCK	-0.006	0.12	-10000	0	-0.42	63	63
MAPKKK cascade	0.009	0.13	-10000	0	-0.57	30	30
bone resorption	-0.067	0.2	0.52	3	-0.64	8	11
IRF1	-0.049	0.19	0.63	1	-0.64	3	4
mol:GDP	-0.083	0.15	-10000	0	-0.44	56	56
SOS1	0.027	0.006	-10000	0	-10000	0	0
VAV1	-0.084	0.15	-10000	0	-0.45	56	56
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.028	0.17	-10000	0	-0.65	32	32
PTPN11	0.013	0.02	-10000	0	-10000	0	0
IL6/IL6RA	-0.026	0.16	-10000	0	-0.44	89	89
gp130 (dimer)/TYK2/TYK2/LMO4	0.014	0.13	-10000	0	-0.42	70	70
gp130 (dimer)/JAK2/JAK2/LMO4	0.013	0.13	-10000	0	-0.42	71	71
IL6	-0.054	0.2	-10000	0	-0.56	117	117
PIAS3	0.027	0.007	-10000	0	-10000	0	0
PTPRE	0.025	0.02	-10000	0	-0.39	1	1
PIAS1	0.028	0.003	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.035	0.12	-10000	0	-0.4	35	35
LMO4	0.026	0.013	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.075	0.19	-10000	0	-0.67	8	8
MCL1	0.05	0.04	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1	0.023	0.18	0.32	11	-0.59	50	61
MAP3K8	0.025	0.023	-10000	0	-0.42	2	2
FOS	0.019	0.16	0.31	15	-0.57	45	60
PRKCA	0.024	0.012	-10000	0	-10000	0	0
PTPN7	0.004	0.099	-10000	0	-0.44	41	41
HRAS	0.027	0.016	-10000	0	-0.42	1	1
PRKCB	0.019	0.067	-10000	0	-0.59	10	10
NRAS	0.026	0.008	-10000	0	-10000	0	0
RAS family/GTP	0.048	0.023	-10000	0	-10000	0	0
MAPK3	0.007	0.15	-10000	0	-0.59	43	43
MAP2K1	0.026	0.087	-10000	0	-0.6	12	12
ELK1	0.026	0.014	-10000	0	-10000	0	0
BRAF	0.019	0.065	-10000	0	-0.66	7	7
mol:GTP	0	0.003	-10000	0	-0.008	56	56
MAPK1	0.002	0.16	-10000	0	-0.54	58	58
RAF1	0.019	0.067	-10000	0	-0.67	7	7
KRAS	0.027	0.006	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.031	0.034	-10000	0	-0.29	7	7
CRKL	0.035	0.095	0.32	12	-0.46	9	21
mol:PIP3	-0.008	0.049	-10000	0	-0.65	5	5
AKT1	0.005	0.061	0.36	2	-0.5	5	7
PTK2B	0.027	0.006	-10000	0	-10000	0	0
RAPGEF1	0.039	0.097	0.35	18	-0.44	8	26
RANBP10	0.026	0.007	-10000	0	-10000	0	0
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.025	0.1	-10000	0	-0.43	38	38
MAP3K5	0.036	0.11	0.37	38	-0.47	6	44
HGF/MET/CIN85/CBL/ENDOPHILINS	0.039	0.1	-10000	0	-0.4	37	37
AP1	0.015	0.11	-10000	0	-0.39	52	52
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.026	0.016	-10000	0	-0.42	1	1
apoptosis	-0.052	0.28	-10000	0	-0.8	97	97
STAT3 (dimer)	0.016	0.075	-10000	0	-0.43	10	10
GAB1/CRKL/SHP2/PI3K	0.061	0.086	0.35	2	-0.53	3	5
INPP5D	0.022	0.048	-10000	0	-0.42	10	10
CBL/CRK	0.061	0.11	0.36	48	-0.46	10	58
PTPN11	0.027	0.006	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.027	0.007	-10000	0	-10000	0	0
PTEN	0.027	0.007	-10000	0	-10000	0	0
ELK1	0.039	0.14	0.35	120	-10000	0	120
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.013	0.049	-10000	0	-0.27	9	9
PAK1	0.008	0.071	0.5	7	-0.47	5	12
HGF/MET/RANBP10	0.026	0.099	-10000	0	-0.43	32	32
HRAS	-0.002	0.13	-10000	0	-0.46	42	42
DOCK1	0.039	0.1	0.39	17	-0.5	7	24
GAB1	0.028	0.09	0.26	2	-0.43	14	16
CRK	0.044	0.11	0.38	41	-0.47	9	50
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.005	0.14	-10000	0	-0.55	36	36
JUN	0.027	0.007	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.003	0.051	-10000	0	-0.23	37	37
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
cell morphogenesis	0.045	0.12	0.4	40	-0.53	4	44
GRB2/SHC	0.031	0.057	-10000	0	-0.34	2	2
FOS	-0.015	0.16	-10000	0	-0.62	57	57
GLMN	0.004	0.001	-10000	0	-10000	0	0
cell motility	0.038	0.14	0.35	120	-10000	0	120
HGF/MET/MUC20	0.01	0.098	-10000	0	-0.4	46	46
cell migration	0.03	0.056	-10000	0	-0.34	2	2
GRB2	0.025	0.009	-10000	0	-10000	0	0
CBL	0.027	0.023	-10000	0	-0.65	1	1
MET/RANBP10	0.033	0.033	-10000	0	-0.29	7	7
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.017	0.072	-10000	0	-0.32	30	30
MET/MUC20	0.016	0.029	-10000	0	-0.29	7	7
RAP1B	0.05	0.12	0.44	39	-0.46	5	44
RAP1A	0.042	0.1	0.44	17	-0.48	4	21
HGF/MET/RANBP9	0.023	0.1	-10000	0	-0.42	38	38
RAF1	0.005	0.13	0.35	1	-0.54	16	17
STAT3	0.012	0.072	-10000	0	-0.44	10	10
cell proliferation	0.022	0.093	0.28	4	-0.4	28	32
RPS6KB1	0.008	0.046	-10000	0	-0.39	9	9
MAPK3	0.024	0.12	0.48	33	-10000	0	33
MAPK1	0.035	0.16	0.56	49	-10000	0	49
RANBP9	0.027	0.007	-10000	0	-10000	0	0
MAPK8	0.046	0.15	0.43	62	-0.47	12	74
SRC	0.014	0.065	-10000	0	-0.46	6	6
PI3K	0.033	0.056	-10000	0	-0.3	1	1
MET/Glomulin	0.011	0.037	-10000	0	-0.25	7	7
SOS1	0.027	0.006	-10000	0	-10000	0	0
MAP2K1	0.021	0.13	0.38	13	-0.51	14	27
MET	0.021	0.04	-10000	0	-0.42	7	7
MAP4K1	0.036	0.11	0.35	36	-0.47	8	44
PTK2	0.027	0.005	-10000	0	-10000	0	0
MAP2K2	0.02	0.13	0.36	12	-0.51	14	26
BAD	0.008	0.072	0.5	7	-0.45	6	13
MAP2K4	0.047	0.13	0.42	63	-0.44	5	68
SHP2/GRB2/SOS1/GAB1	0.033	0.074	-10000	0	-0.46	5	5
INPPL1	0.028	0.004	-10000	0	-10000	0	0
PXN	0.027	0.006	-10000	0	-10000	0	0
SH3KBP1	0.028	0.002	-10000	0	-10000	0	0
HGS	0.003	0.046	-10000	0	-0.28	4	4
PLCgamma1/PKC	0.02	0.005	-10000	0	-10000	0	0
HGF	-0.007	0.14	-10000	0	-0.59	45	45
RASA1	0.027	0.023	-10000	0	-0.65	1	1
NCK1	0.027	0.006	-10000	0	-10000	0	0
PTPRJ	0.028	0.004	-10000	0	-10000	0	0
NCK/PLCgamma1	0.035	0.059	-10000	0	-0.33	1	1
PDPK1	0.002	0.06	-10000	0	-0.53	5	5
HGF/MET/SHIP	0.02	0.11	-10000	0	-0.43	37	37

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.041	0.068	0.36	1	-10000	0	1
CRKL	0.016	0.12	0.37	33	-10000	0	33
mol:DAG	0.01	0.067	-10000	0	-0.36	1	1
HRAS	0.029	0.12	0.36	59	-10000	0	59
MAPK8	-0.006	0.11	0.25	1	-0.39	2	3
RAP1A	0.019	0.12	0.38	40	-10000	0	40
GAB1	0.017	0.12	0.38	33	-10000	0	33
MAPK14	-0.003	0.11	0.25	1	-0.38	1	2
EPO	-0.067	0.18	-10000	0	-0.41	184	184
PLCG1	0.01	0.068	-10000	0	-0.36	1	1
EPOR/TRPC2/IP3 Receptors	0.023	0.026	-10000	0	-10000	0	0
RAPGEF1	0.028	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.014	0.12	-10000	0	-0.39	7	7
GAB1/SHC/GRB2/SOS1	0.022	0.094	-10000	0	-10000	0	0
EPO/EPOR (dimer)	-0.029	0.13	-10000	0	-0.29	183	183
IRS2	0.014	0.12	0.38	37	-0.35	1	38
STAT1	0.015	0.071	-10000	0	-0.35	2	2
STAT5B	0.012	0.069	-10000	0	-0.4	1	1
cell proliferation	-0.003	0.12	0.39	12	-0.35	2	14
GAB1/SHIP/PIK3R1/SHP2/SHC	0.003	0.079	-10000	0	-10000	0	0
TEC	0.018	0.12	0.37	34	-10000	0	34
SOCS3	0.02	0.052	-10000	0	-0.44	10	10
STAT1 (dimer)	0.017	0.072	-10000	0	-0.34	2	2
JAK2	0.022	0.026	-10000	0	-10000	0	0
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.024	0.1	-10000	0	-10000	0	0
EPO/EPOR	-0.029	0.13	-10000	0	-0.29	183	183
LYN	0.028	0.024	-10000	0	-0.65	1	1
TEC/VAV2	0.019	0.097	0.28	10	-10000	0	10
elevation of cytosolic calcium ion concentration	0.023	0.026	-10000	0	-10000	0	0
SHC1	0.026	0.016	-10000	0	-0.42	1	1
EPO/EPOR (dimer)/LYN	-0.004	0.12	-10000	0	-0.44	1	1
mol:IP3	0.01	0.067	-10000	0	-0.36	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.028	0.12	0.35	27	-10000	0	27
SH2B3	0.02	0.023	-10000	0	-10000	0	0
NFKB1	-0.003	0.11	-10000	0	-0.48	2	2
EPO/EPOR (dimer)/JAK2/SOCS3	-0.016	0.058	-10000	0	-0.26	3	3
PTPN6	0.003	0.097	0.3	4	-10000	0	4
TEC/VAV2/GRB2	0.02	0.096	-10000	0	-10000	0	0
EPOR	0.023	0.026	-10000	0	-10000	0	0
INPP5D	0.022	0.048	-10000	0	-0.42	10	10
mol:GDP	0.022	0.094	-10000	0	-10000	0	0
SOS1	0.027	0.006	-10000	0	-10000	0	0
PLCG2	0.005	0.11	-10000	0	-0.51	35	35
CRKL/CBL/C3G	0.027	0.1	0.29	10	-0.47	1	11
VAV2	0.02	0.12	0.38	38	-10000	0	38
CBL	0.018	0.12	0.38	35	-0.5	1	36
SHC/Grb2/SOS1	0.002	0.08	-10000	0	-10000	0	0
STAT5A	0.012	0.069	-10000	0	-0.4	1	1
GRB2	0.025	0.009	-10000	0	-10000	0	0
STAT5 (dimer)	0.028	0.078	-10000	0	-10000	0	0
LYN/PLCgamma2	0.023	0.082	-10000	0	-0.36	36	36
PTPN11	0.027	0.006	-10000	0	-10000	0	0
BTK	-0.029	0.16	0.39	36	-0.35	55	91
BCL2	0.043	0.08	0.42	4	-0.75	1	5

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.023	0.01	-10000	0	-10000	0	0
AES	0.025	0.008	-10000	0	-10000	0	0
FBXW11	0.027	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.035	0.026	-10000	0	-0.39	2	2
SMAD4	0.028	0.005	-10000	0	-10000	0	0
DKK2	0.002	0.11	-10000	0	-0.49	42	42
TLE1	0.025	0.008	-10000	0	-10000	0	0
MACF1	0.027	0.008	-10000	0	-10000	0	0
CTNNB1	0.059	0.12	0.41	44	-0.35	1	45
WIF1	0.006	0.047	-10000	0	-0.45	7	7
beta catenin/RanBP3	0.004	0.065	0.33	6	-10000	0	6
KREMEN2	-0.023	0.14	-10000	0	-0.42	92	92
DKK1	0.007	0.093	-10000	0	-0.44	36	36
beta catenin/beta TrCP1	0.06	0.11	0.39	38	-10000	0	38
FZD1	0.024	0.029	-10000	0	-0.53	2	2
AXIN2	0.035	0.16	0.56	52	-1.5	2	54
AXIN1	0.027	0.007	-10000	0	-10000	0	0
RAN	0.027	0.006	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.029	0.067	-10000	0	-0.53	9	9
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.045	0.093	0.28	2	-0.5	7	9
Axin1/APC/GSK3	0.055	0.075	0.3	16	-0.36	1	17
Axin1/APC/GSK3/beta catenin/Macf1	0.046	0.088	0.38	18	-10000	0	18
HNF1A	0.012	0.091	-10000	0	-0.66	16	16
CTBP1	0.025	0.008	-10000	0	-10000	0	0
MYC	0.002	0.1	0.56	13	-1.4	1	14
RANBP3	0.028	0.003	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.006	0.11	-10000	0	-0.43	14	14
NKD1	-0.14	0.29	-10000	0	-0.65	213	213
TCF4	0.021	0.049	-10000	0	-0.61	5	5
TCF3	0.025	0.008	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.043	0.072	-10000	0	-0.38	1	1
Ran/GTP	0.02	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.004	0.087	0.4	5	-0.44	2	7
LEF1	-0.015	0.15	-10000	0	-0.56	61	61
DVL1	0.019	0.043	-10000	0	-0.42	6	6
CSNK2A1	0.027	0.007	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.052	0.1	0.33	9	-0.55	5	14
DKK1/LRP6/Kremen 2	0.008	0.11	-10000	0	-0.42	8	8
LRP6	0.027	0.006	-10000	0	-10000	0	0
CSNK1A1	0.025	0.011	-10000	0	-10000	0	0
NLK	0.026	0.009	-10000	0	-10000	0	0
CCND1	-0.007	0.091	0.74	2	-1.5	1	3
WNT1	-0.004	0.11	-10000	0	-0.42	58	58
GSK3A	0.029	0.004	-10000	0	-10000	0	0
GSK3B	0.027	0.006	-10000	0	-10000	0	0
FRAT1	0.026	0.007	-10000	0	-10000	0	0
PPP2R5D	0.068	0.16	0.33	194	-0.39	35	229
APC	0.034	0.095	0.36	29	-0.36	1	30
WNT1/LRP6/FZD1	0.023	0.038	0.25	1	-0.28	1	2
CREBBP	0.024	0.01	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.014	0.089	0.56	20	-10000	0	20
PI3K Class IB/PDE3B	0.014	0.089	-10000	0	-0.56	20	20
PDE3B	0.014	0.089	-10000	0	-0.56	20	20

