PARADIGM pathway analysis of mRNASeq expression and copy number data - Stomach and Esophageal carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXA2 and FOXA3 transcription factor networks	139
Reelin signaling pathway	137
Signaling events regulated by Ret tyrosine kinase	85
Signaling events mediated by Stem cell factor receptor (c-Kit)	83
Signaling events mediated by the Hedgehog family	81
Lissencephaly gene (LIS1) in neuronal migration and development	77
Glypican 1 network	74
Effects of Botulinum toxin	73
p75(NTR)-mediated signaling	67
Glypican 2 network	63

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
FOXA2 and FOXA3 transcription factor networks	0.2321	139	6425	46	-0.83	0.03	1000	-1000	-0.14	-1000
Reelin signaling pathway	0.2287	137	7699	56	-0.22	0.063	1000	-1000	-0.044	-1000
Signaling events regulated by Ret tyrosine kinase	0.1419	85	7013	82	-0.13	0.027	1000	-1000	-0.059	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1386	83	6492	78	-0.27	0.085	1000	-1000	-0.072	-1000
Signaling events mediated by the Hedgehog family	0.1352	81	4241	52	-0.11	0.066	1000	-1000	-0.043	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1285	77	4174	54	-0.17	0.037	1000	-1000	-0.042	-1000
Glypican 1 network	0.1235	74	3584	48	-0.12	0.033	1000	-1000	-0.038	-1000
Effects of Botulinum toxin	0.1219	73	1916	26	-0.13	0.026	1000	-1000	-0.011	-1000
p75(NTR)-mediated signaling	0.1119	67	8395	125	-0.17	0.069	1000	-1000	-0.064	-1000
Glypican 2 network	0.1052	63	253	4	-0.002	-0.002	1000	-1000	0.011	-1000
Wnt signaling	0.1018	61	432	7	-0.053	-0.004	1000	-1000	-0.016	-1000
HIF-1-alpha transcription factor network	0.0952	57	4333	76	-0.34	0.035	1000	-1000	-0.16	-1000
IL4-mediated signaling events	0.0952	57	5259	91	-0.67	0.51	1000	-1000	-0.19	-1000
Visual signal transduction: Cones	0.0885	53	2016	38	-0.062	0.046	1000	-1000	-0.016	-1000
Fc-epsilon receptor I signaling in mast cells	0.0868	52	5073	97	-0.11	0.039	1000	-1000	-0.059	-1000
Ephrin B reverse signaling	0.0835	50	2402	48	-0.11	0.054	1000	-1000	-0.037	-1000
Syndecan-1-mediated signaling events	0.0768	46	1585	34	-0.12	0.026	1000	-1000	-0.047	-1000
Ephrin A reverse signaling	0.0768	46	328	7	-0.012	0.01	1000	-1000	-0.013	-1000
amb2 Integrin signaling	0.0768	46	3801	82	-0.16	0.037	1000	-1000	-0.039	-1000
Nongenotropic Androgen signaling	0.0768	46	2424	52	-0.075	0.039	1000	-1000	-0.045	-1000
BMP receptor signaling	0.0751	45	3691	81	-0.14	0.048	1000	-1000	-0.061	-1000
Syndecan-2-mediated signaling events	0.0718	43	2993	69	-0.15	0.042	1000	-1000	-0.044	-1000
Canonical Wnt signaling pathway	0.0718	43	2207	51	-0.13	0.13	1000	-1000	-0.048	-1000
Noncanonical Wnt signaling pathway	0.0684	41	1073	26	-0.053	0.026	1000	-1000	-0.044	-1000
EPHB forward signaling	0.0684	41	3540	85	-0.12	0.096	1000	-1000	-0.067	-1000
TCGA08_retinoblastoma	0.0684	41	333	8	-0.069	0.045	1000	-1000	-0.007	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0618	37	4493	120	-0.11	0.078	1000	-1000	-0.051	-1000
TCGA08_p53	0.0601	36	257	7	-0.054	0.036	1000	-1000	-0.009	-1000
TCR signaling in naïve CD8+ T cells	0.0601	36	3362	93	-0.1	0.05	1000	-1000	-0.047	-1000
BCR signaling pathway	0.0601	36	3616	99	-0.09	0.034	1000	-1000	-0.053	-1000
Visual signal transduction: Rods	0.0584	35	1861	52	-0.046	0.027	1000	-1000	-0.039	-1000
LPA receptor mediated events	0.0568	34	3542	102	-0.12	0.037	1000	-1000	-0.075	-1000
Nectin adhesion pathway	0.0551	33	2124	63	-0.19	0.046	1000	-1000	-0.058	-1000
Endothelins	0.0551	33	3172	96	-0.17	0.042	1000	-1000	-0.058	-1000
Coregulation of Androgen receptor activity	0.0534	32	2436	76	-0.13	0.049	1000	-1000	-0.029	-1000
Presenilin action in Notch and Wnt signaling	0.0534	32	1986	61	-0.13	0.069	1000	-1000	-0.045	-1000
S1P5 pathway	0.0534	32	549	17	-0.041	0.033	1000	-1000	-0.021	-1000
IL23-mediated signaling events	0.0534	32	1967	60	-0.4	0.026	1000	-1000	-0.15	-1000
LPA4-mediated signaling events	0.0434	26	316	12	-0.057	0.007	1000	-1000	-0.024	-1000
Arf6 signaling events	0.0434	26	1616	62	-0.07	0.058	1000	-1000	-0.041	-1000
Glucocorticoid receptor regulatory network	0.0434	26	2984	114	-0.27	0.16	1000	-1000	-0.061	-1000
Integrins in angiogenesis	0.0434	26	2234	84	-0.15	0.059	1000	-1000	-0.046	-1000
IGF1 pathway	0.0434	26	1533	57	-0.022	0.051	1000	-1000	-0.041	-1000
S1P4 pathway	0.0434	26	665	25	-0.041	0.041	1000	-1000	-0.031	-1000
Calcium signaling in the CD4+ TCR pathway	0.0417	25	781	31	-0.12	0.027	1000	-1000	-0.048	-1000
Plasma membrane estrogen receptor signaling	0.0417	25	2222	86	-0.098	0.048	1000	-1000	-0.058	-1000
Regulation of Androgen receptor activity	0.0384	23	1622	70	-0.22	0.033	1000	-1000	-0.057	-1000
Signaling events mediated by PTP1B	0.0367	22	1716	76	-0.13	0.045	1000	-1000	-0.043	-1000
Osteopontin-mediated events	0.0351	21	827	38	-0.15	0.037	1000	-1000	-0.044	-1000
EGFR-dependent Endothelin signaling events	0.0351	21	453	21	-0.031	0.039	1000	-1000	-0.041	-1000
Syndecan-4-mediated signaling events	0.0351	21	1445	67	-0.17	0.036	1000	-1000	-0.044	-1000
PDGFR-beta signaling pathway	0.0351	21	2058	97	-0.093	0.071	1000	-1000	-0.055	-1000
Aurora B signaling	0.0351	21	1434	67	-0.3	0.078	1000	-1000	-0.036	-1000
ErbB4 signaling events	0.0334	20	1422	69	-0.1	0.051	1000	-1000	-0.055	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0334	20	1071	52	-0.091	0.052	1000	-1000	-0.06	-1000
IL27-mediated signaling events	0.0334	20	1047	51	-0.21	0.05	1000	-1000	-0.045	-1000
IL12-mediated signaling events	0.0317	19	1723	87	-0.12	0.026	1000	-1000	-0.1	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0317	19	543	28	-0.035	0.04	1000	-1000	-0.023	-1000
Ceramide signaling pathway	0.0317	19	1458	76	-0.031	0.07	1000	-1000	-0.041	-1000
Syndecan-3-mediated signaling events	0.0317	19	693	35	-0.15	0.069	1000	-1000	-0.035	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0317	19	643	33	-0.096	0.062	1000	-1000	-0.042	-1000
JNK signaling in the CD4+ TCR pathway	0.0301	18	309	17	-0.036	0.051	1000	-1000	-0.036	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0284	17	600	34	-0.018	0.042	1000	-1000	-0.03	-1000
PLK1 signaling events	0.0284	17	1525	85	-0.028	0.047	1000	-1000	-0.026	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0284	17	654	37	-0.087	0.061	1000	-1000	-0.031	-1000
IL1-mediated signaling events	0.0284	17	1107	62	-0.067	0.05	1000	-1000	-0.047	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0284	17	1195	68	-0.2	0.027	1000	-1000	-0.11	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0284	17	1498	88	-0.07	0.044	1000	-1000	-0.073	-1000
ErbB2/ErbB3 signaling events	0.0267	16	1095	65	-0.082	0.038	1000	-1000	-0.068	-1000
Caspase cascade in apoptosis	0.0267	16	1205	74	-0.038	0.06	1000	-1000	-0.058	-1000
ceramide signaling pathway	0.0267	16	809	49	0	0.038	1000	-1000	-0.041	-1000
S1P1 pathway	0.0267	16	592	36	-0.042	0.026	1000	-1000	-0.049	-1000
S1P3 pathway	0.0267	16	702	42	-0.027	0.046	1000	-1000	-0.037	-1000
FAS signaling pathway (CD95)	0.0250	15	726	47	-0.052	0.038	1000	-1000	-0.052	-1000
Regulation of p38-alpha and p38-beta	0.0234	14	798	54	-0.063	0.058	1000	-1000	-0.053	-1000
FOXM1 transcription factor network	0.0234	14	740	51	-0.071	0.04	1000	-1000	-0.16	-1000
Ras signaling in the CD4+ TCR pathway	0.0234	14	250	17	-0.006	0.041	1000	-1000	-0.043	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0217	13	1126	85	-0.027	0.045	1000	-1000	-0.043	-1000
EPO signaling pathway	0.0217	13	741	55	0.002	0.051	1000	-1000	-0.05	-1000
mTOR signaling pathway	0.0217	13	707	53	-0.024	0.049	1000	-1000	-0.035	-1000
Class I PI3K signaling events mediated by Akt	0.0217	13	938	68	-0.048	0.054	1000	-1000	-0.037	-1000
IL6-mediated signaling events	0.0217	13	986	75	-0.21	0.041	1000	-1000	-0.085	-1000
IFN-gamma pathway	0.0200	12	872	68	-0.06	0.037	1000	-1000	-0.055	-1000
Signaling mediated by p38-gamma and p38-delta	0.0200	12	187	15	-0.04	0.026	1000	-1000	-0.034	-1000
IL2 signaling events mediated by PI3K	0.0200	12	753	58	-0.044	0.057	1000	-1000	-0.05	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0200	12	936	74	-0.087	0.062	1000	-1000	-0.063	-1000
Class I PI3K signaling events	0.0200	12	942	73	-0.063	0.045	1000	-1000	-0.054	-1000
PLK2 and PLK4 events	0.0184	11	34	3	0.005	-1000	1000	-1000	-0.013	-1000
Cellular roles of Anthrax toxin	0.0184	11	454	39	-0.018	0.03	1000	-1000	-0.025	-1000
Hedgehog signaling events mediated by Gli proteins	0.0184	11	741	65	-0.12	0.06	1000	-1000	-0.05	-1000
Retinoic acid receptors-mediated signaling	0.0184	11	694	58	-0.1	0.048	1000	-1000	-0.048	-1000
Thromboxane A2 receptor signaling	0.0167	10	1119	105	-0.037	0.037	1000	-1000	-0.043	-1000
Aurora C signaling	0.0167	10	74	7	0	0.033	1000	-1000	-0.012	-1000
PDGFR-alpha signaling pathway	0.0167	10	478	44	-0.041	0.057	1000	-1000	-0.037	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0167	10	462	45	-0.003	0.061	1000	-1000	-0.065	-1000
IL2 signaling events mediated by STAT5	0.0167	10	221	22	-0.013	0.033	1000	-1000	-0.062	-1000
p38 MAPK signaling pathway	0.0167	10	479	44	-0.06	0.052	1000	-1000	-0.029	-1000
TCGA08_rtk_signaling	0.0150	9	257	26	-0.047	0.083	1000	-1000	-0.02	-1000
E-cadherin signaling in the nascent adherens junction	0.0150	9	706	76	-0.011	0.056	1000	-1000	-0.06	-1000
Signaling events mediated by PRL	0.0150	9	311	34	-0.051	0.038	1000	-1000	-0.044	-1000
E-cadherin signaling in keratinocytes	0.0150	9	388	43	-0.034	0.043	1000	-1000	-0.039	-1000
Aurora A signaling	0.0134	8	533	60	-0.066	0.056	1000	-1000	-0.025	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0134	8	689	83	-0.095	0.051	1000	-1000	-0.045	-1000
Signaling mediated by p38-alpha and p38-beta	0.0134	8	357	44	-0.088	0.027	1000	-1000	-0.037	-1000
Regulation of Telomerase	0.0134	8	838	102	-0.065	0.061	1000	-1000	-0.062	-1000
E-cadherin signaling events	0.0134	8	42	5	0.019	0.038	1000	-1000	0.004	-1000
Regulation of nuclear SMAD2/3 signaling	0.0117	7	1026	136	-0.11	0.073	1000	-1000	-0.055	-1000
FoxO family signaling	0.0117	7	457	64	-0.009	0.068	1000	-1000	-0.066	-1000
Rapid glucocorticoid signaling	0.0117	7	141	20	-0.009	0.033	1000	-1000	-0.011	-1000
Insulin-mediated glucose transport	0.0100	6	215	32	-0.067	0.05	1000	-1000	-0.033	-1000
HIF-2-alpha transcription factor network	0.0100	6	276	43	-0.048	0.052	1000	-1000	-0.075	-1000
Arf6 trafficking events	0.0100	6	491	71	-0.096	0.048	1000	-1000	-0.034	-1000
Insulin Pathway	0.0100	6	474	74	-0.026	0.072	1000	-1000	-0.049	-1000
Canonical NF-kappaB pathway	0.0083	5	230	39	0	0.056	1000	-1000	-0.042	-1000
Signaling events mediated by HDAC Class III	0.0083	5	232	40	-0.048	0.049	1000	-1000	-0.019	-1000
a4b1 and a4b7 Integrin signaling	0.0067	4	23	5	0.023	0.035	1000	-1000	0.006	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0067	4	594	125	0	0.067	1000	-1000	-0.052	-1000
VEGFR1 specific signals	0.0067	4	238	56	-0.017	0.055	1000	-1000	-0.053	-1000
Class IB PI3K non-lipid kinase events	0.0067	4	12	3	-0.024	0.024	1000	-1000	-0.009	-1000
Arf6 downstream pathway	0.0050	3	171	43	-0.036	0.045	1000	-1000	-0.038	-1000
Signaling events mediated by HDAC Class I	0.0050	3	342	104	-0.05	0.064	1000	-1000	-0.039	-1000
BARD1 signaling events	0.0033	2	151	57	-0.054	0.066	1000	-1000	-0.044	-1000
TRAIL signaling pathway	0.0033	2	98	48	0	0.052	1000	-1000	-0.043	-1000
Paxillin-dependent events mediated by a4b1	0.0033	2	77	36	-0.049	0.051	1000	-1000	-0.04	-1000
Atypical NF-kappaB pathway	0.0033	2	89	31	-0.004	0.032	1000	-1000	-0.03	-1000
Arf1 pathway	0.0033	2	128	54	-0.001	0.042	1000	-1000	-0.024	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0017	1	32	23	0.01	0.044	1000	-1000	-0.036	-1000
Signaling events mediated by HDAC Class II	0.0017	1	143	75	-0.027	0.068	1000	-1000	-0.032	-1000
Circadian rhythm pathway	0.0017	1	31	22	-0.008	0.06	1000	-1000	-0.039	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	7	27	0	0.057	1000	-1000	-0.034	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.07	1000	-1000	0	-1000
Total	NA	3218	188101	7203	-12	-990	131000	-131000	-6.1	-131000

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.51	0.36	-10000	0	-0.89	216	216
PCK1	-0.44	0.45	-10000	0	-1.1	155	155
HNF4A	-0.63	0.49	-10000	0	-1.1	261	261
KCNJ11	-0.49	0.37	-10000	0	-0.9	208	208
AKT1	-0.25	0.18	-10000	0	-0.53	81	81
response to starvation	-0.025	0.037	-10000	0	-0.22	6	6
DLK1	-0.49	0.36	-10000	0	-0.9	202	202
NKX2-1	-0.19	0.15	-10000	0	-0.38	142	142
ACADM	-0.51	0.36	-10000	0	-0.86	242	242
TAT	-0.34	0.28	-10000	0	-0.79	125	125
CEBPB	0.01	0.027	-10000	0	-0.17	1	1
CEBPA	0.005	0.047	-10000	0	-0.36	6	6
TTR	-0.49	0.51	0.44	1	-1.2	185	186
PKLR	-0.52	0.36	-10000	0	-0.88	235	235
APOA1	-0.83	0.64	-10000	0	-1.4	281	281
CPT1C	-0.51	0.36	-10000	0	-0.88	231	231
ALAS1	-0.23	0.16	-10000	0	-0.6	31	31
TFRC	-0.42	0.4	-10000	0	-1.1	131	131
FOXF1	0.009	0.08	-10000	0	-0.37	25	25
NF1	0.03	0.004	-10000	0	-10000	0	0
HNF1A (dimer)	-0.075	0.14	-10000	0	-0.32	105	105
CPT1A	-0.49	0.35	-10000	0	-0.86	226	226
HMGCS1	-0.49	0.36	-10000	0	-0.86	224	224
NR3C1	0.002	0.055	-10000	0	-0.38	5	5
CPT1B	-0.51	0.36	-10000	0	-0.87	239	239
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.01	0.044	-10000	0	-10000	0	0
GCK	-0.52	0.37	-10000	0	-0.91	220	220
CREB1	-0.006	0.057	-10000	0	-0.19	11	11
IGFBP1	-0.28	0.19	-10000	0	-0.56	99	99
PDX1	-0.4	0.46	-10000	0	-1.2	115	115
UCP2	-0.5	0.35	-10000	0	-0.87	225	225
ALDOB	-0.59	0.44	-10000	0	-1	260	260
AFP	-0.11	0.16	-10000	0	-0.47	55	55
BDH1	-0.49	0.35	-10000	0	-0.87	210	210
HADH	-0.48	0.36	-10000	0	-0.9	197	197
F2	-0.64	0.48	-10000	0	-1.2	209	209
HNF1A	-0.075	0.14	-10000	0	-0.32	105	105
G6PC	-0.1	0.18	-10000	0	-0.58	51	51
SLC2A2	-0.6	0.53	-10000	0	-1.2	240	240
INS	0.003	0.043	-10000	0	-10000	0	0
FOXA1	-0.054	0.12	-10000	0	-0.32	74	74
FOXA3	-0.12	0.17	-10000	0	-0.38	148	148
FOXA2	-0.55	0.4	-10000	0	-0.98	222	222
ABCC8	-0.63	0.43	-10000	0	-0.97	320	320
ALB	-0.15	0.25	-10000	0	-0.61	100	100

×

Reelin signaling pathway

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.023	0.061	-10000	0	-0.22	33	33
VLDLR	-0.03	0.14	-10000	0	-0.37	79	79
CRKL	0.025	0.015	-10000	0	-0.32	1	1
LRPAP1	0.025	0.007	-10000	0	-10000	0	0
FYN	0.026	0.005	-10000	0	-10000	0	0
ITGA3	0.026	0.02	-10000	0	-0.32	2	2
RELN/VLDLR/Fyn	-0.057	0.15	-10000	0	-0.26	194	194
MAPK8IP1/MKK7/MAP3K11/JNK1	0.063	0.049	-10000	0	-0.19	13	13
AKT1	-0.15	0.17	-10000	0	-0.29	305	305
MAP2K7	0.026	0.006	-10000	0	-10000	0	0
RAPGEF1	0.026	0.005	-10000	0	-10000	0	0
DAB1	-0.16	0.2	-10000	0	-0.37	273	273
RELN/LRP8/DAB1	-0.18	0.18	-10000	0	-0.28	412	412
LRPAP1/LRP8	-0.065	0.13	-10000	0	-0.22	237	237
RELN/LRP8/DAB1/Fyn	-0.17	0.17	-10000	0	-0.27	396	396
DAB1/alpha3/beta1 Integrin	-0.18	0.18	-10000	0	-0.38	200	200
long-term memory	-0.22	0.2	-10000	0	-0.42	236	236
DAB1/LIS1	-0.18	0.18	-10000	0	-0.38	208	208
DAB1/CRLK/C3G	-0.18	0.18	-10000	0	-0.38	197	197
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
DAB1/NCK2	-0.18	0.18	-10000	0	-0.39	202	202
ARHGEF2	0.026	0.005	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.075	0.17	-10000	0	-0.37	150	150
CDK5R1	0.007	0.08	-10000	0	-0.32	33	33
RELN	-0.09	0.18	-10000	0	-0.37	170	170
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
RELN/LRP8/Fyn	-0.1	0.16	-10000	0	-0.25	301	301
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.21	0.2	-10000	0	-0.34	362	362
MAPK8	0.026	0.004	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.14	0.17	-10000	0	-0.27	340	340
ITGB1	0.026	0.005	-10000	0	-10000	0	0
MAP1B	-0.2	0.18	0.16	5	-0.33	315	320
RELN/LRP8	-0.1	0.16	-10000	0	-0.25	300	300
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.18	0.19	-10000	0	-0.36	239	239
PI3K	0.032	0.016	-10000	0	-10000	0	0
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.037	0.018	-10000	0	-0.22	2	2
RAP1A	-0.18	0.16	0.23	4	-0.36	195	199
PAFAH1B1	0.025	0.006	-10000	0	-10000	0	0
MAPK8IP1	0.015	0.064	-10000	0	-0.37	16	16
CRLK/C3G	0.037	0.015	-10000	0	-0.22	1	1
GRIN2B	-0.006	0.097	-10000	0	-0.32	50	50
NCK2	0.026	0.005	-10000	0	-10000	0	0
neuron differentiation	-0.15	0.15	-10000	0	-0.32	201	201
neuron adhesion	-0.17	0.16	0.3	6	-0.36	170	176
LRP8	-0.11	0.17	-10000	0	-0.32	239	239
GSK3B	-0.14	0.17	-10000	0	-0.39	142	142
RELN/VLDLR/DAB1/Fyn	-0.13	0.17	-10000	0	-0.26	337	337
MAP3K11	0.026	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.16	0.19	-10000	0	-0.3	322	322
CDK5	0.025	0.007	-10000	0	-10000	0	0
MAPT	-0.035	0.16	0.82	8	-0.32	102	110
neuron migration	-0.21	0.17	0.23	2	-0.4	205	207
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.15	0.16	-10000	0	-0.33	201	201
RELN/VLDLR	-0.11	0.17	-10000	0	-0.26	293	293

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.026	0.098	-10000	0	-0.43	26	26
Crk/p130 Cas/Paxillin	-0.097	0.14	-10000	0	-0.33	91	91
JUN	-0.087	0.14	-10000	0	-0.36	91	91
HRAS	0.026	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.069	0.16	-10000	0	-0.26	221	221
RAP1A	0.026	0.005	-10000	0	-10000	0	0
FRS2	0.025	0.007	-10000	0	-10000	0	0
RAP1A/GDP	0.02	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.073	0.17	-10000	0	-0.26	229	229
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.026	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.052	0.12	-10000	0	-0.21	217	217
RHOA	0.025	0.007	-10000	0	-10000	0	0
RAP1A/GTP	-0.064	0.15	-10000	0	-0.35	74	74
GRB7	0.021	0.029	-10000	0	-0.36	3	3
RET51/GFRalpha1/GDNF	-0.072	0.16	-10000	0	-0.27	214	214
MAPKKK cascade	-0.081	0.15	-10000	0	-0.38	74	74
BCAR1	0.026	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.052	0.13	-10000	0	-0.21	216	216
lamellipodium assembly	-0.082	0.13	-10000	0	-0.26	166	166
RET51/GFRalpha1/GDNF/SHC	-0.071	0.16	-10000	0	-0.26	222	222
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.051	0.12	-10000	0	-0.21	210	210
RET9/GFRalpha1/GDNF/Shank3	-0.052	0.12	-10000	0	-0.21	214	214
MAPK3	-0.085	0.13	0.27	4	-0.35	68	72
DOK1	0.026	0.022	-10000	0	-0.35	2	2
DOK6	0.023	0.023	-10000	0	-0.35	2	2
PXN	0.027	0.004	-10000	0	-10000	0	0
neurite development	-0.075	0.12	0.33	1	-0.33	56	57
DOK5	0.012	0.062	-10000	0	-0.35	17	17
GFRA1	-0.13	0.2	-10000	0	-0.37	237	237
MAPK8	-0.093	0.15	-10000	0	-0.37	91	91
HRAS/GTP	-0.082	0.17	-10000	0	-0.41	78	78
tube development	-0.046	0.12	0.2	4	-0.2	204	208
MAPK1	-0.084	0.13	0.29	3	-0.35	69	72
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.06	0.11	-10000	0	-0.21	196	196
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
SRC	0.023	0.009	-10000	0	-10000	0	0
PDLIM7	0.024	0.025	-10000	0	-0.32	3	3
RET51/GFRalpha1/GDNF/Dok6	-0.055	0.15	-10000	0	-0.37	59	59
SHC1	0.026	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.072	0.16	-10000	0	-0.27	217	217
RET51/GFRalpha1/GDNF/Dok5	-0.067	0.15	-10000	0	-0.26	202	202
PRKCA	0.025	0.017	-10000	0	-0.37	1	1
HRAS/GDP	0.019	0.004	-10000	0	-10000	0	0
CREB1	-0.098	0.16	-10000	0	-0.39	83	83
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.061	0.11	-10000	0	-0.21	198	198
RET51/GFRalpha1/GDNF/Grb7	-0.063	0.15	-10000	0	-0.26	195	195
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.035	0.14	-10000	0	-0.36	93	93
DOK4	0.025	0.017	-10000	0	-0.37	1	1
JNK cascade	-0.085	0.14	-10000	0	-0.35	91	91
RET9/GFRalpha1/GDNF/FRS2	-0.052	0.12	-10000	0	-0.21	210	210
SHANK3	0.026	0.006	-10000	0	-10000	0	0
RASA1	0.025	0.008	-10000	0	-10000	0	0
NCK1	0.025	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.061	0.11	-10000	0	-0.21	201	201
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.087	0.15	-10000	0	-0.37	89	89
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.089	0.16	-10000	0	-0.39	94	94
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.096	0.17	-10000	0	-0.44	82	82
PI3K	-0.12	0.2	0.19	2	-0.38	177	179
SOS1	0.027	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.04	0.12	-10000	0	-0.2	204	204
GRB10	0.025	0.016	-10000	0	-0.32	1	1
activation of MAPKK activity	-0.073	0.14	-10000	0	-0.34	80	80
RET51/GFRalpha1/GDNF/FRS2	-0.073	0.16	-10000	0	-0.27	216	216
GAB1	0.026	0.006	-10000	0	-10000	0	0
IRS1	0.025	0.023	-10000	0	-0.37	2	2
IRS2	0.014	0.067	-10000	0	-0.37	17	17
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.095	0.17	-10000	0	-0.35	134	134
RET51/GFRalpha1/GDNF/PKC alpha	-0.072	0.16	-10000	0	-0.26	220	220
GRB2	0.026	0.005	-10000	0	-10000	0	0
PRKACA	0.026	0.005	-10000	0	-10000	0	0
GDNF	0.007	0.076	-10000	0	-0.36	24	24
RAC1	0.025	0.007	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.074	0.17	-10000	0	-0.26	225	225
Rac1/GTP	-0.092	0.16	-10000	0	-0.32	160	160
RET9/GFRalpha1/GDNF	-0.067	0.13	-10000	0	-0.23	216	216
GFRalpha1/GDNF	-0.081	0.15	-10000	0	-0.28	216	216

×

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

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
MAP4K1	-0.078	0.17	0.3	2	-0.38	128	130
CRKL	-0.081	0.17	0.26	1	-0.39	133	134
HRAS	-0.059	0.16	0.22	1	-0.35	120	121
mol:PIP3	-0.067	0.17	-10000	0	-0.36	123	123
SPRED1	0.026	0.005	-10000	0	-10000	0	0
SPRED2	0.027	0.003	-10000	0	-10000	0	0
GAB1	-0.084	0.18	-10000	0	-0.41	136	136
FOXO3	-0.067	0.18	0.35	1	-0.37	121	122
AKT1	-0.072	0.19	-10000	0	-0.4	124	124
BAD	-0.068	0.18	-10000	0	-0.38	122	122
megakaryocyte differentiation	-0.093	0.18	-10000	0	-0.41	134	134
GSK3B	-0.061	0.18	0.3	5	-0.38	114	119
RAF1	-0.05	0.14	0.24	3	-0.29	106	109
SHC1	0.026	0.005	-10000	0	-10000	0	0
STAT3	-0.084	0.18	-10000	0	-0.41	135	135
STAT1	-0.21	0.42	-10000	0	-0.95	141	141
HRAS/SPRED1	-0.038	0.14	0.23	3	-0.32	41	44
cell proliferation	-0.083	0.18	-10000	0	-0.4	136	136
PIK3CA	0.023	0.009	-10000	0	-10000	0	0
TEC	0.025	0.017	-10000	0	-0.37	1	1
RPS6KB1	-0.076	0.19	-10000	0	-0.4	137	137
HRAS/SPRED2	-0.038	0.14	0.23	2	-0.34	29	31
LYN/TEC/p62DOK	-0.051	0.19	-10000	0	-0.4	121	121
MAPK3	-0.034	0.1	0.19	7	-0.27	18	25
STAP1	-0.098	0.2	-10000	0	-0.44	137	137
GRAP2	0.018	0.055	-10000	0	-0.36	12	12
JAK2	-0.18	0.38	-10000	0	-0.83	141	141
STAT1 (dimer)	-0.2	0.41	-10000	0	-0.93	141	141
mol:Gleevec	0.002	0.007	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.056	0.19	-10000	0	-0.4	132	132
actin filament polymerization	-0.08	0.17	-10000	0	-0.4	121	121
LYN	0.024	0.022	-10000	0	-0.32	2	2
STAP1/STAT5A (dimer)	-0.14	0.27	-10000	0	-0.6	141	141
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.053	0.17	0.27	1	-0.37	120	121
PI3K	-0.056	0.18	-10000	0	-0.39	119	119
PTEN	0.025	0.007	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.23	0.48	-10000	0	-1.1	140	140
MAPK8	-0.085	0.18	-10000	0	-0.41	136	136
STAT3 (dimer)	-0.082	0.18	-10000	0	-0.4	135	135
positive regulation of transcription	-0.026	0.088	0.17	9	-0.23	16	25
mol:GDP	-0.058	0.17	-10000	0	-0.36	129	129
PIK3C2B	-0.084	0.18	-10000	0	-0.41	133	133
CBL/CRKL	-0.064	0.17	0.26	1	-0.38	124	125
FER	-0.085	0.18	-10000	0	-0.41	137	137
SH2B3	-0.082	0.18	-10000	0	-0.41	136	136
PDPK1	-0.06	0.16	0.23	1	-0.35	107	108
SNAI2	-0.087	0.19	-10000	0	-0.42	126	126
positive regulation of cell proliferation	-0.15	0.32	-10000	0	-0.7	141	141
KITLG	0.013	0.033	-10000	0	-0.36	1	1
cell motility	-0.15	0.32	-10000	0	-0.7	141	141
PTPN6	0.028	0.019	-10000	0	-0.3	1	1
EPOR	-0.07	0.23	-10000	0	-1.1	18	18
STAT5A (dimer)	-0.12	0.26	-10000	0	-0.58	142	142
SOCS1	0.023	0.033	-10000	0	-0.33	5	5
cell migration	0.085	0.18	0.41	135	-10000	0	135
SOS1	0.027	0.003	-10000	0	-10000	0	0
EPO	-0.01	0.084	-10000	0	-0.32	37	37
VAV1	0.018	0.053	-10000	0	-0.34	13	13
GRB10	-0.081	0.18	-10000	0	-0.41	124	124
PTPN11	0.029	0.009	-10000	0	-10000	0	0
SCF/KIT	-0.086	0.19	-10000	0	-0.43	137	137
GO:0007205	0.004	0.01	-10000	0	-10000	0	0
MAP2K1	-0.039	0.11	0.2	6	-0.27	24	30
CBL	0.025	0.007	-10000	0	-10000	0	0
KIT	-0.27	0.52	-10000	0	-1.2	145	145
MAP2K2	-0.04	0.11	0.2	6	-0.28	21	27
SHC/Grb2/SOS1	-0.051	0.19	-10000	0	-0.39	128	128
STAT5A	-0.12	0.27	-10000	0	-0.6	141	141
GRB2	0.026	0.005	-10000	0	-10000	0	0
response to radiation	-0.085	0.18	-10000	0	-0.42	126	126
SHC/GRAP2	0.032	0.042	-10000	0	-0.26	12	12
PTPRO	-0.095	0.19	-10000	0	-0.42	134	134
SH2B2	-0.082	0.18	-10000	0	-0.41	121	121
DOK1	0.026	0.022	-10000	0	-0.35	2	2
MATK	-0.087	0.19	-10000	0	-0.42	135	135
CREBBP	0.007	0.061	-10000	0	-10000	0	0
BCL2	-0.12	0.32	-10000	0	-0.98	54	54

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.065	0.17	-10000	0	-0.44	76	76
IHH	-0.068	0.18	-10000	0	-0.42	119	119
SHH Np/Cholesterol/GAS1	-0.026	0.099	-10000	0	-0.21	124	124
LRPAP1	0.025	0.007	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.026	0.099	0.21	124	-10000	0	124
SMO/beta Arrestin2	-0.068	0.19	0.27	1	-0.46	81	82
SMO	-0.081	0.19	-10000	0	-0.47	84	84
AKT1	-0.039	0.14	-10000	0	-0.5	34	34
ARRB2	0.025	0.007	-10000	0	-10000	0	0
BOC	-0.015	0.12	-10000	0	-0.37	61	61
ADRBK1	0.026	0.006	-10000	0	-10000	0	0
heart looping	-0.08	0.19	-10000	0	-0.46	85	85
STIL	-0.075	0.15	0.36	1	-0.37	85	86
DHH N/PTCH2	0.004	0.093	-10000	0	-0.24	73	73
DHH N/PTCH1	-0.046	0.15	-10000	0	-0.36	80	80
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
DHH	0.009	0.082	-10000	0	-0.37	26	26
PTHLH	-0.1	0.24	-10000	0	-0.64	81	81
determination of left/right symmetry	-0.08	0.19	-10000	0	-0.46	85	85
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
skeletal system development	-0.1	0.24	-10000	0	-0.64	81	81
IHH N/Hhip	-0.11	0.18	-10000	0	-0.32	234	234
DHH N/Hhip	-0.06	0.15	-10000	0	-0.28	184	184
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.08	0.19	-10000	0	-0.46	85	85
pancreas development	-0.09	0.18	-10000	0	-0.37	172	172
HHAT	0.019	0.052	-10000	0	-0.37	10	10
PI3K	0.032	0.016	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.011	0.12	-10000	0	-0.37	56	56
somite specification	-0.08	0.19	-10000	0	-0.46	85	85
SHH Np/Cholesterol/PTCH1	-0.062	0.15	-10000	0	-0.37	89	89
SHH Np/Cholesterol/PTCH2	-0.023	0.094	-10000	0	-0.2	123	123
SHH Np/Cholesterol/Megalin	-0.025	0.094	-10000	0	-0.2	131	131
SHH	-0.028	0.098	-10000	0	-0.27	80	80
catabolic process	-0.055	0.15	-10000	0	-0.37	80	80
SMO/Vitamin D3	-0.073	0.18	-10000	0	-0.44	81	81
SHH Np/Cholesterol/Hhip	-0.066	0.13	-10000	0	-0.24	201	201
LRP2	-0.011	0.11	-10000	0	-0.32	61	61
receptor-mediated endocytosis	-0.084	0.17	-10000	0	-0.44	83	83
SHH Np/Cholesterol/BOC	-0.027	0.1	-10000	0	-0.22	123	123
SHH Np/Cholesterol/CDO	-0.012	0.085	-10000	0	-0.21	90	90
mesenchymal cell differentiation	0.066	0.13	0.24	201	-10000	0	201
mol:Vitamin D3	-0.06	0.16	-10000	0	-0.39	77	77
IHH N/PTCH2	-0.045	0.13	-10000	0	-0.26	161	161
CDON	0.018	0.052	-10000	0	-0.36	11	11
IHH N/PTCH1	-0.05	0.16	-10000	0	-0.37	80	80
Megalin/LRPAP1	0.009	0.079	-10000	0	-0.22	61	61
PTCH2	-0.002	0.097	-10000	0	-0.33	48	48
SHH Np/Cholesterol	-0.015	0.077	-10000	0	-0.2	81	81
PTCH1	-0.055	0.15	-10000	0	-0.37	80	80
HHIP	-0.09	0.18	-10000	0	-0.37	172	172

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.026	0.005	-10000	0	-10000	0	0
VLDLR	-0.03	0.14	-10000	0	-0.37	79	79
LRPAP1	0.025	0.007	-10000	0	-10000	0	0
NUDC	0.026	0.006	-10000	0	-10000	0	0
RELN/LRP8	-0.1	0.16	-10000	0	-0.25	300	300
CaM/Ca2+	0.019	0.004	-10000	0	-10000	0	0
KATNA1	0.026	0.005	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.1	0.14	0.18	13	-0.28	151	164
IQGAP1/CaM	0.037	0.012	-10000	0	-10000	0	0
DAB1	-0.16	0.2	-10000	0	-0.37	273	273
IQGAP1	0.026	0.006	-10000	0	-10000	0	0
PLA2G7	-0.12	0.17	-10000	0	-0.32	249	249
CALM1	0.026	0.005	-10000	0	-10000	0	0
DYNLT1	0.026	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	-0.065	0.13	-10000	0	-0.22	237	237
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.026	0.005	-10000	0	-10000	0	0
CDK5R1	0.007	0.08	-10000	0	-0.32	33	33
LIS1/Poliovirus Protein 3A	0.008	0.003	-10000	0	-10000	0	0
CDK5R2	-0.055	0.16	-10000	0	-0.37	122	122
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.16	0.19	-10000	0	-0.3	340	340
YWHAE	0.025	0.007	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.11	0.15	0.29	5	-0.33	125	130
MAP1B	0.004	0.011	-10000	0	-0.24	1	1
RAC1	0.011	0.006	-10000	0	-10000	0	0
p35/CDK5	-0.092	0.13	0.19	12	-0.32	89	101
RELN	-0.09	0.18	-10000	0	-0.37	170	170
PAFAH/LIS1	-0.06	0.1	-10000	0	-0.19	236	236
LIS1/CLIP170	0.025	0.011	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.089	0.12	-10000	0	-0.28	108	108
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.17	0.21	-10000	0	-0.45	173	173
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.12	0.15	0.28	3	-0.34	129	132
LIS1/IQGAP1	0.024	0.012	-10000	0	-10000	0	0
RHOA	0.011	0.006	-10000	0	-10000	0	0
PAFAH1B1	0.011	0.005	-10000	0	-10000	0	0
PAFAH1B3	0.026	0.005	-10000	0	-10000	0	0
PAFAH1B2	0.025	0.007	-10000	0	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.012	0.038	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.1	0.15	0.31	4	-0.32	123	127
LRP8	-0.11	0.17	-10000	0	-0.32	239	239
NDEL1/Katanin 60	-0.11	0.15	0.29	5	-0.33	126	131
P39/CDK5	-0.12	0.15	0.18	11	-0.34	131	142
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.024	0.011	-10000	0	-10000	0	0
CDK5	-0.1	0.12	0.18	19	-0.33	76	95
PPP2R5D	0.025	0.007	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.021	0.009	-10000	0	-10000	0	0
CSNK2A1	0.024	0.008	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.12	0.17	-10000	0	-0.27	299	299
RELN/VLDLR	-0.11	0.17	-10000	0	-0.26	293	293
CDC42	0.011	0.006	-10000	0	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.019	0.086	-10000	0	-0.22	65	65
fibroblast growth factor receptor signaling pathway	0.018	0.086	-10000	0	-0.22	65	65
LAMA1	-0.057	0.15	-10000	0	-0.33	140	140
PRNP	0.024	0.018	-10000	0	-0.37	1	1
GPC1/SLIT2	-0.036	0.13	-10000	0	-0.26	147	147
SMAD2	0.002	0.049	0.18	6	-0.35	1	7
GPC1/PrPc/Cu2+	0.018	0.056	-10000	0	-0.19	40	40
GPC1/Laminin alpha1	-0.038	0.14	-10000	0	-0.26	149	149
TDGF1	-0.053	0.15	-10000	0	-0.36	120	120
CRIPTO/GPC1	-0.037	0.13	-10000	0	-0.26	147	147
APP/GPC1	0.018	0.066	-10000	0	-0.22	40	40
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.041	0.1	-10000	0	-0.22	128	128
FLT1	0.026	0.006	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.033	0.064	-10000	0	-0.19	41	41
SERPINC1	0.02	0.04	-10000	0	-0.32	8	8
FYN	-0.044	0.1	-10000	0	-0.22	140	140
FGR	-0.044	0.1	-10000	0	-0.22	142	142
positive regulation of MAPKKK cascade	-0.061	0.16	0.21	30	-0.36	87	117
SLIT2	-0.05	0.16	-10000	0	-0.37	112	112
GPC1/NRG	-0.026	0.12	-10000	0	-0.25	127	127
NRG1	-0.037	0.14	-10000	0	-0.36	93	93
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.03	0.062	-10000	0	-0.19	40	40
LYN	-0.041	0.1	-10000	0	-0.22	133	133
mol:Spermine	-0.009	0.058	-10000	0	-0.22	41	41
cell growth	0.018	0.086	-10000	0	-0.22	65	65
BMP signaling pathway	-0.002	0.089	0.32	41	-10000	0	41
SRC	-0.039	0.1	-10000	0	-0.23	120	120
TGFBR1	0.026	0.015	-10000	0	-0.32	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.12	0.18	-10000	0	-0.34	241	241
GPC1	0.002	0.089	-10000	0	-0.33	41	41
TGFBR1 (dimer)	0.026	0.015	-10000	0	-0.32	1	1
VEGFA	0.024	0.016	-10000	0	-0.32	1	1
BLK	-0.086	0.14	-10000	0	-0.27	205	205
HCK	-0.04	0.1	-10000	0	-0.23	127	127
FGF2	0.006	0.087	-10000	0	-0.37	30	30
FGFR1	0.021	0.038	-10000	0	-0.35	6	6
VEGFR1 homodimer	0.026	0.006	-10000	0	-10000	0	0
TGFBR2	0.024	0.024	-10000	0	-0.37	2	2
cell death	0.018	0.066	-10000	0	-0.22	40	40
ATIII/GPC1	0.015	0.072	-10000	0	-0.23	48	48
PLA2G2A/GPC1	-0.089	0.15	-10000	0	-0.25	260	260
LCK	-0.061	0.12	-10000	0	-0.23	182	182
neuron differentiation	-0.026	0.12	-10000	0	-0.25	127	127
PrPc/Cu2+	0.018	0.013	-10000	0	-0.26	1	1
APP	0.025	0.008	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.024	0.024	-10000	0	-0.37	2	2

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.004	0.021	-10000	0	-0.22	5	5
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	-0.045	0.13	-10000	0	-0.26	159	159
STXBP1	0.024	0.029	-10000	0	-0.32	4	4
ACh/CHRNA1	-0.091	0.11	0.11	3	-0.2	279	282
RAB3GAP2/RIMS1/UNC13B	-0.024	0.12	-10000	0	-0.22	155	155
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	-0.086	0.18	-10000	0	-0.37	166	166
mol:ACh	-0.013	0.054	0.083	53	-0.11	107	160
RAB3GAP2	0.026	0.005	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.041	0.11	-10000	0	-0.26	56	56
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.091	0.11	0.11	3	-0.2	279	282
UNC13B	0.024	0.024	-10000	0	-0.37	2	2
CHRNA1	-0.13	0.17	-10000	0	-0.32	270	270
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.029	0.093	-10000	0	-0.21	103	103
SNAP25	-0.04	0.093	-10000	0	-0.23	111	111
VAMP2	0.004	0.001	-10000	0	-10000	0	0
SYT1	-0.032	0.13	-10000	0	-0.34	96	96
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.02	0.026	-10000	0	-0.18	9	9
STX1A/SNAP25 fragment 1/VAMP2	-0.041	0.11	-10000	0	-0.26	56	56

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.037	0.02	-10000	0	-0.26	2	2
Necdin/E2F1	0.026	0.05	-10000	0	-0.25	17	17
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.017	0.14	-10000	0	-0.33	37	37
NGF (dimer)/p75(NTR)/BEX1	-0.14	0.18	-10000	0	-0.28	341	341
NT-4/5 (dimer)/p75(NTR)	-0.096	0.15	-10000	0	-0.26	269	269
IKBKB	0.024	0.008	-10000	0	-10000	0	0
AKT1	-0.049	0.11	0.19	46	-0.36	17	63
IKBKG	0.026	0.006	-10000	0	-10000	0	0
BDNF	0.009	0.076	-10000	0	-0.32	29	29
MGDIs/NGR/p75(NTR)/LINGO1	-0.041	0.13	-10000	0	-0.22	200	200
FURIN	0.026	0.006	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.036	0.13	-10000	0	-0.22	190	190
LINGO1	0.003	0.088	-10000	0	-0.32	40	40
Sortilin/TRAF6/NRIF	0.028	0.023	-10000	0	-10000	0	0
proBDNF (dimer)	0.009	0.076	-10000	0	-0.32	29	29
NTRK1	0.014	0.068	-10000	0	-0.37	18	18
RTN4R	0.023	0.032	-10000	0	-0.32	5	5
neuron apoptosis	-0.06	0.15	0.31	4	-0.48	27	31
IRAK1	0.026	0.005	-10000	0	-10000	0	0
SHC1	-0.062	0.12	-10000	0	-0.24	178	178
ARHGDIA	0.026	0.004	-10000	0	-10000	0	0
RhoA/GTP	0.019	0.005	-10000	0	-10000	0	0
Gamma Secretase	0.069	0.029	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.027	0.14	-10000	0	-0.23	182	182
MAGEH1	0.019	0.054	-10000	0	-0.37	11	11
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.03	0.14	-10000	0	-0.23	185	185
Mammalian IAPs/DIABLO	0.06	0.035	-10000	0	-0.2	7	7
proNGF (dimer)	0.004	0.088	-10000	0	-0.36	33	33
MAGED1	0.024	0.029	-10000	0	-0.37	3	3
APP	0.025	0.008	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.045	0.14	-10000	0	-0.32	117	117
ZNF274	0.023	0.029	-10000	0	-0.37	3	3
RhoA/GDP/RHOGDI	-0.038	0.11	-10000	0	-0.21	154	154
NGF	0.004	0.088	-10000	0	-0.36	33	33
cell cycle arrest	-0.031	0.12	0.26	11	-0.33	21	32
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.034	0.1	-10000	0	-0.32	28	28
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.068	0.13	-10000	0	-0.22	261	261
NCSTN	0.026	0.005	-10000	0	-10000	0	0
mol:GTP	-0.039	0.14	-10000	0	-0.24	185	185
PSENEN	0.026	0.006	-10000	0	-10000	0	0
mol:ceramide	-0.053	0.11	0.18	8	-0.22	151	159
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.029	0.094	-10000	0	-0.3	35	35
p75(NTR)/beta APP	-0.048	0.13	-10000	0	-0.26	172	172
BEX1	-0.14	0.19	-10000	0	-0.37	247	247
mol:GDP	-0.077	0.11	-10000	0	-0.23	184	184
NGF (dimer)	-0.053	0.12	-10000	0	-0.26	43	43
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.025	0.13	-10000	0	-0.21	150	150
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
RAC1/GTP	-0.027	0.11	-10000	0	-0.2	169	169
MYD88	0.025	0.006	-10000	0	-10000	0	0
CHUK	0.026	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.039	0.14	-10000	0	-0.24	185	185
RHOB	0.027	0.002	-10000	0	-10000	0	0
RHOA	0.025	0.007	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.034	0.022	-10000	0	-0.22	3	3
NT3 (dimer)	-0.02	0.13	-10000	0	-0.37	67	67
TP53	-0.052	0.1	0.2	31	-0.33	9	40
PRDM4	-0.055	0.11	0.18	9	-0.22	156	165
BDNF (dimer)	-0.16	0.14	-10000	0	-0.33	150	150
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
SORT1	0.025	0.024	-10000	0	-0.37	2	2
activation of caspase activity	-0.021	0.13	-10000	0	-0.32	37	37
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.023	0.13	-10000	0	-0.22	158	158
RHOC	0.026	0.005	-10000	0	-10000	0	0
XIAP	0.027	0.004	-10000	0	-10000	0	0
MAPK10	-0.08	0.16	0.3	6	-0.42	60	66
DIABLO	0.026	0.004	-10000	0	-10000	0	0
SMPD2	-0.053	0.11	0.18	8	-0.23	151	159
APH1B	0.026	0.004	-10000	0	-10000	0	0
APH1A	0.026	0.005	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.038	0.14	-10000	0	-0.24	182	182
PSEN1	0.026	0.005	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.038	0.009	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.076	0.16	-10000	0	-0.28	207	207
MAPK8	-0.059	0.13	0.3	7	-0.35	30	37
MAPK9	-0.061	0.13	0.3	7	-0.35	34	41
APAF1	0.027	0.004	-10000	0	-10000	0	0
NTF3	-0.02	0.13	-10000	0	-0.37	67	67
NTF4	-0.045	0.14	-10000	0	-0.32	117	117
NDN	0.013	0.07	-10000	0	-0.37	19	19
RAC1/GDP	0.019	0.005	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.017	0.12	-10000	0	-0.34	20	20
p75 CTF/Sortilin/TRAF6/NRIF	0.059	0.035	-10000	0	-0.2	5	5
RhoA-B-C/GTP	-0.04	0.14	-10000	0	-0.24	185	185
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.011	0.12	-10000	0	-0.35	9	9
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.02	0.12	-10000	0	-0.2	182	182
PRKACB	0.024	0.033	-10000	0	-0.37	4	4
proBDNF (dimer)/p75 ECD	0.026	0.057	-10000	0	-0.22	29	29
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.021	0.043	-10000	0	-0.37	7	7
BIRC2	0.026	0.006	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.034	0.14	0.26	9	-0.26	102	111
BAD	-0.073	0.14	0.26	9	-0.36	67	76
RIPK2	0.024	0.009	-10000	0	-10000	0	0
NGFR	-0.087	0.18	-10000	0	-0.37	172	172
CYCS	-0.063	0.099	0.2	10	-0.36	19	29
ADAM17	0.026	0.015	-10000	0	-0.32	1	1
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.016	0.12	-10000	0	-0.22	132	132
BCL2L11	-0.073	0.15	0.26	10	-0.36	66	76
BDNF (dimer)/p75(NTR)	-0.058	0.14	-10000	0	-0.26	192	192
PI3K	-0.024	0.13	-10000	0	-0.22	167	167
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.023	0.13	-10000	0	-0.22	180	180
NDNL2	0.026	0.004	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
PRKCI	0.023	0.017	-10000	0	-0.32	1	1
NGF (dimer)/p75(NTR)	-0.061	0.15	-10000	0	-0.28	184	184
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.024	0.14	-10000	0	-0.23	158	158
TRAF6	0.026	0.005	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
PLG	0.013	0.042	-10000	0	-0.32	9	9
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.061	0.12	-10000	0	-0.26	148	148
SQSTM1	0.025	0.007	-10000	0	-10000	0	0
NGFRAP1	0.018	0.059	-10000	0	-0.37	13	13
CASP3	-0.071	0.14	0.26	8	-0.34	67	75
E2F1	0.022	0.026	-10000	0	-0.32	3	3
CASP9	0.026	0.005	-10000	0	-10000	0	0
IKK complex	-0.006	0.12	-10000	0	-0.33	24	24
NGF (dimer)/TRKA	0.012	0.083	-10000	0	-0.26	50	50
MMP7	-0.12	0.17	-10000	0	-0.33	246	246
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.014	0.13	-10000	0	-0.36	22	22
MMP3	-0.17	0.17	-10000	0	-0.32	325	325
APAF-1/Caspase 9	-0.062	0.075	-10000	0	-0.31	16	16

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0	0.092	-9999	-0.32	45	45
GPC2	-0.002	0.091	-9999	-0.32	44	44
GPC2/Midkine	-0.002	0.094	-9999	-0.23	82	82
neuron projection morphogenesis	-0.002	0.094	-9999	-0.23	82	82

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.053	0.12	-9999	-0.26	122	122
FZD6	0.017	0.047	-9999	-0.33	10	10
WNT6	-0.017	0.12	-9999	-0.36	66	66
WNT4	-0.009	0.11	-9999	-0.37	52	52
FZD3	0.022	0.033	-9999	-0.37	4	4
WNT5A	-0.004	0.098	-9999	-0.33	50	50
WNT11	-0.052	0.15	-9999	-0.34	128	128

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.29	0.32	-10000	0	-0.88	83	83
HDAC7	0.023	0.014	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.24	0.33	-10000	0	-0.89	68	68
SMAD4	0.024	0.01	-10000	0	-10000	0	0
ID2	-0.28	0.33	0.41	1	-0.89	79	80
AP1	0.025	0.064	-10000	0	-0.26	27	27
ABCG2	-0.29	0.34	0.41	1	-0.9	84	85
HIF1A	-0.053	0.067	-10000	0	-0.37	1	1
TFF3	-0.34	0.36	0.41	1	-0.93	99	100
GATA2	0.023	0.037	-10000	0	-0.37	5	5
AKT1	-0.054	0.077	-10000	0	-0.26	9	9
response to hypoxia	-0.062	0.066	-10000	0	-0.22	39	39
MCL1	-0.28	0.33	-10000	0	-0.89	79	79
NDRG1	-0.27	0.32	0.41	1	-0.89	74	75
SERPINE1	-0.29	0.34	0.41	1	-0.91	82	83
FECH	-0.28	0.33	0.41	1	-0.89	79	80
FURIN	-0.28	0.33	0.41	1	-0.89	78	79
NCOA2	0.023	0.019	-10000	0	-0.37	1	1
EP300	-0.053	0.098	-10000	0	-0.34	36	36
HMOX1	-0.28	0.33	0.41	1	-0.89	79	80
BHLHE40	-0.28	0.33	0.41	1	-0.89	80	81
BHLHE41	-0.28	0.33	-10000	0	-0.91	73	73
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.028	0.1	-10000	0	-10000	0	0
ENG	-0.041	0.081	0.23	1	-10000	0	1
JUN	0.027	0.005	-10000	0	-10000	0	0
RORA	-0.28	0.33	0.41	1	-0.9	80	81
ABCB1	-0.11	0.26	-10000	0	-0.99	41	41
TFRC	-0.27	0.32	0.41	1	-0.89	75	76
CXCR4	-0.28	0.33	0.41	1	-0.9	79	80
TF	-0.33	0.36	0.41	1	-0.89	111	112
CITED2	-0.28	0.33	0.41	1	-0.89	78	79
HIF1A/ARNT	-0.29	0.39	-10000	0	-1	79	79
LDHA	-0.032	0.11	-10000	0	-0.73	10	10
ETS1	-0.28	0.33	0.41	1	-0.89	79	80
PGK1	-0.28	0.33	0.41	1	-0.9	79	80
NOS2	-0.33	0.35	0.41	1	-0.92	96	97
ITGB2	-0.28	0.33	0.41	1	-0.9	81	82
ALDOA	-0.28	0.33	0.41	1	-0.9	78	79
Cbp/p300/CITED2	-0.29	0.37	0.4	1	-1	77	78
FOS	0.008	0.083	-10000	0	-0.37	27	27
HK2	-0.28	0.34	0.41	1	-0.91	80	81
SP1	0.024	0.031	-10000	0	-10000	0	0
GCK	-0.15	0.32	-10000	0	-1.2	39	39
HK1	-0.28	0.33	0.41	1	-0.89	80	81
NPM1	-0.28	0.33	0.41	1	-0.89	79	80
EGLN1	-0.28	0.33	-10000	0	-0.89	79	79
CREB1	0.031	0.005	-10000	0	-10000	0	0
PGM1	-0.28	0.33	0.41	1	-0.89	81	82
SMAD3	0.027	0.005	-10000	0	-10000	0	0
EDN1	-0.066	0.15	-10000	0	-0.6	24	24
IGFBP1	-0.31	0.34	0.41	1	-0.91	90	91
VEGFA	-0.22	0.28	0.36	1	-0.79	61	62
HIF1A/JAB1	-0.02	0.055	-10000	0	-0.26	1	1
CP	-0.3	0.35	0.41	1	-0.93	87	88
CXCL12	-0.3	0.35	0.41	1	-0.93	87	88
COPS5	0.024	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4	0.035	0.015	-10000	0	-10000	0	0
BNIP3	-0.28	0.34	0.41	1	-0.9	83	84
EGLN3	-0.28	0.33	0.41	1	-0.9	80	81
CA9	-0.32	0.35	0.41	1	-0.91	100	101
TERT	-0.29	0.33	0.41	1	-0.9	81	82
ENO1	-0.28	0.33	0.41	1	-0.89	79	80
PFKL	-0.28	0.33	0.41	1	-0.89	79	80
NCOA1	0.027	0.003	-10000	0	-10000	0	0
ADM	-0.28	0.34	0.41	1	-0.9	81	82
ARNT	-0.051	0.064	-10000	0	-0.23	1	1
HNF4A	-0.043	0.14	-10000	0	-0.37	93	93
ADFP	-0.29	0.32	-10000	0	-0.88	83	83
SLC2A1	-0.25	0.3	0.36	1	-0.8	82	83
LEP	-0.29	0.34	0.41	1	-0.91	84	85
HIF1A/ARNT/Cbp/p300	-0.25	0.33	-10000	0	-0.9	69	69
EPO	-0.15	0.22	-10000	0	-0.71	21	21
CREBBP	-0.056	0.11	-10000	0	-0.35	41	41
HIF1A/ARNT/Cbp/p300/HDAC7	-0.24	0.34	-10000	0	-0.92	68	68
PFKFB3	-0.28	0.33	0.41	1	-0.9	76	77
NT5E	-0.28	0.33	0.41	1	-0.9	79	80

