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

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	383
HIF-1-alpha transcription factor network	212
Nephrin/Neph1 signaling in the kidney podocyte	188
TCGA08_p53	146
TCR signaling in naïve CD8+ T cells	141
FOXA2 and FOXA3 transcription factor networks	120
Syndecan-4-mediated signaling events	119
Aurora B signaling	119
FOXM1 transcription factor network	110
IL12-mediated signaling events	107

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
TCGA08_retinoblastoma	0.7213	383	3069	8	-0.84	0.22	1000	-1000	-0.031	-1000
HIF-1-alpha transcription factor network	0.3992	212	16112	76	-1.3	0.026	1000	-1000	-0.16	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.3540	188	6408	34	-0.61	0.016	1000	-1000	-0.098	-1000
TCGA08_p53	0.2750	146	1023	7	-0.65	0.31	1000	-1000	-0.022	-1000
TCR signaling in naïve CD8+ T cells	0.2655	141	13123	93	-0.66	0.33	1000	-1000	-0.12	-1000
FOXA2 and FOXA3 transcription factor networks	0.2260	120	5537	46	-1.2	0.025	1000	-1000	-0.1	-1000
Syndecan-4-mediated signaling events	0.2241	119	7998	67	-0.64	0.11	1000	-1000	-0.14	-1000
Aurora B signaling	0.2241	119	7979	67	-0.4	0.016	1000	-1000	-0.11	-1000
FOXM1 transcription factor network	0.2072	110	5633	51	-0.82	0.04	1000	-1000	-0.19	-1000
IL12-mediated signaling events	0.2015	107	9370	87	-0.69	0.16	1000	-1000	-0.16	-1000
Glypican 1 network	0.1996	106	5100	48	-0.56	0.045	1000	-1000	-0.069	-1000
PDGFR-alpha signaling pathway	0.1959	104	4618	44	-0.28	0.034	1000	-1000	-0.09	-1000
JNK signaling in the CD4+ TCR pathway	0.1582	84	1429	17	-0.41	0.016	1000	-1000	-0.092	-1000
amb2 Integrin signaling	0.1582	84	6941	82	-0.55	0.016	1000	-1000	-0.12	-1000
IL4-mediated signaling events	0.1412	75	6852	91	-0.84	0.54	1000	-1000	-0.18	-1000
EGFR-dependent Endothelin signaling events	0.1394	74	1561	21	-0.67	0.016	1000	-1000	-0.12	-1000
HIF-2-alpha transcription factor network	0.1356	72	3104	43	-0.76	0.34	1000	-1000	-0.11	-1000
Aurora C signaling	0.1337	71	497	7	-0.39	0.012	1000	-1000	-0.064	-1000
Caspase cascade in apoptosis	0.1318	70	5239	74	-0.32	0.16	1000	-1000	-0.076	-1000
Glypican 2 network	0.1299	69	278	4	-0.12	-1000	1000	-1000	-0.054	-1000
Syndecan-1-mediated signaling events	0.1262	67	2282	34	-0.41	0.016	1000	-1000	-0.1	-1000
BMP receptor signaling	0.1205	64	5240	81	-0.69	0.016	1000	-1000	-0.13	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.1130	60	2004	33	-0.83	0.016	1000	-1000	-0.094	-1000
IL23-mediated signaling events	0.1111	59	3582	60	-0.39	0.021	1000	-1000	-0.18	-1000
Signaling events mediated by the Hedgehog family	0.0923	49	2577	52	-0.44	0.12	1000	-1000	-0.12	-1000
Fc-epsilon receptor I signaling in mast cells	0.0866	46	4510	97	-0.32	0.04	1000	-1000	-0.12	-1000
S1P1 pathway	0.0810	43	1562	36	-0.38	0.018	1000	-1000	-0.088	-1000
IL27-mediated signaling events	0.0791	42	2159	51	-0.62	0.074	1000	-1000	-0.13	-1000
Ephrin A reverse signaling	0.0772	41	292	7	-0.059	0	1000	-1000	-0.042	-1000
Effects of Botulinum toxin	0.0772	41	1083	26	-0.36	0.016	1000	-1000	-0.099	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0772	41	2829	68	-0.54	0.063	1000	-1000	-0.18	-1000
Arf6 signaling events	0.0734	39	2448	62	-0.67	0.016	1000	-1000	-0.089	-1000
VEGFR1 specific signals	0.0716	38	2131	56	-0.47	0.045	1000	-1000	-0.11	-1000
Calcium signaling in the CD4+ TCR pathway	0.0697	37	1175	31	-0.46	0.016	1000	-1000	-0.17	-1000
p75(NTR)-mediated signaling	0.0678	36	4539	125	-0.42	0.016	1000	-1000	-0.15	-1000
LPA4-mediated signaling events	0.0640	34	417	12	-0.17	0.026	1000	-1000	-0.033	-1000
IL2 signaling events mediated by STAT5	0.0640	34	759	22	-0.44	0.038	1000	-1000	-0.07	-1000
IL2 signaling events mediated by PI3K	0.0621	33	1953	58	-0.43	0.032	1000	-1000	-0.11	-1000
PLK1 signaling events	0.0584	31	2651	85	-0.38	0.016	1000	-1000	-0.075	-1000
IL6-mediated signaling events	0.0584	31	2367	75	-0.29	0.076	1000	-1000	-0.12	-1000
BCR signaling pathway	0.0584	31	3150	99	-0.34	0.035	1000	-1000	-0.14	-1000
Coregulation of Androgen receptor activity	0.0565	30	2349	76	-0.92	0.033	1000	-1000	-0.07	-1000
Regulation of Telomerase	0.0546	29	3020	102	-0.67	0.051	1000	-1000	-0.15	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0546	29	2335	78	-0.32	0.045	1000	-1000	-0.11	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0527	28	1550	54	-0.65	0.031	1000	-1000	-0.14	-1000
Reelin signaling pathway	0.0527	28	1570	56	-0.24	0.016	1000	-1000	-0.11	-1000
Glucocorticoid receptor regulatory network	0.0508	27	3146	114	-0.41	0.16	1000	-1000	-0.11	-1000
Integrins in angiogenesis	0.0508	27	2331	84	-0.38	0.04	1000	-1000	-0.13	-1000
Aurora A signaling	0.0452	24	1484	60	-0.24	0.053	1000	-1000	-0.091	-1000
EPO signaling pathway	0.0452	24	1372	55	-0.29	0.018	1000	-1000	-0.14	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0452	24	2125	88	-0.31	0.075	1000	-1000	-0.15	-1000
Visual signal transduction: Rods	0.0452	24	1285	52	-0.29	0.016	1000	-1000	-0.11	-1000
Signaling events mediated by PTP1B	0.0433	23	1755	76	-0.67	0.049	1000	-1000	-0.11	-1000
Syndecan-2-mediated signaling events	0.0377	20	1439	69	-0.55	0.053	1000	-1000	-0.092	-1000
Endothelins	0.0377	20	1958	96	-0.35	0.086	1000	-1000	-0.11	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0377	20	900	45	-0.57	0.062	1000	-1000	-0.12	-1000
Regulation of nuclear SMAD2/3 signaling	0.0358	19	2673	136	-0.45	0.1	1000	-1000	-0.11	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0358	19	2347	120	-0.16	0.14	1000	-1000	-0.13	-1000
Wnt signaling	0.0339	18	127	7	-0.068	0.016	1000	-1000	-0.077	-1000
S1P3 pathway	0.0320	17	719	42	-0.38	0.062	1000	-1000	-0.084	-1000
Thromboxane A2 receptor signaling	0.0301	16	1732	105	-0.67	0.067	1000	-1000	-0.11	-1000
Presenilin action in Notch and Wnt signaling	0.0301	16	1035	61	-0.19	0.093	1000	-1000	-0.11	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0301	16	609	37	-0.29	0.026	1000	-1000	-0.12	-1000
Ceramide signaling pathway	0.0282	15	1159	76	-0.67	0.23	1000	-1000	-0.085	-1000
FoxO family signaling	0.0282	15	1003	64	-0.57	0.12	1000	-1000	-0.1	-1000
LPA receptor mediated events	0.0282	15	1612	102	-0.4	0.061	1000	-1000	-0.12	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0264	14	416	28	-0.14	0.024	1000	-1000	-0.076	-1000
PLK2 and PLK4 events	0.0264	14	44	3	-0.016	0.011	1000	-1000	-0.046	-1000
E-cadherin signaling events	0.0264	14	71	5	-0.023	0.016	1000	-1000	-0.066	-1000
FAS signaling pathway (CD95)	0.0245	13	638	47	-0.42	0.027	1000	-1000	-0.066	-1000
Canonical Wnt signaling pathway	0.0245	13	708	51	-0.19	0.096	1000	-1000	-0.085	-1000
Class I PI3K signaling events	0.0245	13	1003	73	-0.47	0.036	1000	-1000	-0.11	-1000
Regulation of Androgen receptor activity	0.0245	13	932	70	-0.96	0.04	1000	-1000	-0.096	-1000
ErbB4 signaling events	0.0226	12	839	69	-0.18	0.1	1000	-1000	-0.13	-1000
IFN-gamma pathway	0.0226	12	879	68	-0.37	0.018	1000	-1000	-0.14	-1000
Nongenotropic Androgen signaling	0.0226	12	638	52	-0.18	0.07	1000	-1000	-0.088	-1000
S1P5 pathway	0.0207	11	193	17	-0.14	0.045	1000	-1000	-0.08	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0207	11	1495	125	-0.39	0.043	1000	-1000	-0.16	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0207	11	863	74	-0.67	0.098	1000	-1000	-0.13	-1000
S1P4 pathway	0.0207	11	277	25	-0.14	0.034	1000	-1000	-0.078	-1000
Noncanonical Wnt signaling pathway	0.0188	10	270	26	-0.12	0.016	1000	-1000	-0.13	-1000
Visual signal transduction: Cones	0.0169	9	370	38	-0.041	0.016	1000	-1000	-0.088	-1000
a4b1 and a4b7 Integrin signaling	0.0169	9	48	5	-0.02	0.016	1000	-1000	-0.048	-1000
TCGA08_rtk_signaling	0.0169	9	239	26	-0.28	0.041	1000	-1000	-0.033	-1000
Signaling events regulated by Ret tyrosine kinase	0.0151	8	731	82	-0.064	0.025	1000	-1000	-0.12	-1000
Class IB PI3K non-lipid kinase events	0.0151	8	24	3	-0.003	0.003	1000	-1000	-0.016	-1000
Signaling events mediated by PRL	0.0132	7	245	34	-0.055	0.045	1000	-1000	-0.089	-1000
Canonical NF-kappaB pathway	0.0113	6	270	39	-0.19	0.075	1000	-1000	-0.11	-1000
Insulin-mediated glucose transport	0.0113	6	194	32	-0.083	0.068	1000	-1000	-0.091	-1000
Signaling events mediated by HDAC Class III	0.0113	6	240	40	-0.057	0.032	1000	-1000	-0.074	-1000
IL1-mediated signaling events	0.0113	6	401	62	-0.091	0.059	1000	-1000	-0.14	-1000
Ephrin B reverse signaling	0.0113	6	319	48	-0.03	0.031	1000	-1000	-0.12	-1000
p38 MAPK signaling pathway	0.0113	6	276	44	-0.099	0.049	1000	-1000	-0.088	-1000
ErbB2/ErbB3 signaling events	0.0094	5	388	65	-0.13	0.059	1000	-1000	-0.11	-1000
Arf6 downstream pathway	0.0094	5	225	43	-0.033	0.033	1000	-1000	-0.063	-1000
Signaling mediated by p38-gamma and p38-delta	0.0094	5	85	15	0	0.036	1000	-1000	-0.05	-1000
Paxillin-dependent events mediated by a4b1	0.0094	5	211	36	-0.027	0.031	1000	-1000	-0.098	-1000
Syndecan-3-mediated signaling events	0.0094	5	209	35	-0.039	0.016	1000	-1000	-0.099	-1000
E-cadherin signaling in the nascent adherens junction	0.0094	5	430	76	-0.026	0.067	1000	-1000	-0.12	-1000
Arf6 trafficking events	0.0094	5	411	71	-0.12	0.058	1000	-1000	-0.1	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0075	4	369	85	-0.037	0.079	1000	-1000	-0.1	-1000
EPHB forward signaling	0.0075	4	369	85	-0.075	0.069	1000	-1000	-0.14	-1000
Plasma membrane estrogen receptor signaling	0.0075	4	372	86	-0.16	0.07	1000	-1000	-0.12	-1000
Ras signaling in the CD4+ TCR pathway	0.0075	4	84	17	-0.038	0.055	1000	-1000	-0.069	-1000
BARD1 signaling events	0.0056	3	222	57	-0.17	0.044	1000	-1000	-0.096	-1000
Osteopontin-mediated events	0.0056	3	122	38	-0.03	0.097	1000	-1000	-0.16	-1000
Cellular roles of Anthrax toxin	0.0056	3	119	39	-0.022	0.027	1000	-1000	-0.042	-1000
PDGFR-beta signaling pathway	0.0056	3	380	97	-0.056	0.087	1000	-1000	-0.12	-1000
E-cadherin signaling in keratinocytes	0.0056	3	164	43	-0.29	0.054	1000	-1000	-0.11	-1000
Hedgehog signaling events mediated by Gli proteins	0.0038	2	135	65	-0.06	0.093	1000	-1000	-0.09	-1000
ceramide signaling pathway	0.0038	2	131	49	-0.12	0.054	1000	-1000	-0.068	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0038	2	130	52	-0.031	0.092	1000	-1000	-0.088	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0038	2	181	83	-0.083	0.081	1000	-1000	-0.11	-1000
Retinoic acid receptors-mediated signaling	0.0038	2	126	58	-0.025	0.062	1000	-1000	-0.11	-1000
Signaling mediated by p38-alpha and p38-beta	0.0038	2	115	44	-0.046	0.049	1000	-1000	-0.072	-1000
Regulation of p38-alpha and p38-beta	0.0038	2	153	54	-0.04	0.073	1000	-1000	-0.086	-1000
Insulin Pathway	0.0038	2	214	74	-0.032	0.055	1000	-1000	-0.12	-1000
Signaling events mediated by HDAC Class II	0.0019	1	124	75	-0.026	0.051	1000	-1000	-0.099	-1000
Circadian rhythm pathway	0.0019	1	33	22	-0.019	0.064	1000	-1000	-0.089	-1000
mTOR signaling pathway	0.0019	1	103	53	-0.01	0.044	1000	-1000	-0.089	-1000
Class I PI3K signaling events mediated by Akt	0.0019	1	104	68	-0.083	0.059	1000	-1000	-0.1	-1000
Nectin adhesion pathway	0.0019	1	98	63	-0.016	0.078	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class I	0.0019	1	194	104	-0.028	0.063	1000	-1000	-0.1	-1000
Atypical NF-kappaB pathway	0.0019	1	55	31	-0.02	0.037	1000	-1000	-0.099	-1000
IGF1 pathway	0.0019	1	98	57	-0.065	0.071	1000	-1000	-0.14	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	2	23	-0.001	0.062	1000	-1000	-0.1	-1000
TRAIL signaling pathway	0.0000	0	27	48	-0.002	0.07	1000	-1000	-0.092	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.039	1000	-1000	-0.087	-1000
Rapid glucocorticoid signaling	0.0000	0	16	20	-0.006	0.016	1000	-1000	-0.068	-1000
Arf1 pathway	0.0000	0	31	54	-0.01	0.043	1000	-1000	-0.077	-1000
Alternative NF-kappaB pathway	0.0000	0	10	13	-0.005	0.016	1000	-1000	-0.097	-1000
Total	NA	4254	222079	7203	-40	-990	131000	-131000	-13	-131000

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.011	0.099	-10000	0	-0.87	7	7
CDKN2C	0.079	0.017	-10000	0	-10000	0	0
CDKN2A	-0.84	0.17	-10000	0	-0.87	511	511
CCND2	0.18	0.049	0.19	510	-10000	0	510
RB1	-0.2	0.051	-10000	0	-0.21	510	510
CDK4	0.22	0.052	0.23	510	-10000	0	510
CDK6	0.2	0.055	0.21	510	-0.18	1	511
G1/S progression	0.2	0.055	0.21	510	-10000	0	510

×

HIF-1-alpha transcription factor network

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
PKM2	-0.98	0.53	-9999	-1.3	324	324
HDAC7	0.014	0.005	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.68	0.33	-9999	-0.91	317	317
SMAD4	0.017	0	-9999	-10000	0	0
ID2	-0.98	0.53	-9999	-1.3	336	336
AP1	-0.014	0.087	-9999	-0.56	13	13
ABCG2	-0.98	0.53	-9999	-1.3	325	325
HIF1A	-0.1	0.068	-9999	-0.89	2	2
TFF3	-0.99	0.53	-9999	-1.3	326	326
GATA2	-0.001	0.12	-9999	-0.74	13	13
AKT1	-0.093	0.053	-9999	-10000	0	0
response to hypoxia	-0.13	0.058	-9999	-10000	0	0
MCL1	-0.98	0.53	-9999	-1.3	324	324
NDRG1	-0.98	0.53	-9999	-1.4	308	308
SERPINE1	-1	0.56	-9999	-1.4	335	335
FECH	-0.98	0.53	-9999	-1.3	326	326
FURIN	-0.98	0.53	-9999	-1.3	326	326
NCOA2	-0.005	0.11	-9999	-0.74	11	11
EP300	-0.1	0.076	-9999	-0.36	6	6
HMOX1	-1	0.54	-9999	-1.4	328	328
BHLHE40	-0.98	0.53	-9999	-1.3	334	334
BHLHE41	-1.1	0.58	-9999	-1.4	342	342
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.08	0.056	-9999	-0.6	2	2
ENG	-0.059	0.064	-9999	-0.55	1	1
JUN	0.016	0.003	-9999	-10000	0	0
RORA	-0.98	0.53	-9999	-1.4	308	308
ABCB1	-0.3	0.42	-9999	-1.3	70	70
TFRC	-0.98	0.53	-9999	-1.3	326	326
CXCR4	-1.1	0.59	-9999	-1.5	341	341
TF	-1	0.58	-9999	-1.4	334	334
CITED2	-0.98	0.53	-9999	-1.4	308	308
HIF1A/ARNT	-1.3	0.85	-9999	-1.8	346	346
LDHA	-0.086	0.062	-9999	-0.86	2	2
ETS1	-0.98	0.53	-9999	-1.3	326	326
PGK1	-0.98	0.53	-9999	-1.3	326	326
NOS2	-0.99	0.53	-9999	-1.3	326	326
ITGB2	-1	0.57	-9999	-1.4	331	331
ALDOA	-0.98	0.53	-9999	-1.3	323	323
Cbp/p300/CITED2	-0.98	0.53	-9999	-1.4	302	302
FOS	-0.002	0.12	-9999	-0.75	13	13
HK2	-1.2	0.58	-9999	-1.5	396	396
SP1	0.021	0.029	-9999	-10000	0	0
GCK	-0.18	0.18	-9999	-1.1	10	10
HK1	-0.98	0.53	-9999	-1.4	301	301
NPM1	-0.98	0.53	-9999	-1.3	324	324
EGLN1	-0.98	0.53	-9999	-1.3	325	325
CREB1	0.026	0.002	-9999	-10000	0	0
PGM1	-0.98	0.53	-9999	-1.3	326	326
SMAD3	0.017	0	-9999	-10000	0	0
EDN1	-0.092	0.17	-9999	-0.8	19	19
IGFBP1	-1	0.57	-9999	-1.4	315	315
VEGFA	-0.78	0.41	-9999	-1.2	243	243
HIF1A/JAB1	-0.055	0.047	-9999	-0.69	2	2
CP	-1.2	0.59	-9999	-1.5	393	393
CXCL12	-0.99	0.53	-9999	-1.3	330	330
COPS5	0.011	0.008	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.98	0.53	-9999	-1.3	324	324
EGLN3	-1.3	0.51	-9999	-1.5	419	419
CA9	-1.3	0.48	-9999	-1.5	429	429
TERT	-1	0.55	-9999	-1.4	335	335
ENO1	-0.98	0.53	-9999	-1.3	324	324
PFKL	-0.98	0.53	-9999	-1.3	336	336
NCOA1	0.015	0.003	-9999	-10000	0	0
ADM	-1.1	0.57	-9999	-1.4	341	341
ARNT	-0.1	0.047	-9999	-10000	0	0
HNF4A	-0.043	0.21	-9999	-0.74	44	44
ADFP	-0.99	0.53	-9999	-1.3	340	340
SLC2A1	-0.63	0.34	-9999	-0.97	177	177
LEP	-1	0.54	-9999	-1.4	316	316
HIF1A/ARNT/Cbp/p300	-0.71	0.34	-9999	-0.93	319	319
EPO	-0.61	0.4	-9999	-1.1	186	186
CREBBP	-0.099	0.074	-9999	-0.35	5	5
HIF1A/ARNT/Cbp/p300/HDAC7	-0.75	0.39	-9999	-1	322	322
PFKFB3	-0.98	0.53	-9999	-1.4	306	306
NT5E	-0.98	0.53	-9999	-1.3	324	324

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.48	0.26	0.62	414	-10000	0	414
KIRREL	-0.056	0.11	-10000	0	-0.81	10	10
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.49	0.26	-10000	0	-0.62	414	414
PLCG1	0.016	0	-10000	0	-10000	0	0
ARRB2	0.014	0.038	-10000	0	-0.86	1	1
WASL	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.53	0.31	-10000	0	-0.84	230	230
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.41	0.26	-10000	0	-0.66	230	230
FYN	-0.5	0.3	-10000	0	-0.79	230	230
mol:Ca2+	-0.52	0.3	-10000	0	-0.82	230	230
mol:DAG	-0.52	0.3	-10000	0	-0.83	230	230
NPHS2	-0.41	0.38	-10000	0	-0.8	254	254
mol:IP3	-0.52	0.3	-10000	0	-0.83	230	230
regulation of endocytosis	-0.47	0.28	-10000	0	-0.74	230	230
Nephrin/NEPH1/podocin/Cholesterol	-0.54	0.31	-10000	0	-0.65	441	441
establishment of cell polarity	-0.48	0.26	-10000	0	-0.62	414	414
Nephrin/NEPH1/podocin/NCK1-2	-0.49	0.29	-10000	0	-0.78	230	230
Nephrin/NEPH1/beta Arrestin2	-0.48	0.28	-10000	0	-0.76	230	230
NPHS1	-0.61	0.32	-10000	0	-0.78	411	411
Nephrin/NEPH1/podocin	-0.5	0.3	-10000	0	-0.8	230	230
TJP1	0.016	0	-10000	0	-10000	0	0
NCK1	0.014	0.033	-10000	0	-0.74	1	1
NCK2	0.016	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.53	0.31	-10000	0	-0.84	230	230
CD2AP	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.53	0.31	-10000	0	-0.84	230	230
GRB2	0.016	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.49	0.3	-10000	0	-0.78	230	230
cytoskeleton organization	-0.53	0.32	-10000	0	-0.84	230	230
Nephrin/NEPH1	-0.36	0.2	-10000	0	-0.46	414	414
Nephrin/NEPH1/ZO-1	-0.39	0.21	-10000	0	-0.5	414	414

×

TCGA08_p53

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
CDKN2A	-0.65	0.13	-10000	0	-0.68	511	511
TP53	-0.17	0.037	-10000	0	-10000	0	0
Senescence	-0.17	0.037	-10000	0	-10000	0	0
Apoptosis	-0.17	0.037	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.31	0.062	0.32	511	-10000	0	511
MDM4	0.014	0.038	-10000	0	-0.86	1	1

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.34	0.33	-10000	0	-0.69	229	229
FYN	-0.41	0.49	-10000	0	-0.93	235	235
LAT/GRAP2/SLP76	-0.36	0.38	-10000	0	-0.76	236	236
IKBKB	0.016	0	-10000	0	-10000	0	0
AKT1	-0.25	0.28	-10000	0	-0.54	241	241
B2M	0.009	0.009	-10000	0	-10000	0	0
IKBKG	-0.079	0.072	-10000	0	-0.19	84	84
MAP3K8	0.012	0.054	-10000	0	-0.86	2	2
mol:Ca2+	-0.11	0.045	-10000	0	-0.14	281	281
integrin-mediated signaling pathway	-0.02	0.1	-10000	0	-0.58	18	18
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.41	0.45	-10000	0	-0.85	249	249
TRPV6	-0.66	0.26	-10000	0	-0.76	459	459
CD28	-0.058	0.23	-10000	0	-0.87	40	40
SHC1	-0.44	0.49	-10000	0	-0.94	244	244
receptor internalization	-0.51	0.56	-10000	0	-1.1	251	251
PRF1	-0.48	0.59	-10000	0	-1.1	244	244
KRAS	0.016	0	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
COT/AKT1	-0.18	0.22	-10000	0	-0.41	225	225
LAT	-0.5	0.53	-10000	0	-1	260	260
EntrezGene:6955	-0.003	0.005	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	239	239
CD3E	-0.34	0.44	-10000	0	-0.87	213	213
CD3G	-0.32	0.43	-10000	0	-0.87	203	203
RASGRP2	-0.023	0.029	-10000	0	-0.14	2	2
RASGRP1	-0.23	0.27	-10000	0	-0.5	238	238
HLA-A	0.005	0.055	-10000	0	-0.87	2	2
RASSF5	-0.014	0.16	-10000	0	-0.86	18	18
RAP1A/GTP/RAPL	-0.02	0.11	-10000	0	-0.59	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.036	0.081	-10000	0	-0.14	3	3
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.15	0.13	-10000	0	-0.34	103	103
PRKCA	-0.14	0.17	-10000	0	-0.31	199	199
GRAP2	-0.042	0.22	-10000	0	-0.86	35	35
mol:IP3	-0.16	0.34	0.28	113	-0.5	220	333
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.52	0.63	-10000	0	-1.1	251	251
ORAI1	0.33	0.13	-10000	0	-10000	0	0
CSK	-0.45	0.51	-10000	0	-0.97	243	243
B7 family/CD28	-0.51	0.51	-10000	0	-1	246	246
CHUK	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.56	0.62	-10000	0	-1.2	251	251
PTPN6	-0.43	0.52	-10000	0	-1	232	232
VAV1	-0.48	0.53	-10000	0	-1	256	256
Monovalent TCR/CD3	-0.45	0.53	-10000	0	-0.99	239	239
CBL	0.014	0.033	-10000	0	-0.74	1	1
LCK	-0.44	0.53	-10000	0	-0.98	239	239
PAG1	-0.45	0.51	-10000	0	-0.97	244	244
RAP1A	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.53	0.63	-10000	0	-1.2	241	241
CD80	-0.18	0.36	-10000	0	-0.87	115	115
CD86	-0.13	0.32	-10000	0	-0.87	82	82
PDK1/CARD11/BCL10/MALT1	-0.18	0.17	-10000	0	-0.36	192	192
HRAS	0.014	0.038	-10000	0	-0.86	1	1
GO:0035030	-0.35	0.41	-10000	0	-0.77	245	245
CD8A	-0.38	0.44	-10000	0	-0.87	236	236
CD8B	-0.3	0.42	-10000	0	-0.87	186	186
PTPRC	-0.084	0.27	-10000	0	-0.87	56	56
PDK1/PKC theta	-0.32	0.36	-10000	0	-0.69	242	242
CSK/PAG1	-0.43	0.49	-10000	0	-0.95	240	240
SOS1	0.016	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.003	0.042	-10000	0	-0.68	2	2
GRAP2/SLP76	-0.43	0.44	-10000	0	-0.88	243	243
STIM1	0.17	0.064	-10000	0	-10000	0	0
RAS family/GTP	-0.063	0.11	-10000	0	-0.25	1	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.59	0.65	-10000	0	-1.2	251	251
mol:DAG	-0.2	0.26	-10000	0	-0.46	236	236
RAP1A/GDP	-0.014	0.035	-10000	0	-10000	0	0
PLCG1	0.016	0	-10000	0	-10000	0	0
CD247	-0.27	0.41	-10000	0	-0.87	172	172
cytotoxic T cell degranulation	-0.44	0.55	-10000	0	-0.99	244	244
RAP1A/GTP	-0.008	0.008	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.31	0.35	-10000	0	-0.66	248	248
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.26	0.44	0.3	107	-0.7	233	340
NRAS	0.016	0	-10000	0	-10000	0	0
ZAP70	-0.47	0.44	-10000	0	-0.86	294	294
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.38	0.35	-10000	0	-0.73	244	244
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.49	0.56	-10000	0	-1.1	242	242
CARD11	-0.17	0.36	-10000	0	-0.86	110	110
PRKCB	-0.14	0.17	-10000	0	-0.32	200	200
PRKCE	-0.14	0.17	-10000	0	-0.31	208	208
PRKCQ	-0.39	0.42	-10000	0	-0.8	252	252
LCP2	-0.04	0.22	-10000	0	-0.86	34	34
BCL10	0.016	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.2	0.24	-10000	0	-0.45	239	239
IKK complex	-0.028	0.084	-10000	0	-10000	0	0
RAS family/GDP	-0.011	0.012	-10000	0	-0.11	1	1
MAP3K14	-0.13	0.18	-10000	0	-0.32	141	141
PDPK1	-0.23	0.27	-10000	0	-0.51	237	237
TCR/CD3/MHC I/CD8/Fyn	-0.55	0.65	-10000	0	-1.2	242	242

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.45	0.47	-10000	0	-1.2	112	112
PCK1	-0.93	0.71	-10000	0	-1.5	285	285
HNF4A	-0.58	0.58	-10000	0	-1.4	140	140
KCNJ11	-0.44	0.51	-10000	0	-1.3	105	105
AKT1	-0.17	0.18	-10000	0	-10000	0	0
response to starvation	-0.02	0.038	-10000	0	-10000	0	0
DLK1	-0.55	0.57	-10000	0	-1.2	174	174
NKX2-1	-0.057	0.21	0.58	1	-0.84	4	5
ACADM	-0.45	0.47	-10000	0	-1.1	121	121
TAT	-0.51	0.35	-10000	0	-0.94	161	161
CEBPB	-0.024	0.14	-10000	0	-0.92	12	12
CEBPA	-0.019	0.12	-10000	0	-0.9	10	10
TTR	-0.88	0.48	-10000	0	-1.2	330	330
PKLR	-0.5	0.56	-10000	0	-1.3	128	128
APOA1	-0.55	0.56	-10000	0	-1.3	141	141
CPT1C	-0.45	0.48	-10000	0	-1.1	122	122
ALAS1	-0.17	0.19	-10000	0	-10000	0	0
TFRC	-0.62	0.42	-10000	0	-1	228	228
FOXF1	-0.001	0.12	-10000	0	-0.84	10	10
NF1	0.025	0.001	-10000	0	-10000	0	0
HNF1A (dimer)	-0.003	0.086	-10000	0	-0.79	5	5
CPT1A	-0.45	0.47	-10000	0	-1.1	129	129
HMGCS1	-0.45	0.47	-10000	0	-1.1	118	118
NR3C1	0.003	0.065	-10000	0	-0.96	1	1
CPT1B	-0.46	0.5	-10000	0	-1.2	121	121
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.017	0.005	-10000	0	-10000	0	0
GCK	-0.45	0.48	-10000	0	-1.1	133	133
CREB1	-0.028	0.066	-10000	0	-10000	0	0
IGFBP1	-0.32	0.42	-10000	0	-1	120	120
PDX1	-0.19	0.22	-10000	0	-1	6	6
UCP2	-0.45	0.47	-10000	0	-1.1	118	118
ALDOB	-0.94	0.62	-10000	0	-1.2	408	408
AFP	-0.7	0.49	-10000	0	-0.96	329	329
BDH1	-0.59	0.57	-10000	0	-1.2	191	191
HADH	-0.44	0.49	-10000	0	-1.2	104	104
F2	-0.65	0.62	-10000	0	-1.3	192	192
HNF1A	-0.003	0.086	-10000	0	-0.79	5	5
G6PC	-0.81	0.66	-10000	0	-1.5	254	254
SLC2A2	-0.32	0.48	-10000	0	-1.7	48	48
INS	0.009	0.055	-10000	0	-10000	0	0
FOXA1	-0.36	0.38	-10000	0	-1	127	127
FOXA3	-0.61	0.37	-10000	0	-0.84	334	334
FOXA2	-0.51	0.57	-10000	0	-1.3	139	139
ABCC8	-0.44	0.49	-10000	0	-1.2	111	111
ALB	-1.2	0.48	-10000	0	-1.4	460	460

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.053	0.14	-9999	-0.54	38	38
Syndecan-4/Syndesmos	-0.46	0.39	-9999	-0.84	234	234
positive regulation of JNK cascade	-0.53	0.37	-9999	-0.84	285	285
Syndecan-4/ADAM12	-0.56	0.49	-9999	-1	258	258
CCL5	-0.35	0.43	-9999	-0.86	223	223
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
ITGA5	-0.047	0.23	-9999	-0.86	38	38
SDCBP	0.016	0	-9999	-10000	0	0
PLG	-0.36	0.37	-9999	-0.72	273	273
ADAM12	-0.22	0.39	-9999	-0.86	141	141
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.1	0.071	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.47	0.4	-9999	-0.86	236	236
Syndecan-4/CXCL12/CXCR4	-0.59	0.43	-9999	-0.94	285	285
Syndecan-4/Laminin alpha3	-0.46	0.39	-9999	-0.85	239	239
MDK	-0.049	0.23	-9999	-0.86	39	39
Syndecan-4/FZD7	-0.46	0.39	-9999	-0.84	235	235
Syndecan-4/Midkine	-0.49	0.41	-9999	-0.88	247	247
FZD7	0.014	0.033	-9999	-0.74	1	1
Syndecan-4/FGFR1/FGF	-0.43	0.33	-9999	-0.77	236	236
THBS1	0.011	0.057	-9999	-0.74	3	3
integrin-mediated signaling pathway	-0.44	0.36	-9999	-0.79	240	240
positive regulation of MAPKKK cascade	-0.53	0.37	-9999	-0.84	285	285
Syndecan-4/TACI	-0.5	0.42	-9999	-0.9	247	247
CXCR4	-0.29	0.42	-9999	-0.86	184	184
cell adhesion	-0.007	0.12	-9999	-0.51	14	14
Syndecan-4/Dynamin	-0.46	0.39	-9999	-0.84	234	234
Syndecan-4/TSP1	-0.46	0.39	-9999	-0.84	236	236
Syndecan-4/GIPC	-0.46	0.39	-9999	-0.84	235	235
Syndecan-4/RANTES	-0.64	0.46	-9999	-1	292	292
ITGB1	0.016	0	-9999	-10000	0	0
LAMA1	-0.006	0.13	-9999	-0.75	15	15
LAMA3	0.004	0.1	-9999	-0.86	7	7
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.11	0.066	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.46	0.39	-9999	-0.85	235	235
TFPI	0.002	0.11	-9999	-0.81	9	9
F2	-0.32	0.42	-9999	-0.87	199	199
alpha5/beta1 Integrin	-0.048	0.17	-9999	-0.66	38	38
positive regulation of cell adhesion	-0.45	0.38	-9999	-0.82	241	241
ACTN1	0.013	0.05	-9999	-0.8	2	2
TNC	-0.004	0.12	-9999	-0.74	14	14
Syndecan-4/CXCL12	-0.47	0.39	-9999	-0.85	240	240
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CXCL12	-0.001	0.11	-9999	-0.74	12	12
TNFRSF13B	-0.069	0.26	-9999	-0.86	50	50
FGF2	0.008	0.076	-9999	-0.77	5	5
FGFR1	0.016	0	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.47	0.39	-9999	-0.85	234	234
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.038	0.22	-9999	-0.83	38	38
cell migration	-0.03	0.022	-9999	-10000	0	0
PRKCD	0.024	0.045	-9999	-0.85	1	1
vasculogenesis	-0.44	0.36	-9999	-0.79	236	236
SDC4	-0.5	0.43	-9999	-0.93	234	234
Syndecan-4/Tenascin C	-0.47	0.39	-9999	-0.84	240	240
Syndecan-4/PI-4-5-P2/PKC alpha	-0.079	0.055	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.46	0.39	-9999	-0.84	234	234
MMP9	-0.4	0.44	-9999	-0.86	249	249
Rac1/GTP	-0.007	0.12	-9999	-0.53	14	14
cytoskeleton organization	-0.43	0.36	-9999	-0.79	234	234
GIPC1	0.014	0.033	-9999	-0.74	1	1
Syndecan-4/TFPI	-0.46	0.39	-9999	-0.85	238	238

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.24	0.32	-9999	-0.68	162	162
STMN1	-0.29	0.34	-9999	-0.66	247	247
Aurora B/RasGAP/Survivin	-0.4	0.48	-9999	-0.87	252	252
Chromosomal passenger complex/Cul3 protein complex	-0.16	0.23	-9999	-0.49	151	151
BIRC5	-0.25	0.41	-9999	-0.89	154	154
DES	-0.38	0.34	-9999	-0.6	315	315
Aurora C/Aurora B/INCENP	-0.24	0.28	-9999	-0.53	248	248
Aurora B/TACC1	-0.26	0.3	-9999	-0.58	247	247
Aurora B/PP2A	-0.3	0.34	-9999	-0.66	247	247
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.072	0.09	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.008	-9999	-10000	0	0
NDC80	-0.4	0.5	-9999	-0.89	252	252
Cul3 protein complex	-0.015	0.083	-9999	-0.47	17	17
KIF2C	-0.15	0.18	-9999	-0.35	192	192
PEBP1	0.007	0.008	-9999	-10000	0	0
KIF20A	-0.38	0.44	-9999	-0.86	237	237
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.3	0.34	-9999	-0.66	248	248
SEPT1	-0.095	0.29	-9999	-0.86	67	67
SMC2	0.016	0	-9999	-10000	0	0
SMC4	0.016	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.18	0.24	-9999	-0.46	181	181
PSMA3	0.016	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.004	-9999	-10000	0	0
H3F3B	-0.17	0.21	-9999	-0.39	247	247
AURKB	-0.4	0.44	-9999	-0.87	247	247
AURKC	0.012	0.054	-9999	-0.86	2	2
CDCA8	-0.026	0.17	-9999	-0.89	20	20
cytokinesis	-0.34	0.37	-9999	-0.76	211	211
Aurora B/Septin1	-0.36	0.42	-9999	-0.84	207	207
AURKA	0.002	0.094	-9999	-0.87	6	6
INCENP	0.008	0.009	-9999	-10000	0	0
KLHL13	-0.009	0.13	-9999	-0.74	17	17
BUB1	-0.37	0.44	-9999	-0.86	232	232
hSgo1/Aurora B/Survivin	-0.4	0.48	-9999	-0.85	253	253
EVI5	0.01	0.008	-9999	-10000	0	0
RhoA/GTP	-0.31	0.34	-9999	-0.72	193	193
SGOL1	-0.014	0.16	-9999	-0.86	18	18
CENPA	-0.29	0.35	-9999	-0.63	254	254
NCAPG	-0.27	0.41	-9999	-0.86	175	175
Aurora B/HC8 Proteasome	-0.3	0.34	-9999	-0.66	247	247
NCAPD2	0.016	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.3	0.34	-9999	-0.66	247	247
RHOA	0.016	0	-9999	-10000	0	0
NCAPH	-0.13	0.33	-9999	-0.86	90	90
NPM1	-0.21	0.24	-9999	-0.47	247	247
RASA1	0.014	0.033	-9999	-0.74	1	1
KLHL9	0.016	0	-9999	-10000	0	0
mitotic prometaphase	-0.01	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.3	0.34	-9999	-0.66	247	247
PPP1CC	0.016	0	-9999	-10000	0	0
Centraspindlin	-0.34	0.38	-9999	-0.78	200	200
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.21	0.24	-9999	-0.47	247	247
MYLK	-0.17	0.21	-9999	-0.39	247	247
KIF23	-0.006	0.11	-9999	-0.88	8	8
VIM	-0.34	0.4	-9999	-0.73	262	262
RACGAP1	0.004	0.055	-9999	-0.88	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.21	0.24	-9999	-0.47	247	247
Chromosomal passenger complex	-0.34	0.41	-9999	-0.76	239	239
Chromosomal passenger complex/EVI5	-0.36	0.48	-9999	-1	149	149
TACC1	0.016	0	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
CUL3	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.18	0.68	-10000	0	-1.2	124	124
PLK1	-0.098	0.41	-10000	0	-0.8	129	129
BIRC5	-0.13	0.43	-10000	0	-0.79	154	154
HSPA1B	-0.18	0.68	-10000	0	-1.2	125	125
MAP2K1	0.04	0.047	-10000	0	-10000	0	0
BRCA2	-0.19	0.68	-10000	0	-1.2	130	130
FOXM1	-0.37	1	-10000	0	-1.9	135	135
XRCC1	-0.18	0.68	-10000	0	-1.2	125	125
FOXM1B/p19	-0.49	0.49	0.5	1	-1.2	137	138
Cyclin D1/CDK4	-0.18	0.61	-10000	0	-1.1	119	119
CDC2	-0.21	0.72	-10000	0	-1.3	135	135
TGFA	-0.16	0.6	-10000	0	-1	125	125
SKP2	-0.18	0.68	-10000	0	-1.2	124	124
CCNE1	0.002	0.11	-10000	0	-0.88	8	8
CKS1B	-0.18	0.68	-10000	0	-1.2	124	124
RB1	-0.19	0.26	-10000	0	-0.69	95	95
FOXM1C/SP1	-0.28	0.78	-10000	0	-1.4	137	137
AURKB	-0.25	0.46	-10000	0	-0.74	243	243
CENPF	-0.21	0.72	-10000	0	-1.3	127	127
CDK4	0.021	0.022	-10000	0	-10000	0	0
MYC	-0.15	0.6	-10000	0	-1	123	123
CHEK2	0.037	0.075	-10000	0	-0.91	2	2
ONECUT1	-0.19	0.65	-10000	0	-1.2	125	125
CDKN2A	-0.82	0.17	-10000	0	-0.86	511	511
LAMA4	-0.28	0.69	-10000	0	-1.3	137	137
FOXM1B/HNF6	-0.27	0.79	-10000	0	-1.5	127	127
FOS	-0.2	0.69	-10000	0	-1.2	128	128
SP1	0.016	0.005	-10000	0	-10000	0	0
CDC25B	-0.18	0.68	-10000	0	-1.2	125	125
response to radiation	0.014	0.05	-10000	0	-10000	0	0
CENPB	-0.18	0.68	-10000	0	-1.2	124	124
CENPA	-0.28	0.78	-10000	0	-1.3	162	162
NEK2	-0.24	0.75	-10000	0	-1.3	141	141
HIST1H2BA	-0.19	0.68	-10000	0	-1.2	124	124
CCNA2	-0.15	0.35	-10000	0	-0.88	102	102
EP300	0.014	0.033	-10000	0	-0.74	1	1
CCNB1/CDK1	-0.27	0.81	-10000	0	-1.5	134	134
CCNB2	-0.24	0.75	-10000	0	-1.4	135	135
CCNB1	-0.21	0.72	-10000	0	-1.3	134	134
ETV5	-0.18	0.68	-10000	0	-1.2	125	125
ESR1	-0.19	0.68	-10000	0	-1.2	126	126
CCND1	-0.18	0.63	-10000	0	-1.1	121	121
GSK3A	0.036	0.041	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.08	0.28	-10000	0	-0.64	103	103
CDK2	0.015	0.015	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.015	0.059	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.42	0.58	-10000	0	-1.3	139	139
GAS1	-0.23	0.7	-10000	0	-1.2	138	138
MMP2	-0.19	0.68	-10000	0	-1.2	125	125
RB1/FOXM1C	-0.21	0.67	-10000	0	-1.2	124	124
CREBBP	0.016	0	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.16	0.26	-10000	0	-0.64	72	72
TBX21	-0.54	0.67	-10000	0	-1.3	212	212
B2M	0.011	0.009	-10000	0	-10000	0	0
TYK2	0.012	0.021	-10000	0	-10000	0	0
IL12RB1	-0.26	0.42	-10000	0	-0.9	160	160
GADD45B	-0.29	0.42	-10000	0	-0.83	139	139
IL12RB2	-0.11	0.31	-10000	0	-0.87	75	75
GADD45G	-0.3	0.43	-10000	0	-0.82	161	161
natural killer cell activation	-0.01	0.03	-10000	0	-10000	0	0
RELB	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL18	0.002	0.1	-10000	0	-0.87	7	7
IL2RA	-0.16	0.35	-10000	0	-0.86	104	104
IFNG	-0.38	0.44	-10000	0	-0.86	238	238
STAT3 (dimer)	-0.37	0.46	-10000	0	-0.88	200	200
HLA-DRB5	-0.036	0.21	-10000	0	-0.86	32	32
FASLG	-0.6	0.7	-10000	0	-1.3	233	233
NF kappa B2 p52/RelB	-0.51	0.53	-10000	0	-1.1	216	216
CD4	0.001	0.11	-10000	0	-0.86	9	9
SOCS1	0.006	0.093	-10000	0	-0.86	6	6
EntrezGene:6955	-0.002	0.009	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	239	239
CD3E	-0.34	0.43	-10000	0	-0.87	213	213
CD3G	-0.32	0.43	-10000	0	-0.87	203	203
IL12Rbeta2/JAK2	-0.083	0.25	-10000	0	-0.68	75	75
CCL3	-0.48	0.63	-10000	0	-1.2	197	197
CCL4	-0.5	0.66	-10000	0	-1.3	193	193
HLA-A	0.007	0.054	-10000	0	-0.86	2	2
IL18/IL18R	-0.12	0.3	-10000	0	-0.6	147	147
NOS2	-0.36	0.49	-10000	0	-0.95	172	172
IL12/IL12R/TYK2/JAK2/SPHK2	-0.16	0.26	-10000	0	-0.51	136	136
IL1R1	-0.44	0.59	-10000	0	-1.2	177	177
IL4	0.013	0.031	-10000	0	-10000	0	0
JAK2	0.012	0.021	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.69	0.81	-10000	0	-1.4	260	260
RAB7A	-0.23	0.37	-10000	0	-0.79	51	51
lysosomal transport	-0.22	0.36	-10000	0	-0.74	52	52
FOS	-0.37	0.5	-10000	0	-0.95	201	201
STAT4 (dimer)	-0.4	0.53	-10000	0	-0.98	202	202
STAT5A (dimer)	-0.65	0.61	-10000	0	-1.3	240	240
GZMA	-0.56	0.7	-10000	0	-1.3	218	218
GZMB	-0.53	0.67	-10000	0	-1.3	206	206
HLX	-0.092	0.29	-10000	0	-0.86	65	65
LCK	-0.51	0.69	-10000	0	-1.2	213	213
TCR/CD3/MHC II/CD4	-0.37	0.47	-10000	0	-0.86	230	230
IL2/IL2R	-0.41	0.42	-10000	0	-0.71	306	306
MAPK14	-0.3	0.44	-10000	0	-0.82	161	161
CCR5	-0.45	0.59	-10000	0	-1.1	200	200
IL1B	0.002	0.095	-10000	0	-0.86	6	6
STAT6	-0.083	0.15	-10000	0	-10000	0	0
STAT4	-0.034	0.2	-10000	0	-0.86	30	30
STAT3	0.016	0	-10000	0	-10000	0	0
STAT1	0.014	0.038	-10000	0	-0.86	1	1
NFKB1	0.014	0.033	-10000	0	-0.74	1	1
NFKB2	0.016	0	-10000	0	-10000	0	0
IL12B	-0.091	0.29	-10000	0	-0.89	61	61
CD8A	-0.38	0.44	-10000	0	-0.87	236	236
CD8B	-0.3	0.42	-10000	0	-0.87	186	186
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.16	0.26	0.64	72	-10000	0	72
IL2RB	-0.44	0.44	-10000	0	-0.86	273	273
proteasomal ubiquitin-dependent protein catabolic process	-0.36	0.47	-10000	0	-0.87	201	201
IL2RG	-0.04	0.21	-10000	0	-0.86	34	34
IL12	-0.069	0.24	-10000	0	-0.71	62	62
STAT5A	0.016	0	-10000	0	-10000	0	0
CD247	-0.27	0.41	-10000	0	-0.87	172	172
IL2	-0.007	0.12	-10000	0	-0.86	10	10
SPHK2	0.013	0.046	-10000	0	-0.74	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.01	0.046	-10000	0	-0.91	1	1
IL12/IL12R/TYK2/JAK2	-0.57	0.77	-10000	0	-1.4	220	220
MAP2K3	-0.3	0.44	-10000	0	-0.83	162	162
RIPK2	0.014	0.038	-10000	0	-0.86	1	1
MAP2K6	-0.3	0.44	-10000	0	-0.83	165	165
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.01	0.076	-10000	0	-0.86	4	4
IL18RAP	-0.21	0.39	-10000	0	-0.87	135	135
IL12Rbeta1/TYK2	-0.2	0.34	-10000	0	-0.72	160	160
EOMES	-0.29	0.37	-10000	0	-0.74	215	215
STAT1 (dimer)	-0.44	0.51	-10000	0	-0.96	232	232
T cell proliferation	-0.26	0.37	-10000	0	-0.68	171	171
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.002	0.1	-10000	0	-0.8	8	8
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.36	0.33	-10000	0	-0.75	190	190
ATF2	-0.27	0.41	-10000	0	-0.78	136	136