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.035	0.027	-10000	0	-10000	0	0
BIRC5	-0.1	0.2	-10000	0	-0.42	256	256
NFKBIA	0.02	0.026	0.26	2	-10000	0	2
CPEB1	-0.058	0.21	-10000	0	-0.57	120	120
AKT1	0.02	0.025	0.26	1	-10000	0	1
NDEL1	0.025	0.009	-10000	0	-10000	0	0
Aurora A/BRCA1	0.027	0.028	-10000	0	-0.32	1	1
NDEL1/TACC3	0.043	0.038	-10000	0	-0.3	4	4
GADD45A	0.027	0.007	-10000	0	-10000	0	0
GSK3B	0.029	0.012	-10000	0	-10000	0	0
PAK1/Aurora A	0.038	0.03	-10000	0	-0.27	1	1
MDM2	0.027	0.006	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.069	0.14	0.21	10	-0.29	251	261
TP53	0.025	0.024	-10000	0	-0.29	1	1
DLG7	0.018	0.025	-10000	0	-0.27	1	1
AURKAIP1	0.024	0.036	-10000	0	-0.57	3	3
ARHGEF7	0.027	0.006	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.046	0.04	-10000	0	-0.32	4	4
G2/M transition of mitotic cell cycle	0.027	0.028	-10000	0	-0.31	1	1
AURKA	0.027	0.032	-10000	0	-0.32	1	1
AURKB	-0.027	0.062	-10000	0	-0.32	13	13
CDC25B	0.026	0.024	-10000	0	-10000	0	0
G2/M transition checkpoint	0.013	0.019	-10000	0	-0.24	1	1
mRNA polyadenylation	-0.016	0.13	-10000	0	-0.38	80	80
Aurora A/CPEB	-0.016	0.13	-10000	0	-0.38	80	80
Aurora A/TACC1/TRAP/chTOG	0.065	0.037	-10000	0	-0.35	1	1
BRCA1	0.023	0.031	-10000	0	-0.42	4	4
centrosome duplication	0.038	0.03	-10000	0	-0.27	1	1
regulation of centrosome cycle	0.041	0.037	-10000	0	-0.29	4	4
spindle assembly	0.063	0.036	-10000	0	-0.35	1	1
TDRD7	0.028	0.004	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	-0.016	0.12	-10000	0	-0.41	6	6
CENPA	-0.016	0.056	-10000	0	-0.35	9	9
Aurora A/PP2A	0.035	0.025	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.022	0.024	-10000	0	-10000	0	0
negative regulation of DNA binding	0.025	0.025	-10000	0	-0.28	1	1
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.037	0.014	-10000	0	-10000	0	0
RASA1	0.027	0.023	-10000	0	-0.65	1	1
Ajuba/Aurora A	0.013	0.019	-10000	0	-0.24	1	1
mitotic prometaphase	0.013	0.02	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.032	-10000	0	-0.32	1	1
TACC1	0.026	0.024	-10000	0	-0.65	1	1
TACC3	0.024	0.04	-10000	0	-0.42	7	7
Aurora A/Antizyme1	0.049	0.037	-10000	0	-0.37	2	2
Aurora A/RasGAP	0.037	0.033	-10000	0	-0.34	2	2
OAZ1	0.028	0.015	-10000	0	-0.42	1	1
RAN	0.027	0.006	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.03	0.011	-10000	0	-10000	0	0
GIT1	0.025	0.009	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.05	0.02	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.069	0.14	0.21	10	-0.29	251	261
PPP2R5D	0.026	0.007	-10000	0	-10000	0	0
Aurora A/TPX2	-0.039	0.11	-10000	0	-0.31	13	13
PAK1	0.028	0.003	-10000	0	-10000	0	0
CKAP5	0.028	0.004	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.002	0.018	0.26	1	-10000	0	1
RFC1	0.003	0.017	0.25	1	-10000	0	1
PRKDC	0.003	0.02	0.26	2	-10000	0	2
RIPK1	0.027	0.008	-10000	0	-10000	0	0
CASP7	0.001	0.091	-10000	0	-0.63	15	15
FASLG/FAS/FADD/FAF1	-0.027	0.072	0.25	9	-10000	0	9
MAP2K4	-0.057	0.21	0.34	5	-0.77	50	55
mol:ceramide	-0.032	0.087	-10000	0	-0.41	2	2
GSN	0.002	0.018	0.26	1	-10000	0	1
FASLG/FAS/FADD/FAF1/Caspase 8	-0.032	0.075	0.24	1	-10000	0	1
FAS	0.022	0.028	-10000	0	-0.67	1	1
BID	-0.004	0.026	-10000	0	-10000	0	0
MAP3K1	-0.03	0.16	0.3	6	-0.58	50	56
MAP3K7	0.026	0.008	-10000	0	-10000	0	0
RB1	0.002	0.018	0.25	1	-10000	0	1
CFLAR	0.028	0.007	-10000	0	-10000	0	0
HGF/MET	0.014	0.12	-10000	0	-0.44	55	55
ARHGDIB	0.002	0.022	0.26	2	-10000	0	2
FADD	0.023	0.015	-10000	0	-10000	0	0
actin filament polymerization	-0.003	0.022	-10000	0	-0.24	2	2
NFKB1	-0.016	0.088	-10000	0	-0.61	8	8
MAPK8	-0.074	0.23	0.34	8	-0.58	115	123
DFFA	0.003	0.017	0.25	1	-10000	0	1
DNA fragmentation during apoptosis	0.003	0.02	0.23	2	-10000	0	2
FAS/FADD/MET	0.041	0.037	-10000	0	-0.26	2	2
CFLAR/RIP1	0.04	0.013	-10000	0	-10000	0	0
FAIM3	-0.004	0.11	-10000	0	-0.42	62	62
FAF1	0.021	0.021	-10000	0	-0.35	1	1
PARP1	0.002	0.018	0.25	1	-10000	0	1
DFFB	0.003	0.017	0.25	1	-10000	0	1
CHUK	-0.013	0.078	-10000	0	-0.56	7	7
FASLG	-0.14	0.21	-10000	0	-0.42	314	314
FAS/FADD	0.032	0.029	-10000	0	-0.51	1	1
HGF	-0.007	0.14	-10000	0	-0.59	45	45
LMNA	0.003	0.021	-10000	0	-10000	0	0
CASP6	0.003	0.017	0.25	1	-10000	0	1
CASP10	0.023	0.015	-10000	0	-10000	0	0
CASP3	0.003	0.023	0.31	1	-10000	0	1
PTPN13	0.01	0.11	-10000	0	-0.65	23	23
CASP8	-0.002	0.048	-10000	0	-10000	0	0
IL6	-0.14	0.41	-10000	0	-1.3	99	99
MET	0.021	0.04	-10000	0	-0.42	7	7
ICAD/CAD	0.005	0.018	0.22	1	-10000	0	1
FASLG/FAS/FADD/FAF1/Caspase 10	-0.033	0.088	-10000	0	-0.41	2	2
activation of caspase activity by cytochrome c	-0.004	0.025	-10000	0	-10000	0	0
PAK2	0.003	0.018	0.25	1	-10000	0	1
BCL2	0.027	0.023	-10000	0	-0.65	1	1

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.021	0.034	0.29	2	-10000	0	2
DAPP1	0.005	0.13	0.34	17	-0.41	41	58
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.042	0.17	0.32	6	-0.53	51	57
mol:DAG	-0.011	0.12	0.33	46	-0.28	4	50
HRAS	0.029	0.017	-10000	0	-0.42	1	1
RAP1A	0.028	0.01	-10000	0	-10000	0	0
ARF5/GDP	0.015	0.078	0.27	2	-0.38	15	17
PLCG2	0.005	0.11	-10000	0	-0.51	35	35
PLCG1	0.027	0.007	-10000	0	-10000	0	0
ARF5	0.025	0.01	-10000	0	-10000	0	0
mol:GTP	0.001	0.046	0.3	4	-10000	0	4
ARF1/GTP	0.012	0.038	0.38	1	-10000	0	1
RHOA	0.026	0.008	-10000	0	-10000	0	0
YES1	0.028	0.005	-10000	0	-10000	0	0
RAP1A/GTP	0.023	0.044	0.3	3	-0.32	6	9
ADAP1	0.009	0.049	0.28	3	-0.35	3	6
ARAP3	0.001	0.046	0.3	4	-0.32	6	10
INPPL1	0.028	0.004	-10000	0	-10000	0	0
PREX1	0.025	0.033	-10000	0	-0.65	2	2
ARHGEF6	0.028	0.001	-10000	0	-10000	0	0
ARHGEF7	0.027	0.006	-10000	0	-10000	0	0
ARF1	0.027	0.007	-10000	0	-10000	0	0
NRAS	0.028	0.01	-10000	0	-10000	0	0
FYN	0.026	0.007	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
FGR	0.021	0.053	-10000	0	-0.44	11	11
mol:Ca2+	0.004	0.076	0.33	24	-10000	0	24
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.026	0.024	-10000	0	-0.65	1	1
ZAP70	-0.12	0.21	-10000	0	-0.42	299	299
mol:IP3	-0.001	0.089	0.34	26	-10000	0	26
LYN	0.026	0.024	-10000	0	-0.65	1	1
ARF1/GDP	0.027	0.084	0.27	10	-0.37	15	25
RhoA/GDP	0.034	0.062	0.33	8	-10000	0	8
PDK1/Src/Hsp90	0.051	0.019	-10000	0	-10000	0	0
BLNK	0.017	0.079	-10000	0	-0.65	12	12
actin cytoskeleton reorganization	0.034	0.1	0.38	26	-0.39	2	28
SRC	0.027	0.007	-10000	0	-10000	0	0
PLEKHA2	0.009	0.028	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
PTEN	0.022	0.013	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
ARF6/GTP	0.025	0.04	0.29	1	-10000	0	1
RhoA/GTP	0.021	0.04	0.3	4	-10000	0	4
Src family/SYK family/BLNK-LAT	-0.047	0.14	-10000	0	-0.44	47	47
BLK	-0.001	0.1	-10000	0	-0.42	48	48
PDPK1	0.027	0.007	-10000	0	-10000	0	0
CYTH1	0.014	0.051	0.3	9	-10000	0	9
HCK	-0.006	0.12	-10000	0	-0.42	63	63
CYTH3	0.01	0.043	0.28	3	-10000	0	3
CYTH2	0.015	0.053	0.29	7	-10000	0	7
KRAS	0.028	0.009	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.027	0.043	-10000	0	-0.51	2	2
SGK1	0.027	0.056	-10000	0	-0.55	2	2
INPP5D	0.022	0.048	-10000	0	-0.42	10	10
mol:GDP	0.015	0.086	0.26	13	-0.38	19	32
SOS1	0.027	0.006	-10000	0	-10000	0	0
SYK	0.024	0.048	-10000	0	-0.59	5	5
ARF6/GDP	0.029	0.062	0.29	12	-10000	0	12
mol:PI-3-4-5-P3	0.009	0.04	-10000	0	-10000	0	0
ARAP3/RAP1A/GTP	0.023	0.044	0.3	3	-0.32	6	9
VAV1	-0.069	0.18	-10000	0	-0.42	191	191
mol:PI-3-4-P2	0.015	0.034	-10000	0	-0.29	10	10
RAS family/GTP/PI3K Class I	0.047	0.05	-10000	0	-0.32	6	6
PLEKHA1	0.009	0.028	-10000	0	-10000	0	0
Rac1/GDP	0.015	0.078	0.27	2	-0.37	17	19
LAT	-0.047	0.16	-10000	0	-0.42	145	145
Rac1/GTP	0.017	0.056	-10000	0	-0.57	1	1
ITK	-0.03	0.09	0.28	4	-10000	0	4
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.03	0.13	0.32	32	-0.34	16	48
LCK	0.003	0.1	-10000	0	-0.44	44	44
BTK	-0.033	0.11	0.3	12	-10000	0	12

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.017	0.07	-10000	0	-0.42	22	22
mol:Halofuginone	0.004	0.001	-10000	0	-10000	0	0
ITGA1	0.021	0.065	-10000	0	-0.65	8	8
CDKN1A	0.01	0.083	-10000	0	-0.42	22	22
PRL-3/alpha Tubulin	0.034	0.043	-10000	0	-0.29	14	14
mol:Ca2+	-0.043	0.1	-10000	0	-0.35	80	80
AGT	-0.02	0.15	-10000	0	-0.48	83	83
CCNA2	-0.04	0.11	-10000	0	-0.4	36	36
TUBA1B	0.027	0.006	-10000	0	-10000	0	0
EGR1	-0.007	0.11	-10000	0	-0.48	48	48
CDK2/Cyclin E1	0.021	0.12	-10000	0	-0.39	45	45
MAPK3	0.013	0.039	-10000	0	-0.29	14	14
PRL-2 /Rab GGTase beta	0.039	0.01	-10000	0	-10000	0	0
MAPK1	0.014	0.039	-10000	0	-0.29	14	14
PTP4A1	-0.004	0.081	-10000	0	-0.37	41	41
PTP4A3	0.02	0.056	-10000	0	-0.42	14	14
PTP4A2	0.027	0.007	-10000	0	-10000	0	0
ITGB1	0.013	0.039	-10000	0	-0.29	14	14
SRC	0.027	0.007	-10000	0	-10000	0	0
RAC1	0.014	0.048	-10000	0	-0.45	4	4
Rab GGTase beta/Rab GGTase alpha	0.037	0.028	-10000	0	-0.49	2	2
PRL-1/ATF-5	0.022	0.095	-10000	0	-0.35	41	41
RABGGTA	0.026	0.033	-10000	0	-0.65	2	2
BCAR1	-0.012	0.029	-10000	0	-0.5	1	1
RHOC	0.01	0.076	-10000	0	-0.43	18	18
RHOA	0.001	0.085	-10000	0	-0.58	5	5
cell motility	0.02	0.09	0.29	9	-0.39	17	26
PRL-1/alpha Tubulin	0.021	0.089	-10000	0	-0.35	32	32
PRL-3/alpha1 Integrin	0.03	0.065	-10000	0	-0.37	21	21
ROCK1	0.019	0.081	0.28	5	-0.44	10	15
RABGGTB	0.027	0.007	-10000	0	-10000	0	0
CDK2	0.027	0.006	-10000	0	-10000	0	0
mitosis	-0.004	0.08	-10000	0	-0.36	41	41
ATF5	0.026	0.03	-10000	0	-0.42	4	4

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.032	0.16	0.28	5	-0.53	48	53
CaM/Ca2+	0.02	0.004	-10000	0	-10000	0	0
AKT1	0.027	0.005	-10000	0	-10000	0	0
AKT2	0.028	0.003	-10000	0	-10000	0	0
STXBP4	0.025	0.015	-10000	0	-0.35	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.033	0.18	0.33	48	-0.57	51	99
YWHAZ	0.027	0.005	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
YWHAQ	0.027	0.006	-10000	0	-10000	0	0
TBC1D4	0.018	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.027	0.005	-10000	0	-10000	0	0
YWHAB	0.027	0.007	-10000	0	-10000	0	0
SNARE/Synip	0.049	0.022	-10000	0	-10000	0	0
YWHAG	0.025	0.009	-10000	0	-10000	0	0
ASIP	-0.054	0.16	-10000	0	-0.42	142	142
PRKCI	0.027	0.006	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.02	0.004	-10000	0	-10000	0	0
RHOQ	0.027	0.006	-10000	0	-10000	0	0
GYS1	0.02	0.006	-10000	0	-10000	0	0
PRKCZ	0.024	0.04	-10000	0	-0.65	3	3
TRIP10	0.028	0.003	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.036	0.009	-10000	0	-10000	0	0
AS160/14-3-3	0.007	0.075	-10000	0	-0.4	12	12
VAMP2	0.025	0.009	-10000	0	-10000	0	0
SLC2A4	0.029	0.2	0.35	43	-0.66	51	94
STX4	0.026	0.007	-10000	0	-10000	0	0
GSK3B	0.026	0.008	-10000	0	-10000	0	0
SFN	-0.072	0.2	-10000	0	-0.44	185	185
LNPEP	0.023	0.056	-10000	0	-0.65	6	6
YWHAE	0.025	0.009	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.01	0.073	0.36	5	-10000	0	5
GNAI2	0.026	0.008	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.007	0.098	-10000	0	-0.25	125	125
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.011	0.095	-10000	0	-0.56	23	23
RhoA/GTP	0.01	0.075	-10000	0	-0.37	5	5
negative regulation of cAMP metabolic process	0.002	0.075	-10000	0	-0.32	15	15
GNAZ	0.025	0.04	-10000	0	-0.65	3	3
GNAI3	0.027	0.007	-10000	0	-10000	0	0
GNA12	0.025	0.009	-10000	0	-10000	0	0
S1PR5	-0.036	0.16	-10000	0	-0.42	125	125
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.002	0.076	-10000	0	-0.32	15	15
RhoA/GDP	0.019	0.006	-10000	0	-10000	0	0
RHOA	0.026	0.008	-10000	0	-10000	0	0
GNAI1	0.022	0.041	-10000	0	-0.65	3	3

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.002	0.12	-10000	0	-0.39	74	74
cell-cell adhesion	0.002	0.059	0.5	2	-10000	0	2
Ephrin B/EPHB2/RasGAP	0.058	0.08	-10000	0	-0.36	21	21
ITSN1	0.027	0.007	-10000	0	-10000	0	0
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
SHC1	0.026	0.016	-10000	0	-0.42	1	1
Ephrin B1/EPHB3	-0.013	0.14	-10000	0	-0.42	95	95
Ephrin B1/EPHB1	0.029	0.054	-10000	0	-0.32	19	19
HRAS/GDP	0.016	0.076	-10000	0	-0.45	3	3
Ephrin B/EPHB1/GRB7	0.052	0.092	-10000	0	-0.37	28	28
Endophilin/SYNJ1	0.019	0.074	0.35	5	-0.34	21	26
KRAS	0.027	0.006	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.054	0.085	-10000	0	-0.36	22	22
endothelial cell migration	0.049	0.024	-10000	0	-10000	0	0
GRB2	0.025	0.009	-10000	0	-10000	0	0
GRB7	0.018	0.069	-10000	0	-0.65	9	9
PAK1	0.029	0.091	0.41	19	-10000	0	19
HRAS	0.027	0.015	-10000	0	-0.42	1	1
RRAS	0.022	0.077	0.35	6	-0.34	19	25
DNM1	-0.039	0.16	-10000	0	-0.42	129	129
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.01	0.068	-10000	0	-0.34	19	19
lamellipodium assembly	-0.002	0.059	-10000	0	-0.5	2	2
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.023	0.062	-10000	0	-0.38	4	4
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
EPHB2	0.02	0.058	-10000	0	-0.45	12	12
EPHB3	-0.046	0.21	-10000	0	-0.65	95	95
EPHB1	0.015	0.083	-10000	0	-0.53	19	19
EPHB4	0.025	0.009	-10000	0	-10000	0	0
mol:GDP	0.026	0.096	0.4	25	-0.38	12	37
Ephrin B/EPHB2	0.044	0.074	-10000	0	-0.36	21	21
Ephrin B/EPHB3	0.006	0.15	-10000	0	-0.4	88	88
JNK cascade	0.023	0.079	0.36	23	-0.41	11	34
Ephrin B/EPHB1	0.041	0.08	-10000	0	-0.36	22	22
RAP1/GDP	0.049	0.1	0.38	22	-0.39	3	25
EFNB2	0.027	0.006	-10000	0	-10000	0	0
EFNB3	0.007	0.1	-10000	0	-0.57	27	27
EFNB1	0.028	0.001	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.038	0.067	-10000	0	-0.43	11	11
RAP1B	0.027	0.006	-10000	0	-10000	0	0
RAP1A	0.027	0.007	-10000	0	-10000	0	0
CDC42/GTP	0.034	0.083	-10000	0	-0.47	4	4
Rap1/GTP	0.015	0.067	-10000	0	-0.5	2	2
axon guidance	-0.002	0.12	-10000	0	-0.4	71	71
MAPK3	0.018	0.055	-10000	0	-0.41	1	1
MAPK1	0.018	0.056	-10000	0	-0.41	1	1
Rac1/GDP	0.022	0.085	0.34	3	-0.42	3	6
actin cytoskeleton reorganization	0	0.053	-10000	0	-0.4	3	3
CDC42/GDP	0.045	0.11	0.4	26	-0.41	3	29
PI3K	0.054	0.027	-10000	0	-10000	0	0
EFNA5	-0.021	0.17	-10000	0	-0.64	63	63
Ephrin B2/EPHB4	0.032	0.015	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.021	0.059	-10000	0	-0.3	21	21
CDC42	0.027	0.007	-10000	0	-10000	0	0
RAS family/GTP	0.01	0.066	-10000	0	-0.48	3	3
PTK2	0.016	0.072	0.52	17	-10000	0	17
MAP4K4	0.023	0.079	0.36	23	-0.41	11	34
SRC	0.027	0.007	-10000	0	-10000	0	0
KALRN	0.027	0.014	-10000	0	-0.35	1	1
Intersectin/N-WASP	0.035	0.016	-10000	0	-10000	0	0
neuron projection morphogenesis	0.043	0.11	0.38	55	-0.43	2	57
MAP2K1	0.021	0.059	-10000	0	-0.36	4	4
WASL	0.025	0.01	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.054	0.07	-10000	0	-0.44	10	10
cell migration	0.039	0.12	0.41	39	-0.43	2	41
NRAS	0.027	0.007	-10000	0	-10000	0	0
SYNJ1	0.019	0.075	0.35	5	-0.34	21	26
PXN	0.027	0.006	-10000	0	-10000	0	0
TF	-0.021	0.098	-10000	0	-0.41	5	5
HRAS/GTP	0.035	0.08	-10000	0	-0.52	3	3
Ephrin B1/EPHB1-2	0.038	0.066	-10000	0	-0.44	10	10
cell adhesion mediated by integrin	0.015	0.082	0.4	21	-10000	0	21
RAC1	0.025	0.01	-10000	0	-10000	0	0
mol:GTP	0.039	0.083	-10000	0	-0.36	24	24
RAC1-CDC42/GTP	-0.024	0.12	-10000	0	-0.55	15	15
RASA1	0.027	0.023	-10000	0	-0.65	1	1
RAC1-CDC42/GDP	0.033	0.084	0.33	3	-0.4	3	6
ruffle organization	0.037	0.12	0.36	63	-0.5	2	65
NCK1	0.027	0.006	-10000	0	-10000	0	0
receptor internalization	-0.016	0.095	0.34	5	-0.39	10	15
Ephrin B/EPHB2/KALRN	0.058	0.078	-10000	0	-0.36	19	19
ROCK1	-0.022	0.12	-10000	0	-0.38	92	92
RAS family/GDP	-0.013	0.05	-10000	0	-0.38	3	3
Rac1/GTP	0.005	0.065	-10000	0	-0.53	2	2
Ephrin B/EPHB1/Src/Paxillin	0.022	0.059	-10000	0	-0.34	3	3