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.44	0.46	-10000	0	-1.3	98	98
STAT6 (cleaved dimer)	-0.47	0.48	-10000	0	-1.2	138	138
IGHG1	-0.15	0.15	-10000	0	-10000	0	0
IGHG3	-0.44	0.45	-10000	0	-1.1	134	134
AKT1	-0.22	0.26	-10000	0	-0.86	43	43
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.17	0.22	-10000	0	-0.81	37	37
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.23	0.25	-10000	0	-0.86	37	37
THY1	-0.47	0.46	-10000	0	-1.3	104	104
MYB	-0.037	0.13	-10000	0	-0.32	106	106
HMGA1	0.025	0.015	-10000	0	-0.32	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.27	0.27	-10000	0	-0.75	65	65
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.23	0.25	-10000	0	-0.85	39	39
SP1	0.02	0.027	-10000	0	-10000	0	0
INPP5D	0.024	0.03	-10000	0	-0.34	4	4
SOCS5	0.037	0.02	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.45	0.47	-10000	0	-1.2	117	117
SOCS1	-0.31	0.29	-10000	0	-0.76	94	94
SOCS3	-0.23	0.23	-10000	0	-0.76	26	26
FCER2	-0.53	0.57	-10000	0	-1.4	161	161
PARP14	0.018	0.028	-10000	0	-0.32	2	2
CCL17	-0.49	0.5	-10000	0	-1.3	111	111
GRB2	0.026	0.005	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.19	0.21	-10000	0	-0.73	36	36
T cell proliferation	-0.46	0.48	-10000	0	-1.3	108	108
IL4R/JAK1	-0.46	0.47	-10000	0	-1.2	108	108
EGR2	-0.5	0.51	-10000	0	-1.3	123	123
JAK2	-0.026	0.039	-10000	0	-10000	0	0
JAK3	0.018	0.064	-10000	0	-0.33	19	19
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
JAK1	0	0.024	-10000	0	-10000	0	0
COL1A2	-0.16	0.19	-10000	0	-0.96	9	9
CCL26	-0.48	0.47	-10000	0	-1.2	114	114
IL4R	-0.49	0.5	-10000	0	-1.3	107	107
PTPN6	0.035	0.02	-10000	0	-0.31	1	1
IL13RA2	-0.49	0.47	-10000	0	-1.3	109	109
IL13RA1	-0.028	0.04	-10000	0	-10000	0	0
IRF4	-0.15	0.28	-10000	0	-0.96	49	49
ARG1	-0.1	0.14	-10000	0	-0.89	3	3
CBL	-0.26	0.25	-10000	0	-0.73	56	56
GTF3A	0.006	0.037	-10000	0	-10000	0	0
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.031	0.053	-10000	0	-10000	0	0
IRF4/BCL6	-0.12	0.25	-10000	0	-0.85	48	48
CD40LG	-0.002	0.094	-10000	0	-0.36	36	36
MAPK14	-0.25	0.25	-10000	0	-0.78	42	42
mitosis	-0.22	0.24	-10000	0	-0.8	43	43
STAT6	-0.53	0.56	-10000	0	-1.4	126	126
SPI1	0.024	0.036	-10000	0	-0.33	5	5
RPS6KB1	-0.21	0.23	-10000	0	-0.77	43	43
STAT6 (dimer)	-0.53	0.56	-10000	0	-1.4	126	126
STAT6 (dimer)/PARP14	-0.5	0.52	-10000	0	-1.3	128	128
mast cell activation	0.012	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.22	0.26	-10000	0	-0.83	48	48
FRAP1	-0.22	0.26	-10000	0	-0.86	43	43
LTA	-0.46	0.47	-10000	0	-1.3	104	104
FES	0.025	0.017	-10000	0	-0.37	1	1
T-helper 1 cell differentiation	0.51	0.53	1.3	127	-10000	0	127
CCL11	-0.48	0.5	-10000	0	-1.3	119	119
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.21	0.24	-10000	0	-0.8	41	41
IL2RG	0.007	0.086	-10000	0	-0.32	37	37
IL10	-0.46	0.47	-10000	0	-1.3	103	103
IRS1	0.025	0.023	-10000	0	-0.37	2	2
IRS2	0.014	0.067	-10000	0	-0.37	17	17
IL4	-0.16	0.26	-10000	0	-1.1	35	35
IL5	-0.47	0.46	-10000	0	-1.3	104	104
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.39	0.39	-10000	0	-1	113	113
COL1A1	-0.21	0.22	-10000	0	-1.2	8	8
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.47	0.49	-10000	0	-1.3	99	99
IL2R gamma/JAK3	0.014	0.082	-10000	0	-0.24	52	52
TFF3	-0.55	0.54	-10000	0	-1.4	129	129
ALOX15	-0.49	0.48	-10000	0	-1.3	116	116
MYBL1	0.02	0.042	-10000	0	-0.33	8	8
T-helper 2 cell differentiation	-0.42	0.43	-10000	0	-1.1	123	123
SHC1	0.026	0.005	-10000	0	-10000	0	0
CEBPB	0.022	0.018	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.21	0.23	-10000	0	-0.77	36	36
mol:PI-3-4-5-P3	-0.22	0.26	-10000	0	-0.86	43	43
PI3K	-0.24	0.28	-10000	0	-0.93	43	43
DOK2	0.022	0.033	-10000	0	-0.37	4	4
ETS1	0.034	0.02	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.17	0.19	-10000	0	-0.66	31	31
ITGB3	-0.47	0.47	-10000	0	-1.3	105	105
PIGR	-0.67	0.65	-10000	0	-1.4	228	228
IGHE	0.052	0.068	0.19	67	-10000	0	67
MAPKKK cascade	-0.17	0.18	-10000	0	-0.64	31	31
BCL6	0.026	0.011	-10000	0	-10000	0	0
OPRM1	-0.47	0.47	-10000	0	-1.3	100	100
RETNLB	-0.52	0.52	-10000	0	-1.3	132	132
SELP	-0.55	0.57	-10000	0	-1.4	149	149
AICDA	-0.45	0.45	-10000	0	-1.2	105	105

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.042	0.025	-10000	0	-0.21	4	4
RGS9BP	-0.014	0.12	-10000	0	-0.37	58	58
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.018	0.015	-10000	0	-0.32	1	1
mol:Na +	-0.057	0.12	-10000	0	-0.22	201	201
mol:ADP	-0.015	0.036	-10000	0	-0.23	15	15
GNAT2	0.026	0.005	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.02	0.13	-10000	0	-0.24	139	139
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.028	0.018	-10000	0	-0.18	3	3
GRK7	0.015	0.053	-10000	0	-0.32	14	14
CNGB3	-0.062	0.15	-10000	0	-0.32	144	144
Cone Metarhodopsin II/X-Arrestin	0.015	0.017	-10000	0	-0.22	3	3
mol:Ca2+	-0.053	0.12	0.18	45	-0.21	186	231
Cone PDE6	-0.005	0.12	-10000	0	-0.22	123	123
Cone Metarhodopsin II	0.02	0.032	-10000	0	-0.17	15	15
Na + (4 Units)	-0.05	0.12	-10000	0	-0.21	211	211
GNAT2/GDP	-0.007	0.12	-10000	0	-0.21	137	137
GNB5	0.026	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.005	0.041	0.18	20	-0.27	3	23
Cone Transducin	0.046	0.027	-10000	0	-0.22	4	4
SLC24A2	0.008	0.069	-10000	0	-0.33	24	24
GNB3/GNGT2	0.035	0.03	-10000	0	-0.3	4	4
GNB3	0.023	0.032	-10000	0	-0.36	4	4
GNAT2/GTP	0.019	0.004	-10000	0	-10000	0	0
CNGA3	-0.041	0.15	-10000	0	-0.37	100	100
ARR3	0.02	0.025	-10000	0	-0.32	3	3
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	-0.057	0.12	-10000	0	-0.22	201	201
mol:Pi	-0.021	0.13	-10000	0	-0.24	139	139
Cone CNG Channel	-0.034	0.12	-10000	0	-0.24	77	77
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.008	0.069	-10000	0	-0.32	24	24
RGS9	-0.046	0.15	-10000	0	-0.37	108	108
PDE6C	0.022	0.021	-10000	0	-0.32	2	2
GNGT2	0.026	0.015	-10000	0	-0.32	1	1
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.017	0.025	-10000	0	-0.32	3	3

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.025	0.018	-10000	0	-0.37	1	1
LAT2	-0.067	0.13	0.17	1	-0.33	80	81
AP1	-0.052	0.17	0.26	2	-0.43	61	63
mol:PIP3	-0.082	0.16	0.26	15	-0.41	65	80
IKBKB	-0.043	0.11	0.2	30	-0.25	59	89
AKT1	-0.053	0.12	0.27	27	-0.29	39	66
IKBKG	-0.047	0.1	0.19	23	-0.25	62	85
MS4A2	-0.04	0.15	-10000	0	-0.37	98	98
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.023	0.009	-10000	0	-10000	0	0
MAP3K1	-0.039	0.14	0.23	39	-0.35	53	92
mol:Ca2+	-0.062	0.13	0.23	16	-0.31	65	81
LYN	0.022	0.023	-10000	0	-0.33	2	2
CBLB	-0.065	0.13	-10000	0	-0.31	89	89
SHC1	0.026	0.005	-10000	0	-10000	0	0
RasGAP/p62DOK	0.039	0.046	-10000	0	-0.2	19	19
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.024	0.03	-10000	0	-0.34	4	4
PLD2	-0.079	0.12	0.26	19	-0.33	56	75
PTPN13	-0.079	0.17	-10000	0	-0.52	36	36
PTPN11	0.013	0.025	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.044	0.12	0.26	19	-0.29	39	58
SYK	0.024	0.019	-10000	0	-0.37	1	1
GRB2	0.026	0.005	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.077	0.16	-10000	0	-0.4	72	72
LAT	-0.068	0.13	-10000	0	-0.31	92	92
PAK2	-0.045	0.15	0.24	40	-0.38	57	97
NFATC2	-0.038	0.11	-10000	0	-0.56	21	21
HRAS	-0.066	0.15	0.22	9	-0.41	65	74
GAB2	0.026	0.006	-10000	0	-10000	0	0
PLA2G1B	-0.02	0.17	-10000	0	-0.83	24	24
Fc epsilon R1	-0.074	0.16	-10000	0	-0.27	228	228
Antigen/IgE/Fc epsilon R1	-0.065	0.15	-10000	0	-0.24	227	227
mol:GDP	-0.068	0.16	0.23	2	-0.43	66	68
JUN	0.027	0.003	-10000	0	-10000	0	0
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.024	0.008	-10000	0	-10000	0	0
FOS	0.008	0.083	-10000	0	-0.37	27	27
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.067	0.14	-10000	0	-0.32	95	95
CHUK	-0.051	0.1	0.19	16	-0.25	63	79
KLRG1	-0.062	0.12	-10000	0	-0.32	69	69
VAV1	-0.068	0.13	0.21	1	-0.33	84	85
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.065	0.13	-10000	0	-0.33	73	73
negative regulation of mast cell degranulation	-0.05	0.12	0.18	8	-0.3	67	75
BTK	-0.07	0.17	0.23	1	-0.45	67	68
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.099	0.18	-10000	0	-0.45	91	91
GAB2/PI3K/SHP2	-0.078	0.095	-10000	0	-0.3	46	46
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.068	0.14	-10000	0	-0.37	66	66
RAF1	-0.002	0.19	-10000	0	-0.9	24	24
Fc epsilon R1/FcgammaRIIB/SHIP	-0.054	0.17	-10000	0	-0.27	185	185
FCER1G	0.022	0.047	-10000	0	-0.33	10	10
FCER1A	-0.11	0.19	-10000	0	-0.38	193	193
Antigen/IgE/Fc epsilon R1/Fyn	-0.052	0.14	-10000	0	-0.23	213	213
MAPK3	-0.005	0.17	-10000	0	-0.82	24	24
MAPK1	-0.005	0.17	-10000	0	-0.83	24	24
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MAPK8	-0.046	0.2	-10000	0	-0.58	57	57
DUSP1	0.014	0.069	-10000	0	-0.37	18	18
NF-kappa-B/RelA	-0.024	0.068	0.14	4	-0.19	15	19
actin cytoskeleton reorganization	-0.066	0.16	-10000	0	-0.53	25	25
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.052	0.14	0.22	1	-0.38	56	57
FER	-0.063	0.13	-10000	0	-0.32	85	85
RELA	0.026	0.005	-10000	0	-10000	0	0
ITK	-0.025	0.071	-10000	0	-0.27	32	32
SOS1	0.027	0.003	-10000	0	-10000	0	0
PLCG1	-0.055	0.16	0.22	12	-0.43	58	70
cytokine secretion	-0.021	0.046	-10000	0	-10000	0	0
SPHK1	-0.075	0.14	-10000	0	-0.33	93	93
PTK2	-0.069	0.17	-10000	0	-0.56	25	25
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.076	0.17	0.21	1	-0.43	66	67
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.081	0.16	0.25	12	-0.41	66	78
MAP2K2	-0.009	0.17	-10000	0	-0.84	24	24
MAP2K1	-0.007	0.17	-10000	0	-0.83	24	24
MAP2K7	0.026	0.006	-10000	0	-10000	0	0
KLRG1/SHP2	-0.05	0.12	0.19	8	-0.28	67	75
MAP2K4	-0.074	0.31	-10000	0	-0.89	71	71
Fc epsilon R1/FcgammaRIIB	-0.064	0.17	-10000	0	-0.27	227	227
mol:Choline	-0.078	0.12	0.26	19	-0.32	56	75
SHC/Grb2/SOS1	-0.036	0.14	0.23	2	-0.35	58	60
FYN	0.026	0.005	-10000	0	-10000	0	0
DOK1	0.026	0.022	-10000	0	-0.35	2	2
PXN	-0.066	0.16	-10000	0	-0.53	22	22
HCLS1	-0.065	0.13	-10000	0	-0.32	83	83
PRKCB	-0.07	0.14	0.22	15	-0.34	73	88
FCGR2B	0.005	0.089	-10000	0	-0.37	31	31
IGHE	-0.002	0.006	-10000	0	-10000	0	0
KLRG1/SHIP	-0.051	0.12	0.19	8	-0.31	67	75
LCP2	0.023	0.03	-10000	0	-0.34	4	4
PLA2G4A	-0.07	0.13	-10000	0	-0.32	91	91
RASA1	0.025	0.008	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.078	0.12	0.26	19	-0.32	56	75
IKK complex	-0.028	0.089	0.19	32	-0.22	17	49
WIPF1	0.026	0.017	-10000	0	-0.37	1	1

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.025	0.018	-10000	0	-0.37	1	1
EPHB2	-0.11	0.17	-10000	0	-0.32	238	238
EFNB1	-0.001	0.038	-10000	0	-0.22	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.052	0.13	-10000	0	-0.3	66	66
Ephrin B2/EPHB1-2	-0.056	0.12	-10000	0	-0.2	226	226
neuron projection morphogenesis	-0.058	0.12	-10000	0	-0.28	66	66
Ephrin B1/EPHB1-2/Tiam1	-0.063	0.13	-10000	0	-0.31	69	69
DNM1	0.017	0.055	-10000	0	-0.32	15	15
cell-cell signaling	0	0.004	-10000	0	-10000	0	0
MAP2K4	-0.047	0.15	0.28	2	-0.5	59	61
YES1	-0.06	0.22	-10000	0	-0.72	61	61
Ephrin B1/EPHB1-2/NCK2	-0.053	0.13	-10000	0	-0.31	59	59
PI3K	-0.018	0.16	-10000	0	-0.5	56	56
mol:GDP	-0.063	0.13	-10000	0	-0.31	69	69
ITGA2B	0.006	0.081	-10000	0	-0.32	34	34
endothelial cell proliferation	0.031	0.017	-10000	0	-0.22	1	1
FYN	-0.061	0.23	-10000	0	-0.72	62	62
MAP3K7	-0.051	0.16	0.23	1	-0.52	60	61
FGR	-0.058	0.22	-10000	0	-0.71	60	60
TIAM1	0.009	0.076	-10000	0	-0.34	27	27
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
RGS3	0.026	0.005	-10000	0	-10000	0	0
cell adhesion	-0.034	0.15	-10000	0	-0.48	54	54
LYN	-0.059	0.22	-10000	0	-0.71	61	61
Ephrin B1/EPHB1-2/Src Family Kinases	-0.06	0.2	-10000	0	-0.65	62	62
Ephrin B1/EPHB1-2	-0.051	0.17	-10000	0	-0.58	56	56
SRC	-0.057	0.22	-10000	0	-0.7	60	60
ITGB3	0.023	0.038	-10000	0	-0.36	6	6
EPHB1	-0.023	0.12	-10000	0	-0.32	82	82
EPHB4	0.024	0.008	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.031	0.017	-10000	0	-0.22	1	1
alphaIIb/beta3 Integrin	0.021	0.067	-10000	0	-0.23	40	40
BLK	-0.088	0.23	-10000	0	-0.74	60	60
HCK	-0.058	0.22	-10000	0	-0.7	60	60
regulation of stress fiber formation	0.053	0.13	0.3	59	-10000	0	59
MAPK8	-0.046	0.15	0.25	2	-0.48	59	61
Ephrin B1/EPHB1-2/RGS3	-0.054	0.13	-10000	0	-0.3	62	62
endothelial cell migration	-0.019	0.15	0.23	23	-0.44	50	73
NCK2	0.026	0.005	-10000	0	-10000	0	0
PTPN13	-0.014	0.14	-10000	0	-0.46	51	51
regulation of focal adhesion formation	0.053	0.13	0.3	59	-10000	0	59
chemotaxis	0.054	0.13	0.3	62	-10000	0	62
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
Rac1/GTP	-0.055	0.12	-10000	0	-0.29	66	66
angiogenesis	-0.052	0.17	-10000	0	-0.57	58	58
LCK	-0.062	0.22	-10000	0	-0.71	62	62

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.026	0.006	-10000	0	-10000	0	0
CCL5	0.009	0.076	-10000	0	-0.33	29	29
SDCBP	0.025	0.008	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.064	0.11	0.26	10	-0.27	65	75
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.065	0.099	0.22	5	-0.32	29	34
Syndecan-1/Syntenin	-0.058	0.11	0.26	7	-0.31	29	36
MAPK3	-0.06	0.099	0.21	7	-0.33	18	25
HGF/MET	0.021	0.065	-10000	0	-0.24	33	33
TGFB1/TGF beta receptor Type II	0.026	0.006	-10000	0	-10000	0	0
BSG	0.026	0.006	-10000	0	-10000	0	0
keratinocyte migration	-0.064	0.098	0.22	5	-0.31	29	34
Syndecan-1/RANTES	-0.066	0.12	0.25	11	-0.32	42	53
Syndecan-1/CD147	-0.054	0.11	0.25	9	-0.34	19	28
Syndecan-1/Syntenin/PIP2	-0.057	0.1	0.24	7	-0.3	29	36
LAMA5	0.023	0.01	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	-0.056	0.1	0.23	7	-0.3	29	36
MMP7	-0.12	0.17	-10000	0	-0.33	246	246
HGF	0.011	0.074	-10000	0	-0.36	23	23
Syndecan-1/CASK	-0.069	0.098	0.17	1	-0.26	68	69
Syndecan-1/HGF/MET	-0.062	0.12	0.25	8	-0.32	34	42
regulation of cell adhesion	-0.06	0.097	0.23	8	-0.33	17	25
HPSE	0.02	0.048	-10000	0	-0.33	11	11
positive regulation of cell migration	-0.064	0.11	0.26	10	-0.27	65	75
SDC1	-0.068	0.1	0.21	2	-0.27	65	67
Syndecan-1/Collagen	-0.064	0.11	0.26	10	-0.27	65	75
PPIB	0.026	0.004	-10000	0	-10000	0	0
MET	0.018	0.05	-10000	0	-0.33	12	12
PRKACA	0.026	0.005	-10000	0	-10000	0	0
MMP9	-0.082	0.16	-10000	0	-0.32	178	178
MAPK1	-0.057	0.1	0.23	9	-0.33	18	27
homophilic cell adhesion	-0.063	0.11	0.27	11	-0.26	65	76
MMP1	-0.12	0.17	-10000	0	-0.32	240	240

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.004	0.08	-10000	0	-0.22	65	65
EFNA5	0.01	0.075	-10000	0	-0.37	22	22
FYN	-0.012	0.068	0.18	5	-0.2	61	66
neuron projection morphogenesis	0.004	0.08	-10000	0	-0.22	65	65
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.004	0.081	-10000	0	-0.22	65	65
EPHA5	-0.005	0.1	-10000	0	-0.37	45	45

×

amb2 Integrin signaling

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
alphaM/beta2 Integrin/proMMP-2	0.024	0.065	-10000	0	-0.21	25	25
alphaM/beta2 Integrin/GPIbA	0.02	0.071	-10000	0	-0.21	34	34
alphaM/beta2 Integrin/proMMP-9	-0.044	0.12	-10000	0	-0.21	179	179
PLAUR	0.022	0.038	-10000	0	-0.32	7	7
HMGB1	0.016	0.026	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.025	0.059	-10000	0	-0.2	21	21
AGER	0.015	0.031	-10000	0	-0.32	1	1
RAP1A	0.026	0.005	-10000	0	-10000	0	0
SELPLG	0.022	0.039	-10000	0	-0.33	7	7
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.023	0.093	-10000	0	-0.28	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.082	0.16	-10000	0	-0.32	178	178
CYR61	0.024	0.03	-10000	0	-0.34	4	4
TLN1	0.025	0.008	-10000	0	-10000	0	0
Rap1/GTP	-0.012	0.087	-10000	0	-0.28	18	18
RHOA	0.025	0.007	-10000	0	-10000	0	0
P-selectin oligomer	-0.035	0.14	-10000	0	-0.37	91	91
MYH2	-0.03	0.09	-10000	0	-0.29	25	25
MST1R	0.021	0.04	-10000	0	-0.37	6	6
leukocyte activation during inflammatory response	-0.092	0.13	-10000	0	-0.21	306	306
APOB	-0.16	0.2	-10000	0	-0.36	287	287
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.024	0.028	-10000	0	-0.36	3	3
JAM3	0.025	0.007	-10000	0	-10000	0	0
GP1BA	0.018	0.054	-10000	0	-0.36	12	12
alphaM/beta2 Integrin/CTGF	0.023	0.067	-10000	0	-0.2	30	30
alphaM/beta2 Integrin	-0.022	0.084	-10000	0	-0.27	30	30
JAM3 homodimer	0.025	0.007	-10000	0	-10000	0	0
ICAM2	0.024	0.032	-10000	0	-0.36	4	4
ICAM1	0.017	0.057	-10000	0	-0.32	16	16
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.022	0.085	-10000	0	-0.27	30	30
cell adhesion	0.019	0.071	-10000	0	-0.21	34	34
NFKB1	-0.012	0.12	0.38	1	-0.34	45	46
THY1	0.007	0.078	-10000	0	-0.32	31	31
RhoA/GDP	0.019	0.005	-10000	0	-10000	0	0
Lipoprotein(a)	-0.11	0.14	-10000	0	-0.23	315	315
alphaM/beta2 Integrin/LRP/tPA	0.037	0.061	-10000	0	-0.18	24	24
IL6	-0.041	0.17	0.37	1	-0.57	41	42
ITGB2	0.006	0.064	-10000	0	-0.34	17	17
elevation of cytosolic calcium ion concentration	0.011	0.095	-10000	0	-0.19	92	92
alphaM/beta2 Integrin/JAM2/JAM3	0.014	0.097	-10000	0	-0.2	84	84
JAM2	-0.019	0.12	-10000	0	-0.37	66	66
alphaM/beta2 Integrin/ICAM1	0.029	0.09	-10000	0	-0.24	19	19
alphaM/beta2 Integrin/uPA/Plg	0.007	0.095	-10000	0	-0.19	81	81
RhoA/GTP	-0.032	0.092	-10000	0	-0.3	28	28
positive regulation of phagocytosis	-0.011	0.079	0.17	1	-0.28	11	12
Ron/MSP	0.019	0.07	-10000	0	-0.23	41	41
alphaM/beta2 Integrin/uPAR/uPA	0.012	0.096	-10000	0	-0.19	92	92
alphaM/beta2 Integrin/uPAR	0.022	0.067	-10000	0	-0.2	30	30
PLAU	-0.015	0.11	-10000	0	-0.32	69	69
PLAT	0.024	0.016	-10000	0	-0.32	1	1
actin filament polymerization	-0.029	0.089	0.19	1	-0.29	24	25
MST1	0.004	0.084	-10000	0	-0.32	36	36
alphaM/beta2 Integrin/lipoprotein(a)	-0.089	0.13	-10000	0	-0.21	306	306
TNF	-0.029	0.13	0.29	1	-0.49	20	21
RAP1B	0.026	0.006	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0	0.094	-10000	0	-0.2	90	90
fibrinolysis	0.003	0.093	-10000	0	-0.19	81	81
HCK	0.023	0.022	-10000	0	-0.32	2	2
dendritic cell antigen processing and presentation	-0.022	0.085	-10000	0	-0.27	30	30
VTN	-0.044	0.15	-10000	0	-0.35	111	111
alphaM/beta2 Integrin/CYR61	0.024	0.065	-10000	0	-0.2	28	28
LPA	-0.018	0.11	-10000	0	-0.32	69	69
LRP1	0.026	0.005	-10000	0	-10000	0	0
cell migration	-0.036	0.11	0.17	20	-0.24	51	71
FN1	0	0.093	-10000	0	-0.33	45	45
alphaM/beta2 Integrin/Thy1	0.014	0.079	-10000	0	-0.2	52	52
MPO	0.022	0.038	-10000	0	-0.32	7	7
KNG1	0.005	0.073	-10000	0	-0.32	28	28
RAP1/GDP	0.034	0.01	-10000	0	-10000	0	0
ROCK1	-0.026	0.092	0.19	6	-0.29	25	31
ELA2	0	0	-10000	0	-10000	0	0
PLG	0.013	0.042	-10000	0	-0.32	9	9
CTGF	0.022	0.039	-10000	0	-0.36	6	6
alphaM/beta2 Integrin/Hck	0.022	0.062	-10000	0	-0.2	24	24
ITGAM	0.011	0.05	-10000	0	-0.35	8	8
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.003	0.11	-10000	0	-0.22	97	97
HP	-0.012	0.11	-10000	0	-0.32	63	63
leukocyte adhesion	-0.011	0.1	-10000	0	-0.31	22	22
SELP	-0.035	0.14	-10000	0	-0.37	91	91

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.005	0.003	-10000	0	-10000	0	0
GNB1/GNG2	-0.014	0.11	-10000	0	-0.2	147	147
regulation of S phase of mitotic cell cycle	-0.026	0.091	-10000	0	-0.21	109	109
GNAO1	-0.019	0.12	-10000	0	-0.37	68	68
HRAS	0.026	0.006	-10000	0	-10000	0	0
SHBG/T-DHT	0.009	0.036	-10000	0	-0.18	20	20
PELP1	0.025	0.007	-10000	0	-10000	0	0
AKT1	0.006	0.001	-10000	0	-10000	0	0
MAP2K1	-0.029	0.093	0.18	51	-0.28	8	59
T-DHT/AR	-0.051	0.12	-10000	0	-0.26	150	150
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-0.007	30	30
GNAI2	0.025	0.007	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNAI1	0.019	0.052	-10000	0	-0.37	10	10
mol:GDP	-0.075	0.14	-10000	0	-0.32	134	134
cell proliferation	-0.038	0.13	0.29	7	-0.42	30	37
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
FOS	-0.038	0.18	0.25	4	-0.71	33	37
mol:Ca2+	-0.015	0.031	-10000	0	-0.076	103	103
MAPK3	-0.034	0.11	0.24	13	-0.32	27	40
MAPK1	-0.017	0.097	0.21	3	-0.45	15	18
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.005	30	30
cAMP biosynthetic process	0.002	0.039	-10000	0	-0.17	18	18
GNG2	0.025	0.022	-10000	0	-0.35	2	2
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	30	30
HRAS/GTP	-0.008	0.092	-10000	0	-0.18	112	112
actin cytoskeleton reorganization	0.031	0.019	-10000	0	-10000	0	0
SRC	0.023	0.009	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	30	30
PI3K	0.03	0.015	-10000	0	-10000	0	0
apoptosis	0.023	0.12	0.39	38	-0.26	5	43
T-DHT/AR/PELP1	-0.029	0.11	-10000	0	-0.22	150	150
HRAS/GDP	-0.063	0.14	-10000	0	-0.32	115	115
CREB1	-0.025	0.12	0.26	5	-0.41	38	43
RAC1-CDC42/GTP	0.039	0.024	-10000	0	-10000	0	0
AR	-0.074	0.17	-10000	0	-0.37	150	150
GNB1	0.026	0.006	-10000	0	-10000	0	0
RAF1	-0.014	0.099	0.19	54	-0.25	8	62
RAC1-CDC42/GDP	-0.034	0.15	-10000	0	-0.32	102	102
T-DHT/AR/PELP1/Src	-0.01	0.099	-10000	0	-0.2	125	125
MAP2K2	-0.03	0.091	0.17	48	-0.27	8	56
T-DHT/AR/PELP1/Src/PI3K	-0.026	0.091	-10000	0	-0.21	109	109
GNAZ	-0.012	0.12	-10000	0	-0.37	56	56
SHBG	0.012	0.063	-10000	0	-0.32	20	20
Gi family/GNB1/GNG2/GDP	-0.063	0.18	-10000	0	-0.44	81	81
mol:T-DHT	0	0.001	-10000	0	-0.003	20	20
RAC1	0.025	0.007	-10000	0	-10000	0	0
GNRH1	0.005	0.016	-10000	0	-0.26	2	2
Gi family/GTP	-0.059	0.12	-10000	0	-0.3	106	106
CDC42	0.026	0.006	-10000	0	-10000	0	0

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.029	0.14	-10000	0	-0.35	38	38
SMAD6-7/SMURF1	0.042	0.024	-10000	0	-10000	0	0
NOG	0.005	0.086	-10000	0	-0.35	33	33
SMAD9	-0.063	0.2	-10000	0	-0.56	76	76
SMAD4	0.023	0.01	-10000	0	-10000	0	0
SMAD5	-0.041	0.12	-10000	0	-0.33	61	61
BMP7/USAG1	-0.11	0.17	-10000	0	-0.3	256	256
SMAD5/SKI	-0.044	0.14	0.21	1	-0.34	72	73
SMAD1	0.013	0.062	-10000	0	-0.47	5	5
BMP2	0.021	0.037	-10000	0	-0.37	5	5
SMAD1/SMAD1/SMAD4	0.02	0.06	-10000	0	-0.38	4	4
BMPR1A	0.025	0.017	-10000	0	-0.37	1	1
BMPR1B	-0.028	0.14	-10000	0	-0.37	80	80
BMPR1A-1B/BAMBI	-0.018	0.12	-10000	0	-0.22	141	141
AHSG	0.002	0.079	-10000	0	-0.32	33	33
CER1	0.01	0.051	-10000	0	-0.33	13	13
BMP2-4/CER1	0.029	0.055	-10000	0	-0.2	27	27
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.057	0.14	-10000	0	-0.36	72	72
BMP2-4 (homodimer)	0.026	0.052	-10000	0	-0.25	19	19
RGMB	0.024	0.018	-10000	0	-0.37	1	1
BMP6/BMPR2/BMPR1A-1B	0.025	0.093	-10000	0	-0.21	71	71
RGMA	-0.084	0.18	-10000	0	-0.37	163	163
SMURF1	0.024	0.009	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.051	0.13	-10000	0	-0.33	72	72
BMP2-4/USAG1	-0.067	0.13	-10000	0	-0.23	240	240
SMAD6/SMURF1/SMAD5	-0.04	0.14	0.21	1	-0.34	70	71
SOSTDC1	-0.14	0.2	-10000	0	-0.37	242	242
BMP7/BMPR2/BMPR1A-1B	-0.013	0.12	-10000	0	-0.22	101	101
SKI	0.026	0.006	-10000	0	-10000	0	0
BMP6 (homodimer)	0.024	0.018	-10000	0	-0.37	1	1
HFE2	0.016	0.042	-10000	0	-0.32	9	9
ZFYVE16	0.025	0.007	-10000	0	-10000	0	0
MAP3K7	0.026	0.005	-10000	0	-10000	0	0
BMP2-4/CHRD	0.031	0.061	-10000	0	-0.24	23	23
SMAD5/SMAD5/SMAD4	-0.043	0.14	-10000	0	-0.34	64	64
MAPK1	0.026	0.005	-10000	0	-10000	0	0
TAK1/TAB family	-0.033	0.12	-10000	0	-0.3	56	56
BMP7 (homodimer)	-0.039	0.14	-10000	0	-0.35	98	98
NUP214	0.026	0.005	-10000	0	-10000	0	0
BMP6/FETUA	0.018	0.059	-10000	0	-0.22	32	32
SMAD1/SKI	0.018	0.077	-10000	0	-0.44	8	8
SMAD6	0.027	0.004	-10000	0	-10000	0	0
CTDSP2	0.026	0.005	-10000	0	-10000	0	0
BMP2-4/FETUA	0.025	0.063	-10000	0	-0.2	38	38
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.024	0.13	-10000	0	-0.34	82	82
BMPR2 (homodimer)	0.027	0.003	-10000	0	-10000	0	0
GADD34/PP1CA	0.048	0.019	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	-0.003	0.1	-10000	0	-0.26	80	80
CHRDL1	-0.14	0.2	-10000	0	-0.37	244	244
ENDOFIN/SMAD1	0.018	0.075	-10000	0	-0.44	8	8
SMAD6-7/SMURF1/SMAD1	0.033	0.073	-10000	0	-0.38	7	7
SMAD6/SMURF1	0.024	0.009	-10000	0	-10000	0	0
BAMBI	-0.024	0.12	-10000	0	-0.32	86	86
SMURF2	0.026	0.005	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.059	0.14	-10000	0	-0.23	226	226
BMP2-4/GREM1	0.008	0.092	-10000	0	-0.2	92	92
SMAD7	0.024	0.009	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.055	0.2	-10000	0	-0.52	83	83
SMAD1/SMAD6	0.014	0.073	-10000	0	-0.4	8	8
TAK1/SMAD6	0.034	0.014	-10000	0	-10000	0	0
BMP7	-0.039	0.14	-10000	0	-0.35	98	98
BMP6	0.024	0.018	-10000	0	-0.37	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.044	0.13	-10000	0	-0.34	72	72
PPM1A	0.026	0.005	-10000	0	-10000	0	0
SMAD1/SMURF2	0.018	0.078	-10000	0	-0.45	7	7
SMAD7/SMURF1	0.031	0.017	-10000	0	-10000	0	0
CTDSPL	0.025	0.007	-10000	0	-10000	0	0
PPP1CA	0.026	0.006	-10000	0	-10000	0	0
XIAP	0.027	0.004	-10000	0	-10000	0	0
CTDSP1	0.027	0.004	-10000	0	-10000	0	0
PPP1R15A	0.026	0.005	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.089	0.18	-10000	0	-0.42	109	109
CHRD	0.012	0.067	-10000	0	-0.37	17	17
BMPR2	0.027	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.06	0.13	-10000	0	-0.33	86	86
BMP4	0.016	0.061	-10000	0	-0.35	16	16
FST	-0.025	0.12	-10000	0	-0.34	80	80
BMP2-4/NOG	0.025	0.074	-10000	0	-0.21	51	51
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.007	0.11	-10000	0	-0.37	11	11

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.009	0.057	-10000	0	-0.18	46	46
EPHB2	-0.11	0.17	-10000	0	-0.32	238	238
Syndecan-2/TACI	-0.022	0.092	-10000	0	-0.21	110	110
LAMA1	-0.057	0.15	-10000	0	-0.33	140	140
Syndecan-2/alpha2 ITGB1	0.026	0.066	-10000	0	-0.26	11	11
HRAS	0.026	0.005	-10000	0	-10000	0	0
Syndecan-2/CASK	0.006	0.015	-10000	0	-0.2	3	3
ITGA5	0.024	0.029	-10000	0	-0.32	4	4
BAX	0.002	0.015	-10000	0	-10000	0	0
EPB41	0.026	0.006	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.021	0.017	-10000	0	-0.18	3	3
LAMA3	0.009	0.073	-10000	0	-0.33	26	26
EZR	0.026	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.023	0.029	-10000	0	-0.32	4	4
Syndecan-2/MMP2	0.022	0.025	-10000	0	-0.2	6	6
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.022	0.059	-10000	0	-0.22	31	31
dendrite morphogenesis	-0.045	0.1	-10000	0	-0.18	207	207
Syndecan-2/GM-CSF	-0.028	0.091	-10000	0	-0.18	151	151
determination of left/right symmetry	0.009	0.019	-10000	0	-0.24	3	3
Syndecan-2/PKC delta	0.022	0.02	-10000	0	-0.2	3	3
GNB2L1	0.026	0.006	-10000	0	-10000	0	0
MAPK3	-0.02	0.095	0.19	40	-0.19	5	45
MAPK1	-0.021	0.095	0.19	41	-0.19	9	50
Syndecan-2/RACK1	0.033	0.022	-10000	0	-0.17	3	3
NF1	0.027	0.004	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.009	0.019	-10000	0	-0.24	3	3
ITGA2	0.007	0.078	-10000	0	-0.32	31	31
MAPK8	0.007	0.016	-10000	0	-0.21	2	2
Syndecan-2/alpha2/beta1 Integrin	-0.003	0.095	-10000	0	-0.28	15	15
Syndecan-2/Kininogen	0.012	0.045	-10000	0	-0.19	25	25
ITGB1	0.026	0.005	-10000	0	-10000	0	0
SRC	0.025	0.05	0.18	50	-10000	0	50
Syndecan-2/CASK/Protein 4.1	0.021	0.018	-10000	0	-0.18	3	3
extracellular matrix organization	0.023	0.018	-10000	0	-0.21	2	2
actin cytoskeleton reorganization	0.009	0.057	-10000	0	-0.18	46	46
Syndecan-2/Caveolin-2/Ras	0.034	0.028	-10000	0	-0.18	6	6
Syndecan-2/Laminin alpha3	0.014	0.045	-10000	0	-0.19	26	26
Syndecan-2/RasGAP	0.042	0.027	-10000	0	-0.18	2	2
alpha5/beta1 Integrin	0.036	0.023	-10000	0	-0.22	4	4
PRKCD	0.025	0.007	-10000	0	-10000	0	0
Syndecan-2 dimer	-0.045	0.1	-10000	0	-0.18	207	207
GO:0007205	0.002	0.002	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.027	0.022	0.18	3	-10000	0	3
RHOA	0.025	0.007	-10000	0	-10000	0	0
SDCBP	0.025	0.008	-10000	0	-10000	0	0
TNFRSF13B	-0.061	0.16	-10000	0	-0.37	128	128
RASA1	0.025	0.008	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.022	0.059	-10000	0	-0.22	31	31
Syndecan-2/Synbindin	0.023	0.02	-10000	0	-0.2	3	3
TGFB1	0.026	0.006	-10000	0	-10000	0	0
CASP3	0.026	0.052	0.19	49	-0.19	2	51
FN1	0	0.093	-10000	0	-0.33	45	45
Syndecan-2/IL8	-0.067	0.11	-10000	0	-0.18	271	271
SDC2	0.009	0.019	-10000	0	-0.24	3	3
KNG1	0.005	0.073	-10000	0	-0.32	28	28
Syndecan-2/Neurofibromin	0.024	0.019	-10000	0	-0.2	3	3
TRAPPC4	0.025	0.007	-10000	0	-10000	0	0
CSF2	-0.073	0.16	-10000	0	-0.32	165	165
Syndecan-2/TGFB1	0.023	0.018	-10000	0	-0.21	2	2
Syndecan-2/Syntenin/PI-4-5-P2	0.021	0.017	-10000	0	-0.18	3	3
Syndecan-2/Ezrin	0.035	0.024	-10000	0	-0.18	3	3
PRKACA	0.029	0.055	0.19	58	-0.19	2	60
angiogenesis	-0.066	0.11	-10000	0	-0.18	271	271
MMP2	0.024	0.028	-10000	0	-0.36	3	3
IL8	-0.15	0.18	-10000	0	-0.32	304	304
calcineurin-NFAT signaling pathway	-0.022	0.092	-10000	0	-0.21	110	110

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.026	0.013	-10000	0	-10000	0	0
AES	0.026	0.014	0.21	1	-10000	0	1
FBXW11	0.026	0.006	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.034	0.015	-10000	0	-10000	0	0
SMAD4	0.023	0.01	-10000	0	-10000	0	0
DKK2	-0.054	0.15	-10000	0	-0.32	136	136
TLE1	0.026	0.021	0.22	1	-0.38	1	2
MACF1	0.026	0.006	-10000	0	-10000	0	0
CTNNB1	0.022	0.12	0.28	23	-0.44	14	37
WIF1	-0.082	0.16	-10000	0	-0.37	148	148
beta catenin/RanBP3	0.003	0.11	0.39	20	-0.39	10	30
KREMEN2	-0.069	0.16	-10000	0	-0.32	162	162
DKK1	-0.13	0.18	-10000	0	-0.33	265	265
beta catenin/beta TrCP1	0.032	0.12	0.29	21	-0.4	13	34
FZD1	0.024	0.009	-10000	0	-10000	0	0
AXIN2	-0.016	0.21	0.57	13	-1.2	14	27
AXIN1	0.026	0.006	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	-0.002	0.14	-10000	0	-0.55	31	31
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.028	0.19	0.22	5	-0.57	46	51
Axin1/APC/GSK3	0.039	0.074	0.23	19	-0.31	8	27
Axin1/APC/GSK3/beta catenin/Macf1	0.021	0.11	0.28	9	-0.42	17	26
HNF1A	-0.009	0.11	0.22	1	-0.37	53	54
CTBP1	0.025	0.015	0.22	1	-10000	0	1
MYC	0.13	0.26	0.59	129	-1.3	2	131
RANBP3	0.026	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.062	0.13	-10000	0	-0.2	256	256
NKD1	-0.013	0.12	-10000	0	-0.35	62	62
TCF4	0.023	0.021	0.22	1	-0.3	1	2
TCF3	0.026	0.015	0.22	1	-10000	0	1
WNT1/LRP6/FZD1/Axin1	0.052	0.038	-10000	0	-0.17	7	7
Ran/GTP	0.02	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.026	0.13	0.43	12	-0.46	19	31
LEF1	0.017	0.056	0.22	1	-0.32	15	16
DVL1	0.027	0.053	0.21	2	-0.51	2	4
CSNK2A1	0.025	0.008	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0	0.16	0.23	4	-0.55	27	31
DKK1/LRP6/Kremen 2	-0.11	0.15	-10000	0	-0.23	325	325
LRP6	0.026	0.007	-10000	0	-10000	0	0
CSNK1A1	0.026	0.016	0.26	1	-10000	0	1
NLK	0.026	0.007	-10000	0	-10000	0	0
CCND1	0.091	0.22	0.61	83	-10000	0	83
WNT1	0.021	0.038	-10000	0	-0.32	7	7
GSK3A	0.026	0.006	-10000	0	-10000	0	0
GSK3B	0.026	0.007	-10000	0	-10000	0	0
FRAT1	0.025	0.017	-10000	0	-0.37	1	1
PPP2R5D	0.044	0.069	0.24	37	-0.29	4	41
APC	0.017	0.072	0.19	75	-10000	0	75
WNT1/LRP6/FZD1	0.044	0.075	0.19	100	-0.26	1	101
CREBBP	0.026	0.013	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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
NFATC2	0.008	0.075	-10000	0	-0.37	22	22
GNB1/GNG2	-0.036	0.13	-10000	0	-0.33	48	48
mol:DAG	-0.039	0.11	0.2	9	-0.32	40	49
PLCG1	-0.04	0.11	0.2	9	-0.33	40	49
YES1	-0.053	0.11	-10000	0	-0.35	45	45
FZD3	0.022	0.033	-10000	0	-0.37	4	4
FZD6	0.017	0.047	-10000	0	-0.33	10	10
G protein	-0.014	0.14	0.26	9	-0.33	40	49
MAP3K7	-0.044	0.1	0.19	17	-0.32	31	48
mol:Ca2+	-0.038	0.11	0.2	9	-0.31	40	49
mol:IP3	-0.039	0.11	0.2	9	-0.32	40	49
NLK	0.008	0.051	-10000	0	-0.85	2	2
GNB1	0.026	0.006	-10000	0	-10000	0	0
CAMK2A	-0.043	0.11	0.2	17	-0.33	35	52
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.053	0.12	-10000	0	-0.26	122	122
CSNK1A1	0.025	0.007	-10000	0	-10000	0	0
GNAS	-0.047	0.11	0.18	1	-0.35	41	42
GO:0007205	-0.041	0.11	0.21	12	-0.32	41	53
WNT6	-0.017	0.12	-10000	0	-0.36	66	66
WNT4	-0.009	0.11	-10000	0	-0.37	52	52
NFAT1/CK1 alpha	-0.033	0.12	0.35	2	-0.37	30	32
GNG2	0.025	0.022	-10000	0	-0.35	2	2
WNT5A	-0.004	0.098	-10000	0	-0.33	50	50
WNT11	-0.052	0.15	-10000	0	-0.34	128	128
CDC42	-0.045	0.11	0.19	8	-0.33	42	50

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.061	0.12	-10000	0	-0.2	242	242
cell-cell adhesion	0.074	0.088	0.27	60	-10000	0	60
Ephrin B/EPHB2/RasGAP	-0.027	0.12	-10000	0	-0.33	12	12
ITSN1	0.025	0.006	-10000	0	-10000	0	0
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
SHC1	0.026	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.026	0.04	-10000	0	-0.22	14	14
Ephrin B1/EPHB1	0.003	0.076	-10000	0	-0.19	83	83
HRAS/GDP	-0.018	0.1	-10000	0	-0.29	25	25
Ephrin B/EPHB1/GRB7	0.022	0.088	-10000	0	-0.23	15	15
Endophilin/SYNJ1	-0.059	0.085	0.17	13	-0.31	12	25
KRAS	0.024	0.009	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.023	0.089	-10000	0	-0.33	4	4
endothelial cell migration	0.041	0.028	-10000	0	-0.17	1	1
GRB2	0.026	0.005	-10000	0	-10000	0	0
GRB7	0.021	0.029	-10000	0	-0.36	3	3
PAK1	-0.06	0.1	0.19	29	-0.32	16	45
HRAS	0.026	0.005	-10000	0	-10000	0	0
RRAS	-0.062	0.086	0.17	11	-0.33	12	23
DNM1	0.017	0.055	-10000	0	-0.32	15	15
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.017	0.088	0.2	49	-0.31	4	53
lamellipodium assembly	-0.074	0.088	-10000	0	-0.27	60	60
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.008	0.057	-10000	0	-0.27	3	3
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
EPHB2	-0.11	0.17	-10000	0	-0.32	238	238
EPHB3	0.015	0.059	-10000	0	-0.37	13	13
EPHB1	-0.023	0.12	-10000	0	-0.32	82	82
EPHB4	0.024	0.008	-10000	0	-10000	0	0
mol:GDP	-0.034	0.093	0.25	6	-0.3	24	30
Ephrin B/EPHB2	-0.033	0.11	-10000	0	-0.26	23	23
Ephrin B/EPHB3	0.037	0.059	-10000	0	-0.18	30	30
JNK cascade	-0.071	0.13	0.3	33	-0.3	55	88
Ephrin B/EPHB1	0.016	0.086	-10000	0	-0.17	89	89
RAP1/GDP	-0.021	0.1	0.25	10	-0.32	11	21
EFNB2	0.025	0.018	-10000	0	-0.37	1	1
EFNB3	0.01	0.075	-10000	0	-0.36	24	24
EFNB1	0.026	0.015	-10000	0	-0.32	1	1
Ephrin B2/EPHB1-2	-0.058	0.13	-10000	0	-0.2	236	236
RAP1B	0.026	0.006	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.046	0.12	-10000	0	-0.28	59	59
Rap1/GTP	-0.06	0.1	-10000	0	-0.28	59	59
axon guidance	-0.061	0.12	-10000	0	-0.2	242	242
MAPK3	0.003	0.053	0.18	8	-0.25	2	10
MAPK1	0.004	0.055	0.18	10	-0.25	2	12
Rac1/GDP	-0.031	0.096	0.26	5	-0.28	22	27
actin cytoskeleton reorganization	-0.067	0.08	-10000	0	-0.24	52	52
CDC42/GDP	-0.027	0.1	0.25	11	-0.29	24	35
PI3K	0.045	0.031	-10000	0	-0.17	1	1
EFNA5	0.01	0.075	-10000	0	-0.37	22	22
Ephrin B2/EPHB4	0.031	0.017	-10000	0	-0.22	1	1
Ephrin B/EPHB2/Intersectin/N-WASP	-0.024	0.075	-10000	0	-0.25	28	28
CDC42	0.026	0.006	-10000	0	-10000	0	0
RAS family/GTP	-0.058	0.1	-10000	0	-0.27	58	58
PTK2	0.096	0.22	0.62	84	-10000	0	84
MAP4K4	-0.072	0.13	0.31	33	-0.31	55	88
SRC	0.023	0.009	-10000	0	-10000	0	0
KALRN	0.012	0.072	-10000	0	-0.37	20	20
Intersectin/N-WASP	0.037	0.011	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.038	0.12	0.3	31	-0.29	12	43
MAP2K1	0.004	0.054	0.2	1	-0.25	3	4
WASL	0.026	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.056	0.14	-10000	0	-0.21	250	250
cell migration	0.011	0.082	0.22	18	-0.29	5	23
NRAS	0.026	0.006	-10000	0	-10000	0	0
SYNJ1	-0.059	0.086	0.18	13	-0.31	12	25
PXN	0.027	0.004	-10000	0	-10000	0	0
TF	-0.12	0.11	0.17	4	-0.32	88	92
HRAS/GTP	-0.05	0.12	-10000	0	-0.28	64	64
Ephrin B1/EPHB1-2	-0.062	0.13	-10000	0	-0.2	251	251
cell adhesion mediated by integrin	0.004	0.056	0.2	13	-0.19	19	32
RAC1	0.025	0.007	-10000	0	-10000	0	0
mol:GTP	-0.052	0.12	-10000	0	-0.29	64	64
RAC1-CDC42/GTP	-0.08	0.09	-10000	0	-0.28	61	61
RASA1	0.025	0.008	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.024	0.098	0.26	5	-0.31	12	17
ruffle organization	-0.043	0.14	0.36	23	-0.32	9	32
NCK1	0.025	0.007	-10000	0	-10000	0	0
receptor internalization	-0.063	0.086	0.17	13	-0.3	19	32
Ephrin B/EPHB2/KALRN	-0.035	0.12	-10000	0	-0.26	34	34
ROCK1	0.027	0.064	0.18	66	-0.2	14	80
RAS family/GDP	-0.067	0.078	-10000	0	-0.3	14	14
Rac1/GTP	-0.062	0.1	-10000	0	-0.28	60	60
Ephrin B/EPHB1/Src/Paxillin	0.003	0.055	-10000	0	-0.28	5	5

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.018	0.038	-10000	0	-0.33	6	6
CDKN2C	0.029	0.024	-10000	0	-10000	0	0
CDKN2A	-0.069	0.15	-10000	0	-0.33	153	153
CCND2	0.015	0.037	0.14	14	-10000	0	14
RB1	-0.022	0.053	0.3	1	-0.2	25	26
CDK4	0.019	0.045	0.19	14	-10000	0	14
CDK6	0.019	0.045	0.18	18	-10000	0	18
G1/S progression	0.045	0.074	0.18	101	-0.3	1	102

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.025	0.015	-10000	0	-0.32	1	1
RAS family/GTP/Tiam1	-0.039	0.093	-10000	0	-0.3	25	25
NT3 (dimer)/TRKC	-0.069	0.16	-10000	0	-0.3	183	183
NT3 (dimer)/TRKB	-0.097	0.18	-10000	0	-0.29	259	259
SHC/Grb2/SOS1/GAB1/PI3K	0.023	0.013	-10000	0	-10000	0	0
RAPGEF1	0.026	0.005	-10000	0	-10000	0	0
BDNF	0.009	0.076	-10000	0	-0.32	29	29
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
DYNLT1	0.026	0.005	-10000	0	-10000	0	0
NTRK1	0.014	0.068	-10000	0	-0.37	18	18
NTRK2	-0.061	0.16	-10000	0	-0.35	137	137
NTRK3	-0.084	0.18	-10000	0	-0.37	163	163
NT-4/5 (dimer)/TRKB	-0.11	0.18	-10000	0	-0.28	295	295
neuron apoptosis	0.078	0.17	0.38	105	-10000	0	105
SHC 2-3/Grb2	-0.085	0.19	-10000	0	-0.42	105	105
SHC1	0.026	0.005	-10000	0	-10000	0	0
SHC2	-0.093	0.2	-10000	0	-0.45	105	105
SHC3	-0.089	0.18	-10000	0	-0.43	103	103
STAT3 (dimer)	0.026	0.04	-10000	0	-0.28	10	10
NT3 (dimer)/TRKA	-0.056	0.15	-10000	0	-0.25	206	206
RIN/GDP	-0.009	0.093	0.21	13	-0.25	17	30
GIPC1	0.026	0.005	-10000	0	-10000	0	0
KRAS	0.024	0.009	-10000	0	-10000	0	0
DNAJA3	-0.066	0.13	-10000	0	-0.29	135	135
RIN/GTP	0.012	0.011	-10000	0	-0.22	1	1
CCND1	0.016	0.01	-10000	0	-10000	0	0
MAGED1	0.024	0.029	-10000	0	-0.37	3	3
PTPN11	0.026	0.004	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.045	0.14	-10000	0	-0.32	117	117
SHC/GRB2/SOS1	0.051	0.014	-10000	0	-10000	0	0
GRB2	0.026	0.005	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.02	0.087	-10000	0	-0.23	61	61
TRKA/NEDD4-2	0.025	0.053	-10000	0	-0.26	19	19
ELMO1	0.024	0.023	-10000	0	-0.35	2	2
RhoG/GTP/ELMO1/DOCK1	0.032	0.018	-10000	0	-0.2	2	2
NGF	0.004	0.088	-10000	0	-0.36	33	33
HRAS	0.026	0.005	-10000	0	-10000	0	0
DOCK1	0.026	0.006	-10000	0	-10000	0	0
GAB2	0.026	0.006	-10000	0	-10000	0	0
RIT2	0.017	0.016	-10000	0	-0.32	1	1
RIT1	0.026	0.005	-10000	0	-10000	0	0
FRS2	0.025	0.007	-10000	0	-10000	0	0
DNM1	0.017	0.055	-10000	0	-0.32	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.007	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.053	0.14	-10000	0	-0.28	135	135
mol:GDP	-0.022	0.13	0.26	16	-0.38	20	36
NGF (dimer)	0.004	0.088	-10000	0	-0.36	33	33
RhoG/GDP	0.018	0.016	-10000	0	-0.24	2	2
RIT1/GDP	-0.009	0.094	0.2	11	-0.26	15	26
TIAM1	0.009	0.076	-10000	0	-0.34	27	27
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.017	0.12	-10000	0	-0.22	147	147
KIDINS220/CRKL/C3G	0.037	0.015	-10000	0	-0.22	1	1
SHC/RasGAP	0.036	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2	0.047	0.019	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.062	0.022	-10000	0	-10000	0	0
RIT1/GTP	0.019	0.004	-10000	0	-10000	0	0
NT3 (dimer)	-0.02	0.13	-10000	0	-0.37	67	67
RAP1/GDP	-0.012	0.075	0.13	2	-0.22	15	17
KIDINS220/CRKL	0.025	0.015	-10000	0	-0.32	1	1
BDNF (dimer)	0.009	0.076	-10000	0	-0.32	29	29
ubiquitin-dependent protein catabolic process	0.022	0.076	-10000	0	-0.22	51	51
Schwann cell development	-0.027	0.029	-10000	0	-10000	0	0
EHD4	0.026	0.005	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.058	0.026	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.026	0.039	-10000	0	-0.33	2	2
RAP1B	0.026	0.006	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.071	0.15	-10000	0	-0.35	95	95
ABL1	0.026	0.005	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.039	0.008	-10000	0	-10000	0	0
Rap1/GTP	0.004	0.073	-10000	0	-0.42	4	4
STAT3	0.027	0.04	-10000	0	-0.28	10	10
axon guidance	-0.074	0.14	-10000	0	-0.34	95	95
MAPK3	-0.006	0.075	0.18	19	-0.22	44	63
MAPK1	-0.004	0.075	0.18	22	-0.34	5	27
CDC42/GDP	-0.006	0.097	0.22	15	-0.26	16	31
NTF3	-0.02	0.13	-10000	0	-0.37	67	67
NTF4	-0.045	0.14	-10000	0	-0.32	117	117
NGF (dimer)/TRKA/FAIM	0.027	0.074	-10000	0	-0.22	45	45
PI3K	0.032	0.016	-10000	0	-10000	0	0
FRS3	0.025	0.007	-10000	0	-10000	0	0
FAIM	0.024	0.018	-10000	0	-0.37	1	1
GAB1	0.026	0.006	-10000	0	-10000	0	0
RASGRF1	-0.08	0.14	-10000	0	-0.3	142	142
SOS1	0.027	0.003	-10000	0	-10000	0	0
MCF2L	-0.065	0.13	-10000	0	-0.26	167	167
RGS19	0.02	0.033	-10000	0	-0.32	5	5
CDC42	0.026	0.006	-10000	0	-10000	0	0
RAS family/GTP	0.018	0.1	0.28	8	-0.47	8	16
Rac1/GDP	-0.006	0.094	0.21	15	-0.26	15	30
NGF (dimer)/TRKA/GRIT	0.013	0.07	-10000	0	-0.22	50	50
neuron projection morphogenesis	-0.057	0.16	-10000	0	-0.8	6	6
NGF (dimer)/TRKA/NEDD4-2	0.022	0.076	-10000	0	-0.22	51	51
MAP2K1	0	0.054	0.2	39	-10000	0	39
NGFR	-0.087	0.18	-10000	0	-0.37	172	172
NGF (dimer)/TRKA/GIPC/GAIP	0.006	0.058	-10000	0	-0.25	10	10
RAS family/GTP/PI3K	0.018	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.067	0.031	-10000	0	-10000	0	0
NRAS	0.026	0.006	-10000	0	-10000	0	0
GRB2/SOS1	0.039	0.008	-10000	0	-10000	0	0
PRKCI	0.023	0.017	-10000	0	-0.32	1	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
MAPKKK cascade	-0.052	0.18	-10000	0	-0.57	57	57
RASA1	0.025	0.008	-10000	0	-10000	0	0
TRKA/c-Abl	0.029	0.051	-10000	0	-0.26	17	17
SQSTM1	0.025	0.007	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.003	0.12	-10000	0	-0.21	142	142
NGF (dimer)/TRKA/p62/Atypical PKCs	0.041	0.071	-10000	0	-0.19	32	32
MATK	0.016	0.061	-10000	0	-0.36	15	15
NEDD4L	0.023	0.019	-10000	0	-0.37	1	1
RAS family/GDP	-0.032	0.052	-10000	0	-0.2	9	9
NGF (dimer)/TRKA	-0.073	0.14	-10000	0	-0.29	154	154
Rac1/GTP	-0.065	0.1	-10000	0	-0.26	85	85
FRS2 family/SHP2/CRK family	0.064	0.034	-10000	0	-10000	0	0