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.006	0.052	-10000	0	-0.49	6	6
fibroblast growth factor receptor signaling pathway	-0.006	0.052	-10000	0	-0.49	6	6
LAMA1	-0.006	0.13	-10000	0	-0.75	15	15
PRNP	0.016	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.12	0.23	-10000	0	-0.56	118	118
SMAD2	0.045	0.02	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.001	0.021	-10000	0	-0.48	1	1
GPC1/Laminin alpha1	-0.017	0.096	-10000	0	-0.56	16	16
TDGF1	-0.56	0.32	-10000	0	-0.74	399	399
CRIPTO/GPC1	-0.42	0.24	-10000	0	-0.56	399	399
APP/GPC1	-0.002	0.034	-10000	0	-0.56	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.35	0.22	-10000	0	-0.47	399	399
FLT1	0.007	0.085	-10000	0	-0.86	5	5
GPC1/TGFB/TGFBR1/TGFBR2	-0.001	0.02	-10000	0	-0.47	1	1
SERPINC1	-0.052	0.22	-10000	0	-0.76	45	45
FYN	-0.35	0.22	-10000	0	-0.47	399	399
FGR	-0.35	0.22	-10000	0	-0.48	399	399
positive regulation of MAPKKK cascade	-0.36	0.24	-10000	0	-0.67	65	65
SLIT2	-0.15	0.32	-10000	0	-0.75	117	117
GPC1/NRG	-0.019	0.1	-10000	0	-0.56	18	18
NRG1	-0.009	0.13	-10000	0	-0.74	17	17
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.27	0.3	-10000	0	-0.58	241	241
LYN	-0.35	0.22	-10000	0	-0.47	399	399
mol:Spermine	0.014	0.025	-10000	0	-0.57	1	1
cell growth	-0.006	0.052	-10000	0	-0.49	6	6
BMP signaling pathway	-0.014	0.033	0.74	1	-10000	0	1
SRC	-0.35	0.22	-10000	0	-0.47	399	399
TGFBR1	0.016	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.06	0.24	-10000	0	-0.86	43	43
GPC1	0.014	0.033	-10000	0	-0.74	1	1
TGFBR1 (dimer)	0.016	0	-10000	0	-10000	0	0
VEGFA	-0.38	0.44	-10000	0	-0.86	240	240
BLK	-0.38	0.26	-10000	0	-0.51	404	404
HCK	-0.38	0.24	-10000	0	-0.5	410	410
FGF2	0.008	0.076	-10000	0	-0.77	5	5
FGFR1	0.016	0	-10000	0	-10000	0	0
VEGFR1 homodimer	0.007	0.085	-10000	0	-0.86	5	5
TGFBR2	0.016	0	-10000	0	-10000	0	0
cell death	-0.002	0.034	-10000	0	-0.56	2	2
ATIII/GPC1	-0.05	0.16	-10000	0	-0.57	46	46
PLA2G2A/GPC1	-0.055	0.18	-10000	0	-0.66	44	44
LCK	-0.37	0.24	-10000	0	-0.49	407	407
neuron differentiation	-0.019	0.1	-10000	0	-0.56	18	18
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0.014	0.033	-10000	0	-0.74	1	1
TGFBR2 (dimer)	0.016	0	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.28	0.37	-9999	-0.74	205	205
PDGF/PDGFRA/CRKL	-0.21	0.26	-9999	-0.54	205	205
positive regulation of JUN kinase activity	-0.16	0.2	-9999	-0.52	1	1
CRKL	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.22	0.27	-9999	-0.55	208	208
AP1	-0.16	0.24	-9999	-1.2	13	13
mol:IP3	-0.19	0.29	-9999	-0.55	205	205
PLCG1	-0.19	0.29	-9999	-0.56	205	205
PDGF/PDGFRA/alphaV Integrin	-0.21	0.26	-9999	-0.54	205	205
RAPGEF1	0.016	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.19	0.29	-9999	-0.55	205	205
CAV3	0	0.065	-9999	-0.86	3	3
CAV1	-0.046	0.22	-9999	-0.86	37	37
SHC/Grb2/SOS1	-0.16	0.2	-9999	-0.52	1	1
PDGF/PDGFRA/Shf	-0.21	0.26	-9999	-0.54	206	206
FOS	-0.12	0.27	-9999	-1.2	13	13
JUN	-0.013	0.017	-9999	-10000	0	0
oligodendrocyte development	-0.21	0.26	-9999	-0.54	205	205
GRB2	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
mol:DAG	-0.19	0.29	-9999	-0.55	205	205
PDGF/PDGFRA	-0.28	0.37	-9999	-0.74	205	205
actin cytoskeleton reorganization	-0.21	0.26	-9999	-0.54	205	205
SRF	0.034	0.009	-9999	-10000	0	0
SHC1	0.014	0.038	-9999	-0.86	1	1
PI3K	-0.18	0.22	-9999	-0.46	206	206
PDGF/PDGFRA/Crk/C3G	-0.18	0.22	-9999	-0.45	205	205
JAK1	-0.19	0.28	-9999	-0.54	205	205
ELK1/SRF	-0.15	0.19	-9999	-10000	0	0
SHB	0.016	0	-9999	-10000	0	0
SHF	0.014	0.033	-9999	-0.74	1	1
CSNK2A1	0.017	0.022	-9999	-10000	0	0
GO:0007205	-0.2	0.29	-9999	-0.56	205	205
SOS1	0.016	0	-9999	-10000	0	0
Ras protein signal transduction	-0.16	0.2	-9999	-0.52	1	1
PDGF/PDGFRA/SHB	-0.21	0.26	-9999	-0.54	205	205
PDGF/PDGFRA/Caveolin-1	-0.25	0.3	-9999	-0.58	234	234
ITGAV	0.016	0	-9999	-10000	0	0
ELK1	-0.16	0.26	-9999	-0.49	205	205
PIK3CA	0.014	0.033	-9999	-0.74	1	1
PDGF/PDGFRA/Crk	-0.21	0.26	-9999	-0.54	205	205
JAK-STAT cascade	-0.19	0.28	-9999	-0.54	205	205
cell proliferation	-0.21	0.26	-9999	-0.54	206	206

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.41	0.54	-9999	-0.9	243	243
MAP4K1	-0.34	0.43	-9999	-0.86	216	216
MAP3K8	0.012	0.054	-9999	-0.86	2	2
PRKCB	0.008	0.08	-9999	-0.82	5	5
DBNL	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
MAP3K1	-0.15	0.29	-9999	-0.62	123	123
JUN	0	0.087	-9999	-0.6	6	6
MAP3K7	-0.15	0.29	-9999	-0.62	123	123
GRAP2	-0.042	0.22	-9999	-0.86	35	35
CRK	0.016	0	-9999	-10000	0	0
MAP2K4	-0.13	0.28	-9999	-0.59	123	123
LAT	-0.23	0.39	-9999	-0.86	147	147
LCP2	-0.041	0.22	-9999	-0.86	34	34
MAPK8	-0.012	0.092	-9999	-0.64	6	6
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.2	0.29	-9999	-0.67	123	123
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.39	0.51	-9999	-0.85	243	243

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.14	0.28	-9999	-0.67	108	108
alphaM/beta2 Integrin/GPIbA	-0.13	0.28	-9999	-0.67	104	104
alphaM/beta2 Integrin/proMMP-9	-0.39	0.43	-9999	-0.74	280	280
PLAUR	-0.029	0.19	-9999	-0.86	27	27
HMGB1	0.015	0.013	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.13	0.28	-9999	-0.67	103	103
AGER	-0.14	0.34	-9999	-0.86	95	95
RAP1A	0.016	0	-9999	-10000	0	0
SELPLG	-0.042	0.22	-9999	-0.86	35	35
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.23	0.33	-9999	-0.65	175	175
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.4	0.44	-9999	-0.86	249	249
CYR61	0.007	0.08	-9999	-0.74	6	6
TLN1	0.016	0	-9999	-10000	0	0
Rap1/GTP	-0.25	0.2	-9999	-0.56	115	115
RHOA	0.016	0	-9999	-10000	0	0
P-selectin oligomer	-0.02	0.16	-9999	-0.74	25	25
MYH2	-0.34	0.26	-9999	-0.65	184	184
MST1R	0.005	0.091	-9999	-0.78	7	7
leukocyte activation during inflammatory response	-0.27	0.35	-9999	-0.63	223	223
APOB	-0.26	0.41	-9999	-0.86	169	169
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.006	0.091	-9999	-0.84	6	6
JAM3	0.016	0	-9999	-10000	0	0
GP1BA	0.014	0.033	-9999	-0.74	1	1
alphaM/beta2 Integrin/CTGF	-0.14	0.29	-9999	-0.68	105	105
alphaM/beta2 Integrin	-0.3	0.25	-9999	-0.53	229	229
JAM3 homodimer	0.016	0	-9999	-10000	0	0
ICAM2	0.016	0	-9999	-10000	0	0
ICAM1	-0.002	0.12	-9999	-0.86	11	11
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.3	0.24	-9999	-0.52	229	229
cell adhesion	-0.13	0.28	-9999	-0.67	104	104
NFKB1	-0.18	0.36	-9999	-0.94	63	63
THY1	0.014	0.033	-9999	-0.74	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.19	0.28	-9999	-0.59	170	170
alphaM/beta2 Integrin/LRP/tPA	-0.13	0.27	-9999	-0.63	103	103
IL6	-0.2	0.41	-9999	-0.91	101	101
ITGB2	-0.15	0.34	-9999	-0.86	100	100
elevation of cytosolic calcium ion concentration	-0.15	0.29	-9999	-0.64	121	121
alphaM/beta2 Integrin/JAM2/JAM3	-0.12	0.26	-9999	-0.62	103	103
JAM2	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/ICAM1	-0.13	0.28	-9999	-0.91	35	35
alphaM/beta2 Integrin/uPA/Plg	-0.35	0.34	-9999	-0.86	109	109
RhoA/GTP	-0.37	0.27	-9999	-0.68	189	189
positive regulation of phagocytosis	-0.25	0.27	-9999	-0.81	72	72
Ron/MSP	-0.018	0.1	-9999	-0.62	15	15
alphaM/beta2 Integrin/uPAR/uPA	-0.15	0.3	-9999	-0.64	121	121
alphaM/beta2 Integrin/uPAR	-0.16	0.32	-9999	-0.7	120	120
PLAU	0.003	0.098	-9999	-0.74	9	9
PLAT	-0.004	0.12	-9999	-0.74	14	14
actin filament polymerization	-0.33	0.24	-9999	-0.61	184	184
MST1	0.003	0.1	-9999	-0.85	8	8
alphaM/beta2 Integrin/lipoprotein(a)	-0.28	0.36	-9999	-0.64	223	223
TNF	-0.15	0.34	-9999	-0.84	67	67
RAP1B	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.14	0.28	-9999	-0.66	112	112
fibrinolysis	-0.34	0.33	-9999	-0.84	109	109
HCK	-0.032	0.2	-9999	-0.86	29	29
dendritic cell antigen processing and presentation	-0.3	0.24	-9999	-0.52	229	229
VTN	-0.1	0.28	-9999	-0.75	82	82
alphaM/beta2 Integrin/CYR61	-0.14	0.28	-9999	-0.66	109	109
LPA	0.003	0.066	-9999	-0.86	3	3
LRP1	0.016	0	-9999	-10000	0	0
cell migration	-0.37	0.4	-9999	-0.69	282	282
FN1	-0.047	0.23	-9999	-0.86	38	38
alphaM/beta2 Integrin/Thy1	-0.13	0.28	-9999	-0.67	104	104
MPO	-0.013	0.16	-9999	-0.86	17	17
KNG1	-0.55	0.32	-9999	-0.74	395	395
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.33	0.26	-9999	-0.64	176	176
ELA2	0	0	-9999	-10000	0	0
PLG	-0.38	0.38	-9999	-0.74	273	273
CTGF	0.006	0.086	-9999	-0.74	7	7
alphaM/beta2 Integrin/Hck	-0.16	0.35	-9999	-0.79	107	107
ITGAM	-0.022	0.18	-9999	-0.86	22	22
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.17	0.34	-9999	-0.74	111	111
HP	-0.2	0.38	-9999	-0.86	132	132
leukocyte adhesion	-0.18	0.27	-9999	-0.77	61	61
SELP	-0.02	0.16	-9999	-0.74	25	25

×

IL4-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
BCL2L1	-0.48	0.48	-10000	0	-1.2	108	108
STAT6 (cleaved dimer)	-0.58	0.49	-10000	0	-1.2	167	167
IGHG1	-0.17	0.18	-10000	0	-0.69	11	11
IGHG3	-0.48	0.46	-10000	0	-1.1	127	127
AKT1	-0.28	0.33	-10000	0	-0.84	83	83
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.24	0.31	-10000	0	-0.82	84	84
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.27	0.3	-10000	0	-0.8	64	64
THY1	-0.48	0.48	-10000	0	-1.2	106	106
MYB	-0.21	0.39	-10000	0	-0.86	139	139
HMGA1	0.014	0.038	-10000	0	-0.86	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.39	0.42	-10000	0	-1	118	118
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.27	0.3	-10000	0	-0.82	62	62
SP1	0.022	0.015	-10000	0	-10000	0	0
INPP5D	0.009	0.076	-10000	0	-0.86	4	4
SOCS5	0.026	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.55	0.48	-10000	0	-1.2	150	150
SOCS1	-0.33	0.34	-10000	0	-0.83	67	67
SOCS3	-0.3	0.34	-10000	0	-0.91	74	74
FCER2	-0.41	0.44	-10000	0	-1.1	78	78
PARP14	0.016	0.004	-10000	0	-10000	0	0
CCL17	-0.5	0.5	-10000	0	-1.2	114	114
GRB2	0.016	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.22	0.28	-10000	0	-0.78	55	55
T cell proliferation	-0.5	0.51	-10000	0	-1.2	126	126
IL4R/JAK1	-0.48	0.47	-10000	0	-1.2	113	113
EGR2	-0.49	0.5	-10000	0	-1.2	109	109
JAK2	0.006	0.023	-10000	0	-10000	0	0
JAK3	-0.16	0.35	-10000	0	-0.86	106	106
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
JAK1	0.007	0.015	-10000	0	-10000	0	0
COL1A2	-0.21	0.3	-10000	0	-0.89	66	66
CCL26	-0.49	0.49	-10000	0	-1.2	109	109
IL4R	-0.51	0.51	-10000	0	-1.2	114	114
PTPN6	0.027	0.012	-10000	0	-10000	0	0
IL13RA2	-0.56	0.56	-10000	0	-1.3	132	132
IL13RA1	0.006	0.023	-10000	0	-10000	0	0
IRF4	-0.27	0.42	-10000	0	-1	115	115
ARG1	-0.18	0.26	-10000	0	-0.77	50	50
CBL	-0.36	0.4	-10000	0	-0.96	109	109
GTF3A	0.01	0.03	-10000	0	-10000	0	0
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
IL13RA1/JAK2	-0.007	0.043	-10000	0	-10000	0	0
IRF4/BCL6	-0.26	0.37	-10000	0	-0.93	114	114
CD40LG	-0.075	0.29	-10000	0	-0.92	55	55
MAPK14	-0.35	0.39	-10000	0	-0.96	108	108
mitosis	-0.26	0.31	-10000	0	-0.79	83	83
STAT6	-0.55	0.56	-10000	0	-1.3	121	121
SPI1	-0.1	0.3	-10000	0	-0.86	73	73
RPS6KB1	-0.24	0.3	-10000	0	-0.78	69	69
STAT6 (dimer)	-0.56	0.56	-10000	0	-1.3	121	121
STAT6 (dimer)/PARP14	-0.51	0.51	-10000	0	-1.3	121	121
mast cell activation	0.012	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.3	0.36	-10000	0	-0.91	96	96
FRAP1	-0.28	0.33	-10000	0	-0.84	83	83
LTA	-0.6	0.56	-10000	0	-1.3	143	143
FES	0.013	0.046	-10000	0	-0.74	2	2
T-helper 1 cell differentiation	0.54	0.54	1.3	121	-10000	0	121
CCL11	-0.69	0.6	-10000	0	-1.3	225	225
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.29	0.34	-10000	0	-0.88	89	89
IL2RG	-0.035	0.21	-10000	0	-0.85	34	34
IL10	-0.5	0.5	-10000	0	-1.2	115	115
IRS1	0.01	0.066	-10000	0	-0.74	4	4
IRS2	0.002	0.11	-10000	0	-0.86	8	8
IL4	-0.11	0.12	-10000	0	-10000	0	0
IL5	-0.49	0.48	-10000	0	-1.2	108	108
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.39	0.37	-10000	0	-0.9	97	97
COL1A1	-0.41	0.43	-10000	0	-0.92	204	204
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.48	0.48	-10000	0	-1.3	94	94
IL2R gamma/JAK3	-0.16	0.36	-10000	0	-0.83	110	110
TFF3	-0.5	0.51	-10000	0	-1.2	119	119
ALOX15	-0.49	0.48	-10000	0	-1.2	108	108
MYBL1	-0.044	0.22	-10000	0	-0.86	36	36
T-helper 2 cell differentiation	-0.43	0.41	-10000	0	-0.98	123	123
SHC1	0.014	0.038	-10000	0	-0.86	1	1
CEBPB	0	0.13	-10000	0	-0.87	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.26	0.29	-10000	0	-0.78	68	68
mol:PI-3-4-5-P3	-0.28	0.33	-10000	0	-0.84	83	83
PI3K	-0.29	0.36	-10000	0	-0.92	83	83
DOK2	-0.035	0.2	-10000	0	-0.86	31	31
ETS1	0.028	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.21	0.27	-10000	0	-0.77	55	55
ITGB3	-0.49	0.49	-10000	0	-1.2	103	103
PIGR	-0.84	0.7	-10000	0	-1.4	274	274
IGHE	0.028	0.089	0.29	14	-0.37	4	18
MAPKKK cascade	-0.2	0.26	-10000	0	-0.75	55	55
BCL6	0.014	0.004	-10000	0	-10000	0	0
OPRM1	-0.49	0.48	-10000	0	-1.2	111	111
RETNLB	-0.49	0.48	-10000	0	-1.2	112	112
SELP	-0.51	0.52	-10000	0	-1.3	119	119
AICDA	-0.62	0.54	-10000	0	-1.2	180	180

×

EGFR-dependent Endothelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.014	0.038	-9999	-0.86	1	1
EGFR	0.001	0.11	-9999	-0.85	9	9
EGF/EGFR	-0.37	0.16	-9999	-0.86	27	27
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.36	0.14	-9999	-0.89	9	9
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.012	0.054	-9999	-0.86	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.67	0.23	-9999	-0.74	478	478
EGF/EGFR dimer/SHC	-0.44	0.16	-9999	-0.48	479	479
mol:GDP	-0.36	0.13	-9999	-0.88	9	9
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.014	0.16	-9999	-0.86	18	18
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.33	0.12	-9999	-0.82	10	10
SHC1	0.014	0.038	-9999	-0.86	1	1
HRAS/GDP	-0.33	0.13	-9999	-0.82	10	10
FRAP1	-0.34	0.14	-9999	-0.85	9	9
EGF/EGFR dimer	-0.51	0.18	-9999	-0.57	479	479
SOS1	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.025	0.13	-9999	-0.66	20	20

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.03	0.089	-10000	0	-0.71	8	8
oxygen homeostasis	-0.001	0.015	-10000	0	-10000	0	0
TCEB2	0.011	0.063	-10000	0	-0.82	3	3
TCEB1	0.016	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.23	0.14	-10000	0	-0.56	7	7
EPO	-0.4	0.41	-10000	0	-0.83	202	202
FIH (dimer)	0.014	0.02	-10000	0	-10000	0	0
APEX1	0.013	0.013	-10000	0	-10000	0	0
SERPINE1	-0.35	0.41	-10000	0	-0.92	121	121
FLT1	-0.019	0.077	-10000	0	-0.76	5	5
ADORA2A	-0.3	0.34	-10000	0	-0.82	84	84
germ cell development	-0.41	0.44	-10000	0	-0.89	211	211
SLC11A2	-0.29	0.34	-10000	0	-0.81	84	84
BHLHE40	-0.29	0.34	-10000	0	-0.81	84	84
HIF1AN	0.014	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.3	0.22	-10000	0	-0.52	220	220
ETS1	0.037	0.004	-10000	0	-10000	0	0
CITED2	-0.023	0.056	-10000	0	-1.2	1	1
KDR	-0.015	0.065	-10000	0	-1.4	1	1
PGK1	-0.29	0.34	-10000	0	-0.81	84	84
SIRT1	0.014	0.005	-10000	0	-10000	0	0
response to hypoxia	-0.002	0.005	-10000	0	-10000	0	0
HIF2A/ARNT	-0.36	0.42	-10000	0	-0.86	160	160
EPAS1	-0.27	0.19	-10000	0	-0.44	223	223
SP1	0.026	0.006	-10000	0	-10000	0	0
ABCG2	-0.3	0.35	-10000	0	-0.81	85	85
EFNA1	-0.3	0.34	-10000	0	-0.81	85	85
FXN	-0.3	0.34	-10000	0	-0.82	84	84
POU5F1	-0.43	0.47	-10000	0	-0.95	211	211
neuron apoptosis	0.34	0.4	0.82	160	-10000	0	160
EP300	0.014	0.033	-10000	0	-0.74	1	1
EGLN3	-0.76	0.29	-10000	0	-0.87	468	468
EGLN2	0.011	0.016	-10000	0	-10000	0	0
EGLN1	0.014	0.02	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.004	0.046	-10000	0	-0.52	4	4
VHL	0.014	0.033	-10000	0	-0.74	1	1
ARNT	0.013	0.014	-10000	0	-10000	0	0
SLC2A1	-0.32	0.37	-10000	0	-0.89	88	88
TWIST1	-0.31	0.34	-10000	0	-0.83	87	87
ELK1	0.026	0.001	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.26	0.2	-10000	0	-0.55	85	85
VEGFA	-0.47	0.49	-10000	0	-0.94	247	247
CREBBP	0.016	0	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.016	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.25	0.27	-9999	-0.53	248	248
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.063	0.068	-9999	-10000	0	0
AURKB	-0.39	0.44	-9999	-0.86	247	247
AURKC	0.012	0.054	-9999	-0.86	2	2

×

Caspase cascade in apoptosis

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
TOP1	-0.13	0.26	-10000	0	-0.57	109	109
ACTA1	-0.19	0.36	-10000	0	-0.67	172	172
NUMA1	-0.13	0.26	-10000	0	-0.57	109	109
SPTAN1	-0.19	0.35	-10000	0	-0.66	171	171
LIMK1	-0.19	0.35	-10000	0	-0.66	172	172
BIRC3	-0.12	0.31	-10000	0	-0.86	80	80
BIRC2	0.012	0.007	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
CASP10	-0.28	0.46	-10000	0	-0.86	189	189
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.016	0	-10000	0	-10000	0	0
PTK2	-0.13	0.26	-10000	0	-0.49	171	171
DIABLO	0.016	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.18	0.34	-10000	0	-0.65	171	171
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
GSN	-0.19	0.35	-10000	0	-0.66	171	171
MADD	0.016	0	-10000	0	-10000	0	0
TFAP2A	-0.3	0.28	-10000	0	-0.54	293	293
BID	-0.09	0.17	-10000	0	-0.37	105	105
MAP3K1	-0.044	0.11	-10000	0	-0.22	78	78
TRADD	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.19	0.35	-10000	0	-0.66	171	171
CASP9	0.016	0.001	-10000	0	-10000	0	0
DNA repair	0.013	0.094	-10000	0	-0.21	35	35
neuron apoptosis	0.011	0.044	-10000	0	-0.61	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.17	0.34	-10000	0	-0.77	105	105
APAF1	0.016	0.001	-10000	0	-10000	0	0
CASP6	-0.05	0.15	-10000	0	-0.49	4	4
TRAF2	0.016	0	-10000	0	-10000	0	0
ICAD/CAD	-0.17	0.34	-10000	0	-0.77	105	105
CASP7	0.05	0.12	0.34	80	-10000	0	80
KRT18	-0.002	0.046	-10000	0	-0.3	2	2
apoptosis	-0.17	0.32	-10000	0	-0.7	113	113
DFFA	-0.19	0.35	-10000	0	-0.66	171	171
DFFB	-0.19	0.35	-10000	0	-0.66	171	171
PARP1	-0.014	0.094	0.21	35	-10000	0	35
actin filament polymerization	0.16	0.32	0.72	106	-10000	0	106
TNF	0.003	0.1	-10000	0	-0.8	8	8
CYCS	-0.069	0.13	-10000	0	-0.28	105	105
SATB1	-0.037	0.15	-10000	0	-0.48	3	3
SLK	-0.19	0.35	-10000	0	-0.67	171	171
p15 BID/BAX	-0.073	0.15	-10000	0	-10000	0	0
CASP2	0.031	0.088	-10000	0	-0.42	1	1
JNK cascade	0.044	0.11	0.22	78	-10000	0	78
CASP3	-0.21	0.37	-10000	0	-0.71	171	171
LMNB2	0.011	0.085	-10000	0	-0.39	4	4
RIPK1	0.016	0	-10000	0	-10000	0	0
CASP4	0.016	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.079	0.19	-10000	0	-0.52	80	80
negative regulation of DNA binding	-0.3	0.28	-10000	0	-0.54	293	293
stress fiber formation	-0.18	0.35	-10000	0	-0.65	171	171
GZMB	-0.32	0.5	-10000	0	-0.97	189	189
CASP1	0.023	0	-10000	0	-10000	0	0
LMNB1	0.009	0.089	-10000	0	-0.37	7	7
APP	0.011	0.045	-10000	0	-0.62	1	1
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.015	0	-10000	0	-10000	0	0
VIM	-0.17	0.31	-10000	0	-0.66	114	114
LMNA	0.011	0.085	-10000	0	-0.39	4	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.005	0.09	-10000	0	-0.41	7	7
LRDD	0.003	0.1	-10000	0	-0.85	8	8
SREBF1	-0.19	0.35	-10000	0	-0.66	172	172
APAF-1/Caspase 9	-0.01	0.062	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.13	0.26	-10000	0	-0.5	148	148
CFL2	-0.17	0.34	-10000	0	-0.75	106	106
GAS2	-0.2	0.36	-10000	0	-0.67	173	173
positive regulation of apoptosis	0.015	0.085	-10000	0	-0.4	3	3
PRF1	-0.2	0.38	-10000	0	-0.86	132	132

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.049	0.23	-9999	-0.86	39	39
GPC2	-0.085	0.28	-9999	-0.86	61	61
GPC2/Midkine	-0.12	0.28	-9999	-0.73	89	89
neuron projection morphogenesis	-0.12	0.28	-9999	-0.73	89	89

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.085	-9999	-0.86	5	5
CCL5	-0.35	0.43	-9999	-0.86	223	223
SDCBP	0.016	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.22	0.23	-9999	-0.59	92	92
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.2	0.22	-9999	-0.56	93	93
Syndecan-1/Syntenin	-0.2	0.22	-9999	-0.56	92	92
MAPK3	-0.16	0.2	-9999	-0.7	15	15
HGF/MET	-0.032	0.15	-9999	-0.66	26	26
TGFB1/TGF beta receptor Type II	0.007	0.085	-9999	-0.86	5	5
BSG	0.014	0.038	-9999	-0.86	1	1
keratinocyte migration	-0.2	0.21	-9999	-0.55	93	93
Syndecan-1/RANTES	-0.41	0.33	-9999	-0.68	278	278
Syndecan-1/CD147	-0.2	0.18	-9999	-0.53	93	93
Syndecan-1/Syntenin/PIP2	-0.21	0.19	-9999	-0.54	92	92
LAMA5	0.013	0.05	-9999	-0.8	2	2
positive regulation of cell-cell adhesion	-0.2	0.18	-9999	-0.52	92	92
MMP7	-0.13	0.3	-9999	-0.75	98	98
HGF	-0.02	0.17	-9999	-0.8	23	23
Syndecan-1/CASK	-0.21	0.22	-9999	-0.56	92	92
Syndecan-1/HGF/MET	-0.22	0.22	-9999	-0.58	108	108
regulation of cell adhesion	-0.15	0.2	-9999	-0.67	15	15
HPSE	0.013	0.046	-9999	-0.74	2	2
positive regulation of cell migration	-0.22	0.23	-9999	-0.59	92	92
SDC1	-0.22	0.23	-9999	-0.6	92	92
Syndecan-1/Collagen	-0.22	0.23	-9999	-0.59	92	92
PPIB	0.016	0	-9999	-10000	0	0
MET	0.007	0.085	-9999	-0.86	5	5
PRKACA	0.016	0	-9999	-10000	0	0
MMP9	-0.4	0.44	-9999	-0.86	249	249
MAPK1	-0.16	0.2	-9999	-0.7	15	15
homophilic cell adhesion	-0.21	0.22	-9999	-0.58	92	92
MMP1	-0.15	0.34	-9999	-0.83	105	105

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.59	0.31	-9999	-0.84	289	289
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.12	0.32	-9999	-0.84	85	85
SMAD9	-0.065	0.086	-9999	-0.57	11	11
SMAD4	0.016	0	-9999	-10000	0	0
SMAD5	-0.18	0.17	-9999	-0.51	19	19
BMP7/USAG1	-0.69	0.34	-9999	-0.8	461	461
SMAD5/SKI	-0.17	0.16	-9999	-0.5	15	15
SMAD1	0.002	0.041	-9999	-10000	0	0
BMP2	0.01	0.068	-9999	-0.77	4	4
SMAD1/SMAD1/SMAD4	0	0.001	-9999	-10000	0	0
BMPR1A	0.016	0	-9999	-10000	0	0
BMPR1B	-0.51	0.35	-9999	-0.74	365	365
BMPR1A-1B/BAMBI	-0.33	0.22	-9999	-0.48	369	369
AHSG	-0.014	0.14	-9999	-0.86	13	13
CER1	0.004	0.007	-9999	-10000	0	0
BMP2-4/CER1	-0.007	0.057	-9999	-0.5	7	7
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.14	0.11	-9999	-0.49	19	19
BMP2-4 (homodimer)	-0.008	0.065	-9999	-0.57	7	7
RGMB	0.012	0.054	-9999	-0.86	2	2
BMP6/BMPR2/BMPR1A-1B	-0.3	0.2	-9999	-0.78	5	5
RGMA	0.009	0.073	-9999	-0.74	5	5
SMURF1	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.15	0.15	-9999	-0.56	19	19
BMP2-4/USAG1	-0.31	0.24	-9999	-0.48	342	342
SMAD6/SMURF1/SMAD5	-0.17	0.16	-9999	-0.5	15	15
SOSTDC1	-0.47	0.36	-9999	-0.74	341	341
BMP7/BMPR2/BMPR1A-1B	-0.58	0.3	-9999	-0.85	263	263
SKI	0.016	0	-9999	-10000	0	0
BMP6 (homodimer)	0.004	0.092	-9999	-0.74	8	8
HFE2	-0.019	0.16	-9999	-0.86	19	19
ZFYVE16	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.017	0.098	-9999	-0.55	16	16
SMAD5/SMAD5/SMAD4	-0.17	0.16	-9999	-0.5	15	15
MAPK1	0.016	0	-9999	-10000	0	0
TAK1/TAB family	-0.13	0.1	-9999	-0.5	15	15
BMP7 (homodimer)	-0.5	0.35	-9999	-0.74	357	357
NUP214	0.016	0	-9999	-10000	0	0
BMP6/FETUA	-0.025	0.12	-9999	-0.62	21	21
SMAD1/SKI	0.012	0.039	-9999	-10000	0	0
SMAD6	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.021	0.1	-9999	-0.55	20	20
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.18	0.33	-9999	-0.75	134	134
BMPR2 (homodimer)	0.016	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.38	0.26	-9999	-0.56	365	365
CHRDL1	-0.38	0.38	-9999	-0.74	277	277
ENDOFIN/SMAD1	0.012	0.039	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.005	0.004	-9999	-10000	0	0
SMAD6/SMURF1	0.016	0	-9999	-10000	0	0
BAMBI	0.004	0.092	-9999	-0.74	8	8
SMURF2	0.014	0.033	-9999	-0.74	1	1
BMP2-4/CHRDL1	-0.25	0.24	-9999	-0.48	279	279
BMP2-4/GREM1	-0.13	0.22	-9999	-0.49	139	139
SMAD7	0.016	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.038	0.09	-9999	-0.53	11	11
SMAD1/SMAD6	0.012	0.039	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.5	0.35	-9999	-0.74	357	357
BMP6	0.004	0.092	-9999	-0.74	8	8
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.12	0.12	-9999	-0.46	19	19
PPM1A	0.016	0	-9999	-10000	0	0
SMAD1/SMURF2	0.011	0.042	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.016	0	-9999	-10000	0	0
PPP1CA	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
PPP1R15A	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.2	0.19	-9999	-0.6	65	65
CHRD	-0.001	0.11	-9999	-0.78	11	11
BMPR2	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.17	0.13	-9999	-0.58	19	19
BMP4	0.011	0.057	-9999	-0.74	3	3
FST	-0.077	0.25	-9999	-0.76	63	63
BMP2-4/NOG	-0.096	0.21	-9999	-0.56	91	91
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.55	0.29	-9999	-0.8	263	263

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.007	0.13	-9999	-0.78	15	15
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.011	0.063	-9999	-0.82	3	3
TCEB1	0.016	0	-9999	-10000	0	0
HIF1A/p53	-0.08	0.047	-9999	-0.39	1	1
HIF1A	-0.099	0.039	-9999	-0.42	1	1
COPS5	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.038	-9999	-10000	0	0
FIH (dimer)	0.016	0	-9999	-10000	0	0
CDKN2A	-0.83	0.17	-9999	-0.86	511	511
ARNT/IPAS	-0.017	0.097	-9999	-0.58	15	15
HIF1AN	0.016	0	-9999	-10000	0	0
GNB2L1	0.014	0.038	-9999	-0.86	1	1
HIF1A/ARNT	-0.08	0.047	-9999	-0.39	1	1
CUL2	0.016	0	-9999	-10000	0	0
OS9	0.016	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.004	0.048	-9999	-0.55	4	4
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.08	0.047	-9999	-0.39	1	1
PHD1-3/OS9	-0.46	0.17	-9999	-0.52	466	466
HIF1A/RACK1/Elongin B/Elongin C	-0.067	0.049	-9999	-0.59	3	3
VHL	0.014	0.033	-9999	-0.74	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
HIF1A/JAB1	-0.08	0.047	-9999	-0.39	1	1
EGLN3	-0.76	0.28	-9999	-0.86	468	468
EGLN2	0.016	0	-9999	-10000	0	0
EGLN1	0.016	0	-9999	-10000	0	0
TP53	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.003	0.038	-9999	-0.61	1	1
ARNT	0.016	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.016	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.55	0.11	-9999	-0.57	511	511

×

IL23-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
CCL2	-0.25	0.47	-10000	0	-1.1	67	67
IL23A	-0.24	0.47	-10000	0	-1.1	62	62
NF kappa B1 p50/RelA/I kappa B alpha	-0.32	0.39	-10000	0	-1	80	80
positive regulation of T cell mediated cytotoxicity	-0.28	0.52	-10000	0	-1.1	86	86
ITGA3	-0.24	0.46	-10000	0	-1	65	65
IL17F	-0.15	0.34	-10000	0	-0.74	36	36
IL12B	-0.084	0.29	-10000	0	-0.88	61	61
STAT1 (dimer)	-0.27	0.5	-10000	0	-1.1	75	75
CD4	-0.24	0.47	-10000	0	-1.1	62	62
IL23	-0.27	0.48	-10000	0	-1.1	78	78
IL23R	-0.012	0.15	-10000	0	-0.8	10	10
IL1B	-0.25	0.48	-10000	0	-1.1	67	67
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.24	0.47	-10000	0	-1.1	65	65
TYK2	0.016	0.025	-10000	0	-10000	0	0
STAT4	-0.034	0.2	-10000	0	-0.86	30	30
STAT3	0.016	0.001	-10000	0	-10000	0	0
IL18RAP	-0.22	0.39	-10000	0	-0.88	135	135
IL12RB1	-0.26	0.42	-10000	0	-0.89	160	160
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
IL12Rbeta1/TYK2	-0.2	0.33	-10000	0	-0.7	160	160
IL23R/JAK2	-0.011	0.16	-10000	0	-0.78	9	9
positive regulation of chronic inflammatory response	-0.28	0.52	-10000	0	-1.1	86	86
natural killer cell activation	0.002	0.012	0.063	10	-10000	0	10
JAK2	0.021	0.034	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
NFKB1	0.01	0.033	-10000	0	-0.74	1	1
RELA	0.012	0.009	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.26	0.46	-10000	0	-1	79	79
ALOX12B	-0.31	0.5	-10000	0	-1.1	77	77
CXCL1	-0.28	0.52	-10000	0	-1.2	73	73
T cell proliferation	-0.28	0.52	-10000	0	-1.1	86	86
NFKBIA	0.012	0.009	-10000	0	-10000	0	0
IL17A	-0.099	0.29	-10000	0	-0.59	13	13
PI3K	-0.33	0.4	-10000	0	-1	88	88
IFNG	-0.051	0.069	0.13	4	-0.12	214	218
STAT3 (dimer)	-0.31	0.38	-10000	0	-1	76	76
IL18R1	-0.003	0.1	-10000	0	-0.8	8	8
IL23/IL23R/JAK2/TYK2/SOCS3	-0.18	0.38	-10000	0	-0.8	80	80
IL18/IL18R	-0.17	0.28	-10000	0	-0.61	147	147
macrophage activation	-0.017	0.018	-10000	0	-0.045	13	13
TNF	-0.25	0.49	-10000	0	-1.1	68	68
STAT3/STAT4	-0.35	0.43	-10000	0	-1.1	89	89
STAT4 (dimer)	-0.3	0.53	-10000	0	-1.2	88	88
IL18	-0.002	0.1	-10000	0	-0.86	7	7
IL19	-0.25	0.46	-10000	0	-1.1	64	64
STAT5A (dimer)	-0.27	0.5	-10000	0	-1.2	70	70
STAT1	0.014	0.038	-10000	0	-0.86	1	1
SOCS3	0.011	0.066	-10000	0	-0.86	3	3
CXCL9	-0.39	0.59	-10000	0	-1.1	163	163
MPO	-0.25	0.48	-10000	0	-1.1	67	67
positive regulation of humoral immune response	-0.28	0.52	-10000	0	-1.1	86	86
IL23/IL23R/JAK2/TYK2	-0.3	0.54	-10000	0	-1.2	82	82
IL6	-0.3	0.53	-10000	0	-1.2	93	93
STAT5A	0.016	0	-10000	0	-10000	0	0
IL2	-0.016	0.12	-10000	0	-0.86	10	10
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.012	0.063	10	-10000	0	10
CD3E	-0.38	0.6	-10000	0	-1.1	163	163
keratinocyte proliferation	-0.28	0.52	-10000	0	-1.1	86	86
NOS2	-0.25	0.47	-10000	0	-1.1	67	67

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.24	0.26	-10000	0	-0.74	32	32
IHH	-0.096	0.23	-10000	0	-0.82	47	47
SHH Np/Cholesterol/GAS1	-0.036	0.12	-10000	0	-0.45	43	43
LRPAP1	0.016	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.036	0.12	0.45	43	-10000	0	43
SMO/beta Arrestin2	-0.14	0.15	-10000	0	-0.6	33	33
SMO	-0.13	0.19	-10000	0	-0.64	33	33
AKT1	-0.04	0.092	-10000	0	-0.46	1	1
ARRB2	0.014	0.038	-10000	0	-0.86	1	1
BOC	0.016	0	-10000	0	-10000	0	0
ADRBK1	0.016	0	-10000	0	-10000	0	0
heart looping	-0.13	0.19	-10000	0	-0.62	33	33
STIL	-0.093	0.16	-10000	0	-0.81	5	5
DHH N/PTCH2	-0.044	0.16	-10000	0	-0.63	37	37
DHH N/PTCH1	-0.16	0.16	-10000	0	-0.62	37	37
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
DHH	-0.002	0.11	-10000	0	-0.74	12	12
PTHLH	-0.44	0.41	-10000	0	-0.74	327	327
determination of left/right symmetry	-0.13	0.19	-10000	0	-0.62	33	33
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
skeletal system development	-0.43	0.4	-10000	0	-0.73	327	327
IHH N/Hhip	-0.2	0.31	-10000	0	-0.65	164	164
DHH N/Hhip	-0.15	0.26	-10000	0	-0.57	142	142
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.13	0.19	-10000	0	-0.62	33	33
pancreas development	-0.18	0.33	-10000	0	-0.75	133	133
HHAT	0.016	0	-10000	0	-10000	0	0
PI3K	-0.002	0.034	-10000	0	-0.56	2	2
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.032	0.18	-10000	0	-0.75	33	33
somite specification	-0.13	0.19	-10000	0	-0.62	33	33
SHH Np/Cholesterol/PTCH1	-0.13	0.14	-10000	0	-0.67	10	10
SHH Np/Cholesterol/PTCH2	-0.034	0.13	-10000	0	-0.5	36	36
SHH Np/Cholesterol/Megalin	-0.047	0.15	-10000	0	-0.48	52	52
SHH	0.018	0.085	-10000	0	-0.57	11	11
catabolic process	-0.15	0.19	-10000	0	-0.65	32	32
SMO/Vitamin D3	-0.11	0.18	-10000	0	-0.72	7	7
SHH Np/Cholesterol/Hhip	-0.12	0.21	-10000	0	-0.46	139	139
LRP2	-0.05	0.21	-10000	0	-0.74	46	46
receptor-mediated endocytosis	-0.15	0.18	-10000	0	-0.76	19	19
SHH Np/Cholesterol/BOC	-0.009	0.063	-10000	0	-0.44	11	11
SHH Np/Cholesterol/CDO	-0.069	0.18	-10000	0	-0.53	70	70
mesenchymal cell differentiation	0.12	0.2	0.46	139	-10000	0	139
mol:Vitamin D3	-0.11	0.17	-10000	0	-0.67	10	10
IHH N/PTCH2	-0.081	0.21	-10000	0	-0.62	70	70
CDON	-0.084	0.28	-10000	0	-0.86	60	60
IHH N/PTCH1	-0.16	0.19	-10000	0	-0.66	32	32
Megalin/LRPAP1	-0.048	0.16	-10000	0	-0.56	46	46
PTCH2	-0.026	0.19	-10000	0	-0.86	25	25
SHH Np/Cholesterol	-0.009	0.065	-10000	0	-0.45	11	11
PTCH1	-0.15	0.19	-10000	0	-0.65	32	32
HHIP	-0.18	0.33	-10000	0	-0.75	133	133

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.016	0	-9999	-10000	0	0
LAT2	-0.16	0.23	-9999	-0.7	62	62
AP1	-0.16	0.21	-9999	-0.57	81	81
mol:PIP3	-0.23	0.34	-9999	-0.7	144	144
IKBKB	-0.086	0.17	-9999	-0.34	73	73
AKT1	-0.16	0.21	-9999	-0.73	22	22
IKBKG	-0.086	0.17	-9999	-0.34	81	81
MS4A2	-0.18	0.36	-9999	-0.86	116	116
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.011	0.034	-9999	-0.75	1	1
MAP3K1	-0.12	0.26	-9999	-0.6	78	78
mol:Ca2+	-0.16	0.24	-9999	-0.49	134	134
LYN	0.011	0.009	-9999	-10000	0	0
CBLB	-0.11	0.15	-9999	-0.54	21	21
SHC1	0.014	0.038	-9999	-0.86	1	1
RasGAP/p62DOK	-0.002	0.03	-9999	-0.48	2	2
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.009	0.076	-9999	-0.86	4	4
PLD2	-0.17	0.28	-9999	-0.62	62	62
PTPN13	-0.067	0.16	-9999	-0.5	17	17
PTPN11	0.014	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.042	0.17	-9999	-0.4	14	14
SYK	0.008	0.048	-9999	-0.75	2	2
GRB2	0.015	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.29	0.32	-9999	-0.76	140	140
LAT	-0.25	0.29	-9999	-0.65	157	157
PAK2	-0.15	0.29	-9999	-0.64	113	113
NFATC2	-0.069	0.097	-9999	-0.7	4	4
HRAS	-0.17	0.32	-9999	-0.71	117	117
GAB2	0.016	0	-9999	-10000	0	0
PLA2G1B	0.039	0.027	-9999	-10000	0	0
Fc epsilon R1	-0.25	0.32	-9999	-0.62	215	215
Antigen/IgE/Fc epsilon R1	-0.23	0.3	-9999	-0.58	215	215
mol:GDP	-0.2	0.35	-9999	-0.77	128	128
JUN	0.016	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.011	0.033	-9999	-0.74	1	1
FOS	-0.003	0.12	-9999	-0.75	13	13
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.12	0.16	-9999	-0.58	21	21
CHUK	-0.086	0.17	-9999	-0.34	74	74
KLRG1	-0.12	0.15	-9999	-0.55	21	21
VAV1	-0.2	0.32	-9999	-0.69	135	135
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.12	0.15	-9999	-0.55	22	22
negative regulation of mast cell degranulation	-0.11	0.15	-9999	-0.56	23	23
BTK	-0.18	0.24	-9999	-0.63	91	91
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.17	0.22	-9999	-0.58	85	85
GAB2/PI3K/SHP2	-0.18	0.24	-9999	-0.82	22	22
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.12	0.15	-9999	-0.55	21	21
RAF1	0.026	0.027	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.3	0.39	-9999	-0.81	144	144
FCER1G	-0.15	0.34	-9999	-0.87	97	97
FCER1A	-0.021	0.16	-9999	-0.77	22	22
Antigen/IgE/Fc epsilon R1/Fyn	-0.22	0.28	-9999	-0.54	202	202
MAPK3	0.04	0.025	-9999	-10000	0	0
MAPK1	0.04	0.025	-9999	-10000	0	0
NFKB1	0.014	0.033	-9999	-0.74	1	1
MAPK8	-0.012	0.079	-9999	-0.58	2	2
DUSP1	0.014	0.038	-9999	-0.86	1	1
NF-kappa-B/RelA	-0.069	0.074	-9999	-0.33	1	1
actin cytoskeleton reorganization	-0.072	0.16	-9999	-0.48	20	20
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.22	0.29	-9999	-0.72	115	115
FER	-0.12	0.15	-9999	-0.55	23	23
RELA	0.016	0	-9999	-10000	0	0
ITK	-0.14	0.19	-9999	-0.42	163	163
SOS1	0.016	0	-9999	-10000	0	0
PLCG1	-0.2	0.36	-9999	-0.76	128	128
cytokine secretion	-0.05	0.053	-9999	-10000	0	0
SPHK1	-0.15	0.22	-9999	-0.64	59	59
PTK2	-0.075	0.16	-9999	-0.5	20	20
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.24	0.31	-9999	-0.77	109	109
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.18	0.31	-9999	-0.68	109	109
MAP2K2	0.034	0.031	-9999	-0.42	1	1
MAP2K1	0.035	0.024	-9999	-10000	0	0
MAP2K7	0.016	0	-9999	-10000	0	0
KLRG1/SHP2	-0.11	0.15	-9999	-0.53	21	21
MAP2K4	0.017	0.015	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.32	0.4	-9999	-0.73	227	227
mol:Choline	-0.17	0.28	-9999	-0.56	86	86
SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.52	13	13
FYN	0.016	0	-9999	-10000	0	0
DOK1	0.016	0	-9999	-10000	0	0
PXN	-0.06	0.15	-9999	-0.48	10	10
HCLS1	-0.13	0.18	-9999	-0.68	30	30
PRKCB	-0.14	0.23	-9999	-0.49	107	107
FCGR2B	-0.14	0.34	-9999	-0.86	96	96
IGHE	-0.005	0.01	-9999	-10000	0	0
KLRG1/SHIP	-0.11	0.15	-9999	-0.57	23	23
LCP2	-0.041	0.22	-9999	-0.87	34	34
PLA2G4A	-0.12	0.16	-9999	-0.56	25	25
RASA1	0.014	0.033	-9999	-0.74	1	1
mol:Phosphatidic acid	-0.17	0.28	-9999	-0.56	86	86
IKK complex	-0.046	0.13	-9999	-0.28	1	1
WIPF1	0.016	0	-9999	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	240	240
PDGFRB	0.016	0.004	-9999	-10000	0	0
SPHK1	-0.031	0.1	-9999	-0.36	44	44
mol:S1P	-0.024	0.095	-9999	-0.37	16	16
S1P1/S1P/Gi	-0.048	0.14	-9999	-0.51	15	15
GNAO1	0.01	0.083	-9999	-0.84	5	5
PDGFB-D/PDGFRB/PLCgamma1	-0.055	0.089	-9999	-0.63	2	2
PLCG1	-0.029	0.13	-9999	-0.5	10	10
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0.004	-9999	-10000	0	0
GNAI2	0.018	0.005	-9999	-10000	0	0
GNAI3	0.015	0.006	-9999	-10000	0	0
GNAI1	0.011	0.057	-9999	-0.75	3	3
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.25	0.3	-9999	-0.58	240	240
S1P1/S1P	-0.21	0.21	-9999	-0.42	241	241
negative regulation of cAMP metabolic process	-0.046	0.14	-9999	-0.49	15	15
MAPK3	-0.039	0.17	-9999	-0.57	26	26
calcium-dependent phospholipase C activity	0	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.014	0.033	-9999	-0.74	1	1
PLCB2	-0.2	0.26	-9999	-0.6	78	78
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.18	0.17	-9999	-0.51	24	24
receptor internalization	-0.2	0.2	-9999	-0.39	241	241
PTGS2	-0.049	0.24	-9999	-0.99	27	27
Rac1/GTP	-0.18	0.17	-9999	-0.5	25	25
RHOA	0.016	0	-9999	-10000	0	0
VEGFA	-0.38	0.44	-9999	-0.86	240	240
negative regulation of T cell proliferation	-0.046	0.14	-9999	-0.49	15	15
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.011	0.057	-9999	-0.75	3	3
MAPK1	-0.039	0.17	-9999	-0.57	26	26
S1P1/S1P/PDGFB-D/PDGFRB	-0.17	0.24	-9999	-0.63	25	25
ABCC1	0.016	0.002	-9999	-10000	0	0

×

IL27-mediated signaling events

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
TGFB1	0.009	0.085	-10000	0	-0.86	5	5
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.074	0.2	0.63	28	-0.44	3	31
IL27/IL27R/JAK1	-0.08	0.35	0.58	1	-1	30	31
TBX21	-0.2	0.41	0.5	1	-0.76	157	158
IL12B	-0.092	0.28	-10000	0	-0.87	61	61
IL12A	0.008	0.031	-10000	0	-0.68	1	1
IL6ST	-0.016	0.14	-10000	0	-0.75	19	19
IL27RA/JAK1	0.011	0.062	-10000	0	-0.7	1	1
IL27	-0.044	0.21	-10000	0	-0.88	32	32
TYK2	0.011	0.012	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.025	0.13	-10000	0	-0.74	2	2
T-helper 2 cell differentiation	0.074	0.2	0.63	28	-0.44	3	31
T cell proliferation during immune response	0.074	0.2	0.63	28	-0.44	3	31
MAPKKK cascade	-0.074	0.2	0.44	3	-0.63	28	31
STAT3	0.016	0	-10000	0	-10000	0	0
STAT2	0.016	0	-10000	0	-10000	0	0
STAT1	0.015	0.039	-10000	0	-0.86	1	1
IL12RB1	-0.25	0.4	-10000	0	-0.87	160	160
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.16	0.35	0.5	1	-0.72	95	96
IL27/IL27R/JAK2/TYK2	-0.078	0.2	0.44	3	-0.64	28	31
positive regulation of T cell mediated cytotoxicity	-0.074	0.2	0.44	3	-0.63	28	31
STAT1 (dimer)	-0.063	0.51	0.54	125	-1	65	190
JAK2	0.011	0.012	-10000	0	-10000	0	0
JAK1	0.017	0.006	-10000	0	-10000	0	0
STAT2 (dimer)	-0.08	0.18	0.39	3	-0.63	23	26
T cell proliferation	-0.12	0.25	0.4	1	-0.72	49	50
IL12/IL12R/TYK2/JAK2	-0.17	0.27	-10000	0	-0.74	47	47
IL17A	-0.025	0.13	-10000	0	-0.74	2	2
mast cell activation	0.074	0.2	0.63	28	-0.44	3	31
IFNG	-0.04	0.066	0.13	3	-0.11	236	239
T cell differentiation	-0.011	0.011	0.03	3	-0.026	140	143
STAT3 (dimer)	-0.08	0.18	0.39	3	-0.63	23	26
STAT5A (dimer)	-0.08	0.18	0.39	3	-0.63	23	26
STAT4 (dimer)	-0.11	0.24	0.39	2	-0.76	43	45
STAT4	-0.034	0.2	-10000	0	-0.86	30	30
T cell activation	-0.012	0.007	0.1	1	-10000	0	1
IL27R/JAK2/TYK2	-0.043	0.1	-10000	0	-0.71	1	1
GATA3	-0.62	0.68	-10000	0	-1.3	262	262
IL18	0.005	0.079	-10000	0	-0.68	7	7
positive regulation of mast cell cytokine production	-0.08	0.18	0.38	3	-0.62	23	26
IL27/EBI3	-0.12	0.33	-10000	0	-0.83	86	86
IL27RA	-0.003	0.063	-10000	0	-0.76	1	1
IL6	-0.088	0.28	-10000	0	-0.81	67	67
STAT5A	0.016	0	-10000	0	-10000	0	0
monocyte differentiation	-0.002	0.003	-10000	0	-10000	0	0
IL2	0.001	0.086	-10000	0	-0.59	10	10
IL1B	0.006	0.071	-10000	0	-0.66	6	6
EBI3	-0.12	0.31	-10000	0	-0.88	76	76
TNF	0.004	0.078	-10000	0	-0.62	8	8