×

Osteopontin-mediated 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
IKK alpha homodimer	0.029	0.092	-10000	0	-0.54	8	8
NF kappa B1 p50/RelA/I kappa B alpha	0.052	0.12	0.36	44	-0.55	8	52
alphaV/beta3 Integrin/Osteopontin/Src	0.034	0.072	-10000	0	-0.42	19	19
AP1	0.044	0.14	-10000	0	-0.55	20	20
ILK	0.025	0.097	-10000	0	-0.55	8	8
bone resorption	0.023	0.11	-10000	0	-0.58	9	9
PTK2B	0.027	0.006	-10000	0	-10000	0	0
PYK2/p130Cas	0.051	0.097	-10000	0	-0.55	6	6
ITGAV	0.028	0.03	-10000	0	-0.52	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.018	0.089	-10000	0	-0.33	51	51
alphaV/beta3 Integrin/Osteopontin	0.038	0.1	-10000	0	-0.46	29	29
MAP3K1	0.025	0.099	-10000	0	-0.42	29	29
JUN	0.027	0.007	-10000	0	-10000	0	0
MAPK3	0.011	0.09	0.35	1	-0.55	8	9
MAPK1	0.011	0.092	0.35	1	-0.55	9	10
Rac1/GDP	0.018	0.007	-10000	0	-10000	0	0
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
MAPK8	0.023	0.1	0.39	9	-0.5	12	21
ITGB3	0.009	0.11	-10000	0	-0.61	25	25
NFKBIA	0.011	0.094	0.35	1	-0.53	10	11
FOS	-0.014	0.16	-10000	0	-0.62	57	57
CD44	0.006	0.098	-10000	0	-0.42	43	43
CHUK	0.027	0.007	-10000	0	-10000	0	0
PLAU	-0.006	0.29	0.5	23	-1.1	49	72
NF kappa B1 p50/RelA	0.046	0.11	-10000	0	-0.56	8	8
BCAR1	0.026	0.024	-10000	0	-0.65	1	1
RELA	0.028	0.003	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.027	0.087	-10000	0	-0.47	23	23
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	0.024	0.1	-10000	0	-0.41	32	32
VAV3	0.017	0.11	0.39	8	-0.44	20	28
MAP3K14	0.017	0.093	-10000	0	-0.42	29	29
ROCK2	0.02	0.066	-10000	0	-0.62	9	9
SPP1	0.018	0.086	-10000	0	-0.58	17	17
RAC1	0.025	0.01	-10000	0	-10000	0	0
Rac1/GTP	0.016	0.09	-10000	0	-0.51	8	8
MMP2	0.017	0.12	0.38	4	-0.53	9	13

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.027	0.007	-9999	-10000	0	0
ITGB7	0.027	0.006	-9999	-10000	0	0
ITGA4	0.012	0.08	-9999	-0.42	29	29
alpha4/beta7 Integrin	0.027	0.06	-9999	-0.29	29	29
alpha4/beta1 Integrin	0.028	0.06	-9999	-0.29	29	29

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.021	0.041	-10000	0	-10000	0	0
CRKL	0.027	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.007	-10000	0	-10000	0	0
DOCK1	0.026	0.024	-10000	0	-0.65	1	1
ITGA4	0.012	0.08	-10000	0	-0.42	29	29
alpha4/beta7 Integrin/MAdCAM1	0.036	0.082	-10000	0	-0.43	1	1
EPO	-0.076	0.18	-10000	0	-0.42	184	184
alpha4/beta7 Integrin	0.027	0.06	-10000	0	-0.29	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.028	0.06	-10000	0	-0.29	29	29
EPO/EPOR (dimer)	-0.035	0.13	-10000	0	-0.29	184	184
lamellipodium assembly	0.022	0.057	-10000	0	-0.52	3	3
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
PI3K	0.039	0.011	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
JAK2	-0.008	0.069	-10000	0	-0.48	1	1
PXN	0.027	0.006	-10000	0	-10000	0	0
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
MADCAM1	-0.005	0.1	-10000	0	-0.42	52	52
cell adhesion	0.035	0.081	-10000	0	-0.42	1	1
CRKL/CBL	0.04	0.02	-10000	0	-0.49	1	1
ITGB1	0.027	0.007	-10000	0	-10000	0	0
SRC	-0.005	0.086	-10000	0	-0.4	14	14
ITGB7	0.027	0.006	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.018	0.1	-10000	0	-0.43	17	17
p130Cas/Crk/Dock1	0.017	0.083	0.35	1	-0.68	1	2
VCAM1	-0.012	0.13	-10000	0	-0.43	74	74
RHOA	0.026	0.008	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.052	0.057	-10000	0	-10000	0	0
BCAR1	-0.009	0.08	0.38	1	-0.41	12	13
EPOR	0.028	0.003	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.027	0.023	-10000	0	-0.65	1	1
GIT1	0.025	0.009	-10000	0	-10000	0	0
Rac1/GTP	0.022	0.059	-10000	0	-0.64	2	2

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.032	0.052	-10000	0	-0.27	6	6
RGS9BP	0.014	0.093	-10000	0	-0.63	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	-0.009	0.032	-10000	0	-0.46	3	3
mol:Na +	0.012	0.062	-10000	0	-0.25	47	47
mol:ADP	-0.01	0.029	-10000	0	-0.32	6	6
GNAT2	0.02	0.017	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.025	0.1	-10000	0	-0.36	48	48
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.028	0.014	-10000	0	-0.24	1	1
GRK7	0.01	0.033	-10000	0	-0.42	3	3
CNGB3	-0.021	0.093	-10000	0	-0.42	42	42
Cone Metarhodopsin II/X-Arrestin	0.015	0.003	-10000	0	-10000	0	0
mol:Ca2+	-0.029	0.073	0.26	1	-0.3	42	43
Cone PDE6	0.04	0.095	-10000	0	-0.37	31	31
Cone Metarhodopsin II	0.024	0.024	-10000	0	-0.24	6	6
Na + (4 Units)	0.014	0.083	-10000	0	-0.29	49	49
GNAT2/GDP	0.034	0.09	-10000	0	-0.37	31	31
GNB5	0.028	0.003	-10000	0	-10000	0	0
mol:GMP (4 units)	0.001	0.02	-10000	0	-0.22	3	3
Cone Transducin	0.035	0.056	-10000	0	-0.23	29	29
SLC24A2	-0.024	0.079	-10000	0	-0.42	33	33
GNB3/GNGT2	0.024	0.066	-10000	0	-0.31	31	31
GNB3	0.01	0.081	-10000	0	-0.42	30	30
GNAT2/GTP	0.019	0.006	-10000	0	-10000	0	0
CNGA3	-0.006	0.037	-10000	0	-0.42	5	5
ARR3	-0.007	0.02	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.012	0.063	-10000	0	-0.25	47	47
mol:Pi	0.025	0.1	-10000	0	-0.36	48	48
Cone CNG Channel	0.034	0.061	-10000	0	-0.4	1	1
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	-0.024	0.079	-10000	0	-0.42	33	33
RGS9	0.001	0.11	-10000	0	-0.49	41	41
PDE6C	0	0.03	-10000	0	-0.42	2	2
GNGT2	0.023	0.032	-10000	0	-0.5	3	3
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	-0.005	0.025	-10000	0	-0.42	1	1

×

PDGFR-beta signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0	0.095	0.41	1	-0.48	13	14
PDGFB-D/PDGFRB/SLAP	0.014	0.097	-10000	0	-0.34	58	58
PDGFB-D/PDGFRB/APS/CBL	0.039	0.057	-10000	0	-0.34	12	12
AKT1	0.062	0.13	0.47	60	-10000	0	60
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.009	0.11	0.36	8	-0.48	18	26
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
FGR	-0.009	0.13	0.31	3	-0.44	52	55
mol:Ca2+	0.027	0.1	0.34	17	-0.51	18	35
MYC	0.05	0.13	0.46	34	-0.69	2	36
SHC1	0.026	0.016	-10000	0	-0.42	1	1
HRAS/GDP	0.034	0.053	-10000	0	-0.36	11	11
LRP1/PDGFRB/PDGFB	0.043	0.062	-10000	0	-0.41	14	14
GRB10	0.025	0.009	-10000	0	-10000	0	0
PTPN11	0.027	0.006	-10000	0	-10000	0	0
GO:0007205	0.027	0.1	0.34	15	-0.52	18	33
PTEN	0.027	0.007	-10000	0	-10000	0	0
GRB2	0.025	0.009	-10000	0	-10000	0	0
GRB7	0.018	0.069	-10000	0	-0.65	9	9
PDGFB-D/PDGFRB/SHP2	0.031	0.063	-10000	0	-0.47	13	13
PDGFB-D/PDGFRB/GRB10	0.029	0.053	-10000	0	-0.39	11	11
cell cycle arrest	0.014	0.097	-10000	0	-0.34	58	58
HRAS	0.027	0.015	-10000	0	-0.42	1	1
HIF1A	0.055	0.13	0.46	60	-10000	0	60
GAB1	0.025	0.11	0.34	23	-0.48	18	41
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.024	0.11	0.37	26	-0.47	12	38
PDGFB-D/PDGFRB	0.045	0.057	-10000	0	-0.42	10	10
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.031	0.063	-10000	0	-0.47	13	13
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.001	0.089	-10000	0	-0.51	8	8
positive regulation of MAPKKK cascade	0.031	0.063	-10000	0	-0.47	13	13
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
mol:IP3	0.027	0.11	0.35	15	-0.52	18	33
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.027	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.024	0.079	-10000	0	-0.45	22	22
SHB	0.028	0.004	-10000	0	-10000	0	0
BLK	-0.003	0.095	-10000	0	-0.41	16	16
PTPN2	0.028	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.032	0.063	-10000	0	-0.47	13	13
BCAR1	0.026	0.024	-10000	0	-0.65	1	1
VAV2	0.027	0.12	0.36	24	-0.48	18	42
CBL	0.027	0.023	-10000	0	-0.65	1	1
PDGFB-D/PDGFRB/DEP1	0.032	0.063	-10000	0	-0.47	13	13
LCK	-0.014	0.13	0.32	2	-0.53	25	27
PDGFRB	0.018	0.081	-10000	0	-0.64	13	13
ACP1	0.027	0.006	-10000	0	-10000	0	0
HCK	0.008	0.072	-10000	0	-0.48	8	8
ABL1	0.023	0.11	0.33	24	-0.46	19	43
PDGFB-D/PDGFRB/CBL	0.02	0.11	0.36	3	-0.53	21	24
PTPN1	0.027	0.007	-10000	0	-10000	0	0
SNX15	0.028	0.003	-10000	0	-10000	0	0
STAT3	0.025	0.009	-10000	0	-10000	0	0
STAT1	0.026	0.022	-10000	0	-0.42	2	2
cell proliferation	0.05	0.13	0.44	38	-0.52	3	41
SLA	0.004	0.1	-10000	0	-0.42	47	47
actin cytoskeleton reorganization	0.044	0.065	0.35	13	-10000	0	13
SRC	0.015	0.062	-10000	0	-0.43	9	9
PI3K	0.01	0.034	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.037	0.073	-10000	0	-0.41	19	19
SH2B2	0.022	0.038	-10000	0	-0.42	6	6
PLCgamma1/SPHK1	0.009	0.11	0.37	8	-0.5	18	26
LYN	0.01	0.08	-10000	0	-0.41	17	17
LRP1	0.027	0.006	-10000	0	-10000	0	0
SOS1	0.027	0.006	-10000	0	-10000	0	0
STAT5B	0.025	0.009	-10000	0	-10000	0	0
STAT5A	0.025	0.009	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.065	0.056	-10000	0	-0.35	2	2
SPHK1	-0.04	0.16	-10000	0	-0.42	131	131
EDG1	0.001	0.004	-10000	0	-10000	0	0
mol:DAG	0.027	0.11	0.35	15	-0.52	18	33
PLCG1	0.027	0.11	0.35	15	-0.54	18	33
NHERF/PDGFRB	0.041	0.055	-10000	0	-0.42	9	9
YES1	0.008	0.1	0.32	2	-0.54	22	24
cell migration	0.04	0.055	-10000	0	-0.42	9	9
SHC/Grb2/SOS1	0.064	0.057	-10000	0	-0.35	2	2
SLC9A3R2	0.026	0.024	-10000	0	-0.65	1	1
SLC9A3R1	0.025	0.009	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.052	0.056	-10000	0	-0.38	9	9
FYN	-0.009	0.12	-10000	0	-0.43	49	49
DOK1	0.023	0.056	-10000	0	-0.38	10	10
HRAS/GTP	0.02	0.011	-10000	0	-0.29	1	1
PDGFB	0.026	0.033	-10000	0	-0.65	2	2
RAC1	0.05	0.13	0.46	31	-0.51	7	38
PRKCD	0.021	0.059	-10000	0	-0.38	9	9
FER	0.022	0.058	-10000	0	-0.38	12	12
MAPKKK cascade	0.026	0.094	0.41	29	-10000	0	29
RASA1	0.024	0.058	-10000	0	-0.38	11	11
NCK1	0.027	0.006	-10000	0	-10000	0	0
NCK2	0.027	0.006	-10000	0	-10000	0	0
p62DOK/Csk	0.039	0.057	-10000	0	-0.36	10	10
PDGFB-D/PDGFRB/SHB	0.032	0.063	-10000	0	-0.47	13	13
chemotaxis	0.023	0.11	0.33	24	-0.44	19	43
STAT1-3-5/STAT1-3-5	0.053	0.05	-10000	0	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.012	0.06	-10000	0	-0.47	13	13
PTPRJ	0.028	0.004	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	0.008	0.007	-10000	0	-10000	0	0
RAS family/GTP	-0.004	0.12	-10000	0	-0.57	16	16
NFATC4	0.004	0.089	0.31	29	-0.38	5	34
ERBB2IP	0.027	0.007	-10000	0	-10000	0	0
HSP90 (dimer)	0.027	0.005	-10000	0	-10000	0	0
mammary gland morphogenesis	0.004	0.085	-10000	0	-0.38	13	13
JUN	0.019	0.078	0.37	15	-0.34	3	18
HRAS	0.027	0.015	-10000	0	-0.42	1	1
DOCK7	-0.001	0.083	0.29	2	-0.5	3	5
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.019	0.1	-10000	0	-0.4	44	44
AKT1	0.01	0.006	-10000	0	-10000	0	0
BAD	0.007	0.018	-10000	0	-0.34	2	2
MAPK10	0.006	0.063	0.2	14	-0.29	10	24
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.005	0.092	0.32	1	-0.42	13	14
RAF1	-0.016	0.11	0.45	8	-0.57	13	21
ErbB2/ErbB3/neuregulin 2	0.008	0.087	-10000	0	-0.42	19	19
STAT3	-0.004	0.18	-10000	0	-0.86	37	37
cell migration	0.03	0.11	0.33	64	-0.28	8	72
mol:PI-3-4-5-P3	0	0.003	-10000	0	-10000	0	0
cell proliferation	-0.065	0.17	0.53	8	-0.57	16	24
FOS	-0.05	0.16	0.48	11	-0.5	57	68
NRAS	0.026	0.007	-10000	0	-10000	0	0
mol:Ca2+	0.004	0.085	-10000	0	-0.38	13	13
MAPK3	-0.048	0.15	0.48	8	-0.55	10	18
MAPK1	-0.054	0.16	0.48	9	-0.61	21	30
JAK2	-0.001	0.082	0.29	2	-0.51	3	5
NF2	0.013	0.037	-10000	0	-0.71	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.006	0.13	0.23	2	-0.41	62	64
NRG1	-0.001	0.13	-10000	0	-0.6	39	39
GRB2/SOS1	0.037	0.013	-10000	0	-10000	0	0
MAPK8	0.002	0.084	0.3	2	-0.34	22	24
MAPK9	0.009	0.055	0.22	13	-0.26	2	15
ERBB2	-0.015	0.019	-10000	0	-0.5	1	1
ERBB3	0.013	0.094	-10000	0	-0.65	17	17
SHC1	0.026	0.016	-10000	0	-0.42	1	1
RAC1	0.025	0.01	-10000	0	-10000	0	0
apoptosis	-0.004	0.017	0.32	1	-0.16	2	3
STAT3 (dimer)	-0.003	0.18	-10000	0	-0.84	37	37
RNF41	0.005	0.006	-10000	0	-10000	0	0
FRAP1	0.004	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.001	0.057	-10000	0	-0.35	3	3
ErbB2/ErbB2/HSP90 (dimer)	0.016	0.018	-10000	0	-0.43	1	1
CHRNA1	-0.078	0.16	0.45	10	-0.46	19	29
myelination	0.01	0.12	0.41	41	-0.38	4	45
PPP3CB	0	0.078	0.28	2	-0.46	3	5
KRAS	0.026	0.006	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.016	0.12	-10000	0	-0.53	20	20
NRG2	0.001	0.11	-10000	0	-0.43	49	49
mol:GDP	-0.006	0.12	0.23	2	-0.4	62	64
SOS1	0.026	0.006	-10000	0	-10000	0	0
MAP2K2	-0.026	0.11	0.38	6	-0.54	12	18
SRC	0.027	0.007	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	0.001	0.084	0.29	2	-0.51	3	5
MAP2K1	-0.052	0.16	0.48	4	-0.58	18	22
heart morphogenesis	0.004	0.085	-10000	0	-0.38	13	13
RAS family/GDP	0.026	0.12	-10000	0	-0.57	16	16
GRB2	0.025	0.009	-10000	0	-10000	0	0
PRKACA	0.014	0.038	-10000	0	-0.75	2	2
CHRNE	0.013	0.032	0.16	22	-0.15	5	27
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
activation of caspase activity	-0.01	0.006	-10000	0	-10000	0	0
nervous system development	0.004	0.085	-10000	0	-0.38	13	13
CDC42	0.027	0.007	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.02	0.004	-10000	0	-10000	0	0
PRKCZ	0.024	0.04	-10000	0	-0.65	3	3
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.027	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.015	0.06	-10000	0	-0.37	4	4
IRAK/TOLLIP	0.034	0.009	-10000	0	-10000	0	0
IKBKB	0.027	0.006	-10000	0	-10000	0	0
IKBKG	0.028	0.002	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.078	0.21	-10000	0	-0.45	203	203
IL1A	0.002	0.093	-10000	0	-0.42	40	40
IL1B	0.009	0.062	-10000	0	-0.37	21	21
IRAK/TRAF6/p62/Atypical PKCs	0.063	0.044	-10000	0	-0.33	2	2
IL1R2	-0.11	0.26	-10000	0	-0.6	189	189
IL1R1	0.026	0.03	-10000	0	-0.45	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.016	0.046	-10000	0	-0.38	2	2
TOLLIP	0.028	0.004	-10000	0	-10000	0	0
TICAM2	0.026	0.024	-10000	0	-0.65	1	1
MAP3K3	0.025	0.009	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.018	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0.041	0.062	-10000	0	-10000	0	0
JUN	0.013	0.039	0.33	4	-0.3	4	8
MAP3K7	0.027	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.06	0.06	-10000	0	-0.35	7	7
IL1 alpha/IL1R1/IL1RAP/MYD88	0.046	0.07	-10000	0	-0.39	2	2
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.054	0.071	-10000	0	-0.37	2	2
IL1 beta fragment/IL1R1/IL1RAP	0.036	0.06	-10000	0	-0.38	8	8
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
MAPK8	0.016	0.04	0.34	4	-0.32	4	8
IRAK1	0.018	0.004	-10000	0	-10000	0	0
IL1RN/IL1R1	0.024	0.081	-10000	0	-0.34	36	36
IRAK4	0.027	0.006	-10000	0	-10000	0	0
PRKCI	0.027	0.006	-10000	0	-10000	0	0
TRAF6	0.028	0.003	-10000	0	-10000	0	0
PI3K	0.039	0.011	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.02	0.054	-10000	0	-0.31	4	4
CHUK	0.027	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.036	0.06	-10000	0	-0.38	8	8
IL1 beta/IL1R2	-0.058	0.18	-10000	0	-0.43	152	152
IRAK/TRAF6/TAK1/TAB1/TAB2	0.039	0.014	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.046	0.056	-10000	0	-0.64	1	1
IRAK3	0.026	0.022	-10000	0	-0.42	2	2
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.058	0.06	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.025	0.039	-10000	0	-0.28	2	2
IL1 alpha/IL1R1/IL1RAP	0.035	0.071	-10000	0	-0.43	2	2
RELA	0.028	0.003	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.024	0.034	-10000	0	-0.42	5	5
MYD88	0.026	0.008	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.045	0.019	-10000	0	-10000	0	0
IL1RAP	0.024	0.041	-10000	0	-0.46	6	6
UBE2N	0.027	0.006	-10000	0	-10000	0	0
IRAK/TRAF6	0.03	0.044	-10000	0	-10000	0	0
CASP1	0.026	0.03	-10000	0	-0.42	4	4
IL1RN/IL1R2	-0.077	0.21	-10000	0	-0.45	200	200
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.047	0.061	-10000	0	-0.36	8	8
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.011	0.08	-10000	0	-0.37	7	7
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
IL1RN	0.007	0.099	-10000	0	-0.46	36	36
TRAF6/TAK1/TAB1/TAB2	0.037	0.013	-10000	0	-10000	0	0
MAP2K6	0.023	0.04	0.34	4	-0.34	3	7