×

TCGA08_p53

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
CDKN2A	-0.054	0.1	-10000	0	-0.22	153	153
TP53	-0.017	0.052	-10000	0	-0.24	23	23
Senescence	-0.017	0.051	-10000	0	-0.24	23	23
Apoptosis	-0.017	0.051	-10000	0	-0.24	23	23
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.036	0.08	0.27	35	-10000	0	35
MDM4	0.026	0.005	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.015	0.12	0.28	20	-0.36	34	54
FYN	-0.004	0.14	0.26	23	-0.39	40	63
LAT/GRAP2/SLP76	0.007	0.13	0.25	8	-0.38	36	44
IKBKB	0.024	0.008	-10000	0	-10000	0	0
AKT1	-0.008	0.11	0.21	21	-0.32	41	62
B2M	0.026	0.009	-10000	0	-10000	0	0
IKBKG	-0.008	0.044	0.093	26	-0.13	14	40
MAP3K8	0.026	0.015	-10000	0	-0.32	1	1
mol:Ca2+	-0.021	0.021	0.088	1	-0.078	19	20
integrin-mediated signaling pathway	0.033	0.014	-10000	0	-0.22	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.015	0.14	0.27	16	-0.43	42	58
TRPV6	-0.1	0.24	1.1	10	-0.56	2	12
CD28	0.015	0.066	-10000	0	-0.33	21	21
SHC1	-0.009	0.14	0.24	21	-0.39	45	66
receptor internalization	-0.011	0.13	0.22	2	-0.41	47	49
PRF1	-0.003	0.14	-10000	0	-0.62	15	15
KRAS	0.024	0.009	-10000	0	-10000	0	0
GRB2	0.026	0.005	-10000	0	-10000	0	0
COT/AKT1	0.003	0.096	0.2	20	-0.27	33	53
LAT	-0.012	0.13	0.24	11	-0.4	43	54
EntrezGene:6955	0	0.002	-10000	0	-10000	0	0
CD3D	0.017	0.056	-10000	0	-0.34	14	14
CD3E	0.019	0.051	-10000	0	-0.33	12	12
CD3G	0.016	0.058	-10000	0	-0.36	14	14
RASGRP2	-0.005	0.048	0.069	4	-0.15	52	56
RASGRP1	0.002	0.12	0.25	22	-0.34	31	53
HLA-A	0	0.003	-10000	0	-10000	0	0
RASSF5	0.025	0.017	-10000	0	-0.37	1	1
RAP1A/GTP/RAPL	0.034	0.014	-10000	0	-0.22	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.054	0.14	44	-0.12	12	56
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.028	0.057	-10000	0	-0.2	27	27
PRKCA	0.009	0.077	0.14	55	-0.22	22	77
GRAP2	0.018	0.055	-10000	0	-0.36	12	12
mol:IP3	0.026	0.12	0.18	141	-0.3	30	171
EntrezGene:6957	0	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.005	0.1	-10000	0	-0.38	30	30
ORAI1	0.05	0.17	0.56	2	-0.95	10	12
CSK	-0.009	0.13	0.22	16	-0.38	46	62
B7 family/CD28	-0.01	0.15	0.26	5	-0.4	42	47
CHUK	0.026	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.019	0.14	0.18	4	-0.41	50	54
PTPN6	-0.013	0.13	0.22	16	-0.38	46	62
VAV1	-0.016	0.14	0.23	12	-0.39	49	61
Monovalent TCR/CD3	0.008	0.055	-10000	0	-0.24	23	23
CBL	0.025	0.007	-10000	0	-10000	0	0
LCK	-0.009	0.14	0.26	20	-0.4	43	63
PAG1	-0.003	0.14	0.21	48	-0.38	45	93
RAP1A	0.026	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.019	0.14	0.19	6	-0.4	49	55
CD80	-0.053	0.15	-10000	0	-0.32	134	134
CD86	0.018	0.051	-10000	0	-0.33	12	12
PDK1/CARD11/BCL10/MALT1	-0.023	0.074	0.12	1	-0.23	30	31
HRAS	0.026	0.005	-10000	0	-10000	0	0
GO:0035030	-0.031	0.12	0.19	11	-0.35	44	55
CD8A	0.009	0.083	-10000	0	-0.36	29	29
CD8B	0.004	0.093	-10000	0	-0.36	36	36
PTPRC	0.014	0.066	-10000	0	-0.33	21	21
PDK1/PKC theta	-0.009	0.13	0.26	22	-0.39	35	57
CSK/PAG1	-0.003	0.14	0.21	50	-0.39	39	89
SOS1	0.027	0.003	-10000	0	-10000	0	0
peptide-MHC class I	0.02	0.009	-10000	0	-10000	0	0
GRAP2/SLP76	0.008	0.14	0.24	8	-0.4	44	52
STIM1	0.032	0.11	1.2	4	-10000	0	4
RAS family/GTP	0.023	0.068	0.18	30	-0.19	10	40
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.012	0.14	0.22	2	-0.43	47	49
mol:DAG	-0.009	0.084	0.1	4	-0.27	33	37
RAP1A/GDP	0.012	0.026	0.073	32	-0.063	3	35
PLCG1	0.023	0.01	-10000	0	-10000	0	0
CD247	0.018	0.057	-10000	0	-0.33	15	15
cytotoxic T cell degranulation	-0.002	0.14	-10000	0	-0.58	16	16
RAP1A/GTP	-0.002	0.018	-10000	0	-0.058	53	53
mol:PI-3-4-5-P3	-0.01	0.13	0.24	19	-0.36	42	61
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.029	0.14	0.2	115	-0.38	31	146
NRAS	0.026	0.006	-10000	0	-10000	0	0
ZAP70	0.013	0.069	-10000	0	-0.33	23	23
GRB2/SOS1	0.039	0.008	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.005	0.12	0.23	4	-0.39	33	37
MALT1	0.024	0.009	-10000	0	-10000	0	0
TRAF6	0.026	0.005	-10000	0	-10000	0	0
CD8 heterodimer	0.011	0.1	-10000	0	-0.3	52	52
CARD11	-0.048	0.14	-10000	0	-0.32	124	124
PRKCB	0	0.082	0.14	47	-0.24	31	78
PRKCE	0.009	0.078	0.16	35	-0.22	23	58
PRKCQ	-0.011	0.14	0.26	20	-0.42	42	62
LCP2	0.023	0.03	-10000	0	-0.34	4	4
BCL10	0.027	0.004	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.005	0.099	0.2	22	-0.28	37	59
IKK complex	0.016	0.055	0.13	66	-0.11	9	75
RAS family/GDP	0	0.009	-10000	0	-10000	0	0
MAP3K14	-0.001	0.076	0.16	26	-0.22	26	52
PDPK1	-0.008	0.1	0.23	18	-0.32	33	51
TCR/CD3/MHC I/CD8/Fyn	-0.018	0.16	-10000	0	-0.47	46	46

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.051	0.14	0.28	4	-0.38	56	60
IKBKB	-0.018	0.093	0.23	4	-0.31	16	20
AKT1	-0.022	0.1	0.22	33	-0.23	32	65
IKBKG	-0.011	0.08	0.21	3	-0.26	13	16
CALM1	-0.032	0.11	0.2	1	-0.36	41	42
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
MAP3K1	-0.062	0.18	0.27	2	-0.51	58	60
MAP3K7	0.026	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.032	0.12	0.21	2	-0.37	45	47
DOK1	0.026	0.022	-10000	0	-0.35	2	2
AP-1	-0.029	0.094	0.22	11	-0.24	37	48
LYN	0.024	0.022	-10000	0	-0.32	2	2
BLNK	0.007	0.085	-10000	0	-0.37	28	28
SHC1	0.026	0.005	-10000	0	-10000	0	0
BCR complex	-0.038	0.14	-10000	0	-0.3	133	133
CD22	-0.071	0.17	-10000	0	-0.46	65	65
CAMK2G	-0.028	0.11	0.24	2	-0.34	40	42
CSNK2A1	0.024	0.008	-10000	0	-10000	0	0
INPP5D	0.024	0.03	-10000	0	-0.34	4	4
SHC/GRB2/SOS1	-0.024	0.11	-10000	0	-0.33	37	37
GO:0007205	-0.033	0.12	0.21	2	-0.37	46	48
SYK	0.025	0.017	-10000	0	-0.37	1	1
ELK1	-0.032	0.12	0.24	1	-0.36	42	43
NFATC1	-0.06	0.15	0.24	4	-0.4	67	71
B-cell antigen/BCR complex	-0.038	0.14	-10000	0	-0.3	133	133
PAG1/CSK	0.034	0.018	-10000	0	-0.22	1	1
NFKBIB	0.007	0.042	0.11	7	-0.12	23	30
HRAS	-0.03	0.11	0.21	4	-0.34	41	45
NFKBIA	0.007	0.042	0.11	8	-0.12	23	31
NF-kappa-B/RelA/I kappa B beta	0.012	0.037	0.12	7	-10000	0	7
RasGAP/Csk	-0.006	0.14	-10000	0	-0.26	113	113
mol:GDP	-0.03	0.12	-10000	0	-0.36	44	44
PTEN	0.025	0.007	-10000	0	-10000	0	0
CD79B	-0.001	0.098	-10000	0	-0.35	44	44
NF-kappa-B/RelA/I kappa B alpha	0.012	0.037	0.12	6	-10000	0	6
GRB2	0.026	0.005	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.084	0.19	0.29	1	-0.47	81	82
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
mol:IP3	-0.032	0.12	0.22	2	-0.38	43	45
CSK	0.026	0.005	-10000	0	-10000	0	0
FOS	-0.038	0.12	0.3	3	-0.34	48	51
CHUK	-0.018	0.09	0.22	2	-0.3	22	24
IBTK	0.026	0.005	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.034	0.13	0.26	2	-0.36	37	39
PTPN6	-0.068	0.15	-10000	0	-0.44	63	63
RELA	0.026	0.005	-10000	0	-10000	0	0
BCL2A1	0.007	0.03	0.14	2	-10000	0	2
VAV2	-0.075	0.19	-10000	0	-0.51	66	66
ubiquitin-dependent protein catabolic process	0.01	0.042	0.11	8	-0.12	23	31
BTK	-0.008	0.17	-10000	0	-1	17	17
CD19	-0.078	0.18	-10000	0	-0.45	84	84
MAP4K1	0.012	0.071	-10000	0	-0.35	22	22
CD72	-0.002	0.093	-10000	0	-0.32	46	46
PAG1	0.023	0.017	-10000	0	-0.32	1	1
MAPK14	-0.05	0.16	0.31	5	-0.45	50	55
SH3BP5	0.026	0.006	-10000	0	-10000	0	0
PIK3AP1	-0.038	0.12	-10000	0	-0.38	44	44
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.058	0.17	-10000	0	-0.46	60	60
RAF1	-0.03	0.11	0.21	4	-0.34	36	40
RasGAP/p62DOK/SHIP	-0.004	0.14	-10000	0	-0.36	46	46
CD79A	-0.055	0.16	-10000	0	-0.37	122	122
re-entry into mitotic cell cycle	-0.029	0.093	0.22	11	-0.24	37	48
RASA1	0.025	0.008	-10000	0	-10000	0	0
MAPK3	-0.024	0.098	0.28	6	-0.31	27	33
MAPK1	-0.025	0.096	0.25	5	-0.3	26	31
CD72/SHP1	-0.058	0.17	0.28	5	-0.44	65	70
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MAPK8	-0.053	0.16	0.29	4	-0.44	55	59
actin cytoskeleton organization	-0.056	0.16	0.26	2	-0.44	61	63
NF-kappa-B/RelA	0.027	0.072	0.21	9	-0.2	10	19
Calcineurin	-0.008	0.11	-10000	0	-0.35	26	26
PI3K	-0.064	0.14	-10000	0	-0.37	77	77
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.03	0.12	-10000	0	-0.39	46	46
SOS1	0.027	0.003	-10000	0	-10000	0	0
Bam32/HPK1	-0.073	0.24	-10000	0	-0.73	57	57
DAPP1	-0.09	0.26	-10000	0	-0.82	57	57
cytokine secretion	-0.056	0.14	0.23	4	-0.37	65	69
mol:DAG	-0.032	0.12	0.22	2	-0.38	43	45
PLCG2	0.023	0.032	-10000	0	-0.32	5	5
MAP2K1	-0.028	0.1	0.23	5	-0.32	32	37
B-cell antigen/BCR complex/FcgammaRIIB	-0.028	0.15	-10000	0	-0.28	139	139
mol:PI-3-4-5-P3	-0.054	0.1	0.21	2	-0.28	66	68
ETS1	-0.026	0.1	0.34	1	-0.32	32	33
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.003	0.13	-10000	0	-0.36	37	37
B-cell antigen/BCR complex/LYN	-0.052	0.16	-10000	0	-0.48	49	49
MALT1	0.024	0.009	-10000	0	-10000	0	0
TRAF6	0.026	0.005	-10000	0	-10000	0	0
RAC1	-0.06	0.17	0.29	1	-0.47	60	61
B-cell antigen/BCR complex/LYN/SYK	-0.041	0.17	-10000	0	-0.44	58	58
CARD11	-0.053	0.13	0.26	6	-0.37	52	58
FCGR2B	0.005	0.089	-10000	0	-0.37	31	31
PPP3CA	0.026	0.005	-10000	0	-10000	0	0
BCL10	0.027	0.004	-10000	0	-10000	0	0
IKK complex	0.003	0.047	0.14	22	-0.12	6	28
PTPRC	0.014	0.066	-10000	0	-0.33	21	21
PDPK1	-0.03	0.089	0.21	22	-0.22	37	59
PPP3CB	0.026	0.005	-10000	0	-10000	0	0
PPP3CC	0.024	0.008	-10000	0	-10000	0	0
POU2F2	0.01	0.027	0.12	4	-10000	0	4

×

Visual signal transduction: Rods

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
mol:K +	0.027	0.004	-10000	0	-10000	0	0
GNAT1/GTP	0.011	0.032	-10000	0	-0.22	11	11
Metarhodopsin II/Arrestin	0.024	0.024	-10000	0	-0.19	7	7
PDE6G/GNAT1/GTP	0.018	0.052	-10000	0	-0.19	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.015	0.047	-10000	0	-0.33	11	11
GRK1	0.018	0.015	-10000	0	-0.32	1	1
CNG Channel	-0.015	0.1	-10000	0	-0.32	23	23
mol:Na +	-0.017	0.1	-10000	0	-0.31	23	23
mol:ADP	0.018	0.015	-10000	0	-0.32	1	1
RGS9-1/Gbeta5/R9AP	-0.02	0.13	-10000	0	-0.24	139	139
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.011	0.11	-10000	0	-0.31	23	23
CNGB1	-0.022	0.12	-10000	0	-0.32	79	79
RDH5	0.013	0.072	-10000	0	-0.37	20	20
SAG	0.02	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.035	0.13	0.33	40	-0.3	23	63
Na + (4 Units)	-0.02	0.097	-10000	0	-0.29	23	23
RGS9	-0.046	0.15	-10000	0	-0.37	108	108
GNB1/GNGT1	-0.016	0.099	-10000	0	-0.22	109	109
GNAT1/GDP	-0.014	0.12	-10000	0	-0.21	145	145
GUCY2D	0.008	0.073	-10000	0	-0.32	27	27
GNGT1	-0.044	0.13	-10000	0	-0.32	111	111
GUCY2F	0.02	0.004	-10000	0	-10000	0	0
GNB5	0.026	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.005	0.071	-10000	0	-0.19	65	65
mol:11-cis-retinal	0.013	0.072	-10000	0	-0.37	20	20
mol:cGMP	0.011	0.079	-10000	0	-0.22	25	25
GNB1	0.026	0.006	-10000	0	-10000	0	0
Rhodopsin	0.021	0.057	-10000	0	-0.25	24	24
SLC24A1	0.027	0.004	-10000	0	-10000	0	0
CNGA1	0.007	0.084	-10000	0	-0.37	28	28
Metarhodopsin II	0.021	0.024	-10000	0	-0.17	8	8
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.02	0.086	-10000	0	-0.2	66	66
RGS9BP	-0.014	0.12	-10000	0	-0.37	58	58
Metarhodopsin II/Transducin	-0.012	0.056	-10000	0	-0.21	29	29
GCAP Family/Ca ++	0.018	0.07	-10000	0	-0.18	61	61
PDE6A/B	0.013	0.077	-10000	0	-0.25	45	45
mol:Pi	-0.021	0.13	-10000	0	-0.24	139	139
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	-0.003	0.086	-10000	0	-0.18	110	110
PDE6B	0.01	0.074	-10000	0	-0.36	23	23
PDE6A	0.01	0.074	-10000	0	-0.34	26	26
PDE6G	0.013	0.066	-10000	0	-0.32	22	22
RHO	0.016	0.038	-10000	0	-0.32	7	7
PDE6	-0.021	0.13	-10000	0	-0.34	32	32
GUCA1A	-0.001	0.089	-10000	0	-0.32	42	42
GC2/GCAP Family	0.026	0.076	-10000	0	-0.19	55	55
GUCA1C	0.006	0.069	-10000	0	-0.37	19	19
GUCA1B	0.024	0.018	-10000	0	-0.37	1	1

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.039	0.058	-10000	0	-0.2	28	28
NF kappa B1 p50/RelA/I kappa B alpha	-0.019	0.098	0.22	1	-0.34	7	8
AP1	-0.04	0.095	-10000	0	-0.32	14	14
mol:PIP3	-0.03	0.076	-10000	0	-0.32	9	9
AKT1	0.021	0.078	0.26	17	-0.28	4	21
PTK2B	-0.019	0.079	0.16	1	-0.27	30	31
RHOA	-0.001	0.071	0.22	5	-0.29	24	29
PIK3CB	0.025	0.008	-10000	0	-10000	0	0
mol:Ca2+	-0.032	0.08	0.19	5	-0.26	18	23
MAGI3	0.026	0.005	-10000	0	-10000	0	0
RELA	0.026	0.005	-10000	0	-10000	0	0
apoptosis	-0.035	0.092	-10000	0	-0.22	83	83
HRAS/GDP	0.019	0.004	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.04	0.1	0.2	17	-0.31	29	46
NF kappa B1 p50/RelA	-0.047	0.093	-10000	0	-0.34	11	11
endothelial cell migration	0.005	0.058	-10000	0	-0.24	30	30
ADCY4	-0.027	0.12	0.24	2	-0.4	41	43
ADCY5	-0.067	0.17	-10000	0	-0.42	82	82
ADCY6	-0.026	0.12	0.24	2	-0.4	40	42
ADCY7	-0.026	0.12	0.24	2	-0.4	40	42
ADCY1	-0.028	0.12	0.24	1	-0.4	40	41
ADCY2	-0.053	0.15	0.24	1	-0.43	65	66
ADCY3	-0.026	0.12	0.24	2	-0.4	39	41
ADCY8	-0.027	0.11	-10000	0	-0.42	32	32
ADCY9	-0.029	0.12	0.24	2	-0.41	43	45
GSK3B	-0.012	0.08	0.2	13	-0.28	19	32
arachidonic acid secretion	-0.034	0.12	-10000	0	-0.39	44	44
GNG2	0.025	0.022	-10000	0	-0.35	2	2
TRIP6	0.017	0.01	-10000	0	-10000	0	0
GNAO1	-0.019	0.094	-10000	0	-0.25	80	80
HRAS	0.026	0.005	-10000	0	-10000	0	0
NFKBIA	-0.036	0.094	0.23	1	-0.34	11	12
GAB1	0.026	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.03	0.24	-10000	0	-0.82	49	49
JUN	0.026	0.003	-10000	0	-10000	0	0
LPA/LPA2/NHERF2	0.034	0.012	-10000	0	-10000	0	0
TIAM1	-0.054	0.28	-10000	0	-0.96	52	52
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
mol:IP3	-0.033	0.075	0.18	7	-0.25	16	23
PLCB3	0.017	0.025	0.18	12	-10000	0	12
FOS	0.008	0.083	-10000	0	-0.37	27	27
positive regulation of mitosis	-0.034	0.12	-10000	0	-0.39	44	44
LPA/LPA1-2-3	-0.014	0.11	-10000	0	-0.2	119	119
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.026	0.005	-10000	0	-10000	0	0
stress fiber formation	-0.018	0.088	0.19	3	-0.33	21	24
GNAZ	-0.015	0.084	-10000	0	-0.23	78	78
EGFR/PI3K-beta/Gab1	-0.021	0.084	-10000	0	-0.33	9	9
positive regulation of dendritic cell cytokine production	-0.015	0.11	-10000	0	-0.19	119	119
LPA/LPA2/MAGI-3	0.035	0.012	-10000	0	-10000	0	0
ARHGEF1	0.02	0.068	0.19	52	-0.35	1	53
GNAI2	0.005	0.052	-10000	0	-0.22	29	29
GNAI3	0.006	0.051	-10000	0	-0.22	28	28
GNAI1	0.002	0.065	-10000	0	-0.26	31	31
LPA/LPA3	-0.042	0.11	-10000	0	-0.23	145	145
LPA/LPA2	0.02	0.008	-10000	0	-10000	0	0
LPA/LPA1	0.01	0.062	-10000	0	-0.26	30	30
HB-EGF/EGFR	-0.042	0.097	-10000	0	-0.19	168	168
HBEGF	-0.061	0.11	-10000	0	-0.22	178	178
mol:DAG	-0.033	0.075	0.18	7	-0.25	16	23
cAMP biosynthetic process	-0.042	0.14	0.22	9	-0.38	55	64
NFKB1	0.026	0.004	-10000	0	-10000	0	0
SRC	0.023	0.009	-10000	0	-10000	0	0
GNB1	0.026	0.006	-10000	0	-10000	0	0
LYN	-0.03	0.099	0.24	5	-0.34	11	16
GNAQ	-0.025	0.076	-10000	0	-0.21	57	57
LPAR2	0.026	0.005	-10000	0	-10000	0	0
LPAR3	-0.067	0.16	-10000	0	-0.34	145	145
LPAR1	0.009	0.086	-10000	0	-0.37	28	28
IL8	-0.12	0.13	0.28	2	-0.36	38	40
PTK2	-0.03	0.083	0.23	5	-0.34	6	11
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
CASP3	-0.035	0.092	-10000	0	-0.23	83	83
EGFR	0.016	0.052	-10000	0	-0.36	11	11
PLCG1	-0.031	0.083	0.16	3	-0.23	67	70
PLD2	-0.035	0.092	0.2	11	-0.3	12	23
G12/G13	0.037	0.057	-10000	0	-0.2	28	28
PI3K-beta	0.003	0.058	-10000	0	-0.31	5	5
cell migration	-0.009	0.083	-10000	0	-0.25	40	40
SLC9A3R2	0.026	0.006	-10000	0	-10000	0	0
PXN	-0.018	0.09	0.2	3	-0.34	21	24
HRAS/GTP	-0.035	0.12	-10000	0	-0.41	42	42
RAC1	0.025	0.007	-10000	0	-10000	0	0
MMP9	-0.082	0.16	-10000	0	-0.32	178	178
PRKCE	0.027	0.003	-10000	0	-10000	0	0
PRKCD	-0.034	0.078	0.18	4	-0.32	8	12
Gi(beta/gamma)	-0.025	0.11	0.16	1	-0.38	39	40
mol:LPA	0.002	0.008	-10000	0	-0.14	1	1
TRIP6/p130 Cas/FAK1/Paxillin	-0.005	0.096	0.22	1	-0.36	10	11
MAPKKK cascade	-0.034	0.12	-10000	0	-0.39	44	44
contractile ring contraction involved in cytokinesis	-0.002	0.079	0.21	5	-0.29	27	32
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.033	0.092	-10000	0	-0.24	77	77
GNA15	-0.037	0.094	-10000	0	-0.23	100	100
GNA12	0.025	0.007	-10000	0	-10000	0	0
GNA13	0.026	0.005	-10000	0	-10000	0	0
MAPT	-0.041	0.1	0.2	17	-0.32	29	46
GNA11	-0.026	0.076	-10000	0	-0.21	57	57
Rac1/GTP	-0.033	0.26	-10000	0	-0.87	49	49
MMP2	0.005	0.059	-10000	0	-0.24	30	30

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.06	-10000	0	-0.32	18	18
alphaV beta3 Integrin	0.035	0.03	-10000	0	-0.24	6	6
PTK2	-0.01	0.11	-10000	0	-0.38	32	32
positive regulation of JNK cascade	-0.003	0.1	-10000	0	-0.31	32	32
CDC42/GDP	0.017	0.14	0.3	3	-0.41	33	36
Rac1/GDP	0.015	0.14	0.31	3	-0.41	31	34
RAP1B	0.026	0.006	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CTNNB1	0.025	0.007	-10000	0	-10000	0	0
CDC42/GTP	0.006	0.13	-10000	0	-0.39	31	31
nectin-3/I-afadin	0.016	0.077	-10000	0	-0.26	41	41
RAPGEF1	-0.003	0.13	0.3	5	-0.42	30	35
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.017	0.14	-10000	0	-0.47	34	34
PDGFB-D/PDGFRB	0.015	0.06	-10000	0	-0.32	18	18
TLN1	-0.006	0.037	-10000	0	-0.39	2	2
Rap1/GTP	-0.002	0.094	-10000	0	-0.32	26	26
IQGAP1	0.026	0.006	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.046	0.017	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.016	0.077	-10000	0	-0.26	41	41
PVR	0.026	0.006	-10000	0	-10000	0	0
Necl-5(dimer)	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	0.003	0.16	0.32	3	-0.49	34	37
MLLT4	0.026	0.006	-10000	0	-10000	0	0
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
PI3K	0.042	0.073	-10000	0	-0.19	22	22
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.007	0.098	-10000	0	-0.23	98	98
positive regulation of lamellipodium assembly	0.004	0.1	-10000	0	-0.31	33	33
PVRL1	-0.033	0.13	-10000	0	-0.33	99	99
PVRL3	-0.003	0.1	-10000	0	-0.37	42	42
PVRL2	0.026	0.006	-10000	0	-10000	0	0
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
CDH1	0.019	0.052	-10000	0	-0.37	10	10
CLDN1	-0.19	0.17	-10000	0	-0.32	365	365
JAM-A/CLDN1	-0.095	0.11	-10000	0	-0.18	351	351
SRC	-0.02	0.15	-10000	0	-0.5	40	40
ITGB3	0.023	0.038	-10000	0	-0.36	6	6
nectin-1(dimer)/I-afadin/I-afadin	-0.007	0.098	-10000	0	-0.23	98	98
FARP2	-0.003	0.17	-10000	0	-0.56	24	24
RAC1	0.025	0.007	-10000	0	-10000	0	0
CTNNA1	0.025	0.007	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.03	0.069	-10000	0	-0.22	39	39
nectin-1/I-afadin	-0.007	0.098	-10000	0	-0.23	98	98
nectin-2/I-afadin	0.037	0.012	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.032	0.012	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.001	0.11	-10000	0	-0.24	97	97
CDC42/GTP/IQGAP1/filamentous actin	0.033	0.011	-10000	0	-10000	0	0
F11R	0.026	0.005	-10000	0	-10000	0	0
positive regulation of filopodium formation	-0.003	0.1	-10000	0	-0.31	32	32
alphaV/beta3 Integrin/Talin	0.027	0.071	0.21	24	-0.34	3	27
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.037	0.012	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.037	0.012	-10000	0	-10000	0	0
PIP5K1C	-0.005	0.044	-10000	0	-0.38	3	3
VAV2	0.005	0.16	-10000	0	-0.48	35	35
RAP1/GDP	0.019	0.13	0.31	2	-0.38	29	31
ITGAV	0.026	0.006	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.03	0.068	-10000	0	-0.22	38	38
nectin-3(dimer)/I-afadin/I-afadin	0.016	0.077	-10000	0	-0.26	41	41
Rac1/GTP	0.008	0.13	-10000	0	-0.38	32	32
PTPRM	-0.001	0.052	-10000	0	-0.18	40	40
E-cadherin/beta catenin/alpha catenin	0.026	0.089	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.026	0.006	-10000	0	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.009	0.12	0.26	9	-0.4	15	24
PTK2B	0.025	0.008	-10000	0	-10000	0	0
mol:Ca2+	0.002	0.13	-10000	0	-0.6	7	7
EDN1	0.009	0.099	0.21	2	-0.3	15	17
EDN3	-0.05	0.15	-10000	0	-0.37	107	107
EDN2	-0.033	0.14	-10000	0	-0.36	91	91
HRAS/GDP	-0.022	0.13	0.25	5	-0.43	25	30
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.003	0.089	0.2	1	-0.33	17	18
ADCY4	-0.014	0.11	0.23	7	-0.4	17	24
ADCY5	-0.056	0.14	0.21	1	-0.37	58	59
ADCY6	-0.013	0.12	0.25	7	-0.41	16	23
ADCY7	-0.014	0.11	0.25	7	-0.4	16	23
ADCY1	-0.017	0.11	0.2	12	-0.4	18	30
ADCY2	-0.044	0.13	0.24	5	-0.36	45	50
ADCY3	-0.014	0.12	0.24	8	-0.41	16	24
ADCY8	-0.021	0.11	0.24	4	-0.38	18	22
ADCY9	-0.016	0.11	0.23	7	-0.42	16	23
arachidonic acid secretion	-0.026	0.15	0.26	3	-0.46	38	41
ETB receptor/Endothelin-1/Gq/GTP	-0.009	0.089	-10000	0	-0.31	29	29
GNAO1	-0.019	0.12	-10000	0	-0.37	68	68
HRAS	0.026	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.041	0.14	0.3	7	-0.38	15	22
ETA receptor/Endothelin-1/Gs/GTP	0.025	0.15	0.28	7	-0.39	19	26
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
COL3A1	-0.027	0.16	0.29	4	-0.39	71	75
EDNRB	0.006	0.069	-10000	0	-0.37	15	15
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.016	0.14	0.29	4	-0.5	21	25
CYSLTR1	-0.024	0.16	0.28	5	-0.52	38	43
SLC9A1	0.001	0.075	0.17	3	-0.27	16	19
mol:GDP	-0.031	0.14	0.24	6	-0.44	29	35
SLC9A3	-0.17	0.28	-10000	0	-0.61	102	102
RAF1	-0.036	0.14	0.24	6	-0.42	41	47
JUN	-0.002	0.13	-10000	0	-0.62	8	8
JAK2	-0.011	0.12	0.24	9	-0.4	17	26
mol:IP3	-0.001	0.094	-10000	0	-0.37	18	18
ETA receptor/Endothelin-1	0.028	0.18	0.34	7	-0.46	17	24
PLCB1	0.024	0.017	-10000	0	-0.32	1	1
PLCB2	0.022	0.034	-10000	0	-0.34	5	5
ETA receptor/Endothelin-3	-0.034	0.13	-10000	0	-0.27	115	115
FOS	-0.051	0.21	0.28	2	-0.79	37	39
Gai/GDP	-0.11	0.3	-10000	0	-0.71	110	110
CRK	0.026	0.007	-10000	0	-10000	0	0
mol:Ca ++	-0.014	0.12	0.22	1	-0.41	22	23
BCAR1	0.026	0.005	-10000	0	-10000	0	0
PRKCB1	-0.005	0.099	-10000	0	-0.36	24	24
GNAQ	0.026	0.009	-10000	0	-10000	0	0
GNAZ	-0.012	0.12	-10000	0	-0.37	56	56
GNAL	0.004	0.089	-10000	0	-0.37	31	31
Gs family/GDP	-0.032	0.13	0.23	6	-0.41	31	37
ETA receptor/Endothelin-1/Gq/GTP	-0.001	0.096	0.2	3	-0.32	19	22
MAPK14	-0.007	0.086	0.22	4	-0.32	24	28
TRPC6	0.001	0.13	-10000	0	-0.63	7	7
GNAI2	0.025	0.007	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNAI1	0.019	0.052	-10000	0	-0.37	10	10
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.003	0.088	-10000	0	-0.33	22	22
ETB receptor/Endothelin-2	-0.02	0.11	-10000	0	-0.26	97	97
ETB receptor/Endothelin-3	-0.033	0.12	-10000	0	-0.27	113	113
ETB receptor/Endothelin-1	0.012	0.1	-10000	0	-0.28	25	25
MAPK3	-0.05	0.2	0.29	2	-0.7	38	40
MAPK1	-0.049	0.19	0.29	2	-0.67	39	41
Rac1/GDP	-0.021	0.13	0.23	3	-0.42	25	28
cAMP biosynthetic process	-0.044	0.14	0.23	11	-0.38	54	65
MAPK8	-0.004	0.15	-10000	0	-0.58	20	20
SRC	0.023	0.009	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.033	0.12	-10000	0	-0.34	52	52
p130Cas/CRK/Src/PYK2	-0.024	0.14	0.29	9	-0.5	20	29
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.021	0.13	0.24	4	-0.42	25	29
COL1A2	-0.022	0.15	-10000	0	-0.41	32	32
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.022	0.12	-10000	0	-0.25	105	105
mol:DAG	-0.001	0.094	-10000	0	-0.37	18	18
MAP2K2	-0.041	0.16	0.26	3	-0.52	41	44
MAP2K1	-0.043	0.16	0.28	4	-0.52	41	45
EDNRA	0.008	0.1	0.21	2	-0.3	20	22
positive regulation of muscle contraction	0.002	0.11	0.23	34	-0.36	14	48
Gq family/GDP	-0.021	0.13	-10000	0	-0.41	29	29
HRAS/GTP	-0.033	0.13	0.25	4	-0.42	33	37
PRKCH	-0.001	0.09	0.22	3	-0.34	18	21
RAC1	0.025	0.007	-10000	0	-10000	0	0
PRKCA	-0.005	0.1	0.24	6	-0.37	22	28
PRKCB	-0.015	0.12	-10000	0	-0.4	31	31
PRKCE	-0.006	0.1	0.24	3	-0.37	22	25
PRKCD	-0.001	0.087	0.24	1	-0.34	16	17
PRKCG	-0.052	0.12	0.22	7	-0.38	28	35
regulation of vascular smooth muscle contraction	-0.064	0.25	0.33	1	-0.94	36	37
PRKCQ	-0.01	0.11	0.23	3	-0.4	24	27
PLA2G4A	-0.029	0.16	0.28	2	-0.5	38	40
GNA14	0.012	0.076	-10000	0	-0.37	22	22
GNA15	-0.006	0.1	-10000	0	-0.32	56	56
GNA12	0.025	0.007	-10000	0	-10000	0	0
GNA11	0.026	0.007	-10000	0	-10000	0	0
Rac1/GTP	0.042	0.14	0.3	7	-0.38	15	22
MMP1	-0.1	0.16	0.47	4	-0.3	163	167

×

Coregulation of Androgen receptor activity

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
NRIP1	0.023	0.014	-9999	-10000	0	0
SVIL	0.022	0.03	-9999	-0.36	3	3
ZNF318	0.026	0.012	-9999	-10000	0	0
JMJD2C	-0.001	0.015	-9999	-0.059	36	36
T-DHT/AR/Ubc9	-0.043	0.12	-9999	-0.23	150	150
CARM1	0.026	0.005	-9999	-10000	0	0
PRDX1	0.027	0.004	-9999	-10000	0	0
PELP1	0.026	0.007	-9999	-10000	0	0
CTNNB1	0.023	0.013	-9999	-10000	0	0
AKT1	0.026	0.006	-9999	-10000	0	0
PTK2B	0.022	0.013	-9999	-10000	0	0
MED1	0.026	0.008	-9999	-10000	0	0
MAK	0.02	0.05	-9999	-0.33	11	11
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.023	0.013	-9999	-10000	0	0
GSN	0.021	0.035	-9999	-0.37	4	4
NCOA2	0.024	0.018	-9999	-0.37	1	1
NCOA6	0.022	0.014	-9999	-10000	0	0
DNA-PK	0.049	0.023	-9999	-0.19	1	1
NCOA4	0.026	0.005	-9999	-10000	0	0
PIAS3	0.023	0.012	-9999	-10000	0	0
cell proliferation	-0.02	0.1	-9999	-0.5	23	23
XRCC5	0.027	0.004	-9999	-10000	0	0
UBE3A	0.023	0.014	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.086	0.15	-9999	-0.26	222	222
FHL2	-0.013	0.092	-9999	-0.66	7	7
RANBP9	0.023	0.013	-9999	-10000	0	0
JMJD1A	-0.014	0.045	-9999	-0.12	85	85
CDK6	0.022	0.026	-9999	-0.32	3	3
TGFB1I1	0.022	0.029	-9999	-0.34	3	3
T-DHT/AR/CyclinD1	-0.033	0.11	-9999	-0.22	127	127
XRCC6	0.027	0.005	-9999	-10000	0	0
T-DHT/AR	-0.048	0.13	-9999	-0.24	154	154
CTDSP1	0.026	0.004	-9999	-10000	0	0
CTDSP2	0.027	0.008	-9999	-10000	0	0
BRCA1	0.022	0.031	-9999	-0.33	4	4
TCF4	0.023	0.018	-9999	-0.32	1	1
CDKN2A	-0.07	0.15	-9999	-0.33	153	153
SRF	0.028	0.016	-9999	-10000	0	0
NKX3-1	-0.051	0.086	-9999	-0.22	98	98
KLK3	0	0.067	-9999	-10000	0	0
TMF1	0.025	0.007	-9999	-10000	0	0
HNRNPA1	0.027	0.005	-9999	-10000	0	0
AOF2	0	0.004	-9999	-10000	0	0
APPL1	0.012	0.007	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.041	0.12	-9999	-0.23	148	148
AR	-0.087	0.17	-9999	-0.38	150	150
UBA3	0.025	0.007	-9999	-10000	0	0
PATZ1	0.027	0.006	-9999	-10000	0	0
PAWR	0.025	0.017	-9999	-0.37	1	1
PRKDC	0.024	0.016	-9999	-0.32	1	1
PA2G4	0.027	0.006	-9999	-10000	0	0
UBE2I	0.026	0.006	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.034	0.1	-9999	-0.2	137	137
RPS6KA3	0.024	0.013	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.042	0.11	-9999	-0.23	148	148
LATS2	0.026	0.007	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.036	0.1	-9999	-0.2	148	148
Cyclin D3/CDK11 p58	0.019	0.006	-9999	-10000	0	0
VAV3	0.013	0.064	-9999	-0.34	18	18
KLK2	-0.039	0.092	-9999	-0.31	42	42
CASP8	0.027	0.004	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.024	0.11	-9999	-0.21	132	132
TMPRSS2	-0.13	0.29	-9999	-0.74	103	103
CCND1	0.023	0.01	-9999	-10000	0	0
PIAS1	0.024	0.014	-9999	-10000	0	0
mol:T-DHT	-0.007	0.022	-9999	-0.061	70	70
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.023	0.017	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.035	0.11	-9999	-0.23	126	126
CMTM2	0.016	0.06	-9999	-0.34	16	16
SNURF	-0.051	0.15	-9999	-0.37	110	110
ZMIZ1	0.012	0.035	-9999	-10000	0	0
CCND3	0.025	0.007	-9999	-10000	0	0
TGIF1	0.026	0.007	-9999	-10000	0	0
FKBP4	0.023	0.013	-9999	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.036	0.067	-10000	0	-0.36	15	15
HDAC1	0.024	0.005	-10000	0	-10000	0	0
AES	0.025	0.006	-10000	0	-10000	0	0
FBXW11	0.026	0.006	-10000	0	-10000	0	0
DTX1	0.024	0.03	-10000	0	-0.34	4	4
LRP6/FZD1	0.033	0.015	-10000	0	-10000	0	0
TLE1	0.025	0.017	-10000	0	-0.37	1	1
AP1	-0.013	0.082	-10000	0	-0.24	58	58
NCSTN	0.026	0.005	-10000	0	-10000	0	0
ADAM10	0.026	0.004	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.012	0.16	-10000	0	-0.64	30	30
NICD/RBPSUH	0.033	0.067	-10000	0	-0.37	15	15
WIF1	-0.076	0.17	-10000	0	-0.37	148	148
NOTCH1	0.017	0.061	-10000	0	-0.38	13	13
PSENEN	0.026	0.006	-10000	0	-10000	0	0
KREMEN2	-0.069	0.16	-10000	0	-0.32	162	162
DKK1	-0.13	0.18	-10000	0	-0.33	265	265
beta catenin/beta TrCP1	0.031	0.081	0.26	3	-0.4	6	9
APH1B	0.026	0.004	-10000	0	-10000	0	0
APH1A	0.026	0.005	-10000	0	-10000	0	0
AXIN1	-0.005	0.082	-10000	0	-0.35	22	22
CtBP/CBP/TCF1/TLE1/AES	-0.006	0.073	-10000	0	-0.32	7	7
PSEN1	0.026	0.005	-10000	0	-10000	0	0
FOS	0.008	0.083	-10000	0	-0.37	27	27
JUN	0.027	0.003	-10000	0	-10000	0	0
MAP3K7	0.025	0.005	-10000	0	-10000	0	0
CTNNB1	0.018	0.085	0.24	5	-0.35	12	17
MAPK3	0.026	0.005	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.062	0.13	-10000	0	-0.2	256	256
HNF1A	-0.01	0.11	-10000	0	-0.37	53	53
CTBP1	0.024	0.007	-10000	0	-10000	0	0
MYC	0.015	0.085	-10000	0	-1.1	3	3
NKD1	-0.013	0.12	-10000	0	-0.35	62	62
FZD1	0.024	0.009	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.033	0.068	-10000	0	-0.37	15	15
apoptosis	-0.013	0.081	-10000	0	-0.24	58	58
Delta 1/NOTCHprecursor	0.033	0.067	-10000	0	-0.36	15	15
DLL1	0.025	0.021	-10000	0	-0.32	2	2
PPARD	0.013	0.11	-10000	0	-0.85	10	10
Gamma Secretase	0.069	0.029	-10000	0	-10000	0	0
APC	-0.016	0.11	-10000	0	-0.37	39	39
DVL1	0.003	0.048	-10000	0	-0.34	8	8
CSNK2A1	0.025	0.008	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.001	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.11	0.15	-10000	0	-0.23	327	327
LRP6	0.025	0.007	-10000	0	-10000	0	0
CSNK1A1	0.026	0.007	-10000	0	-10000	0	0
NLK	0.011	0.004	-10000	0	-10000	0	0
CCND1	0.012	0.091	-10000	0	-0.87	5	5
WNT1	0.022	0.038	-10000	0	-0.32	7	7
Axin1/APC/beta catenin	0.015	0.11	0.28	4	-0.42	17	21
DKK2	-0.054	0.15	-10000	0	-0.32	136	136
NOTCH1 precursor/DVL1	0.018	0.097	-10000	0	-0.5	13	13
GSK3B	0.025	0.007	-10000	0	-10000	0	0
FRAT1	0.025	0.017	-10000	0	-0.37	1	1
NOTCH/Deltex homolog 1	0.037	0.068	-10000	0	-0.37	15	15
PPP2R5D	0.028	0.06	0.23	23	-0.35	3	26
MAPK1	0.026	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.002	0.11	-10000	0	-0.2	121	121
RBPJ	0.026	0.006	-10000	0	-10000	0	0
CREBBP	0.027	0.007	-10000	0	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.033	0.11	0.3	51	-10000	0	51
GNAI2	0.025	0.007	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.002	0.08	-10000	0	-0.18	95	95
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.019	0.12	-10000	0	-0.37	68	68
RhoA/GTP	-0.033	0.11	-10000	0	-0.31	51	51
negative regulation of cAMP metabolic process	-0.04	0.12	-10000	0	-0.32	57	57
GNAZ	-0.012	0.12	-10000	0	-0.37	56	56
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNA12	0.025	0.007	-10000	0	-10000	0	0
S1PR5	-0.035	0.13	-10000	0	-0.32	104	104
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.041	0.12	-10000	0	-0.32	57	57
RhoA/GDP	0.019	0.005	-10000	0	-10000	0	0
RHOA	0.025	0.007	-10000	0	-10000	0	0
GNAI1	0.019	0.052	-10000	0	-0.37	10	10

×

IL23-mediated signaling events

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
CCL2	-0.34	0.33	-10000	0	-1.2	44	44
IL23A	-0.34	0.31	-10000	0	-1.1	40	40
NF kappa B1 p50/RelA/I kappa B alpha	-0.34	0.31	-10000	0	-0.99	57	57
positive regulation of T cell mediated cytotoxicity	-0.36	0.34	-10000	0	-1.1	59	59
ITGA3	-0.33	0.3	-10000	0	-1	37	37
IL17F	-0.27	0.22	-10000	0	-0.71	58	58
IL12B	-0.029	0.046	-10000	0	-0.36	7	7
STAT1 (dimer)	-0.35	0.32	-10000	0	-1.1	55	55
CD4	-0.33	0.3	-10000	0	-1.1	35	35
IL23	-0.33	0.3	-10000	0	-1	40	40
IL23R	-0.096	0.25	-10000	0	-1.1	30	30
IL1B	-0.35	0.32	-10000	0	-1.1	41	41
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.36	0.32	-10000	0	-1	48	48
TYK2	-0.018	0.027	-10000	0	-10000	0	0
STAT4	0.024	0.032	-10000	0	-0.32	5	5
STAT3	0.025	0.007	-10000	0	-10000	0	0
IL18RAP	0.005	0.074	-10000	0	-0.36	22	22
IL12RB1	-0.041	0.089	-10000	0	-0.35	42	42
PIK3CA	0.023	0.01	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.033	0.072	-10000	0	-0.26	42	42
IL23R/JAK2	-0.1	0.24	-10000	0	-1.1	28	28
positive regulation of chronic inflammatory response	-0.36	0.34	-10000	0	-1.1	59	59
natural killer cell activation	0.008	0.013	0.079	18	-10000	0	18
JAK2	-0.021	0.03	-10000	0	-10000	0	0
PIK3R1	0.024	0.009	-10000	0	-10000	0	0
NFKB1	0.023	0.004	-10000	0	-10000	0	0
RELA	0.023	0.005	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.32	0.29	-10000	0	-0.98	41	41
ALOX12B	-0.36	0.31	-10000	0	-1.1	42	42
CXCL1	-0.4	0.31	-10000	0	-1.1	47	47
T cell proliferation	-0.36	0.34	-10000	0	-1.1	59	59
NFKBIA	0.023	0.004	-10000	0	-10000	0	0
IL17A	-0.25	0.2	-10000	0	-0.57	82	82
PI3K	-0.34	0.31	-10000	0	-1	50	50
IFNG	-0.019	0.041	0.13	20	-0.11	17	37
STAT3 (dimer)	-0.33	0.31	-10000	0	-1	51	51
IL18R1	0.019	0.024	-10000	0	-0.37	1	1
IL23/IL23R/JAK2/TYK2/SOCS3	-0.23	0.21	-10000	0	-0.72	43	43
IL18/IL18R	0.023	0.067	-10000	0	-0.21	28	28
macrophage activation	-0.021	0.014	-10000	0	-0.044	19	19
TNF	-0.34	0.32	-10000	0	-1.1	38	38
STAT3/STAT4	-0.34	0.32	-10000	0	-1	55	55
STAT4 (dimer)	-0.35	0.33	-10000	0	-1.1	55	55
IL18	0.014	0.043	-10000	0	-0.35	7	7
IL19	-0.34	0.32	-10000	0	-1.1	44	44
STAT5A (dimer)	-0.35	0.33	-10000	0	-1	56	56
STAT1	0.021	0.043	-10000	0	-0.32	9	9
SOCS3	0.026	0.005	-10000	0	-10000	0	0
CXCL9	-0.37	0.31	-10000	0	-1	52	52
MPO	-0.33	0.3	-10000	0	-1	41	41
positive regulation of humoral immune response	-0.36	0.34	-10000	0	-1.1	59	59
IL23/IL23R/JAK2/TYK2	-0.37	0.35	-10000	0	-1.1	58	58
IL6	-0.36	0.36	-10000	0	-1.2	60	60
STAT5A	0.026	0.004	-10000	0	-10000	0	0
IL2	0.013	0.03	-10000	0	-0.32	2	2
positive regulation of tyrosine phosphorylation of STAT protein	0.008	0.013	0.079	18	-10000	0	18
CD3E	-0.34	0.3	-10000	0	-1	38	38
keratinocyte proliferation	-0.36	0.34	-10000	0	-1.1	59	59
NOS2	-0.37	0.32	-10000	0	-1.1	49	49

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.007	0.009	-10000	0	-0.22	1	1
ADCY5	-0.057	0.09	-10000	0	-0.22	142	142
ADCY6	-0.007	0.009	-10000	0	-0.22	1	1
ADCY7	-0.007	0.002	-10000	0	-10000	0	0
ADCY1	-0.009	0.028	0.2	3	-0.19	10	13
ADCY2	-0.042	0.081	0.2	2	-0.22	103	105
ADCY3	-0.007	0.007	-10000	0	-0.19	1	1
ADCY8	-0.011	0.029	0.2	3	-0.19	12	15
PRKCE	0.007	0.001	-10000	0	-10000	0	0
ADCY9	-0.008	0.015	-10000	0	-0.22	3	3
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.002	0.084	0.21	33	-0.24	2	35

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.027	0.031	-10000	0	-0.24	6	6
ARNO/beta Arrestin1-2	-0.026	0.14	-10000	0	-0.8	13	13
EGFR	0.017	0.052	-10000	0	-0.36	11	11
EPHA2	0.024	0.029	-10000	0	-0.32	4	4
USP6	0.023	0.031	-10000	0	-0.35	4	4
IQSEC1	0.026	0.006	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.007	0.096	-10000	0	-0.23	91	91
ARRB2	0.01	0.013	-10000	0	-10000	0	0
mol:GTP	0.018	0.047	0.13	44	-0.15	5	49
ARRB1	0.003	0.091	-10000	0	-0.37	33	33
FBXO8	0.025	0.007	-10000	0	-10000	0	0
TSHR	0.011	0.073	-10000	0	-0.37	21	21
EGF	-0.033	0.13	-10000	0	-0.32	94	94
somatostatin receptor activity	0	0	0.001	15	-0.001	38	53
ARAP2	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	-0.042	0.1	0.2	3	-0.26	68	71
mol:PI-3-4-5-P3	0	0	0.001	3	-0.001	8	11
ITGA2B	0.005	0.081	-10000	0	-0.32	34	34
ARF6	0.026	0.005	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.058	0.031	-10000	0	-0.17	4	4
ADAP1	0.021	0.039	-10000	0	-0.36	6	6
KIF13B	0.024	0.018	-10000	0	-0.37	1	1
HGF/MET	0.021	0.065	-10000	0	-0.24	33	33
PXN	0.027	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.03	0.099	0.22	8	-0.25	38	46
EGFR/EGFR/EGF/EGF/ARFGEP100	0.008	0.088	-10000	0	-0.19	91	91
ADRB2	-0.057	0.16	-10000	0	-0.37	122	122
receptor agonist activity	0	0	0	13	0	33	46
actin filament binding	0	0	0	11	0	39	50
SRC	0.023	0.009	-10000	0	-10000	0	0
ITGB3	0.023	0.038	-10000	0	-0.36	6	6
GNAQ	0.026	0.006	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0	0.001	20	-0.001	22	42
ARF6/GDP	-0.007	0.13	0.25	9	-0.44	32	41
ARF6/GDP/GULP/ACAP1	-0.025	0.12	0.26	1	-0.32	44	45
alphaIIb/beta3 Integrin/paxillin/GIT1	0.049	0.062	-10000	0	-0.18	40	40
ACAP1	0.017	0.055	-10000	0	-0.33	14	14
ACAP2	0.023	0.009	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	0.016	0.026	-10000	0	-0.17	6	6
EFNA1	0.026	0.004	-10000	0	-10000	0	0
HGF	0.011	0.074	-10000	0	-0.36	23	23
CYTH3	0.006	0.002	-10000	0	-10000	0	0
CYTH2	-0.003	0.15	-10000	0	-1	13	13
NCK1	0.025	0.007	-10000	0	-10000	0	0
fibronectin binding	0	0	0	17	0	28	45
endosomal lumen acidification	0	0	0	39	0	19	58
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	0.011	0.077	-10000	0	-0.37	23	23
GNAQ/ARNO	0.012	0.14	-10000	0	-0.91	13	13
mol:Phosphatidic acid	0	0	0	2	-10000	0	2
PIP3-E	0	0	0	3	0	4	7
MET	0.018	0.05	-10000	0	-0.33	12	12
GNA14	0.011	0.076	-10000	0	-0.37	22	22
GNA15	-0.007	0.1	-10000	0	-0.32	56	56
GIT1	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	17	-0.001	32	49
GNA11	0.026	0.006	-10000	0	-10000	0	0
LHCGR	0.011	0.038	-10000	0	-0.32	6	6
AGTR1	-0.07	0.17	-10000	0	-0.37	140	140
desensitization of G-protein coupled receptor protein signaling pathway	0.016	0.026	-10000	0	-0.17	6	6
IPCEF1/ARNO	-0.006	0.14	-10000	0	-0.84	13	13
alphaIIb/beta3 Integrin	0.021	0.067	-10000	0	-0.23	40	40

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.051	0.066	-10000	0	-10000	0	0
SMARCC2	0.026	0.011	-10000	0	-10000	0	0
SMARCC1	0.025	0.013	-10000	0	-10000	0	0
TBX21	-0.069	0.13	0.35	1	-0.46	29	30
SUMO2	0.027	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.026	0.043	-10000	0	-0.32	9	9
FKBP4	0.025	0.007	-10000	0	-10000	0	0
FKBP5	0.022	0.04	-10000	0	-0.37	6	6
GR alpha/HSP90/FKBP51/HSP90	0.084	0.089	0.28	22	-0.24	4	26
PRL	-0.043	0.096	-10000	0	-0.61	2	2
cortisol/GR alpha (dimer)/TIF2	0.14	0.19	0.49	60	-0.38	1	61
RELA	-0.04	0.068	-10000	0	-0.22	6	6
FGG	0.032	0.23	0.42	30	-0.4	83	113
GR beta/TIF2	0.073	0.093	0.28	32	-0.33	2	34
IFNG	-0.2	0.18	-10000	0	-0.53	64	64
apoptosis	-0.008	0.15	0.5	14	-0.57	10	24
CREB1	0.022	0.034	-10000	0	-10000	0	0
histone acetylation	0.006	0.12	0.34	25	-0.33	10	35
BGLAP	-0.043	0.089	0.34	2	-0.37	4	6
GR/PKAc	0.087	0.088	0.28	17	-0.24	3	20
NF kappa B1 p50/RelA	-0.064	0.11	-10000	0	-0.3	39	39
SMARCD1	0.027	0.011	-10000	0	-10000	0	0
MDM2	0.051	0.065	0.21	35	-10000	0	35
GATA3	0.01	0.081	-10000	0	-0.32	33	33
AKT1	0.022	0.005	-10000	0	-10000	0	0
CSF2	-0.063	0.12	-10000	0	-0.46	2	2
GSK3B	0.026	0.009	-10000	0	-10000	0	0
NR1I3	0.003	0.14	0.49	13	-0.52	6	19
CSN2	0.074	0.13	0.37	24	-0.31	2	26
BRG1/BAF155/BAF170/BAF60A	0.062	0.039	-10000	0	-0.24	4	4
NFATC1	0.021	0.034	-10000	0	-0.37	3	3
POU2F1	0.026	0.018	-10000	0	-10000	0	0
CDKN1A	0.01	0.072	-10000	0	-1.2	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.007	-10000	0	-10000	0	0
SFN	-0.009	0.1	-10000	0	-0.33	58	58
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.074	0.1	0.28	19	-0.21	8	27
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.011	0.16	0.46	12	-0.72	14	26
JUN	-0.16	0.12	-10000	0	-0.39	62	62
IL4	-0.052	0.094	-10000	0	-0.51	2	2
CDK5R1	0.008	0.08	-10000	0	-0.32	33	33
PRKACA	0.026	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.18	0.15	0.2	3	-0.34	194	197
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.092	0.088	0.29	20	-0.26	2	22
cortisol/GR alpha (monomer)	0.16	0.22	0.56	65	-0.39	2	67
NCOA2	0.024	0.018	-10000	0	-0.37	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.077	0.09	-10000	0	-0.41	28	28
AP-1/NFAT1-c-4	-0.25	0.18	-10000	0	-0.52	111	111
AFP	-0.13	0.11	-10000	0	-0.53	1	1
SUV420H1	0.025	0.007	-10000	0	-10000	0	0
IRF1	0.083	0.11	0.38	13	-0.49	1	14
TP53	0.036	0.025	-10000	0	-0.5	1	1
PPP5C	0.026	0.005	-10000	0	-10000	0	0
KRT17	-0.27	0.2	-10000	0	-0.58	89	89
KRT14	-0.2	0.33	0.75	1	-1	65	66
TBP	0.031	0.007	-10000	0	-10000	0	0
CREBBP	0.078	0.09	0.32	48	-0.25	5	53
HDAC1	0.025	0.006	-10000	0	-10000	0	0
HDAC2	0.032	0.012	-10000	0	-10000	0	0
AP-1	-0.25	0.18	-10000	0	-0.52	111	111
MAPK14	0.026	0.009	-10000	0	-10000	0	0
MAPK10	-0.017	0.12	-10000	0	-0.37	65	65
MAPK11	0.026	0.009	-10000	0	-10000	0	0
KRT5	-0.24	0.22	-10000	0	-0.6	91	91
interleukin-1 receptor activity	0.006	0.011	-10000	0	-10000	0	0
NCOA1	0.028	0.003	-10000	0	-10000	0	0
STAT1	0.026	0.043	-10000	0	-0.32	9	9
CGA	-0.059	0.1	-10000	0	-0.41	5	5
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.094	0.14	0.34	63	-0.4	4	67
MAPK3	0.027	0.01	-10000	0	-10000	0	0
MAPK1	0.026	0.009	-10000	0	-10000	0	0
ICAM1	-0.1	0.14	-10000	0	-0.46	33	33
NFKB1	-0.041	0.07	-10000	0	-0.22	9	9
MAPK8	-0.12	0.11	-10000	0	-0.34	52	52
MAPK9	0.026	0.009	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.009	0.15	0.5	14	-0.59	10	24
BAX	0.013	0.055	-10000	0	-10000	0	0
POMC	-0.12	0.3	-10000	0	-1.3	33	33
EP300	0.079	0.091	0.32	48	-0.25	6	54
cortisol/GR alpha (dimer)/p53	0.16	0.19	0.5	60	-0.36	1	61
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.055	0.21	15	-10000	0	15
SGK1	0.068	0.19	0.47	3	-1.2	8	11
IL13	-0.14	0.13	-10000	0	-0.55	10	10
IL6	-0.14	0.23	-10000	0	-0.76	50	50
PRKACG	0.02	0.025	-10000	0	-0.32	3	3
IL5	-0.12	0.12	-10000	0	-0.61	2	2
IL2	-0.18	0.16	-10000	0	-0.56	35	35
CDK5	0.026	0.007	-10000	0	-10000	0	0
PRKACB	0.024	0.033	-10000	0	-0.37	4	4
HSP90AA1	0.026	0.006	-10000	0	-10000	0	0
IL8	-0.18	0.18	-10000	0	-0.49	66	66
CDK5R1/CDK5	0.023	0.061	-10000	0	-0.22	33	33
NF kappa B1 p50/RelA/PKAc	-0.033	0.1	-10000	0	-0.32	8	8
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.15	0.18	0.46	65	-0.35	1	66
SMARCA4	0.026	0.012	-10000	0	-10000	0	0
chromatin remodeling	0.082	0.12	0.33	32	-0.42	6	38
NF kappa B1 p50/RelA/Cbp	0.03	0.14	0.37	17	-0.39	6	23
JUN (dimer)	-0.16	0.12	-10000	0	-0.39	62	62
YWHAH	0.026	0.005	-10000	0	-10000	0	0
VIPR1	-0.069	0.14	-10000	0	-0.6	22	22
NR3C1	0.093	0.13	0.36	48	-0.41	3	51
NR4A1	-0.01	0.13	-10000	0	-0.47	43	43
TIF2/SUV420H1	0.034	0.019	-10000	0	-0.26	1	1
MAPKKK cascade	-0.008	0.15	0.5	14	-0.57	10	24
cortisol/GR alpha (dimer)/Src-1	0.16	0.19	0.5	65	-0.38	1	66
PBX1	0.014	0.07	-10000	0	-0.37	18	18
POU1F1	0.019	0.027	-10000	0	-0.32	2	2
SELE	-0.13	0.17	-10000	0	-0.48	69	69
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.082	0.12	0.33	32	-0.42	6	38
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.15	0.18	0.46	65	-0.35	1	66
mol:cortisol	0.08	0.12	0.31	64	-0.17	1	65
MMP1	-0.17	0.19	-10000	0	-0.81	23	23