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.057	0.17	-9999	-0.52	58	58
EFNA5	-0.059	0.23	-9999	-0.75	52	52
FYN	-0.028	0.16	-9999	-0.47	58	58
neuron projection morphogenesis	-0.057	0.17	-9999	-0.52	58	58
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.057	0.17	-9999	-0.53	58	58
EPHA5	-0.008	0.11	-9999	-0.86	8	8

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.008	0.072	-9999	-0.66	6	6
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.02	0.11	-9999	-0.66	16	16
STXBP1	0.014	0.033	-9999	-0.74	1	1
ACh/CHRNA1	-0.27	0.31	-9999	-0.63	227	227
RAB3GAP2/RIMS1/UNC13B	-0.017	0.098	-9999	-0.57	16	16
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.014	0.15	-9999	-0.86	16	16
mol:ACh	-0.01	0.053	-9999	-0.13	83	83
RAB3GAP2	0.016	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.039	0.099	-9999	-0.62	4	4
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.27	0.31	-9999	-0.62	227	227
UNC13B	0.016	0	-9999	-10000	0	0
CHRNA1	-0.36	0.43	-9999	-0.86	227	227
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.082	0.2	-9999	-0.53	85	85
SNAP25	-0.04	0.12	-9999	-0.33	79	79
VAMP2	0.009	0	-9999	-10000	0	0
SYT1	-0.11	0.28	-9999	-0.74	85	85
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.007	0.064	-9999	-0.56	7	7
STX1A/SNAP25 fragment 1/VAMP2	-0.039	0.099	-9999	-0.62	4	4

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.19	0.35	-10000	0	-1.1	69	69
NFATC2	-0.08	0.24	-10000	0	-0.69	30	30
NFATC3	-0.021	0.063	-10000	0	-10000	0	0
CD40LG	-0.23	0.44	-10000	0	-1.2	58	58
ITCH	0.054	0.057	-10000	0	-10000	0	0
CBLB	0.054	0.057	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.54	0.56	-10000	0	-1.2	192	192
JUNB	0.013	0.046	-10000	0	-0.74	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.011	0.057	-10000	0	-10000	0	0
T cell anergy	0.023	0.093	-10000	0	-0.6	1	1
TLE4	-0.031	0.17	-10000	0	-0.7	8	8
Jun/NFAT1-c-4/p21SNFT	-0.24	0.28	-10000	0	-1	25	25
AP-1/NFAT1-c-4	-0.29	0.37	-10000	0	-1.2	34	34
IKZF1	-0.12	0.36	-10000	0	-0.88	93	93
T-helper 2 cell differentiation	-0.35	0.28	-10000	0	-0.74	104	104
AP-1/NFAT1	-0.093	0.16	-10000	0	-0.69	12	12
CALM1	0.029	0.036	-10000	0	-10000	0	0
EGR2	-0.11	0.29	-10000	0	-1.3	10	10
EGR3	-0.11	0.29	-10000	0	-1.4	9	9
NFAT1/FOXP3	-0.28	0.4	-10000	0	-0.96	111	111
EGR1	0	0.11	-10000	0	-0.74	12	12
JUN	0.006	0.022	-10000	0	-10000	0	0
EGR4	0.004	0.085	-10000	0	-0.86	5	5
mol:Ca2+	0.01	0.04	-10000	0	-10000	0	0
GBP3	-0.034	0.18	-10000	0	-0.78	10	10
FOSL1	-0.027	0.19	-10000	0	-0.86	26	26
NFAT1-c-4/MAF/IRF4	-0.26	0.36	-10000	0	-0.94	86	86
DGKA	-0.034	0.19	-10000	0	-0.96	8	8
CREM	0.015	0.002	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.17	0.22	-10000	0	-1.1	8	8
CTLA4	-0.43	0.58	-10000	0	-1	241	241
NFAT1-c-4 (dimer)/EGR1	-0.17	0.24	-10000	0	-1.2	12	12
NFAT1-c-4 (dimer)/EGR4	-0.17	0.23	-10000	0	-1.1	10	10
FOS	-0.013	0.12	-10000	0	-0.75	13	13
IFNG	-0.49	0.52	-10000	0	-1	225	225
T cell activation	-0.049	0.22	-10000	0	-0.83	16	16
MAF	0.016	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.063	0.2	0.91	3	-10000	0	3
TNF	-0.096	0.28	-10000	0	-1.1	14	14
FASLG	-0.33	0.48	-10000	0	-1.1	36	36
TBX21	-0.3	0.44	-10000	0	-0.93	172	172
BATF3	-0.059	0.24	-10000	0	-0.86	45	45
PRKCQ	-0.034	0.13	-10000	0	-0.74	16	16
PTPN1	-0.031	0.17	-10000	0	-0.7	8	8
NFAT1-c-4/ICER1	-0.17	0.22	-10000	0	-1.1	7	7
GATA3	-0.36	0.38	-10000	0	-0.74	262	262
T-helper 1 cell differentiation	-0.48	0.5	-10000	0	-1	227	227
IL2RA	-0.38	0.46	-10000	0	-1.1	127	127
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.031	0.17	-10000	0	-0.7	8	8
E2F1	-0.081	0.29	-10000	0	-0.85	64	64
PPARG	0.016	0.001	-10000	0	-10000	0	0
SLC3A2	-0.031	0.17	-10000	0	-0.7	8	8
IRF4	-0.18	0.36	-10000	0	-0.86	118	118
PTGS2	-0.21	0.4	-10000	0	-1.1	34	34
CSF2	-0.21	0.4	-10000	0	-1.1	32	32
JunB/Fra1/NFAT1-c-4	-0.18	0.22	-10000	0	-0.99	11	11
IL4	-0.36	0.29	-10000	0	-0.78	95	95
IL5	-0.2	0.38	-10000	0	-1.1	25	25
IL2	-0.05	0.22	-10000	0	-0.85	16	16
IL3	-0.049	0.049	-10000	0	-10000	0	0
RNF128	0.034	0.16	-10000	0	-0.78	19	19
NFATC1	-0.064	0.2	-10000	0	-0.91	3	3
CDK4	0.034	0.18	-10000	0	-10000	0	0
PTPRK	-0.032	0.18	-10000	0	-0.73	9	9
IL8	-0.22	0.42	-10000	0	-1.1	40	40
POU2F1	0.016	0.003	-10000	0	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.004	0.042	-9999	-0.48	4	4
ARNO/beta Arrestin1-2	-0.019	0.064	-9999	-10000	0	0
EGFR	0.001	0.11	-9999	-0.85	9	9
EPHA2	0.014	0.033	-9999	-0.74	1	1
USP6	0.014	0.038	-9999	-0.86	1	1
IQSEC1	0.015	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.51	0.18	-9999	-0.57	479	479
ARRB2	-0.017	0.11	-9999	-0.39	42	42
mol:GTP	-0.011	0.048	-9999	-0.23	2	2
ARRB1	0.016	0	-9999	-10000	0	0
FBXO8	0.016	0	-9999	-10000	0	0
TSHR	-0.086	0.28	-9999	-0.86	61	61
EGF	-0.67	0.23	-9999	-0.74	478	478
somatostatin receptor activity	0	0	-9999	-0.001	11	11
ARAP2	0.013	0.046	-9999	-0.74	2	2
mol:GDP	-0.058	0.094	-9999	-0.34	24	24
mol:PI-3-4-5-P3	0	0	-9999	-0.001	8	8
ITGA2B	-0.016	0.16	-9999	-0.86	19	19
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.034	-9999	-0.52	1	1
ADAP1	0.01	0.066	-9999	-0.74	4	4
KIF13B	0.016	0	-9999	-10000	0	0
HGF/MET	-0.032	0.15	-9999	-0.66	26	26
PXN	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.088	0.091	-9999	-0.34	19	19
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.44	0.16	-9999	-0.48	479	479
ADRB2	0.013	0.046	-9999	-0.74	2	2
receptor agonist activity	0	0	-9999	0	12	12
actin filament binding	0	0	-9999	-0.001	17	17
SRC	0.016	0	-9999	-10000	0	0
ITGB3	0.007	0.08	-9999	-0.74	6	6
GNAQ	0.015	0.001	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	10	10
ARF6/GDP	-0.069	0.14	-9999	-0.4	6	6
ARF6/GDP/GULP/ACAP1	-0.23	0.26	-9999	-0.53	205	205
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.023	0.11	-9999	-0.55	18	18
ACAP1	-0.32	0.43	-9999	-0.86	202	202
ACAP2	0.016	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.047	0.16	-9999	-0.59	42	42
EFNA1	0.014	0.038	-9999	-0.86	1	1
HGF	-0.02	0.17	-9999	-0.8	23	23
CYTH3	0.015	0	-9999	-10000	0	0
CYTH2	0.01	0.001	-9999	-10000	0	0
NCK1	0.014	0.033	-9999	-0.74	1	1
fibronectin binding	0	0	-9999	-0.001	10	10
endosomal lumen acidification	0	0	-9999	-0.001	18	18
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.012	0.14	-9999	-0.75	19	19
GNAQ/ARNO	0.009	0.01	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	-10000	0	0
MET	0.007	0.085	-9999	-0.86	5	5
GNA14	0.006	0.087	-9999	-0.74	7	7
GNA15	-0.011	0.15	-9999	-0.86	16	16
GIT1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	11	11
GNA11	0.011	0.057	-9999	-0.74	3	3
LHCGR	-0.062	0.23	-9999	-0.86	41	41
AGTR1	-0.026	0.17	-9999	-0.74	29	29
desensitization of G-protein coupled receptor protein signaling pathway	-0.047	0.16	-9999	-0.59	42	42
IPCEF1/ARNO	-0.34	0.12	-9999	-0.81	8	8
alphaIIb/beta3 Integrin	-0.03	0.14	-9999	-0.66	24	24

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.008	0.071	-9999	-0.68	5	5
VEGFR1 homodimer/NRP1	-0.008	0.072	-9999	-0.62	7	7
mol:DAG	-0.26	0.29	-9999	-0.97	7	7
VEGFR1 homodimer/NRP1/VEGFR 121	-0.24	0.27	-9999	-0.54	241	241
CaM/Ca2+	-0.27	0.25	-9999	-0.92	7	7
HIF1A	0.02	0.057	-9999	-0.72	2	2
GAB1	0.016	0	-9999	-10000	0	0
AKT1	-0.22	0.21	-9999	-0.94	6	6
PLCG1	-0.26	0.29	-9999	-0.98	7	7
NOS3	-0.18	0.24	-9999	-0.85	6	6
CBL	0.014	0.033	-9999	-0.74	1	1
mol:NO	-0.17	0.24	-9999	-0.8	6	6
FLT1	0.031	0.086	-9999	-0.71	7	7
PGF	-0.47	0.44	-9999	-0.86	291	291
VEGFR1 homodimer/NRP2/VEGFR121	-0.25	0.27	-9999	-1	7	7
CALM1	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
eNOS/Hsp90	-0.16	0.23	-9999	-0.76	6	6
endothelial cell proliferation	-0.2	0.26	-9999	-0.86	8	8
mol:Ca2+	-0.26	0.29	-9999	-0.95	7	7
MAPK3	-0.21	0.26	-9999	-0.88	6	6
MAPK1	-0.21	0.26	-9999	-0.88	6	6
PIK3R1	0.014	0.033	-9999	-0.74	1	1
PLGF homodimer	-0.46	0.44	-9999	-0.86	291	291
PRKACA	0.016	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.046	0.22	-9999	-0.86	37	37
VEGFA homodimer	-0.38	0.44	-9999	-0.86	240	240
VEGFR1 homodimer/VEGFA homodimer	-0.26	0.29	-9999	-0.58	241	241
platelet activating factor biosynthetic process	-0.2	0.25	-9999	-0.85	6	6
PI3K	-0.27	0.25	-9999	-0.99	7	7
PRKCA	-0.23	0.27	-9999	-0.89	7	7
PRKCB	-0.24	0.28	-9999	-0.91	9	9
VEGFR1 homodimer/PLGF homodimer	-0.32	0.3	-9999	-0.58	292	292
VEGFA	-0.38	0.44	-9999	-0.86	240	240
VEGFB	0.016	0	-9999	-10000	0	0
mol:IP3	-0.26	0.29	-9999	-0.97	7	7
RASA1	0.045	0.078	-9999	-0.65	6	6
NRP2	0.004	0.1	-9999	-0.86	7	7
VEGFR1 homodimer	0.031	0.086	-9999	-0.7	7	7
VEGFB homodimer	0.016	0	-9999	-10000	0	0
NCK1	0.014	0.033	-9999	-0.74	1	1
eNOS/Caveolin-1	-0.19	0.26	-9999	-0.8	31	31
PTPN11	0.016	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.27	0.25	-9999	-0.96	7	7
mol:L-citrulline	-0.17	0.24	-9999	-0.8	6	6
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.22	0.25	-9999	-0.94	6	6
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.24	0.27	-9999	-0.99	6	6
CD2AP	0.016	0	-9999	-10000	0	0
PI3K/GAB1	-0.25	0.23	-9999	-0.99	6	6
PDPK1	-0.22	0.27	-9999	-0.94	7	7
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.24	0.27	-9999	-1	5	5
mol:NADP	-0.17	0.24	-9999	-0.8	6	6
HSP90AA1	0.016	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.22	0.25	-9999	-0.92	6	6
VEGFR1 homodimer/NRP2	-0.016	0.095	-9999	-0.61	12	12

×

Calcium signaling in the CD4+ TCR pathway

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
NFATC1	-0.013	0.047	-9999	-10000	0	0
NFATC2	-0.017	0.068	-9999	-0.58	4	4
NFATC3	-0.013	0.047	-9999	-10000	0	0
CD40LG	-0.3	0.42	-9999	-0.94	101	101
PTGS2	-0.29	0.39	-9999	-0.86	95	95
JUNB	0.013	0.046	-9999	-0.74	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.02	0.018	-9999	-10000	0	0
CaM/Ca2+	-0.02	0.018	-9999	-10000	0	0
CALM1	0.006	0.013	-9999	-10000	0	0
JUN	0.006	0.013	-9999	-10000	0	0
mol:Ca2+	-0.02	0.019	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.002	0.003	-9999	-10000	0	0
FOSL1	-0.027	0.19	-9999	-0.86	26	26
CREM	0.015	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.19	0.2	-9999	-0.73	36	36
FOS	-0.013	0.12	-9999	-0.76	13	13
IFNG	-0.43	0.52	-9999	-0.99	225	225
AP-1/NFAT1-c-4	-0.41	0.41	-9999	-1.1	92	92
FASLG	-0.46	0.52	-9999	-0.98	228	228
NFAT1-c-4/ICER1	-0.08	0.083	-9999	-0.57	3	3
IL2RA	-0.34	0.44	-9999	-1	106	106
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.28	0.38	-9999	-0.87	92	92
JunB/Fra1/NFAT1-c-4	-0.094	0.12	-9999	-0.63	8	8
IL4	-0.28	0.37	-9999	-0.84	89	89
IL2	-0.012	0.11	-9999	-0.77	10	10
IL3	-0.028	0.026	-9999	-10000	0	0
FKBP1A	0.016	0	-9999	-10000	0	0
BATF3	-0.059	0.24	-9999	-0.86	45	45
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.016	0.003	-9999	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.024	-9999	-0.56	1	1
Necdin/E2F1	-0.083	0.22	-9999	-0.68	65	65
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.079	0.2	-9999	-0.98	8	8
NGF (dimer)/p75(NTR)/BEX1	-0.26	0.3	-9999	-0.56	252	252
NT-4/5 (dimer)/p75(NTR)	-0.053	0.18	-9999	-0.67	42	42
IKBKB	0.016	0	-9999	-10000	0	0
AKT1	-0.033	0.22	-9999	-0.54	77	77
IKBKG	0.016	0	-9999	-10000	0	0
BDNF	-0.1	0.3	-9999	-0.86	71	71
MGDIs/NGR/p75(NTR)/LINGO1	-0.071	0.2	-9999	-0.61	62	62
FURIN	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.12	0.25	-9999	-0.61	100	100
LINGO1	-0.022	0.18	-9999	-0.86	23	23
Sortilin/TRAF6/NRIF	-0.001	0.014	-9999	-10000	0	0
proBDNF (dimer)	-0.1	0.3	-9999	-0.86	71	71
NTRK1	-0.045	0.2	-9999	-0.75	41	41
RTN4R	0.004	0.098	-9999	-0.85	7	7
neuron apoptosis	-0.066	0.23	-9999	-0.68	32	32
IRAK1	0.016	0	-9999	-10000	0	0
SHC1	-0.061	0.24	-9999	-0.62	79	79
ARHGDIA	0.014	0.033	-9999	-0.74	1	1
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.085	0.21	-9999	-0.57	77	77
MAGEH1	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.087	0.22	-9999	-0.58	78	78
Mammalian IAPs/DIABLO	-0.079	0.19	-9999	-0.52	80	80
proNGF (dimer)	-0.067	0.26	-9999	-0.86	50	50
MAGED1	0.014	0.038	-9999	-0.86	1	1
APP	0.014	0.033	-9999	-0.74	1	1
NT-4/5 (dimer)	-0.004	0.092	-9999	-0.86	6	6
ZNF274	0.016	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.08	0.2	-9999	-0.54	77	77
NGF	-0.067	0.26	-9999	-0.86	50	50
cell cycle arrest	-0.014	0.25	-9999	-0.59	59	59
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.045	0.11	-9999	-0.57	8	8
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.046	0.16	-9999	-0.58	42	42
NCSTN	0.016	0	-9999	-10000	0	0
mol:GTP	-0.092	0.23	-9999	-0.62	78	78
PSENEN	0.016	0	-9999	-10000	0	0
mol:ceramide	-0.045	0.22	-9999	-0.56	77	77
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.035	0.086	-9999	-0.44	8	8
p75(NTR)/beta APP	-0.046	0.17	-9999	-0.66	37	37
BEX1	-0.26	0.37	-9999	-0.75	194	194
mol:GDP	-0.072	0.24	-9999	-0.64	78	78
NGF (dimer)	-0.35	0.3	-9999	-0.84	91	91
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.065	0.18	-9999	-0.56	62	62
PIK3R1	0.014	0.033	-9999	-0.74	1	1
RAC1/GTP	-0.081	0.2	-9999	-0.55	78	78
MYD88	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.092	0.23	-9999	-0.63	78	78
RHOB	0.016	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.08	0.22	-9999	-0.66	64	64
NT3 (dimer)	0.005	0.09	-9999	-0.78	7	7
TP53	-0.041	0.22	-9999	-0.91	8	8
PRDM4	-0.046	0.23	-9999	-0.57	77	77
BDNF (dimer)	-0.42	0.36	-9999	-0.87	143	143
PIK3CA	0.014	0.033	-9999	-0.74	1	1
SORT1	0.014	0.033	-9999	-0.74	1	1
activation of caspase activity	-0.078	0.2	-9999	-0.96	8	8
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.085	0.21	-9999	-0.57	77	77
RHOC	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
MAPK10	-0.024	0.21	-9999	-0.64	23	23
DIABLO	0.016	0	-9999	-10000	0	0
SMPD2	-0.046	0.23	-9999	-0.57	77	77
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.093	0.23	-9999	-0.62	79	79
PSEN1	0.016	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.053	0.18	-9999	-0.67	42	42
MAPK8	-0.023	0.21	-9999	-0.63	22	22
MAPK9	-0.021	0.2	-9999	-0.63	22	22
APAF1	0.016	0	-9999	-10000	0	0
NTF3	0.005	0.091	-9999	-0.78	7	7
NTF4	-0.004	0.092	-9999	-0.86	6	6
NDN	0.011	0.057	-9999	-0.74	3	3
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.072	0.18	-9999	-0.91	8	8
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.018	-9999	-10000	0	0
RhoA-B-C/GTP	-0.091	0.23	-9999	-0.62	78	78
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.098	0.21	-9999	-0.97	8	8
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.1	0.23	-9999	-0.56	98	98
PRKACB	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.089	0.22	-9999	-0.66	71	71
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.12	0.31	-9999	-0.86	80	80
BIRC2	0.016	0	-9999	-10000	0	0
neuron projection morphogenesis	0.006	0.24	-9999	-0.53	58	58
BAD	-0.011	0.2	-9999	-0.6	22	22
RIPK2	0.014	0.038	-9999	-0.86	1	1
NGFR	-0.044	0.22	-9999	-0.86	36	36
CYCS	-0.035	0.22	-9999	-0.97	9	9
ADAM17	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.085	0.21	-9999	-0.57	78	78
BCL2L11	-0.01	0.2	-9999	-0.6	22	22
BDNF (dimer)/p75(NTR)	-0.13	0.28	-9999	-0.7	100	100
PI3K	-0.085	0.21	-9999	-0.58	77	77
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.085	0.21	-9999	-0.57	77	77
NDNL2	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
PRKCI	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.11	0.26	-9999	-0.72	78	78
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.086	0.21	-9999	-0.57	78	78
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
PRKCZ	0.011	0.057	-9999	-0.74	3	3
PLG	-0.38	0.38	-9999	-0.74	273	273
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.12	0.23	-9999	-0.88	22	22
SQSTM1	0.016	0	-9999	-10000	0	0
NGFRAP1	0.016	0	-9999	-10000	0	0
CASP3	-0.005	0.18	-9999	-0.53	22	22
E2F1	-0.09	0.29	-9999	-0.86	64	64
CASP9	0.016	0	-9999	-10000	0	0
IKK complex	-0.07	0.15	-9999	-0.59	13	13
NGF (dimer)/TRKA	-0.11	0.24	-9999	-0.63	89	89
MMP7	-0.13	0.3	-9999	-0.75	98	98
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.079	0.2	-9999	-0.98	8	8
MMP3	-0.069	0.25	-9999	-0.86	47	47
APAF-1/Caspase 9	-0.11	0.17	-9999	-0.69	11	11

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.026	0.022	-9999	-0.48	1	1
ADCY5	0.006	0.1	-9999	-0.49	22	22
ADCY6	0.025	0.041	-9999	-0.92	1	1
ADCY7	0.009	0.1	-9999	-0.58	16	16
ADCY1	0.013	0.085	-9999	-0.5	14	14
ADCY2	-0.13	0.27	-9999	-0.58	141	141
ADCY3	0.026	0.022	-9999	-0.48	1	1
ADCY8	-0.17	0.28	-9999	-0.59	165	165
PRKCE	0.014	0.025	-9999	-0.57	1	1
ADCY9	0.026	0.022	-9999	-0.48	1	1
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.093	0.17	-9999	-0.5	54	54

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.017	0	-9999	-10000	0	0
ELF1	-0.044	0.14	-9999	-0.72	1	1
CCNA2	-0.15	0.35	-9999	-0.86	102	102
PIK3CA	0.015	0.033	-9999	-0.74	1	1
JAK3	-0.16	0.35	-9999	-0.86	106	106
PIK3R1	0.015	0.033	-9999	-0.74	1	1
JAK1	0.017	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.1	0.25	-9999	-0.66	59	59
SHC1	0.015	0.038	-9999	-0.86	1	1
SP1	0.025	0.022	-9999	-10000	0	0
IL2RA	-0.12	0.32	-9999	-0.77	105	105
IL2RB	-0.44	0.44	-9999	-0.86	273	273
SOS1	0.017	0	-9999	-10000	0	0
IL2RG	-0.039	0.21	-9999	-0.86	34	34
G1/S transition of mitotic cell cycle	-0.045	0.2	-9999	-0.55	13	13
PTPN11	0.017	0	-9999	-10000	0	0
CCND2	0.038	0.05	-9999	-0.78	2	2
LCK	-0.019	0.17	-9999	-0.85	22	22
GRB2	0.017	0	-9999	-10000	0	0
IL2	-0.006	0.12	-9999	-0.86	10	10
CDK6	0.014	0.033	-9999	-0.74	1	1
CCND3	-0.074	0.21	-9999	-0.66	28	28

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.12	0.24	-10000	0	-0.77	35	35
UGCG	-0.024	0.055	-10000	0	-0.77	2	2
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.077	0.19	-10000	0	-0.52	43	43
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.009	0.064	-10000	0	-0.76	2	2
mol:DAG	-0.004	0.006	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.11	0.16	-10000	0	-0.56	36	36
FRAP1	-0.081	0.23	-10000	0	-0.61	50	50
FOXO3	-0.072	0.22	-10000	0	-0.64	36	36
AKT1	-0.089	0.24	-10000	0	-0.64	52	52
GAB2	0.016	0.003	-10000	0	-10000	0	0
SMPD1	-0.021	0.03	-10000	0	-10000	0	0
SGMS1	-0.021	0.03	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.027	0.032	-10000	0	-0.48	2	2
CALM1	0.016	0	-10000	0	-10000	0	0
cell proliferation	-0.021	0.1	-10000	0	-0.49	2	2
EIF3A	0.016	0	-10000	0	-10000	0	0
PI3K	-0.002	0.034	-10000	0	-0.55	2	2
RPS6KB1	-0.026	0.087	-10000	0	-10000	0	0
mol:sphingomyelin	-0.004	0.006	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-10000	0	0
JAK3	-0.16	0.35	-10000	0	-0.86	106	106
PIK3R1	0.017	0.033	-10000	0	-0.74	1	1
JAK1	0.018	0.004	-10000	0	-10000	0	0
NFKB1	0.014	0.033	-10000	0	-0.74	1	1
MYC	-0.073	0.23	-10000	0	-0.66	36	36
MYB	-0.18	0.34	-10000	0	-0.74	139	139
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.12	0.26	-10000	0	-0.68	63	63
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.035	0.067	-10000	0	-0.47	2	2
mol:PI-3-4-5-P3	-0.11	0.25	-10000	0	-0.65	63	63
Rac1/GDP	0.021	0.033	-10000	0	-0.43	2	2
T cell proliferation	-0.093	0.24	-10000	0	-0.64	51	51
SHC1	0.014	0.038	-10000	0	-0.86	1	1
RAC1	0.015	0.003	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.008	0.026	-10000	0	-0.05	139	139
PRKCZ	-0.098	0.25	-10000	0	-0.67	52	52
NF kappa B1 p50/RelA	-0.1	0.16	-10000	0	-0.58	31	31
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.14	0.26	-10000	0	-0.58	102	102
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL2RA	-0.16	0.35	-10000	0	-0.86	104	104
IL2RB	-0.43	0.44	-10000	0	-0.86	273	273
TERT	-0.11	0.3	-10000	0	-0.86	74	74
E2F1	-0.1	0.2	-10000	0	-0.38	166	166
SOS1	0.016	0.003	-10000	0	-10000	0	0
RPS6	0.012	0.054	-10000	0	-0.86	2	2
mol:cAMP	0.003	0.013	0.025	139	-10000	0	139
PTPN11	0.016	0.003	-10000	0	-10000	0	0
IL2RG	-0.038	0.22	-10000	0	-0.86	34	34
actin cytoskeleton organization	-0.093	0.24	-10000	0	-0.64	51	51
GRB2	0.016	0.003	-10000	0	-10000	0	0
IL2	-0.004	0.12	-10000	0	-0.86	10	10
PIK3CA	0.017	0.033	-10000	0	-0.74	1	1
Rac1/GTP	0.032	0.034	-10000	0	-0.41	2	2
LCK	-0.017	0.17	-10000	0	-0.85	22	22
BCL2	-0.049	0.18	-10000	0	-0.53	24	24

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.001	0.057	0.29	18	-10000	0	18
BUB1B	-0.022	0.12	-10000	0	-0.51	26	26
PLK1	-0.011	0.059	-10000	0	-0.2	10	10
PLK1S1	0.001	0.031	-10000	0	-10000	0	0
KIF2A	-0.003	0.072	-10000	0	-0.56	4	4
regulation of mitotic centrosome separation	-0.012	0.058	-10000	0	-0.2	10	10
GOLGA2	0.016	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.18	0.33	-10000	0	-0.72	129	129
WEE1	-0.001	0.055	-10000	0	-0.3	5	5
cytokinesis	-0.2	0.27	-10000	0	-0.5	237	237
PP2A-alpha B56	-0.14	0.16	-10000	0	-10000	0	0
AURKA	-0.002	0.044	-10000	0	-0.3	6	6
PICH/PLK1	-0.045	0.16	-10000	0	-0.82	19	19
CENPE	-0.063	0.21	-10000	0	-0.62	62	62
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.003	0.071	-10000	0	-0.55	4	4
PPP2CA	0.016	0	-10000	0	-10000	0	0
FZR1	0.014	0.033	-10000	0	-0.74	1	1
TPX2	-0.049	0.12	-10000	0	-0.25	127	127
PAK1	0.016	0.002	-10000	0	-10000	0	0
SPC24	-0.077	0.27	-10000	0	-0.86	56	56
FBXW11	0.016	0	-10000	0	-10000	0	0
CLSPN	-0.025	0.096	-10000	0	-0.28	60	60
GORASP1	0.016	0	-10000	0	-10000	0	0
metaphase	-0.004	0.009	-10000	0	-0.02	129	129
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.006	0.031	-10000	0	-0.098	10	10
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.014	6	6
STAG2	0.016	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.009	0.013	-10000	0	-10000	0	0
spindle elongation	-0.012	0.058	-10000	0	-0.2	10	10
ODF2	0.016	0.002	-10000	0	-10000	0	0
BUB1	-0.16	0.19	-10000	0	-0.46	9	9
TPT1	0.001	0.031	-10000	0	-10000	0	0
CDC25C	-0.13	0.17	-10000	0	-0.31	242	242
CDC25B	0.007	0.086	-10000	0	-0.88	5	5
SGOL1	0.001	0.057	-10000	0	-0.29	18	18
RHOA	0.016	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.023	0.1	-10000	0	-0.74	9	9
CDC14B	0.016	0.002	-10000	0	-10000	0	0
CDC20	-0.055	0.24	-10000	0	-0.86	43	43
PLK1/PBIP1	-0.041	0.12	-10000	0	-0.59	19	19
mitosis	-0.001	0.004	0.03	6	-10000	0	6
FBXO5	0.003	0.044	-10000	0	-0.19	5	5
CDC2	-0.001	0.004	-10000	0	-0.023	9	9
NDC80	-0.17	0.36	-10000	0	-0.86	111	111
metaphase plate congression	-0.004	0.041	-10000	0	-10000	0	0
ERCC6L	-0.037	0.16	-10000	0	-0.81	19	19
NLP/gamma Tubulin	-0.003	0.034	-10000	0	-0.12	5	5
microtubule cytoskeleton organization	0.001	0.031	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0.001	0.001	-10000	0	-10000	0	0
PPP1R12A	0.016	0.002	-10000	0	-10000	0	0
interphase	0.001	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.25	0.29	-10000	0	-0.56	237	237
GRASP65/GM130/RAB1/GTP/PLK1	-0.013	0.027	-10000	0	-10000	0	0
RAB1A	0.016	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.007	0.038	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.005	-10000	0	-0.012	121	121
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.043	-10000	0	-10000	0	0
microtubule-based process	-0.24	0.3	-10000	0	-0.58	237	237
Golgi organization	-0.012	0.058	-10000	0	-0.2	10	10
Cohesin/SA2	-0.024	0.044	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.38	0.44	-10000	0	-0.86	237	237
APC/C/CDC20	-0.045	0.18	-10000	0	-0.64	43	43
PPP2R1A	0.016	0	-10000	0	-10000	0	0
chromosome segregation	-0.04	0.11	-10000	0	-0.58	19	19
PRC1	0.006	0.093	-10000	0	-0.86	6	6
ECT2	0.001	0.053	-10000	0	-10000	0	0
C13orf34	0.004	0.042	-10000	0	-10000	0	0
NUDC	-0.004	0.041	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.022	0.12	-10000	0	-0.5	26	26
spindle assembly	-0.006	0.047	-10000	0	-0.16	8	8
spindle stabilization	0.001	0.031	-10000	0	-10000	0	0
APC/C/HCDH1	-0.001	0.021	-10000	0	-0.49	1	1
MKLP2/PLK1	-0.25	0.31	-10000	0	-0.59	237	237
CCNB1	0.002	0.11	-10000	0	-0.87	8	8
PPP1CB	0.016	0.002	-10000	0	-10000	0	0
BTRC	0.016	0	-10000	0	-10000	0	0
ROCK2	0.004	0.058	-10000	0	-0.48	4	4
TUBG1	0.001	0.031	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.025	0.097	-10000	0	-0.71	9	9
MLF1IP	-0.013	0.13	-10000	0	-0.69	19	19
INCENP	0.009	0.008	-10000	0	-10000	0	0

×

IL6-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.14	0.3	-9999	-0.75	42	42
CRP	-0.2	0.39	-9999	-0.9	95	95
cell cycle arrest	-0.18	0.35	-9999	-0.78	84	84
TIMP1	-0.15	0.33	-9999	-0.77	70	70
IL6ST	-0.015	0.14	-9999	-0.74	19	19
Rac1/GDP	-0.14	0.26	-9999	-0.59	95	95
AP1	0.021	0.1	-9999	-0.58	2	2
GAB2	0.011	0.008	-9999	-10000	0	0
TNFSF11	-0.19	0.37	-9999	-0.86	77	77
HSP90B1	0.004	0.087	-9999	-10000	0	0
GAB1	0.013	0.006	-9999	-10000	0	0
MAPK14	0.015	0.14	-9999	-0.72	5	5
AKT1	0.06	0.035	-9999	-10000	0	0
FOXO1	0.076	0.023	-9999	-10000	0	0
MAP2K6	-0.019	0.14	-9999	-0.66	7	7
mol:GTP	-0.001	0.003	-9999	-10000	0	0
MAP2K4	-0.14	0.27	-9999	-0.61	96	96
MITF	-0.026	0.14	-9999	-0.64	6	6
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.016	0	-9999	-10000	0	0
A2M	0.028	0.005	-9999	-10000	0	0
CEBPB	0.003	0.13	-9999	-0.86	12	12
GRB2/SOS1/GAB family/SHP2	0	0.069	-9999	-10000	0	0
STAT3	-0.18	0.36	-9999	-0.83	84	84
STAT1	-0.005	0.025	-9999	-0.49	1	1
CEBPD	-0.14	0.3	-9999	-0.76	39	39
PIK3CA	0.017	0.033	-9999	-0.74	1	1
PI3K	-0.002	0.034	-9999	-0.56	2	2
JUN	0.01	0.008	-9999	-10000	0	0
PIAS3/MITF	-0.02	0.13	-9999	-0.71	4	4
MAPK11	0.013	0.14	-9999	-0.78	6	6
STAT3 (dimer)/FOXO1	-0.073	0.27	-9999	-0.64	22	22
GRB2/SOS1/GAB family	-0.048	0.11	-9999	-0.66	4	4
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.04	0.16	-9999	-0.65	13	13
GRB2	0.013	0.006	-9999	-10000	0	0
JAK2	0.016	0	-9999	-10000	0	0
LBP	-0.29	0.45	-9999	-0.88	165	165
PIK3R1	0.016	0.033	-9999	-0.74	1	1
JAK1	0.015	0.006	-9999	-10000	0	0
MYC	-0.15	0.32	-9999	-0.78	53	53
FGG	-0.27	0.43	-9999	-0.85	144	144
macrophage differentiation	-0.18	0.35	-9999	-0.78	84	84
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.07	0.17	-9999	-0.55	39	39
JUNB	-0.14	0.3	-9999	-0.74	43	43
FOS	-0.009	0.12	-9999	-0.75	13	13
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.037	0.15	-9999	-0.45	29	29
STAT1/PIAS1	-0.049	0.16	-9999	-0.49	25	25
GRB2/SOS1/GAB family/SHP2/PI3K	0.022	0.038	-9999	-10000	0	0
STAT3 (dimer)	-0.18	0.36	-9999	-0.82	84	84
PRKCD	-0.14	0.3	-9999	-0.69	68	68
IL6R	0.015	0.006	-9999	-10000	0	0
SOCS3	0.029	0.14	-9999	-0.69	7	7
gp130 (dimer)/JAK1/JAK1/LMO4	-0.005	0.093	-9999	-0.47	19	19
Rac1/GTP	-0.18	0.23	-9999	-0.59	105	105
HCK	-0.033	0.2	-9999	-0.86	29	29
MAPKKK cascade	0.025	0.061	-9999	-10000	0	0
bone resorption	-0.18	0.35	-9999	-0.8	78	78
IRF1	-0.14	0.3	-9999	-0.76	41	41
mol:GDP	-0.15	0.27	-9999	-0.55	135	135
SOS1	0.01	0.008	-9999	-10000	0	0
VAV1	-0.15	0.27	-9999	-0.56	135	135
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.01	0.13	-9999	-0.67	5	5
PTPN11	-0.004	0.012	-9999	-10000	0	0
IL6/IL6RA	-0.079	0.21	-9999	-0.63	67	67
gp130 (dimer)/TYK2/TYK2/LMO4	-0.014	0.088	-9999	-0.47	19	19
gp130 (dimer)/JAK2/JAK2/LMO4	-0.014	0.088	-9999	-0.47	19	19
IL6	-0.092	0.28	-9999	-0.82	67	67
PIAS3	0.016	0	-9999	-10000	0	0
PTPRE	0.017	0.017	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
RAC1	0.015	0.002	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.037	0.14	-9999	-0.4	26	26
LMO4	0.012	0.014	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.22	0.29	-9999	-0.76	81	81
MCL1	0.075	0.023	-9999	-10000	0	0

×

BCR signaling pathway

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
JUN	-0.053	0.16	-10000	0	-0.41	42	42
IKBKB	-0.022	0.1	-10000	0	-0.28	2	2
AKT1	-0.022	0.12	-10000	0	-0.32	4	4
IKBKG	-0.022	0.11	-10000	0	-0.3	3	3
CALM1	-0.041	0.1	-10000	0	-0.5	3	3
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
MAP3K1	-0.11	0.25	-10000	0	-0.63	71	71
MAP3K7	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.054	0.11	0.27	1	-0.5	4	5
DOK1	0.016	0	-10000	0	-10000	0	0
AP-1	-0.011	0.089	-10000	0	-10000	0	0
LYN	0.016	0	-10000	0	-10000	0	0
BLNK	0.014	0.033	-10000	0	-0.74	1	1
SHC1	0.014	0.038	-10000	0	-0.86	1	1
BCR complex	-0.16	0.29	-10000	0	-0.68	129	129
CD22	-0.14	0.23	-10000	0	-0.67	51	51
CAMK2G	-0.029	0.097	-10000	0	-0.49	2	2
CSNK2A1	0.016	0	-10000	0	-10000	0	0
INPP5D	0.009	0.076	-10000	0	-0.86	4	4
SHC/GRB2/SOS1	-0.1	0.18	-10000	0	-0.85	4	4
GO:0007205	-0.054	0.11	0.27	1	-0.51	4	5
SYK	0.013	0.046	-10000	0	-0.74	2	2
ELK1	-0.042	0.1	-10000	0	-0.51	3	3
NFATC1	-0.069	0.2	-10000	0	-0.5	66	66
B-cell antigen/BCR complex	-0.16	0.29	-10000	0	-0.68	129	129
PAG1/CSK	-0.003	0.041	-10000	0	-0.66	2	2
NFKBIB	0.005	0.039	-10000	0	-0.13	1	1
HRAS	-0.037	0.12	-10000	0	-0.49	4	4
NFKBIA	0.006	0.038	-10000	0	-0.14	1	1
NF-kappa-B/RelA/I kappa B beta	0.013	0.032	-10000	0	-0.18	1	1
RasGAP/Csk	-0.21	0.32	-10000	0	-0.99	47	47
mol:GDP	-0.05	0.1	0.29	1	-0.47	4	5
PTEN	0.016	0	-10000	0	-10000	0	0
CD79B	0.011	0.066	-10000	0	-0.86	3	3
NF-kappa-B/RelA/I kappa B alpha	0.014	0.032	-10000	0	-0.19	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.076	0.22	-10000	0	-0.57	63	63
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
mol:IP3	-0.065	0.1	0.27	1	-0.51	4	5
CSK	0.016	0	-10000	0	-10000	0	0
FOS	-0.039	0.11	-10000	0	-0.48	6	6
CHUK	-0.022	0.11	-10000	0	-0.3	2	2
IBTK	0.016	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.12	0.2	-10000	0	-0.54	84	84
PTPN6	-0.13	0.21	-10000	0	-0.68	39	39
RELA	0.016	0	-10000	0	-10000	0	0
BCL2A1	-0.011	0.068	-10000	0	-0.14	108	108
VAV2	-0.16	0.28	-10000	0	-0.79	74	74
ubiquitin-dependent protein catabolic process	0.011	0.037	-10000	0	-0.12	1	1
BTK	-0.085	0.17	0.46	1	-0.42	106	107
CD19	-0.19	0.32	-10000	0	-0.88	79	79
MAP4K1	-0.34	0.43	-10000	0	-0.86	216	216
CD72	-0.19	0.37	-10000	0	-0.86	123	123
PAG1	0.012	0.054	-10000	0	-0.86	2	2
MAPK14	-0.082	0.21	-10000	0	-0.52	67	67
SH3BP5	0.014	0.033	-10000	0	-0.74	1	1
PIK3AP1	-0.036	0.11	-10000	0	-0.54	6	6
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.11	0.23	-10000	0	-0.58	77	77
RAF1	-0.024	0.11	-10000	0	-0.53	2	2
RasGAP/p62DOK/SHIP	-0.2	0.31	-10000	0	-0.97	48	48
CD79A	-0.2	0.38	-10000	0	-0.86	129	129
re-entry into mitotic cell cycle	-0.011	0.089	-10000	0	-0.26	1	1
RASA1	0.014	0.033	-10000	0	-0.74	1	1
MAPK3	-0.001	0.099	-10000	0	-10000	0	0
MAPK1	-0.001	0.099	-10000	0	-10000	0	0
CD72/SHP1	-0.22	0.33	-10000	0	-0.82	100	100
NFKB1	0.014	0.033	-10000	0	-0.74	1	1
MAPK8	-0.084	0.21	-10000	0	-0.53	65	65
actin cytoskeleton organization	-0.094	0.26	-10000	0	-0.66	67	67
NF-kappa-B/RelA	0.035	0.059	-10000	0	-10000	0	0
Calcineurin	-0.042	0.069	-10000	0	-0.44	2	2
PI3K	-0.14	0.22	-10000	0	-0.6	69	69
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.061	0.1	-10000	0	-0.55	4	4
SOS1	0.016	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.27	0.32	-10000	0	-0.74	135	135
DAPP1	-0.11	0.18	-10000	0	-0.61	36	36
cytokine secretion	-0.063	0.19	-10000	0	-0.46	66	66
mol:DAG	-0.065	0.1	0.27	1	-0.51	4	5
PLCG2	0.003	0.1	-10000	0	-0.82	8	8
MAP2K1	-0.012	0.11	-10000	0	-0.48	2	2
B-cell antigen/BCR complex/FcgammaRIIB	-0.24	0.37	-10000	0	-0.72	178	178
mol:PI-3-4-5-P3	-0.096	0.15	-10000	0	-0.4	65	65
ETS1	-0.016	0.091	-10000	0	-0.44	2	2
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.12	0.22	-10000	0	-0.98	3	3
B-cell antigen/BCR complex/LYN	-0.14	0.21	-10000	0	-0.57	71	71
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
RAC1	-0.1	0.28	-10000	0	-0.73	67	67
B-cell antigen/BCR complex/LYN/SYK	-0.16	0.25	-10000	0	-0.76	37	37
CARD11	-0.14	0.26	-10000	0	-0.62	110	110
FCGR2B	-0.14	0.34	-10000	0	-0.86	96	96
PPP3CA	0.016	0	-10000	0	-10000	0	0
BCL10	0.016	0	-10000	0	-10000	0	0
IKK complex	0.006	0.047	-10000	0	-10000	0	0
PTPRC	-0.077	0.27	-10000	0	-0.86	56	56
PDPK1	-0.06	0.1	-10000	0	-0.34	4	4
PPP3CB	0.016	0	-10000	0	-10000	0	0
PPP3CC	0.016	0	-10000	0	-10000	0	0
POU2F2	0.001	0.057	-10000	0	-0.14	66	66

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.013	0.035	-9999	-0.78	1	1
SVIL	0.015	0.007	-9999	-10000	0	0
ZNF318	0.016	0.023	-9999	-10000	0	0
JMJD2C	-0.001	0.022	-9999	-0.11	19	19
T-DHT/AR/Ubc9	-0.078	0.11	-9999	-0.54	26	26
CARM1	0.015	0.003	-9999	-10000	0	0
PRDX1	0.016	0.001	-9999	-10000	0	0
PELP1	0.016	0.003	-9999	-10000	0	0
CTNNB1	0.015	0.003	-9999	-10000	0	0
AKT1	0.017	0.006	-9999	-10000	0	0
PTK2B	0.015	0.003	-9999	-10000	0	0
MED1	0.013	0.009	-9999	-10000	0	0
MAK	0.014	0.044	-9999	-0.86	1	1
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.009	0.068	-9999	-0.77	4	4
GSN	0.015	0.008	-9999	-10000	0	0
NCOA2	0	0.11	-9999	-0.74	11	11
NCOA6	0.016	0.003	-9999	-10000	0	0
DNA-PK	0.005	0.026	-9999	-10000	0	0
NCOA4	0.015	0.002	-9999	-10000	0	0
PIAS3	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.028	0.036	-9999	-0.61	1	1
XRCC5	0.016	0.005	-9999	-10000	0	0
UBE3A	0.014	0.013	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.094	0.15	-9999	-0.59	39	39
FHL2	-0.04	0.11	-9999	-1.1	5	5
RANBP9	0.016	0.003	-9999	-10000	0	0
JMJD1A	-0.12	0.056	-9999	-0.14	458	458
CDK6	0.014	0.033	-9999	-0.74	1	1
TGFB1I1	0.013	0.039	-9999	-0.86	1	1
T-DHT/AR/CyclinD1	-0.1	0.15	-9999	-0.59	46	46
XRCC6	0.016	0.005	-9999	-10000	0	0
T-DHT/AR	-0.15	0.12	-9999	-0.58	26	26
CTDSP1	0.015	0.003	-9999	-10000	0	0
CTDSP2	0.015	0.017	-9999	-10000	0	0
BRCA1	0.015	0.007	-9999	-10000	0	0
TCF4	0.014	0.013	-9999	-10000	0	0
CDKN2A	-0.83	0.17	-9999	-0.86	511	511
SRF	0.026	0.012	-9999	-10000	0	0
NKX3-1	-0.19	0.07	-9999	-10000	0	0
KLK3	0.024	0.15	-9999	-0.7	21	21
TMF1	0.015	0.003	-9999	-10000	0	0
HNRNPA1	0.014	0.013	-9999	-10000	0	0
AOF2	-0.001	0.01	-9999	-10000	0	0
APPL1	0.033	0.013	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.077	0.11	-9999	-0.54	26	26
AR	-0.07	0.16	-9999	-0.78	26	26
UBA3	0.015	0.003	-9999	-10000	0	0
PATZ1	0.014	0.013	-9999	-10000	0	0
PAWR	0.014	0.033	-9999	-0.74	1	1
PRKDC	0.016	0.005	-9999	-10000	0	0
PA2G4	0.014	0.012	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.069	0.1	-9999	-0.5	26	26
RPS6KA3	0.013	0.035	-9999	-0.78	1	1
T-DHT/AR/ARA70	-0.079	0.11	-9999	-0.54	26	26
LATS2	0.014	0.011	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.069	0.1	-9999	-0.5	26	26
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	-0.005	0.12	-9999	-0.74	14	14
KLK2	-0.085	0.14	-9999	-0.8	19	19
CASP8	0.016	0.003	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.069	0.13	-9999	-0.6	26	26
TMPRSS2	-0.92	0.36	-9999	-1.1	458	458
CCND1	-0.018	0.17	-9999	-0.86	20	20
PIAS1	0.014	0.013	-9999	-10000	0	0
mol:T-DHT	-0.062	0.027	-9999	-0.072	454	454
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.013	0.019	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.079	0.11	-9999	-0.56	26	26
CMTM2	-0.004	0.13	-9999	-0.86	12	12
SNURF	-0.009	0.13	-9999	-0.74	17	17
ZMIZ1	-0.031	0.022	-9999	-10000	0	0
CCND3	0.016	0.001	-9999	-10000	0	0
TGIF1	0.014	0.013	-9999	-10000	0	0
FKBP4	0.016	0.003	-9999	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.23	0.28	-9999	-0.85	76	76
RAD9A	0.016	0	-9999	-10000	0	0
AP1	-0.014	0.088	-9999	-0.57	13	13
IFNAR2	0.015	0.007	-9999	-10000	0	0
AKT1	0.013	0.069	-9999	-0.43	10	10
ER alpha/Oestrogen	-0.006	0.057	-9999	-0.59	5	5
NFX1/SIN3/HDAC complex	0.044	0.055	-9999	-10000	0	0
EGF	-0.67	0.23	-9999	-0.74	478	478
SMG5	0.016	0	-9999	-10000	0	0
SMG6	0.016	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.22	0.26	-9999	-0.79	74	74
SAP18	0.013	0.006	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.34	0.38	-9999	-0.74	246	246
WRN	0.016	0	-9999	-10000	0	0
SP1	0.015	0.007	-9999	-10000	0	0
SP3	0.014	0.006	-9999	-10000	0	0
TERF2IP	0.016	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.18	0.23	-9999	-0.72	63	63
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.24	0.29	-9999	-0.88	76	76
CCND1	-0.22	0.27	-9999	-0.8	78	78
MAX	0.014	0.006	-9999	-10000	0	0
RBBP7	0.013	0.006	-9999	-10000	0	0
RBBP4	0.012	0.033	-9999	-0.74	1	1
TERF2	0	0.004	-9999	-10000	0	0
PTGES3	0.016	0	-9999	-10000	0	0
SIN3A	0.013	0.006	-9999	-10000	0	0
Telomerase/911	0.004	0.029	-9999	-10000	0	0
CDKN1B	-0.22	0.3	-9999	-0.55	238	238
RAD1	0.016	0	-9999	-10000	0	0
XRCC5	0.016	0	-9999	-10000	0	0
XRCC6	0.016	0	-9999	-10000	0	0
SAP30	-0.018	0.16	-9999	-0.86	19	19
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.014	0.006	-9999	-10000	0	0
JUN	0.014	0.006	-9999	-10000	0	0
E6	-0.001	0.003	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.005	0.12	-9999	-0.75	13	13
IFN-gamma/IRF1	-0.29	0.32	-9999	-0.65	238	238
PARP2	0.016	0	-9999	-10000	0	0
BLM	-0.004	0.13	-9999	-0.86	12	12
Telomerase	-0.02	0.16	-9999	-0.48	8	8
IRF1	0.016	0.039	-9999	-0.86	1	1
ESR1	0.006	0.076	-9999	-0.77	5	5
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.021	-9999	-0.49	1	1
ubiquitin-dependent protein catabolic process	0.051	0.051	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	-0.007	0.034	-9999	-10000	0	0
HDAC1	0.013	0.006	-9999	-10000	0	0
HDAC2	0.015	0.007	-9999	-10000	0	0
ATM	-0.001	0.023	-9999	-0.52	1	1
SMAD3	0.025	0.067	-9999	-0.66	5	5
ABL1	0.016	0	-9999	-10000	0	0
MXD1	0.014	0.006	-9999	-10000	0	0
MRE11A	0.016	0	-9999	-10000	0	0
HUS1	0.016	0	-9999	-10000	0	0
RPS6KB1	0.016	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.17	0.25	-9999	-0.76	64	64
NR2F2	0.01	0.012	-9999	-10000	0	0
MAPK3	0.009	0.094	-9999	-0.67	10	10
MAPK1	0.009	0.094	-9999	-0.67	10	10
TGFB1/TGF beta receptor Type II	0.008	0.084	-9999	-0.86	5	5
NFKB1	0.014	0.033	-9999	-0.74	1	1
HNRNPC	0.016	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.023	-9999	-0.52	1	1
NBN	0.016	0	-9999	-10000	0	0
EGFR	0.001	0.11	-9999	-0.85	9	9
mol:Oestrogen	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.51	0.18	-9999	-0.57	479	479
MYC	-0.019	0.17	-9999	-0.86	20	20
IL2	-0.008	0.12	-9999	-0.86	10	10
KU	0	0	-9999	-10000	0	0
RAD50	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
TGFB1	0.008	0.085	-9999	-0.86	5	5
TRF2/BLM	-0.014	0.093	-9999	-0.62	12	12
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.21	0.26	-9999	-0.79	73	73
SP1/HDAC2	0.007	0.014	-9999	-10000	0	0
PINX1	0.016	0	-9999	-10000	0	0
Telomerase/EST1A	-0.18	0.23	-9999	-0.72	63	63
Smad3/Myc	-0.02	0.13	-9999	-0.6	24	24
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.37	0.43	-9999	-0.85	238	238
Telomerase/PinX1	-0.18	0.23	-9999	-0.74	52	52
Telomerase/AKT1/mTOR/p70S6K	-0.012	0.079	-9999	-0.53	2	2
SIN3B	0.013	0.006	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
Telomerase/EST1B	-0.18	0.23	-9999	-0.72	63	63
response to DNA damage stimulus	0.004	0.006	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0.004	-9999	-10000	0	0
TRF2/WRN	0	0.004	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.18	0.23	-9999	-0.72	62	62
E2F1	-0.091	0.29	-9999	-0.87	64	64
ZNFX1	0.013	0.006	-9999	-10000	0	0
PIF1	-0.14	0.33	-9999	-0.86	92	92
NCL	0.016	0	-9999	-10000	0	0
DKC1	0.016	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