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.031	0.082	-10000	0	-10000	0	0
VDR	0.024	0.046	-10000	0	-0.65	4	4
FAM120B	0.026	0.007	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.045	0.055	-10000	0	-0.4	6	6
RXRs/LXRs/DNA/Oxysterols	0.047	0.067	-10000	0	-0.42	11	11
MED1	0.025	0.009	-10000	0	-10000	0	0
mol:9cRA	0.005	0.007	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.02	0.062	-10000	0	-10000	0	0
RXRs/NUR77	0.004	0.16	-10000	0	-0.38	122	122
RXRs/PPAR	0.034	0.041	-10000	0	-0.46	4	4
NCOR2	0.027	0.006	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.018	0.035	-10000	0	-0.49	4	4
RARs/VDR/DNA/Vit D3	0.052	0.042	-10000	0	-0.36	5	5
RARA	0.025	0.009	-10000	0	-10000	0	0
NCOA1	0.027	0.006	-10000	0	-10000	0	0
VDR/VDR/DNA	0.024	0.046	-10000	0	-0.65	4	4
RARs/RARs/DNA/9cRA	0.042	0.03	-10000	0	-0.36	2	2
RARG	0.027	0.016	-10000	0	-0.42	1	1
RPS6KB1	0.046	0.13	0.51	62	-10000	0	62
RARs/THRs/DNA/SMRT	0.02	0.063	-10000	0	-10000	0	0
THRA	0.025	0.024	-10000	0	-0.65	1	1
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.018	0.035	-10000	0	-0.49	4	4
RXRs/PPAR/9cRA/PGJ2/DNA	0.057	0.047	-10000	0	-0.35	1	1
NR1H4	-0.017	0.16	-10000	0	-0.65	56	56
RXRs/LXRs/DNA	0.088	0.061	-10000	0	-0.43	1	1
NR1H2	0.031	0.026	-10000	0	-0.67	1	1
NR1H3	0.032	0.012	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.059	0.053	-10000	0	-0.34	5	5
NR4A1	-0.068	0.24	-10000	0	-0.65	123	123
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.005	0.13	-10000	0	-0.41	71	71
RXRG	0.021	0.055	-10000	0	-0.44	11	11
RXR alpha/CCPG	0.041	0.014	-10000	0	-10000	0	0
RXRA	0.031	0.012	-10000	0	-10000	0	0
RXRB	0.03	0.013	-10000	0	-10000	0	0
THRB	-0.001	0.13	-10000	0	-0.64	35	35
PPARG	0.025	0.017	-10000	0	-0.42	1	1
PPARD	0.026	0.007	-10000	0	-10000	0	0
TNF	0.037	0.12	-10000	0	-1	8	8
mol:Oxysterols	0.005	0.006	-10000	0	-10000	0	0
cholesterol transport	0.047	0.067	-10000	0	-0.42	11	11
PPARA	0.027	0.005	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.024	0.033	-10000	0	-0.65	2	2
RXRs/NUR77/BCL2	-0.02	0.12	-10000	0	-0.31	125	125
SREBF1	0.041	0.065	-10000	0	-0.49	5	5
RXRs/RXRs/DNA/9cRA	0.058	0.047	-10000	0	-0.35	1	1
ABCA1	0.044	0.066	-10000	0	-0.47	5	5
RARs/THRs	0.05	0.09	-10000	0	-0.36	34	34
RXRs/FXR	0.041	0.12	-10000	0	-0.38	54	54
BCL2	0.027	0.023	-10000	0	-0.65	1	1

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.005	0.13	-10000	0	-0.51	40	40
KLHL20	0.023	0.069	0.21	3	-0.31	2	5
CYFIP2	0.018	0.076	-10000	0	-0.65	11	11
Rac1/GDP	0.023	0.091	0.31	13	-0.37	2	15
ENAH	-0.005	0.12	-10000	0	-0.51	40	40
AP1M1	0.028	0.003	-10000	0	-10000	0	0
RAP1B	0.027	0.006	-10000	0	-10000	0	0
RAP1A	0.027	0.007	-10000	0	-10000	0	0
CTNNB1	0.026	0.008	-10000	0	-10000	0	0
CDC42/GTP	0.021	0.061	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.013	0.036	-10000	0	-0.2	8	8
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.037	0.094	-10000	0	-0.38	37	37
RAPGEF1	0.004	0.12	0.26	4	-0.44	34	38
CTNND1	0.028	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.006	0.13	-10000	0	-0.53	40	40
CRK	-0.005	0.12	-10000	0	-0.48	35	35
E-cadherin/gamma catenin/alpha catenin	0.026	0.1	-10000	0	-0.43	36	36
alphaE/beta7 Integrin	0.036	0.015	-10000	0	-10000	0	0
IQGAP1	0.028	0.003	-10000	0	-10000	0	0
NCKAP1	0.027	0.006	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.047	0.019	-10000	0	-10000	0	0
DLG1	-0.005	0.13	-10000	0	-0.51	39	39
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.036	-10000	0	-10000	0	0
MLLT4	0.026	0.007	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.045	0.027	-10000	0	-10000	0	0
PI3K	0.004	0.051	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.012	0.11	-10000	0	-0.47	42	42
TIAM1	0.026	0.024	-10000	0	-0.65	1	1
E-cadherin(dimer)/Ca2+	0.036	0.09	-10000	0	-0.36	39	39
AKT1	0.014	0.036	-10000	0	-10000	0	0
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
CDH1	-0.005	0.14	-10000	0	-0.65	40	40
RhoA/GDP	0.04	0.1	0.34	29	-0.36	2	31
actin cytoskeleton organization	0.022	0.057	0.17	17	-0.22	2	19
CDC42/GDP	0.047	0.13	0.4	51	-0.36	2	53
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.008	0.069	-10000	0	-0.3	36	36
ITGB7	0.027	0.006	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.04	0.096	-10000	0	-0.38	39	39
E-cadherin/Ca2+/beta catenin/alpha catenin	0.023	0.086	-10000	0	-0.36	39	39
mol:GDP	0.034	0.14	0.44	42	-0.4	5	47
CDC42/GTP/IQGAP1	0.036	0.01	-10000	0	-10000	0	0
JUP	0.023	0.04	-10000	0	-0.65	3	3
p120 catenin/RhoA/GDP	0.033	0.097	0.31	13	-0.37	2	15
RAC1/GTP/IQGAP1	0.033	0.013	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.042	0.005	-10000	0	-10000	0	0
RHOA	0.026	0.008	-10000	0	-10000	0	0
CDC42	0.027	0.007	-10000	0	-10000	0	0
CTNNA1	0.027	0.007	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.026	0.068	0.22	42	-0.17	33	75
NME1	0.024	0.027	-10000	0	-0.42	3	3
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.006	0.13	-10000	0	-0.51	40	40
regulation of cell-cell adhesion	0.011	0.051	-10000	0	-10000	0	0
WASF2	0.012	0.029	-10000	0	-10000	0	0
Rap1/GTP	0.027	0.074	0.24	2	-10000	0	2
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.048	0.095	-10000	0	-0.37	36	36
CCND1	0.023	0.067	0.19	24	-0.21	33	57
VAV2	0.005	0.15	-10000	0	-0.57	17	17
RAP1/GDP	0.037	0.09	0.32	16	-0.35	1	17
adherens junction assembly	-0.005	0.12	-10000	0	-0.5	40	40
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.027	0.007	-10000	0	-10000	0	0
PIP5K1C	0.028	0.003	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.04	0.092	-10000	0	-0.67	1	1
E-cadherin/beta catenin	-0.005	0.092	-10000	0	-0.43	40	40
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.006	0.12	-10000	0	-0.51	38	38
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
Rac1/GTP	-0.027	0.073	-10000	0	-0.55	2	2
E-cadherin/beta catenin/alpha catenin	0.026	0.099	-10000	0	-0.42	39	39
ITGAE	0.025	0.009	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.006	0.13	-10000	0	-0.54	40	40

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.011	0.095	-10000	0	-0.56	23	23
CDC42/GTP	0.025	0.066	-10000	0	-0.35	6	6
PLCG1	0.014	0.06	-10000	0	-0.37	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.026	0.008	-10000	0	-10000	0	0
GNAI3	0.027	0.007	-10000	0	-10000	0	0
G12/G13	0.034	0.017	-10000	0	-10000	0	0
cell migration	0.025	0.064	-10000	0	-0.35	6	6
S1PR5	-0.036	0.16	-10000	0	-0.42	125	125
S1PR4	0.014	0.077	-10000	0	-0.42	27	27
MAPK3	0.014	0.061	-10000	0	-0.37	6	6
MAPK1	0.016	0.059	-10000	0	-0.37	6	6
S1P/S1P5/Gi	0.002	0.076	-10000	0	-0.32	15	15
GNAI1	0.022	0.041	-10000	0	-0.65	3	3
CDC42/GDP	0.02	0.005	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.007	0.098	-10000	0	-0.25	125	125
RHOA	0.038	0.085	0.36	28	-10000	0	28
S1P/S1P4/Gi	0.017	0.065	-10000	0	-0.32	15	15
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.025	0.04	-10000	0	-0.65	3	3
S1P/S1P4/G12/G13	0.036	0.05	-10000	0	-10000	0	0
GNA12	0.025	0.009	-10000	0	-10000	0	0
GNA13	0.025	0.009	-10000	0	-10000	0	0
CDC42	0.027	0.007	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.027	0.016	-10000	0	-0.42	1	1
ANTXR2	0.026	0.036	-10000	0	-0.57	3	3
negative regulation of myeloid dendritic cell antigen processing and presentation	0.001	0.005	-10000	0	-0.067	4	4
monocyte activation	-0.024	0.14	-10000	0	-0.44	81	81
MAP2K2	0.014	0.052	-10000	0	-0.6	6	6
MAP2K1	0.002	0.004	-10000	0	-10000	0	0
MAP2K7	0.002	0.004	-10000	0	-10000	0	0
MAP2K6	0	0.023	0.16	1	-0.32	4	5
CYAA	0.002	0.02	-10000	0	-0.28	4	4
MAP2K4	0.002	0.004	-10000	0	-10000	0	0
IL1B	0.004	0.046	0.24	1	-0.26	17	18
Channel	0.033	0.025	-10000	0	-0.3	4	4
NLRP1	0	0.018	-10000	0	-0.21	6	6
CALM1	0.027	0.005	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.004	0.063	-10000	0	-0.38	23	23
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	-0.001	0.005	0.067	4	-10000	0	4
MAPK3	0.002	0.006	0.14	1	-10000	0	1
MAPK1	0.002	0.004	-10000	0	-10000	0	0
PGR	-0.059	0.14	-10000	0	-0.36	150	150
PA/Cellular Receptors	0.034	0.027	-10000	0	-0.33	4	4
apoptosis	0.001	0.005	-10000	0	-0.067	4	4
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.032	0.023	-10000	0	-0.27	4	4
macrophage activation	0.002	0.006	0.13	1	-10000	0	1
TNF	0.012	0.082	-10000	0	-0.46	25	25
VCAM1	-0.011	0.12	-10000	0	-0.45	54	54
platelet activation	0.004	0.063	-10000	0	-0.38	23	23
MAPKKK cascade	-0.013	0.033	-10000	0	-0.13	56	56
IL18	0	0.052	-10000	0	-0.21	39	39
negative regulation of macrophage activation	0.001	0.005	-10000	0	-0.067	4	4
LEF	0.001	0.005	-10000	0	-0.067	4	4
CASP1	0.003	0.01	-10000	0	-0.11	6	6
mol:cAMP	0.004	0.063	-10000	0	-0.38	23	23
necrosis	0.001	0.005	-10000	0	-0.067	4	4
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.032	0.024	-10000	0	-0.28	4	4
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.026	0.007	-10000	0	-10000	0	0
HDAC2	0.026	0.007	-10000	0	-10000	0	0
GNB1/GNG2	0.044	0.037	-10000	0	-0.42	3	3
forebrain development	0.044	0.18	0.49	28	-0.56	38	66
GNAO1	0.012	0.095	-10000	0	-0.56	23	23
SMO/beta Arrestin2	0.033	0.043	-10000	0	-0.43	6	6
SMO	0.022	0.047	-10000	0	-0.65	4	4
ARRB2	0.024	0.03	-10000	0	-0.46	3	3
GLI3/SPOP	0.024	0.14	0.28	1	-0.57	34	35
mol:GTP	0	0.002	-10000	0	-10000	0	0
GSK3B	0.027	0.006	-10000	0	-10000	0	0
GNAI2	0.026	0.008	-10000	0	-10000	0	0
SIN3/HDAC complex	0.046	0.076	-10000	0	-0.3	1	1
GNAI1	0.023	0.041	-10000	0	-0.65	3	3
XPO1	0.029	0.008	-10000	0	-10000	0	0
GLI1/Su(fu)	0.029	0.12	-10000	0	-0.85	12	12
SAP30	-0.004	0.11	-10000	0	-0.42	62	62
mol:GDP	0.022	0.047	-10000	0	-0.65	4	4
MIM/GLI2A	0.026	0.039	-10000	0	-0.65	2	2
IFT88	0.027	0.006	-10000	0	-10000	0	0
GNAI3	0.027	0.008	-10000	0	-10000	0	0
GLI2	0.039	0.077	0.29	15	-0.33	5	20
GLI3	0.016	0.15	0.31	7	-0.6	36	43
CSNK1D	0.025	0.009	-10000	0	-10000	0	0
CSNK1E	0.027	0.005	-10000	0	-10000	0	0
SAP18	0.027	0.006	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.027	0.006	-10000	0	-10000	0	0
GNG2	0.027	0.005	-10000	0	-10000	0	0
Gi family/GTP	0.017	0.061	-10000	0	-0.32	18	18
SIN3B	0.028	0.003	-10000	0	-10000	0	0
SIN3A	0.028	0.003	-10000	0	-10000	0	0
GLI3/Su(fu)	0.015	0.15	0.28	1	-0.64	39	40
GLI2/Su(fu)	0.042	0.064	0.42	1	-0.48	5	6
FOXA2	0.015	0.12	-10000	0	-0.8	12	12
neural tube patterning	0.044	0.18	0.49	28	-0.56	38	66
SPOP	0.025	0.009	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.036	0.057	-10000	0	-0.46	2	2
GNB1	0.026	0.007	-10000	0	-10000	0	0
CSNK1G2	0.027	0.023	-10000	0	-0.65	1	1
CSNK1G3	0.027	0.006	-10000	0	-10000	0	0
MTSS1	0.026	0.039	-10000	0	-0.65	2	2
embryonic limb morphogenesis	0.044	0.18	0.49	28	-0.56	38	66
SUFU	0.024	0.032	-10000	0	-0.5	2	2
LGALS3	0.001	0.11	-10000	0	-0.42	52	52
catabolic process	0.046	0.14	0.38	7	-0.56	33	40
GLI3A/CBP	0.025	0.057	-10000	0	-0.39	13	13
KIF3A	0.027	0.007	-10000	0	-10000	0	0
GLI1	0.044	0.18	0.5	28	-0.58	38	66
RAB23	0.027	0.007	-10000	0	-10000	0	0
CSNK1A1	0.027	0.007	-10000	0	-10000	0	0
IFT172	0.027	0.006	-10000	0	-10000	0	0
RBBP7	0.028	0.002	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.021	0.093	-10000	0	-0.36	34	34
GNAZ	0.026	0.04	-10000	0	-0.65	3	3
RBBP4	0.026	0.024	-10000	0	-0.65	1	1
CSNK1G1	0.028	0.003	-10000	0	-10000	0	0
PIAS1	0.028	0.003	-10000	0	-10000	0	0
PRKACA	0.028	0.003	-10000	0	-10000	0	0
GLI2/SPOP	0.045	0.061	0.36	4	-0.31	3	7
STK36	0.029	0.009	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.023	0.058	-10000	0	-0.44	8	8
PTCH1	0.045	0.16	0.53	18	-0.83	9	27
MIM/GLI1	0.049	0.17	0.51	15	-0.77	15	30
CREBBP	0.025	0.057	-10000	0	-0.39	13	13
Su(fu)/SIN3/HDAC complex	0.006	0.16	0.27	4	-0.61	49	53