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.035	0.017	-10000	0	-0.22	1	1
alphaV beta3 Integrin	0.034	0.067	-10000	0	-0.22	35	35
PTK2	0.008	0.12	0.28	30	-0.4	7	37
IGF1R	0.024	0.024	-10000	0	-0.37	2	2
PI4KB	0.026	0.006	-10000	0	-10000	0	0
MFGE8	0.026	0.005	-10000	0	-10000	0	0
SRC	0.023	0.009	-10000	0	-10000	0	0
CDKN1B	-0.036	0.13	-10000	0	-0.41	60	60
VEGFA	0.024	0.016	-10000	0	-0.32	1	1
ILK	-0.037	0.13	-10000	0	-0.4	63	63
ROCK1	0.026	0.006	-10000	0	-10000	0	0
AKT1	-0.038	0.12	-10000	0	-0.38	58	58
PTK2B	0.004	0.059	0.18	54	-10000	0	54
alphaV/beta3 Integrin/JAM-A	0	0.1	-10000	0	-0.21	80	80
CBL	0.025	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.02	0.087	-10000	0	-0.22	65	65
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.031	0.089	-10000	0	-0.2	70	70
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.009	0.073	-10000	0	-0.29	15	15
alphaV/beta3 Integrin/Syndecan-1	0.046	0.04	-10000	0	-0.22	11	11
PI4KA	0.026	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0	0.11	-10000	0	-0.36	21	21
PI4 Kinase	0.037	0.011	-10000	0	-10000	0	0
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.071	0.12	-10000	0	-0.19	298	298
RPS6KB1	-0.042	0.093	0.26	2	-0.34	20	22
TLN1	0.025	0.008	-10000	0	-10000	0	0
MAPK3	-0.041	0.13	-10000	0	-0.49	34	34
GPR124	0.024	0.018	-10000	0	-0.37	1	1
MAPK1	-0.042	0.13	-10000	0	-0.49	35	35
PXN	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.01	0.099	-10000	0	-0.22	90	90
cell adhesion	0.019	0.073	-10000	0	-0.2	48	48
ANGPTL3	-0.015	0.12	-10000	0	-0.37	62	62
VEGFR2 homodimer/VEGFA homodimer/Src	0.042	0.025	-10000	0	-0.19	1	1
IGF-1R heterotetramer	0.024	0.024	-10000	0	-0.37	2	2
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
TGFBR2	0.024	0.024	-10000	0	-0.37	2	2
ITGB3	0.023	0.038	-10000	0	-0.36	6	6
IGF1	-0.021	0.13	-10000	0	-0.36	74	74
RAC1	0.025	0.007	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.043	0.034	-10000	0	-0.21	7	7
apoptosis	0.026	0.006	-10000	0	-10000	0	0
CD47	0.026	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.047	0.031	-10000	0	-0.21	6	6
VCL	0.026	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.038	0.058	-10000	0	-0.26	18	18
CSF1	0.026	0.015	-10000	0	-0.32	1	1
PIK3C2A	-0.037	0.13	-10000	0	-0.4	63	63
PI4 Kinase/Pyk2	-0.011	0.087	-10000	0	-0.32	11	11
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.054	0.038	-10000	0	-0.19	7	7
FAK1/Vinculin	0.018	0.11	0.26	36	-0.33	7	43
alphaV beta3/Integrin/ppsTEM5	0.044	0.034	-10000	0	-0.21	7	7
RHOA	0.025	0.007	-10000	0	-10000	0	0
VTN	-0.044	0.15	-10000	0	-0.35	111	111
BCAR1	0.026	0.005	-10000	0	-10000	0	0
FGF2	0.006	0.087	-10000	0	-0.37	30	30
F11R	-0.001	0.058	-10000	0	-0.26	28	28
alphaV/beta3 Integrin/Lactadherin	0.047	0.03	-10000	0	-0.21	6	6
alphaV/beta3 Integrin/TGFBR2	0.045	0.035	-10000	0	-0.21	8	8
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.059	0.027	-10000	0	-10000	0	0
HSP90AA1	0.026	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.042	0.03	-10000	0	-0.19	6	6
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0	0.093	-10000	0	-0.33	45	45
alphaV/beta3 Integrin/Pyk2	0.048	0.049	-10000	0	-0.19	3	3
SDC1	0.023	0.037	-10000	0	-0.34	6	6
VAV3	-0.012	0.04	0.18	14	-10000	0	14
PTPN11	0.026	0.004	-10000	0	-10000	0	0
IRS1	0.025	0.023	-10000	0	-0.37	2	2
FAK1/Paxillin	0.017	0.11	0.25	38	-0.33	7	45
cell migration	0.013	0.1	0.23	43	-0.31	6	49
ITGAV	0.026	0.006	-10000	0	-10000	0	0
PI3K	0.012	0.098	-10000	0	-0.33	10	10
SPP1	-0.15	0.18	-10000	0	-0.32	297	297
KDR	0.026	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.026	0.006	-10000	0	-10000	0	0
COL4A3	-0.031	0.14	-10000	0	-0.36	89	89
angiogenesis	-0.049	0.14	-10000	0	-0.5	35	35
Rac1/GTP	0.022	0.038	0.17	14	-10000	0	14
EDIL3	0.013	0.067	-10000	0	-0.37	17	17
cell proliferation	0.045	0.034	-10000	0	-0.21	8	8

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.026	0.005	-10000	0	-10000	0	0
PTK2	0.023	0.01	-10000	0	-10000	0	0
CRKL	-0.008	0.065	0.16	1	-0.2	46	47
GRB2/SOS1/SHC	0.051	0.014	-10000	0	-10000	0	0
HRAS	0.026	0.005	-10000	0	-10000	0	0
IRS1/Crk	0	0.068	-10000	0	-0.2	47	47
IGF-1R heterotetramer/IGF1/PTP1B	0.016	0.078	-10000	0	-0.2	60	60
AKT1	-0.003	0.082	0.18	63	-0.44	1	64
BAD	-0.007	0.077	0.17	60	-0.42	1	61
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.007	0.063	0.16	1	-0.21	41	42
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.006	0.072	0.2	3	-0.21	47	50
RAF1	0.002	0.099	0.27	6	-0.42	14	20
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.031	0.078	-10000	0	-0.2	43	43
YWHAZ	0.023	0.01	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.006	0.076	-10000	0	-0.19	69	69
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
RPS6KB1	-0.002	0.083	0.18	67	-0.36	2	69
GNB2L1	0.026	0.006	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.001	0.088	0.28	8	-0.33	10	18
PXN	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.039	0.008	-10000	0	-10000	0	0
HRAS/GTP	0.007	0.064	-10000	0	-0.38	2	2
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.043	0.08	-10000	0	-0.35	2	2
IGF-1R heterotetramer	0.015	0.04	-10000	0	-0.45	2	2
IGF-1R heterotetramer/IGF1/IRS/Nck	0.019	0.077	-10000	0	-0.21	46	46
Crk/p130 Cas/Paxillin	0.029	0.076	0.22	2	-0.38	2	4
IGF1R	0.015	0.04	-10000	0	-0.45	2	2
IGF1	-0.02	0.13	-10000	0	-0.37	74	74
IRS2/Crk	-0.004	0.071	0.16	1	-0.2	56	57
PI3K	0.024	0.075	-10000	0	-0.2	41	41
apoptosis	0.004	0.069	0.37	1	-0.17	52	53
HRAS/GDP	0.019	0.004	-10000	0	-10000	0	0
PRKCD	-0.016	0.088	-10000	0	-0.3	44	44
RAF1/14-3-3 E	0.011	0.099	0.28	6	-0.35	16	22
BAD/14-3-3	-0.004	0.072	0.18	52	-0.39	1	53
PRKCZ	-0.003	0.082	0.18	64	-0.36	2	66
Crk/p130 Cas/Paxillin/FAK1	0.019	0.062	-10000	0	-0.4	1	1
PTPN1	0.022	0.01	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.017	0.099	-10000	0	-0.31	51	51
BCAR1	0.026	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.031	0.079	-10000	0	-0.2	44	44
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.027	0.003	-10000	0	-10000	0	0
IRS1/NCK2	0.008	0.073	-10000	0	-0.2	46	46
GRB10	0.025	0.016	-10000	0	-0.32	1	1
PTPN11	-0.008	0.066	0.16	1	-0.2	47	48
IRS1	-0.006	0.074	-10000	0	-0.22	47	47
IRS2	-0.013	0.072	0.16	1	-0.21	56	57
IGF-1R heterotetramer/IGF1	0.001	0.1	-10000	0	-0.27	70	70
GRB2	0.026	0.005	-10000	0	-10000	0	0
PDPK1	-0.005	0.082	0.18	58	-0.37	2	60
YWHAE	0.025	0.007	-10000	0	-10000	0	0
PRKD1	-0.022	0.1	-10000	0	-0.33	50	50
SHC1	0.026	0.005	-10000	0	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.019	0.12	-10000	0	-0.37	68	68
CDC42/GTP	-0.021	0.11	-10000	0	-0.31	38	38
PLCG1	-0.027	0.093	-10000	0	-0.32	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.025	0.007	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
G12/G13	0.036	0.012	-10000	0	-10000	0	0
cell migration	-0.021	0.1	-10000	0	-0.3	38	38
S1PR5	-0.035	0.13	-10000	0	-0.32	104	104
S1PR4	0.019	0.05	-10000	0	-0.33	12	12
MAPK3	-0.027	0.098	-10000	0	-0.32	34	34
MAPK1	-0.027	0.097	-10000	0	-0.32	32	32
S1P/S1P5/Gi	-0.041	0.12	-10000	0	-0.32	57	57
GNAI1	0.019	0.052	-10000	0	-0.37	10	10
CDC42/GDP	0.019	0.004	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.002	0.08	-10000	0	-0.18	95	95
RHOA	0.019	0.05	0.18	41	-0.19	1	42
S1P/S1P4/Gi	-0.024	0.11	-10000	0	-0.34	35	35
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	-0.012	0.12	-10000	0	-0.37	56	56
S1P/S1P4/G12/G13	0.041	0.035	-10000	0	-0.17	12	12
GNA12	0.025	0.007	-10000	0	-10000	0	0
GNA13	0.026	0.005	-10000	0	-10000	0	0
CDC42	0.026	0.006	-10000	0	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.013	0.036	-10000	0	-0.21	3	3
NFATC2	-0.019	0.052	-10000	0	-0.25	20	20
NFATC3	-0.013	0.034	-10000	0	-10000	0	0
CD40LG	-0.091	0.2	0.35	1	-0.5	64	65
PTGS2	-0.093	0.2	0.35	1	-0.49	70	71
JUNB	0.026	0.005	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.027	-10000	0	-10000	0	0
CaM/Ca2+	-0.004	0.027	-10000	0	-10000	0	0
CALM1	0.009	0.026	-10000	0	-10000	0	0
JUN	0.01	0.026	-10000	0	-10000	0	0
mol:Ca2+	-0.008	0.011	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.009	0.014	-10000	0	-10000	0	0
FOSL1	-0.001	0.094	-10000	0	-0.32	46	46
CREM	0.026	0.005	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.034	0.13	-10000	0	-0.33	22	22
FOS	-0.007	0.085	-10000	0	-0.38	27	27
IFNG	-0.11	0.21	0.35	1	-0.49	99	100
AP-1/NFAT1-c-4	-0.086	0.21	-10000	0	-0.54	56	56
FASLG	-0.088	0.2	0.35	1	-0.51	58	59
NFAT1-c-4/ICER1	-0.031	0.078	-10000	0	-0.3	10	10
IL2RA	-0.094	0.2	0.35	1	-0.51	71	72
FKBP12/FK506	0.018	0.006	-10000	0	-10000	0	0
CSF2	-0.12	0.21	0.35	1	-0.49	95	96
JunB/Fra1/NFAT1-c-4	-0.024	0.11	-10000	0	-0.31	21	21
IL4	-0.088	0.18	0.34	1	-0.48	53	54
IL2	-0.013	0.16	-10000	0	-0.83	20	20
IL3	-0.028	0.16	-10000	0	-0.61	36	36
FKBP1A	0.024	0.008	-10000	0	-10000	0	0
BATF3	0.024	0.025	-10000	0	-0.32	3	3
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.027	0.006	-10000	0	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.048	0.054	-10000	0	-0.19	23	23
ER alpha/Gai/GDP/Gbeta gamma	-0.055	0.18	-10000	0	-0.47	67	67
AKT1	-0.02	0.2	-10000	0	-0.76	37	37
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.017	0.2	-10000	0	-0.77	37	37
mol:Ca2+	-0.002	0.088	0.18	33	-0.34	24	57
IGF1R	0.024	0.024	-10000	0	-0.37	2	2
E2/ER alpha (dimer)/Striatin	0.025	0.051	-10000	0	-0.21	25	25
SHC1	0.026	0.005	-10000	0	-10000	0	0
apoptosis	0.018	0.19	0.72	37	-10000	0	37
RhoA/GTP	0.014	0.036	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.012	0.16	0.2	4	-0.42	50	54
regulation of stress fiber formation	-0.005	0.065	-10000	0	-0.21	14	14
E2/ERA-ERB (dimer)	0.024	0.051	-10000	0	-0.21	26	26
KRAS	0.024	0.009	-10000	0	-10000	0	0
G13/GTP	0.024	0.044	-10000	0	-0.19	23	23
pseudopodium formation	0.005	0.065	0.21	14	-10000	0	14
E2/ER alpha (dimer)/PELP1	0.023	0.05	-10000	0	-0.21	25	25
GRB2	0.026	0.005	-10000	0	-10000	0	0
GNG2	0.025	0.022	-10000	0	-0.35	2	2
GNAO1	-0.019	0.12	-10000	0	-0.37	68	68
HRAS	0.026	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.032	0.17	0.22	1	-0.57	39	40
E2/ER beta (dimer)	0.019	0.014	-10000	0	-0.22	2	2
mol:GDP	0.005	0.063	-10000	0	-0.32	18	18
mol:NADP	-0.032	0.17	0.22	1	-0.57	39	40
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
mol:IP3	-0.013	0.079	0.17	3	-0.35	24	27
IGF-1R heterotetramer	0.024	0.024	-10000	0	-0.37	2	2
PLCB1	-0.006	0.079	0.17	3	-0.36	22	25
PLCB2	-0.007	0.082	-10000	0	-0.37	24	24
IGF1	-0.021	0.13	-10000	0	-0.36	74	74
mol:L-citrulline	-0.032	0.17	0.22	1	-0.57	39	40
RHOA	0.025	0.007	-10000	0	-10000	0	0
Gai/GDP	-0.098	0.27	-10000	0	-0.63	111	111
JNK cascade	0.019	0.014	-10000	0	-0.22	2	2
BCAR1	0.026	0.005	-10000	0	-10000	0	0
ESR2	0.025	0.021	-10000	0	-0.32	2	2
GNAQ	0.026	0.006	-10000	0	-10000	0	0
ESR1	0.01	0.079	-10000	0	-0.37	25	25
Gq family/GDP/Gbeta gamma	-0.023	0.17	-10000	0	-0.67	31	31
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.02	0.098	-10000	0	-0.74	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.011	0.16	0.2	7	-0.42	50	57
GNAZ	-0.012	0.12	-10000	0	-0.37	56	56
E2/ER alpha (dimer)	0.008	0.055	-10000	0	-0.25	25	25
STRN	0.027	0.003	-10000	0	-10000	0	0
GNAL	0.004	0.089	-10000	0	-0.37	31	31
PELP1	0.025	0.007	-10000	0	-10000	0	0
MAPK11	0.012	0.012	-10000	0	-0.18	2	2
GNAI2	0.025	0.007	-10000	0	-10000	0	0
GNAI3	0.026	0.005	-10000	0	-10000	0	0
GNAI1	0.019	0.052	-10000	0	-0.37	10	10
HBEGF	-0.037	0.2	0.32	57	-0.48	51	108
cAMP biosynthetic process	0.01	0.063	-10000	0	-0.19	48	48
SRC	-0.036	0.18	0.21	46	-0.47	55	101
PI3K	0.032	0.016	-10000	0	-10000	0	0
GNB1	0.026	0.006	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.03	0.068	-10000	0	-0.28	19	19
SOS1	0.027	0.003	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.048	0.13	-10000	0	-0.38	55	55
Gs family/GTP	0.016	0.066	-10000	0	-0.2	48	48
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.042	0.021	-10000	0	-10000	0	0
vasodilation	-0.03	0.16	0.22	1	-0.54	39	40
mol:DAG	-0.013	0.079	0.17	3	-0.35	24	27
Gs family/GDP/Gbeta gamma	0.002	0.074	-10000	0	-0.31	20	20
MSN	0.005	0.068	0.21	14	-10000	0	14
Gq family/GTP	0	0.086	-10000	0	-0.38	24	24
mol:PI-3-4-5-P3	-0.015	0.19	-10000	0	-0.74	37	37
NRAS	0.026	0.006	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.03	0.16	0.54	39	-0.22	1	40
GRB2/SOS1	0.039	0.008	-10000	0	-10000	0	0
RhoA/GDP	0.016	0.066	-10000	0	-0.3	18	18
NOS3	-0.035	0.18	0.22	1	-0.61	39	40
GNA11	0.026	0.006	-10000	0	-10000	0	0
MAPKKK cascade	-0.004	0.16	0.3	3	-0.56	36	39
E2/ER alpha (dimer)/PELP1/Src	-0.012	0.17	0.22	50	-0.43	51	101
ruffle organization	0.005	0.065	0.21	14	-10000	0	14
ROCK2	0.009	0.073	0.22	16	-10000	0	16
GNA14	0.011	0.076	-10000	0	-0.37	22	22
GNA15	-0.007	0.1	-10000	0	-0.32	56	56
GNA13	0.026	0.005	-10000	0	-10000	0	0
MMP9	-0.054	0.2	0.34	56	-0.49	48	104
MMP2	-0.029	0.18	0.26	23	-0.48	47	70

×

Regulation of Androgen receptor activity

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
HDAC1	0.011	0.007	-10000	0	-10000	0	0
SMARCC1	0.01	0.014	-10000	0	-10000	0	0
REL	0.027	0.004	-10000	0	-10000	0	0
HDAC7	-0.044	0.1	0.23	1	-0.38	13	14
JUN	0.027	0.004	-10000	0	-10000	0	0
EP300	0.026	0.005	-10000	0	-10000	0	0
KAT2B	0.021	0.043	-10000	0	-0.37	7	7
KAT5	0.026	0.005	-10000	0	-10000	0	0
MAPK14	-0.002	0.037	-10000	0	-0.28	7	7
FOXO1	0.025	0.007	-10000	0	-10000	0	0
T-DHT/AR	-0.028	0.12	0.25	1	-0.37	17	18
MAP2K6	0.011	0.048	-10000	0	-0.38	7	7
BRM/BAF57	0.032	0.02	-10000	0	-0.26	1	1
MAP2K4	0.014	0.022	-10000	0	-10000	0	0
SMARCA2	0.023	0.019	-10000	0	-0.37	1	1
PDE9A	-0.14	0.34	-10000	0	-0.94	83	83
NCOA2	0.024	0.018	-10000	0	-0.37	1	1
CEBPA	0.021	0.038	-10000	0	-0.35	6	6
EHMT2	0.026	0.006	-10000	0	-10000	0	0
cell proliferation	-0.019	0.14	0.28	21	-0.38	24	45
NR0B1	0.006	0.07	-10000	0	-0.32	25	25
EGR1	0.019	0.052	-10000	0	-0.37	10	10
RXRs/9cRA	-0.023	0.11	-10000	0	-0.2	164	164
AR/RACK1/Src	-0.004	0.092	0.2	28	-0.32	7	35
AR/GR	-0.044	0.11	0.2	1	-0.28	58	59
GNB2L1	0.026	0.006	-10000	0	-10000	0	0
PKN1	0.026	0.005	-10000	0	-10000	0	0
RCHY1	0.026	0.005	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-10000	0	-0.016	1	1
MAPK8	0.001	0.021	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.008	0.078	0.22	2	-0.3	7	9
SRC	-0.017	0.049	0.19	16	-0.26	6	22
NR3C1	0.022	0.037	-10000	0	-0.37	5	5
KLK3	-0.096	0.11	-10000	0	-0.47	3	3
APPBP2	0.016	0.022	-10000	0	-10000	0	0
TRIM24	0.026	0.006	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.021	0.074	0.21	2	-0.33	7	9
TMPRSS2	-0.16	0.36	-10000	0	-0.89	103	103
RXRG	-0.091	0.18	-10000	0	-0.37	170	170
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	0.026	0.017	-10000	0	-0.38	1	1
RXRB	0.026	0.005	-10000	0	-10000	0	0
CARM1	0.026	0.006	-10000	0	-10000	0	0
NR2C2	0.026	0.006	-10000	0	-10000	0	0
KLK2	-0.011	0.088	0.28	3	-0.32	12	15
AR	-0.048	0.11	0.16	1	-0.25	119	120
SENP1	0.026	0.004	-10000	0	-10000	0	0
HSP90AA1	0.026	0.006	-10000	0	-10000	0	0
MDM2	0.026	0.007	-10000	0	-10000	0	0
SRY	0	0.003	0.014	16	-10000	0	16
GATA2	0.022	0.037	-10000	0	-0.37	5	5
MYST2	0	0	-10000	0	-10000	0	0
HOXB13	-0.22	0.16	-10000	0	-0.32	417	417
T-DHT/AR/RACK1/Src	0	0.095	0.21	36	-0.32	7	43
positive regulation of transcription	0.022	0.037	-10000	0	-0.37	5	5
DNAJA1	0.015	0.022	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.006	-10000	0	-10000	0	0
NCOA1	0.033	0.017	-10000	0	-10000	0	0
SPDEF	-0.084	0.18	-10000	0	-0.37	161	161
T-DHT/AR/TIF2	-0.012	0.074	0.21	1	-0.34	9	10
T-DHT/AR/Hsp90	-0.02	0.073	0.21	2	-0.33	7	9
GSK3B	0.025	0.008	-10000	0	-10000	0	0
NR2C1	0.027	0.004	-10000	0	-10000	0	0
mol:T-DHT	-0.023	0.038	-10000	0	-0.27	6	6
SIRT1	0.026	0.004	-10000	0	-10000	0	0
ZMIZ2	0.026	0.007	-10000	0	-10000	0	0
POU2F1	0.004	0.059	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.031	0.08	0.23	1	-0.32	8	9
CREBBP	0.026	0.006	-10000	0	-10000	0	0
SMARCE1	0.025	0.008	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.06	-10000	0	-0.32	18	18
Jak2/Leptin Receptor	-0.037	0.14	-10000	0	-0.37	60	60
PTP1B/AKT1	-0.004	0.078	0.18	1	-0.29	18	19
FYN	0.026	0.005	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.012	0.079	0.2	2	-0.3	20	22
EGFR	0.015	0.053	-10000	0	-0.36	11	11
EGF/EGFR	-0.022	0.089	0.2	1	-0.28	23	24
CSF1	0.026	0.015	-10000	0	-0.32	1	1
AKT1	0.026	0.006	-10000	0	-10000	0	0
INSR	0.026	0.007	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.019	0.087	-10000	0	-0.29	25	25
Insulin Receptor/Insulin	0.015	0.077	-10000	0	-0.27	16	16
HCK	0.023	0.022	-10000	0	-0.32	2	2
CRK	0.025	0.007	-10000	0	-10000	0	0
TYK2	-0.013	0.076	0.21	3	-0.29	18	21
EGF	-0.033	0.13	-10000	0	-0.32	94	94
YES1	0.025	0.007	-10000	0	-10000	0	0
CAV1	-0.002	0.089	0.21	19	-0.29	19	38
TXN	0.025	0.015	-10000	0	-0.33	1	1
PTP1B/IRS1/GRB2	0.002	0.084	0.2	1	-0.28	18	19
cell migration	0.012	0.079	0.3	20	-0.2	2	22
STAT3	0.026	0.005	-10000	0	-10000	0	0
PRLR	-0.017	0.12	-10000	0	-0.37	61	61
ITGA2B	0.004	0.081	-10000	0	-0.32	34	34
CSF1R	0.019	0.052	-10000	0	-0.37	10	10
Prolactin Receptor/Prolactin	-0.004	0.096	-10000	0	-0.26	69	69
FGR	0.025	0.022	-10000	0	-0.35	2	2
PTP1B/p130 Cas	-0.005	0.079	0.19	2	-0.29	17	19
Crk/p130 Cas	0.003	0.083	0.2	1	-0.29	14	15
DOK1	-0.013	0.083	0.18	1	-0.33	18	19
JAK2	-0.048	0.15	-10000	0	-0.38	64	64
Jak2/Leptin Receptor/Leptin	-0.001	0.11	0.23	1	-0.38	15	16
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
PTPN1	-0.012	0.08	0.2	2	-0.3	20	22
LYN	0.024	0.022	-10000	0	-0.32	2	2
CDH2	-0.01	0.11	-10000	0	-0.36	53	53
SRC	0.013	0.075	-10000	0	-0.45	11	11
ITGB3	0.023	0.039	-10000	0	-0.36	6	6
CAT1/PTP1B	-0.059	0.15	0.23	24	-0.38	53	77
CAPN1	0.026	0.005	-10000	0	-10000	0	0
CSK	0.026	0.005	-10000	0	-10000	0	0
PI3K	0.028	0.065	-10000	0	-0.29	5	5
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	0.002	0.097	0.21	1	-0.35	13	14
negative regulation of transcription	-0.048	0.14	-10000	0	-0.37	64	64
FCGR2A	0.021	0.041	-10000	0	-0.33	8	8
FER	0.023	0.025	-10000	0	-0.38	2	2
alphaIIb/beta3 Integrin	0.02	0.067	-10000	0	-0.23	40	40
BLK	-0.063	0.16	-10000	0	-0.37	130	130
Insulin Receptor/Insulin/Shc	0.045	0.016	-10000	0	-10000	0	0
RHOA	0.025	0.007	-10000	0	-10000	0	0
LEPR	0.024	0.033	-10000	0	-0.37	4	4
BCAR1	0.026	0.005	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.026	0.005	-10000	0	-10000	0	0
mol:NADPH	0	0.003	-10000	0	-10000	0	0
TRPV6	-0.078	0.17	0.23	7	-0.4	74	81
PRL	0.001	0.053	-10000	0	-0.32	13	13
SOCS3	0.019	0.11	-10000	0	-1	6	6
SPRY2	0.026	0.018	-10000	0	-0.38	1	1
Insulin Receptor/Insulin/IRS1	0.044	0.022	-10000	0	-0.23	2	2
CSF1/CSF1R	0	0.084	0.2	1	-0.29	15	16
Ras protein signal transduction	0.011	0.09	0.55	15	-10000	0	15
IRS1	0.025	0.023	-10000	0	-0.37	2	2
INS	0.012	0.015	-10000	0	-10000	0	0
LEP	0.005	0.082	-10000	0	-0.35	30	30
STAT5B	-0.02	0.095	0.17	1	-0.33	27	28
STAT5A	-0.02	0.095	0.17	1	-0.33	27	28
GRB2	0.026	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.008	0.083	0.19	2	-0.28	19	21
CSN2	-0.003	0.068	-10000	0	-0.52	1	1
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
LAT	0.011	0.069	-10000	0	-0.41	11	11
YBX1	0.033	0.006	-10000	0	-10000	0	0
LCK	-0.004	0.099	-10000	0	-0.32	52	52
SHC1	0.026	0.005	-10000	0	-10000	0	0
NOX4	-0.13	0.17	-10000	0	-0.32	269	269

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.062	0.1	-10000	0	-0.35	3	3
NF kappa B1 p50/RelA/I kappa B alpha	-0.048	0.1	0.32	1	-0.38	3	4
alphaV/beta3 Integrin/Osteopontin/Src	-0.09	0.13	-10000	0	-0.22	296	296
AP1	-0.055	0.11	-10000	0	-0.38	7	7
ILK	-0.07	0.1	-10000	0	-0.35	3	3
bone resorption	-0.051	0.095	-10000	0	-0.33	3	3
PTK2B	0.024	0.008	-10000	0	-10000	0	0
PYK2/p130Cas	-0.042	0.11	-10000	0	-0.33	4	4
ITGAV	0.027	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.037	0.011	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.066	0.12	-10000	0	-0.22	60	60
MAP3K1	-0.068	0.099	0.19	6	-0.3	5	11
JUN	0.027	0.004	-10000	0	-10000	0	0
MAPK3	-0.076	0.097	0.19	7	-0.31	7	14
MAPK1	-0.074	0.097	0.19	7	-0.32	5	12
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MAPK8	-0.072	0.089	0.19	6	-0.34	3	9
ITGB3	0.024	0.039	-10000	0	-0.36	6	6
NFKBIA	-0.067	0.091	0.19	1	-0.36	3	4
FOS	0.008	0.083	-10000	0	-0.37	27	27
CD44	0.025	0.007	-10000	0	-10000	0	0
CHUK	0.026	0.005	-10000	0	-10000	0	0
PLAU	-0.071	0.12	-10000	0	-0.48	3	3
NF kappa B1 p50/RelA	-0.05	0.12	-10000	0	-0.4	2	2
BCAR1	0.026	0.005	-10000	0	-10000	0	0
RELA	0.026	0.005	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.037	0.032	-10000	0	-0.25	6	6
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.071	0.1	0.19	7	-0.36	4	11
VAV3	-0.076	0.093	0.19	6	-0.33	11	17
MAP3K14	-0.073	0.1	-10000	0	-0.27	11	11
ROCK2	0.027	0.003	-10000	0	-10000	0	0
SPP1	-0.15	0.18	-10000	0	-0.32	297	297
RAC1	0.025	0.007	-10000	0	-10000	0	0
Rac1/GTP	-0.061	0.091	-10000	0	-0.31	10	10
MMP2	-0.06	0.091	0.3	1	-0.37	6	7

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.026	0.005	-10000	0	-10000	0	0
EGFR	0.017	0.052	-10000	0	-0.36	11	11
EGF/EGFR	0.008	0.079	-10000	0	-0.16	98	98
EGF/EGFR dimer/SHC/GRB2/SOS1	0.03	0.086	-10000	0	-0.2	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.021	0.041	-10000	0	-0.32	8	8
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	-0.031	0.13	-10000	0	-0.32	94	94
EGF/EGFR dimer/SHC	0.01	0.087	-10000	0	-0.2	86	86
mol:GDP	0.026	0.083	-10000	0	-0.2	11	11
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.022	0.033	-10000	0	-0.33	5	5
GRB2/SOS1	0.039	0.008	-10000	0	-10000	0	0
HRAS/GTP	0.012	0.072	-10000	0	-0.28	1	1
SHC1	0.026	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.024	0.08	-10000	0	-0.29	1	1
FRAP1	-0.029	0.058	0.14	12	-0.19	11	23
EGF/EGFR dimer	-0.007	0.096	-10000	0	-0.23	91	91
SOS1	0.027	0.003	-10000	0	-10000	0	0
GRB2	0.026	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	0.03	0.04	-10000	0	-0.23	13	13

×

Syndecan-4-mediated signaling events

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
PTK2	0	0.096	0.22	1	-0.42	15	16
Syndecan-4/Syndesmos	-0.002	0.11	0.29	5	-0.41	2	7
positive regulation of JNK cascade	-0.012	0.12	0.29	5	-0.4	4	9
Syndecan-4/ADAM12	-0.077	0.14	0.29	4	-0.43	7	11
CCL5	0.009	0.076	-10000	0	-0.33	29	29
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
DNM2	0.026	0.005	-10000	0	-10000	0	0
ITGA5	0.024	0.029	-10000	0	-0.32	4	4
SDCBP	0.025	0.008	-10000	0	-10000	0	0
PLG	0.005	0.049	-10000	0	-0.34	9	9
ADAM12	-0.17	0.17	-10000	0	-0.32	340	340
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.026	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.043	0.033	-10000	0	-0.13	1	1
Syndecan-4/Laminin alpha1	-0.034	0.13	0.3	5	-0.39	5	10
Syndecan-4/CXCL12/CXCR4	-0.011	0.13	0.31	5	-0.45	3	8
Syndecan-4/Laminin alpha3	-0.006	0.11	0.3	4	-0.48	3	7
MDK	0	0.092	-10000	0	-0.32	45	45
Syndecan-4/FZD7	-0.001	0.11	0.3	5	-0.4	3	8
Syndecan-4/Midkine	-0.01	0.11	0.29	4	-0.4	3	7
FZD7	0.023	0.039	-10000	0	-0.33	7	7
Syndecan-4/FGFR1/FGF	-0.007	0.11	0.29	2	-0.41	3	5
THBS1	0.023	0.033	-10000	0	-0.33	5	5
integrin-mediated signaling pathway	-0.01	0.12	0.29	5	-0.43	3	8
positive regulation of MAPKKK cascade	-0.012	0.12	0.29	5	-0.4	4	9
Syndecan-4/TACI	-0.037	0.12	0.3	2	-0.4	4	6
CXCR4	0.015	0.062	-10000	0	-0.32	19	19
cell adhesion	0.007	0.044	0.19	10	-0.23	4	14
Syndecan-4/Dynamin	0.002	0.11	0.3	6	-0.41	2	8
Syndecan-4/TSP1	0	0.11	0.3	5	-0.41	2	7
Syndecan-4/GIPC	0.001	0.11	0.3	5	-0.41	2	7
Syndecan-4/RANTES	-0.006	0.12	0.3	6	-0.41	2	8
ITGB1	0.026	0.005	-10000	0	-10000	0	0
LAMA1	-0.057	0.15	-10000	0	-0.33	140	140
LAMA3	0.009	0.073	-10000	0	-0.33	26	26
RAC1	0.025	0.007	-10000	0	-10000	0	0
PRKCA	0.017	0.11	0.74	12	-0.35	1	13
Syndecan-4/alpha-Actinin	0	0.11	0.3	3	-0.41	2	5
TFPI	0.025	0.021	-10000	0	-0.32	2	2
F2	-0.016	0.11	-10000	0	-0.32	65	65
alpha5/beta1 Integrin	0.036	0.023	-10000	0	-0.22	4	4
positive regulation of cell adhesion	-0.04	0.13	0.29	4	-0.4	13	17
ACTN1	0.025	0.021	-10000	0	-0.32	2	2
TNC	-0.004	0.099	-10000	0	-0.32	52	52
Syndecan-4/CXCL12	-0.014	0.12	0.3	5	-0.44	4	9
FGF6	0.015	0.032	-10000	0	-0.32	5	5
RHOA	0.025	0.007	-10000	0	-10000	0	0
CXCL12	-0.008	0.11	-10000	0	-0.37	52	52
TNFRSF13B	-0.061	0.16	-10000	0	-0.37	128	128
FGF2	0.006	0.087	-10000	0	-0.37	30	30
FGFR1	0.021	0.038	-10000	0	-0.35	6	6
Syndecan-4/PI-4-5-P2	-0.031	0.073	-10000	0	-0.4	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.008	0.095	-10000	0	-0.33	45	45
cell migration	-0.021	0.015	-10000	0	-10000	0	0
PRKCD	0.017	0.024	-10000	0	-10000	0	0
vasculogenesis	0	0.11	0.3	5	-0.39	2	7
SDC4	-0.028	0.075	-10000	0	-0.42	2	2
Syndecan-4/Tenascin C	-0.01	0.12	0.3	4	-0.45	3	7
Syndecan-4/PI-4-5-P2/PKC alpha	-0.035	0.027	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0	0.1	0.3	5	-0.4	2	7
MMP9	-0.082	0.16	-10000	0	-0.32	178	178
Rac1/GTP	0.007	0.044	0.2	10	-0.23	4	14
cytoskeleton organization	-0.002	0.1	0.29	5	-0.39	2	7
GIPC1	0.026	0.005	-10000	0	-10000	0	0
Syndecan-4/TFPI	0.001	0.11	0.3	4	-0.41	2	6

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.016	0.09	0.21	27	-0.31	14	41
PDGFB-D/PDGFRB/SLAP	0.022	0.055	-10000	0	-0.23	24	24
PDGFB-D/PDGFRB/APS/CBL	0.038	0.047	-10000	0	-0.18	20	20
AKT1	0.038	0.1	0.29	34	-10000	0	34
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.031	0.11	0.24	49	-0.34	16	65
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
FGR	0.01	0.091	0.34	2	-0.4	14	16
mol:Ca2+	0.028	0.11	0.24	47	-0.37	16	63
MYC	0.071	0.14	0.38	49	-0.75	2	51
SHC1	0.026	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.041	0.061	0.18	2	-10000	0	2
LRP1/PDGFRB/PDGFB	0.043	0.045	-10000	0	-0.18	19	19
GRB10	0.025	0.016	-10000	0	-0.32	1	1
PTPN11	0.026	0.004	-10000	0	-10000	0	0
GO:0007205	0.027	0.11	0.24	44	-0.38	16	60
PTEN	0.025	0.007	-10000	0	-10000	0	0
GRB2	0.026	0.005	-10000	0	-10000	0	0
GRB7	0.021	0.029	-10000	0	-0.36	3	3
PDGFB-D/PDGFRB/SHP2	0.03	0.045	-10000	0	-0.22	18	18
PDGFB-D/PDGFRB/GRB10	0.028	0.047	-10000	0	-0.22	19	19
cell cycle arrest	0.022	0.055	-10000	0	-0.23	24	24
HRAS	0.026	0.005	-10000	0	-10000	0	0
HIF1A	0.032	0.094	0.26	38	-10000	0	38
GAB1	0.023	0.11	0.23	38	-0.34	16	54
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.026	0.1	0.24	50	-0.32	9	59
PDGFB-D/PDGFRB	0.035	0.045	-10000	0	-0.18	17	17
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.031	0.045	-10000	0	-0.22	18	18
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.009	0.069	0.21	2	-0.29	3	5
positive regulation of MAPKKK cascade	0.03	0.045	-10000	0	-0.22	18	18
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
mol:IP3	0.028	0.11	0.24	44	-0.38	16	60
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.025	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.025	0.049	-10000	0	-0.22	20	20
SHB	0.025	0.007	-10000	0	-10000	0	0
BLK	-0.093	0.22	0.35	1	-0.49	128	129
PTPN2	0.026	0.008	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.03	0.045	-10000	0	-0.22	18	18
BCAR1	0.026	0.005	-10000	0	-10000	0	0
VAV2	0.029	0.11	0.26	44	-0.35	15	59
CBL	0.025	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.03	0.048	-10000	0	-0.22	20	20
LCK	0.008	0.091	0.34	2	-0.45	10	12
PDGFRB	0.016	0.06	-10000	0	-0.32	18	18
ACP1	0.027	0.003	-10000	0	-10000	0	0
HCK	0.019	0.054	0.36	2	-10000	0	2
ABL1	0.023	0.1	0.23	51	-0.34	10	61
PDGFB-D/PDGFRB/CBL	0.018	0.12	0.27	10	-0.41	18	28
PTPN1	0.023	0.011	-10000	0	-10000	0	0
SNX15	0.026	0.005	-10000	0	-10000	0	0
STAT3	0.026	0.005	-10000	0	-10000	0	0
STAT1	0.021	0.043	-10000	0	-0.32	9	9
cell proliferation	0.07	0.14	0.35	59	-0.66	2	61
SLA	0.019	0.04	-10000	0	-0.34	7	7
actin cytoskeleton reorganization	0.054	0.088	0.33	21	-10000	0	21
SRC	0.013	0.052	0.34	1	-0.36	1	2
PI3K	-0.015	0.025	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.036	0.047	-10000	0	-0.19	20	20
SH2B2	0.023	0.026	-10000	0	-0.32	3	3
PLCgamma1/SPHK1	0.032	0.11	0.25	46	-0.35	16	62
LYN	0.016	0.076	0.35	2	-0.44	6	8
LRP1	0.026	0.005	-10000	0	-10000	0	0
SOS1	0.027	0.003	-10000	0	-10000	0	0
STAT5B	0.026	0.005	-10000	0	-10000	0	0
STAT5A	0.026	0.004	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.05	0.053	-10000	0	-10000	0	0
SPHK1	0.003	0.089	-10000	0	-0.32	42	42
EDG1	0.001	0.003	-10000	0	-10000	0	0
mol:DAG	0.028	0.11	0.24	44	-0.38	16	60
PLCG1	0.028	0.11	0.25	41	-0.39	16	57
NHERF/PDGFRB	0.043	0.044	-10000	0	-0.18	18	18
YES1	0.011	0.098	0.36	2	-0.52	12	14
cell migration	0.042	0.043	-10000	0	-0.18	18	18
SHC/Grb2/SOS1	0.052	0.052	-10000	0	-10000	0	0
SLC9A3R2	0.026	0.006	-10000	0	-10000	0	0
SLC9A3R1	0.026	0.004	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.053	0.046	-10000	0	-0.17	17	17
FYN	0.009	0.092	0.35	2	-0.4	15	17
DOK1	0.03	0.073	0.18	97	-0.2	1	98
HRAS/GTP	0.019	0.004	-10000	0	-10000	0	0
PDGFB	0.026	0.015	-10000	0	-0.32	1	1
RAC1	0.04	0.12	0.32	36	-0.38	8	44
PRKCD	0.03	0.073	0.18	95	-10000	0	95
FER	0.026	0.07	0.18	83	-0.2	1	84
MAPKKK cascade	0.019	0.084	0.29	15	-10000	0	15
RASA1	0.028	0.071	0.18	88	-10000	0	88
NCK1	0.025	0.007	-10000	0	-10000	0	0
NCK2	0.026	0.005	-10000	0	-10000	0	0
p62DOK/Csk	0.044	0.065	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.029	0.046	-10000	0	-0.22	18	18
chemotaxis	0.023	0.1	0.23	52	-0.34	10	62
STAT1-3-5/STAT1-3-5	0.04	0.051	-10000	0	-0.29	1	1
Bovine Papilomavirus E5/PDGFRB	0.012	0.041	-10000	0	-0.22	18	18
PTPRJ	0.025	0.022	-10000	0	-0.35	2	2

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.011	0.044	-10000	0	-0.26	6	6
STMN1	0.003	0.048	-10000	0	-0.22	25	25
Aurora B/RasGAP/Survivin	0.036	0.069	-10000	0	-0.21	34	34
Chromosomal passenger complex/Cul3 protein complex	-0.011	0.077	-10000	0	-0.28	23	23
BIRC5	0.012	0.073	-10000	0	-0.33	26	26
DES	-0.3	0.32	-10000	0	-0.58	319	319
Aurora C/Aurora B/INCENP	0.038	0.058	-10000	0	-0.18	35	35
Aurora B/TACC1	0.028	0.039	-10000	0	-0.18	19	19
Aurora B/PP2A	0.03	0.048	-10000	0	-0.22	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.007	0.012	-10000	0	-0.14	1	1
mitotic metaphase/anaphase transition	0.001	0.004	-10000	0	-10000	0	0
NDC80	-0.002	0.072	0.22	8	-0.24	41	49
Cul3 protein complex	0.025	0.074	-10000	0	-0.22	48	48
KIF2C	0.007	0.054	-10000	0	-0.41	5	5
PEBP1	0.027	0.005	-10000	0	-10000	0	0
KIF20A	0.005	0.083	-10000	0	-0.32	36	36
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.029	0.05	-10000	0	-0.21	22	22
SEPT1	0.022	0.039	-10000	0	-0.33	7	7
SMC2	0.025	0.021	-10000	0	-0.32	2	2
SMC4	0.023	0.017	-10000	0	-0.32	1	1
NSUN2/NPM1/Nucleolin	-0.019	0.15	-10000	0	-0.57	37	37
PSMA3	0.026	0.005	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.002	-10000	0	-10000	0	0
H3F3B	0.011	0.025	-10000	0	-0.12	12	12
AURKB	0.018	0.067	-10000	0	-0.32	22	22
AURKC	0.016	0.058	-10000	0	-0.34	15	15
CDCA8	0.027	0.016	-10000	0	-0.33	1	1
cytokinesis	-0.021	0.09	0.17	1	-0.43	16	17
Aurora B/Septin1	0.002	0.11	0.22	3	-0.36	23	26
AURKA	0.014	0.055	-10000	0	-0.32	15	15
INCENP	0.027	0.007	-10000	0	-10000	0	0
KLHL13	-0.007	0.11	-10000	0	-0.37	51	51
BUB1	-0.005	0.1	-10000	0	-0.32	55	55
hSgo1/Aurora B/Survivin	0.029	0.08	-10000	0	-0.21	53	53
EVI5	0.027	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.019	0.096	-10000	0	-0.3	18	18
SGOL1	0.012	0.069	-10000	0	-0.32	24	24
CENPA	0.013	0.064	0.16	1	-0.24	20	21
NCAPG	0.023	0.032	-10000	0	-0.32	5	5
Aurora B/HC8 Proteasome	0.032	0.05	-10000	0	-0.22	22	22
NCAPD2	0.025	0.007	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.032	0.05	-10000	0	-0.22	22	22
RHOA	0.025	0.007	-10000	0	-10000	0	0
NCAPH	0.022	0.04	-10000	0	-0.32	8	8
NPM1	-0.023	0.13	-10000	0	-0.4	46	46
RASA1	0.025	0.008	-10000	0	-10000	0	0
KLHL9	0.023	0.01	-10000	0	-10000	0	0
mitotic prometaphase	0	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.031	0.05	-10000	0	-0.22	22	22
PPP1CC	0.026	0.004	-10000	0	-10000	0	0
Centraspindlin	0.012	0.1	-10000	0	-0.31	22	22
RhoA/GDP	0.019	0.005	-10000	0	-10000	0	0
NSUN2	-0.007	0.091	-10000	0	-0.32	36	36
MYLK	0.001	0.047	-10000	0	-0.16	36	36
KIF23	-0.019	0.12	-10000	0	-0.32	80	80
VIM	0.006	0.042	-10000	0	-0.22	20	20
RACGAP1	0.027	0.005	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
NCL	-0.011	0.091	-10000	0	-0.31	39	39
Chromosomal passenger complex	0.003	0.07	-10000	0	-0.26	23	23
Chromosomal passenger complex/EVI5	0.078	0.083	-10000	0	-0.29	8	8
TACC1	0.025	0.008	-10000	0	-10000	0	0
PPP2R5D	0.025	0.007	-10000	0	-10000	0	0
CUL3	0.027	0.004	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

ErbB4 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.023	0.06	-10000	0	-10000	0	0
epithelial cell differentiation	0.015	0.08	-10000	0	-10000	0	0
ITCH	0.029	0.016	-10000	0	-10000	0	0
WWP1	0.014	0.064	-10000	0	-10000	0	0
FYN	0.026	0.005	-10000	0	-10000	0	0
EGFR	0.017	0.052	-10000	0	-0.36	11	11
PRL	0.014	0.051	-10000	0	-0.32	13	13
neuron projection morphogenesis	-0.004	0.094	0.29	19	-10000	0	19
PTPRZ1	-0.1	0.18	-10000	0	-0.37	193	193
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.013	0.093	-10000	0	-0.33	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.015	0.079	-10000	0	-0.34	1	1
ADAM17	0.029	0.022	-10000	0	-0.32	1	1
ErbB4/ErbB4	0.009	0.056	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.004	0.099	-10000	0	-0.32	20	20
NCOR1	0.025	0.008	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.006	0.084	-10000	0	-0.3	1	1
GRIN2B	-0.02	0.091	0.24	9	-0.31	4	13
ErbB4/ErbB2/betacellulin	0.019	0.072	-10000	0	-0.35	1	1
STAT1	0.021	0.043	-10000	0	-0.32	9	9
HBEGF	0.023	0.029	-10000	0	-0.37	3	3
PRLR	-0.017	0.12	-10000	0	-0.37	61	61
E4ICDs/ETO2	0.016	0.069	-10000	0	-0.32	2	2
axon guidance	0.035	0.08	0.36	4	-10000	0	4
NEDD4	0.03	0.017	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.003	0.095	-10000	0	-0.26	69	69
CBFA2T3	0.01	0.076	-10000	0	-0.37	23	23
ErbB4/ErbB2/HBEGF	0.029	0.055	-10000	0	-10000	0	0
MAPK3	0.001	0.095	0.3	16	-0.32	1	17
STAT1 (dimer)	0.021	0.065	-10000	0	-10000	0	0
MAPK1	0.002	0.096	0.3	16	-0.32	1	17
JAK2	0.023	0.009	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.009	0.083	-10000	0	-0.34	2	2
NRG1	-0.03	0.099	0.23	1	-0.26	93	94
NRG3	-0.034	0.14	-10000	0	-0.37	88	88
NRG2	-0.082	0.18	-10000	0	-0.37	160	160
NRG4	-0.097	0.18	-10000	0	-0.37	183	183
heart development	0.035	0.08	0.36	4	-10000	0	4
neural crest cell migration	-0.008	0.082	-10000	0	-0.33	2	2
ERBB2	0.015	0.036	0.24	9	-0.25	3	12
WWOX/E4ICDs	0.017	0.047	-10000	0	-10000	0	0
SHC1	0.026	0.005	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.034	0.11	-10000	0	-0.35	5	5
apoptosis	0.031	0.14	0.4	54	-10000	0	54
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.028	0.11	-10000	0	-0.32	24	24
ErbB4/ErbB2/epiregulin	-0.011	0.098	-10000	0	-0.32	2	2
ErbB4/ErbB4/betacellulin/betacellulin	0.012	0.079	-10000	0	-0.32	7	7
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.018	0.094	-10000	0	-0.35	2	2
MDM2	0.011	0.062	0.27	10	-10000	0	10
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.01	0.076	-10000	0	-0.28	1	1
STAT5A	0.036	0.082	0.33	7	-10000	0	7
ErbB4/EGFR/neuregulin 1 beta	-0.01	0.088	-10000	0	-0.32	7	7
DLG4	0.025	0.018	-10000	0	-0.37	1	1
GRB2/SHC	0.038	0.01	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.02	0.054	-10000	0	-10000	0	0
STAT5A (dimer)	0.029	0.096	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.051	0.083	0.32	5	-10000	0	5
LRIG1	0.023	0.033	-10000	0	-0.37	4	4
EREG	-0.086	0.16	-10000	0	-0.32	190	190
BTC	-0.003	0.1	-10000	0	-0.37	44	44
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.027	0.072	0.36	4	-10000	0	4
ERBB4	0.001	0.046	-10000	0	-10000	0	0
STAT5B	0.026	0.005	-10000	0	-10000	0	0
YAP1	0.014	0.084	-10000	0	-0.45	15	15
GRB2	0.026	0.005	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.023	0.1	-10000	0	-0.34	2	2
glial cell differentiation	-0.02	0.053	-10000	0	-10000	0	0
WWOX	0.018	0.013	-10000	0	-10000	0	0
cell proliferation	-0.009	0.12	0.31	12	-0.51	2	14

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.016	0.064	0.35	8	-10000	0	8
VDR	0.026	0.004	-10000	0	-10000	0	0
FAM120B	0.026	0.006	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.033	0.1	-10000	0	-0.28	15	15
RXRs/LXRs/DNA/Oxysterols	-0.024	0.1	-10000	0	-0.36	4	4
MED1	0.025	0.007	-10000	0	-10000	0	0
mol:9cRA	0.001	0.008	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.008	0.06	-10000	0	-0.2	44	44
RXRs/NUR77	-0.017	0.12	-10000	0	-0.25	15	15
RXRs/PPAR	-0.049	0.12	-10000	0	-0.31	42	42
NCOR2	0.026	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.02	0.003	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.052	0.034	-10000	0	-0.17	7	7
RARA	0.025	0.008	-10000	0	-10000	0	0
NCOA1	0.027	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.026	0.004	-10000	0	-10000	0	0
RARs/RARs/DNA/9cRA	0.039	0.03	-10000	0	-0.17	7	7
RARG	0.024	0.029	-10000	0	-0.32	4	4
RPS6KB1	0.027	0.074	0.56	10	-10000	0	10
RARs/THRs/DNA/SMRT	0.008	0.061	-10000	0	-0.32	3	3
THRA	0.024	0.018	-10000	0	-0.37	1	1
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.02	0.003	-10000	0	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.021	0.11	-10000	0	-0.24	11	11
NR1H4	-0.045	0.14	-10000	0	-0.34	112	112
RXRs/LXRs/DNA	0	0.12	-10000	0	-0.25	11	11
NR1H2	0.025	0.017	-10000	0	-10000	0	0
NR1H3	0.025	0.017	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.012	0.11	-10000	0	-0.22	11	11
NR4A1	0.018	0.059	-10000	0	-0.37	13	13
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.052	0.11	-10000	0	-0.23	73	73
RXRG	-0.091	0.18	-10000	0	-0.37	170	170
RXR alpha/CCPG	0.038	0.018	-10000	0	-0.26	1	1
RXRA	0.024	0.023	-10000	0	-0.37	1	1
RXRB	0.025	0.017	-10000	0	-10000	0	0
THRB	0	0.098	-10000	0	-0.37	38	38
PPARG	0.001	0.096	-10000	0	-0.37	37	37
PPARD	0.026	0.005	-10000	0	-10000	0	0
TNF	-0.034	0.12	-10000	0	-0.9	4	4
mol:Oxysterols	0.002	0.007	-10000	0	-10000	0	0
cholesterol transport	-0.024	0.1	-10000	0	-0.36	4	4
PPARA	0.026	0.006	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.023	0.033	-10000	0	-0.37	4	4
RXRs/NUR77/BCL2	-0.05	0.11	-10000	0	-0.22	173	173
SREBF1	-0.023	0.09	-10000	0	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.02	0.11	-10000	0	-0.24	11	11
ABCA1	-0.025	0.093	-10000	0	-10000	0	0
RARs/THRs	0.047	0.073	-10000	0	-0.19	38	38
RXRs/FXR	-0.055	0.14	-10000	0	-0.22	196	196
BCL2	0.022	0.029	-10000	0	-0.37	3	3

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.05	0.17	-10000	0	-0.43	103	103
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.017	0.094	0.37	10	-10000	0	10
IL27/IL27R/JAK1	0.042	0.11	0.38	1	-0.41	1	2
TBX21	-0.002	0.12	0.36	2	-0.46	5	7
IL12B	0.018	0.039	-10000	0	-0.33	7	7
IL12A	-0.007	0.05	-10000	0	-0.26	22	22
IL6ST	0.017	0.041	-10000	0	-0.38	5	5
IL27RA/JAK1	0.017	0.04	-10000	0	-10000	0	0
IL27	0.01	0.056	-10000	0	-0.33	14	14
TYK2	0.016	0.021	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.21	0.49	0.44	4	-1.2	107	111
T-helper 2 cell differentiation	0.017	0.094	0.37	10	-10000	0	10
T cell proliferation during immune response	0.017	0.094	0.37	10	-10000	0	10
MAPKKK cascade	-0.017	0.094	-10000	0	-0.37	10	10
STAT3	0.026	0.005	-10000	0	-10000	0	0
STAT2	0.027	0.004	-10000	0	-10000	0	0
STAT1	0.022	0.043	-10000	0	-0.32	9	9
IL12RB1	0.001	0.091	-10000	0	-0.33	42	42
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.013	0.13	0.36	2	-0.42	9	11
IL27/IL27R/JAK2/TYK2	-0.017	0.094	-10000	0	-0.37	10	10
positive regulation of T cell mediated cytotoxicity	-0.017	0.094	-10000	0	-0.37	10	10
STAT1 (dimer)	0.05	0.18	0.42	55	-0.55	3	58
JAK2	0.015	0.02	-10000	0	-10000	0	0
JAK1	0.028	0.005	-10000	0	-10000	0	0
STAT2 (dimer)	-0.011	0.1	-10000	0	-0.36	11	11
T cell proliferation	-0.059	0.11	-10000	0	-0.38	20	20
IL12/IL12R/TYK2/JAK2	-0.053	0.22	-10000	0	-0.77	45	45
IL17A	-0.21	0.49	0.44	4	-1.2	107	111
mast cell activation	0.017	0.094	0.37	10	-10000	0	10
IFNG	-0.009	0.033	-10000	0	-0.099	18	18
T cell differentiation	-0.002	0.006	-10000	0	-0.016	26	26
STAT3 (dimer)	-0.011	0.1	-10000	0	-0.36	11	11
STAT5A (dimer)	-0.011	0.1	-10000	0	-0.36	11	11
STAT4 (dimer)	-0.012	0.1	-10000	0	-0.36	12	12
STAT4	0.024	0.032	-10000	0	-0.32	5	5
T cell activation	-0.005	0.005	0.047	4	-10000	0	4
IL27R/JAK2/TYK2	0.023	0.061	-10000	0	-10000	0	0
GATA3	0.004	0.11	0.65	14	-10000	0	14
IL18	0	0.027	-10000	0	-0.24	7	7
positive regulation of mast cell cytokine production	-0.011	0.099	-10000	0	-0.36	11	11
IL27/EBI3	0.016	0.064	-10000	0	-0.24	27	27
IL27RA	0.005	0.033	-10000	0	-10000	0	0
IL6	-0.082	0.2	-10000	0	-0.41	149	149
STAT5A	0.026	0.004	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	-0.011	0.023	-10000	0	-10000	0	0
IL1B	-0.015	0.063	-10000	0	-0.23	48	48
EBI3	0.014	0.058	-10000	0	-0.34	14	14
TNF	-0.013	0.059	-10000	0	-0.22	42	42