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

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
MAP4K1	-0.17	0.27	-10000	0	-0.54	95	95
CRKL	0.015	0.12	-10000	0	-0.55	9	9
HRAS	-0.043	0.18	-10000	0	-0.51	41	41
mol:PIP3	-0.005	0.11	-10000	0	-0.44	24	24
SPRED1	0.016	0	-10000	0	-10000	0	0
SPRED2	0.014	0.033	-10000	0	-0.74	1	1
GAB1	0.004	0.12	-10000	0	-0.49	24	24
FOXO3	0.022	0.11	-10000	0	-0.49	9	9
AKT1	0.012	0.12	-10000	0	-0.45	24	24
BAD	0.02	0.11	-10000	0	-0.59	6	6
megakaryocyte differentiation	-0.074	0.22	-10000	0	-0.45	117	117
GSK3B	0.022	0.11	-10000	0	-0.59	5	5
RAF1	-0.011	0.15	-10000	0	-0.54	3	3
SHC1	0.014	0.038	-10000	0	-0.86	1	1
STAT3	0.005	0.12	-10000	0	-0.49	24	24
STAT1	-0.02	0.25	-10000	0	-1	24	24
HRAS/SPRED1	-0.068	0.12	-10000	0	-0.42	20	20
cell proliferation	0.004	0.13	-10000	0	-0.51	24	24
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
TEC	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.006	0.12	-10000	0	-0.44	33	33
HRAS/SPRED2	-0.068	0.12	-10000	0	-0.43	21	21
LYN/TEC/p62DOK	-0.02	0.1	-10000	0	-0.66	5	5
MAPK3	0.011	0.12	-10000	0	-0.37	2	2
STAP1	-0.32	0.22	-10000	0	-0.42	406	406
GRAP2	-0.042	0.22	-10000	0	-0.86	35	35
JAK2	-0.071	0.2	-10000	0	-0.9	24	24
STAT1 (dimer)	-0.019	0.24	-10000	0	-1	24	24
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.13	0.22	-10000	0	-0.47	131	131
actin filament polymerization	-0.002	0.14	-10000	0	-0.49	30	30
LYN	0.016	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.3	0.23	-10000	0	-0.88	33	33
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
CBL/CRKL/GRB2	-0.016	0.096	-10000	0	-0.59	5	5
PI3K	-0.022	0.11	-10000	0	-0.45	25	25
PTEN	0.016	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.13	0.35	-10000	0	-1.3	26	26
MAPK8	0.003	0.13	-10000	0	-0.52	24	24
STAT3 (dimer)	0.005	0.12	-10000	0	-0.48	24	24
positive regulation of transcription	0.015	0.099	-10000	0	-0.31	1	1
mol:GDP	-0.11	0.19	-10000	0	-0.62	44	44
PIK3C2B	0.005	0.12	-10000	0	-0.49	24	24
CBL/CRKL	0.024	0.11	-10000	0	-0.62	5	5
FER	0.003	0.13	-10000	0	-0.5	26	26
SH2B3	0.005	0.12	-10000	0	-0.49	24	24
PDPK1	0.005	0.1	-10000	0	-0.48	10	10
SNAI2	0.004	0.13	-10000	0	-0.5	24	24
positive regulation of cell proliferation	-0.004	0.19	-10000	0	-0.78	24	24
KITLG	0	0.11	-10000	0	-0.76	10	10
cell motility	-0.004	0.19	-10000	0	-0.78	24	24
PTPN6	0.008	0.011	-10000	0	-10000	0	0
EPOR	0.039	0.073	-10000	0	-10000	0	0
STAT5A (dimer)	0.001	0.17	-10000	0	-0.65	25	25
SOCS1	0.006	0.093	-10000	0	-0.86	6	6
cell migration	0.045	0.2	0.5	72	-10000	0	72
SOS1	0.016	0	-10000	0	-10000	0	0
EPO	-0.29	0.42	-10000	0	-0.86	186	186
VAV1	-0.19	0.37	-10000	0	-0.86	124	124
GRB10	0.004	0.12	-10000	0	-0.49	24	24
PTPN11	0.008	0.01	-10000	0	-10000	0	0
SCF/KIT	-0.037	0.12	-10000	0	-0.46	36	36
GO:0007205	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	0.005	0.13	-10000	0	-0.42	2	2
CBL	0.014	0.033	-10000	0	-0.74	1	1
KIT	-0.016	0.29	-10000	0	-1.2	31	31
MAP2K2	0.004	0.13	-10000	0	-0.42	2	2
SHC/Grb2/SOS1	-0.021	0.1	-10000	0	-0.66	5	5
STAT5A	0	0.17	-10000	0	-0.67	25	25
GRB2	0.016	0	-10000	0	-10000	0	0
response to radiation	0.004	0.13	-10000	0	-0.49	24	24
SHC/GRAP2	-0.045	0.17	-10000	0	-0.66	36	36
PTPRO	-0.076	0.22	-10000	0	-0.46	117	117
SH2B2	-0.002	0.14	-10000	0	-0.5	30	30
DOK1	0.016	0	-10000	0	-10000	0	0
MATK	-0.047	0.2	-10000	0	-0.52	72	72
CREBBP	0.044	0.012	-10000	0	-10000	0	0
BCL2	0.041	0.071	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.016	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
NUDC	0.016	0	-9999	-10000	0	0
RELN/LRP8	-0.16	0.22	-9999	-0.48	179	179
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.016	0.001	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.11	0.22	-9999	-0.52	6	6
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.011	0.14	-9999	-0.86	13	13
IQGAP1	0.016	0	-9999	-10000	0	0
PLA2G7	-0.65	0.38	-9999	-0.86	403	403
CALM1	0.016	0	-9999	-10000	0	0
DYNLT1	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.001	0.029	-9999	-0.66	1	1
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.016	0	-9999	-10000	0	0
CDK5R1	0.016	0.001	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.1	0.29	-9999	-0.86	67	67
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.18	0.24	-9999	-0.49	190	190
YWHAE	0.016	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.13	0.16	-9999	-0.59	16	16
MAP1B	-0.001	0.02	-9999	-0.33	2	2
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.12	0.17	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.75	178	178
PAFAH/LIS1	-0.44	0.25	-9999	-0.57	403	403
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.098	0.12	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.1	0.14	-9999	-0.7	1	1
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.13	0.19	-9999	-0.64	16	16
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.031	0	-9999	-10000	0	0
PAFAH1B3	0.014	0.033	-9999	-0.74	1	1
PAFAH1B2	0.014	0.033	-9999	-0.74	1	1
MAP1B/LIS1/Dynein heavy chain	-0.001	0.013	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.13	0.15	-9999	-0.56	16	16
LRP8	0.014	0.038	-9999	-0.86	1	1
NDEL1/Katanin 60	-0.13	0.16	-9999	-0.59	16	16
P39/CDK5	-0.18	0.22	-9999	-0.86	16	16
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.094	0.21	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.14	0.2	-9999	-0.51	18	18
RELN/VLDLR	-0.14	0.2	-9999	-0.52	6	6
CDC42	0	0	-9999	-10000	0	0

×

Reelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ITGA3	0.012	0.054	-9999	-0.86	2	2
RELN/VLDLR/Fyn	-0.16	0.22	-9999	-0.48	178	178
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.004	0.045	-9999	-0.8	1	1
AKT1	-0.068	0.16	-9999	-0.57	2	2
MAP2K7	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
DAB1	-0.011	0.14	-9999	-0.86	13	13
RELN/LRP8/DAB1	-0.16	0.22	-9999	-0.45	191	191
LRPAP1/LRP8	-0.001	0.029	-9999	-0.66	1	1
RELN/LRP8/DAB1/Fyn	-0.15	0.2	-9999	-0.52	19	19
DAB1/alpha3/beta1 Integrin	-0.13	0.18	-9999	-0.82	1	1
long-term memory	-0.2	0.24	-9999	-0.88	24	24
DAB1/LIS1	-0.14	0.18	-9999	-0.85	1	1
DAB1/CRLK/C3G	-0.13	0.18	-9999	-0.82	1	1
PIK3CA	0.014	0.033	-9999	-0.74	1	1
DAB1/NCK2	-0.14	0.18	-9999	-0.86	1	1
ARHGEF2	0.016	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.11	0.3	-9999	-0.83	76	76
CDK5R1	0.016	0.001	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.75	178	178
PIK3R1	0.014	0.033	-9999	-0.74	1	1
RELN/LRP8/Fyn	-0.16	0.22	-9999	-0.48	179	179
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.21	0.25	-9999	-0.62	77	77
MAPK8	0.013	0.046	-9999	-0.74	2	2
RELN/VLDLR/DAB1	-0.16	0.22	-9999	-0.45	190	190
ITGB1	0.016	0	-9999	-10000	0	0
MAP1B	-0.15	0.2	-9999	-0.51	19	19
RELN/LRP8	-0.16	0.22	-9999	-0.48	179	179
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.15	0.2	-9999	-0.61	7	7
PI3K	-0.002	0.034	-9999	-0.56	2	2
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.003	0.041	-9999	-0.66	2	2
RAP1A	-0.11	0.17	-9999	-0.75	1	1
PAFAH1B1	0.016	0	-9999	-10000	0	0
MAPK8IP1	0.013	0.046	-9999	-0.74	2	2
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0.008	0.054	-9999	-0.86	2	2
NCK2	0.016	0	-9999	-10000	0	0
neuron differentiation	-0.03	0.12	-9999	-0.53	3	3
neuron adhesion	-0.051	0.19	-9999	-0.7	1	1
LRP8	0.014	0.038	-9999	-0.86	1	1
GSK3B	-0.054	0.15	-9999	-0.53	2	2
RELN/VLDLR/DAB1/Fyn	-0.15	0.2	-9999	-0.42	190	190
MAP3K11	0.014	0.033	-9999	-0.74	1	1
RELN/VLDLR/DAB1/P13K	-0.11	0.15	-9999	-0.61	2	2
CDK5	0.016	0	-9999	-10000	0	0
MAPT	0.016	0.082	-9999	-0.69	6	6
neuron migration	-0.061	0.21	-9999	-0.54	2	2
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.031	0.12	-9999	-0.54	3	3
RELN/VLDLR	-0.14	0.2	-9999	-0.52	6	6

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.019	0.11	-10000	0	-1.4	1	1
SMARCC2	0.018	0	-10000	0	-10000	0	0
SMARCC1	0.018	0	-10000	0	-10000	0	0
TBX21	-0.25	0.41	-10000	0	-0.82	175	175
SUMO2	0.011	0.007	-10000	0	-10000	0	0
STAT1 (dimer)	0.025	0.053	-10000	0	-1.2	1	1
FKBP4	0.016	0	-10000	0	-10000	0	0
FKBP5	0.004	0.098	-10000	0	-0.85	7	7
GR alpha/HSP90/FKBP51/HSP90	0.055	0.13	0.39	5	-0.57	8	13
PRL	-0.015	0.11	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.13	0.29	0.57	82	-0.58	3	85
RELA	0.005	0.076	-10000	0	-10000	0	0
FGG	-0.14	0.43	0.53	20	-0.7	172	192
GR beta/TIF2	0.051	0.14	0.42	6	-0.53	10	16
IFNG	-0.41	0.44	-10000	0	-0.9	184	184
apoptosis	-0.094	0.21	-10000	0	-0.64	11	11
CREB1	-0.015	0.1	-10000	0	-0.4	5	5
histone acetylation	0.02	0.13	0.39	10	-0.55	3	13
BGLAP	-0.008	0.13	-10000	0	-0.74	3	3
GR/PKAc	0.065	0.1	0.37	4	-0.6	1	5
NF kappa B1 p50/RelA	0.011	0.14	-10000	0	-0.56	8	8
SMARCD1	0.018	0	-10000	0	-10000	0	0
MDM2	0.047	0.093	0.35	6	-10000	0	6
GATA3	-0.35	0.38	-10000	0	-0.74	262	262
AKT1	0	0.005	-10000	0	-10000	0	0
CSF2	-0.027	0.15	-10000	0	-0.69	16	16
GSK3B	0.011	0.007	-10000	0	-10000	0	0
NR1I3	-0.057	0.22	-10000	0	-0.82	13	13
CSN2	0.045	0.19	0.48	5	-0.66	1	6
BRG1/BAF155/BAF170/BAF60A	0.004	0.014	-10000	0	-10000	0	0
NFATC1	0.018	0.005	-10000	0	-10000	0	0
POU2F1	0.019	0.005	-10000	0	-10000	0	0
CDKN1A	0.05	0.052	-10000	0	-0.72	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.083	0.27	-10000	0	-0.83	62	62
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.004	0.21	0.37	3	-0.55	37	40
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.058	0.22	-10000	0	-0.85	13	13
JUN	-0.22	0.25	-10000	0	-0.67	63	63
IL4	-0.023	0.12	-10000	0	-0.63	1	1
CDK5R1	0.012	0.007	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.25	0.26	0.31	2	-0.7	79	81
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.061	0.12	0.38	4	-0.6	4	8
cortisol/GR alpha (monomer)	0.15	0.34	0.66	96	-0.8	1	97
NCOA2	0	0.11	-10000	0	-0.74	11	11
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.054	0.14	-10000	0	-0.82	13	13
AP-1/NFAT1-c-4	-0.32	0.34	-10000	0	-0.88	79	79
AFP	-0.35	0.56	-10000	0	-1.4	112	112
SUV420H1	0.016	0	-10000	0	-10000	0	0
IRF1	0.085	0.15	0.55	5	-0.62	1	6
TP53	0.044	0.021	-10000	0	-10000	0	0
PPP5C	0.016	0	-10000	0	-10000	0	0
KRT17	-0.25	0.41	-10000	0	-1.2	67	67
KRT14	-0.15	0.3	-10000	0	-0.83	81	81
TBP	0.028	0.01	-10000	0	-10000	0	0
CREBBP	0.049	0.082	-10000	0	-10000	0	0
HDAC1	0.01	0.008	-10000	0	-10000	0	0
HDAC2	0.011	0.014	-10000	0	-10000	0	0
AP-1	-0.33	0.34	-10000	0	-0.88	81	81
MAPK14	0.012	0.007	-10000	0	-10000	0	0
MAPK10	0.005	0.074	-10000	0	-0.75	5	5
MAPK11	0.008	0.055	-10000	0	-0.88	2	2
KRT5	-0.27	0.39	-10000	0	-0.95	104	104
interleukin-1 receptor activity	0	0.011	-10000	0	-10000	0	0
NCOA1	0.019	0.002	-10000	0	-10000	0	0
STAT1	0.025	0.053	-10000	0	-1.2	1	1
CGA	-0.13	0.37	-10000	0	-1.2	52	52
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.091	0.15	0.45	35	-10000	0	35
MAPK3	0.012	0.007	-10000	0	-10000	0	0
MAPK1	0.012	0.007	-10000	0	-10000	0	0
ICAM1	-0.049	0.23	-10000	0	-0.81	24	24
NFKB1	0.003	0.085	-10000	0	-0.9	1	1
MAPK8	-0.14	0.2	-10000	0	-0.57	34	34
MAPK9	0.012	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.099	0.22	-10000	0	-0.68	11	11
BAX	0.052	0.028	-10000	0	-10000	0	0
POMC	-0.037	0.17	-10000	0	-0.86	6	6
EP300	0.047	0.086	-10000	0	-0.6	1	1
cortisol/GR alpha (dimer)/p53	0.16	0.29	0.6	77	-0.7	1	78
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.071	0.29	1	-10000	0	1
SGK1	0.1	0.098	-10000	0	-10000	0	0
IL13	-0.36	0.28	-10000	0	-0.81	92	92
IL6	-0.12	0.38	-10000	0	-0.98	75	75
PRKACG	0.004	0.007	-10000	0	-10000	0	0
IL5	-0.29	0.21	-10000	0	-0.71	41	41
IL2	-0.17	0.25	-10000	0	-0.86	26	26
CDK5	0.012	0.007	-10000	0	-10000	0	0
PRKACB	0.016	0	-10000	0	-10000	0	0
HSP90AA1	0.016	0	-10000	0	-10000	0	0
IL8	-0.077	0.3	-10000	0	-0.9	46	46
CDK5R1/CDK5	0	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.027	0.1	-10000	0	-0.62	1	1
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.15	0.26	0.55	77	-0.65	1	78
SMARCA4	0.018	0	-10000	0	-10000	0	0
chromatin remodeling	0.1	0.15	0.42	27	-10000	0	27
NF kappa B1 p50/RelA/Cbp	0.065	0.14	-10000	0	-0.94	1	1
JUN (dimer)	-0.21	0.25	-10000	0	-0.67	64	64
YWHAH	0.016	0	-10000	0	-10000	0	0
VIPR1	-0.057	0.22	-10000	0	-1	16	16
NR3C1	0.081	0.19	0.48	37	-0.95	1	38
NR4A1	0.002	0.13	-10000	0	-0.73	16	16
TIF2/SUV420H1	-0.012	0.079	-10000	0	-0.56	11	11
MAPKKK cascade	-0.094	0.21	-10000	0	-0.64	11	11
cortisol/GR alpha (dimer)/Src-1	0.15	0.28	0.58	82	-0.8	1	83
PBX1	-0.003	0.13	-10000	0	-0.74	16	16
POU1F1	0.009	0.009	-10000	0	-10000	0	0
SELE	-0.095	0.36	-10000	0	-1.3	39	39
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.1	0.15	0.42	27	-10000	0	27
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.15	0.26	0.55	77	-0.65	1	78
mol:cortisol	0.064	0.2	0.42	61	-10000	0	61
MMP1	-0.23	0.4	-10000	0	-0.98	105	105

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	240	240
alphaV beta3 Integrin	-0.01	0.074	-9999	-0.53	10	10
PTK2	-0.15	0.23	-9999	-0.67	6	6
IGF1R	0.016	0	-9999	-10000	0	0
PI4KB	0.016	0	-9999	-10000	0	0
MFGE8	0.014	0.038	-9999	-0.86	1	1
SRC	0.016	0	-9999	-10000	0	0
CDKN1B	-0.084	0.19	-9999	-0.52	82	82
VEGFA	-0.38	0.44	-9999	-0.86	240	240
ILK	-0.084	0.19	-9999	-0.52	82	82
ROCK1	0.016	0	-9999	-10000	0	0
AKT1	-0.077	0.18	-9999	-0.49	74	74
PTK2B	-0.19	0.27	-9999	-0.88	1	1
alphaV/beta3 Integrin/JAM-A	-0.07	0.16	-9999	-0.52	10	10
CBL	0.014	0.033	-9999	-0.74	1	1
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.22	0.24	-9999	-0.47	252	252
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.009	0.066	-9999	-0.52	6	6
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.13	0.14	-9999	-0.47	46	46
alphaV/beta3 Integrin/Syndecan-1	-0.011	0.07	-9999	-0.47	12	12
PI4KA	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.046	0.14	-9999	-0.8	4	4
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
alphaV/beta3 Integrin/Osteopontin	-0.009	0.064	-9999	-0.47	10	10
RPS6KB1	-0.043	0.13	-9999	-0.73	4	4
TLN1	0.016	0	-9999	-10000	0	0
MAPK3	-0.044	0.1	-9999	-0.7	5	5
GPR124	0.011	0.066	-9999	-0.86	3	3
MAPK1	-0.044	0.1	-9999	-0.82	3	3
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
alphaV/beta3 Integrin/Tumstatin	-0.058	0.16	-9999	-0.49	63	63
cell adhesion	-0.17	0.18	-9999	-0.83	1	1
ANGPTL3	-0.34	0.38	-9999	-0.74	246	246
VEGFR2 homodimer/VEGFA homodimer/Src	-0.26	0.29	-9999	-0.58	240	240
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.016	0	-9999	-10000	0	0
ITGB3	0.007	0.08	-9999	-0.74	6	6
IGF1	0.006	0.093	-9999	-0.86	6	6
RAC1	0.016	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.009	0.065	-9999	-0.5	9	9
apoptosis	0.016	0	-9999	-10000	0	0
CD47	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.005	0.05	-9999	-0.47	6	6
VCL	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.019	0.099	-9999	-0.52	19	19
CSF1	0.014	0.033	-9999	-0.74	1	1
PIK3C2A	-0.086	0.2	-9999	-0.53	83	83
PI4 Kinase/Pyk2	-0.24	0.24	-9999	-0.75	48	48
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.24	0.26	-9999	-0.52	240	240
FAK1/Vinculin	-0.11	0.19	-9999	-0.56	3	3
alphaV beta3/Integrin/ppsTEM5	-0.009	0.066	-9999	-0.51	9	9
RHOA	0.016	0	-9999	-10000	0	0
VTN	-0.1	0.28	-9999	-0.75	82	82
BCAR1	0.014	0.033	-9999	-0.74	1	1
FGF2	0.008	0.076	-9999	-0.77	5	5
F11R	0.025	0.059	-9999	-0.58	5	5
alphaV/beta3 Integrin/Lactadherin	-0.006	0.056	-9999	-0.49	7	7
alphaV/beta3 Integrin/TGFBR2	-0.005	0.05	-9999	-0.47	6	6
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.002	0.041	-9999	-0.85	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.005	0.046	-9999	-0.44	6	6
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.047	0.23	-9999	-0.86	38	38
alphaV/beta3 Integrin/Pyk2	-0.22	0.24	-9999	-0.88	1	1
SDC1	0.007	0.08	-9999	-0.74	6	6
VAV3	0.04	0.082	-9999	-0.8	1	1
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.01	0.066	-9999	-0.74	4	4
FAK1/Paxillin	-0.11	0.19	-9999	-0.56	3	3
cell migration	-0.092	0.17	-9999	-0.52	2	2
ITGAV	0.016	0	-9999	-10000	0	0
PI3K	-0.063	0.14	-9999	-1.1	1	1
SPP1	0.01	0.066	-9999	-0.74	4	4
KDR	0.014	0.033	-9999	-0.74	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.016	0	-9999	-10000	0	0
COL4A3	-0.069	0.24	-9999	-0.74	59	59
angiogenesis	0.002	0.15	-9999	-0.8	3	3
Rac1/GTP	-0.011	0.066	-9999	-0.72	1	1
EDIL3	-0.005	0.13	-9999	-0.78	14	14
cell proliferation	-0.005	0.05	-9999	-0.47	6	6

×

Aurora A 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.019	0.045	-9999	-10000	0	0
BIRC5	-0.24	0.4	-9999	-0.86	154	154
NFKBIA	0.047	0.039	-9999	-10000	0	0
CPEB1	-0.14	0.31	-9999	-0.76	109	109
AKT1	0.047	0.039	-9999	-10000	0	0
NDEL1	0.016	0	-9999	-10000	0	0
Aurora A/BRCA1	0.017	0.04	-9999	-10000	0	0
NDEL1/TACC3	0.016	0.075	-9999	-0.74	4	4
GADD45A	0.016	0	-9999	-10000	0	0
GSK3B	0.013	0.019	-9999	-10000	0	0
PAK1/Aurora A	0.019	0.045	-9999	-10000	0	0
MDM2	0.016	0	-9999	-10000	0	0
JUB	0.011	0.057	-9999	-0.74	3	3
TPX2	-0.14	0.3	-9999	-0.67	127	127
TP53	0.024	0.036	-9999	-10000	0	0
DLG7	0.019	0.043	-9999	-0.29	6	6
AURKAIP1	0.011	0.06	-9999	-0.78	3	3
ARHGEF7	0.016	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.017	0.078	-9999	-0.77	4	4
G2/M transition of mitotic cell cycle	0.017	0.04	-9999	-10000	0	0
AURKA	0.026	0.054	-9999	-0.34	6	6
AURKB	-0.14	0.15	-9999	-0.29	247	247
CDC25B	0.017	0.061	-9999	-0.58	2	2
G2/M transition checkpoint	0.014	0.052	-9999	-0.44	3	3
mRNA polyadenylation	-0.076	0.19	-9999	-0.44	109	109
Aurora A/CPEB	-0.076	0.19	-9999	-0.44	109	109
Aurora A/TACC1/TRAP/chTOG	0.023	0.044	-9999	-10000	0	0
BRCA1	0.016	0	-9999	-10000	0	0
centrosome duplication	0.019	0.045	-9999	-10000	0	0
regulation of centrosome cycle	-0.006	0.064	-9999	-0.73	4	4
spindle assembly	-0.002	0.022	-9999	-10000	0	0
TDRD7	0.016	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.14	0.21	-9999	-0.47	151	151
CENPA	-0.12	0.14	-9999	-0.3	170	170
Aurora A/PP2A	0.019	0.045	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.053	0.035	-9999	-10000	0	0
negative regulation of DNA binding	0.024	0.036	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.014	0.033	-9999	-0.74	1	1
Ajuba/Aurora A	0.015	0.053	-9999	-0.44	3	3
mitotic prometaphase	0.037	0.04	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.049	-9999	-0.34	6	6
TACC1	0.016	0	-9999	-10000	0	0
TACC3	0.009	0.076	-9999	-0.86	4	4
Aurora A/Antizyme1	0.017	0.06	-9999	-0.49	3	3
Aurora A/RasGAP	0.018	0.05	-9999	-0.47	1	1
OAZ1	0.014	0.038	-9999	-0.86	1	1
RAN	0.016	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.019	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.14	0.3	-9999	-0.66	127	127
PPP2R5D	0.016	0	-9999	-10000	0	0
Aurora A/TPX2	-0.086	0.24	-9999	-0.52	127	127
PAK1	0.016	0	-9999	-10000	0	0
CKAP5	0.016	0	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.02	0.18	-9999	-10000	0	0
CRKL	-0.094	0.22	-9999	-10000	0	0
mol:DAG	-0.12	0.17	-9999	-10000	0	0
HRAS	-0.11	0.15	-9999	-0.7	1	1
MAPK8	-0.14	0.26	-9999	-0.7	2	2
RAP1A	-0.094	0.22	-9999	-10000	0	0
GAB1	-0.094	0.22	-9999	-10000	0	0
MAPK14	-0.13	0.25	-9999	-0.48	186	186
EPO	-0.29	0.42	-9999	-0.85	186	186
PLCG1	-0.13	0.17	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.007	0.019	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.19	0.26	-9999	-0.55	187	187
GAB1/SHC/GRB2/SOS1	-0.12	0.16	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.23	0.31	-9999	-0.65	186	186
IRS2	-0.1	0.23	-9999	-0.88	2	2
STAT1	-0.065	0.21	-9999	-10000	0	0
STAT5B	-0.069	0.21	-9999	-10000	0	0
cell proliferation	-0.12	0.24	-9999	-0.86	1	1
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.11	0.15	-9999	-0.71	1	1
TEC	-0.094	0.22	-9999	-10000	0	0
SOCS3	0.011	0.066	-9999	-0.86	3	3
STAT1 (dimer)	-0.063	0.21	-9999	-10000	0	0
JAK2	0.006	0.018	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
EPO/EPOR (dimer)/JAK2	-0.1	0.24	-9999	-10000	0	0
EPO/EPOR	-0.23	0.31	-9999	-0.65	186	186
LYN	0.018	0.001	-9999	-10000	0	0
TEC/VAV2	-0.081	0.22	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.007	0.019	-9999	-10000	0	0
SHC1	0.014	0.038	-9999	-0.86	1	1
EPO/EPOR (dimer)/LYN	-0.16	0.28	-9999	-0.54	186	186
mol:IP3	-0.12	0.17	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.13	0.18	-9999	-0.79	3	3
SH2B3	0.006	0.018	-9999	-10000	0	0
NFKB1	-0.13	0.26	-9999	-0.48	186	186
EPO/EPOR (dimer)/JAK2/SOCS3	-0.11	0.15	-9999	-0.53	2	2
PTPN6	-0.11	0.23	-9999	-10000	0	0
TEC/VAV2/GRB2	-0.12	0.17	-9999	-10000	0	0
EPOR	0.007	0.019	-9999	-10000	0	0
INPP5D	0.009	0.076	-9999	-0.86	4	4
mol:GDP	-0.12	0.16	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
PLCG2	0.003	0.1	-9999	-0.82	8	8
CRKL/CBL/C3G	-0.12	0.17	-9999	-0.73	1	1
VAV2	-0.094	0.22	-9999	-10000	0	0
CBL	-0.094	0.22	-9999	-0.8	1	1
SHC/Grb2/SOS1	-0.12	0.17	-9999	-10000	0	0
STAT5A	-0.069	0.21	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
STAT5 (dimer)	-0.045	0.21	-9999	-10000	0	0
LYN/PLCgamma2	-0.009	0.076	-9999	-0.62	8	8
PTPN11	0.016	0	-9999	-10000	0	0
BTK	-0.2	0.29	-9999	-0.88	30	30
BCL2	-0.02	0.18	-9999	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.084	0.31	-10000	0	-0.9	30	30
NCK1/PAK1/Dok-R	-0.083	0.11	-10000	0	-0.41	34	34
NCK1/Dok-R	-0.083	0.26	-10000	0	-1	32	32
PIK3CA	0.005	0.033	-10000	0	-0.74	1	1
mol:beta2-estradiol	-0.006	0.038	0.3	7	-10000	0	7
RELA	0.016	0	-10000	0	-10000	0	0
SHC1	0.007	0.039	-10000	0	-0.87	1	1
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.31	0.42	-10000	0	-0.85	199	199
TNIP2	0.016	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.058	0.23	-10000	0	-0.96	31	31
FN1	-0.047	0.23	-10000	0	-0.86	38	38
PLD2	0.032	0.3	-10000	0	-1.1	31	31
PTPN11	0.016	0	-10000	0	-10000	0	0
GRB14	-0.024	0.17	-10000	0	-0.74	28	28
ELK1	0.061	0.27	-10000	0	-0.96	31	31
GRB7	0.006	0.086	-10000	0	-0.74	7	7
PAK1	0.016	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.11	0.29	-10000	0	-1	43	43
CDKN1A	-0.11	0.31	-10000	0	-0.68	20	20
ITGA5	-0.047	0.23	-10000	0	-0.86	38	38
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.083	0.26	-10000	0	-1	32	32
CRK	0.016	0	-10000	0	-10000	0	0
mol:NO	-0.049	0.26	-10000	0	-0.65	30	30
PLG	-0.19	0.34	-10000	0	-1.2	31	31
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.12	0.21	-10000	0	-0.84	30	30
GRB2	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.034	-10000	0	-0.74	1	1
ANGPT2	-0.2	0.38	-10000	0	-0.65	172	172
BMX	-0.036	0.34	-10000	0	-1.1	31	31
ANGPT1	0.075	0.19	-10000	0	-1.2	8	8
tube development	-0.13	0.34	-10000	0	-0.7	33	33
ANGPT4	-0.018	0.15	-10000	0	-0.87	16	16
response to hypoxia	-0.003	0.017	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.024	0.32	-10000	0	-1.2	31	31
alpha5/beta1 Integrin	-0.048	0.17	-10000	0	-0.66	38	38
FGF2	0.01	0.077	-10000	0	-0.76	5	5
STAT5A (dimer)	-0.15	0.36	-10000	0	-0.85	26	26
mol:L-citrulline	-0.049	0.26	-10000	0	-0.65	30	30
AGTR1	-0.036	0.17	-10000	0	-0.75	29	29
MAPK14	-0.003	0.31	-10000	0	-1.1	30	30
Tie2/SHP2	-0.061	0.25	-10000	0	-1.1	29	29
TEK	-0.046	0.29	-10000	0	-1.2	29	29
RPS6KB1	-0.047	0.28	-10000	0	-0.86	30	30
Angiotensin II/AT1	-0.043	0.13	-10000	0	-0.58	29	29
Tie2/Ang1/GRB2	-0.004	0.3	-10000	0	-1.1	31	31
MAPK3	0.045	0.27	-10000	0	-0.99	31	31
MAPK1	0.045	0.27	-10000	0	-0.99	31	31
Tie2/Ang1/GRB7	-0.009	0.31	-10000	0	-1.2	31	31
NFKB1	0.014	0.033	-10000	0	-0.74	1	1
MAPK8	0.031	0.3	-10000	0	-1.1	31	31
PI3K	-0.07	0.32	-10000	0	-1	30	30
FES	-0.008	0.31	-10000	0	-1.1	31	31
Crk/Dok-R	-0.083	0.26	-10000	0	-1	31	31
Tie2/Ang1/ABIN2	-0.004	0.3	-10000	0	-1.1	31	31
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.073	0.29	-10000	0	-0.8	30	30
STAT5A	0.016	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.047	0.28	-10000	0	-0.86	30	30
Tie2/Ang2	-0.19	0.41	-10000	0	-0.98	33	33
Tie2/Ang1	0.024	0.33	-10000	0	-1.2	31	31
FOXO1	-0.11	0.31	-10000	0	-0.8	30	30
ELF1	0.023	0.035	-10000	0	-0.73	1	1
ELF2	0.028	0.3	-10000	0	-1.1	31	31
mol:Choline	0.035	0.28	-10000	0	-1	31	31
cell migration	-0.055	0.071	-10000	0	-10000	0	0
FYN	-0.15	0.36	-10000	0	-0.8	33	33
DOK2	-0.035	0.2	-10000	0	-0.86	31	31
negative regulation of cell cycle	-0.095	0.3	-10000	0	-0.61	20	20
ETS1	0.028	0.037	-10000	0	-10000	0	0
PXN	-0.025	0.25	-10000	0	-0.7	30	30
ITGB1	0.016	0	-10000	0	-10000	0	0
NOS3	-0.06	0.28	-10000	0	-0.74	30	30
RAC1	0.016	0	-10000	0	-10000	0	0
TNF	0.009	0.11	-10000	0	-0.79	8	8
MAPKKK cascade	0.035	0.28	-10000	0	-1	31	31
RASA1	0.014	0.033	-10000	0	-0.74	1	1
Tie2/Ang1/Shc	-0.003	0.3	-10000	0	-1.1	31	31
NCK1	0.014	0.033	-10000	0	-0.74	1	1
vasculogenesis	-0.04	0.24	-10000	0	-0.58	30	30
mol:Phosphatidic acid	0.035	0.28	-10000	0	-1	31	31
mol:Angiotensin II	-0.016	0.022	-10000	0	-10000	0	0
mol:NADP	-0.049	0.26	-10000	0	-0.65	30	30
Rac1/GTP	-0.13	0.19	-10000	0	-0.8	30	30
MMP2	0.027	0.3	-10000	0	-1.1	31	31

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.016	0	-9999	-10000	0	0
GNAT1/GTP	-0.01	0.082	-9999	-0.68	8	8
Metarhodopsin II/Arrestin	-0.019	0.1	-9999	-0.59	17	17
PDE6G/GNAT1/GTP	-0.014	0.086	-9999	-0.56	13	13
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.007	0.11	-9999	-0.86	8	8
GRK1	0.003	0.006	-9999	-10000	0	0
CNG Channel	-0.11	0.21	-9999	-0.94	12	12
mol:Na +	-0.11	0.21	-9999	-0.81	22	22
mol:ADP	0.003	0.006	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.036	0.13	-9999	-0.5	38	38
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.12	0.22	-9999	-0.85	22	22
CNGB1	-0.009	0.12	-9999	-0.86	11	11
RDH5	-0.003	0.13	-9999	-0.83	12	12
SAG	0.001	0.038	-9999	-0.86	1	1
mol:Ca2+	-0.069	0.22	-9999	-0.78	22	22
Na + (4 Units)	-0.1	0.2	-9999	-0.74	22	22
RGS9	-0.008	0.14	-9999	-0.82	15	15
GNB1/GNGT1	-0.23	0.32	-9999	-0.66	182	182
GNAT1/GDP	-0.038	0.13	-9999	-0.53	16	16
GUCY2D	-0.031	0.19	-9999	-0.86	26	26
GNGT1	-0.29	0.42	-9999	-0.86	182	182
GUCY2F	0.002	0.005	-9999	-10000	0	0
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.038	0.15	-9999	-0.59	29	29
mol:11-cis-retinal	-0.003	0.13	-9999	-0.83	12	12
mol:cGMP	-0.041	0.14	-9999	-0.53	39	39
GNB1	0.016	0	-9999	-10000	0	0
Rhodopsin	-0.034	0.15	-9999	-0.65	28	28
SLC24A1	0.016	0	-9999	-10000	0	0
CNGA1	-0.13	0.3	-9999	-0.74	99	99
Metarhodopsin II	-0.017	0.094	-9999	-0.55	16	16
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.043	0.15	-9999	-0.55	41	41
RGS9BP	-0.018	0.15	-9999	-0.74	23	23
Metarhodopsin II/Transducin	-0.12	0.16	-9999	-0.62	11	11
GCAP Family/Ca ++	-0.017	0.098	-9999	-0.56	16	16
PDE6A/B	-0.035	0.15	-9999	-0.66	28	28
mol:Pi	-0.035	0.13	-9999	-0.5	38	38
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.19	0.27	-9999	-0.55	185	185
PDE6B	0.007	0.08	-9999	-0.74	6	6
PDE6A	-0.024	0.18	-9999	-0.86	23	23
PDE6G	0.008	0.076	-9999	-0.77	5	5
RHO	-0.016	0.15	-9999	-0.86	16	16
PDE6	-0.056	0.16	-9999	-0.82	8	8
GUCA1A	-0.01	0.12	-9999	-0.86	10	10
GC2/GCAP Family	-0.017	0.098	-9999	-0.56	16	16
GUCA1C	0.001	0.046	-9999	-0.74	2	2
GUCA1B	0.007	0.085	-9999	-0.86	5	5

×

Signaling events mediated by PTP1B

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
PDGFRB	0.016	0	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.048	0.1	-10000	0	-0.55	5	5
PTP1B/AKT1	-0.032	0.047	-10000	0	-0.39	3	3
FYN	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.049	0.053	-10000	0	-0.41	4	4
EGFR	-0.013	0.11	-10000	0	-0.87	9	9
EGF/EGFR	-0.37	0.14	-10000	0	-0.41	476	476
CSF1	0.014	0.033	-10000	0	-0.74	1	1
AKT1	0.016	0.001	-10000	0	-10000	0	0
INSR	0.016	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.05	0.091	-10000	0	-0.45	20	20
Insulin Receptor/Insulin	-0.008	0.035	-10000	0	-10000	0	0
HCK	-0.032	0.2	-10000	0	-0.86	29	29
CRK	0.016	0	-10000	0	-10000	0	0
TYK2	-0.035	0.05	-10000	0	-0.44	2	2
EGF	-0.67	0.23	-10000	0	-0.75	478	478
YES1	0.016	0	-10000	0	-10000	0	0
CAV1	-0.15	0.1	-10000	0	-0.42	40	40
TXN	0.002	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.033	0.055	-10000	0	-0.45	6	6
cell migration	0.049	0.053	0.41	4	-10000	0	4
STAT3	0.015	0.002	-10000	0	-10000	0	0
PRLR	-0.087	0.26	-10000	0	-0.74	70	70
ITGA2B	-0.02	0.16	-10000	0	-0.86	19	19
CSF1R	0.004	0.1	-10000	0	-0.86	7	7
Prolactin Receptor/Prolactin	-0.074	0.19	-10000	0	-0.56	70	70
FGR	0.011	0.066	-10000	0	-0.86	3	3
PTP1B/p130 Cas	-0.036	0.052	-10000	0	-0.42	3	3
Crk/p130 Cas	-0.031	0.042	-10000	0	-0.42	2	2
DOK1	-0.019	0.046	-10000	0	-0.36	3	3
JAK2	-0.054	0.11	-10000	0	-0.49	10	10
Jak2/Leptin Receptor/Leptin	-0.053	0.13	-10000	0	-0.69	4	4
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
PTPN1	-0.049	0.053	-10000	0	-0.41	4	4
LYN	0.016	0	-10000	0	-10000	0	0
CDH2	-0.01	0.14	-10000	0	-0.74	18	18
SRC	0	0.021	-10000	0	-10000	0	0
ITGB3	0.003	0.08	-10000	0	-0.74	6	6
CAT1/PTP1B	-0.23	0.13	-10000	0	-0.58	35	35
CAPN1	0.002	0.006	-10000	0	-10000	0	0
CSK	0.016	0	-10000	0	-10000	0	0
PI3K	0.008	0.043	-10000	0	-0.63	1	1
mol:H2O2	-0.007	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.035	0.12	-10000	0	-0.67	4	4
negative regulation of transcription	-0.053	0.11	-10000	0	-0.48	10	10
FCGR2A	-0.024	0.18	-10000	0	-0.86	24	24
FER	-0.001	0.047	-10000	0	-0.75	2	2
alphaIIb/beta3 Integrin	-0.03	0.14	-10000	0	-0.66	24	24
BLK	-0.04	0.21	-10000	0	-0.86	33	33
Insulin Receptor/Insulin/Shc	-0.001	0.026	-10000	0	-0.59	1	1
RHOA	0.002	0.006	-10000	0	-10000	0	0
LEPR	0.014	0.004	-10000	0	-10000	0	0
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
p210 bcr-abl/Grb2	0.016	0	-10000	0	-10000	0	0
mol:NADPH	-0.007	0.003	-10000	0	-10000	0	0
TRPV6	-0.22	0.15	-10000	0	-0.55	61	61
PRL	0.004	0.007	-10000	0	-10000	0	0
SOCS3	0.027	0.058	-10000	0	-0.73	3	3
SPRY2	0.002	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.004	0.042	-10000	0	-0.49	4	4
CSF1/CSF1R	-0.037	0.075	-10000	0	-0.53	10	10
Ras protein signal transduction	0.039	0.016	-10000	0	-10000	0	0
IRS1	0.01	0.066	-10000	0	-0.74	4	4
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.071	0.26	-10000	0	-0.86	50	50
STAT5B	-0.045	0.068	-10000	0	-0.46	5	5
STAT5A	-0.045	0.068	-10000	0	-0.46	5	5
GRB2	0.016	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.036	0.05	-10000	0	-0.42	3	3
CSN2	-0.008	0.069	-10000	0	-10000	0	0
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
LAT	-0.1	0.17	-10000	0	-0.35	149	149
YBX1	0.003	0.008	-10000	0	-10000	0	0
LCK	-0.02	0.17	-10000	0	-0.85	22	22
SHC1	0.014	0.038	-10000	0	-0.86	1	1
NOX4	-0.006	0.073	-10000	0	-0.75	5	5

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.041	0.15	-9999	-0.58	38	38
EPHB2	0	0.11	-9999	-0.76	11	11
Syndecan-2/TACI	-0.054	0.17	-9999	-0.58	50	50
LAMA1	-0.006	0.13	-9999	-0.75	15	15
Syndecan-2/alpha2 ITGB1	-0.01	0.067	-9999	-0.49	7	7
HRAS	0.014	0.038	-9999	-0.86	1	1
Syndecan-2/CASK	0	0	-9999	-10000	0	0
ITGA5	-0.047	0.23	-9999	-0.86	38	38
BAX	0.053	0.028	-9999	-10000	0	0
EPB41	0.016	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0	0	-9999	-10000	0	0
LAMA3	0.004	0.1	-9999	-0.86	7	7
EZR	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.001	0.11	-9999	-0.85	9	9
Syndecan-2/MMP2	-0.006	0.059	-9999	-0.56	6	6
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.005	0.054	-9999	-0.56	5	5
dendrite morphogenesis	-0.01	0.07	-9999	-0.49	11	11
Syndecan-2/GM-CSF	-0.016	0.096	-9999	-0.58	15	15
determination of left/right symmetry	0.027	0	-9999	-10000	0	0
Syndecan-2/PKC delta	-0.001	0.025	-9999	-0.58	1	1
GNB2L1	0.014	0.038	-9999	-0.86	1	1
MAPK3	0.022	0.093	-9999	-0.52	15	15
MAPK1	0.022	0.093	-9999	-0.52	15	15
Syndecan-2/RACK1	-0.002	0.031	-9999	-0.5	2	2
NF1	0.016	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.027	0	-9999	-10000	0	0
ITGA2	0.009	0.073	-9999	-0.74	5	5
MAPK8	0.045	0.031	-9999	-0.46	2	2
Syndecan-2/alpha2/beta1 Integrin	-0.015	0.08	-9999	-0.65	2	2
Syndecan-2/Kininogen	-0.35	0.21	-9999	-0.48	395	395
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.048	0.032	-9999	-0.46	2	2
Syndecan-2/CASK/Protein 4.1	0	0	-9999	-10000	0	0
extracellular matrix organization	-0.005	0.055	-9999	-0.57	5	5
actin cytoskeleton reorganization	-0.041	0.15	-9999	-0.57	38	38
Syndecan-2/Caveolin-2/Ras	-0.01	0.07	-9999	-0.51	10	10
Syndecan-2/Laminin alpha3	-0.008	0.066	-9999	-0.58	7	7
Syndecan-2/RasGAP	-0.003	0.043	-9999	-0.67	2	2
alpha5/beta1 Integrin	-0.048	0.17	-9999	-0.66	38	38
PRKCD	0.014	0.038	-9999	-0.86	1	1
Syndecan-2 dimer	-0.01	0.071	-9999	-0.49	11	11
GO:0007205	0.005	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.041	-9999	-0.83	1	1
RHOA	0.016	0	-9999	-10000	0	0
SDCBP	0.016	0	-9999	-10000	0	0
TNFRSF13B	-0.069	0.26	-9999	-0.86	50	50
RASA1	0.014	0.033	-9999	-0.74	1	1
alpha2/beta1 Integrin	-0.005	0.054	-9999	-0.56	5	5
Syndecan-2/Synbindin	0	0	-9999	-10000	0	0
TGFB1	0.007	0.085	-9999	-0.86	5	5
CASP3	0.043	0.025	-9999	-0.52	1	1
FN1	-0.047	0.23	-9999	-0.86	38	38
Syndecan-2/IL8	-0.036	0.14	-9999	-0.56	34	34
SDC2	0.027	0	-9999	-10000	0	0
KNG1	-0.55	0.32	-9999	-0.74	395	395
Syndecan-2/Neurofibromin	0	0	-9999	-10000	0	0
TRAPPC4	0.016	0	-9999	-10000	0	0
CSF2	-0.018	0.14	-9999	-0.86	15	15
Syndecan-2/TGFB1	-0.005	0.056	-9999	-0.58	5	5
Syndecan-2/Syntenin/PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-2/Ezrin	0	0	-9999	-10000	0	0
PRKACA	0.044	0	-9999	-10000	0	0
angiogenesis	-0.035	0.14	-9999	-0.55	34	34
MMP2	0.006	0.091	-9999	-0.84	6	6
IL8	-0.039	0.21	-9999	-0.84	34	34
calcineurin-NFAT signaling pathway	-0.054	0.17	-9999	-0.57	50	50