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.027	0.007	-10000	0	-10000	0	0
mol:PIP3	0.008	0.042	-10000	0	-0.32	10	10
FRAP1	0.027	0.06	0.38	14	-0.3	1	15
AKT1	0.009	0.042	0.2	2	-0.28	9	11
INSR	0.028	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.03	0.017	-10000	0	-0.24	3	3
mol:GTP	0.036	0.048	0.24	1	-0.3	1	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.011	0.028	-10000	0	-10000	0	0
TSC2	0.026	0.007	-10000	0	-10000	0	0
RHEB/GDP	0.02	0.032	-10000	0	-0.26	1	1
TSC1	0.028	0.005	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.016	0.062	-10000	0	-0.38	10	10
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.024	0.037	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.027	0.007	-10000	0	-10000	0	0
RPS6KB1	0.033	0.088	0.39	24	-0.32	2	26
MAP3K5	-0.005	0.049	-10000	0	-0.18	63	63
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
apoptosis	-0.005	0.049	-10000	0	-0.18	63	63
mol:LY294002	0	0	-10000	0	-0.001	51	51
EIF4B	0.04	0.1	0.4	39	-0.28	2	41
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.05	0.077	0.37	20	-0.4	1	21
eIF4E/eIF4G1/eIF4A1	0.02	0.018	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.031	0.059	-10000	0	-0.34	10	10
mTOR/RHEB/GTP/Raptor/GBL	0.02	0.042	0.26	13	-10000	0	13
FKBP1A	0.027	0.007	-10000	0	-10000	0	0
RHEB/GTP	0.034	0.041	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	51	51
FKBP12/Rapamycin	0.02	0.005	-10000	0	-10000	0	0
PDPK1	0.005	0.038	-10000	0	-0.3	10	10
EIF4E	0.028	0.004	-10000	0	-10000	0	0
ASK1/PP5C	0.002	0.16	0.3	1	-0.54	63	64
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.018	0.027	-10000	0	-10000	0	0
TSC1/TSC2	0.041	0.052	0.27	2	-0.32	1	3
tumor necrosis factor receptor activity	0	0	0.001	51	-10000	0	51
RPS6	0.027	0.022	-10000	0	-0.42	2	2
PPP5C	0.028	0.003	-10000	0	-10000	0	0
EIF4G1	0.027	0.006	-10000	0	-10000	0	0
IRS1	-0.002	0.062	-10000	0	-0.24	51	51
INS	-0.018	0.024	-10000	0	-0.42	3	3
PTEN	0.025	0.009	-10000	0	-10000	0	0
PDK2	0.005	0.038	0.21	2	-0.3	9	11
EIF4EBP1	-0.017	0.2	-10000	0	-1	33	33
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
PPP2R5D	0.029	0.059	0.36	15	-10000	0	15
peptide biosynthetic process	0.014	0.015	-10000	0	-10000	0	0
RHEB	0.025	0.01	-10000	0	-10000	0	0
EIF4A1	0.025	0.009	-10000	0	-10000	0	0
mol:Rapamycin	0.001	0.002	0.007	38	-10000	0	38
EEF2	0.014	0.014	-10000	0	-10000	0	0
eIF4E/4E-BP1	0	0.19	-10000	0	-0.94	33	33

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.017	0.08	-10000	0	-0.63	13	13
alphaV beta3 Integrin	0.022	0.085	-10000	0	-0.45	26	26
PTK2	0.019	0.089	-10000	0	-0.52	9	9
positive regulation of JNK cascade	0.012	0.1	-10000	0	-0.36	42	42
CDC42/GDP	0.045	0.14	0.4	9	-0.44	49	58
Rac1/GDP	0.028	0.13	0.52	1	-0.44	47	48
RAP1B	0.027	0.006	-10000	0	-10000	0	0
RAP1A	0.027	0.007	-10000	0	-10000	0	0
CTNNB1	0.026	0.008	-10000	0	-10000	0	0
CDC42/GTP	0.023	0.13	-10000	0	-0.45	41	41
nectin-3/I-afadin	0.032	0.052	-10000	0	-0.49	8	8
RAPGEF1	0.028	0.12	0.29	7	-0.49	9	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.015	0.12	-10000	0	-0.52	12	12
PDGFB-D/PDGFRB	0.017	0.08	-10000	0	-0.63	13	13
TLN1	0.01	0.021	-10000	0	-10000	0	0
Rap1/GTP	0.015	0.082	-10000	0	-0.36	7	7
IQGAP1	0.028	0.003	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.047	0.019	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.032	0.052	-10000	0	-0.49	8	8
PVR	0.028	0.015	-10000	0	-0.42	1	1
Necl-5(dimer)	0.028	0.015	-10000	0	-0.42	1	1
mol:GDP	0.031	0.17	0.42	9	-0.54	49	58
MLLT4	0.026	0.007	-10000	0	-10000	0	0
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
PI3K	0.061	0.07	-10000	0	-0.36	18	18
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.038	0.016	-10000	0	-0.28	1	1
positive regulation of lamellipodium assembly	0.016	0.099	-10000	0	-0.36	27	27
PVRL1	0.027	0.015	-10000	0	-0.42	1	1
PVRL3	0.02	0.066	-10000	0	-0.62	9	9
PVRL2	0.028	0.003	-10000	0	-10000	0	0
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
CDH1	-0.005	0.14	-10000	0	-0.65	40	40
CLDN1	-0.006	0.12	-10000	0	-0.46	59	59
JAM-A/CLDN1	0.038	0.092	-10000	0	-0.39	19	19
SRC	0.01	0.13	-10000	0	-0.5	25	25
ITGB3	0.007	0.11	-10000	0	-0.61	25	25
nectin-1(dimer)/I-afadin/I-afadin	0.038	0.016	-10000	0	-0.28	1	1
FARP2	0.016	0.18	-10000	0	-0.66	43	43
RAC1	0.025	0.01	-10000	0	-10000	0	0
CTNNA1	0.027	0.007	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.046	0.05	-10000	0	-0.42	8	8
nectin-1/I-afadin	0.038	0.016	-10000	0	-0.28	1	1
nectin-2/I-afadin	0.039	0.012	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.033	0.013	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.046	0.05	-10000	0	-0.42	8	8
CDC42/GTP/IQGAP1/filamentous actin	0.036	0.01	-10000	0	-10000	0	0
F11R	0.027	0.007	-10000	0	-10000	0	0
positive regulation of filopodium formation	0.012	0.1	-10000	0	-0.36	42	42
alphaV/beta3 Integrin/Talin	0.029	0.071	0.35	1	-0.46	3	4
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.039	0.012	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.039	0.012	-10000	0	-10000	0	0
PIP5K1C	0.012	0.023	-10000	0	-10000	0	0
VAV2	0.025	0.16	0.4	2	-0.6	26	28
RAP1/GDP	0.04	0.12	0.26	1	-0.38	42	43
ITGAV	0.026	0.028	-10000	0	-0.53	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.046	0.049	-10000	0	-0.42	8	8
nectin-3(dimer)/I-afadin/I-afadin	0.032	0.052	-10000	0	-0.49	8	8
Rac1/GTP	0.021	0.12	-10000	0	-0.44	26	26
PTPRM	0.015	0.026	-10000	0	-0.24	8	8
E-cadherin/beta catenin/alpha catenin	0.046	0.093	-10000	0	-0.35	36	36
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.027	0.007	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.03	0.064	-10000	0	-0.42	16	16
ATM	0.027	0.023	-10000	0	-0.65	1	1
UBE2D3	0.028	0.004	-10000	0	-10000	0	0
PRKDC	0.027	0.006	-10000	0	-10000	0	0
ATR	0.027	0.006	-10000	0	-10000	0	0
UBE2L3	0.027	0.005	-10000	0	-10000	0	0
FANCD2	0.024	0.018	-10000	0	-0.37	1	1
protein ubiquitination	0.051	0.071	-10000	0	-0.36	11	11
XRCC5	0.027	0.006	-10000	0	-10000	0	0
XRCC6	0.027	0.005	-10000	0	-10000	0	0
M/R/N Complex	0.051	0.024	-10000	0	-0.42	1	1
MRE11A	0.028	0.004	-10000	0	-10000	0	0
DNA-PK	0.051	0.018	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.005	0.092	-10000	0	-0.5	13	13
FANCF	0.028	0.004	-10000	0	-10000	0	0
BRCA1	0.023	0.031	-10000	0	-0.42	4	4
CCNE1	0.017	0.07	-10000	0	-0.42	22	22
CDK2/Cyclin E1	0.032	0.053	-10000	0	-0.29	22	22
FANCG	0.028	0.004	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.027	0.069	-10000	0	-0.41	19	19
FANCE	0.026	0.017	-10000	0	-0.42	1	1
FANCC	0.028	0.004	-10000	0	-10000	0	0
NBN	0.027	0.005	-10000	0	-10000	0	0
FANCA	-0.066	0.18	-10000	0	-0.42	182	182
DNA repair	0.027	0.13	0.46	31	-0.48	6	37
BRCA1/BARD1/ubiquitin	0.027	0.069	-10000	0	-0.41	19	19
BARD1/DNA-PK	0.057	0.063	-10000	0	-0.38	15	15
FANCL	0.027	0.006	-10000	0	-10000	0	0
mRNA polyadenylation	-0.029	0.064	0.42	16	-10000	0	16
BRCA1/BARD1/CTIP/M/R/N Complex	0.026	0.057	-10000	0	-0.72	1	1
BRCA1/BACH1/BARD1/TopBP1	0.041	0.062	-10000	0	-0.42	11	11
BRCA1/BARD1/P53	0.055	0.059	-10000	0	-0.38	11	11
BARD1/CSTF1/BRCA1	0.041	0.059	-10000	0	-0.42	9	9
BRCA1/BACH1	0.023	0.031	-10000	0	-0.42	4	4
BARD1	0.014	0.089	-10000	0	-0.63	16	16
PCNA	0.027	0.006	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.041	0.063	-10000	0	-0.42	12	12
BRCA1/BARD1/UbcH7	0.04	0.064	-10000	0	-0.42	12	12
BRCA1/BARD1/RAD51/PCNA	0.043	0.082	-10000	0	-0.39	15	15
BARD1/DNA-PK/P53	0.063	0.061	-10000	0	-0.36	12	12
BRCA1/BARD1/Ubiquitin	0.027	0.069	-10000	0	-0.41	19	19
BRCA1/BARD1/CTIP	0.035	0.065	-10000	0	-0.41	14	14
FA complex	0.008	0.064	-10000	0	-0.34	6	6
BARD1/EWS	0.029	0.07	-10000	0	-0.49	15	15
RBBP8	0.017	0.035	-10000	0	-0.68	2	2
TP53	0.025	0.009	-10000	0	-10000	0	0
TOPBP1	0.027	0.006	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.053	0.058	0.38	11	-10000	0	11
BRCA1/BARD1	0.057	0.074	-10000	0	-0.36	11	11
CSTF1	0.027	0.007	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.011	0.067	-10000	0	-0.47	16	16
CDK2	0.027	0.006	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.008	0.092	-10000	0	-0.42	39	39
RAD50	0.026	0.024	-10000	0	-0.65	1	1
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.027	0.069	-10000	0	-0.41	19	19
EWSR1	0.027	0.005	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.027	0.007	-10000	0	-10000	0	0
NFATC1	0.04	0.11	0.34	26	-0.46	4	30
NFATC2	0.004	0.095	0.25	14	-0.28	60	74
NFATC3	0.02	0.028	-10000	0	-0.41	3	3
YWHAE	0.025	0.009	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.002	0.11	0.27	16	-0.41	25	41
Exportin 1/Ran/NUP214	0.051	0.018	-10000	0	-10000	0	0
mol:DAG	-0.001	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.017	0.1	0.27	1	-0.48	11	12
BCL2/BAX	0.04	0.023	-10000	0	-0.39	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.017	-10000	0	-10000	0	0
CaM/Ca2+	0.015	0.017	-10000	0	-10000	0	0
BAX	0.028	0.015	-10000	0	-0.42	1	1
MAPK14	0.025	0.008	-10000	0	-10000	0	0
BAD	0.027	0.028	-10000	0	-0.53	2	2
CABIN1/MEF2D	0.015	0.1	0.29	6	-0.44	15	21
Calcineurin A alpha-beta B1/BCL2	0.027	0.023	-10000	0	-0.65	1	1
FKBP8	0.027	0.023	-10000	0	-0.65	1	1
activation-induced cell death of T cells	-0.015	0.1	0.44	15	-0.29	6	21
KPNB1	0.025	0.009	-10000	0	-10000	0	0
KPNA2	0.025	0.009	-10000	0	-10000	0	0
XPO1	0.027	0.006	-10000	0	-10000	0	0
SFN	-0.072	0.2	-10000	0	-0.44	185	185
MAP3K8	0.024	0.023	-10000	0	-0.42	2	2
NFAT4/CK1 alpha	0.027	0.031	-10000	0	-0.3	2	2
MEF2D/NFAT1/Cbp/p300	0.007	0.16	-10000	0	-0.44	33	33
CABIN1	0.001	0.1	0.24	12	-0.41	25	37
CALM1	0.025	0.01	-10000	0	-10000	0	0
RAN	0.027	0.006	-10000	0	-10000	0	0
MAP3K1	0.028	0.005	-10000	0	-10000	0	0
CAMK4	0.018	0.074	-10000	0	-0.63	11	11
mol:Ca2+	-0.002	0.009	-10000	0	-10000	0	0
MAPK3	0.026	0.007	-10000	0	-10000	0	0
YWHAH	0.027	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.031	0.067	-10000	0	-0.49	14	14
YWHAB	0.027	0.007	-10000	0	-10000	0	0
MAPK8	0.02	0.058	-10000	0	-0.61	7	7
MAPK9	0.027	0.007	-10000	0	-10000	0	0
YWHAG	0.025	0.009	-10000	0	-10000	0	0
FKBP1A	0.027	0.006	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.044	0.1	0.29	10	-0.42	7	17
PRKCH	0.027	0.024	-10000	0	-0.65	1	1
CABIN1/Cbp/p300	0.031	0.03	-10000	0	-0.49	1	1
CASP3	0.026	0.006	-10000	0	-10000	0	0
PIM1	0.025	0.022	-10000	0	-0.42	2	2
Calcineurin A alpha-beta B1/FKBP12/FK506	0.015	0.01	-10000	0	-10000	0	0
apoptosis	0.023	0.013	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.009	0.064	-10000	0	-0.37	11	11
PRKCB	0.019	0.066	-10000	0	-0.58	10	10
PRKCE	0.026	0.024	-10000	0	-0.65	1	1
JNK2/NFAT4	0.025	0.047	-10000	0	-0.42	2	2
BAD/BCL-XL	0.038	0.023	-10000	0	-0.39	2	2
PRKCD	0.021	0.045	-10000	0	-0.42	9	9
NUP214	0.027	0.004	-10000	0	-10000	0	0
PRKCZ	0.022	0.041	-10000	0	-0.66	3	3
PRKCA	0.025	0.009	-10000	0	-10000	0	0
PRKCG	-0.042	0.14	-10000	0	-0.42	98	98
PRKCQ	-0.006	0.14	-10000	0	-0.55	51	51
FKBP38/BCL2	0.039	0.026	-10000	0	-0.49	2	2
EP300	0.021	0.029	-10000	0	-0.65	1	1
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.027	0.006	-10000	0	-10000	0	0
NFATc/JNK1	0.049	0.11	0.34	25	-0.42	5	30
CaM/Ca2+/FKBP38	0.03	0.026	-10000	0	-0.44	1	1
FKBP12/FK506	0.02	0.005	-10000	0	-10000	0	0
CSNK1A1	0.012	0.017	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.024	0.052	-10000	0	-0.4	11	11
NFATc/ERK1	0.042	0.093	0.31	3	-0.42	5	8
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.019	0.1	0.27	1	-0.48	11	12
NR4A1	-0.052	0.23	0.3	2	-0.59	121	123
GSK3B	0.026	0.008	-10000	0	-10000	0	0
positive T cell selection	0.02	0.028	-10000	0	-0.41	3	3
NFAT1/CK1 alpha	0.003	0.064	-10000	0	-0.26	11	11
RCH1/ KPNB1	0.037	0.013	-10000	0	-10000	0	0
YWHAQ	0.027	0.006	-10000	0	-10000	0	0
PRKACA	0.027	0.005	-10000	0	-10000	0	0
AKAP5	0.016	0.085	-10000	0	-0.65	14	14
MEF2D	0.02	0.019	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.027	0.005	-10000	0	-10000	0	0
NFATc/p38 alpha	0.054	0.11	0.34	27	-0.43	4	31
CREBBP	0.022	0.016	-10000	0	-10000	0	0
BCL2	0.027	0.023	-10000	0	-0.65	1	1

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.022	0.01	-10000	0	-10000	0	0
TRAF2/ASK1	0.035	0.011	-10000	0	-10000	0	0
ATM	0.027	0.023	-10000	0	-0.65	1	1
MAP2K3	0.033	0.085	0.28	35	-0.36	7	42
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.026	0.099	0.26	21	-0.35	34	55
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.005	0.1	-10000	0	-0.44	42	42
TXN	0.009	0.006	-10000	0	-0.16	1	1
CALM1	0.027	0.005	-10000	0	-10000	0	0
GADD45A	0.027	0.007	-10000	0	-10000	0	0
GADD45B	0.027	0.023	-10000	0	-0.65	1	1
MAP3K1	0.028	0.005	-10000	0	-10000	0	0
MAP3K6	0.027	0.007	-10000	0	-10000	0	0
MAP3K7	0.027	0.007	-10000	0	-10000	0	0
MAP3K4	0.026	0.015	-10000	0	-0.35	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.038	0.012	-10000	0	-10000	0	0
TAK1/TAB family	-0.003	0.013	-10000	0	-10000	0	0
RAC1/OSM/MEKK3	0.044	0.022	-10000	0	-10000	0	0
TRAF2	0.028	0.004	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.029	0.056	-10000	0	-0.33	1	1
TRAF6	0.009	0.001	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.059	0.2	-10000	0	-0.54	129	129
CCM2	0.025	0.009	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.023	0.14	-10000	0	-0.34	129	129
MAPK11	0.027	0.016	-10000	0	-0.42	1	1
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.007	0.13	-10000	0	-0.38	68	68
OSM/MEKK3	0.034	0.017	-10000	0	-10000	0	0
TAOK1	0.011	0.047	-10000	0	-0.37	13	13
TAOK2	0.017	0.014	-10000	0	-0.38	1	1
TAOK3	0.017	0.014	-10000	0	-0.38	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.027	0.007	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.026	0.007	-10000	0	-10000	0	0
MAP3K10	0.027	0.023	-10000	0	-0.65	1	1
MAP3K3	0.025	0.009	-10000	0	-10000	0	0
TRX/ASK1	0.025	0.014	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.05	0.061	-10000	0	-0.36	4	4