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.019	0.095	-10000	0	-0.36	17	17
TBX21	-0.1	0.26	-10000	0	-0.99	27	27
B2M	0.018	0.02	-10000	0	-10000	0	0
TYK2	0.01	0.031	-10000	0	-10000	0	0
IL12RB1	-0.013	0.095	-10000	0	-0.34	42	42
GADD45B	-0.081	0.23	-10000	0	-0.86	25	25
IL12RB2	-0.021	0.11	-10000	0	-0.33	58	58
GADD45G	-0.072	0.22	-10000	0	-1	14	14
natural killer cell activation	-0.004	0.016	0.043	1	-0.043	14	15
RELB	0.026	0.006	-10000	0	-10000	0	0
RELA	0.026	0.005	-10000	0	-10000	0	0
IL18	0.015	0.043	-10000	0	-0.34	7	7
IL2RA	-0.009	0.1	-10000	0	-0.32	59	59
IFNG	-0.057	0.15	-10000	0	-0.32	139	139
STAT3 (dimer)	-0.075	0.2	-10000	0	-0.68	24	24
HLA-DRB5	0	0.005	-10000	0	-0.023	26	26
FASLG	-0.095	0.26	-10000	0	-0.98	23	23
NF kappa B2 p52/RelB	-0.082	0.22	-10000	0	-0.76	24	24
CD4	0.02	0.038	-10000	0	-0.33	6	6
SOCS1	0.023	0.033	-10000	0	-0.33	5	5
EntrezGene:6955	-0.003	0.009	-10000	0	-0.029	32	32
CD3D	0.008	0.059	-10000	0	-0.34	14	14
CD3E	0.009	0.055	-10000	0	-0.34	12	12
CD3G	0.007	0.061	-10000	0	-0.36	14	14
IL12Rbeta2/JAK2	-0.005	0.081	-10000	0	-0.23	54	54
CCL3	-0.12	0.24	-10000	0	-0.82	23	23
CCL4	-0.093	0.23	-10000	0	-0.9	18	18
HLA-A	-0.002	0.007	-10000	0	-0.03	8	8
IL18/IL18R	0.015	0.075	-10000	0	-0.22	26	26
NOS2	-0.12	0.25	-10000	0	-0.92	23	23
IL12/IL12R/TYK2/JAK2/SPHK2	-0.019	0.095	-10000	0	-0.35	20	20
IL1R1	-0.087	0.22	-10000	0	-0.85	16	16
IL4	0.006	0.047	-10000	0	-0.32	7	7
JAK2	0.009	0.029	-10000	0	-10000	0	0
EntrezGene:6957	-0.003	0.009	-10000	0	-0.026	31	31
TCR/CD3/MHC I/CD8	-0.034	0.15	-10000	0	-0.58	23	23
RAB7A	-0.055	0.2	-10000	0	-0.76	13	13
lysosomal transport	-0.052	0.19	-10000	0	-0.72	13	13
FOS	-0.084	0.29	-10000	0	-1	42	42
STAT4 (dimer)	-0.063	0.22	0.36	2	-0.74	23	25
STAT5A (dimer)	-0.11	0.24	-10000	0	-0.74	37	37
GZMA	-0.099	0.25	-10000	0	-0.98	23	23
GZMB	-0.1	0.24	-10000	0	-0.89	19	19
HLX	0.025	0.015	-10000	0	-0.32	1	1
LCK	-0.11	0.24	-10000	0	-0.83	27	27
TCR/CD3/MHC II/CD4	-0.003	0.071	-10000	0	-0.27	22	22
IL2/IL2R	0.019	0.1	-10000	0	-0.24	47	47
MAPK14	-0.074	0.23	-10000	0	-0.83	22	22
CCR5	-0.081	0.22	-10000	0	-0.83	20	20
IL1B	-0.017	0.1	-10000	0	-0.34	48	48
STAT6	-0.019	0.091	-10000	0	-0.66	4	4
STAT4	0.024	0.032	-10000	0	-0.32	5	5
STAT3	0.026	0.005	-10000	0	-10000	0	0
STAT1	0.021	0.043	-10000	0	-0.32	9	9
NFKB1	0.026	0.004	-10000	0	-10000	0	0
NFKB2	0.026	0.005	-10000	0	-10000	0	0
IL12B	0.005	0.048	-10000	0	-0.34	7	7
CD8A	0.001	0.084	-10000	0	-0.36	29	29
CD8B	-0.004	0.093	-10000	0	-0.36	36	36
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.019	0.095	0.36	17	-10000	0	17
IL2RB	0.019	0.05	-10000	0	-0.33	12	12
proteasomal ubiquitin-dependent protein catabolic process	-0.058	0.21	0.36	2	-0.68	23	25
IL2RG	0.005	0.084	-10000	0	-0.32	37	37
IL12	0.002	0.072	-10000	0	-0.26	29	29
STAT5A	0.026	0.004	-10000	0	-10000	0	0
CD247	0.008	0.06	-10000	0	-0.34	15	15
IL2	0.021	0.021	-10000	0	-0.32	2	2
SPHK2	0.026	0.005	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.005	0.079	-10000	0	-0.38	22	22
IL12/IL12R/TYK2/JAK2	-0.099	0.24	-10000	0	-0.84	26	26
MAP2K3	-0.082	0.23	-10000	0	-0.78	28	28
RIPK2	0.024	0.009	-10000	0	-10000	0	0
MAP2K6	-0.074	0.23	-10000	0	-0.85	23	23
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.001	0.006	-10000	0	-0.027	27	27
IL18RAP	0.006	0.075	-10000	0	-0.37	22	22
IL12Rbeta1/TYK2	0.001	0.079	-10000	0	-0.25	42	42
EOMES	-0.037	0.17	-10000	0	-0.72	21	21
STAT1 (dimer)	-0.084	0.21	-10000	0	-0.67	27	27
T cell proliferation	-0.046	0.18	0.44	2	-0.56	21	23
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.019	0.024	-10000	0	-0.38	1	1
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.066	0.19	-10000	0	-0.64	20	20
ATF2	-0.068	0.22	0.51	1	-0.76	22	23

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.026	0.005	-9999	-10000	0	0
SPHK1	0.002	0.09	-9999	-0.32	42	42
GNAI2	0.025	0.007	-9999	-10000	0	0
mol:S1P	0.004	0.034	-9999	-0.22	4	4
GNAO1	-0.019	0.12	-9999	-0.37	68	68
mol:Sphinganine-1-P	-0.004	0.059	-9999	-0.22	41	41
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.04	0.05	-9999	-10000	0	0
GNAI3	0.026	0.005	-9999	-10000	0	0
G12/G13	0.036	0.012	-9999	-10000	0	0
S1PR3	0.023	0.036	-9999	-0.36	5	5
S1PR2	0.026	0.015	-9999	-0.32	1	1
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.037	-9999	-0.2	8	8
S1PR5	-0.035	0.13	-9999	-0.32	104	104
S1PR4	0.019	0.05	-9999	-0.33	12	12
GNAI1	0.019	0.052	-9999	-0.37	10	10
S1P/S1P5/G12	0	0.089	-9999	-0.24	36	36
S1P/S1P3/Gq	0.001	0.083	-9999	-0.32	26	26
S1P/S1P4/Gi	-0.026	0.11	-9999	-0.34	42	42
GNAQ	0.026	0.006	-9999	-10000	0	0
GNAZ	-0.012	0.12	-9999	-0.37	56	56
GNA14	0.011	0.076	-9999	-0.37	22	22
GNA15	-0.007	0.1	-9999	-0.32	56	56
GNA12	0.025	0.007	-9999	-10000	0	0
GNA13	0.026	0.005	-9999	-10000	0	0
GNA11	0.026	0.006	-9999	-10000	0	0
ABCC1	0.02	0.046	-9999	-0.33	10	10

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.011	0.004	-10000	0	-10000	0	0
MAP4K4	0.012	0.058	0.2	7	-0.38	4	11
BAG4	0.024	0.008	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.003	0.058	-10000	0	-0.18	49	49
NFKBIA	0.026	0.004	-10000	0	-10000	0	0
BIRC3	0.021	0.043	-10000	0	-0.37	7	7
BAX	-0.004	0.058	-10000	0	-0.35	13	13
RIPK1	0.025	0.007	-10000	0	-10000	0	0
AKT1	-0.001	0.064	0.68	5	-10000	0	5
BAD	-0.018	0.055	0.2	3	-0.18	52	55
SMPD1	0.012	0.061	0.17	20	-0.29	9	29
RB1	-0.011	0.063	0.19	20	-0.18	45	65
FADD/Caspase 8	0.034	0.083	0.22	58	-0.43	4	62
MAP2K4	-0.019	0.05	-10000	0	-0.18	37	37
NSMAF	0.025	0.008	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.015	0.058	0.18	14	-0.18	42	56
EGF	-0.031	0.13	-10000	0	-0.32	94	94
mol:ceramide	-0.018	0.057	-10000	0	-0.19	52	52
MADD	0.027	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.01	0.005	-10000	0	-10000	0	0
ASAH1	0.024	0.009	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.011	0.062	0.19	20	-0.18	45	65
cell proliferation	-0.014	0.08	0.19	2	-0.27	10	12
BID	-0.005	0.16	-10000	0	-0.7	25	25
MAP3K1	-0.019	0.052	-10000	0	-0.18	52	52
EIF2A	-0.004	0.074	0.19	34	-0.2	7	41
TRADD	0.026	0.005	-10000	0	-10000	0	0
CRADD	0.027	0.004	-10000	0	-10000	0	0
MAPK3	-0.014	0.058	0.18	10	-0.2	6	16
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.015	0.058	0.18	11	-0.2	6	17
Cathepsin D/ceramide	-0.003	0.06	-10000	0	-0.18	52	52
FADD	0.027	0.065	0.2	46	-0.35	1	47
KSR1	-0.016	0.059	0.19	9	-0.18	50	59
MAPK8	-0.013	0.06	-10000	0	-0.22	11	11
PRKRA	-0.017	0.058	0.19	7	-0.18	52	59
PDGFA	0.025	0.008	-10000	0	-10000	0	0
TRAF2	0.026	0.005	-10000	0	-10000	0	0
IGF1	-0.021	0.13	-10000	0	-0.36	74	74
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.018	0.056	-10000	0	-0.19	52	52
CTSD	0.026	0.005	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.038	0.009	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.014	0.085	0.21	2	-0.29	10	12
PRKCD	0.025	0.007	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.01	0.005	-10000	0	-10000	0	0
RelA/NF kappa B1	0.038	0.009	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.026	0.017	-10000	0	-0.37	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.012	0.045	-10000	0	-0.34	4	4
TNFR1A/BAG4/TNF-alpha	0.03	0.061	-10000	0	-0.19	37	37
mol:Sphingosine-1-phosphate	0.011	0.004	-10000	0	-10000	0	0
MAP2K1	-0.016	0.057	0.18	14	-0.2	6	20
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.026	0.005	-10000	0	-10000	0	0
CYCS	0.005	0.047	0.16	3	-0.19	7	10
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
NFKB1	0.026	0.004	-10000	0	-10000	0	0
TNFR1A/BAG4	0.034	0.014	-10000	0	-10000	0	0
EIF2AK2	-0.017	0.058	0.18	10	-0.18	42	52
TNF-alpha/TNFR1A/FAN	0.031	0.06	-10000	0	-0.19	35	35
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.022	0.069	-10000	0	-0.42	9	9
MAP2K2	-0.016	0.056	0.18	13	-0.2	6	19
SMPD3	-0.016	0.11	0.2	7	-0.3	63	70
TNF	0.001	0.091	-10000	0	-0.33	42	42
PKC zeta/PAR4	0.037	0.016	-10000	0	-0.26	1	1
mol:PHOSPHOCHOLINE	0.005	0.054	0.17	5	-0.17	8	13
NF kappa B1/RelA/I kappa B alpha	0.07	0.029	-10000	0	-0.19	1	1
AIFM1	0.001	0.051	0.15	6	-0.2	6	12
BCL2	0.022	0.029	-10000	0	-0.37	3	3

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.023	0.01	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	0.023	0.081	-10000	0	-0.36	11	11
Syndecan-3/Neurocan	0.014	0.074	-10000	0	-0.38	16	16
POMC	-0.005	0.1	-10000	0	-0.35	49	49
EGFR	0.017	0.052	-10000	0	-0.36	11	11
Syndecan-3/EGFR	0.015	0.07	-10000	0	-0.38	14	14
AGRP	0.019	0.04	-10000	0	-0.32	8	8
NCSTN	0.026	0.005	-10000	0	-10000	0	0
PSENEN	0.026	0.006	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.026	0.004	-10000	0	-10000	0	0
APH1A	0.026	0.005	-10000	0	-10000	0	0
NCAN	0.014	0.058	-10000	0	-0.32	17	17
long-term memory	0.03	0.065	-10000	0	-0.36	13	13
Syndecan-3/IL8	-0.064	0.11	-10000	0	-0.46	17	17
PSEN1	0.026	0.005	-10000	0	-10000	0	0
Src/Cortactin	0.03	0.018	-10000	0	-10000	0	0
FYN	0.026	0.005	-10000	0	-10000	0	0
limb bud formation	0.002	0.066	-10000	0	-0.39	16	16
MC4R	0.019	0.016	-10000	0	-0.32	1	1
SRC	0.023	0.009	-10000	0	-10000	0	0
PTN	-0.003	0.1	-10000	0	-0.37	44	44
FGFR/FGF/Syndecan-3	0.002	0.066	-10000	0	-0.39	16	16
neuron projection morphogenesis	0.025	0.097	0.26	2	-0.36	11	13
Syndecan-3/AgRP	0.016	0.071	-10000	0	-0.38	16	16
Syndecan-3/AgRP/MC4R	0.025	0.072	-10000	0	-0.36	16	16
Fyn/Cortactin	0.033	0.015	-10000	0	-10000	0	0
SDC3	0.002	0.067	-10000	0	-0.4	16	16
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	-0.063	0.11	-10000	0	-0.45	17	17
IL8	-0.15	0.18	-10000	0	-0.32	304	304
Syndecan-3/Fyn/Cortactin	0.031	0.067	-10000	0	-0.36	13	13
Syndecan-3/CASK	0	0.064	-10000	0	-0.38	16	16
alpha-MSH/MC4R	0.01	0.077	-10000	0	-0.24	49	49
Gamma Secretase	0.069	0.029	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.096	0.18	-9999	-0.37	182	182
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.026	0.006	-9999	-10000	0	0
TCEB1	0.024	0.008	-9999	-10000	0	0
HIF1A/p53	0.022	0.052	-9999	-0.26	14	14
HIF1A	0.006	0.044	-9999	-0.26	13	13
COPS5	0.024	0.008	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.062	0.034	-9999	-10000	0	0
FIH (dimer)	0.026	0.005	-9999	-10000	0	0
CDKN2A	-0.07	0.15	-9999	-0.33	153	153
ARNT/IPAS	-0.05	0.14	-9999	-0.26	173	173
HIF1AN	0.026	0.005	-9999	-10000	0	0
GNB2L1	0.026	0.006	-9999	-10000	0	0
HIF1A/ARNT	0.021	0.053	-9999	-0.26	15	15
CUL2	0.026	0.006	-9999	-10000	0	0
OS9	0.026	0.005	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.045	0.021	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.022	0.051	-9999	-0.26	14	14
PHD1-3/OS9	0.057	0.038	-9999	-0.2	8	8
HIF1A/RACK1/Elongin B/Elongin C	0.038	0.053	-9999	-0.25	7	7
VHL	0.026	0.006	-9999	-10000	0	0
HSP90AA1	0.026	0.006	-9999	-10000	0	0
HIF1A/JAB1	0.019	0.052	-9999	-0.26	15	15
EGLN3	0.02	0.049	-9999	-0.37	9	9
EGLN2	0.026	0.006	-9999	-10000	0	0
EGLN1	0.026	0.006	-9999	-10000	0	0
TP53	0.025	0.007	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.016	0.11	-9999	-0.49	25	25
ARNT	0.026	0.006	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.026	0.005	-9999	-10000	0	0
HIF1A/p19ARF	-0.024	0.084	-9999	-0.32	15	15

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.043	0.076	-10000	0	-0.23	34	34
MAP4K1	0.012	0.071	-10000	0	-0.35	22	22
MAP3K8	0.026	0.015	-10000	0	-0.32	1	1
PRKCB	0.001	0.097	-10000	0	-0.37	38	38
DBNL	0.025	0.007	-10000	0	-10000	0	0
CRKL	0.025	0.015	-10000	0	-0.32	1	1
MAP3K1	0.009	0.053	-10000	0	-0.3	7	7
JUN	-0.036	0.18	-10000	0	-0.54	66	66
MAP3K7	0.007	0.06	-10000	0	-0.3	11	11
GRAP2	0.018	0.055	-10000	0	-0.36	12	12
CRK	0.025	0.007	-10000	0	-10000	0	0
MAP2K4	0.009	0.057	0.18	2	-0.31	7	9
LAT	0.022	0.038	-10000	0	-0.32	7	7
LCP2	0.023	0.03	-10000	0	-0.34	4	4
MAPK8	-0.035	0.2	-10000	0	-0.57	67	67
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.014	0.064	-10000	0	-0.29	15	15
LAT/GRAP2/SLP76/HPK1/HIP-55	0.051	0.074	-10000	0	-0.29	15	15

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.007	0.084	0.23	67	-10000	0	67
KIRREL	0.02	0.032	-10000	0	-0.38	2	2
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.007	0.085	-10000	0	-0.23	67	67
PLCG1	0.023	0.01	-10000	0	-10000	0	0
ARRB2	0.025	0.007	-10000	0	-10000	0	0
WASL	0.026	0.005	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.033	0.072	-10000	0	-0.22	4	4
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.009	0.039	-10000	0	-0.22	4	4
FYN	0.002	0.069	0.2	31	-0.21	5	36
mol:Ca2+	0.028	0.069	-10000	0	-0.22	5	5
mol:DAG	0.029	0.07	-10000	0	-0.22	5	5
NPHS2	0.011	0.032	-10000	0	-0.34	2	2
mol:IP3	0.029	0.07	-10000	0	-0.22	5	5
regulation of endocytosis	0.027	0.061	-10000	0	-0.21	3	3
Nephrin/NEPH1/podocin/Cholesterol	0.021	0.068	-10000	0	-0.16	66	66
establishment of cell polarity	0.007	0.084	-10000	0	-0.23	67	67
Nephrin/NEPH1/podocin/NCK1-2	0.042	0.073	-10000	0	-0.28	1	1
Nephrin/NEPH1/beta Arrestin2	0.029	0.062	-10000	0	-0.21	3	3
NPHS1	-0.018	0.11	-10000	0	-0.32	67	67
Nephrin/NEPH1/podocin	0.024	0.061	0.18	1	-0.2	6	7
TJP1	0.026	0.004	-10000	0	-10000	0	0
NCK1	0.025	0.007	-10000	0	-10000	0	0
NCK2	0.026	0.005	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.03	0.07	-10000	0	-0.22	5	5
CD2AP	0.026	0.006	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.033	0.075	-10000	0	-0.21	6	6
GRB2	0.026	0.005	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.008	0.071	0.21	29	-0.21	4	33
cytoskeleton organization	0.001	0.051	0.2	11	-0.23	5	16
Nephrin/NEPH1	0.011	0.059	-10000	0	-0.15	67	67
Nephrin/NEPH1/ZO-1	0.024	0.073	-10000	0	-0.18	62	62

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	0.001	0.033	0.12	28	-0.12	1	29
BUB1B	-0.001	0.048	0.12	8	-0.14	23	31
PLK1	0.012	0.027	0.079	37	-0.1	2	39
PLK1S1	0.014	0.036	0.1	28	-0.2	8	36
KIF2A	0.008	0.026	0.16	4	-10000	0	4
regulation of mitotic centrosome separation	0.012	0.027	0.079	37	-0.1	2	39
GOLGA2	0.026	0.005	-10000	0	-10000	0	0
Hec1/SPC24	0.031	0.047	-10000	0	-0.16	18	18
WEE1	0.016	0.05	0.19	2	-0.32	8	10
cytokinesis	0.005	0.058	0.15	2	-0.23	10	12
PP2A-alpha B56	0.041	0.085	-10000	0	-0.52	11	11
AURKA	0.015	0.024	0.093	13	-10000	0	13
PICH/PLK1	0.007	0.042	0.14	4	-0.17	11	15
CENPE	-0.028	0.07	0.1	2	-0.16	105	107
RhoA/GTP	0.019	0.005	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.009	0.027	0.16	4	-10000	0	4
PPP2CA	0.025	0.007	-10000	0	-10000	0	0
FZR1	0.026	0.006	-10000	0	-10000	0	0
TPX2	0.016	0.034	0.11	41	-0.11	1	42
PAK1	0.026	0.007	-10000	0	-10000	0	0
SPC24	0.025	0.021	-10000	0	-0.32	2	2
FBXW11	0.026	0.006	-10000	0	-10000	0	0
CLSPN	-0.007	0.044	0.14	2	-0.23	9	11
GORASP1	0.025	0.006	-10000	0	-10000	0	0
metaphase	0.001	0.003	0.014	20	-0.011	1	21
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.005	0.015	0.044	37	-0.053	2	39
G2 phase of mitotic cell cycle	0	0.003	0.012	9	-10000	0	9
STAG2	0.026	0.005	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	-0.006	0.12	-10000	0	-0.49	31	31
spindle elongation	0.012	0.027	0.079	37	-0.1	2	39
ODF2	0.027	0.006	-10000	0	-10000	0	0
BUB1	0.012	0.084	-10000	0	-0.56	11	11
TPT1	0.01	0.035	0.12	3	-0.19	13	16
CDC25C	0	0.068	-10000	0	-0.26	35	35
CDC25B	0.02	0.034	-10000	0	-0.32	5	5
SGOL1	-0.001	0.033	0.12	1	-0.12	28	29
RHOA	0.025	0.007	-10000	0	-10000	0	0
CCNB1/CDK1	0.031	0.037	-10000	0	-0.19	1	1
CDC14B	0.006	0.012	-10000	0	-0.26	1	1
CDC20	0.023	0.038	-10000	0	-0.32	7	7
PLK1/PBIP1	0.007	0.027	0.087	3	-0.15	8	11
mitosis	-0.001	0.003	0.016	7	-10000	0	7
FBXO5	0.009	0.031	0.13	13	-0.13	4	17
CDC2	0.001	0.003	0.008	1	-0.01	15	16
NDC80	0.01	0.071	-10000	0	-0.32	26	26
metaphase plate congression	0.002	0.059	-10000	0	-0.23	33	33
ERCC6L	0.007	0.048	0.14	3	-0.21	5	8
NLP/gamma Tubulin	0.008	0.018	0.07	12	-0.09	4	16
microtubule cytoskeleton organization	0.01	0.035	0.12	3	-0.19	13	16
G2/M transition DNA damage checkpoint	0	0.002	0.012	13	-10000	0	13
PPP1R12A	0.027	0.005	-10000	0	-10000	0	0
interphase	0	0.002	0.012	13	-10000	0	13
PLK1/PRC1-2	0.026	0.055	-10000	0	-0.17	27	27
GRASP65/GM130/RAB1/GTP/PLK1	0.047	0.028	-10000	0	-10000	0	0
RAB1A	0.027	0.003	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.013	0.028	0.069	85	-0.07	1	86
mitotic prometaphase	0	0.004	0.016	33	-10000	0	33
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.036	0.17	2	-0.22	2	4
microtubule-based process	0.015	0.049	0.1	6	-0.16	33	39
Golgi organization	0.012	0.027	0.079	37	-0.1	2	39
Cohesin/SA2	0.024	0.023	0.099	4	-10000	0	4
PPP1CB/MYPT1	0.039	0.008	-10000	0	-10000	0	0
KIF20A	0.004	0.083	-10000	0	-0.32	36	36
APC/C/CDC20	0.024	0.035	0.11	7	-0.18	8	15
PPP2R1A	0.026	0.005	-10000	0	-10000	0	0
chromosome segregation	0.007	0.027	0.086	3	-0.15	8	11
PRC1	0.023	0.032	-10000	0	-0.32	5	5
ECT2	0.012	0.098	0.21	80	-0.16	73	153
C13orf34	0.011	0.024	0.071	42	-0.086	1	43
NUDC	0.002	0.059	-10000	0	-0.23	33	33
regulation of attachment of spindle microtubules to kinetochore	-0.001	0.048	0.12	8	-0.14	23	31
spindle assembly	0.01	0.024	0.082	23	-0.085	2	25
spindle stabilization	0.014	0.035	0.1	28	-0.2	8	36
APC/C/HCDH1	0.023	0.012	-10000	0	-0.22	1	1
MKLP2/PLK1	0.015	0.049	0.11	6	-0.16	33	39
CCNB1	0.025	0.022	-10000	0	-0.32	2	2
PPP1CB	0.027	0.003	-10000	0	-10000	0	0
BTRC	0.026	0.005	-10000	0	-10000	0	0
ROCK2	0.012	0.043	0.16	1	-0.26	3	4
TUBG1	0.012	0.023	0.12	1	-0.19	4	5
G2/M transition of mitotic cell cycle	0.004	0.03	0.14	3	-0.19	1	4
MLF1IP	0.002	0.025	-10000	0	-0.22	7	7
INCENP	0.027	0.004	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.016	0.023	-10000	0	-0.26	1	1
CRKL	0.025	0.015	-10000	0	-0.32	1	1
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
DOCK1	0.026	0.006	-10000	0	-10000	0	0
ITGA4	0.023	0.038	-10000	0	-0.32	7	7
alpha4/beta7 Integrin/MAdCAM1	-0.016	0.12	-10000	0	-0.2	160	160
EPO	0	0.083	-10000	0	-0.32	37	37
alpha4/beta7 Integrin	0.035	0.032	-10000	0	-0.23	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.025	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.035	0.03	-10000	0	-0.22	7	7
EPO/EPOR (dimer)	0.017	0.061	-10000	0	-0.22	35	35
lamellipodium assembly	0.021	0.071	-10000	0	-0.43	8	8
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
PI3K	0.032	0.016	-10000	0	-10000	0	0
ARF6	0.026	0.005	-10000	0	-10000	0	0
JAK2	0.013	0.04	-10000	0	-0.25	4	4
PXN	0.027	0.004	-10000	0	-10000	0	0
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
MADCAM1	-0.087	0.18	-10000	0	-0.37	169	169
cell adhesion	-0.018	0.12	-10000	0	-0.2	160	160
CRKL/CBL	0.036	0.016	-10000	0	-0.22	1	1
ITGB1	0.026	0.005	-10000	0	-10000	0	0
SRC	0.011	0.038	0.18	13	-0.32	1	14
ITGB7	0.026	0.017	-10000	0	-0.37	1	1
RAC1	0.025	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.046	0.039	-10000	0	-0.2	12	12
p130Cas/Crk/Dock1	0.041	0.052	-10000	0	-0.28	1	1
VCAM1	0.023	0.035	-10000	0	-0.32	6	6
RHOA	0.025	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.061	0.032	-10000	0	-10000	0	0
BCAR1	-0.01	0.037	0.18	13	-0.3	1	14
EPOR	0.026	0.005	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.025	0.007	-10000	0	-10000	0	0
GIT1	0.027	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.021	0.073	-10000	0	-0.44	8	8

×

IL1-mediated signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.02	0.003	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.025	0.007	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.005	0.055	-10000	0	-0.34	5	5
IRAK/TOLLIP	0.028	0.008	-10000	0	-10000	0	0
IKBKB	0.024	0.008	-10000	0	-10000	0	0
IKBKG	0.026	0.006	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.056	0.14	-10000	0	-0.24	200	200
IL1A	-0.067	0.16	-10000	0	-0.32	158	158
IL1B	-0.009	0.069	-10000	0	-0.23	52	52
IRAK/TRAF6/p62/Atypical PKCs	0.05	0.032	-10000	0	-10000	0	0
IL1R2	-0.009	0.11	-10000	0	-0.37	54	54
IL1R1	0.026	0.015	-10000	0	-0.32	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.008	0.06	0.24	1	-0.37	4	5
TOLLIP	0.026	0.005	-10000	0	-10000	0	0
TICAM2	0.022	0.033	-10000	0	-0.37	4	4
MAP3K3	0.026	0.005	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.018	0.003	-10000	0	-10000	0	0
IKK complex/ELKS	0.026	0.063	-10000	0	-0.35	1	1
JUN	-0.009	0.033	0.15	18	-10000	0	18
MAP3K7	0.026	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.032	0.075	-10000	0	-0.3	2	2
IL1 alpha/IL1R1/IL1RAP/MYD88	0.006	0.11	-10000	0	-0.31	18	18
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.014	0.11	-10000	0	-0.31	16	16
IL1 beta fragment/IL1R1/IL1RAP	0.014	0.07	-10000	0	-0.23	7	7
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MAPK8	-0.007	0.035	0.16	18	-10000	0	18
IRAK1	0.013	0.003	-10000	0	-10000	0	0
IL1RN/IL1R1	0.009	0.088	-10000	0	-0.25	62	62
IRAK4	0.026	0.005	-10000	0	-10000	0	0
PRKCI	0.023	0.017	-10000	0	-0.32	1	1
TRAF6	0.026	0.005	-10000	0	-10000	0	0
PI3K	0.032	0.016	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.015	0.052	-10000	0	-0.31	2	2
CHUK	0.026	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.014	0.07	-10000	0	-0.23	7	7
IL1 beta/IL1R2	-0.007	0.095	0.21	4	-0.21	99	103
IRAK/TRAF6/TAK1/TAB1/TAB2	0.035	0.012	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.021	0.067	-10000	0	-0.28	2	2
IRAK3	0.02	0.048	-10000	0	-0.37	9	9
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.03	0.078	-10000	0	-0.3	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.001	0.056	-10000	0	-0.23	8	8
IL1 alpha/IL1R1/IL1RAP	-0.007	0.11	-10000	0	-0.21	125	125
RELA	0.026	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.025	0.007	-10000	0	-10000	0	0
MYD88	0.025	0.006	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.042	0.016	-10000	0	-10000	0	0
IL1RAP	0.012	0.062	-10000	0	-0.32	19	19
UBE2N	0.027	0.004	-10000	0	-10000	0	0
IRAK/TRAF6	0.008	0.059	-10000	0	-0.27	3	3
CASP1	0.021	0.038	-10000	0	-0.32	7	7
IL1RN/IL1R2	-0.015	0.12	-10000	0	-0.28	101	101
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.024	0.072	-10000	0	-0.31	2	2
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.006	0.065	-10000	0	-0.27	14	14
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
IL1RN	-0.012	0.12	-10000	0	-0.35	61	61
TRAF6/TAK1/TAB1/TAB2	0.037	0.011	-10000	0	-10000	0	0
MAP2K6	0.014	0.035	0.18	19	-10000	0	19

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.031	0.14	-10000	0	-0.36	79	79
NFATC2	0.007	0.11	-10000	0	-0.49	7	7
NFATC3	-0.012	0.058	-10000	0	-0.25	5	5
CD40LG	-0.14	0.24	-10000	0	-0.79	25	25
ITCH	0.012	0.053	-10000	0	-10000	0	0
CBLB	0.014	0.053	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.12	0.22	-10000	0	-0.66	44	44
JUNB	0.026	0.005	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.018	0.068	-10000	0	-0.24	38	38
T cell anergy	0.008	0.096	0.26	2	-0.36	32	34
TLE4	0.001	0.089	-10000	0	-0.57	7	7
Jun/NFAT1-c-4/p21SNFT	-0.053	0.18	-10000	0	-0.74	12	12
AP-1/NFAT1-c-4	-0.15	0.26	-10000	0	-0.87	19	19
IKZF1	-0.001	0.081	-10000	0	-0.39	5	5
T-helper 2 cell differentiation	-0.026	0.13	-10000	0	-0.7	8	8
AP-1/NFAT1	-0.029	0.12	-10000	0	-0.37	14	14
CALM1	0.023	0.045	-10000	0	-10000	0	0
EGR2	-0.023	0.15	-10000	0	-0.99	7	7
EGR3	-0.023	0.16	-10000	0	-1.1	8	8
NFAT1/FOXP3	-0.018	0.15	-10000	0	-0.42	43	43
EGR1	0.015	0.053	-10000	0	-0.37	10	10
JUN	-0.019	0.042	-10000	0	-10000	0	0
EGR4	-0.047	0.14	-10000	0	-0.33	121	121
mol:Ca2+	-0.001	0.037	-10000	0	-10000	0	0
GBP3	0.002	0.082	-10000	0	-0.52	5	5
FOSL1	-0.001	0.094	-10000	0	-0.32	46	46
NFAT1-c-4/MAF/IRF4	-0.02	0.15	-10000	0	-0.7	12	12
DGKA	0.004	0.072	-10000	0	-0.4	3	3
CREM	0.026	0.005	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.037	0.16	-10000	0	-0.72	12	12
CTLA4	-0.048	0.16	-10000	0	-0.41	80	80
NFAT1-c-4 (dimer)/EGR1	-0.027	0.16	-10000	0	-0.78	11	11
NFAT1-c-4 (dimer)/EGR4	-0.056	0.17	-10000	0	-0.77	10	10
FOS	-0.036	0.088	-10000	0	-0.39	27	27
IFNG	-0.063	0.17	-10000	0	-0.74	12	12
T cell activation	-0.027	0.12	-10000	0	-0.64	2	2
MAF	0.017	0.059	-10000	0	-0.37	13	13
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.022	0.12	0.66	12	-10000	0	12
TNF	-0.066	0.17	-10000	0	-0.73	13	13
FASLG	-0.049	0.26	-10000	0	-1.2	21	21
TBX21	-0.003	0.077	-10000	0	-0.37	19	19
BATF3	0.024	0.025	-10000	0	-0.32	3	3
PRKCQ	0.008	0.08	-10000	0	-0.37	24	24
PTPN1	0.004	0.072	-10000	0	-0.44	2	2
NFAT1-c-4/ICER1	-0.022	0.15	-10000	0	-0.74	10	10
GATA3	0.006	0.08	-10000	0	-0.32	33	33
T-helper 1 cell differentiation	-0.062	0.17	-10000	0	-0.72	12	12
IL2RA	-0.1	0.2	-10000	0	-0.64	31	31
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.003	0.07	-10000	0	-0.44	2	2
E2F1	0.025	0.027	-10000	0	-0.32	3	3
PPARG	0.001	0.096	-10000	0	-0.37	37	37
SLC3A2	0.004	0.074	-10000	0	-0.52	2	2
IRF4	0.012	0.068	-10000	0	-0.35	20	20
PTGS2	-0.15	0.24	-10000	0	-0.73	34	34
CSF2	-0.18	0.26	-10000	0	-0.75	39	39
JunB/Fra1/NFAT1-c-4	-0.023	0.16	-10000	0	-0.71	11	11
IL4	-0.027	0.13	-10000	0	-0.73	8	8
IL5	-0.14	0.23	-10000	0	-0.78	19	19
IL2	-0.028	0.13	-10000	0	-0.65	2	2
IL3	-0.041	0.14	-10000	0	-0.62	22	22
RNF128	-0.005	0.12	-10000	0	-0.46	40	40
NFATC1	-0.022	0.12	-10000	0	-0.66	12	12
CDK4	0.014	0.081	0.55	1	-10000	0	1
PTPRK	0.004	0.071	-10000	0	-0.44	2	2
IL8	-0.2	0.27	-10000	0	-0.75	42	42
POU2F1	0.027	0.006	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.018	0.16	0.42	1	-0.81	17	18
NCK1/PAK1/Dok-R	-0.02	0.071	-10000	0	-0.4	17	17
NCK1/Dok-R	0.026	0.17	-10000	0	-0.88	17	17
PIK3CA	0.023	0.009	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.003	0.026	0.22	7	-10000	0	7
RELA	0.026	0.005	-10000	0	-10000	0	0
SHC1	0.027	0.005	-10000	0	-10000	0	0
Rac/GDP	0.019	0.005	-10000	0	-10000	0	0
F2	-0.037	0.11	0.25	7	-0.34	65	72
TNIP2	0.025	0.007	-10000	0	-10000	0	0
NF kappa B/RelA	0.044	0.16	-10000	0	-0.82	17	17
FN1	0	0.093	-10000	0	-0.33	45	45
PLD2	0.001	0.16	-10000	0	-0.9	17	17
PTPN11	0.026	0.004	-10000	0	-10000	0	0
GRB14	-0.026	0.13	-10000	0	-0.34	86	86
ELK1	0.011	0.16	-10000	0	-0.83	17	17
GRB7	0.021	0.029	-10000	0	-0.36	3	3
PAK1	0.025	0.006	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	0.03	0.17	-10000	0	-0.86	17	17
CDKN1A	0.019	0.14	0.42	1	-0.58	18	19
ITGA5	0.024	0.029	-10000	0	-0.32	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.027	0.17	-10000	0	-0.87	17	17
CRK	0.025	0.007	-10000	0	-10000	0	0
mol:NO	0.026	0.14	0.37	5	-0.6	17	22
PLG	-0.003	0.16	-10000	0	-0.9	17	17
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.018	0.15	-10000	0	-0.77	17	17
GRB2	0.026	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
ANGPT2	-0.015	0.16	-10000	0	-0.6	10	10
BMX	-0.022	0.18	-10000	0	-0.98	17	17
ANGPT1	0.009	0.14	-10000	0	-1.2	7	7
tube development	0.008	0.15	0.42	1	-0.63	17	18
ANGPT4	0.018	0.031	-10000	0	-0.32	4	4
response to hypoxia	0	0.012	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	0.001	0.18	-10000	0	-0.93	17	17
alpha5/beta1 Integrin	0.036	0.023	-10000	0	-0.22	4	4
FGF2	0.006	0.087	-10000	0	-0.37	30	30
STAT5A (dimer)	0.018	0.16	0.44	1	-0.71	17	18
mol:L-citrulline	0.026	0.14	0.37	5	-0.6	17	22
AGTR1	-0.07	0.17	-10000	0	-0.37	140	140
MAPK14	0.004	0.19	-10000	0	-1	17	17
Tie2/SHP2	0.009	0.15	-10000	0	-0.93	11	11
TEK	0.011	0.15	-10000	0	-1	11	11
RPS6KB1	0.019	0.16	0.38	1	-0.78	17	18
Angiotensin II/AT1	-0.047	0.12	-10000	0	-0.26	140	140
Tie2/Ang1/GRB2	0.021	0.17	-10000	0	-0.91	17	17
MAPK3	0.001	0.15	-10000	0	-0.84	17	17
MAPK1	0.001	0.15	-10000	0	-0.84	17	17
Tie2/Ang1/GRB7	0.013	0.17	-10000	0	-0.89	17	17
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MAPK8	0.002	0.16	-10000	0	-0.9	17	17
PI3K	0.009	0.18	-10000	0	-0.92	17	17
FES	0.008	0.18	-10000	0	-0.99	17	17
Crk/Dok-R	0.029	0.17	-10000	0	-0.88	17	17
Tie2/Ang1/ABIN2	0.021	0.17	-10000	0	-0.91	17	17
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.022	0.15	0.41	1	-0.73	17	18
STAT5A	0.027	0.004	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.035	0.17	0.41	9	-0.77	17	26
Tie2/Ang2	-0.005	0.17	-10000	0	-0.83	17	17
Tie2/Ang1	0.006	0.17	-10000	0	-0.95	17	17
FOXO1	0.026	0.16	0.43	4	-0.73	17	21
ELF1	0.029	0.022	-10000	0	-10000	0	0
ELF2	0.005	0.16	-10000	0	-0.89	17	17
mol:Choline	0.002	0.16	-10000	0	-0.86	17	17
cell migration	-0.007	0.045	-10000	0	-0.22	17	17
FYN	0.005	0.16	0.43	1	-0.71	17	18
DOK2	0.022	0.033	-10000	0	-0.37	4	4
negative regulation of cell cycle	0.021	0.13	0.38	2	-0.53	18	20
ETS1	0.028	0.03	-10000	0	-0.24	6	6
PXN	0.042	0.16	0.37	17	-0.65	17	34
ITGB1	0.026	0.005	-10000	0	-10000	0	0
NOS3	0.024	0.15	0.39	4	-0.7	16	20
RAC1	0.025	0.007	-10000	0	-10000	0	0
TNF	0.003	0.096	-10000	0	-0.32	48	48
MAPKKK cascade	0.002	0.16	-10000	0	-0.86	17	17
RASA1	0.025	0.008	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.021	0.17	-10000	0	-0.94	16	16
NCK1	0.025	0.007	-10000	0	-10000	0	0
vasculogenesis	0.027	0.13	0.33	9	-0.54	17	26
mol:Phosphatidic acid	0.002	0.16	-10000	0	-0.86	17	17
mol:Angiotensin II	0	0.003	-10000	0	-10000	0	0
mol:NADP	0.026	0.14	0.37	5	-0.6	17	22
Rac1/GTP	0.02	0.15	-10000	0	-0.72	17	17
MMP2	0.001	0.16	-10000	0	-0.91	17	17

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.005	0.009	-10000	0	-10000	0	0
RAS family/GTP	-0.002	0.086	0.23	1	-0.5	2	3
NFATC4	-0.01	0.088	0.28	18	-0.32	2	20
ERBB2IP	0.025	0.009	-10000	0	-10000	0	0
HSP90 (dimer)	0.026	0.006	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.02	0.078	-10000	0	-0.3	5	5
JUN	0	0.065	0.19	4	-0.25	6	10
HRAS	0.026	0.005	-10000	0	-10000	0	0
DOCK7	-0.022	0.084	0.27	2	-0.4	2	4
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.01	0.089	-10000	0	-0.21	58	58
AKT1	0.004	0.007	-10000	0	-10000	0	0
BAD	-0.005	0.006	-10000	0	-10000	0	0
MAPK10	-0.013	0.078	0.2	25	-0.22	14	39
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.019	0.085	-10000	0	-0.32	5	5
RAF1	-0.012	0.089	0.21	18	-0.49	2	20
ErbB2/ErbB3/neuregulin 2	-0.03	0.1	-10000	0	-0.21	135	135
STAT3	0.021	0.074	-10000	0	-0.76	5	5
cell migration	-0.007	0.081	0.23	25	-0.21	11	36
mol:PI-3-4-5-P3	-0.001	0.002	-10000	0	-10000	0	0
cell proliferation	-0.058	0.16	0.31	2	-0.51	21	23
FOS	-0.042	0.14	0.3	3	-0.44	36	39
NRAS	0.026	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.02	0.078	-10000	0	-0.3	5	5
MAPK3	-0.046	0.14	0.31	2	-0.51	15	17
MAPK1	-0.048	0.15	0.31	2	-0.57	15	17
JAK2	-0.023	0.079	-10000	0	-0.4	2	2
NF2	-0.005	0.086	-10000	0	-0.63	11	11
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.006	0.087	0.19	10	-0.23	57	67
NRG1	-0.037	0.14	-10000	0	-0.36	93	93
GRB2/SOS1	0.038	0.008	-10000	0	-10000	0	0
MAPK8	-0.015	0.095	0.2	7	-0.24	53	60
MAPK9	-0.003	0.069	0.2	28	-0.21	2	30
ERBB2	-0.018	0.018	-10000	0	-0.28	2	2
ERBB3	0.023	0.033	-10000	0	-0.38	4	4
SHC1	0.026	0.005	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
apoptosis	0.007	0.013	-10000	0	-0.18	1	1
STAT3 (dimer)	0.021	0.073	-10000	0	-0.74	5	5
RNF41	-0.008	0.01	-10000	0	-10000	0	0
FRAP1	-0.002	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.031	0.047	-10000	0	-0.29	2	2
ErbB2/ErbB2/HSP90 (dimer)	-0.013	0.019	-10000	0	-0.23	2	2
CHRNA1	-0.06	0.14	0.29	2	-0.39	20	22
myelination	-0.001	0.098	0.28	31	-0.32	2	33
PPP3CB	-0.021	0.077	0.27	1	-0.37	2	3
KRAS	0.023	0.009	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.016	0.089	0.23	1	-0.41	3	4
NRG2	-0.082	0.18	-10000	0	-0.37	160	160
mol:GDP	-0.006	0.087	0.19	10	-0.22	57	67
SOS1	0.027	0.003	-10000	0	-10000	0	0
MAP2K2	-0.021	0.088	0.2	18	-0.48	2	20
SRC	0.023	0.009	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.022	0.084	0.27	4	-0.4	2	6
MAP2K1	-0.046	0.15	0.3	1	-0.53	20	21
heart morphogenesis	-0.02	0.078	-10000	0	-0.3	5	5
RAS family/GDP	0.021	0.089	0.23	2	-0.49	2	4
GRB2	0.026	0.005	-10000	0	-10000	0	0
PRKACA	-0.006	0.1	-10000	0	-0.64	15	15
CHRNE	0.003	0.023	-10000	0	-0.13	10	10
HSP90AA1	0.026	0.006	-10000	0	-10000	0	0
activation of caspase activity	-0.004	0.007	-10000	0	-10000	0	0
nervous system development	-0.02	0.078	-10000	0	-0.3	5	5
CDC42	0.026	0.006	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	-0.01	0.086	-10000	0	-0.37	13	13
ACTA1	-0.019	0.076	0.25	3	-0.25	19	22
NUMA1	-0.012	0.097	-10000	0	-0.41	15	15
SPTAN1	-0.017	0.079	0.25	6	-0.25	19	25
LIMK1	-0.015	0.084	0.24	15	-0.25	18	33
BIRC3	0.021	0.043	-10000	0	-0.37	7	7
BIRC2	0.026	0.006	-10000	0	-10000	0	0
BAX	0.025	0.015	-10000	0	-0.32	1	1
CASP10	-0.036	0.073	0.2	1	-0.22	76	77
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.027	0.004	-10000	0	-10000	0	0
PTK2	-0.012	0.1	-10000	0	-0.43	16	16
DIABLO	0.026	0.004	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.017	0.078	0.24	7	-0.25	19	26
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.027	0.004	-10000	0	-10000	0	0
GSN	-0.02	0.078	0.22	6	-0.25	21	27
MADD	0.027	0.004	-10000	0	-10000	0	0
TFAP2A	-0.036	0.16	-10000	0	-0.61	33	33
BID	-0.008	0.038	0.13	1	-0.16	17	18
MAP3K1	-0.026	0.12	-10000	0	-0.4	47	47
TRADD	0.026	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.038	0.009	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.017	0.085	0.23	18	-0.26	18	36
CASP9	0.026	0.005	-10000	0	-10000	0	0
DNA repair	0	0.042	0.24	4	-0.17	4	8
neuron apoptosis	-0.037	0.19	-10000	0	-0.63	54	54
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.016	0.095	0.23	1	-0.49	6	7
APAF1	0.027	0.004	-10000	0	-10000	0	0
CASP6	-0.013	0.16	-10000	0	-0.87	18	18
TRAF2	0.026	0.005	-10000	0	-10000	0	0
ICAD/CAD	-0.017	0.083	0.36	7	-0.28	3	10
CASP7	-0.005	0.072	0.23	1	-0.37	5	6
KRT18	0.002	0.093	-10000	0	-0.56	13	13
apoptosis	-0.019	0.098	0.39	2	-0.4	16	18
DFFA	-0.018	0.078	0.22	11	-0.25	19	30
DFFB	-0.019	0.076	0.19	9	-0.25	19	28
PARP1	0	0.042	0.17	4	-0.24	4	8
actin filament polymerization	0.014	0.086	0.28	3	-0.31	10	13
TNF	0.001	0.091	-10000	0	-0.33	42	42
CYCS	0.001	0.046	0.18	2	-0.2	6	8
SATB1	-0.015	0.15	-10000	0	-0.82	18	18
SLK	-0.02	0.074	0.24	3	-0.25	19	22
p15 BID/BAX	0.007	0.05	-10000	0	-0.21	2	2
CASP2	0.007	0.059	0.21	5	-0.34	8	13
JNK cascade	0.026	0.12	0.39	47	-10000	0	47
CASP3	-0.021	0.077	0.2	2	-0.26	20	22
LMNB2	0	0.12	0.25	3	-0.47	22	25
RIPK1	0.025	0.007	-10000	0	-10000	0	0
CASP4	0.026	0.006	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.06	0.035	-10000	0	-0.2	7	7
negative regulation of DNA binding	-0.035	0.16	-10000	0	-0.6	33	33
stress fiber formation	-0.02	0.073	0.24	3	-0.25	19	22
GZMB	-0.023	0.093	-10000	0	-0.26	76	76
CASP1	0.012	0.015	-10000	0	-10000	0	0
LMNB1	-0.009	0.14	0.25	3	-0.57	25	28
APP	-0.038	0.2	-10000	0	-0.64	54	54
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.006	0.001	-10000	0	-10000	0	0
VIM	-0.018	0.099	0.31	2	-0.4	19	21
LMNA	0.012	0.088	0.25	3	-0.4	15	18
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.011	0.056	-10000	0	-0.32	7	7
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.02	0.072	0.2	3	-0.25	18	21
APAF-1/Caspase 9	0.005	0.092	-10000	0	-0.63	11	11
nuclear fragmentation during apoptosis	-0.012	0.095	-10000	0	-0.4	15	15
CFL2	-0.015	0.087	0.31	10	-0.28	3	13
GAS2	-0.034	0.085	0.2	5	-0.26	26	31
positive regulation of apoptosis	0.002	0.12	0.26	3	-0.5	22	25
PRF1	0.018	0.055	-10000	0	-0.33	15	15

×

ceramide 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
MAP4K4	0.004	0.11	0.22	9	-0.5	15	24
BAG4	0.024	0.008	-10000	0	-10000	0	0
BAD	0.007	0.038	0.15	5	-0.19	7	12
NFKBIA	0.026	0.004	-10000	0	-10000	0	0
BIRC3	0.021	0.043	-10000	0	-0.37	7	7
BAX	0.009	0.044	0.17	14	-0.2	6	20
EnzymeConsortium:3.1.4.12	0.004	0.025	0.064	9	-0.11	12	21
IKBKB	0.015	0.11	0.26	25	-0.48	13	38
MAP2K2	0.007	0.043	0.18	17	-0.25	2	19
MAP2K1	0.007	0.044	0.18	16	-0.22	4	20
SMPD1	0.005	0.031	0.1	4	-0.17	9	13
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.032	0.12	0.22	57	-0.54	11	68
MAP2K4	0.007	0.033	0.15	4	-0.22	3	7
protein ubiquitination	0.012	0.11	0.26	9	-0.5	14	23
EnzymeConsortium:2.7.1.37	0.007	0.047	0.18	18	-0.24	4	22
response to UV	0	0	0.002	19	-0.002	3	22
RAF1	0.008	0.044	0.18	16	-0.22	5	21
CRADD	0.027	0.004	-10000	0	-10000	0	0
mol:ceramide	0.008	0.039	0.096	16	-0.17	12	28
I-kappa-B-alpha/RELA/p50/ubiquitin	0.035	0.008	-10000	0	-10000	0	0
MADD	0.027	0.004	-10000	0	-10000	0	0
MAP3K1	0.006	0.036	0.13	4	-0.2	6	10
TRADD	0.026	0.005	-10000	0	-10000	0	0
RELA/p50	0.026	0.005	-10000	0	-10000	0	0
MAPK3	0.009	0.049	0.17	18	-0.24	4	22
MAPK1	0.008	0.05	0.18	17	-0.27	5	22
p50/RELA/I-kappa-B-alpha	0.038	0.009	-10000	0	-10000	0	0
FADD	0.026	0.11	0.22	60	-0.5	11	71
KSR1	0.009	0.044	0.19	11	-0.2	7	18
MAPK8	0.004	0.036	0.18	5	-0.21	3	8
TRAF2	0.026	0.005	-10000	0	-10000	0	0
response to radiation	0	0	0.002	7	-10000	0	7
CHUK	0.007	0.098	0.24	4	-0.5	12	16
TNF R/SODD	0.034	0.014	-10000	0	-10000	0	0
TNF	0.001	0.091	-10000	0	-0.33	42	42
CYCS	0.018	0.046	0.13	32	-0.18	3	35
IKBKG	0.011	0.11	0.24	12	-0.5	13	25
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.005	0.11	-10000	0	-0.56	13	13
RELA	0.026	0.005	-10000	0	-10000	0	0
RIPK1	0.025	0.007	-10000	0	-10000	0	0
AIFM1	0.015	0.043	0.13	27	-0.18	4	31
TNF/TNF R/SODD	0.03	0.06	-10000	0	-0.19	37	37
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
response to heat	0	0	0.002	7	-10000	0	7
CASP8	0.017	0.1	-10000	0	-0.65	12	12
NSMAF	0.012	0.11	0.22	29	-0.48	14	43
response to hydrogen peroxide	0	0	0.002	19	-0.002	3	22
BCL2	0.022	0.029	-10000	0	-0.37	3	3

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.035	0.017	-10000	0	-0.22	1	1
PDGFRB	0.015	0.06	-10000	0	-0.32	18	18
SPHK1	-0.004	0.072	-10000	0	-0.67	6	6
mol:S1P	-0.009	0.067	-10000	0	-0.57	6	6
S1P1/S1P/Gi	-0.036	0.14	0.21	1	-0.39	47	48
GNAO1	-0.02	0.12	-10000	0	-0.37	68	68
PDGFB-D/PDGFRB/PLCgamma1	-0.014	0.14	0.26	20	-0.37	34	54
PLCG1	-0.042	0.12	0.25	3	-0.38	41	44
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.06	-10000	0	-0.32	18	18
GNAI2	0.025	0.009	-10000	0	-10000	0	0
GNAI3	0.026	0.006	-10000	0	-10000	0	0
GNAI1	0.019	0.052	-10000	0	-0.38	10	10
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.003	0.011	-10000	0	-0.18	1	1
S1P1/S1P	-0.003	0.056	-10000	0	-0.33	6	6
negative regulation of cAMP metabolic process	-0.034	0.13	0.2	1	-0.38	48	49
MAPK3	-0.037	0.14	0.31	2	-0.43	33	35
calcium-dependent phospholipase C activity	-0.001	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
RhoA/GDP	0.019	0.005	-10000	0	-10000	0	0
KDR	0.026	0.005	-10000	0	-10000	0	0
PLCB2	0.014	0.074	0.23	19	-0.31	5	24
RAC1	0.025	0.007	-10000	0	-10000	0	0
RhoA/GTP	-0.001	0.047	-10000	0	-0.28	6	6
receptor internalization	-0.003	0.052	-10000	0	-0.31	6	6
PTGS2	-0.033	0.14	-10000	0	-0.54	14	14
Rac1/GTP	-0.001	0.048	-10000	0	-0.29	6	6
RHOA	0.025	0.007	-10000	0	-10000	0	0
VEGFA	0.024	0.016	-10000	0	-0.32	1	1
negative regulation of T cell proliferation	-0.034	0.13	0.2	1	-0.38	48	49
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	-0.012	0.12	-10000	0	-0.38	56	56
MAPK1	-0.038	0.13	-10000	0	-0.43	34	34
S1P1/S1P/PDGFB-D/PDGFRB	0.014	0.082	0.24	18	-0.29	4	22
ABCC1	0.02	0.046	-10000	0	-0.33	10	10

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.06	-10000	0	-0.32	18	18
mol:S1P	0.001	0	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.025	0.1	-10000	0	-0.25	69	69
GNAO1	-0.018	0.12	-10000	0	-0.37	68	68
S1P/S1P3/G12/G13	0.046	0.027	-10000	0	-0.19	4	4
AKT1	-0.009	0.11	-10000	0	-0.42	33	33
AKT3	0.009	0.068	-10000	0	-0.52	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.06	-10000	0	-0.32	18	18
GNAI2	0.026	0.007	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.02	0.052	-10000	0	-0.37	10	10
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.024	0.036	-10000	0	-0.36	5	5
S1PR2	0.026	0.015	-10000	0	-0.32	1	1
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.015	0.11	-10000	0	-0.36	30	30
MAPK3	-0.02	0.1	-10000	0	-0.34	30	30
MAPK1	-0.02	0.1	-10000	0	-0.35	29	29
JAK2	-0.018	0.12	0.19	1	-0.36	35	36
CXCR4	-0.027	0.1	-10000	0	-0.36	30	30
FLT1	0.027	0.007	-10000	0	-10000	0	0
RhoA/GDP	0.019	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.019	0.005	-10000	0	-10000	0	0
SRC	-0.021	0.097	-10000	0	-0.35	27	27
S1P/S1P3/Gi	-0.014	0.11	-10000	0	-0.37	29	29
RAC1	0.025	0.007	-10000	0	-10000	0	0
RhoA/GTP	-0.011	0.11	-10000	0	-0.34	31	31
VEGFA	0.025	0.017	-10000	0	-0.32	1	1
S1P/S1P2/Gi	-0.018	0.1	-10000	0	-0.32	36	36
VEGFR1 homodimer/VEGFA homodimer	0.038	0.019	-10000	0	-0.22	1	1
RHOA	0.025	0.007	-10000	0	-10000	0	0
S1P/S1P3/Gq	0.005	0.06	-10000	0	-0.24	26	26
GNAQ	0.026	0.006	-10000	0	-10000	0	0
GNAZ	-0.011	0.12	-10000	0	-0.37	56	56
G12/G13	0.036	0.012	-10000	0	-10000	0	0
GNA14	0.011	0.076	-10000	0	-0.37	22	22
GNA15	-0.007	0.1	-10000	0	-0.32	56	56
GNA12	0.025	0.007	-10000	0	-10000	0	0
GNA13	0.026	0.005	-10000	0	-10000	0	0
GNA11	0.026	0.006	-10000	0	-10000	0	0
Rac1/GTP	-0.013	0.11	-10000	0	-0.33	35	35

×

FAS signaling pathway (CD95)

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
SPTAN1	0	0.035	0.21	13	-0.19	1	14
RFC1	-0.002	0.025	0.18	6	-0.18	3	9
PRKDC	0.009	0.055	0.21	37	-0.18	3	40
RIPK1	0.026	0.008	-10000	0	-10000	0	0
CASP7	0.007	0.089	-10000	0	-0.57	12	12
FASLG/FAS/FADD/FAF1	0.018	0.053	0.18	29	-0.21	3	32
MAP2K4	0.004	0.11	0.28	4	-0.4	17	21
mol:ceramide	0.006	0.06	-10000	0	-0.26	8	8
GSN	-0.002	0.038	0.2	11	-0.22	6	17
FASLG/FAS/FADD/FAF1/Caspase 8	0.021	0.063	0.21	3	-0.25	5	8
FAS	0.023	0.014	-10000	0	-10000	0	0
BID	-0.015	0.021	0.25	1	-0.2	1	2
MAP3K1	0.016	0.087	0.24	6	-0.38	11	17
MAP3K7	0.025	0.007	-10000	0	-10000	0	0
RB1	0.003	0.042	0.21	21	-0.19	1	22
CFLAR	0.027	0.004	-10000	0	-10000	0	0
HGF/MET	0.013	0.093	-10000	0	-0.22	76	76
ARHGDIB	0	0.041	0.2	17	-0.18	3	20
FADD	0.02	0.015	-10000	0	-10000	0	0
actin filament polymerization	0.008	0.049	0.25	3	-0.2	11	14
NFKB1	0.002	0.098	-10000	0	-0.55	13	13
MAPK8	-0.008	0.14	0.31	3	-0.46	34	37
DFFA	0	0.033	0.2	12	-0.18	3	15
DNA fragmentation during apoptosis	-0.006	0.046	0.2	11	-10000	0	11
FAS/FADD/MET	0.033	0.042	-10000	0	-0.19	12	12
CFLAR/RIP1	0.038	0.012	-10000	0	-10000	0	0
FAIM3	0.013	0.067	-10000	0	-0.32	22	22
FAF1	0.022	0.018	-10000	0	-10000	0	0
PARP1	-0.001	0.03	0.2	9	-0.18	3	12
DFFB	0	0.033	0.2	12	-10000	0	12
CHUK	-0.003	0.091	-10000	0	-0.51	13	13
FASLG	0.005	0.077	-10000	0	-0.34	27	27
FAS/FADD	0.029	0.022	-10000	0	-10000	0	0
HGF	0.011	0.074	-10000	0	-0.36	23	23
LMNA	-0.008	0.04	0.19	7	-10000	0	7
CASP6	-0.003	0.021	0.17	4	-10000	0	4
CASP10	0.023	0.021	-10000	0	-0.37	1	1
CASP3	0.001	0.021	0.21	4	-10000	0	4
PTPN13	-0.008	0.11	-10000	0	-0.37	51	51
CASP8	-0.014	0.032	0.14	22	-10000	0	22
IL6	-0.052	0.29	-10000	0	-1.1	38	38
MET	0.018	0.05	-10000	0	-0.33	12	12
ICAD/CAD	0.001	0.046	0.29	11	-10000	0	11
FASLG/FAS/FADD/FAF1/Caspase 10	0.006	0.061	-10000	0	-0.26	8	8
activation of caspase activity by cytochrome c	-0.015	0.021	0.25	1	-0.2	1	2
PAK2	0.014	0.063	0.21	51	-0.19	3	54
BCL2	0.022	0.029	-10000	0	-0.37	3	3