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.008	0.21	-10000	0	-0.88	3	3
PTK2B	0.016	0.001	-10000	0	-10000	0	0
mol:Ca2+	0.083	0.13	-10000	0	-0.83	3	3
EDN1	-0.015	0.19	-10000	0	-0.74	20	20
EDN3	-0.019	0.15	-10000	0	-0.86	17	17
EDN2	-0.09	0.28	-10000	0	-0.82	67	67
HRAS/GDP	0.052	0.17	-10000	0	-0.7	9	9
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.021	0.15	-10000	0	-0.51	15	15
ADCY4	0.01	0.17	-10000	0	-0.74	3	3
ADCY5	-0.007	0.2	-10000	0	-0.71	13	13
ADCY6	0.009	0.17	-10000	0	-0.74	3	3
ADCY7	-0.004	0.19	-10000	0	-0.72	7	7
ADCY1	-0.001	0.18	-10000	0	-0.74	4	4
ADCY2	-0.13	0.27	-10000	0	-0.7	31	31
ADCY3	0.01	0.17	-10000	0	-0.74	3	3
ADCY8	-0.16	0.28	-10000	0	-0.74	35	35
ADCY9	0.01	0.17	-10000	0	-0.74	3	3
arachidonic acid secretion	0.076	0.15	-10000	0	-0.53	10	10
ETB receptor/Endothelin-1/Gq/GTP	0.035	0.11	-10000	0	-0.46	11	11
GNAO1	0.008	0.083	-10000	0	-0.84	5	5
HRAS	0.014	0.038	-10000	0	-0.86	1	1
ETA receptor/Endothelin-1/G12/GTP	-0.013	0.22	0.38	73	-0.82	3	76
ETA receptor/Endothelin-1/Gs/GTP	-0.013	0.21	0.36	73	-0.79	3	76
mol:GTP	0.004	0.002	-10000	0	-10000	0	0
COL3A1	-0.041	0.34	-10000	0	-0.95	52	52
EDNRB	0.007	0.068	-10000	0	-0.78	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.043	0.3	-10000	0	-0.75	51	51
CYSLTR1	0.008	0.22	-10000	0	-0.84	4	4
SLC9A1	-0.013	0.11	-10000	0	-0.39	2	2
mol:GDP	0.045	0.18	-10000	0	-0.64	14	14
SLC9A3	-0.35	0.3	-10000	0	-0.53	333	333
RAF1	0.048	0.17	-10000	0	-0.68	10	10
JUN	0.086	0.12	-10000	0	-0.57	1	1
JAK2	0.008	0.21	-10000	0	-0.88	3	3
mol:IP3	0.018	0.17	-10000	0	-0.57	17	17
ETA receptor/Endothelin-1	-0.026	0.27	0.45	73	-0.57	53	126
PLCB1	0.001	0.11	-10000	0	-0.74	11	11
PLCB2	-0.079	0.27	-10000	0	-0.86	58	58
ETA receptor/Endothelin-3	-0.022	0.15	-10000	0	-0.68	19	19
FOS	0.06	0.2	-10000	0	-0.86	15	15
Gai/GDP	0.039	0.069	-10000	0	-0.62	1	1
CRK	0.016	0.001	-10000	0	-10000	0	0
mol:Ca ++	0.003	0.24	-10000	0	-0.77	16	16
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
PRKCB1	0.019	0.16	-10000	0	-0.54	17	17
GNAQ	0.02	0.004	-10000	0	-10000	0	0
GNAZ	0.011	0.057	-10000	0	-0.74	3	3
GNAL	0.016	0	-10000	0	-10000	0	0
Gs family/GDP	-0.044	0.11	-10000	0	-0.61	11	11
ETA receptor/Endothelin-1/Gq/GTP	0.045	0.14	-10000	0	-0.48	10	10
MAPK14	0.024	0.13	-10000	0	-0.56	10	10
TRPC6	0.083	0.14	-10000	0	-1	2	2
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.057	-10000	0	-0.74	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.014	0.14	-10000	0	-0.54	14	14
ETB receptor/Endothelin-2	-0.085	0.21	-10000	0	-0.62	70	70
ETB receptor/Endothelin-3	-0.028	0.12	-10000	0	-0.66	20	20
ETB receptor/Endothelin-1	-0.032	0.16	-10000	0	-0.62	20	20
MAPK3	0.06	0.19	-10000	0	-0.72	17	17
MAPK1	0.06	0.19	-10000	0	-0.72	17	17
Rac1/GDP	0.052	0.17	-10000	0	-0.63	11	11
cAMP biosynthetic process	-0.061	0.19	-10000	0	-0.61	13	13
MAPK8	0.078	0.13	-10000	0	-0.58	3	3
SRC	0.016	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.03	0.09	-10000	0	-0.51	4	4
p130Cas/CRK/Src/PYK2	0.072	0.17	-10000	0	-0.67	10	10
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.052	0.17	-10000	0	-0.71	8	8
COL1A2	-0.099	0.33	-10000	0	-0.88	68	68
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.079	0.23	-10000	0	-0.63	69	69
mol:DAG	0.018	0.17	-10000	0	-0.57	17	17
MAP2K2	0.057	0.18	-10000	0	-0.68	11	11
MAP2K1	0.058	0.17	-10000	0	-0.68	10	10
EDNRA	-0.007	0.14	-10000	0	-0.98	2	2
positive regulation of muscle contraction	0.019	0.19	-10000	0	-0.78	3	3
Gq family/GDP	-0.035	0.14	-10000	0	-0.7	15	15
HRAS/GTP	0.036	0.17	-10000	0	-0.63	14	14
PRKCH	0.029	0.16	-10000	0	-0.6	12	12
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.029	0.16	-10000	0	-0.6	12	12
PRKCB	0.025	0.18	-10000	0	-0.67	15	15
PRKCE	0.028	0.16	-10000	0	-0.62	11	11
PRKCD	0.028	0.16	-10000	0	-0.6	12	12
PRKCG	0.003	0.2	-10000	0	-0.7	22	22
regulation of vascular smooth muscle contraction	0.059	0.23	-10000	0	-0.99	15	15
PRKCQ	0.016	0.18	-10000	0	-0.64	18	18
PLA2G4A	0.076	0.16	-10000	0	-0.57	10	10
GNA14	0.01	0.087	-10000	0	-0.74	7	7
GNA15	-0.008	0.15	-10000	0	-0.86	16	16
GNA12	0.016	0	-10000	0	-10000	0	0
GNA11	0.014	0.057	-10000	0	-0.74	3	3
Rac1/GTP	-0.013	0.22	0.38	73	-0.83	3	76
MMP1	-0.14	0.37	-10000	0	-0.85	105	105

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.014	0.033	-9999	-0.74	1	1
Caspase 8 (4 units)	-0.096	0.092	-9999	-10000	0	0
NEF	-0.057	0.084	-9999	-10000	0	0
NFKBIA	0.002	0.044	-9999	-10000	0	0
BIRC3	-0.068	0.31	-9999	-0.79	80	80
CYCS	-0.077	0.14	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
CD247	-0.36	0.48	-9999	-1	172	172
MAP2K7	-0.04	0.11	-9999	-10000	0	0
protein ubiquitination	0.061	0.07	-9999	-0.42	3	3
CRADD	0.016	0	-9999	-10000	0	0
DAXX	0.016	0	-9999	-10000	0	0
FAS	0.016	0	-9999	-10000	0	0
BID	-0.091	0.15	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.05	0.12	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
FADD	0.016	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.05	0.12	-9999	-10000	0	0
MAPK8	-0.029	0.1	-9999	-0.51	1	1
APAF1	0.016	0	-9999	-10000	0	0
TRAF1	0.014	0.038	-9999	-0.86	1	1
TRAF2	0.016	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.13	0.13	-9999	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.048	0.066	-9999	-10000	0	0
CHUK	0.062	0.074	-9999	-0.47	3	3
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0	0	-9999	-10000	0	0
TCRz/NEF	-0.4	0.44	-9999	-1	172	172
TNF	0.003	0.1	-9999	-0.8	8	8
FASLG	-0.57	0.61	-9999	-1.1	282	282
NFKB1	0	0.055	-9999	-0.73	1	1
TNFR1A/BAG4/TNF-alpha	-0.009	0.067	-9999	-0.52	9	9
CASP6	-0.048	0.052	-9999	-10000	0	0
CASP7	-0.059	0.21	-9999	-0.55	54	54
RELA	0.002	0.044	-9999	-10000	0	0
CASP2	0.016	0	-9999	-10000	0	0
CASP3	-0.059	0.21	-9999	-0.55	54	54
TNFRSF1A	0.016	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.024	-9999	-0.56	1	1
CASP8	0.016	0	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
MAP3K14	0.054	0.079	-9999	-0.53	3	3
APAF-1/Caspase 9	-0.12	0.18	-9999	-0.56	54	54
BCL2	-0.017	0.099	-9999	-0.46	1	1

×

Regulation of nuclear SMAD2/3 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
EP300	0.014	0.034	-10000	0	-0.73	1	1
HSPA8	0.016	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.02	0.089	-10000	0	-0.51	5	5
AKT1	0.02	0.007	-10000	0	-10000	0	0
GSC	-0.027	0.22	-10000	0	-0.76	44	44
NKX2-5	-0.046	0.21	-10000	0	-0.86	34	34
muscle cell differentiation	0.034	0.11	0.57	10	-10000	0	10
SMAD2-3/SMAD4/SP1	0.043	0.08	-10000	0	-10000	0	0
SMAD4	0.032	0.029	-10000	0	-10000	0	0
CBFB	0.016	0	-10000	0	-10000	0	0
SAP18	0.015	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.003	0.046	-10000	0	-0.57	2	2
SMAD3/SMAD4/VDR	0.011	0.05	-10000	0	-10000	0	0
MYC	-0.032	0.16	-10000	0	-0.86	20	20
CDKN2B	0.055	0.092	-10000	0	-0.68	6	6
AP1	0.064	0.073	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.012	0.049	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.051	0.069	-10000	0	-0.45	4	4
SP3	0.02	0	-10000	0	-10000	0	0
CREB1	0.016	0	-10000	0	-10000	0	0
FOXH1	-0.061	0.25	-10000	0	-0.88	46	46
SMAD3/SMAD4/GR	0.01	0.044	-10000	0	-0.6	1	1
GATA3	-0.36	0.38	-10000	0	-0.74	262	262
SKI/SIN3/HDAC complex/NCoR1	0.054	0.044	-10000	0	-10000	0	0
MEF2C/TIF2	-0.077	0.2	-10000	0	-0.79	23	23
endothelial cell migration	0.095	0.26	0.73	75	-10000	0	75
MAX	0.019	0.016	-10000	0	-10000	0	0
RBBP7	0.015	0.004	-10000	0	-10000	0	0
RBBP4	0.013	0.033	-10000	0	-0.74	1	1
RUNX2	-0.007	0.14	-10000	0	-0.86	14	14
RUNX3	-0.36	0.44	-10000	0	-0.86	227	227
RUNX1	-0.047	0.23	-10000	0	-0.86	38	38
CTBP1	0.016	0	-10000	0	-10000	0	0
NR3C1	0.017	0.042	-10000	0	-0.87	1	1
VDR	0.011	0.057	-10000	0	-0.74	3	3
CDKN1A	0.083	0.074	-10000	0	-0.64	2	2
KAT2B	0.013	0.033	-10000	0	-0.74	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.055	0.18	-10000	0	-0.61	46	46
DCP1A	0.016	0	-10000	0	-10000	0	0
SKI	0.015	0.004	-10000	0	-10000	0	0
SERPINE1	-0.097	0.26	-10000	0	-0.74	75	75
SMAD3/SMAD4/ATF2	0.008	0.037	-10000	0	-0.48	1	1
SMAD3/SMAD4/ATF3	0.004	0.057	-10000	0	-0.49	5	5
SAP30	-0.016	0.16	-10000	0	-0.86	19	19
Cbp/p300/PIAS3	0.007	0.035	-10000	0	-10000	0	0
JUN	0.075	0.071	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.012	0.11	-10000	0	-0.56	19	19
TFE3	0.022	0.012	-10000	0	-10000	0	0
COL1A2	-0.091	0.25	-10000	0	-0.75	66	66
mesenchymal cell differentiation	0.007	0.1	0.59	14	-10000	0	14
DLX1	-0.45	0.44	-10000	0	-0.86	282	282
TCF3	0.016	0	-10000	0	-10000	0	0
FOS	0.006	0.12	-10000	0	-0.74	13	13
SMAD3/SMAD4/Max	0.011	0.035	-10000	0	-10000	0	0
Cbp/p300/SNIP1	-0.001	0.02	-10000	0	-10000	0	0
ZBTB17	-0.001	0.044	-10000	0	-0.71	2	2
LAMC1	0.071	0.041	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.009	0.03	-10000	0	-10000	0	0
IRF7	-0.013	0.16	-10000	0	-0.85	19	19
ESR1	0.001	0.077	-10000	0	-0.76	5	5
HNF4A	-0.047	0.21	-10000	0	-0.74	44	44
MEF2C	-0.008	0.22	-10000	0	-0.8	21	21
SMAD2-3/SMAD4	0.005	0.031	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.005	0.028	-10000	0	-10000	0	0
IGHV3OR16-13	-0.05	0.054	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.016	0	-10000	0	-10000	0	0
CREBBP	0.015	0.008	-10000	0	-10000	0	0
SKIL	0.016	0	-10000	0	-10000	0	0
HDAC1	0.015	0.004	-10000	0	-10000	0	0
HDAC2	0.015	0.004	-10000	0	-10000	0	0
SNIP1	0.015	0.005	-10000	0	-10000	0	0
GCN5L2	-0.002	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.01	0.036	-10000	0	-10000	0	0
MSG1/HSC70	0.002	0.043	-10000	0	-0.67	2	2
SMAD2	0.022	0.019	-10000	0	-10000	0	0
SMAD3	0.032	0.026	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.062	0.033	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.024	0.032	-10000	0	-0.52	1	1
NCOR1	0.015	0.004	-10000	0	-10000	0	0
NCOA2	0	0.11	-10000	0	-0.74	11	11
NCOA1	0.016	0	-10000	0	-10000	0	0
MYOD/E2A	-0.036	0.15	-10000	0	-0.66	29	29
SMAD2-3/SMAD4/SP1/MIZ-1	0.077	0.084	-10000	0	-10000	0	0
IFNB1	0.045	0.11	-10000	0	-0.54	1	1
SMAD3/SMAD4/MEF2C	-0.009	0.21	-10000	0	-0.75	21	21
CITED1	0.011	0.054	-10000	0	-0.86	2	2
SMAD2-3/SMAD4/ARC105	0.007	0.03	-10000	0	-10000	0	0
RBL1	0.016	0.001	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.076	0.067	-10000	0	-0.58	1	1
RUNX1-3/PEBPB2	-0.28	0.32	-10000	0	-0.61	249	249
SMAD7	0.1	0.079	-10000	0	-10000	0	0
MYC/MIZ-1	-0.026	0.13	-10000	0	-0.64	22	22
SMAD3/SMAD4	-0.02	0.12	-10000	0	-10000	0	0
IL10	-0.2	0.31	-10000	0	-0.99	31	31
PIASy/HDAC complex	0.018	0.009	-10000	0	-10000	0	0
PIAS3	0.014	0.006	-10000	0	-10000	0	0
CDK2	0.015	0.008	-10000	0	-10000	0	0
IL5	-0.17	0.25	-10000	0	-0.75	15	15
CDK4	0.015	0.009	-10000	0	-10000	0	0
PIAS4	0.018	0.009	-10000	0	-10000	0	0
ATF3	0.009	0.073	-10000	0	-0.74	5	5
SMAD3/SMAD4/SP1	-0.011	0.053	-10000	0	-10000	0	0
FOXG1	-0.025	0.17	-10000	0	-0.86	20	20
FOXO3	0.036	0.01	-10000	0	-10000	0	0
FOXO1	0.036	0.009	-10000	0	-10000	0	0
FOXO4	0.036	0.009	-10000	0	-10000	0	0
heart looping	-0.007	0.22	-10000	0	-0.78	21	21
CEBPB	-0.002	0.13	-10000	0	-0.86	12	12
SMAD3/SMAD4/DLX1	-0.31	0.29	-10000	0	-0.58	282	282
MYOD1	-0.042	0.2	-10000	0	-0.86	29	29
SMAD3/SMAD4/HNF4	-0.033	0.14	-10000	0	-0.49	44	44
SMAD3/SMAD4/GATA3	-0.23	0.25	-10000	0	-0.5	152	152
SnoN/SIN3/HDAC complex/NCoR1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.23	0.28	-10000	0	-0.59	90	90
SMAD3/SMAD4/SP1-3	-0.005	0.043	-10000	0	-10000	0	0
MED15	0.016	0	-10000	0	-10000	0	0
SP1	0.013	0.049	-10000	0	-10000	0	0
SIN3B	0.015	0.004	-10000	0	-10000	0	0
SIN3A	0.015	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.078	0.22	-10000	0	-0.61	69	69
ITGB5	0.085	0.064	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.053	0.043	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.015	0.11	-10000	0	-0.49	26	26
AR	-0.021	0.16	-10000	0	-0.74	26	26
negative regulation of cell growth	0.065	0.066	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.024	0.14	-10000	0	-0.6	29	29
E2F5	0.014	0.033	-10000	0	-0.74	1	1
E2F4	0.016	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.043	0.15	-10000	0	-0.64	16	16
SMAD2-3/SMAD4/FOXO1-3a-4	0.076	0.045	-10000	0	-10000	0	0
TFDP1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.008	0.068	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	-0.007	0.1	-10000	0	-0.59	14	14
TGIF2	0.016	0	-10000	0	-10000	0	0
TGIF1	0.016	0	-10000	0	-10000	0	0
ATF2	0.014	0.033	-10000	0	-0.74	1	1

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.015	0.058	-10000	0	-0.62	1	1
NT3 (dimer)/TRKC	-0.04	0.15	-10000	0	-0.61	35	35
NT3 (dimer)/TRKB	-0.13	0.24	-10000	0	-0.54	132	132
SHC/Grb2/SOS1/GAB1/PI3K	-0.002	0.021	-10000	0	-10000	0	0
RAPGEF1	0.016	0	-10000	0	-10000	0	0
BDNF	-0.1	0.3	-10000	0	-0.86	71	71
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
DYNLT1	0.016	0	-10000	0	-10000	0	0
NTRK1	-0.045	0.2	-10000	0	-0.75	41	41
NTRK2	-0.13	0.3	-10000	0	-0.74	100	100
NTRK3	-0.029	0.18	-10000	0	-0.75	31	31
NT-4/5 (dimer)/TRKB	-0.14	0.25	-10000	0	-0.55	130	130
neuron apoptosis	0.14	0.18	0.57	48	-10000	0	48
SHC 2-3/Grb2	-0.15	0.2	-10000	0	-0.64	48	48
SHC1	0.014	0.038	-10000	0	-0.86	1	1
SHC2	-0.098	0.14	-10000	0	-0.48	41	41
SHC3	-0.16	0.24	-10000	0	-0.63	87	87
STAT3 (dimer)	0.013	0.067	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.082	0.2	-10000	0	-0.55	79	79
RIN/GDP	0.049	0.064	-10000	0	-0.32	1	1
GIPC1	0.014	0.033	-10000	0	-0.74	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
DNAJA3	-0.069	0.14	-10000	0	-0.63	13	13
RIN/GTP	-0.001	0.029	-10000	0	-0.68	1	1
CCND1	0.01	0.16	-10000	0	-0.78	20	20
MAGED1	0.014	0.038	-10000	0	-0.86	1	1
PTPN11	0.016	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.004	0.092	-10000	0	-0.86	6	6
SHC/GRB2/SOS1	-0.001	0.025	-10000	0	-0.57	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.15	0.27	-10000	0	-0.59	132	132
TRKA/NEDD4-2	-0.044	0.16	-10000	0	-0.57	41	41
ELMO1	0.012	0.054	-10000	0	-0.86	2	2
RhoG/GTP/ELMO1/DOCK1	-0.003	0.042	-10000	0	-0.55	3	3
NGF	-0.067	0.26	-10000	0	-0.86	50	50
HRAS	0.014	0.038	-10000	0	-0.86	1	1
DOCK1	0.014	0.033	-10000	0	-0.74	1	1
GAB2	0.016	0	-10000	0	-10000	0	0
RIT2	0.002	0.038	-10000	0	-0.86	1	1
RIT1	0.016	0	-10000	0	-10000	0	0
FRS2	0.016	0	-10000	0	-10000	0	0
DNM1	-0.006	0.14	-10000	0	-0.86	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.069	0.14	-10000	0	-0.59	15	15
mol:GDP	0.062	0.086	-10000	0	-0.48	2	2
NGF (dimer)	-0.067	0.26	-10000	0	-0.86	50	50
RhoG/GDP	-0.003	0.041	-10000	0	-0.68	2	2
RIT1/GDP	0.055	0.062	-10000	0	-10000	0	0
TIAM1	0.014	0.033	-10000	0	-0.74	1	1
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
BDNF (dimer)/TRKB	-0.16	0.26	-10000	0	-0.55	159	159
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.002	0.038	-10000	0	-0.61	2	2
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	-0.001	0.023	-10000	0	-0.52	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	0.005	0.09	-10000	0	-0.78	7	7
RAP1/GDP	-0.008	0.031	-10000	0	-10000	0	0
KIDINS220/CRKL	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.1	0.3	-10000	0	-0.86	71	71
ubiquitin-dependent protein catabolic process	-0.091	0.21	-10000	0	-0.6	53	53
Schwann cell development	-0.026	0.032	-10000	0	-10000	0	0
EHD4	0.016	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0	0	-10000	0	-10000	0	0
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.14	0.24	-10000	0	-0.81	31	31
ABL1	0.016	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.049	0.078	-10000	0	-10000	0	0
STAT3	0.013	0.067	-10000	0	-10000	0	0
axon guidance	-0.14	0.22	-10000	0	-0.76	31	31
MAPK3	-0.1	0.26	-10000	0	-0.58	97	97
MAPK1	-0.1	0.26	-10000	0	-0.58	97	97
CDC42/GDP	0.055	0.062	-10000	0	-10000	0	0
NTF3	0.005	0.091	-10000	0	-0.78	7	7
NTF4	-0.004	0.092	-10000	0	-0.86	6	6
NGF (dimer)/TRKA/FAIM	-0.091	0.2	-10000	0	-0.54	89	89
PI3K	-0.002	0.034	-10000	0	-0.56	2	2
FRS3	0.016	0	-10000	0	-10000	0	0
FAIM	0.016	0	-10000	0	-10000	0	0
GAB1	0.016	0	-10000	0	-10000	0	0
RASGRF1	-0.08	0.16	-10000	0	-0.61	24	24
SOS1	0.016	0	-10000	0	-10000	0	0
MCF2L	0.001	0.14	-10000	0	-0.74	6	6
RGS19	0.016	0	-10000	0	-10000	0	0
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	0.049	0.066	-10000	0	-10000	0	0
Rac1/GDP	0.055	0.062	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GRIT	-0.093	0.21	-10000	0	-0.55	89	89
neuron projection morphogenesis	-0.022	0.14	-10000	0	-0.54	13	13
NGF (dimer)/TRKA/NEDD4-2	-0.092	0.21	-10000	0	-0.6	53	53
MAP2K1	0.053	0.023	-10000	0	-0.48	1	1
NGFR	-0.044	0.22	-10000	0	-0.86	36	36
NGF (dimer)/TRKA/GIPC/GAIP	-0.056	0.12	-10000	0	-0.62	4	4
RAS family/GTP/PI3K	-0.002	0.029	-10000	0	-0.6	1	1
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.016	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.057	-10000	0	-0.74	3	3
MAPKKK cascade	-0.095	0.18	-10000	0	-0.61	45	45
RASA1	0.014	0.033	-10000	0	-0.74	1	1
TRKA/c-Abl	-0.044	0.15	-10000	0	-0.56	41	41
SQSTM1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.15	0.24	-10000	0	-0.59	70	70
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.079	0.18	-10000	0	-0.86	3	3
MATK	-0.072	0.26	-10000	0	-0.86	53	53
NEDD4L	0.014	0.033	-10000	0	-0.74	1	1
RAS family/GDP	-0.008	0.031	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.075	0.15	-10000	0	-0.47	38	38
Rac1/GTP	-0.045	0.085	-10000	0	-0.41	7	7
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.064	0.13	-9999	-0.6	8	8
FZD6	0.016	0	-9999	-10000	0	0
WNT6	-0.018	0.17	-9999	-0.86	20	20
WNT4	-0.068	0.24	-9999	-0.75	58	58
FZD3	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.057	-9999	-0.74	3	3
WNT11	-0.04	0.2	-9999	-0.76	38	38

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.04	0.044	-9999	-10000	0	0
GNAO1	0.01	0.083	-9999	-0.84	5	5
S1P/S1P3/G12/G13	-0.001	0.019	-9999	-0.43	1	1
AKT1	-0.002	0.012	-9999	-10000	0	0
AKT3	-0.025	0.1	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
GNAI2	0.018	0	-9999	-10000	0	0
GNAI3	0.018	0	-9999	-10000	0	0
GNAI1	0.013	0.057	-9999	-0.74	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.017	0.033	-9999	-0.74	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.053	0.048	-9999	-0.53	1	1
MAPK3	0.062	0.046	-9999	-0.5	1	1
MAPK1	0.062	0.046	-9999	-0.5	1	1
JAK2	-0.024	0.13	-9999	-0.48	2	2
CXCR4	-0.12	0.26	-9999	-0.47	185	185
FLT1	0.011	0.085	-9999	-0.86	5	5
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.062	0.046	-9999	-0.5	1	1
S1P/S1P3/Gi	0.054	0.049	-9999	-0.54	1	1
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.036	-9999	-0.49	1	1
VEGFA	-0.38	0.44	-9999	-0.86	240	240
S1P/S1P2/Gi	0.049	0.043	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.28	0.35	-9999	-0.67	241	241
RHOA	0.016	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.027	0.072	-9999	-10000	0	0
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.013	0.057	-9999	-0.74	3	3
G12/G13	0	0	-9999	-10000	0	0
GNA14	0.006	0.086	-9999	-0.74	7	7
GNA15	-0.011	0.15	-9999	-0.86	16	16
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.011	0.057	-9999	-0.74	3	3
Rac1/GTP	-0.005	0.036	-9999	-0.49	1	1

×

Thromboxane A2 receptor signaling

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
TGM2	-0.004	0.12	-10000	0	-0.86	11	11
GNB1/GNG2	-0.034	0.063	-10000	0	-0.22	14	14
AKT1	0.055	0.1	-10000	0	-0.25	1	1
EGF	-0.67	0.23	-10000	0	-0.74	478	478
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.032	0.08	-10000	0	-0.61	2	2
mol:Ca2+	0.041	0.14	-10000	0	-0.33	28	28
LYN	-0.03	0.071	-10000	0	-10000	0	0
RhoA/GTP	-0.017	0.037	-10000	0	-0.19	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.05	0.15	-10000	0	-0.38	19	19
GNG2	0.016	0	-10000	0	-10000	0	0
ARRB2	0.014	0.038	-10000	0	-0.86	1	1
TP alpha/Gq family/GDP/G beta5/gamma2	0.028	0.079	-10000	0	-0.43	5	5
G beta5/gamma2	-0.044	0.083	-10000	0	-0.3	15	15
PRKCH	0.043	0.15	-10000	0	-0.39	21	21
DNM1	-0.006	0.14	-10000	0	-0.86	13	13
TXA2/TP beta/beta Arrestin3	-0.014	0.045	-10000	0	-0.28	7	7
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.11	0.31	-10000	0	-0.86	77	77
G12 family/GTP	-0.042	0.091	-10000	0	-0.32	25	25
ADRBK1	0.016	0	-10000	0	-10000	0	0
ADRBK2	0.016	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.031	0.11	0.33	8	-10000	0	8
mol:NADP	0.016	0	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
PRKG1	-0.006	0.13	-10000	0	-0.74	15	15
mol:IP3	0.038	0.17	-10000	0	-0.42	28	28
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	0.028	0.22	-10000	0	-0.58	28	28
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.054	0.13	-10000	0	-0.6	15	15
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.051	0.12	-10000	0	-0.6	9	9
RHOA	0.016	0	-10000	0	-10000	0	0
PTGIR	0.013	0.05	-10000	0	-0.8	2	2
PRKCB1	0.037	0.16	-10000	0	-0.39	41	41
GNAQ	0.016	0	-10000	0	-10000	0	0
mol:L-citrulline	0.016	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.036	0.21	-10000	0	-0.53	44	44
LCK	-0.046	0.12	-10000	0	-0.6	13	13
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.04	0.096	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.028	0.036	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.04	0.095	-10000	0	-10000	0	0
MAPK14	0.054	0.11	-10000	0	-0.31	1	1
TGM2/GTP	0.036	0.19	-10000	0	-0.48	30	30
MAPK11	0.053	0.11	-10000	0	-0.35	3	3
ARHGEF1	0.042	0.088	-10000	0	-0.33	1	1
GNAI2	0.016	0	-10000	0	-10000	0	0
JNK cascade	0.045	0.17	-10000	0	-0.39	43	43
RAB11/GDP	0.015	0.002	-10000	0	-10000	0	0
ICAM1	0.045	0.13	-10000	0	-0.35	18	18
cAMP biosynthetic process	0.035	0.16	-10000	0	-0.39	28	28
Gq family/GTP/EBP50	0.025	0.06	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.03	0.071	-10000	0	-10000	0	0
GNB5	0.016	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
EGF/EGFR	-0.085	0.1	-10000	0	-0.42	13	13
VCAM1	0.043	0.14	-10000	0	-0.34	27	27
TP beta/Gq family/GDP/G beta5/gamma2	0.028	0.079	-10000	0	-0.43	5	5
platelet activation	0.067	0.15	-10000	0	-0.34	15	15
PGI2/IP	-0.002	0.038	-10000	0	-0.62	2	2
PRKACA	-0.051	0.12	-10000	0	-0.34	79	79
Gq family/GDP/G beta5/gamma2	0.024	0.079	-10000	0	-0.43	5	5
TXA2/TP beta/beta Arrestin2	-0.015	0.065	-10000	0	-0.41	14	14
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.013	0.12	-10000	0	-10000	0	0
mol:DAG	0.037	0.18	-10000	0	-0.44	42	42
EGFR	0.001	0.11	-10000	0	-0.85	9	9
TXA2/TP alpha	0.034	0.21	-10000	0	-0.54	32	32
Gq family/GTP	-0.006	0.053	-10000	0	-0.26	7	7
YES1	-0.03	0.071	-10000	0	-10000	0	0
GNAI2/GTP	-0.034	0.082	-10000	0	-10000	0	0
PGD2/DP	-0.098	0.24	-10000	0	-0.68	77	77
SLC9A3R1	0.016	0	-10000	0	-10000	0	0
FYN	-0.03	0.071	-10000	0	-10000	0	0
mol:NO	0.016	0	-10000	0	-10000	0	0
GNA15	-0.011	0.15	-10000	0	-0.86	16	16
PGK/cGMP	-0.014	0.08	-10000	0	-0.49	15	15
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.046	0.11	-10000	0	-0.71	1	1
NOS3	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.043	0.15	-10000	0	-0.4	19	19
PRKCB	0.041	0.16	-10000	0	-0.43	22	22
PRKCE	0.044	0.16	-10000	0	-0.41	19	19
PRKCD	0.042	0.16	-10000	0	-0.41	22	22
PRKCG	0.03	0.18	-10000	0	-0.49	32	32
muscle contraction	0.043	0.2	-10000	0	-0.49	44	44
PRKCZ	0.05	0.15	-10000	0	-0.37	27	27
ARR3	0.004	0.007	-10000	0	-10000	0	0
TXA2/TP beta	-0.039	0.093	-10000	0	-10000	0	0
PRKCQ	0.035	0.16	-10000	0	-0.43	23	23
MAPKKK cascade	0.036	0.19	-10000	0	-0.49	29	29
SELE	0.037	0.16	-10000	0	-0.42	38	38
TP beta/GNAI2/GDP/G beta/gamma	-0.038	0.09	-10000	0	-10000	0	0
ROCK1	0.016	0	-10000	0	-10000	0	0
GNA14	0.006	0.086	-10000	0	-0.74	7	7
chemotaxis	0.036	0.23	-10000	0	-0.61	43	43
GNA12	0.016	0	-10000	0	-10000	0	0
GNA13	0.016	0	-10000	0	-10000	0	0
GNA11	0.011	0.057	-10000	0	-0.74	3	3
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.001	0.028	-10000	0	-0.66	1	1
HDAC1	0.003	0.011	-10000	0	-10000	0	0
AES	0.005	0.008	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
DTX1	-0.053	0.22	-10000	0	-0.74	48	48
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.015	0.002	-10000	0	-10000	0	0
AP1	-0.097	0.16	-10000	0	-0.34	151	151
NCSTN	0.016	0	-10000	0	-10000	0	0
ADAM10	0.014	0.033	-10000	0	-0.74	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.012	0.067	-10000	0	-0.45	1	1
NICD/RBPSUH	-0.001	0.028	-10000	0	-0.64	1	1
WIF1	0.001	0.075	-10000	0	-0.77	5	5
NOTCH1	-0.001	0.029	-10000	0	-0.68	1	1
PSENEN	0.016	0	-10000	0	-10000	0	0
KREMEN2	-0.089	0.28	-10000	0	-0.86	63	63
DKK1	-0.019	0.17	-10000	0	-0.82	22	22
beta catenin/beta TrCP1	0.084	0.084	-10000	0	-10000	0	0
APH1B	0.016	0	-10000	0	-10000	0	0
APH1A	0.016	0	-10000	0	-10000	0	0
AXIN1	-0.011	0.035	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.008	0.048	-10000	0	-10000	0	0
PSEN1	0.016	0	-10000	0	-10000	0	0
FOS	-0.003	0.12	-10000	0	-0.75	13	13
JUN	0.016	0	-10000	0	-10000	0	0
MAP3K7	0.002	0.008	-10000	0	-10000	0	0
CTNNB1	0.08	0.091	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.095	0.21	-10000	0	-0.57	88	88
HNF1A	-0.002	0.073	-10000	0	-0.74	5	5
CTBP1	0.005	0.008	-10000	0	-10000	0	0
MYC	0.003	0.15	-10000	0	-0.73	20	20
NKD1	-0.19	0.34	-10000	0	-0.74	142	142
FZD1	0.016	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.036	0.11	-10000	0	-0.64	1	1
apoptosis	-0.096	0.16	-10000	0	-0.34	151	151
Delta 1/NOTCHprecursor	-0.001	0.028	-10000	0	-0.64	1	1
DLL1	0.016	0	-10000	0	-10000	0	0
PPARD	0.029	0.023	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.011	0.035	-10000	0	-10000	0	0
DVL1	-0.005	0.032	-10000	0	-0.47	2	2
CSNK2A1	0.015	0.004	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.004	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.09	0.22	-10000	0	-0.61	78	78
LRP6	0.016	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.004	-10000	0	-10000	0	0
NLK	0.015	0.013	-10000	0	-10000	0	0
CCND1	0.003	0.15	-10000	0	-0.73	20	20
WNT1	-0.027	0.19	-10000	0	-0.86	25	25
Axin1/APC/beta catenin	0.081	0.052	-10000	0	-10000	0	0
DKK2	-0.026	0.18	-10000	0	-0.83	26	26
NOTCH1 precursor/DVL1	-0.003	0.033	-10000	0	-0.58	1	1
GSK3B	0.012	0.007	-10000	0	-10000	0	0
FRAT1	0.012	0.007	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.036	0.11	-10000	0	-0.66	1	1
PPP2R5D	0.093	0.16	0.36	141	-10000	0	141
MAPK1	0.016	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.029	0.12	-10000	0	-0.52	26	26
RBPJ	0.016	0	-10000	0	-10000	0	0
CREBBP	0.019	0.005	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.025	0.096	-9999	-0.52	16	16
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.014	0.033	-9999	-0.74	1	1
ITGA4	-0.011	0.15	-9999	-0.86	16	16
alpha4/beta7 Integrin/MAdCAM1	-0.028	0.12	-9999	-0.52	28	28
EPO	-0.29	0.42	-9999	-0.86	186	186
alpha4/beta7 Integrin	-0.02	0.11	-9999	-0.66	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.02	0.11	-9999	-0.66	16	16
EPO/EPOR (dimer)	-0.23	0.32	-9999	-0.66	186	186
lamellipodium assembly	0	0.035	-9999	-0.53	2	2
PIK3CA	0.014	0.033	-9999	-0.74	1	1
PI3K	-0.002	0.034	-9999	-0.56	2	2
ARF6	0.016	0	-9999	-10000	0	0
JAK2	-0.12	0.17	-9999	-0.66	7	7
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
MADCAM1	-0.007	0.13	-9999	-0.86	12	12
cell adhesion	-0.027	0.12	-9999	-0.52	28	28
CRKL/CBL	-0.001	0.024	-9999	-0.56	1	1
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.014	0.13	-9999	-0.52	25	25
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.032	0.13	-9999	-0.56	30	30
p130Cas/Crk/Dock1	-0.024	0.1	-9999	-0.8	1	1
VCAM1	-0.006	0.13	-9999	-0.82	14	14
RHOA	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.016	0.089	-9999	-0.52	16	16
BCAR1	0.026	0.12	-9999	-0.89	1	1
EPOR	0.016	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0.033	-9999	-0.74	1	1
GIT1	0.016	0	-9999	-10000	0	0
Rac1/GTP	0	0.037	-9999	-0.55	2	2

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.027	0.044	-10000	0	-0.56	3	3
MAP4K4	0.026	0.093	-10000	0	-0.48	1	1
BAG4	0.014	0.033	-10000	0	-0.74	1	1
PKC zeta/ceramide	-0.098	0.046	-10000	0	-0.48	3	3
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.12	0.31	-10000	0	-0.86	80	80
BAX	-0.042	0.018	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AKT1	0.046	0.008	-10000	0	-10000	0	0
BAD	-0.098	0.043	-10000	0	-0.45	2	2
SMPD1	0.027	0.042	-10000	0	-0.28	1	1
RB1	-0.096	0.037	-10000	0	-10000	0	0
FADD/Caspase 8	0.04	0.087	-10000	0	-10000	0	0
MAP2K4	-0.081	0.035	-10000	0	-10000	0	0
NSMAF	0.016	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.084	0.056	-10000	0	-0.59	4	4
EGF	-0.67	0.23	-10000	0	-0.74	478	478
mol:ceramide	-0.11	0.04	0.2	2	-10000	0	2
MADD	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.03	0.025	-10000	0	-0.56	1	1
ASAH1	0.016	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.095	0.037	-10000	0	-10000	0	0
cell proliferation	-0.052	0.059	-10000	0	-0.46	10	10
BID	-0.011	0.065	-10000	0	-10000	0	0
MAP3K1	-0.096	0.037	-10000	0	-10000	0	0
EIF2A	-0.067	0.034	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
MAPK3	-0.065	0.052	-10000	0	-0.54	4	4
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.065	0.052	-10000	0	-0.54	4	4
Cathepsin D/ceramide	-0.097	0.035	-10000	0	-0.26	1	1
FADD	0.026	0.093	-10000	0	-0.48	1	1
KSR1	-0.1	0.059	-10000	0	-0.63	4	4
MAPK8	-0.076	0.041	-10000	0	-0.35	4	4
PRKRA	-0.096	0.037	-10000	0	-10000	0	0
PDGFA	0.014	0.033	-10000	0	-0.74	1	1
TRAF2	0.016	0	-10000	0	-10000	0	0
IGF1	0.006	0.093	-10000	0	-0.86	6	6
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.11	0.039	0.2	2	-10000	0	2
CTSD	0.014	0.033	-10000	0	-0.74	1	1
regulation of nitric oxide biosynthetic process	-0.001	0.024	-10000	0	-0.56	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.055	0.065	-10000	0	-0.5	10	10
PRKCD	0.014	0.038	-10000	0	-0.86	1	1
PRKCZ	0.011	0.057	-10000	0	-0.74	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.03	0.025	-10000	0	-0.56	1	1
RelA/NF kappa B1	-0.001	0.024	-10000	0	-0.56	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.014	0.033	-10000	0	-0.74	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.033	0.077	-10000	0	-0.51	1	1
TNFR1A/BAG4/TNF-alpha	-0.009	0.067	-10000	0	-0.52	9	9
mol:Sphingosine-1-phosphate	0.027	0.044	-10000	0	-0.56	3	3
MAP2K1	-0.07	0.054	-10000	0	-0.55	4	4
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
CYCS	-0.063	0.023	-10000	0	-0.23	1	1
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
NFKB1	0.014	0.033	-10000	0	-0.74	1	1
TNFR1A/BAG4	-0.001	0.024	-10000	0	-0.56	1	1
EIF2AK2	-0.081	0.035	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.008	0.064	-10000	0	-0.52	8	8
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.016	0.037	-10000	0	-10000	0	0
MAP2K2	-0.071	0.053	-10000	0	-0.55	4	4
SMPD3	0.026	0.051	-10000	0	-0.33	2	2
TNF	0.003	0.1	-10000	0	-0.8	8	8
PKC zeta/PAR4	-0.004	0.048	-10000	0	-0.56	4	4
mol:PHOSPHOCHOLINE	0.23	0.083	0.26	480	-10000	0	480
NF kappa B1/RelA/I kappa B alpha	-0.004	0.038	-10000	0	-10000	0	0
AIFM1	-0.063	0.025	-10000	0	-0.23	1	1
BCL2	0.016	0	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.57	0.68	-9999	-1.3	249	249
PLK1	-0.12	0.37	-9999	-0.8	93	93
CDKN1B	0.062	0.16	-9999	-10000	0	0
FOXO3	-0.036	0.23	-9999	-0.66	14	14
KAT2B	0.012	0.04	-9999	-0.78	1	1
FOXO1/SIRT1	-0.14	0.21	-9999	-10000	0	0
CAT	-0.025	0.22	-9999	-0.89	7	7
CTNNB1	0.016	0	-9999	-10000	0	0
AKT1	-0.007	0.038	-9999	-10000	0	0
FOXO1	-0.16	0.23	-9999	-0.41	249	249
MAPK10	0.033	0.049	-9999	-0.43	5	5
mol:GTP	0.003	0.001	-9999	-10000	0	0
FOXO4	0.11	0.048	-9999	-10000	0	0
response to oxidative stress	-0.029	0.045	-9999	-10000	0	0
FOXO3A/SIRT1	0.029	0.2	-9999	-0.58	13	13
XPO1	0.017	0	-9999	-10000	0	0
EP300	-0.006	0.042	-9999	-0.74	1	1
BCL2L11	0.013	0.043	-9999	-10000	0	0
FOXO1/SKP2	-0.14	0.21	-9999	-0.4	3	3
mol:GDP	-0.029	0.045	-9999	-10000	0	0
RAN	0.018	0.001	-9999	-10000	0	0
GADD45A	0.12	0.098	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.031	0.085	-9999	-10000	0	0
MST1	0.001	0.11	-9999	-0.86	8	8
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.043	0.095	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
MAPK8	0.036	0.035	-9999	-0.43	2	2
MAPK9	0.037	0.019	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
SIRT1	0.035	0.028	-9999	-10000	0	0
SOD2	0.015	0.2	-9999	-0.68	7	7
RBL2	0.024	0.17	-9999	-1.3	1	1
RAL/GDP	0.009	0.024	-9999	-10000	0	0
CHUK	0.014	0.02	-9999	-10000	0	0
Ran/GTP	0.017	0.003	-9999	-10000	0	0
CSNK1G2	0.014	0.033	-9999	-0.74	1	1
RAL/GTP	0.024	0.026	-9999	-10000	0	0
CSNK1G1	0.016	0	-9999	-10000	0	0
FASLG	-0.34	0.39	-9999	-0.73	265	265
SKP2	0.016	0	-9999	-10000	0	0
USP7	0.018	0.001	-9999	-10000	0	0
IKBKB	0.014	0.02	-9999	-10000	0	0
CCNB1	-0.028	0.23	-9999	-0.92	10	10
FOXO1-3a-4/beta catenin	-0.069	0.1	-9999	-0.43	1	1
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.21	-9999	-0.4	3	3
CSNK1A1	0.016	0	-9999	-10000	0	0
SGK1	0.014	0.02	-9999	-10000	0	0
CSNK1G3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.014	-9999	-10000	0	0
ZFAND5	0.11	0.044	-9999	-10000	0	0
SFN	-0.083	0.27	-9999	-0.83	62	62
CDK2	-0.019	0.041	-9999	-10000	0	0
FOXO3A/14-3-3	0.013	0.099	-9999	-10000	0	0
CREBBP	-0.019	0.041	-9999	-10000	0	0
FBXO32	-0.025	0.22	-9999	-0.79	8	8
BCL6	0.026	0.16	-9999	-10000	0	0
RALB	0.018	0	-9999	-10000	0	0
RALA	0.018	0	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.021	0.088	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.038	-9999	-10000	0	0
AP1	-0.03	0.1	-9999	-0.6	1	1
mol:PIP3	-0.026	0.091	-9999	-0.54	1	1
AKT1	-0.014	0.057	-9999	-10000	0	0
PTK2B	0.033	0.059	-9999	-0.28	1	1
RHOA	0.036	0.035	-9999	-10000	0	0
PIK3CB	0.015	0	-9999	-10000	0	0
mol:Ca2+	0.05	0.051	-9999	-0.45	2	2
MAGI3	0.013	0.046	-9999	-0.74	2	2
RELA	0.016	0	-9999	-10000	0	0
apoptosis	-0.022	0.085	-9999	-0.37	27	27
HRAS/GDP	-0.001	0.029	-9999	-0.68	1	1
positive regulation of microtubule depolymerization	0.046	0.068	-9999	-0.38	3	3
NF kappa B1 p50/RelA	-0.018	0.073	-9999	-10000	0	0
endothelial cell migration	0.007	0.13	-9999	-0.53	29	29
ADCY4	0.032	0.12	-9999	-0.47	25	25
ADCY5	0.023	0.13	-9999	-0.49	28	28
ADCY6	0.031	0.12	-9999	-0.47	25	25
ADCY7	0.026	0.12	-9999	-0.48	25	25
ADCY1	0.026	0.13	-9999	-0.48	26	26
ADCY2	-0.019	0.14	-9999	-0.51	26	26
ADCY3	0.032	0.12	-9999	-0.47	25	25
ADCY8	-0.027	0.14	-9999	-0.48	25	25
ADCY9	0.032	0.12	-9999	-0.47	25	25
GSK3B	0.042	0.056	-9999	-10000	0	0
arachidonic acid secretion	0.038	0.11	-9999	-0.44	23	23
GNG2	0.015	0	-9999	-10000	0	0
TRIP6	0.001	0.008	-9999	-10000	0	0
GNAO1	0.007	0.12	-9999	-0.48	28	28
HRAS	0.014	0.038	-9999	-0.86	1	1
NFKBIA	0.061	0.061	-9999	-10000	0	0
GAB1	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.002	0.053	-9999	-0.86	2	2
JUN	0.016	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.002	0.023	-9999	-0.48	1	1
TIAM1	-0.003	0.062	-9999	-1	2	2
PIK3R1	0.014	0.033	-9999	-0.74	1	1
mol:IP3	0.051	0.052	-9999	-0.46	2	2
PLCB3	0.037	0.023	-9999	-0.43	1	1
FOS	-0.003	0.12	-9999	-0.75	13	13
positive regulation of mitosis	0.038	0.11	-9999	-0.44	23	23
LPA/LPA1-2-3	-0.025	0.1	-9999	-0.52	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.014	0.033	-9999	-0.74	1	1
stress fiber formation	0.039	0.076	-9999	-10000	0	0
GNAZ	0.01	0.12	-9999	-0.48	26	26
EGFR/PI3K-beta/Gab1	-0.027	0.094	-9999	-0.57	1	1
positive regulation of dendritic cell cytokine production	-0.025	0.099	-9999	-0.52	4	4
LPA/LPA2/MAGI-3	-0.003	0.031	-9999	-0.48	2	2
ARHGEF1	0.03	0.095	-9999	-0.49	1	1
GNAI2	0.013	0.11	-9999	-0.46	23	23
GNAI3	0.013	0.11	-9999	-0.46	23	23
GNAI1	0.01	0.12	-9999	-0.48	26	26
LPA/LPA3	-0.007	0.06	-9999	-0.67	4	4
LPA/LPA2	-0.001	0.013	-9999	-10000	0	0
LPA/LPA1	-0.028	0.12	-9999	-0.51	29	29
HB-EGF/EGFR	-0.28	0.29	-9999	-0.58	255	255
HBEGF	-0.3	0.35	-9999	-0.66	249	249
mol:DAG	0.051	0.052	-9999	-0.46	2	2
cAMP biosynthetic process	0.019	0.12	-9999	-0.46	27	27
NFKB1	0.014	0.033	-9999	-0.74	1	1
SRC	0.016	0	-9999	-10000	0	0
GNB1	0.015	0	-9999	-10000	0	0
LYN	0.061	0.061	-9999	-10000	0	0
GNAQ	-0.004	0.035	-9999	-0.4	4	4
LPAR2	0.016	0	-9999	-10000	0	0
LPAR3	0.003	0.076	-9999	-0.86	4	4
LPAR1	-0.013	0.15	-9999	-0.73	23	23
IL8	-0.077	0.2	-9999	-0.49	44	44
PTK2	0.024	0.1	-9999	-0.48	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.022	0.085	-9999	-0.37	27	27
EGFR	0	0.11	-9999	-0.85	9	9
PLCG1	0.019	0.054	-9999	-0.41	4	4
PLD2	0.024	0.1	-9999	-0.48	4	4
G12/G13	-0.021	0.088	-9999	-0.42	23	23
PI3K-beta	-0.016	0.067	-9999	-0.52	1	1
cell migration	-0.009	0.034	-9999	-10000	0	0
SLC9A3R2	0.014	0.033	-9999	-0.74	1	1
PXN	0.039	0.077	-9999	-10000	0	0
HRAS/GTP	-0.026	0.098	-9999	-0.45	23	23
RAC1	0.016	0	-9999	-10000	0	0
MMP9	-0.4	0.44	-9999	-0.86	249	249
PRKCE	0.013	0.033	-9999	-0.74	1	1
PRKCD	0.058	0.054	-9999	-10000	0	0
Gi(beta/gamma)	-0.025	0.097	-9999	-0.44	25	25
mol:LPA	0.004	0.023	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.017	0.08	-9999	-10000	0	0
MAPKKK cascade	0.038	0.11	-9999	-0.44	23	23
contractile ring contraction involved in cytokinesis	0.036	0.035	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.009	0.058	-9999	-0.4	11	11
GNA15	-0.016	0.08	-9999	-0.42	19	19
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
MAPT	0.046	0.07	-9999	-0.39	3	3
GNA11	-0.006	0.045	-9999	-0.39	7	7
Rac1/GTP	-0.002	0.056	-9999	-0.91	2	2
MMP2	0.007	0.13	-9999	-0.53	29	29

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.013	0.046	-9999	-0.74	2	2
SPHK1	-0.057	0.24	-9999	-0.86	44	44
GNAI2	0.016	0	-9999	-10000	0	0
mol:S1P	0.001	0.095	-9999	-0.31	46	46
GNAO1	0.008	0.083	-9999	-0.84	5	5
mol:Sphinganine-1-P	-0.029	0.2	-9999	-0.66	46	46
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.017	0.055	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.014	0.033	-9999	-0.74	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.023	0.074	-9999	-0.29	2	2
S1PR5	-0.14	0.33	-9999	-0.86	91	91
S1PR4	-0.031	0.2	-9999	-0.86	28	28
GNAI1	0.011	0.057	-9999	-0.74	3	3
S1P/S1P5/G12	-0.11	0.21	-9999	-0.54	91	91
S1P/S1P3/Gq	0.023	0.097	-9999	-0.42	16	16
S1P/S1P4/Gi	0.024	0.096	-9999	-0.38	12	12
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.011	0.057	-9999	-0.74	3	3
GNA14	0.006	0.086	-9999	-0.74	7	7
GNA15	-0.011	0.15	-9999	-0.86	16	16
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.011	0.057	-9999	-0.74	3	3
ABCC1	0.016	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.016	0.16	-9999	-0.86	19	19
PLK4	0.011	0.066	-9999	-0.86	3	3
regulation of centriole replication	0.002	0.14	-9999	-0.66	22	22

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.022	0.1	-9999	-0.49	24	24
E-cadherin/beta catenin	-0.023	0.11	-9999	-0.56	22	22
CTNNB1	0.016	0	-9999	-10000	0	0
JUP	0.011	0.057	-9999	-0.74	3	3
CDH1	-0.016	0.15	-9999	-0.74	22	22

×

FAS signaling pathway (CD95)