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.03	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.062	0.074	0.29	32	-10000	0	32
ERC1	0.027	0.006	-10000	0	-10000	0	0
RIP2/NOD2	-0.02	0.13	-10000	0	-0.3	151	151
NFKBIA	0.025	0.018	-10000	0	-0.37	1	1
BIRC2	0.028	0.004	-10000	0	-10000	0	0
IKBKB	0.027	0.006	-10000	0	-10000	0	0
RIPK2	0.027	0.016	-10000	0	-0.42	1	1
IKBKG	0.02	0.039	-10000	0	-10000	0	0
IKK complex/A20	0.043	0.078	-10000	0	-0.47	2	2
NEMO/A20/RIP2	0.027	0.016	-10000	0	-0.42	1	1
XPO1	0.027	0.006	-10000	0	-10000	0	0
NEMO/ATM	0.038	0.061	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.027	0.006	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.035	0.011	-10000	0	-10000	0	0
IKK complex/ELKS	0.035	0.056	-10000	0	-0.41	1	1
BCL10/MALT1/TRAF6	0.052	0.017	-10000	0	-10000	0	0
NOD2	-0.053	0.17	-10000	0	-0.42	155	155
NFKB1	0.03	0.023	-10000	0	-0.65	1	1
RELA	0.031	0.004	-10000	0	-10000	0	0
MALT1	0.027	0.005	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.041	0.008	-10000	0	-10000	0	0
ATM	0.027	0.023	-10000	0	-0.65	1	1
TNF/TNFR1A	0.028	0.061	-10000	0	-0.34	19	19
TRAF6	0.028	0.003	-10000	0	-10000	0	0
PRKCA	0.025	0.009	-10000	0	-10000	0	0
CHUK	0.027	0.007	-10000	0	-10000	0	0
UBE2D3	0.028	0.004	-10000	0	-10000	0	0
TNF	0.012	0.082	-10000	0	-0.46	25	25
NF kappa B1 p50/RelA	0.062	0.024	-10000	0	-0.41	1	1
BCL10	0.027	0.007	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.018	-10000	0	-0.36	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.03	0.007	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
IKK complex	0.047	0.066	-10000	0	-0.44	1	1
CYLD	0.027	0.007	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.047	0.066	-10000	0	-0.42	1	1

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.008	0.035	-10000	0	-0.42	4	4
SNTA1	0.023	0.051	-10000	0	-0.57	6	6
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	0.007	0.038	-10000	0	-0.42	6	6
MAPK12	0.002	0.037	-10000	0	-0.36	4	4
CCND1	0.007	0.035	-10000	0	-0.42	3	3
p38 gamma/SNTA1	0.026	0.061	-10000	0	-0.42	5	5
MAP2K3	0.025	0.009	-10000	0	-10000	0	0
PKN1	0.028	0.003	-10000	0	-10000	0	0
G2/M transition checkpoint	0.001	0.037	-10000	0	-0.35	4	4
MAP2K6	0.006	0.026	0.19	1	-0.41	3	4
MAPT	0.007	0.12	0.32	47	-0.39	54	101
MAPK13	0.013	0.044	-10000	0	-0.49	6	6
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.009	0.001	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.019	0.005	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.046	0.023	-10000	0	-0.38	1	1
CDKN1B	0.022	0.073	-10000	0	-0.6	5	5
CDKN1A	0.023	0.061	-10000	0	-0.6	3	3
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.027	0.006	-10000	0	-10000	0	0
FOXO3	0.023	0.061	-10000	0	-0.6	3	3
AKT1	0.013	0.07	-10000	0	-0.39	17	17
BAD	0.027	0.028	-10000	0	-0.53	2	2
AKT3	0.016	0.015	-10000	0	-0.38	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.021	0.073	-10000	0	-0.6	5	5
AKT1/ASK1	0.033	0.075	-10000	0	-0.58	5	5
BAD/YWHAZ	0.054	0.022	-10000	0	-0.42	1	1
RICTOR	0.027	0.005	-10000	0	-10000	0	0
RAF1	0.026	0.008	-10000	0	-10000	0	0
JNK cascade	-0.032	0.073	0.56	5	-10000	0	5
TSC1	0.022	0.065	-10000	0	-0.6	3	3
YWHAZ	0.027	0.005	-10000	0	-10000	0	0
AKT1/RAF1	0.035	0.078	0.31	2	-0.6	5	7
EP300	0.027	0.024	-10000	0	-0.65	1	1
mol:GDP	0.012	0.071	-10000	0	-0.38	19	19
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.015	0.07	-10000	0	-0.6	5	5
YWHAQ	0.027	0.006	-10000	0	-10000	0	0
TBC1D4	0.013	0.005	-10000	0	-10000	0	0
MAP3K5	0.026	0.007	-10000	0	-10000	0	0
MAPKAP1	0.028	0.004	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.023	0.1	0.41	17	-0.29	21	38
YWHAH	0.027	0.005	-10000	0	-10000	0	0
AKT1S1	0.021	0.073	-10000	0	-0.6	5	5
CASP9	0.024	0.055	-10000	0	-0.6	2	2
YWHAB	0.027	0.007	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.041	0.082	0.3	15	-0.57	5	20
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.051	0.019	-10000	0	-10000	0	0
YWHAE	0.025	0.009	-10000	0	-10000	0	0
SRC	0.027	0.007	-10000	0	-10000	0	0
AKT2/p21CIP1	0.019	0.063	-10000	0	-0.55	5	5
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0.021	-10000	0	-10000	0	0
CHUK	0.022	0.068	-10000	0	-0.6	5	5
BAD/BCL-XL	0.042	0.074	-10000	0	-0.57	5	5
mTORC2	0.035	0.008	-10000	0	-10000	0	0
AKT2	0.018	0.005	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.028	0.12	0.36	23	-0.54	15	38
PDPK1	0.027	0.007	-10000	0	-10000	0	0
MDM2	0.022	0.074	-10000	0	-0.6	5	5
MAPKKK cascade	-0.034	0.077	0.59	5	-0.3	2	7
MDM2/Cbp/p300	0.049	0.078	0.31	2	-0.55	5	7
TSC1/TSC2	0.03	0.089	0.29	41	-0.58	5	46
proteasomal ubiquitin-dependent protein catabolic process	0.046	0.075	0.3	2	-0.52	5	7
glucose import	-0.004	0.063	0.21	1	-0.29	30	31
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.022	0.045	0.24	1	-0.33	5	6
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.004	0.063	-10000	0	-0.29	30	30
GSK3A	0.021	0.073	-10000	0	-0.6	5	5
FOXO1	0.023	0.058	-10000	0	-0.6	2	2
GSK3B	0.02	0.07	-10000	0	-0.6	5	5
SFN	-0.072	0.2	-10000	0	-0.44	185	185
G1/S transition of mitotic cell cycle	0.029	0.083	0.31	22	-0.59	5	27
p27Kip1/14-3-3 family	0.021	0.082	-10000	0	-0.48	7	7
PRKACA	0.028	0.003	-10000	0	-10000	0	0
KPNA1	0.027	0.006	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
YWHAG	0.025	0.009	-10000	0	-10000	0	0
RHEB	0.025	0.01	-10000	0	-10000	0	0
CREBBP	0.027	0.007	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.007	-10000	0	-10000	0	0
HDAC3	0.027	0.007	-10000	0	-10000	0	0
VDR	0.024	0.046	-10000	0	-0.65	4	4
Cbp/p300/PCAF	0.048	0.035	-10000	0	-0.79	1	1
EP300	0.027	0.024	-10000	0	-0.65	1	1
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.018	0.076	-10000	0	-0.39	9	9
KAT2B	0.025	0.024	-10000	0	-0.65	1	1
MAPK14	0.027	0.007	-10000	0	-10000	0	0
AKT1	0.011	0.06	0.22	7	-10000	0	7
RAR alpha/9cRA/Cyclin H	0.041	0.078	-10000	0	-0.34	1	1
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.027	0.065	0.24	2	-0.41	5	7
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.01	0.088	-10000	0	-0.35	40	40
NCOR2	0.027	0.006	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.018	0.035	-10000	0	-0.49	4	4
RXRs/RARs/NRIP1/9cRA	0.018	0.098	0.31	3	-0.5	6	9
NCOA2	-0.004	0.14	-10000	0	-0.65	40	40
NCOA3	0.027	0.007	-10000	0	-10000	0	0
NCOA1	0.027	0.006	-10000	0	-10000	0	0
VDR/VDR/DNA	0.024	0.046	-10000	0	-0.65	4	4
RARG	0.027	0.016	-10000	0	-0.42	1	1
RAR gamma1/9cRA	0.037	0.013	-10000	0	-0.24	1	1
MAPK3	0.027	0.007	-10000	0	-10000	0	0
MAPK1	0.027	0.005	-10000	0	-10000	0	0
MAPK8	0.023	0.058	-10000	0	-0.61	7	7
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.024	0.079	-10000	0	-0.44	4	4
RARA	0.012	0.042	-10000	0	-0.28	8	8
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.017	0.081	0.24	1	-0.4	10	11
PRKCA	0.028	0.01	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.019	0.11	0.31	5	-0.43	33	38
RXRG	0.003	0.063	-10000	0	-0.41	7	7
RXRA	0.016	0.041	-10000	0	-0.28	4	4
RXRB	0.008	0.056	-10000	0	-0.38	5	5
VDR/Vit D3/DNA	0.018	0.035	-10000	0	-0.49	4	4
RBP1	0.026	0.027	-10000	0	-0.42	3	3
CRBP1/9-cic-RA	0.019	0.019	-10000	0	-0.29	3	3
RARB	0.026	0.034	-10000	0	-0.65	2	2
PRKCG	-0.023	0.14	-10000	0	-0.42	98	98
MNAT1	0.027	0.005	-10000	0	-10000	0	0
RAR alpha/RXRs	0.013	0.089	-10000	0	-0.5	3	3
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.023	0.089	0.28	5	-0.42	6	11
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.12	0.3	47	-0.37	37	84
RXRs/RARs/NRIP1/9cRA/HDAC3	0.023	0.11	0.34	6	-0.52	8	14
positive regulation of DNA binding	0.026	0.068	-10000	0	-0.32	1	1
NRIP1	0.016	0.11	0.39	1	-0.62	4	5
RXRs/RARs	0.006	0.11	0.29	1	-0.4	34	35
RXRs/RXRs/DNA/9cRA	0.01	0.072	-10000	0	-0.45	4	4
PRKACA	0.028	0.003	-10000	0	-10000	0	0
CDK7	0.028	0.005	-10000	0	-10000	0	0
TFIIH	0.054	0.014	-10000	0	-10000	0	0
RAR alpha/9cRA	0.045	0.078	-10000	0	-10000	0	0
CCNH	0.028	0.005	-10000	0	-10000	0	0
CREBBP	0.027	0.007	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.049	0.022	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.005	0.12	-10000	0	-0.49	53	53
CLTC	0.023	0.063	-10000	0	-0.37	18	18
calcium ion-dependent exocytosis	0.022	0.029	-10000	0	-0.26	2	2
Dynamin 2/GTP	0.027	0.018	-10000	0	-10000	0	0
EXOC4	0.025	0.01	-10000	0	-10000	0	0
CD59	0.018	0.051	-10000	0	-0.31	18	18
CPE	0.008	0.054	-10000	0	-0.26	33	33
CTNNB1	0.026	0.008	-10000	0	-10000	0	0
membrane fusion	0.017	0.012	-10000	0	-10000	0	0
CTNND1	0.03	0.045	-10000	0	-10000	0	0
DNM2	0.028	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.022	0.043	0.25	4	-0.34	4	8
TSHR	-0.006	0.075	-10000	0	-0.24	78	78
INS	0.014	0.054	-10000	0	-0.5	8	8
BIN1	0.025	0.036	-10000	0	-0.57	3	3
mol:Choline	0.017	0.012	-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	-0.24	3	3
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	0.027	0.018	-10000	0	-10000	0	0
JUP	0.016	0.051	-10000	0	-0.3	18	18
ASAP2/amphiphysin II	0.047	0.04	-10000	0	-0.38	6	6
ARF6/GTP	0.02	0.004	-10000	0	-10000	0	0
CDH1	0.008	0.07	-10000	0	-0.32	18	18
clathrin-independent pinocytosis	0.02	0.004	-10000	0	-10000	0	0
MAPK8IP3	0.01	0.083	-10000	0	-0.42	32	32
positive regulation of endocytosis	0.02	0.004	-10000	0	-10000	0	0
EXOC2	0.027	0.007	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.028	0.042	-10000	0	-0.35	7	7
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.025	0.009	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.031	0.07	0.41	4	-10000	0	4
positive regulation of phagocytosis	0.017	0.006	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.025	0.053	-10000	0	-0.24	32	32
ACAP1	0.021	0.025	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.01	0.048	-10000	0	-0.3	18	18
clathrin heavy chain/ACAP1	0.025	0.056	0.27	3	-0.4	4	7
JIP4/KLC1	0.047	0.019	-10000	0	-10000	0	0
EXOC1	0.028	0.004	-10000	0	-10000	0	0
exocyst	0.028	0.042	-10000	0	-0.35	7	7
RALA/GTP	0.018	0.007	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.033	0.013	-10000	0	-10000	0	0
receptor recycling	0.02	0.004	-10000	0	-10000	0	0
CTNNA1	0.029	0.045	-10000	0	-10000	0	0
NME1	0.016	0.017	-10000	0	-0.24	3	3
clathrin coat assembly	0.028	0.082	0.25	23	-0.36	18	41
IL2RA	0	0.066	-10000	0	-0.32	18	18
VAMP3	0.017	0.006	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.013	0.088	-10000	0	-0.35	30	30
EXOC6	0.027	0.007	-10000	0	-10000	0	0
PLD1	0.018	0.008	-10000	0	-10000	0	0
PLD2	0.017	0.009	-10000	0	-10000	0	0
EXOC5	0.027	0.005	-10000	0	-10000	0	0
PIP5K1C	0.021	0.04	-10000	0	-0.35	4	4
SDC1	0.016	0.054	-10000	0	-0.3	18	18
ARF6/GDP	0.024	0.019	-10000	0	-0.24	3	3
EXOC7	0.025	0.009	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.033	0.073	-10000	0	-0.42	4	4
mol:Phosphatidic acid	0.017	0.012	-10000	0	-10000	0	0
endocytosis	-0.045	0.039	0.38	6	-10000	0	6
SCAMP2	0.028	0.003	-10000	0	-10000	0	0
ADRB2	0.038	0.1	0.32	25	-0.4	10	35
EXOC3	0.027	0.005	-10000	0	-10000	0	0
ASAP2	0.024	0.046	-10000	0	-0.65	4	4
Dynamin 2/GDP	0.03	0.019	-10000	0	-10000	0	0
KLC1	0.027	0.005	-10000	0	-10000	0	0
AVPR2	-0.15	0.18	0.29	6	-0.53	31	37
RALA	0.025	0.009	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.036	0.074	0.33	1	-0.53	1	2

×

Insulin 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.04	0.054	-10000	0	-0.34	11	11
TC10/GTP	0.04	0.033	-10000	0	-0.33	1	1
Insulin Receptor/Insulin/IRS1/Shp2	0.057	0.056	-10000	0	-0.4	10	10
HRAS	0.027	0.015	-10000	0	-0.42	1	1
APS homodimer	0.022	0.038	-10000	0	-0.42	6	6
GRB14	-0.01	0.15	-10000	0	-0.65	48	48
FOXO3	-0.016	0.17	-10000	0	-0.62	60	60
AKT1	0.019	0.12	0.44	27	-0.6	3	30
INSR	0.031	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.058	0.022	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.025	0.009	-10000	0	-10000	0	0
SORBS1	0.027	0.007	-10000	0	-10000	0	0
CRK	0.025	0.009	-10000	0	-10000	0	0
PTPN1	0.016	0.013	-10000	0	-10000	0	0
CAV1	0	0.068	0.5	1	-0.37	10	11
CBL/APS/CAP/Crk-II/C3G	0.063	0.044	-10000	0	-0.36	1	1
Insulin Receptor/Insulin/IRS1/NCK2	0.06	0.055	-10000	0	-0.4	10	10
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.046	0.048	-10000	0	-0.35	10	10
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.033	0.046	-10000	0	-10000	0	0
RPS6KB1	0.002	0.086	0.36	7	-0.5	3	10
PARD6A	0.024	0.04	-10000	0	-0.65	3	3
CBL	0.027	0.023	-10000	0	-0.65	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	-0.002	0.11	-10000	0	-0.52	35	35
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.026	0.084	-10000	0	-0.56	2	2
HRAS/GTP	0.012	0.045	-10000	0	-0.48	2	2
Insulin Receptor	0.031	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.064	0.057	-10000	0	-0.37	9	9
PRKCI	0.022	0.066	-10000	0	-0.5	2	2
Insulin Receptor/Insulin/GRB14/PDK1	0.009	0.093	-10000	0	-0.65	3	3
SHC1	0.026	0.016	-10000	0	-0.42	1	1
negative regulation of MAPKKK cascade	0.026	0.096	-10000	0	-0.43	34	34
PI3K	0.056	0.052	-10000	0	-0.36	10	10
NCK2	0.027	0.006	-10000	0	-10000	0	0
RHOQ	0.027	0.006	-10000	0	-10000	0	0
mol:H2O2	0	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.02	0.011	-10000	0	-0.29	1	1
AKT2	0.02	0.12	0.43	29	-0.6	3	32
PRKCZ	0.022	0.073	-10000	0	-0.63	5	5
SH2B2	0.022	0.038	-10000	0	-0.42	6	6
SHC/SHIP	0.028	0.057	0.3	2	-0.39	10	12
F2RL2	-0.008	0.13	-10000	0	-0.47	62	62
TRIP10	0.028	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.048	0.024	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.036	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.069	0.034	-10000	0	-10000	0	0
RAPGEF1	0.028	0.004	-10000	0	-10000	0	0
RASA1	0.027	0.023	-10000	0	-0.65	1	1
NCK1	0.027	0.006	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.055	0.041	-10000	0	-0.38	1	1
TC10/GDP	0.02	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.056	0.032	-10000	0	-10000	0	0
INPP5D	0.013	0.056	0.31	2	-0.41	10	12
SOS1	0.027	0.006	-10000	0	-10000	0	0
SGK1	-0.033	0.17	-10000	0	-0.65	64	64
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.027	0.006	-10000	0	-10000	0	0
IRS1	0.019	0.072	-10000	0	-0.65	10	10
p62DOK/RasGAP	0.027	0.097	-10000	0	-0.43	34	34
INS	0.021	0.025	-10000	0	-0.39	3	3
mol:PI-3-4-P2	0.013	0.056	0.31	2	-0.41	10	12
GRB2	0.025	0.009	-10000	0	-10000	0	0
EIF4EBP1	0.007	0.12	0.42	25	-0.52	7	32
PTPRA	0.028	0.007	-10000	0	-10000	0	0
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.036	0.009	-10000	0	-10000	0	0
PDPK1	0.027	0.007	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.028	0.036	-10000	0	-0.28	9	9
Insulin Receptor/Insulin/IRS1	0.043	0.052	-10000	0	-0.4	10	10
Insulin Receptor/Insulin/IRS3	0.039	0.022	-10000	0	-0.29	2	2
Par3/Par6	0.037	0.082	-10000	0	-0.36	14	14