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.033	0.011	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.025	0.007	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.022	0.043	-10000	0	-0.37	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.025	0.008	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.01	0.062	-10000	0	-0.18	71	71
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.025	0.007	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.026	0.005	-10000	0	-10000	0	0
FYN	0.026	0.005	-10000	0	-10000	0	0
MAP3K12	0.026	0.005	-10000	0	-10000	0	0
FGR	0.025	0.022	-10000	0	-0.35	2	2
p38 alpha/TAB1	-0.039	0.096	-10000	0	-0.38	32	32
PRKG1	0.02	0.048	-10000	0	-0.37	9	9
DUSP8	0.026	0.017	-10000	0	-0.37	1	1
PGK/cGMP/p38 alpha	-0.003	0.12	0.17	3	-0.4	27	30
apoptosis	-0.037	0.091	-10000	0	-0.36	32	32
RAL/GTP	0.034	0.01	-10000	0	-10000	0	0
LYN	0.024	0.022	-10000	0	-0.32	2	2
DUSP1	0.014	0.069	-10000	0	-0.37	18	18
PAK1	0.025	0.006	-10000	0	-10000	0	0
SRC	0.023	0.009	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.058	0.026	-10000	0	-10000	0	0
TRAF6	0.026	0.005	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.025	0.007	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.033	0.012	-10000	0	-10000	0	0
MAPK11	-0.001	0.12	0.23	23	-0.4	24	47
BLK	-0.063	0.16	-10000	0	-0.37	130	130
HCK	0.023	0.022	-10000	0	-0.32	2	2
MAP2K3	0.025	0.007	-10000	0	-10000	0	0
DUSP16	0.025	0.007	-10000	0	-10000	0	0
DUSP10	0.025	0.021	-10000	0	-0.32	2	2
TRAF6/MEKK3	0.033	0.009	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	-0.001	0.13	0.2	26	-0.43	28	54
positive regulation of innate immune response	-0.002	0.15	0.25	25	-0.48	26	51
LCK	-0.004	0.099	-10000	0	-0.32	52	52
p38alpha-beta/MKP7	0.007	0.14	0.26	22	-0.47	23	45
p38alpha-beta/MKP5	0.006	0.14	0.26	21	-0.47	24	45
PGK/cGMP	0.015	0.034	-10000	0	-0.26	9	9
PAK2	0.023	0.009	-10000	0	-10000	0	0
p38alpha-beta/MKP1	0.004	0.15	0.25	22	-0.47	26	48
CDC42	0.026	0.006	-10000	0	-10000	0	0
RALB	0.026	0.005	-10000	0	-10000	0	0
RALA	0.025	0.007	-10000	0	-10000	0	0
PAK3	-0.047	0.15	-10000	0	-0.37	109	109

×

FOXM1 transcription factor network

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
NFATC3	0.004	0.27	-10000	0	-0.98	9	9
PLK1	0.009	0.19	-10000	0	-0.95	18	18
BIRC5	0.019	0.14	-10000	0	-0.96	8	8
HSPA1B	0.005	0.27	-10000	0	-0.98	10	10
MAP2K1	0.024	0.038	-10000	0	-10000	0	0
BRCA2	0.006	0.27	-10000	0	-0.96	10	10
FOXM1	-0.004	0.3	-10000	0	-1.1	13	13
XRCC1	0.005	0.27	0.54	1	-0.95	10	11
FOXM1B/p19	-0.042	0.28	-10000	0	-1	18	18
Cyclin D1/CDK4	-0.005	0.26	-10000	0	-0.9	11	11
CDC2	0.002	0.28	-10000	0	-0.97	13	13
TGFA	0.002	0.26	-10000	0	-0.89	11	11
SKP2	0.019	0.27	-10000	0	-0.95	11	11
CCNE1	0.011	0.067	-10000	0	-0.32	22	22
CKS1B	0.003	0.27	-10000	0	-0.93	13	13
RB1	0.019	0.16	-10000	0	-0.72	8	8
FOXM1C/SP1	0.006	0.29	-10000	0	-1	13	13
AURKB	-0.02	0.23	-10000	0	-0.86	37	37
CENPF	-0.019	0.29	0.54	1	-0.99	14	15
CDK4	0.024	0.021	-10000	0	-10000	0	0
MYC	0.003	0.23	-10000	0	-0.84	10	10
CHEK2	0.024	0.038	-10000	0	-10000	0	0
ONECUT1	-0.001	0.28	-10000	0	-0.98	11	11
CDKN2A	-0.071	0.15	-10000	0	-0.33	153	153
LAMA4	0.002	0.27	-10000	0	-0.96	11	11
FOXM1B/HNF6	-0.006	0.3	-10000	0	-1.1	11	11
FOS	-0.029	0.35	-10000	0	-1.1	38	38
SP1	0.027	0.006	-10000	0	-10000	0	0
CDC25B	0.014	0.27	0.57	1	-0.97	9	10
response to radiation	0.006	0.021	-10000	0	-10000	0	0
CENPB	0.015	0.27	0.57	1	-0.96	9	10
CENPA	-0.001	0.28	-10000	0	-0.96	12	12
NEK2	-0.002	0.28	0.54	1	-0.99	12	13
HIST1H2BA	0	0.27	-10000	0	-0.96	11	11
CCNA2	0.025	0.02	-10000	0	-0.34	1	1
EP300	0.026	0.005	-10000	0	-10000	0	0
CCNB1/CDK1	-0.003	0.29	-10000	0	-1	13	13
CCNB2	0.001	0.27	0.57	1	-0.96	13	14
CCNB1	0.002	0.28	-10000	0	-0.97	13	13
ETV5	0.02	0.27	0.54	1	-0.96	11	12
ESR1	-0.018	0.33	-10000	0	-1.2	28	28
CCND1	-0.015	0.25	-10000	0	-0.92	11	11
GSK3A	0.024	0.034	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.04	0.06	-10000	0	-0.2	14	14
CDK2	0.025	0.014	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.006	0.024	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	0.011	0.28	-10000	0	-0.99	13	13
GAS1	-0.053	0.39	-10000	0	-1.1	56	56
MMP2	0.001	0.28	-10000	0	-1	11	11
RB1/FOXM1C	0.013	0.26	0.5	1	-0.93	12	13
CREBBP	0.026	0.006	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1	0.013	0.12	-9999	-0.49	15	15
MAP3K8	0.026	0.016	-9999	-0.33	1	1
FOS	0.005	0.11	-9999	-0.51	12	12
PRKCA	0.024	0.02	-9999	-0.37	1	1
PTPN7	0.016	0.057	-9999	-0.33	15	15
HRAS	0.026	0.005	-9999	-10000	0	0
PRKCB	-0.001	0.097	-9999	-0.37	38	38
NRAS	0.026	0.006	-9999	-10000	0	0
RAS family/GTP	0.041	0.024	-9999	-10000	0	0
MAPK3	0.009	0.11	-9999	-0.54	16	16
MAP2K1	-0.004	0.11	-9999	-0.38	39	39
ELK1	0.024	0.013	-9999	-10000	0	0
BRAF	-0.003	0.089	-9999	-0.34	35	35
mol:GTP	0	0.001	-9999	-0.005	30	30
MAPK1	0.008	0.098	-9999	-0.5	12	12
RAF1	-0.006	0.099	-9999	-0.38	36	36
KRAS	0.024	0.009	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.03	0.039	-10000	0	-0.23	12	12
CRKL	0.014	0.1	0.27	7	-0.44	19	26
mol:PIP3	0	0.034	-10000	0	-0.8	1	1
AKT1	-0.003	0.039	-10000	0	-0.7	1	1
PTK2B	0.024	0.008	-10000	0	-10000	0	0
RAPGEF1	0.016	0.1	0.28	11	-0.44	16	27
RANBP10	0.026	0.006	-10000	0	-10000	0	0
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
HGF/MET/SHIP2	0.033	0.059	-10000	0	-0.2	31	31
MAP3K5	0.013	0.11	0.28	7	-0.42	22	29
HGF/MET/CIN85/CBL/ENDOPHILINS	0.045	0.061	-10000	0	-0.18	33	33
AP1	0.018	0.061	0.18	2	-0.23	25	27
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.026	0.005	-10000	0	-10000	0	0
apoptosis	-0.027	0.21	-10000	0	-0.71	49	49
STAT3 (dimer)	0.009	0.057	-10000	0	-0.29	7	7
GAB1/CRKL/SHP2/PI3K	0.038	0.097	0.28	3	-0.4	15	18
INPP5D	0.024	0.03	-10000	0	-0.34	4	4
CBL/CRK	0.026	0.1	0.27	8	-0.43	17	25
PTPN11	0.026	0.004	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.023	0.01	-10000	0	-10000	0	0
PTEN	0.025	0.007	-10000	0	-10000	0	0
ELK1	0.006	0.1	0.36	29	-10000	0	29
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.005	0.048	-10000	0	-0.22	12	12
PAK1	0.002	0.051	-10000	0	-0.67	1	1
HGF/MET/RANBP10	0.034	0.06	-10000	0	-0.2	32	32
HRAS	-0.001	0.11	-10000	0	-0.44	21	21
DOCK1	0.015	0.1	0.27	10	-0.43	17	27
GAB1	0.009	0.097	0.25	2	-0.47	17	19
CRK	0.012	0.1	0.26	10	-0.44	19	29
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.11	-10000	0	-0.4	32	32
JUN	0.027	0.003	-10000	0	-10000	0	0
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.003	0.04	-10000	0	-0.19	17	17
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
cell morphogenesis	0.041	0.11	0.3	32	-0.38	5	37
GRB2/SHC	0.024	0.057	0.17	4	-0.22	7	11
FOS	0.008	0.083	-10000	0	-0.37	27	27
GLMN	0.003	0.001	-10000	0	-10000	0	0
cell motility	0.006	0.1	0.36	29	-10000	0	29
HGF/MET/MUC20	0.02	0.055	-10000	0	-0.2	33	33
cell migration	0.023	0.056	0.17	4	-0.22	7	11
GRB2	0.026	0.005	-10000	0	-10000	0	0
CBL	0.025	0.007	-10000	0	-10000	0	0
MET/RANBP10	0.031	0.038	-10000	0	-0.23	11	11
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.014	0.043	-10000	0	-0.28	3	3
MET/MUC20	0.014	0.034	-10000	0	-0.22	12	12
RAP1B	0.021	0.1	0.26	19	-0.42	16	35
RAP1A	0.014	0.098	0.27	10	-0.42	16	26
HGF/MET/RANBP9	0.033	0.06	-10000	0	-0.2	33	33
RAF1	0.002	0.11	-10000	0	-0.42	21	21
STAT3	0.009	0.058	-10000	0	-0.29	7	7
cell proliferation	0.014	0.087	0.29	9	-0.34	14	23
RPS6KB1	0.007	0.031	-10000	0	-0.26	5	5
MAPK3	0.001	0.12	0.65	15	-10000	0	15
MAPK1	0.006	0.13	0.65	19	-10000	0	19
RANBP9	0.026	0.006	-10000	0	-10000	0	0
MAPK8	0.021	0.11	0.28	7	-0.39	14	21
SRC	0.004	0.04	-10000	0	-0.28	2	2
PI3K	0.021	0.052	0.17	4	-0.22	6	10
MET/Glomulin	0.005	0.043	-10000	0	-0.19	14	14
SOS1	0.027	0.003	-10000	0	-10000	0	0
MAP2K1	0.002	0.1	-10000	0	-0.4	20	20
MET	0.018	0.05	-10000	0	-0.33	12	12
MAP4K1	0.012	0.12	0.27	4	-0.46	23	27
PTK2	0.023	0.01	-10000	0	-10000	0	0
MAP2K2	0.002	0.1	-10000	0	-0.4	20	20
BAD	-0.004	0.04	-10000	0	-0.67	1	1
MAP2K4	0.012	0.1	0.27	8	-0.41	17	25
SHP2/GRB2/SOS1/GAB1	0.029	0.093	-10000	0	-0.38	19	19
INPPL1	0.025	0.007	-10000	0	-10000	0	0
PXN	0.027	0.004	-10000	0	-10000	0	0
SH3KBP1	0.026	0.005	-10000	0	-10000	0	0
HGS	-0.004	0.038	-10000	0	-0.18	15	15
PLCgamma1/PKC	0.017	0.007	-10000	0	-10000	0	0
HGF	0.011	0.074	-10000	0	-0.36	23	23
RASA1	0.025	0.008	-10000	0	-10000	0	0
NCK1	0.025	0.007	-10000	0	-10000	0	0
PTPRJ	0.025	0.022	-10000	0	-0.35	2	2
NCK/PLCgamma1	0.028	0.048	-10000	0	-0.19	11	11
PDPK1	-0.002	0.036	-10000	0	-0.74	1	1
HGF/MET/SHIP	0.033	0.063	-10000	0	-0.2	36	36

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.039	0.065	0.37	2	-10000	0	2
CRKL	0.024	0.066	0.22	19	-0.27	1	20
mol:DAG	0.021	0.043	-10000	0	-10000	0	0
HRAS	0.012	0.076	0.27	18	-10000	0	18
MAPK8	0.021	0.073	0.17	83	-10000	0	83
RAP1A	0.025	0.064	0.22	17	-10000	0	17
GAB1	0.024	0.064	0.22	17	-10000	0	17
MAPK14	0.021	0.072	0.17	82	-10000	0	82
EPO	0.002	0.083	-10000	0	-0.32	37	37
PLCG1	0.021	0.043	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.027	0.016	-10000	0	-10000	0	0
RAPGEF1	0.026	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.034	0.057	-10000	0	-0.18	29	29
GAB1/SHC/GRB2/SOS1	0.051	0.06	0.27	5	-10000	0	5
EPO/EPOR (dimer)	0.021	0.062	-10000	0	-0.22	33	33
IRS2	0.019	0.071	0.22	17	-0.27	3	20
STAT1	0.026	0.052	0.25	3	-10000	0	3
STAT5B	0.025	0.047	-10000	0	-10000	0	0
cell proliferation	0.011	0.078	0.18	86	-10000	0	86
GAB1/SHIP/PIK3R1/SHP2/SHC	0.036	0.051	-10000	0	-0.26	1	1
TEC	0.026	0.063	0.22	18	-10000	0	18
SOCS3	0.026	0.005	-10000	0	-10000	0	0
STAT1 (dimer)	0.026	0.052	0.24	3	-10000	0	3
JAK2	0.024	0.017	-10000	0	-10000	0	0
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.049	0.06	0.22	8	-10000	0	8
EPO/EPOR	0.021	0.062	-10000	0	-0.22	33	33
LYN	0.024	0.022	-10000	0	-0.32	2	2
TEC/VAV2	0.034	0.059	0.22	13	-10000	0	13
elevation of cytosolic calcium ion concentration	0.027	0.016	-10000	0	-10000	0	0
SHC1	0.026	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.035	0.055	-10000	0	-0.2	1	1
mol:IP3	0.021	0.043	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.038	0.073	0.29	6	-0.3	3	9
SH2B3	0.027	0.015	-10000	0	-10000	0	0
NFKB1	0.022	0.073	0.17	85	-10000	0	85
EPO/EPOR (dimer)/JAK2/SOCS3	0.003	0.038	-10000	0	-0.21	11	11
PTPN6	0.023	0.06	0.3	1	-10000	0	1
TEC/VAV2/GRB2	0.043	0.061	0.28	5	-10000	0	5
EPOR	0.027	0.016	-10000	0	-10000	0	0
INPP5D	0.024	0.03	-10000	0	-0.34	4	4
mol:GDP	0.05	0.061	0.27	5	-10000	0	5
SOS1	0.027	0.003	-10000	0	-10000	0	0
PLCG2	0.023	0.032	-10000	0	-0.32	5	5
CRKL/CBL/C3G	0.042	0.061	0.28	5	-0.26	1	6
VAV2	0.023	0.064	0.22	18	-10000	0	18
CBL	0.024	0.062	0.22	17	-10000	0	17
SHC/Grb2/SOS1	0.027	0.045	-10000	0	-10000	0	0
STAT5A	0.025	0.047	-10000	0	-10000	0	0
GRB2	0.026	0.005	-10000	0	-10000	0	0
STAT5 (dimer)	0.04	0.059	0.26	3	-0.3	2	5
LYN/PLCgamma2	0.033	0.03	-10000	0	-0.22	7	7
PTPN11	0.026	0.004	-10000	0	-10000	0	0
BTK	0.019	0.075	0.22	18	-0.29	4	22
BCL2	0.034	0.1	0.3	4	-0.74	6	10

×

mTOR signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.027	0.003	-10000	0	-10000	0	0
mol:PIP3	0.005	0.021	-10000	0	-0.23	3	3
FRAP1	0.02	0.062	0.22	1	-0.36	9	10
AKT1	0.018	0.056	0.16	74	-0.22	2	76
INSR	0.026	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.029	0.009	-10000	0	-10000	0	0
mol:GTP	0.044	0.055	0.21	15	-10000	0	15
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.01	0.022	-10000	0	-0.18	1	1
TSC2	0.026	0.006	-10000	0	-10000	0	0
RHEB/GDP	0.018	0.023	-10000	0	-10000	0	0
TSC1	0.026	0.005	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.021	0.032	-10000	0	-0.21	10	10
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.025	0.033	-10000	0	-0.2	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.026	0.005	-10000	0	-10000	0	0
RPS6KB1	0.036	0.068	0.25	18	-0.29	4	22
MAP3K5	0.007	0.036	0.19	13	-0.18	9	22
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
apoptosis	0.007	0.036	0.19	13	-0.18	9	22
mol:LY294002	0	0	-10000	0	-0.001	10	10
EIF4B	0.035	0.065	0.23	20	-0.26	4	24
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.048	0.056	0.22	12	-0.26	3	15
eIF4E/eIF4G1/eIF4A1	0.015	0.032	-10000	0	-0.24	7	7
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.032	0.031	-10000	0	-0.2	6	6
mTOR/RHEB/GTP/Raptor/GBL	0.023	0.049	0.14	66	-0.15	1	67
FKBP1A	0.025	0.008	-10000	0	-10000	0	0
RHEB/GTP	0.042	0.044	0.2	2	-10000	0	2
mol:Amino Acids	0	0	-10000	0	-0.001	10	10
FKBP12/Rapamycin	0.019	0.007	-10000	0	-10000	0	0
PDPK1	0.007	0.051	0.16	54	-0.24	2	56
EIF4E	0.026	0.005	-10000	0	-10000	0	0
ASK1/PP5C	0.033	0.089	-10000	0	-0.5	12	12
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	-0.002	0.074	-10000	0	-0.25	35	35
TSC1/TSC2	0.049	0.062	0.24	18	-10000	0	18
tumor necrosis factor receptor activity	0	0	0.001	10	-10000	0	10
RPS6	0.024	0.008	-10000	0	-10000	0	0
PPP5C	0.026	0.005	-10000	0	-10000	0	0
EIF4G1	0.024	0.009	-10000	0	-10000	0	0
IRS1	0.006	0.031	-10000	0	-0.22	10	10
INS	0.018	0.004	-10000	0	-10000	0	0
PTEN	0.025	0.007	-10000	0	-10000	0	0
PDK2	0.006	0.05	0.16	52	-0.24	2	54
EIF4EBP1	-0.024	0.22	-10000	0	-1	28	28
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
PPP2R5D	0.03	0.073	0.24	17	-0.33	9	26
peptide biosynthetic process	-0.009	0.02	0.18	6	-10000	0	6
RHEB	0.026	0.007	-10000	0	-10000	0	0
EIF4A1	0.025	0.007	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	93	-0.002	1	94
EEF2	-0.009	0.02	0.18	6	-10000	0	6
eIF4E/4E-BP1	-0.01	0.21	-10000	0	-0.94	28	28

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.011	0.005	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.034	0.02	-10000	0	-10000	0	0
CDKN1B	0.015	0.054	0.19	5	-0.28	10	15
CDKN1A	0.014	0.054	0.2	3	-0.28	10	13
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.024	0.016	-10000	0	-0.32	1	1
FOXO3	0.015	0.054	0.2	3	-0.27	16	19
AKT1	0.006	0.047	-10000	0	-0.28	15	15
BAD	0.027	0.004	-10000	0	-10000	0	0
AKT3	0.013	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.014	0.054	-10000	0	-0.28	12	12
AKT1/ASK1	0.036	0.067	0.2	4	-0.27	12	16
BAD/YWHAZ	0.045	0.022	-10000	0	-10000	0	0
RICTOR	0.024	0.009	-10000	0	-10000	0	0
RAF1	0.026	0.006	-10000	0	-10000	0	0
JNK cascade	-0.034	0.064	0.27	12	-0.19	1	13
TSC1	0.014	0.054	0.2	1	-0.28	11	12
YWHAZ	0.023	0.01	-10000	0	-10000	0	0
AKT1/RAF1	0.037	0.071	0.21	3	-0.28	13	16
EP300	0.026	0.005	-10000	0	-10000	0	0
mol:GDP	0.017	0.058	-10000	0	-0.28	18	18
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.014	0.053	-10000	0	-0.28	10	10
YWHAQ	0.027	0.003	-10000	0	-10000	0	0
TBC1D4	0.005	0.013	-10000	0	-0.17	3	3
MAP3K5	0.026	0.005	-10000	0	-10000	0	0
MAPKAP1	0.026	0.005	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.037	0.078	0.3	10	-0.19	36	46
YWHAH	0.026	0.005	-10000	0	-10000	0	0
AKT1S1	0.014	0.055	0.2	2	-0.28	11	13
CASP9	0.015	0.051	0.2	2	-0.28	10	12
YWHAB	0.023	0.01	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.038	0.075	0.27	11	-0.27	9	20
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.045	0.022	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
SRC	0.023	0.009	-10000	0	-10000	0	0
AKT2/p21CIP1	0.018	0.062	0.24	9	-0.26	12	21
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.004	0.068	-10000	0	-0.29	26	26
CHUK	0.014	0.053	0.2	1	-0.28	11	12
BAD/BCL-XL	0.033	0.063	0.22	3	-0.27	9	12
mTORC2	0.03	0.012	-10000	0	-10000	0	0
AKT2	0.013	0.004	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.041	0.097	0.23	32	-0.35	14	46
PDPK1	0.026	0.006	-10000	0	-10000	0	0
MDM2	0.02	0.064	0.2	14	-0.28	11	25
MAPKKK cascade	-0.036	0.07	0.28	13	-0.2	3	16
MDM2/Cbp/p300	0.054	0.078	0.28	11	-0.28	1	12
TSC1/TSC2	0.015	0.055	0.25	6	-0.28	9	15
proteasomal ubiquitin-dependent protein catabolic process	0.051	0.075	0.26	11	-0.26	7	18
glucose import	-0.047	0.09	0.21	12	-0.19	154	166
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.015	0.056	0.19	8	-0.38	2	10
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.048	0.089	0.21	10	-0.19	154	164
GSK3A	0.014	0.056	0.2	3	-0.28	12	15
FOXO1	0.015	0.057	0.2	8	-0.27	16	24
GSK3B	0.017	0.058	0.2	11	-0.28	10	21
SFN	-0.009	0.1	-10000	0	-0.33	58	58
G1/S transition of mitotic cell cycle	0.026	0.072	0.26	14	-0.28	8	22
p27Kip1/14-3-3 family	0.031	0.052	-10000	0	-0.39	1	1
PRKACA	0.026	0.005	-10000	0	-10000	0	0
KPNA1	0.025	0.006	-10000	0	-10000	0	0
HSP90AA1	0.026	0.006	-10000	0	-10000	0	0
YWHAG	0.026	0.006	-10000	0	-10000	0	0
RHEB	0.025	0.007	-10000	0	-10000	0	0
CREBBP	0.026	0.006	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.081	0.19	-10000	0	-0.62	8	8
CRP	-0.1	0.2	0.45	1	-0.63	14	15
cell cycle arrest	-0.11	0.21	-10000	0	-0.62	25	25
TIMP1	-0.072	0.18	-10000	0	-0.62	9	9
IL6ST	0.012	0.042	-10000	0	-0.38	5	5
Rac1/GDP	-0.035	0.1	-10000	0	-0.36	15	15
AP1	0.028	0.11	-10000	0	-0.48	10	10
GAB2	0.026	0.007	-10000	0	-10000	0	0
TNFSF11	-0.13	0.21	-10000	0	-0.59	32	32
HSP90B1	0.003	0.1	-10000	0	-0.72	8	8
GAB1	0.026	0.006	-10000	0	-10000	0	0
MAPK14	-0.013	0.078	-10000	0	-0.42	5	5
AKT1	0.025	0.074	0.25	2	-0.56	6	8
FOXO1	0.032	0.079	0.26	10	-0.54	5	15
MAP2K6	-0.025	0.08	-10000	0	-0.42	7	7
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.051	0.12	-10000	0	-0.43	11	11
MITF	-0.033	0.086	-10000	0	-0.35	19	19
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.026	0.005	-10000	0	-10000	0	0
A2M	-0.02	0.22	-10000	0	-1.1	23	23
CEBPB	0.025	0.012	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.012	0.084	-10000	0	-0.42	11	11
STAT3	-0.12	0.21	-10000	0	-0.65	25	25
STAT1	0.007	0.057	-10000	0	-0.74	3	3
CEBPD	-0.089	0.19	-10000	0	-0.62	9	9
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
PI3K	0.034	0.017	-10000	0	-10000	0	0
JUN	0.027	0.004	-10000	0	-10000	0	0
PIAS3/MITF	-0.024	0.094	-10000	0	-0.38	12	12
MAPK11	-0.013	0.077	-10000	0	-0.4	6	6
STAT3 (dimer)/FOXO1	-0.064	0.17	0.39	1	-0.54	6	7
GRB2/SOS1/GAB family	0.032	0.091	-10000	0	-0.39	4	4
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.01	0.076	-10000	0	-0.3	19	19
GRB2	0.027	0.005	-10000	0	-10000	0	0
JAK2	0.023	0.009	-10000	0	-10000	0	0
LBP	-0.064	0.18	0.4	2	-0.51	14	16
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
JAK1	0.021	0.016	-10000	0	-10000	0	0
MYC	-0.064	0.21	-10000	0	-0.68	11	11
FGG	-0.21	0.39	-10000	0	-0.97	117	117
macrophage differentiation	-0.11	0.21	-10000	0	-0.62	25	25
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.019	0.093	-10000	0	-0.26	18	18
JUNB	-0.095	0.18	0.44	1	-0.57	15	16
FOS	0.008	0.083	-10000	0	-0.37	27	27
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.03	0.092	-10000	0	-0.33	23	23
STAT1/PIAS1	-0.032	0.11	-10000	0	-0.35	12	12
GRB2/SOS1/GAB family/SHP2/PI3K	0.026	0.078	-10000	0	-0.58	6	6
STAT3 (dimer)	-0.11	0.22	-10000	0	-0.65	25	25
PRKCD	-0.06	0.15	0.32	8	-0.47	14	22
IL6R	0.013	0.058	-10000	0	-0.37	12	12
SOCS3	0.003	0.081	-10000	0	-0.58	1	1
gp130 (dimer)/JAK1/JAK1/LMO4	0.03	0.049	-10000	0	-0.23	6	6
Rac1/GTP	-0.042	0.11	-10000	0	-0.36	18	18
HCK	0.023	0.022	-10000	0	-0.32	2	2
MAPKKK cascade	0.02	0.1	-10000	0	-0.51	13	13
bone resorption	-0.12	0.21	-10000	0	-0.56	37	37
IRF1	-0.098	0.19	-10000	0	-0.61	10	10
mol:GDP	-0.037	0.09	-10000	0	-0.34	18	18
SOS1	0.027	0.003	-10000	0	-10000	0	0
VAV1	-0.037	0.091	-10000	0	-0.34	20	20
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.004	0.09	-10000	0	-0.4	17	17
PTPN11	-0.001	0.11	-10000	0	-0.76	11	11
IL6/IL6RA	-0.009	0.096	-10000	0	-0.26	68	68
gp130 (dimer)/TYK2/TYK2/LMO4	0.041	0.036	-10000	0	-0.23	6	6
gp130 (dimer)/JAK2/JAK2/LMO4	0.037	0.037	-10000	0	-0.23	6	6
IL6	-0.022	0.11	-10000	0	-0.35	61	61
PIAS3	0.026	0.006	-10000	0	-10000	0	0
PTPRE	0.028	0.024	-10000	0	-0.32	2	2
PIAS1	0.027	0.004	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.019	0.082	-10000	0	-0.29	28	28
LMO4	0.016	0.027	-10000	0	-0.39	1	1
STAT3 (dimer)/PIAS3	-0.1	0.21	-10000	0	-0.65	17	17
MCL1	0.031	0.079	-10000	0	-0.65	3	3

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.012	0.084	0.21	4	-10000	0	4
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.025	0.015	-10000	0	-0.32	1	1
STAT1 (dimer)/Cbp/p300	0.015	0.086	0.28	5	-0.25	5	10
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.027	0.044	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.02	0.058	-10000	0	-0.24	5	5
CaM/Ca2+	0.013	0.082	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.003	0.08	0.26	1	-0.27	5	6
AKT1	-0.001	0.091	0.28	15	-10000	0	15
MAP2K1	-0.021	0.069	0.22	8	-10000	0	8
MAP3K11	-0.012	0.074	0.2	6	-10000	0	6
IFNGR1	0.016	0.024	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.048	0.13	-10000	0	-0.38	25	25
Rap1/GTP	-0.011	0.056	-10000	0	-10000	0	0
CRKL/C3G	0.037	0.015	-10000	0	-0.22	1	1
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.014	0.094	-10000	0	-10000	0	0
CEBPB	0.008	0.12	0.27	10	-0.48	15	25
STAT3	0.026	0.005	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.003	0.14	-10000	0	-0.65	18	18
STAT1	-0.014	0.078	0.22	6	-0.27	5	11
CALM1	0.026	0.005	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.055	0.15	-10000	0	-0.32	139	139
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	0.002	0.083	0.28	5	-0.26	5	10
CEBPB/PTGES2/Cbp/p300	0.011	0.074	-10000	0	-0.36	7	7
mol:Ca2+	0.01	0.082	0.2	4	-10000	0	4
MAPK3	-0.014	0.12	-10000	0	-0.68	13	13
STAT1 (dimer)	-0.021	0.081	-10000	0	-0.33	5	5
MAPK1	-0.019	0.13	-10000	0	-0.68	17	17
JAK2	0.014	0.024	-10000	0	-10000	0	0
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
JAK1	0.017	0.024	-10000	0	-10000	0	0
CAMK2D	0.026	0.005	-10000	0	-10000	0	0
DAPK1	0.01	0.1	0.26	9	-0.5	13	22
SMAD7	0.002	0.048	0.15	16	-10000	0	16
CBL/CRKL/C3G	0.01	0.08	0.28	4	-10000	0	4
PI3K	0.01	0.076	-10000	0	-10000	0	0
IFNG	-0.056	0.15	-10000	0	-0.32	139	139
apoptosis	0.003	0.1	0.26	4	-0.42	21	25
CAMK2G	0.026	0.006	-10000	0	-10000	0	0
STAT3 (dimer)	0.026	0.005	-10000	0	-10000	0	0
CAMK2A	0.006	0.082	-10000	0	-0.34	31	31
CAMK2B	-0.06	0.16	-10000	0	-0.37	127	127
FRAP1	-0.002	0.085	0.23	21	-10000	0	21
PRKCD	-0.003	0.09	0.28	13	-10000	0	13
RAP1B	0.026	0.006	-10000	0	-10000	0	0
negative regulation of cell growth	-0.02	0.058	-10000	0	-0.24	5	5
PTPN2	0.025	0.007	-10000	0	-10000	0	0
EP300	0.027	0.005	-10000	0	-10000	0	0
IRF1	-0.009	0.066	0.26	6	-10000	0	6
STAT1 (dimer)/PIASy	-0.001	0.084	0.28	5	-0.26	5	10
SOCS1	-0.005	0.18	-10000	0	-1	18	18
mol:GDP	0.007	0.075	0.26	2	-10000	0	2
CASP1	0.001	0.051	0.15	14	-0.19	8	22
PTGES2	0.026	0.006	-10000	0	-10000	0	0
IRF9	0.018	0.046	0.15	21	-10000	0	21
mol:PI-3-4-5-P3	0	0.067	-10000	0	-10000	0	0
RAP1/GDP	0.003	0.066	-10000	0	-10000	0	0
CBL	-0.013	0.073	0.2	6	-10000	0	6
MAP3K1	-0.011	0.073	0.21	7	-10000	0	7
PIAS1	0.027	0.004	-10000	0	-10000	0	0
PIAS4	0.026	0.006	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.02	0.058	-10000	0	-0.24	5	5
PTPN11	-0.009	0.08	0.17	42	-10000	0	42
CREBBP	0.026	0.006	-10000	0	-10000	0	0
RAPGEF1	0.026	0.005	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.009	0.004	-10000	0	-10000	0	0
SNTA1	0.015	0.059	-10000	0	-0.37	13	13
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.011	0.017	-10000	0	-0.19	5	5
MAPK12	-0.007	0.027	0.19	1	-0.18	12	13
CCND1	0.007	0.035	-10000	0	-0.34	4	4
p38 gamma/SNTA1	0.011	0.048	0.19	11	-0.18	18	29
MAP2K3	0.025	0.007	-10000	0	-10000	0	0
PKN1	0.026	0.005	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.007	0.027	0.19	1	-0.18	12	13
MAP2K6	0	0.022	-10000	0	-0.2	7	7
MAPT	-0.04	0.11	0.15	9	-0.27	94	103
MAPK13	0.011	0.004	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.007	0.001	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.024	0.076	-10000	0	-0.4	1	1
UGCG	0.013	0.071	-10000	0	-0.61	7	7
AKT1/mTOR/p70S6K/Hsp90/TERT	0.017	0.1	0.22	8	-0.41	11	19
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.015	0.07	-10000	0	-0.6	7	7
mol:DAG	-0.006	0.12	-10000	0	-0.76	13	13
CaM/Ca2+/Calcineurin A alpha-beta B1	0.028	0.091	-10000	0	-0.37	11	11
FRAP1	0.022	0.098	-10000	0	-0.42	11	11
FOXO3	0.022	0.088	-10000	0	-0.4	6	6
AKT1	0.024	0.093	-10000	0	-0.42	7	7
GAB2	0.026	0.007	-10000	0	-10000	0	0
SMPD1	0.009	0.093	-10000	0	-0.65	11	11
SGMS1	0.01	0.078	-10000	0	-0.52	12	12
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	0.003	0.006	-10000	0	-10000	0	0
CALM1	0.026	0.005	-10000	0	-10000	0	0
cell proliferation	0.039	0.079	0.24	1	-0.36	6	7
EIF3A	0.026	0.005	-10000	0	-10000	0	0
PI3K	0.035	0.018	-10000	0	-10000	0	0
RPS6KB1	0.003	0.085	-10000	0	-0.81	5	5
mol:sphingomyelin	-0.006	0.12	-10000	0	-0.76	13	13
natural killer cell activation	0	0.001	-10000	0	-10000	0	0
JAK3	0.017	0.062	-10000	0	-0.32	19	19
PIK3R1	0.026	0.009	-10000	0	-10000	0	0
JAK1	0.028	0.004	-10000	0	-10000	0	0
NFKB1	0.026	0.004	-10000	0	-10000	0	0
MYC	0.057	0.12	0.34	10	-0.77	3	13
MYB	-0.021	0.13	-10000	0	-1	5	5
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.02	0.081	-10000	0	-0.36	6	6
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.025	0.086	-10000	0	-0.74	5	5
mol:PI-3-4-5-P3	0.02	0.08	-10000	0	-0.36	6	6
Rac1/GDP	0.018	0.012	-10000	0	-10000	0	0
T cell proliferation	0.023	0.078	0.25	7	-0.34	5	12
SHC1	0.027	0.005	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.003	0.013	-10000	0	-0.029	116	116
PRKCZ	0.022	0.077	0.23	6	-0.35	5	11
NF kappa B1 p50/RelA	0.04	0.097	-10000	0	-0.39	8	8
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.01	0.051	-10000	0	-0.34	4	4
HSP90AA1	0.026	0.006	-10000	0	-10000	0	0
RELA	0.026	0.005	-10000	0	-10000	0	0
IL2RA	-0.009	0.1	-10000	0	-0.32	59	59
IL2RB	0.021	0.05	-10000	0	-0.33	12	12
TERT	-0.044	0.14	-10000	0	-0.32	114	114
E2F1	-0.005	0.076	-10000	0	-0.4	7	7
SOS1	0.027	0.004	-10000	0	-10000	0	0
RPS6	0.024	0.008	-10000	0	-10000	0	0
mol:cAMP	0.001	0.006	0.014	116	-10000	0	116
PTPN11	0.027	0.005	-10000	0	-10000	0	0
IL2RG	0.007	0.084	-10000	0	-0.32	37	37
actin cytoskeleton organization	0.023	0.078	0.25	7	-0.34	5	12
GRB2	0.026	0.005	-10000	0	-10000	0	0
IL2	0.022	0.022	-10000	0	-0.32	2	2
PIK3CA	0.025	0.01	-10000	0	-10000	0	0
Rac1/GTP	0.04	0.025	-10000	0	-10000	0	0
LCK	-0.003	0.099	-10000	0	-0.32	52	52
BCL2	0.019	0.11	-10000	0	-0.74	7	7

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.018	0.03	-10000	0	-0.2	9	9
epithelial cell differentiation	0.046	0.036	-10000	0	-0.19	9	9
CYFIP2	0.008	0.081	-10000	0	-0.37	26	26
ENAH	-0.003	0.053	0.22	8	-10000	0	8
EGFR	0.017	0.052	-10000	0	-0.36	11	11
EPHA2	0.024	0.029	-10000	0	-0.32	4	4
MYO6	-0.005	0.043	0.18	21	-10000	0	21
CTNNB1	0.025	0.007	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.038	0.056	-10000	0	-0.22	24	24
AQP5	-0.087	0.16	0.21	1	-0.42	98	99
CTNND1	0.026	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.006	0.04	0.18	19	-10000	0	19
regulation of calcium-dependent cell-cell adhesion	-0.013	0.051	0.18	17	-0.32	1	18
EGF	-0.031	0.13	-10000	0	-0.32	94	94
NCKAP1	0.027	0.004	-10000	0	-10000	0	0
AQP3	-0.008	0.081	0.21	1	-0.42	14	15
cortical microtubule organization	0.046	0.036	-10000	0	-0.19	9	9
GO:0000145	-0.006	0.038	0.16	18	-10000	0	18
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.051	0.038	-10000	0	-0.19	9	9
MLLT4	0.026	0.006	-10000	0	-10000	0	0
ARF6/GDP	-0.019	0.023	-10000	0	-10000	0	0
ARF6	0.026	0.005	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.058	0.031	-10000	0	-0.17	4	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.004	0.033	0.17	12	-10000	0	12
PVRL2	0.026	0.006	-10000	0	-10000	0	0
ZYX	-0.006	0.042	0.18	20	-10000	0	20
ARF6/GTP	0.062	0.035	-10000	0	-10000	0	0
CDH1	0.019	0.052	-10000	0	-0.37	10	10
EGFR/EGFR/EGF/EGF	0.007	0.076	-10000	0	-0.33	2	2
RhoA/GDP	0.046	0.036	-10000	0	-10000	0	0
actin cytoskeleton organization	-0.006	0.039	0.17	21	-10000	0	21
IGF-1R heterotetramer	0.024	0.024	-10000	0	-0.37	2	2
GIT1	0.027	0.004	-10000	0	-10000	0	0
IGF1R	0.024	0.024	-10000	0	-0.37	2	2
IGF1	-0.021	0.13	-10000	0	-0.36	74	74
DIAPH1	-0.001	0.17	-10000	0	-0.53	36	36
Wnt receptor signaling pathway	-0.046	0.036	0.19	9	-10000	0	9
RHOA	0.025	0.007	-10000	0	-10000	0	0
RhoA/GTP	-0.019	0.023	-10000	0	-10000	0	0
CTNNA1	0.025	0.007	-10000	0	-10000	0	0
VCL	-0.007	0.04	0.17	21	-10000	0	21
EFNA1	0.026	0.004	-10000	0	-10000	0	0
LPP	-0.01	0.037	0.17	12	-0.29	1	13
Ephrin A1/EPHA2	0.038	0.037	-10000	0	-10000	0	0
SEC6/SEC8	-0.016	0.021	-10000	0	-10000	0	0
MGAT3	-0.013	0.051	0.18	17	-0.32	1	18
HGF/MET	0.027	0.057	-10000	0	-0.31	1	1
HGF	0.011	0.074	-10000	0	-0.36	23	23
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.018	0.031	-10000	0	-0.2	9	9
actin cable formation	0.024	0.082	0.24	37	-0.3	2	39
KIAA1543	-0.007	0.042	0.17	20	-10000	0	20
KIFC3	-0.008	0.038	0.18	15	-10000	0	15
NCK1	0.025	0.007	-10000	0	-10000	0	0
EXOC3	0.024	0.009	-10000	0	-10000	0	0
ACTN1	-0.007	0.042	0.18	19	-10000	0	19
NCK1/GIT1	0.036	0.012	-10000	0	-10000	0	0
mol:GDP	0.046	0.036	-10000	0	-0.19	9	9
EXOC4	0.025	0.007	-10000	0	-10000	0	0
STX4	-0.006	0.041	0.18	19	-10000	0	19
PIP5K1C	-0.006	0.041	0.18	19	-10000	0	19
LIMA1	0.027	0.004	-10000	0	-10000	0	0
ABI1	0.026	0.005	-10000	0	-10000	0	0
ROCK1	0.004	0.066	0.25	14	-10000	0	14
adherens junction assembly	-0.008	0.083	0.26	4	-0.59	6	10
IGF-1R heterotetramer/IGF1	0.014	0.076	-10000	0	-0.32	3	3
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.037	0.012	-10000	0	-10000	0	0
MET	0.018	0.05	-10000	0	-0.33	12	12
PLEKHA7	-0.007	0.044	0.18	20	-10000	0	20
mol:GTP	0.056	0.031	-10000	0	-0.17	4	4
establishment of epithelial cell apical/basal polarity	0.02	0.087	0.3	24	-10000	0	24
cortical actin cytoskeleton stabilization	0.018	0.03	-10000	0	-0.2	9	9
regulation of cell-cell adhesion	-0.006	0.039	0.17	21	-10000	0	21
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.018	0.031	-10000	0	-0.2	9	9

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.002	0.058	0.29	2	-10000	0	2
DAPP1	-0.001	0.11	0.21	27	-0.36	20	47
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.018	0.14	0.24	3	-0.47	23	26
mol:DAG	0.014	0.087	0.19	55	-0.21	7	62
HRAS	0.028	0.008	-10000	0	-10000	0	0
RAP1A	0.028	0.007	-10000	0	-10000	0	0
ARF5/GDP	0.03	0.076	0.2	3	-0.3	12	15
PLCG2	0.023	0.032	-10000	0	-0.32	5	5
PLCG1	0.023	0.01	-10000	0	-10000	0	0
ARF5	0.026	0.005	-10000	0	-10000	0	0
mol:GTP	0.001	0.052	0.2	5	-10000	0	5
ARF1/GTP	0.01	0.051	0.24	8	-10000	0	8
RHOA	0.025	0.007	-10000	0	-10000	0	0
YES1	0.025	0.007	-10000	0	-10000	0	0
RAP1A/GTP	0.001	0.054	0.16	61	-10000	0	61
ADAP1	-0.003	0.05	0.22	2	-10000	0	2
ARAP3	0.001	0.051	0.19	6	-10000	0	6
INPPL1	0.025	0.007	-10000	0	-10000	0	0
PREX1	0.023	0.01	-10000	0	-10000	0	0
ARHGEF6	0.022	0.043	-10000	0	-0.37	7	7
ARHGEF7	0.025	0.007	-10000	0	-10000	0	0
ARF1	0.026	0.005	-10000	0	-10000	0	0
NRAS	0.028	0.008	-10000	0	-10000	0	0
FYN	0.026	0.005	-10000	0	-10000	0	0
ARF6	0.026	0.005	-10000	0	-10000	0	0
FGR	0.025	0.022	-10000	0	-0.35	2	2
mol:Ca2+	0.012	0.058	0.18	30	-10000	0	30
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.009	0.076	-10000	0	-0.34	27	27
ZAP70	0.013	0.069	-10000	0	-0.33	23	23
mol:IP3	0.009	0.067	0.15	58	-0.17	2	60
LYN	0.024	0.022	-10000	0	-0.32	2	2
ARF1/GDP	0.029	0.077	0.19	5	-0.31	11	16
RhoA/GDP	0.042	0.058	0.22	19	-10000	0	19
PDK1/Src/Hsp90	0.045	0.022	-10000	0	-10000	0	0
BLNK	0.007	0.085	-10000	0	-0.37	28	28
actin cytoskeleton reorganization	0.035	0.08	0.24	35	-10000	0	35
SRC	0.023	0.009	-10000	0	-10000	0	0
PLEKHA2	-0.009	0.015	0.2	1	-0.19	2	3
RAC1	0.025	0.007	-10000	0	-10000	0	0
PTEN	0.021	0.016	-10000	0	-10000	0	0
HSP90AA1	0.026	0.006	-10000	0	-10000	0	0
ARF6/GTP	-0.001	0.054	0.28	1	-10000	0	1
RhoA/GTP	-0.001	0.052	0.2	3	-10000	0	3
Src family/SYK family/BLNK-LAT	-0.019	0.1	-10000	0	-0.36	21	21
BLK	-0.063	0.16	-10000	0	-0.37	130	130
PDPK1	0.026	0.006	-10000	0	-10000	0	0
CYTH1	-0.001	0.05	0.2	3	-10000	0	3
HCK	0.023	0.022	-10000	0	-0.32	2	2
CYTH3	-0.002	0.047	0.22	2	-10000	0	2
CYTH2	-0.001	0.05	0.2	3	-10000	0	3
KRAS	0.025	0.01	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.013	0.058	-10000	0	-0.39	7	7
SGK1	0.017	0.065	-10000	0	-0.39	9	9
INPP5D	0.024	0.03	-10000	0	-0.34	4	4
mol:GDP	0.018	0.077	0.19	6	-0.32	12	18
SOS1	0.027	0.003	-10000	0	-10000	0	0
SYK	0.025	0.017	-10000	0	-0.37	1	1
ARF6/GDP	0.029	0.057	0.21	20	-10000	0	20
mol:PI-3-4-5-P3	-0.001	0.046	-10000	0	-10000	0	0
ARAP3/RAP1A/GTP	0.001	0.054	0.16	61	-10000	0	61
VAV1	0.018	0.053	-10000	0	-0.34	13	13
mol:PI-3-4-P2	0.01	0.02	-10000	0	-0.23	4	4
RAS family/GTP/PI3K Class I	0.04	0.038	0.2	6	-10000	0	6
PLEKHA1	-0.01	0.018	0.2	1	-0.2	3	4
Rac1/GDP	0.026	0.075	0.19	2	-0.31	12	14
LAT	0.022	0.038	-10000	0	-0.32	7	7
Rac1/GTP	0.011	0.064	-10000	0	-0.34	8	8
ITK	-0.005	0.053	0.22	2	-10000	0	2
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.009	0.099	0.21	47	-0.3	7	54
LCK	-0.004	0.099	-10000	0	-0.32	52	52
BTK	-0.006	0.056	0.22	2	-10000	0	2

×

PLK2 and PLK4 events

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
PLK2	0.021	0.036	-9999	-0.32	6	6
PLK4	0.02	0.047	-9999	-0.32	11	11
regulation of centriole replication	0.005	0.038	-9999	-0.22	17	17

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.023	0.038	-10000	0	-0.32	7	7
ANTXR2	0.023	0.037	-10000	0	-0.37	5	5
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.006	-10000	0	-0.044	12	12
monocyte activation	0.001	0.074	-10000	0	-0.35	23	23
MAP2K2	-0.012	0.12	-10000	0	-0.56	29	29
MAP2K1	-0.004	0.006	-10000	0	-10000	0	0
MAP2K7	-0.004	0.006	-10000	0	-10000	0	0
MAP2K6	-0.006	0.02	-10000	0	-0.18	7	7
CYAA	-0.009	0.023	-10000	0	-0.17	12	12
MAP2K4	-0.004	0.006	-10000	0	-10000	0	0
IL1B	-0.013	0.05	0.18	9	-0.16	49	58
Channel	0.029	0.031	-10000	0	-0.18	12	12
NLRP1	-0.006	0.019	-10000	0	-0.16	8	8
CALM1	0.026	0.005	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.002	0.071	-10000	0	-0.38	20	20
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.006	0.044	12	-10000	0	12
MAPK3	-0.004	0.006	-10000	0	-10000	0	0
MAPK1	-0.004	0.006	-10000	0	-10000	0	0
PGR	-0.018	0.048	-10000	0	-0.18	45	45
PA/Cellular Receptors	0.03	0.034	-10000	0	-0.2	12	12
apoptosis	-0.002	0.006	-10000	0	-0.044	12	12
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.029	0.028	-10000	0	-0.16	12	12
macrophage activation	-0.007	0.006	-10000	0	-10000	0	0
TNF	0.001	0.091	-10000	0	-0.33	42	42
VCAM1	0.005	0.063	-10000	0	-0.34	17	17
platelet activation	-0.002	0.071	-10000	0	-0.38	20	20
MAPKKK cascade	0.001	0.017	0.1	1	-0.097	2	3
IL18	-0.005	0.024	0.15	2	-0.17	9	11
negative regulation of macrophage activation	-0.002	0.006	-10000	0	-0.044	12	12
LEF	-0.002	0.006	-10000	0	-0.044	12	12
CASP1	-0.002	0.015	-10000	0	-0.12	7	7
mol:cAMP	-0.002	0.072	-10000	0	-0.38	20	20
necrosis	-0.002	0.006	-10000	0	-0.044	12	12
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.029	0.029	-10000	0	-0.17	12	12
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC2	0.026	0.005	-10000	0	-10000	0	0
GNB1/GNG2	0.039	0.051	-10000	0	-0.22	20	20
forebrain development	-0.03	0.14	-10000	0	-0.49	22	22
GNAO1	-0.02	0.12	-10000	0	-0.37	68	68
SMO/beta Arrestin2	0.022	0.054	-10000	0	-0.26	18	18
SMO	0.009	0.069	-10000	0	-0.37	18	18
ARRB2	0.024	0.009	-10000	0	-10000	0	0
GLI3/SPOP	0.028	0.089	0.24	2	-0.41	8	10
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
GSK3B	0.025	0.007	-10000	0	-10000	0	0
GNAI2	0.024	0.008	-10000	0	-10000	0	0
SIN3/HDAC complex	0.06	0.025	-10000	0	-10000	0	0
GNAI1	0.018	0.052	-10000	0	-0.37	10	10
XPO1	0.021	0.019	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.027	0.14	-10000	0	-0.52	20	20
SAP30	0.026	0.007	-10000	0	-10000	0	0
mol:GDP	0.009	0.069	-10000	0	-0.37	18	18
MIM/GLI2A	0.004	0.067	-10000	0	-0.4	9	9
IFT88	0.026	0.006	-10000	0	-10000	0	0
GNAI3	0.026	0.006	-10000	0	-10000	0	0
GLI2	0.006	0.072	0.2	4	-0.28	17	21
GLI3	0.016	0.09	0.25	2	-0.4	10	12
CSNK1D	0.026	0.005	-10000	0	-10000	0	0
CSNK1E	0.026	0.005	-10000	0	-10000	0	0
SAP18	0.026	0.006	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.026	0.006	-10000	0	-10000	0	0
GNG2	0.025	0.022	-10000	0	-0.35	2	2
Gi family/GTP	-0.032	0.12	-10000	0	-0.36	48	48
SIN3B	0.027	0.005	-10000	0	-10000	0	0
SIN3A	0.026	0.005	-10000	0	-10000	0	0
GLI3/Su(fu)	0.021	0.088	0.28	1	-0.44	9	10
GLI2/Su(fu)	0.008	0.087	0.19	1	-0.35	15	16
FOXA2	-0.12	0.36	-10000	0	-0.93	96	96
neural tube patterning	-0.03	0.14	-10000	0	-0.49	22	22
SPOP	0.027	0.003	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.022	0.047	-10000	0	-0.31	1	1
GNB1	0.026	0.006	-10000	0	-10000	0	0
CSNK1G2	0.026	0.006	-10000	0	-10000	0	0
CSNK1G3	0.025	0.007	-10000	0	-10000	0	0
MTSS1	0.004	0.067	-10000	0	-0.4	9	9
embryonic limb morphogenesis	-0.03	0.14	-10000	0	-0.49	22	22
SUFU	0.013	0.033	-10000	0	-0.34	1	1
LGALS3	0.025	0.024	-10000	0	-0.37	2	2
catabolic process	0.024	0.12	0.28	1	-0.44	19	20
GLI3A/CBP	0.021	0.041	-10000	0	-0.31	1	1
KIF3A	0.025	0.007	-10000	0	-10000	0	0
GLI1	-0.031	0.14	-10000	0	-0.5	22	22
RAB23	0.02	0.045	-10000	0	-0.32	10	10
CSNK1A1	0.025	0.007	-10000	0	-10000	0	0
IFT172	0.027	0.003	-10000	0	-10000	0	0
RBBP7	0.026	0.005	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.021	0.049	-10000	0	-0.27	2	2
GNAZ	-0.012	0.12	-10000	0	-0.37	56	56
RBBP4	0.027	0.004	-10000	0	-10000	0	0
CSNK1G1	0.026	0.005	-10000	0	-10000	0	0
PIAS1	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.026	0.005	-10000	0	-10000	0	0
GLI2/SPOP	0.016	0.081	0.2	1	-0.33	11	12
STK36	0.021	0.019	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.029	0.12	-10000	0	-0.37	43	43
PTCH1	-0.031	0.15	-10000	0	-0.8	11	11
MIM/GLI1	-0.046	0.19	-10000	0	-0.48	77	77
CREBBP	0.021	0.041	-10000	0	-0.31	1	1
Su(fu)/SIN3/HDAC complex	0.018	0.073	-10000	0	-0.43	11	11

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.026	0.005	-10000	0	-10000	0	0
HDAC3	0.025	0.006	-10000	0	-10000	0	0
VDR	0.026	0.004	-10000	0	-10000	0	0
Cbp/p300/PCAF	0.046	0.034	-10000	0	-0.22	7	7
EP300	0.026	0.005	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.006	0.056	-10000	0	-0.34	8	8
KAT2B	0.021	0.043	-10000	0	-0.37	7	7
MAPK14	0.026	0.005	-10000	0	-10000	0	0
AKT1	-0.006	0.06	0.21	3	-0.23	12	15
RAR alpha/9cRA/Cyclin H	0.012	0.07	-10000	0	-0.31	3	3
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0	0.068	-10000	0	-0.3	16	16
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.003	0.057	-10000	0	-0.29	3	3
NCOR2	0.026	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.02	0.003	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.031	0.1	-10000	0	-0.56	8	8
NCOA2	0.024	0.018	-10000	0	-0.37	1	1
NCOA3	0.023	0.01	-10000	0	-10000	0	0
NCOA1	0.027	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.026	0.004	-10000	0	-10000	0	0
RARG	0.025	0.029	-10000	0	-0.32	4	4
RAR gamma1/9cRA	0.033	0.02	-10000	0	-0.18	4	4
MAPK3	0.027	0.005	-10000	0	-10000	0	0
MAPK1	0.026	0.005	-10000	0	-10000	0	0
MAPK8	0.027	0.004	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.029	0.094	-10000	0	-0.39	17	17
RARA	-0.011	0.055	-10000	0	-0.22	17	17
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.002	0.067	-10000	0	-0.3	16	16
PRKCA	0.027	0.017	-10000	0	-0.37	1	1
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.035	0.11	-10000	0	-0.53	10	10
RXRG	-0.1	0.14	-10000	0	-0.31	169	169
RXRA	-0.007	0.054	-10000	0	-0.26	3	3
RXRB	-0.027	0.071	-10000	0	-0.26	15	15
VDR/Vit D3/DNA	0.02	0.003	-10000	0	-10000	0	0
RBP1	0.008	0.077	-10000	0	-0.33	29	29
CRBP1/9-cic-RA	0.007	0.053	-10000	0	-0.22	29	29
RARB	0.024	0.033	-10000	0	-0.37	4	4
PRKCG	-0.093	0.17	-10000	0	-0.32	203	203
MNAT1	0.026	0.005	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.034	0.097	0.26	1	-0.44	16	17
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.026	0.1	0.24	1	-0.44	15	16
proteasomal ubiquitin-dependent protein catabolic process	0.004	0.084	0.22	3	-0.31	15	18
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.036	0.11	-10000	0	-0.54	10	10
positive regulation of DNA binding	0.005	0.062	-10000	0	-0.29	3	3
NRIP1	-0.034	0.11	-10000	0	-0.58	6	6
RXRs/RARs	-0.038	0.12	-10000	0	-0.48	16	16
RXRs/RXRs/DNA/9cRA	-0.039	0.088	-10000	0	-0.4	17	17
PRKACA	0.026	0.005	-10000	0	-10000	0	0
CDK7	0.025	0.008	-10000	0	-10000	0	0
TFIIH	0.048	0.018	-10000	0	-10000	0	0
RAR alpha/9cRA	0.019	0.064	-10000	0	-0.24	2	2
CCNH	0.025	0.008	-10000	0	-10000	0	0
CREBBP	0.026	0.006	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.044	0.026	-10000	0	-10000	0	0