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
SPTAN1	0.011	0.042	-10000	0	-10000	0	0
RFC1	0.011	0.042	-10000	0	-10000	0	0
PRKDC	0.011	0.042	-10000	0	-10000	0	0
RIPK1	0.015	0.004	-10000	0	-10000	0	0
CASP7	-0.024	0.065	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.14	0.16	-10000	0	-0.35	22	22
MAP2K4	-0.084	0.16	-10000	0	-0.43	23	23
mol:ceramide	-0.15	0.2	-10000	0	-0.48	32	32
GSN	0.011	0.042	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.17	0.18	-10000	0	-0.44	22	22
FAS	0.015	0.006	-10000	0	-10000	0	0
BID	0.018	0.066	-10000	0	-10000	0	0
MAP3K1	-0.035	0.1	-10000	0	-10000	0	0
MAP3K7	0.014	0.005	-10000	0	-10000	0	0
RB1	0.011	0.042	-10000	0	-10000	0	0
CFLAR	0.015	0.004	-10000	0	-10000	0	0
HGF/MET	-0.036	0.15	-10000	0	-0.57	33	33
ARHGDIB	0.011	0.042	-10000	0	-10000	0	0
FADD	0.015	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.011	0.042	-10000	0	-10000	0	0
NFKB1	-0.065	0.077	-10000	0	-0.71	1	1
MAPK8	-0.085	0.18	-10000	0	-0.53	25	25
DFFA	0.011	0.042	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.011	0.042	-10000	0	-10000	0	0
FAS/FADD/MET	-0.005	0.055	-10000	0	-0.57	5	5
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.044	0.22	-10000	0	-0.86	36	36
FAF1	0.015	0.006	-10000	0	-10000	0	0
PARP1	0.011	0.042	-10000	0	-10000	0	0
DFFB	0.011	0.042	-10000	0	-10000	0	0
CHUK	-0.053	0.067	-10000	0	-0.65	1	1
FASLG	-0.42	0.44	-10000	0	-0.86	265	265
FAS/FADD	0	0	-10000	0	-10000	0	0
HGF	-0.02	0.17	-10000	0	-0.8	23	23
LMNA	0.01	0.046	-10000	0	-0.52	1	1
CASP6	0.011	0.042	-10000	0	-10000	0	0
CASP10	0.015	0.006	-10000	0	-10000	0	0
CASP3	0.013	0.049	-10000	0	-10000	0	0
PTPN13	0.003	0.098	-10000	0	-0.74	9	9
CASP8	0.027	0.1	0.4	36	-10000	0	36
IL6	-0.13	0.34	-10000	0	-0.96	67	67
MET	0.007	0.085	-10000	0	-0.86	5	5
ICAD/CAD	0.011	0.042	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.15	0.2	-10000	0	-0.49	32	32
activation of caspase activity by cytochrome c	0.018	0.065	-10000	0	-10000	0	0
PAK2	0.011	0.042	-10000	0	-10000	0	0
BCL2	0.016	0.001	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.005	0.019	-10000	0	-10000	0	0
AES	0.005	0.016	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.016	0	-10000	0	-10000	0	0
DKK2	-0.026	0.18	-10000	0	-0.83	26	26
TLE1	0.005	0.016	-10000	0	-10000	0	0
MACF1	0.016	0.001	-10000	0	-10000	0	0
CTNNB1	0.049	0.1	-10000	0	-0.45	1	1
WIF1	-0.001	0.075	-10000	0	-0.77	5	5
beta catenin/RanBP3	0.004	0.1	0.36	20	-10000	0	20
KREMEN2	-0.089	0.28	-10000	0	-0.86	63	63
DKK1	-0.019	0.17	-10000	0	-0.82	22	22
beta catenin/beta TrCP1	0.056	0.094	-10000	0	-10000	0	0
FZD1	0.016	0.002	-10000	0	-10000	0	0
AXIN2	0.009	0.099	-10000	0	-1.4	2	2
AXIN1	0.016	0.004	-10000	0	-10000	0	0
RAN	0.016	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.002	0.017	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.072	0.064	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.04	0.083	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.059	0.1	-10000	0	-10000	0	0
HNF1A	-0.002	0.074	-10000	0	-0.74	5	5
CTBP1	0.005	0.017	-10000	0	-10000	0	0
MYC	-0.009	0.15	-10000	0	-0.75	20	20
RANBP3	0.016	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.095	0.21	-10000	0	-0.57	88	88
NKD1	-0.19	0.34	-10000	0	-0.74	142	142
TCF4	0.005	0.017	-10000	0	-10000	0	0
TCF3	0.005	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.024	0.11	-10000	0	-0.52	25	25
Ran/GTP	0	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.019	0.11	0.48	4	-10000	0	4
LEF1	-0.021	0.15	-10000	0	-0.86	16	16
DVL1	0.003	0.034	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.082	0.07	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.09	0.22	-10000	0	-0.61	78	78
LRP6	0.016	0.002	-10000	0	-10000	0	0
CSNK1A1	0.005	0.019	-10000	0	-10000	0	0
NLK	0.016	0.005	-10000	0	-10000	0	0
CCND1	-0.009	0.15	-10000	0	-0.75	20	20
WNT1	-0.026	0.19	-10000	0	-0.86	25	25
GSK3A	0.016	0.004	-10000	0	-10000	0	0
GSK3B	0.016	0.002	-10000	0	-10000	0	0
FRAT1	0.015	0.004	-10000	0	-10000	0	0
PPP2R5D	0.096	0.15	0.35	141	-10000	0	141
APC	-0.005	0.11	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.012	0.063	0.27	5	-10000	0	5
CREBBP	0.005	0.017	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.017	-9999	-10000	0	0
DAPP1	0.03	0.11	-9999	-0.45	17	17
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.14	0.26	-9999	-0.73	54	54
mol:DAG	-0.071	0.15	-9999	-0.33	39	39
HRAS	0.015	0.038	-9999	-0.86	1	1
RAP1A	0.017	0.001	-9999	-10000	0	0
ARF5/GDP	0.019	0.073	-9999	-10000	0	0
PLCG2	0.003	0.1	-9999	-0.82	8	8
PLCG1	0.016	0	-9999	-10000	0	0
ARF5	0.016	0	-9999	-10000	0	0
mol:GTP	-0.001	0.019	-9999	-10000	0	0
ARF1/GTP	-0.001	0.017	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.001	0.018	-9999	-10000	0	0
ADAP1	-0.004	0.036	-9999	-10000	0	0
ARAP3	-0.001	0.018	-9999	-10000	0	0
INPPL1	0.016	0	-9999	-10000	0	0
PREX1	0.016	0	-9999	-10000	0	0
ARHGEF6	0.016	0	-9999	-10000	0	0
ARHGEF7	0.016	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
NRAS	0.017	0.001	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
FGR	0.011	0.066	-9999	-0.86	3	3
mol:Ca2+	-0.023	0.077	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.014	0.033	-9999	-0.74	1	1
ZAP70	-0.47	0.44	-9999	-0.86	294	294
mol:IP3	-0.037	0.1	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
ARF1/GDP	0.019	0.073	-9999	-10000	0	0
RhoA/GDP	-0.004	0.017	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.02	-9999	-0.47	1	1
BLNK	0.014	0.033	-9999	-0.74	1	1
actin cytoskeleton reorganization	0.045	0.081	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PLEKHA2	0.036	0.053	-9999	-0.57	4	4
RAC1	0.016	0	-9999	-10000	0	0
PTEN	0	0.002	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.017	-9999	-10000	0	0
RhoA/GTP	-0.001	0.017	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.2	0.24	-9999	-0.56	131	131
BLK	-0.04	0.21	-9999	-0.86	33	33
PDPK1	0.014	0.033	-9999	-0.74	1	1
CYTH1	-0.001	0.017	-9999	-10000	0	0
HCK	-0.032	0.2	-9999	-0.86	29	29
CYTH3	-0.001	0.017	-9999	-10000	0	0
CYTH2	-0.001	0.017	-9999	-10000	0	0
KRAS	0.017	0.001	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.001	0.024	-9999	-0.54	1	1
SGK1	-0.001	0.026	-9999	-0.6	1	1
INPP5D	0.009	0.076	-9999	-0.86	4	4
mol:GDP	0.01	0.077	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
SYK	0.013	0.046	-9999	-0.74	2	2
ARF6/GDP	-0.004	0.016	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.019	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.001	0.019	-9999	-10000	0	0
VAV1	-0.19	0.37	-9999	-0.86	124	124
mol:PI-3-4-P2	0.025	0.06	-9999	-0.66	4	4
RAS family/GTP/PI3K Class I	-0.001	0.019	-9999	-10000	0	0
PLEKHA1	0.036	0.053	-9999	-0.57	4	4
Rac1/GDP	0.019	0.073	-9999	-10000	0	0
LAT	-0.23	0.39	-9999	-0.86	147	147
Rac1/GTP	0	0.1	-9999	-10000	0	0
ITK	-0.14	0.21	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.11	0.2	-9999	-0.46	77	77
LCK	-0.02	0.17	-9999	-0.85	22	22
BTK	-0.094	0.18	-9999	-10000	0	0

×

Regulation of Androgen receptor activity

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
HDAC1	0.03	0.002	-9999	-10000	0	0
SMARCC1	0.026	0.01	-9999	-10000	0	0
REL	0.008	0.066	-9999	-0.74	4	4
HDAC7	-0.098	0.088	-9999	-0.66	3	3
JUN	0.015	0.003	-9999	-10000	0	0
EP300	0.014	0.033	-9999	-0.74	1	1
KAT2B	0.014	0.033	-9999	-0.74	1	1
KAT5	0.016	0	-9999	-10000	0	0
MAPK14	0.001	0.046	-9999	-0.59	3	3
FOXO1	0.016	0.001	-9999	-10000	0	0
T-DHT/AR	-0.11	0.091	-9999	-0.68	4	4
MAP2K6	-0.002	0.058	-9999	-0.76	3	3
BRM/BAF57	0	0	-9999	-10000	0	0
MAP2K4	0.002	0.006	-9999	-10000	0	0
SMARCA2	0.015	0.003	-9999	-10000	0	0
PDE9A	-0.12	0.13	-9999	-0.82	11	11
NCOA2	0	0.11	-9999	-0.74	11	11
CEBPA	-0.001	0.12	-9999	-0.86	10	10
EHMT2	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.093	0.098	-9999	-0.54	3	3
NR0B1	-0.051	0.21	-9999	-0.86	34	34
EGR1	-0.002	0.11	-9999	-0.74	12	12
RXRs/9cRA	-0.004	0.047	-9999	-0.54	4	4
AR/RACK1/Src	-0.016	0.064	-9999	-0.58	2	2
AR/GR	0	0.088	-9999	-0.69	4	4
GNB2L1	0.014	0.038	-9999	-0.86	1	1
PKN1	0.015	0.003	-9999	-10000	0	0
RCHY1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.002	0.037	-9999	-0.57	2	2
T-DHT/AR/TIF2/CARM1	-0.022	0.098	-9999	-0.77	5	5
SRC	0.003	0.049	-9999	-10000	0	0
NR3C1	0.014	0.038	-9999	-0.86	1	1
KLK3	-0.052	0.19	-9999	-0.74	24	24
APPBP2	0.002	0.006	-9999	-10000	0	0
TRIM24	0.015	0.003	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.027	0.057	-9999	-0.57	4	4
TMPRSS2	-0.96	0.38	-9999	-1.1	458	458
RXRG	0.006	0.076	-9999	-0.86	4	4
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.016	0.001	-9999	-10000	0	0
RXRB	0.016	0.001	-9999	-10000	0	0
CARM1	0.015	0.003	-9999	-10000	0	0
NR2C2	0.014	0.033	-9999	-0.74	1	1
KLK2	-0.025	0.14	-9999	-0.63	22	22
AR	-0.011	0.089	-9999	-0.43	14	14
SENP1	0.016	0.001	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
MDM2	0.013	0.009	-9999	-10000	0	0
SRY	0.002	0.007	-9999	-10000	0	0
GATA2	-0.003	0.12	-9999	-0.74	13	13
MYST2	0.016	0.001	-9999	-10000	0	0
HOXB13	-0.16	0.35	-9999	-0.86	104	104
T-DHT/AR/RACK1/Src	-0.016	0.063	-9999	-0.59	2	2
positive regulation of transcription	-0.003	0.12	-9999	-0.74	13	13
DNAJA1	0.002	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.002	-9999	-10000	0	0
NCOA1	0.024	0.005	-9999	-10000	0	0
SPDEF	-0.17	0.36	-9999	-0.86	114	114
T-DHT/AR/TIF2	0.018	0.076	-9999	-0.66	4	4
T-DHT/AR/Hsp90	-0.028	0.056	-9999	-0.57	4	4
GSK3B	0.002	0.005	-9999	-10000	0	0
NR2C1	0.016	0.001	-9999	-10000	0	0
mol:T-DHT	-0.011	0.053	-9999	-0.49	4	4
SIRT1	0.015	0.003	-9999	-10000	0	0
ZMIZ2	0.014	0.008	-9999	-10000	0	0
POU2F1	0.005	0.015	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.067	0.14	-9999	-0.6	28	28
CREBBP	0.015	0.003	-9999	-10000	0	0
SMARCE1	0.015	0.003	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.11	0.07	-10000	0	-0.4	1	1
epithelial cell differentiation	-0.051	0.11	-10000	0	-0.57	1	1
ITCH	0.055	0.017	-10000	0	-10000	0	0
WWP1	-0.097	0.067	-10000	0	-10000	0	0
FYN	0.016	0	-10000	0	-10000	0	0
EGFR	0.001	0.11	-10000	0	-0.85	9	9
PRL	0.006	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.019	0.081	-10000	0	-0.57	1	1
PTPRZ1	-0.083	0.25	-10000	0	-0.75	65	65
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.054	0.074	-10000	0	-0.6	2	2
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.084	0.094	-10000	0	-0.55	12	12
ADAM17	0.055	0.017	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.14	0.085	-10000	0	-0.46	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.12	0.1	-10000	0	-0.61	13	13
NCOR1	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.076	0.078	-10000	0	-0.53	10	10
GRIN2B	-0.058	0.092	-10000	0	-0.61	3	3
ErbB4/ErbB2/betacellulin	-0.13	0.16	-10000	0	-0.51	74	74
STAT1	0.014	0.038	-10000	0	-0.86	1	1
HBEGF	0.016	0	-10000	0	-10000	0	0
PRLR	-0.084	0.26	-10000	0	-0.74	70	70
E4ICDs/ETO2	-0.11	0.079	-10000	0	-0.7	2	2
axon guidance	-0.017	0.072	-10000	0	-10000	0	0
NEDD4	0.052	0.051	-10000	0	-0.73	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.074	0.19	-10000	0	-0.56	70	70
CBFA2T3	0.012	0.054	-10000	0	-0.86	2	2
ErbB4/ErbB2/HBEGF	-0.064	0.038	-10000	0	-0.51	1	1
MAPK3	-0.03	0.082	-10000	0	-0.6	1	1
STAT1 (dimer)	-0.11	0.072	-10000	0	-0.54	1	1
MAPK1	-0.03	0.082	-10000	0	-0.6	1	1
JAK2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.078	0.082	-10000	0	-0.53	11	11
NRG1	0.035	0.11	-10000	0	-0.56	17	17
NRG3	-0.004	0.13	-10000	0	-0.86	12	12
NRG2	-0.001	0.12	-10000	0	-0.85	10	10
NRG4	-0.055	0.22	-10000	0	-0.77	47	47
heart development	-0.017	0.072	-10000	0	-10000	0	0
neural crest cell migration	-0.077	0.081	-10000	0	-0.52	11	11
ERBB2	0.052	0.039	-10000	0	-0.56	2	2
WWOX/E4ICDs	-0.11	0.075	-10000	0	-0.55	2	2
SHC1	0.014	0.038	-10000	0	-0.86	1	1
ErbB4/EGFR/neuregulin 4	-0.14	0.15	-10000	0	-0.56	51	51
apoptosis	0.1	0.064	0.39	8	-10000	0	8
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.12	0.088	-10000	0	-0.52	11	11
ErbB4/ErbB2/epiregulin	-0.097	0.13	-10000	0	-0.57	34	34
ErbB4/ErbB4/betacellulin/betacellulin	-0.18	0.19	-10000	0	-0.58	82	82
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.13	0.14	-10000	0	-0.73	1	1
MDM2	-0.1	0.073	-10000	0	-0.4	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.054	0.078	-10000	0	-0.51	10	10
STAT5A	-0.005	0.067	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.085	0.1	-10000	0	-0.56	18	18
DLG4	0.016	0	-10000	0	-10000	0	0
GRB2/SHC	-0.001	0.029	-10000	0	-0.66	1	1
E4ICDs/TAB2/NCoR1	-0.1	0.048	-10000	0	-10000	0	0
STAT5A (dimer)	-0.054	0.12	-10000	0	-0.62	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.007	0.064	-10000	0	-10000	0	0
LRIG1	0.016	0	-10000	0	-10000	0	0
EREG	-0.04	0.21	-10000	0	-0.86	33	33
BTC	-0.1	0.27	-10000	0	-0.74	81	81
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.017	0.072	-10000	0	-10000	0	0
ERBB4	-0.14	0.085	-10000	0	-0.46	1	1
STAT5B	0.016	0	-10000	0	-10000	0	0
YAP1	-0.034	0.016	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.1	0.13	-10000	0	-0.52	37	37
glial cell differentiation	0.1	0.048	-10000	0	-10000	0	0
WWOX	0.014	0.038	-10000	0	-0.86	1	1
cell proliferation	-0.076	0.16	-10000	0	-0.63	12	12

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.19	0.22	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.15	0.17	-9999	-1.2	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.026	0.029	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.1	0.09	-9999	-0.37	1	1
CaM/Ca2+	-0.18	0.2	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.18	0.2	-9999	-1	1	1
AKT1	-0.16	0.17	-9999	-10000	0	0
MAP2K1	-0.12	0.22	-9999	-10000	0	0
MAP3K11	-0.14	0.23	-9999	-0.8	1	1
IFNGR1	0.001	0.019	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.27	0.29	-9999	-0.73	115	115
Rap1/GTP	-0.13	0.14	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.21	0.23	-9999	-10000	0	0
CEBPB	-0.067	0.2	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.19	0.21	-9999	-1	2	2
STAT1	-0.14	0.23	-9999	-1	1	1
CALM1	0.016	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.37	0.43	-9999	-0.85	238	238
PIK3CA	0.014	0.033	-9999	-0.74	1	1
STAT1 (dimer)/PIAS1	-0.17	0.19	-9999	-0.95	1	1
CEBPB/PTGES2/Cbp/p300	-0.075	0.084	-9999	-0.47	1	1
mol:Ca2+	-0.19	0.21	-9999	-10000	0	0
MAPK3	-0.087	0.2	-9999	-10000	0	0
STAT1 (dimer)	-0.14	0.12	-9999	-0.54	1	1
MAPK1	-0.087	0.2	-9999	-10000	0	0
JAK2	0.001	0.019	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
JAK1	0.001	0.019	-9999	-10000	0	0
CAMK2D	0.016	0	-9999	-10000	0	0
DAPK1	-0.024	0.15	-9999	-0.63	3	3
SMAD7	-0.02	0.082	-9999	-10000	0	0
CBL/CRKL/C3G	-0.16	0.18	-9999	-10000	0	0
PI3K	-0.17	0.19	-9999	-10000	0	0
IFNG	-0.37	0.43	-9999	-0.85	238	238
apoptosis	-0.036	0.12	-9999	-0.44	3	3
CAMK2G	0.016	0	-9999	-10000	0	0
STAT3 (dimer)	0.016	0	-9999	-10000	0	0
CAMK2A	-0.24	0.36	-9999	-0.74	178	178
CAMK2B	-0.099	0.27	-9999	-0.76	79	79
FRAP1	-0.1	0.2	-9999	-10000	0	0
PRKCD	-0.12	0.21	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
negative regulation of cell growth	-0.1	0.09	-9999	-0.37	1	1
PTPN2	0.016	0	-9999	-10000	0	0
EP300	0.015	0.033	-9999	-0.74	1	1
IRF1	-0.057	0.19	-9999	-0.93	1	1
STAT1 (dimer)/PIASy	-0.17	0.19	-9999	-0.95	1	1
SOCS1	0.011	0.082	-9999	-0.73	6	6
mol:GDP	-0.15	0.17	-9999	-10000	0	0
CASP1	-0.02	0.082	-9999	-10000	0	0
PTGES2	0.013	0.046	-9999	-0.74	2	2
IRF9	0.018	0.076	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.17	0.18	-9999	-10000	0	0
RAP1/GDP	-0.13	0.14	-9999	-10000	0	0
CBL	-0.15	0.23	-9999	-10000	0	0
MAP3K1	-0.14	0.23	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PIAS4	0.015	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.1	0.09	-9999	-0.37	1	1
PTPN11	-0.16	0.24	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.015	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.021	0.094	-10000	0	-0.43	26	26
regulation of S phase of mitotic cell cycle	-0.015	0.069	-10000	0	-0.62	1	1
GNAO1	0.008	0.083	-10000	0	-0.84	5	5
HRAS	0.014	0.038	-10000	0	-0.86	1	1
SHBG/T-DHT	-0.05	0.15	-10000	0	-0.5	54	54
PELP1	0.016	0.001	-10000	0	-10000	0	0
AKT1	0.015	0	-10000	0	-10000	0	0
MAP2K1	0.046	0.092	-10000	0	-10000	0	0
T-DHT/AR	-0.028	0.12	-10000	0	-0.57	26	26
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.007	13	13
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.057	-10000	0	-0.74	3	3
mol:GDP	-0.027	0.12	-10000	0	-0.55	26	26
cell proliferation	0.07	0.11	-10000	0	-0.64	4	4
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
FOS	0.056	0.15	-10000	0	-0.81	13	13
mol:Ca2+	-0.003	0.014	-10000	0	-0.11	4	4
MAPK3	0.062	0.1	-10000	0	-0.57	4	4
MAPK1	0.044	0.054	-10000	0	-0.3	1	1
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
mol:IP3	0	0.001	-10000	0	-0.004	13	13
cAMP biosynthetic process	-0.045	0.15	-10000	0	-0.48	54	54
GNG2	0.016	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	13	13
HRAS/GTP	-0.02	0.086	-10000	0	-0.48	1	1
actin cytoskeleton reorganization	-0.001	0.023	-10000	0	-10000	0	0
SRC	0.016	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	13	13
PI3K	-0.002	0.03	-10000	0	-0.48	2	2
apoptosis	-0.06	0.094	0.59	4	-10000	0	4
T-DHT/AR/PELP1	-0.024	0.1	-10000	0	-0.48	26	26
HRAS/GDP	-0.027	0.12	-10000	0	-0.52	27	27
CREB1	0.061	0.1	-10000	0	-0.64	4	4
RAC1-CDC42/GTP	-0.001	0.024	-10000	0	-10000	0	0
AR	-0.021	0.16	-10000	0	-0.74	26	26
GNB1	0.016	0	-10000	0	-10000	0	0
RAF1	0.035	0.094	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.024	0.11	-10000	0	-0.49	26	26
T-DHT/AR/PELP1/Src	-0.021	0.094	-10000	0	-0.44	26	26
MAP2K2	0.045	0.094	-10000	0	-10000	0	0
T-DHT/AR/PELP1/Src/PI3K	-0.015	0.07	-10000	0	-0.62	1	1
GNAZ	0.011	0.057	-10000	0	-0.74	3	3
SHBG	-0.062	0.23	-10000	0	-0.74	54	54
Gi family/GNB1/GNG2/GDP	-0.008	0.044	-10000	0	-0.45	2	2
mol:T-DHT	0	0	-10000	0	-0.003	9	9
RAC1	0.016	0	-10000	0	-10000	0	0
GNRH1	-0.18	0.31	-10000	0	-0.68	147	147
Gi family/GTP	-0.014	0.058	-10000	0	-0.48	4	4
CDC42	0.016	0	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	0.045	0.092	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.1	0.22	-9999	-0.59	91	91
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	0.008	0.083	-9999	-0.84	5	5
RhoA/GTP	-0.046	0.094	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.014	0.12	-9999	-10000	0	0
GNAZ	0.011	0.057	-9999	-0.74	3	3
GNAI3	0.016	0	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
S1PR5	-0.14	0.33	-9999	-0.86	91	91
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.052	0.11	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
GNAI1	0.011	0.057	-9999	-0.74	3	3

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.006	0.059	-9999	-0.56	6	6
AKT1	-0.056	0.2	-9999	-0.71	3	3
PTK2B	-0.16	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/Frs2	-0.002	0.041	-9999	-0.83	1	1
CAV1	-0.046	0.22	-9999	-0.86	37	37
CALM1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.23	0.25	-9999	-1.2	1	1
endothelial cell proliferation	-0.042	0.19	-9999	-0.69	1	1
mol:Ca2+	-0.16	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.21	0.24	-9999	-1.2	1	1
RP11-342D11.1	-0.17	0.26	-9999	-1.1	1	1
CDH5	0.014	0.038	-9999	-0.86	1	1
VEGFA homodimer	-0.24	0.26	-9999	-0.52	240	240
SHC1	0.014	0.038	-9999	-0.86	1	1
SHC2	0.006	0.089	-9999	-0.82	6	6
HRAS/GDP	-0.17	0.19	-9999	-0.83	2	2
SH2D2A	-0.27	0.41	-9999	-0.86	171	171
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.14	0.15	-9999	-0.78	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.39	0.33	-9999	-1	67	67
VEGFR1 homodimer	0.007	0.085	-9999	-0.86	5	5
SHC/GRB2/SOS1	-0.19	0.21	-9999	-1.1	1	1
GRB10	-0.16	0.26	-9999	-1.1	1	1
PTPN11	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
PAK1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.2	0.22	-9999	-1	2	2
HRAS	0.014	0.038	-9999	-0.86	1	1
VEGF/Rho/ROCK1/Integrin Complex	-0.086	0.094	-9999	-0.58	1	1
HIF1A	0.013	0.046	-9999	-0.74	2	2
FRS2	0.016	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.21	0.23	-9999	-1.2	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.016	0	-9999	-10000	0	0
Nck/Pak	-0.001	0.024	-9999	-0.56	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.23	0.25	-9999	-1.2	1	1
mol:GDP	-0.18	0.2	-9999	-1	1	1
mol:NADP	-0.064	0.19	-9999	-0.62	1	1
eNOS/Hsp90	-0.053	0.18	-9999	-0.57	1	1
PIK3R1	0.014	0.033	-9999	-0.74	1	1
mol:IP3	-0.16	0.27	-9999	-1.1	1	1
HIF1A/ARNT	-0.002	0.034	-9999	-0.56	2	2
SHB	0.016	0	-9999	-10000	0	0
VEGFA	-0.38	0.44	-9999	-0.86	240	240
VEGFC	0.014	0.038	-9999	-0.86	1	1
FAK1/Vinculin	-0.11	0.22	-9999	-0.99	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.22	0.24	-9999	-1.2	1	1
PTPN6	0.016	0	-9999	-10000	0	0
EPAS1	0.026	0.036	-9999	-0.72	1	1
mol:L-citrulline	-0.064	0.19	-9999	-0.62	1	1
ITGAV	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.21	0.24	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer	-0.23	0.25	-9999	-1.2	1	1
VEGFR2/3 heterodimer	-0.002	0.041	-9999	-0.83	1	1
VEGFB	0.016	0	-9999	-10000	0	0
MAPK11	-0.15	0.26	-9999	-0.83	2	2
VEGFR2 homodimer	0.043	0.049	-9999	-0.73	2	2
FLT1	0.007	0.085	-9999	-0.86	5	5
NEDD4	0.015	0.046	-9999	-0.74	2	2
MAPK3	-0.14	0.25	-9999	-0.76	2	2
MAPK1	-0.14	0.25	-9999	-0.76	2	2
VEGFA145/NRP2	-0.31	0.33	-9999	-0.66	245	245
VEGFR1/2 heterodimer	-0.008	0.068	-9999	-0.61	6	6
KDR	0.043	0.049	-9999	-0.73	2	2
VEGFA165/NRP1/VEGFR2 homodimer	-0.21	0.23	-9999	-1.2	2	2
SRC	0.016	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.14	0.25	-9999	-0.77	2	2
PI3K	-0.16	0.18	-9999	-0.78	6	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.23	0.25	-9999	-1.2	1	1
FES	-0.17	0.27	-9999	-1	2	2
GAB1	-0.17	0.19	-9999	-0.8	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.23	0.25	-9999	-1.2	1	1
CTNNB1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.083	0.2	-9999	-0.61	13	13
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.23	0.25	-9999	-1.2	1	1
PI3K/GAB1	-0.056	0.19	-9999	-0.64	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.2	0.22	-9999	-1.1	1	1
PRKACA	0.016	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.003	0.043	-9999	-0.77	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
CDC42	-0.17	0.27	-9999	-1.2	1	1
actin cytoskeleton reorganization	-0.39	0.33	-9999	-1	67	67
PTK2	-0.12	0.24	-9999	-1.1	1	1
EDG1	-0.17	0.26	-9999	-1.1	1	1
mol:DAG	-0.16	0.27	-9999	-1.1	1	1
CaM/Ca2+	-0.19	0.2	-9999	-1	1	1
MAP2K3	-0.15	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.21	0.23	-9999	-1.2	1	1
PLCG1	-0.17	0.27	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.21	0.24	-9999	-1.2	1	1
IQGAP1	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.23	0.25	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.23	0.25	-9999	-1.2	1	1
cell migration	-0.055	0.2	-9999	-0.77	1	1
mol:PI-3-4-5-P3	-0.15	0.17	-9999	-0.7	6	6
FYN	0.016	0	-9999	-10000	0	0
VEGFB/NRP1	-0.19	0.21	-9999	-1	1	1
mol:NO	-0.064	0.19	-9999	-0.62	1	1
PXN	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.17	0.19	-9999	-0.82	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.21	0.23	-9999	-1.2	1	1
VHL	0.014	0.033	-9999	-0.74	1	1
ITGB3	0.007	0.08	-9999	-0.74	6	6
NOS3	-0.075	0.2	-9999	-0.73	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.23	0.26	-9999	-1	4	4
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	-0.14	0.25	-9999	-1	1	1
PRKCB	-0.15	0.25	-9999	-0.96	2	2
VCL	0.016	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.22	0.24	-9999	-1.2	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	-0.23	0.26	-9999	-1.1	5	5
VEGFA165/NRP2	-0.31	0.33	-9999	-0.66	245	245
MAPKKK cascade	-0.17	0.18	-9999	-0.8	2	2
NRP2	0.004	0.1	-9999	-0.86	7	7
VEGFC homodimer	0.014	0.038	-9999	-0.86	1	1
NCK1	0.014	0.033	-9999	-0.74	1	1
ROCK1	0.016	0	-9999	-10000	0	0
FAK1/Paxillin	-0.11	0.22	-9999	-0.99	1	1
MAP3K13	-0.17	0.27	-9999	-1.2	1	1
PDPK1	-0.074	0.2	-9999	-0.65	6	6

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.012	0.059	-9999	-10000	0	0
epithelial cell differentiation	-0.016	0.079	-9999	-10000	0	0
CYFIP2	0.004	0.092	-9999	-0.74	8	8
ENAH	0.078	0.065	-9999	-10000	0	0
EGFR	0.001	0.11	-9999	-0.85	9	9
EPHA2	0.014	0.033	-9999	-0.74	1	1
MYO6	0.032	0.096	-9999	-0.78	2	2
CTNNB1	0.016	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.007	0.058	-9999	-0.47	8	8
AQP5	-0.17	0.24	-9999	-0.52	161	161
CTNND1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.034	0.083	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.018	0.12	-9999	-0.49	15	15
EGF	-0.67	0.23	-9999	-0.74	478	478
NCKAP1	0.016	0	-9999	-10000	0	0
AQP3	-0.051	0.16	-9999	-0.58	39	39
cortical microtubule organization	-0.016	0.079	-9999	-10000	0	0
GO:0000145	0.034	0.08	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.017	0.08	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GDP	-0.014	0.063	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.034	-9999	-0.52	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.05	0.084	-9999	-0.58	1	1
PVRL2	0.016	0	-9999	-10000	0	0
ZYX	0.034	0.084	-9999	-10000	0	0
ARF6/GTP	-0.002	0.031	-9999	-0.48	1	1
CDH1	-0.016	0.15	-9999	-0.74	22	22
EGFR/EGFR/EGF/EGF	-0.34	0.14	-9999	-0.77	28	28
RhoA/GDP	-0.015	0.073	-9999	-10000	0	0
actin cytoskeleton organization	0.041	0.092	-9999	-0.71	2	2
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
IGF1R	0.016	0	-9999	-10000	0	0
IGF1	0.006	0.093	-9999	-0.86	6	6
DIAPH1	-0.01	0.085	-9999	-0.69	8	8
Wnt receptor signaling pathway	0.016	0.079	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.014	0.063	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
VCL	0.042	0.094	-9999	-0.74	2	2
EFNA1	0.014	0.038	-9999	-0.86	1	1
LPP	0.043	0.089	-9999	-0.8	1	1
Ephrin A1/EPHA2	-0.016	0.074	-9999	-10000	0	0
SEC6/SEC8	-0.013	0.063	-9999	-10000	0	0
MGAT3	0.018	0.12	-9999	-0.5	15	15
HGF/MET	-0.036	0.13	-9999	-0.95	4	4
HGF	-0.02	0.17	-9999	-0.8	23	23
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.012	0.059	-9999	-10000	0	0
actin cable formation	0.098	0.07	-9999	-10000	0	0
KIAA1543	0.036	0.12	-9999	-0.85	6	6
KIFC3	0.034	0.086	-9999	-10000	0	0
NCK1	0.014	0.033	-9999	-0.74	1	1
EXOC3	0.016	0	-9999	-10000	0	0
ACTN1	0.033	0.093	-9999	-0.86	1	1
NCK1/GIT1	-0.001	0.024	-9999	-0.56	1	1
mol:GDP	-0.016	0.079	-9999	-10000	0	0
EXOC4	0.016	0	-9999	-10000	0	0
STX4	0.034	0.084	-9999	-10000	0	0
PIP5K1C	0.034	0.084	-9999	-10000	0	0
LIMA1	0.016	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
ROCK1	-0.012	0.055	-9999	-10000	0	0
adherens junction assembly	0.058	0.12	-9999	-0.79	7	7
IGF-1R heterotetramer/IGF1	-0.02	0.084	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	0.007	0.085	-9999	-0.86	5	5
PLEKHA7	0.03	0.1	-9999	-0.78	3	3
mol:GTP	-0.003	0.034	-9999	-0.52	1	1
establishment of epithelial cell apical/basal polarity	0.07	0.076	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	-0.012	0.059	-9999	-10000	0	0
regulation of cell-cell adhesion	0.041	0.092	-9999	-0.71	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.012	0.059	-9999	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.008	0.083	-9999	-0.84	5	5
CDC42/GTP	-0.017	0.061	-9999	-10000	0	0
PLCG1	0.034	0.078	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.017	0.06	-9999	-10000	0	0
S1PR5	-0.14	0.33	-9999	-0.86	91	91
S1PR4	-0.031	0.2	-9999	-0.86	28	28
MAPK3	0.034	0.078	-9999	-10000	0	0
MAPK1	0.034	0.078	-9999	-10000	0	0
S1P/S1P5/Gi	-0.052	0.11	-9999	-10000	0	0
GNAI1	0.011	0.057	-9999	-0.74	3	3
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.1	0.22	-9999	-0.59	91	91
RHOA	0.015	0.12	-9999	-0.49	28	28
S1P/S1P4/Gi	-0.02	0.07	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.011	0.057	-9999	-0.74	3	3
S1P/S1P4/G12/G13	-0.028	0.12	-9999	-0.53	28	28
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.01	0.068	-9999	-0.77	4	4
GNB1/GNG2	-0.054	0.11	-9999	-0.53	8	8
mol:DAG	0.009	0.13	-9999	-10000	0	0
PLCG1	0.009	0.13	-9999	-10000	0	0
YES1	-0.012	0.14	-9999	-0.56	8	8
FZD3	0.016	0	-9999	-10000	0	0
FZD6	0.016	0	-9999	-10000	0	0
G protein	-0.05	0.1	-9999	-0.5	7	7
MAP3K7	-0.095	0.22	-9999	-0.54	50	50
mol:Ca2+	0.009	0.12	-9999	-10000	0	0
mol:IP3	0.009	0.13	-9999	-10000	0	0
NLK	-0.007	0.009	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CAMK2A	-0.12	0.24	-9999	-0.61	50	50
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.064	0.13	-9999	-0.6	8	8
CSNK1A1	0.016	0	-9999	-10000	0	0
GNAS	-0.012	0.14	-9999	-0.56	8	8
GO:0007205	0.01	0.13	-9999	-10000	0	0
WNT6	-0.018	0.17	-9999	-0.86	20	20
WNT4	-0.068	0.24	-9999	-0.75	58	58
NFAT1/CK1 alpha	-0.05	0.1	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.057	-9999	-0.74	3	3
WNT11	-0.04	0.2	-9999	-0.76	38	38
CDC42	0	0.14	-9999	-0.52	8	8

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.032	0.12	-9999	-0.51	33	33
RGS9BP	-0.018	0.15	-9999	-0.74	23	23
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.003	0.006	-9999	-10000	0	0
mol:Na +	-0.012	0.084	-9999	-0.59	11	11
mol:ADP	0.012	0.043	-9999	-0.68	2	2
GNAT2	0.014	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.036	0.13	-9999	-0.5	38	38
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.025	-9999	-0.59	1	1
GRK7	0.008	0.054	-9999	-0.86	2	2
CNGB3	-0.007	0.11	-9999	-0.86	8	8
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.009	0.11	-9999	-0.64	15	15
Cone PDE6	-0.033	0.12	-9999	-0.53	12	12
Cone Metarhodopsin II	-0.002	0.034	-9999	-0.55	2	2
Na + (4 Units)	-0.018	0.11	-9999	-0.64	15	15
GNAT2/GDP	-0.03	0.11	-9999	-0.5	9	9
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	0.015	0.043	-9999	-0.54	3	3
Cone Transducin	-0.033	0.13	-9999	-0.54	33	33
SLC24A2	-0.008	0.099	-9999	-0.86	7	7
GNB3/GNGT2	-0.041	0.16	-9999	-0.66	33	33
GNB3	-0.038	0.21	-9999	-0.86	32	32
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	0	0.065	-9999	-0.86	3	3
ARR3	0.004	0.007	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.012	0.085	-9999	-0.6	11	11
mol:Pi	-0.035	0.13	-9999	-0.5	38	38
Cone CNG Channel	-0.013	0.084	-9999	-0.52	13	13
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.008	0.099	-9999	-0.86	7	7
RGS9	-0.008	0.14	-9999	-0.82	15	15
PDE6C	0.004	0.054	-9999	-0.86	2	2
GNGT2	0.014	0.038	-9999	-0.86	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.003	0.038	-9999	-0.86	1	1

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.016	0	-9999	-10000	0	0
ITGA4	-0.011	0.15	-9999	-0.86	16	16
alpha4/beta7 Integrin	-0.02	0.11	-9999	-0.66	16	16
alpha4/beta1 Integrin	-0.02	0.11	-9999	-0.66	16	16

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.28	0.37	-9999	-0.74	205	205
HRAS	0.014	0.038	-9999	-0.86	1	1
EGFR	0.001	0.11	-9999	-0.85	9	9
AKT	0.035	0.029	-9999	-10000	0	0
FOXO3	0.016	0	-9999	-10000	0	0
AKT1	0.016	0	-9999	-10000	0	0
FOXO1	0.016	0	-9999	-10000	0	0
AKT3	0.016	0	-9999	-10000	0	0
FOXO4	0.016	0	-9999	-10000	0	0
MET	0.007	0.085	-9999	-0.86	5	5
PIK3CA	0.014	0.033	-9999	-0.74	1	1
PIK3CB	0.016	0	-9999	-10000	0	0
NRAS	0.016	0	-9999	-10000	0	0
PIK3CG	0.011	0.066	-9999	-0.86	3	3
PIK3R3	0.016	0	-9999	-10000	0	0
PIK3R2	0.016	0	-9999	-10000	0	0
NF1	0.016	0	-9999	-10000	0	0
RAS	-0.041	0.097	-9999	-0.38	5	5
ERBB2	0.013	0.046	-9999	-0.74	2	2
proliferation/survival/translation	-0.041	0.013	-9999	-10000	0	0
PI3K	-0.022	0.092	-9999	-0.28	7	7
PIK3R1	0.014	0.033	-9999	-0.74	1	1
KRAS	0.016	0	-9999	-10000	0	0
FOXO	0.041	0.034	-9999	-10000	0	0
AKT2	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.012	0.036	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.036	0.097	-9999	-0.48	7	7
JUN	0.025	0.12	-9999	-0.56	8	8
HRAS	0.014	0.038	-9999	-0.86	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.052	0.16	-9999	-0.7	11	11
RAP1A	0.016	0	-9999	-10000	0	0
FRS2	0.016	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.052	0.16	-9999	-0.5	47	47
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.041	0.13	-9999	-0.46	47	47
RHOA	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.046	0.14	-9999	-0.67	9	9
GRB7	0.006	0.086	-9999	-0.74	7	7
RET51/GFRalpha1/GDNF	-0.052	0.16	-9999	-0.7	11	11
MAPKKK cascade	-0.041	0.12	-9999	-0.7	6	6
BCAR1	0.014	0.033	-9999	-0.74	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.04	0.13	-9999	-0.46	46	46
lamellipodium assembly	-0.034	0.091	-9999	-0.44	7	7
RET51/GFRalpha1/GDNF/SHC	-0.053	0.16	-9999	-0.69	12	12
PIK3CA	0.014	0.033	-9999	-0.74	1	1
RET9/GFRalpha1/GDNF/SHC	-0.038	0.13	-9999	-0.46	44	44
RET9/GFRalpha1/GDNF/Shank3	-0.037	0.12	-9999	-0.46	43	43
MAPK3	0.006	0.15	-9999	-0.77	5	5
DOK1	0.016	0	-9999	-10000	0	0
DOK6	-0.001	0.11	-9999	-0.74	12	12
PXN	0.016	0	-9999	-10000	0	0
neurite development	-0.042	0.13	-9999	-0.73	5	5
DOK5	-0.006	0.13	-9999	-0.76	15	15
GFRA1	-0.042	0.2	-9999	-0.75	40	40
MAPK8	0.014	0.12	-9999	-0.6	8	8
HRAS/GTP	-0.048	0.14	-9999	-0.84	6	6
tube development	-0.034	0.12	-9999	-0.5	6	6
MAPK1	0.006	0.15	-9999	-0.77	5	5
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.024	0.082	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PDLIM7	0.009	0.076	-9999	-0.86	4	4
RET51/GFRalpha1/GDNF/Dok6	-0.058	0.17	-9999	-0.87	12	12
SHC1	0.014	0.038	-9999	-0.86	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.052	0.16	-9999	-0.7	11	11
RET51/GFRalpha1/GDNF/Dok5	-0.064	0.19	-9999	-0.8	19	19
PRKCA	0.016	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.029	-9999	-0.68	1	1
CREB1	-0.032	0.098	-9999	-0.53	5	5
PIK3R1	0.014	0.033	-9999	-0.74	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.025	0.083	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Grb7	-0.058	0.18	-9999	-0.79	14	14
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.012	0.14	-9999	-0.76	19	19
DOK4	0.016	0	-9999	-10000	0	0
JNK cascade	0.025	0.11	-9999	-0.54	8	8
RET9/GFRalpha1/GDNF/FRS2	-0.037	0.12	-9999	-0.46	43	43
SHANK3	0.016	0	-9999	-10000	0	0
RASA1	0.014	0.033	-9999	-0.74	1	1
NCK1	0.014	0.033	-9999	-0.74	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.025	0.083	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.034	0.1	-9999	-0.6	5	5
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.036	0.11	-9999	-0.6	6	6
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.036	0.11	-9999	-0.77	5	5
PI3K	-0.051	0.14	-9999	-0.73	7	7
SOS1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.034	0.12	-9999	-0.5	6	6
GRB10	0.016	0	-9999	-10000	0	0
activation of MAPKK activity	-0.031	0.092	-9999	-0.52	5	5
RET51/GFRalpha1/GDNF/FRS2	-0.052	0.16	-9999	-0.7	11	11
GAB1	0.016	0	-9999	-10000	0	0
IRS1	0.01	0.066	-9999	-0.74	4	4
IRS2	0.002	0.11	-9999	-0.86	8	8
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.036	0.11	-9999	-0.77	5	5
RET51/GFRalpha1/GDNF/PKC alpha	-0.052	0.16	-9999	-0.7	11	11
GRB2	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GDNF	0.001	0.066	-9999	-0.86	3	3
RAC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.055	0.16	-9999	-0.72	12	12
Rac1/GTP	-0.04	0.11	-9999	-0.54	7	7
RET9/GFRalpha1/GDNF	-0.041	0.14	-9999	-0.51	43	43
GFRalpha1/GDNF	-0.047	0.16	-9999	-0.58	43	43

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.003	0.1	0.8	8	-10000	0	8
PI3K Class IB/PDE3B	0.003	0.1	-10000	0	-0.8	8	8
PDE3B	0.003	0.1	-10000	0	-0.8	8	8

×

Signaling events mediated by PRL

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
CCNE1	0.002	0.11	-10000	0	-0.86	8	8
mol:Halofuginone	0.007	0.001	-10000	0	-10000	0	0
ITGA1	0.016	0	-10000	0	-10000	0	0
CDKN1A	0.04	0.035	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	-0.024	0.12	-10000	0	-0.66	19	19
mol:Ca2+	-0.016	0.16	0.4	19	-0.65	25	44
AGT	-0.024	0.18	-10000	0	-0.82	25	25
CCNA2	-0.055	0.23	-10000	0	-0.88	7	7
TUBA1B	0.016	0	-10000	0	-10000	0	0
EGR1	0.019	0.086	-10000	0	-0.55	12	12
CDK2/Cyclin E1	-0.01	0.063	-10000	0	-0.49	8	8
MAPK3	0.006	0.13	-10000	0	-0.66	19	19
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.13	-10000	0	-0.66	19	19
PTP4A1	0.041	0.069	-10000	0	-10000	0	0
PTP4A3	-0.016	0.16	-10000	0	-0.86	19	19
PTP4A2	0.016	0	-10000	0	-10000	0	0
ITGB1	0.006	0.13	-10000	0	-0.66	19	19
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.03	0.062	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	-0.002	0.034	-10000	0	-0.56	2	2
PRL-1/ATF-5	0.042	0.075	-10000	0	-10000	0	0
RABGGTA	0.013	0.046	-10000	0	-0.74	2	2
BCAR1	0.013	0.079	0.4	19	-0.58	1	20
RHOC	0.03	0.062	-10000	0	-10000	0	0
RHOA	0.03	0.062	-10000	0	-10000	0	0
cell motility	0.035	0.064	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.045	0.064	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.024	0.12	-10000	0	-0.66	19	19
ROCK1	0.036	0.065	-10000	0	-10000	0	0
RABGGTB	0.016	0	-10000	0	-10000	0	0
CDK2	0.016	0	-10000	0	-10000	0	0
mitosis	0.041	0.068	-10000	0	-10000	0	0
ATF5	0.011	0.066	-10000	0	-0.86	3	3

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.075	0.074	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
RIP2/NOD2	-0.16	0.28	-9999	-0.67	124	124
NFKBIA	0.063	0.02	-9999	-10000	0	0
BIRC2	0.016	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
RIPK2	0.014	0.038	-9999	-0.86	1	1
IKBKG	-0.046	0.084	-9999	-10000	0	0
IKK complex/A20	-0.041	0.079	-9999	-0.59	2	2
NEMO/A20/RIP2	0.014	0.038	-9999	-0.86	1	1
XPO1	0.016	0	-9999	-10000	0	0
NEMO/ATM	-0.042	0.077	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.034	0.062	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.19	0.37	-9999	-0.86	124	124
NFKB1	0.019	0.033	-9999	-0.73	1	1
RELA	0.02	0	-9999	-10000	0	0
MALT1	0.016	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.014	0.033	-9999	-0.74	1	1
TNF/TNFR1A	-0.009	0.075	-9999	-0.61	8	8
TRAF6	0.016	0	-9999	-10000	0	0
PRKCA	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
UBE2D3	0.016	0	-9999	-10000	0	0
TNF	0.003	0.1	-9999	-0.8	8	8
NF kappa B1 p50/RelA	-0.001	0.02	-9999	-10000	0	0
BCL10	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.063	0.02	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.02	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
IKK complex	-0.038	0.07	-9999	-10000	0	0
CYLD	0.016	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.035	0.064	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.006	0.034	-10000	0	-10000	0	0
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.016	0	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
STXBP4	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.066	0.09	0.32	36	-0.36	2	38
YWHAZ	0.016	0	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
TBC1D4	0.031	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
ASIP	-0.072	0.26	-10000	0	-0.86	51	51
PRKCI	0.016	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.016	0	-10000	0	-10000	0	0
GYS1	0.043	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.057	-10000	0	-0.74	3	3
TRIP10	0.016	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.033	0.083	-10000	0	-10000	0	0
VAMP2	0.016	0	-10000	0	-10000	0	0
SLC2A4	0.068	0.094	0.33	36	-0.4	2	38
STX4	0.016	0	-10000	0	-10000	0	0
GSK3B	0.034	0	-10000	0	-10000	0	0
SFN	-0.083	0.27	-10000	0	-0.83	62	62
LNPEP	0.013	0.046	-10000	0	-0.74	2	2
YWHAE	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.014	0.033	-10000	0	-0.74	1	1
HDAC4	0.016	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.025	0.043	0.67	2	-10000	0	2
CDKN1A	-0.002	0.04	-10000	0	-0.65	2	2
KAT2B	0.014	0.033	-10000	0	-0.74	1	1
BAX	0.016	0	-10000	0	-10000	0	0
FOXO3	0.001	0.023	0.53	1	-10000	0	1
FOXO1	0.016	0	-10000	0	-10000	0	0
FOXO4	0.03	0.016	-10000	0	-0.33	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
TAT	-0.006	0.12	-10000	0	-0.86	11	11
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.018	0.16	-10000	0	-0.66	30	30
PPARGC1A	-0.057	0.22	-10000	0	-0.74	51	51
FHL2	0.008	0.076	-10000	0	-0.77	5	5
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.008	-10000	0	-10000	0	0
HIST2H4A	0.025	0.043	-10000	0	-0.67	2	2
SIRT1/FOXO3a	0.001	0.016	0.32	1	-10000	0	1
SIRT1	0.001	0.01	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.008	-10000	0	-10000	0	0
SIRT1/Histone H1b	0	0.019	-10000	0	-10000	0	0
apoptosis	0	0.008	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.046	0.14	-10000	0	-0.48	51	51
p53/SIRT1	0.001	0.023	0.38	2	-10000	0	2
SIRT1/FOXO4	0	0.015	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.004	0.045	-10000	0	-0.46	5	5
HIST1H1E	0.029	0.022	-10000	0	-0.32	2	2
SIRT1/p300	-0.001	0.026	-10000	0	-0.56	1	1
muscle cell differentiation	0.032	0.13	0.57	30	-10000	0	30
TP53	0.001	0.01	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.008	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
MEF2D	0.016	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.013	0.095	-10000	0	-0.67	11	11
ACSS2	0.027	0.005	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.032	0.13	-10000	0	-0.57	30	30