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.052	0.062	-10000	0	-0.41	4	4
Ran/GTP/Exportin 1/HDAC1	0.007	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.039	0.065	-10000	0	-0.39	3	3
SUMO1	0.027	0.006	-10000	0	-10000	0	0
ZFPM1	0.024	0.043	-10000	0	-0.59	4	4
NPC/RanGAP1/SUMO1/Ubc9	0.018	0.007	-10000	0	-10000	0	0
FKBP3	0.027	0.005	-10000	0	-10000	0	0
Histones	0.064	0.042	-10000	0	-10000	0	0
YY1/LSF	0.028	0.05	-10000	0	-0.67	1	1
SMG5	0.027	0.007	-10000	0	-10000	0	0
RAN	0.027	0.006	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.026	0.034	-10000	0	-0.3	3	3
I kappa B alpha/HDAC1	0.036	0.037	-10000	0	-10000	0	0
SAP18	0.027	0.006	-10000	0	-10000	0	0
RELA	0.026	0.04	-10000	0	-10000	0	0
HDAC1/Smad7	0.046	0.023	-10000	0	-10000	0	0
RANGAP1	0.027	0.005	-10000	0	-10000	0	0
HDAC3/TR2	0.033	0.036	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.017	0.1	-10000	0	-0.44	37	37
NF kappa B1 p50/RelA	0.044	0.065	0.29	4	-0.57	1	5
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.028	0.18	-10000	0	-0.64	72	72
GATA1	-0.002	0.097	-10000	0	-0.42	44	44
Mad/Max	0.038	0.016	-10000	0	-0.29	1	1
NuRD/MBD3 Complex/GATA1/Fog1	0.02	0.093	-10000	0	-0.37	36	36
RBBP7	0.028	0.002	-10000	0	-10000	0	0
NPC	0.016	0.004	-10000	0	-10000	0	0
RBBP4	0.026	0.024	-10000	0	-0.65	1	1
MAX	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.027	0.007	-10000	0	-10000	0	0
NFKBIA	0.022	0.028	-10000	0	-10000	0	0
KAT2B	0.025	0.024	-10000	0	-0.65	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.029	0.033	-10000	0	-0.32	1	1
SIN3 complex	0.047	0.076	-10000	0	-0.3	1	1
SMURF1	0.025	0.01	-10000	0	-10000	0	0
CHD3	0.025	0.009	-10000	0	-10000	0	0
SAP30	-0.004	0.11	-10000	0	-0.42	62	62
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.025	0.009	-10000	0	-10000	0	0
YY1/HDAC3	0.027	0.049	-10000	0	-0.59	1	1
YY1/HDAC2	0.03	0.048	-10000	0	-0.67	1	1
YY1/HDAC1	0.029	0.049	-10000	0	-0.67	1	1
NuRD/MBD2 Complex (MeCP1)	0.018	0.1	-10000	0	-0.45	36	36
PPARG	0.02	0.048	-10000	0	-0.38	7	7
HDAC8/hEST1B	0.054	0.015	-10000	0	-10000	0	0
UBE2I	0.026	0.007	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.027	0.007	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.006	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.033	0.036	-10000	0	-0.31	1	1
MBD3L2	-0.018	0.002	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.045	0.023	-10000	0	-10000	0	0
CREBBP	0.027	0.007	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.028	0.093	-10000	0	-0.37	32	32
HDAC1	0.027	0.007	-10000	0	-10000	0	0
HDAC3	0.022	0.029	-10000	0	-0.34	1	1
HDAC2	0.026	0.007	-10000	0	-10000	0	0
YY1	0.023	0.028	-10000	0	-0.74	1	1
HDAC8	0.028	0.001	-10000	0	-10000	0	0
SMAD7	0.028	0.005	-10000	0	-10000	0	0
NCOR2	0.027	0.006	-10000	0	-10000	0	0
MXD1	0.027	0.016	-10000	0	-0.42	1	1
STAT3	0.023	0.017	-10000	0	-0.37	1	1
NFKB1	0.027	0.023	-10000	0	-0.65	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.027	0.006	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.041	0.05	-10000	0	-0.63	1	1
YY1/SAP30/HDAC1	0.024	0.08	-10000	0	-0.46	3	3
EP300	0.027	0.024	-10000	0	-0.65	1	1
STAT3 (dimer non-phopshorylated)	0.023	0.017	-10000	0	-0.37	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.028	-10000	0	-10000	0	0
histone deacetylation	0.025	0.1	-10000	0	-0.45	36	36
STAT3 (dimer non-phopshorylated)/HDAC3	0.031	0.032	-10000	0	-10000	0	0
nuclear export	-0.053	0.014	-10000	0	-10000	0	0
PRKACA	0.028	0.003	-10000	0	-10000	0	0
GATAD2B	0.027	0.007	-10000	0	-10000	0	0
GATAD2A	0.028	0.003	-10000	0	-10000	0	0
GATA2/HDAC3	0.003	0.12	-10000	0	-0.38	65	65
GATA1/HDAC1	0.021	0.073	-10000	0	-0.29	44	44
GATA1/HDAC3	0.024	0.063	-10000	0	-0.32	3	3
CHD4	0.027	0.006	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.028	0.061	-10000	0	-0.34	19	19
SIN3/HDAC complex/Mad/Max	0.017	0.091	-10000	0	-0.41	34	34
NuRD Complex	0.031	0.093	-10000	0	-0.37	32	32
positive regulation of chromatin silencing	0.061	0.041	-10000	0	-10000	0	0
SIN3B	0.028	0.003	-10000	0	-10000	0	0
MTA2	0.028	0.003	-10000	0	-10000	0	0
SIN3A	0.028	0.003	-10000	0	-10000	0	0
XPO1	0.027	0.006	-10000	0	-10000	0	0
SUMO1/HDAC1	0.041	0.042	-10000	0	-10000	0	0
HDAC complex	0.066	0.026	-10000	0	-0.38	1	1
GATA1/Fog1	0.02	0.076	-10000	0	-0.31	43	43
FKBP25/HDAC1/HDAC2	0.052	0.018	-10000	0	-10000	0	0
TNF	0.012	0.082	-10000	0	-0.46	25	25
negative regulation of cell growth	0.019	0.091	-10000	0	-0.4	34	34
NuRD/MBD2/PRMT5 Complex	0.018	0.1	-10000	0	-0.45	36	36
Ran/GTP/Exportin 1	0.041	0.043	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.028	0.046	-10000	0	-0.34	3	3
SIN3/HDAC complex/NCoR1	0.034	0.037	-10000	0	-10000	0	0
TFCP2	0.027	0.006	-10000	0	-10000	0	0
NR2C1	0.027	0.006	-10000	0	-10000	0	0
MBD3	0.027	0.028	-10000	0	-0.53	2	2
MBD2	0.028	0.005	-10000	0	-10000	0	0

×

IGF1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.027	0.006	-10000	0	-10000	0	0
PTK2	0.027	0.005	-10000	0	-10000	0	0
CRKL	0.013	0.054	-10000	0	-0.3	17	17
GRB2/SOS1/SHC	0.05	0.022	-10000	0	-10000	0	0
HRAS	0.027	0.015	-10000	0	-0.42	1	1
IRS1/Crk	0.019	0.053	-10000	0	-0.3	17	17
IGF-1R heterotetramer/IGF1/PTP1B	0.04	0.063	-10000	0	-0.4	8	8
AKT1	0.016	0.054	0.3	4	-10000	0	4
BAD	0.012	0.053	0.29	4	-10000	0	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.012	0.051	-10000	0	-0.3	17	17
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.024	0.057	-10000	0	-0.3	19	19
RAF1	0.002	0.11	0.34	1	-0.41	41	42
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.049	0.059	-10000	0	-0.32	6	6
YWHAZ	0.027	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.023	0.061	-10000	0	-0.33	19	19
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
RPS6KB1	0.015	0.052	0.31	4	-10000	0	4
GNB2L1	0.027	0.007	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.007	0.1	0.32	7	-0.35	1	8
PXN	0.027	0.006	-10000	0	-10000	0	0
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.037	0.014	-10000	0	-10000	0	0
HRAS/GTP	0.023	0.046	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.062	0.058	-10000	0	-0.32	5	5
IGF-1R heterotetramer	0.028	0.021	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.038	0.06	-10000	0	-0.3	18	18
Crk/p130 Cas/Paxillin	0.052	0.063	-10000	0	-0.34	1	1
IGF1R	0.028	0.021	-10000	0	-10000	0	0
IGF1	0.01	0.098	-10000	0	-0.48	32	32
IRS2/Crk	0.017	0.06	-10000	0	-0.32	8	8
PI3K	0.051	0.06	-10000	0	-0.33	7	7
apoptosis	-0.034	0.066	-10000	0	-0.3	17	17
HRAS/GDP	0.02	0.011	-10000	0	-0.29	1	1
PRKCD	0.015	0.069	-10000	0	-0.42	13	13
RAF1/14-3-3 E	0.018	0.11	0.34	5	-0.4	2	7
BAD/14-3-3	0.039	0.078	0.35	24	-10000	0	24
PRKCZ	0.015	0.057	0.3	5	-0.33	2	7
Crk/p130 Cas/Paxillin/FAK1	0.033	0.046	-10000	0	-10000	0	0
PTPN1	0.027	0.007	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.017	0.06	-10000	0	-0.36	16	16
BCAR1	0.026	0.024	-10000	0	-0.65	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.047	0.058	-10000	0	-0.35	5	5
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.027	0.006	-10000	0	-10000	0	0
IRS1/NCK2	0.029	0.058	-10000	0	-0.3	18	18
GRB10	0.025	0.009	-10000	0	-10000	0	0
PTPN11	0.013	0.054	-10000	0	-0.3	19	19
IRS1	0.014	0.06	0.22	2	-0.33	19	21
IRS2	0.008	0.062	-10000	0	-0.31	19	19
IGF-1R heterotetramer/IGF1	0.026	0.077	-10000	0	-0.37	23	23
GRB2	0.025	0.009	-10000	0	-10000	0	0
PDPK1	0.022	0.058	0.3	5	-0.31	6	11
YWHAE	0.025	0.009	-10000	0	-10000	0	0
PRKD1	0.016	0.071	-10000	0	-0.44	13	13
SHC1	0.026	0.016	-10000	0	-0.42	1	1

×

Signaling events mediated by HDAC Class III

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.027	0.024	-10000	0	-0.65	1	1
HDAC4	0.026	0.014	-10000	0	-0.35	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.015	0.016	0.29	2	-10000	0	2
CDKN1A	-0.005	0.015	-10000	0	-0.26	3	3
KAT2B	0.025	0.024	-10000	0	-0.65	1	1
BAX	0.028	0.015	-10000	0	-0.42	1	1
FOXO3	-0.006	0.017	0.48	1	-10000	0	1
FOXO1	0.027	0.006	-10000	0	-10000	0	0
FOXO4	0.02	0.013	-10000	0	-0.31	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.027	0.005	-10000	0	-10000	0	0
TAT	0.008	0.066	-10000	0	-0.42	19	19
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.01	0.052	-10000	0	-0.3	26	26
PPARGC1A	-0.012	0.16	-10000	0	-0.65	52	52
FHL2	0.018	0.074	-10000	0	-0.5	16	16
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.035	0.012	-10000	0	-10000	0	0
HIST2H4A	0.015	0.016	-10000	0	-0.29	2	2
SIRT1/FOXO3a	0.012	0.028	0.32	1	-10000	0	1
SIRT1	0.023	0.007	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.049	0.019	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.028	0.035	-10000	0	-0.28	1	1
apoptosis	-0.049	0.019	-10000	0	-10000	0	0
SIRT1/PGC1A	0.006	0.11	-10000	0	-0.42	51	51
p53/SIRT1	0.026	0.014	-10000	0	-10000	0	0
SIRT1/FOXO4	0.032	0.025	-10000	0	-0.27	1	1
FOXO1/FHL2/SIRT1	0.042	0.048	-10000	0	-0.38	8	8
HIST1H1E	0.018	0.014	-10000	0	-0.32	1	1
SIRT1/p300	0.035	0.021	-10000	0	-0.49	1	1
muscle cell differentiation	-0.021	0.051	0.43	1	-10000	0	1
TP53	0.021	0.008	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.049	0.019	-10000	0	-10000	0	0
CREBBP	0.027	0.007	-10000	0	-10000	0	0
MEF2D	0.027	0.007	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.026	0.049	-10000	0	-0.29	19	19
ACSS2	0.016	0.006	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.022	0.051	-10000	0	-0.43	1	1

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.061	0.031	-10000	0	-0.38	1	1
HDAC3	0.027	0.007	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.007	0.006	-10000	0	-10000	0	0
GATA1/HDAC4	0.022	0.073	-10000	0	-0.29	44	44
GATA1/HDAC5	0.021	0.07	-10000	0	-0.3	39	39
GATA2/HDAC5	-0.003	0.14	-10000	0	-0.46	71	71
HDAC5/BCL6/BCoR	0.05	0.025	-10000	0	-0.42	1	1
HDAC9	0.024	0.025	-10000	0	-0.65	1	1
Glucocorticoid receptor/Hsp90/HDAC6	0.052	0.02	-10000	0	-10000	0	0
HDAC4/ANKRA2	0.038	0.015	-10000	0	-10000	0	0
HDAC5/YWHAB	0.036	0.023	-10000	0	-0.49	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.018	0.007	-10000	0	-10000	0	0
GATA2	-0.028	0.18	-10000	0	-0.64	72	72
HDAC4/RFXANK	0.039	0.018	-10000	0	-0.29	1	1
BCOR	0.028	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.027	0.024	-10000	0	-0.65	1	1
HDAC5	0.025	0.024	-10000	0	-0.65	1	1
GNB1/GNG2	0.038	0.012	-10000	0	-10000	0	0
Histones	0.032	0.035	-10000	0	-10000	0	0
ADRBK1	0.028	0.003	-10000	0	-10000	0	0
HDAC4	0.026	0.014	-10000	0	-0.35	1	1
XPO1	0.027	0.006	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.036	0.023	-10000	0	-0.49	1	1
HDAC4/Ubc9	0.037	0.016	-10000	0	-10000	0	0
HDAC7	0.027	0.006	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.037	0.022	-10000	0	-0.49	1	1
TUBA1B	0.027	0.006	-10000	0	-10000	0	0
HDAC6	0.028	0.002	-10000	0	-10000	0	0
HDAC5/RFXANK	0.036	0.025	-10000	0	-0.39	2	2
CAMK4	0.018	0.074	-10000	0	-0.63	11	11
Tubulin/HDAC6	0.05	0.024	-10000	0	-0.42	1	1
SUMO1	0.027	0.006	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.027	0.007	-10000	0	-10000	0	0
GATA1	-0.002	0.097	-10000	0	-0.42	44	44
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.025	0.009	-10000	0	-10000	0	0
NR3C1	0.026	0.016	-10000	0	-0.42	1	1
SUMO1/HDAC4	0.041	0.042	-10000	0	-10000	0	0
SRF	0.026	0.007	-10000	0	-10000	0	0
HDAC4/YWHAB	0.037	0.016	-10000	0	-10000	0	0
Tubulin	0.037	0.022	-10000	0	-0.49	1	1
HDAC4/14-3-3 E	0.037	0.017	-10000	0	-10000	0	0
GNB1	0.026	0.007	-10000	0	-10000	0	0
RANGAP1	0.027	0.005	-10000	0	-10000	0	0
BCL6/BCoR	0.04	0.009	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.049	0.022	-10000	0	-10000	0	0
HDAC4/SRF	0.044	0.055	-10000	0	-0.42	10	10
HDAC4/ER alpha	0.022	0.087	-10000	0	-0.47	23	23
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.032	0.035	-10000	0	-10000	0	0
cell motility	0.05	0.024	-10000	0	-0.42	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.026	0.007	-10000	0	-10000	0	0
HDAC7/HDAC3	0.038	0.012	-10000	0	-10000	0	0
BCL6	0.027	0.006	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.026	0.014	-10000	0	-0.35	1	1
Hsp90/HDAC6	0.04	0.008	-10000	0	-10000	0	0
ESR1	0.005	0.11	-10000	0	-0.56	32	32
HDAC6/HDAC11	0.038	0.016	-10000	0	-0.28	1	1
Ran/GTP/Exportin 1	0.041	0.043	-10000	0	-10000	0	0
NPC	0.016	0.004	-10000	0	-10000	0	0
MEF2C	0.027	0.016	-10000	0	-0.42	1	1
RAN	0.027	0.006	-10000	0	-10000	0	0
HDAC4/MEF2C	0.069	0.035	-10000	0	-10000	0	0
GNG2	0.027	0.005	-10000	0	-10000	0	0
NCOR2	0.027	0.006	-10000	0	-10000	0	0
TUBB2A	0.026	0.024	-10000	0	-0.65	1	1
HDAC11	0.025	0.024	-10000	0	-0.65	1	1
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
RANBP2	0.027	0.006	-10000	0	-10000	0	0
ANKRA2	0.028	0.005	-10000	0	-10000	0	0
RFXANK	0.028	0.015	-10000	0	-0.42	1	1
nuclear import	-0.034	0.022	0.36	1	-10000	0	1