×

Thromboxane A2 receptor 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
TGM2	0.019	0.04	-10000	0	-0.34	7	7
GNB1/GNG2	-0.028	0.036	-10000	0	-0.17	8	8
AKT1	-0.008	0.077	0.19	9	-0.29	15	24
EGF	-0.031	0.13	-10000	0	-0.32	94	94
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	0.008	0.058	0.22	11	-0.34	1	12
mol:Ca2+	-0.015	0.084	0.25	4	-0.27	16	20
LYN	0.006	0.053	0.2	12	-0.34	1	13
RhoA/GTP	-0.009	0.036	-10000	0	-0.13	3	3
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.019	0.089	0.25	5	-0.3	7	12
GNG2	0.025	0.022	-10000	0	-0.35	2	2
ARRB2	0.025	0.007	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.014	0.12	-10000	0	-0.58	21	21
G beta5/gamma2	-0.029	0.05	-10000	0	-0.23	6	6
PRKCH	-0.018	0.089	0.26	5	-0.31	7	12
DNM1	0.017	0.055	-10000	0	-0.32	15	15
TXA2/TP beta/beta Arrestin3	0.005	0.064	-10000	0	-0.5	8	8
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.008	0.083	-10000	0	-0.37	27	27
G12 family/GTP	-0.024	0.071	-10000	0	-0.27	6	6
ADRBK1	0.026	0.006	-10000	0	-10000	0	0
ADRBK2	0.026	0.005	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.032	0.012	-10000	0	-10000	0	0
mol:GDP	0.008	0.079	0.31	15	-0.22	4	19
mol:NADP	0.023	0.029	-10000	0	-0.32	4	4
RAB11A	0.026	0.004	-10000	0	-10000	0	0
PRKG1	0.02	0.048	-10000	0	-0.37	9	9
mol:IP3	-0.02	0.098	0.27	4	-0.33	16	20
cell morphogenesis	0.032	0.012	-10000	0	-10000	0	0
PLCB2	-0.031	0.12	0.31	2	-0.44	16	18
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	-0.026	0.08	0.24	5	-0.27	12	17
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.007	0.053	0.22	9	-0.34	1	10
RHOA	0.025	0.007	-10000	0	-10000	0	0
PTGIR	0.025	0.017	-10000	0	-0.37	1	1
PRKCB1	-0.02	0.093	0.25	4	-0.32	12	16
GNAQ	0.026	0.006	-10000	0	-10000	0	0
mol:L-citrulline	0.023	0.029	-10000	0	-0.32	4	4
TXA2/TXA2-R family	-0.031	0.12	0.3	3	-0.44	9	12
LCK	-0.002	0.069	0.21	14	-0.3	2	16
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.02	0.055	-10000	0	-0.41	1	1
TXA2-R family/G12 family/GDP/G beta/gamma	0.015	0.074	-10000	0	-0.41	16	16
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.023	0.053	-10000	0	-0.41	1	1
MAPK14	-0.01	0.069	0.2	10	-0.22	4	14
TGM2/GTP	-0.03	0.1	-10000	0	-0.38	12	12
MAPK11	-0.012	0.066	0.19	7	-0.22	4	11
ARHGEF1	-0.013	0.048	0.18	1	-0.17	4	5
GNAI2	0.025	0.007	-10000	0	-10000	0	0
JNK cascade	-0.022	0.096	0.27	4	-0.33	9	13
RAB11/GDP	0.026	0.004	-10000	0	-10000	0	0
ICAM1	-0.015	0.077	0.22	4	-0.26	8	12
cAMP biosynthetic process	-0.023	0.094	0.27	4	-0.32	13	17
Gq family/GTP/EBP50	0.003	0.055	0.22	7	-0.23	13	20
actin cytoskeleton reorganization	0.032	0.012	-10000	0	-10000	0	0
SRC	0.006	0.05	0.22	6	-0.34	1	7
GNB5	0.026	0.004	-10000	0	-10000	0	0
GNB1	0.026	0.006	-10000	0	-10000	0	0
EGF/EGFR	0.001	0.087	0.22	28	-0.25	13	41
VCAM1	-0.016	0.077	0.23	4	-0.26	8	12
TP beta/Gq family/GDP/G beta5/gamma2	-0.014	0.12	-10000	0	-0.58	21	21
platelet activation	-0.013	0.088	0.26	7	-0.28	7	14
PGI2/IP	0.019	0.012	-10000	0	-0.26	1	1
PRKACA	0.007	0.048	-10000	0	-0.21	26	26
Gq family/GDP/G beta5/gamma2	-0.012	0.11	-10000	0	-0.49	23	23
TXA2/TP beta/beta Arrestin2	0.003	0.046	-10000	0	-0.3	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0	0.043	-10000	0	-0.2	24	24
mol:DAG	-0.021	0.1	0.27	4	-0.35	12	16
EGFR	0.017	0.052	-10000	0	-0.36	11	11
TXA2/TP alpha	-0.03	0.12	0.31	4	-0.43	13	17
Gq family/GTP	-0.013	0.066	0.23	1	-0.21	49	50
YES1	0.008	0.055	0.22	9	-0.34	1	10
GNAI2/GTP	0.013	0.044	-10000	0	-0.38	1	1
PGD2/DP	0.007	0.058	-10000	0	-0.26	27	27
SLC9A3R1	0.026	0.004	-10000	0	-10000	0	0
FYN	0.009	0.056	0.22	10	-0.34	1	11
mol:NO	0.023	0.029	-10000	0	-0.32	4	4
GNA15	-0.007	0.1	-10000	0	-0.32	56	56
PGK/cGMP	0.027	0.037	-10000	0	-0.21	13	13
RhoA/GDP	0.025	0.007	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.032	0.058	-10000	0	-0.37	2	2
NOS3	0.023	0.029	-10000	0	-0.32	4	4
RAC1	0.025	0.007	-10000	0	-10000	0	0
PRKCA	-0.018	0.09	0.26	6	-0.31	7	13
PRKCB	-0.023	0.091	0.24	3	-0.33	10	13
PRKCE	-0.017	0.088	0.24	4	-0.31	7	11
PRKCD	-0.019	0.09	0.25	3	-0.34	6	9
PRKCG	-0.037	0.11	0.26	4	-0.35	12	16
muscle contraction	-0.03	0.11	0.3	3	-0.42	9	12
PRKCZ	-0.019	0.088	0.25	4	-0.3	8	12
ARR3	0.02	0.025	-10000	0	-0.32	3	3
TXA2/TP beta	0.025	0.054	-10000	0	-0.42	1	1
PRKCQ	-0.02	0.093	0.28	6	-0.33	8	14
MAPKKK cascade	-0.027	0.11	0.28	4	-0.39	12	16
SELE	-0.025	0.089	0.23	4	-0.31	7	11
TP beta/GNAI2/GDP/G beta/gamma	0.037	0.057	-10000	0	-0.41	1	1
ROCK1	0.026	0.006	-10000	0	-10000	0	0
GNA14	0.011	0.076	-10000	0	-0.37	22	22
chemotaxis	-0.035	0.12	0.31	1	-0.48	8	9
GNA12	0.025	0.007	-10000	0	-10000	0	0
GNA13	0.026	0.005	-10000	0	-10000	0	0
GNA11	0.026	0.006	-10000	0	-10000	0	0
Rac1/GTP	0.018	0.005	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.027	0.004	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.033	0.057	-9999	-0.18	35	35
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.007	0.023	-9999	-0.3	2	2
AURKB	0.012	0.066	-9999	-0.32	22	22
AURKC	0.016	0.058	-9999	-0.34	15	15

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.016	0.064	-10000	0	-0.38	14	14
PDGF/PDGFRA/CRKL	0.028	0.049	-10000	0	-0.26	15	15
positive regulation of JUN kinase activity	0.055	0.044	-10000	0	-0.2	14	14
CRKL	0.025	0.015	-10000	0	-0.32	1	1
PDGF/PDGFRA/Caveolin-3	0.024	0.05	-10000	0	-0.26	16	16
AP1	-0.031	0.17	0.32	4	-0.72	29	33
mol:IP3	0.004	0.041	-10000	0	-0.27	11	11
PLCG1	0.004	0.041	-10000	0	-0.27	11	11
PDGF/PDGFRA/alphaV Integrin	0.029	0.048	-10000	0	-0.26	14	14
RAPGEF1	0.026	0.005	-10000	0	-10000	0	0
CRK	0.025	0.007	-10000	0	-10000	0	0
mol:Ca2+	0.004	0.041	-10000	0	-0.27	11	11
CAV3	0.02	0.021	-10000	0	-0.32	2	2
CAV1	0.023	0.029	-10000	0	-0.32	4	4
SHC/Grb2/SOS1	0.057	0.045	-10000	0	-0.2	14	14
PDGF/PDGFRA/Shf	0.025	0.061	-10000	0	-0.27	22	22
FOS	-0.041	0.16	0.31	2	-0.72	28	30
JUN	-0.017	0.02	-10000	0	-10000	0	0
oligodendrocyte development	0.028	0.048	-10000	0	-0.26	14	14
GRB2	0.026	0.005	-10000	0	-10000	0	0
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
mol:DAG	0.004	0.041	-10000	0	-0.27	11	11
PDGF/PDGFRA	0.016	0.064	-10000	0	-0.38	14	14
actin cytoskeleton reorganization	0.028	0.046	-10000	0	-0.26	13	13
SRF	0.009	0.01	-10000	0	-10000	0	0
SHC1	0.026	0.005	-10000	0	-10000	0	0
PI3K	0.039	0.04	-10000	0	-0.21	10	10
PDGF/PDGFRA/Crk/C3G	0.043	0.042	-10000	0	-0.21	13	13
JAK1	0.005	0.042	-10000	0	-0.26	14	14
ELK1/SRF	-0.003	0.054	0.16	43	-0.22	9	52
SHB	0.025	0.007	-10000	0	-10000	0	0
SHF	0.02	0.048	-10000	0	-0.37	9	9
CSNK2A1	0.022	0.018	-10000	0	-10000	0	0
GO:0007205	-0.003	0.043	-10000	0	-0.3	11	11
SOS1	0.027	0.003	-10000	0	-10000	0	0
Ras protein signal transduction	0.055	0.044	-10000	0	-0.2	14	14
PDGF/PDGFRA/SHB	0.029	0.046	-10000	0	-0.26	13	13
PDGF/PDGFRA/Caveolin-1	0.027	0.052	-10000	0	-0.25	17	17
ITGAV	0.026	0.006	-10000	0	-10000	0	0
ELK1	-0.01	0.039	0.26	1	-0.27	10	11
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	0.029	0.047	-10000	0	-0.25	14	14
JAK-STAT cascade	0.005	0.042	-10000	0	-0.26	14	14
cell proliferation	0.025	0.061	-10000	0	-0.27	22	22

×

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

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
BAG4	0.024	0.008	-10000	0	-10000	0	0
Caspase 8 (4 units)	0.043	0.057	-10000	0	-10000	0	0
NEF	-0.003	0.027	-10000	0	-0.16	10	10
NFKBIA	0.026	0.015	-10000	0	-10000	0	0
BIRC3	0.016	0.052	-10000	0	-0.41	7	7
CYCS	0.021	0.059	0.19	33	-10000	0	33
RIPK1	0.025	0.007	-10000	0	-10000	0	0
CD247	0.014	0.067	-10000	0	-0.36	15	15
MAP2K7	0.011	0.16	0.28	1	-0.61	29	30
protein ubiquitination	0.025	0.082	0.24	12	-0.4	8	20
CRADD	0.027	0.004	-10000	0	-10000	0	0
DAXX	0.026	0.005	-10000	0	-10000	0	0
FAS	0.026	0.006	-10000	0	-10000	0	0
BID	0.017	0.048	0.18	6	-0.22	5	11
NF-kappa-B/RelA/I kappa B alpha	0.053	0.038	-10000	0	-0.24	8	8
TRADD	0.026	0.005	-10000	0	-10000	0	0
MAP3K5	0.026	0.005	-10000	0	-10000	0	0
CFLAR	0.027	0.003	-10000	0	-10000	0	0
FADD	0.023	0.01	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.053	0.038	-10000	0	-0.24	8	8
MAPK8	0.01	0.15	0.28	3	-0.58	28	31
APAF1	0.027	0.004	-10000	0	-10000	0	0
TRAF1	0.024	0.025	-10000	0	-0.32	3	3
TRAF2	0.026	0.005	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.025	0.05	0.19	6	-0.23	5	11
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.022	0.088	0.24	1	-0.53	9	10
CHUK	0.025	0.087	0.25	12	-0.45	8	20
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.061	0.035	-10000	0	-10000	0	0
TCRz/NEF	0.009	0.064	-10000	0	-0.23	37	37
TNF	0.001	0.091	-10000	0	-0.33	42	42
FASLG	-0.003	0.09	-10000	0	-0.38	28	28
NFKB1	0.027	0.015	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.03	0.061	-10000	0	-0.19	37	37
CASP6	0.041	0.097	-10000	0	-0.48	5	5
CASP7	0.033	0.087	0.26	18	-0.4	8	26
RELA	0.026	0.015	-10000	0	-10000	0	0
CASP2	0.026	0.006	-10000	0	-10000	0	0
CASP3	0.027	0.088	0.26	16	-0.39	9	25
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
TNFR1A/BAG4	0.034	0.014	-10000	0	-10000	0	0
CASP8	0.027	0.003	-10000	0	-10000	0	0
CASP9	0.026	0.005	-10000	0	-10000	0	0
MAP3K14	0.024	0.089	0.23	4	-0.5	8	12
APAF-1/Caspase 9	0.026	0.056	-10000	0	-0.35	2	2
BCL2	0.009	0.13	0.26	3	-0.52	28	31

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.026	0.007	-10000	0	-10000	0	0
ELF1	0.01	0.059	-10000	0	-0.28	1	1
CCNA2	0.026	0.015	-10000	0	-0.32	1	1
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
JAK3	0.016	0.062	-10000	0	-0.32	19	19
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
JAK1	0.027	0.004	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.024	0.078	0.23	5	-0.4	3	8
SHC1	0.027	0.005	-10000	0	-10000	0	0
SP1	0.028	0.033	-10000	0	-0.29	6	6
IL2RA	-0.013	0.088	-10000	0	-0.28	59	59
IL2RB	0.019	0.05	-10000	0	-0.33	12	12
SOS1	0.027	0.003	-10000	0	-10000	0	0
IL2RG	0.006	0.084	-10000	0	-0.32	37	37
G1/S transition of mitotic cell cycle	0.025	0.1	0.29	6	-0.56	8	14
PTPN11	0.027	0.005	-10000	0	-10000	0	0
CCND2	0.012	0.054	-10000	0	-0.64	4	4
LCK	-0.004	0.099	-10000	0	-0.32	52	52
GRB2	0.027	0.005	-10000	0	-10000	0	0
IL2	0.021	0.021	-10000	0	-0.32	2	2
CDK6	0.022	0.026	-10000	0	-0.32	3	3
CCND3	0.033	0.087	0.36	3	-10000	0	3

×

p38 MAPK signaling pathway

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
TRAF6/ASK1	0.019	0.012	-10000	0	-10000	0	0
TRAF2/ASK1	0.034	0.009	-10000	0	-10000	0	0
ATM	0.025	0.007	-10000	0	-10000	0	0
MAP2K3	-0.015	0.11	0.2	1	-0.38	30	31
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.005	0.093	0.2	2	-0.38	17	19
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.021	0.043	-10000	0	-0.37	7	7
TXN	0.007	0.005	-10000	0	-0.12	1	1
CALM1	0.026	0.005	-10000	0	-10000	0	0
GADD45A	0.027	0.004	-10000	0	-10000	0	0
GADD45B	0.022	0.04	-10000	0	-0.37	6	6
MAP3K1	0.025	0.007	-10000	0	-10000	0	0
MAP3K6	0.026	0.006	-10000	0	-10000	0	0
MAP3K7	0.026	0.005	-10000	0	-10000	0	0
MAP3K4	0.026	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.037	0.01	-10000	0	-10000	0	0
TAK1/TAB family	-0.001	0.015	-10000	0	-0.14	2	2
RAC1/OSM/MEKK3	0.046	0.017	-10000	0	-10000	0	0
TRAF2	0.026	0.005	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.003	0.091	-10000	0	-0.32	24	24
TRAF6	0.007	0.001	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.06	0.16	-10000	0	-0.37	127	127
CCM2	0.025	0.007	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.021	0.1	-10000	0	-0.22	127	127
MAPK11	0.026	0.006	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.006	0.099	-10000	0	-0.2	124	124
OSM/MEKK3	0.037	0.011	-10000	0	-10000	0	0
TAOK1	0.013	0.004	-10000	0	-10000	0	0
TAOK2	0.013	0.004	-10000	0	-10000	0	0
TAOK3	0.013	0.004	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.026	0.005	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.026	0.005	-10000	0	-10000	0	0
MAP3K10	0.026	0.006	-10000	0	-10000	0	0
MAP3K3	0.026	0.005	-10000	0	-10000	0	0
TRX/ASK1	0.023	0.014	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.052	0.041	-10000	0	-0.2	11	11

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.017	0.061	-10000	0	-0.37	14	14
HRAS	0.026	0.005	-10000	0	-10000	0	0
EGFR	0.017	0.052	-10000	0	-0.36	11	11
AKT	0.065	0.068	0.22	39	-0.24	1	40
FOXO3	0.026	0.005	-10000	0	-10000	0	0
AKT1	0.026	0.005	-10000	0	-10000	0	0
FOXO1	0.025	0.007	-10000	0	-10000	0	0
AKT3	0.026	0.005	-10000	0	-10000	0	0
FOXO4	0.027	0.003	-10000	0	-10000	0	0
MET	0.018	0.05	-10000	0	-0.33	12	12
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
PIK3CB	0.025	0.008	-10000	0	-10000	0	0
NRAS	0.026	0.006	-10000	0	-10000	0	0
PIK3CG	0.017	0.055	-10000	0	-0.36	12	12
PIK3R3	0.027	0.003	-10000	0	-10000	0	0
PIK3R2	0.026	0.005	-10000	0	-10000	0	0
NF1	0.027	0.004	-10000	0	-10000	0	0
RAS	0.031	0.053	0.17	10	-0.28	5	15
ERBB2	0.022	0.025	-10000	0	-0.37	2	2
proliferation/survival/translation	-0.047	0.061	0.26	4	-0.21	25	29
PI3K	0.046	0.067	0.19	54	-0.23	3	57
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
KRAS	0.024	0.009	-10000	0	-10000	0	0
FOXO	0.083	0.059	0.2	65	-10000	0	65
AKT2	0.026	0.006	-10000	0	-10000	0	0
PTEN	0.025	0.007	-10000	0	-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.003	0.083	-10000	0	-0.35	22	22
KLHL20	0.024	0.065	0.17	21	-0.22	4	25
CYFIP2	0.008	0.081	-10000	0	-0.37	26	26
Rac1/GDP	0.033	0.083	0.26	16	-0.28	1	17
ENAH	0	0.09	-10000	0	-0.35	26	26
AP1M1	0.026	0.005	-10000	0	-10000	0	0
RAP1B	0.026	0.006	-10000	0	-10000	0	0
RAP1A	0.026	0.005	-10000	0	-10000	0	0
CTNNB1	0.025	0.007	-10000	0	-10000	0	0
CDC42/GTP	0.014	0.037	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.011	0.03	-10000	0	-0.15	7	7
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.054	0.042	-10000	0	-0.2	9	9
RAPGEF1	0.013	0.097	0.23	10	-0.35	11	21
CTNND1	0.026	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.004	0.1	-10000	0	-0.35	32	32
CRK	0.012	0.094	-10000	0	-0.34	22	22
E-cadherin/gamma catenin/alpha catenin	0.038	0.047	-10000	0	-0.21	17	17
alphaE/beta7 Integrin	0.037	0.016	-10000	0	-0.26	1	1
IQGAP1	0.026	0.006	-10000	0	-10000	0	0
NCKAP1	0.027	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.046	0.017	-10000	0	-10000	0	0
DLG1	0.002	0.084	-10000	0	-0.35	23	23
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.001	0.021	-10000	0	-10000	0	0
MLLT4	0.026	0.006	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.036	0.05	-10000	0	-0.18	27	27
PI3K	0.004	0.028	-10000	0	-10000	0	0
ARF6	0.026	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.027	0.049	-10000	0	-0.25	17	17
TIAM1	0.009	0.076	-10000	0	-0.34	27	27
E-cadherin(dimer)/Ca2+	0.051	0.038	-10000	0	-0.19	9	9
AKT1	0.005	0.037	0.14	4	-10000	0	4
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
CDH1	0.019	0.052	-10000	0	-0.37	10	10
RhoA/GDP	0.039	0.084	0.27	19	-0.28	1	20
actin cytoskeleton organization	0.022	0.054	0.15	28	-0.17	3	31
CDC42/GDP	0.037	0.086	0.27	19	-0.28	1	20
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.011	0.033	-10000	0	-0.2	10	10
ITGB7	0.026	0.017	-10000	0	-0.37	1	1
RAC1	0.025	0.007	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.055	0.041	-10000	0	-0.2	9	9
E-cadherin/Ca2+/beta catenin/alpha catenin	0.038	0.032	-10000	0	-0.18	9	9
mol:GDP	0.025	0.092	0.27	19	-0.33	1	20
CDC42/GTP/IQGAP1	0.033	0.011	-10000	0	-10000	0	0
JUP	0.021	0.038	-10000	0	-0.32	7	7
p120 catenin/RhoA/GDP	0.046	0.084	0.27	18	-10000	0	18
RAC1/GTP/IQGAP1	0.032	0.012	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.038	0.01	-10000	0	-10000	0	0
RHOA	0.025	0.007	-10000	0	-10000	0	0
CDC42	0.026	0.006	-10000	0	-10000	0	0
CTNNA1	0.025	0.007	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.017	0.037	0.13	15	-0.14	1	16
NME1	0.026	0.015	-10000	0	-0.32	1	1
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.001	0.093	-10000	0	-0.35	29	29
regulation of cell-cell adhesion	0.008	0.03	-10000	0	-10000	0	0
WASF2	0.009	0.027	0.084	1	-10000	0	1
Rap1/GTP	0.033	0.063	0.29	5	-10000	0	5
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.056	0.053	-10000	0	-0.19	9	9
CCND1	0.019	0.043	0.15	15	-0.17	1	16
VAV2	0.02	0.12	-10000	0	-0.49	8	8
RAP1/GDP	0.043	0.077	0.27	15	-10000	0	15
adherens junction assembly	0	0.091	-10000	0	-0.34	29	29
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.026	0.005	-10000	0	-10000	0	0
PIP5K1C	0.026	0.006	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.051	0.056	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.005	0.042	-10000	0	-0.27	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.003	0.092	-10000	0	-0.35	29	29
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
Rac1/GTP	-0.008	0.066	-10000	0	-0.33	7	7
E-cadherin/beta catenin/alpha catenin	0.043	0.038	-10000	0	-0.22	9	9
ITGAE	0.025	0.007	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.003	0.1	-10000	0	-0.36	32	32

×

Signaling events mediated by PRL

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
CCNE1	0.011	0.066	-10000	0	-0.32	22	22
mol:Halofuginone	0.003	0	-10000	0	-10000	0	0
ITGA1	0.021	0.038	-10000	0	-0.32	7	7
CDKN1A	0.01	0.049	-10000	0	-0.33	11	11
PRL-3/alpha Tubulin	0.034	0.015	-10000	0	-10000	0	0
mol:Ca2+	-0.051	0.081	-10000	0	-0.24	92	92
AGT	-0.034	0.14	-10000	0	-0.34	99	99
CCNA2	-0.007	0.02	-10000	0	-10000	0	0
TUBA1B	0.027	0.004	-10000	0	-10000	0	0
EGR1	0.009	0.034	-10000	0	-0.25	10	10
CDK2/Cyclin E1	0.038	0.077	0.27	1	-0.32	12	13
MAPK3	0.01	0.005	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0.038	0.009	-10000	0	-10000	0	0
MAPK1	0.01	0.005	-10000	0	-10000	0	0
PTP4A1	-0.005	0.022	-10000	0	-10000	0	0
PTP4A3	0.023	0.01	-10000	0	-10000	0	0
PTP4A2	0.026	0.005	-10000	0	-10000	0	0
ITGB1	0.01	0.005	-10000	0	-10000	0	0
SRC	0.023	0.009	-10000	0	-10000	0	0
RAC1	0.013	0.023	-10000	0	-0.3	2	2
Rab GGTase beta/Rab GGTase alpha	0.038	0.009	-10000	0	-10000	0	0
PRL-1/ATF-5	0.035	0.062	-10000	0	-10000	0	0
RABGGTA	0.026	0.005	-10000	0	-10000	0	0
BCAR1	-0.017	0.008	-10000	0	-10000	0	0
RHOC	0.011	0.039	-10000	0	-0.3	8	8
RHOA	0.007	0.054	-10000	0	-0.32	15	15
cell motility	0.032	0.072	0.28	4	-0.28	11	15
PRL-1/alpha Tubulin	0.037	0.062	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.029	0.032	-10000	0	-0.22	7	7
ROCK1	0.036	0.06	0.28	4	-0.27	4	8
RABGGTB	0.026	0.004	-10000	0	-10000	0	0
CDK2	0.026	0.005	-10000	0	-10000	0	0
mitosis	-0.005	0.022	-10000	0	-10000	0	0
ATF5	0.025	0.021	-10000	0	-0.32	2	2

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.02	0.056	0.22	4	-0.24	4	8
adherens junction organization	0.021	0.071	0.22	4	-0.36	7	11
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.033	0.066	0.25	8	-0.26	1	9
FMN1	0.018	0.071	0.23	2	-0.34	8	10
mol:IP3	0.011	0.038	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.024	0.066	-10000	0	-0.33	6	6
CTNNB1	0.025	0.007	-10000	0	-10000	0	0
AKT1	0.024	0.053	0.19	9	-0.22	2	11
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.013	0.11	-10000	0	-0.48	14	14
CTNND1	0.029	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.021	0.065	0.17	8	-0.31	7	15
VASP	0.022	0.062	0.18	8	-0.31	5	13
ZYX	0.021	0.064	0.18	7	-0.32	6	13
JUB	0.022	0.065	0.16	6	-0.32	6	12
EGFR(dimer)	0.03	0.074	0.23	2	-0.3	8	10
E-cadherin/beta catenin-gamma catenin	0.036	0.045	-10000	0	-0.2	16	16
mol:PI-3-4-5-P3	0.042	0.066	0.22	11	-0.22	4	15
PIK3CA	0.025	0.01	-10000	0	-10000	0	0
PI3K	0.043	0.068	0.23	11	-0.23	4	15
FYN	0.003	0.065	0.21	3	-0.35	4	7
mol:Ca2+	0.01	0.037	-10000	0	-10000	0	0
JUP	0.021	0.039	-10000	0	-0.32	7	7
PIK3R1	0.027	0.009	-10000	0	-10000	0	0
mol:DAG	0.011	0.038	-10000	0	-10000	0	0
CDH1	0.019	0.051	-10000	0	-0.37	10	10
RhoA/GDP	0.036	0.066	0.24	11	-0.24	1	12
establishment of polarity of embryonic epithelium	0.023	0.062	0.17	8	-0.31	5	13
SRC	0.023	0.009	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
RHOA	0.025	0.007	-10000	0	-10000	0	0
EGFR	0.017	0.052	-10000	0	-0.36	11	11
CASR	0.001	0.063	0.16	19	-0.29	3	22
RhoA/GTP	0.028	0.049	-10000	0	-10000	0	0
AKT2	0.024	0.055	0.19	11	-0.22	1	12
actin cable formation	0.018	0.07	0.2	10	-0.34	7	17
apoptosis	-0.034	0.07	0.25	5	-0.21	20	25
CTNNA1	0.027	0.008	-10000	0	-10000	0	0
mol:GDP	0.017	0.057	0.16	47	-0.24	3	50
PIP5K1A	0.021	0.066	0.18	8	-0.31	7	15
PLCG1	0.011	0.038	-10000	0	-10000	0	0
Rac1/GTP	0.034	0.073	0.22	2	-0.29	7	9
homophilic cell adhesion	0.002	0.004	-10000	0	-10000	0	0

×

Aurora A 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
Aurora A/GADD45A	0.023	0.039	-10000	0	-0.24	3	3
BIRC5	0.011	0.072	-10000	0	-0.33	26	26
NFKBIA	0.004	0.033	0.25	5	-0.24	3	8
CPEB1	-0.066	0.17	-10000	0	-0.37	136	136
AKT1	0.003	0.03	0.25	3	-0.24	3	6
NDEL1	0.025	0.007	-10000	0	-10000	0	0
Aurora A/BRCA1	0.018	0.038	-10000	0	-0.22	3	3
NDEL1/TACC3	0.042	0.044	-10000	0	-0.28	2	2
GADD45A	0.027	0.004	-10000	0	-10000	0	0
GSK3B	0.024	0.007	-10000	0	-10000	0	0
PAK1/Aurora A	0.023	0.039	-10000	0	-0.24	3	3
MDM2	0.025	0.006	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.001	0.052	-10000	0	-0.22	31	31
TP53	0.018	0.028	-10000	0	-0.21	1	1
DLG7	0.004	0.024	0.14	2	-0.24	3	5
AURKAIP1	0.026	0.006	-10000	0	-10000	0	0
ARHGEF7	0.025	0.007	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.044	0.045	-10000	0	-0.29	2	2
G2/M transition of mitotic cell cycle	0.018	0.038	-10000	0	-0.22	3	3
AURKA	0.01	0.031	0.17	2	-0.28	3	5
AURKB	0.009	0.019	-10000	0	-0.16	2	2
CDC25B	0.01	0.023	-10000	0	-0.22	3	3
G2/M transition checkpoint	0.003	0.025	-10000	0	-0.21	3	3
mRNA polyadenylation	-0.024	0.09	-10000	0	-0.2	104	104
Aurora A/CPEB	-0.024	0.091	-10000	0	-0.2	104	104
Aurora A/TACC1/TRAP/chTOG	0.056	0.047	-10000	0	-0.21	1	1
BRCA1	0.024	0.029	-10000	0	-0.32	4	4
centrosome duplication	0.023	0.038	-10000	0	-0.24	3	3
regulation of centrosome cycle	0.04	0.043	-10000	0	-0.27	2	2
spindle assembly	0.054	0.046	-10000	0	-0.21	1	1
TDRD7	0.026	0.005	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.044	0.062	-10000	0	-0.25	6	6
CENPA	0.01	0.025	-10000	0	-0.22	3	3
Aurora A/PP2A	0.022	0.04	-10000	0	-0.24	3	3
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.014	0.038	0.2	1	-0.23	3	4
negative regulation of DNA binding	0.014	0.043	-10000	0	-0.21	1	1
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.036	0.012	-10000	0	-10000	0	0
RASA1	0.025	0.008	-10000	0	-10000	0	0
Ajuba/Aurora A	0.003	0.026	-10000	0	-0.21	3	3
mitotic prometaphase	0.002	0.018	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.01	0.031	0.17	2	-0.28	3	5
TACC1	0.025	0.008	-10000	0	-10000	0	0
TACC3	0.024	0.021	-10000	0	-0.32	2	2
Aurora A/Antizyme1	0.046	0.043	-10000	0	-0.22	1	1
Aurora A/RasGAP	0.022	0.037	-10000	0	-0.23	3	3
OAZ1	0.026	0.006	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.025	0.006	-10000	0	-10000	0	0
GIT1	0.027	0.004	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.048	0.019	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.001	0.052	-10000	0	-0.22	31	31
PPP2R5D	0.025	0.007	-10000	0	-10000	0	0
Aurora A/TPX2	0.004	0.052	-10000	0	-0.27	10	10
PAK1	0.025	0.006	-10000	0	-10000	0	0
CKAP5	0.026	0.004	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.024	0.009	-10000	0	-10000	0	0
NFATC1	0.012	0.1	0.24	3	-0.45	11	14
NFATC2	0.017	0.06	0.15	11	-0.23	13	24
NFATC3	0.019	0.007	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.03	0.1	0.19	3	-0.36	30	33
Exportin 1/Ran/NUP214	0.051	0.014	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.015	0.1	-10000	0	-0.35	27	27
BCL2/BAX	0.032	0.028	-10000	0	-0.25	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.019	0.007	-10000	0	-10000	0	0
CaM/Ca2+	0.019	0.007	-10000	0	-10000	0	0
BAX	0.025	0.015	-10000	0	-0.32	1	1
MAPK14	0.026	0.005	-10000	0	-10000	0	0
BAD	0.027	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.021	0.099	0.2	1	-0.35	26	27
Calcineurin A alpha-beta B1/BCL2	0.022	0.029	-10000	0	-0.37	3	3
FKBP8	0.026	0.004	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.021	0.097	0.35	26	-0.2	1	27
KPNB1	0.027	0.002	-10000	0	-10000	0	0
KPNA2	0.025	0.021	-10000	0	-0.32	2	2
XPO1	0.027	0.003	-10000	0	-10000	0	0
SFN	-0.009	0.1	-10000	0	-0.33	58	58
MAP3K8	0.026	0.015	-10000	0	-0.32	1	1
NFAT4/CK1 alpha	0.027	0.018	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	0.051	0.075	-10000	0	-0.32	3	3
CABIN1	-0.031	0.1	0.19	3	-0.36	30	33
CALM1	0.026	0.006	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
MAP3K1	0.025	0.007	-10000	0	-10000	0	0
CAMK4	0.014	0.064	-10000	0	-0.37	16	16
mol:Ca2+	0	0.002	-10000	0	-10000	0	0
MAPK3	0.026	0.005	-10000	0	-10000	0	0
YWHAH	0.026	0.005	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.037	0.014	-10000	0	-0.22	1	1
YWHAB	0.023	0.01	-10000	0	-10000	0	0
MAPK8	0.026	0.005	-10000	0	-10000	0	0
MAPK9	0.026	0.006	-10000	0	-10000	0	0
YWHAG	0.026	0.006	-10000	0	-10000	0	0
FKBP1A	0.024	0.008	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.03	0.11	0.23	9	-0.41	14	23
PRKCH	0.026	0.005	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.036	0.015	-10000	0	-10000	0	0
CASP3	0.025	0.007	-10000	0	-10000	0	0
PIM1	0.025	0.017	-10000	0	-0.37	1	1
Calcineurin A alpha-beta B1/FKBP12/FK506	0.016	0.007	-10000	0	-10000	0	0
apoptosis	0.016	0.012	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.04	-10000	0	-0.22	1	1
PRKCB	0.001	0.097	-10000	0	-0.37	38	38
PRKCE	0.027	0.003	-10000	0	-10000	0	0
JNK2/NFAT4	0.026	0.035	-10000	0	-10000	0	0
BAD/BCL-XL	0.035	0.014	-10000	0	-10000	0	0
PRKCD	0.025	0.007	-10000	0	-10000	0	0
NUP214	0.026	0.005	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
PRKCA	0.025	0.017	-10000	0	-0.37	1	1
PRKCG	-0.095	0.17	-10000	0	-0.33	203	203
PRKCQ	0.01	0.078	-10000	0	-0.37	24	24
FKBP38/BCL2	0.033	0.025	-10000	0	-0.26	3	3
EP300	0.026	0.009	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.024	0.008	-10000	0	-10000	0	0
NFATc/JNK1	0.024	0.1	0.25	2	-0.43	10	12
CaM/Ca2+/FKBP38	0.034	0.012	-10000	0	-10000	0	0
FKBP12/FK506	0.018	0.006	-10000	0	-10000	0	0
CSNK1A1	0.012	0.007	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.026	0.042	-10000	0	-0.21	16	16
NFATc/ERK1	0.025	0.1	0.24	3	-0.46	8	11
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.016	0.1	-10000	0	-0.35	29	29
NR4A1	0.022	0.082	0.22	8	-0.4	12	20
GSK3B	0.025	0.007	-10000	0	-10000	0	0
positive T cell selection	0.019	0.007	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.019	0.04	0.13	8	-0.18	6	14
RCH1/ KPNB1	0.038	0.017	-10000	0	-0.22	2	2
YWHAQ	0.027	0.003	-10000	0	-10000	0	0
PRKACA	0.026	0.005	-10000	0	-10000	0	0
AKAP5	0.026	0.015	-10000	0	-0.32	1	1
MEF2D	0.026	0.009	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.023	0.01	-10000	0	-10000	0	0
NFATc/p38 alpha	0.024	0.1	0.24	3	-0.43	10	13
CREBBP	0.025	0.009	-10000	0	-10000	0	0
BCL2	0.022	0.029	-10000	0	-0.37	3	3

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.044	0.1	-10000	0	-0.57	3	3
MKNK1	0.027	0.003	-10000	0	-10000	0	0
MAPK14	-0.032	0.082	-10000	0	-0.29	7	7
ATF2/c-Jun	-0.02	0.054	-10000	0	-10000	0	0
MAPK11	-0.035	0.085	-10000	0	-0.3	10	10
MITF	-0.039	0.091	-10000	0	-0.37	16	16
MAPKAPK5	-0.032	0.077	-10000	0	-0.32	9	9
KRT8	-0.04	0.094	-10000	0	-0.43	11	11
MAPKAPK3	0.025	0.007	-10000	0	-10000	0	0
MAPKAPK2	0.026	0.006	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.042	0.11	-10000	0	-0.34	19	19
CEBPB	-0.026	0.072	-10000	0	-0.32	9	9
SLC9A1	-0.032	0.076	-10000	0	-0.32	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.032	0.079	-10000	0	-0.31	9	9
p38alpha-beta/MNK1	-0.022	0.096	-10000	0	-0.33	7	7
JUN	-0.019	0.054	-10000	0	-10000	0	0
PPARGC1A	-0.058	0.11	-10000	0	-0.4	28	28
USF1	-0.031	0.076	-10000	0	-0.32	9	9
RAB5/GDP/GDI1	-0.019	0.06	-10000	0	-0.24	5	5
NOS2	-0.088	0.16	-10000	0	-0.65	14	14
DDIT3	-0.031	0.077	-10000	0	-0.32	8	8
RAB5A	0.026	0.006	-10000	0	-10000	0	0
HSPB1	-0.021	0.082	0.28	16	-0.28	10	26
p38alpha-beta/HBP1	-0.022	0.094	-10000	0	-0.33	7	7
CREB1	-0.025	0.074	-10000	0	-0.34	8	8
RAB5/GDP	0.019	0.004	-10000	0	-10000	0	0
EIF4E	-0.034	0.071	-10000	0	-0.3	7	7
RPS6KA4	-0.031	0.076	-10000	0	-0.32	8	8
PLA2G4A	-0.039	0.079	-10000	0	-0.32	12	12
GDI1	-0.03	0.075	-10000	0	-0.32	8	8
TP53	-0.046	0.085	-10000	0	-0.42	7	7
RPS6KA5	-0.031	0.075	-10000	0	-0.33	7	7
ESR1	-0.042	0.09	-10000	0	-0.35	16	16
HBP1	0.025	0.007	-10000	0	-10000	0	0
MEF2C	-0.035	0.08	-10000	0	-0.32	10	10
MEF2A	-0.03	0.075	-10000	0	-0.32	8	8
EIF4EBP1	-0.028	0.079	-10000	0	-0.37	8	8
KRT19	-0.035	0.093	-10000	0	-0.4	12	12
ELK4	-0.031	0.077	-10000	0	-0.32	9	9
ATF6	-0.031	0.076	-10000	0	-0.32	9	9
ATF1	-0.025	0.074	-10000	0	-0.34	8	8
p38alpha-beta/MAPKAPK2	-0.022	0.095	-10000	0	-0.33	7	7
p38alpha-beta/MAPKAPK3	-0.022	0.094	-10000	0	-0.32	7	7

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.033	0.13	-10000	0	-0.5	2	2
RAD9A	0.026	0.006	-10000	0	-10000	0	0
AP1	0.022	0.064	-10000	0	-0.27	27	27
IFNAR2	0.017	0.019	-10000	0	-10000	0	0
AKT1	0.004	0.04	-10000	0	-0.23	7	7
ER alpha/Oestrogen	0.006	0.055	-10000	0	-0.26	25	25
NFX1/SIN3/HDAC complex	0.025	0.037	-10000	0	-0.3	2	2
EGF	-0.033	0.13	-10000	0	-0.33	94	94
SMG5	0.026	0.004	-10000	0	-10000	0	0
SMG6	0.025	0.007	-10000	0	-10000	0	0
SP3/HDAC2	0.026	0.028	-10000	0	-10000	0	0
TERT/c-Abl	-0.023	0.13	-10000	0	-0.48	2	2
SAP18	0.025	0.006	-10000	0	-10000	0	0
MRN complex	0.045	0.022	-10000	0	-10000	0	0
WT1	-0.065	0.15	-10000	0	-0.32	141	141
WRN	0.024	0.008	-10000	0	-10000	0	0
SP1	0.016	0.022	-10000	0	-10000	0	0
SP3	0.025	0.005	-10000	0	-10000	0	0
TERF2IP	0.026	0.005	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.01	0.13	-10000	0	-0.45	2	2
Mad/Max	0.036	0.012	-10000	0	-10000	0	0
TERT	-0.033	0.13	-10000	0	-0.52	2	2
CCND1	-0.006	0.14	-10000	0	-10000	0	0
MAX	0.025	0.006	-10000	0	-10000	0	0
RBBP7	0.026	0.005	-10000	0	-10000	0	0
RBBP4	0.026	0.004	-10000	0	-10000	0	0
TERF2	0.023	0.019	-10000	0	-0.34	1	1
PTGES3	0.027	0.004	-10000	0	-10000	0	0
SIN3A	0.026	0.005	-10000	0	-10000	0	0
Telomerase/911	0.031	0.061	0.22	1	-0.48	2	3
CDKN1B	-0.029	0.083	0.18	3	-10000	0	3
RAD1	0.024	0.009	-10000	0	-10000	0	0
XRCC5	0.027	0.004	-10000	0	-10000	0	0
XRCC6	0.026	0.005	-10000	0	-10000	0	0
SAP30	0.025	0.007	-10000	0	-10000	0	0
TRF2/PARP2	0.037	0.018	-10000	0	-0.27	1	1
UBE3A	0.025	0.006	-10000	0	-10000	0	0
JUN	0.026	0.005	-10000	0	-10000	0	0
E6	-0.001	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.012	0.015	-10000	0	-10000	0	0
FOS	0.007	0.084	-10000	0	-0.38	27	27
IFN-gamma/IRF1	-0.022	0.11	-10000	0	-0.22	138	138
PARP2	0.026	0.005	-10000	0	-10000	0	0
BLM	0.019	0.049	-10000	0	-0.32	12	12
Telomerase	0.013	0.08	-10000	0	-0.49	6	6
IRF1	0.027	0.008	-10000	0	-10000	0	0
ESR1	0.009	0.079	-10000	0	-0.37	25	25
KU/TER	0.038	0.009	-10000	0	-10000	0	0
ATM/TRF2	0.036	0.017	-10000	0	-0.26	1	1
ubiquitin-dependent protein catabolic process	0.025	0.05	-10000	0	-0.33	4	4
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.026	0.051	-10000	0	-0.34	4	4
HDAC1	0.026	0.005	-10000	0	-10000	0	0
HDAC2	0.015	0.022	-10000	0	-10000	0	0
ATM	0.011	0.01	-10000	0	-10000	0	0
SMAD3	0.013	0.005	-10000	0	-10000	0	0
ABL1	0.026	0.005	-10000	0	-10000	0	0
MXD1	0.026	0.005	-10000	0	-10000	0	0
MRE11A	0.026	0.006	-10000	0	-10000	0	0
HUS1	0.025	0.007	-10000	0	-10000	0	0
RPS6KB1	0.026	0.004	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.011	0.14	-10000	0	-0.55	2	2
NR2F2	0.026	0.023	-10000	0	-0.34	2	2
MAPK3	-0.006	0.02	-10000	0	-0.23	2	2
MAPK1	-0.006	0.02	-10000	0	-0.23	2	2
TGFB1/TGF beta receptor Type II	0.026	0.006	-10000	0	-10000	0	0
NFKB1	0.026	0.004	-10000	0	-10000	0	0
HNRNPC	0.026	0.005	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.011	0.01	-10000	0	-10000	0	0
NBN	0.024	0.008	-10000	0	-10000	0	0
EGFR	0.016	0.052	-10000	0	-0.36	11	11
mol:Oestrogen	-0.001	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.01	0.096	-10000	0	-0.23	91	91
MYC	0.019	0.026	-10000	0	-0.37	2	2
IL2	0.01	0.03	-10000	0	-0.33	2	2
KU	0.038	0.009	-10000	0	-10000	0	0
RAD50	0.025	0.007	-10000	0	-10000	0	0
HSP90AA1	0.026	0.006	-10000	0	-10000	0	0
TGFB1	0.026	0.006	-10000	0	-10000	0	0
TRF2/BLM	0.031	0.04	-10000	0	-0.23	12	12
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	-0.015	0.13	-10000	0	-0.48	1	1
SP1/HDAC2	0.024	0.032	-10000	0	-10000	0	0
PINX1	0.023	0.009	-10000	0	-10000	0	0
Telomerase/EST1A	-0.01	0.13	-10000	0	-0.45	2	2
Smad3/Myc	0.021	0.02	-10000	0	-0.22	2	2
911 complex	0.044	0.022	-10000	0	-10000	0	0
IFNG	-0.055	0.15	-10000	0	-0.32	139	139
Telomerase/PinX1	-0.011	0.12	-10000	0	-0.45	2	2
Telomerase/AKT1/mTOR/p70S6K	-0.001	0.093	-10000	0	-0.37	19	19
SIN3B	0.026	0.005	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
Telomerase/EST1B	-0.01	0.13	-10000	0	-0.45	1	1
response to DNA damage stimulus	0.001	0.023	-10000	0	-0.12	1	1
MRN complex/TRF2/Rap1	0.061	0.034	-10000	0	-0.21	1	1
TRF2/WRN	0.034	0.019	-10000	0	-0.27	1	1
Telomerase/hnRNP C1/C2	-0.009	0.13	-10000	0	-0.45	1	1
E2F1	0.015	0.03	-10000	0	-0.33	3	3
ZNFX1	0.022	0.01	-10000	0	-10000	0	0
PIF1	0.021	0.045	-10000	0	-0.32	10	10
NCL	0.027	0.004	-10000	0	-10000	0	0
DKC1	0.026	0.005	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

E-cadherin signaling 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
E-cadherin/beta catenin-gamma catenin	0.038	0.046	-9999	-0.21	16	16
E-cadherin/beta catenin	0.031	0.038	-9999	-0.26	9	9
CTNNB1	0.025	0.007	-9999	-10000	0	0
JUP	0.021	0.038	-9999	-0.32	7	7
CDH1	0.019	0.052	-9999	-0.37	10	10

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.022	0.017	-10000	0	-10000	0	0
HSPA8	0.025	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.047	0.074	-10000	0	-0.25	4	4
AKT1	0.025	0.018	-10000	0	-10000	0	0
GSC	-0.021	0.14	-10000	0	-0.88	7	7
NKX2-5	0.001	0.004	-10000	0	-10000	0	0
muscle cell differentiation	-0.011	0.092	0.35	6	-10000	0	6
SMAD2-3/SMAD4/SP1	0.057	0.069	-10000	0	-10000	0	0
SMAD4	0.026	0.029	-10000	0	-10000	0	0
CBFB	0.026	0.005	-10000	0	-10000	0	0
SAP18	0.026	0.006	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.029	0.068	-10000	0	-0.19	42	42
SMAD3/SMAD4/VDR	0.073	0.045	-10000	0	-10000	0	0
MYC	0.019	0.026	-10000	0	-0.38	2	2
CDKN2B	-0.11	0.26	-10000	0	-0.99	26	26
AP1	0.032	0.053	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.013	0.089	-10000	0	-0.38	14	14
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.007	0.08	-10000	0	-0.34	19	19
SP3	0.028	0.004	-10000	0	-10000	0	0
CREB1	0.027	0.004	-10000	0	-10000	0	0
FOXH1	-0.029	0.12	-10000	0	-0.32	82	82
SMAD3/SMAD4/GR	0.052	0.05	-10000	0	-10000	0	0
GATA3	0.008	0.08	-10000	0	-0.32	33	33
SKI/SIN3/HDAC complex/NCoR1	0.017	0.06	-10000	0	-0.41	6	6
MEF2C/TIF2	0.011	0.082	-10000	0	-0.4	1	1
endothelial cell migration	0.012	0.097	0.55	5	-10000	0	5
MAX	0.028	0.008	-10000	0	-10000	0	0
RBBP7	0.026	0.005	-10000	0	-10000	0	0
RBBP4	0.026	0.004	-10000	0	-10000	0	0
RUNX2	0.018	0.049	-10000	0	-0.32	12	12
RUNX3	0.016	0.058	-10000	0	-0.32	17	17
RUNX1	0.022	0.027	-10000	0	-0.33	3	3
CTBP1	0.025	0.007	-10000	0	-10000	0	0
NR3C1	0.024	0.038	-10000	0	-0.38	5	5
VDR	0.026	0.004	-10000	0	-10000	0	0
CDKN1A	0.012	0.085	-10000	0	-0.66	6	6
KAT2B	0.021	0.043	-10000	0	-0.37	7	7
SMAD2/SMAD2/SMAD4/FOXH1	0.007	0.091	-10000	0	-0.26	10	10
DCP1A	0.025	0.007	-10000	0	-10000	0	0
SKI	0.026	0.006	-10000	0	-10000	0	0
SERPINE1	-0.012	0.097	-10000	0	-0.55	5	5
SMAD3/SMAD4/ATF2	0.053	0.039	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.051	0.045	-10000	0	-0.26	1	1
SAP30	0.025	0.007	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.042	0.034	-10000	0	-10000	0	0
JUN	0.019	0.048	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	0.054	0.041	-10000	0	-10000	0	0
TFE3	0.023	0.021	-10000	0	-10000	0	0
COL1A2	-0.012	0.091	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.046	0.054	0.28	2	-10000	0	2
DLX1	-0.03	0.13	-10000	0	-0.35	88	88
TCF3	0.026	0.006	-10000	0	-10000	0	0
FOS	0.01	0.084	-10000	0	-0.38	27	27
SMAD3/SMAD4/Max	0.055	0.043	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.05	0.017	-10000	0	-10000	0	0
ZBTB17	0.025	0.007	-10000	0	-10000	0	0
LAMC1	0.019	0.033	0.25	1	-10000	0	1
TGIF2/HDAC complex/SMAD3/SMAD4	0.049	0.041	-10000	0	-0.24	1	1
IRF7	0.025	0.022	-10000	0	-0.32	2	2
ESR1	0.011	0.08	-10000	0	-0.37	25	25
HNF4A	-0.04	0.14	-10000	0	-0.37	93	93
MEF2C	0.008	0.086	0.22	1	-0.42	1	2
SMAD2-3/SMAD4	0.054	0.045	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.049	0.019	-10000	0	-10000	0	0
IGHV3OR16-13	0.01	0.03	-10000	0	-0.33	4	4
TGIF2/HDAC complex	0.023	0.017	-10000	0	-0.32	1	1
CREBBP	0.023	0.014	-10000	0	-10000	0	0
SKIL	0.023	0.01	-10000	0	-10000	0	0
HDAC1	0.026	0.005	-10000	0	-10000	0	0
HDAC2	0.026	0.005	-10000	0	-10000	0	0
SNIP1	0.026	0.005	-10000	0	-10000	0	0
GCN5L2	0	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.055	0.043	-10000	0	-0.3	1	1
MSG1/HSC70	0.017	0.071	-10000	0	-0.23	45	45
SMAD2	0.019	0.027	-10000	0	-10000	0	0
SMAD3	0.03	0.026	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.021	0.037	-10000	0	-0.26	1	1
SMAD2/SMAD2/SMAD4	-0.024	0.084	-10000	0	-0.34	22	22
NCOR1	0.025	0.008	-10000	0	-10000	0	0
NCOA2	0.024	0.018	-10000	0	-0.37	1	1
NCOA1	0.027	0.003	-10000	0	-10000	0	0
MYOD/E2A	0.029	0.031	-10000	0	-0.22	8	8
SMAD2-3/SMAD4/SP1/MIZ-1	0.068	0.07	-10000	0	-10000	0	0
IFNB1	0.012	0.026	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.032	0.097	0.26	2	-0.44	1	3
CITED1	0	0.094	-10000	0	-0.33	45	45
SMAD2-3/SMAD4/ARC105	0.064	0.049	-10000	0	-10000	0	0
RBL1	0.022	0.022	-10000	0	-0.32	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.01	0.099	0.23	1	-0.56	11	12
RUNX1-3/PEBPB2	0.04	0.045	-10000	0	-0.19	18	18
SMAD7	0.028	0.06	-10000	0	-10000	0	0
MYC/MIZ-1	0.028	0.026	-10000	0	-0.26	2	2
SMAD3/SMAD4	-0.003	0.073	0.27	3	-0.34	2	5
IL10	0.011	0.062	-10000	0	-0.37	4	4
PIASy/HDAC complex	0.025	0.011	-10000	0	-10000	0	0
PIAS3	0.026	0.006	-10000	0	-10000	0	0
CDK2	0.025	0.009	-10000	0	-10000	0	0
IL5	0.009	0.057	-10000	0	-0.29	3	3
CDK4	0.022	0.016	-10000	0	-10000	0	0
PIAS4	0.025	0.011	-10000	0	-10000	0	0
ATF3	0.024	0.029	-10000	0	-0.37	3	3
SMAD3/SMAD4/SP1	0.042	0.064	-10000	0	-10000	0	0
FOXG1	-0.022	0.091	-10000	0	-0.32	47	47
FOXO3	0.011	0.019	-10000	0	-0.16	1	1
FOXO1	0.011	0.017	-10000	0	-10000	0	0
FOXO4	0.012	0.018	-10000	0	-10000	0	0
heart looping	0.008	0.085	0.21	1	-0.41	1	2
CEBPB	0.021	0.015	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.015	0.1	-10000	0	-0.26	8	8
MYOD1	0.015	0.04	-10000	0	-0.32	8	8
SMAD3/SMAD4/HNF4	0.004	0.11	-10000	0	-0.26	29	29
SMAD3/SMAD4/GATA3	0.042	0.07	-10000	0	-10000	0	0
SnoN/SIN3/HDAC complex/NCoR1	0.023	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.062	0.061	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.056	0.066	-10000	0	-10000	0	0
MED15	0.025	0.015	-10000	0	-0.32	1	1
SP1	0.017	0.037	-10000	0	-10000	0	0
SIN3B	0.026	0.005	-10000	0	-10000	0	0
SIN3A	0.026	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.011	0.083	-10000	0	-0.24	3	3
ITGB5	0.013	0.044	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.02	0.056	-10000	0	-0.45	4	4
SMAD3/SMAD4/AR	-0.013	0.13	-10000	0	-0.28	14	14
AR	-0.074	0.17	-10000	0	-0.37	150	150
negative regulation of cell growth	0.012	0.064	-10000	0	-0.29	4	4
SMAD3/SMAD4/MYOD	0.046	0.046	-10000	0	-10000	0	0
E2F5	0.021	0.035	-10000	0	-0.34	5	5
E2F4	0.026	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.023	0.088	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.018	0.068	-10000	0	-0.35	13	13
TFDP1	0.025	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.051	0.061	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	0.046	0.054	-10000	0	-0.28	2	2
TGIF2	0.023	0.017	-10000	0	-0.32	1	1
TGIF1	0.025	0.007	-10000	0	-10000	0	0
ATF2	0.026	0.004	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.005	0.1	0.35	1	-1.2	3	4
PLK1	0.033	0.1	-10000	0	-1.2	1	1
CDKN1B	0.064	0.091	0.31	4	-0.35	5	9
FOXO3	0.046	0.088	-10000	0	-0.51	5	5
KAT2B	0.025	0.045	-10000	0	-0.37	7	7
FOXO1/SIRT1	0.026	0.059	0.27	3	-0.38	3	6
CAT	0.042	0.11	0.45	1	-0.89	2	3
CTNNB1	0.025	0.007	-10000	0	-10000	0	0
AKT1	0.031	0.017	-10000	0	-10000	0	0
FOXO1	0.015	0.063	0.33	3	-0.41	3	6
MAPK10	0.01	0.076	0.19	35	-0.18	60	95
mol:GTP	0.001	0	-10000	0	-10000	0	0
FOXO4	0.031	0.071	0.27	4	-10000	0	4
response to oxidative stress	0.007	0.008	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.049	0.093	-10000	0	-0.49	5	5
XPO1	0.027	0.003	-10000	0	-10000	0	0
EP300	0.026	0.011	-10000	0	-10000	0	0
BCL2L11	0.027	0.071	-10000	0	-0.7	5	5
FOXO1/SKP2	0.023	0.056	0.27	3	-0.38	3	6
mol:GDP	0.007	0.008	-10000	0	-10000	0	0
RAN	0.027	0.004	-10000	0	-10000	0	0
GADD45A	0.048	0.12	-10000	0	-0.59	12	12
YWHAQ	0.027	0.003	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.023	0.12	-10000	0	-0.47	20	20
MST1	0.008	0.084	-10000	0	-0.32	36	36
CSNK1D	0.026	0.005	-10000	0	-10000	0	0
CSNK1E	0.026	0.005	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.008	0.1	-10000	0	-0.45	18	18
YWHAB	0.023	0.01	-10000	0	-10000	0	0
MAPK8	0.032	0.042	0.19	38	-10000	0	38
MAPK9	0.031	0.042	0.19	37	-10000	0	37
YWHAG	0.026	0.006	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0
YWHAZ	0.023	0.01	-10000	0	-10000	0	0
SIRT1	0.026	0.01	-10000	0	-10000	0	0
SOD2	0.054	0.093	0.36	1	-0.51	3	4
RBL2	0.034	0.15	-10000	0	-0.68	18	18
RAL/GDP	0.04	0.015	-10000	0	-10000	0	0
CHUK	0.031	0.015	-10000	0	-10000	0	0
Ran/GTP	0.022	0.004	-10000	0	-10000	0	0
CSNK1G2	0.026	0.006	-10000	0	-10000	0	0
RAL/GTP	0.043	0.015	-10000	0	-10000	0	0
CSNK1G1	0.026	0.005	-10000	0	-10000	0	0
FASLG	0.005	0.17	-10000	0	-1.2	11	11
SKP2	0.024	0.009	-10000	0	-10000	0	0
USP7	0.027	0.006	-10000	0	-10000	0	0
IKBKB	0.028	0.016	-10000	0	-10000	0	0
CCNB1	0.038	0.087	-10000	0	-0.55	2	2
FOXO1-3a-4/beta catenin	0.068	0.084	0.27	8	-10000	0	8
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.056	0.27	3	-0.38	3	6
CSNK1A1	0.025	0.007	-10000	0	-10000	0	0
SGK1	0.026	0.046	-10000	0	-0.37	7	7
CSNK1G3	0.025	0.007	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.039	0.008	-10000	0	-10000	0	0
ZFAND5	0.031	0.068	0.28	3	-10000	0	3
SFN	-0.009	0.1	-10000	0	-0.33	58	58
CDK2	0.025	0.013	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.015	0.096	-10000	0	-0.44	14	14
CREBBP	0.025	0.013	-10000	0	-10000	0	0
FBXO32	0.062	0.14	0.44	2	-0.99	4	6
BCL6	0.048	0.093	-10000	0	-0.66	3	3
RALB	0.027	0.005	-10000	0	-10000	0	0
RALA	0.026	0.007	-10000	0	-10000	0	0
YWHAH	0.026	0.005	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.029	0.055	-10000	0	-0.19	32	32
MAPK9	0.007	0.002	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.009	0.022	-10000	0	-0.22	6	6
GNB1/GNG2	0.033	0.017	-10000	0	-0.2	2	2
GNB1	0.026	0.006	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0.001	-10000	0	-10000	0	0
Gs family/GTP	0.005	0.047	-10000	0	-0.19	31	31
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.004	0.012	0.055	31	-10000	0	31
GNAL	0.004	0.089	-10000	0	-0.37	31	31
GNG2	0.025	0.022	-10000	0	-0.35	2	2
CRH	0.014	0.035	-10000	0	-0.32	6	6
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0.001	-10000	0	-10000	0	0
MAPK11	0.007	0.002	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.044	0.14	0.22	2	-0.39	42	44
CaM/Ca2+	0.019	0.004	-10000	0	-10000	0	0
AKT1	0.026	0.005	-10000	0	-10000	0	0
AKT2	0.026	0.006	-10000	0	-10000	0	0
STXBP4	0.027	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.06	0.15	0.23	2	-0.41	46	48
YWHAZ	0.023	0.01	-10000	0	-10000	0	0
CALM1	0.026	0.005	-10000	0	-10000	0	0
YWHAQ	0.027	0.003	-10000	0	-10000	0	0
TBC1D4	0.01	0.017	-10000	0	-0.22	3	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.026	0.005	-10000	0	-10000	0	0
YWHAB	0.023	0.01	-10000	0	-10000	0	0
SNARE/Synip	0.05	0.016	-10000	0	-10000	0	0
YWHAG	0.026	0.006	-10000	0	-10000	0	0
ASIP	0.019	0.038	-10000	0	-0.32	7	7
PRKCI	0.023	0.017	-10000	0	-0.32	1	1
AS160/CaM/Ca2+	0.019	0.004	-10000	0	-10000	0	0
RHOQ	0.027	0.002	-10000	0	-10000	0	0
GYS1	0.01	0.014	0.24	2	-10000	0	2
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
TRIP10	0.026	0.006	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.035	0.008	-10000	0	-10000	0	0
AS160/14-3-3	0.012	0.048	-10000	0	-0.27	4	4
VAMP2	0.025	0.007	-10000	0	-10000	0	0
SLC2A4	-0.067	0.16	0.23	2	-0.46	46	48
STX4	0.026	0.005	-10000	0	-10000	0	0
GSK3B	0.018	0.007	-10000	0	-10000	0	0
SFN	-0.009	0.1	-10000	0	-0.33	58	58
LNPEP	0.025	0.007	-10000	0	-10000	0	0
YWHAE	0.025	0.007	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.024	0.11	-10000	0	-0.64	13	13
oxygen homeostasis	0.002	0.01	-10000	0	-10000	0	0
TCEB2	0.026	0.006	-10000	0	-10000	0	0
TCEB1	0.024	0.008	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.046	0.076	0.26	1	-0.3	1	2
EPO	0.024	0.15	0.3	1	-0.54	9	10
FIH (dimer)	0.023	0.021	-10000	0	-10000	0	0
APEX1	0.022	0.024	-10000	0	-10000	0	0
SERPINE1	0.015	0.16	0.3	1	-0.56	9	10
FLT1	0.011	0.15	-10000	0	-0.66	22	22
ADORA2A	0.021	0.15	0.33	5	-0.48	13	18
germ cell development	0.019	0.15	0.3	2	-0.52	8	10
SLC11A2	0.025	0.15	0.3	2	-0.52	6	8
BHLHE40	0.025	0.15	0.3	2	-0.51	6	8
HIF1AN	0.023	0.021	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.039	0.11	0.27	3	-0.37	4	7
ETS1	0.034	0.009	-10000	0	-10000	0	0
CITED2	0.023	0.097	-10000	0	-0.58	11	11
KDR	0.014	0.14	-10000	0	-0.63	23	23
PGK1	0.025	0.15	0.3	2	-0.52	6	8
SIRT1	0.026	0.006	-10000	0	-10000	0	0
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	0.049	0.18	-10000	0	-0.57	7	7
EPAS1	0.016	0.066	-10000	0	-0.28	5	5
SP1	0.03	0.008	-10000	0	-10000	0	0
ABCG2	0.018	0.16	0.3	2	-0.58	11	13
EFNA1	0.026	0.15	0.3	2	-0.52	6	8
FXN	0.022	0.15	0.34	4	-0.49	12	16
POU5F1	0.018	0.16	0.3	2	-0.53	8	10
neuron apoptosis	-0.048	0.17	0.56	7	-10000	0	7
EP300	0.026	0.005	-10000	0	-10000	0	0
EGLN3	0.017	0.053	-10000	0	-0.38	9	9
EGLN2	0.023	0.021	-10000	0	-10000	0	0
EGLN1	0.023	0.021	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.045	0.022	-10000	0	-10000	0	0
VHL	0.026	0.006	-10000	0	-10000	0	0
ARNT	0.022	0.024	-10000	0	-10000	0	0
SLC2A1	-0.001	0.18	0.34	4	-0.55	19	23
TWIST1	0.016	0.16	0.33	5	-0.5	12	17
ELK1	0.031	0.005	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.052	0.11	0.29	1	-0.38	2	3
VEGFA	0.023	0.14	0.3	2	-0.5	6	8
CREBBP	0.026	0.006	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.096	0.18	-10000	0	-0.37	181	181
CLTC	0.018	0.064	-10000	0	-0.39	11	11
calcium ion-dependent exocytosis	0.012	0.031	0.2	1	-0.26	1	2
Dynamin 2/GTP	0.024	0.011	-10000	0	-0.17	1	1
EXOC4	0.025	0.007	-10000	0	-10000	0	0
CD59	0.013	0.043	-10000	0	-0.33	7	7
CPE	-0.009	0.067	-10000	0	-0.22	56	56
CTNNB1	0.025	0.007	-10000	0	-10000	0	0
membrane fusion	0.014	0.021	-10000	0	-10000	0	0
CTNND1	-0.005	0.033	0.18	18	-10000	0	18
DNM2	0.026	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.017	0.047	0.19	7	-0.3	5	12
TSHR	0.004	0.041	-10000	0	-0.22	20	20
INS	0.003	0.087	-10000	0	-0.5	16	16
BIN1	0.027	0.004	-10000	0	-10000	0	0
mol:Choline	0.014	0.021	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.013	0.009	-10000	0	-0.18	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.026	0.005	-10000	0	-10000	0	0
mol:Ca2+	0.024	0.011	-10000	0	-0.17	1	1
JUP	0.015	0.045	0.2	2	-0.32	6	8
ASAP2/amphiphysin II	0.048	0.014	-10000	0	-10000	0	0
ARF6/GTP	0.019	0.004	-10000	0	-10000	0	0
CDH1	0.009	0.044	-10000	0	-0.33	6	6
clathrin-independent pinocytosis	0.019	0.004	-10000	0	-10000	0	0
MAPK8IP3	0.025	0.017	-10000	0	-0.37	1	1
positive regulation of endocytosis	0.019	0.004	-10000	0	-10000	0	0
EXOC2	0.025	0.007	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.016	0.038	-10000	0	-0.31	4	4
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.026	0.004	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.033	0.054	0.3	8	-10000	0	8
positive regulation of phagocytosis	0.013	0.004	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.033	0.015	-10000	0	-0.22	1	1
ACAP1	0.017	0.026	0.2	1	-0.21	1	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.027	0.08	-10000	0	-0.42	7	7
clathrin heavy chain/ACAP1	0.021	0.055	0.21	3	-0.33	8	11
JIP4/KLC1	0.048	0.015	-10000	0	-10000	0	0
EXOC1	0.026	0.005	-10000	0	-10000	0	0
exocyst	0.017	0.036	-10000	0	-0.32	3	3
RALA/GTP	0.019	0.005	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.034	0.009	-10000	0	-10000	0	0
receptor recycling	0.019	0.004	-10000	0	-10000	0	0
CTNNA1	-0.004	0.035	0.18	20	-10000	0	20
NME1	0.013	0.009	-10000	0	-0.19	1	1
clathrin coat assembly	0.02	0.064	0.21	1	-0.39	11	12
IL2RA	0.005	0.048	-10000	0	-0.33	7	7
VAMP3	0.013	0.004	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.022	0.093	-10000	0	-0.34	11	11
EXOC6	0.026	0.005	-10000	0	-10000	0	0
PLD1	0.011	0.009	-10000	0	-10000	0	0
PLD2	0.012	0.009	-10000	0	-10000	0	0
EXOC5	0.026	0.005	-10000	0	-10000	0	0
PIP5K1C	0.012	0.037	0.2	1	-0.3	5	6
SDC1	0.011	0.042	-10000	0	-0.32	7	7
ARF6/GDP	0.023	0.01	-10000	0	-0.18	1	1
EXOC7	0.026	0.004	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.036	0.056	-10000	0	-0.3	8	8
mol:Phosphatidic acid	0.014	0.021	-10000	0	-10000	0	0
endocytosis	-0.047	0.013	-10000	0	-10000	0	0
SCAMP2	0.026	0.005	-10000	0	-10000	0	0
ADRB2	-0.018	0.089	0.22	1	-0.36	13	14
EXOC3	0.024	0.009	-10000	0	-10000	0	0
ASAP2	0.027	0.004	-10000	0	-10000	0	0
Dynamin 2/GDP	0.028	0.012	-10000	0	-0.17	1	1
KLC1	0.026	0.006	-10000	0	-10000	0	0
AVPR2	0.008	0.084	0.25	10	-0.37	11	21
RALA	0.025	0.007	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.03	0.053	0.22	1	-0.3	4	5