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.011	0.057	-9999	-0.74	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.004	0.029	-9999	-10000	0	0
IRAK/TOLLIP	0	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.087	0.22	-9999	-0.62	74	74
IL1A	-0.009	0.14	-9999	-0.86	14	14
IL1B	0.023	0.072	-9999	-0.65	6	6
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.026	-9999	-10000	0	0
IL1R2	-0.078	0.26	-9999	-0.79	62	62
IL1R1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.003	0.025	-9999	-10000	0	0
TOLLIP	0.016	0	-9999	-10000	0	0
TICAM2	0.016	0.001	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.04	0.046	-9999	-10000	0	0
JUN	0.059	0.037	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.01	0.069	-9999	-0.77	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.018	0.094	-9999	-0.52	17	17
PIK3R1	0.014	0.033	-9999	-0.74	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.016	0.087	-9999	-0.5	1	1
IL1 beta fragment/IL1R1/IL1RAP	-0.009	0.068	-9999	-0.52	8	8
NFKB1	0.014	0.033	-9999	-0.74	1	1
MAPK8	0.05	0.039	-9999	-10000	0	0
IRAK1	0.03	0.006	-9999	-10000	0	0
IL1RN/IL1R1	-0.021	0.12	-9999	-0.66	17	17
IRAK4	0.016	0	-9999	-10000	0	0
PRKCI	0.016	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
PI3K	-0.002	0.034	-9999	-0.56	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.004	0.031	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.009	0.068	-9999	-0.52	8	8
IL1 beta/IL1R2	-0.066	0.17	-9999	-0.52	68	68
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.009	0.069	-9999	-1	1	1
IRAK3	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.008	0.06	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.009	0.05	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP	-0.019	0.1	-9999	-0.57	18	18
RELA	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.016	0	-9999	-10000	0	0
MYD88	0.016	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0	0	-9999	-10000	0	0
IL1RAP	0.009	0.073	-9999	-0.83	4	4
UBE2N	0.016	0	-9999	-10000	0	0
IRAK/TRAF6	-0.007	0.048	-9999	-10000	0	0
CASP1	0.016	0	-9999	-10000	0	0
IL1RN/IL1R2	-0.091	0.22	-9999	-0.62	77	77
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.009	0.064	-9999	-10000	0	0
TMEM189-UBE2V1	0.007	0.008	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.006	0.034	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
IL1RN	-0.012	0.16	-9999	-0.86	17	17
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.042	0.032	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.016	0	-10000	0	-10000	0	0
EPHB2	0	0.11	-10000	0	-0.77	11	11
EFNB1	0.014	0.11	-10000	0	-0.66	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.022	0.11	-10000	0	-0.79	5	5
Ephrin B2/EPHB1-2	-0.013	0.085	-10000	0	-0.53	13	13
neuron projection morphogenesis	-0.021	0.1	-10000	0	-0.75	5	5
Ephrin B1/EPHB1-2/Tiam1	-0.024	0.12	-10000	0	-0.86	5	5
DNM1	-0.006	0.14	-10000	0	-0.86	13	13
cell-cell signaling	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	0.023	0.092	-10000	0	-0.67	9	9
YES1	-0.015	0.12	-10000	0	-0.89	9	9
Ephrin B1/EPHB1-2/NCK2	-0.024	0.11	-10000	0	-0.87	4	4
PI3K	-0.011	0.096	-10000	0	-0.69	10	10
mol:GDP	-0.024	0.12	-10000	0	-0.84	5	5
ITGA2B	-0.016	0.16	-10000	0	-0.86	19	19
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.015	0.12	-10000	0	-0.89	9	9
MAP3K7	-0.012	0.093	-10000	0	-0.71	9	9
FGR	-0.015	0.12	-10000	0	-0.89	9	9
TIAM1	0.014	0.033	-10000	0	-0.74	1	1
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
RGS3	0.016	0	-10000	0	-10000	0	0
cell adhesion	0.016	0.15	-10000	0	-0.66	14	14
LYN	-0.015	0.12	-10000	0	-0.89	9	9
Ephrin B1/EPHB1-2/Src Family Kinases	-0.015	0.11	-10000	0	-0.84	9	9
Ephrin B1/EPHB1-2	-0.015	0.1	-10000	0	-0.78	9	9
SRC	-0.015	0.12	-10000	0	-0.89	9	9
ITGB3	0.007	0.08	-10000	0	-0.74	6	6
EPHB1	0.009	0.071	-10000	0	-0.8	4	4
EPHB4	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.03	0.14	-10000	0	-0.66	24	24
BLK	-0.022	0.12	-10000	0	-0.88	9	9
HCK	-0.021	0.12	-10000	0	-0.93	9	9
regulation of stress fiber formation	0.023	0.11	0.85	4	-10000	0	4
MAPK8	0.031	0.091	-10000	0	-0.63	9	9
Ephrin B1/EPHB1-2/RGS3	-0.024	0.11	-10000	0	-0.87	4	4
endothelial cell migration	-0.009	0.08	-10000	0	-0.61	9	9
NCK2	0.016	0	-10000	0	-10000	0	0
PTPN13	-0.01	0.11	-10000	0	-0.85	9	9
regulation of focal adhesion formation	0.023	0.11	0.85	4	-10000	0	4
chemotaxis	0.023	0.11	0.85	4	-10000	0	4
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
Rac1/GTP	-0.022	0.11	-10000	0	-0.78	5	5
angiogenesis	-0.015	0.1	-10000	0	-0.77	9	9
LCK	-0.02	0.12	-10000	0	-0.9	9	9

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-10000	0	-10000	0	0
TRAF2/ASK1	0	0	-10000	0	-10000	0	0
ATM	0.014	0.033	-10000	0	-0.74	1	1
MAP2K3	0.038	0.044	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.049	0.045	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.002	0.12	-10000	0	-0.85	11	11
TXN	0.011	0	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
GADD45A	0.016	0	-10000	0	-10000	0	0
GADD45B	0.016	0	-10000	0	-10000	0	0
MAP3K1	0.016	0	-10000	0	-10000	0	0
MAP3K6	0.014	0.033	-10000	0	-0.74	1	1
MAP3K7	0.016	0	-10000	0	-10000	0	0
MAP3K4	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.001	0.024	-10000	0	-0.56	1	1
TAK1/TAB family	0.001	0.012	0.2	2	-10000	0	2
RAC1/OSM/MEKK3	0	0	-10000	0	-10000	0	0
TRAF2	0.016	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.004	0.014	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.099	0.27	-10000	0	-0.76	79	79
CCM2	0.016	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.074	0.18	-10000	0	-0.49	79	79
MAPK11	0.012	0.054	-10000	0	-0.86	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.066	0.16	-10000	0	-0.44	79	79
OSM/MEKK3	0	0	-10000	0	-10000	0	0
TAOK1	0.016	0.053	-10000	0	-0.41	8	8
TAOK2	0.022	0.019	-10000	0	-0.41	1	1
TAOK3	0.022	0.019	-10000	0	-0.41	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.016	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.016	0	-10000	0	-10000	0	0
MAP3K10	0.014	0.033	-10000	0	-0.74	1	1
MAP3K3	0.016	0	-10000	0	-10000	0	0
TRX/ASK1	0	0	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	-0.01	0.07	-10000	0	-0.5	10	10

×

ErbB2/ErbB3 signaling events

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
USP8	0.028	0.003	-10000	0	-10000	0	0
RAS family/GTP	-0.015	0.073	-10000	0	-0.72	3	3
NFATC4	0.047	0.077	-10000	0	-0.54	2	2
ERBB2IP	0.008	0.008	-10000	0	-10000	0	0
HSP90 (dimer)	0.016	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.018	0.077	-10000	0	-0.64	1	1
JUN	0.037	0.079	-10000	0	-0.41	2	2
HRAS	0.013	0.038	-10000	0	-0.86	1	1
DOCK7	0.02	0.091	-10000	0	-0.62	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.022	0.1	-10000	0	-0.87	2	2
AKT1	0.016	0.002	-10000	0	-10000	0	0
BAD	0.026	0.035	-10000	0	-0.54	2	2
MAPK10	-0.011	0.044	-10000	0	-0.39	1	1
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.019	0.083	-10000	0	-0.72	1	1
RAF1	0.04	0.095	-10000	0	-0.68	3	3
ErbB2/ErbB3/neuregulin 2	-0.019	0.095	-10000	0	-0.48	21	21
STAT3	0	0.002	-10000	0	-10000	0	0
cell migration	0.059	0.057	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	-0.085	0.26	-10000	0	-0.6	9	9
FOS	-0.035	0.19	-10000	0	-0.51	12	12
NRAS	0.015	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.018	0.077	-10000	0	-0.64	1	1
MAPK3	-0.055	0.21	-10000	0	-0.56	8	8
MAPK1	-0.055	0.21	-10000	0	-0.74	2	2
JAK2	0.021	0.088	-10000	0	-0.6	1	1
NF2	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.006	0.09	-10000	0	-0.45	8	8
NRG1	-0.015	0.13	-10000	0	-0.74	17	17
GRB2/SOS1	0	0	-10000	0	-10000	0	0
MAPK8	0.024	0.086	-10000	0	-0.47	3	3
MAPK9	-0.008	0.036	-10000	0	-10000	0	0
ERBB2	-0.002	0.035	-10000	0	-0.58	2	2
ERBB3	-0.004	0.098	-10000	0	-0.74	9	9
SHC1	0.008	0.039	-10000	0	-0.86	1	1
RAC1	0.016	0	-10000	0	-10000	0	0
apoptosis	0.002	0.022	0.35	2	-10000	0	2
STAT3 (dimer)	0	0.002	-10000	0	-10000	0	0
RNF41	0.038	0.005	-10000	0	-10000	0	0
FRAP1	0.014	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.012	0.052	-10000	0	-0.41	2	2
ErbB2/ErbB2/HSP90 (dimer)	-0.002	0.03	-10000	0	-0.49	2	2
CHRNA1	-0.13	0.28	-10000	0	-0.45	227	227
myelination	0.05	0.074	-10000	0	-0.48	2	2
PPP3CB	0.02	0.082	-10000	0	-0.55	1	1
KRAS	0.015	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.014	0.069	-10000	0	-0.72	2	2
NRG2	-0.001	0.12	-10000	0	-0.85	10	10
mol:GDP	0.007	0.089	-10000	0	-0.45	8	8
SOS1	0.009	0.008	-10000	0	-10000	0	0
MAP2K2	0.046	0.097	-10000	0	-0.7	2	2
SRC	0.016	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.02	0.087	-10000	0	-0.6	1	1
MAP2K1	-0.039	0.18	-10000	0	-0.57	8	8
heart morphogenesis	-0.018	0.077	-10000	0	-0.64	1	1
RAS family/GDP	-0.015	0.073	-10000	0	-0.72	3	3
GRB2	0.009	0.008	-10000	0	-10000	0	0
PRKACA	-0.001	0.005	-10000	0	-10000	0	0
CHRNE	0.021	0.026	-10000	0	-0.24	2	2
HSP90AA1	0.016	0	-10000	0	-10000	0	0
activation of caspase activity	-0.016	0.002	-10000	0	-10000	0	0
nervous system development	-0.018	0.077	-10000	0	-0.64	1	1
CDC42	0.016	0	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.02	0.17	-10000	0	-0.72	27	27
regulation of axonogenesis	-0.033	0.034	-10000	0	-10000	0	0
myoblast fusion	0.016	0.07	0.32	27	-10000	0	27
mol:GTP	-0.01	0.043	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.01	0.047	0.49	2	-10000	0	2
ARF1/GTP	-0.007	0.029	-10000	0	-10000	0	0
mol:GM1	0.007	0.035	-10000	0	-10000	0	0
mol:Choline	0.033	0.031	-10000	0	-10000	0	0
lamellipodium assembly	-0.016	0.073	-10000	0	-0.33	27	27
MAPK3	0.024	0.069	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.01	0.047	-10000	0	-0.5	2	2
ARF1	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	-0.016	0.07	-10000	0	-0.32	27	27
ARF1/GDP	0.02	0.07	-10000	0	-10000	0	0
ARF6	0.009	0.024	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
TIAM1	0.016	0.033	-10000	0	-0.74	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.024	0.069	-10000	0	-10000	0	0
actin filament bundle formation	0.014	0.062	-10000	0	-10000	0	0
KALRN	-0.012	0.055	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	-0.001	0.024	-10000	0	-0.56	1	1
RhoA/GDP	-0.014	0.062	-10000	0	-10000	0	0
NME1	0.016	0.038	-10000	0	-0.86	1	1
Rac1/GDP	-0.014	0.062	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.01	0.043	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.016	0.074	-10000	0	-0.33	27	27
RAC1	0.016	0	-10000	0	-10000	0	0
liver development	-0.01	0.043	-10000	0	-10000	0	0
ARF6/GTP	-0.01	0.043	-10000	0	-10000	0	0
RhoA/GTP	-0.007	0.029	-10000	0	-10000	0	0
mol:GDP	-0.016	0.071	-10000	0	-0.32	27	27
ARF6/GTP/RAB11FIP3/RAB11A	-0.006	0.029	-10000	0	-0.45	1	1
RHOA	0.016	0	-10000	0	-10000	0	0
PLD1	0.021	0.035	-10000	0	-10000	0	0
RAB11FIP3	0.014	0.033	-10000	0	-0.74	1	1
tube morphogenesis	-0.016	0.073	-10000	0	-0.33	27	27
ruffle organization	0.033	0.034	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.01	0.043	-10000	0	-10000	0	0
PLD2	0.021	0.035	-10000	0	-10000	0	0
PIP5K1A	0.033	0.034	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.033	0.031	-10000	0	-10000	0	0
Rac1/GTP	-0.016	0.074	-10000	0	-0.33	27	27

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.035	0.056	-9999	-0.49	6	6
SNTA1	0.013	0.05	-9999	-0.8	2	2
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.036	0.05	-9999	-0.47	5	5
MAPK12	0.028	0.084	-9999	-0.49	13	13
CCND1	0.014	0.07	-9999	-0.3	20	20
p38 gamma/SNTA1	0.033	0.088	-9999	-0.51	11	11
MAP2K3	0.016	0	-9999	-10000	0	0
PKN1	0.016	0	-9999	-10000	0	0
G2/M transition checkpoint	0.028	0.083	-9999	-0.49	13	13
MAP2K6	0.03	0.041	-9999	-0.47	3	3
MAPT	0.032	0.069	-9999	-0.49	6	6
MAPK13	0.025	0.057	-9999	-0.56	5	5
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.022	0.018	-9999	-0.39	1	1

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.016	0	-10000	0	-10000	0	0
Rac1/GDP	0.002	0.013	-10000	0	-10000	0	0
DOCK1	0.014	0.033	-10000	0	-0.74	1	1
ITGA4	-0.011	0.15	-10000	0	-0.86	16	16
RAC1	0.016	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.02	0.11	-10000	0	-0.66	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.017	0.098	-10000	0	-0.57	16	16
alpha4/beta7 Integrin/Paxillin	-0.016	0.089	-10000	0	-0.52	16	16
lamellipodium assembly	-0.001	0.043	-10000	0	-0.77	1	1
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
PI3K	-0.002	0.034	-10000	0	-0.56	2	2
ARF6	0.016	0	-10000	0	-10000	0	0
TLN1	0.016	0	-10000	0	-10000	0	0
PXN	0.031	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
ARF6/GTP	-0.013	0.075	-10000	0	-10000	0	0
cell adhesion	-0.014	0.082	-10000	0	-0.48	16	16
CRKL/CBL	-0.001	0.024	-10000	0	-0.56	1	1
alpha4/beta1 Integrin/Paxillin	-0.016	0.089	-10000	0	-0.52	16	16
ITGB1	0.016	0	-10000	0	-10000	0	0
ITGB7	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	0.002	0.013	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.027	0.11	-10000	0	-0.49	25	25
p130Cas/Crk/Dock1	-0.002	0.029	-10000	0	-0.47	2	2
VCAM1	-0.006	0.13	-10000	0	-0.82	14	14
alpha4/beta1 Integrin/Paxillin/Talin	-0.015	0.083	-10000	0	-0.49	16	16
alpha4/beta1 Integrin/Paxillin/GIT1	-0.015	0.083	-10000	0	-0.49	16	16
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
mol:GDP	0.014	0.082	0.48	16	-10000	0	16
CBL	0.014	0.033	-10000	0	-0.74	1	1
PRKACA	0.016	0	-10000	0	-10000	0	0
GIT1	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.015	0.083	-10000	0	-0.49	16	16
Rac1/GTP	-0.001	0.05	-10000	0	-0.93	1	1

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.016	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.014	0.069	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.013	0.078	-9999	-0.48	14	14
POMC	0.012	0.05	-9999	-0.8	2	2
EGFR	0.001	0.11	-9999	-0.85	9	9
Syndecan-3/EGFR	-0.009	0.064	-9999	-0.47	10	10
AGRP	0.007	0.047	-9999	-0.74	2	2
NCSTN	0.016	0	-9999	-10000	0	0
PSENEN	0.016	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
NCAN	-0.01	0.14	-9999	-0.86	13	13
long-term memory	-0.001	0.016	-9999	-10000	0	0
Syndecan-3/IL8	-0.031	0.12	-9999	-0.47	35	35
PSEN1	0.016	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
limb bud formation	-0.001	0.018	-9999	-0.43	1	1
MC4R	-0.01	0.11	-9999	-0.86	9	9
SRC	0.016	0	-9999	-10000	0	0
PTN	-0.012	0.14	-9999	-0.75	19	19
FGFR/FGF/Syndecan-3	-0.001	0.019	-9999	-0.43	1	1
neuron projection morphogenesis	-0.023	0.091	-9999	-10000	0	0
Syndecan-3/AgRP	-0.002	0.03	-9999	-0.4	3	3
Syndecan-3/AgRP/MC4R	-0.01	0.066	-9999	-0.47	9	9
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.001	0.019	-9999	-0.43	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.03	0.12	-9999	-0.46	35	35
IL8	-0.039	0.21	-9999	-0.84	34	34
Syndecan-3/Fyn/Cortactin	-0.001	0.016	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.018	-9999	-0.41	1	1
alpha-MSH/MC4R	-0.014	0.094	-9999	-0.66	11	11
Gamma Secretase	0	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.021	0.1	-9999	-0.51	22	22
KLHL20	-0.013	0.046	-9999	-0.35	2	2
CYFIP2	0.004	0.092	-9999	-0.74	8	8
Rac1/GDP	0.067	0.076	-9999	-10000	0	0
ENAH	-0.021	0.1	-9999	-0.51	22	22
AP1M1	0.016	0	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.015	0.003	-9999	-10000	0	0
CDC42/GTP	-0.01	0.047	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.01	0.036	-9999	-0.22	7	7
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.084	-9999	-10000	0	0
RAPGEF1	0.053	0.099	-9999	-10000	0	0
CTNND1	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.022	0.11	-9999	-0.53	22	22
CRK	0.042	0.11	-9999	-0.47	22	22
E-cadherin/gamma catenin/alpha catenin	-0.022	0.1	-9999	-0.49	24	24
alphaE/beta7 Integrin	0	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
NCKAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	-0.021	0.1	-9999	-0.51	22	22
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.035	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.002	0.03	-9999	-0.48	2	2
PI3K	-0.01	0.044	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.026	0.12	-9999	-0.58	24	24
TIAM1	0.014	0.033	-9999	-0.74	1	1
E-cadherin(dimer)/Ca2+	-0.017	0.08	-9999	-10000	0	0
AKT1	-0.005	0.025	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
CDH1	-0.016	0.15	-9999	-0.74	22	22
RhoA/GDP	0.067	0.076	-9999	-10000	0	0
actin cytoskeleton organization	-0.01	0.034	-9999	-0.24	2	2
CDC42/GDP	0.067	0.076	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.014	0.068	-9999	-0.32	24	24
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.018	0.084	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.017	0.082	-9999	-0.41	22	22
mol:GDP	0.063	0.087	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.011	0.057	-9999	-0.74	3	3
p120 catenin/RhoA/GDP	-0.012	0.06	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.035	0.063	-9999	-0.26	20	20
NME1	0.014	0.038	-9999	-0.86	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.021	0.1	-9999	-0.51	22	22
regulation of cell-cell adhesion	-0.009	0.041	-9999	-10000	0	0
WASF2	-0.005	0.018	-9999	-10000	0	0
Rap1/GTP	-0.011	0.054	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.087	-9999	-0.8	1	1
CCND1	-0.016	0.065	-9999	-0.33	20	20
VAV2	0.049	0.1	-9999	-0.5	1	1
RAP1/GDP	-0.011	0.056	-9999	-10000	0	0
adherens junction assembly	0.032	0.11	-9999	-0.49	22	22
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
PIP5K1C	0.016	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.017	0.081	-9999	-0.77	1	1
E-cadherin/beta catenin	-0.019	0.09	-9999	-0.45	22	22
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.021	0.1	-9999	-0.51	22	22
PIK3CA	0.014	0.033	-9999	-0.74	1	1
Rac1/GTP	-0.021	0.072	-9999	-0.6	1	1
E-cadherin/beta catenin/alpha catenin	-0.02	0.094	-9999	-0.47	22	22
ITGAE	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.023	0.11	-9999	-0.55	22	22

×

Arf6 trafficking 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
SLC2A4	-0.003	0.12	-10000	0	-0.81	12	12
CLTC	0.043	0.014	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.036	0.001	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.001	0.023	-10000	0	-0.53	1	1
EXOC4	0.016	0	-10000	0	-10000	0	0
CD59	0.039	0.009	-10000	0	-10000	0	0
CPE	0	0.12	-10000	0	-0.58	22	22
CTNNB1	0.016	0	-10000	0	-10000	0	0
membrane fusion	0	0	-10000	0	-10000	0	0
CTNND1	0.042	0.023	-10000	0	-0.49	1	1
DNM2	0.016	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.044	0.006	-10000	0	-10000	0	0
TSHR	-0.045	0.2	-10000	0	-0.59	61	61
INS	0.016	0.002	-10000	0	-10000	0	0
BIN1	0.016	0	-10000	0	-10000	0	0
mol:Choline	0	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.026	-10000	0	-0.58	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.023	-10000	0	-0.53	1	1
JUP	0.037	0.023	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.001	0.019	-10000	0	-0.44	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.027	0.056	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	-0.049	0.23	-10000	0	-0.86	39	39
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.016	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.058	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.016	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.007	0.035	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.025	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	-0.043	0.15	-10000	0	-0.59	39	39
ACAP1	-0.019	0.025	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.032	0.015	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.042	0.017	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.016	0	-10000	0	-10000	0	0
exocyst	0	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.042	0.023	-10000	0	-0.49	1	1
NME1	0.024	0.027	-10000	0	-0.59	1	1
clathrin coat assembly	0.042	0.014	-10000	0	-10000	0	0
IL2RA	-0.015	0.11	-10000	0	-10000	0	0
VAMP3	0.025	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.009	0.06	-10000	0	-0.43	7	7
EXOC6	0.016	0	-10000	0	-10000	0	0
PLD1	0	0	-10000	0	-10000	0	0
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.016	0	-10000	0	-10000	0	0
PIP5K1C	0.044	0.006	-10000	0	-10000	0	0
SDC1	0.036	0.031	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.025	-10000	0	-0.58	1	1
EXOC7	0.016	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.007	0.036	-10000	0	-10000	0	0
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
endocytosis	0.001	0.019	0.43	1	-10000	0	1
SCAMP2	0.016	0	-10000	0	-10000	0	0
ADRB2	0.049	0.029	-10000	0	-10000	0	0
EXOC3	0.016	0	-10000	0	-10000	0	0
ASAP2	0.014	0.033	-10000	0	-0.74	1	1
Dynamin 2/GDP	-0.001	0.023	-10000	0	-0.53	1	1
KLC1	0.016	0	-10000	0	-10000	0	0
AVPR2	-0.12	0.21	-10000	0	-0.37	220	220
RALA	0.016	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.006	0.03	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.006	0.064	-9999	-0.66	5	5
CRKL	0.04	0.064	-9999	-0.46	2	2
mol:PIP3	-0.03	0.003	-9999	-10000	0	0
AKT1	0	0.019	-9999	-0.45	1	1
PTK2B	0.016	0	-9999	-10000	0	0
RAPGEF1	0.049	0.061	-9999	-0.43	2	2
RANBP10	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
HGF/MET/SHIP2	-0.028	0.13	-9999	-0.57	26	26
MAP3K5	-0.024	0.12	-9999	-0.41	1	1
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.026	0.12	-9999	-0.61	15	15
AP1	-0.014	0.081	-9999	-0.51	13	13
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0.038	-9999	-0.86	1	1
apoptosis	0.004	0.11	-9999	-0.7	12	12
STAT3 (dimer)	0.041	0.077	-9999	-0.53	3	3
GAB1/CRKL/SHP2/PI3K	-0.011	0.054	-9999	-0.58	2	2
INPP5D	0.009	0.076	-9999	-0.86	4	4
CBL/CRK	0.047	0.067	-9999	-0.51	3	3
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
ELK1	0.001	0.029	-9999	-0.29	5	5
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.008	0.038	-9999	-0.34	2	2
PAK1	0.01	0.019	-9999	-0.41	1	1
HGF/MET/RANBP10	-0.028	0.13	-9999	-0.57	26	26
HRAS	0.032	0.097	-9999	-0.71	3	3
DOCK1	0.048	0.068	-9999	-0.51	3	3
GAB1	0.031	0.067	-9999	-0.44	3	3
CRK	0.04	0.064	-9999	-0.46	2	2
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.022	0.1	-9999	-0.54	14	14
JUN	0.016	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.013	0.059	-9999	-0.4	5	5
PIK3R1	0.014	0.033	-9999	-0.74	1	1
cell morphogenesis	0.079	0.083	-9999	-0.65	2	2
GRB2/SHC	-0.011	0.056	-9999	-0.54	3	3
FOS	-0.003	0.12	-9999	-0.75	13	13
GLMN	0	0	-9999	-10000	0	0
cell motility	0.001	0.029	-9999	-0.29	5	5
HGF/MET/MUC20	-0.028	0.13	-9999	-0.58	26	26
cell migration	-0.011	0.055	-9999	-0.52	3	3
GRB2	0.016	0	-9999	-10000	0	0
CBL	0.014	0.033	-9999	-0.74	1	1
MET/RANBP10	-0.006	0.064	-9999	-0.66	5	5
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.015	0.071	-9999	-0.58	3	3
MET/MUC20	-0.006	0.065	-9999	-0.68	5	5
RAP1B	0.058	0.059	-9999	-10000	0	0
RAP1A	0.058	0.059	-9999	-10000	0	0
HGF/MET/RANBP9	-0.028	0.13	-9999	-0.57	26	26
RAF1	0.041	0.092	-9999	-0.66	3	3
STAT3	-0.014	0.066	-9999	-0.54	3	3
cell proliferation	0.055	0.1	-9999	-0.62	4	4
RPS6KB1	-0.004	0.019	-9999	-10000	0	0
MAPK3	-0.006	0.026	-9999	-0.27	5	5
MAPK1	-0.006	0.026	-9999	-0.27	5	5
RANBP9	0.016	0	-9999	-10000	0	0
MAPK8	0.011	0.1	-9999	-0.56	2	2
SRC	0.042	0.078	-9999	-0.54	3	3
PI3K	-0.012	0.06	-9999	-0.53	4	4
MET/Glomulin	0.009	0.06	-9999	-0.61	5	5
SOS1	0.016	0	-9999	-10000	0	0
MAP2K1	0.05	0.086	-9999	-0.6	3	3
MET	0.007	0.085	-9999	-0.86	5	5
MAP4K1	-0.037	0.12	-9999	-0.4	12	12
PTK2	0.016	0	-9999	-10000	0	0
MAP2K2	0.05	0.088	-9999	-0.6	3	3
BAD	0.008	0.044	-9999	-0.66	2	2
MAP2K4	-0.012	0.11	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.011	0.055	-9999	-0.57	2	2
INPPL1	0.016	0	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
SH3KBP1	0.016	0	-9999	-10000	0	0
HGS	-0.011	0.053	-9999	-0.49	2	2
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.02	0.17	-9999	-0.8	23	23
RASA1	0.014	0.033	-9999	-0.74	1	1
NCK1	0.014	0.033	-9999	-0.74	1	1
PTPRJ	0.016	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.012	0.059	-9999	-0.53	3	3
PDPK1	-0.014	0.021	-9999	-0.49	1	1
HGF/MET/SHIP	-0.032	0.14	-9999	-0.59	29	29

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.058	0.16	-10000	0	-0.49	63	63
cell-cell adhesion	0.014	0.074	0.63	3	-10000	0	3
Ephrin B/EPHB2/RasGAP	-0.015	0.081	-10000	0	-0.8	1	1
ITSN1	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
SHC1	0.014	0.038	-10000	0	-0.86	1	1
Ephrin B1/EPHB3	-0.013	0.079	-10000	0	-0.49	14	14
Ephrin B1/EPHB1	-0.004	0.046	-10000	0	-0.54	4	4
HRAS/GDP	-0.009	0.055	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	-0.014	0.075	-10000	0	-10000	0	0
Endophilin/SYNJ1	0.035	0.086	-10000	0	-0.74	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.009	0.061	-10000	0	-10000	0	0
endothelial cell migration	-0.001	0.024	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
GRB7	0.006	0.086	-10000	0	-0.74	7	7
PAK1	0.047	0.084	-10000	0	-0.76	1	1
HRAS	0.014	0.038	-10000	0	-0.86	1	1
RRAS	0.035	0.087	-10000	0	-0.76	1	1
DNM1	-0.006	0.14	-10000	0	-0.86	13	13
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.042	0.065	-10000	0	-10000	0	0
lamellipodium assembly	-0.014	0.074	-10000	0	-0.63	3	3
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.006	0.038	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
EPHB2	0	0.11	-10000	0	-0.76	11	11
EPHB3	-0.005	0.12	-10000	0	-0.75	14	14
EPHB1	0.01	0.071	-10000	0	-0.8	4	4
EPHB4	0.016	0	-10000	0	-10000	0	0
mol:GDP	-0.004	0.061	-10000	0	-10000	0	0
Ephrin B/EPHB2	-0.015	0.081	-10000	0	-0.6	3	3
Ephrin B/EPHB3	-0.017	0.089	-10000	0	-0.71	3	3
JNK cascade	0.04	0.086	-10000	0	-0.78	2	2
Ephrin B/EPHB1	-0.009	0.062	-10000	0	-0.5	2	2
RAP1/GDP	-0.003	0.053	-10000	0	-10000	0	0
EFNB2	0.016	0	-10000	0	-10000	0	0
EFNB3	0.004	0.092	-10000	0	-0.74	8	8
EFNB1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.013	0.085	-10000	0	-0.53	13	13
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.016	0.082	-10000	0	-0.7	3	3
Rap1/GTP	-0.014	0.074	-10000	0	-0.64	3	3
axon guidance	-0.058	0.16	-10000	0	-0.49	63	63
MAPK3	0.064	0.042	-10000	0	-10000	0	0
MAPK1	0.064	0.042	-10000	0	-10000	0	0
Rac1/GDP	-0.004	0.056	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.011	0.059	-10000	0	-0.49	2	2
CDC42/GDP	-0.004	0.056	-10000	0	-10000	0	0
PI3K	-0.002	0.025	-10000	0	-10000	0	0
EFNA5	-0.059	0.23	-10000	0	-0.75	52	52
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.01	0.057	-10000	0	-0.6	1	1
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	-0.015	0.077	-10000	0	-0.64	4	4
PTK2	0.003	0.018	-10000	0	-10000	0	0
MAP4K4	0.04	0.087	-10000	0	-0.8	2	2
SRC	0.016	0	-10000	0	-10000	0	0
KALRN	0.016	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.012	0.059	-10000	0	-0.5	1	1
MAP2K1	0.056	0.044	-10000	0	-10000	0	0
WASL	0.016	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.014	0.085	-10000	0	-0.63	6	6
cell migration	0.066	0.05	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
SYNJ1	0.035	0.088	-10000	0	-0.76	1	1
PXN	0.016	0	-10000	0	-10000	0	0
TF	-0.075	0.23	-10000	0	-0.79	3	3
HRAS/GTP	-0.016	0.086	-10000	0	-0.71	4	4
Ephrin B1/EPHB1-2	-0.013	0.085	-10000	0	-0.53	13	13
cell adhesion mediated by integrin	0.01	0.064	0.63	2	-10000	0	2
RAC1	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.017	0.087	-10000	0	-0.74	3	3
RAC1-CDC42/GTP	-0.022	0.099	-10000	0	-0.77	5	5
RASA1	0.014	0.033	-10000	0	-0.74	1	1
RAC1-CDC42/GDP	-0.003	0.053	-10000	0	-10000	0	0
ruffle organization	0.069	0.09	-10000	0	-0.64	3	3
NCK1	0.014	0.033	-10000	0	-0.74	1	1
receptor internalization	0.033	0.12	-10000	0	-0.77	2	2
Ephrin B/EPHB2/KALRN	-0.014	0.079	-10000	0	-0.8	1	1
ROCK1	0.022	0.076	-10000	0	-0.44	14	14
RAS family/GDP	-0.011	0.059	-10000	0	-0.53	1	1
Rac1/GTP	-0.015	0.079	-10000	0	-0.68	3	3
Ephrin B/EPHB1/Src/Paxillin	-0.006	0.042	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.01	0.067	-10000	0	-0.5	6	6
ER alpha/Gai/GDP/Gbeta gamma	0.053	0.057	-10000	0	-10000	0	0
AKT1	0.045	0.08	-10000	0	-0.8	4	4
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.04	0.08	-10000	0	-0.73	5	5
mol:Ca2+	-0.015	0.18	-10000	0	-0.68	12	12
IGF1R	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.008	0.07	-10000	0	-0.55	8	8
SHC1	0.014	0.038	-10000	0	-0.86	1	1
apoptosis	-0.045	0.076	0.76	4	-10000	0	4
RhoA/GTP	-0.004	0.04	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.008	0.048	-10000	0	-10000	0	0
regulation of stress fiber formation	-0.066	0.053	0.54	2	-10000	0	2
E2/ERA-ERB (dimer)	-0.012	0.08	-10000	0	-0.54	12	12
KRAS	0.016	0	-10000	0	-10000	0	0
G13/GTP	-0.004	0.045	-10000	0	-0.46	5	5
pseudopodium formation	0.066	0.053	-10000	0	-0.54	2	2
E2/ER alpha (dimer)/PELP1	-0.005	0.049	-10000	0	-0.5	5	5
GRB2	0.016	0	-10000	0	-10000	0	0
GNG2	0.016	0	-10000	0	-10000	0	0
GNAO1	0.008	0.083	-10000	0	-0.84	5	5
HRAS	0.014	0.038	-10000	0	-0.86	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.062	0.064	-10000	0	-0.46	5	5
E2/ER beta (dimer)	-0.009	0.074	-10000	0	-0.65	7	7
mol:GDP	-0.01	0.063	-10000	0	-0.47	5	5
mol:NADP	0.062	0.064	-10000	0	-0.46	5	5
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
mol:IP3	-0.018	0.19	-10000	0	-0.72	12	12
IGF-1R heterotetramer	0.016	0	-10000	0	-10000	0	0
PLCB1	-0.025	0.099	-10000	0	-0.58	9	9
PLCB2	-0.067	0.16	-10000	0	-0.48	64	64
IGF1	0.006	0.093	-10000	0	-0.86	6	6
mol:L-citrulline	0.062	0.064	-10000	0	-0.46	5	5
RHOA	0.016	0	-10000	0	-10000	0	0
Gai/GDP	-0.007	0.047	-10000	0	-0.63	1	1
JNK cascade	-0.008	0.074	-10000	0	-0.64	7	7
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
ESR2	0.004	0.096	-10000	0	-0.83	7	7
GNAQ	0.016	0	-10000	0	-10000	0	0
ESR1	0.008	0.076	-10000	0	-0.77	5	5
Gq family/GDP/Gbeta gamma	-0.016	0.074	-10000	0	-0.49	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.051	0.035	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.008	0.049	-10000	0	-10000	0	0
GNAZ	0.011	0.057	-10000	0	-0.74	3	3
E2/ER alpha (dimer)	-0.006	0.057	-10000	0	-0.59	5	5
STRN	0.01	0.066	-10000	0	-0.74	4	4
GNAL	0.016	0	-10000	0	-10000	0	0
PELP1	0.016	0	-10000	0	-10000	0	0
MAPK11	0.015	0.076	-10000	0	-0.56	9	9
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.057	-10000	0	-0.74	3	3
HBEGF	-0.041	0.14	-10000	0	-0.5	7	7
cAMP biosynthetic process	-0.01	0.065	-10000	0	-0.43	12	12
SRC	0.062	0.055	-10000	0	-10000	0	0
PI3K	-0.002	0.034	-10000	0	-0.56	2	2
GNB1	0.016	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.008	0.054	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.01	0.051	-10000	0	-10000	0	0
Gs family/GTP	-0.01	0.066	-10000	0	-0.44	12	12
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.023	-10000	0	-0.53	1	1
vasodilation	0.062	0.062	-10000	0	-0.44	5	5
mol:DAG	-0.018	0.19	-10000	0	-0.72	12	12
Gs family/GDP/Gbeta gamma	-0.008	0.049	-10000	0	-10000	0	0
MSN	0.068	0.057	-10000	0	-0.59	2	2
Gq family/GTP	-0.019	0.077	-10000	0	-0.46	10	10
mol:PI-3-4-5-P3	0.04	0.077	-10000	0	-0.7	5	5
NRAS	0.016	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.062	0.062	0.44	5	-10000	0	5
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.009	0.058	-10000	0	-0.45	4	4
NOS3	0.063	0.067	-10000	0	-0.48	5	5
GNA11	0.011	0.057	-10000	0	-0.74	3	3
MAPKKK cascade	0.07	0.075	-10000	0	-0.58	5	5
E2/ER alpha (dimer)/PELP1/Src	-0.008	0.049	-10000	0	-0.47	4	4
ruffle organization	0.066	0.053	-10000	0	-0.54	2	2
ROCK2	-0.006	0.055	-10000	0	-0.68	2	2
GNA14	0.006	0.086	-10000	0	-0.74	7	7
GNA15	-0.011	0.15	-10000	0	-0.86	16	16
GNA13	0.016	0	-10000	0	-10000	0	0
MMP9	-0.16	0.25	-10000	0	-0.66	8	8
MMP2	0.065	0.081	-10000	0	-0.66	3	3

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.049	0.12	-9999	-0.68	5	5
MAP3K8	0.013	0.054	-9999	-0.86	2	2
FOS	0.041	0.11	-9999	-0.57	5	5
PRKCA	0.017	0.003	-9999	-10000	0	0
PTPN7	-0.038	0.22	-9999	-0.86	34	34
HRAS	0.014	0.038	-9999	-0.86	1	1
PRKCB	0.009	0.082	-9999	-0.82	5	5
NRAS	0.016	0.001	-9999	-10000	0	0
RAS family/GTP	-0.001	0.023	-9999	-0.53	1	1
MAPK3	0.029	0.085	-9999	-0.52	3	3
MAP2K1	0.055	0.055	-9999	-0.48	5	5
ELK1	0.017	0.003	-9999	-10000	0	0
BRAF	-0.004	0.043	-9999	-0.46	4	4
mol:GTP	0	0.001	-9999	-0.006	12	12
MAPK1	0.029	0.085	-9999	-0.52	3	3
RAF1	-0.004	0.043	-9999	-0.46	4	4
KRAS	0.016	0.001	-9999	-10000	0	0

×

BARD1 signaling events

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
BARD1/CSTF1	-0.004	0.048	-10000	0	-0.56	4	4
ATM	0.014	0.033	-10000	0	-0.74	1	1
UBE2D3	0.016	0	-10000	0	-10000	0	0
PRKDC	0.016	0	-10000	0	-10000	0	0
ATR	0.016	0	-10000	0	-10000	0	0
UBE2L3	0.016	0	-10000	0	-10000	0	0
FANCD2	0.034	0.019	-10000	0	-0.4	1	1
protein ubiquitination	-0.011	0.074	-10000	0	-0.87	1	1
XRCC5	0.016	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.016	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.034	0.068	-10000	0	-0.52	1	1
FANCF	0.016	0	-10000	0	-10000	0	0
BRCA1	0.016	0	-10000	0	-10000	0	0
CCNE1	0.002	0.11	-10000	0	-0.86	8	8
CDK2/Cyclin E1	-0.01	0.081	-10000	0	-0.66	8	8
FANCG	0.016	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.048	-10000	0	-0.56	4	4
FANCE	0.014	0.038	-10000	0	-0.86	1	1
FANCC	0.016	0	-10000	0	-10000	0	0
NBN	0.016	0	-10000	0	-10000	0	0
FANCA	-0.17	0.36	-10000	0	-0.86	111	111
DNA repair	0.044	0.13	-10000	0	-0.67	5	5
BRCA1/BARD1/ubiquitin	-0.004	0.048	-10000	0	-0.56	4	4
BARD1/DNA-PK	-0.003	0.037	-10000	0	-10000	0	0
FANCL	0.016	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.004	0.048	0.56	4	-10000	0	4
BRCA1/BARD1/CTIP/M/R/N Complex	-0.004	0.041	-10000	0	-0.78	1	1
BRCA1/BACH1/BARD1/TopBP1	-0.004	0.041	-10000	0	-0.47	4	4
BRCA1/BARD1/P53	-0.003	0.037	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	-0.004	0.041	-10000	0	-0.47	4	4
BRCA1/BACH1	0.016	0	-10000	0	-10000	0	0
BARD1	0.01	0.066	-10000	0	-0.74	4	4
PCNA	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.004	0.041	-10000	0	-0.47	4	4
BRCA1/BARD1/UbcH7	-0.004	0.041	-10000	0	-0.47	4	4
BRCA1/BARD1/RAD51/PCNA	-0.017	0.091	-10000	0	-0.52	14	14
BARD1/DNA-PK/P53	-0.003	0.034	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.048	-10000	0	-0.56	4	4
BRCA1/BARD1/CTIP	-0.005	0.052	-10000	0	-0.86	1	1
FA complex	-0.057	0.11	-10000	0	-0.57	1	1
BARD1/EWS	-0.004	0.048	-10000	0	-0.56	4	4
RBBP8	0.029	0.045	-10000	0	-1	1	1
TP53	0.016	0	-10000	0	-10000	0	0
TOPBP1	0.016	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.003	0.036	-10000	0	-10000	0	0
BRCA1/BARD1	-0.011	0.075	-10000	0	-0.89	1	1
CSTF1	0.016	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.004	0.049	-10000	0	-0.57	4	4
CDK2	0.016	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.007	0.14	-10000	0	-0.86	14	14
RAD50	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.004	0.048	-10000	0	-0.56	4	4
EWSR1	0.016	0	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.011	0.063	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.011	0.059	-9999	-0.67	1	1
alphaV/beta3 Integrin/Osteopontin/Src	-0.004	0.047	-9999	-0.54	4	4
AP1	-0.019	0.092	-9999	-0.69	6	6
ILK	0.06	0.065	-9999	-10000	0	0
bone resorption	-0.026	0.1	-9999	-0.72	4	4
PTK2B	0.016	0	-9999	-10000	0	0
PYK2/p130Cas	-0.008	0.054	-9999	-10000	0	0
ITGAV	0.022	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.03	0.14	-9999	-0.65	25	25
alphaV/beta3 Integrin/Osteopontin	-0.009	0.062	-9999	-0.48	2	2
MAP3K1	0.06	0.066	-9999	-10000	0	0
JUN	0.016	0.002	-9999	-10000	0	0
MAPK3	0.072	0.081	-9999	-10000	0	0
MAPK1	0.072	0.081	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.014	0.033	-9999	-0.74	1	1
MAPK8	0.072	0.078	-9999	-0.77	2	2
ITGB3	0.014	0.08	-9999	-0.73	6	6
NFKBIA	0.085	0.081	-9999	-10000	0	0
FOS	-0.002	0.12	-9999	-0.75	13	13
CD44	-0.019	0.17	-9999	-0.86	21	21
CHUK	0.016	0	-9999	-10000	0	0
PLAU	0.084	0.17	-9999	-1.1	9	9
NF kappa B1 p50/RelA	-0.012	0.06	-9999	-0.64	1	1
BCAR1	0.014	0.033	-9999	-0.74	1	1
RELA	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.006	0.057	-9999	-0.54	6	6
mol:GDP	0	0	-9999	-10000	0	0
SYK	0.057	0.071	-9999	-10000	0	0
VAV3	0.055	0.1	-9999	-0.78	1	1
MAP3K14	0.059	0.082	-9999	-0.5	4	4
ROCK2	0.01	0.066	-9999	-0.74	4	4
SPP1	0.017	0.065	-9999	-0.73	4	4
RAC1	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.016	0.075	-9999	-0.71	1	1
MMP2	0.097	0.12	-9999	-0.76	6	6