×

Circadian rhythm 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
chromatin modification	0.054	0.032	-9999	-10000	0	0
CLOCK	0.022	0.076	-9999	-0.65	11	11
TIMELESS/CRY2	0.044	0.03	-9999	-10000	0	0
DEC1/BMAL1	0.036	0.014	-9999	-0.29	1	1
ATR	0.027	0.006	-9999	-10000	0	0
NR1D1	0.02	0.05	-9999	-10000	0	0
ARNTL	0.031	0.005	-9999	-10000	0	0
TIMELESS	0.027	0.025	-9999	-10000	0	0
NPAS2	-0.002	0.14	-9999	-0.51	54	54
CRY2	0.028	0.004	-9999	-10000	0	0
mol:CO	-0.012	0.004	-9999	-10000	0	0
CHEK1	0.028	0.004	-9999	-10000	0	0
mol:HEME	0.012	0.004	-9999	-10000	0	0
PER1	0.025	0.009	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.042	0.1	-9999	-0.41	36	36
BMAL1/CLOCK	0.033	0.078	-9999	-10000	0	0
S phase of mitotic cell cycle	0.054	0.032	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.055	0.032	-9999	-10000	0	0
mol:NADPH	0.012	0.004	-9999	-10000	0	0
PER1/TIMELESS	0.042	0.028	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.009	0.023	-9999	-0.42	1	1

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.027	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.022	0.012	-10000	0	-10000	0	0
DOCK1	0.026	0.024	-10000	0	-0.65	1	1
ITGA4	0.012	0.08	-10000	0	-0.42	29	29
RAC1	0.025	0.01	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.027	0.06	-10000	0	-0.29	29	29
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.043	0.055	-10000	0	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.038	0.05	-10000	0	-10000	0	0
lamellipodium assembly	0.033	0.05	0.27	1	-0.38	8	9
PIK3CA	0.027	0.006	-10000	0	-10000	0	0
PI3K	0.039	0.011	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
TLN1	0.028	0.004	-10000	0	-10000	0	0
PXN	0.019	0.004	-10000	0	-10000	0	0
PIK3R1	0.028	0.005	-10000	0	-10000	0	0
ARF6/GTP	0.045	0.05	-10000	0	-10000	0	0
cell adhesion	0.048	0.051	-10000	0	-10000	0	0
CRKL/CBL	0.04	0.02	-10000	0	-0.49	1	1
alpha4/beta1 Integrin/Paxillin	0.037	0.05	-10000	0	-10000	0	0
ITGB1	0.027	0.007	-10000	0	-10000	0	0
ITGB7	0.027	0.006	-10000	0	-10000	0	0
ARF6/GDP	0.023	0.011	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.03	0.091	-10000	0	-0.38	13	13
p130Cas/Crk/Dock1	0.047	0.031	-10000	0	-0.42	2	2
VCAM1	-0.012	0.13	-10000	0	-0.43	74	74
alpha4/beta1 Integrin/Paxillin/Talin	0.05	0.052	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.048	0.053	-10000	0	-10000	0	0
BCAR1	0.026	0.024	-10000	0	-0.65	1	1
mol:GDP	-0.046	0.052	-10000	0	-10000	0	0
CBL	0.027	0.023	-10000	0	-0.65	1	1
PRKACA	0.028	0.003	-10000	0	-10000	0	0
GIT1	0.025	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.05	0.052	-10000	0	-10000	0	0
Rac1/GTP	0.034	0.055	0.28	1	-0.41	8	9

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.028	0.005	-10000	0	-10000	0	0
SMAD2	-0.008	0.05	-10000	0	-0.27	10	10
SMAD3	0.031	0.024	-10000	0	-10000	0	0
SMAD3/SMAD4	0.015	0.13	0.35	2	-0.49	49	51
SMAD4/Ubc9/PIASy	0.052	0.017	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.044	0.057	-10000	0	-10000	0	0
PPM1A	0.027	0.005	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
SMAD2/SMAD4	0.008	0.053	-10000	0	-0.29	2	2
MAP3K1	0.028	0.005	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.036	0.045	-10000	0	-0.49	6	6
MAPK3	0.026	0.007	-10000	0	-10000	0	0
MAPK1	0.027	0.005	-10000	0	-10000	0	0
NUP214	0.028	0.004	-10000	0	-10000	0	0
CTDSP1	0.027	0.007	-10000	0	-10000	0	0
CTDSP2	0.027	0.006	-10000	0	-10000	0	0
CTDSPL	0.026	0.008	-10000	0	-10000	0	0
KPNB1	0.025	0.009	-10000	0	-10000	0	0
TGFBRAP1	0.022	0.056	-10000	0	-0.65	6	6
UBE2I	0.026	0.007	-10000	0	-10000	0	0
NUP153	0.027	0.007	-10000	0	-10000	0	0
KPNA2	0.025	0.009	-10000	0	-10000	0	0
PIAS4	0.028	0.003	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.025	0.033	-10000	0	-0.65	2	2
positive regulation of NF-kappaB transcription factor activity	0.036	0.033	-10000	0	-0.49	3	3
MAP2K4	0.036	0.044	-10000	0	-0.44	2	2
IKBKB	0.027	0.006	-10000	0	-10000	0	0
TNFRSF10B	0.026	0.016	-10000	0	-0.42	1	1
TNFRSF10A	0.023	0.048	-10000	0	-0.59	5	5
SMPD1	0.017	0.014	-10000	0	-0.24	2	2
IKBKG	0.028	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.026	0.024	-10000	0	-0.65	1	1
TRAIL/TRAILR2	0.037	0.028	-10000	0	-0.49	2	2
TRAIL/TRAILR3	0.033	0.046	-10000	0	-0.35	11	11
TRAIL/TRAILR1	0.034	0.046	-10000	0	-0.45	7	7
TRAIL/TRAILR4	0.036	0.033	-10000	0	-0.49	3	3
TRAIL/TRAILR1/DAP3/GTP	0.044	0.04	-10000	0	-0.37	6	6
IKK complex	0.027	0.05	-10000	0	-0.45	1	1
RIPK1	0.027	0.007	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.02	0.005	-10000	0	-10000	0	0
MAPK3	0.017	0.025	-10000	0	-0.49	2	2
MAP3K1	0.033	0.042	-10000	0	-0.43	3	3
TRAILR4 (trimer)	0.026	0.024	-10000	0	-0.65	1	1
TRADD	0.026	0.007	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.023	0.048	-10000	0	-0.59	5	5
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.03	0.04	-10000	0	-0.42	5	5
CFLAR	0.027	0.006	-10000	0	-10000	0	0
MAPK1	0.017	0.025	0.21	1	-0.49	2	3
TRAIL/TRAILR1/FADD/TRADD/RIP	0.067	0.048	-10000	0	-0.35	6	6
mol:ceramide	0.017	0.014	-10000	0	-0.24	2	2
FADD	0.028	0.004	-10000	0	-10000	0	0
MAPK8	0.037	0.051	0.29	6	-0.38	1	7
TRAF2	0.028	0.004	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.021	0.053	-10000	0	-0.44	11	11
CHUK	0.027	0.007	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.048	0.043	-10000	0	-0.42	6	6
DAP3	0.027	0.007	-10000	0	-10000	0	0
CASP10	0.012	0.033	-10000	0	-0.43	4	4
JNK cascade	0.036	0.033	-10000	0	-0.49	3	3
TRAIL (trimer)	0.025	0.033	-10000	0	-0.65	2	2
TNFRSF10C	0.021	0.053	-10000	0	-0.44	11	11
TRAIL/TRAILR1/DAP3/GTP/FADD	0.055	0.042	-10000	0	-0.35	6	6
TRAIL/TRAILR2/FADD	0.05	0.029	-10000	0	-0.42	2	2
cell death	0.017	0.014	-10000	0	-0.24	2	2
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.032	0.025	-10000	0	-0.37	2	2
TRAILR2 (trimer)	0.026	0.016	-10000	0	-0.42	1	1
CASP8	-0.006	0.11	-10000	0	-0.61	29	29
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.069	0.038	-10000	0	-0.36	2	2

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.041	0.017	-9999	-0.29	2	2
FBXW11	0.027	0.007	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.027	0.051	-9999	-0.42	10	10
NF kappa B1 p50/RelA/I kappa B alpha	0.029	0.066	-9999	-0.38	2	2
NFKBIA	0.012	0.037	-9999	-0.29	8	8
MAPK14	0.027	0.007	-9999	-10000	0	0
NF kappa B1 p105/p50	0.031	0.019	-9999	-0.42	1	1
ARRB2	0.015	0.02	-9999	-0.5	1	1
REL	0.019	0.071	-9999	-0.6	11	11
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.032	0.022	-9999	-0.42	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.033	0.018	-9999	-0.42	1	1
PIK3CA	0.027	0.006	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.025	0.025	-9999	-0.49	1	1
PIK3R1	0.028	0.005	-9999	-10000	0	0
NFKB1	0.018	0.018	-9999	-0.49	1	1
RELA	0.028	0.003	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.015	0.056	-9999	-0.35	5	5
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.029	0.074	-9999	-0.44	2	2
SRC	0.027	0.007	-9999	-10000	0	0
PI3K	0.039	0.011	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.015	0.056	-9999	-0.35	5	5
IKBKB	0.027	0.006	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.027	0.007	-9999	-10000	0	0
SYK	0.024	0.048	-9999	-0.59	5	5
I kappa B alpha/PIK3R1	0.021	0.066	-9999	-0.36	4	4
cell death	0.028	0.071	-9999	-0.42	2	2
NF kappa B1 p105/c-Rel	0.027	0.051	-9999	-0.42	10	10
LCK	0.003	0.1	-9999	-0.44	44	44
BCL3	0.027	0.021	-9999	-0.42	2	2

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.044	0.023	-10000	0	-0.36	1	1
MAPK9	0.009	0.002	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.013	0.055	0.2	3	-0.3	29	32
GNB1/GNG2	0.035	0.011	-10000	0	-10000	0	0
GNB1	0.026	0.007	-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	0.009	0.002	-10000	0	-10000	0	0
Gs family/GTP	0.017	0.016	-10000	0	-0.3	2	2
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	0.004	0.078	2	-10000	0	2
GNAL	0.026	0.028	-10000	0	-0.53	2	2
GNG2	0.027	0.005	-10000	0	-10000	0	0
CRH	-0.016	0.079	-10000	0	-0.42	29	29
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.006	0.034	-10000	0	-0.37	7	7
MAPK11	0.009	0.006	-10000	0	-0.16	1	1

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.022	0.044	0.3	5	-0.47	1	6
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.002	0.08	-10000	0	-0.35	38	38
AP2	0.04	0.01	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.033	0.016	-10000	0	-10000	0	0
CLTB	0.027	0.007	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.024	0.009	-10000	0	-10000	0	0
CD4	0.012	0.081	-10000	0	-0.42	30	30
CLTA	0.028	0.004	-10000	0	-10000	0	0
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
ARFGAP1	0.009	0.017	-10000	0	-0.49	1	1
mol:PI-4-5-P2	0.009	0.013	-10000	0	-0.36	1	1
ARF1/GTP	0.031	0.014	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.016	0.016	-10000	0	-0.41	1	1
mol:Choline	0.008	0.013	-10000	0	-0.36	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.028	0.007	-10000	0	-10000	0	0
DDEF1	0.008	0.014	-10000	0	-0.36	1	1
ARF1/GDP	0.004	0.02	-10000	0	-0.4	1	1
AP2M1	0.027	0.006	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.014	0.007	-10000	0	-10000	0	0
Rac/GTP	0.019	0.008	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.036	0.021	-10000	0	-0.37	1	1
ARFIP2	0.023	0.012	-10000	0	-10000	0	0
COPA	0.027	0.007	-10000	0	-10000	0	0
RAC1	0.025	0.01	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.009	0.064	-10000	0	-0.28	35	35
ARF1/GTP/ARHGAP10	0.019	0.005	-10000	0	-10000	0	0
GGA3	0.025	0.009	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.022	0.054	-10000	0	-0.24	33	33
AP2A1	0.028	0.003	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.019	0.025	-10000	0	-0.26	5	5
ARF1/GDP/Membrin	0.018	0.068	-10000	0	-0.32	33	33
Arfaptin 2/Rac/GDP	0.033	0.014	-10000	0	-10000	0	0
CYTH2	0.029	0.005	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.034	0.014	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.018	0.007	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.017	0.045	-10000	0	-0.25	6	6
PLD2	0.008	0.013	-10000	0	-0.36	1	1
ARF-GAP1/v-SNARE	0.009	0.017	-10000	0	-0.49	1	1
PIP5K1A	0.009	0.013	-10000	0	-0.36	1	1
ARF1/GTP/Membrin/GBF1/p115	0.025	0.031	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.008	0.013	-10000	0	-0.36	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.009	0.017	-10000	0	-0.49	1	1
GOSR2	0.015	0.008	-10000	0	-10000	0	0
USO1	0.013	0.025	-10000	0	-0.31	5	5
GBF1	0.01	0.038	-10000	0	-0.31	12	12
ARF1/GTP/Arfaptin 2	0.038	0.011	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.042	0.056	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.018	0.07	-10000	0	-10000	0	0
regulation of axonogenesis	-0.012	0.035	0.26	1	-10000	0	1
myoblast fusion	-0.021	0.043	-10000	0	-10000	0	0
mol:GTP	0.012	0.038	-10000	0	-0.25	2	2
regulation of calcium-dependent cell-cell adhesion	-0.043	0.046	-10000	0	-10000	0	0
ARF1/GTP	0.027	0.034	-10000	0	-0.24	1	1
mol:GM1	0.005	0.027	-10000	0	-0.24	1	1
mol:Choline	0.012	0.023	-10000	0	-10000	0	0
lamellipodium assembly	0.007	0.062	-10000	0	-0.34	17	17
MAPK3	0.02	0.042	-10000	0	-0.34	1	1
ARF6/GTP/NME1/Tiam1	0.043	0.047	-10000	0	-10000	0	0
ARF1	0.027	0.007	-10000	0	-10000	0	0
ARF6/GDP	0.021	0.043	-10000	0	-10000	0	0
ARF1/GDP	0.024	0.055	0.27	1	-10000	0	1
ARF6	0.028	0.022	-10000	0	-10000	0	0
RAB11A	0.028	0.003	-10000	0	-10000	0	0
TIAM1	0.027	0.022	-10000	0	-0.59	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.021	0.04	-10000	0	-10000	0	0
actin filament bundle formation	-0.027	0.054	-10000	0	-10000	0	0
KALRN	0.012	0.032	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0.039	0.011	-10000	0	-10000	0	0
RhoA/GDP	0.027	0.054	-10000	0	-10000	0	0
NME1	0.025	0.028	-10000	0	-0.42	3	3
Rac1/GDP	0.025	0.053	-10000	0	-0.26	1	1
substrate adhesion-dependent cell spreading	0.012	0.038	-10000	0	-0.25	2	2
cortical actin cytoskeleton organization	0.007	0.063	-10000	0	-0.34	17	17
RAC1	0.025	0.01	-10000	0	-10000	0	0
liver development	0.012	0.038	-10000	0	-0.25	2	2
ARF6/GTP	0.012	0.038	-10000	0	-0.25	2	2
RhoA/GTP	0.027	0.034	-10000	0	-0.24	1	1
mol:GDP	0.01	0.044	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.044	0.035	-10000	0	-10000	0	0
RHOA	0.026	0.008	-10000	0	-10000	0	0
PLD1	0.017	0.028	-10000	0	-10000	0	0
RAB11FIP3	0.026	0.007	-10000	0	-10000	0	0
tube morphogenesis	0.007	0.062	-10000	0	-0.34	17	17
ruffle organization	0.012	0.035	-10000	0	-0.26	1	1
regulation of epithelial cell migration	0.012	0.038	-10000	0	-0.25	2	2
PLD2	0.015	0.03	-10000	0	-0.24	1	1
PIP5K1A	0.012	0.035	-10000	0	-0.26	1	1
mol:Phosphatidic acid	0.012	0.023	-10000	0	-10000	0	0
Rac1/GTP	0.007	0.063	-10000	0	-0.34	17	17

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.027	0.007	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.007	0.007	-9999	-10000	0	0
MDM2/SUMO1	0.038	0.044	-9999	-10000	0	0
HDAC4	0.026	0.014	-9999	-0.35	1	1
Ran/GTP/Exportin 1/HDAC1	0.008	0.005	-9999	-10000	0	0
SUMO1	0.027	0.006	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.009	0.037	-9999	-0.18	31	31
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.017	0.01	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.027	0.006	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.027	0.006	-9999	-10000	0	0
SUMO1/HDAC4	0.041	0.042	-9999	-10000	0	0
SUMO1/HDAC1	0.041	0.042	-9999	-10000	0	0
RANGAP1	0.027	0.005	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.064	0.024	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.018	0.007	-9999	-10000	0	0
Ran/GTP	0.027	0.042	-9999	-0.24	2	2
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.027	0.006	-9999	-10000	0	0
UBE2I	0.026	0.007	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.028	0.039	-9999	-10000	0	0
NPC	0.016	0.004	-9999	-10000	0	0
PIAS2	0.028	0.005	-9999	-10000	0	0
PIAS1	0.028	0.003	-9999	-10000	0	0
EntrezGene:9972	0	0	-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	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.036	0.018	-9999	-0.29	1	1
FBXW11	0.027	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.027	0.007	-9999	-10000	0	0
CHUK	0.027	0.007	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.069	0.034	-9999	-10000	0	0
NFKB1	0.027	0.023	-9999	-0.65	1	1
MAP3K14	0.025	0.017	-9999	-0.42	1	1
NF kappa B1 p50/RelB	0.04	0.019	-9999	-0.49	1	1
RELB	0.028	0.003	-9999	-10000	0	0
NFKB2	0.027	0.007	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.036	0.01	-9999	-10000	0	0
regulation of B cell activation	0.035	0.01	-9999	-10000	0	0

pid_entity	TCGA.Y8.A8S1	TCGA.Y8.A8S0	TCGA.Y8.A8RZ	TCGA.Y8.A8RY
109_MAP3K5	-0.02	0.17	0.055	0.17
47_PPARGC1A	0.028	0.028	0.028	0.028
105_BMP4	0.028	0.028	0.028	0.028
105_BMP6	0.028	0.028	-0.65	0.028
105_BMP7	0.028	0.028	-0.65	0.028
105_BMP2	0.028	0.028	0.028	0.028
131_RELN/VLDLR	0.073	0	0.073	0
30_TGFB1/TGF beta receptor Type II	0.028	0.028	0.028	0.028
84_STAT5B	-0.034	-0.11	-0.22	-0.11
84_STAT5A	-0.034	-0.11	-0.22	-0.11