×

Insulin Pathway

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
CBL/APS/CAP	0.026	0.068	-10000	0	-0.33	2	2
TC10/GTP	0.022	0.064	-10000	0	-0.31	1	1
Insulin Receptor/Insulin/IRS1/Shp2	0.064	0.031	-10000	0	-0.21	2	2
HRAS	0.026	0.005	-10000	0	-10000	0	0
APS homodimer	0.023	0.026	-10000	0	-0.32	3	3
GRB14	-0.026	0.13	-10000	0	-0.34	86	86
FOXO3	0.008	0.1	-10000	0	-0.54	20	20
AKT1	-0.003	0.081	0.22	20	-10000	0	20
INSR	0.031	0.013	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.061	0.05	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.025	0.016	-10000	0	-0.32	1	1
SORBS1	-0.014	0.12	-10000	0	-0.37	59	59
CRK	0.025	0.007	-10000	0	-10000	0	0
PTPN1	0	0.022	-10000	0	-10000	0	0
CAV1	-0.002	0.034	0.18	8	-0.2	1	9
CBL/APS/CAP/Crk-II/C3G	0.042	0.077	-10000	0	-0.34	1	1
Insulin Receptor/Insulin/IRS1/NCK2	0.063	0.032	-10000	0	-0.21	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.043	0.03	-10000	0	-0.19	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.029	0.079	-10000	0	-0.3	19	19
RPS6KB1	-0.006	0.076	0.2	24	-10000	0	24
PARD6A	0.018	0.056	-10000	0	-0.37	12	12
CBL	0.025	0.007	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.018	0.032	-10000	0	-0.73	1	1
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.024	0.068	0.18	2	-10000	0	2
HRAS/GTP	-0.011	0.024	-10000	0	-10000	0	0
Insulin Receptor	0.031	0.013	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.071	0.036	-10000	0	-0.2	2	2
PRKCI	0.012	0.065	-10000	0	-0.37	2	2
Insulin Receptor/Insulin/GRB14/PDK1	0.006	0.061	-10000	0	-10000	0	0
SHC1	0.026	0.005	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.04	0.036	-10000	0	-0.63	1	1
PI3K	0.053	0.035	-10000	0	-0.19	2	2
NCK2	0.026	0.005	-10000	0	-10000	0	0
RHOQ	0.027	0.002	-10000	0	-10000	0	0
mol:H2O2	0	0.005	-10000	0	-10000	0	0
HRAS/GDP	0.019	0.004	-10000	0	-10000	0	0
AKT2	-0.003	0.081	0.22	16	-10000	0	16
PRKCZ	0.008	0.077	-10000	0	-0.38	4	4
SH2B2	0.023	0.026	-10000	0	-0.32	3	3
SHC/SHIP	0.031	0.031	0.19	7	-10000	0	7
F2RL2	-0.009	0.1	-10000	0	-0.33	57	57
TRIP10	0.026	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.049	0.022	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.035	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.072	0.032	-10000	0	-10000	0	0
RAPGEF1	0.026	0.005	-10000	0	-10000	0	0
RASA1	0.025	0.008	-10000	0	-10000	0	0
NCK1	0.025	0.007	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.034	0.075	-10000	0	-0.21	40	40
TC10/GDP	0.02	0.001	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.06	0.03	-10000	0	-10000	0	0
INPP5D	-0.002	0.036	0.18	9	-0.2	3	12
SOS1	0.027	0.003	-10000	0	-10000	0	0
SGK1	-0.004	0.11	-10000	0	-0.7	15	15
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.026	0.004	-10000	0	-10000	0	0
IRS1	0.025	0.023	-10000	0	-0.37	2	2
p62DOK/RasGAP	0.041	0.037	-10000	0	-0.64	1	1
INS	0.024	0.011	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.002	0.036	0.18	9	-0.19	3	12
GRB2	0.026	0.005	-10000	0	-10000	0	0
EIF4EBP1	-0.009	0.071	0.21	16	-10000	0	16
PTPRA	0.028	0.011	-10000	0	-10000	0	0
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.035	0.008	-10000	0	-10000	0	0
PDPK1	0.026	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.026	0.024	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.049	0.026	-10000	0	-0.21	2	2
Insulin Receptor/Insulin/IRS3	0.04	0.02	-10000	0	-10000	0	0
Par3/Par6	0.029	0.074	-10000	0	-0.2	14	14

×

Canonical NF-kappaB pathway

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
FBXW11	0.027	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.041	0.079	0.2	20	-0.34	6	26
ERC1	0.025	0.007	-10000	0	-10000	0	0
RIP2/NOD2	0.021	0.06	-10000	0	-0.22	32	32
NFKBIA	0.012	0.021	0.21	6	-10000	0	6
BIRC2	0.026	0.006	-10000	0	-10000	0	0
IKBKB	0.024	0.008	-10000	0	-10000	0	0
RIPK2	0.024	0.009	-10000	0	-10000	0	0
IKBKG	0.025	0.04	-10000	0	-10000	0	0
IKK complex/A20	0.034	0.09	0.26	1	-0.4	7	8
NEMO/A20/RIP2	0.024	0.009	-10000	0	-10000	0	0
XPO1	0.027	0.003	-10000	0	-10000	0	0
NEMO/ATM	0.034	0.078	0.26	1	-0.36	13	14
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.035	0.007	-10000	0	-10000	0	0
IKK complex/ELKS	0.035	0.073	-10000	0	-0.38	6	6
BCL10/MALT1/TRAF6	0.047	0.02	-10000	0	-10000	0	0
NOD2	0.007	0.08	-10000	0	-0.32	33	33
NFKB1	0.028	0.005	-10000	0	-10000	0	0
RELA	0.028	0.005	-10000	0	-10000	0	0
MALT1	0.024	0.009	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.037	0.011	-10000	0	-10000	0	0
ATM	0.025	0.007	-10000	0	-10000	0	0
TNF/TNFR1A	0.019	0.065	-10000	0	-0.23	38	38
TRAF6	0.026	0.005	-10000	0	-10000	0	0
PRKCA	0.025	0.017	-10000	0	-0.37	1	1
CHUK	0.026	0.005	-10000	0	-10000	0	0
UBE2D3	0.026	0.005	-10000	0	-10000	0	0
TNF	0.001	0.091	-10000	0	-0.33	42	42
NF kappa B1 p50/RelA	0.056	0.019	-10000	0	-10000	0	0
BCL10	0.027	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.02	0.21	6	-10000	0	6
beta TrCP1/SCF ubiquitin ligase complex	0.027	0.007	-10000	0	-10000	0	0
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
IKK complex	0.04	0.08	0.27	1	-0.38	9	10
CYLD	0.026	0.005	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.046	0.082	0.27	1	-0.39	7	8

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.026	0.005	-10000	0	-10000	0	0
HDAC4	0.026	0.005	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.006	0.031	0.22	10	-10000	0	10
CDKN1A	-0.009	0.024	-10000	0	-0.6	1	1
KAT2B	0.021	0.043	-10000	0	-0.37	7	7
BAX	0.025	0.015	-10000	0	-0.32	1	1
FOXO3	-0.005	0.003	-10000	0	-10000	0	0
FOXO1	0.025	0.007	-10000	0	-10000	0	0
FOXO4	0.014	0.004	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.026	0.005	-10000	0	-10000	0	0
TAT	0.02	0.038	-10000	0	-0.32	7	7
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.016	0.038	-10000	0	-0.24	15	15
PPARGC1A	-0.012	0.12	-10000	0	-0.37	57	57
FHL2	0.024	0.033	-10000	0	-0.37	4	4
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.036	0.01	-10000	0	-10000	0	0
HIST2H4A	0.006	0.031	-10000	0	-0.22	10	10
SIRT1/FOXO3a	0.017	0.019	-10000	0	-0.2	1	1
SIRT1	0.024	0.008	0.19	1	-10000	0	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.049	0.016	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.016	0.045	-10000	0	-0.21	9	9
apoptosis	-0.048	0.018	0.19	1	-10000	0	1
SIRT1/PGC1A	0.008	0.073	-10000	0	-0.22	57	57
p53/SIRT1	0.03	0.017	0.37	1	-10000	0	1
SIRT1/FOXO4	0.019	0.036	-10000	0	-0.2	3	3
FOXO1/FHL2/SIRT1	0.044	0.023	-10000	0	-0.2	2	2
HIST1H1E	0.012	0.015	-10000	0	-0.23	1	1
SIRT1/p300	0.036	0.01	-10000	0	-10000	0	0
muscle cell differentiation	-0.023	0.04	0.21	15	-0.22	2	17
TP53	0.023	0.009	0.19	1	-10000	0	1
KU70/SIRT1/BAX	0.048	0.018	-10000	0	-0.19	1	1
CREBBP	0.026	0.006	-10000	0	-10000	0	0
MEF2D	0.026	0.005	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.032	0.03	-10000	0	-0.22	7	7
ACSS2	0.009	0.013	-10000	0	-0.26	1	1
SIRT1/PCAF/MYOD	0.024	0.04	0.22	2	-0.21	15	17

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.026	0.005	-9999	-10000	0	0
ITGB7	0.026	0.017	-9999	-0.37	1	1
ITGA4	0.023	0.038	-9999	-0.32	7	7
alpha4/beta7 Integrin	0.035	0.032	-9999	-0.23	8	8
alpha4/beta1 Integrin	0.035	0.03	-9999	-0.22	7	7

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.035	0.03	-10000	0	-0.24	6	6
AKT1	0.056	0.078	0.29	24	-10000	0	24
PTK2B	0.025	0.05	-10000	0	-10000	0	0
VEGFR2 homodimer/Frs2	0.032	0.011	-10000	0	-10000	0	0
CAV1	0.023	0.029	-10000	0	-0.32	4	4
CALM1	0.026	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.043	0.022	-10000	0	-10000	0	0
endothelial cell proliferation	0.061	0.11	0.28	63	-0.33	2	65
mol:Ca2+	0.018	0.025	0.19	5	-10000	0	5
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.052	0.03	-10000	0	-10000	0	0
RP11-342D11.1	0.009	0.021	0.18	8	-10000	0	8
CDH5	0.025	0.017	-10000	0	-0.37	1	1
VEGFA homodimer	0.056	0.031	-10000	0	-10000	0	0
SHC1	0.026	0.005	-10000	0	-10000	0	0
SHC2	0.019	0.052	-10000	0	-0.37	10	10
HRAS/GDP	0.041	0.023	-10000	0	-10000	0	0
SH2D2A	0.012	0.069	-10000	0	-0.32	24	24
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.045	0.099	0.27	4	-0.46	9	13
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.036	0.046	-10000	0	-10000	0	0
VEGFR1 homodimer	0.026	0.006	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.067	0.035	-10000	0	-10000	0	0
GRB10	0.02	0.028	-10000	0	-10000	0	0
PTPN11	0.026	0.004	-10000	0	-10000	0	0
GRB2	0.026	0.005	-10000	0	-10000	0	0
PAK1	0.025	0.006	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.061	0.037	-10000	0	-10000	0	0
HRAS	0.026	0.005	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.017	0.043	-10000	0	-0.29	2	2
HIF1A	0.026	0.015	-10000	0	-0.32	1	1
FRS2	0.025	0.007	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.05	0.029	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.025	0.017	-10000	0	-0.37	1	1
Nck/Pak	0.035	0.013	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.044	0.021	-10000	0	-10000	0	0
mol:GDP	0.053	0.027	-10000	0	-10000	0	0
mol:NADP	0.043	0.11	0.28	25	-0.44	10	35
eNOS/Hsp90	0.053	0.1	0.28	25	-0.44	8	33
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
mol:IP3	0.019	0.025	0.19	4	-10000	0	4
HIF1A/ARNT	0.037	0.015	-10000	0	-0.22	1	1
SHB	0.025	0.007	-10000	0	-10000	0	0
VEGFA	0.025	0.017	-10000	0	-0.32	1	1
VEGFC	0.022	0.035	-10000	0	-0.32	6	6
FAK1/Vinculin	0.054	0.075	0.27	19	-10000	0	19
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.025	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.052	0.036	-10000	0	-10000	0	0
PTPN6	0.025	0.016	-10000	0	-0.32	1	1
EPAS1	0.033	0.004	-10000	0	-10000	0	0
mol:L-citrulline	0.043	0.11	0.28	25	-0.44	10	35
ITGAV	0.026	0.006	-10000	0	-10000	0	0
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.053	0.029	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer	0.047	0.023	-10000	0	-10000	0	0
VEGFR2/3 heterodimer	0.032	0.014	-10000	0	-10000	0	0
VEGFB	0.027	0.004	-10000	0	-10000	0	0
MAPK11	0.019	0.055	0.24	8	-10000	0	8
VEGFR2 homodimer	0.02	0.004	-10000	0	-10000	0	0
FLT1	0.026	0.006	-10000	0	-10000	0	0
NEDD4	0.028	0.005	-10000	0	-10000	0	0
MAPK3	0.029	0.084	0.32	21	-10000	0	21
MAPK1	0.028	0.084	0.32	22	-10000	0	22
VEGFA145/NRP2	0.036	0.02	-10000	0	-0.22	2	2
VEGFR1/2 heterodimer	0.032	0.011	-10000	0	-10000	0	0
KDR	0.02	0.004	-10000	0	-10000	0	0
VEGFA165/NRP1/VEGFR2 homodimer	0.047	0.025	-10000	0	-10000	0	0
SRC	0.023	0.009	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.036	0.089	0.32	25	-10000	0	25
PI3K	0.033	0.037	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.042	0.023	-10000	0	-10000	0	0
FES	0.021	0.027	0.19	5	-10000	0	5
GAB1	0.032	0.033	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.04	0.024	-10000	0	-10000	0	0
CTNNB1	0.025	0.007	-10000	0	-10000	0	0
SOS1	0.027	0.003	-10000	0	-10000	0	0
ARNT	0.026	0.006	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.05	0.1	0.28	21	-0.42	10	31
VEGFR2 homodimer/VEGFA homodimer/Yes	0.043	0.022	-10000	0	-10000	0	0
PI3K/GAB1	0.044	0.056	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.058	0.038	-10000	0	-10000	0	0
PRKACA	0.026	0.005	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.042	0.028	-10000	0	-10000	0	0
HSP90AA1	0.026	0.006	-10000	0	-10000	0	0
CDC42	0.022	0.027	0.19	6	-10000	0	6
actin cytoskeleton reorganization	0.035	0.045	-10000	0	-10000	0	0
PTK2	0.028	0.05	0.24	9	-10000	0	9
EDG1	0.009	0.021	0.18	8	-10000	0	8
mol:DAG	0.019	0.025	0.19	4	-10000	0	4
CaM/Ca2+	0.037	0.038	-10000	0	-10000	0	0
MAP2K3	0.018	0.045	0.18	4	-10000	0	4
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.052	0.044	-10000	0	-10000	0	0
PLCG1	0.019	0.025	0.19	4	-10000	0	4
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.049	0.031	-10000	0	-10000	0	0
IQGAP1	0.026	0.006	-10000	0	-10000	0	0
YES1	0.025	0.007	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.045	0.021	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.042	0.024	-10000	0	-10000	0	0
cell migration	0.058	0.081	0.28	27	-10000	0	27
mol:PI-3-4-5-P3	0.034	0.038	-10000	0	-10000	0	0
FYN	0.026	0.005	-10000	0	-10000	0	0
VEGFB/NRP1	0.026	0.025	-10000	0	-10000	0	0
mol:NO	0.043	0.11	0.28	25	-0.44	10	35
PXN	0.027	0.004	-10000	0	-10000	0	0
HRAS/GTP	0.025	0.015	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.036	0.023	-10000	0	-10000	0	0
VHL	0.026	0.006	-10000	0	-10000	0	0
ITGB3	0.023	0.038	-10000	0	-0.36	6	6
NOS3	0.043	0.12	0.29	23	-0.5	10	33
VEGFR2 homodimer/VEGFA homodimer/Sck	0.04	0.035	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
PRKCA	0.016	0.042	-10000	0	-10000	0	0
PRKCB	0.009	0.057	-10000	0	-10000	0	0
VCL	0.026	0.006	-10000	0	-10000	0	0
VEGFA165/NRP1	0.028	0.023	-10000	0	-10000	0	0
VEGFR1/2 heterodimer/VEGFA homodimer	0.043	0.022	-10000	0	-10000	0	0
VEGFA165/NRP2	0.036	0.02	-10000	0	-0.22	2	2
MAPKKK cascade	0.03	0.032	-10000	0	-10000	0	0
NRP2	0.026	0.015	-10000	0	-0.32	1	1
VEGFC homodimer	0.022	0.035	-10000	0	-0.32	6	6
NCK1	0.025	0.007	-10000	0	-10000	0	0
ROCK1	0.026	0.006	-10000	0	-10000	0	0
FAK1/Paxillin	0.056	0.076	0.27	19	-10000	0	19
MAP3K13	0.018	0.026	0.19	5	-10000	0	5
PDPK1	0.032	0.049	0.24	12	-10000	0	12

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.03	0.013	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	0.012	0.008	-10000	0	-10000	0	0
mol:DAG	0.007	0.044	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.025	0.015	-10000	0	-10000	0	0
CaM/Ca2+	0.02	0.044	-10000	0	-10000	0	0
HIF1A	0.031	0.015	-10000	0	-0.32	1	1
GAB1	0.026	0.006	-10000	0	-10000	0	0
AKT1	0.022	0.061	0.32	5	-10000	0	5
PLCG1	0.007	0.044	-10000	0	-10000	0	0
NOS3	0.025	0.083	0.29	13	-0.45	5	18
CBL	0.025	0.007	-10000	0	-10000	0	0
mol:NO	0.027	0.09	0.32	15	-0.42	7	22
FLT1	0.016	0.01	-10000	0	-10000	0	0
PGF	0.011	0.072	-10000	0	-0.32	26	26
VEGFR1 homodimer/NRP2/VEGFR121	0.039	0.024	-10000	0	-10000	0	0
CALM1	0.026	0.005	-10000	0	-10000	0	0
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
eNOS/Hsp90	0.038	0.093	0.3	12	-0.43	7	19
endothelial cell proliferation	0.017	0.081	0.32	14	-10000	0	14
mol:Ca2+	0.007	0.044	-10000	0	-10000	0	0
MAPK3	-0.012	0.041	0.35	1	-10000	0	1
MAPK1	-0.011	0.043	0.35	2	-10000	0	2
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
PLGF homodimer	0.011	0.072	-10000	0	-0.32	26	26
PRKACA	0.026	0.005	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.023	0.029	-10000	0	-0.32	4	4
VEGFA homodimer	0.024	0.016	-10000	0	-0.32	1	1
VEGFR1 homodimer/VEGFA homodimer	0.027	0.017	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.013	0.04	0.34	1	-10000	0	1
PI3K	0.042	0.044	-10000	0	-10000	0	0
PRKCA	-0.01	0.042	0.2	11	-10000	0	11
PRKCB	-0.017	0.058	0.2	12	-0.32	4	16
VEGFR1 homodimer/PLGF homodimer	0.022	0.043	-10000	0	-10000	0	0
VEGFA	0.024	0.016	-10000	0	-0.32	1	1
VEGFB	0.027	0.004	-10000	0	-10000	0	0
mol:IP3	0.007	0.044	-10000	0	-10000	0	0
RASA1	0.019	0.036	-10000	0	-10000	0	0
NRP2	0.026	0.015	-10000	0	-0.32	1	1
VEGFR1 homodimer	0.016	0.01	-10000	0	-10000	0	0
VEGFB homodimer	0.027	0.004	-10000	0	-10000	0	0
NCK1	0.025	0.007	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.035	0.094	0.31	12	-0.42	8	20
PTPN11	0.026	0.004	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.04	0.043	-10000	0	-10000	0	0
mol:L-citrulline	0.027	0.09	0.32	15	-0.42	7	22
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.049	0.028	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.037	0.022	-10000	0	-10000	0	0
CD2AP	0.026	0.006	-10000	0	-10000	0	0
PI3K/GAB1	0.055	0.051	-10000	0	-10000	0	0
PDPK1	0.009	0.07	0.34	5	-10000	0	5
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.039	0.022	-10000	0	-10000	0	0
mol:NADP	0.027	0.09	0.32	15	-0.42	7	22
HSP90AA1	0.026	0.006	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.048	0.028	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.029	0.015	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.024	0.032	0.36	4	-10000	0	4
PI3K Class IB/PDE3B	0.024	0.032	-10000	0	-0.36	4	4
PDE3B	0.024	0.032	-10000	0	-0.36	4	4

×

Arf6 downstream 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
PLAUR	0.017	0.033	-10000	0	-10000	0	0
regulation of axonogenesis	-0.007	0.023	0.23	4	-10000	0	4
myoblast fusion	-0.022	0.04	0.31	3	-10000	0	3
mol:GTP	0.017	0.027	-10000	0	-0.16	8	8
regulation of calcium-dependent cell-cell adhesion	-0.036	0.056	0.21	8	-10000	0	8
ARF1/GTP	0.032	0.025	-10000	0	-10000	0	0
mol:GM1	0.007	0.02	-10000	0	-0.15	1	1
mol:Choline	0.006	0.021	-10000	0	-0.26	2	2
lamellipodium assembly	0.009	0.051	-10000	0	-0.36	8	8
MAPK3	0.018	0.024	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.037	0.056	-10000	0	-0.21	8	8
ARF1	0.026	0.005	-10000	0	-10000	0	0
ARF6/GDP	0.022	0.04	-10000	0	-0.31	3	3
ARF1/GDP	0.025	0.046	-10000	0	-0.31	3	3
ARF6	0.032	0.015	-10000	0	-10000	0	0
RAB11A	0.026	0.004	-10000	0	-10000	0	0
TIAM1	0.009	0.076	-10000	0	-0.34	27	27
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.018	0.024	-10000	0	-10000	0	0
actin filament bundle formation	-0.027	0.044	0.29	3	-10000	0	3
KALRN	0.007	0.04	-10000	0	-0.2	14	14
RAB11FIP3/RAB11A	0.037	0.011	-10000	0	-10000	0	0
RhoA/GDP	0.028	0.044	-10000	0	-0.29	3	3
NME1	0.026	0.016	-10000	0	-0.32	1	1
Rac1/GDP	0.027	0.045	-10000	0	-0.31	3	3
substrate adhesion-dependent cell spreading	0.017	0.027	-10000	0	-0.16	8	8
cortical actin cytoskeleton organization	0.009	0.051	-10000	0	-0.36	8	8
RAC1	0.025	0.007	-10000	0	-10000	0	0
liver development	0.017	0.027	-10000	0	-0.16	8	8
ARF6/GTP	0.017	0.027	-10000	0	-0.16	8	8
RhoA/GTP	0.031	0.025	-10000	0	-10000	0	0
mol:GDP	0.01	0.036	-10000	0	-0.29	2	2
ARF6/GTP/RAB11FIP3/RAB11A	0.045	0.028	-10000	0	-10000	0	0
RHOA	0.025	0.007	-10000	0	-10000	0	0
PLD1	0.013	0.023	-10000	0	-0.17	2	2
RAB11FIP3	0.026	0.006	-10000	0	-10000	0	0
tube morphogenesis	0.009	0.051	-10000	0	-0.36	8	8
ruffle organization	0.007	0.023	-10000	0	-0.23	4	4
regulation of epithelial cell migration	0.017	0.027	-10000	0	-0.16	8	8
PLD2	0.015	0.024	-10000	0	-0.21	2	2
PIP5K1A	0.007	0.023	-10000	0	-0.23	4	4
mol:Phosphatidic acid	0.006	0.021	-10000	0	-0.26	2	2
Rac1/GTP	0.009	0.051	-10000	0	-0.36	8	8

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.037	0.073	-10000	0	-0.28	8	8
Ran/GTP/Exportin 1/HDAC1	-0.009	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.017	0.08	-10000	0	-0.29	18	18
SUMO1	0.027	0.003	-10000	0	-10000	0	0
ZFPM1	0.026	0.006	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.013	0.004	-10000	0	-10000	0	0
FKBP3	0.026	0.005	-10000	0	-10000	0	0
Histones	0.044	0.065	-10000	0	-0.27	4	4
YY1/LSF	0.014	0.057	-10000	0	-0.23	11	11
SMG5	0.026	0.004	-10000	0	-10000	0	0
RAN	0.026	0.004	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.015	0.039	-10000	0	-0.24	6	6
I kappa B alpha/HDAC1	0.022	0.052	-10000	0	-0.27	2	2
SAP18	0.026	0.006	-10000	0	-10000	0	0
RELA	0.02	0.043	0.28	1	-0.48	1	2
HDAC1/Smad7	0.042	0.024	-10000	0	-10000	0	0
RANGAP1	0.026	0.005	-10000	0	-10000	0	0
HDAC3/TR2	0.022	0.057	-10000	0	-0.29	4	4
NuRD/MBD3 Complex	0.025	0.043	-10000	0	-0.39	2	2
NF kappa B1 p50/RelA	0.014	0.084	0.21	2	-0.34	15	17
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.022	0.037	-10000	0	-0.37	5	5
GATA1	0.024	0.015	-10000	0	-0.32	1	1
Mad/Max	0.039	0.008	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.022	0.065	-10000	0	-0.37	7	7
RBBP7	0.026	0.005	-10000	0	-10000	0	0
NPC	0.016	0.002	-10000	0	-10000	0	0
RBBP4	0.026	0.004	-10000	0	-10000	0	0
MAX	0.026	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.026	0.006	-10000	0	-10000	0	0
NFKBIA	0.013	0.033	-10000	0	-0.29	2	2
KAT2B	0.021	0.043	-10000	0	-0.37	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.022	0.018	-10000	0	-10000	0	0
SIN3 complex	0.06	0.025	-10000	0	-10000	0	0
SMURF1	0.024	0.009	-10000	0	-10000	0	0
CHD3	0.025	0.007	-10000	0	-10000	0	0
SAP30	0.025	0.007	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.025	0.008	-10000	0	-10000	0	0
YY1/HDAC3	0.01	0.058	-10000	0	-0.36	7	7
YY1/HDAC2	0.014	0.057	-10000	0	-0.27	5	5
YY1/HDAC1	0.015	0.056	-10000	0	-0.23	12	12
NuRD/MBD2 Complex (MeCP1)	0.021	0.047	-10000	0	-0.39	2	2
PPARG	0.001	0.08	-10000	0	-0.27	38	38
HDAC8/hEST1B	0.051	0.015	-10000	0	-10000	0	0
UBE2I	0.026	0.006	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.006	-10000	0	-10000	0	0
TNFRSF1A	0.025	0.007	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.022	0.056	-10000	0	-0.29	4	4
MBD3L2	0.017	0.015	-10000	0	-0.32	1	1
ubiquitin-dependent protein catabolic process	0.042	0.023	-10000	0	-10000	0	0
CREBBP	0.026	0.006	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.018	0.072	-10000	0	-0.36	11	11
HDAC1	0.026	0.005	-10000	0	-10000	0	0
HDAC3	0.014	0.033	-10000	0	-0.33	2	2
HDAC2	0.026	0.005	-10000	0	-10000	0	0
YY1	0.014	0.027	-10000	0	-0.22	7	7
HDAC8	0.027	0.004	-10000	0	-10000	0	0
SMAD7	0.024	0.009	-10000	0	-10000	0	0
NCOR2	0.026	0.005	-10000	0	-10000	0	0
MXD1	0.027	0.003	-10000	0	-10000	0	0
STAT3	0.019	0.006	-10000	0	-10000	0	0
NFKB1	0.026	0.004	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.027	0.003	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.029	0.057	-10000	0	-0.25	4	4
YY1/SAP30/HDAC1	0.029	0.056	-10000	0	-0.26	4	4
EP300	0.026	0.005	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.019	0.006	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.033	-10000	0	-0.29	2	2
histone deacetylation	0.018	0.055	-10000	0	-0.27	10	10
STAT3 (dimer non-phopshorylated)/HDAC3	0.017	0.042	-10000	0	-0.32	4	4
nuclear export	-0.05	0.015	-10000	0	-10000	0	0
PRKACA	0.026	0.005	-10000	0	-10000	0	0
GATAD2B	0.026	0.005	-10000	0	-10000	0	0
GATAD2A	0.026	0.005	-10000	0	-10000	0	0
GATA2/HDAC3	0.019	0.06	-10000	0	-0.36	3	3
GATA1/HDAC1	0.037	0.009	-10000	0	-10000	0	0
GATA1/HDAC3	0.02	0.058	-10000	0	-0.3	4	4
CHD4	0.025	0.007	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.019	0.065	-10000	0	-0.23	38	38
SIN3/HDAC complex/Mad/Max	0.022	0.047	-10000	0	-0.51	2	2
NuRD Complex	0.014	0.076	-10000	0	-0.37	10	10
positive regulation of chromatin silencing	0.042	0.063	-10000	0	-0.26	4	4
SIN3B	0.026	0.005	-10000	0	-10000	0	0
MTA2	0.027	0.004	-10000	0	-10000	0	0
SIN3A	0.026	0.005	-10000	0	-10000	0	0
XPO1	0.027	0.003	-10000	0	-10000	0	0
SUMO1/HDAC1	0.035	0.032	-10000	0	-10000	0	0
HDAC complex	0.064	0.02	-10000	0	-10000	0	0
GATA1/Fog1	0.035	0.015	-10000	0	-0.22	1	1
FKBP25/HDAC1/HDAC2	0.051	0.014	-10000	0	-10000	0	0
TNF	0.001	0.091	-10000	0	-0.33	42	42
negative regulation of cell growth	0.021	0.051	-10000	0	-0.33	6	6
NuRD/MBD2/PRMT5 Complex	0.021	0.047	-10000	0	-0.39	2	2
Ran/GTP/Exportin 1	0.036	0.034	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.006	0.065	-10000	0	-0.3	15	15
SIN3/HDAC complex/NCoR1	0.013	0.051	-10000	0	-0.3	6	6
TFCP2	0.027	0.004	-10000	0	-10000	0	0
NR2C1	0.027	0.004	-10000	0	-10000	0	0
MBD3	0.026	0.006	-10000	0	-10000	0	0
MBD2	0.023	0.009	-10000	0	-10000	0	0

×

BARD1 signaling events

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.032	0.019	-10000	0	-0.22	1	1
ATM	0.025	0.007	-10000	0	-10000	0	0
UBE2D3	0.026	0.005	-10000	0	-10000	0	0
PRKDC	0.024	0.016	-10000	0	-0.32	1	1
ATR	0.025	0.008	-10000	0	-10000	0	0
UBE2L3	0.026	0.006	-10000	0	-10000	0	0
FANCD2	0.016	0.019	-10000	0	-0.28	1	1
protein ubiquitination	0.048	0.053	-10000	0	-10000	0	0
XRCC5	0.027	0.004	-10000	0	-10000	0	0
XRCC6	0.026	0.005	-10000	0	-10000	0	0
M/R/N Complex	0.045	0.022	-10000	0	-10000	0	0
MRE11A	0.026	0.006	-10000	0	-10000	0	0
DNA-PK	0.048	0.021	-10000	0	-0.19	1	1
FA complex/FANCD2/Ubiquitin	0.021	0.067	-10000	0	-0.37	8	8
FANCF	0.027	0.004	-10000	0	-10000	0	0
BRCA1	0.024	0.029	-10000	0	-0.32	4	4
CCNE1	0.011	0.066	-10000	0	-0.32	22	22
CDK2/Cyclin E1	0.026	0.049	-10000	0	-0.22	20	20
FANCG	0.025	0.007	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.036	0.025	-10000	0	-0.22	5	5
FANCE	0.026	0.015	-10000	0	-0.32	1	1
FANCC	0.026	0.005	-10000	0	-10000	0	0
NBN	0.024	0.008	-10000	0	-10000	0	0
FANCA	0.017	0.055	-10000	0	-0.32	15	15
DNA repair	0.027	0.069	0.25	15	-10000	0	15
BRCA1/BARD1/ubiquitin	0.036	0.025	-10000	0	-0.22	5	5
BARD1/DNA-PK	0.06	0.026	-10000	0	-0.17	1	1
FANCL	0.026	0.015	-10000	0	-0.32	1	1
mRNA polyadenylation	-0.032	0.019	0.22	1	-10000	0	1
BRCA1/BARD1/CTIP/M/R/N Complex	0.026	0.044	-10000	0	-0.26	2	2
BRCA1/BACH1/BARD1/TopBP1	0.047	0.028	-10000	0	-0.19	5	5
BRCA1/BARD1/P53	0.056	0.034	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	0.042	0.031	-10000	0	-0.19	5	5
BRCA1/BACH1	0.024	0.029	-10000	0	-0.32	4	4
BARD1	0.026	0.015	-10000	0	-0.32	1	1
PCNA	0.025	0.008	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.049	0.026	-10000	0	-0.19	5	5
BRCA1/BARD1/UbcH7	0.048	0.027	-10000	0	-0.19	5	5
BRCA1/BARD1/RAD51/PCNA	0.057	0.033	-10000	0	-10000	0	0
BARD1/DNA-PK/P53	0.066	0.032	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.036	0.025	-10000	0	-0.22	5	5
BRCA1/BARD1/CTIP	0.036	0.029	0.17	3	-0.17	5	8
FA complex	0.026	0.032	-10000	0	-0.25	1	1
BARD1/EWS	0.037	0.015	-10000	0	-0.22	1	1
RBBP8	0.01	0.011	-10000	0	-0.22	1	1
TP53	0.025	0.007	-10000	0	-10000	0	0
TOPBP1	0.025	0.007	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.054	0.033	-10000	0	-10000	0	0
BRCA1/BARD1	0.053	0.056	-10000	0	-10000	0	0
CSTF1	0.023	0.01	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.019	0.01	-10000	0	-0.22	1	1
CDK2	0.026	0.005	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.026	0.005	-10000	0	-10000	0	0
RAD50	0.025	0.007	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.036	0.025	-10000	0	-0.22	5	5
EWSR1	0.026	0.005	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.023	0.01	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0.029	0.031	-10000	0	-0.25	5	5
MAP2K4	0.025	0.04	0.21	2	-0.29	1	3
IKBKB	0.024	0.008	-10000	0	-10000	0	0
TNFRSF10B	0.024	0.008	-10000	0	-10000	0	0
TNFRSF10A	0.024	0.008	-10000	0	-10000	0	0
SMPD1	0.011	0.006	-10000	0	-10000	0	0
IKBKG	0.026	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.02	0.04	-10000	0	-0.36	6	6
TRAIL/TRAILR2	0.032	0.017	-10000	0	-10000	0	0
TRAIL/TRAILR3	0.026	0.04	-10000	0	-0.24	11	11
TRAIL/TRAILR1	0.032	0.017	-10000	0	-10000	0	0
TRAIL/TRAILR4	0.029	0.031	-10000	0	-0.26	5	5
TRAIL/TRAILR1/DAP3/GTP	0.04	0.022	-10000	0	-10000	0	0
IKK complex	0.015	0.036	-10000	0	-10000	0	0
RIPK1	0.025	0.007	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.02	0.003	-10000	0	-10000	0	0
MAPK3	0.01	0.005	-10000	0	-10000	0	0
MAP3K1	0.027	0.032	0.23	1	-10000	0	1
TRAILR4 (trimer)	0.02	0.04	-10000	0	-0.36	6	6
TRADD	0.026	0.005	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.024	0.008	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.02	0.016	-10000	0	-10000	0	0
CFLAR	0.027	0.003	-10000	0	-10000	0	0
MAPK1	0.01	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	0.052	0.039	-10000	0	-10000	0	0
mol:ceramide	0.011	0.006	-10000	0	-10000	0	0
FADD	0.023	0.01	-10000	0	-10000	0	0
MAPK8	0.03	0.055	0.23	5	-0.32	2	7
TRAF2	0.026	0.005	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.014	0.063	-10000	0	-0.35	17	17
CHUK	0.026	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.038	0.025	-10000	0	-10000	0	0
DAP3	0.026	0.005	-10000	0	-10000	0	0
CASP10	0.032	0.066	0.31	11	-10000	0	11
JNK cascade	0.029	0.031	-10000	0	-0.25	5	5
TRAIL (trimer)	0.023	0.01	-10000	0	-10000	0	0
TNFRSF10C	0.014	0.063	-10000	0	-0.35	17	17
TRAIL/TRAILR1/DAP3/GTP/FADD	0.044	0.03	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD	0.038	0.025	-10000	0	-10000	0	0
cell death	0.011	0.006	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.02	0.017	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.024	0.008	-10000	0	-10000	0	0
CASP8	0.009	0.05	-10000	0	-0.56	4	4
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.052	0.039	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.025	0.015	-9999	-0.32	1	1
Rac1/GDP	0.024	0.011	-9999	-10000	0	0
DOCK1	0.026	0.006	-9999	-10000	0	0
ITGA4	0.023	0.038	-9999	-0.32	7	7
RAC1	0.025	0.007	-9999	-10000	0	0
alpha4/beta7 Integrin	0.035	0.032	-9999	-0.23	8	8
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.025	0.007	-9999	-10000	0	0
alpha4/beta1 Integrin	0.047	0.03	-9999	-0.19	7	7
alpha4/beta7 Integrin/Paxillin	0.039	0.028	-9999	-0.2	1	1
lamellipodium assembly	0.003	0.088	-9999	-0.38	22	22
PIK3CA	0.024	0.009	-9999	-10000	0	0
PI3K	0.032	0.016	-9999	-10000	0	0
ARF6	0.026	0.005	-9999	-10000	0	0
TLN1	0.025	0.008	-9999	-10000	0	0
PXN	0.012	0.003	-9999	-10000	0	0
PIK3R1	0.025	0.008	-9999	-10000	0	0
ARF6/GTP	0.048	0.03	-9999	-10000	0	0
cell adhesion	0.046	0.032	-9999	-10000	0	0
CRKL/CBL	0.036	0.016	-9999	-0.22	1	1
alpha4/beta1 Integrin/Paxillin	0.038	0.027	-9999	-10000	0	0
ITGB1	0.026	0.005	-9999	-10000	0	0
ITGB7	0.026	0.017	-9999	-0.37	1	1
ARF6/GDP	0.025	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.049	0.038	-9999	-0.31	1	1
p130Cas/Crk/Dock1	0.048	0.018	-9999	-10000	0	0
VCAM1	0.023	0.035	-9999	-0.32	6	6
alpha4/beta1 Integrin/Paxillin/Talin	0.048	0.032	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.051	0.03	-9999	-10000	0	0
BCAR1	0.026	0.005	-9999	-10000	0	0
mol:GDP	-0.049	0.03	-9999	-10000	0	0
CBL	0.025	0.007	-9999	-10000	0	0
PRKACA	0.026	0.005	-9999	-10000	0	0
GIT1	0.027	0.004	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.048	0.032	-9999	-10000	0	0
Rac1/GTP	0.002	0.097	-9999	-0.42	22	22

×

Atypical NF-kappaB 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
BCL3/RelA	0.037	0.011	-10000	0	-10000	0	0
FBXW11	0.026	0.006	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.026	0.01	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.03	0.054	0.22	7	-0.26	2	9
NFKBIA	0.017	0.043	-10000	0	-10000	0	0
MAPK14	0.026	0.005	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.025	0.011	-10000	0	-10000	0	0
ARRB2	0.013	0.004	-10000	0	-10000	0	0
REL	0.027	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.025	0.011	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.025	0.01	-10000	0	-10000	0	0
PIK3CA	0.024	0.009	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	0.018	0.007	-10000	0	-10000	0	0
PIK3R1	0.025	0.008	-10000	0	-10000	0	0
NFKB1	0.011	0.004	-10000	0	-10000	0	0
RELA	0.026	0.005	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.017	0.044	-10000	0	-0.31	1	1
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.03	0.055	0.2	7	-0.29	2	9
SRC	0.023	0.009	-10000	0	-10000	0	0
PI3K	0.032	0.016	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.017	0.044	-10000	0	-0.31	1	1
IKBKB	0.024	0.008	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.006	-10000	0	-10000	0	0
SYK	0.025	0.017	-10000	0	-0.37	1	1
I kappa B alpha/PIK3R1	0.03	0.054	0.23	8	-0.27	2	10
cell death	0.027	0.051	0.18	4	-0.28	2	6
NF kappa B1 p105/c-Rel	0.026	0.01	-10000	0	-10000	0	0
LCK	-0.004	0.099	-10000	0	-0.32	52	52
BCL3	0.026	0.006	-10000	0	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.023	0.047	0.15	73	-10000	0	73
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.015	0.032	0.15	10	-0.2	1	11
AP2	0.034	0.015	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.034	0.012	-10000	0	-10000	0	0
CLTB	0.026	0.006	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.017	0.008	-10000	0	-10000	0	0
CD4	0.022	0.036	-10000	0	-0.33	6	6
CLTA	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ARFGAP1	0.006	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.007	0.012	-10000	0	-10000	0	0
ARF1/GTP	0.031	0.013	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.008	0.005	-10000	0	-10000	0	0
mol:Choline	0.006	0.012	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.027	0.007	-10000	0	-10000	0	0
DDEF1	0.005	0.012	-10000	0	-10000	0	0
ARF1/GDP	0.004	0.011	-10000	0	-10000	0	0
AP2M1	0.024	0.009	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.011	0.006	-10000	0	-10000	0	0
Rac/GTP	0.02	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.031	0.017	-10000	0	-10000	0	0
ARFIP2	0.022	0.015	-10000	0	-10000	0	0
COPA	0.026	0.005	-10000	0	-10000	0	0
RAC1	0.025	0.007	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.012	0.039	-10000	0	-0.19	8	8
ARF1/GTP/ARHGAP10	0.018	0.006	-10000	0	-10000	0	0
GGA3	0.026	0.005	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.023	0.021	-10000	0	-0.24	3	3
AP2A1	0.026	0.005	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.008	0.028	-10000	0	-0.21	6	6
ARF1/GDP/Membrin	0.023	0.025	-10000	0	-0.27	3	3
Arfaptin 2/Rac/GDP	0.032	0.012	-10000	0	-10000	0	0
CYTH2	0.028	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.035	0.011	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.019	0.005	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.018	0.025	-10000	0	-10000	0	0
PLD2	0.006	0.012	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	0.005	0.002	-10000	0	-10000	0	0
PIP5K1A	0.007	0.012	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.018	0.021	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.006	0.012	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.005	0.002	-10000	0	-10000	0	0
GOSR2	0.012	0.015	-10000	0	-0.31	1	1
USO1	0.011	0.024	-10000	0	-0.31	3	3
GBF1	0.008	0.038	-10000	0	-0.31	8	8
ARF1/GTP/Arfaptin 2	0.036	0.012	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.042	0.032	-10000	0	-0.19	6	6

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.023	0.01	-10000	0	-10000	0	0
SMAD2	0.01	0.039	0.19	2	-0.25	1	3
SMAD3	0.023	0.025	-10000	0	-10000	0	0
SMAD3/SMAD4	0.017	0.093	-10000	0	-0.41	24	24
SMAD4/Ubc9/PIASy	0.044	0.022	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.043	0.049	-10000	0	-10000	0	0
PPM1A	0.026	0.005	-10000	0	-10000	0	0
CALM1	0.026	0.005	-10000	0	-10000	0	0
SMAD2/SMAD4	0.015	0.037	-10000	0	-0.23	3	3
MAP3K1	0.025	0.007	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.033	0.015	-10000	0	-10000	0	0
MAPK3	0.026	0.005	-10000	0	-10000	0	0
MAPK1	0.026	0.005	-10000	0	-10000	0	0
NUP214	0.026	0.005	-10000	0	-10000	0	0
CTDSP1	0.027	0.004	-10000	0	-10000	0	0
CTDSP2	0.026	0.005	-10000	0	-10000	0	0
CTDSPL	0.025	0.007	-10000	0	-10000	0	0
KPNB1	0.027	0.002	-10000	0	-10000	0	0
TGFBRAP1	0.026	0.004	-10000	0	-10000	0	0
UBE2I	0.026	0.006	-10000	0	-10000	0	0
NUP153	0.026	0.006	-10000	0	-10000	0	0
KPNA2	0.025	0.021	-10000	0	-0.32	2	2
PIAS4	0.026	0.006	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.06	0.027	-9999	-0.18	2	2
HDAC3	0.025	0.006	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.009	0.003	-9999	-10000	0	0
GATA1/HDAC4	0.036	0.014	-9999	-0.22	1	1
GATA1/HDAC5	0.037	0.013	-9999	-0.22	1	1
GATA2/HDAC5	0.035	0.029	-9999	-0.26	5	5
HDAC5/BCL6/BCoR	0.047	0.02	-9999	-10000	0	0
HDAC9	0.013	0.068	-9999	-0.37	18	18
Glucocorticoid receptor/Hsp90/HDAC6	0.047	0.03	-9999	-0.22	5	5
HDAC4/ANKRA2	0.036	0.013	-9999	-10000	0	0
HDAC5/YWHAB	0.033	0.016	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.013	0.004	-9999	-10000	0	0
GATA2	0.022	0.037	-9999	-0.37	5	5
HDAC4/RFXANK	0.038	0.01	-9999	-10000	0	0
BCOR	0.026	0.005	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.026	0.006	-9999	-10000	0	0
HDAC5	0.027	0.003	-9999	-10000	0	0
GNB1/GNG2	0.036	0.019	-9999	-0.24	2	2
Histones	0.018	0.048	-9999	-0.27	2	2
ADRBK1	0.026	0.006	-9999	-10000	0	0
HDAC4	0.026	0.005	-9999	-10000	0	0
XPO1	0.027	0.003	-9999	-10000	0	0
HDAC5/ANKRA2	0.036	0.012	-9999	-10000	0	0
HDAC4/Ubc9	0.037	0.011	-9999	-10000	0	0
HDAC7	0.026	0.004	-9999	-10000	0	0
HDAC5/14-3-3 E	0.037	0.011	-9999	-10000	0	0
TUBA1B	0.027	0.004	-9999	-10000	0	0
HDAC6	0.026	0.004	-9999	-10000	0	0
HDAC5/RFXANK	0.038	0.009	-9999	-10000	0	0
CAMK4	0.014	0.064	-9999	-0.37	16	16
Tubulin/HDAC6	0.048	0.022	-9999	-0.19	2	2
SUMO1	0.027	0.003	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.023	0.01	-9999	-10000	0	0
GATA1	0.024	0.015	-9999	-0.32	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.025	0.007	-9999	-10000	0	0
NR3C1	0.022	0.037	-9999	-0.37	5	5
SUMO1/HDAC4	0.034	0.034	-9999	-10000	0	0
SRF	0.025	0.008	-9999	-10000	0	0
HDAC4/YWHAB	0.032	0.016	-9999	-10000	0	0
Tubulin	0.036	0.019	-9999	-0.23	2	2
HDAC4/14-3-3 E	0.037	0.012	-9999	-10000	0	0
GNB1	0.026	0.006	-9999	-10000	0	0
RANGAP1	0.026	0.005	-9999	-10000	0	0
BCL6/BCoR	0.035	0.014	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.05	0.017	-9999	-10000	0	0
HDAC4/SRF	0.038	0.047	-9999	-0.22	16	16
HDAC4/ER alpha	0.025	0.06	-9999	-0.26	25	25
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.018	0.048	-9999	-0.27	2	2
cell motility	0.048	0.022	-9999	-0.19	2	2
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.026	0.006	-9999	-10000	0	0
HDAC7/HDAC3	0.037	0.011	-9999	-10000	0	0
BCL6	0.024	0.009	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.026	0.005	-9999	-10000	0	0
Hsp90/HDAC6	0.037	0.01	-9999	-10000	0	0
ESR1	0.01	0.079	-9999	-0.37	25	25
HDAC6/HDAC11	0.037	0.01	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.036	0.034	-9999	-10000	0	0
NPC	0.016	0.002	-9999	-10000	0	0
MEF2C	0.024	0.024	-9999	-0.37	2	2
RAN	0.026	0.004	-9999	-10000	0	0
HDAC4/MEF2C	0.068	0.033	-9999	-10000	0	0
GNG2	0.025	0.022	-9999	-0.35	2	2
NCOR2	0.026	0.005	-9999	-10000	0	0
TUBB2A	0.024	0.023	-9999	-0.35	2	2
HDAC11	0.026	0.006	-9999	-10000	0	0
HSP90AA1	0.026	0.006	-9999	-10000	0	0
RANBP2	0.027	0.003	-9999	-10000	0	0
ANKRA2	0.025	0.008	-9999	-10000	0	0
RFXANK	0.026	0.005	-9999	-10000	0	0
nuclear import	-0.027	0.016	-9999	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.044	0.028	-9999	-10000	0	0
CLOCK	0.028	0.006	-9999	-10000	0	0
TIMELESS/CRY2	0.036	0.023	-9999	-10000	0	0
DEC1/BMAL1	0.032	0.026	-9999	-0.23	5	5
ATR	0.025	0.008	-9999	-10000	0	0
NR1D1	0.018	0.011	-9999	-10000	0	0
ARNTL	0.028	0.017	-9999	-0.37	1	1
TIMELESS	0.02	0.013	-9999	-10000	0	0
NPAS2	0.028	0.005	-9999	-10000	0	0
CRY2	0.026	0.005	-9999	-10000	0	0
mol:CO	-0.008	0.004	-9999	-10000	0	0
CHEK1	0.025	0.016	-9999	-0.32	1	1
mol:HEME	0.008	0.004	-9999	-10000	0	0
PER1	0.015	0.065	-9999	-0.37	16	16
BMAL/CLOCK/NPAS2	0.06	0.021	-9999	-0.22	1	1
BMAL1/CLOCK	0.026	0.054	-9999	-0.37	2	2
S phase of mitotic cell cycle	0.044	0.028	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.045	0.028	-9999	-10000	0	0
mol:NADPH	0.008	0.004	-9999	-10000	0	0
PER1/TIMELESS	0.03	0.039	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.016	0.032	-9999	-0.32	5	5

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.026	0.005	-10000	0	-9999	0
Ran/GTP/Exportin 1/HDAC4	0.005	0.011	-10000	0	-9999	0
MDM2/SUMO1	0.034	0.033	-10000	0	-9999	0
HDAC4	0.026	0.005	-10000	0	-9999	0
Ran/GTP/Exportin 1/HDAC1	0.005	0.01	-10000	0	-9999	0
SUMO1	0.027	0.003	-10000	0	-9999	0
NPC/RanGAP1/SUMO1	0.011	0.007	-10000	0	-9999	0
mol:GTP	0	0	-10000	0	-9999	0
XPO1	0.008	0.007	-10000	0	-9999	0
EntrezGene:23636	0	0	-10000	0	-9999	0
RAN	0.026	0.004	-10000	0	-9999	0
EntrezGene:8021	0	0	-10000	0	-9999	0
RANBP2	0.027	0.003	-10000	0	-9999	0
SUMO1/HDAC4	0.034	0.034	-10000	0	-9999	0
SUMO1/HDAC1	0.035	0.032	-10000	0	-9999	0
RANGAP1	0.026	0.005	-10000	0	-9999	0
MDM2/SUMO1/SUMO1	0.057	0.027	-10000	0	-9999	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.013	0.004	-10000	0	-9999	0
Ran/GTP	0.024	0.029	-10000	0	-9999	0
EntrezGene:23225	0	0	-10000	0	-9999	0
MDM2	0.025	0.006	-10000	0	-9999	0
UBE2I	0.026	0.006	-10000	0	-9999	0
Ran/GTP/Exportin 1	0.023	0.034	0.19	7	-9999	7
NPC	0.016	0.002	-10000	0	-9999	0
PIAS2	0.024	0.009	-10000	0	-9999	0
PIAS1	0.027	0.004	-10000	0	-9999	0
EntrezGene:9972	0	0	-10000	0	-9999	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.038	0.009	-9999	-9999
FBXW11	0.026	0.006	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.006	-9999	-9999
CHUK	0.026	0.005	-9999	-9999
NF kappa B2 p100/RelB	0.07	0.028	-9999	-9999
NFKB1	0.026	0.004	-9999	-9999
MAP3K14	0.027	0.004	-9999	-9999
NF kappa B1 p50/RelB	0.037	0.01	-9999	-9999
RELB	0.026	0.006	-9999	-9999
NFKB2	0.026	0.005	-9999	-9999
NF kappa B2 p52/RelB	0.034	0.01	-9999	-9999
regulation of B cell activation	0.034	0.01	-9999	-9999

pid_entity	TCGA.ZR.A9CJ	TCGA.ZQ.A9CR	TCGA.ZA.A8F6	TCGA.Z6.AAPN
109_MAP3K5	0.028	0.028	0.028	0.028
47_PPARGC1A	0.027	0.027	0.027	0.027
105_BMP4	0.027	0.027	0.027	0.027
105_BMP6	0.027	0.027	0.027	0.027
105_BMP7	-0.37	0.027	0.027	0.027
105_BMP2	0.027	0.027	0.027	0.027
131_RELN/VLDLR	0.07	-0.35	0.07	-0.2
30_TGFB1/TGF beta receptor Type II	0.027	0.027	0.027	0.027
84_STAT5B	0.087	-0.014	0.004	-0.076
84_STAT5A	0.087	-0.014	0.004	-0.076