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.014	0.033	-10000	0	-0.74	1	1
ANTXR2	0.014	0.033	-10000	0	-0.74	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.006	-10000	0	-0.093	2	2
monocyte activation	0.006	0.083	-10000	0	-0.37	21	21
MAP2K2	-0.002	0.035	-10000	0	-0.8	1	1
MAP2K1	0	0.005	-10000	0	-10000	0	0
MAP2K7	0	0.005	-10000	0	-10000	0	0
MAP2K6	-0.003	0.032	-10000	0	-0.43	3	3
CYAA	0.02	0.027	-10000	0	-0.42	2	2
MAP2K4	0	0.005	-10000	0	-10000	0	0
IL1B	0.017	0.059	-10000	0	-0.49	6	6
Channel	-0.002	0.027	-10000	0	-0.44	2	2
NLRP1	-0.005	0.051	-10000	0	-0.52	5	5
CALM1	0.016	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.007	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.006	0.093	2	-10000	0	2
MAPK3	0	0.005	-10000	0	-10000	0	0
MAPK1	0	0.005	-10000	0	-10000	0	0
PGR	-0.015	0.08	-10000	0	-0.44	18	18
PA/Cellular Receptors	-0.002	0.03	-10000	0	-0.48	2	2
apoptosis	0	0.006	-10000	0	-0.093	2	2
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.002	0.025	-10000	0	-0.42	2	2
macrophage activation	0.027	0.005	-10000	0	-10000	0	0
TNF	0.003	0.1	-10000	0	-0.8	8	8
VCAM1	-0.015	0.08	-10000	0	-0.37	21	21
platelet activation	0	0.007	-10000	0	-10000	0	0
MAPKKK cascade	-0.022	0.01	-10000	0	-10000	0	0
IL18	0.016	0.066	-10000	0	-0.52	7	7
negative regulation of macrophage activation	0	0.006	-10000	0	-0.093	2	2
LEF	0	0.006	-10000	0	-0.094	2	2
CASP1	-0.002	0.023	-10000	0	-0.23	5	5
mol:cAMP	0	0.007	-10000	0	-10000	0	0
necrosis	0	0.006	-10000	0	-0.093	2	2
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.002	0.026	-10000	0	-0.42	2	2
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.036	0.12	-9999	-0.42	44	44
PDGFB-D/PDGFRB/SLAP	-0.033	0.14	-9999	-0.67	26	26
PDGFB-D/PDGFRB/APS/CBL	-0.008	0.069	-9999	-0.56	8	8
AKT1	-0.002	0.022	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.013	0.14	-9999	-0.44	44	44
PIK3CA	0.014	0.033	-9999	-0.74	1	1
FGR	-0.004	0.029	-9999	-10000	0	0
mol:Ca2+	0.038	0.041	-9999	-10000	0	0
MYC	0.042	0.14	-9999	-0.57	20	20
SHC1	0.014	0.038	-9999	-0.86	1	1
HRAS/GDP	-0.002	0.038	-9999	-0.88	1	1
LRP1/PDGFRB/PDGFB	0	0	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0.038	0.041	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
GRB7	0.006	0.086	-9999	-0.74	7	7
PDGFB-D/PDGFRB/SHP2	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0	0	-9999	-10000	0	0
cell cycle arrest	-0.033	0.14	-9999	-0.67	26	26
HRAS	0.014	0.038	-9999	-0.86	1	1
HIF1A	0.087	0.04	-9999	-0.6	1	1
GAB1	0.032	0.075	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.036	0.082	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.012	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.038	0.12	-9999	-0.47	18	18
positive regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
mol:IP3	0.038	0.041	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.015	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.007	0.064	-9999	-0.56	7	7
SHB	0.016	0	-9999	-10000	0	0
BLK	-0.023	0.085	-9999	-0.43	6	6
PTPN2	0.016	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0	-9999	-10000	0	0
BCAR1	0.014	0.033	-9999	-0.74	1	1
VAV2	0.035	0.088	-9999	-10000	0	0
CBL	0.014	0.033	-9999	-0.74	1	1
PDGFB-D/PDGFRB/DEP1	0	0	-9999	-10000	0	0
LCK	-0.017	0.081	-9999	-0.54	4	4
PDGFRB	0.016	0.006	-9999	-10000	0	0
ACP1	0.016	0	-9999	-10000	0	0
HCK	-0.02	0.082	-9999	-10000	0	0
ABL1	0.033	0.059	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	0.033	0.07	-9999	-10000	0	0
PTPN1	0.016	0.003	-9999	-10000	0	0
SNX15	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
STAT1	0.014	0.038	-9999	-0.86	1	1
cell proliferation	0.043	0.12	-9999	-0.52	20	20
SLA	-0.027	0.19	-9999	-0.86	26	26
actin cytoskeleton reorganization	0.001	0.025	-9999	-10000	0	0
SRC	-0.001	0.013	-9999	-10000	0	0
PI3K	-0.002	0.024	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.007	0.06	-9999	-0.49	8	8
SH2B2	0.004	0.1	-9999	-0.86	7	7
PLCgamma1/SPHK1	0.012	0.14	-9999	-0.45	44	44
LYN	-0.001	0.014	-9999	-10000	0	0
LRP1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
STAT5A	0.016	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.001	0.023	-9999	-10000	0	0
SPHK1	-0.056	0.24	-9999	-0.86	44	44
EDG1	0.001	0.003	-9999	-10000	0	0
mol:DAG	0.038	0.041	-9999	-10000	0	0
PLCG1	0.038	0.041	-9999	-10000	0	0
NHERF/PDGFRB	-0.001	0.021	-9999	-0.47	1	1
YES1	-0.001	0.014	-9999	-10000	0	0
cell migration	-0.001	0.02	-9999	-0.47	1	1
SHC/Grb2/SOS1	-0.001	0.02	-9999	-10000	0	0
SLC9A3R2	0.014	0.033	-9999	-0.74	1	1
SLC9A3R1	0.016	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	-0.001	0.018	-9999	-10000	0	0
FYN	-0.001	0.013	-9999	-10000	0	0
DOK1	0.044	0.009	-9999	-10000	0	0
HRAS/GTP	-0.001	0.029	-9999	-0.68	1	1
PDGFB	0.016	0	-9999	-10000	0	0
RAC1	0.045	0.1	-9999	-0.48	3	3
PRKCD	0.042	0.028	-9999	-0.53	1	1
FER	0.041	0.033	-9999	-0.44	2	2
MAPKKK cascade	0	0.021	-9999	-10000	0	0
RASA1	0.042	0.025	-9999	-0.44	1	1
NCK1	0.014	0.033	-9999	-0.74	1	1
NCK2	0.016	0	-9999	-10000	0	0
p62DOK/Csk	0.007	0.018	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0	0	-9999	-10000	0	0
chemotaxis	0.033	0.059	-9999	-10000	0	0
STAT1-3-5/STAT1-3-5	-0.001	0.02	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0	0	-9999	-10000	0	0
PTPRJ	0.016	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.057	0.052	-10000	0	-0.46	1	1
adherens junction organization	0.039	0.08	-10000	0	-0.53	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.013	0.06	-10000	0	-10000	0	0
FMN1	0.021	0.12	-10000	0	-0.66	2	2
mol:IP3	-0.008	0.04	-10000	0	-0.48	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.014	0.065	-10000	0	-0.71	1	1
CTNNB1	0.001	0.006	-10000	0	-10000	0	0
AKT1	0.054	0.057	-10000	0	-0.5	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.014	0.11	-10000	0	-0.53	22	22
CTNND1	0.016	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.044	0.074	-10000	0	-0.56	2	2
VASP	0.044	0.072	-10000	0	-0.66	1	1
ZYX	0.044	0.072	-10000	0	-0.66	1	1
JUB	0.042	0.08	-10000	0	-0.58	2	2
EGFR(dimer)	-0.02	0.082	-10000	0	-0.48	9	9
E-cadherin/beta catenin-gamma catenin	-0.021	0.1	-10000	0	-0.47	24	24
mol:PI-3-4-5-P3	-0.01	0.048	-10000	0	-0.54	1	1
PIK3CA	0.015	0.033	-10000	0	-0.74	1	1
PI3K	-0.01	0.048	-10000	0	-0.56	1	1
FYN	-0.23	0.13	-10000	0	-0.45	18	18
mol:Ca2+	-0.008	0.039	-10000	0	-0.46	1	1
JUP	-0.003	0.056	-10000	0	-0.74	3	3
PIK3R1	0.015	0.033	-10000	0	-0.74	1	1
mol:DAG	-0.008	0.04	-10000	0	-0.48	1	1
CDH1	-0.031	0.15	-10000	0	-0.74	22	22
RhoA/GDP	-0.013	0.06	-10000	0	-10000	0	0
establishment of polarity of embryonic epithelium	0.044	0.071	-10000	0	-0.64	1	1
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
EGFR	0.001	0.11	-10000	0	-0.85	9	9
CASR	-0.29	0.15	-10000	0	-0.53	19	19
RhoA/GTP	-0.007	0.035	-10000	0	-10000	0	0
AKT2	0.054	0.057	-10000	0	-0.5	1	1
actin cable formation	0.031	0.12	-10000	0	-0.63	2	2
apoptosis	0.009	0.043	0.49	1	-10000	0	1
CTNNA1	0.016	0.004	-10000	0	-10000	0	0
mol:GDP	-0.015	0.066	-10000	0	-0.48	1	1
PIP5K1A	0.044	0.076	-10000	0	-0.58	2	2
PLCG1	-0.008	0.041	-10000	0	-0.49	1	1
Rac1/GTP	-0.018	0.074	-10000	0	-0.43	9	9
homophilic cell adhesion	0.002	0.001	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.015	0.001	-9999	-10000	0	0
HDAC2	0.015	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.02	-9999	-0.47	1	1
forebrain development	0.055	0.094	-9999	-0.5	2	2
GNAO1	0.008	0.083	-9999	-0.84	5	5
SMO/beta Arrestin2	-0.002	0.038	-9999	-0.61	2	2
SMO	0.016	0.033	-9999	-0.74	1	1
ARRB2	0.014	0.038	-9999	-0.86	1	1
GLI3/SPOP	0.061	0.024	-9999	-10000	0	0
mol:GTP	0.001	0.002	-9999	-10000	0	0
GSK3B	0.016	0	-9999	-10000	0	0
GNAI2	0.016	0.004	-9999	-10000	0	0
SIN3/HDAC complex	-0.019	0.097	-9999	-0.52	19	19
GNAI1	0.011	0.057	-9999	-0.74	3	3
XPO1	0.019	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.013	0.061	-9999	-10000	0	0
SAP30	-0.016	0.16	-9999	-0.86	19	19
mol:GDP	0.016	0.033	-9999	-0.74	1	1
MIM/GLI2A	0.023	0.008	-9999	-10000	0	0
IFT88	0.014	0.033	-9999	-0.74	1	1
GNAI3	0.016	0.004	-9999	-10000	0	0
GLI2	0.058	0.031	-9999	-10000	0	0
GLI3	0.055	0.026	-9999	-10000	0	0
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
SAP18	0.015	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.014	0.033	-9999	-0.74	1	1
GNG2	0.016	0	-9999	-10000	0	0
Gi family/GTP	0.044	0.051	-9999	-0.55	1	1
SIN3B	0.015	0.001	-9999	-10000	0	0
SIN3A	0.015	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.073	0.034	-9999	-10000	0	0
GLI2/Su(fu)	0.075	0.037	-9999	-10000	0	0
FOXA2	-0.06	0.22	-9999	-0.83	38	38
neural tube patterning	0.055	0.094	-9999	-0.5	2	2
SPOP	0.016	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.001	0.013	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CSNK1G2	0.014	0.033	-9999	-0.74	1	1
CSNK1G3	0.016	0	-9999	-10000	0	0
MTSS1	0.023	0.008	-9999	-10000	0	0
embryonic limb morphogenesis	0.055	0.094	-9999	-0.5	2	2
SUFU	0.038	0.021	-9999	-10000	0	0
LGALS3	-0.006	0.14	-9999	-0.86	13	13
catabolic process	0.093	0.03	-9999	-10000	0	0
GLI3A/CBP	0.017	0.056	-9999	-10000	0	0
KIF3A	0.016	0	-9999	-10000	0	0
GLI1	0.055	0.095	-9999	-0.51	2	2
RAB23	0.016	0	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
IFT172	0.016	0	-9999	-10000	0	0
RBBP7	0.015	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.014	0.084	-9999	-0.54	13	13
GNAZ	0.011	0.057	-9999	-0.74	3	3
RBBP4	0.014	0.033	-9999	-0.74	1	1
CSNK1G1	0.016	0	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GLI2/SPOP	0.061	0.028	-9999	-10000	0	0
STK36	0.019	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.052	0.047	-9999	-0.48	1	1
PTCH1	0.062	0.1	-9999	-1.1	1	1
MIM/GLI1	0.052	0.15	-9999	-0.71	1	1
CREBBP	0.017	0.056	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.056	0.048	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.028	0.1	-9999	-10000	0	0
BAG4	0.014	0.033	-9999	-0.74	1	1
BAD	0.03	0.045	-9999	-0.42	2	2
NFKBIA	0.016	0	-9999	-10000	0	0
BIRC3	-0.12	0.31	-9999	-0.86	80	80
BAX	0.032	0.036	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.012	0.027	-9999	-0.099	1	1
IKBKB	0.038	0.096	-9999	-10000	0	0
MAP2K2	0.046	0.052	-9999	-0.38	4	4
MAP2K1	0.047	0.05	-9999	-0.38	4	4
SMPD1	0.019	0.027	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.038	0.097	-9999	-10000	0	0
MAP2K4	0.041	0.035	-9999	-10000	0	0
protein ubiquitination	0.04	0.097	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.054	0.051	-9999	-0.38	4	4
response to UV	0.001	0	-9999	-10000	0	0
RAF1	0.039	0.052	-9999	-0.41	4	4
CRADD	0.016	0.001	-9999	-10000	0	0
mol:ceramide	0.022	0.037	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.016	0.001	-9999	-10000	0	0
MAP3K1	0.032	0.036	-9999	-10000	0	0
TRADD	0.016	0.001	-9999	-10000	0	0
RELA/p50	0.016	0	-9999	-10000	0	0
MAPK3	0.05	0.05	-9999	-0.37	4	4
MAPK1	0.05	0.05	-9999	-0.37	4	4
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.028	0.1	-9999	-10000	0	0
KSR1	0.03	0.055	-9999	-0.45	4	4
MAPK8	0.048	0.04	-9999	-10000	0	0
TRAF2	0.016	0.001	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.038	0.096	-9999	-10000	0	0
TNF R/SODD	-0.001	0.024	-9999	-0.56	1	1
TNF	0.004	0.1	-9999	-0.8	8	8
CYCS	0.033	0.038	-9999	-10000	0	0
IKBKG	0.038	0.096	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.018	0.1	-9999	-0.44	1	1
RELA	0.016	0	-9999	-10000	0	0
RIPK1	0.016	0.001	-9999	-10000	0	0
AIFM1	0.033	0.037	-9999	-10000	0	0
TNF/TNF R/SODD	-0.009	0.067	-9999	-0.52	9	9
TNFRSF1A	0.016	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.029	0.029	-9999	-10000	0	0
NSMAF	0.029	0.098	-9999	-10000	0	0
response to hydrogen peroxide	0.001	0	-9999	-10000	0	0
BCL2	0.016	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.005	0.072	-9999	-0.73	5	5
VDR	0.011	0.057	-9999	-0.74	3	3
FAM120B	0.016	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.077	0.05	-9999	-10000	0	0
RXRs/LXRs/DNA/Oxysterols	0.087	0.062	-9999	-10000	0	0
MED1	0.016	0	-9999	-10000	0	0
mol:9cRA	0.009	0.008	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.02	0.073	-9999	-10000	0	0
RXRs/NUR77	-0.007	0.087	-9999	-0.5	6	6
RXRs/PPAR	0.058	0.029	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.003	0.043	-9999	-0.57	3	3
RARs/VDR/DNA/Vit D3	-0.004	0.039	-9999	-10000	0	0
RARA	0.016	0	-9999	-10000	0	0
NCOA1	0.016	0	-9999	-10000	0	0
VDR/VDR/DNA	0.011	0.057	-9999	-0.74	3	3
RARs/RARs/DNA/9cRA	-0.001	0.025	-9999	-0.41	2	2
RARG	0.016	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.034	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.02	0.073	-9999	-10000	0	0
THRA	0.014	0.033	-9999	-0.74	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.003	0.043	-9999	-0.57	3	3
RXRs/PPAR/9cRA/PGJ2/DNA	0.005	0.056	-9999	-0.5	4	4
NR1H4	-0.009	0.14	-9999	-0.75	17	17
RXRs/LXRs/DNA	0.008	0.056	-9999	-10000	0	0
NR1H2	0.023	0.033	-9999	-0.73	1	1
NR1H3	0.025	0.006	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.005	0.052	-9999	-0.48	4	4
NR4A1	-0.006	0.13	-9999	-0.75	15	15
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.041	0.067	-9999	-0.41	2	2
RXRG	0.015	0.076	-9999	-0.85	4	4
RXR alpha/CCPG	0	0.004	-9999	-10000	0	0
RXRA	0.024	0.005	-9999	-10000	0	0
RXRB	0.025	0.006	-9999	-10000	0	0
THRB	-0.031	0.18	-9999	-0.74	33	33
PPARG	0.016	0	-9999	-10000	0	0
PPARD	0.016	0	-9999	-10000	0	0
TNF	0.084	0.13	-9999	-0.87	8	8
mol:Oxysterols	0.009	0.007	-9999	-10000	0	0
cholesterol transport	0.086	0.061	-9999	-10000	0	0
PPARA	0.016	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.013	0.046	-9999	-0.74	2	2
RXRs/NUR77/BCL2	-0.01	0.055	-9999	-10000	0	0
SREBF1	0.092	0.064	-9999	-0.66	1	1
RXRs/RXRs/DNA/9cRA	0.005	0.056	-9999	-0.5	4	4
ABCA1	0.092	0.071	-9999	-0.66	2	2
RARs/THRs	-0.027	0.098	-9999	-10000	0	0
RXRs/FXR	-0.008	0.091	-9999	-0.5	7	7
BCL2	0.016	0	-9999	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.016	0	-10000	0	-10000	0	0
NFATC1	0.075	0.027	-10000	0	-10000	0	0
NFATC2	0.053	0.036	-10000	0	-0.32	2	2
NFATC3	0.029	0.039	-10000	0	-0.49	3	3
YWHAE	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.032	0.072	-10000	0	-0.46	4	4
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.013	0.053	-10000	0	-0.52	2	2
BCL2/BAX	0	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+	0	0.001	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
MAPK14	0.016	0.003	-10000	0	-10000	0	0
BAD	0.013	0.05	-10000	0	-0.8	2	2
CABIN1/MEF2D	0.038	0.067	-10000	0	-0.43	4	4
Calcineurin A alpha-beta B1/BCL2	0.016	0	-10000	0	-10000	0	0
FKBP8	0.014	0.033	-10000	0	-0.74	1	1
activation-induced cell death of T cells	-0.037	0.067	0.43	4	-10000	0	4
KPNB1	0.016	0	-10000	0	-10000	0	0
KPNA2	0.016	0	-10000	0	-10000	0	0
XPO1	0.016	0	-10000	0	-10000	0	0
SFN	-0.083	0.27	-10000	0	-0.83	62	62
MAP3K8	0.013	0.054	-10000	0	-0.86	2	2
NFAT4/CK1 alpha	-0.002	0.023	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.011	0.056	-10000	0	-10000	0	0
CABIN1	0.032	0.072	-10000	0	-0.47	4	4
CALM1	0.016	0.003	-10000	0	-10000	0	0
RAN	0.016	0	-10000	0	-10000	0	0
MAP3K1	0.016	0	-10000	0	-10000	0	0
CAMK4	0.013	0.046	-10000	0	-0.74	2	2
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.002	0.034	-10000	0	-0.56	2	2
YWHAB	0.016	0	-10000	0	-10000	0	0
MAPK8	0.013	0.047	-10000	0	-0.74	2	2
MAPK9	0.016	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.002	0.028	-10000	0	-10000	0	0
PRKCH	0.016	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.001	0.024	-10000	0	-0.55	1	1
CASP3	0.016	0.003	-10000	0	-10000	0	0
PIM1	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.001	0.019	-10000	0	-0.39	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.03	0.076	-10000	0	-0.47	2	2
PRKCB	0.008	0.08	-10000	0	-0.82	5	5
PRKCE	0.014	0.033	-10000	0	-0.74	1	1
JNK2/NFAT4	-0.002	0.033	-10000	0	-0.44	3	3
BAD/BCL-XL	-0.002	0.038	-10000	0	-0.61	2	2
PRKCD	0.014	0.038	-10000	0	-0.86	1	1
NUP214	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.057	-10000	0	-0.75	3	3
PRKCA	0.016	0	-10000	0	-10000	0	0
PRKCG	-0.03	0.18	-10000	0	-0.86	23	23
PRKCQ	-0.007	0.13	-10000	0	-0.74	16	16
FKBP38/BCL2	-0.001	0.024	-10000	0	-0.56	1	1
EP300	0.015	0.033	-10000	0	-0.74	1	1
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
NFATc/JNK1	0.079	0.038	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	-0.001	0.022	-10000	0	-0.5	1	1
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.027	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.002	0.03	-10000	0	-0.48	2	2
NFATc/ERK1	0.081	0.025	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.013	0.054	-10000	0	-0.52	2	2
NR4A1	0.073	0.13	-10000	0	-0.67	15	15
GSK3B	0.016	0.003	-10000	0	-10000	0	0
positive T cell selection	0.029	0.039	-10000	0	-0.48	3	3
NFAT1/CK1 alpha	-0.003	0.02	-10000	0	-10000	0	0
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
PRKACA	0.016	0.003	-10000	0	-10000	0	0
AKAP5	0.013	0.046	-10000	0	-0.74	2	2
MEF2D	0.016	0.003	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.08	0.028	-10000	0	-10000	0	0
CREBBP	0.016	0.003	-10000	0	-10000	0	0
BCL2	0.016	0	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-10000	0	-10000	0	0
HDAC3	0.016	0	-10000	0	-10000	0	0
VDR	0.011	0.057	-10000	0	-0.74	3	3
Cbp/p300/PCAF	-0.002	0.04	-10000	0	-0.91	1	1
EP300	0.014	0.033	-10000	0	-0.74	1	1
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.056	0.034	-10000	0	-0.43	1	1
KAT2B	0.014	0.033	-10000	0	-0.74	1	1
MAPK14	0.016	0	-10000	0	-10000	0	0
AKT1	0.03	0.038	0.24	1	-0.3	2	3
RAR alpha/9cRA/Cyclin H	-0.009	0.038	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.052	0.037	-10000	0	-0.48	1	1
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.002	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.011	0.053	-10000	0	-0.58	2	2
NCOR2	0.016	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.003	0.043	-10000	0	-0.57	3	3
RXRs/RARs/NRIP1/9cRA	0.062	0.082	-10000	0	-0.52	1	1
NCOA2	0	0.11	-10000	0	-0.74	11	11
NCOA3	0.016	0	-10000	0	-10000	0	0
NCOA1	0.016	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.011	0.057	-10000	0	-0.74	3	3
RARG	0.017	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.017	0.001	-10000	0	-10000	0	0
MAPK1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.015	0.046	-10000	0	-0.74	2	2
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.018	0.073	-10000	0	-10000	0	0
RARA	0.024	0.06	-10000	0	-0.28	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.046	0.065	-10000	0	-0.89	1	1
PRKCA	0.02	0.001	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.054	0.083	-10000	0	-0.57	1	1
RXRG	0.013	0.091	-10000	0	-0.38	27	27
RXRA	0.035	0.056	-10000	0	-10000	0	0
RXRB	0.017	0.084	-10000	0	-0.37	23	23
VDR/Vit D3/DNA	-0.003	0.043	-10000	0	-0.57	3	3
RBP1	0.009	0.073	-10000	0	-0.83	4	4
CRBP1/9-cic-RA	-0.005	0.056	-10000	0	-0.65	4	4
RARB	0.016	0.047	-10000	0	-0.74	2	2
PRKCG	-0.025	0.18	-10000	0	-0.86	23	23
MNAT1	0.016	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.053	0.084	-10000	0	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.06	0.074	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.055	0.047	-10000	0	-0.33	1	1
RXRs/RARs/NRIP1/9cRA/HDAC3	0.054	0.083	-10000	0	-0.57	1	1
positive regulation of DNA binding	-0.008	0.037	-10000	0	-10000	0	0
NRIP1	0.052	0.091	-10000	0	-1.2	1	1
RXRs/RARs	0.046	0.081	-10000	0	-0.41	1	1
RXRs/RXRs/DNA/9cRA	-0.017	0.073	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
CDK7	0.016	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.006	0.026	-10000	0	-10000	0	0
CCNH	0.016	0	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	0.006	0.26	-9999	-1.1	27	27
MKNK1	0.016	0	-9999	-10000	0	0
MAPK14	0.022	0.075	-9999	-0.44	1	1
ATF2/c-Jun	0.043	0.066	-9999	-0.61	1	1
MAPK11	0.019	0.091	-9999	-0.69	3	3
MITF	0.042	0.094	-9999	-0.55	1	1
MAPKAPK5	0.042	0.094	-9999	-0.46	2	2
KRT8	0.041	0.095	-9999	-0.55	1	1
MAPKAPK3	0.016	0	-9999	-10000	0	0
MAPKAPK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.03	0.12	-9999	-0.65	3	3
CEBPB	0.033	0.11	-9999	-0.55	1	1
SLC9A1	0.042	0.094	-9999	-0.55	1	1
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.049	0.098	-9999	-0.68	2	2
p38alpha-beta/MNK1	-0.021	0.079	-9999	-0.53	3	3
JUN	0.044	0.065	-9999	-0.6	1	1
PPARGC1A	0.001	0.16	-9999	-0.68	3	3
USF1	0.042	0.094	-9999	-0.46	2	2
RAB5/GDP/GDI1	-0.014	0.053	-9999	-0.41	1	1
NOS2	0.036	0.14	-9999	-0.87	8	8
DDIT3	0.04	0.099	-9999	-0.46	2	2
RAB5A	0.016	0	-9999	-10000	0	0
HSPB1	0.045	0.095	-9999	-0.65	4	4
p38alpha-beta/HBP1	-0.021	0.079	-9999	-0.53	3	3
CREB1	0.048	0.097	-9999	-0.55	1	1
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	0.046	0.083	-9999	-0.54	1	1
RPS6KA4	0.042	0.094	-9999	-0.46	2	2
PLA2G4A	0.04	0.11	-9999	-0.74	4	4
GDI1	0.042	0.094	-9999	-0.46	2	2
TP53	0.044	0.12	-9999	-0.56	3	3
RPS6KA5	0.042	0.094	-9999	-0.46	2	2
ESR1	0.038	0.1	-9999	-0.66	2	2
HBP1	0.016	0	-9999	-10000	0	0
MEF2C	0.042	0.094	-9999	-0.55	1	1
MEF2A	0.042	0.094	-9999	-0.46	2	2
EIF4EBP1	0.041	0.1	-9999	-0.47	4	4
KRT19	-0.046	0.21	-9999	-0.82	11	11
ELK4	0.042	0.094	-9999	-0.55	1	1
ATF6	0.042	0.094	-9999	-0.46	2	2
ATF1	0.048	0.097	-9999	-0.55	1	1
p38alpha-beta/MAPKAPK2	-0.021	0.079	-9999	-0.53	3	3
p38alpha-beta/MAPKAPK3	-0.021	0.079	-9999	-0.53	3	3

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.011	0.057	-9999	-0.74	3	3
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.006	0.037	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
MAP3K12	0.014	0.033	-9999	-0.74	1	1
FGR	0.011	0.066	-9999	-0.86	3	3
p38 alpha/TAB1	-0.012	0.038	-9999	-0.31	2	2
PRKG1	-0.006	0.13	-9999	-0.74	15	15
DUSP8	0.014	0.033	-9999	-0.74	1	1
PGK/cGMP/p38 alpha	-0.02	0.064	-9999	-0.43	3	3
apoptosis	-0.012	0.036	-9999	-0.3	2	2
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
DUSP1	0.014	0.038	-9999	-0.86	1	1
PAK1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.056	0.084	-9999	-0.42	2	2
BLK	-0.04	0.21	-9999	-0.86	33	33
HCK	-0.032	0.2	-9999	-0.86	29	29
MAP2K3	0.016	0	-9999	-10000	0	0
DUSP16	0.016	0	-9999	-10000	0	0
DUSP10	0.011	0.066	-9999	-0.86	3	3
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.057	0.065	-9999	-0.34	2	2
positive regulation of innate immune response	0.068	0.09	-9999	-0.44	2	2
LCK	-0.02	0.17	-9999	-0.85	22	22
p38alpha-beta/MKP7	0.073	0.087	-9999	-10000	0	0
p38alpha-beta/MKP5	0.071	0.092	-9999	-10000	0	0
PGK/cGMP	-0.016	0.094	-9999	-0.57	15	15
PAK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.072	0.089	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
RALB	0.016	0	-9999	-10000	0	0
RALA	0.016	0	-9999	-10000	0	0
PAK3	-0.007	0.14	-9999	-0.83	14	14

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.01	0.064	-9999	-10000	0	0
TC10/GTP	-0.007	0.054	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.003	0.038	-9999	-0.44	4	4
HRAS	0.014	0.038	-9999	-0.86	1	1
APS homodimer	0.004	0.1	-9999	-0.86	7	7
GRB14	-0.024	0.17	-9999	-0.74	28	28
FOXO3	-0.003	0.012	-9999	-10000	0	0
AKT1	-0.021	0.084	-9999	-0.66	2	2
INSR	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
SORBS1	0.014	0.033	-9999	-0.74	1	1
CRK	0.016	0	-9999	-10000	0	0
PTPN1	0.049	0.001	-9999	-10000	0	0
CAV1	-0.005	0.14	-9999	-0.51	37	37
CBL/APS/CAP/Crk-II/C3G	-0.008	0.06	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.003	0.038	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.04	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.002	0.023	-9999	-10000	0	0
RPS6KB1	0.055	0.094	-9999	-0.58	2	2
PARD6A	0.011	0.057	-9999	-0.74	3	3
CBL	0.014	0.033	-9999	-0.74	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.002	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.018	0.073	-9999	-0.59	2	2
HRAS/GTP	-0.007	0.055	-9999	-0.73	1	1
Insulin Receptor	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.004	0.041	-9999	-0.5	1	1
PRKCI	-0.005	0.019	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.023	0.092	-9999	-0.72	2	2
SHC1	0.014	0.038	-9999	-0.86	1	1
negative regulation of MAPKKK cascade	-0.001	0.035	-9999	-0.82	1	1
PI3K	-0.004	0.041	-9999	-10000	0	0
NCK2	0.016	0	-9999	-10000	0	0
RHOQ	0.016	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.029	-9999	-0.68	1	1
AKT2	-0.021	0.084	-9999	-0.66	2	2
PRKCZ	-0.008	0.055	-9999	-0.69	3	3
SH2B2	0.004	0.1	-9999	-0.86	7	7
SHC/SHIP	-0.007	0.062	-9999	-0.55	5	5
F2RL2	-0.032	0.2	-9999	-0.86	29	29
TRIP10	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.001	0.024	-9999	-0.55	1	1
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.001	0.022	-9999	-0.5	1	1
RAPGEF1	0.016	0	-9999	-10000	0	0
RASA1	0.014	0.033	-9999	-0.74	1	1
NCK1	0.014	0.033	-9999	-0.74	1	1
CBL/APS/CAP/Crk-II	-0.008	0.065	-9999	-0.52	7	7
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.001	0.023	-9999	-0.54	1	1
INPP5D	0.029	0.067	-9999	-0.53	7	7
SOS1	0.016	0	-9999	-10000	0	0
SGK1	-0.001	0.006	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.01	0.066	-9999	-0.74	4	4
p62DOK/RasGAP	-0.001	0.036	-9999	-0.83	1	1
INS	0.005	0.001	-9999	-10000	0	0
mol:PI-3-4-P2	0.029	0.066	-9999	-0.52	7	7
GRB2	0.016	0	-9999	-10000	0	0
EIF4EBP1	0.031	0.15	-9999	-0.73	6	6
PTPRA	0.018	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.014	0.033	-9999	-0.74	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.003	0.028	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.003	0.039	-9999	-0.45	4	4
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.029	0.12	-9999	-0.5	29	29

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	0.018	-9999	-10000	0	0
HDAC3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.025	0.13	-9999	-0.66	20	20
GATA1/HDAC5	-0.026	0.13	-9999	-0.66	21	21
GATA2/HDAC5	-0.015	0.089	-9999	-0.56	14	14
HDAC5/BCL6/BCoR	-0.001	0.02	-9999	-0.47	1	1
HDAC9	0.016	0	-9999	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	-0.001	0.025	-9999	-0.57	1	1
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	-0.001	0.024	-9999	-0.56	1	1
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
GATA2	-0.003	0.12	-9999	-0.74	13	13
HDAC4/RFXANK	-0.001	0.029	-9999	-0.66	1	1
BCOR	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.014	0.033	-9999	-0.74	1	1
HDAC5	0.014	0.033	-9999	-0.74	1	1
GNB1/GNG2	0	0	-9999	-10000	0	0
Histones	-0.003	0.039	-9999	-0.83	1	1
ADRBK1	0.016	0	-9999	-10000	0	0
HDAC4	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
HDAC5/ANKRA2	-0.001	0.024	-9999	-0.56	1	1
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.016	0	-9999	-10000	0	0
HDAC5/14-3-3 E	-0.001	0.024	-9999	-0.56	1	1
TUBA1B	0.016	0	-9999	-10000	0	0
HDAC6	0.016	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.002	0.038	-9999	-0.61	2	2
CAMK4	0.013	0.046	-9999	-0.74	2	2
Tubulin/HDAC6	-0.001	0.02	-9999	-0.47	1	1
SUMO1	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
GATA1	-0.02	0.17	-9999	-0.86	20	20
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
NR3C1	0.014	0.038	-9999	-0.86	1	1
SUMO1/HDAC4	0	0	-9999	-10000	0	0
SRF	0.016	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.001	0.024	-9999	-0.56	1	1
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.002	0.029	-9999	-0.47	2	2
HDAC4/ER alpha	-0.005	0.056	-9999	-0.58	5	5
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.051	0.042	-9999	-0.82	1	1
cell motility	-0.001	0.02	-9999	-0.47	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.016	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.016	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	0.008	0.076	-9999	-0.77	5	5
HDAC6/HDAC11	-0.002	0.034	-9999	-0.56	2	2
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
HDAC4/MEF2C	0	0	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
TUBB2A	0.014	0.033	-9999	-0.74	1	1
HDAC11	0.013	0.046	-9999	-0.74	2	2
HSP90AA1	0.016	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
ANKRA2	0.016	0	-9999	-10000	0	0
RFXANK	0.014	0.038	-9999	-0.86	1	1
nuclear import	0.001	0.017	-9999	-10000	0	0

×

Circadian rhythm 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
chromatin modification	-0.001	0.016	-10000	0	-10000	0	0
CLOCK	0.019	0.033	-10000	0	-0.74	1	1
TIMELESS/CRY2	0.056	0.025	-10000	0	-10000	0	0
DEC1/BMAL1	-0.001	0.029	-10000	0	-0.66	1	1
ATR	0.016	0	-10000	0	-10000	0	0
NR1D1	0.053	0.069	-10000	0	-1	2	2
ARNTL	0.02	0.003	-10000	0	-10000	0	0
TIMELESS	0.055	0.028	-10000	0	-10000	0	0
NPAS2	0.006	0.1	-10000	0	-0.74	10	10
CRY2	0.016	0	-10000	0	-10000	0	0
mol:CO	-0.019	0.009	0.12	2	-10000	0	2
CHEK1	0.016	0	-10000	0	-10000	0	0
mol:HEME	0.019	0.009	-10000	0	-0.12	2	2
PER1	0.016	0	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.044	0.074	-10000	0	-0.46	11	11
BMAL1/CLOCK	0.064	0.055	-10000	0	-0.82	1	1
S phase of mitotic cell cycle	-0.001	0.016	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.016	-10000	0	-10000	0	0
mol:NADPH	0.019	0.009	-10000	0	-0.12	2	2
PER1/TIMELESS	0.056	0.025	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.001	0.038	-10000	0	-0.86	1	1

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.016	0	-10000	0	-10000	0	0
mol:PIP3	-0.004	0.036	-10000	0	-0.4	2	2
FRAP1	0.02	0.012	-10000	0	-10000	0	0
AKT1	-0.004	0.036	-10000	0	-0.47	2	2
INSR	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.003	0.028	-10000	0	-0.46	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.009	-10000	0	-10000	0	0
TSC2	0.016	0	-10000	0	-10000	0	0
RHEB/GDP	-0.002	0.025	-10000	0	-0.42	1	1
TSC1	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.018	0.035	-10000	0	-0.39	4	4
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.011	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.036	0.024	-10000	0	-0.34	1	1
MAP3K5	0.014	0.001	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
apoptosis	0.014	0.001	-10000	0	-10000	0	0
mol:LY294002	0	0	0.001	1	-0.002	4	5
EIF4B	0.044	0.022	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.003	0.031	-10000	0	-0.45	2	2
eIF4E/eIF4G1/eIF4A1	0	0.004	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.004	0.039	-10000	0	-0.36	6	6
mTOR/RHEB/GTP/Raptor/GBL	0.042	0.018	-10000	0	-10000	0	0
FKBP1A	0.016	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.002	0.024	-10000	0	-0.41	1	1
mol:Amino Acids	0	0	0.001	1	-0.002	4	5
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.004	0.043	-10000	0	-0.75	1	1
EIF4E	0.016	0	-10000	0	-10000	0	0
ASK1/PP5C	0.027	0.008	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.023	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.003	0.03	-10000	0	-0.5	1	1
tumor necrosis factor receptor activity	0	0	0.002	4	-0.001	1	5
RPS6	0.012	0.054	-10000	0	-0.86	2	2
PPP5C	0.016	0	-10000	0	-10000	0	0
EIF4G1	0.016	0	-10000	0	-10000	0	0
IRS1	0.008	0.038	-10000	0	-0.42	4	4
INS	0	0.001	-10000	0	-10000	0	0
PTEN	0.015	0	-10000	0	-10000	0	0
PDK2	-0.004	0.033	-10000	0	-0.38	1	1
EIF4EBP1	-0.01	0.1	-10000	0	-0.46	28	28
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
PPP2R5D	0.029	0.012	-10000	0	-10000	0	0
peptide biosynthetic process	0.023	0.001	-10000	0	-10000	0	0
RHEB	0.016	0	-10000	0	-10000	0	0
EIF4A1	0.016	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-0.004	1	1
EEF2	0.023	0.001	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.001	0.094	-10000	0	-0.4	28	28

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.031	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	-0.002	0.029	-9999	-0.52	1	1
CDKN1B	0.05	0.007	-9999	-10000	0	0
CDKN1A	0.048	0.032	-9999	-0.47	2	2
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.016	0	-9999	-10000	0	0
FOXO3	0.05	0.007	-9999	-10000	0	0
AKT1	0	0.006	-9999	-10000	0	0
BAD	0.013	0.05	-9999	-0.8	2	2
AKT3	0.022	0.019	-9999	-0.41	1	1
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.05	0.007	-9999	-10000	0	0
AKT1/ASK1	0	0.005	-9999	-10000	0	0
BAD/YWHAZ	-0.002	0.032	-9999	-0.52	2	2
RICTOR	0.016	0	-9999	-10000	0	0
RAF1	0.016	0	-9999	-10000	0	0
JNK cascade	0	0.005	-9999	-10000	0	0
TSC1	0.05	0.007	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
AKT1/RAF1	0.048	0.007	-9999	-10000	0	0
EP300	0.014	0.033	-9999	-0.74	1	1
mol:GDP	0	0.006	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.05	0.007	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
TBC1D4	0.033	0.016	-9999	-0.34	1	1
MAP3K5	0.016	0	-9999	-10000	0	0
MAPKAP1	0.016	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.041	0.052	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0
AKT1S1	0.05	0.007	-9999	-10000	0	0
CASP9	0.05	0.007	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.057	0.007	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.02	-9999	-0.47	1	1
YWHAE	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
AKT2/p21CIP1	-0.002	0.03	-9999	-0.45	2	2
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.024	0.002	-9999	-10000	0	0
CHUK	0.05	0.007	-9999	-10000	0	0
BAD/BCL-XL	-0.002	0.028	-9999	-0.56	1	1
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.022	0.019	-9999	-0.41	1	1
FOXO1-3a-4/14-3-3 family	0.059	0.059	-9999	-10000	0	0
PDPK1	0.014	0.033	-9999	-0.74	1	1
MDM2	0.05	0.007	-9999	-10000	0	0
MAPKKK cascade	-0.048	0.007	-9999	-10000	0	0
MDM2/Cbp/p300	-0.001	0.021	-9999	-0.48	1	1
TSC1/TSC2	0.059	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.02	-9999	-0.46	1	1
glucose import	0.03	0.079	-9999	-0.48	12	12
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.043	0.005	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.03	0.08	-9999	-0.48	12	12
GSK3A	0.05	0.007	-9999	-10000	0	0
FOXO1	0.05	0.007	-9999	-10000	0	0
GSK3B	0.05	0.007	-9999	-10000	0	0
SFN	-0.083	0.27	-9999	-0.83	62	62
G1/S transition of mitotic cell cycle	0.059	0.007	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.036	0.078	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
KPNA1	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
RHEB	0.016	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0

×

Nectin adhesion 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
PDGFRB	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.006	0.059	-9999	-0.56	6	6
PTK2	-0.005	0.045	-9999	-0.77	1	1
positive regulation of JNK cascade	-0.003	0.027	-9999	-0.37	1	1
CDC42/GDP	0.076	0.041	-9999	-0.51	1	1
Rac1/GDP	0.078	0.04	-9999	-0.5	1	1
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.003	0.033	-9999	-0.46	1	1
nectin-3/I-afadin	-0.003	0.042	-9999	-0.56	3	3
RAPGEF1	0.073	0.044	-9999	-0.49	3	3
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.066	0.049	-9999	-0.57	3	3
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
TLN1	0.045	0.018	-9999	-10000	0	0
Rap1/GTP	-0.002	0.025	-9999	-0.39	1	1
IQGAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.003	0.042	-9999	-0.56	3	3
PVR	0.016	0	-9999	-10000	0	0
Necl-5(dimer)	0.016	0	-9999	-10000	0	0
mol:GDP	0.077	0.049	-9999	-0.53	3	3
MLLT4	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
PI3K	-0.004	0.038	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.002	0.025	-9999	-0.33	3	3
PVRL1	0.016	0	-9999	-10000	0	0
PVRL3	0.011	0.057	-9999	-0.74	3	3
PVRL2	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
CDH1	-0.016	0.15	-9999	-0.74	22	22
CLDN1	0.008	0.078	-9999	-0.79	5	5
JAM-A/CLDN1	-0.007	0.055	-9999	-0.52	2	2
SRC	-0.004	0.049	-9999	-0.64	3	3
ITGB3	0.007	0.08	-9999	-0.74	6	6
nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
FARP2	0.068	0.053	-9999	-0.53	4	4
RAC1	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.003	0.035	-9999	-0.47	3	3
nectin-1/I-afadin	0	0	-9999	-10000	0	0
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.003	0.035	-9999	-0.47	3	3
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.016	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.003	0.027	-9999	-0.37	1	1
alphaV/beta3 Integrin/Talin	-0.005	0.043	-9999	-0.57	1	1
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	-0.001	0.017	-9999	-10000	0	0
VAV2	0.068	0.047	-9999	-0.54	3	3
RAP1/GDP	-0.003	0.03	-9999	-0.46	1	1
ITGAV	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.003	0.035	-9999	-0.47	3	3
nectin-3(dimer)/I-afadin/I-afadin	-0.003	0.042	-9999	-0.56	3	3
Rac1/GTP	-0.003	0.031	-9999	-0.41	3	3
PTPRM	-0.001	0.02	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	-0.015	0.073	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.008	0.058	-9999	-0.55	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.047	-9999	-0.54	1	1
SUMO1	0.016	0	-9999	-10000	0	0
ZFPM1	0.011	0.057	-9999	-0.74	3	3
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0.016	0	-9999	-10000	0	0
Histones	-0.003	0.022	-9999	-10000	0	0
YY1/LSF	-0.001	0.031	-9999	-0.72	1	1
SMG5	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.005	0.039	-9999	-10000	0	0
I kappa B alpha/HDAC1	-0.003	0.027	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
RELA	0.046	0.042	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
HDAC3/TR2	-0.003	0.027	-9999	-10000	0	0
NuRD/MBD3 Complex	0.062	0.025	-9999	-0.46	1	1
NF kappa B1 p50/RelA	0.048	0.047	-9999	-0.64	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.003	0.12	-9999	-0.74	13	13
GATA1	-0.02	0.17	-9999	-0.86	20	20
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.008	0.045	-9999	-0.53	2	2
RBBP7	0.016	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.014	0.033	-9999	-0.74	1	1
MAX	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
NFKBIA	-0.004	0.031	-9999	-10000	0	0
KAT2B	0.014	0.033	-9999	-0.74	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	-0.008	0.038	-9999	-10000	0	0
SIN3 complex	-0.019	0.097	-9999	-0.52	19	19
SMURF1	0.016	0	-9999	-10000	0	0
CHD3	0.016	0	-9999	-10000	0	0
SAP30	-0.016	0.16	-9999	-0.86	19	19
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.016	0	-9999	-10000	0	0
YY1/HDAC3	-0.004	0.036	-9999	-0.64	1	1
YY1/HDAC2	-0.001	0.031	-9999	-0.72	1	1
YY1/HDAC1	-0.001	0.031	-9999	-0.72	1	1
NuRD/MBD2 Complex (MeCP1)	0.063	0.01	-9999	-10000	0	0
PPARG	-0.006	0.046	-9999	-10000	0	0
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.003	0.027	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	-0.001	0.024	-9999	-0.52	1	1
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	-0.004	0.031	-9999	-10000	0	0
HDAC2	0.016	0	-9999	-10000	0	0
YY1	0.039	0.037	-9999	-0.81	1	1
HDAC8	0.016	0	-9999	-10000	0	0
SMAD7	0.016	0	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
MXD1	0.016	0	-9999	-10000	0	0
STAT3	0.034	0.019	-9999	-0.4	1	1
NFKB1	0.014	0.033	-9999	-0.74	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.001	0.029	-9999	-0.67	1	1
YY1/SAP30/HDAC1	-0.019	0.098	-9999	-0.52	20	20
EP300	0.014	0.033	-9999	-0.74	1	1
STAT3 (dimer non-phopshorylated)	0.033	0.019	-9999	-0.4	1	1
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.031	-9999	-10000	0	0
histone deacetylation	0.063	0.01	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.003	0.026	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GATAD2B	0.016	0	-9999	-10000	0	0
GATAD2A	0.016	0	-9999	-10000	0	0
GATA2/HDAC3	-0.014	0.07	-9999	-10000	0	0
GATA1/HDAC1	-0.025	0.13	-9999	-0.66	20	20
GATA1/HDAC3	-0.023	0.1	-9999	-0.52	20	20
CHD4	0.016	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.009	0.075	-9999	-0.61	8	8
SIN3/HDAC complex/Mad/Max	0.056	0.041	-9999	-10000	0	0
NuRD Complex	-0.001	0.019	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.021	-9999	-10000	0	0
SIN3B	0.016	0	-9999	-10000	0	0
MTA2	0.016	0	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	-0.001	0.018	-9999	-10000	0	0
GATA1/Fog1	-0.028	0.13	-9999	-0.65	23	23
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	0.003	0.1	-9999	-0.8	8	8
negative regulation of cell growth	0.056	0.041	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.063	0.01	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.045	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.053	0.041	-9999	-10000	0	0
TFCP2	0.016	0	-9999	-10000	0	0
NR2C1	0.016	0	-9999	-10000	0	0
MBD3	0.013	0.05	-9999	-0.8	2	2
MBD2	0.016	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.003	0.041	-9999	-0.66	2	2
FBXW11	0.016	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.004	0.046	-9999	-0.48	5	5
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.038	-9999	-10000	0	0
NFKBIA	0.028	0.055	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
NF kappa B1 p105/p50	-0.001	0.02	-9999	-0.47	1	1
ARRB2	0.022	0.018	-9999	-0.39	1	1
REL	0.01	0.066	-9999	-0.74	4	4
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.003	0.041	-9999	-0.54	3	3
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	-0.001	0.02	-9999	-0.47	1	1
PIK3CA	0.014	0.033	-9999	-0.74	1	1
NF kappa B1 p50 dimer	0.025	0.025	-9999	-0.56	1	1
PIK3R1	0.014	0.033	-9999	-0.74	1	1
NFKB1	0.03	0.026	-9999	-0.56	1	1
RELA	0.016	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.037	0.054	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.008	0.037	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PI3K	-0.002	0.034	-9999	-0.56	2	2
NF kappa B1 p50/RelA	0.037	0.055	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
SYK	0.013	0.046	-9999	-0.74	2	2
I kappa B alpha/PIK3R1	0.034	0.055	-9999	-0.39	1	1
cell death	-0.008	0.035	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.004	0.046	-9999	-0.48	5	5
LCK	-0.02	0.17	-9999	-0.85	22	22
BCL3	0.012	0.054	-9999	-0.86	2	2

×

IGF1 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
NCK2	0.016	0	-10000	0	-10000	0	0
PTK2	0.016	0	-10000	0	-10000	0	0
CRKL	0.029	0.055	-10000	0	-10000	0	0
GRB2/SOS1/SHC	-0.001	0.025	-10000	0	-0.57	1	1
HRAS	0.014	0.038	-10000	0	-0.86	1	1
IRS1/Crk	-0.007	0.051	-10000	0	-0.41	6	6
IGF-1R heterotetramer/IGF1/PTP1B	-0.006	0.055	-10000	0	-0.52	6	6
AKT1	0.054	0.061	-10000	0	-0.71	1	1
BAD	0.062	0.071	-10000	0	-1	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.029	0.055	-10000	0	-0.41	6	6
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.007	0.051	-10000	0	-0.41	6	6
RAF1	0.067	0.057	-10000	0	-0.7	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.006	0.047	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.008	0.056	-10000	0	-0.45	6	6
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
RPS6KB1	0.054	0.061	-10000	0	-0.71	1	1
GNB2L1	0.014	0.038	-10000	0	-0.86	1	1
positive regulation of MAPKKK cascade	0.059	0.049	-10000	0	-0.57	1	1
PXN	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.007	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.006	0.048	-10000	0	-0.5	1	1
IGF-1R heterotetramer	0.015	0.012	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.007	0.051	-10000	0	-10000	0	0
Crk/p130 Cas/Paxillin	-0.007	0.047	-10000	0	-10000	0	0
IGF1R	0.015	0.012	-10000	0	-10000	0	0
IGF1	0.006	0.092	-10000	0	-0.85	6	6
IRS2/Crk	0.029	0.083	-10000	0	-0.49	8	8
PI3K	-0.008	0.052	-10000	0	-10000	0	0
apoptosis	-0.065	0.059	0.79	1	-10000	0	1
HRAS/GDP	-0.001	0.029	-10000	0	-0.68	1	1
PRKCD	0.05	0.057	-10000	0	-0.82	1	1
RAF1/14-3-3 E	0.071	0.05	-10000	0	-0.57	1	1
BAD/14-3-3	0.068	0.064	-10000	0	-0.89	1	1
PRKCZ	0.052	0.068	-10000	0	-0.71	1	1
Crk/p130 Cas/Paxillin/FAK1	-0.006	0.043	-10000	0	-0.56	1	1
PTPN1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.042	0.047	-10000	0	-10000	0	0
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.006	0.053	-10000	0	-0.55	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.007	0.05	-10000	0	-10000	0	0
GRB10	0.016	0	-10000	0	-10000	0	0
PTPN11	0.029	0.055	-10000	0	-0.41	6	6
IRS1	0.018	0.059	-10000	0	-0.45	6	6
IRS2	0.02	0.087	-10000	0	-0.47	14	14
IGF-1R heterotetramer/IGF1	-0.008	0.07	-10000	0	-0.66	6	6
GRB2	0.016	0	-10000	0	-10000	0	0
PDPK1	0.044	0.064	-10000	0	-0.76	1	1
YWHAE	0.016	0	-10000	0	-10000	0	0
PRKD1	0.05	0.049	-10000	0	-10000	0	0
SHC1	0.014	0.038	-10000	0	-0.86	1	1

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.016	0	-9999	-10000	0	0
SMAD2	0.019	0	-9999	-10000	0	0
SMAD3	0.056	0	-9999	-10000	0	0
SMAD3/SMAD4	0.062	0	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0	0	-9999	-10000	0	0
PPM1A	0.016	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
SMAD2/SMAD4	0.027	0	-9999	-10000	0	0
MAP3K1	0.016	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.001	0.024	-9999	-0.56	1	1
MAPK3	0.016	0	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
NUP214	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
CTDSPL	0.016	0	-9999	-10000	0	0
KPNB1	0.016	0	-9999	-10000	0	0
TGFBRAP1	0.014	0.033	-9999	-0.74	1	1
UBE2I	0.016	0	-9999	-10000	0	0
NUP153	0.016	0	-9999	-10000	0	0
KPNA2	0.016	0	-9999	-10000	0	0
PIAS4	0.016	0	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.014	0.033	-9999	-0.74	1	1
positive regulation of NF-kappaB transcription factor activity	-0.001	0.024	-9999	-0.56	1	1
MAP2K4	0.063	0.017	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
TNFRSF10B	0.014	0.038	-9999	-0.86	1	1
TNFRSF10A	0.014	0.033	-9999	-0.74	1	1
SMPD1	-0.001	0.016	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.002	0.038	-9999	-0.61	2	2
TRAIL/TRAILR3	-0.002	0.038	-9999	-0.61	2	2
TRAIL/TRAILR1	-0.002	0.034	-9999	-0.56	2	2
TRAIL/TRAILR4	-0.001	0.024	-9999	-0.56	1	1
TRAIL/TRAILR1/DAP3/GTP	-0.002	0.027	-9999	-0.44	2	2
IKK complex	-0.001	0.009	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.03	0.025	-9999	-0.56	1	1
MAP3K1	-0.001	0.014	-9999	-10000	0	0
TRAILR4 (trimer)	0.016	0	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.014	0.033	-9999	-0.74	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.001	0.018	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
MAPK1	0.03	0.025	-9999	-0.56	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.001	0.024	-9999	-10000	0	0
mol:ceramide	-0.001	0.016	-9999	-10000	0	0
FADD	0.016	0	-9999	-10000	0	0
MAPK8	0.07	0.031	-9999	-10000	0	0
TRAF2	0.016	0	-9999	-10000	0	0
TRAILR3 (trimer)	0.014	0.038	-9999	-0.86	1	1
CHUK	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.002	0.029	-9999	-0.47	2	2
DAP3	0.016	0	-9999	-10000	0	0
CASP10	-0.002	0.025	-9999	-0.45	1	1
JNK cascade	-0.001	0.024	-9999	-0.56	1	1
TRAIL (trimer)	0.014	0.033	-9999	-0.74	1	1
TNFRSF10C	0.014	0.038	-9999	-0.86	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.002	0.025	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	-0.002	0.032	-9999	-0.52	2	2
cell death	-0.001	0.016	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.001	0.017	-9999	-10000	0	0
TRAILR2 (trimer)	0.014	0.038	-9999	-0.86	1	1
CASP8	0	0.007	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.002	0.027	-9999	-0.49	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.016	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0	-9999	-9999
HDAC4	0.016	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.016	-9999	-9999
NPC/RanGAP1/SUMO1	0.023	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.039	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.016	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.016	-9999	-9999
SUMO1/HDAC4	0	-9999	-9999
SUMO1/HDAC1	0	-9999	-9999
RANGAP1	0.016	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	-9999	-9999
Ran/GTP	0	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.016	-9999	-9999
UBE2I	0.016	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.016	-9999	-9999
PIAS1	0.016	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0	0	-9999	-10000	0	0
MAPK9	0.011	0	-9999	-10000	0	0
adrenocorticotropin secretion	-0.004	0.072	-9999	-0.68	6	6
GNB1/GNG2	0	0	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0.011	0	-9999	-10000	0	0
Gs family/GTP	0	0	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0	0	-9999	-10000	0	0
GNAL	0.016	0	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
CRH	-0.006	0.092	-9999	-0.86	6	6
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.01	0.027	-9999	-0.42	2	2
MAPK11	0.01	0.025	-9999	-0.4	2	2

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	-0.001	0.022	-9999	-0.52	1	1
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.027	0.009	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.002	-9999	-10000	0	0
CLTB	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.001	-9999	-10000	0	0
CD4	0.001	0.11	-9999	-0.86	9	9
CLTA	0.016	0	-9999	-10000	0	0
mol:GTP	0.002	0.001	-9999	-10000	0	0
ARFGAP1	0.014	0.025	-9999	-0.57	1	1
mol:PI-4-5-P2	-0.001	0.017	-9999	-0.38	1	1
ARF1/GTP	0	0.009	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.001	0.02	-9999	-0.46	1	1
mol:Choline	-0.001	0.016	-9999	-0.38	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
DDEF1	-0.001	0.017	-9999	-0.38	1	1
ARF1/GDP	-0.001	0.021	-9999	-0.46	1	1
AP2M1	0.016	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0.001	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	-0.001	0.018	-9999	-0.42	1	1
ARFIP2	0	0.003	-9999	-10000	0	0
COPA	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.034	0.005	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.001	-9999	-10000	0	0
GGA3	0.016	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0.006	-9999	-10000	0	0
AP2A1	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.01	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0.005	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.003	-9999	-10000	0	0
CYTH2	0.016	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.002	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.043	0.034	-9999	-10000	0	0
PLD2	-0.001	0.016	-9999	-0.38	1	1
ARF-GAP1/v-SNARE	0.014	0.025	-9999	-0.57	1	1
PIP5K1A	-0.001	0.017	-9999	-0.38	1	1
ARF1/GTP/Membrin/GBF1/p115	0	0.009	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.001	0.016	-9999	-0.38	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.014	0.025	-9999	-0.57	1	1
GOSR2	0	0.007	-9999	-10000	0	0
USO1	0	0.007	-9999	-10000	0	0
GBF1	0	0.007	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0.002	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.01	0.074	-9999	-0.57	9	9

×

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	-0.005	0.058	-9999	-0.66	4	4
FBXW11	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.004	0.042	-9999	-10000	0	0
NFKB1	0.014	0.033	-9999	-0.74	1	1
MAP3K14	0.009	0.076	-9999	-0.86	4	4
NF kappa B1 p50/RelB	-0.001	0.024	-9999	-0.56	1	1
RELB	0.016	0	-9999	-10000	0	0
NFKB2	0.016	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0	0	-9999	-10000	0	0
regulation of B cell activation	0	0	-9999	-10000	0	0

pid_entity	TCGA.T7.A92I	TCGA.MW.A4EC	TCGA.MM.A84U	TCGA.MM.A564
109_MAP3K5	0.074	0.074	-0.13	0.074
47_PPARGC1A	0.016	0.016	0.016	0.016
105_BMP4	0.016	0.016	0.016	0.016
105_BMP6	0.016	0.016	0.016	0.016
105_BMP7	0.016	1.4e-15	-0.74	-0.74
105_BMP2	0.016	0.016	0.016	0.016
131_RELN/VLDLR	-0.42	-0.42	0	-0.42
30_TGFB1/TGF beta receptor Type II	0.015	0.015	0.015	0.021
84_STAT5B	-0.03	-0.031	-0.14	-0.14
84_STAT5A	-0.03	-0.031	-0.14	-0.14